condition_label
int64
1
5
medical_abstract
stringlengths
170
4k
3
Plasticity of integrin expression by nerve-derived connective tissue cells. Human Schwann cells, perineurial cells, and fibroblasts express markedly different patterns of beta 1 integrins during nerve development, neoplasia, and in vitro. Strikingly selective expression patterns of beta 1, alpha 2, alpha 3, and alpha 5 integrin subunits were revealed in endoneurium, perineurium, and epineurium of fetal and adult human peripheral nerve by immunostaining with specific antibodies. The alpha 2 subunit was expressed only on Schwann cells both in fetal and adult nerve, whereas the alpha 3 epitopes were expressed exclusively in the adult tissue and were primarily present on perineurial cells. The alpha 5 epitopes were expressed only on the innermost cell layer of perineurium of fetal and adult nerve. The tumor cells within schwannomas and cutaneous neurofibromas expressed both alpha 2 and alpha 3 subunits, indicating that Schwann cells have the potential to express also the alpha 3 subunit in vivo. Cell cultures established from human fetal nerve and neurofibromas revealed expression of the alpha 2 and alpha 5 epitopes on Schwann cells, perineurial cells, and fibroblasts, whereas only Schwann cells contained the alpha 3 epitopes which were occasionally concentrated on the adjacent Schwann cells at cell-cell contacts. Our findings emphasize that nerve connective tissue cells change their profiles for expression of extracellular matrix receptors under conditions which have different regulatory control signals exerted by, for example, axons, humoral factors, or the extracellular matrix of the peripheral nerve. This plasticity may play an important role during nerve development and in neoplastic processes affecting the connective tissue compartments of peripheral nerve.
1
Development and characterization of a new, highly specific antibody to the human chorionic gonadotropin-beta fragment. In addition to high concentrations of hCG, pregnancy urine contains even higher concentrations of a fragment of the hCG beta-subunit. This biologically inactive material complicates immunological measurement of hCG, since it cross-reacts with many polyclonal and monoclonal antibodies to the hCG beta-subunit that are employed for assays of hCG in urine. Although we and others have developed antibodies to this fragment, specific measurement of the fragment in the presence of free hCG beta has remained difficult due to intrinsic cross-reactivity of these antibodies with the intact hCG beta. Rather than attempt to increase specificity by assay optimization, we developed a new, highly specific monoclonal antibody, designated B210, which cross-reacts less than 0.1% with the free hCG beta-subunit in both liquid and solid phase immunoassay formats. We have used this new monoclonal antibody in immunoradiometric assays to measure specifically the hCG beta fragment in urine throughout pregnancy as well as in the sera of two individuals with cancers producing the hCG beta-subunit. We discovered that the hCG beta fragment can bind three monoclonal antibodies simultaneously, indicating that although the epitope for antibody B210 is a new determinant exposed on the hCG beta fragment and not on intact hCG or on free hCG beta-subunit, the hCG beta fragment retains at least two other hCG beta-related epitopes intact, i.e. those that bind monoclonal antibodies B108 and B201.
3
The role of conditioning and verbal expectancy in the placebo response. Both conditioning and expectancy models have been offered in recent years as explanations for the placebo response. Following our earlier work on conditioning placebo responses in human subjects the current study examined the relative contribution made by conditioning and verbal expectancy. Group 1 received a Combined Expectancy and Conditioning Manipulation; group 2 received Expectancy Alone; group 3, Conditioning Alone; and group 4 was the control group. Subjects' responses were compared with and without a placebo cream, using iontophoretic pain stimulation. The results suggest that conditioning was more powerful than verbal expectancy in creating a placebo response.
4
Ceftriaxone-sulbactam combination in rabbit endocarditis caused by a strain of Klebsiella pneumoniae producing extended-broad-spectrum TEM-3 beta-lactamase. We studied the activity of the combination of sulbactam and ceftriaxone against a Klebsiella pneumoniae strain producing TEM-3, a new extended-broad-spectrum beta-lactamase, in an endocarditis model. In vitro, ceftriaxone was strongly inactivated in the presence of TEM-3 (MBC, 128 micrograms/ml with an inoculum of 5 x 10(5) CFU/ml). A marked inoculum effect was demonstrated with sulbactam: effective concentrations of inhibitor needed to reduce the MIC and MBC of ceftriaxone to similar levels increased from 1 microgram/ml in the presence of an inoculum of 5 x 10(5) CFU/ml to 20 micrograms/ml in the presence of an inoculum of 1 x 10(7) CFU/ml. In vivo, sulbactam given at 200 mg/kg of body weight every 12 h, a dosage higher than that previously reported to be effective against rabbit endocarditis caused by other microorganisms, was not sufficient to restore the complete activity of ceftriaxone given at 30 mg/kg once daily for 4 days. This insufficient activity may be correlated with the presence of a high level of beta-lactamase inside the vegetations, as indicated by a quantitative in vitro assay of beta-lactamase activity in the cardiac vegetation, suggesting an insufficient inactivation of the extended-broad-spectrum beta-lactamase in vivo.
5
Results of coronary surgery after failed elective coronary angioplasty in patients with prior coronary surgery The results of coronary artery bypass surgery after failed elective coronary angioplasty in patients who have undergone prior coronary surgery are unknown. Coronary angioplasty may be performed to relieve angina after surgery either to the native coronary vessels or to grafts. Failure of attempted coronary angioplasty may mandate repeat coronary surgery, often in the setting of acute ischemia. From 1980 to 1989, 1,263 patients with prior coronary bypass surgery underwent angioplasty; of these patients, 46 (3.6%) underwent reoperation for failed angioplasty during the same hospital stay. Of the 46 patients who underwent reoperation, 33 had and 13 did not have acute ischemia. In the group with ischemia, 3 patients (9.1%) died and 14 (42.4%) died or had a Q wave myocardial infarction in the hospital compared with no deaths (p = NS) and no deaths or Q wave myocardial infarction (p = 0.005) in the group without ischemia. At 3 years, the actuarial survival rate was 88 +/- 6% in the group with ischemia, whereas there were no deaths in the group without ischemia (p = NS), and freedom from death or myocardial infarction was 51 +/- 10% in the group with ischemia, versus no events in the group without ischemia (p = 0.006). In most patients with prior coronary bypass surgery, coronary angioplasty was performed without the need for repeat coronary bypass surgery. Should coronary angioplasty fail, reoperation in patients without acute ischemia can be performed with overall patient survival comparable to that of elective reoperative coronary bypass without coronary angioplasty.
5
Postinduction repression of the beta-interferon gene is mediated through two positive regulatory domains. Virus induction of the human beta-interferon (beta-IFN) gene results in an increase in the rate of beta-IFN mRNA synthesis, followed by a rapid postinduction decrease. In this paper, we show that two beta-IFN promoter elements, positive regulatory domains I and II (PRDI and PRDII), which are required for virus induction of the beta-IFN gene are also required for the postinduction turnoff. Although protein synthesis is not necessary for activation, it is necessary for repression of these promoter elements. Examination of nuclear extracts from cells infected with virus reveals the presence of virus-inducible, cycloheximide-sensitive, DNA-binding activities that interact specifically with PRDI or PRDII. We propose that the postinduction repression of beta-IFN gene transcription involves virus-inducible repressors that either bind directly to the positive regulatory elements of the beta-IFN promoter or inactivate the positive regulatory factors bound to PRDI and PRDII.
2
Gastric injury and invasion of parietal cells by spiral bacteria in rhesus monkeys. Are gastritis and hyperchlorhydria infectious diseases? The possibility of using the rhesus monkey as a model for studying gastric function in the presence of infection with spiral bacteria was studied. Endoscopic evaluation of the gastric mucosa was performed under general anesthesia in 29 colony-bred rhesus monkeys, and gastric pinch biopsy specimens were obtained from each animal. On a separate day, gastric emptying and acid output were determined using a 99mTc dilution technique. Biopsy samples were fixed for light microscopy (H&E, Gram, and Warthin-Starry stains) and for transmission electron microscopy. The presence of spiral bacteria and gastritis was assessed and rated on coded slides. In 8 of 29 monkeys, Helicobacter pylori-like organisms were observed in close proximity to the mucosal epithelial cells or in the lumen of the gastric pits. In 14 other monkeys, "Gastrospirillum hominis"-like organisms were observed in the mucus covering the surface of epithelial cells, in the lumina of the gastric glands, and overlying parietal cells. Gastritis was present in 8 of 8 animals positive for H. pylori-like organisms, in 2 of 14 animals positive for "G. hominis"-like organisms, and in none of the uninfected monkeys, and the mean gastritis index was significantly greater in animals positive for H. pylori-like organisms. Moreover, acid output was significantly higher in monkeys positive for "G. hominis"-like organisms than in controls or animals positive for H. pylori-like organisms. Gastric emptying was not significantly different in the three groups. In conclusion, (a) H. pylori-like, but not "G. hominis"-like, organisms cause gastritis while not modifying acid output; (b) "G. hominis"-like, but not H. pylori-like organisms, invade and on occasion damage parietal cells while apparently causing hyperchlorhydria; and (c) the rhesus monkey appears to be a good model for the study of gastric infection with spiral bacteria.
5
Angiographic follow-up and clinical outcome of 126 patients after percutaneous directional atherectomy (Simpson AtheroCath) for occlusive peripheral vascular disease. Angiographic and clinical follow-up data were obtained in 115/126 patients who underwent directional atherectomy for peripheral vascular disease; of the 126, ten were excluded for appropriate reasons and one was lost to follow-up. Thus, 115/116 successful atherectomy patients (99%) had follow-up of 182/213 lesions (86%): 74 patients (64%) with angiography (mean time 5.4 mon), and 41 patients (36%) clinically. One hundred twenty-eight of 183 lesions (70%) had angiographic follow-up; the lesion recurrence as a stenosis or as an occlusion was 53%. Lesion distribution did not differ between angiography and clinical follow-up groups: nearly 85% were within the superficial femoral or popliteal arteries. Despite data stratification, angiographic follow-up indicated that patients after successful directional atherectomy, at a mean follow-up time of 5 mos, have more than a 50% lesion recurrence rate. Although directional atherectomy (Simpson AtheroCath) utilizing present techniques has excellent primary success and acceptable complication rates, angiographic follow-up statistics are bothersome.
5
A controlled trial of clobetasol propionate ointment 0.05% in the treatment of experimentally induced Rhus dermatitis. We studied the effectiveness of clobetasol propionate ointment 0.05% in experimentally induced Rhus dermatitis. Clobetasol rapidly decreased the vesiculation at each treated site, although the effect was most prominent at the site to which clobetasol was applied the earliest, that is, at 12 hours after exposure to Rhus extract. On the basis of this experimental model, clobetasol propionate ointment 0.05% may be effective therapy for naturally occurring Rhus dermatitis.
1
Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2. The erbB2 oncogene encodes a 185-kilodalton transmembrane protein whose sequence is similar to the epidermal growth factor receptor (EGFR). A 30-kilodalton factor (gp30) secreted from MDA-MB-231 human breast cancer cells was shown to be a ligand for p185erbB2. An antibody to EGFR abolished the tyrosine phosphorylation induced by EGF and transforming growth factor-alpha (TGF-alpha) but only partially blocked that produced by gp30 in SK-BR-3 breast cancer cells. In two cell lines that overexpress erbB2 but do not expresss EGFR (MDA-MB-453 breast cancer cells and a Chinese hamster ovary cell line that had been transfected with erbB2), phosphorylation of p185erbB2 was induced only by gp30. The gp30 specifically inhibited the growth of cells that overexpressed p185erbB2. An antibody to EGFR had no effect on the inhibition of SK-BR-3 cell colony formation obtained with gp30. Thus, it appeared that gp30 interacted directly with the EGFR and erbB2. Direct binding of gp30 to p185erbB2 was confirmed by binding competition experiments, where gp30 was found to displace the p185erbB2 binding of a specific antibody to p185erbB2. The evidence described here suggests that gp30 is a ligand for p185erbB2.
4
Lower extremity revascularization via the lateral plantar artery. Lower extremity bypass grafts to the tibial and crural arteries are commonly employed to treat patients with atherosclerotic limb-threatening ischemia. Although occasional series have mentioned bypasses to a plantar artery, few of these specifically examine the results of arterial reconstructions using these vessels. Six patients underwent femoral to lateral plantar artery (LPA) bypass within a 19-month period for gangrene of the forefoot. There was one early graft failure and in the five completely autogenous reconstructions, graft patency and limb salvage had been achieved during a follow-up ranging from three to 22 months. The LPA is an acceptable site for anastomosis of lower extremity bypass grafts and the early results presented herein support its more liberal use when proximal sites are unavailable.
