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Acute hemorrhagic edema of infancy (AHEI)--a variant of Henoch-Schonlein purpura or a distinct clinical entity? Acute hemorrhagic edema of infancy (AHEI) is an acute cutaneous leukocytoclastic vasculitis (LCV) of infants. The clinical picture has a violent onset with a short benign course followed by spontaneous complete recovery. We report 12 infants with AHEI who were studied clinically, serologically, and immunohistologically. Edema and palpable purpuric skin lesions were present in all infants who were in good general condition. Serologic studies were unremarkable. Light microscopic examination of the skin biopsy specimens revealed LCV as in Henoch-Schonlein purpura (HSP). Direct immunofluorescent study revealed depositions of various immunoreactants, including fibrinogen, C3, IgG, IgM, IgA, and IgE (100%, 100%, 22%, 78%, 33%, and 33%, respectively) in the wall and around the small vessels. Similar deposition of Clq was also present in three infants in whom Clq could be studied (100%). The clinical similarities and differences between AHEI and HSP have been discussed in the literature. AHEI is observed before 2 years of age and is confined to the skin. The skin lesions of HSP are more polymorphic. Although histopathologic findings are similar, the immunohistologic pattern found in our series of AHEI is rather different from the pattern of HSP. Taking all of these findings into account, we suggest that AHEI should be considered as a separate, clinicopathologic entity or a possible variant of HSP. The more descriptive term "acute benign cutaneous LCV of infancy" is offered for this clinicopathologic entity.
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Syncope and presyncope associated with probable adverse drug reactions. The purpose of this study was to determine whether syncope and presyncope were associated with drug therapy in 70 patients referred to a tertiary care ambulatory clinic. Drug use information was obtained, validated, and classified by its potential to cause syncope and presyncope. Utilizing a standardized adverse drug reaction algorithm, nine (13%) of the 70 patients were rated as having probable drug-induced syncope and presyncope events. Overall, 12 medications were implicated. Patients with probable adverse drug reactions were older, and taking more medications, or taking an antihypertensive. Seven of the nine patients with probable adverse drug reactions were previously classified as having syncope of unknown origin after their initial clinic evaluation. Syncope and presyncope are commonly associated with adverse drug reactions, especially in the elderly and those taking multiple medications.
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Primary angioplasty in myocardial infarction: assessment of improved myocardial perfusion with technetium-99m isonitrile. Technetium-99m-hexakis-2-methoxy-2-isobutyl-isonitrile (technetium-99m isonitrile) is a new radiopharmaceutical compound that reflects myocardial perfusion. Its kinetics, especially its lack of redistribution after intravenous administration, permits the assessment of changes in myocardial perfusion without delay of therapy. Tomographic images at rest were obtained immediately and 6 to 10 days later in 17 consecutive patients undergoing successful primary angioplasty during their first transmural myocardial infarction. Thirteen patients had anterior infarction. The initial (acute) defect size before angioplasty of 48 +/- 17% of the left ventricle decreased significantly (p less than 0.0001) to 29 +/- 19% on the late scans. There was no correlation between the time to therapy and the reduction in defect size. Twelve of the 17 patients, including 7 of the 11 patients treated after 4 h, demonstrated a definite reduction in the initial defect size. Eight patients with angiographically proved persistent coronary occlusion underwent a similar imaging sequence. The initial defect size in this group remained unchanged on the late scans (24 +/- 16% versus 26 +/- 18%, p = NS). Primary angioplasty is an effective approach toward salvaging myocardium; comparison with thrombolytic drug therapy must await the results of controlled clinical trials.
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Deletion of the human retinoblastoma gene in primary leukemias. As an initial step in evaluating the role of tumor suppressor genes in leukemogenesis, we surveyed primary leukemia cells from 130 patients for possible deletion of the retinoblastoma susceptibility (Rb) gene by Southern blot analysis. Two of them clearly showed homozygous deletion of Rb alleles. The first patient was a pre-B acute lymphoid leukemia (ALL) associated with a cytogenetic translocation: t(14;16)(q24;q22). The deletion was located at the 3' portion of the Rb gene, very close to the site of Rb gene deletion recently identified in an ALL cell line. The absence of Rb110 protein was further confirmed by Western blot analysis. The second patient was a chronic myelomonocytic leukemia (CMMoL), terminated in acute blastic transformation. Deletion of the 5' portion of Rb gene was found in leukemic cells in the chronic stage. The results indicated that inactivation of the Rb gene occurred in certain cases of leukemia. Its significance warrants further study.
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Syncope of unknown origin: clinical, noninvasive, and electrophysiologic determinants of arrhythmia induction and symptom recurrence during long-term follow-up. Ninety-one consecutive patients with syncope of unknown origin underwent electrophysiologic studies (EPS). Univariate analysis identified the following variables: age, + signal-averaged ECG (SAECG), left ventricular ejection fraction (LVEF), history of myocardial infarction, coronary artery disease, left ventricular aneurysm, and history of sustained monomorphic ventricular tachycardia (SMVT) on Holter; multivariate analysis identified +SAECG, LVEF, and history of SMVT as risk factors for induction of SMVT at EPS. All patients were followed up for 19.0 +/- 8.3 months and 17 had recurrence of syncope. Patients were divided into empiric, EP-guided, and no therapy groups. The EP-guided therapy group included all patients with SMVT at EPS. Recurrence rates among all three groups were similar. We conclude that: (1) Patients who have inducible SMVT at EPS can be identified using certain clinical and noninvasive variables. When these patients undergo EP-guided therapy, their rate of recurrence of syncope becomes compatible with that of patients who had no arrhythmia induced at EPS. (2) Empiric therapy does not offer any benefit over no therapy in reducing the rate of recurrent of scope.
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Effect of suramin on human prostate cancer cells in vitro. Suramin, a polyanionic compound with known antiparasitic activity, has been shown to be adrenocorticolytic in primates and to have clinical efficacy in the treatment of patients with metastatic prostate cancer refractory to conventional hormonal manipulation. To better characterize the activity of suramin on prostate cancer biology, we studied the effect of the drug on plasma adrenal androgens of patients and on the human prostate adenocarcinoma cell lines PC-3, DU 145 and LNCaP-FGC. Five cancer patients treated with suramin had an approximate 40% decline in circulating androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate levels. The drug inhibited the colony formation in two of the three cell lines at concentrations clinically achievable in humans without excessive drug-related toxicity. The presence of suramin 300 micrograms./ml. partially inhibited the growth stimulatory effect of testosterone and basic fibroblast growth factor, but not that of epidermal growth factor. The cellular concentration of suramin following exposure to a single dose increases linearly over time in each of the cell lines with LNCaP-FGC accumulating the highest levels of the drug; cellular levels of suramin, not androgen or growth factor sensitivity, correlated with the sensitivity to the drug. The concentrations of prostatic acid phosphatase and prostatic specific antigen released by LNCaP-FGC cells in cell culture medium declined in the presence of increasing levels of suramin in a manner which exceeded the decrease in cell number. We conclude that suramin, aside from decreasing circulating androgens through its adrenocorticolytic effect, is also capable exerting a direct inhibitory effect on cell proliferation of prostate cancer cells, and interfere at a cellular level with the growth stimulatory effects of exogenous testosterone and basic fibroblast growth factor.
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Drug therapy for ventricular tachyarrhythmias: how many electropharmacologic trials are appropriate? To determine how many electropharmacologic drug trials should be performed to select therapy for patients with ventricular tachyarrhythmias, the outcome of 150 consecutive patients with inducible ventricular tachyarrhythmias undergoing serial electropharmacologic testing was examined. The probability of identifying predicted effective therapy (inductive of fewer than five ventricular responses with three ventricular extrastimuli at three pacing cycle lengths) and the probability of that therapy preventing sustained ventricular tachyarrhythmia recurrences were determined as a function of the number of preceding trials. The probability ( +/- SE) of identifying predicted effective therapy by the first trial (0.23 +/- 0.03) was significantly higher than that of the second (0.09 +/- 0.04), third (0.08 +/- 0.04) and fourth (0.05 +/- 0.04) trials (p = 0.001). No patient had predicted effective therapy identified by subsequent trials. The 2 year actuarial probability of freedom from sustained ventricular tachyarrhythmias on predicted effective therapy was higher for the first (0.79 +/- 0.08), second (0.73 +/- 0.13) and third (0.86 +/- 0.13) trials than for the fourth (0.33 +/- 0.27) trial (p = 0.02). Thus, the probability of selecting therapy with long-term efficacy was highest for the first trial (0.18), intermediate for the second (0.07) and third (0.07) trials and lowest for the fourth (0.02) and subsequent (0.00) trials. Accordingly, the electropharmacologic approach to therapy selection should be abandoned after three unsuccessful trials.
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Cocaine babies: the scourge of the '90s. Six cases of cocaine-related deaths of infants have covered the spectrum of potentially devastating effects. They include an intrauterine death of a 35-week-old fetus following acute maternal cocaine abuse; anoxic encephalopathy at birth with 3 months' vegetative survival from a similar episode; traumatic compression asphyxia in a 4-month-old; infectious cardiomyopathy with heart failure in a twin at age 21 months following maternal cocaine abuse at birth; malnutrition and dehydration in a 7-week-old during continuing cocaine abuse by the parents; and a teenage sibling's cocaine lacing of a baby milk bottle ingested by his 6-week-old brother. All the cases had positive toxicological screening for cocaine or metabolites or both in the mother at delivery or in the infant at birth, or both. There were no instances of sudden infant death syndrome (SIDS, or "crib death"). Pathologic and toxicologic, as well as birth, developmental, and social data are presented. An integrated medical, public health, law enforcement, and educational policy to prevent or at least ameliorate these tragic cases, now approaching epidemic proportions, has yet to be developed. A careful obstetrical history and examination of the mother, indication on the birth certificate of maternal drug abuse, and notification of health authorities (by birth certificate checking, among other ways) may send an early warning message to providers for intercession. Active ingestion/injection and passive inhalation by older children and teenagers require more intensive monitoring and aggressive interaction by pediatricians, social workers, school authorities, and employers.
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Spontaneous myocardial ischemia and the signal-averaged electrocardiogram. The effects of transient myocardial ischemia on the signal-averaged electrocardiogram were investigated in 13 patients with coronary artery disease and spontaneous angina undergoing 3-channel ambulatory electrocardiography. Ischemia was seen as ST elevation in 2 patients or ST depression in 11; it was anterior in 5 patients, inferior in 4 and undefined in 4. Signal-averaged electrocardiograms with noise levels less than or equal to 1 microV were obtained from Holter tapes during 54 of 61 ischemic attacks recorded in the study group (88%), and compared with 54 tracings recorded within 60 minutes of the index attacks. Baseline tracings were normal in 8 patients (62%), showed a long QRS duration in 2 (15%), and both a long QRS duration and a late potential in the remaining 3 (23%). Comparison of recordings at baseline and during ischemic attacks revealed no significant changes in signal-averaged electrocardiographic parameters. Absence of significant differences was also noted when analysis was performed according to the type of ischemic attacks (associated with ST elevation [n = 14] or ST depression [n = 40]), their location (anterior [n = 21] or inferior [n = 23]), their duration (greater than 10 minutes [n = 29] or less than or equal to 10 minutes [n = 25]), and their magnitude (greater than 2 mm [n = 18] or less than or equal to 2 mm [n = 36]). It is concluded that spontaneous transient myocardial ischemia, independent of its type, location, duration and magnitude, does not generate a substrate for late potentials on the signal-averaged electrocardiogram.
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Immunophenotypic analysis of acute lymphoblastic leukemia using routinely processed bone marrow specimens. Monoclonal antibodies have been recently developed that react with antigens expressed on T and B lymphocytes in routinely processed, paraffin-embedded lymphoid tissues. In this study, we assessed bone marrow clot and/or core biopsy sections of 19 cases of acute lymphoblastic leukemia (ALL) using routinely decalcified, B5- or formalin-fixed, paraffin-embedded sections and a panel of monoclonal antibodies, including LN1, LN2, L26, Leu-22, UCHL-1, and LCA. Each case had been previously phenotyped using freshly obtained aspirate material and a standard immunophenotypic protocol. Our results demonstrate the utility of the LN2 antibody in differentiating between precursor B-cell (pre-B) and precursor T-cell ALL. The LN2 antibody stained 11 of 12 cases of pre-B ALL and did not react with any of the seven T-cell ALLs. The other antibodies tested were less helpful. The Leu-22 antibody stained both pre-B and T-cell ALLs, while the results with UCHL-1 revealed peculiar nuclear staining of pre-B and T-cell ALLs; this we attributed to processing artifact. The L26 antibody reacted with only one case of pre-B ALL (also CD20 antigen positive), while the LN1 antibody did not react with any pre-B ALLs. Neither L26 nor LN1 stained any cases of T-cell ALL. The LCA antibody stained in only four (21%) of 19 cases, two pre-B and two T-cell ALLs. The results also suggest that this panel of antibodies may be useful in differentiating ALL from mature B-cell and T-cell lymphomas involving the bone marrow.
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Esophageal contribution to chest pain in patients with coronary artery disease. We conducted a prospective study to determine the role of the esophagus in causing chest pain in patients with established CAD on optimum therapy. Thirty-two men with documented CAD who complained of frequent and usually daily retrosternal chest pain were evaluated. Following a standard esophageal manometry and acid perfusion test, simultaneous two-channel ambulatory Holter monitor and esophageal pH record tests were performed for 24 hours. Fifty-three episodes of chest pain were documented in 20 patients; 11 patients were free of pain. Of the 20 patients who complained of chest pains, 17 (85 percent) demonstrated at least one episode of PPR, defined as a drop in distal esophageal pH to less than 4 within ten minutes before or after the onset chest pain. Episodes of asymptomatic GER were common. The correlation of PPR with chest pain was 70 percent (37/53 episodes) and of ischemic ECG changes with chest pain 13 percent (7/53); in the remaining, there was no correlation with either. Two patients demonstrated simultaneous PPR and ischemic ECG changes. Seventeen esophageal motility abnormalities were observed in 14 patients (45 percent). It is our conclusion that esophageal disorders contribute to chest pain in patients with documented CAD. In this group, GER plays a greater role than in those with normal coronary arteries. In addition, esophageal motility disorders are common in these patients. Esophageal testing can be undertaken safely in these patients.
