shukoor65/lab-rag-model huggingface dataset:
Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy BACKGROUND. Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation of unknown pathogenesis. Transforming growth factor (TGF) beta 1 induces the production of extracellular matrix proteins by liver cells and has been implicated in the pathogenesis of hepatic fibrosis in laboratory animals. TGF alpha is a hepatocyte mitogen that participates in liver regeneration. METHODS. Using Northern blot analysis, we studied the expression of TGF beta 1 messenger RNA (mRNA) in liver specimens from 42 patients with chronic hepatitis and cirrhosis and 12 subjects with either normal or fatty livers. The results were correlated with measurements of procollagen Type I mRNA in liver tissue, procollagen Type III peptide in serum, and the degree of histologic injury. We also investigated whether TGF alpha mRNA would be detectable in biopsy specimens of livers with proliferative activity. RESULTS. TGF beta 1 mRNA expression correlated closely with the expression of procollagen Type I mRNA (r = 0.94) and serum procollagen Type III peptide (r = 0.89) and with the histologic activity index (r = 0.73). All patients with increased fibrogenic activity (serum procollagen Type III peptide level, greater than 11.9 micrograms per liter) had increased levels of TGF beta 1 mRNA (2 to 14 times the levels in the control group or in patients with normal fibrogenic activity), and both TGF alpha and H3 histone (a marker of DNA synthesis) mRNAs were detectable in patients with regenerative nodules. Six of eight patients with hepatitis C treated with interferon alfa for one year had sustained clinical responses with normalization of serum procollagen Type III peptide and aminotransferase activity. All these patients had normal levels of TGF beta 1 mRNA in liver specimens obtained at the end of the year. CONCLUSIONS. TGF beta 1 may have an important role in the pathogenesis of fibrosis in patients with chronic liver disease, and TGF alpha expression may be associated with liver regeneration in these patients.
Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor gamma/delta in inflammatory bowel disease. Phenotypic characterization and distribution of gamma/delta T lymphocytes in the intestinal mucosa were investigated in ulcerative colitis and Crohn's disease by immunohistochemistry. The ratio of delta(+) cells to CD3(+) cells in the intraepithelial space of colon was decreased in Crohn's disease (13%) and strikingly decreased in ulcerative colitis (8%) compared with the control (36%). Delta(+) cells in the lamina propria were also decreased, particularly in the distal ileum of Crohn's disease (4%), compared with the control (15%). On the contrary, the cells gathered at the severe inflammatory sites with other inflammatory cells, including beta(+) cells, and were densely distributed in the T-cell zone around lymphoid follicles. Phenotypic characterization showed that delta(+) lamina proprial lymphocytes of colon were mainly CD4(-)CD8(-) in the control (80%) and Crohn's disease (59%). However, in ulcerative colitis, CD4(-)CD8(-) delta(+) lymphocytes were rarely found (3%). This reflects the difference of immunologic background between the two diseases. Immunoelectron microscopically, these cells in inflammatory bowel disease were rich with vesicular structures in cytoplasms, whereas those in the control group contained electron-opaque granules. The decrease and the morphological change may be closely related to the weakness of mucosal defense.
Haemodynamic considerations in the management of patients with subarachnoid haemorrhage. Cerebral vasospasm occurs, following subarachnoid haemorrhage, in the majority of patients and is accompanied by cerebral ischaemia in 30%. The objectives of this article are to review (1) the effects of subarachnoid haemorrhage and vasospasm on cerebral blood flow (CBF); (2) the effects of induced hypotension and hypocapnia on CBF in these patients; (3) current therapy for cerebral ischaemia from vasospasm. The medical literature was searched using Index Medicus; for the period 1983-90 this search was done on a computer with the CD-ROM version of Index Medicus, Silver Platter. Papers were selected on the basis of validity and applicability to clinical practice; animal studies are included when human data is lacking. Cerebral vasospasm may decrease cerebral blood flow, disturb autoregulation and place the patient at risk for delayed cerebral ischaemia. Intraoperative induced hypotension and hypocapnia can decrease CBF further, although effects of either on outcome have not been evaluated. Calcium antagonists are effective for both the prevention and the treatment of delayed cerebral ischaemia. Of the mechanical treatments, systemic-arterial hypertension has the firmest scientific foundation, although this is frequently combined with haemodilution and blood volume expansion. There is a need for randomized clinical trials to assess the efficacy of these latter treatments.