1
Merkel cell carcinoma metastatic to the testis. Tumor metastases to the testes are rare and are usually found incidentally at autopsy or after orchiectomy for prostatic carcinoma. It is even more unusual for testicular metastases to be clinically detected or symptomatic. The authors report two cases of clinically detected testicular metastases from Merkel cell carcinoma of the skin. Merkel cell carcinoma metastatic to the testes has not been reported previously. The two tumors, to some degree, resembled testicular lymphomas and the interstitial type of seminoma.
2
Pathophysiologic changes in the critically ill patient: risk factors for ulceration and altered drug metabolism. Virtually all patients who are under the physiologic stress of an intensive care unit (ICU) are vulnerable to stress-related mucosal damage and ulceration. Although clinically significant hemorrhage from stress ulceration occurs in only 5-20 percent of patients in the ICU, the associated mortality is greater than 50 percent. The pathophysiologic mechanisms of stress ulcer are not well understood; however, a number of risk factors such as intraluminal gastric acidity and mucosal ischemia have been implicated. To prevent the development of stress ulcers and subsequent complications, it is important to identify and correct these underlying risk factors. Improving mucosal blood flow (i.e., fluid resuscitation and low-dose dopamine) and providing adequate nutritional support are invaluable adjuncts in minimizing the risk of stress ulcer formation. The use of pharmacologic prophylaxis controls the gastric acidity and prevents the formation of stress ulcers. The potential for drug-induced adverse effects and drug-drug interactions are of particular concern in the care of critically ill patients. Multiple organ system dysfunction or failure, malnutrition, fluid and electrolyte abnormalities, as well as the use of multiple pharmacologic agents predispose these patients to alterations in drug pharmacokinetics, drug-induced adverse effects and drug-drug interactions. These changes may alter the pharmacodynamic response to therapy and must be considered when designing drug dosage regimens for critically ill patients.
4
The origin and fate of complex coronary lesions. Complex irregular coronary artery stenoses, representing plaque rupture/thrombosis, are associated with the acute coronary syndromes. However, the natural history (origin and fate) of these lesions is not known. To examine this issue we studied 255 patients who had had two to four arteriograms within a mean interval of 2.6 +/- 1.7 years. Of 53 irregular lesions that had progressed on a later arteriogram, 35 (66%) originated from areas that were smooth and less than 50% in stenosis diameter. Of 44 irregular lesions on an earlier study, 10 (23%) became totally occluded, five (11%) progressed in severity (all remained irregular), 25 (57%) showed no change in severity (all remained irregular), and four (9%) regressed (two became smooth). Nine of the 10 lesions progressing to occlusion were greater than or equal to 95% stenosed on the earlier study. Only 2 of 44 lesions (5%) showed smoothing. These findings are in agreement with the concept that irregular lesions represent ruptured atherosclerotic plaques and demonstrate that they usually originate from mildly occlusive smooth plaques. Markedly narrowed irregular lesions (greater than or equal to 95% stenosis) frequently progress to occlusion. Irregular lesions less than 90% narrowed commonly remain angiographically stable, and irregular over several years. They were found rarely to evolve into smooth-walled plaques.
4
The value of pulmonary artery and central venous monitoring in patients undergoing abdominal aortic reconstructive surgery: a comparative study of two selected, randomized groups. One hundred two patients undergoing abdominal aortic reconstructive surgery were prospectively, randomly allocated to two groups, one of which was monitored with a central venous catheter and the other with a pulmonary artery catheter. Patients with uncompensated cardiopulmonary or renal disease were excluded from the study. General anesthesia was administered for the surgical procedure, and the patients were followed through hospital discharge. No statistically significant differences occurred between the two groups with regard to morbidity (perioperative cardiac, pulmonary or renal sequelae), mortality rate, duration of intensive care, postoperative hospital stay, or cost of hospitalization. The one statistically significant difference between groups was the professional fee charged for anesthetic care, which was higher for patients with pulmonary artery catheters than for those with central venous catheters. In conclusion, we prospectively gathered data from most patients presented for abdominal aortic reconstructive surgery. Our data seem to indicate that the choice of central venous catheter or pulmonary artery catheter monitoring makes little difference in outcome after abdominal aortic reconstructive surgery, and that for many patients pulmonary artery catheters are not necessary to give appropriate, adequate care. Because of the size of the sample, however, declarations of epidemiologic significance would be unfounded. Therefore large-scale, multicenter studies addressing such outcomes remain necessary.
3
Prognosis of Wilsonian chronic active hepatitis. Twenty of 320 patients with Wilson's disease initially presented with chemical and laboratory features of chronic active hepatitis, confirmed histologically in 17. When first seen, cirrhosis was present in all 20 and was complicated by ascites and/or jaundice in 11. Within 1 week to 8 years of the onset of over liver disease the diagnosis of Wilson's disease was established, and treatment with D-penicillamine was promptly initiated in 19 patients. One man refused treatment and died 4 months later. Treated patients received D-penicillamine or trientine for a total of 264 patient-years (median, 14 patient-years). Abnormal water retention, for which salt restriction and diuretics were added to penicillamine or trientine, disappeared in all but 1 of the patients so affected. Symptomatic improvement and virtually normal levels of serum albumin, bilirubin, aspartate aminotransferase, and alanine aminotransferase followed within 1 year in the majority of subjects. One woman died after 9 months of treatment. Two patients, who became noncompliant with the therapeutic regimen after 9 and 17 years of successful pharmacological treatment, required liver transplants. These results indicate that the prognosis of specifically treated Wilsonian chronic active hepatitis is very good in spite of the presence of cirrhosis.
4
Prognosis of hospital survivors after salvage from cardiopulmonary bypass with centrifugal cardiac assist. Since October 1986, 6 hospital survivors who were salvaged from cardiopulmonary bypass (CPB) with the Sarns centrifugal pump were observed. Centrifugal assist was employed only after failure to wean with usual resuscitative measures, including multiple high dose inotropes and intraaortic balloon pumping. There were five men and one woman, 46-59 years of age (mean 61 years). All patients had undergone coronary artery bypass grafting, with two patients having had concomitant left ventricular aneurysmectomy and two aortic valve replacement. Five patients had left ventricular assist only and one had biventricular assist. Duration of assist ranged from 26 to 72 hr (mean 48 hr). Complications were ubiquitous, and the resultant prolonged hospitalization was resource intensive. All hospital survivors remain alive and are in New York Heart Association functional Class II, with an average follow-up of 24 months, (6-41 months). Compared with preoperative values, current left ventricular function is improved in 2 patients, has deteriorated in 3, and is unchanged in 1. Thus, the Sarns centrifugal pump will allow salvage of some patients who otherwise are not weanable from CPB. Survivors can expect a reasonable functional capacity as reflected by this experience.
2
Hepatitis B virus nucleocapsid/pre-S2 fusion proteins expressed in attenuated Salmonella for oral vaccination. Hybrid HBV nucleocapsid-pre-S(2) fusion proteins were stably expressed in several aromatic-dependent attenuated Salmonella typhimurium and Salmonella dublin strains. When these live recombinant bacteria were administered i.p. to BALB/c mice they induced high titer anti-hepatitis B virus core Ag (HBc) and detectable anti-pre-S2 serum antibodies. Upon oral feeding of the recombinant salmonellae to mice, the rate of seroconversion to anti-HBc was dependent on the salmonella strain used. With the best carrier strain high titer anti-HBc antibodies and lower titer anti-pre-S2 serum IgG antibodies were observed two weeks after a single oral immunization. The Ig class and IgG subclass distribution of anti-HBc antibodies after i.p. and oral immunization is consistent with the induction of functional T cell help.
4
Patients' observations of bioprosthetic valve failure: "my heart is honking, doctor". Audible cardiac murmurs are uncommon and may indicate severe native valve dysfunction. In six patients with bioprosthetic mitral valves audible honking systolic murmurs suddenly developed. Doppler echocardiography showed characteristic striated regurgitant signals. At operation each prosthesis had torn cusps. New audible murmurs and striated Doppler signals originating from mitral bioprosthetic valves are indicators of cusp tears. Recognition of this is important because early detection of prosthetic valve dysfunction may improve subsequent surgical outcome.
5
Arthroscopic treatment of temporomandibular joint locking resulting from disc derangement: two-year results. This article reports 2-year postarthroscopic surgical treatment data for 18 subjects (17 female and 1 male) who had a diagnosis of restricted mandibular movement due to an internal derangement of the temporomandibular joint (TMJ). These subjects had been treated by an average of 2.1 +/- 1.1 doctors for their TMJ problem before seeing the surgeon for arthroscopic treatment. The subjects' mean pain score at the final time point (21 to 30 months after surgery) was decreased by 57% in usual pain intensity. Jaw function showed an average improvement of 67%. These subjects also showed a 13-mm mean increase in their maximum active opening ability at the 2-year postsurgical time point. Slight to definite clicking noises were present presurgically in 11 of 18 patients, and similar joint noises were reported in 14 of 18 patients postsurgically. The mean overall improvement was rated as 8.18 +/- 2.4, with 10 the highest possible rating. One subject rated her improvement as 0, two subjects rated their improvement as 6 out of 10. No significant morbidity was reported by the subjects as a result of their surgery.
4
Indications, timing, and optimal technique for diagnostic angiography and angioplasty in acute myocardial infarction. Emergency cardiac catheterization and coronary angioplasty for acute myocardial infarction (MI) have a continuing role in the thrombolytic era. Although thrombolytic therapy has revolutionized the treatment of MI, it has significant shortcomings: about 75% of patients with acute MI cannot be treated with thrombolytic agents, 25% of treated patients will have persistent occlusion of the infarct-related artery, 70% will have a residual stenosis greater than or equal to 70%, and 20% of treated patients will experience reocclusion. Cardiac catheterization identifies the coronary anatomy for mechanical revascularization and allows the unstable patient to receive special therapy, such as intra-aortic balloon pumping. Many large clinical studies have evaluated approaches to coronary angioplasty for acute MI. Deferred angioplasty has indisputable advantages over immediate routine angioplasty. Direct angioplasty without concomitant thrombolytic therapy has acceptable success and complication rates, so that it can be considered the treatment of choice for acute MI in centers with an angioplasty program if thrombolytic therapy is contraindicated. Patients at very low risk may not require cardiac catheterization routinely before discharge, since their good prognosis cannot be improved by invasive evaluation and intervention. Emergency surgical revascularization is indicated in a very small percentage of cases.
3
Malignant glandular triton tumor. A case of left brachial plexus-related malignant peripheral nerve sheath tumor showing neoplastic, glandular, and rhabdomyoblastic elements in a 39-year-old Chinese man is reported. The authors suggested that this tumor be termed a malignant glandular triton tumor in view of the presence of the adenocarcinomatous component. The patient had extensive local recurrence comprising mainly the Schwann spindle cells within a year after complete piecemeal removal and died 15 months later after the initial presentation. The natural behavior of this tumor, as in other reported cases of malignant triton tumor, is extremely aggressive, unlike malignant schwannoma or glandular malignant schwannoma. The histogenesis of this tumor is likely to be from primitive neural crest cells, Schwann's cell precursors, or metaplastic malignant Schwann's cells.
1
The history of nitrite in human nutrition: a contribution from German cookery books. In order to settle the question of when saltpetre (nitrate) came in use as an additive to human food, a number of historic cookery books from Germany and Austria were reviewed. Obviously, the change from vegetable dyes to saltpetre for the coloring or color preservation, respectively, of meat occurred between 1600 and 1750, probably near 1700. The addition of sugar which favours the reduction of nitrate to the active agent nitrite became common practice during the 19th century. Thus some historic parallels to the appearance of colorectal cancer, multiple sclerosis and rheumatoid arthritis in the medical literature became apparent.
5
Immunological studies before and during interferon therapy in chronic HBV infection: identification of factors predicting response. Lymphoblastoid interferon is effective therapy in some but not all patients with chronic hepatitis B virus infection. To assess whether immunological parameters were predictive of response to interferon therapy, we determined the human leukocyte antigen type, CD4/CD8 ratio, natural killer cell activity, IgM anti-HBc antibody levels and concanavalin A-induced lymphocyte proliferative response in 30 patients before treatment. In addition, to investigate the mechanisms of action of interferon in promoting hepatitis B virus clearance, we serially measured the CD4/CD8 ratios, natural killer activity and lymphocyte proliferative response at wk 4, 8 and 12 of treatment. A beneficial response to therapy was defined as the sustained clearance of HBeAg and serum hepatitis B virus DNA within 1 yr of commencing therapy. Elevated IgM anti-HBc levels were associated with a beneficial response to therapy, but there was no correlation observed between response and pretreatment CD4/CD8 ratio, natural killer activity or lymphocyte proliferative response. Six of seven human leukocyte antigen DR3-positive patients responded. No measurable changes in the immunological parameters studied were observed in the nonresponder group, whereas a significant rise in CD4/CD8 ratio, associated with a fall in peripheral CD8 number and a decline in measurable NK activity, was seen in the responder group. These changes were maximal at the time of hepatitis B virus DNA clearance, which was associated with a transient increase in hepatic inflammation.
