Verapamil ameliorates acute cyclosporine A (CsA) nephrotoxicity and improves immunosuppression after cadaver renal transplantation.
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Biomedical subjects
Publications and source records attributed to D Fisher.
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Gastric aspiration was performed continuously overnight and at hourly intervals during the daytime in 20 healthy male volunteers. Medications used included enisoprost 100, 200 or 400 micrograms, misoprostol 200 micrograms and placebo, given at bedtime. Each dose of enisoprost markedly inhibited nocturnal mean acid output, hydrogen ion activity, pH and peptic activity. The duration of these effects was up to 10 h. Misoprostol, given at bedtime, also decreased acid secretion, but the effect was significantly less than that observed with any of the doses of enisoprost. A dose-response effect for enisoprost was found for the mean nocturnal hydrogen ion activity and pH, as well as for maximum pH attained. Although enisoprost, given at bedtime, had a marked inhibitory effect on acid and pepsin secretion for the overnight interval, this did not result in rebound hyperacidity or a rise in serum total gastrin concentration. The results of this study suggest that enisoprost should be tested by clinical trial for the treatment of peptic ulcer disease.
A case of a multiply malformed liveborn infant with mosaic tetraploidy on examination of bone marrow but not of peripheral lymphocytes or skin fibroblasts is presented. The literature is reviewed and the clinical features of our patient are compared with those of the nine previously reported cases. We suggest that when the clinical suspicion of polyploidy is strong, it may be prudent to expand the search for the abnormality to include cytogenetic studies of the bone marrow, despite a normal karyotype in peripheral blood.
This study explored whether atrial natriuretic hormone (ANH) might be involved in the escape from salt and water retention that occurs in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Sixteen patients with low serum Na+ concentrations [123 +/- 1 (+/- SE) mmol/L] were studied. Each patient excreted urine that was hyperosmolar (mean, 391 +/- 4 mosmol/kg) in relation to serum osmolality (mean, 258 +/- 4 mosmol/kg). Sodium excretion (81 +/- 20 mmol/L) also was inappropriate to the low serum Na+ level. The probable causes of SIADH were head trauma (4), pneumonia (5), lung cancer (3), and chlorpropamide therapy (4). In the nontumor patients, plasma and/or urinary vasopressin (AVP) concentrations were in the normal range, but inappropriate for serum osmolality. Urinary AVP values of 50 pg/mL or more (greater than 46 pmol/L) were found in the three tumor patients. The mean plasma ANH concentration was 6-fold higher than that in normal subjects [296 +/- 51 vs. 51 +/- 13 pg/mL (100 +/- 20 vs. 17 +/- 4 pmol/L); P less than 0.01]. Six SIADH patients were studied again after brief (1-3 days) water restriction. Although serum osmolality increased in each, their plasma AVP concentrations decreased very little, and urinary AVP excretion and plasma ANH did not change. These results indicate that plasma ANH levels are markedly increased in patients with SIADH. Their increased ANH secretion may antagonize water retention resulting from the inappropriate AVP secretion.
The DNA adduct O4-ethylthymine can be alkylated under mild conditions with pentafluorobenzyl bromide. The product has good gas chromatographic characteristics and also forms a structurally characteristic anion in high yield when subjected to electron capture mass spectrometry. Related adducts for other DNA bases behave similarly. These properties stimulated us to develop a general analytical method based on the derivatization reaction. Important for this method is an oxidation-elimination reaction that mildly releases a base from a nucleoside. Thus, a general analytical method based on pentafluorobenzylation is now available for determining many alkyl and related DNA adducts.
Alpha 1-antitrypsin-Pittsburgh (AT-P), a naturally occurring lethal mutation (358Met----Arg), has been genetically engineered (rAT-P). The protein has been shown to be a potent active site-directed inhibitor of thrombin and the contact enzymes Factor XIIf, Factor XIa, and kallikrein. Because activation of the contact system is known to occur in gram-negative septicemia, the authors have hypothesized that the administration of rAT-P might modulate the course of this syndrome. Yorkshire piglets anesthetized with pentobarbital and infused with viable Pseudomonas aeruginosa (2 X 10(8) CFU) were untreated (Group I) or treated with rAT-P (Group II) and studied in a 6-hour protocol. Coagulation studies revealed that rAT-P significantly inhibited the rapid decrease in the functional concentrations of Antithrombin III, Factor XI, and fibrinogen. In addition, rAT-P markedly reduced the serum levels of fibrinogen degradation products. Survival in Group II was significantly increased during 2-5 hours but not at 6 hours when the functional levels of rAT-P in plasma were the lowest. These results indicate that this recombinant inhibitor, even at low concentrations, affords protection in experimental gram-negative septicemia.
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The surface properties of two isolates of Staphylococcus epidermis were compared by cell partitioning in aqueous two-phase systems. Strain K805 was isolated from the cerebrospinal fluid of a child with a shunt infection and strain 1105 was obtained from human faeces and not known to have caused infection. Strain K805 was significantly more negatively charged than strain 1105 but there was no significant difference in hydrophobicity when cultures were grown for 18 h. However, prolonged incubation of strain K805 caused the production of extracellular slime and a marked increase in surface hydrophobicity. Both strains showed enhanced growth in biphasic cultures.
