shukoor65/lab-rag-model huggingface dataset:
Antihypertensive effect of cicletanine is exaggerated in NaCl-sensitive hypertension. Cicletanine (CIC), a furopyridine derivative, lowers blood pressure in hypertensive animals and humans. We have previously identified an NaCl-sensitive substrain of spontaneously hypertensive rat (SHR-S) that displays enhanced sensitivity to the depressor effects of exogenous atrial natriuretic peptide (ANP) when fed a high NaCl diet. The current study tested the hypotheses that CIC has an exaggerated antihypertensive effect in NaCl-supplemented SHR-S and that this effect might be ANP dependent. CIC (40 mg/kg/day) or vehicle was administered by gavage in a single daily dose for three weeks beginning immediately prior to initiation of 1% or 8% NaCl diets in seven-week-old male SHR-S. CIC significantly decreased mean arterial pressure (MAP) and the ratio of left ventricular and septum weight to body weight (LV + S/BW) in both 8% NaCl- and 1% NaCl-fed SHR-S. The depressor effect of CIC was greater in the 8% NaCl group (-26 mmHg) than in the 1% NaCl group (-13 mmHg). CIC was associated with significant reduction in RAP in the 8% NaCl group but not in the 1% NaCl group. Neither CIC treatment nor 8% NaCl significantly altered plasma ANP or cyclic guanosine monophosphate (GMP) levels in plasma, aorta, or kidney. CIC was associated with significant decreases in plasma norepinephrine (NE) levels in the 1% NaCl group but not in the 8% NaCl group. The data demonstrate that the antihypertensive effect of CIC is exaggerated in NaCl-sensitive hypertension. The antihypertensive effect of CIC appears not to be related to ANP or cyclic GMP but may be related to a combination of a sympatholytic and natriuretic/diuretic effects in SHR-S.
Hyperdiploidy and trisomy of chromosome 15 in peritoneal macrophages of hyperimmune, older Swiss mice. Chromosome analysis was carried out in resident and exudate peritoneal macrophages and, also, in bone marrow cells of groups of mice either immunized with ovalbumin in complete Freund's adjuvant and challenged with the antigen, or stimulated with the irritant thioglycollic acid. Labeling of the phagocytic cells with colloidal carbon showed that dividing cells in the peritoneal cavity of experimental mice are resident macrophages. Also shown was an increase in number of hyperdiploid metaphases in hyperimmune, older mice but not in the young ones. Statistical analysis showed these differences to be significant. G-banding of hyperdiploid cells of hyperimmune older mice showed trisomy of chromosome 15 in several metaphases analyzed. The absence of hyperdiploid metaphases in the bone marrow cells of hyperimmune mice and in exudate macrophages of mice that received the irritant thioglycollic acid suggests that hyperdiploidy occurs in resident macrophages in the peritoneal cavity but not in their precursors in the bone marrow. These results raise some questions such as, hyperimmune older mice resident macrophages being prone to hyperdiploidy and trisomy of chromosome 15.
Relationship between length and surface area of each segment of the large intestine and the incidence of colorectal cancer. In investigating the occurrence and clinical characteristics of diseases of the large intestine, particularly tumors, the number, distribution, and incidence of the lesions were compared between segments of the large intestine. If the distribution and incidence of lesions are correlated with the length or surface area of each segment, the incidence of lesions will be the same throughout the large intestine. If the lesions are unrelated to length or surface area, the factors that affect the occurrence of lesions must be determined and will be characteristic for each segment. However, the length and surface area of each segment of the large intestine and the ratios of each to both the total length and surface area of the large intestine are not clear. In this study the length and surface area of each segment of the large intestine were measured and calculated using the barium enema technique, and the incidence rates of cancer per unit length and surface area of each segment were determined and compared.
Fistulous degeneration of a giant esophageal ulcer in a patient with acquired immune deficiency syndrome. Esophageal involvement in human immunodeficiency virus (HIV) disease can take many forms, including the recently described giant solitary ulcerations thought to be due to cytomegalovirus or, more recently, Mycobacterium species. Current experience suggests that steroids may provide symptom relief and healing in selected patients. We report a case of fistulous change in one such ulcer, with documented endoscopic, radiologic, and pathologic findings. No organism was identified by culture or pathologic staining, leading to a postulated role for the persistent irritation of medications.
