shukoor65/lab-rag-model huggingface dataset:
Importance of the renin-angiotensin system in sodium regulation in essential hypertension. To elucidate the effect of natriuretic and antinatriuretic factors on the excretion of an intravenous sodium load, we observed the natriuretic responses of 12 patients with essential hypertension (EHT) and 7 age- and sex-matched normotensive (NT) subjects following the intravenous administration of 1500 mL of normal saline over a 3 h period. After saline infusion, both groups showed increases in urinary sodium excretion (UNaV). The increases in glomerular filtration rate (GFR), atrial natriuretic peptide (ANP) and urinary dopamine excretion (UDAV) and the suppression of plasma renin activity (PRA) were similar in both groups. However, no significant change in blood pressure (BP) was seen in either group. Since significant negative linear correlations between the basal level of PRA and percent change in UNaV or GFR were seen only in EHT, we observed the influence of suppressing the renin-angiotensin system with a converting enzyme inhibitor. After a 7 day treatment with enalapril, GFR and UNaV in EHT after saline infusion were comparable to data obtained in the absence of enalapril, despite a reduction in preexpansion BP. Furthermore, a significant positive correlation between the basal BP and the percent increase in UNaV was seen among EHT after enalapril treatment. These results suggest that the state of the renin-angiotensin system is important in renal sodium excretion in EHT.
Mechanisms of otitis media development. Involvement of neurogenic inflammation. The mucosal lining of the middle ear cavity, in particular that of the tympanic membrane and its pars flaccida, exhibits a number of sensory nerves containing the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP). The mucosa is not only rich in nerves and blood vessels but also contains numerous mast cells. It is possible that interactions between histamine-containing mast cells and SP-containing and CGRP-containing nerves--neurogenic inflammation--is one of the mechanisms involved in vessel permeability changes in otitis media with effusion.
Clinical features of 31 patients with Ki-1 anaplastic large-cell lymphoma Thirty-one patients were diagnosed by morphologic and immunophenotypic features as having primary Ki-1 anaplastic large-cell lymphoma (Ki-1 ALCL). the median age was 35 years (range, 4 months to 78 years); the male:female ratio was 18:13. B symptoms were observed in 13 patients. Peripheral adenopathy was present in 26 patients, while mediastinal adenopathy occurred in five. There was extranodal disease in 13 patients; the most common extranodal site was skin with seven affected. Seventeen patients had stage III/IV disease. Immunophenotypes were T cell in 24 patients and B cell in four patients; immunophenotype could not be determined in three patients. Cytogenetic abnormalities in chromosomes 2, 5, and 7 were detected in three patients. Although therapy was heterogeneous, the actuarial 2-year survival was 73%. Two-year disease-free survival was 39% for all patients; for stages I and II, it was 62% compared with 20% for stages III and IV (P = .001). Complete remission (CR) occurred in 21 of 23 patients receiving combination chemotherapy; however, nine relapses, including six of seven stage IV patients, occurred within 21 months of diagnosis. Preliminary observations suggest that Ki-1 ALCL may have a quiescent phase in the rare patient with only localized skin disease. However, the disease generally behaves as an intermediate- to high-grade lymphoma, and patients with Ki-1 ALCL should receive curative-intent combination chemotherapy.
Renal vascular response to sodium loading in sons of hypertensive parents. Studies of normotensive offspring of hypertensive parents offer the potential to identify inherited abnormalities that contribute to essential hypertension. We compared renal and systemic hemodynamic responses to saline infusion between normotensive sons of two hypertensive parents (SOHT) and sons of two normotensive parents (SONT) selected from the general population of Rochester, Minn. Hemodynamic measurements were performed after a week of low sodium intake (10 meq/day) and were repeated after a week of high sodium intake (200 meq/day). Despite being in the normotensive range, blood pressures in SOHT were higher than those in SONT during low sodium (124 +/- 3/85 +/- 3 versus 118 +/- 2/71 +/- 2 mm Hg, p less than 0.01) and high sodium (122 +/- 3/80 +/- 3 versus 112 +/- 2/70 +/- 2 mm Hg, p less than 0.05) conditions. Higher pressures in SOHT were associated with elevated systemic and renal vascular resistance. After a high sodium diet, renal vascular resistance in SOHT rose further during acute saline infusion, whereas systemic vascular resistance did not change. After a low sodium diet, this renal vasoconstrictor response to saline infusion in SOHT was not present, and renal vascular resistance fell to levels not different from SONT. Plasma renin activity, aldosterone, and atrial natriuretic peptide did not differ between SONT and SOHT. Circulating levels of norepinephrine were higher in SOHT. These data demonstrate a renal vasoconstrictor response to saline infusion in normotensive SOHT, which depends on prior sodium intake. This alteration in renal hemodynamics may represent an inherited abnormality related to the development of hypertension.