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Drug response at electropharmacologic study in patients with ventricular tachyarrhythmias: the importance of ventricular refractoriness. The clinical and electrophysiologic predictors of successful antiarrhythmic drug therapy for patients with inducible ventricular tachycardia were evaluated in 59 consecutive patients undergoing serial electropharmacologic trials. Structural heart disease was less frequently present in patients for whom effective therapy was found (p less than 0.05). The presence of coronary artery disease and a history of prior myocardial infarction were significantly more frequently present in patients for whom antiarrhythmic drug therapy could not be found (p less than 0.05). The corrected QT interval and ventricular effective refractory period measured at a pacing cycle length of 400 ms were significantly shorter in responders compared with nonresponders (QT interval 428 +/- 52 versus 460 +/- 59 ms; ventricular effective refractory period 237 +/- 28 versus 254 +/- 24 ms; (p less than 0.05). In addition, the interelectrogram coupling interval of the ventricular extrastimulus initiating ventricular tachycardia was significantly shorter in responders compared with nonresponders (223 +/- 37 versus 251 +/- 33 ms; p = 0.003). Logistic regression analysis identified a short ventricular interelectrogram coupling interval (p less than 0.01) and absence of prior myocardial infarction (p less than 0.05) as the only independent predictors of antiarrhythmic drug suppression of the induction of ventricular tachycardia. Greater drug-induced increments in the ventricular effective and functional refractory periods were observed in responders than in nonresponders as was the shortest ventricular interelectrogram coupling interval. Thus, baseline electrophysiologic measurements identify patients with inducible ventricular tachycardia who are likely to respond to antiarrhythmic drug therapy. Furthermore, these patients demonstrate greater drug-induced electrophysiologic changes.
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Surgical repair of postinfarction ventricular septal defect. Thirty-one patients underwent repair of postinfarction ventricular septal defect (VSD) from 1980 to 1989. All patients were in New York Heart Association functional class IV, and 15 of them were in cardiogenic shock when operated on. Coronary arteriography was performed in all patients before surgery: nine had one-vessel, 11 had two-vessel, and 11 had three-vessel disease. The VSD was anterior in 15 patients and posterior in 16. The operative technique evolved over the years from a fairly extensive infarctectomy and reconstruction of the septum and right and left ventricular walls with a double Dacron patch, to minimal or no infarctectomy and closure of the VSD by excluding the infarcted muscle from the left ventricular cavity. This is accomplished by suturing a single patch of bovine pericardium to healthy endocardium surrounding the infarcted muscle. The right ventricle is left intact. Overall mortality was 10%, with three operative deaths. All deaths occurred in patients in cardiogenic shock who had three-vessel coronary artery disease. Thus, the mortality for patients in shock was 20%, and the mortality for patients with three-vessel disease was 27%. The operative mortality for patients with posterior VSD was twice as high as in patients with anterior VSD. However, univariate analysis of various clinical, hemodynamic, and operative variables indicated that only three-vessel disease was predictive of operative mortality. Because the number of patients was small and the overall operative mortality relatively low, the results of this analysis may not be valid.
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Perinatal mortality rates in isolated general practitioner maternity units OBJECTIVE--To determine the perinatal mortality rate among normally formed, singleton babies with birth weights greater than or equal to 2500 g in Bath health district based on the intended place of delivery at the time of onset of labour or at the time of diagnosis of intrauterine death. DESIGN--The numbers of live births and stillbirths were collected monthly returns from the maternity units concerned. Deaths of infants aged less than or equal to 1 week were collected in the same returns. The intended place of delivery was confirmed at the monthly perinatal mortality meeting, during which maternal and fetal factors were discussed. SETTING--A rural health district of 400,000 population where one third of all deliveries occurred in seven isolated general practitioner maternity units, 8% in the integrated general practitioner unit, and the remainder in the consultant unit. SUBJECTS--All babies of women whose deliveries were booked in the district before the onset of labour or the diagnosis of intrauterine death, excluding twins, babies with lethal congenital malformations, and those less than 2500 g. MAIN OUTCOME MEASURES--Outcome of all deliveries and parity of mothers. RESULTS--14,415 Deliveries were analysed. The perinatal mortality rate was 2.8/1000 births in the consultant unit (7950 deliveries), 4.8 in the isolated general practitioner units (5237 deliveries), and zero in the integrated general practitioner unit (1228 deliveries). Perinatal deaths attributable to asphyxia were more common in the isolated general practitioner units (1.5 per 1000) than the consultant unit (0.6 per 1000). The perinatal mortality rate among babies born to nulliparous women was 3.2/1000 births in the consultant unit and 5.7 in the isolated general practitioner units; for those born to multigravid women it was 2.4 and 4.2 respectively. CONCLUSIONS--The outcome of delivery was not influenced by parity. Both antenatal and intrapartum care were responsible for the higher perinatal mortality rate in the isolated general practitioner units. The integrated unit, which shared midwifery staff with the consultant unit, seemed to work well. Analysis by intended place of delivery at the time of onset of labour or diagnosis of intrauterine death suggested that the care given in isolated units needs to be improved, perhaps by better training of general practitioners and consultant supervision of antenatal care.
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Treatment of pruritus of primary biliary cirrhosis with rifampin. Pruritus can be a debilitating symptom in patients with chronic cholestasis. Based on previous reports of its efficacy, we evaluated the impact of rifampin on the pruritus associated with primary biliary cirrhosis. Fourteen patients were included in a randomized, crossover study. After a 15-day washout period, subjects were followed for three weeks. During the first and third week, patients received 600 mg of rifampin or placebo; no treatment was administered during the second week. Pruritus was subjectively scored on a scale from 0 to 100. With rifampin, pruritus disappeared in 11 patients and partially improved in three; with placebo, only two had a partial response (P less than 0.001). Six patients with a prior poor or no response to cholestyramine improved with rifampin. No changes in biochemical tests or side effects were observed during this period. We conclude that short-term administration of rifampin relieves pruritus in primary biliary cirrhosis. When administered over a period of eight months in an open study, the relief of pruritus was maintained, while one individual developed an allergic reaction. Rifampin appears to be a safe drug in the management of the pruritus of primary biliary cirrhosis.
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Predictive value of tumor estrogen and progesterone receptor levels in postmenopausal women with advanced breast cancer treated with toremifene. The predictive value of estrogen receptor (ER) concentrations was evaluated in a group of 113 postmenopausal patients with estrogen-receptor-positive (ER greater than 7 fmol/mg protein) advanced breast cancer. In 103 patients, tumors were also sampled for progesterone receptor (PgR) determination. All patients were treated with toremifene, a novel antiestrogen, 60 mg daily. The median ER in 51 responders was 78 fmol/mg protein, and in 62 nonresponders, 51 fmol/mg protein; the median PgR levels were 40 and 37 fmol/mg protein, respectively. The response rate in patients with ER less than 50 fmol/mg protein was 38%, and 51% in the group with ER greater than 50 fmol/mg protein (not significant [NS]). The response rate in patients with PgR less than 10 fmol/mg protein was 42%, and in patients with greater than 10 fmol/mg protein, 44%. The duration of response in patients with ER greater than 50 fmol/mg protein was significantly longer than with lower ER levels (P = 0.002). PgR was not associated with the duration of response. In Cox's multiple regression analysis, ER was an independent prognostic factor (P = 0.005) for response duration. Thus, the ER concentration of tumor tissue predicts the duration of response but not the response rate to toremifene in patients with advanced breast cancer. The PgR status does not predict the response rate or the duration of response.
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Effect of systemic medetomidine, an alpha 2 adrenoceptor agonist, on experimental pain in humans. The effect of systemic (intravenous) medetomidine, an alpha-2 adrenoceptor agonist, on pain thresholds was studied in healthy human subjects (n = 6). Medetomidine produced a dose-dependent (cumulative doses: 25 and 50 micrograms) sedative effect evaluated by visual analog scale. Also, a dose-dependent decrease of blood pressure but not of heart rate was seen after administration of medetomidine. Pain threshold to electric stimulation of the tooth pulp and cutaneous heat pain threshold were uninfluenced by medetomidine. An index of cutaneous thermal sensitivity to innocuous stimuli, the width of the thermoneutral zone, also was uninfluenced by medetomidine. Medetomidine produced a significant attenuation of the affective-motivational component (unpleasantness) of tourniquet-induced ischemic pain, whereas the sensory-discriminative component (pain magnitude estimate) of the ischemic pain was not attenuated. The results suggest that systemic medetomidine alone at subanesthetic but sedative and hypotensive doses does not significantly influence the intensity and thresholds of experimental pain, whereas the affective-motivational component of pain can be attenuated.
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IL-2-PE40 prevents the development of tumors in mice injected with IL-2 receptor expressing EL4 transfectant tumor cells. A number of different immunotherapeutic reagents are currently being developed to target IL-2R for the treatment of leukemia, graft rejection, and certain autoimmune diseases. Previously, we have shown that IL-2-PE40, a chimeric protein composed of human IL-2 linked to the N-terminus of a truncated form of Pseudomonas exotoxin (PE), could effectively kill a variety of cell lines in vitro expressing either low, intermediate, or high affinity IL-2R. Here, we demonstrate that IL-2-PE40 can successfully retard or prevent the growth of a lethal ascites tumor or a solid tumor composed of EL4J murine thymoma cells transfected with the p55 murine IL-2R. The transfected line, EL4J-3.4, expresses 1,000 to 3,000 high affinity IL-2R. Survival extension in the ascites model was achieved by initiating treatment either after 4 to 6 h or within 5 days post-tumor injection in both athymic nude and C57BL/6 mice. Similarly, the growth of an aggressive s.c. solid tumor could also be inhibited. Extension of survival was not achieved either by using the truncated toxin alone not attached to IL-2 or by using an IL-2-PE40Asp553 mutant lacking a functional toxin. Survival extension was not caused by IL-2 activated NK or other host effector mechanisms as IL-2-PE40 was unable to prevent the receptor-negative EL4J parental line from forming a lethal ascites or a solid tumor. Thus, IL-2-PE40 is a potent, specific cytolytic reagent that may prove useful in the arsenal of anti-IL-2R immunotherapeutics.
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Baroreflex sensitivity and electrophysiological correlates in patients after acute myocardial infarction. BACKGROUND. Several studies have identified transient disturbances of autonomic function during the acute and recovery phases of myocardial infarction, and it has recently been suggested that survivors of acute myocardial infarction with depressed vagal tone may be at increased risk of sudden or arrhythmic death. METHODS AND RESULTS. To investigate this hypothesis, parasympathetic function was assessed by arterial baroreflex sensitivity (BRS) testing (using the phenylephrine method) and by heart rate variability (HRV) analysis from 24-hour Holter recording in 68 patients at day 7-10 after infarction. The relation between autonomic tone and markers of arrhythmic propensity, including programmed ventricular stimulation (PVS) and late potentials in addition to other clinical variables, was examined. BRS for the whole group was 7.0 +/- 4.7 msec/mm Hg and was inversely correlated with age (r = 0.53, p less than 0.001) but not with left ventricular ejection fraction (r = 0.035, p = NS). In those patients in whom sustained monomorphic ventricular tachycardia (SMVT) was induced, BRS was significantly reduced (p = 0.001) as was HRV (p = 0.007) and left ventricular ejection fraction (p = 0.022). The strongest association between any variable (including HRV, BRS, late potentials, left ventricular ejection fraction, exercise testing, Q waves, and infarct site) and the induction of sustained monomorphic ventricular tachycardia was depressed BRS with a relative risk of 36.28 (95% confidence interval, 5-266). CONCLUSIONS. This study confirms that depressed BRS identifies a subgroup at high risk for arrhythmic events after myocardial infarction and that programmed ventricular stimulation may be safely limited to this group without any loss of predictive accuracy.
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Correlation between essential tremor and migraine headache. The relationship between essential tremor (ET) and migraine was investigated in a prospective study. In a group of 74 ET patients 36.5% had migraine compared with 17.7% of 102 control subjects without tremor. In a group of 58 patients with migraine 17.2% had ET compared with 1.2% of 85 controls without migraine. The prevalence of ET in migraine controls was greater than controls without migraine (22% compared with 1%; p = 0.002). It is concluded that there is an association between essential tremor and migraine.
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Changes in cerebral blood flow velocity after release of intraoperative tourniquets in humans: a transcranial Doppler study. The effect of release of intraoperative thigh tourniquets on velocity of blood flow in the middle cerebral artery was examined in five patients given general anesthesia with controlled ventilation for lower extremity orthopedic procedures using transcranial Doppler sonography. Middle cerebral artery blood flow velocity increased significantly from 52 +/- 6 (SEM) to 82 +/- 24 cm/s (an increase of 58% +/- 13%) within 4 +/- 1 min after tourniquet release and remained significantly elevated for 7 min. A positive linear correlation was found between middle cerebral artery blood flow velocity and PETCO2 on each occasion (0.97 greater than or equal to r greater than or equal to 0.84, 0.001 greater than P greater than 0.0001) after tourniquet deflation. Assuming a linear relationship between flow velocity and flow, these findings suggest that significant increase in cerebral blood flow can occur after intraoperative tourniquet release and that this increase appears to be mostly CO2-dependent.
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Gleason's histologic grading as clinical prognostic marker in patients with advanced prostatic carcinoma. We have found that the Gleason's histologic grading system is a good clinical marker to predict long-term response and prognosis in symptomatic Stage D-2 adenocarcinoma of the prostate. In this retrospective study, 56 cases were reviewed and correlated with bone scan, acid phosphatase, and symptomatology following bilateral orchiectomy.
