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Biomedical subjects

B F Murphy

Publications and source records attributed to B F Murphy.

At least 55 records · Page 3Linked to original sources
PubMed1985

Subchronic toxicity studies of N-D-ornithyl amphotericin B methyl ester in dogs and rats.

Two subchronic studies were conducted to assess the potential toxicity of N-D-ornithyl amphotericin B methyl ester (OAME). In both studies the comparative control substance was amphotericin B (AMB). Dogs (5/sex/group) were given OAME (82% pure, based on high-pressure liquid chromatographic (HPLC) analysis) at 0.6, 2.5, and 10 mg/kg or AMB at 0.6 mg/kg intravenously once daily for 3 months. Two dogs per sex per group were retained for a 7-week postdose observation period. Rats (15/sex/group) were given daily doses of OAME at 4, 12, 24, and 36 mg/kg or AMB at 5 and 12 mg/kg intraperitoneally for 3 months. The principal organs of toxicity in both species were the liver, kidneys, and circulating erythrocytes. Hepatic changes in dogs consisted of periportal and centrilobular inflammation in animals of all dosed groups and were equivalent in dogs given 0.6 mg/kg OAME or AMB. In rats, acute hepatic necrosis with periportal, centrilobular, or panlobular distribution in animals of all OAME (except 4 mg/kg) and AMB-dosed groups was observed. These changes were equivalent in the 36-mg/kg OAME- and 12-mg/kg AMB-dosed animals. Renal changes, evidenced by increases in serum urea nitrogen water consumption, urine volume, decreased urine osmolality, and renal tubular changes (ranging from degeneration and regeneration to necrosis), were observed in both species. In dogs, these changes in the OAME-dosed animals were less severe at all doses than those observed in the AMB-dosed dogs. Renal changes in rats, which were mild in comparison to the dogs, were equivalent at doses of 5 and 12 mg/kg AMB and 36 mg/kg OAME. Decreased erythrocyte counts, hematocrit, and hemoglobin values were observed in both species. Unique to the dog study, however, were irreversible behavioral (somnolence, ataxia, tremors, and compulsive searching) and/or morphologic brain changes (gliosis with astrocytic hypertrophy and hyperplasia) at doses of 2.5 and 10 mg/kg OAME. Similar changes were observed in two dogs given 10 mg/kg OAME (100% pure, based on HPLC analysis) in a 6-week pilot study, indicating that the neurological changes were induced by OAME rather than by an impurity. These changes appear related to prolonged exposure to high plasma concentrations of OAME.

Alkaline Phosphatase↗
PubMed1985

Ketanserin in the acute management of severe hypertension.

Ketanserin is a 5-HT2 antagonist with alpha-adrenoreceptor blocking activity. This study examines the efficacy and safety of ketanserin in the control of severe primary and secondary hypertension, including renal hypertension. Patients with uncontrolled hypertension were admitted to hospital and entered the study if the supine diastolic blood pressure phase V (SDBP) was greater than 110 mm Hg after 2 h continuous BP monitoring (Dynamap). Ketanserin was administered as an intravenous (i.v.) 5 mg bolus every 60 s until SDBP fell greater than 15 mm Hg or maximum dose (30 mg) was reached, then by i.v. infusion at 4-20 mg/h to maintain SDBP fall greater than 15 mm Hg over 6 h. Twenty five patients were monitored and 20 (seven men, 13 women, ages 14-65 years) fulfilled the entry criteria. Seventeen of 20 were on antihypertensive medication, and 14 had underlying renal disease. Preinjection mean BP was 188/123 mm Hg for the 20 patients, falling at 5 min to 175/103 mm Hg. Supine diastolic blood pressure fell greater than 15 mm Hg in 16 of 20 patients. In these patients, BP remained satisfactorily controlled over the 6-h ketanserin infusion. Heart rate was unchanged. The four patients who did not respond were receiving the alpha-blocker prazosin, but seven other patients on high-dose prazosin did respond. We conclude that i.v. ketanserin is effective in the acute management of severe hypertension, including hypertension secondary to renal disease.

Adolescent↗
PubMed1985

Malignant hypertension due to an aldosterone producing adrenal adenoma.

Malignant hypertension in Conn's syndrome is rare. We report an 18 year old boy who presented with visual and renal impairment due to malignant hypertension which subsequently proved to be secondary to an aldosterone secreting adrenal adenoma. Diagnosis was delayed in this patient as plasma renin concentrations (PRC) were not invariably low and it is emphasized that suppression of PRC is not always a feature of primary hyperaldosteronism. The diagnosis of primary hyperaldosteronism is only excluded adequately by the demonstration of suppression of aldosterone secretion.

Adenoma↗
PubMed1984

Tapetal changes in beagle dogs. I. Ocular changes after oral administration of a beta-adrenergic blocking agent--SCH 19927.

