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Further evaluation of radical surgery following radiotherapy for advanced parotid carcinoma. A series of 30 patients who have been treated for advanced carcinoma of the parotid gland using radiotherapy followed by radical surgery is presented. Three patients deteriorated during preoperative radiotherapy and remained unfit for surgery; the remaining 27 underwent radical parotidectomy with block dissection of the neck. Twelve patients received additional radiotherapy after operation. Of those patients undergoing surgery, three have been lost to follow-up, 17 have died and seven remain alive; the period of follow-up ranges from 3 to 133 months. Fourteen patients remained free of recurrent disease at death or when last seen, and six patients developed a local recurrence at a medium period of 10.5 (range 3-36) months after surgery. For all 30 patients, the cumulative proportion surviving for 5 years was 30 per cent.
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Guidelines for transfusion support in patients undergoing coronary artery bypass grafting. Transfusion Practices Committee of the American Association of Blood Banks. We have reviewed the impact of evolving issues in coronary artery bypass grafting (CABG) on transfusion support for these patients. Issues include increased awareness of transfusion risks, reappraisal of traditional indicators triggering transfusion, and evolving alternatives to homologous blood transfusion such as autologous blood and pharmacologic therapy. These issues have been prompted by programs, such as the National Institutes of Health Consensus Conferences, to provide physicians with guidelines for appropriate use of blood components. However, evidence suggests that transfusion practice in coronary artery bypass grafting procedures remains variable and does not take into account the results of recently published clinical studies. We have therefore developed guidelines and recommendations for transfusion support in patients undergoing coronary artery bypass grafting. In summary, they are the following. 1. Institutions with coronary artery bypass grafting programs should establish a multidisciplinary approach to use a combination of interventions designed to minimize homologous blood exposure. 2. Prophylactic transfusion of plasma and platelets are of no benefit and therefore carry an unnecessary risk to the patient. 3. Special request products such as designated blood donation from first-degree relatives should not be used because of the risk of transfusion-associated graft versus host disease. 4. For support of intravascular volume, crystalloids or colloids should be used because they do not have the potential to transmit infection.
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Aggressive granulomatous lesions in cementless total hip arthroplasty. We describe six patients with aggressive granulomatous lesions around cementless total hip prostheses. Two patients previously had a cemented prosthesis in the same hip. The Lord prosthesis was used in five patients, the PCA in one. Both prostheses were made of chrome-cobalt alloy. Pain on weight-bearing occurred on average 3.2 years after the cementless arthroplasty, and at that time radiography revealed aggressive granulomatosis around the proximal femoral stem and the acetabular component in five of the patients; one had a large solitary granuloma in the proximal femur. Revision was performed on average 4.8 years after the cementless arthroplasty. At that time all granulomas had grown large in size; while waiting for revision operation, two femoral stem components fractured. All the granulomas showed a uniform histopathology, which included histiocytosis; the cause for these lesions was thought to be plastic debris from the acetabular socket.
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Cross-national changes in the effects of peptic ulcer disease. OBJECTIVE: To describe and to analyze the changing effects of peptic ulcer disease over time. DESIGN: Variables relating to peptic ulcer disease from 1970-1986 were compared. The variables included rates of mortality, hospitalizations, operations, physician visits, and endoscopies, and the amount of disability-related loss of work and early retirement in six countries (Belgium, England and Wales, the Federal Republic of Germany, The Netherlands, Sweden, and the United States). MEASUREMENTS: Nonparametric epidemiologic time-trend analysis. MAIN RESULTS: The historic, slow, declining trend in mortality and hospitalization rates continued. The rate of operations for peptic ulcer disease exhibited a large, one-time reduction, then returned to a parallel declining trend, but at a lower level. The rate of physician visits declined by 50%. The greatest changes were found in the rate of endoscopy use and in disability-related loss of work and early retirement, where increasing trends were quickly followed by decreasing trends. The elderly, especially women, generally did not share many of these benefits. CONCLUSIONS: The effects of new interventions can be understood more fully by examining several variables in many countries over a long time. Contrary to expectations, the effects of the widespread use of histamine H2 antagonists have been more indirect (affecting work loss and disability retirement more) than direct (affecting high-cost medical service use and mortality less).
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Immunophenotypic aberrancy in adult acute lymphoblastic leukemia. Some recent reports indicate a high frequency of immunophenotypic aberrancy in acute lymphoblastic leukemia (ALL). To investigate this issue with regard to adult ALL, the authors reviewed the immunophenotyping data from 39 cases analyzed in their clinical laboratory. Flow cytometric analysis of peripheral blood and/or bone marrow was performed with the use of a panel of 21 B-cell, T-cell, and myeloid monoclonal antibodies (MoAbs). The surface antigen profiles of the leukemic cells were compared with those of normal bone marrow and thymic counterparts, as defined by current models. Twenty-six cases were B-precursor ALL, 8 were T-ALL, and 3 were B-ALL (Burkitt's leukemia). Only two cases coexpressed lymphoid and myeloid antigens. In contrast, intralineage aberrancy was quite common. Immunophenotypes from 13 of 26 B-precursor ALL cases deviated from normal B-lineage marrow cells as defined by a recent classification. The T-ALL cases were also immunophenotypically heterogeneous. This high incidence of aberrant antigen expression in adult ALL suggests that leukemogenesis also involves aberrant differentiation rather than purely a process of maturational arrest.
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Decreased osmotic stability of dystrophin-less muscle cells from the mdx mouse Human X-linked Duchenne and Becker muscular dystrophies are due to defects in dystrophin, the product of an exceptionally large gene. Although dystrophin has been characterized as a spectrin-like submembranous cytoskeletal protein, there is no experimental evidence for its function in the structural maintenance of muscle. Current hypotheses attribute necrosis of dystrophin-less fibres in situ to mechanical weakening of the outer membrane, to an excessive influx of Ca2+ ions, or to a combination of these two mechanism, possibly mediated by stretch-sensitive ion channels. Using hypo-osmotic shock to determine stress resistance and a mouse model (mdx) for the human disease, we show that functional dystrophin contributes to the stability of both cultured myotubes and isolated mature muscle fibres.
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Paraesthesia with lumbar epidural catheters. A comparison of air and saline in a loss-of-resistance technique. The epidural space was located in 32 obstetric patients using loss of resistance to air, while in a further 35 saline was used. The incidence of paraesthesia was 56% in the air group and 57% in the saline group. There was no significant difference between the groups in terms of other complications or in the quality of analgesia provided.
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Improving compliance and increasing control of hypertension: needs of special hypertensive populations. Approximately 60 million people in the United States have hypertension. More than half are either untreated or treated without blood pressure control, despite the well-known risks of hypertension and the established benefits of treatment. The major reason for inadequate control of hypertension is poor adherence to treatment. Approximately 50% of patients with hypertension fail to keep follow-up appointments, and only 60% take their medications as prescribed. Barriers to effective therapeutic adherence include poor doctor-patient communication, cost of antihypertensive therapy, and side effects of the drugs. To increase control of hypertension, compliance with therapy must be improved. Physicians and patients must be mutually committed to achieving control of blood pressure. Physicians should communicate instructions clearly and prescribe therapies that are effective, affordable, and have minimal or no adverse effects on patient quality of life or overall cardiac risk profile. The needs of special hypertensive populations (i.e., elderly, black, and young patients) must also be recognized and addressed. Patients must follow recommendations and alert their physicians to any problems with their medications--particularly those relating to side effects and cost. When selecting drug therapy it should be noted that older patients are sensitive to volume depletion and sympathetic inhibition. In this group of patients, initial drug doses should be low and increments smaller and more gradual than in younger patients. Black patients with hypertension show an accentuated response to diuretics and blunted responses to beta-blockers and angiotensin-converting enzyme (ACE) inhibitors as monotherapy. However, when used with a diuretic, there are no racial differences in the blood pressure lowering effects of beta-blockers and ACE inhibitors.
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Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts. In vivo studies in the rat. The protective effect of ursodeoxycholate conjugates against bile salt hepatotoxicity was studied in chronic bile fistula rats. Taurochenodeoxycholate or taurodeoxycholate, infused intraduodenally at 24 or 16 mumols/100 g rat per hour, respectively, caused cholestasis and severe hepatocellular necrosis within 8 hours. In contrast, tauroursodeoxycholate or taurocholate at 48 mumols/100 g rat per hour were choleretic. Tauroursodeoxycholate was not hepatotoxic, whereas taurocholate produced moderate hepatocellular necrosis. Simultaneous infusion of tauroursodeoxycholate to rats receiving taurochenoxycholate or taurodeoxycholate preserved bile flow and ameliorated hepatic injury in a dose-dependent manner. Tauroursodeoxycholate protected equally by intravenous and intraduodenal routes. Intravenous glycoursodeoxycholate also was protective. The hydrophobicity index of infused bile salts correlated well with their toxicity. Concurrent administration of ursodeoxycholate conjugates did not reduce biliary recovery of intraduodenally infused [24-14C]-taurocholate. Biliary alkaline phosphatase secretion was stimulated by infusion of taurocholate, taurodeoxycholate, or taurochenodeoxycholate; simultaneous infusion of ursodeoxycholate conjugates failed to prevent this increase. We conclude that ursodeoxycholate counteracts hepatoxicity of more hydrophobic bile salts via a direct effect at the level of the liver.
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Motility factor produced by malignant glioma cells: role in tumor invasion. To better understand the cellular mechanism of tumor invasion, the production of a cell motility-stimulating factor by malignant glioma cells was studied in vitro. Serum-free conditioned media from cultures of rat C6 and human T98G cell lines contained a factor that stimulated the locomotion of the producer cells. This factor was termed the "glioma-derived motility factor." The glioma-derived motility factor is a heat-labile protein with a molecular weight greater than 10 kD and has relative stability to acid. The factor showed not only chemotactic activity but also chemokinetic (stimulated random locomotion) activity in the two types of glioma cells studied. Although glioma-derived motility factors in conditioned media obtained from two different cell origins are likely to be the same, chemokinetic migration of T98G cells to their conditioned medium was much stronger than that of C6 cells to theirs. Coincubation of cells with cytochalasin B, which disrupts the assembly of cellular actin microfilaments, almost completely inhibited the cell migration stimulated by glioma-derived motility factor. Cytochalasin B also induced marked alterations in cell morphology, including cell retraction and arborization, while the drug did not affect cell attachment to culture dishes. These results indicate that glioma cells produce a motility factor which may play a role particularly when tumor cells are detached and migrate away from the original tumor mass, thus promoting tumor invasion. Also, glioma cell migration stimulated by the motility factor requires the normal organization of cytoskeletons such as actin microfilaments.
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Endoscopy versus x-ray studies of the gastrointestinal tract: future health care implications. I did esophagogastroduodenoscopy in 147 patients and colonoscopy in 59 patients who had had gastrointestinal x-ray studies. The endoscopic procedure was done within 7 days after the x-ray study and/or while the patient was still symptomatic. The barium swallow findings were confirmed in only 40%; in the other 60%, the x-ray findings could not be confirmed. These unconfirmed x-ray findings were false-positive in 37.4%, false-negative in 16.3%, and suboptimal or nondiagnostic in 6.2%. The barium enema findings were confirmed in 32%. In the other 68%, the x-ray findings were false-positive in 42.3%, false-negative in 22%, and suboptimal in 3.3%. We conclude that in clinical or private practice, relying on x-ray studies alone may be associated with a high margin of diagnostic errors. When all factors are considered, the initial cost advantage of the x-ray studies appears to be lost. In future recommendations on the continuing dilemma of x-ray studies versus endoscopy, consideration should be given to factors other than the initial lower price of the x-ray studies.
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Anaplastic large cell (Ki-1) lymphoma with histiocytic phenotype simulating carcinoma. Histiocytic and epithelial cell types share many cytomorphologic and functional characteristics; it is predictable, therefore, that corresponding malignancies might be difficult to distinguish. Described is the case of a 52-year-old woman in whom disseminated anaplastic large-cell lymphoma simulated carcinomatosis by conventional morphologic criteria. Evidence of histiocytic differentiation was derived from immunocytochemical, fine structural, and genetic probe analyses. The diagnosis of histiocytic neoplasia is discussed in relation to categories previously termed malignant histiocytosis, "Ki-1" lymphoma, and regressing atypical histiocytosis, and comparisons are made with animal tumor models.
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Giant cell tumor of bone. Giant cell tumor is the second most common benign tumor of bone. Plain radiographs may demonstrate distinctive features but can also be misleading. The diagnosis may be aided by the use of other imaging modalities, such as bone scan, computed tomography and angiography. The recurrence rate is high, but some of the newer treatments seem to be associated with better outcomes.