Maintenance therapy with sucralfate in duodenal ulcer: genuine prevention or accelerated healing of ulcer recurrence? We sought to compare the efficacy of sucralfate to placebo for the prevention of duodenal ulcer recurrence and to determine that the efficacy of sucralfate was due to a true reduction in ulcer prevalence and not due to secondary effects such as analgesic activity or accelerated healing. This was a double-blind, randomized, placebo-controlled, parallel groups, multicenter clinical study with 254 patients. All patients had a past history of at least two duodenal ulcers with at least one ulcer diagnosed by endoscopic examination 3 months or less before the start of the study. Complete ulcer healing without erosions was required to enter the study. Sucralfate or placebo were dosed as a 1-g tablet twice a day for 4 months, or until ulcer recurrence. Endoscopic examinations once a month and when symptoms developed determined the presence or absence of duodenal ulcers. If a patient developed an ulcer between monthly scheduled visits, the patient was dosed with a 1-g sucralfate tablet twice a day until the next scheduled visit. Statistical analyses of the results determined the efficacy of sucralfate compared with placebo for preventing duodenal ulcer recurrence. Comparisons of therapeutic agents for preventing duodenal ulcers have usually been made by testing for statistical differences in the cumulative rates for all ulcers developed during a follow-up period, regardless of the time of detection. Statistical experts at the United States Food and Drug Administration (FDA) and on the FDA Advisory Panel expressed doubts about clinical study results based on this type of analysis. They suggested three possible mechanisms for reducing the number of observed ulcers: (a) analgesic effects, (b) accelerated healing, and (c) true ulcer prevention. Traditional ulcer analysis could miss recurring ulcers due to an analgesic effect or accelerated healing. Point-prevalence analysis could miss recurring ulcers due to accelerated healing between endoscopic examinations. Maximum ulcer analyses, a novel statistical method, eliminated analgesic effects by regularly scheduled endoscopies and accelerated healing of recurring ulcers by frequent endoscopies and an open-label phase. Maximum ulcer analysis reflects true ulcer recurrence and prevention. Sucralfate was significantly superior to placebo in reducing ulcer prevalence by all analyses. Significance (p less than 0.05) was found at months 3 and 4 for all analyses. All months were significant in the traditional analysis, months 2-4 in point-prevalence analysis, and months 3-4 in the maximal ulcer prevalence analysis. Sucralfate was shown to be effective for the prevention of duodenal ulcer recurrence by a true reduction in new ulcer development.
Consolidation with intraperitoneal cisplatin in first-line therapy of advanced ovarian cancer. Seventy-five patients with advanced epithelial ovarian cancer were treated with a combined modality regimen of systemic, induction chemotherapy followed by intraperitoneal therapy (IPT). All patients underwent initial surgery for staging and/or cytoreduction followed by cisplatin 20 mg/m2 intravenously (IV) for 5 days and cyclophosphamide 600 mg/m2 on day 4 every 3 to 4 weeks for two to four cycles. Patients were then evaluated for IPT and, if eligible, had an intraperitoneal (IP) catheter placed. IPT consisted of cisplatin 60 mg/m2 in 2 L on day 1 and IV cyclophosphamide 600 mg/m2 on day 2 every 3 weeks for three to six cycles. Patients who demonstrated a clinical complete response (CCR) were then referred for second-look laparotomy (SLL). Of 71 patients who completed the induction phase, 53 (75%) were eligible for IPT, and 49 patients entered the therapy phase. Toxicity of the combined modality approach was acceptable and did not differ from our previous experience using the same drugs systemically. Thirty-two of the 49 patients who completed IPT achieved a CCR, which was confirmed by SLL in 20 patients. Twenty recurrences were documented in the 32 CCR patients, 13 occurred in patients after SLL. Projected median survival of all patients is 38 months. Median survival correlated with amount of residual disease following initial surgery (23 months for bulky v 45 months for minimal residual; P less than .001) and with performance status ([PS]; 24 months for PS 2, 3 v greater than 46 months for PS O; P less than .001). Patients who presented with bulky tumors were less likely to reach the consolidation IPT phase. Incorporation of IP cisplatin into the first-line regimen for treatment of ovarian cancer does not appear to have major impact on the survival of all treated patients when compared with our historical control series. Combined IV and IPT cisplatin and cyclophosphamide is feasible with acceptable toxicity. Its impact on response and survival may be limited to only "good-prognosis" patients.