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Bile acids and the increased risk of colorectal tumours after truncal vagotomy. An association between colorectal cancer and previous peptic ulcer surgery is reported. In a prospective screening study, 100 asymptomatic patients (80 men and 20 women) who had undergone truncal vagotomy at least 10 years previously were investigated by barium enema, colonoscopy and gallbladder ultrasonography. Control data were obtained from forensic autopsy subjects. The incidence of neoplasms greater than or equal to 1.0 cm in the vagotomized group was 14 per cent (11 adenomas, 3 carcinomas) and 3 per cent in controls (P = 0.01). Duodenal bile obtained at endoscopy from 21 vagotomized patients with normal gallbladders and from 21 control patients undergoing endoscopy was analysed by high performance liquid chromatography. The mean percentage of cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA) and lithocholic (LCA) acids in the bile of vagotomized patients was 32.3, 45.6, 20.7 and 1.4 per cent respectively compared with 45.3, 36.2, 17.9 and 0.7 per cent respectively in controls. The increased proportions of CDCA and LCA and decreased proportions of CA in the duodenal bile of vagotomized patients were significant (P less than 0.001; P = 0.02; P = 0.007). Abnormalities in bile acid metabolism may help to explain the increased risk of colorectal neoplasia 10 years after truncal vagotomy.
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Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation: no causal relation with diabetic autonomic neuropathy OBJECTIVE--To examine the traditional view that unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation in insulin dependent diabetes mellitus are manifestations of autonomic neuropathy. DESIGN--Perspective assessment of unawareness of hypoglycaemia and detailed assessment of autonomic neuropathy in patients with insulin dependent diabetes according to the adequacy of their hypoglycaemic counterregulation. SETTING--One routine diabetic unit in a university teaching hospital. PATIENTS--23 Patients aged 21-52 with insulin dependent diabetes mellitus (seven with symptoms suggesting autonomic neuropathy, nine with a serious clinical problem with hypoglycaemia, and seven without symptoms of autonomic neuropathy and without problems with hypoglycaemia) and 10 controls with a similar age distribution, without a personal or family history of diabetes. MAIN OUTCOME MEASURES--Presence of autonomic neuropathy as assessed with a test of the longest sympathetic fibres (acetylcholine sweatspot test), a pupil test, and a battery of seven cardiovascular autonomic function tests; adequacy of hypoglycaemic glucose counterregulation during a 40 mU/kg/h insulin infusion test; history of unawareness of hypoglycaemia; and response of plasma pancreatic polypeptide during hypoglycaemia, which depends on an intact and responding autonomic innervation of the pancreas. RESULTS--There was little evidence of autonomic neuropathy in either the 12 diabetic patients with a history of unawareness of hypoglycaemia or the seven patients with inadequate hypoglycaemic counterregulation. By contrast, in all seven patients with clear evidence of autonomic neuropathy there was no history of unawareness of hypoglycaemia and in six out of seven there was adequate hypoglycaemic counterregulation. Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation were significantly associated (p less than 0.01). The response of plasma pancreatic polypeptide in the diabetic patients with adequate counterregulation but without autonomic neuropathy was not significantly different from that of the controls (change in plasma pancreatic polypeptide 226.8 v 414 pmol/l). The patients with autonomic neuropathy had a negligible plasma pancreatic polypeptide response (3.7 pmol/l), but this response was also blunted in the patients with inadequate hypoglycaemic counterregulation (72.4 pmol/l) compared with that of the controls (p less than 0.05). CONCLUSIONS--Unawareness of hypoglycaemia and inadequate glucose counterregulation during hypoglycaemia are related to each other but are not due to autonomic neuropathy. The blunted plasma pancreatic polypeptide responses of the patients with inadequate hypoglycaemic counterregulation may reflect diminished autonomic activity consequent upon reduced responsiveness of a central glucoregulatory centre, rather than classical autonomic neuropathy.
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The role of calcium channel blockers in the treatment of essential hypertension. Calcium channel blockers, originally developed for the treatment of angina and supraventricular arrhythmias, have been shown to lower elevated blood pressure effectively in hypertensive patients. Verapamil, nifedipine, and diltiazem represent prototype compounds for unique chemical classes with differing pharmacologic properties. These drugs lower elevated blood pressure with efficacy comparable with other commonly used antihypertensives. Combination therapy with other agents usually results in an additive response. Side effects are usually mild and reversible and usually are an extension of the drug's pharmacologic effects. Moreover, adverse metabolic effects on lipid, glucose, or potassium levels are not common. Because of the excellent antihypertensive effects of calcium channel blockers and their potential importance in a variety of other disease states, these agents should be routinely considered for use as a first-line antihypertensive agent in appropriately selected patients with hypertension of any severity as part of a comprehensive plan to minimize cardiovascular risk.
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Postural hypotension: pressor effect of octreotide not mediated by norepinephrine. Orthostatic hypotension of the Shy-Drager syndrome is a chronic incapacitating condition characterized by lack of an appropriate increase in the plasma norepinephrine level in response to standing. Recently, the somatostatin analogue octreotide has been reported to induce a pressor response in patients having this syndrome. We have reported a case of Shy-Drager syndrome in which octreotide was effective, but the rise in blood pressure was not accompanied by an increase in the plasma norepinephrine level. Hence, the pressor effect of octreotide is not mediated by stimulation of the sympathetic nervous system, but probably through splanchnic vasoconstriction.
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Successful treatment of metastatic thymic carcinoma with cisplatin, vinblastine, bleomycin, and etoposide chemotherapy. Thymic carcinomas are rare malignant neoplasms of the thymic epithelium that are distinguished from the malignant thymomas by the presence of cytologic atypia. Thymic carcinomas may metastasize outside of the thorax and are associated with a very poor prognosis. Complete responses of thymic carcinoma to chemotherapy alone have not been reported. A 21-year-old man with metastatic undifferentiated carcinoma of probable thymic origin is presented who achieved a pathologic complete response with cisplatin, vinblastine, and bleomycin chemotherapy. Additional consolidative chemotherapy with cisplatin and etoposide was administered. The patient remains disease-free 5 years after diagnosis. Cisplatin, vinblastine, and bleomycin chemotherapy appears to have significant activity against thymic carcinoma.
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Intramyocardial shotgun pellets diagnosed on initial emergency room chest X-ray: case report. The diagnosis of retained intracardiac missile is usually made at thoracotomy or fluoroscopy. Close inspection of plain chest X-rays may reveal blurring of radiopaque objects that are moving with the beating heart. In a gunshot wound victim who is initially stable, observation of this phenomenon should prompt a very high index of suspicion for cardiac injury. Invasive hemodynamic monitoring is indicated, and thoracotomy should be performed if penetrating cardiac injury is confirmed.
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Prognostic significance of valvular regurgitation in patients with infective endocarditis. PURPOSE: Doppler ultrasound is a sensitive modality for detecting and quantitating valvular regurgitation in patients with infective endocarditis. Because valvular regurgitation leads to heart failure, we evaluated the prognostic significance of Doppler-detected valvular regurgitation in patients with endocarditis who had not yet developed clinical heart failure. PATIENTS AND METHODS: We reviewed the medical records of 65 patients with a clinical diagnosis of infective endocarditis from May 1985 to March 1990. A total of 49 patients were included in the study: 33 patients with native valve endocarditis and 16 patients with prosthetic valve endocarditis. The initial Doppler echocardiogram was examined in these patients to determine the presence and degree of valvular regurgitation. RESULTS: Significant (moderate to severe) valvular regurgitation was detected in 23 (47%) patients. The presence or absence of significant valvular regurgitation did not predict the development of congestive heart failure, the need for surgery, or death (p = NS). The development of congestive heart failure was significantly associated with the need for surgery (p less than 0.0001) and death (p less than 0.05). CONCLUSION: We conclude that the detection of significant valvular regurgitation in patients with infective endocarditis who have not yet developed heart failure is not predictive of future complications nor does the absence of significant valvular regurgitation identify a group of patients with a more favorable prognosis. In our series, patients who developed congestive heart failure had a significantly higher incidence of surgery and death. Therefore, decisions regarding clinical management in patients with infective endocarditis should not be made solely on the presence or absence of echocardiographically detected valvular regurgitation.
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Cancer incidence among foundry workers in Denmark. Cancer incidence was studied among 6,144 male foundry workers who were invited to participate in either of two Danish national silicosis surveys conducted during 1967-1969 and 1972-1974. Cancer incidence was followed through to the end of 1985 by computerized linkage to the Danish Cancer Registry, and Standardized Morbidity Ratios (SMRs) were calculated based on incidence rates for the Danish population. For the entire cohort, significantly elevated SMRs were seen for all cancers (SMR, 1.09; 95% CI, 1.01-1.18) and lung cancer (SMR, 1.30; 95% CI, 1.12-1.51), and SMRs were at the borderline of statistical significance for bladder cancer (SMR, 1.24; 95% CI, 0.97-1.59). Excess lung and bladder cancer risk were confined to workers who had worked in foundries for at least 20 y. There was a positive correlation between silicosis prevalence in employees at the foundries at the time of the x-ray examinations and lung cancer incidence during the follow-up period. Squamous cell carcinomas, anaplastic carcinomas, and other lung cancers accounted for the excess lung cancer risk, whereas there was not excess risk among the foundry workers for adenocarcinomas of the lung.
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Normal pituitary gland: coronal MR imaging of infundibular tilt. To determine the prevalence of pituitary infundibular deviation or tilt as a normal variant, coronal magnetic resonance (MR) images of 50 patients who had been examined for reasons other than pituitary disease were evaluated retrospectively. Forty-six percent of the patients had a more or less pronounced tilt of the pituitary stalk. This tilt was due to developmental lateral eccentricity of the pituitary gland in relationship to the midline of the brain in 34% and to ontogenic eccentric insertion of the pituitary infundibulum off the midline of the gland in the other 12%. This high frequency of stalk deviation in patients without pituitary disease suggests that such displacement by itself should not be used to support the presence of pituitary microadenoma on MR images or computed tomograms.
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Two siblings with phenotypes mimicking peroxisomal disorders but with discordant biochemical findings. The authors present a report on two sibling with a nearly identical phenotype mimicking peroxisomal disorder but with totally discordant biochemical findings. In an attempt to confirm the diagnosis of a peroxisomal disorder, plasma levels of very long chain fatty acids (VLCFA) and phytanic acid were determined. In addition, fibroblasts profile of VLCFA and plasmalogen levels were evaluated for Case 2. Pathomorphological examinations represented by lymph node and kidney biopsies as well as postmortem examinations of liver, adrenals and brain were performed in Case 1. The phenotypes of both siblings showed marked resemblance to those observed in children with Zellweger syndrome. The results of biochemical tests performed in Case 1, together with abundant peroxisomes in the liver and the wide spectrum of clinical abnormalities suggest pseudo-Zellweger or Zellweger-like syndromes, but no conclusive data have been found. The plasmalogen level in fibroblasts as well as the fibroblasts profile of VLCFA noted in Case 2 were within the normal range, thus excluding the possibility of a peroxisomal disorder. The striking phenotype resemblance of the siblings mimicking Zellweger, together with discordant biochemical findings, are difficult to explain on the basis of currently available tests.
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Long-chain (sphingoid) bases inhibit multistage carcinogenesis in mouse C3H/10T1/2 cells treated with radiation and phorbol 12-myristate 13-acetate. Sphingosine and other long-chain (sphingoid) bases inhibit protein kinase C, the putative cellular receptor for the tumor promoter phorbol 12-myristate 13-acetate (PMA), and exert potent effects on diverse cell functions. We tested the ability of long-chain bases to modulate multistage carcinogenesis in mouse C3H/10T1/2 cells exposed to gamma-rays and PMA. Sphingosine and sphinganine completely blocked the enhancement of radiation-induced transformation by PMA (promotion) and partially suppressed transformation by radiation alone. N-Acetylsphingosine, a ceramide analog, did not inhibit transformation. Sphingosine was rapidly taken up by the cells and metabolized; hence, the long-chain bases were added daily to achieve prolonged inhibition. Long-chain bases inhibited protein kinase C activity in C3H/10T1/2 cells and suppressed the down-regulation of this enzyme by PMA. Our results establish that long-chain bases are highly effective inhibitors of carcinogenesis in this model. Our results also indicate that the suppressive effects may be mediated, in part, by inhibition of protein kinase C. The data suggest that sphingosine and other long-chain bases derived from complex sphingolipids may act as cancer-preventative agents.
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Femoropopliteal angioplasty. Factors influencing long-term success. Prospective data was recorded on 217 percutaneous transluminal angioplasty (PTA) procedures performed in the superficial femoral and popliteal arteries over an 8-year period. After the initial procedure, patients were followed with serial noninvasive studies and, in 71 patients, repeat angiography. The mean follow-up period was 7 years (range, 2-11 years). Standard life-table survival analysis was used to assess the factors potentially affecting long-term outcome. Excluding an initial technical failure rate of 10%, overall patencies at 1, 3, and 5 years were 81%, 61%, and 58%, respectively. After the first year, the prognosis (i.e., failure rate) appears to be linear over the long term (i.e., up to 10 years). Factors negatively influencing long-term patency include the presence of diabetes mellitus, diffuse atherosclerotic cardiovascular disease, or threatened limb loss. Technical factors correlated with failure include lesion length, moderate eccentricity, and a poor post-PTA appearance.
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Bone metastases: pathophysiology and management policy. The pathophysiology and options for management of bone metastases as well as criteria for determining response to therapy are reviewed. Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. In the majority of patients, the primary tumor is in the breast, prostate, or lungs. Although almost all patients will die of their disease, a proportion of the patients will survive for several years. Treatment is primarily palliative: the intention is to relieve pain, prevent fractures, maintain activity and mobility, and, if possible, to prolong survival. Therapeutic options include local treatment with radiotherapy and/or surgery, and systemic treatment using chemotherapy, endocrine therapy, radioisotopes, agents such as diphosphonates, which inhibit resorption of bone, as well as analgesic and antiinflammatory drugs. The mechanisms by which pain is relieved by several of these therapies remain unclear but actions beyond a simple tumoricidal effect appear to be important. There have been few randomized trials comparing the therapeutic options, and the criteria for assessing response to therapy have, in general, been poorly defined. There is a need for rigorous clinical investigations that assess the efficacy of the various therapeutic possibilities by using well-defined and validated criteria of response.