Caffeine clearance by enzyme multiplied immunoassay technique: a simple, inexpensive, and useful indicator of liver function. The clinical value and sensitivity of serum caffeine clearance measurement has been evaluated as an indicator of hepatic disease. After a 17 hour caffeine exclusion period, 300 mg of caffeine citrate was administered orally to the study subjects. Serum samples were taken four and 16 hours later. Serum caffeine concentrations were measured using an enzyme multiplied immunoassay technique (EMIT) and a clearance value derived. Conventional liver function tests were measured at the same time. A total of 103 subjects attending the medical unit in a district general hospital were studied. Twenty one had alcoholic liver disease, 11 non-alcoholic cirrhosis, nine non-cirrhotic liver disease, 21 suspected liver disease, six hepatic tumours, and 35 were hospital and normal control subjects. Caffeine clearance values were lowest in subjects with alcoholic liver disease (median 0.19 ml/min/kg, range 0.04-0.61 ml/min/kg) and significantly reduced in all subjects with liver disease (median 0.32 ml/min/kg, range 0.04-2.68 ml/min/kg) compared with control subjects (median 1.27 ml/min/kg, p less than 0.001). In subjects with suspected liver disease subsequently shown to have another explanation for abnormal liver function test results, caffeine clearance values were normal (median 1.31 ml/min/kg, range 0.23-2.64 ml/min/kg) and significantly different, p less than 0.001, from those of subjects with liver disease. Serum albumen values were not different for these latter two groups. Using a cut off value of 0.86 ml/min/kg, caffeine clearance measurement was 100% sensitive for alcoholic liver disease and 89% sensitive for all liver disease. The respective sensitivities for conventional liver function test measurement were 76% and 83%. In the suspected liver disease group, caffeine clearance was abnormal in only 24%, conventional liver function tests were abnormal in 95%.
Bronchioloalveolar carcinoma of the lung and congenital cystic adenomatoid malformation. A case of bronchioloalveolar carcinoma of the lung is described in a 19-year-old man who had had a lobectomy in infancy, for removal of a congenital cystic adenomatoid malformation. It is suggested that congenital cystic adenomatoid malformation may predispose a patient to development of epithelial malignancies of the lung, whereas mesenchymal hamartomas usually are associated with nonepithelial neoplasms.
Expression of perforin in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3. BACKGROUND. Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of viral myocarditis. METHODS AND RESULTS. Using a murine model of acute myocarditis caused by coxsackievirus B3, we analyzed the phenotypes and morphology of the infiltrating cells in the hearts by immunofluorescence and electron microscopy. We also examined the expression of a cytolytic factor, perforin, in the infiltrating cells by immunoperoxidase and in situ hybridization. We found that the dominant population of the infiltrating cells were asialo GM1 positive, were negative for T-cell markers, and had electron-dense cytoplasmic granules, which is consistent with a morphology of large granular lymphocytes. Perforin was found in the cytoplasmic granules of the infiltrating cells expressing perforin messenger RNA. These findings provide for the first time the direct evidence that the first wave of cell infiltration in hearts mainly consists of killer cells and strongly suggests that perforin plays, in part, an important role in myocardial cell damage involved in acute viral myocarditis. T-helper cells and cytotoxic T lymphocytes made up the second wave of cell infiltration. CONCLUSIONS. As we previously reported, the expression of major histocompatibility complex class I antigen on cardiac myocytes induced by the infiltrating cells, such as killer cells, may facilitate the interaction between cardiac myocytes and cytotoxic T lymphocytes, and may lead to further myocardial cell damage in a later phase.