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, etc. (SUNCT): III. Another Norwegian case. "SUNCT" is a recently reported head pain syndrome characterized by shortlasting, unilateral neuralgiform paroxysms with conjunctival injection and tearing, and to a lesser extent nasal secretion, and (subclinical) sweating. Another case--that of a 56 year old male--is reported herein. The attacks lasted 1/2-1 min. and occurred only infrequently, i.e. once or twice in 1-4 weeks, except for a week recently when there were up to 20 or more typical attacks per day, with the usual ipsilateral, autonomic accompaniments. Due to the benign nature and low frequency of attacks, the diagnosis would have been most difficult to establish prior to the occurrence of this shortlasting period with more marked symptoms. A variety of precipitation mechanisms were present, partly concerning the V 2-3 areas, partly concerning the neck. Precipitation mechanisms in "SUNCT" to some extent seem to differ from those in trigeminal neuralgia. It is remarkable that all four hitherto reported cases are males.
Comparison of usefulness of high-dose dipyridamole echocardiography and exercise electrocardiography for detection of asymptomatic restenosis after coronary angioplasty. The present study compares the relative usefulness of the maximal treadmill exercise electrocardiography test with the high-dose dipyridamole echocardiography test (echocardiographic monitoring during dipyridamole infusion up to 0.84 mg/kg in 10 minutes) in detecting severe restenosis or coronary artery disease progression (greater than 70% stenosis) in asymptomatic patients 12 months after a primary successful coronary angioplasty. Criteria of positivity were: for the exercise electrocardiography test, an ST-segment shift greater than or equal to 0.1 mV from baseline, 0.08 second from the J point; for the dipyridamole echocardiography test, a transient dyssynergy of contraction, absent or of a lesser degree than that in the baseline examination. The exercise electrocardiography and dipyridamole echocardiography tests revealed a similar feasibility (91 vs 87%, difference not significant). Both tests could be performed in 75 patients. For detection of restenosis or disease progression, or both, the exercise electrocardiography test revealed a sensitivity similar to the dipyridamole echocardiography test (71 vs 71%, difference not significant), but a lower specificity (61 vs 90%). It is concluded that the high-dose dipyridamole echocardiography test is equally feasible but more accurate than the exercise electrocardiography test for noninvasive detection of severe asymptomatic restenosis or disease progression at 1 year after successful coronary angioplasty.
Cis- and trans-repression of class I major histocompatibility gene expression in Abelson virus-transformed murine leukemia. Numerous tumor cell lines of leukemic origin are known to modulate cell surface expression of major histocompatibility complex (MHC) class I antigens resulting in alterations in their immune detection and tumorigenicity. We have been studying the mechanisms responsible for attenuation of MHC class I gene expression in an H-2 heterozygous (H-2b x H-2d) Abelson-Murine leukemia virus (A-MuLV)-transformed leukemic cell line (designated R8). Here we report that treatment of the R8 cell line with the protein synthesis inhibitor cycloheximide (CHX) increased H-2Kb steady-state messenger RNA (mRNA) levels several fold. The induced H-2Kb mRNA transcripts were functional, as demonstrated by their ability to be translated into immunoprecipitable H-2Kb alloantigen. H-2Kb null variants derived from the R8 cell line were shown to be the product of both cis- and trans-acting mechanisms, insomuch as the treatment of R8-derived H-2Kb non-expressor lines with CHX re-established expression of H-2Kb mRNA to the same extent as transfection of the variant cell line with the wild-type H-2Kb gene. Such findings indicate that downregulation of MHC class I gene expression is constitutive for the R8 leukemic cell line, a phenomenon that may be related to the immature pre-B-cell phenotype of this A-MuLV transformant.