Temperature and total white blood cell count as indicators of bacteremia. This study was designed to quantify more precisely the accuracy of magnitude of rectal temperature and total white blood cell (WBC) count as indicators of bacteremia in children with an obvious focal bacterial infection. A total of 955 children, aged 3 to 36 months, who had rectal temperature greater than or equal to 39.0 degrees C and were seeking care at either of two urban pediatric emergency departments had blood drawn for culture; 885 had blood drawn for WBC count. Twenty-seven had bacteremia. Various combinations of temperature and WBC count were selected to construct receiver-operating-characteristic curves by plotting sensitivity vs false-positive rate (1 - specificity). The receiver-operating-characteristic curve of WBC count provided significantly better diagnostic information than the curve for temperature increments above 39.0 degrees C. Each increment of 0.5 degrees C led to large decrements in sensitivity and false-positive rates. At a WBC count cutoff of 10,000/mm3, the sensitivity was 92% while the false-positive rate was 57%. Using this cutoff point, the clinician could have avoided performing 368 of 955 blood cultures and missed only 2 of 26 children with bacteremia. Receiver-operating-characteristic curves combining WBC count and temperature increments above 39.0 degrees C provided no better diagnostic information than that of WBC count at a temperature cutoff of 39.0 degrees C. It is concluded that increments in temperature above 39.0 degrees C provided additional diagnostic specificity for bacteremia only at the expense of unacceptable decreases in sensitivity. Total WBC count provided better information. A WBC count cutoff of 10,000/mm3 increased specificity with minimal decrease in sensitivity.
Pulmonary veno-occlusive disease. Fatal progression of pulmonary hypertension despite steroid-induced remission of interstitial pneumonitis. This report describes a 28-yr-old patient with pulmonary veno-occlusive disease (PVOD). She presented with pulmonary hypertension, hypoxemia, and interstitial pneumonitis. We report the discordance between the response of her hypoxemia and interstitial pneumonitis, which resolved with corticosteroid therapy, and her progressive pulmonary hypertension, which caused fatal right heart failure. This report emphasizes that the radiographic interstitial shadowing of PVOD may be caused by either (1) an inflammatory interstitial pneumonitis (which may be responsive to anti-inflammatory therapy) or (2) interstitial pulmonary edema, or both.
Low-dose isradipine once daily effectively controls 24-h blood pressure in essential hypertension. In one study of 10 patients with mild-to-moderate hypertension, equivalent total daily doses (13 +/- 2 mg) of isradipine given twice daily and a modified-release formulation of isradipine (isradipine MR) given once daily were found to control adequately 24 h ambulatory blood pressure compared with placebo (P less than .001 for each v placebo). In another study of 22 patients with essential hypertension, 5 and 10 mg isradipine MR once daily has been shown to reduce the average 24 h blood pressure by 11 +/- 1/6 +/- 1 mm Hg (P less than .001) and 13 +/- 2/9 +/- 1 mm Hg (P less than .001), respectively, compared with placebo. There was no loss of efficacy with isradipine MR during the 24 h observation period with either dose. In conclusion, low-dose isradipine MR once daily is an effective first-line treatment in essential hypertension.
Pediatric endoscopic retrograde cholangiopancreatography. Endoscopic retrograde cholangiopancreatography (ERCP) was performed 42 times in 38 patients aged 14 months to 20 yr at Children's Hospital of Pittsburgh from 1982 to 1990. The adult side-viewing duodenoscope, Olympus JF1T, was used for all procedures. Intravenous sedation was used in 68% of the patients, whereas general anesthesia was employed in the remainder. Visualization of the appropriate ductal system was accomplished in 35 patients (92%). No therapeutic maneuvers were performed at endoscopy. Eleven of the 22 patients with ductal abnormalities underwent surgical treatment, based on the ERCP findings. The only complication encountered was mild pancreatitis in three patients (8%), all with a history of pancreatitis. We conclude that ERCP is a safe, useful procedure in the evaluation of children with pancreaticobiliary disorders, and in the identification of surgically correctable lesions in 29% of those patients.