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High survival rate in advanced-stage B-cell lymphomas and leukemias without CNS involvement with a short intensive polychemotherapy: results from the French Pediatric Oncology Society of a randomized trial of 216 children. From April 1984 to December 1987, the French Pediatric Oncology Society (SFOP) organized a randomized trial for advanced-stage B-cell lymphoma without CNS involvement to study the possibility of reducing the length of treatment to 4 months. After receiving the same three intensive six-drug induction courses based on high-dose fractionated cyclophosphamide, high-dose methotrexate (HD MTX), and cytarabine in continuous infusion, patients were evaluated for remission. Those who achieved complete remission (CR) were randomized between a long arm (five additional courses with two additional drugs; 16 weeks of treatment) and a short arm (two additional courses; 5 weeks). For patients in partial remission (PR), intensification of treatment was indicated. Two hundred sixteen patients were registered: 15 stage II nasopharyngeal and extensive facial tumors, 167 stage III, and 34 stage IV, 20 of the latter having more than 25% blast cells in bone marrow. The primary sites of involvement were abdomen in 172, head and neck in 30, thorax in two, and other sites in 12. One hundred sixty-seven patients are alive in first CR with a minimum follow-up of 18 months; four are lost to follow-up. Eight patients died from initial treatment failure, 14 died from toxicity or deaths unrelated to tumor or treatment, and 27 relapsed. The event-free survival (EFS), with a median follow-up of 38 months, is 78% (SE 3) for all the patients, 73% (SE 11) for the stage II patients, 80% (SE 3) for the stage III patients, and 68% (SE 8) for the stage IV and acute lymphoblastic leukemia (ALL) patients. One hundred sixty-six patients were randomized: 82 in the short arm and 84 in the long arm. EFS is, respectively, 89% and 87%. Statistical analysis confirms equivalence of both treatment arms with regard to EFS. Moreover, morbidity was lower in the short arm. This study confirms the high survival rate obtained in the previous LMB 0281 study without radiotherapy or debulking surgery and demonstrates the effectiveness of short treatment.
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Angioplasty of coronary bifurcation stenoses: immediate and long-term results of the protecting branch technique. Percutaneous transluminal angioplasty (PTCA) of coronary stenoses involving major bifurcations carries a small but significant risk of side branch occlusion which can be avoided by simultaneously using multiple dilatation systems. Among 1,275 PTCA procedures performed between 1984 and 1988 in 1,035 consecutive patients, 42 double wire procedures were applied (4%) to protect and/or dilate major coronary side branches. A total of 80 coronary stenoses were attempted of which 76 were located on a bifurcation and 4 on other segments. In the first 11 patients (group A), 2 guiding catheters were used and PTCA of each vessel was successfully performed by means of separate double lumen over-the-wire balloon catheters. In the next 31 patients (group B), 2 guidewires were advanced through a single guiding catheter and PTCA was attempted using "Monorail" balloon catheters sequentially advanced over the wires. In group B, a successful PTCA was obtained in 29 patients (93%) but twisting of the wires hampered balloon progression in 5 cases, such that dilatation could only be performed by stepping back to a single wire technique. The procedure time in group B was significantly shorter than in group A: 144 +/- 30 versus 230 +/- 52 minutes (p = .01). Repeat angiography was performed in 35 out of 40 patients (87%) after a mean of 180 +/- 46 days following successful PTCA. Angiographic restenosis was present in 37% (24/65) of bifurcation segments which, in our experience, is not significantly different from the angiographic restenosis rate in less complex lesions (248/740; 34%; NS).
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Diagnostic value of anti-neuronal antibodies for paraneoplastic disorders of the nervous system. The diagnostic value of the presence of anti-neuronal antibodies in serum was examined in 21 patients suspected of paraneoplastic disorders of the nervous system (NS) (group 1) and was compared to three control groups; group 2: 25 patients with a neurological disease, without cancer and no sign of paraneoplastic disorder; group 3: 27 patients with neurological disease and cancer and no signs of a paraneoplastic disorder; group 4: 94 patients with cancer and without neurological disease. In group 1, anti-neuronal nuclear antibodies were detected in eight patients (38%), in titres from 1:1000 to 1:32,000. A small cell lung cancer was present in six patients, ovarian cancer in one patient and in one patient no tumour could be detected. The neurological symptoms preceded a diagnosis of cancer in five out of eight patients. Anti-neuronal antibodies were found in the serum of two out of 94 patients (2%) from control group 3 but not in serum from any of the other control groups. These data indicate a moderate sensitivity of 38%, but a high specificity of 98.6% (95% confidence interval 95.5-99.8%) for the presence of anti-neuronal nuclear antibodies if a paraneoplastic NS disorder is suspected.
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Accuracy of exercise electrocardiography in detecting physiologically significant coronary arterial lesions. The accuracy of exercise electrocardiography in detecting a physiologically significant coronary artery stenosis has been assessed previously by comparing the exercise test with a coronary arteriogram. The inherent inaccuracy of visually determined percent diameter stenosis measurements might have lead to the conclusion that the exercise electrocardiogram was less accurate than it truly was. To determine the accuracy of the exercise electrocardiography in detecting a physiologically significant coronary stenosis, we studied 40 patients with one-vessel, one-lesion coronary artery disease, a normal resting electrocardiogram, and no hypertrophy or prior infarction. Each patient underwent exercise electrocardiography (Bruce protocol) that was interpreted as abnormal if the ST segment developed 0.1-mV or greater depression 80 msec after the J point. The physiological significance of each coronary stenosis was assessed by measuring of coronary flow reserve (peak divided by resting blood flow velocity) in the stenotic artery using a Doppler catheter and intracoronary papaverine (normal, 3.5 or greater peak/resting velocity). The percent diameter and percent area stenosis produced by each lesion were determined using quantitative angiography (Brown/Dodge method). Of the 17 patients with reduced coronary flow reserve (3.5 or greater peak/resting blood flow velocity) in the stenotic artery, 14 had an abnormal exercise electrocardiogram (sensitivity, 0.82; 95% confidence interval, 0.70-0.94). Conversely, 20 of 23 patients with normal coronary flow reserves had normal exercise tests (specificity, 0.87; 95% confidence interval, 0.77-0.97). The exercise electrocardiogram was abnormal in each of 11 patients with markedly reduced coronary flow reserve (less than 2.5 peak/resting velocity) and in three of six patients with moderately reduced reserve (2.5-3.4 peak/resting velocity). The products of systolic blood pressure and heart rate at peak exercise were significantly correlated with coronary reserve in patients with truly abnormal exercise tests. In comparison, the sensitivity (0.61; 95% confidence interval, 0.46-0.76) and specificity (0.73; 95% confidence interval, 0.60-0.86) of exercise electrocardiography in detecting a 60% or greater diameter stenosis may be significantly lower (p less than 0.05). Exercise electrocardiography, therefore, was a good predictor of the physiological significance (assessed by coronary flow reserve) of a coronary stenosis in patients with a normal resting electrocardiogram and no hypertrophy or prior infarction. Its value in a broader and larger patient population will require further study. These results, however, underscore the importance of a physiological gold standard in assessing the accuracy of noninvasive studies for detecting coronary artery disease.
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Closure of leaking filtering blebs with cyanoacrylate tissue adhesive. Five leaking filtering blebs, occurring between 10 months and 21 years after trabeculectomy, were closed with cyanoacrylate tissue adhesive. Filtering bleb integrity was preserved in four cases, so that additional microsurgery was avoided. The only problem associated with use of tissue adhesive was the development of corneal abrasions in three cases. Although it is an accepted treatment for these conjunctival fistulas, only nine previous cases have been reported to our knowledge. We strongly recommend the use of tissue adhesive as a presurgical treatment in the management of leaking filtering blebs which present as a late postoperative complication of glaucoma surgery.
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Effect of age on the efficacy of blood pressure treatment strategies. To study whether the proportion of excess cardiovascular events attributable to various levels of systolic blood pressure varies with age, we calculated the population-attributable risk of all-cause mortality, fatal and nonfatal cardiovascular events (stroke, coronary heart disease, angina, congestive heart failure, and peripheral vascular disease), and stroke incidence due to systolic blood pressure in men and women 45 years of age or older in the United States during 1980. Our estimates are based on US census counts, blood pressure prevalence distributions from the second National Health and Nutrition Examination Survey, and the annual risk of cardiovascular complications during 18 years of follow-up in the Framingham cohort. We then determined the impact of age on the relative efficacy of mass treatment and case-finding strategies in preventing systolic blood pressure-related events. At 45-54 years of age, only 30-40% of systolic blood pressure-related excess events occur in hypertensive individuals (systolic blood pressure greater than or equal to 160 mm Hg). With increasing age, however, the percentage of systolic blood pressure-related events that occur in hypertensive individuals rose substantially; in the older age group (greater than or equal to 75 years), 65-70% of fatal and nonfatal cardiovascular disease events occur in hypertensive persons. The pattern is similar for men and women. The potential impact of a mass treatment strategy designed to shift the distribution of blood pressure downward by a small amount is greater in younger than in older groups, whereas an opposite trend is seen for a high-risk, hypertensive case-finding and treatment approach.
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Ultrastructural evidence of the effects of shear stress variation on intimal thickening in dogs with arterially transplanted autologous vein grafts. Based on our findings that changes in wall shear stress, not the rate of blood flow, were the main hemodynamic factor related to intimal hyperplasia of autologous vein grafts, we further investigated the effect of wall shear stress variation on sequential ultrastructural changes in the intimal hyperplasia of arterially transplanted autovein grafts, using canine models. As noted, wall shear stress variation (tau-variation) could be defined by the variation in wall shear stress within a cardiac cycle, using a desktop flow waveform analyzer. In Group I, which had a high flow rate of 78.4 +/- 4.6 ml/min and low tau-variation of 36.1 +/- 2.2 dynes/cm2, intimal hyperplasia was significant. Ultrastructurally, there was a marked transformation of intimal smooth muscle cells to secretory cells 2 to 4 weeks after implantation. The surface of the intima was lined with modified smooth muscle cells at 2 weeks after implantation. In Group II, which had a low flow rate of 5.6 +/- 2.2 ml/min and normal tau-variation value (174.6 +/- 13.0 dynes/cm2), intimal hyperplasia was minimal, and there were several layers of contractile type smooth muscle cells, with characteristic myofibrillae. The surface of the intima was lined with endothelial cells at 2 weeks after implantation. These findings suggest that, in regions of low wall shear stress variation, intimal smooth muscle cells of autovein grafts may well become secretory cells, and enhanced platelet adherence could occur during early intimal repair, causing intimal hyperplasia to develop.
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Using a state cancer registry to increase screening behaviors of sisters and daughters of breast cancer patients. The Pennsylvania Cancer Registry was used to contact breast cancer patients and, through them, their adult sisters and daughters. The sisters and daughters were counseled concerning their higher than average risks for breast cancer and their need for mammography and breast self-examination. Results showed a 9 percent increase in mammography and a 10 percent increase in breast self-examination rates for the counseled over control group. Costs were $49 per counseled sister or daughter indicating a need to increase cost effectiveness before implementation is practical.
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Naproxen sodium in menstrual migraine prophylaxis: a double-blind placebo controlled study. In this study, the efficacy of Naproxen sodium (Nxs) in the prophylaxis of Menstrual Migraine (MM) was tested, versus Placebo (PL). Forty women suffering from MM were admitted to a double-blind treatment protocol with Nxs 550 mg twice each day by mouth or Placebo (PL), for 3 months; in the next 3 months all the women were treated with the active drug in an open study. The headache intensity and duration, as well as the number of days of headache and the analgesic consumption, were significantly reduced with Nxs compared to PL. The efficacy of Nxs, shown also in improving premenstrual pain, and its good tolerability, support the use of this drug in the prophylactic therapy of MM.
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Episodic hyperammonemia in adult siblings with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. A 39-year-old man and his 42-year-old sister, both vegetarians, had episodic confusion for many years, but their mental function was normal between those episodes. They were recently diagnosed with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. Hyperammonemia was documented during an episode of confusion in the male sibling but not in his sister. Both had elevated plasma ornithine, glutamine, and alanine levels and persistently low plasma lysine levels. Homocitrulline was present in their urine, and orotic aciduria and orotidinuria developed in the male sibling following ingestion of allopurinol. Studies on their cultured skin fibroblasts showed deficient metabolism of ornithine, indicating a defect in ornithine transport across the mitochondrial membrane. During therapy with citrulline and phenylbutyrate sodium, plasma ornithine levels increased in both patients, while plasma levels of glutamine and alanine decreased to normal. Since therapy started, their clinical conditions have also improved, and no recurrent neurologic dysfunction has occurred during a follow-up period of 20 months.
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Handcuff neuropathies Compressive neuropathy due to tight application of handcuffs occurred in 5 patients. The superficial radial nerve was affected in 8 hands and the median nerve in two. Neurologic deficits persisted as long as 3 years after handcuffing. Nerve conduction studies helped to exclude malingering and other diagnoses. All patients had been intoxicated when handcuffed or had been arrested with force. The handcuff mechanism, which allows accidental overtightening after application, is an unrecognized factor in these neuropathies.
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The World Health Organization's histologic classification of gastrointestinal tumors. A commentary on the second edition. The World Health Organization's (WHO) histologic classification of gastrointestinal tumors has been revised. Although the general basis of classification and the overall outline remain similar to the first edition, advances in the last decade justified changes in classifying certain entities; among them were malignant lymphomas, endocrine tumors, and dysplasias. Several newly recognized entities have also been added.