SCH 19927 [R,R)-(-)-2-Hydroxy-5-[1-hydroxy-2-[(1-methyl -3-phenylpropyl)amino]ethyl]benzamide hydrochloride) is a beta-adrenergic blocking agent which has vasodilating properties. In a subchronic oral toxicity study in beagle dogs, SCH 19927 was given by gavage at doses of 30, 60, and 90 mg/kg. Lesions were observed at weeks 13 and 19 in the tapetum lucidum, a light reflecting structure of the eye. The lesions consisted of focal to multifocal areas of discoloration of the tapetal portion of the ocular fundus, pigmentation in the tapetal area, and, in one dog, subretinal edema resulting in a focal retinal detachment. Light and electron microscopic examination of the ocular lesions demonstrated tapetal cell degeneration and necrosis with macrophages, lymphocytes, and occasional plasma cells in the tapetum and adjacent choroid. Local cellular infiltrates within the retina internal to the pigmented epithelium were observed in one dog (60 mg/kg) which was demonstrated to have focal retinal edema during the study. In a repeat study the lesion again occurred in tapetal beagle dogs but not in atapetal beagle dogs (90 mg/kg) or cynomolgous monkeys (360 mg/kg). The lesion had not occurred in a previous subchronic study in albino rats. These results demonstrated that the tapetum lucidum was a target organ of toxicity for SCH 19927 and indicated that the finding was without observable toxicological significance in animals, including man, whose eyes do not have this structure.

Animals↗
PubMed1984

Culture of mid catheter urine collected via an open-ended catheter: a reliable guide to bladder bacteriuria.

Colony counts were compared from urine samples obtained by suprapubic aspiration and via a short, wide bore, open-ended urethral catheter. We studied 30 female patients in whom suprapubic aspiration of bladder urine was necessary to confirm the presence of bacteriuria with conventional or fastidious organisms. Catheterization was done immediately following suprapubic aspiration. Culture results of mid catheter urine specimens were similar to those from suprapubic aspiration urine specimens in 27 of 30 patients, a result considerably superior to that obtained with a conventional side-hole catheter. We conclude that a short, wide bore, open-ended catheter should be used to obtain urine specimens from female patients. Results confirm catheter specimens to be a satisfactory alternative to bladder aspiration of urine for detection of bacteriuria caused by fastidious micro-organisms or in patients with low numbers of conventional urinary tract pathogens.

Bacteriuria↗
PubMed1977

Probucol (Lorelco) in treatment of hyperlipemia.

The chemical structure of probucol differs from that of other hypolipemic agents, and its mechanism of action is unknown. This agent lowers elevated serum cholesterol (and low-density lipoprotein) levels and appears to be effective when used as an adjunct to a low-cholesterol, low-saturated-fat diet for treatment of type IIa hyperlipoproteinimia in adults; however, it is less effective than cholestyramine resin in patients with familial type IIa disorder. Although probucol has no consistent effect on elevated triglyceride levels, it may be useful as an adjunct to other drugs that lower these concentrations in patients with types IIb, III, and IV hyperlipoproteinemia when hypercholesterolemia persists. Probucol is generally well tolerated.

Cholesterol↗
PubMedDate not supplied

Sublytic complement injury does not activate NF-kappa B, or induce mitogenesis in rat mesangial cells.

Sublytic complement injury to glomerular mesangial cells, mediated by the terminal membrane attack complex of complement (C5b-9), is a potential initiating mechanism in IgA nephropathy. Sublytic complement injury has been reported to result in the production of a variety of pro-inflammatory molecules and growth factors, including many regulated by the transcription factor NF-kappa B. To determine the importance of complement injury in the pro-inflammatory signalling which occurs in IgA nephropathy, we investigated NF-kappa B activation following sublytic complement injury to cultured rat glomerular mesangial cells (RMCs). A sublytic dose of rabbit anti-Thy 1.1 (THY) serum and normal human serum was selected based upon flow cytometry, chromium-release assay, and induction of superoxide production. No significant C5b-9-induced NF-kappa B activation was detected by electrophoretic mobility shift assays, luciferase activity of RMCs transfected with a NF-kappa B-driven luciferase reporter construct, nor by Northern blots for the NF-kappa B-responsive mRNA species monocyte chemoattractant protein-1 or I kappa B alpha. Furthermore, measurements of (3)H incorporation following sublytic complement injury showed inhibition of mesangial cell mitogenesis in comparison to the heat-inactivated serum treatment and to THY alone. The results of this study suggest that sublytic complement injury to RMC does not directly activate NF-kappa B nor induce mesangial cell proliferation in mesangial cells. Other mechanisms such as IgA immune complex formation must be required to produce these events in IgA nephropathy.

Animals↗