Venous emboli occurring caesarean section: the effect of patient position. The effect of position, horizontal versus 5 degrees reverse Trendelenburg's, on the incidence of venous emboli during Caesarean section was evaluated in 207 patients. Venous emboli were diagnosed using precordial ultrasonic Doppler monitoring. In the horizontal position, 44% (60 of 134) parturients had venous emboli compared with 1% (1 of 73) parturients in the 5 degrees reverse Trendelenburg's position (P less than 0.0001). Epidural anaesthesia was performed in 171 patients, and 36 patients had general anaesthesia. In the epidural group, pulse oximetric haemoglobin oxygen desaturation and complaints of chest pain and/or dyspnoea were associated with the venous emboli. Venous emboli, probably air, occur frequently during Caesarean section with the patient in the horizontal position. This occurrence was minimized by placing the patient in the 5 degrees reverse Trendelenburg's position.
Recognizing early Parkinson's disease. Differential diagnosis of Parkinson's disease should cover not only the classic disorder described by James Parkinson in 1817 (paralysis agitans) but also numerous other idiopathic and secondary disorders that have varying degrees of parkinsonian features. Because treatment options can vary greatly among mimicking disorders and differ from those effective for Parkinson's disease, a prompt, accurate diagnosis is essential. Physicians can distinguish between these often-overlapping disorders by differentiating primary from secondary parkinsonism and by classifying primary syndromes into disorders with prominent tremor and those without.
An in vivo model of experimental arterial stenosis, intimal damage, and periodic thrombosis. Coronary artery bypass grafts, angioplasty, and thrombolysis are beneficial procedures for patients with coronary artery disease. However, these procedures can fail by mechanisms related to interactions between platelets and the damaged arterial wall. An experimental model for studying some of the mechanisms of platelet interaction with endothelial- and medial-damaged stenosed arteries is described. Dogs or pigs are anesthetized, and the chest opened. The heart is exposed, the circumflex or left anterior descending coronary artery is dissected out, and an EMF or Doppler flow probe is placed on it. Distal to the flow probe, the artery is clamped with a vascular clamp to produce endothelial and/or medial injury. Then, an encircling plastic cylinder is placed around the outside of the injured artery, producing a "critical stenosis." Acute platelet thrombus formation begins to occur in the stenosed lumen, gradually increasing the amount of stenosis. This causes the coronary flow to decline and reach zero flow when the artery is completely occluded. Then, the thrombus is embolized into the distal circulation, and flow is restored to normal levels. This occurs repeatedly causing cyclic flow reductions (CFRs). These CFRs can be made larger and to occur more frequently by increasing in vivo platelet activity, by raising the plasma catecholamine levels, or by increasing the collagen exposed in the stenosed lumen by increased medial damage. If an effective dose of an antiplatelet agent is given, the CFRs will be decreased in size and frequency or abolished entirely. Aspirin and other agents abolish the CFRs in this model; however, CFRs can be renewed by infusions of catecholamines or platelet activating factor. Thus, the model may be useful for studying mechanisms that enhance or inhibit arterial thrombosis in stenosed arteries with endothelial and medial injury.
Characterization of recombinant factor VIII and a recombinant factor VIII deletion mutant using a rabbit immunogenicity model system. The use of factor VIII prepared genetically engineered cell lines (rFVIII) may avoid some of the problems inherently associated with administering plasma-derived factor VIII (pdFVIII) concentrates to hemophilia A patients. Although rFVIII may represent an improvement over traditional therapeutics, the chance exists that protein production in cell culture may result in the presence of novel epitopes that may enhance the formation of inhibitor antibodies capable of neutralizing either rFVIII or pdFVIII. To assess the differences between rFVIII and its plasma-derived homologue, a rabbit immunogenicity model system was developed. Antibodies raised to rFVIII in rabbits were tested for the presence of antibodies capable of binding rFVIII but not pdFVIII, the presence of which would suggest that novel epitope(s) were present. This analysis was performed using a competitive enzyme-linked immunosorbent assay, as well as immunoadsorption. For either technique, rFVIII-specific antibodies were not detected, indicating that differences between rFVIII and pdFVIII were not found. When a rFVIII B-region deletion mutant was similarly tested, antibodies specific for this protein were found. These specific antibodies appeared to bind in the vicinity of the deletion site and their binding was not affected by carbohydrate removal. These results indicate that the rabbit immunogenicity model system is sensitive to alterations in the factor VIII molecule and suggest that full-length rFVIII will not be any more immunogenic in human patients than pdFVIII.