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Assessment of "squamous cell carcinoma antigen" (SCC) as a marker of epidermoid carcinoma of the anal canal. We measured squamous cell carcinoma antigen (SCC) in epidermoid carcinoma of the anal canal in 66 patients. Samples were taken at diagnosis, before treatment, and during follow-up; 353 samples were analyzed. The positive threshold was taken as 2 ng/ml. At diagnosis, the sensitivity of the marker was 44 percent and its specificity 92 percent. In our series, the pretherapeutic level of SCC does not correlate with T as in Papillons' Clinical Staging System, but it does correlate with nodal invasion (P less than 0.05). It is of no prognostic value at the time of diagnosis. During follow-up, at relapse the level of SCC is 20.3 +/- 43 ng/ml. This increase is significant (P less than 0.01): the sensitivity of the marker is 77 percent. In patients who have relapsed, development of the illness correlates with the level of SCC, which is of prognostic value (P less than 0.01). In conclusion, the level of SCC should be associated with the clinical follow-up of patients with epidermoid carcinoma of the anal canal.
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Efficacy of doxazosin in specific hypertensive patient groups. In practice, some of the major problems for the physician who treats hypertension are patients who are resistant to treatment or who have other complicating risk syndromes. Therefore the overall efficacy of an antihypertensive agent must include an assessment of effect in patients with serious ancillary problems. In this article, doxazosin is reviewed for its efficacy in the treatment of severe essential hypertension and specific complications or conditions of mild or moderate essential hypertension, namely, left ventricular hypertrophy, hyperlipidemia, noninsulin-dependent diabetes mellitus, renal insufficiency, pheochromocytoma, chronic obstructive pulmonary disease, peripheral vascular disease, and smoking. Doxazosin is particularly efficacious in many specific subgroups of patients with hypertension, and the results of relevant studies are discussed.
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Role of angiotensin-converting enzyme inhibitors in congestive heart failure. Conventional therapy for congestive heart failure (CHF) includes sodium-restricted diet, diuretics, digitalis, vasodilators, and short-term intravenous administration of beta-adrenergic agonists during episodes of decompensation. A specific class of vasodilators, the angiotensin-converting enzyme inhibitors, has recently gained predominance in the treatment of congestive heart failure. The primary mechanism of action is to reduce production of angiotensin II by competitive inhibition of the enzyme that converts angiotensin I into angiotensin II. Reduced levels of angiotensin II, in turn, promote vasodilation and lower aldosterone production. The benefits of angiotensin-converting enzyme inhibitor therapy in chronic congestive heart failure have been demonstrated by improvement in left ventricular performance, exercise capacity, functional status (using New York Heart Association classification), and survival.
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Evaluating hematuria in children. Where to start and how to proceed. Bleeding from somewhere along the urinary tract is not unusual in children. Of the many causes, systemic infection and trauma are among the most common. History taking and physical examination should be careful and complete, because the results obtained help direct the laboratory evaluation. Diagnostic testing always begins with urinalysis but may progress to intravenous urography, voiding cystourethrography, endoscopic procedures in the upper and lower urinary tract, sonography, arteriography, or renal biopsy. Some cases remain unexplained and require follow-up to assess renal function.
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Hydromyelic hydrocephalus. Correlation of hydromyelia with various stages of hydrocephalus in postshunt isolated compartments. The clinical features and pathophysiology of specific forms of hydromyelia are analyzed in this report together with the chronological changes of associated hydrocephalus. Nine patients were studied; all had hydromyelia with varying degrees of associated hydrocephalus. Clinically applicable classification systems were used to evaluate the progression of hydrocephalus (Stages I to IV) and to define the compartment isolated after shunting in the previously communicating cerebral ventricles (Types I to IV). Four patients had Stage IV disease (holoneural canal dilatation); one had Stage II and four had Stage I disease (both Stages I and II with supratentorial hydrocephalus). All patients were initially treated by ventriculoperitoneal shunting at an average age of 9.9 years. Five patients had progressive spinal symptoms before or after treatment of their hydrocephalus. Two patients had Type III isolation (an isolated rhombencephalic ventricle) with a functioning ventricular shunt; ventriculography confirmed a communication between the fourth ventricle and the hydromyelia, and both patients improved after placement of a shunt in the fourth ventricle. The remaining patients had Type IV isolation (isolated central canal dilatation) with a functioning ventricular shunt. This study indicates that in some cases the pathophysiology of hydromyelia is closely related to associated hydrocephalus. A new concept of the development of an isolated compartment after shunting is proposed to explain the progression of hydromyelia in these cases.
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Experience with photocoagulation in Behcet's disease. Between 1973 and 1987 we examined both eyes of 300 patients with the uveoretinitis-type lesions characteristic of Behcet's disease. Of the 556 eyes whose fundus could be examined, 38 eyes (6.8%) in 33 patients (11%) had developed retinal capillary nonperfusion, branch retinal vein occlusion, or retinal or disc neovascularization. These eyes were treated by photocoagulation, primarily to forestall vitreous hemorrhage and the development of neovascular glaucoma, as well as to decrease the macular edema resulting from vein occlusion. The treatment, which was well tolerated, was successful in closing retinal capillary nonperfusion areas and eliminating retinal neovascularization. Disc neovascularization was resolved completely in some cases, and partially in others.
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Idiopathic hypereosinophilic syndrome terminating as disseminated T-cell lymphoma. The authors describe a case of idiopathic hypereosinophilic syndrome (HES) terminated as a T-cell lymphoma in a 3-year-old girl. The clinical course was chronic and characterized by chronic eczema, persistent peripheral blood eosinophilia, organomegaly, interstitial lung change, and pericarditis. Postmortem examination demonstrated a disseminated T-cell lymphoma involving the inguinal lymph node, liver, lung, and kidney. The findings of the current case suggest a possibility that certain abnormalities in this case of idiopathic HES per se may have triggered the development of malignant lymphoma, and it may represent a transition of idiopathic HES into a T-cell lymphoma. Other possible sequences are discussed. The development of T-cell malignancy in idiopathic HES in a girl is quite an unusual presentation.
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Drug-induced colonic pseudo-obstruction. Report of a case. Colonic pseudo-obstruction may have many possible causes. Some of these are well described and pose no diagnostic problems. Drug-related colonic pseudo-obstruction remains underreported, but is of importance in modern society where drugs are endemically abused. This case highlights the importance of drugs in altering colonic motility and emphasizes the nonsurgical management of this condition.
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Safe use of codeine in the recovering alcoholic or addict. The effect that codeine has on the process of addiction and recovery is unclear. Confusion about definitions, study endpoints, and a lack of well-controlled clinical studies has led to this uncertainty. Codeine addiction is uncommon in people who do not have existing vulnerability to addiction, including alcoholism. Codeine use can sustain addiction or increase the risk of relapse in patients afflicted with addiction. The risk of relapse must be considered when treating conditions such as pain or cough in a person recovering from addiction. Codeine use may be circumvented with the appropriate use of alternative treatments for pain or cough. If codeine use becomes necessary, cautious prescribing and reliance on the patient's recovery support network become imperative.
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Ranitidine in the treatment of non-steroidal anti-inflammatory drug associated gastric and duodenal ulcers. In a multicentre study the effect of ranitidine on healing non-steroidal anti-inflammatory drug (NSAID) associated peptic ulcers was compared in a group of patients who had stopped NSAID treatment with another group who continued with NSAID treatment. A total of 190 patients with confirmed ulcers were randomised to continue or stop NSAID treatment. All patients in addition received ranitidine 150 mg twice daily. Patients were endoscopically monitored at four, eight, and 12 weeks. Gastric ulcers at eight weeks had healed in 63% of those taking NSAIDs compared with 95% of those who had stopped NSAID treatment. For duodenal ulcer the healing rates at eight weeks were 84% in the group continuing NSAIDs compared with 100% in those who stopped NSAIDs. The differences in healing rates were statistically significant for both gastric ulcer (p = 0.001) and for duodenal ulcer (p = 0.006). At 12 weeks, 79% of gastric ulcers and 92% of duodenal ulcers were healed in the group continuing with NSAIDs. All patients with gastric and duodenal ulcers who stopped taking NSAIDs were healed at 12 weeks. The study shows that ranitidine 150 mg twice daily effectively heals NSAID associated peptic ulcers. Healing is more successful when NSAID treatment stops but even if these drugs are continued, substantial healing rates are achievable.
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Alternation of gastric mucosal glycoprotein (lectin-binding pattern) in gastric mucosa in stress. A light and electron microscopic study. Gastric mucosal cells of the rat glandular stomach were studied by light and electron microscopic procedures by use of lectins in the development of acute gastric mucosal lesions. Effects of the H2-receptor antagonist sofalcone (2'carboxymethoxy-4,4'-bis 3-methyl-2) and truncal vagotomy with pyloroplasty on lectin binding sites and distribution were also investigated. Biotinylated lectins in combination with ABC (avidin-biotinyl peroxidase complex) method were used for light and horseradish peroxidase (HRP)-labeled lectins for electron microscopic studies. Gastric mucosal cells showed the specific binding pattern for each lectin by light microscopy. Especially, binding sites and distribution of peanut agglutinin (PNA) were characteristic after induction of stress, truncal vagotomy, and administration of each drug. Staining and distribution increased in the gastric mucosa upward and downward after that. In electron microscopic studies, PNA strongly stained the membranes of the intracellular secretory canaliculi of a parietal cell. These results suggested that alternation of binding sites and distribution was regulated by change of gastric mucosal blood flow and of acidity in the parietal cells. Therefore, increase of glycoconjugate distribution is supposed to be a possibility of cytoprotective effect for a change of environment in the parietal cells.
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Abnormal cardiac sensitivity in patients with chest pain and normal coronary arteries. The causes of chest pain in patients found to have angiographically normal coronary arteries during cardiac catheterization remain controversial. Cardiac sensitivity to catheter manipulation, pacing at various stimulus intensities and intracoronary injection of contrast medium was examined in several groups of patients who underwent cardiac catheterization. Right heart (especially right ventricular) catheter manipulation and pacing and intracoronary contrast medium provoked chest pain typical of that previously experienced in 29 (81%) of 36 patients with chest pain and angiographically normal coronary arteries and 15 (46%) of 33 symptomatic patients with hypertrophic cardiomyopathy. In contrast, only 2 (6%) of 33 symptomatic patients with coronary artery disease experienced their typical chest pain with these sensitivity tests (p less than 0.001). None of 10 patients with valvular heart disease but without a chest pain syndrome experienced any sensation with these tests. Cutaneous pain threshold testing demonstrated that patients with chest pain and normal coronary arteries had a higher pain threshold to thermal stimulation compared with patients who had coronary artery disease or hypertrophic cardiomyopathy. No relation existed between cardiac sensitivity and cutaneous sensitivity testing. Thus, patients who have chest pain despite angiographically normal coronary arteries may have abnormal cardiac sensitivity to a variety of stimuli. This increased sensitivity may be of causal importance to their chest pain syndrome or may contribute to their perception of ischemia-induced pain. The same phenomenon was also commonly seen in symptomatic patients with hypertrophic cardiomyopathy. Whether this phenomenon represents abnormal activation of pain receptors within the heart or abnormal processing of visceral afferent neural impulses in the peripheral or central nervous system is unknown.
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Headache. Public health problem. Headache is, and apparently always has been, a frequent pain syndrome. It is reported in American and Western European societies in very high percentages of the population. Headache, and specifically severe headache, have also been reported as prevalent from a variety of societies worldwide, although prevalence rates have varied (they are very low, for example, in the People's Republic of China). Whether prevalence varies with different socioeconomic groups remains uncertain. Severe headache and specifically migraine is, for reasons still unknown, much more common in women, and, in most studies, is reported to decrease in prevalence in older age groups. Positive family histories are common, but the precise role of genetics is unknown. A major problem in the epidemiologic studies remains the difficulty of uniform definition of headache syndromes.
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Lymphoproliferative disorders associated with carbamazepine. Carbamazepine-induced lymphoproliferative disorders are relatively rare. A 32-year-old woman developed cervical lymphadenopathy while taking carbamazepine. Histologic evaluation of the lymph node biopsy specimen demonstrated near-total effacement of the nodal architecture by a population of pleomorphic immunoblasts. The predominant cell population expressed CD3, CD2, CD5, and CD4, while results of testing for CD8 were negative. On the basis of the morphologic and immunohistologic features, a diagnosis of high-grade, non-Hodgkin's lymphoma, T-cell immunoblastic type, was made. Despite the fact that aggressive behavior is usually associated with immunoblastic lymphomas, the patient has done well for 33 months after cessation of carbamazepine in the absence of chemotherapeutic treatment. The clinical features of this patient's illness, therefore, suggest that it is best regarded as a so-called pseudolymphoma.
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Clinical results of axillobifemoral bypass using externally supported polytetrafluoroethylene Seventy-six axillobifemoral grafts with externally supported polytetrafluoroethylene prostheses were performed since 1983. The indications for operation were absolute (aortic sepsis) in 20 (26%) patients and relative (excessive operative risk or technical difficulty) in 56 (74%) patients. The life-table primary patency for these operations at 4 years follow-up (mean follow-up, 2 years, 4 months) was 85%. We conclude that the patency results achieved in this patient series are sufficiently satisfactory to warrant use of axillobifemoral grafts in an expanded number of patients with high operative risk and need for bypass of aortoiliac occlusive disease.