2
Carcinoma of the gallbladder. Gallbladder cancer remains difficult to diagnose preoperatively. However, recent work suggests that ultrasound may be effective. Gallbladder cancer remains highly lethal despite aggressive therapy. Extension of the disease beyond the mucosa predicts a poor chance of long-term survival.
3
Persistent segmental cutaneous anesthesia after a brown recluse spider bite. Patients with brown recluse spider bites commonly suffer from pain, muscular aching, and a variety of local dysesthesias during the acute and resolution phases of toxin-induced injury. This is our first well-documented observation of persistent cutaneous anesthesia caused by a spider bite. The anesthetic area conformed to the distribution of a specific nerve, the transverse cervical cutaneous nerve. The identification of the spider as a brown recluse and the location of the bite over the nerve's usual pathway strongly suggest that the venom was responsible for this complication.
2
Gynecomastia. A bothersome but readily treatable problem. Although breast enlargement in boys and men can cause both psychological and physical distress, the disorder is rarely serious and is readily treatable. Several factors can lead to the estrogenic excess that causes growth of breast tissue. Dr Jacobs describes a patient with gynecomastia related to cirrhosis of the liver who responded promptly to a brief course of tamoxifen citrate therapy.
4
Circulating plasma platelet activating factor in persistent pulmonary hypertension of the newborn. Platelet activating factor (PAF) is an endogenous phospholipid mediator that causes pulmonary hypertension and thrombocytopenia in experimental animal models. To investigate circulating PAF in persistent pulmonary hypertension of the newborn (PPHN), we studied PAF and its degradative enzyme, acetylhydrolase. Thirteen neonates with PPHN, diagnosed by routine clinical methods including echocardiography, were compared to six age-matched control patients with respiratory distress. Overall, plasma PAF levels were elevated in patients with PPHN compared to control patients (20.1 +/- 3.9 versus 1.6 +/- 0.7 ng/ml, p less than 0.01). In addition, plasma PAF concentrations in patients with PPHN correlated with the severity of disease as defined by the delta AaPO2 (r = 0.65, p = 0.015). In three patients with elevated PAF levels, as the clinical status improved, the plasma PAF values decreased. Acetylhydrolase activity was similar in both groups (3.96 +/- 0.90 versus 3.78 +/- 1.44 nmol/ml/min, p = NS). We conclude that PAF production is increased in PPHN and that abnormal production of PAF may be associated with pulmonary hypertension.
5
Ratio of immunochemically determined amniotic fluid acetylcholinesterase to butyrylcholinesterase in the differential diagnosis of fetal abnormalities. A total of 111 amniotic fluid samples, clear or blood stained, with elevated levels of alpha-fetoprotein and acetylcholinesterase was analysed by immunoassays specific for acetylcholinesterase and butyrylcholinesterase and the acetylcholinesterase/butyrylcholinesterase-ratios determined. Samples from 40 pregnancies associated with anencephaly, 47 pregnancies associated with open spina bifida or encephalocele and six pregnancies with fetal intrauterine death or miscarriage all had ratios of greater than 0.14. All 11 pregnancies with fetal ventral wall defects had ratios less than 0.14 as had four pregnancies with normal outcome and elevated levels of alpha-fetoprotein and acetylcholinesterase. Three fetuses with both open spina bifida and ventral wall defects were associated with ratios above 0.14. These results suggest that immunochemical determination of acetylcholinesterase and butyrylcholinesterase can be used to distinguish pregnancies complicated by anencephaly, open spina bifida, encephalocele and miscarriage from those with ventral wall defects and samples with false positive elevated levels of alpha-fetoprotein and acetylcholinesterase. The procedure is accurate and simple to carry out and well suited to routine use in a clinical chemistry laboratory.
5
Malignant potential of juvenile polyposis coli. Report of a case and review of the literature. Juvenile polyps of the colon and rectum traditionally have been viewed as being benign inflammatory or harmartomatous lesions without potential for malignant change. The authors report a case of adenocarcinoma developing in a patient with sporadic juvenile polyposis. Juvenile polyposis was diagnosed in the patient at age 4 years. He underwent subtotal colectomy at age 6 years. At age 12, he underwent a proctectomy and a Swenson pull-through because of adenomatous changes in the rectal stump. At age 19 surveillance endoscopy revealed invasive cancer in a juvenile polyp.
1
Malignant left-sided large bowel obstruction managed by subtotal/total colectomy. Of 60 patients presenting with acute obstructing carcinoma of the left colon, 49 underwent immediate resection either by radical subtotal/total colectomy (31 patients, group I) or by radical segmental resection (18 patients, group II) of whom three had immediate anastomosis after on-table bowel irrigation and 15 had a planned staged procedure. The operative mortality rate was 3 per cent in group I and 11 per cent in group II (not a statistically significant difference). However, substantial differences were found for major morbidity (6 versus 44 per cent in groups I and II respectively; P less than 0.01) and mean length of hospital stay (17 days in group I versus 35 days in group II; P less than 0.05). All three patients who had on-table lavage developed anastomotic leaks which necessitated a second operation to form a stoma. Six patients (19 per cent) in group I required antidiarrhoeal medication in the immediate postoperative period. However, subsequent improvement in stool frequency was noted in all patients. It is concluded that subtotal/total colectomy is an acceptable means of managing patients with obstructing carcinoma of the left colon in that it is associated with a low morbidity and mortality rate and good functional results.
1
The reliability of frozen sections in the evaluation of surgical margins for melanoma. As the width of surgical margins declines, histologic evaluation of the margins is needed to assess the completeness of excision of a malignant melanoma. We studied 221 specimens in 59 patients and compared the interpretations of frozen and paraffin sections from the same block. Frozen sections had a sensitivity of 100% in detecting melanoma when present and a specificity of 90%.
3
Histopathologic correlation of magnetic resonance imaging signal patterns in a spinal cord injury model. Magnetic resonance imaging (MRI) provides a noninvasive method of monitoring the pathologic response to spinal cord injury. Specific MR signal intensity patterns appear to correlate with degrees of improvement in the neurologic status in spinal cord injury patients. Histologic correlation of two types of MR signal intensity patterns are confirmed in the current study using a rat animal model. Adult male Sprague-Dawley rats underwent spinal cord trauma at the midthoracic level using a weight-dropping technique. After laminectomy, 5- and 10-gm brass weights were dropped from designated heights onto a 0.1-gm impounder placed on the exposed dura. Animals allowed to regain consciousness demonstrated variable recovery of hind limb paraplegia. Magnetic resonance images were obtained from 2 hours to 1 week after injury using a 2-tesla MRI/spectrometer. Sacrifice under anesthesia was performed by perfusive fixation; spinal columns were excised en bloc, embedded, sectioned, and observed with the compound light microscope. Magnetic resonance axial images obtained during the time sequence after injury demonstrate a distinct correlation between MR signal intensity patterns and the histologic appearance of the spinal cord. Magnetic resonance imaging delineates the pathologic processes resulting from acute spinal cord injury and can be used to differentiate the type of injury and prognosis.
5
Intrathecal anaesthesia for day-care surgery. A retrospective study of 160 cases using 25- and 26-gauge spinal needles. The records of 160 day-care surgical patients who received intrathecal anaesthesia were reviewed. No major complications were recorded. The incidence of postspinal headache after puncture with a 25-gauge spinal needle was nearly four times more frequent compared to a 26-gauge needle. The occurrence of postspinal headache in patients over the age of 45 years was significantly less frequent (p less than 0.05) than in younger patients. Intrathecal anaesthesia was acceptable to 91% of outpatients in this group.
5
Soft tissue sarcoma with additional anaplastic components. A clinicopathologic and immunohistochemical study of 27 cases. This clinicopathologic study concerns 27 cases of "dedifferentiated" soft tissue sarcoma (DSTS), including 14 liposarcomas, six leiomyosarcomas, five chondrosarcomas, and two rhabdomyosarcomas. In addition, the authors conducted an immunohistochemical survey of 23 cases and an electron microscopic examination of three. The findings were compared with observations of 32 cases of de novo malignant fibrous histiocytoma (MFH). All tumors contained additional distinct anaplastic portions indistinguishable from MFH under conventional light microscopy, ultrastructurally, and in cases of immunoreactivity for alpha-1-antichymotrypsin and alpha-1-antitrypsin and on lectin histochemical findings for ricinus communis agglutinin and concanavalin agglutinin. The desmin reactivity present in anaplastic portions of 14 DSTS and in eight de novo MFH is taken to mean that myofibroblasts are present in these tumors. The anaplastic components of DSTS are presumed to represent the proliferation of another clone of undifferentiated mesenchymal cells that fail to differentiate along any specific lineage other than fibroblast-like cells, histiocyte-like cells, and myofibroblasts. Nineteen patients died of tumor and four are alive and well 1.6, 1.7, 2.1, and 5.2 years after the initial treatment, respectively.
5
Extracorporeal photopheresis in psoriasis vulgaris: clinical and immunologic observations. Four patients with chronic refractory plaque-type psoriasis without arthropathy were treated with extracorporeal photopheresis every other week for 6 to 13 months. In patients 1 and 2, methotrexate was administered concomitantly during the initial part of the trial; the dose was gradually tapered and the drug was discontinued by 6 months. Both patients improved to 23% and 62% of baseline values for percentage of body surface involvement, but their disease then flared when maintenance extracorporeal photopheresis was used alone. Substantial improvement again occurred when lower doses of methotrexate were administered with extracorporeal photopheresis. Patients 3 and 4 were treated initially with extracorporeal photopheresis alone and both improved to 50% and 52% of baseline body surface involvement, respectively, after 4 months of treatment. However, their disease flared because of factors unrelated to treatment. Extracorporeal photopheresis was well tolerated by all patients without evidence of overt toxicity. However, prolonged treatment with extracorporeal photopheresis/methotrexate was accompanied by a decrease in skin reactivity to recall antigens and by decreased capacity of lymphocytes to produce interleukin 2 in response to polyclonal stimuli in vitro. These findings indicate that alternate-week extracorporeal photopheresis has a definite but incomplete suppressive effect on psoriasis vulgaris that may be mediated through an effect on lymphokine production by photomodified cells and that the therapeutic effect of extracorporeal photopheresis may be enhanced by concomitant administration of low doses of methotrexate.
3
Microsaccadic flutter. Microsaccadic flutter is a rare symptomatic saccadic oscillation that has been reported only twice previously. Here we describe 5 patients with this disorder. The oscillation is horizontal, has a frequency of 15-30 Hz, an amplitude of 0.1-0.5 degrees, and cannot be seen with the unaided eye. It is usually not associated with any underlying neurological disorder. We hypothesize that microsaccadic flutter is due to malfunction of the brainstem omnipause neurons.
4
Acute dissection of the internal mammary artery: a fatal complication of coronary artery bypass grafting. A case of acute traumatic dissection of the right internal mammary artery is presented in a patient who had both IMAs grafted for recurrent angina 10 years after initial vein coronary revascularisation. The event was mistaken for spasm, but because of severe circulatory collapse no time was available to treat the patient appropriately. The purpose of this report is to facilitate the early recognition and avoidance of this potentially fatal complication.
1
Intraoperative pancreatic fine needle aspiration biopsy. Results in 166 patients. Intraoperative fine needle aspiration biopsy (NAB) of undiagnosed pancreatic masses was studied in 166 patients over a 17-year period. The cytologic diagnoses were correlated with histologic specimens, autopsy results, or clinical follow-up (benign disease was documented if the patient was alive without malignancy at least 2 years after laparotomy). Aspirates were interpreted as benign, suspicious, malignant, or unsatisfactory. Malignant disease was the final diagnosis in 109 patients; the cytology was concordant in 101 and was interpreted as suspicious in four. Four patients with benign cytology later proved to have malignant disease--a false-negative rate of 2.5 per cent. A total of 57 patients had benign disease; 51 of these had benign cytology. The remaining patients had "unsatisfactory" cytology reports. A 93 per cent sensitivity, 100 per cent specificity, and 0 per cent complication rate are reported. There were no false-positive cytology reports. Complications are rare and represent case reports, thus, additional sampling is at minimal risk. Intraoperative pancreatic NAB is a safe, easy, more accurate biopsy technique than historical wedge or core needle biopsies. It is the biopsy method of choice for pancreatic masses found at laparotomy.