Thrombin and parathyroid hormone mobilize intracellular calcium in rat osteosarcoma cells by distinct pathways. The mechanisms by which PTH and thrombin mobilize intracellular Ca2+ (Cai2+) were examined in UMR 106-H5 rat osteosarcoma cells. Bovine PTH-(1-34) (24 pM to 240 nM) produced a dose-dependent increase in Cai2+ (EC50, 3 nM), which returned to baseline within 75 sec. Human alpha-thrombin produced an increase in Cai2+ (ECmax, 10 U/ml) which was similar to that of PTH with respect to both magnitude and time course. Chelation of extracellular calcium with 5.0 mM EGTA did not alter the Cai2+ response to either PTH or thrombin. When added together at maximally effective concentrations, PTH and thrombin produced additive effects on Cai2+ in the presence and absence of EGTA. The additive effects of PTH and thrombin on Cai2+ were confirmed at the single cell level, using laser-based image analysis. Bradykinin (1 microM) produced a significant increase in Cai2+ in UMR 106-H5 cells which was of lesser magnitude than the peak 2- to 3-fold increase elicited by PTH or thrombin. Preexposure of cells to 10 U/ml thrombin for 2 min abolished the Cai2+ response to bradykinin, whereas preexposure to 240 nM PTH had no effect on the Cai2+ response to bradykinin. Thrombin elicited a rapid increase in the accumulation of 3H-labeled inositol phosphates (IP2 and IP3) in UMR 106-H5 cells, with increases in [3H]1,4,5-IP3 detectable as early as 15 sec after the addition of thrombin. Bradykinin increased [3H]IP production to a lesser extent than thrombin, whereas PTH neither increased [3H]IP accumulation nor potentiated the [3H]IP response to thrombin. The results suggest that thrombin and bradykinin mobilize Cai2+ from a shared IP3-responsive calcium pool, whereas PTH may use signals in addition to 1,4,5-IP3 to mobilize calcium from a distinct cellular calcium pool. Alternatively, specific calcium compartmentalization exists, and there is differential coupling of these agonists to the 1,4,5-IP3/Cai2+ pathway.
Disturbed secretion of atrial natriuretic peptide in patients with persistent atrial standstill: endocrinologic silence. Persistent atrial standstill is a very rare pathophysiologic condition whose diagnosis is established when both electrical and mechanical silence of the atria are confirmed. To test the hypothesis that secretion of atrial natriuretic peptide is disturbed in patients with persistent atrial standstill, the response of atrial natriuretic peptide secretion and other neurohormonal factors during exercise was investigated in three patients with a rate-responsive ventricular demand (VVI) pacemaker implanted for confirmed persistent atrial standstill. The results were compared with those observed in eight normal subjects and patients with a rate-responsive VVI (Group A) or atrial demand (AAI) (Group B) pacemaker implanted for confirmed sick sinus syndrome. Patients in Group A displayed significant elevation of alpha-human atrial natriuretic peptide secretion both before and during exercise (122.5 +/- 14.8 and 207.5 +/- 8.3 pg/ml, respectively) compared with those in Group B (55 +/- 14.1 and 116.4 +/- 51.5 pg/ml, respectively) and the normal subjects (18.9 +/- 9.8 and 30.8 +/- 19.2 pg/ml, respectively). This indicated development of a nonphysiologic increase in atrial volume or pressure overload, or both, in rate-responsive VVI pacing because of lack of atrioventricular synchrony. However, patients with persistent atrial standstill had undetectable (less than 10 pg/ml) or almost undetectable secretion of atrial natriuretic peptide as well as lower levels of cyclic guanosine monophosphate in the circulation both before and during exercise. Changes in plasma catecholamines during exercise were similar in patients with persistent atrial standstill compared with the other groups. This study indicates that "endocrinologic silence" accompanies electrical and mechanical silence of the atria, which may constitute a third diagnostic clue to persistent atrial standstill.