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Flow cytometric analysis of the mechanism of methylmercury cytotoxicity. Flow cytometric analysis of murine erythroleukemic cells (MELC) exposed in vitro to 2.5 to 7.5 mumol/l (micromolar) methylmercury (MeHg) reveals a dose-dependent decrease in the rate of DNA synthesis (rate of passage through the S phase of the cell cycle), manifested as the accumulation of most of the cells in the S phase, and a modest accumulation of cells in the G2/M phase of the cycle. Light microscopy reveals a progressive increase in chromosomal damage (condensation, pulverization). At or above 10 mumol/l MeHg, progression through all the phases of the cell cycle is blocked and mitotic cells are arrested irreversibly in anaphase, with most exhibiting arrangement of chromosomes in a wreathlike ring formation. Also the cells exhibit both nuclear propidium iodide (PI) fluorescence (indicative of loss of viability) and concurrent cytoplasmic carboxyfluorescein (CF) fluorescence (viable cells exhibit CF fluorescence and exclude PI). In addition, there is a dose-dependent increase in cellular refractive index (90 degrees light scatter), an apparent decrease in cell volume (axial light loss), and progressive resistance to detergent (NP-40)-mediated cytolysis. Resistance to detergent-mediated cytolysis is indicative of fixation (protein denaturation, cross-linking, and so on) of the plasma membrane/cytoplasm complex. Our findings indicate that DNA synthesis is the primary target of MeHg cytotoxicity and that apparent targets and degree of cytotoxicity are a complex function of dose.
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A histologic evaluation of the accuracy of TMJ diagnostic arthroscopy. Sixty-seven temporomandibular joints with internal derangement were examined with arthroscopy, and synovial biopsies were taken for histologic evaluation. Histologically, in 10 cases, the synovium appeared to be normal in appearance, 24 cases had moderate to severe synovitis, 11 cases showed hyperplastic synovitis, 13 cases showed synovial fibrosis, and foreign body granuloma was found in 9 cases. Correlation between arthroscopic observation and histologic findings disclosed an 89.1% specificity and 100% sensitivity.
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Function in athymic nude mice of parathyroid heterografts from patients with primary hyperparathyroidism and secondary hyperparathyroidism. Heterotransplantation of adenomatous parathyroid glandular tissue from humans with primary hyperparathyroidism into athymic nude mice creates a unique animal model of this disease. The mice manifest high concentrations of both midregion/C-terminal human parathyroid hormone and biologically active intact human parathyroid hormone relative to either mice with no implants or mice that received normal human parathyroid tissue. Secretion of these substances is maintained in most mice for at least 9 to 13 months after implantation. In addition, animals that have experienced implantation exhibit other characteristics associated with human primary hyperparathyroidism including relative hypercalcemia and increased renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity. We also measured these parameters in a group of nude mice that received transplantation of a similar mass of hyperplastic parathyroid tissue that was obtained from patients with uremic secondary hyperparathyroidism. Although we hypothesized that the level of human parathyroid hormone secretion from these implants would fall over time in response to the normal host environment, hormone levels remained as high as those in recipients of adenomatous heterografts, even after 9 to 13 months. Moreover, similar biologic effect of the excess parathyroid hormone (i.e., relative hypercalcemia, hyperphosphatasemia, and increased 1,25-dihydroxyvitamin D biosynthesis) were detected. These animal models should prove extremely useful in supplementing our understanding of hyperparathyroid disorder in man.
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Ultrasonography and magnetic resonance imaging in Leigh disease. An infant with Leigh disease, who was the younger sister of a similarly affected infant, had been examined before the onset of the disease. Ultrasonography revealed hyperechoic lesions in the putamen and caudate nucleus during the preclinical stage. At onset, these changes extended into the cerebral cortex and medulla. These lesions were also detected by T2-weighted magnetic resonance imaging (MRI) as areas of increased signal intensity. Her brother demonstrated the same ultrasonographic results; cranial computed tomography disclosed low-density areas in the basal ganglia which were detected as hyperechoic lesions by ultrasonography. These findings suggest that ultrasonography is useful in detecting early intracranial lesions in Leigh disease.
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Left ventricular regional wall stress in dilated cardiomyopathy. Left ventriculography with simultaneous pressure micromanometry was performed in 11 normal control subjects and 17 patients with dilated cardiomyopathy (DCM). Left ventricular silhouettes in the right anterior oblique projection were divided into eight areas, and regional wall stress was computed by Janz's method in each area excluding the two most basal areas. Wall stress was higher in DCM patients than in control subjects (p less than 0.01). The percent area changes from end diastole to end systole in each area were lower in DCM patients than in control subjects (mean for six areas, 22 +/- 14% versus 54 +/- 9%, respectively, p less than 0.01), but the coefficient of variation for the percent area changes in the six areas of the left ventricle in DCM patients was greater than that in control subjects (32 +/- 17% versus 15 +/- 4%, respectively, p less than 0.01), indicating regional differences in hypokinesis. There was a significant negative correlation between end-systolic regional wall stress and percent area change (r = -0.60 to -0.86, p less than 0.05) in each area. Thus, excessive regional afterload may play an important role in causing regional hypokinesis in DCM.
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Liver cirrhosis: changes of Doppler waveform of hepatic veins [published erratum appears in Radiology 1991 Aug;100(2):586] The authors compared the Doppler ultrasonographic pattern of hepatic veins (HVs) in a group of 60 patients affected by liver cirrhosis and in 65 healthy subjects comparable for sex and age to (a) detect possible differences in HV waveform in the two groups and (b) investigate the relationship of these differences with the severity of the disease (according to Child-Pugh classification) and the modifications of systemic hemodynamics. The waveform of HVs was arbitrarily classified into three patterns: HV0, a normal waveform; HV1, lower oscillations without the reversed phase; and HV2, completely flat waveform. The resistivity index of the superior mesenteric artery, reflecting the peripheral splanchnic impedance and the hyperdynamic circulation, was also measured in a subgroup of 45 cirrhotic patients. The waveform of HVs in all healthy subjects corresponded to the HV0 pattern. Among cirrhotic patients, HV0 was found in 30 (50%), HV1 in 19 (31.7%), and HV2 in 11 (81.3%). The severity of functional impairment was greatest in the HV2 group and least in the HV0 group. This was significantly correlated with the decrease of the resistivity index in the superior mesenteric artery in the subgroup of 45 patients. Changes in the normal HV waveform could be considered a useful adjunctive tool for the noninvasive evaluation of liver disease. The pathophysiology of these changes in HV blood flow is still unclear. The significant correlation with the severity of the disease and with the decrease of splanchnic resistances indicates that these changes in the HV waveform occur in the presence of marked rearrangements of liver tissue and of hyperdynamic systemic circulation.
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Phase I study of interleukin-2 and interferon alfa-2a as outpatient therapy for patients with advanced malignancy. Twenty-six patients were treated in this phase I study with the combination of interleukin-2 (IL2) administered as a continuous infusion and interferon alfa-2a (IFN alpha-2a) administered intramuscularly to patients in an outpatient setting. The maximum-tolerated dose of both agents given as outpatient therapy was 2 x 10(6) U/m2 days 1 to 5 of IL2 and 9 x 10(6) U/m2 days 1, 3, and 5 of IFN alpha-2a for 4 consecutive weeks. A 2- to 4-week rest period was permitted after each 4 weeks of treatment. Fatigue was the treatment-limiting toxicity, and serious clinical or laboratory abnormalities occurred infrequently during this study. Patients with colon cancer metastatic to the liver tolerated treatment worse than patients with other tumors. Twelve of the 15 patients with renal cell cancer were assessable for response determinations. Of these 12 patients, three exhibited complete tumor regression, three have had partial objective regression, and three patients experienced stabilization of rapidly progressive disease. This therapy appears to be well tolerated in an outpatient treatment setting and shows significant activity against advanced renal cell cancer.
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Control of hypertensive emergencies Although uncommon, hypertensive emergencies require prompt recognition and treatment to reduce very high morbidity and mortality rates. Admission to an intensive care unit for treatment and monitoring is essential for optimal care. A Swan-Ganz catheter is often helpful in management. Intravenous nitroprusside sodium (Nipride, Nitropress) is probably the drug of choice for hypertensive emergencies other than those due to eclampsia or pheochromocytoma.
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Arteriovenous malformation of the tongue. Polyvinyl alcohol particles used to embolize an arteriovenous malformation of the tongue were only temporarily successful. Additional embolization therapy was necessary and was complicated by ischemic ulcers of the tongue. We conclude that embolization therapy can be used, but the efficacy of this therapy in the longer term remains to be determined.
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The management of the painful first metatarsophalangeal joint in the older patient. Arthrodesis or Keller's arthroplasty? We report a prospective randomised trial comparing Keller's arthroplasty and arthrodesis of the first metatarsophalangeal joint for the management of symptomatic hallux valgus and hallux rigidus in the older patient. In 81 patients (110 feet), with a minimum of two years follow-up, both procedures gave a similar degree of patient satisfaction and symptom relief. The incidence of metatarsalgia was also similar. As there were no obvious advantages to arthrodesis, and since six out of 50 arthrodesed toes required revision, we suggest that Keller's arthroplasty is the better operation in these patients.
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The presence of human papillomavirus (HPV) in solitary adult laryngeal papillomas demonstrated by in-situ DNA hybridization with sulphonated probes. Human papilloma virus (HPV) types 6 and 11 have been repeatedly demonstrated in multiple laryngeal papillomas, and there is little doubt that these lesions are caused by HPV. It has been clearly demonstrated in recent reports that the clinical course of solitary adult onset laryngeal papillomas is entirely different from that of multiple papillomas of juvenile as well as of adult onset. We here report the presence of HPV types 6 and 11 in 19 out of 20 solitary papillomas from 16 patients, while HPV types 16 and 18 were totally absent. We conclude that the milder clinical course in such patients is most likely to be due to host factors, rather than to viral factors.
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Ulcerative colitis and colorectal cancer. A population-based study. BACKGROUND. The risk of colorectal cancer is increased among patients with ulcerative colitis. The magnitude of this increase in risk and the effects of the length of follow-up, the extent of disease at diagnosis, and age at diagnosis vary substantially in different studies. METHODS. To provide accurate estimates of the risk of colorectal cancer among patients with ulcerative colitis, we studied a population-based cohort of 3117 patients given a diagnosis of ulcerative colitis from 1922 through 1983 who were followed up through 1984. RESULTS. Ninety-two cases of colorectal cancer occurred in 91 patients. As compared with the expected incidence, the incidence of colorectal cancer in the cohort was increased (standardized incidence ratio [ratio of observed to expected cases] = 5.7; 95 percent confidence interval, 4.6 to 7.0). Less extensive disease at diagnosis was associated with a lower risk; for patients with ulcerative proctitis, the standardized incidence ratio was 1.7 (95 percent confidence interval, 0.8 to 3.2); for those with left-sided colitis, 2.8 (95 percent confidence interval, 1.6 to 4.4); and for those with pancolitis (extensive colitis, or inflammation of the entire colon), 14.8 (95 percent confidence interval, 11.4 to 18.9). Age at diagnosis and the extent of disease at diagnosis were strong and independent risk factors for colorectal cancer. For each increase in age group at diagnosis (less than 15 years, 15 to 29 years, 30 to 39 years, 40 to 49 years, 50 to 59 years, and greater than or equal to 60 years), the relative risk of colorectal cancer, adjusted for the extent of disease at diagnosis, decreased by about half (adjusted standardized incidence ratio = 0.51; 95 percent confidence interval, 0.46 to 0.56). The absolute risk of colorectal cancer 35 years after diagnosis was 30 percent for patients with pancolitis at diagnosis and 40 percent for those given this diagnosis at less than 15 years of age. CONCLUSIONS. Close surveillance and perhaps even prophylactic proctocolectomy should be recommended for patients given a diagnosis of pancolitis, especially those who are less than 15 years of age at diagnosis.
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Efficacy and toxicity of sodium stibogluconate for mucosal leishmaniasis. OBJECTIVE: To determine the efficacy and toxicity of the World Health Organization's (WHO) recommended treatment for mucosal leishmaniasis: antimony, 20 mg/kg body weight per day for 28 days. DESIGN: Open trial with 12-month follow-up. SETTING: Inpatient unit of a regional referral hospital in a developing country. PATIENTS: Twenty-nine consecutive eligible patients with culture-confirmed infection of the mucosa with Leishmania species who were otherwise healthy. Eight patients (28%) had mild to moderate disease (confined to the nasal mucosa). Twenty-one patients (72%) had severe disease (including the oropharynx as well as the nasal mucosa). INTERVENTION: Antimony, 20 mg/kg body weight intravenously every day for 28 days. Patients received antimony in the form of sodium stibogluconate. MEASUREMENTS AND MAIN RESULTS: Initial results of therapy were as follows: 63 of 72 lesions (88%) healed or markedly improved; all lesions were culture-negative for parasites; and 18 of 29 patients (62%) showed complete clinical and parasitologic cure of all lesions. By the 12-month follow-up examinations, however, 37 lesions had recurred, 8 new lesions had appeared, and only 8 patients (30%) showed clinical cure of all lesions. Of the 8 patients with mild to moderate disease, 6 were cured compared with only 2 of the 21 patients with severe disease. Side effects of this treatment regimen included T-wave inversion on electrocardiogram (4 patients), abnormal liver function tests (10 patients), and musculoskeletal pain (24 patients). No side effects occurred during week 1 of therapy. CONCLUSIONS: The only recommended treatment for mucosal leishmaniasis is ineffective in patients with severe disease. The acceptable toxicity of the regimen suggests that longer courses of therapy with antimony, or that trials with other antileishmanial agents alone or combined with antimony be evaluated as initial therapy for this disease.