5
Total hip arthroplasty in ankylosing spondylitis. Total hip arthroplasty was performed on 29 hips in 19 patients diagnosed with ankylosing spondylitis over a 13-year period. The results were analyzed retrospectively with an average follow-up period of more than four years. Complete pain relief was achieved in 97%, and significant gains were made in ambulatory capacity. The limited gains in total range of motion (average improvement 75 degrees) were felt to be primarily due to the high incidence of Brooker Class III and IV myositis ossificans (23%) and long-standing soft tissue contractures.
5
Vascular complications after orthotopic liver transplantation. Over a 57-month period, we performed 430 orthotopic liver transplants in 372 patients. A total of 38 vascular complications were identified including hepatic artery thrombosis (n = 24), portal vein thrombosis (n = 6), combined hepatic artery thrombosis/portal vein thrombosis (n = 3), and hepatic artery rupture (n = 5). A number of potential risk factors for the development of vascular thrombosis were evaluated with only children, weight less than 10 kg, and cold ischemia time found to be significant. The clinical presentation included fulminant hepatic failure, allograft dysfunction, biliary sepsis, and screening ultrasound. Duplex ultrasonography was diagnostic in nearly all cases. Therapeutic modalities included revascularization, revascularization followed by retransplantation, retransplantation alone, and observation. Five cases of hepatic artery rupture occurred in four patients. Infectious arteritis was present in four patients. The 6-month actuarial survival in patients with vascular complications was 70%. Early diagnosis is critical for graft salvage, with surgical intervention the mainstay of therapy.
1
Defining the role of subtotal colectomy in the treatment of carcinoma of the colon. Seventy-two patients with colon cancer were treated by primary subtotal colectomy, including 23 patients with acute and subacute left colon obstruction. There were two operative deaths and no cases of disabling diarrhea. One death occurred in the group with colon obstruction. Other indications for subtotal colectomy included multiple polyps associated with the primary tumor (32), synchronous carcinomas (15), a previous transverse colostomy for obstruction (8), associated severe sigmoid diverticular disease (2), age less than 50 years with a positive family history (3), adherence of the sigmoid loop to a cecal tumor (2), and metachronous carcinoma (2). There were multiple indications in several patients. Subtotal colectomy has a defined role in a wide variety of clinical settings associated with colon cancer, including management of obstruction of the left and sigmoid colon, particularly if the proximal colon cannot be evaluated before operation by colonoscopy or barium enema. Segmental or regional colonic resections are appropriate if the entire colon can be evaluated before operation and no associated neoplasms are revealed.
1
Paratesticular myxoma: an unusual benign intrascrotal neoplasm. We have presented a case of paratesticular myxoma and have described the clinical history, findings on light microscopy and immunohistochemistry, and possible pathogenesis. Although primary paratesticular myxoma is a rare lesion, it should be considered in the differential diagnosis of intrascrotal mesenchymal tumors.
2
Amelioration of cholinergic-induced pancreatitis with a selective cholecystokinin receptor antagonist. Acute edematous pancreatitis follows excessive cholinergic stimulation in patients exposed to anticholinesterase-containing insecticides. We describe the role of cholecystokinin and the benefits of cholecystokinin receptor blockade in this form of pancreatitis. A cholinergic mimetic (carbachol) was administered to rats weighing 300 to 350 g and produced a form of edematous pancreatitis that mimics that seen in humans. Animals received carbachol intraperitoneally, either alone (250 micrograms/kg of body weight) or with cholecystokinin-receptor antagonist devazepide (3 mg/kg of body weight) and were killed 4 hours later. Carbachol administration resulted in a 19% increase in pancreatic weight, a fourfold increase in serum amylase levels, and a 14-fold increase in serum lipase levels. Plasma cholecystokinin levels, however, were not altered. Devazepide administered prior to cholinergic hyperstimulation blocked pancreatic weight increase and reduced elevations in serum amylase levels twofold and lipase levels fourfold. Although cholecystokinin levels are not elevated in this model of pancreatitis, blockade of even low, background concentrations of this regulatory peptide is beneficial.
3
Tardive dyskinesia. Tardive dyskinesia is a potentially irreversible syndrome of involuntary hyperkinetic movements that occur in predisposed persons receiving extended neuroleptic (antipsychotic) drug therapy. It is usually characterized by choreoathetoid dyskinesias in the orofacial, limb, and truncal regions, but subtypes of this syndrome may include tardive dystonia and tardive akathisia. Although the mechanisms underlying the pathogenesis and pathophysiology of this disorder are unproven, altered dopaminergic functions will likely play a role in any explanation of it. Tardive dyskinesia develops in 20% of neuroleptic-treated patients, but high-risk groups such as the elderly have substantially higher rates. Risk factors include age, female sex, affective disorders, and probably those without psychotic diagnoses, including patients receiving drugs with antidopaminergic activity for nausea or gastrointestinal dysfunction for extended periods. Total drug exposure is positively correlated with tardive dyskinesia risk. Management strategies include a careful evaluation of both the psychiatric and neurologic states, a broad differential diagnosis, and adjustment of neuroleptic agents to the lowest effective dose that controls psychosis and minimizes motor side effects. No drug therapy is uniformly safe and effective for treating this disorder. A favorable long-term outcome of improvement or resolution correlates with younger age, early detection, lower drug exposure, and duration of follow-up.
4
Clinical experience with technetium-99m teboroxime, a neutral, lipophilic myocardial perfusion imaging agent. Technetium-99m (Tc-99m) teboroxime is a new technetium-based myocardial perfusion imaging agent (investigational code = SQ30217 [Cardiotec, Squibb Diagnostics]). A member of a class of neutral, lipophilic, technetium-containing complexes known as boronic acid adducts of technetium dioxime (BATO) complexes, this agent is chemically very different from the cationic tracer thallium-201 (Tl-201) and from the cationic technetium complex Tc-99m sestamibi (Cardiolite, Du Pont Imaging Agents). Tc-99m teboroxime has high myocardial extraction, rapid blood clearance, little lung uptake and rapid myocardial washout. A biexponential pattern of myocardial washout is demonstrated in animals and in man. Effective half-lives of the 2 washout components in man are 5.2 minutes and 3.8 hours and represent approximately 66 and 33% of the myocardial activity, respectively. The first half-life for the myocardium is approximately 11 minutes. As the agent washes out of the heart, hepatic uptake occurs, peaking at about 5 minutes after injection. The liver is the major organ of excretion and receives, along with the large bowel, the largest radiation dose. Rapid imaging protocols using standard cameras have achieved good myocardial counts from 3 planar views acquired over a 4- to 5-minute period or for single photon emission computed tomography (SPECT) images acquired over a 10-minute period. An entire stress/rest procedure can be completed in 1 hour. Analysis of data from 155 patients from 4 centers using planar or SPECT imaging showed a sensitivity and specificity for blinded readings of 82 and 91%, respectively, when compared against overall clinical impression.
1
Early gastric cancer. Endoscopic diagnosis of depth of invasion. In order to decide on a treatment strategy against gastric cancers, an accurate preoperative evaluation of the depth of cancer invasion is essential. Preoperative endoscopic diagnosis of the depth of invasion was compared with pathological results of the resected specimen in 206 early gastric cancers and 32 early-like advanced gastric cancers. The endoscopic distinction between early and early-like advanced cancers was correctly made in 83.6% of the cases. Among the early gastric cancers, mucosal and submucosal invasion was correctly presumed in 71.9% of the cases. When the tumor was an elevated type, or located in the antrum, the endoscopic diagnosis tended to be deeper than the true depth. The size of tumor contributed little to the depth diagnosis. Pathomorphological changes on the tips of converging folds were the important clue for diagnosing depth.
5
A histological and flow cytometric study of dog brain endothelial cell injuries in delayed radiation necrosis. The pathogenesis of delayed cerebral radiation necrosis was studied histologically and biochemically in 25 dogs with special attention to vascular endothelial cell injuries. The dogs were sacrificed 3 to 30 months after irradiation with a single dose of 15 Gy to the head. Brain specimens were appropriately fixed for light and electron microscopic studies, and capillary endothelial cells were isolated for flow cytometric study. The endothelial cells were stained with acridine orange, then the cell ratios in the reproductive phase (S + G2 + M) were investigated with flow cytometry. Thereafter, Feulgen hydrolysis and computer analysis of the hydrolysis curves were performed to examine the qualitative changes in deoxyribonucleic acid (DNA) of endothelial cells after irradiation. Under light microscopy, spongy degeneration with small cell infiltration was observed, especially in the frontal white matter, at 6 months after irradiation. At 9 months, necrotic foci appeared and developed until 15 months after irradiation. Blood vessels around the necrotic area showed luminal narrowing with endothelial hyperplasia and proliferation. At 30 months, no fresh necrotic lesions were observed. Under electron microscopy, endothelial cells of capillaries and small vessels around the necrotic area showed an increase of pinocytosis, and in the nuclei there was an increase of infoldings and euchromatin. The cell ratios in the reproductive phase were 14.5% to 23.3% (maximum at 9 months) in the irradiated group compared to 6.4% in the control group. The rate constant of apurinic acid production, a parameter correlating with DNA transcriptional activity, was minimum at 3 months and maximum at 9 months after irradiation. The data suggest that impairment of the microcirculation plays an important role in the pathogenesis of delayed radiation necrosis, and that the time of necrosis occurrence closely correlates with the cell cycle of vascular endothelial cells.
2
Twelve hour overnight oesophageal pH monitoring in patients with reflux symptoms. Results of continuous 12 hour overnight pH monitoring (duration of pH less than 4) were reviewed in 112 patients with heartburn or regurgitation, or both, and in 56 normal subjects. Patients had more reflux than normal subjects. Medically controlled patients (n = 51) had less acid reflux than patients who subsequently underwent reflux surgery (n = 61), but there was a considerable overlap between those two groups. Surgery was followed by a reduction in acid reflux to a value similar to that in normal subjects. Patients in whom surgery was deemed to have failed had more reflux after the operation than those in whom it was successful, but no difference could be found in the preoperative reflux values of these two subgroups. Monitoring pH is not of value in selecting candidates for surgery since the results are not a good predictor of outcome, but it is useful in the objective evaluation of surgical results.
5
HLA-D locus associations in alopecia areata. DRw52a may confer disease resistance. Because predisposition to autoimmunity has been associated with HLA-D alleles and alopecia areata is hypothesized to be a T-cell mediated autoimmune hair loss, we determined DR and DQ alleles in 88 white and 10 American black patients with alopecia areata as well as controls with the use of restriction fragment length polymorphism typing with cDNA probes. White patients with alopecia areata have an increase in the phenotype frequencies of DR4 and DQw8 and an increase in genotype frequencies of DR4 and DR5 (now DRw11[5]). These associations are in agreement with those reported in two other studies but are not significant when corrected by the number of HLA antigens tested. Sixty-one percent of all patients with AA have DR4 and/or DRw11(5) specificities vs 40% of controls, with more DR4,DRw11(5) and DQw7(w3), DQw8(w3) heterozygotes among patients. DQw6(w1) phenotype frequencies and DRw52a phenotype and genotype frequencies are significantly decreased in patients with alopecia areata relative to controls. This highly significant negative association with the HLA DRB3 allele DRw52a in whites persisted even when DR4- or DRw11(5)-positive individuals were excluded from the patient and control groups. These data suggest that HLA-DR4 and DRw11(5) with their associated DQw7(w3) and DQw8(w3) specificities may confer susceptibility to alopecia areata, while DRw52a may confer resistance.