Smoking cessation following admission to a coronary care unit. OBJECTIVE: To determine the impact of an episode of serious cardiovascular disease on smoking behavior and to identify factors associated with smoking cessation in this setting. DESIGN: Prospective observational study in which smokers admitted to a coronary care unit (CCU) were followed for one year after hospital discharge to determine subsequent smoking behavior. SETTING: Coronary care unit of a teaching hospital. PATIENTS: Preadmission smoking status was assessed in all 828 patients admitted to the CCU during one year. The 310 smokers surviving to hospital discharge were followed and their smoking behaviors assessed by self-report at six and 12 months. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Six months after discharge, 32% of survivors were not smoking; the rate of sustained cessation at one year was 25%. Smokers with a new diagnosis of coronary heart disease (CHD) made during hospitalization had the highest cessation rate (53% vs. 31%, p = 0.01). On multivariate analysis, smoking cessation was more likely if patients were discharged with a diagnosis of CHD, had no prior history of CHD, were lighter smokers (less than 1 pack/day), and had congestive heart failure during hospitalization. Among smokers admitted because of suspected myocardial infarction (MI), cessation was more likely if the diagnosis was CHD than if it was noncoronary (37% vs. 19%, p less than 0.05), but a diagnosis of MI led to no more smoking cessation than did coronary insufficiency. CONCLUSION: Hospitalization in a CCU is a stimulus to long-term smoking cessation, especially for lighter smokers and those with a new diagnosis of CHD. Admission to a CCU may represent a time when smoking habits are particularly susceptible to intervention. Smoking cessation in this setting should improve patient outcomes because cessation reduces cardiovascular mortality, even when quitting occurs after the onset of CHD.
Cerebral abnormalities in congenital myotonic dystrophy. The brain structure of 14 infants born with congenital myotonic dystrophy at 2 hospitals was evaluated by cranial ultrasonography, and the findings were correlated with clinical and neuropathologic data. Ventricular dilation was diagnosed in 11 infants (78%). Seven infants died during the neonatal period; all had ventricular dilation which remained essentially static. In the ultrasound scans of the 5 infants with ventricular dilation. Of the 7 survivors, 4 had ventricular dilation born at 1 hospital, 4 had widening of the interhemispheric fissure. Macrocephaly, a previously unrecognized finding in congenital myotonic dystrophy, was present in 10 infants (71%), 8 of whom presented with ventricular dilation. None had clinical evidence of increased intracranial pressure. There was no ventricular obstruction in the 4 brains examined pathologically. Histologic examination revealed minor expression of neuronal migrational disturbances in each patient. Macrocephaly together with the ultrasonographic and neuropathologic findings in our patients suggest that these abnormalities may originate in an external hydrocephalus.
The treatment of atypical lipoma with liposuction. Large lipomas may best be treated with liposuction. Once a lipoma enlarges to 4 cm or more, liposuction has several advantages over conventional surgery. A well-demarcated lipoma 15 cm in diameter and deep to muscle was treated by liposuction. Biopsy showed an atypical lipoma. Because the entire tumor was removed by liposuction, we feel that the prognosis is excellent. The cosmesis and morbidity results were far superior to those anticipated with conventional excisional surgery. Small superficial lipomas may be treated by suction lipectomy and the surrounding area can be contoured symmetrically at the same time, whereas large ones can be liposuctioned completely without extensive surgical extirpation and morbidity. Because such big lesions may represent atypical lipomas or liposarcomas, care must be taken to remove the entire tumor.