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Magnitude and time course of beta-adrenergic antagonism during oral amiodarone therapy. To examine the presence and time course of beta-adrenergic antagonism produced by amiodarone, the heart rate, QT interval and arrhythmia frequency in response to graded doses of isoproterenol were evaluated in eight patients treated with oral amiodarone for sustained ventricular tachycardia. Measurements were made before and every 2 days after beginning oral amiodarone therapy (600 mg twice daily). Isoproterenol was given in doses of 12.5, 25 and 50 ng/kg body weight per min. The mean heart rate at rest decreased from 73.1 +/- 17.8 beats/min on day 0 to 57.8 +/- 15.0 beats/min after 12 days of amiodarone therapy. A significant linear decline in heart rate at rest was observed until day 6 (p less than 0.05 for all comparisons). On all days isoproterenol produced a progressive increase in heart rate that reached 115.5 +/- 20.2 beats/min on day 0 and 94.2 +/- 18.5 beats/min on day 12. Amiodarone blunted the heart rate increase produced by isoproterenol on days 2 to 12 (p less than 0.05 versus day 0). This effect was present by day 2 and did not change significantly thereafter. The mean corrected QT (QTc) interval increased from 430 +/- 30 ms on day 0 to 449 +/- 63 ms on day 12. A significant linear increase in QTc interval was observed until day 6 (p less than 0.05 for all comparisons). There was no systematic effect of isoproterenol on the QTc interval. Five of eight patients had a significant number of isoproterenol-induced premature ventricular complexes. Ventricular ectopic activity in response to isoproterenol was abolished after 4 days of amiodarone therapy.
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Functional comparison between double and triple ileal loop pouches. Ileal pouch function in 35 patients operated upon by the same surgeon were compared. Seventeen of the patients had a double loop (J) ileal pouch-anal anastomosis (IPAA) and 18 a triple loop (S) pouch. The patients were examined a mean of 27.9 months and 5.1 months, respectively, after ileostomy closure. Ten of the S-pouch patients were evaluated more than 6 months (S greater than 6 months), mean 9.1 after ileostomy closure. There were no differences in the mean maximum resting pressures or maximum squeeze pressures between the groups. The incidence of daytime and nocturnal leakage was lower in the S-pouch group, 22 and 29 percent, than in the J group 29, and 53 percent. Though the mean maximum tolerated volume (MTV) of the S-pouch group was greater than the J group, the difference was not statistically significant. The difference in the mean compliance between the J- and S-pouch groups and the J and S greater than 6 months group was statistically significant (P less than 0.01) and (P less than 0.008). All the patients could evacuate spontaneously. The difference in the 24-hour frequency of defecation between the S greater than 6 months and J group was significant (P less than 0.05), but not between the S and J groups. The median frequency of nocturnal defecation between the S greater than 6 months and J pouch groups was significant (P less than 0.005), but not between the S and J groups. The triple loop S-pouches were more compliant than the J-pouches and had a better functional result as shown by a lower incidence of nocturnal leakage, and a lower frequency of defecation during the day and night.
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Insulin resistance and compensatory hyperinsulinemia: role in hypertension, dyslipidemia, and coronary heart disease. Resistance to insulin-stimulated glucose uptake and hyperinsulinemia may play a central role in the cause and clinical course of patients with non-insulin-dependent diabetes mellitus, high blood pressure, abnormalities of lipoprotein metabolism, and coronary heart disease. This article summarizes the evidence in support of this general hypothesis.
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Restricted dose and duration of corticosteroid treatment in patients with polymyalgia rheumatica and temporal arteritis. To analyze whether corticosteroids in low doses during limited time periods could be safely used in the treatment of patients with polymyalgia rheumatica (PMR) or temporal arteritis (TA) the records of 91 patients diagnosed between 1980 and 1987 were reviewed. The mean initial prednisolone dose was in patients with PMR 18 mg/day and the mean duration of treatment was 17 months. In patients with TA the mean initial dose was 31 mg/day and the mean duration of treatment 16 months, and in all the corticosteroid treatment was terminated within 24 months. Patients with coexisting TA and PMR demanded longer treatment compared to patients with either TA or PMR and thus 18/91 patients were treated for more than 2 years. No visual or neurological complications occurred after treatment with corticosteroids had been initiated. Our study indicates that most patients with PMR or TA can be treated safely with an initial prednisolone dose of 10 mg given twice daily. With few exceptions corticosteroid treatment can be terminated within 24 months.
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Fetal choroid plexus cysts: a prospective study and review of the literature. To determine the incidence and significance of fetal choroid plexus cysts, a prospective study was carried out at Queen's Medical Centre, Nottingham. The incidence of cysts was found to be 0.42% and the size of cysts varied from 3 to 13 mm with a mean diameter of 6.2 mm. Choroid plexus cysts were associated with other fetal abnormalities in three cases, two of which were subsequently found to have a chromosomal abnormality, one Trisomy 18 and one Trisomy 21. A review of the reported cases of choroid plexus cysts reveals an overall incidence of 5.8% for Trisomy 18. We therefore recommend that in patients with choroid plexus cysts a detailed scan should be carried out to look for the ultrasound markers of Trisomy 18. If there is an associated abnormality or cysts are large (13 mm or greater in diameter) and bilateral then a karyotyping should be carried out.
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Carotid endarterectomy for chronic retinal ischemia. Carotid arterial disease may result in a variety of ischemic ocular problems that can eventually lead to permanent blindness. From 1984 to 1988, 18 patients underwent reconstruction of the carotid artery in an attempt to restore normal retinal arterial flow and, thereby, reverse or prevent progression of ischemic oculopathy. During a mean period of 21 months after carotid arterial reconstruction, subjective improvement in vision as well as a resolution in eye and periorbital pain was reported in 87.5 per cent of the patients. Measured visual acuity improved or stabilized in 94.4 per cent; macular photostress recovery times improved in 87.5 per cent, funduscopic examinations noted improvement or resolution in ischemic signs in 93.3 per cent and intraocular pressures improved in two of three patients. One patient experienced recurrent episodes of amaurosis fugax, which resolved after two weeks and did not recur. A second patient experienced an increase in intraocular pressures with visual deterioration, required laser photocoagulation after which the condition of the patient stabilized but only after significant visual impairment. Carotid arterial reconstruction is effective for the treatment of ischemic oculopathy and is most beneficial if performed early, before the onset of irreversible neovascular glaucoma.
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Reoperation for recurrent peptic ulcer disease. The patient with recurrent peptic ulcer evidences failure of an initial operation to control the ulcer diathesis. A trial of aggressive medical therapy is warranted in elective presentations and has a moderate chance of success. Failing this, we believe that reoperation should be tailored to the patient's physiologic status and previous operation (Table 5). Nevertheless, in most cases, we believe that the second operation should be the final operation and should consist of the procedure with the lowest recurrence rates. Therefore, we believe that the assurance of an adequate antrectomy and complete vagal section is the preferred procedure for most patients with recurrent peptic ulcer.
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Sequential gradient pneumatic compression enhances venous ulcer healing: a randomized trial. The treatment of venous ulcers has remained largely unchanged for centuries. The application of properly applied graduated compression bandages, the use of graduated compression stockings, and surgery have been shown to achieve healing. However, some ulcers persist despite appropriate management. A randomized study was undertaken to compare two regimens of treatment for such patients. Both regimens included ulcer debridement, cleaning, nonadherent dressing, and graduated compression stockings. In one regimen, sequential gradient intermittent pneumatic compression was applied for 4 hours each day. Only one of 24 patients in the control group had complete healing of all ulcers compared with 10 of 21 patients healed in the intermittent pneumatic compression group. The median rate of ulcer healing in the control group was 2.1% area per week compared to 19.8% area per week in the intermittent pneumatic compression group. The results indicate that sequential gradient intermittent pneumatic compression is beneficial in the treatment of venous ulcers.
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Tricuspid valve papillary fibroelastoma: echocardiographic characterization. We report a tricuspid valve papillary fibroelastoma initially detected by transthoracic two-dimensional echocardiography and subsequently characterized by transesophageal two-dimensional echocardiography. The mass was excised during open heart operation, and the diagnosis was verified grossly and histopathologically. Transesophageal echocardiography usually provides images far superior to those from transthoracic echocardiography and may be a useful adjunct for intraoperative localization of intracardiac tumors for excision.
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Hypercalcemia in infants presenting with apnea. To our knowledge apnea in infants has not been associated with hypercalcemia. We describe seven hypercalcemic infants aged 2 days to 3 months who had presented with apnea; six of the seven were otherwise healthy. The apneic attacks were brief, and normal breathing was restored spontaneously or after tactile stimulation. The attacks stopped and the apnea monitoring was discontinued when the children were 1 month to 2 years of age. The only abnormal finding common to all of the patients was hypercalcemia. Idiopathic infantile hypercalcemia was diagnosed in six of the patients and familial benign hypercalcemia in one. Our findings suggest that determination of the plasma calcium level be included in the investigation of apnea in infancy.
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Hearing loss in elderly patients in a family practice. OBJECTIVE: To investigate hearing loss in elderly patients. DESIGN: Cohort study. SETTING: Family practice. PATIENTS: All ambulatory patients 65 years of age or older who attended the practice from June to August 1989. OUTCOME MEASURES: The Hearing Handicap Inventory for the Elderly--Screening Version (HHIE-S) and the Welch-Allyn Audioscope. Patients who failed one or both of the screening tests were referred to a speech and hearing clinic for audiologic assessment and treatment recommendations. Those with hearing aids were excluded from the main study but were given the opportunity to have them assessed at the clinic. MAIN RESULTS: Of 157 eligible patients 42 were excluded: 16 refused to participate, 13 already had hearing aids, and 13 could not be contacted. Of the remaining 115, 34 failed one or both of the tests (14 failed the HHIE-S, 9 failed the audioscope test, and 11 failed both). Of the 34, 25 completed the audiologic assessment at the clinic. Fifteen were found to have severe hearing impairment; the recommendation was hearing aids for 12, further assessment for 2 and no treatment for 1. Of the remaining 10 patients it was thought that 6 would benefit from hearing aids. Ten of the 11 patients with hearing aids who agreed to undergo testing at the clinic were found to need an adjustment or replacement of their devices. CONCLUSIONS: Hearing loss is a significant problem in elderly patients in primary practice. Further study is required to determine which of the two screening tools is most effective. Most elderly patients with hearing aids may require modification or replacement of their devices.
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Lymph node metastasis in spindle cell carcinoma arising in odontogenic cyst. Report of a case. The majority of primary intraosseous carcinomas of the jaws develop in preexisting odontogenic cysts. These tumors are usually well-differentiated keratinizing carcinomas with relatively good prognosis. Only two of 41 previously reported acceptable cases of primary intraosseous carcinomas from ex-odontogenic cysts were associated with cervical lymph node metastasis. Spindle cell carcinoma is an anaplastic dimorphic neoplasm with poor prognosis. It has a special predilection for the upper aerodigestive tract. This is to our knowledge the first report of spindle cell carcinoma developing in an odontogenic cyst. Cervical lymph node metastasis showing typical histologic features of spindle cell carcinoma was detected 8 months postoperatively. The prognostic implications of this finding are discussed in light of previously reported cases of intraosseous carcinoma arising in odontogenic cysts and of spindle cell carcinoma of the oral cavity.
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Expandable biliary metal stents for malignancies: endoscopic insertion and diathermic cleaning for tumor ingrowth. Seventeen patients with malignant biliary strictures have been treated by endoscopic insertion of self-expandable metallic prostheses. Two patients received two prostheses inserted simultaneously in both the left and right hepatic ducts for Klatskin tumor type III. Immediate results were satisfactory despite an operative mortality of 18%, and neither early nor late clogging was observed even in patients who presented previously with sludge above plastic stents that were removed. However, among five patients followed for more than 4 months, two presented with obstruction due to tumor ingrowth into the stent through the metallic mesh. Accordingly, initial enthusiasm concerning long-term patency of these stents has decreased. However, we describe a technique of "diathermic cleaning" of tumor ingrowth which can easily restore the stent patency. The advantages of these wire mesh 30 F stents are their easier insertion, better immediate drainage, and absence of dislocation or perforation.
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Effect of intravenous streptokinase on early mortality in patients with suspected acute myocardial infarction. A meta-analysis by anatomic location of infarction [published erratum appears in Ann Intern Med 1991 Mar 15;114(6):522] PURPOSE: To determine the effect of intravenous streptokinase on early mortality in patients with suspected acute anterior and acute inferior myocardial infarctions. DATA IDENTIFICATION: A literature search of English-language studies on the use of intravenous streptokinase in the treatment of suspected acute myocardial infarction for the period 1966 to 1989 using Medlars II and the bibliographies of relevant articles. In a number of instances, additional details on early mortality by location of myocardial infarction were provided by the authors. STUDY SELECTION: Of 140 originally identified articles, 6 that specifically met our inclusion criteria were selected: randomized trials that used intravenous streptokinase in a dose of 1.5 million units, with or without additional agents, compared with a group that differed only by the absence of streptokinase. Trials were selected by review of the methods section without regard for the results. DATA EXTRACTION: Data were extracted independently by two observers using specific methodologic criteria for infarct location and early mortality. After they conferred, the observers agreed completely on the data. RESULTS OF DATA SYNTHESIS: Among the 9155 patients with suspected acute anterior myocardial infarction, the mortality rate in the control group was 17.4%. In contrast, patients treated with streptokinase had a 12.5% mortality. The mean risk difference was -4.8% (95% CI, -7.5% to -2.1%) and the summary risk ratio was 0.72 (CI, 0.65 to 0.79). A total of 9650 patients with suspected inferior infarction had a mortality rate in the control group of 7.6% [corrected]. The mortality for streptokinase-treated patients was 6.6%. The mean risk difference was -0.8% (CI, -1.8% to 0.2%) and the summary risk ratio was 0.87 (CI, 0.76 to 1.01). CONCLUSIONS: Intravenous streptokinase clearly confers a protective effect against early mortality in patients with suspected acute anterior myocardial infarction. The magnitude of this effect is on the order of a 5% absolute reduction in risk of death by 21 to 35 days. For these patients, 21 need to be treated to save 1 additional life. For patients with suspected acute inferior infarction, the benefit of treatment on reducing early mortality is of smaller magnitude and less certain. These patients have an estimated absolute reduction of early mortality of approximately 1%, which would require treating 125 patients to save 1 additional life.