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The role of antihistamine therapy in vascular headaches. Migraine (vascular) headache is a complex syndrome that involves vascular hyperreactivity. The functions of systemic mediators in migraine are not fully understood. It is unclear which mediators provoke this probably atopic disorder and which represent an attempt to correct an imbalance. However, it has been demonstrated fairly conclusively that increased histamine levels correlate with migraine attacks in susceptible persons. Recent studies showing that histamine seems to have many different receptors and to adopt different conformations for different receptors may serve as a useful guide to future scientific investigation. Further impetus may come from ongoing studies of H3 histamine receptors, which indicate that H3 agonists offer promise as prophylactic agents for people who suffer from vascular headaches.
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Addition of clonidine enhances postoperative analgesia from epidural morphine: a double-blind study. This study was undertaken to evaluate the analgesic effect of the combination of epidural morphine and clonidine versus epidural morphine alone in patients with postoperative pain. A randomized double-blind design was used, and 91 patients scheduled for post-operative pain relief by epidural morphine were studied. Patients received either a continuous epidural infusion of morphine and clonidine (group 1; n = 45) or morphine alone (group 2; n = 46) over the 72 h after major abdominal surgery. In the first 24 h, the dose of morphine was 6 mg per 24 h; during the second 24 h, it was decreased to 4 mg per 24 h; and in the final 24 h, it was decreased to 2 mg per 24 h in both groups. Group 1 patients received clonidine (450 micrograms) during each 24-h period. Additional epidural bolus injections of 2 mg morphine and intravenous meperidine were given on demand. The pain score, blood pressure, heart rate, respiratory rate, and relative forced vital capacity were measured at fixed times during the first 72 h after operation. Total consumption of analgesics and side effects were recorded. Although the total consumption of analgesics was significantly higher in group 2 (P less than 0.05), pain scores were lower in group 1 than group 2 during the entire observation period (P less than 0.05). Epidural clonidine produced a significant decrease (P less than 0.05) in heart rate and blood pressure, whereas the respiratory rate was not affected. Due to the better pain relief in group 1, the forced vital capacity was increased (P less than 0.05).
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Ocular pathologic features of arteriohepatic dysplasia (Alagille's syndrome). Arteriohepatic dysplasia (Alagille's syndrome), an autosomal dominant condition involving jaundice caused by a developmental scarcity of intrahepatic bile ducts, has characteristic cardiovascular, skeletal, facial, and ocular features that distinguish it from extrahepatic biliary atresia and an array of other neonatal intrahepatic cholestatic disorders. Two children who died of this syndrome had prominent Schwalbe's rings with attached iris strands characteristic of Axenfeld's syndrome. Additional histologic findings of iris atrophy and stromal nodules, however, made the designation Axenfeld-Reiger's syndrome more appropriate. Pigmentary retinopathy, degeneration of Bruch's membrane, and prominent lipofuscin deposition in the ciliary muscle noted in one of the patients were not regarded as primary changes of Alagille's syndrome, but were believed to be secondary to acquired deficiency of the fat-soluble vitamins A and E. Early recognition of the ocular changes in arteriohepatic dysplasia is helpful in establishing the proper diagnosis to avoid unnecessary abdominal surgery and institute vitamin therapy.
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Ability of the c-mos product to associate with and phosphorylate tubulin. The mos proto-oncogene product, pp39mos, is a protein kinase and has been equated with cytostatic factor (CSF), an activity in unfertilized eggs that is thought to be responsible for the arrest of meiosis at metaphase II. The biochemical properties and potential substrates of pp39mos were examined in unfertilized eggs and in transformed cells in order to study how the protein functions both as CSF and in transformation. The pp39mos protein associated with polymers under conditions that favor tubulin oligomerization and was present in an approximately 500-kilodalton "core" complex under conditions that favor depolymerization. beta-Tubulin was preferentially coprecipitated in pp39mos immunoprecipitates and was the major phosphorylated product in a pp39mos-dependent immune complex kinase assay. Immunofluorescence analysis of NIH 3T3 cells transformed with Xenopus c-mos showed that pp39mos colocalizes with tubulin in the spindle during metaphase and in the midbody and asters during telophase. Disruption of microtubules with nocodazole affected tubulin and pp39mos organization in the same way. It therefore appears that pp39mos is a tubulin-associated protein kinase and may thus participate in the modification of microtubules and contribute to the formation of the spindle. This activity expressed during interphase in somatic cells may be responsible for the transforming activity of pp39mos.
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Long-term survival patients with acute and severe renal failure due to multiple myeloma. We selected 37 cases, followed-up for more than 36 months or until death, from a series of 45 patients affected by acute renal failure due to multiple myeloma in order to identify the parameters that could allow the outcome to be predicted. The patients were allocated to group 1, consisting of 27 patients who died within one year and to group 2, consisting of 10 patients who survived for more than 36 months. Renal failure was severe enough to require dialysis in 28 patients, 16 of whom were oliguric. Renal biopsy was performed in 23 cases, whereas light chain isoelectric point and serum beta 2-microglobulin levels were evaluated in each patient. All the patients underwent chemotherapy, which was associated with plasma exchange in 16 patients. Statistical analysis of the potential prognostic factors in the 2 groups showed that the incidence of hypercalcemia, infection, irreversible renal failure and severe tubulo-interstitial damage was significantly higher in group 1. Sex, tumor load, severity of renal failure and light chain isoelectric point had no prognostic significance. Finally, the number of patients treated by plasma exchange was significantly higher in group 2. Our results underline the prognostic role of both hypercalcemia and infection and justify aggressive treatment consisting of chemotherapy, plasma exchange and dialysis, even in cases of severe renal failure and high tumor load.
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Visual disturbance in patients with melanocytoma of the optic disk. Visual disturbance in 11 patients with melanocytoma of the optic disk was analyzed. Goldmann visual field examination showed enlargement of Mariotte's blind spot in 7 of 10 patients (70%) and visual field defect or depression in 7 patients (70%). In 6 of the 7 patients with visual field defect of depression (86%), the portion of visual field damage corresponded with the location of the tumor and retinal nerve fiber bundle defect. In 1 patient, sudden loss of visual acuity occurred, presumably due to anterior ischemic optic neuropathy induced by melanocytoma.
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National Institute of Mental Health longitudinal study of chronic schizophrenia. Prognosis and predictors of outcome [published erratum appears in Arch Gen Psychiatry 1991 Jul;48(7):642] We performed a longitudinal study of chronic schizophrenic patients who were hospitalized for research purposes at the National Institute of Mental Health (NIMH) Intramural Program in the 1970s and early 1980s. We assessed present course, outcome and predictor data from the initial cohort of 58 young chronic schizophrenic patients who were followed up for 2 to 12 years following their NIMH index hospitalization. At follow-up, the sample showed substantial functional impairment and levels of symptoms with only about 20% of the sample demonstrating a good outcome. In addition, strong intercorrelation was noted among the symptom and functioning indexes at follow-up. Moreover, neuropsychologic tests of frontal cortical functioning were significantly correlated with outcome levels of negative symptoms and social functioning but not with levels of positive symptoms. During the period from the index hospitalization to the follow-up assessment, 78% of the sample suffered a relapse, 38% attempted suicide and 24% had episodes of major affective illness. Furthermore, levels of positive and negative symptoms ascertained when patients received optimal neuroleptic treatment during the index hospitalization significantly predicted outcome levels of symptoms and functioning and time spent hospitalized during the follow-up period. In contrast, levels of index positive and negative symptoms ascertained during the drug-free state did not predict outcome symptoms or functioning. These data suggest that treatment response is a critical predictor variable. We examined the implication of these data for the course of illness in schizophrenics.
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Small cell carcinoma of the pancreas and biliary tract. Four cases of anaplastic carcinoma of the pancreas or biliary tract were studied clinicopathologically and immunohistochemically. All four cases were intermediate cell type and contained a minimum amount of microscopic foci of differentiated glandular adenocarcinoma. Argyrophilic tumor cells were not seen in any of the four tumors. Immunohistochemically, no tumor was positive for hormonal products, but all tumors were positive for epithelial markers. These findings suggest that the anaplastic carcinoma are not derived from argyrophilic cells, but rather from adenocarcinomas which have the potential for anaplastic metaplasia. The long-term survival of one patient emphasized the importance of chemotherapy in the treatment of small cell carcinoma of the pancreas and biliary tract.
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Down's syndrome and acute leukemia in children: an analysis of phenotype by use of monoclonal antibodies and electron microscopic platelet peroxidase reaction The clinical, hematologic, and immunophenotypic features in 20 patients with Down's syndrome (DS) and acute leukemia were analyzed. Of the 20 patients, all 14 patients who were 3 years old and less were diagnosed as having acute megakaryoblastic leukemia (AMKL) by use of platelet-specific monoclonal antibodies and platelet peroxidase (PPO) reaction in electron microscopy. They were characterized by the presence of bone marrow fibrosis, having a history of myelodysplastic syndrome (MDS) and a poor response to chemotherapy. Only one patient has remained in continuous complete remission for more than 1 year. Acute leukemia in six patients who were older than 4 years was classified as common acute lymphoblastic leukemia antigen (CALLA)-positive acute lymphoblastic leukemia (ALL). In one of six patients classified as ALL, the leukemic blasts simultaneously expressed myeloid-associated surface antigens. All six patients achieved a complete remission and have remained in continuous complete remission and have remained in continuous complete remission from 10 to 52 months from the initial diagnosis. Although it has been suggested that the distribution of types of acute leukemia in patients with DS is similar to that in normal children, the present study shows that the distribution of acute leukemia types is quite different from that in patients without Down's syndrome.
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Hormonal dependency of cerebral meningiomas. Part 2: In vitro effect of steroids, bromocriptine, and epidermal growth factor on growth of meningiomas. Cell culture and biochemical techniques have been employed to examine the effects of steroids, bromocriptine, and epidermal growth factor (EGF) on the growth and proliferative potential of meningiomas. In cell culture, the growth of meningiomas was not altered by progestogens, antiprogestogens, or 17beta-estradiol. The progestogen, norethisterone, had no effect on the uptake by meningiomas cell cultures of 3H-thymidine. Furthermore, cytosolic deoxyribonucleic acid (DNA) polymerase activity of meningiomas did not correlate with the progesterone receptor status of the same tumors. In contrast, the androgen antagonists, cyproterone acetate and 11-alpha-hydroxyprogesterone, and the dopamine agonist, bromocriptine, all inhibited the in vitro growth of meningioma cells. The growth of meningioma cell cultures was stimulated by EGF, and there was a positive correlation between the EGF content and DNA polymerase activity in meningioma cytosols. These results demonstrate that female sex steroids do not influence growth of meningiomas in vitro, whereas antiandrogens and bromocriptine have an antiproliferative effect. Consequently, bromocriptine and antiandrogens may have a role in the medical treatment of meningiomas. In addition, these results suggest that EGF may be involved in the genesis and/or progression of meningiomas.
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Course of diabetic retinopathy following cataract surgery Five patients with mild to moderate retinopathy to both eyes underwent complication-free cataract surgery in one eye. Within three months of surgery deterioration of the retinopathy was observed in the operated eye only. In four patients there was an increase of intraretinal haemorrhages and hard exudates, accompanied by clinically significant macular oedema manifested as retinal thickening and extensive fluorescein leakage from both the macular and the peripapillary capillary networks. Of these four patients one also developed retinal ischaemia, evident ophthalmoscopically by flame-shaped haemorrhages and cotton-wool spots and angiographically by areas of capillary non-perfusion. The fifth patient showed proliferation of new blood vessels and vitreous haemorrhage. Diabetic patients scheduled for cataract surgery should undergo a thorough preoperative evaluation of any existing retinopathy. Postoperatively they should be followed up at close intervals so that any progression of retinopathy can be promptly detected and considered for laser treatment.