Characteristics of serial electrocardiograms in heart transplant recipients. To characterize "normal electrocardiogram patterns" after transplantation, serial surface 12-lead electrocardiograms (ECGs) taken 2 weeks, 1 month, and 1 year postoperatively in a group of 50 heart transplant recipients were analyzed and were correlated with clinical parameters. Some recipient atrial activity was evident in 40% of patients at 2 weeks, but in only 16% at 1 year; donor atrial activity was normal in 90% to 94% of patients at all times. ECG intervals generally were normal and did not change over time. The most prevalent abnormality was the presence of incomplete (IRBBB) or complete right bundle branch block (RBBB) patterns (14% at 2 weeks, 16% at 1 month, and 22% at 1 year). In patients with hemodynamic measurements available approximately at the time of the ECG recording 1 year following transplantation, there was a significant correlation between the presence of IRBBB and RBBB patterns and somewhat higher levels of right atrial mean pressure (6.8 versus 3.9 mm Hg, p = 0.01), pulmonary artery systolic pressure (32.5 versus 24.5 mm Hg, p = 0.001) and diastolic pressure (16.2 versus 11.2 mm Hg, p = 0.004), and right ventricular systolic pressure (31.4 versus 26.9 mm Hg, p = 0.019) and pulmonary artery wedge mean pressure (11.3 versus 7.9 mm Hg, p = 0.010). Repolarization changes were also common but decreased in frequency over time (78% at 2 weeks to 34% at 1 year) and did not correlate with the presence or absence of rejection. We conclude that ECG abnormalities in heart transplant recipients are generally mild and that IRBBB and RBBB patterns correlate with increased right heart pressures.
Myasthenia gravis. T epitopes on the delta subunit of human muscle acetylcholine receptor. Autoimmune T cell lines specific for muscle nicotinic acetylcholine receptor (AChR) were propagated from the blood of three myasthenia gravis patients by the use of a pool of synthetic peptides (delta-pool) corresponding to the complete sequence of the delta-subunit of human muscle AChR. Propagation of AChR-specific T cell lines was attempted unsuccessfully from four other myasthenia gravis patients and from four healthy controls. The lines had CD3+, CD4+, CD8- phenotype, strongly recognized the delta-pool, and cross-reacted vigorously with non-denatured AChR purified from mammalian muscle. They did not cross-react detectably with pools of similar overlapping synthetic peptides corresponding to the complete sequences of the alpha- and gamma-subunits of human muscle AChR. The sequence segments of the delta-subunit that contain T epitopes were identified by investigating the response of the three CD4+ T cell lines to the individual synthetic peptides forming the delta-pool. Each line had an individual pattern of peptide recognition. Although no immunodominant region, recognized in association with different DR haplotypes, could be identified, the sequence segments most strongly recognized by the CD4+ T cell lines were clustered within residues 121-290. One of the peptides more strongly recognized by the T cells corresponded to a sequence segment with high predicted propensity to form an amphipathic alpha-helix, a structural motif proposed to be typical of T epitopes.
Cell associated urokinase activity and colonic epithelial cells in health and disease. It is not known if urokinase-type plasminogen activator (uPA) is associated with normal colonic epithelial cells. The aims of this study were to determine if normal colonic epithelial cells have uPA activity and whether this is concentrated at the cell membrane. In addition, the contribution of colonic epithelial cell associated uPA activity to disease related pertubations of mucosal uPA activity were examined. A highly enriched population of colonic epithelial cells was isolated from resected colon or biopsy specimens by an enzymatic technique. uPA activity was measured in cell homogenates by a specific and sensitive colorimetric method and expressed relative to cellular DNA. In two experiments subcellular fractionation of colonic epithelial cells was performed by nitrogen cavitation followed by ultracentrifugation over a linear sucrose gradient. The fractions collected were analysed for uPA and organelle-specific enzyme activities. Normal colonic epithelial cells have cell associated uPA activity (mean (SEM) 5.6 (1.1) IU/mg, n = 18). This colocalised with fractions enriched for leucine-beta-naphthylamidase and 5'-nucleotidase, markers of plasma membrane. uPA activities in epithelial cells from cancerous colons (9.8 (3.1) n = 7) or from mucosa affected by inflammatory bowel disease (3.8 (0.7) n = 15) were not significantly different from normal (paired t test), while that in epithelial cells from greatly inflamed mucosa was similar to that from autologous normal or mildly inflamed areas (4.4 (1.2) v 5.9 (3.6), n = 9). Thus normal colonic epithelial cells have cell associated uPA activity which is concentrated on the plasma membranes, suggesting the presence of uPA receptors.