5
Six year follow up of infants with bacteriuria on screening. OBJECTIVE--To determine the value of screening for bacteriuria in infants with special emphasis on the natural course of untreated asymptomatic bacteriuria, renal growth, and renal damage. DESIGN--Prospective six year follow up of infants with bacteriuria on screening in an unselected infant population. SETTING--Paediatric outpatient clinic. PATIENTS--50 Infants (14 girls, 36 boys) with bacteriuria on screening verified by suprapubic aspiration from an unselected population of 3581 infants in a defined area of Gothenburg. INTERVENTIONS--Children with asymptomatic bacteriuria and normal findings on initial urography were untreated, although other infections were treated. MAIN OUTCOME MEASURES--Culture of urine and determination of C reactive protein concentration every six weeks for the first six months after diagnosis, every three months from six months to two years, and every six months between two and three years; thereafter yearly urine culture. Evaluation of renal concentrating capacity with a desmopressin test; radiological examination, including first and follow up urography and micturition cystourethrography without antibiotic cover; and measurement of renal parenchymal thickness and renal surface area. RESULTS--Of the original 50 infants, 37 (12 girls, 25 boys) were followed up for at least six years. Two infants developed pyelonephritis within two weeks after bacteriuria was diagnosed; the others remained free of symptoms. 45 Infants were untreated; the bacteriuria cleared spontaneously in 36 and in response to antibiotics given for infections in the respiratory tract in eight. Recurrences of bacteriuria were observed in 10 of the 50 children, of whom one had pyelonephritis. No child had more than one recurrence. At follow up urography in 36 of the 50 children (9 girls, 27 boys) after a median of 32 months no child had developed renal damage. First samples tested for renal concentrating capacity showed significantly higher values than those from a reference population (mean SD score 0.50, 95% confidence interval 0.21 to 0.79; p less than 0.001), but the last samples showed no significant difference (mean SD score 0.08, -0.24 to 0.40; p greater than 0.05). CONCLUSIONS--Mass screening for bacteriuria in infancy results primarily in detection of innocent bacteriuric episodes and is not recommended.
1
Human tumor fluorouracil trapping: clinical correlations of in vivo 19F nuclear magnetic resonance spectroscopy pharmacokinetics. We previously reported that fluorouracil (5FU) accumulation and metabolism in human livers and tumors can be studied by in vivo nuclear magnetic resonance spectroscopy (NMRS). We have extended these observations by evaluating the pharmacokinetics of 5FU in the tumors of 11 patients with carcinoma of the breast, colon, endometrium, cervix, and kidney, using 19F-NMRS in a 1.5 Magnetom (Siemens Medical Systems, Cerrito, CA) magnetic resonance imaging unit (MRI). These NMRS measurements detected a long-lived tumor pool of 5FU in six of 11 tumors in our patients including carcinomas in the pelvis, breast, lung, and liver. The half-life (T1/2) of this tumor pool of "trapped" 5FU was 0.33 to 1.3 hours (20 to 78 minutes), much longer than the T1/2 of 5FU in blood (5 to 15 minutes). Neither the anabolites of 5FU (fluorinated nucleosides, nucleotides, 5FU-RNA, or 5FU-thymidylate synthase) nor the catabolites (eg, fluorobetaalanine [FBAL]) were detectable by 19F NMRS. Patient response to chemotherapy appeared to correlate with the extent of trapping of free 5FU in the human tumors: in the seven patients receiving 5FU, or 5FU or FUdR plus leucovorin, four of four patients whose tumors trapped 5FU responded to fluorinated pyrimidine chemotherapy, whereas three patients in whom there was a failure to detect tumor trapping were resistant to 5FU. We conclude that NMRS is clinically feasible, and enables investigators to study 5FU pharmacokinetics and metabolism in tumors in vivo. 19F-NMRS of 5FU allows for in vivo evaluation of 5FU metabolic modulation and might be able to guide therapeutic decisions.
1
Gallbladder carcinoma producing human chorionic gonadotropin. A primary carcinoma of the gallbladder producing human chorionic gonadotropin (HCG) was encountered in an 83-yr-old Japanese woman, with elevation of HCG/beta-HCG in urine and serum. Remarkable elevation of serum estradiol was an associated finding, with increased HCG. At autopsy, we found that the primary carcinoma of the gallbladder extensively involved the liver. Histologically, the tumor revealed adenosquamous cell carcinoma in the primary site, and moderately to poorly differentiated adenocarcinoma in metastatic foci. Immunohistochemical staining for beta-HCG showed a positive reaction in adenocarcinoma components. This is an extremely rare case of an HCG-producing gallbladder carcinoma, which leads us to speculate that HCG-positive tumor cells may occur due to dedifferentiation.
3
Osseointegration of titanium implants in total hip arthroplasty. Osseointegration is defined as direct contact on the light microscopic level between living bone tissue and the implant. Using titanium screw dental implants in the jaw, a lasting interface under loaded conditions extending over a 20-year follow-up period has been demonstrated. This demonstration brings up the question whether a similar interface can be achieved in total hip arthroplasty (THA) between living bone and a titanium alloy implant under necessitated conditions of immediate loading. Two series of cases are reported. The first series used a femoral, press-fit, titanium alloy component and the second used a press-fit titanium acetabular component and redesigned femoral, press-fit, titanium alloy component. Both demonstrated a high percentage of good to excellent results. Roentgenograms showed that the geometrical changes in the redesigned femoral component gave early indications of a better fixation with loading in valgus, less subsidence, and less evidence of distal stress transfer. A two-and-one-half-year postoperative anatomic specimen study confirmed osseointegration to the press-fit titanium alloy femoral component. Multiple areas of contact between bone and metal without fibrous interposition were seen. Examination by electron microscopy supported the light microscopic findings. These findings support further use of smooth, press-fit titanium components in THAs without the need for porous coating, mesh, or other surface modifications.
4
Early outcome after placement of a metallic intracoronary stent: initial Mayo Clinic experience After percutaneous transluminal coronary angioplasty, 3 to 7% of patients have in-hospital coronary closure, and the risk of subsequent myocardial infarction is high, even with an urgent bypass operation. Disrupted coronary morphologic integrity, particularly with large dissections, may be associated with an increased risk of acute coronary closure. A percutaneously placed coronary vascular stent may rapidly alleviate acute or threatened coronary closure and could reduce morbidity. Between October 1989 and June 1990, placement of a balloon-expandable, flexible metallic coil (Gianturco-Roubin) coronary stent was attempted 16 times in 15 Mayo Clinic patients--for treatment of actual or threatened abrupt coronary closure in 10 patients, for primary treatment of a lesion judged to be at high risk for dissection with conventional balloon angioplasty in 1, and for elective treatment of restenotic lesions in 5. Placement of the stent was successful in 15 attempts (94%). Associated complications, which were uncommon, were similar to those noted after balloon angioplasty. No early deaths occurred, and no patient required coronary artery bypass grafting. Stents were successfully placed in both urgent and elective circumstances in native coronary arteries and saphenous vein grafts, and they were used in primary atheromatous and restenotic lesions. Our initial experience with this metallic coil stent indicates that it is efficacious for vascular disruption that is threatening or causing coronary closure after angioplasty. Furthermore, elective placement of a stent may be safely undertaken in patients with high-risk coronary lesions or recurrent restenotic lesions. The long-term outcome in all groups of patients who receive coronary stents is unknown.
4
Splinter hemorrhages as a possible clinical manifestation of cholesterol crystal embolization. We describe a patient with cholesterol crystal embolization who demonstrated splinter hemorrhages of multiple fingernails and toenails as part of her clinical presentations. Our patient's clinical presentation, and review of the medical literature, raise the possibility that cholesterol crystal embolization may be associated with splinter hemorrhages.
5
Colorectal adenocarcinoma in patients less than 40 years of age. From 1973 to 1985, 105 patients under 40 years of age were treated for colorectal adenocarcinoma at Roswell Park Cancer Institute. There were 51 males and 54 females. The mean age was 32 years. The majority of patients were treated for left colon or rectal carcinomas. Ninety-seven of 105 patients underwent surgical resection of their primary cancer, 70 (67 percent) of which were potentially curative. Twenty-seven patients underwent palliative resections. Dukes' A or B lesions were not seen in patients less than 20 years old, whereas these early lesions were seen in 11 percent of patients 20 to 29 years old and in 26 percent of patients greater than 30 years of age. The mean survival for patients between 20 and 29 years was 39 months and 46 months for patients 30 years and older.
5
Current status of organ preservation with University of Wisconsin solution. A retrospective analysis of all organs that were preserved with University of Wisconsin solution was undertaken to assess the impact of this solution on early allograft function. From May 1987 until June 1990, 181 livers, 92 pancreata, and 92 kidneys were preserved with University of Wisconsin solution for extended periods of time. The mean (+/- SD) preservation times were as follows: liver, 12.6 +/- 4.5 hours; pancreas, 16.7 +/- 4.4 hours; and kidney, 18.3 +/- 4.3 hours. The overall rate of primary nonfunction and hepatic artery thrombosis were 6.1% and 3.9%, respectively. No differences in the rates of primary nonfunction and hepatic artery thrombosis were noted for combined liver-pancreas procurement vs isolated liver retrievals or when reduced-size liver transplants were compared with nonreduced liver transplants. Likewise, no difference in primary nonfunction or hepatic artery thrombosis was seen in livers that were preserved for less than 6, 6 to 12, and greater than 12 hours. However, serum aminotransferase levels and prothrombin times were lower on the first postoperative day in livers that were preserved for less than 6 hours when compared with 6 to 12 or greater than 12 hours. Early pancreatic allograft function was also excellent for up to 24 hours of cold-storage preservation. All patients were immediately insulin independent, and there were no cases of initial nonfunction or graft pancreatitis. There were only two cases (2.2%) of pancreatic vascular thrombosis in this series. No difference in pancreatic function was noted for organs that were preserved for less than 6, 6 to 12, or greater than 12 hours. Likewise, renal allograft function was excellent, with only two patients (2.2%) requiring postoperative hemodialysis. The actuarial 1-month patient survival for liver and pancreas-kidney transplant recipients was 91.5% and 98.9%, respectively. Actuarial 1-month allograft survival for liver, pancreas, and kidney transplants was 83.0%, 96.7%, and 97.8%, respectively. In conclusion, University of Wisconsin solution represents a significant advancement in cold-storage organ preservation and is ideally suited as a universal intra-abdominal aortic-flush and cold-storage solution.
4
Incidence and clinical significance of ST segment elevation after electrical cardioversion of atrial fibrillation and atrial flutter. To study the incidence and clinical significance of postshock ST segment elevations, we recorded 12-lead ECGs immediately after transthoracic direct-current electrical cardioversion in 146 patients with atrial fibrillation or flutter. Among 23 patients (19%), acute ST segment elevations amounted to 1.4 +/- 0.8 mV (mean +/- SD) and occurred after 243 +/- 114 joules (cumulative dose) in the precordial leads only in 14, concomitantly in precordial and inferior leads in two, and in the precordial and anterolateral leads in seven. They normalized within 1.5 +/- 0.8 minutes. Occurrence of ST segment elevation was related to previous pericardiotomy (p less than 0.00001) and age (p = 0.01). Estimation of myocardial enzyme release did not show evidence of myocardial damage. Patients with ST segment elevations had a lower conversion rate (48% versus 76%, p = 0.005). Long-term maintenance of sinus rhythm was also diminished (35% versus 59%, p = 0.03). Results of this study show that postcardioversion ST segment elevation occurs predominantly in postpericardiotomy patients and may be associated with an unfavorable arrhythmia prognosis.
5
Accumulation of p21ras.GTP in response to stimulation with epidermal growth factor and oncogene products with tyrosine kinase activity. The ras gene product (p21) is a GTP-binding protein and has been thought to transduce signals regulating proliferation or differentiation of cells. Like other GTP-binding proteins, p21.GTP is an active conformation, which can transduce the signals downstream, whereas p21.GDP is an inactive one. Recently, we have shown that p21.GTP levels increased in cells treated with fetal bovine serum or platelet-derived growth factor to initiate DNA synthesis. In this paper, we report that epidermal growth factor can also increase the amounts of p21.GTP in the cells. Effects of epidermal growth factor and platelet-derived growth factor are not additive. In contrast, mutant [Val12]p21, which has transforming activity, responded neither to platelet-derived growth factor nor to epidermal growth factor. We also found that the ratio of p21.GTP to p21.GDP increased 3- to 4-fold in transformants carrying activated erbB-2/neu or v-src oncogenes. These results strongly suggest an important role of p21 in transduction of signals for both normal proliferation and malignant transformation through growth factor receptors with tyrosine kinase activity or related oncogene products.
5
Reduction of gastric ulcer recurrence after suppression of Helicobacter pylori by cefixime. The effect on the recurrence of gastric ulcers after suppression of Helicobacter pylori by combined treatment with cimetidine and the antimicrobial drug cefixime was investigated. Twenty one of 43 patients with endoscopically proved gastric ulcer and H pylori infection were randomly assigned to receive cimetidine 800 mg daily for 12 weeks; the remaining 22 patients received cimetidine 800 mg daily for 12 weeks plus cefixime 100 mg daily for the last two weeks. After treatment, 88% of 17 patients on cimetidine only remained H pylori positive, whereas combined administration of cimetidine and cefixime had suppressed H pylori in 78% of 18 patients (p less than 0.05). Seventeen patients in the former group whose ulcers healed but who remained H pylori positive and 18 patients in the latter group whose ulcers healed and who were no longer infected with H pylori continued to be followed after treatment. These patients underwent endoscopy to detect ulcer recurrence if symptomatic, or at 12 and 24 weeks if asymptomatic. At 12 weeks, recurrence was observed in seven of 15 (47%) patients in whom H pylori persisted, but in only one of 14 (7%) patients in whom H pylori had been suppressed (p less than 0.05). At 24 weeks, however, recurrence rates were similar between the two groups. These findings indicate that H pylori infection may be closely related to early ulcer recurrence.