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Computed tomography in the evaluation of the aorta in patients sustaining blunt chest trauma. Computed tomography is used with increasing frequency to evaluate blunt chest trauma. Since traumatic aortic rupture (TAR) is a rapidly lethal condition, unnecessary CT scanning may not be justified. To determine the accuracy of chest CT scanning for TAR, we reviewed 17 patients who underwent both chest CT scanning and aortography. Five patients had TAR by aortography. CT scanning yielded three true positives and two false negatives. In 12 patients with a negative aortogram, CT scanning recorded four false positives and eight true negatives. The specificity was 23% and the sensitivity was 83% compared with aortography. The overall accuracy for CT scanning was 53%. From these data we conclude that in the presence of an unstable patient or where there is a strong clinical suspicion of TAR the patient should proceed directly to aortography.
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Effects of adenosine on human coronary arterial circulation Adenosine is a potent vasodilator used extensively to study the coronary circulation of animals. Its use in humans, however, has been hampered by lack of knowledge about its effects on the human coronary circulation and by concern about its safety. We investigated in humans the effects of adenosine, administered by intracoronary bolus (2-16 micrograms), intracoronary infusion (10-240 micrograms/min), or intravenous infusion (35-140 micrograms/kg/min) on coronary and systemic hemodynamics and the electrocardiogram. Coronary blood flow velocity (CBFV) was measured with a 3F coronary Doppler catheter. The maximal CBFV was determined with intracoronary papaverine (4.5 +/- 0.2.resting CBFV). In normal left coronary arteries (n = 20), 16-micrograms boluses of adenosine caused coronary hyperemia similar to that caused by papaverine (4.6 +/- 0.7.resting CBFV). In the right coronary artery (n = 5), 12-micrograms boluses caused maximal hyperemia (4.4 +/- 1.0.resting CBFV). Intracoronary boluses caused a small, brief decrease in arterial pressure (similar to that caused by papaverine) and no changes in heart rate or in the electrocardiogram. The duration of hyperemia was much shorter after adenosine than after papaverine administration. Intracoronary infusions of 80 micrograms/min or more into the left coronary artery (n = 6) also caused maximal hyperemia (4.4 +/- 0.1.resting CBFV), and doses up to 240 micrograms/min caused a minimal decrease in arterial pressure (-6 +/- 2 mm Hg) and no significant change in heart rate or in electrocardiographic variables. Intravenous infusions in normal patients (n = 25) at 140 micrograms/kg/min caused coronary vasodilation similar to that caused by papaverine in 84% of patients (4.4 +/- 0.9.resting CBFV). At submaximal infusion rates, however, CBFV often fluctuated widely. During the 140-micrograms/kg/min infusion, arterial pressure decreased 6 +/- 7 mm Hg, and heart rate increased 24 +/- 14 beats/min. One patient developed 1 cycle of 2:1 atrioventricular block, but otherwise, the electrocardiogram did not change. In eight patients with microvascular vasodilator dysfunction (delta CBFV, less than 3.5 peak/resting velocity after a maximally vasodilating dose of intracoronary papaverine), the dose-response characteristics to intracoronary boluses and intravenous infusions of adenosine were similar to those found in normal patients.(ABSTRACT TRUNCATED AT 400 WORDS).
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Silent ischemia after coronary angioplasty: evaluation of restenosis and extent of ischemia in asymptomatic patients by tomographic thallium-201 exercise imaging and comparison with symptomatic patients. One hundred sixteen patients were evaluated to determine the ability of single photon emission computed tomographic (SPECT) thallium-201 exercise and redistribution imaging to detect silent ischemia secondary to restenosis in asymptomatic patients after single and multiple vessel percutaneous transluminal coronary angioplasty and the findings were compared with SPECT imaging detection of restenosis in symptomatic patients. The value of exercise electrocardiography (ECG) and the amount of ischemic myocardium in symptomatic and asymptomatic patients were determined. Forty-one patients were asymptomatic after angioplasty; 77% of these had chest pain before angioplasty. Seventy-five patients had chest pain after angioplasty; 99% of these had chest pain before angioplasty. Restenosis occurred in 61% of asymptomatic and 59% of symptomatic patients and in 46% of the vessels in both asymptomatic and symptomatic patients. Sensitivity, specificity and accuracy for detection of restenosis by SPECT in individual patients were 96%, 75% and 88% versus 91%, 77% and 85%, respectively, in the asymptomatic versus symptomatic groups (p = NS). Sensitivity, specificity and accuracy for restenosis detection in individual vessels were 90%, 89% and 89% versus 84%, 77% and 84%, respectively, in the asymptomatic and symptomatic groups (p = NS), with similar results for the three major arteries. Sensitivity and accuracy of exercise ECG were significantly less than those of SPECT imaging for the patients with silent (40% and 44%) and symptomatic (59% and 64%) ischemia (p less than 0.001). Restenosis of vessels in the patients with silent and symptomatic ischemia was associated with an equal amount and degree of severity of ischemic myocardium in the two groups.
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Serum ferritin and stomach cancer risk among a Japanese population. Using stored serum samples collected during from 1970 to 1972 and/or 1977 to 1979 from a fixed population in Hiroshima and Nagasaki, Japan, serum ferritin, transferrin, and ceruloplasmin levels were determined immunologically for persons in whom stomach (233 cases) or lung cancer (84 cases) subsequently developed as well as for their controls. An elevated stomach cancer risk was associated with low antecedent serum ferritin levels, with more than a threefold excess among those in the lowest compared with the highest ferritin quintile. The risk did not vary with the time between blood collection and stomach cancer onset, remaining high among those with low ferritin levels 5 or more years before cancer diagnosis. Achlorhydria, diagnosed in a sample of the population about 10 years before the 1970-to-1972 blood collection and up to 25 years before cancer, was an independent marker of stomach cancer risk. In combination, low serum ferritin and achlorhydria were associated with a tenfold increase in the subsequent risk. No effect of transferrin or ceruloplasmin, independent of ferritin, was observed in the gastric cancer risk, and the risk of lung cancer was not related to these three serum proteins. These prospective findings indicate that biologic markers of an increased risk of stomach cancer can be detected long before cancer onset.
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Long-term results of operation for non-small cell lung cancer in the elderly. We surgically treated 185 patients with non-small cell lung cancer who were 70 years old or older. The operative mortality rate was 3%, and the 5-year survival rate was 48%. The mortality and prognosis were similar to those in younger patients. The number of elderly patients who smoked heavily or who had ventilatory defects was high, but the incidence of pneumonectomy was low. There were no differences based on age in regard to histological type, TNM classification, and curability. Pulmonary complications occurred in 21% of the elderly patients and were correlated with preoperative pulmonary function and smoking habits. When the elderly are to undergo elective pulmonary resection for lung cancer, the preoperative evaluation of pulmonary function should be thorough, and both preoperative and postoperative physical therapy should be given. If postoperative pulmonary function is predicted to be less than 0.8 L/m2 of vital capacity and 0.6 L/m2 of forced expiratory volume in 1 second, a limited resection or nonsurgical therapy should be considered.
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Venous stasis and vein lumen changes during surgery The mechanisms underlying the development of postoperative deep vein thrombosis remain to be fully elucidated. Previous studies have suggested that peroperative venous distension may be a factor associated with venous thromboembolism. In this study we have obtained high resolution ultrasound images of gastrocnemius and posterior tibial veins in 62 patients undergoing a range of general surgical procedures. From these we determined the changes in vein diameter occurring during the operative procedures, in response to induction of anaesthesia, and after completion of surgery. Veins showed no evidence of dilatation in response to the induction of anaesthesia, but by the end of the operative procedure showed distension of 22-28 per cent. Distension was most prominent in the gastrocnemius veins, and lesser distension was observed in the posterior tibial veins. In a series of patients who received an infusion of 1 litre of saline in addition to basal requirements, distension was 57 per cent compared with 22 per cent in the corresponding control group. Intraoperative venous distension is associated with factors that lead to deep vein thrombosis and may be involved in the mechanisms which result in the commencement of deep vein thrombosis.
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Thrombectomy for late graft limb occlusion: our experience in 182 consecutive cases. Late occlusion of an aortofemoral bypass graft is usually caused by fibrointimal hyperplasia or progressive atherosclerosis. Several surgical approaches have been advocated in order to minimize the operative risk, to correct the impaired inflow and to provide a satisfactory outflow. In the last 16 years, in the Institute of Vascular Surgery and Angiology of the University of Milan, we have operated upon 182 consecutive thrombosed grafts. Inflow was restored by performing a graft limb thrombectomy using a Fogarty balloon catheter and simultaneously employing an endarterectomy ring stripper to dislodge tenaciously adherent fibrinous material and thrombotic plug. As the superficial femoral artery was generally occluded, usually a good outflow was achieved by profundaplasty in 101 cases (55.5%) or direct bypass (interposition graft), to a more distal segment of the profunda femoris artery in 55 cases (30.2%). Concomitant popliteal or tibial revascularization was done in the remaining 26 cases (14.3%) when pre-operative or intra-operative findings suggested an inadequate collateral network through the profunda femoris artery. Early re-occlusion, which occurred in 14 cases (7.6%), generally due to insufficient outflow, was corrected by additional intervention in 7 cases (3.8%), while 7 legs were amputated for extensive atherosclerotic disease. Six patients died giving a mortality rate of 3.3%. This low rate in a high risk population is probably related to our policy of operating under loco-regional anaesthesia. Long term results, with a patency rate of 62.0% at 3 years and 60.2% at 5 years (life table method), prove that this operation is a durable procedure for correction of graft limb thrombosis.
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Sleepwalking precipitated by treatment of sleep apnea with nasal CPAP. A 33-year-old man with a long history of snoring, observed apneic episodes, and excessive daytime sleepiness, underwent all-night polysomnography, which demonstrated severe obstructive sleep apnea. During the nasal CPAP trial, two episodes of sleepwalking were observed during a period of delta sleep rebound.
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Treatment of angiomas with sclerosing injection of hydroxypolyethoxydodecan. The authors discuss the indications for hydroxypolyethoxydodecan in the sclerosing treatment of angiomas, with particular reference to cavernous, venous, and evolutive angiomas (ie, immature angiomas that fail to involute by eight to ten months). Moreover, the sclerosing agent may be employed, in connection with embolization and subsequent surgery, in arteriovenous angiomas with a relevant cutaneous-subcutaneous development. The authors have successfully used the "interstitial" sclerosing technique, according to Andrews' method. This technique involves interstitial injections to obtain the sclerosis of the thin threads of fibrous tissue stroma between the blood vessels. The sclerosing therapy may cause the complete regression of "low flow" angiomas or, at least, a partial reduction that simplifies the ensuing surgical excision. In the case of partial regression of the angioma obtained with the sclerosing therapy, the surgery of the remaining angioma causes a lesser degree of bleeding (especially in areas that do not particularly lend themselves to surgical exploration, ie, the oral cavity); an increased reliability in the radicality of the intervention (due also to the reduced size of the lesion); and better results from an aesthetic-functional point of view.
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Resting metabolic rate and energy balance in amenorrheic and eumenorrheic runners. This study investigated metabolic and nutritional factors in association with athletic menstrual dysfunction (AMD). Three groups of women were studied: amenorrheic runners (amenorrheic), eumenorrheic runners (eumenorrheic), and eumenorrheic sedentary controls (sedentary). Amenorrheic and eumenorrheic were similar in age, weight, percent body fat by hydrodensitometry, training pace and mileage, best 10 km race time, years running, and maximal oxygen consumption. When adjusted for body weight or for fat-free mass by analysis of covariance, RMR was significantly lower in amenorrheic than in eumenorrheic and sedentary. The daily caloric intakes of the groups did not differ significantly, but the amenorrheic scored significantly higher than the eumenorrheic and sedentary on a scale of aberrant eating patterns. Amenorrheic high mileage runners seem to have a less adequate diet than eumenorrheic runners but appear to maintain energy balance and stable weight through a reduction in RMR.
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Delayed presentation of intrapericardial diaphragmatic hernia, an unusual cause of colon obstruction. The earliest symptoms of diaphragmatic hernia may not appear until viscera incarcerate in it years after the causal injury. The most unusual site for a diaphragmatic hernia to occur is through the central tendon of the diaphragm into the pericardium. We present the case of a 43-year-old man who suffered a bowel obstruction when the transverse colon and omentum became incarcerated in the intrapericardial diaphragmatic hernia. The defect presumably resulted from blunt chest and abdominal trauma received 15 years earlier. The delayed presentation of intrapericardial diaphragmatic hernia is reviewed, and recommendations for evaluation and treatment are made.
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Abnormal differentiation of human papillomavirus-induced laryngeal papillomas. We studied the proliferation and differentiation of human laryngeal papillomas, which are benign tumors induced by human papillomaviruses. Immunofluorescent stains of tissues for a number of differentiation-specific proteins showed abnormal differentiation. Papilloma tissue fragments in vitro showed a slightly decreased fraction of proliferating cells that incorporated tritiated thymidine and a markedly reduced incorporation of tritiated uridine when compared with normal tissue. We propose that papillomavirus infection results in normal basal cell proliferation but abnormal terminal differentiation and that this abnormality significantly contributes to the hyperplasia of the papillomas.
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Immunohistochemical demonstration of pancreatic secretory trypsin inhibitor in normal and neoplastic colonic mucosa. Specimens of normal and neoplastic colonic mucosa from 52 patients were analysed by immunohistochemistry using a monospecific polyclonal antiserum against human pancreatic secretory trypsin inhibitor (PSTI). In normal colonic mucosa PSTI was found in the goblet cells in the basal parts of the crypts. In adenomas of tubular, villous, and tubulo-villous types PSTI was also found in the upper parts of the polyps, usually occurring in the regeneration zone. There was a more intense staining reaction in polyps with increased atypia. Carcinomas of different types and of various grades of differentiation and of in situ type did not contain PSTI. These findings indicate that PSTI could be a marker for adenomatous rather than carcinomatous epithelium in the colon. Furthermore, the absence of the inhibitor in malignant cells might facilitate tissue invasion by malignant cells because of deficient protease inhibition.