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Tympano-cartilago-stapediopexy: a method to improve hearing in open technique tympanoplasty. Canal wall-down technique tympanoplasty was indicated in about 41 per cent of our cases with chronic suppurative otitis media. In this series done during the last four years, of 576 tympanoplasties, 240 cases needed type III tympanoplasty. In 145 cases, myringostapediopexy was carried out using temporalis fascia grafting over the head of the stapes. Tympano-cartilago-stapediopexy was performed in the other 95 cases by using tragal cartilage and perichondrium over the stapes. A comparison between the results of both methods of grafting is discussed. Improvement in hearing was achieved after tympano-cartilago-stapediopexy. This method proved to be suitable for those cases which need open technique tympanoplasty.
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Relevance of focal cerebral ischemia models. Experience with fibrinolytic agents. Despite the limitations of individual ischemia models, experience with fibrinolytic agents suggests that 1) early intervention with rt-PA may result in rapid thrombolysis, functional recovery, and decreased mortality in small animal stroke thromboembolism models, 2) rt-PA has no general effect on clinical recovery following MCA occlusion and reperfusion in the nonhuman primate at dose rates capable of producing very high circulating rt-PA levels, while u-PA has an apparently salutary effect, and 3) intravenous infusion of rt-PA or u-PA early after ischemia/infarction in several model systems is not associated with significant intracerebral hemorrhage. The true clinical relevance of these general impressions must await the completion of human studies and studies in well-conceived models designed to define the vascular consequences to be expected from reperfusion achievable with thrombolytic agents.
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An outpatient anticoagulation protocol managed by a vascular nurse-clinician. Lifetime anticoagulation has become a therapeutic option for surgical patients with hypercoagulable states or prosthetic arterial bypass grafts. However, physicians may not achieve optimal anticoagulation or may attempt to limit the length of the therapy period because of the perceived morbidity from hemorrhagic complications of Coumadin therapy. A protocol for anticoagulant therapy monitored and regulated by a vascular nurse-clinician was reviewed. Coumadin was prescribed for 1,891 patient-months to 93 patients to maintain their prothrombin time 1.5 to 2 times control (range: 18 to 24 seconds). The mean (+/- SD) prothrombin time for the study population was 19.8 +/- 1.8 seconds. During follow-up, 472 (14%) of 3,479 prothrombin times measured were below the therapeutic range (n = 232) or prolonged (n = 240), prompting an adjustment in the Coumadin dose in 82 (88%) patients. Four patients developed recurrent vascular graft thrombosis while receiving anticoagulation. There were 6 major and 11 minor hemorrhagic complications. Patients with a chronic risk for arterial or venous thrombosis can have out-patient anticoagulant therapy administered at optimal intensity and regulated safely with a low incidence of hemorrhagic and thrombotic events.
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New insights into the causes of cancer. Recent advances in molecular biologic analysis have led to major new insights concerning the genetic mechanisms underlying the development of cancer. This article examines the current state of our understanding of the genetic basis underlying the possible mechanisms of carcinogenesis and metastasis. The nature of the genetic lesions found in some cancer-causing genes, cancer-inhibiting genes, growth factor genes, and metastasis genes is discussed, as is the impact that these may have on clinical oncology.
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Orthostatic hypotension following right ventricular myocardial infarction corrected with mineralocorticoid therapy. Severe hypotension while standing became a problem in a patient after discharge from the hospital following right ventricular myocardial infarction. Hemodynamic studies showed that right ventricular systolic function did not maintain adequate left ventricular preload and that the patient did not compensate for cardiac dysfunction by increasing blood volume. Volume expansion by mineralocorticoid therapy corrected the orthostatic hypotension and ameliorated symptoms. Hypotension eventually resolved and therapy was stopped four months after the myocardial infarction.
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Parental age in sporadic hereditary retinoblastoma. Of 104 children with sporadic hereditary retinoblastoma born between 1945 and 1970, we studied the age of their parents at the birth and compared this age with the mean age of parents at the birth of their children during the same period in The Netherlands. The mean age of fathers at the birth of their children with sporadic hereditary retinoblastoma (33.7 years) was significantly higher than the mean age of fathers at the birth of their children in the general population (32.5 years) (P less than .05, one sided). Similarly, the mean age of mothers at the birth of their children with sporadic hereditary retinoblastoma (31.2 years) was significantly higher than the mean age of mothers at the birth of their children in the general population (29.5 years) (P less than .05, one sided). We further analyzed this parental age factor by measuring the relative risk of age groups and comparing the incidence of sporadic hereditary retinoblastoma in the various parental age groups with the incidence of sporadic hereditary retinoblastoma in the total population. Mothers 35 years of age or older had a relative risk of 1.7 to have a child with sporadic hereditary retinoblastoma compared with mothers in the population in general (P = .006, one sided). Similarly, fathers 50 years of age or older had a relative risk of 5.0 to have a child with sporadic hereditary retinoblastoma compared with fathers in the population in general (P = .04, one sided). No parental age effect was found in children with nonhereditary retinoblastoma. We conclude that a high paternal and a high maternal age are significant risk factors for sporadic hereditary retinoblastoma.
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Genetics and biology of human ovarian teratomas. I. Cytogenetic analysis and mechanism of origin. One hundred and two benign, mature ovarian teratomas and two immature, malignant teratomas were karyotyped and scored for centromeric heteromorphisms as part of an ongoing project to determine the chromosomal karyotype and the genetic origin of ovarian teratomas and to assess their utility for gene-centromere mapping. Karyotypic analysis of the benign cases revealed 95 46,XX teratomas and 7 chromosomally abnormal teratomas (47,XXX, 47,XX,+8 [two cases], 47,XX,+15, 48,XX,+7,+12 91,XXXX,-13 [mosaic], 47,XX,-15,+21,+mar). Our study reports on the first cases of tetraploidy and structural rearrangement in benign ovarian teratomas. The two immature cases had modal chromosome numbers of 78 and 49. Centromeric heteromorphisms that were heterozygous in the host were homozygous in 65.2% (n = 58) of the benign teratomas and heterozygous in the remaining 34.8% (n = 31). Chromosome 13 heteromorphisms were the most informative, with 72.7% heterozygosity in hosts. The cytogenetic data indicate that 65% of teratomas are derived from a single germ cell after meiosis I and failure of meiosis II (type II) or endoreduplication of a mature ovum (type III); 35% arise by failure of meiosis I (type I) or mitotic division of premeiotic germ cells (type IV).
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Auditory brain stem implant: effect of tumor size and preoperative hearing level on function. The auditory brain stem implant is an investigational device designed to provide hearing sensations to patients without functioning auditory nerves. We analyzed results from 17 implants in 15 patients to determine if tumor size or preoperative hearing level might be related to proper device function. We found no significant correlation between preoperative hearing level or tumor size and device function. We also found no significant correlation between preoperative hearing level and tumor size in these 15 patients.
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Adenocarcinoma of the appendiceal stump. We have reported the case of a 58-year-old woman with nonspecific abdominal complaints in whom barium enema and subsequent colonoscopy showed a 3 cm lobulated adenocarcinoma within a villous adenoma arising from the appendiceal stump. Because such appendiceal malignancies have no specific clinical signs, symptoms, or radiologic features, preoperative diagnosis is extremely difficult, and colonoscopy may be required to clarify radiologically demonstrated irregularities.
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Misplaced caval filter and subsequent pericardial tamponade. Use of the Greenfield filter for partial caval interruption is generally accepted as the most reliable mechanical method of pulmonary embolus prophylaxis. However, there have been reports of a variety of (usually nonfatal) complications. We report here the near-fatal complication of acute pericardial tamponade after misplacement of a Greenfield filter. Because of the filter's unusual location, retrieval required cardiopulmonary bypass, profound hyperthermia, and circulatory arrest.
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Ataxia in myxoedema: a neurophysiological reassessment. In a long-standing case of myxoedema with ataxia and dysarthria, neurophysiological investigations were carried out to assess how much of the ataxic dysbasic syndrome depended on the slowness of mechanical contraction and how much resulted from primary cerebellar involvement. It was observed that the Achilles reflexogram showed a marked prolongation of contraction and relaxation time and that in both quadriceps and triceps surae mechanical percussion induced a marked myxoedema and prolonged relaxation time. The EMG of these muscles during voluntary contraction and stopping reaction detected an excessive recruitment of the antagonistic muscles, starting without any abnormal delay, a finding at variance with a typical cerebellar pattern. Post-urographic analysis gave a pattern of oscillations still within the normal range. These findings suggest that the gait alterations of our patient depended on the increase in muscle contraction time and the consequent excessive recruitment of the antagonists.
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T-cell subsets with a naive phenotype are selectively decreased in the peripheral blood of patients with mycosis fungoides. Peripheral blood lymphocytes of 33 patients with histopathologic confirmation of mycosis fungoides and 27 healthy controls matched for age and sex were analyzed with a panel of monoclonal antibodies using both single and dual color immunofluorescence. Patients with mycosis fungoides had a significant reduction in the percentage of circulating T cells with a naive phenotype (i.e., CD4+2H4+ and CD4+Leu8+), as well as a significant reduction in the absolute numbers of circulating lymphocytes with the phenotype CD8+Leu8+ compared to the control cohort. The reduction in circulating naive T cells was found to occur irrespective of stage of disease, duration of disease, or mode of treatment. The depletion of circulating naive T cells may reflect increased conversion to memory T cells in the peripheral blood or skin.
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Improved results with combined donor-specific transfusion (DST) and sequential therapy protocol. A combined DST-sequential CyA therapy protocol has been described that results in optimum graft survival for 1- and 2-haplotype mismatched living related donor-recipient combinations. In addition to the excellent graft survival obtained through 4 years, lower prednisone and CyA dosage levels are achieved with significantly decreased infection rates during the posttransplant period.
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Fallopian tube cancer. The Roswell Park experience. Sixty-four patients with primary fallopian tube cancer treated at Roswell Park Memorial Institute from 1964 to 1987 underwent retrospective clinicopathologic review. In 40 patients fallopian tube cancer was the only primary, but in 24 patients primary fallopian tube cancer was part of a multifocal upper genital tract malignancy. Of the 40 patients with unifocal fallopian disease, the median survival was 28 months. Only 15% of patients were alive and disease free with follow-up ranging from 22 to 141 months (median, 90.5 months). Survival was not associated with stage of disease, tumor histology, grade, or depth of invasion in this series. Fourteen patients who received cisplatin-based chemotherapy were evaluable for response. Three patients (21%) responded; two complete and one partial. Twelve patients without clinical evidence of disease underwent second-look procedures, ten laparotomy and two laparoscopy. Four of ten second-look laparotomies were negative. Secondary debulking was done in three of four patients with gross disease, one of which had a negative third-look laparotomy. Negative laparotomy, second-look or third-look, was associated with improved survival (P = 0.016). One of the two laparoscopies was negative, but the patient recurred. In the remaining 24 patients cancer of the fallopian tube was part of a multifocal upper genital tract malignancy. In 12 patients tubal disease was invasive, and in 12, it was in situ. Separate primaries occurred in the ovaries (n = 20); uterus (n = 7); and cervix (n = 2). This represents 1.3% of ovarian malignancies treated at Roswell Park Memorial Institute during the study period. Fallopian tube cancer seems as virulent as ovarian cancer with few long-term survivors. It is frequently associated with other sites of upper genital tract malignancy. Second-look laparotomy is an important predictor of survival. Second-look laparoscopy may be useful if positive.
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Initial therapy of patients with Wilson's disease with tetrathiomolybdate. Patients with Wilson's disease who present with acute neurological symptoms often become clinically worse when initially treated with penicillamine. Other available anticopper drug therapies do not appear to offer a solution to this treatment problem. We are developing and evaluating a new drug, ammonium tetrathiomolybdate for this purpose. Theoretically, tetrathiomolybdate has optimal properties, including an immediate blockade of copper absorption and the property of forming complexes with copper in the blood, rendering the copper nontoxic. In this article, we present results from six patients treated with tetrathiomolybdate for up to 8 weeks as initial therapy. None of the five patients who had presented with acute neurological symptoms worsened. Also presented are methods of assay, preliminary stability studies, and methods of evaluating therapeutic end points with respect to copper metabolism.
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Interferon-alpha receptor expression and regulation in chronic hepatitis B virus infection. Interferon-alpha elicits antiviral and immunoregulatory activities by binding to specific receptors on the cell surface. In this study, binding characteristics of interferon-alpha to peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection were studied using radioiodinated recombinant interferon-alpha 2b to determine interferon-alpha receptor numbers and dissociation constants. A single class of interferon-alpha receptor was demonstrated on peripheral blood mononuclear cells and mononuclear subsets. Peripheral blood mononuclear cells from patients with chronic hepatitis B virus infection (n = 20) and controls (n = 16) expressed a similar number of interferon-alpha receptors (484 +/- 175 vs. 511 +/- 168 sites/cell respectively, p = NS) with a similar dissociation constant (dissociation constant approximately 0.2 to 0.7 nmol/L). Expression of interferon-alpha receptors was similar in monocyte-enriched and lymphocyte-enriched fractions in both groups. Similar changes were observed in patients receiving alpha-interferon therapy. There was no correlation between interferon-alpha receptors expression and serum transaminase, serum HBsAg, serum HBV DNA, liver histological findings or the response to interferon-alpha therapy. After incubation of lymphocytes in vitro with interferon-alpha 2b (10 to 1,000 U/ml), interferon-alpha receptors number dropped by 42% to 80%, but this was associated with an increase in binding affinity (dissociation constant approximately 0.05 to 0.15 nmol/L) in both patients and controls. There was significant delay in the initial phase of receptor recovery in the patients with chronic hepatitis B virus infection compared with normal controls (days 1 and 2, p less than 0.05).