4
Infrainguinal revascularization for limb salvage in patients with end-stage renal disease. We studied the efficacy of infrainguinal bypass for limb salvage in patients with end-stage renal disease. The patency of 42 femoropopliteal and femorodistal bypasses, performed for limb salvage in 37 patients with end-stage renal disease, was assessed with Doppler ultrasonography and dye tests. Patency rates and limb salvage were determined by life-table analysis. Average age was 45 years (range, 28 to 61 years); 23 of the 37 were men. Twenty-three patients had diabetes mellitus, and 16 were smokers. Bypass procedures were done in 32 instances while the patients were maintained with chronic hemodialysis and in five instances with peritoneal dialysis; in five instances the patients had had successful renal transplantation. Indications for revascularization included pain at rest, nonhealing ulcer, or distal gangrene. Femoropopliteal bypass was done in 32 limbs; 10 were more distal procedures. Reversed saphenous vein was the conduit in 30 cases; prosthetic material was used in the remainder. Autogenous material was used in all distal bypasses. Four patients required graft revision during the initial hospitalization, but none thereafter. Two patients died within the operative period, nine within 18 months of operation. Nine major operations were required. Three-month cumulative graft patency was achieved in 41 cases and corresponding limb salvage in 33 cases; 18-month patency was achieved in 34 cases and overall limb salvage in 33 cases. Success of limb salvage most closely correlated with preoperative ankle-brachial ratio and level of bypass required.
2
Stimulation of glucagon secretion by gastric inhibitory polypeptide in patients with hepatic cirrhosis and hyperglucagonemia. Porcine gastric inhibitory polypeptide (GIP) was infused iv (120 micrograms in 60 min) in seven patients with biopsy-proven hepatic cirrhosis who had surgical porta-caval anastomoses and hyperglucagonemia in the postabsorptive state. The infusions resulted in elevation of blood levels of immunoreactive GIP into the upper range of those observed after ingestion of large mixed meals. This was accompanied by significant increments in immunoreactive glucagon (IRG) in the plasma. Similar infusions in two cirrhotic patients with surgical porta-caval anastomoses who had normal plasma IRG levels in the postabsorptive state had no effect on the plasma IRG level. Ingestion of triglyceride (60 g) in hyperglucagonemic cirrhotic patients with porta-caval anastomoses also resulted in elevation of plasma immunoreactive GIP, and this was again associated with significant elevation of the plasma IRG level. Chromatography studies showed that the increments in plasma IRG after the administration of GIP or triglyceride were largely accounted for by increases in pancreatic-type glucagon. There were no significant effects of administration of GIP or triglyceride on the blood levels of glucose or immunoreactive insulin. It is concluded that porcine GIP is glucagonotropic in patients with cirrhosis of the liver who show elevated levels of IRG in the plasma in the postabsorptive state. This effect is not due to diversion of portal blood to the systemic circulation and may be attributable to hypersensitivity of the alpha-cells to stimulation by GIP.
2
A new method for mapping hepatic subsegment: counterstaining identification technique. Hepatic subsegmentectomy requires identification of the borders of tumor-bearing subsegment, usually achieved by injecting dye into the portal veins feeding the domain. We describe an alternative technique for performing systematic subsegmentectomy in patients with cirrhosis and hepatocellular carcinoma, in whom hepatic arterial and portal venous embolizations were already performed as a preoperative adjuvant. Under ultrasonic guidance, each of the neighboring portal units is sequentially stained, thus defining the avascular subsegment to be resected as the nonstaining area. This allows the subsegment to be totally resected. This counterstaining identification technique can be used for all subsegments undergoing complete embolization and for other situations in which the usual staining method is impossible because of the presence of arterioportal shunting or portal tumor thrombus.
3
Standard v lightweight wheelchair propulsion in spinal cord injured patients. Twenty-six male SCI subjects (six quadriplegics, eight "high paraplegics," and 12 "low paraplegics") propelled both standard and lightweight wheelchairs at a "sprint pace" (Sp) for 400 feet, and at a "duration pace" (Du) for four continuous minutes. Pulse, blood pressure and respirations were measured before and after each trial, and V was calculated. Appropriate training and rest periods were given; order of wheelchair testing was randomized. A questionnaire was later administered. Variations in pulse, systolic blood pressure, and respirations were significant between myelopathic levels (P less than 0.01), but were not affected by the type of wheelchair used. Quadriplegic V was less (P less than 0.01) than that of either paraplegic group for Sp and Du trials; for Sp, lightweight wheelchair V is faster (P less than 0.01) than standard wheelchair V for all groups.
3
Gallbladder surgery following cholecystlithotripsy: suggested guidelines for treatment Twenty-three of 229 symptomatic patients undergoing cholecystlithotripsy underwent surgical intervention: 22 of the patients had cholecystectomy performed (five also undergoing choledochotomy) and one patient had a cholecystostomy. Of these 23 patients, five were lithotripsy failures, five developed acute pancreatitis, one had acute cholecystitis, and one had cholangitis. One patient had her gallbladder removed incidentally at the time of surgery for a bleeding gastric ulcer. Ten patients underwent surgery for recurrent biliary pain, probably related to fragment passage via the cystic duct. We suggest that up to 16 of these 23 patients did not necessarily require cholecystectomy, i.e. five patients with pancreatitis, one patient with cholangitis and ten patients with recurrent biliary colic. Conservative and/or endoscopic management may be successful in the first instance to allow further treatment with lithotripsy in the majority of patients. If, however, the expertise to perform endoscopic sphincterotomy is not available or the patient declines further lithotripsy, then resort to surgery may be necessary. We propose that it is the responsibility of the management team in charge of the lithotripsy unit to inform both the patient and the referring clinicians of the possible side-effects and outcome of treatment in an attempt to avoid unnecessary surgical procedures.
5
Physiologic parameters and perceived exertion with local muscle fatigue in postpolio subjects. Fifty postpolio patients, 34 with and 16 without complaints of progressive loss of muscle strength, and 41 control subjects were studied to compare physiologic measures of the fatiguing process and to determine whether there is a significant interaction between the rating of perceived exertion (RPE) and physiologic measures. Statistical analyses were by ANOVA and repeated-measures ANOVA. The RPE was obtained every 20 seconds during an isometric contraction of the quadriceps at 40% of maximal torque; median frequency (Fm) of the power spectrum of the surface electromyographic signal and neuromuscular efficiency (NME) were constantly monitored. The RPE increased similarly (p greater than .05), whereas Fm and NME decreased similarly (p greater than .05) during endurance exercise at 40% of maximal torque in all three groups. A significant (p less than .05) interaction was found between RPE and both Fm and NME. We conclude that physiologic measures of the fatiguing process (Fm and NME) occur in a similar manner in postpolio and control subjects and that there is a significant interaction between subjective RPE and physiologic measures of the fatiguing process.
4
The role of intracaval filters in patients with COPD and DVT. A retrospective study of the Coney Island Hospital experience with Greenfield filters over a five-year period was undertaken. During this period, a total of 78 intracaval filters were placed in 76 patients. The patients' charts were reviewed for (1) indication for Greenfield filter placement, (2) complications of the procedure, (3) associated medical problems, and (4) follow-up information. The data revealed one statistically significant subpopulation within the group that had particularly poor survival statistics after intracaval filter insertion. These were patients who had a pulmonary embolism and also had chronic obstructive pulmonary disease (COPD). Considering the low morbidity associated with this procedure, it is the author's feeling that prophylactic intracaval filters in patients with deep vein thrombosis and COPD may be warranted.
2
Peptic ulcer perforation as the presentation of Zollinger-Ellison syndrome. We examined the characteristics of patients with Zollinger-Ellison syndrome who developed a perforation prior to diagnosis to determine whether any clinical features were useful markers of the syndrome. Of 160 patients with Zollinger-Ellison syndrome, perforation occurred prior to the diagnosis being made in 11 (7%). At surgery, perforations were found in the duodenum in six cases and in the jejunum in five. In no case was tumor identified at emergency surgery, and the diagnosis of Zollinger-Ellison syndrome was made only in the postoperative period when excessive gastric secretions were noted. Neither acid output nor serum gastrin concentration were useful predictors for perforation. The patients, six men and five women, were 27-61 years old (median 48) and one had MEN-1. Three patients had no symptoms prior to the perforation. The other eight had symptoms for 1-15 years, with diarrhea occurring in 45% of the cases. Following the diagnosis of Zollinger-Ellison syndrome, patients were given medication to control gastric acid hypersecretion. Eight patients remained well, but the three patients who had had a partial gastrectomy had a complicated course despite medical therapy. Although features of perforation in Zollinger-Ellison syndrome are not specific, jejunal perforation or perforation associated with a history of diarrhea is suggestive of the diagnosis. Serum gastrin should be measured in every case and a partial gastrectomy avoided.
1
Metastatic ciliary body carcinoid tumor. A 50-year-old man with a history of systemic carcinoid had decreased right eye vision and a darkly pigmented cilio-choroidal mass. Results of ultrasonographic and fluorescein angiographic examinations were consistent with a malignant melanoma. Fine-needle aspiration biopsy of the lesion identified it as a carcinoid metastasis. The patient refused both radiation and enucleation; complete excision with a cyclochoroidectomy was performed. Histopathologic examination showed a carcinoid neoplasm covered by marked hyperplasia of the retinal pigment epithelium that produced the pigmented appearance of the lesion.
2
Achalasia of the cardia: long-term results of oesophagomyotomy and posterior partial fundoplication. Forty-eight patients with achalasia of the cardia were treated by Heller's myotomy with a posterior fundoplication of approximately 270 degrees, suturing the gastric fundus to the edges of the myotomy. The mean(s.d.) postoperative follow-up period was 5.4(2.8) years. The clinical results were good to excellent in 44 cases (92 per cent) and fair in four cases (8 per cent) (two with residual dysphagia and two with gastrooesophageal reflux). Barium studies showed a decrease in oesophageal diameter and disappearance of distal narrowing but normal oesophageal emptying did not occur. Postoperative manometric studies (29 patients) revealed a significant decrease in lower oesophageal sphincter pressure and a significant increase in the length of the infradiaphragmatic segment. In the oesophageal body a recovery of peristaltic waves in the proximal third was seen in ten of the patients (34 per cent). Twenty-four-hour pH monitoring showed pathological reflux in only three of 25 patients studied, and one of these was asymptomatic. This technique is effective, improving oesophageal symptoms and controlling long-term reflux.
5
Reperfusion arrhythmias after thrombolysis. Electrophysiologic tempest, or much ado about nothing. Arrhythmias that may accompany myocardial reperfusion have generated significant clinical interest. First, there were concerns, based on animal studies, that high-grade ventricular tachyarrhythmias would pose a serious threat following thrombolytic therapy to treat an evolving myocardial infarction. Second, lower-grade arrhythmias, such as accelerated idioventricular rhythm, were cited as useful, noninvasive markers of successful reperfusion. Critical review of the current data, however, indicates that arrhythmias following thrombolytic therapy for acute myocardial infarction are usually neither dangerous clinical events nor consistent markers of reperfusion.
1
Bronchogenic carcinoma in situ on the carina eradicated by endobronchial biopsy. Squamous cell carcinoma in situ of the bronchus is a rare disorder in an isolated clinical setting. We present a case of carcinoma in situ located on the carina with excisional biopsy via a fiberoptic bronchoscope and no recurrence after five years. To our knowledge, this represents the only case of carcinoma in situ treated solely with excisional biopsy. This case further emphasizes the importance of securing biopsy specimens for all mucosal abnormalities and raises the possibility of limited excision as sole therapy for carcinoma in situ.