The behaviour of strains of Klebsiella aerogenes of capsular serotype K21 and strains of Escherichia coli producing a structurally related polysaccharide (colanic acid) was analysed by phagocytic and serum-killing assays. The cell-surface characteristics of these strains and of non-capsulate strains derived from them were also investigated by partitioning experiments in aqueous two-polymer phase systems. The possession of K21-type capsule by K. aerogenes or colanic-acid polysaccharide by E. coli conferred a strong negative charge on capsulate bacteria. Negatively charged bacteria of E. coli producing colanic-acid capsules, however, like non-capsulate K. aerogenes, were susceptible to uptake by polymorphonuclear leukocytes. In contrast, K21 polysaccharide conferred on klebsiellae considerable resistance to phagocytic uptake. The finding that ingested non-capsulate derivative strains of K. aerogenes were less rapidly degraded by phagocytes than E. coli strains suggested that other components of the cell surface of Klebsiella, notably lipopolysaccharide, may be involved in protection against phagocytic killing. The presence of colanic-acid capsules on E. coli conferred little resistance to the bactericidal activity of human serum or phagocytic uptake and did not protect against intracellular killing by polymorphonuclear leukocytes.
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A slowly progressing colloidal goiter of 20 years standing was excised in a 67-year old woman. Two years later, a metastatic tumor inducing facial swelling was diagnosed radiologically in the left parotid gland and left ascending mandibular ramus. The incisional biopsy confirmed papillary carcinoma of thyroid origin. The patient refused treatment. Six months later, she returned to the clinic and presented with advanced destructive changes of the involved structures. This rare case of unrestricted malignant growth may shed light upon the sequence and mode of metastatic invasion.
Intracerebral haemorrhage (ICH), as documented in 77 patients by computerized tomographic (CT) scans, was studied with regard to presentation, neurological features and outcome. Death occurred in 34%, a lower figure than was thought in the pre-CT scan era, and comparable to reported series in the last 10 years. Survival was more common in patients with intralobar haemorrhage, in which there was a less close association with hypertension or with coma. Intraventricular haemorrhages carried a bad prognosis with 14 deaths out of the 24 patients thus diagnosed. Eighty-eight percent of the survivors returned home, and nearly half of them had almost normal function. The main negative prognostic factors as determined by discriminant analysis were: presentation with coma over several hours, abnormalities of pupils or eye movements, inability to be mobilized after an average of 4 days, large volume of haematoma as measured in CT scan and intraventricular bleeding. It is important to make the diagnosis in order not to give anticoagulant treatment inappropriately, and there should be awareness that ICH is more common than was previously thought.
Transilial bone biopsy confirmed heparin-induced osteopenia in a 23-year-old postpartum patient. Histomorphometric measurements during the reversible stage of bone disease that followed discontinuation of the heparin sodium therapy revealed signs of recovery; these were superimposed on a loose trabecular structure typical of osteoporosis. The histomorphometric evidence of recovery correlated well with signs of clinical improvement. In the majority of patients, heparin therapy during pregnancy is innocuous; however, discontinuation of treatment is recommended at the earliest signs of osteoporosis.
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Twenty-four-hour intragastric pH and serum gastrin profiles were monitored in six male asymptomatic patients who previously were found to have esophagitis on endoscopy and biopsy. They received cimetidine 300 mg qid (C), ranitidine 150 mg bid (R), or placebo (P) for one week each, utilizing the Latin-square design. The mean BAO was 0.4 +/- 0.2 mmol/hr, and the pentagastrin-stimulated MAO was 21.2 +/- 3.2 mmol/hr. In the P-treated patients, the pH fluctuated between 1.8 and 3.5 and over 90% of the readings were less than pH 4. As compared to P, both C and R significantly suppressed H+ after breakfast, overnight, and over the 24-hr period. The mean pH after lunch was significantly higher in R than in P, but not in C. Over the 24-hr period, a higher percentage of the readings were above pH 4.0 in R as compared to C. During the night, 50% of the pH readings were above pH 4.0 in C and R, whereas in P 50% of the pH readings were less than pH 2.0. The integrated gastrin responses after each meal were similar in C and R and were greater than in P. The biphasic response of the ratio of H+ and gastrin (H+/G) following each meal was suppressed by both H2-receptor antagonists, with numerically lower values obtained in R than in C. This study suggests that ranitidine 150 mg bid is superior to cimetidine 300 mg qid in suppressing the 24-hr intragastric acidity.
The efficacy of antacid in the treatment of benign gastric ulcer is less well established than in the treatment of duodenal ulcer. The objective of this study was to monitor ulcer healing and symptom relief in 38 patients with gastric ulceration treated for 6 weeks with cimetidine (Tagamet) 300 mg q.i.d. or an aluminum-magnesium containing antacid (Mylanta II) 10 ml q.i.d. (acid neutralizing capacity 203.2 mEq/day). The study was single-blind; the study physicians and those providing endoscopic assessments were not aware of the patients' treatment. Entered into the study were 19 male and 19 female patients ranging in age from 17 to 70 years, with a mean age of 52 years. None of the patients had taken cimetidine in the previous month, and none abused alcohol or nonsteroidal anti-inflammatory agents, but two-thirds of the patients were smokers. Five patients in the antacid group withdrew for numerous reasons including continued pain, noncompliance, and side effects. All patients in the cimetidine group completed the study, and no side effects were noted. There was no difference between the antacid- and the cimetidine-treated patients in the relief of symptoms. There was a significant difference in the 6-week ulcer healing between the groups, with 14/19 (74%) healed in the cimetidine group compared with only 6/14 (43%) healed in the antacid group (p less than 0.025). Thus, Mylanta II, 10 ml four times daily, is comparable to cimetidine 300 mg q.i.d. in the symptomatic relief of benign gastric ulceration, but ulcer healing was superior using cimetidine.
Certain kinetic aspects of the partitioning behavior of erythrocytes in dextran-poly(ethylene glycol) aqueous phase systems have been examined, and their implications for cell partitioning have been considered. It is concluded that the diverse and sometimes unique fractionations attained by use of multiple extractions (e.g., countercurrent distribution) of cells in two-polymer aqueous-phase systems depend on non-equilibrium conditions.