Kinetics of Borrelia burgdorferi dissemination and evolution of disease after intradermal inoculation of mice. Borrelia burgdorferi dissemination to selected target organs was examined on days 1, 2, 3, 4, 7, 10, 15, 21, and 30 after intradermal inoculation of 4-week-old C3H mice. Infection was determined by culture (blood, spleen, kidney, ear punch); polymerase chain reaction (PCR) for outer surface protein A (OSP A) DNA (ear punch); histology and spirochete histochemistry (spleen, kidney, skin, heart, joints); and OSP A DNA in situ hybridization (joints, heart). Blood or spleen of most mice were culture positive by day 3 and ear punch by day 10. Polymerase chain reaction performed on ear punches was also positive by day 10. Inflammation of joints and tendons began on days 4 through 7 and heart on days 7 through 10, which coincided with colonization of tissues with spirochetes. Spirochetes were multifocal in distribution, with a predilection for collagenous connective tissue of joints, heart, arteries, nerves, muscle, skin, and other tissues. Relative numbers of spirochetes peaked at 15 days, then decreased by 21 days. Gamma M immunoglobulin (IgM) antibody was detectable on immunoblots as early as day 4, with subsequent declining reactivity, and IgG antibody was detectable by day 7, with expanding reactivity to multiple antigens through day 30.
Constrictive pericarditis masquerading as Budd-Chiari syndrome. Budd-Chiari syndrome (BCS) and constrictive pericarditis (CP) share many common clinical features. Over the last year we encountered three patients in whom CP clinically mimicked BCS. Two of the three did not even have raised jugular venous pressure. One patient with severe jaundice and hepatic coma ultimately died. Liver biopsy features were not discriminating. The final diagnosis of CP was established by echocardiography, chest computed tomography (CT), or cardiac catheterization. We conclude that in all patients with apparent BCS and atypical features, a noninvasive test like echocardiography or chest CT should be done to rule out treatable illness like CP before embarking on such invasive procedures as liver biopsy for diagnosis.
Calcium and carcinogenesis of the mammary gland. Effects of dietary calcium on mammary carcinogenesis in rats were investigated because of evidence that calcium counteracts the promotion of colon cancer by dietary fat and because experimental diets for rats normally contain higher amounts of calcium and vitamin D than do human diets. Our earlier experiments indicated that yields of tumors induced in young, Sprague-Dawley rats by 7,12-dimethylbenz(a)-anthracene (DMBA) were higher when dietary calcium, phosphate, and vitamin D were decreased. Results of an experiment in which dietary amounts of calcium, phosphate, and vitamin D were varied independently suggested that phosphate and vitamin D have interactive effects with calcium. Another experiment in which dietary vitamin D alone was varied provided evidence that higher amounts inhibited tumorigenesis in the presence of low amounts of calcium and phosphate but the results with a high-calcium and -phosphate diet were inconclusive. The findings suggest that low amounts of dietary calcium and vitamin D and high amounts of phosphate increase susceptibility to DMBA-induced mammary neoplasia.
Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases. Molecular analysis of the human beta-galactosidase gene revealed six different mutations in 10 of 11 Japanese GM1-gangliosidosis patients. They were the only abnormalities in each allele examined in this study. A 165-nucleotide duplication (positions 1103-1267) was found in two infantile patients, producing an abnormally large mRNA; one patient was probably a homozygote, and the other was a heterozygote of this mutation. The other two infantile patients had different mutations; a 123 Gly(GGG)----Arg(AGG) mutation in one patient and a 316 Tyr(TAT)----Cys(TGT) mutation in the other. A 201 Arg(CGC)----Cys(TGC) mutation, eliminating a BspMI site, was detected in a late-infantile/juvenile patient; the restriction-site analysis of amplified genomic DNA confirmed his heterozygosity for this mutation. A 51 Ile(ATC)----Thr(ACC) mutation was found in all five adult/chronic patients examined in this study. It created a SauI site, and restriction-site analysis confirmed that four patients were homozygous mutants. The other was a compound heterozygote for this mutation and another 457 Arg(CGA)----Gln(CAA) mutation. These mutant genes expressed markedly decreased or completely deficient enzyme activities in beta-galactosidase-deficient human fibroblasts transformed by adenovirus-SV40 recombinants. We conclude that gene mutations are heterogeneous in GM1-gangliosidosis but that the 51 Ile(ATC)----Thr(ACC) mutation is common among the Japanese adult/chronic cases. Genotype-phenotype correlations in GM1-gangliosidosis are briefly discussed.