1
Inositol phosphate formation in the human squamous cell carcinoma line SCC-12 F: studies with bradykinin, the calcium ionophore A23187, and sodium fluoride. The phospholipase C (PLC)-mediated hydrolysis of membrane phosphoinositides is an important signal transduction pathway coupled to the cell-surface receptors for several hormones and growth factors. In addition, PLC activity can be modulated by changes in intracellular calcium and activation of GTP binding proteins. In this report, differential activation of PLC in the human keratinocyte cell line SCC-12F was studied as judged by specific patterns of inositol phosphate formation. Several hormones and growth factors previously shown to stimulate PLC in a variety of cell types were screened for activity in SCC-12F cells. Only bradykinin was active, stimulating the PLC-dependent generation of inositol (1,4,5) triphosphate (Ins(1,4,5)P3). Ins(1,4,5)P3 was rapidly metabolized to inositol(1,4)biphosphate (Ins(1,4)P2) and inositol(1,3,4,5)tetrakisphosphate (Ins(1,3,4,5)P4), and subsequently degraded to inositol monophosphates. The response elicited by bradykinin was concentration dependent (EC50 value of 50 nM), suggesting involvement of a specific bradykinin receptor. Treatment of these cells with the calcium ionophore A23187 appeared to result in the direct formation of Ins(1,4)P2 without Ins(1,4,5)P3 as precursor. Treatment of the cells with AIF4-, a putative activator of GTP binding proteins, resulted in the generation of inositol monophosphates as the major metabolites in the absence of detectable Ins(1,4,5)P3 formation. Taken together, these observations suggest that the PLC complex present in SCC-12F cells can be differentially activated to yield either Ins(1,4,5)P3, Ins(1,4)P2, or InsP. The observed effects may be due to a direct PLC-dependent hydrolysis of the appropriate membrane phosphoinositide.
4
Ten-year follow-up of survival and myocardial infarction in the randomized Coronary Artery Surgery Study The Coronary Artery Surgery Study (CASS) randomized 780 patients to an initial strategy of coronary surgery or medical therapy. Of medically randomized patients, 6% had surgery within 6 months and a total of 40% had surgery by 10 years. At 10 years, there was no difference in cumulative survival (medical, 79% vs. surgical, 82%; NS) and no difference in percentage free of death and nonfatal myocardial infarction (medical, 69% vs. surgical, 66%; NS). Patients with an ejection fraction of less than 0.50 exhibited a better survival with initial surgery treatment (medical, 61% vs. surgical, 79%; p = 0.01). Conversely, patients with an ejection fraction greater than or equal to 0.50 exhibited a higher proportion free of death and myocardial infarction with initial medical therapy (medical, 75% vs. surgical, 68%; p = 0.04) although long-term survival remained unaffected (medical, 84% vs. surgical, 83%; p = 0.75). There were no significant differences either in survival and freedom from nonfatal myocardial infarction, whether stratified on presence of heart failure, age, hypertension, or number of vessels diseased. Thus, 10-year follow-up results confirm earlier reports from CASS that patients with left ventricular dysfunction exhibit long-term benefit from an initial strategy of surgical treatment. Patients with mild stable angina and normal left ventricular function randomized to initial medical treatment (with an option for later surgery if symptoms progress) have survival equivalent to those patients randomized to initial surgery.
4
Use of a computerized closed-loop sodium nitroprusside titration system for antihypertensive treatment after open heart surgery. This study evaluates the clinical applicability of administering sodium nitroprusside by a closed-loop titration system compared with a manually adjusted system. The mean arterial pressure (MAP) was registered every 10 and 30 sec during the first 150 min after open heart surgery in 20 patients (group 1: computer regulation) and in ten patients (group 2: manual regulation). The results (16,343 and 2,912 data points in groups 1 and 2, respectively), were then analyzed in four time frames and five pressure ranges to indicate clinical efficacy. Sixty percent of the measured MAP in both groups was within the desired +/- 10% during the first 10 min. Thereafter until the end of observation, the MAP was maintained within +/- 10% of the desired set-point 90% of the time in group 1 vs. 60% of the time in group 2. One percent and 11% of data points were +/- 20% from the set-point in groups 1 and 2, respectively (p less than .05, chi-square test). The computer-assisted therapy provided better control of MAP, was safe to use, and helped to reduce nursing demands.
4
Inverse correlation between plasma vitamin E and mortality from ischemic heart disease in cross-cultural epidemiology. Essential antioxidants were determined in plasma of middle-aged men representing 16 European study populations, which differed sixfold in age-specific mortality from ischemic heart disease (IHD). In 12 populations with "common" plasma cholesterol (5.7-6.2 mmol/L) and blood pressure, both classical risk factors lacked significant correlations to IHD mortality, whereas absolute levels of vitamin E (alpha-tocopherol) showed a strong inverse correlation (r2 = 0.63, P = 0.002). Evaluating all populations, cholesterol and diastolic blood pressure were moderately associated, but their correlation was inferior to that of vitamin E. In stepwise regression and multiple regression analysis, mortality was predictable to 62% by lipid-standardized vitamin E, to 79% by vitamin E and cholesterol, to 83% after inclusion of lipid-standardized vitamin A (retinol), and to 87% by all the above parameters plus blood pressure. Thus, in the present study the cross-cultural differences of IDH mortality are primarily attributable to plasma status of vitamin E, which might have protective functions.
5
Inter-arytenoid glottic bar following intubation. Inter-arytenoid glottic bar is a rare complication of prolonged endotracheal intubation. We present two such cases and their treatment. The aetiology of this complication is multifactorial and involves local factors--local trauma, movement of the endotracheal tube within the larynx, infection, and anatomical influences--together with systemic factors such as in our two cases. The relative importance of these factors is discussed. A comment is also made on the use of a pre-operative topogram and the importance of an ENT assessment in patients with airway problems following prolonged intubation.
5
Pott's puffy tumor: a complication of frontal sinusitis. In children sinusitis is a frequent complication of upper respiratory infections but an infrequently considered diagnosis. Although most sinus infections are resolved without complications, when complications do occur they can be serious or life threatening. The most common ones occur in the orbit, but CNS extension is not infrequent. Osteomyelitis and resulting subperiosteal abscess of the frontal bone--the so-called Pott's puffy tumor--is a less common, and perhaps less frequently recognized, serious complication of frontal sinusitis. This paper describes two patients with subperiosteal abscess resulting from frontal sinusitis, one with CNS and orbital extension. A brief literature review is presented, and presentation, diagnosis, and treatment are discussed.
5
Rupture of a giant carotid aneurysm after extracranial-to-intracranial bypass surgery. We report a case of a fatal rupture of a previously unruptured giant aneurysm of the bifurcation of the internal carotid artery (ICA), which occurred after an extracranial-intracranial (EC-IC) bypass and the partial occlusion of the ICA. Interim angiography showed retrograde filling of the proximal middle cerebral artery to the aneurysm. There have been four previously reported cases of giant aneurysms rupturing after treatment with an EC-IC bypass and carotid ligation, and it appears likely that a change in pressure/flow dynamics produced by the bypass may have been the cause. The technique of carotid ligation with an EC-IC bypass is used frequently to treat unclippable intracranial aneurysms, and the resulting hemodynamic changes need to be considered carefully to prevent this type of complication. To minimize hemodynamic stress on the aneurysm, we suggest that 1) the bypass caliber should be as small as possible consistent with sufficient cerebral blood flow after ICA occlusion, and 2) complete ICA occlusion should be performed as soon as possible after the bypass.
5
Dislocation after total hip arthroplasty. Causes and prevention. In this prospective study, a technique of positioning the acetabulum by bony landmarks of the pelvis in the standing position was developed using a standing lateral preoperative roentgenogram with the X-ray tube centered over the trochanter. Since 1984, 441 total hip arthroplasties (THAs) were done through the posterior approach with a 1.14% dislocation rate through 1988 and no dislocations in 1989. To prevent impingement and dislocation, it was determined that the safest range for cup position was 30 degrees-50 degrees abduction and 20 degrees-40 degrees flexion from the horizontal. To measure postoperative cup position, a standing true lateral roentgenogram of the operated hip allowed direct measurement of cup flexion and was reproducible within 10 degrees. No special instruments are necessary for this technique, which can be used with any THA system.
5
Ehrlichiosis in children. Tick-borne rickettsiae of the genus Ehrlichia have recently been recognized as a cause of human illness in the United States. In the years 1986-1988, 10 cases of ehrlichiosis were diagnosed in children in Oklahoma. Fever and headache were universal: myalgias, nausea, vomiting, and anorexia were also common. Rash was observed in six patients but was a prominent finding in only one. Leukopenia, lymphopenia, and thrombocytopenia were common laboratory abnormalities. Six patients were treated with tetracycline, three with chloramphenicol, and one was not treated with antibiotics: all recovered. The onset of illness in spring and early summer for most cases paralleled the time when Amblyomma americanum and Dermacentor variabilis are most active, suggesting that one or both ticks may be vectors of human ehrlichiosis in Oklahoma.
5
Bronchoalveolar lavage findings in a patient with the organic dust toxic syndrome. A previously healthy student developed the organic dust toxic syndrome after unloading a grain silo for one day. Bronchoalveolar lavage seven days later showed a total cell count six times normal with 70% lymphocytes. This suggests that the previously described acute neutrophil influx into the alveolar spaces in this syndrome is rapidly replaced by a lymphocyte dominated infiltration.
5
Multi-Hospital Eastern Atlantic Restenosis Trial: design, recruitment, and feasibility. M-HEART Investigators. A randomized control trial was set up to examine factors that influence restenosis and determine the effects of corticosteroids on restenosis following successful PTCA. The rationale for the study agent chosen, design, recruitment, and feasibility, as well as initial patient demographic data and initial results are presented.
5
Photic sneeze reflex in nephropathic cystinosis Photic induced sneeze is a reflex that occurs in certain individuals after exposure to bright light. Cystinosis is an autosomal recessive inborn error of metabolism in which nonprotein cystine accumulates within lysosomes. The pathognomonic ocular manifestation of cystinosis is corneal crystal deposition. We observed photic induced sneezes during ophthalmoscopic examination in five of 19 patients with nephropathic cystinosis (26%). We report on this observation and discuss possible pathophysiological mechanisms for photic induced sneezing in cystinosis.
5
Effects of inflammation and fibrosis on pulmonary function in diffuse lung fibrosis. To investigate the relation between lung function and inflammation and fibrosis in patients with diffuse lung fibrosis, a study was made of untreated patients without appreciable airway obstruction (14 patients with cryptogenic fibrosing alveolitis and seven with pneumoconiosis). Quantitative assessment of inflammatory infiltration and fibrosis was carried out on open lung biopsy specimens and compared with lung volumes, carbon monoxide transfer factor (TLCO), TLCO corrected for alveolar volume (TLCO/VA), and arterial blood gases at rest and during exercise. The degree of fibrosis and the degree of cellular infiltration were positively correlated. Lung volumes and TLCO were correlated with the grades of fibrosis and cellular infiltration of alveoli; arterial blood gases during exercise tended to correlate with both fibrosis and infiltration (p less than 0.06). In contrast, morphological data were not correlated with gas exchange at rest or with TLCO/VA. It is concluded that, in untreated patients with diffuse lung fibrosis, lung volumes, TLCO, and arterial blood gases during exercise reflect the lung lesions, and that the pulmonary function tests used cannot discriminate between fibrosis and infiltration of the lung by inflammatory cells.
5
Trial of brief intermittent neuroleptic prophylaxis for selected schizophrenic outpatients: clinical and social outcome at two years. OBJECTIVE--To evaluate a novel approach to the prophylaxis of schizophrenic relapse characterised by administration of brief courses of neuroleptic for the earliest non-psychotic signs of relapse (prodromal symptoms). DESIGN--Two year follow up of subjects randomised, double blind, to receive either active (control group) or placebo (intermittent group) depot neuroleptic medication. Both groups received brief courses of oral neuroleptic when prodromal symptoms or relapse occurred. SETTING--Psychiatric outpatient department, Charing Cross Hospital, London. SUBJECTS--54 Stable patients in remission who met the American Psychiatric Association's DSM-III criteria for schizophrenia on the basis of case notes. MAIN OUTCOME MEASURES--Survival without relapse, survival without hospitalisation, point prevalence of extrapyramidal side effects and tardive dyskinesia, structured assessment of social functioning (social adjustment scale II), and frequency of prodromal symptoms. RESULTS--Of 19 relapses recorded over two years, 10 (53%) were preceded by non-psychotic prodromal signs. Survival rates for both relapse and hospitalisation were worse with intermittent treatment than continuous treatment over the two year follow up: 92% of controls and only 54% of patients given intermittent treatment survived the two year period without hospitalisation. Prolonged or frequent relapses as well as episodes of prodromal symptoms were more frequent with intermittent treatment. Lower scores for extrapyramidal side effects were recorded in the intermittent treatment group, but periodic assessments of social functioning failed to show any social advantages from this. CONCLUSION--The findings are at variance with a previous report of one year follow up in this cohort and attest to the superiority of continuous depot neuroleptic prophylaxis in preventing both psychotic and neurotic or dysphoric morbidity in schizophrenia.