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Cystic rheumatoid arthritis: description of a nonerosive form. In a study of patients with rheumatoid arthritis (RA), 9% (n = 70) were found to have a cystic form. At radiologic examination of these patients with cystic RA, the first abnormality seen consisted of periarticular intraosseous cysts without erosions. The cysts were distributed symmetrically, most often located at the proximal side of the joints and predominantly around the proximal interphalangeal, metacarpophalangeal, and wrist joints of the hands and the first interphalangeal and metatarsophalangeal joints of the feet. Computed tomographic scans showed the peripheral intraosseous location of the cysts. Magnetic resonance images showed that the cysts may contain fluid, inflamed synovia, or both. Cysts can be an important feature in the diagnosis of RA and a supplement to the criteria of the American Rheumatism Association. Osteoporosis, joint-space narrowing, and joint destruction occurred less frequently in patients with cystic RA than in patients with classic RA. Of the patients with cystic RA, 54% were male, and 50% were seronegative. This study is a supplement to and an enlargement on earlier descriptions of cyst predominance in RA.
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Amputation or limb-lengthening for partial or total absence of the fibula. Thirty-two patients who had ablation of the foot by the Syme or Boyd technique for partial or total absence of the fibula, with subsequent fitting of a prosthesis, were compared with eleven patients who had lengthening of the lower limb by the Wagner method, to assess the long-term results of each procedure. The final results were evaluated on the basis of pain, limp, limb-length discrepancy, level of physical activity, and satisfaction of the patient. Of the thirty-two patients who had an amputation, twenty-eight (88 per cent) had a satisfactory result, compared with only six (55 per cent) of the eleven patients who had limb-lengthening. The amount of inequality between the lower limbs was classified as follows: Group I--the foot of the shorter extremity was at the distal third of the contralateral, normal limb, and the percentage of shortening was 15 per cent or less; Group II--the foot of the shorter extremity was at the level of the middle third of the contralateral, normal limb, and the percentage of shortening was between 16 and 25 per cent; and Group III--the foot of the shorter extremity was at the level of the proximal third of the contralateral, normal limb, and the percentage of shortening was greater than 26 per cent. Lengthening was best suited for patients in Group I who had stable hips, knees, and ankles and a plantigrade foot. Patients in Groups II and III were best served by ablation of the foot and fitting of a prosthesis.
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Use of single internal mammary artery grafts in older patients. The indications for use of the internal mammary artery as a coronary bypass conduit in older patients are not clearly established. Between January 1985 and December 1988, 786 patients received single internal mammary artery grafts alone (717) or in conjunction with other procedures (69). Of these patients, 341 were 65 years of age or older (mean, 69.3 years). This group was compared with those patients less than 65 years of age (mean, 56.2 years). There were no significant differences between the two groups in the incidence of diabetes mellitus; the number of distal coronary anastomoses; left ventricular wall motion score; the frequency of isolated bypass procedures, reoperations, or emergent operations; or the durations of aortic clamping and cardiopulmonary bypass. The older group contained more women (34.9% versus 20.7%) and more patients with left main coronary artery disease (15.5% versus 9.4%) (p less than 0.01). No significant differences in the frequency of reoperation for hemorrhage, perioperative infarction, neurological deficits, requirements for intra-aortic balloon pumping, sternal wound infections, necessity for prolonged ventilatory support, or 30-day mortality (2.7% versus 3.2%) were observed. The length of postoperative hospitalization was greater in the older group (11.8 versus 10.2 days) (p = 0.02). Blinded histological examination of biopsies from 61 internal mammary artery grafts (34 patients less than 65 years, 27 patients greater than or equal to 65 years) showed no significant differences in luminal area or wall thickness. No significant degenerative changes were observed in either group. We conclude that the use of the internal mammary artery for bypass grafting in older patients is safe and may provide long-term benefit.
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Differences in expression of cystic fibrosis in blacks and whites. The recent identification of the cystic fibrosis (CF) gene confirms that genetic heterogeneity occurs in CF. A three-base-pair deletion in exon 10 resulting in a loss of the phenylalanine residue at amino acid position 508 of the gene product, termed the CF conductance regulator protein, accounts for 70% of cases of CF in white subjects. However, this gene defect occurs in only 37% of affected blacks. Analysis of CF genes from American blacks has revealed a number of mutations, most of which are unique to that population. We therefore searched for potential differences in expression of CF between 24 black and 48 white patients with CF matched for birth date and gender. Black patients more frequently presented with only respiratory symptoms (38% vs 10%). Black patients had fewer hospitalizations for pulmonary exacerbations (2 vs 6.9), a better mean forced vital capacity (77% vs 62% of predicted), and higher chest roentgenogram scores (18.2 vs 14.4) than white patients. Complication rates were similar except for a higher incidence of hyponatremic dehydration (21% vs 2%) and peptic ulcer disease (13% vs 0%) in blacks. Survival time appeared to be longer in blacks, but the difference was not statistically significant. We conclude that phenotypic differences exist between black and white patients with CF, which may be due to the genetic heterogeneity between these two populations.
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Binding to human jejunum of serum IgA antibody from children with coeliac disease. Jejunal histology and the presence of serum IgA antibodies (JAB) binding to human jejunum in vitro were studied in 139 children with severe malabsorptive symptoms. Among 33 children with confirmed coeliac disease (ESPGAN criteria), 13 (93%) of 14 sampled before starting on a gluten-free diet had JAB, none of 21 sampled had JAB while on a gluten-free diet of long duration, and 90% of 30 sampled during gluten challenge had JAB. 53 children had severe jejunal villous atrophy (probable coeliac disease): 71% of those younger than 2 years and 94% of those aged 2-18 years had JAB during gluten intake. JAB could not be detected in 53 disease control patients (normal jejunal histology) and in 3 coeliac disease patients with selective IgA deficiency. Simultaneous determination of antigliadin (AGA) and antiendomysium (EMA) levels, and gliadin and tissue absorption studies, showed that JAB and AGA are different, whereas JAB and EMA are probably identical. IgA JAB could be the target-organ-related autoantibodies in coeliac disease.
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Fluosol: an oxygen-delivery fluid for use in percutaneous transluminal coronary angioplasty. Fluosol (20% intravascular perfluorochemical emulsion) is an oxygen-carrying emulsion used to deliver oxygen to ischemic myocardium during percutaneous transluminal coronary angioplasty (PTCA). Fluosol is composed of two perfluorochemicals, perfluorodecalin and perfluorotripropylamine. It has a high capacity for oxygen solubility, a low viscosity, and a small particle size. Following administration, the perfluorochemicals in fluosol are not metabolized. Rather, most are expired as gaseous particles through the lungs; the remainder are taken up by the organs of the reticuloendothelial system and later expired. When administered during balloon inflation in PTCA, fluosol preserves ventricular wall motion and global left ventricular ejection fraction. In addition, it minimizes ST segment changes and preserves cardiac output. Fluosol may be especially useful in patients who have poor contractile reserve, multivessel disease, or serious underlying illness. Other uses under investigation include limitation of myocardial infarct size and chemosensitization or radiosensitization of malignant tumors. Adverse effects secondary to the use of fluosol include ventricular arrhythmias, pruritus, bradycardia, chest pain, dyspnea, and increased respiratory rate. Fluosol must be thawed, admixed, warmed to body temperature, and oxygenated prior to intracoronary administration. The usual administration rate is 60 mL/min during each balloon inflation.
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Kinetic abnormalities of the red blood cell sodium-proton exchange in hypertensive patients. The present study was designed to examine the kinetics of Na(+)-H+ exchange in red blood cells of normotensive and hypertensive subjects and its relation to the previously reported abnormalities in Na(+)-Li+ exchange. The Na(+)-H+ antiporter activation kinetics were studied by varying cell pH and measuring net Na+ influx (mmol/l cell x hr = units) driven by an outward H+ gradient. The Na(+)-Li+ exchange was determined at pH 7.4 as sodium-stimulated Li+ efflux. Untreated hypertensive patients (n = 30) had a higher maximal rate of Na(+)-Li+ exchange (0.43 +/- 0.05 versus 0.26 +/- 0.02 units, p less than 0.0003), a higher maximal rate of Na(+)-H+ exchange (62.3 +/- 6.2 versus 47 +/- 4 units; p less than 0.02), but a similar affinity for cell pH compared with normotensive subjects (n = 46). The cell pH activation of the Na(+)-H+ antiporter exhibited a lower Hill coefficient than that of normotensive subjects (1.61 +/- 0.12 versus 2.56 +/- 0.14; p less than 0.0001). This index of occupancy of internal H+ regulatory sites was found reduced in most of the hypertensive patients (73%) whether their hypertension was untreated or treated. Hypertensive patients with Na(+)-Li+ exchange above 0.35 units (0.68 +/- 0.057 units, n = 16) did not exhibit elevated maximal rates of Na(+)-H+ exchange (57.3 +/- 10 units, NS) in comparison with those with Na(+)-Li+ exchange below 0.35 units (66.4 +/- 7.6 units, n = 26), but both groups exhibited reduced Hill coefficients. Hypertensive patients with enhanced Na(+)-H+ exchange activity (more than 90 units) had normal maximal rates of Na(+)-Li+ exchange.
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Genetic analysis as an aid in diagnosis for patients with midline carcinomas of uncertain histologies The tumors of nine patients with carcinomas of uncertain histogenesis (eight with poorly differentiated carcinomas involving primarily midline structures and one with a diagnosis of seminoma and atypical clinical features) were studied by cytogenetic and Southern blot analyses. Four of the eight patients with poorly differentiated carcinomas had abnormalities of chromosome 12 consistent with a diagnosis of germ cell tumor. These abnormalities comprised an i(12p) in two patients and a del(12q) in a third patient detected by cytogenetic analysis and multiple copies of 12p detected by Southern blot analysis in a fourth patient. Three of these four patients with a diagnosis of germ cell tumor established by genetic analysis achieved a complete response to cisplatin-based chemotherapy. The tumor biopsy of one patient showed a t(11;22) (q24;q12), and this patient had chemotherapy directed to neuroepithelioma. Cytogenetic analysis was unsuccessful for the tumors of three patients; these tumors did not have multiple copies of 12p detected by Southern blot analysis. These patients did not respond to cisplatin-based chemotherapy. One patient with a diagnosis of extragonadal seminoma failed to respond to cisplatin-based chemotherapy and had a second tumor biopsy performed that demonstrated a t(8;14) (q24;q32). This patient's diagnosis was changed to a non-Hodgkin's lymphoma. Thus, genetic analysis provided a diagnosis in six of nine patients. Cytogenetic and molecular analyses are useful clinical tools for the determination of histogenesis in some patients with poorly differentiated carcinomas of uncertain histology.
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Ultrasound demonstration of a superior mesenteric artery aneurysm in a patient with Ehlers-Danlos syndrome. A large aneurysm of the superior mesenteric artery was the presumed cause of abdominal pain in an 11-year-old girl with Ehlers-Danlos syndrome. This aneurysm was readily identified by ultrasonography, suggesting that this method could be the diagnostic technique of choice in this disorder.
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Graves orbitopathy: correlation of CT and clinical findings. The clinical and high-resolution computed tomographic (CT) findings in 71 patients (142 orbits) with Graves orbitopathy and 20 healthy patients (40 orbits) were retrospectively reviewed. The orbits with orbitopathy were subgrouped at clinical examination into those with (n = 18) and those without (n = 124) optic neuropathy. Mean extraocular muscle diameters and the calculated muscle diameter index were significantly increased in all orbits with ophthalmopathy, particularly in those with optic neuropathy. Graves orbitopathy affected the superior muscle group (63.4%) more than the medial (61.3%) or inferior (57%) recti. The most common pattern of muscle involvement involved all five measured extraocular muscles. Solitary muscle involvement most frequently involved the superior muscle group (6.3%). Significant enlargements of the retrobulbar optic nerve sheath and superior ophthalmic vein were noted only in orbits with optic neuropathy. Anterior displacement of the lacrimal gland at CT correlated with clinical palpability and occurred more frequently in patients with optic neuropathy. Severe apical crowding was the most sensitive indication of optic neuropathy at CT.