Macroscopic vasovasostomy re-examined. Results of 273 consecutive macroscopic vasovasostomy procedures performed at a single institution over a nine-year period between 1978 and 1987 were reviewed. When patients operated on less than five years after vasectomy were compared with those in whom more than five years had elapsed since vasectomy, significant declines in technical success rates as measured by return of sperm to the ejaculate (93% vs. 74%, p less than 0.004), biologic recovery as measured by mean sperm counts (55 million vs. 35 million) and mean progressive sperm motility (30% vs. 13%), and clinical success as measured by pregnancy rates (52% vs. 30%, p less than 0.02), were observed. Examination of complications of vasovasostomy showed a 7.7 percent overall complication rate and a 1.5 percent incidence of major complications.
Radiologic evaluation of the normal and diseased posterior cervical space. The posterior cervical space seen on cross-sectional imaging of the neck constitutes most of the posterior triangle seen on clinical examination. Although triangular anatomy relates best to the surface perspective of the clinician, a spatial approach to anatomy works better for the radiologist viewing axial images. The posterior cervical space is defined as the area in the posterolateral portion of the neck from the skull base to the clavicles deep to the sternomastoid and trapezius muscles but superficial to the prevertebral space. Its principal contents are fat, the spinal accessory nerve, and lymph nodes. We analyzed CT and MR images and clinical records of 63 patients known or suspected to have disease of the posterior cervical space to determine the imaging features that mark a lesion as originating in the posterior cervical space and the spectrum of diseases that arise there. Of the 63 patients in the study, four had clinical pseudomasses, nine had congenital lesions, 10 had inflammatory disease, six had benign tumors, and 34 had malignant tumors. A typical mass lesion of the posterior cervical space was centered within the fat of the space, between the deep and superficial layers of the deep cervical fascia. Characteristic displacements caused by a mass in the posterior cervical space included anteromedial displacement of the carotid space and posteromedial displacement of the prevertebral space. Our study shows that the differential diagnosis of lesions of the posterior cervical space reflects the normal contents of the space, and that diagnosis can thereby be predicted from knowledge of the normal anatomy and contents of the space.
Adenosine triphosphate-sensitive potassium channels in anoxia. Potassium channels that are activated by decreasing adenosine trisphosphate levels are blocked by sulfonylurea drugs such as glibenclamide but are opened by diazoxide and some endogenous peptides. Judging from the effects of such drugs, it seems that in the hippocampus, these channels are present not on cell bodies but rather on glutamate-releasing nerve terminals (especially those of mossy fibers in the CA3 region). Because activation of these presynaptic potassium channels reduces anoxic glutamate release, they may be a useful target for specific drug therapy that might prevent the excitoxic effects of excessive glutamate release during anoxia/ischemia.
Sexual function of women taking antihypertensive agents: a comparative study. OBJECTIVE: To develop a method to evaluate the effects of clonidine and prazosin on sexual function in hypertensive women. DESIGN: Crossover, active-drug controlled pilot study. SETTING: Community recruitment to a university-based teaching hospital. PATIENTS: Ten premenopausal and eight postmenopausal women with mild hypertension and unimpaired sexual function. INTERVENTION: Periodic, self-administered daily diaries assessed the sexual arousal and desire and orgasmic function of women receiving placebo, clonidine, and prazosin. MEASUREMENTS AND MAIN RESULTS: Using analysis of variance for orgasmic characteristics and comparison of the percentages of yes responses to the sexual function questions, no significant difference in the levels of sexual function of women receiving placebo, clonidine, and prazosin was found. However, there was a suggestion that clonidine and prazosin affected some aspects of sexual function. Of the women who received clonidine first, fewer were receptive to partner approach during medication therapy (49%) than during placebo (61%). Fewer women wished for their partners to approach them (WISH) during therapy (41% and 53% for clonidine and prazosin, respectively) than during placebo (60%). In the group that received prazosin first, WISH was affected (32% for prazosin, 31% for clonidine, 45% for placebo). Orgasmic strength increased from 2.1 on placebo to 2.7 on clonidine (second medication), measured on a four-point Likert scale. CONCLUSIONS: This pilot study developed a method using self-administered daily diaries for evaluating the effects of antihypertensive agents on sexual function in hypertensive women. These potential effects need to be evaluated in larger studies.