1
Giant cell tumor of bone. A clinicopathologic and DNA flow cytometric analysis. Flow cytometric DNA analysis was performed on 60 cases of giant cell tumor of bone and the results were correlated with the clinicopathologic features. Tumors studied were from 31 men and 29 women whose ages ranged from 18 to 62 years (median, 29 years). The most common sites were the distal end of the femur and proximal end of the tibia, accounting for 75% of the lesions. Treatment consisted of resection in 29 patients (48%), curettage with bone chip packing in 15 patients (25%), or curettage with cement packing in 16 patients (27%). Ten patients (17%) had local relapse within 1 to 3 years, and two had lung metastases. Forty-two patients (70%) exhibited tumors with a diploid DNA content, 16 aneuploid (27%), and two tetraploid (3%). Six (37.5%) of the aneuploid patients had relapses: one of those had been treated by resection of the tumor and five by curettage. Of the remaining ten (62.5%) unrelapsed aneuploid patients, nine had been treated by resection of the tumor and one by curettage. Four of the 42 diploid patients (9.5%) had relapses; all had been treated by curettage of the tumor. The two tetraploid tumors were treated by resection and none relapsed. Histologic parameters did not correlate with relapse rate or DNA pattern. Although relapse was more common among aneuploid tumors, our study shows that this appears to be influenced by the treatment modality rather than the ploidy status. Based on this study the DNA analysis of giant cell tumor of bone has a limited utility for predicting the tumor's biologic behavior.
5
Susceptibility to invasive Haemophilus influenzae type b disease and the immunoglobulin G2m(n) allotype. There has been considerable controversy about the role of the immunoglobulin G2m(n) allotype and risk of invasive Haemophilus influenzae type b (Hib) disease. This allotype was studied in a large cohort of Finnish children (178) with invasive Hib disease. The G2m(n) allotype distribution was similar to that in the normal white Finnish population. No increased risk of Hib disease could be associated with the n-/n- genotype [i.e., lack of G2m(n) allotype]. Thus, the G2m(n) allotype does not seem to be a major determinant of susceptibility to Hib infection among white populations in industrialized countries.
4
Prevention of paraplegia during aortic operations. Ischemic spinal cord injury after aortic cross-clamping may be produced by a steal phenomenon. The present study investigates this possibility by directly measuring the oxygen tension on the spinal cord surface in pigs. After simple clamping of the aorta, oxygen tension decreased significantly distal to the clamping site both after occlusion of the thoracic aorta at T3-4 (group 1) and after occlusion of the abdominal aorta at L-1 (group 2). Exclusion of the thoracic aorta by a second clamp at T-13 restored oxygen tension almost to the original level, whereas segmentation of the abdominal aorta up to S-1 hardly affected oxygen tension in the area of the artery of Adamkiewicz in most of the animals. We conclude that after aortic cross-clamping, blood tends to drain away from the spinal cord rather than supplying it longitudinally. Without knowledge of the position of the Adamkiewicz artery in humans as well as of the competence of the collateral circulation in the excluded segment, it is necessary to develop a new strategy for repair of the aorta. We describe and discuss two surgical techniques for the prevention of paraplegia after aortic cross-clamping: the counterocclusion technique and the bypass fractionated technique.
2
Effect of the leukotriene B4 receptor antagonist SC-41930 on colonic inflammation in rat, guinea pig and rabbit. Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that includes ulcerative colitis and Crohn's disease. Leukotriene B4 is thought to be a prominent proinflammatory mediator in these diseases, in that leukotriene B4 levels are increased in the colonic mucosa of inflammatory bowel disease patients and there is increased polymorphonuclear leukocyte infiltration of these tissues. We evaluated the efficacy of 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-3,4-dihydro-8-propyl -2H-1-benzopyran-2-carboxylic acid (SC-41930), a potent, orally active leukotriene B4 receptor antagonist, in a model of inflammatory bowel disease. Colonic mucosal inflammation was induced in rats, guinea pig and rabbits by rectal instillation of a dilute solution of acetic acid. Twenty-four hours later, mucosal levels of myeloperoxidase (a marker enzyme for neutrophil infiltration) and extravasation of i.v. administered Evans blue dye (a marker of vascular disruption and increased permeability) were measured. Tissues were also evaluated histologically. The animals received either SC-41930 or vehicle, intrarectally, 30 min after or 1 hr before and 1 hr after the acetic acid. When given 30 min after acetic acid instillation SC-41930 prevented the rise in myeloperoxidase and dye extravasation observed in the acetic acid inflammed tissue. The SC-41930-treated tissues were less edematous and had fewer neutrophils within the subepithelial space. Median effective dose (ED50) values for vascular protection were approximately 20 mg/kg for both rat and guinea pig. ED50 values for inhibition of granulocyte accumulation were 20 mg/kg for rat, 24 mg/kg for guinea pig and 30 mg/kg for rabbit. These data indicate that SC-41930 is effective locally to prevent acute colonic inflammation.
5
Ocular defects in infants of extremely low birth weight and low gestational age. The eyes of 49 babies who weighed less than 1,000 g at birth or who were born at or before 28 weeks gestation were examined at the age of 4 years. Twenty-one children were normal. The remaining 29 children (59%) had ocular abnormalities which ranged from mild amblyopia to blindness from retinopathy of prematurity. The need to examine children at risk is stressed.
4
Carotid-cavernous sinus fistula associated with a primitive trigeminal artery. Carotid-cavernous sinus fistulas are not rare, but they have never been reported in association with persistent primitive trigeminal artery. We recently encountered such a case. The Jaeger-Hamby procedure was employed, with mandatory occlusion of the primitive trigeminal artery.
5
Caffeine as an analgesic adjuvant. A double-blind study comparing aspirin with caffeine to aspirin and placebo in patients with sore throat. Despite its frequent clinical use in analgesic agents, caffeine has not been accepted unequivocally as an analgesic adjuvant. To evaluate this activity of caffeine, we used new study methods in a randomized controlled trial on patients with acute sore throat due to tonsillopharyngitis. Patients were randomly assigned to receive a single dose of one of three treatments: 800 mg of aspirin with 64 mg of caffeine (n = 70), 800 mg of aspirin (n = 68), or placebo (n = 69). Under double-blind conditions, during a 2-hour evaluation period, patients used different rating scales to assess pain intensity, change in pain, relief, and two qualities of throat pain, how swollen the throat felt, and difficulty swallowing. Aspirin with caffeine and aspirin alone were significantly more effective than placebo for all efficacy measurements from 30 minutes through 2 hours and overall. The aspirin-caffeine combination also showed evidence of activity at 15 minutes on the relief scale. Aspirin with caffeine was more effective than aspirin alone after 30 minutes and over the entire study period. For patients with fever, both active treatments were equally effective antipyretic agents. We conclude, therefore, that 800 mg of aspirin, given alone or with 64 mg of caffeine, is an effective analgesic and antipyretic agent. Because the aspirin-caffeine combination is significantly more effective than aspirin alone as an analgesic, we also conclude that 64 mg of caffeine is an analgesic adjuvant.
5
A cost-minimization study of cancer patients requiring a narcotic infusion in hospital and at home. We conducted a retrospective, non-randomized, cost-minimization study, from the perspective of the Ministry of Health, to compare the cost of managing cancer patients who required narcotic infusions, in hospital and at home. Our medical costs averaged $369.72 per inpatient day and $150.24 per outpatient day (saving $219.48 per diem, 1988 Canadian dollars), while narcotic costs were the same for any given patient in both settings. Sensitivity analysis showed that no reasonable changes in the quantity and cost of services reduced our savings by more than 50%. During incremental analysis, savings increased as more outpatient days were managed by our centre, from $0.00 for 318 days, to more than $500,000 for over 2000 days per annum. As this program has been extremely cost effective and preferred by our patients, other hospitals and central funding agencies might consider establishing a regional outpatient narcotic infusion program to reduce their costs.
3
Cerebrospinal fluid rhinorrhea following acoustic neurinoma surgery. Technical note. The authors describe a method of preventing cerebrospinal fluid (CSF) rhinorrhea following surgery for acoustic neurinoma. Mastoid air cells exposed during craniectomy are skeletonized and packed with bone dust, then covered with Surgicel soaked with Tisseel fibrin glue. The use of this technique has reduced the number of acoustic neurinoma cases requiring secondary mastoidectomy for CSF leakage from 16% to 5%.
5
Caseating hepatic granulomas in Hodgkin's lymphoma. A 68-year-old man presented with recurrent Hodgkin's lymphoma after a 9-year disease-free interval induced by chemotherapy. In addition to histological evidence of recurrent Hodgkin's disease, the liver biopsy specimen showed extensive caseating granulomas. Cultures of bone marrow and liver tissue tested negative for Mycobacterium tuberculosis. No antituberculous treatment was administered, and the patient had an excellent clinical response to additional chemotherapy for lymphoma. Hodgkin's lymphoma should be added to the list of disease entities associated with caseating granulomas in the liver.
5
Secretion of a unique collagen by spontaneously transformed murine keratinocytes (PAM cells) in vitro. A spontaneously transformed murine keratinocyte cell line (PAM cell) was found to secrete two nondisulfide-linked collagenous polypeptides with apparent molecular weight (MW) 190-kd and 120-kd. Pulse-chase experiments indicated that the 190-kd polypeptide was secreted into the culture medium in 2 h and processed to the 120-kd collagen component within 4 h. This process was inhibited by EDTA. The 120-kd polypeptide was sensitive to pepsin, and a 50-kd fragment was produced by a mild pepsin treatment at 4 degrees C. A cyanogen bromide peptide map of the 120-kd polypeptide was distinct from that of types I, II, III, IV, and V collagens. These properties indicate similarities to the type VIII-related collagen produced by human astrocytoma cells. The secretion of the collagen rapidly reached a maximum level on the first day of culture and subsequently declined with cell proliferation. An accelerated processing to the 120-kd polypeptide was observed under culture conditions of high cell density. Similar collagens were also found to be produced by normal human keratinocytes. These results indicate that the 120-kd polypeptide is a potentially functional protein that may participate in the formation of the extracellular matrix of keratinocytes.
4
Angiocentric lymphoma with histologic features of neoplastic angioendotheliomatosis presenting with predominant respiratory and hematologic manifestations. Report of a case and review of the literature Neoplastic angioendotheliomatosis (NAE) is a rare fatal disease characterized by widespread intravascular proliferations of neoplastic mononuclear cells. Clinically, dermatologic and bizarre neurologic manifestations usually predominate. The origin of the neoplastic cells remains still undetermined. The authors report a patient with NAE peculiar with respect to the following points: (1) the patient predominantly manifested respiratory symptoms and hematologic findings and lacked cutaneous or neurologic manifestations; and (2) immunohistochemical and molecular genetic studies showed the B-cell nature of the neoplastic cells, although previous cases with predominant respiratory or hematologic manifestations were reported to be of endothelial origin. Despite the rarity, this type of NAE or angiocentric lymphoma should be recognized because it is easily confused with other disorders, particularly vasculitis or thrombotic thrombocytopenic purpura.
3
Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. The DATATOP database, which includes clinical information on 800 patients with early untreated Parkinson's disease (PD), is well suited to explore clinical heterogeneity in PD. Patients with early-onset PD (less than or equal to 40 years, N = 33) reached the same level of disability as the late-onset PD (greater than or equal to 70 years, N = 85) group at a significantly slower rate (2.9 vs. 1.7 years). Early-onset PD patients functioned cognitively better than late-onset PD patients. Bradykinesia, and postural instability and gait difficulty (PIGD), were more common at onset in patients with a rapid rate of disease progression ("malignant PD"; duration of symptoms less than 1 year and Hoehn/Yahr stage of 2.5, N = 11) as compared with those with a relatively slow rate of progression ("benign PD"; duration of symptoms greater than 4 years, N = 65). Comparisons of tremor-dominant PD (mean tremor score/mean PIGD score less than or equal to 1.5, N = 441) with the PIGD-dominant type (mean tremor score/mean PIGD score greater than or equal to 1.0, N = 233) provided support for the existence of clinical subtypes. The PIGD group reported significantly greater subjective intellectual, motor, and occupational impairment than the tremor group. Stage II patients had higher depression scores than stage I patients. Among the patients participating in the DATATOP, older age at onset with bradykinesia, or with the PIGD form of PD, is associated with more functional disability than when the symptoms are dominated by tremor or begin at a younger age.