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Introduction: nutritional aspects of palm oil. The production, composition, and food uses of palm oil are outlined in this introduction to a detailed appraisal of the nutritional and health implications of the use of palm oil in the food supply. The putative role of dietary fats and oils in general, and of palm oil in particular, in the etiology of coronary heart disease and cancer is critically assessed. It is concluded that the evidence available is difficult to interpret unambiguously. Some evidence to suggest that the minor components of palm oil might have useful biological effects is also discussed.
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CD8+ T cell homing to the pancreas in the nonobese diabetic mouse is CD4+ T cell-dependent. The adoptive transfer of type I diabetes in nonobese diabetic mice requires the contribution of both CD4+ and CD8+ T cells. To further elucidate the cellular pathway(s) of beta-cell destruction and the responsibility of each subset, high doses of committed T cells from diabetic mice purified to single subsets, were injected into syngeneic nonobese diabetic neonates. The recipients of single or mixed subsets were followed for clinical manifestations of diabetes and examined at 30 days of age for in situ lesions. None of the animals injected with either CD4+ or CD8+ T cells became overtly diabetic during the 30 days of observation whereas 8 of 23 mice inoculated with a mixture of the two subsets developed glycosuria and hyperglycemia. However, insulitis was found in 6 of the 13 mice injected with CD4+ T cells whereas only 1 of the 9 mice injected with CD8+ T cells showed marginal infiltration of the pancreas. The lesions initiated by CD4+ T cells alone were considerably less severe than those induced by the mixture of both subsets, corroborating the fact that overt disease did not occur in the former group. Together, these results suggest a distinct function for each diabetogenic T cell subset. CD4+ T cells, which have the capacity to home to the pancreas, promote in turn the influx of CD8+ effector T cells that do not by themselves accumulate in this organ. These results illustrate a novel form of T-T cell interactions leading to organ specific autoimmune lesions.
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Unusual presentation of squamous cell carcinoma of the middle ear and mastoid. An unusual case of squamous cell carcinoma of the middle ear and mastoid in which syncope was a major presenting feature is reported. No such case has been reported in the literature. A possible explanation is offered.
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Ritual and dying: a cultural analysis of social support for caregivers. This study examines the role of social support in the process of caring for someone dying at home. Based on data from in-depth ethnographic interviews with 16 caregivers, it employs a cultural analysis to draw parallels with rituals of transition. Ritual provides a broad context of meanings and routines for securing the doubts and unknowns of individual experience. The way social support is provided plays a key role in the caregiver's transition to bereavement.
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Memory complaints in older adults. Fact or fiction? Complaints of poor memory by patients may be an early symptom of a pathologic process like Alzheimer's disease. It is therefore important to determine if patients' complaints of memory impairments are an accurate reflection of real memory disturbance. The relationship between memory complaints (metamemory) and objective memory performance, mood, age, verbal intelligence, and sex was examined in a group of 199 healthy, community dwelling adults (39 to 89 years old). Memory complaints demonstrated a stronger association with depressed mood than with performance on memory tests. Increasing reports of depressive symptoms were associated with more overall memory complaints. Verbal intelligence, age, and sex also contributed to memory complaints. Patients with higher verbal intelligence reported fewer complaints and placed less emphasis on forgetting. Older individuals reported greater frequency of forgetting and greater frequency of using memory techniques. Specific types of memory complaints, seriousness of forgetting, and types of memory aids employed are also described. These results showed that self-rating of memory disturbance by older adults may be related more to depressed mood than to poor performance on memory tests.
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Mammography and age: are we targeting the wrong women? A community survey of women and physicians. To determine mammography use among women with a broad range of ages, the authors surveyed women aged 30 to 74 years and physicians practicing primary care in two eastern North Carolina counties. Twenty-five percent of women in their 30s had ever had a mammogram, and 34% intended to have one in the coming year. From 45% to 52% of women in their 40s, 50s, and 60s had ever had a mammogram, and 55% to 57% intended to have one in the next year. Thirty-seven percent of women aged 70 to 74 years had ever had a mammogram, and 40% intended to have one in the following year. Nineteen percent of physicians reported screening nearly all women aged 30 to 39 years, and 14% screened few women aged 50 to 74 years. Younger women were more worried about breast cancer than older women and assessed their risk as higher, attitudes that were generally associated with higher mammography utilization. These community surveys suggest that mammography use may be excessive among younger women; older women continue to be underscreened.
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Detection and direct sequencing of hepatitis B virus genome by DNA amplification method. Hepatitis B virus (HBV) DNA was detected with amplification by the polymerase chain reaction method. Cloned HBV DNA equivalent to one virus genome (3 x 10(-6) pg) was detectable by ethidium bromide staining after 50 cycles of polymerase chain reaction. By applying this method, presence of HBV DNA was studied in 23 hepatitis B surface antigen (HBsAg)-positive and 11 HBsAg-negative sera from patients with chronic liver disease. Hepatitis B virus DNA was positive in 8 of 8 hepatitis B e antigen (HBeAg)-positive, in 2 of 2 HBeAg- and anti-HBe-negative, and in 12 of 13 anti-HBe-positive sera. Hepatitis B virus DNA was undetectable in all HBsAg-negative sera even with amplification. To confirm specificity, the amplified product was directly sequenced. Sequences around 122nd and 160th codon of HBs gene, which determines subtypes d/y and w/r, respectively, were analyzed. The results were compatible with recent reports regarding the relation between HBV subtypes and HBV DNA sequence at those codons. Hepatitis B virus DNA could be detected at the level of one virion by gene amplification method, and its sequence could be determined by direct sequencing in a few days.
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A multicenter study of doxazosin in the treatment of patients with mild or moderate essential hypertension and concomitant intermittent claudication. This study assessed the efficacy and safety of once-daily doxazosin in the treatment of patients (n = 19) with mild or moderate essential hypertension (sitting diastolic blood pressure [DBP] 95 to 114 mm Hg) and concomitant intermittent claudication (Doppler ankle/arm ratio of less than 0.80 and walking tolerance of less than 700 m on the treadmill). After 14 weeks of treatment with doxazosin, a significant (p less than 0.05) reduction in systolic blood pressure and DBP was observed. Mean blood pressures were reduced from 170/100 mm Hg at baseline to 161/93 mm Hg at the end of treatment. Minor changes in heart rate occurred, which with continued treatment were not statistically significant from baseline. In 12 of 16 (75.0%) efficacy-evaluable patients blood pressure was normalized (DBP to less than or equal to 90 mm Hg with an greater than or equal to 5 mm Hg reduction from baseline) with a mean daily dose of 7.6 mg/day. Doxazosin improved the hypertension severity category in 13 of 16 (81.3%) patients. The blood pressure ratios between both the thighs and arms and ankles and arms showed no statistically significant changes after treatment with doxazosin. Thigh blood flow at rest and the reactive hyperemia after 3 minutes of arterial occlusion did not change statistically. There was a tendency for pain-free distance to improve. Laboratory data were not significantly changed after treatment with doxazosin. Of the 19 patients studied, 5 reported mild or moderate side effects that were either tolerated or disappeared with continued treatment. No patient had therapy withdrawn and no patient required a dose reduction.
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Hemodynamic and metabolic effects of dobutamine in 18 patients after open heart surgery. Low cardiac output syndrome frequently follows cardiopulmonary bypass (CPB) surgery. In the present study, we used dobutamine to increase cardiac index (CI) and oxygen delivery (DO2) in 18 patients after open heart surgery. Using increasing doses of dobutamine up to 10 micrograms/kg.min-1, we observed statistically significant (p less than .01) increases in mean CI (2.50 +/- 0.10 to 3.56 +/- 0.18 L/min.m2) and in mean heart rate (HR) (83 +/- 3 to 105 +/- 3 beat/min). Mean systemic vascular resistance index decreased significantly (p less than .01) in all patients (2271 +/- 101 to 1648 +/- 83 dyne.sec/cm5.m2). Pulmonary vascular resistance index did not change in the ten coronary artery bypass graft patients, but decreased significantly (p less than .01) in the eight valve replacement patients (561 +/- 98 to 421 +/- 79 dyne.sec/cm5.m2). Mean DO2 increased in all patients, although there was no concomitant increase in oxygen consumption (VO2) in four patients. We observed a significant (p less than .01) increase in mean VO2 in the remaining 14 patients (110 +/- 6 to 148 +/- 12 ml/min.m2), in spite of significant decreases in PaO2 and increases in right-to-left intrapulmonary shunting. Although increases in HR and ventricular arrhythmias may limit its use, dobutamine increases CI and DO2 in patients after CPB. In the present study, dobutamine's varying metabolic effect exemplifies the need for close monitoring of hemodynamic and metabolic variables when using vasoactive drugs in the postoperative period.
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Partial characterization of Chlamydia trachomatis isolates resistant to multiple antibiotics. In vitro susceptibility testing was done on urogenital isolates of Chlamydia trachomatis from five patients, four of whom were suspected treatment failures. At least one isolate from each patient was resistant to tetracycline at concentrations greater than or equal to micrograms/ml, although less than 1% of a population of organisms showed high-level resistance. Fully resistant populations selected by passage through 8 micrograms/ml tetracycline either died or lost their resistance on further passage in antibiotic-free medium. Relatively large inocula were required to demonstrate resistance, and morphology of inclusions was altered at high tetracycline concentrations. The observed resistance may be a new characteristic of the organism or merely newly recognized. Isolates resistant to tetracycline were resistant to doxycycline, erythromycin, sulfamethoxazole, and clindamycin but sensitive to rifampin, ciprofloxacin, and ofloxacin. Thus, resistance to tetracycline, erythromycin, and clindamycin occurs in C. trachomatis and may be a factor in some treatment failures.
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Longitudinal study of diagnoses in children of women with unipolar and bipolar affective disorder. School-age children of unipolar depressed, bipolar, chronically medically ill, or normal women were diagnosed every 6 months for up to 3 years. Offspring of unipolar women had the highest rates of disorder at all evaluations, but children of bipolar and medically ill mothers also experienced significant rates of disorder. Observing diagnoses from both past lifetime and prospective follow-up assessments, it appeared that most children who had diagnoses had onsets in preadolescence and continued a chronic or intermittent course of disorder. Thus, risk to offspring of ill mothers is not transitory and indicates a pernicious course that commonly includes effective disorders alone or in combination with behavior and anxiety disorders.
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Estrogen replacement therapy: is previously treated cancer a contraindication? The benefits of estrogen replacement therapy in preventing vasomotor symptoms, osteoporosis, and cardiovascular disease are well documented. Although estrogen is said to be contraindicated in patients successfully treated for endometrial and breast cancer, there are no data to substantiate this admonition. Experience suggests that it can be used safely in patients treated previously for endometrial cancer. Although there is little or no experience with estrogen use in the woman treated previously for breast cancer, circumstantial evidence suggests that it is not contraindicated in all such cases. Informed consent, patient desires, and risk-benefit considerations must enter into the decision to use estrogen in these patients.
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Scalp necrosis in a neonate treated with cultured autologous keratinocytes. A neonate compromised by a stressful labor, low birth weight, anemia, seizures, and enterocolitis developed necrosis of a caput succedaneum of the calvaria. Coverage with cultured autologous keratinocytes was successful and represents a treatment modality with minimal morbidity compared with conventional split-thickness skin grafts.
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A comparative trial of three agents in the treatment of acute migraine headache. STUDY OBJECTIVES: A study was conducted to evaluate the relative efficacy of three non-narcotic agents, chloropromazine, lidocaine, and dihydroergotamine, in the treatment of migraine headache in an emergency department setting. DESIGN: The trial was randomized and single blinded. SETTING: The study was conducted in two university-affiliated EDs. TYPE OF PARTICIPANTS: All patients had an isolated diagnosis of common or classic migraine. INTERVENTIONS: Patients were pretreated with 500 mL (IV) normal saline before randomization. Study drugs as administered were dihydroergotamine 1 mg IV repeated after 30 minutes if the initial response was inadequate; lidocaine 50 mg IV at 20-minute intervals to a maximum total dose of 150 mg as required; or chloropromazine 12.5 mg IV repeated at 20-minute intervals to a total maximum dose of 37.5 mg as required. Patients were asked to grade headache severity on a ten-point scale before and one hour after the initiation of therapy. Follow-up by phone was sought the following day. MEASUREMENTS AND MAIN RESULTS: Of 76 patients completing the trial, 24 were randomized to receive chloropromazine, 26 to receive dihydroergotamine, and 26 to receive lidocaine. Reduction in mean headache intensity was significantly better among those treated with chloropromazine (P less than .005). Persistent headache relief was experienced by 16 of the chloropromazine-treated patients (88.9%) contacted at 12 to 24 hours follow-up compared with ten of the dihydroergotamine-treated patients (52.6%) and five of the lidocaine-treated group (29.4%). CONCLUSION: The relative effectiveness of these three antimigraine therapies appears to favor chloropromazine in measures of headache relief, incidence of headache rebound, and patient satisfaction with therapy.