A review of 13-years experience of osteosarcoma. Since the inception of the authors' facility, 365 patients with osteogenic sarcoma have been treated. While other facilities were surgically treating patients with primary amputation, this facility attempted limb-salvage surgery. The majority of patients being treated with limb-salvage surgery had the resected bone replaced by a metallic endoprosthetic replacement. The emphasis on conservative surgery led to the development of growing endoprosthetic replacements with the first being used in 1975. The cumulative survival of those patients with Stage 2 osteosarcoma treated at this facility between 1977 and 1984 is 48% at five years.
Sucralfate versus cimetidine in the treatment of reflux esophagitis, with special reference to the esophageal motor function. Sixty patients entered a double-blind clinical trial comparing the effect of 1 g of sucralfate granulate given four times daily and cimetidine, 400 mg twice daily. Twenty-six patients treated with sucralfate and 26 treated with cimetidine were examined with short-term pH monitoring before and after 12 weeks of treatment. Thirty patients, 19 treated with cimetidine and 11 treated with sucralfate, had esophageal motility studied by a radionuclide test before and after 12 weeks of treatment. The efficacy of the treatments was judged by symptoms and endoscopic response after 4, 8, and 12 weeks of treatment. The endpoint healing rate was approximately 60% in both groups and symptoms were relieved in half of the patients in both groups (difference not significant). The effect of the treatments on pH and number of spikes reflected the different pharmacodynamic profiles of the drugs, whereas the mean transit time (MTT) was not changed by the treatments. The residual activity after radionuclide transit in the sitting position was significantly increased after treatment with cimetidine. The data support the hypothesis that primary dysmotility might be involved in the pathogenesis of reflux esophagitis in about 33% of the patients. Possibilities for a combination therapy with sucralfate and cimetidine are stressed.
The plain abdominal film accurately estimates extent of active ulcerative colitis. The aim of our study was to establish whether plain abdominal film can accurately assess the extent of active ulcerative colitis. Ninety-seven ulcerative colitis patients were studied, in whom the extent of the macroscopic lesion was established either by colonoscopy (n = 75) or by resection (n = 22). Of these, 42 had proctosigmoiditis, 12 left-sided colitis, 12 subtotal colitis, and 31 total colitis. Nine well-tested features were used for the radiological classification of lesion extent. The radiologists were not given any clinical information. Seventy-eight patients (80.4%) were correctly classified by plain abdominal film (r = 0.86); the best concordance was achieved for proctosigmoiditis and total colitis (80.9 and 90.3%, respectively). In total colitis the most reliable radiological features were "irregularity of the mucosal edge" and "increased thickness of the colon wall, " which were present in 74.2 and 67.7%, respectively, of the correctly classified patients. The fourfold combination of these two features with "loss of haustral clefts" and "empty right colon" was present only in patients with total colitis, and at least one of these features was present in all but one of them. Conversely, all nine abnormalities were absent in 73.8% of patients with proctosigmoiditis. In conclusion, plain abdominal film is a reliable tool for judging the extent of lesion in active ulcerative colitis. It seems particularly accurate in total colitis, where, in the acute phases, it is most important to avoid invasive examinations.
Phencyclidine increased release of beta-endorphin from anterior lobe of the pituitary. Phencyclidine (PCP) has been found to affect neuroendocrine function by altering the release of the anterior pituitary hormones, adrenocorticotrophin, luteinizing hormone and prolactin. The purpose of this study was to examine the effect of PCP on release of the two pituitary hormones also derived from the adrenocorticotropin precursor, namely, alpha-melanocyte-stimulating hormone and beta-endorphin (beta-E), synthesized in the neurointermediate and anterior lobes of the pituitary. At behaviorally active doses, PCP administered i.c.v. increased plasma levels of immunoreactive beta-E (i beta-E) without affecting the concentration of immunoreactive alpha-melanocyte-stimulating hormone, suggesting that PCP increased the release of beta-E from only the anterior lobe of the pituitary. Dexamethasone pretreatment blocked the PCP-induced increase in i beta-E which indicated further the anterior lobe effects of PCP. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate), a selective PCP ligand, at behaviorally active doses also increased the plasma concentration of i beta-E. The dose-response curves for induction of behavior was very different from that for increasing the concentration of i beta-E in plasma. The increase in release of i beta-E was stereoselective as (+)-(1-(1-phenylcyclohexyl)-3 methylpiperidine but not (-)-(1-(1-phenylcyclohexyl)-3 methylpiperidine increased release of i beta-E. The increase in plasma levels of beta-E was not due to an interaction with opioid receptors because naloxone did not block PCP-induced release of beta-E. In vitro, PCP also significantly increased release of i beta-E from anterior lobe of the pituitary.