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Mammography and early breast cancer detection. Screening mammography has been shown to reduce breast cancer mortality. Both film-screen mammography and xeromammography are highly sensitive and specific. Mammography accreditation programs assure physicians and patients that a facility provides mammography of the highest quality, using the lowest possible radiation dose. Mammographic signs of early cancer include a small mass, calcifications, architectural distortion and a neodensity. Dense tissue may result in a false-negative examination even when a cancer is palpable, with adverse effects if biopsy is delayed.
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Vitreous changes and macular edema in central retinal vein occlusion. The condition of the posterior vitreous was determined in 56 eyes with central retinal vein occlusion (CRVO). Using a life-table analysis, it was studied in 56 eyes. The incidence of posterior vitreous detachment (PVD) in the CRVO eyes at the first vitreous examination did not differ significantly from that in 64 age-matched control eyes. However, the incidence of PVD in CRVO eyes increased from 39.3% at the first vitreous examination to 58.5% after 6 months, and to 69.6% 1 year from the examination. The incidence of PVD in CRVO eyes during follow-up was statistically higher than that of the controls (P = .009). The incidence of PVD after the first vitreous examination was significantly higher in eyes with hemorrhagic retinopathy than in eyes with venous stasis retinopathy (P = .04). In the 34 eyes with macular edema, the edema lasted significantly longer in those with vitreomacular attachment (VMA) at the first examination than in those without VMA at this time (P = .02). VMA may play an important role in the pathogenesis and chronicity of macular edema in CRVO.
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Cat-scratch disease. Acute encephalopathy and other neurologic manifestations. Seventy-six patients with neurologic complications of cat-scratch disease are discussed. Encephalopathy occurred in 61, while 15 had either cranial or peripheral nerve involvement. The average age of the patients with encephalopathy was 10.6 years (range, 1 to 66 years), and almost twice as many males as females were affected in contrast to patients with uncomplicated cat-scratch disease, in which the ratio was almost equal. Fever was not documented in 50% of patients with encephalopathy and only 26% had temperatures higher than 39 degrees C. Convulsions occurred in 46% and combative behavior in 40%. Lethargy with or without coma was accompanied by variable neurologic signs. Results of laboratory studies, including imaging of the central nervous system, were inconsistent and nondiagnostic. Biopsy tissue from 14 patients showed histopathologic findings compatible with cat-scratch disease. The "English-Wear bacillus" was demonstrated by the Warthin-Starry stain in 10 of 14 skin or lymph node specimens. Of the 15 patients without encephalopathy, two children with facial nerve paresis displayed cranial nerve symptoms and/or signs, 10 patients had cat-scratch disease neuroretinitis, and three women had peripheral neuritis. All 76 patients recovered within 12 months; 78% recovered within 1 to 12 weeks. There were no neurologic sequelae. Treatment consisted of control of convulsions and supportive measures. Commonly used antibiotics administered to more than half of the patients were apparently ineffective.
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Centrifugal intensity and duration as countermeasures to soleus muscle atrophy. Mechanical acceleration is a countermeasure that may be employed to prevent atrophy of slow-twitch muscle during non-weight bearing. In the present study, daily centrifugation of rats for different durations (1 or 2 h) and at different gravitational intensities (1.5 or 2.6 G) was used to test whether mechanical acceleration could ameliorate the atrophy of the soleus muscle induced by non-weight bearing (tail-traction model). The soleus muscle atrophied 32% during 7 days of non-weight bearing without countermeasures. Centrifugation treatment did not completely prevent atrophy relative to precontrol wet weight of the soleus muscle. Non-weight-bearing groups receiving 2-h daily treatments of 1, 1.5, or 2.6 G had 48, 56, and 65%, respectively, of the atrophy observed in the non-weight-bearing-only group compared with the precontrol group. No evidence was obtained that centrifugation at 2.6 G was more effective than exposure to 1 or 1.5 G as a countermeasure to non-weight-bearing-induced atrophy of the soleus muscle.
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Expression of HLA-DR and secretory component antigens and lymphocyte infiltration in human gastric nonmalignant and malignant tissues: an immunohistochemical study. The relation between HLA-DR and secretory component (SC) expression and the degree of lymphocyte infiltration was immunohistochemically examined in human gastric mucosa with or without intestinal metaplasia and gastric carcinoma tissues. Gastric mucosa without obvious inflammation showed neither expression of HLA-DR or SC nor remarkable lymphoid infiltration. In contrast, gastric mucosa with chronic inflammation, tissues with incomplete type of intestinal metaplasia, and carcinoma demonstrated both HLA-DR and SC in almost the same area and also prominent lymphoid infiltration in the surrounding stroma. This simultaneous expression of HLA-DR and SC was not observed in complete type of intestinal metaplasia. The results indicate a close relationship between expression of HLA-DR and SC and the presence of lymphocyte infiltration in gastric mucosa, areas of incomplete type of intestinal metaplasia and in gastric carcinomas.
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Diagnostic efficiency of troponin T measurements in acute myocardial infarction BACKGROUND. The present study was designed to evaluate the efficiency of a newly developed troponin T enzyme immunoassay for the detection of acute myocardial infarction. METHODS AND RESULTS. The study comprised 388 patients admitted with chest pain and suspected myocardial infarction and 101 patients with skeletal muscle damage and additional suspected myocardial cell damage. Troponin T was elevated to more than twice the analytical sensitivity of the assay (0.5 microgram/l) in all patients with non-Q wave (range, 1.2-5 micrograms/l) and Q wave infarction (range, 3-220 micrograms/l). Troponin T appeared in serum as early as 3 hours after onset of pain in 50% of the patients and remained elevated in all patients for more than 130 hours, revealing release kinetics of both free cytosolic and structurally bound molecules. The diagnostic efficiency of troponin T was superior to that of creatine kinase-MB (98% versus 97%) and remained at 98% until 5.5 days after admission, if patients with unstable angina were excluded from analysis. In the 79 patients with unstable angina, troponin T was elevated (range, 0.55-3.1 micrograms/l) in at least one blood sample from each of 37 patients (56%). Circulating troponin T was correlated to the presence of reversible ST segment or T wave changes on the electrocardiogram (p less than 0.005) and to the frequency of in-hospital complications. In the 101 patients with skeletal muscle damage and suspected additional cardiac muscle damage, troponin T was the most useful test; its efficiency was 89% or 94% (depending on the discriminator value used) as compared with 63% for creatine kinase-MB. CONCLUSIONS. Thus, the data of the study indicate that the newly developed troponin T test improves the efficiency of serodiagnostic tools for the detection of myocardial cell necrosis as compared with conventionally used cardiac enzymes.
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Petrosal sinus sampling: technique and rationale. Bilateral simultaneous sampling of the inferior petrosal sinuses is an extremely sensitive, specific, and accurate test for diagnosing Cushing disease and distinguishing between that entity and the ectopic ACTH syndrome. It is also valuable for lateralizing small hormone-producing adenomas within the pituitary gland. The inferior petrosal sinuses connect the cavernous sinuses with the ipsilateral internal jugular veins. The anatomy of the anastomoses between the inferior petrosal sinus, the internal jugular vein, and the venous plexuses at the base of the skull varies, but it is almost always possible to catheterize the inferior petrosal sinus. In addition, variations in size and anatomy are often present between the two inferior petrosal sinuses in a patient. Advance preparation is required for petrosal sinus sampling. Teamwork is a critical element, and each member of the staff should know what he or she will be doing during the procedure. The samples must be properly labeled, processed, and stored. Specific needles, guide wires, and catheters are recommended for this procedure. The procedure is performed with specific attention to the three areas of potential technical difficulty: catheterization of the common femoral veins, crossing the valve at the base of the left internal jugular vein, and selective catheterization of the inferior petrosal sinuses. There are specific methods for dealing with each of these areas. The sine qua non of correct catheter position in the inferior petrosal sinus is demonstration of reflux of contrast material into the ipsilateral cavernous sinus. Images must always be obtained to document correct catheter position. Special attention must be paid to two points to prevent potential complications: The patient must be given an adequate dose of heparin, and injection of contrast material into the inferior petrosal sinuses and surrounding veins must be done gently and carefully. When the procedure is performed as outlined, both inferior petrosal sinuses can be catheterized in more than 98% of patients. The complication rate is low, and the theoretical risk of major morbidity or death is less than 1% (neither has yet occurred, to our knowledge). The most common complication is groin hematoma.
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Immunoblastic T-cell lymphoma presenting as an eyelid tumor. A 59-year-old white man presented with an ulcerating mass of the left upper eyelid of 6 months' duration. A biopsy specimen of the tumor was diagnosed as an immunoblastic T-cell malignant lymphoma. The lesion completely regressed after 4000 cGy of cobalt-60 radiation therapy. In the ensuing 33 months, multiple, widespread skin nodules of the same neoplasm developed including a right upper eyelid tumor. To the authors' knowledge, this is the first reported case of an immunoblastic T-cell lymphoma initially manifesting as an eyelid neoplasm.
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Expression of ABH blood group antigens, Ulex europaeus agglutinin I, and type IV collagen in the sinusoids of hepatocellular carcinoma. The expression of blood group antigens (A, B, H, Lewis(a) and Lewis(b)), Ulex europaeus agglutinin I (UEA-I), factor VIII-related antigen, and type IV collagen on the sinusoids was examined immunohistochemically in 15 cases of hepatocellular carcinomas (HCC), 11 cases of cirrhosis, 12 cases of chronic active hepatitis, and in a control sample of 16 normal livers. Sinusoidal endothelial cells of HCC characteristically showed a diffuse and strong immunoreactivity to ABH blood group antigens in the specimen with a comparable ABO blood group. The sinusoidal endothelial cells were also diffusely and strongly positive for UEA-I receptors. In contrast, in cirrhosis and chronic active hepatitis a few sinusoidal endothelial cells were positive for ABH blood group antigens and UEA-I receptors. In normal livers, only a few sinusoidal endothelial cells were positive for ABH blood group antigens and UEA-1 receptors. Tests for factor VIII-related antigen and Lewis blood group antigens were almost negative on sinusoidal endothelial cells. Although type IV collagen was distributed diffusely in the space of Disse in these four groups, its expression was strongest in HCC. Blood vessels of portal tracts and fibrous septa were positive for ABH blood group antigens, UEA-1 receptors, factor VIII-related antigen, and type IV collagen, but negative for Lewis blood group antigens. These findings suggest that some sinusoidal endothelial cells undergo "capillarization" in cirrhosis and chronic active hepatitis, and that the majority of sinusoidal endothelial cells of HCC have phenotypic characteristics of capillaries.
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Bile acids in human plasma interfere with cholecystokinin bioassay using dispersed pancreatic acini. A bioassay using dispersed pancreatic acini was used to measure fasting plasma cholecystokinin (CCK) concentrations in 105 patients with various kinds of gastrointestinal diseases, 17 patients with diabetes mellitus, and 6 healthy volunteers. High plasma CCK bioactivities were observed in patients with obstructive jaundice, choledocolithiasis, and primary biliary cirrhosis. Twenty-three samples with high CCK bioactivities were assayed by the same bioassay after the addition of a specific CCK antagonist and by a CCK radioimmunoassay in order to determine whether the high CCK-like bioactivity was due to circulating CCK or other factors. High CCK bioactivities were partially inhibited by the specific CCK antagonist, CR-1409, but the activities were not totally abolished. The residual bioactivities (not inhibited by CR-1409) correlated with plasma bile acid concentrations. The inhibitable CCK bioactivities correlated with plasma CCK levels obtained by radioimmunoassay. Although the bioassay using dispersed pancreatic acini has several advantages for measuring plasma CCK, this method overestimates CCK bioactivities in patients with high plasma bile acid concentrations.
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Immediate preoperative phlebotomy with autologous blood donation for aortic replacement. The preferential use of autologous blood provided by phlebotomy can reduce the need for homologous blood transfusion in patients undergoing extensive elective operations. This blood is usually provided either by intraoperative isovolemic hemodilution or phlebotomy one to two weeks preoperatively. To minimize the intraoperative time delay or preoperative period between phlebotomy and operation required in these patients, we performed preoperative isovolemic hemodilution in 69 patients one to two days prior to elective aortic replacement for infrarenal aneurysmal disease. Patients underwent phlebotomy a mean of 0.57 +/- 0.01 liter of whole blood; volume was replaced with lactated Ringer's solution. Hematocrit levels decreased from a mean value of 42.9 +/- 0.4 per cent to 33.7 +/- 0.3 per cent. Mean intraoperative blood loss was 1.2 +/- 0.05 liters. Hemodynamic parameters (blood pressure, cardiac output, pulmonary capillary wedge pressure, central venous pressure, oxygen delivery and systemic vascular resistance) remained stable throughout the perioperative and intraoperative time periods. In addition, we evaluated the technical modification of exclusion aneurysmorrhaphy (n = 50) versus open aneurysmorraphy (n = 19) on reduction of intraoperative homologous blood transfusion in these patients. Seventy-two per cent (36 of 50) of patients whose aneurysms were excluded received no homologous blood intraoperatively. Blood loss was decreased in the excluded versus open aneurysmorraphy group, 920 +/- 90 milliliters versus 2,030 +/- 250 milliliters, as were homologous blood transfusion requirements, 175 +/- 35 milliliters versus 570 +/- 119 milliliters. Two patients died (2.9 per cent mortality rate), and there was no increase in morbidity. Surgical treatment of large aortic aneurysms is frequently performed on an urgent basis; thus, provision of autologous blood for this operation in a short period of time may be beneficial. Isovolemic hemodilution performed during the immediate preoperative period can reduce homologous blood requirements and be safely performed without adverse effects on mortality, morbidity and myocardial performance. Exclusion aneurysmorrhaphy may further reduce dependence on homologous blood.
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