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Antibodies to synthetic peptide (125-148) of the alpha-subunit of human nicotinic acetylcholine receptor in sera from patients with myasthenia gravis. We measured the amount of antibodies to a synthetic peptide that corresponds to the alpha-subunit residues Lys125-Thr148 of human acetylcholine receptor (AChR) in myasthenic sera. We detected anti-peptide antibodies in 52% (89/171) of the patients with myasthenia gravis (MG), but none in any of the healthy controls. Anti-peptide antibodies should provide a valuable immunologic parameter for the clinical evaluation of MG, but no apparent correlation was observed between the titers of anti-peptide and anti-AChR antibodies.
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Trends in systolic blood pressure, 24-hour sodium excretion, and stroke mortality in the elderly in Belgium. Data from six surveys of systolic blood pressure conducted in Belgium between 1967 and 1986 were analyzed. The mean ages of the six groups of 3,328 subjects ranged from 70 to 81 years. The prevalence of systolic blood pressure levels above 159 mm Hg decreased between 1967 and 1986 from 51% to 21% in men and 66% to 22% in women; severe hypertension (systolic blood pressure greater than 220 mm Hg) nearly disappeared. During the same period, body mass index increased 1.1 kg/m2 in men and was unchanged in women; mean systolic blood pressure decreased from 159 to 142 mm Hg in men and from 171 to 147 mm Hg in women; the proportion of subjects receiving treatment for hypertension increased from 10% to 36% in men and from 18% to 41% in women; and the mean standardized 24-hour sodium excretion decreased from 265 to 188 mmol in men and from 208 to 160 mmol in women. Systolic blood pressure levels were significantly and independently related to sodium excretion in the 1967 and 1972 studies. The decrease in systolic blood pressure in Belgium was influenced by the combined effects of more and better treatment for hypertension and a decrease in sodium intake.
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Spontaneous regression of giant arteriovenous fistulae during the perinatal period. Case report. A unique case of spontaneous regression of giant arteriovenous fistulae during infancy is described in this report. A female infant, the product of normal labor and delivery, demonstrated severe ventriculomegaly and an intracranial hemorrhage at birth. Cerebral angiography at 5 days of age revealed several large fistulae fed by the anterior and middle cerebral arteries draining into the deep venous system through a dilated internal cerebral vein and ectatic vein of Galen. Two days following the angiogram, a second intracranial hemorrhage occurred. Active hydrocephalus developed over the next 6 months and was treated with ventriculoperitoneal shunting. When the child was 8 months of age, angiography failed to demonstrate the fistulae. It was postulated that pressure effects from the intracranial hematoma and long-standing intracranial hypertension as well as stenosis in the anomalous venous outflow resulted in vascular stasis, venous thrombosis, and selective arterial occlusion. Hydrocephalus was a result of the compression of the intraventricular foramina by dilated embryonic vessels. This anomaly, predominantly involving the anterior circulation, may be homologous to the vein of Galen aneurysm in the posterior circulation.
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Amiodarone versus bretylium for suppression of reperfusion arrhythmias in dogs. Reperfusion arrhythmias are an important complication of interventions to limit infarct size. Recently, amiodarone has been shown to be rapidly effective in suppressing sustained, incessant ventricular tachycardia and ventricular fibrillation in this setting. This study evaluated the time course of arrhythmia suppression and comparative efficacy of amiodarone versus bretylium in a canine model of reperfusion arrhythmias. Of 23 dogs subjected to a Harris two-stage coronary artery ligation followed by release, 18 demonstrated clinically significant ventricular arrhythmias and received either intravenous amiodarone, 5 mg/kg (9 dogs), or intravenous bretylium, 5 mg/kg (9 dogs). Direct-current shocks for sustained ventricular tachycardia or ventricular fibrillation were administered as necessary. Amiodarone rapidly suppressed sustained ventricular tachycardia and ventricular fibrillation in this model with no dog in the amiodarone-treated group requiring cardioversion after completion of the 15-minute infusion versus 4 of 9 dogs in the bretylium-treated group (p less than 0.05). Amiodarone was more effective than bretylium in suppressing episodes of sustained ventricular tachycardia/ventricular fibrillation, episodes of nonsustained ventricular tachycardia, and premature ventricular complexes. The blood pressure and heart rate decreased more after amiodarone administration than after bretylium administration. We conclude that, in the canine reperfusion arrhythmia model, amiodarone is rapidly effective in suppressing ventricular arrhythmias and is more effective than bretylium.
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Granulomatous sialadenitis. Granulomatous inflammation in salivary tissues is most often a response to liberated ductal contents, particularly mucin, in various degrees of obstructive sialadenopathy. Far less often is a granulomatous sialadenitis the result of specific infective granulomas or systemic granuloma-forming diseases. In these instances, the salivary parenchymal involvement is usually secondary to disease localization in regional lymph nodes.
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Immunohistochemical studies on the main entrance-route of CA19-9 into the peripheral venous blood of gastric cancer patients. Correlation with CA19-9 levels in peripheral and portal blood. The correlation between CA19-9 levels of portal and peripheral venous blood, and immunohistochemical variables of cancer lesions was examined in 53 gastric cancer patients and eight patients with benign diseases. Immunohistochemically, CA19-9 was found in 33 (62.5%) of 53 primary lesions. The antigen was found in the cancer cells of invasive lymphatics and node metastases of every CA19-9 localized cancer, although the cancer cells in veins showed little or no CA19-9. There was little or no antigen in the cancer cells in veins, lymphatics, or metastases of 20 CA19-9 nonlocalized primary lesions. Patients with CA19-9 nonlocalized cancer or with benign diseases showed no elevation of the antigen levels in peripheral or portal blood. CA19-9 levels of portal blood (mean, 76.4 U/ml; positive rate, 33.3%) were not different from those of peripheral blood (mean, 91.5 U/ml; positive rate, 33.3%). Additionally, the antigen levels of the blood in patients with lymphatic invasion or node metastases were significantly higher than those in patients without the invasion or the metastases, and every patient without the invasion showed no elevation of the antigen. These results suggest that production of the antigen in cancer cells may be a premise of CA19-9 elevation in peripheral blood and that CA19-9 may be drained by the thoracic duct of the lymphatic system via node metastases or invasive lymphatics, but not by the hematogenous portal system.
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Fatty infiltration: another restrictive cardiomyopathic pattern. Restrictive cardiomyopathies have been shown to occur as result of infiltrative processes from a variety of sources. The current report describes an obese male, who was found to have hemodynamic evidence of a restrictive cardiac process. His pericardium was proven to be normal and an incisional biopsy obtained of the myocardium during coronary artery bypass surgery demonstrated histologic evidence of fatty infiltration of myocardium. Review of the restrictive and pathology literature is discussed and indicates that this is the first report to demonstrate the association between fatty infiltration and hemodynamic findings consistent with a restrictive cardiomyopathy.
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Changes in thermal and mechanical pain thresholds in hand amputees. A clinical and physiological long-term follow-up. In a previous study, allodynia to cold and vibratory stimuli was found in the finger stumps of 24 patients with amputations, control values being obtained from fingers of the intact contralateral hand. When treated with regional intravenous guanethidine block (RGB), some of the patients only had short-lasting relief of symptoms, whereas others experienced a more long-lasting beneficial effect. In the present long-term follow-up study the patients were re-examined 6 years after the RGB treatment. The aim was to investigate whether the earlier symptoms and signs persisted, and whether there were any differences in these respects, between patients with long-lasting (group 1) and short-lasting relief of symptoms after RGB (group 2). All 24 patients were asked to answer a questionnaire concerning their clinical symptoms. In addition, 14 of them visited the laboratory for determination of thermal and vibration-induced pain thresholds. Comparisons were made with values obtained at the first examination before RGB treatment and with values from 14 healthy subjects tested in a similar way on 2 occasions with an interval of 8 years. Twenty of 23 patients reported that cold exposure still evoked stump pain. However, the threshold measurements showed that with time the patients had become more tolerant to thermal stimuli not only in the injured but also in the uninjured hand. A rise in pain threshold was also observed when vibration-induced pain was tested in the injured hand. There was no significant difference between groups 1 and 2. Similar changes in pain thresholds with time were not observed in the group of healthy control subjects.
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The neck-eye reflex in patients with reduced vestibular and optokinetic function. It is accepted that the neck-eye loop (cervico-ocular reflex, COR) is enhanced following loss of vestibular function and that this helps to restore gaze stability during head movements. In this paper we address the question of which structures and/or mechanisms may participate in such plastic enhancement by investigating the COR in 2 patients with absent vestibular function and reduced smooth pursuit-optokinetic eye movements (SP-OKN). The patients had multisystem atrophy involving the vestibular system and the cerebellum. The COR (elicited by angular motion of the trunk relative to the fixed head and angular motion of the head relative to the fixed trunk) was not enhanced in these 2 patients when compared with normal subjects, in contrast to previous findings in a group of patients with absent vestibular function alone. Measurements of slow phase eye movement velocity during SP-OKN stimuli and during combined COR-OKN stimulation (head oscillation relative to the stationary trunk in the light) showed identical values in these two conditions, which indicates that the neck-eye loop did not contribute to gaze stability during head movements. The absence of plastic enhancement of the COR in these patients may be secondary to interruption of SP-OKN pathways at various possible sites and/or to involvement of the vestibulocerebellum, which is known to mediate adaptive plasticity in the vestibulo-ocular reflex.
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Dysphagia following fundoplication: "slipped" fundoplication versus achalasia complicated by fundoplication. Failure to obtain preoperative esophageal manometry in patients being considered for antireflux surgery can result in immediate persistent postoperative dysphagia due to a missed diagnosis of achalasia. We describe the clinical assessment and management of a case of delayed postoperative dysphagia due to a "slipped" fundoplication, which is contrasted with three patients with immediate postoperative dysphagia due to a missed diagnosis of achalasia. Surgical revision was required to correct the "slipped" fundoplication, and pneumatic dilatation was successfully used in two of three cases of achalasia complicated by fundoplication. Careful preoperative esophageal evaluation with manometry is essential to rule out the presence of a primary esophageal motor disorder.
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The effects of an iron chelator on cellular injury induced by vascular stasis caused by hypothermia. Rewarming of a cooled rabbit leg was associated with the generation of oxygen-derived free radicals, shown to be instrumental for tissue injury occurring during rewarming. The present study used a compound that, by its ability to bind with free iron, can remove hydroxyl radical (OH.) from tissue. Deferoxamine reduced tissue injury during cooling and rewarming, as evidenced by its ability to decrease tissue release of lactic acid dehydrogenase and creatine kinase. Deferoxamine also reduced the formation of OH. and lipid peroxidation during the rewarming phase. This compound did not have any effect on the arterial blood flow pattern, which uniformly decreased during cooling and was restored during rewarming. The results of this study indicate the efficacy of deferoxamine in reducing cellular injury associated with cold and rewarming and further suggest a role for oxygen-derived free radicals in the pathophysiology of cold-rewarming injury.
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Relation between sodium intake, renal function, and the regulation of arterial pressure. The long-term regulation of arterial pressure requires the maintenance of a balance between sodium and water intake and sodium and water excretion. Normal salt and water balance leads to stable body fluid volumes and the maintenance of normal renal function is critical to establishing extracellular fluid volume homeostasis. This review focuses on the role of the kidney in the long-term control of salt and water balance with particular emphasis on the relations between sodium intake, the renin-angiotensin-aldosterone system, renal sympathetic nerve activity, and the regulation of arterial pressure via renal sodium and water excretion. The accumulation of evidence in recent years demonstrates that low level elevation of renin release, circulating angiotensin II or aldosterone, or activation of renal sympathetic outflow may alter renal function such that normal natriuretic and diuretic responses to arterial pressure are significantly impeded. Under these circumstances, the maintenance of normal sodium and water excretion requires a significant elevation of arterial pressure. Thus, compromised renal function leads to elevation of arterial pressure to maintain adequate sodium and water balance during periods of increased sodium intake. The resultant chronic elevation of arterial pressure then becomes a compromise that is used by the kidneys to maintain normal extracellular body fluid volumes.