A phase II trial of intraperitoneal cisplatin and etoposide as salvage treatment for minimal residual ovarian carcinoma. We conducted a phase II study of intraperitoneal (IP) cisplatin (CDDP) and etoposide (VP-16) as salvage therapy in patients with ovarian cancer who had persistent disease or who had relapsed after primary systemic chemotherapy and had residual disease of less than 2 cm. Two hundred eleven courses of IP chemotherapy consisting of CDDP 200 mg/m2 and VP-16 350 mg/m2 were administered. All patients received intravenous (IV) thiosulfate protection. Treatment was given once every 4 weeks for a median of six cycles. Twenty-four of 37 assessable patients were clinically free of disease at the end of treatment (normal physical exam, computed tomographic [CT] scan, CA-125 and peritoneal cytology); one patient had a partial response. Ten of these 24 patients consented to reexploration at the end of treatment, and nine were in pathologic complete remission, while one patient had positive peritoneal washings as her only evidence of persistent disease. The median survival of the 37 patients was 26 months from the first day of IP treatment and 51 months from diagnosis. The major toxicity was myelosuppression, with median nadir WBC, granulocyte, and platelet counts of 2,400, 684, and 134,000/mm3, respectively. There was no cumulative renal damage, hypomagnesemia, or chemical peritonitis. We conclude that IP CDDP and VP-16 can produce pathologic complete remissions when used as a second-line regimen for patients with ovarian cancer who have received systemic cisplatin-based therapy and have less than 2 cm disease.
Cancer control following anatomical radical prostatectomy: an interim report. Cancer control following anatomical radical prostatectomy was evaluated in 586 men who were followed for 1 1/2 to 8 years (median followup 4 years, 166 men followed 5 years or longer). The 5-year actuarial rate was 4% for local recurrence alone, 5% for distant metastases alone, 2% for distant metastases in association with local recurrence and 3% for death of or with disease, while 10% of the men had elevated levels of prostate specific antigen without local recurrence or distant metastases. When the actuarial status at 5 years was evaluated by clinical stage there was local recurrence alone in 0% of men with a clinical stage A1 or B1 nodule, and 4% with stage B1, 7% with stage A2 and 8% with stage B2 disease. When evaluated by pathological stage at 5 years local recurrence alone was noted in 2% of men with organ-confined disease, 8% with specimen-confined disease and 8% in whom the disease involved the surgical margin, seminal vesicles or pelvic lymph nodes. Recognizing that two-thirds to three-quarters of all local recurrences occur within the first 5 years, these data suggest that the anatomical approach to radical prostatectomy is associated with local control rates that are equal to or greater than other series reported in the literature. However, without a randomized study it is impossible to compare one clinical series to another, and followup evaluations at 10 and 15 years will be necessary to confirm these findings.
Noncardiac chest pain in patients with heart disease. This is a retrospective study of cardiac patients with noncardiac chest pain referred for evaluation of esophageal motility. Sixty-eight patients with heart disease were compared with 210 patients without heart disease according to findings from symptom questionnaires and a psychologic test (Brief Symptom Inventory). More than 70% of each group qualified for an anxiety or depressive diagnosis on the symptom questionnaire. These diagnoses were supported by significant elevations of scores on the anxiety and depression scales of the Brief Symptom Inventory. Male gender and a diagnosis of panic disorder occurred significantly more often in the patients with heart disease. "Stress" was cited as the cause of illness in about half the sample, but this led to less than satisfactory rates of psychiatric evaluation or pharmacotherapy. This is of particular concern for the cardiac patients because of the known adverse effect of anxiety and depression in those with heart disease.