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Broad spectrum penicillin as an adequate therapy for acute cholangitis. In a previous study of patients with acute cholecystitis, we demonstrated equal efficacy with a broad spectrum penicillin (piperacillin) and a penicillin plus amino-glycoside combination. Whether a single agent broad spectrum penicillin is adequate treatment for more severe infections, such as acute cholangitis, however, is still unclear. We, therefore, conducted a three center, prospective, randomized trial to determine whether or not a broad spectrum penicillin alone is adequate therapy for patients with acute cholangitis. During a 36 month period, 96 patients with sepsis and biliary obstruction were randomly assigned to receive either piperacillin (n = 49) or ampicillin plus tobramycin (n = 47). The two groups receiving antibiotics were similar with respect to all clinical and laboratory parameters. The incidence of blood cultures with positive results (20 versus 21 per cent) and underlying malignant lesions (51 versus 62 per cent) was also similar between the two groups. The percentage of patients with a clinical cure or significant improvement was the same in the two groups (69 versus 70 per cent). However, there was a significant difference in the cure rate between patients with benign and malignant biliary obstructions (83 versus 59 per cent, p less than 0.01). No significant differences were noted between the two antibiotic groups with respect to drug toxicity, but patients with malignant conditions were more prone to antibiotic related toxicities (2 versus 19 per cent, p less than 0.05). These data suggest that outcome of treatment in patients with acute cholangitis is similar with either a broad spectrum penicillin or a penicillin plus aminoglycoside combination and is dependent upon the nature of the biliary obstruction.
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Lyme borreliosis in the severe combined immunodeficiency (scid) mouse manifests predominantly in the joints, heart, and liver. The authors describe the histopathologic evolution of Lyme disease in severe combined immunodeficiency (scid) and normal C.B-17 and C57BL/6 mice inoculated with Borrelia burgdorferi. Starting on day 7 after inoculation, all scid mice infected subcutaneously in the tail with a low-passage European tick isolate of B. burgdorferi had clinical evidence of arthritis characterized by reddening and swelling of tibiotarsal joints. Later on, other joints, ie, metatarsal and ulnacarpal joints were also affected. The infection of scid mice resulted in a persistent spirochetemia and the development of a multisystem disease with chronic progressive inflammation of joints, heart, and liver. Major histopathologic alterations included 1) severe joint lesions, characterized by the presence of hyperplastic inflamed synovial lining cells associated with the erosion and destruction of cartilage and/or bone; 2) pancarditis with infiltrations of mononuclear cells in the endocardium, myocardium, and pericardium; and 3) hepatitis with mononuclear cell infiltrations confined to the portal field and central vein, granulomatous reactions, and eventually the development of liver fibrosis. In addition, smaller more confined lesions were found in kidneys, lung, brain, and striated muscle. The inflammatory infiltrates in the various organs were associated mostly with Mac-1+ cells, largely monocytes and macrophages, as well as some polymorphonuclear leukocytes, but not B and T lymphocytes. Infective spirochetes could be readily isolated from blood and joints and were found at the site of inoculum and the myocardium. In contrast, subcutaneous inoculation of normal C.B-17 or C57BL/6 mice with spirochetes in general did not result in clinical signs of arthritis. Only 10% to 20% of the C57BL/6 mice, but none of the C.B-17 mice, showed clinical evidence of oligoarthritis, which appeared not before day 36 after inoculation. In general, the infection of normal mice resulted in minimal lesions in various organs, and no spirochetes could be visualized or reisolated from their tissues. The data demonstrate that Lyme borreliosis may develop in mice in the absence of detectable specific B and T cells and thus suggest an immunologic control of the disease in this species. The scid mouse model therefore can be used to define the components of the immune system responsible for the suppression and/or the progression of the disease.
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Longitudinal histopathologic assessment of rejection after bladder-drained canine pancreas allograft transplantation. In preparation for assessment of percutaneous biopsies in our clinical pancreas transplant program, a working knowledge of the histopathologic changes after transplantation was obtained in a longitudinal open biopsy study of 16 dogs receiving bladder-drained whole pancreas allografts. Edema, extravasation of polymorphs, and lymphocytes associated with focal parenchymal injury were early, invariable, and probably nonspecific findings. The initial feature of unmodified rejection was the appearance of capillary and small vein endothelial changes with mainly perivascular inflammatory cell infiltration. Acinar cell loss occurred early and was progressive, whereas islets and ducts were relatively preserved, indicating that acinar tissue may be more vulnerable to lytic necrosis when damaged. Functional rejection, determined by fasting urinary amylase levels, was at a stage of extensive and irreversible necrosis. Functioning grafts in immunosuppressed dogs had minor and transient endothelial changes with absence of class II antigen staining of parenchymal cells.
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Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts. In vivo studies in the rat. The protective effect of ursodeoxycholate conjugates against bile salt hepatotoxicity was studied in chronic bile fistula rats. Taurochenodeoxycholate or taurodeoxycholate, infused intraduodenally at 24 or 16 mumols/100 g rat per hour, respectively, caused cholestasis and severe hepatocellular necrosis within 8 hours. In contrast, tauroursodeoxycholate or taurocholate at 48 mumols/100 g rat per hour were choleretic. Tauroursodeoxycholate was not hepatotoxic, whereas taurocholate produced moderate hepatocellular necrosis. Simultaneous infusion of tauroursodeoxycholate to rats receiving taurochenoxycholate or taurodeoxycholate preserved bile flow and ameliorated hepatic injury in a dose-dependent manner. Tauroursodeoxycholate protected equally by intravenous and intraduodenal routes. Intravenous glycoursodeoxycholate also was protective. The hydrophobicity index of infused bile salts correlated well with their toxicity. Concurrent administration of ursodeoxycholate conjugates did not reduce biliary recovery of intraduodenally infused [24-14C]-taurocholate. Biliary alkaline phosphatase secretion was stimulated by infusion of taurocholate, taurodeoxycholate, or taurochenodeoxycholate; simultaneous infusion of ursodeoxycholate conjugates failed to prevent this increase. We conclude that ursodeoxycholate counteracts hepatoxicity of more hydrophobic bile salts via a direct effect at the level of the liver.
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Atelectasis affects the rate of arterial desaturation during obstructive apnea. Chronic hemodynamic disturbances are more profound in patients with obstructive sleep apnea when underlying lung disease with abnormal gas exchange (low arterial PO2) is present. Previous studies suggest that pulmonary gas exchange could influence the rate of fall of arterial oxygen saturation (dSaO2/dt) in obstructive sleep apnea. We postulated that abnormal gas exchange in the form of atelectasis would steepen dSaO2/dt and thereby lower nadir arterial oxyhemoglobin saturation (SaO2) for the same duration of apnea. Apneas were created by clamping an indwelling cuffed endotracheal tube at end expiration in eight spontaneously breathing adult baboons. Apneas of the same duration were then repeated during temporary endobronchial occlusion of one lobe of the lung. SaO2 and mixed venous O2 saturation were continuously monitored, and cardiac output was calculated. Worsening of pulmonary gas exchange during atelectasis was documented by an increase in calculated venous admixture from 10.5 +/- 0.8 to 25.0 +/- 0.7% (P less than 0.001). The dSaO2/dt was independent of apnea duration at 30, 45, and 60 s. During endobronchial occlusion, apnea dSaO2/dt increased 20%, and nadir SaO2 was significantly lower. Possible mechanisms for steepening of dSaO2/dt during atelectasis are discussed.
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Septic arthritis of the C1-C2 lateral facet joint and torticollis: pseudo-Grisel's syndrome. We present the case of a 76-year-old man who experienced the sudden development of fever, rightsided neck pain and stiffness, and torticollis. A soft tissue mass was noted on the right side of his neck, but his head was tilted to the left. Computed tomography scans (with reformatted sagittal and coronal images) of the patient's cervical spine revealed destructive changes of the right lateral masses of C1 and C2 and the clivus, and a well-delineated peridontoid soft tissue mass (confirmed by magnetic resonance imaging). After the second episode of right-sided hemiparesis, he underwent transoral surgical exploration, with anterior decompression and odontoidectomy. Histologic examination of the surgical material revealed granulation tissue, fibrosis, and chronic inflammation, consistent with abscess formation with invasion and compression of the spinal cord and bone. This case suggests that nonreducible rotational head tilt to the side opposite the side of lateral mass collapse should raise the suspicion of a possible infection.
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Differentiation of ventricular tachyarrhythmias. Implantable devices capable of several modes of therapy will require differentiation of various ventricular tachyarrhythmias. Three methods of arrhythmia analysis, magnitude-squared coherence, ventricular rate, and irregularity of cycle length were performed for 45 episodes of induced ventricular tachyarrhythmia in 15 patients. Differentiation of monomorphic ventricular tachycardia from polymorphic ventricular tachycardia and ventricular fibrillation was possible by mean magnitude-squared coherence, less possible by rate, and not possible by beat-to-beat irregularity. Faster monomorphic ventricular tachycardia overlapped with rates of polymorphic ventricular tachycardia and ventricular fibrillation. Differentiation of polymorphic ventricular tachycardia and ventricular fibrillation was not possible by rate or irregularity. A progressive decrease in mean magnitude-squared coherence from monomorphic ventricular tachycardia to polymorphic ventricular tachycardia to ventricular fibrillation strengthens previous observations that coherence is a measure of rhythm "organization.".
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Human T cell lymphotropic virus infection in Guaymi Indians from Panama. Preliminary studies found that 9% of Guaymi Indians from Bocas del Toro province have antibody to human T cell lymphotropic virus (HTLV-I/II). The present study enrolled 317 (21% of the population) Guaymi Indians from Changuinola, the capital of Bocas del Toro province and 333 (70% of the population) from Canquintu, an isolated rural village. Demographic information and family relationships were ascertained and subjects were screened for neurologic diseases. Serum specimens were screened by an enzyme-linked immunosorbent assay for HTLV-I/II antibody and positives were confirmed according to U.S. Public Health Service criteria. Twenty-five (8%) Guaymi residing in Changuinola and 7 (2.1%) from Canquintu were confirmed seropositive. In Changuinola, antibody was virtually limited to residents greater than or equal to 15 years of age (24 [16%] of 153) and rates were slightly higher in males than in females; in Canquintu, antibody rates did not increase significantly with age and appeared higher in females than in males. In Changuinola, there was no evidence for household clustering of infection. In contrast, HTLV antibody among Canquintu residents clustered significantly by household. HTLV-associated neurologic disease was not detected in either population. The atypical seroepidemiology observed in both locations might be explained if the virus endemic to the Guaymi differed from HTLV-I previously described in the Caribbean basin and Japan.
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Dapsone is an effective therapy for the skin lesions of subacute cutaneous lupus erythematosus and urticarial vasculitis in a patient with C2 deficiency. The deficiency of second component of complement (C2d) is the most common hereditary complement deficiency. Patients with C2 deficiency are frequently associated with an auto-immune disease process, in particular, systemic lupus erythematosus (LE)-like syndrome and/or vasculitic syndrome or bacterial infections. C2d has been associated with the LE subset of subacute cutaneous LE (SCLE), the presence of anti-Ro (SSA) antibodies, and the human leukocyte antigen (HLA) types A10, B18, DR2. We describe the clinical, serologic and immunogenetic data in a patient with manifestations of Sjogren's syndrome who developed urticarial vasculitis and photosensitive annular SCLE which were effectively treated with oral dapsone. Our case illustrates the dynamic nature of LE.
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Procarbazine chemotherapy in the treatment of recurrent malignant astrocytomas after radiation and nitrosourea failure. The Brain Tumor Study Group has shown procarbazine (PCB) to be as effective an adjuvant treatment as 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). We treated 35 patients with recurrent malignant astrocytomas after radiation and nitrosourea failure with successive courses of PCB 150 mg/m2/d for 28 days every 8 weeks. After 2 courses, 2 patients had complete responses, 7 had partial responses, 11 had stable disease, and 15 had progression. Significantly more patients receiving PCB had complete or partial responses or stable disease than a similar group of patients in a previous trial who received intra-arterial (IA) cisplatin (DDP). There is a significant advantage in time to disease progression for those receiving PCB compared with those receiving IA diaziquone (AZQ). Our results suggest that PCB is a more effective 2nd agent than IA DDP or AZQ following radiation and nitrosourea failure.
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Intraatrial extension of thyroid cancer: technique and results of a radical surgical approach. An occlusion of the superior vena cava by a tumor thrombus extending into the right atrium was diagnosed in three patients with a follicular thyroid cancer. All patients showed the typical clinical picture of the superior vena cava syndrome. A right parasternal thoracotomy was performed for preparation of the major vessels. The superior vena cava was opened and the entire intravascular tumor thrombus was removed. The cavotomy was closed directly in two patients. In the third patient the left brachiocephalic trunk was resected and reconstructed with a vascular (polytetrafluoroethylene) graft. This patient had bone and brain metastases and an occlusion of the graft 3 months after surgery after anticoagulation was stopped. The other two patients were clinically symptom free without local recurrence 13 and 50 months after surgery. An aggressive surgical approach is justified in grossly invasive thyroid cancer to decrease local recurrence and death rates, to correct the disturbing clinical symptoms of superior vena caval occlusion, and to prevent tumor embolism and the development of distant metastases. By reducing tumor mass, an even better basis for radioiodine treatment can be prepared.
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