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Biomedical subjects

G A Porter

Publications and source records attributed to G A Porter.

At least 91 records · Page 5Linked to original sources

Effect of milk constituents on hepatic cholesterol-genesis.

Two preparations active in reducing hepatic cholesterol biosynthesis were isolated from bovine skim milk. One of the inhibitors was in the dialysate and was identified as orotic acid (OA). The other inhibitor, present in the retentate, was not identified. Orotic acid appears to act by inhibiting cholesterol biosynthesis before the formation of mevalonate, whereas the retentate inhibitor exerts its effect beyond the formation of mevalonate in the biosynthetic pathway. Human milk also inhibited the incorporation of both labeled acetate and mevalonate into cholesterol by rat liver. Orotic acid was not detectable in human milk samples employed in this study. Administration of [6-14C]orotate to rats revealed its conversion to uracil in the liver. Subsequent work demonstrated that uracil had inhibitory activity on hepatic cholesterol biosynthesis similar to that of orotate when incubated with rat liver slices.

Acetates↗

The influence of dosage regimen on experimental gentamicin nephrotoxicity: dissociation of peak serum levels from renal failure.

Peak serum levels of gentamicin were varied in rats by administering a standard nephrotoxic dosage of 40 mg/kg per day in one (QD), two, or three (TID) daily doses. The QD animals had the highest peak serum levels but showed no appreciable increase of serum creatinine concentrations over a 10-day treatment period. The TID rats had the lowest peak serum levels, but, after 10 days of drug administration, the serum creatinine concentration (2.8 +/- 0.2 mg/100 ml, mean +/- SE) was significantly higher than in control rats (0.6 +/- 0.01 mg/100 ml) (P less than 0.001). After two days of gentamicin treatment, the renal concentration of gentamicin was 269 +/- 77 micrograms/g in the QD rats and 820 +/- 29 micrograms/g in the TID rats (P less than 0.001). In this rat model, the frequency of doses was a more important factor in the development of nephrotoxicity than the peak serum concentration of gentamicin. The results suggest that dose frequency should be considered when data from different laboratories are compared.

Acute Kidney Injury↗

Adrenocorticotropin-cortisol axis abnormalities in hemodialysis patients.

The ACTH-cortisol axis was studied in 15 hemodialysis patients. Basal plasma cortisol concentrations were found to be elevated and ACTH to be in the high normal range. Cortisol responded normally to exogenous ACTH, but neither cortisol nor ACTH were suppressed in response to oral dexamethasone. 11-Deoxycortisol and ACTH concentrations did not rise normally in response to either oral or iv metyrapone. We conclude that standard testing of the ACTH-cortisol axis in dialysis patients yields results suggesting Cushing's syndrome.

Adrenocorticotropic Hormone↗

Influence of progestin upon hemodynamics in castrated male pygmy goats.

Effects of progestin administration for 5 to 6 weeks upon hemodynamics were studied in two separate experiments, using trained, adult castrated male Pygmy goats. Measurements of cardiac output, blood pressure, plasma volume, and oxygen content of arterial and mixed venous blood were made before, during, and after treatment. In experiment 1, four animals were used. Progesterone was implanted subcutaneously in silicone envelopes which released an average of 44 mg of progesterone/day/goat. A 20% decrease in cardiac output occurred by the 5th week of treatment. Blood pressure was maintained by an increased peripheral vascular resistance. The five animals in experiment 2 were given (IM) 6 mg of 17-alpha-hydroxyprogesterone/kg of body weight/day. Cardiac output decreased 17% in the 2nd and 3rd weeks of hormone treatment. 17-alpha-Hydroxyprogesterone caused a transient natriuresis followed by sodium retention. Urinary aldosterone excretion increased after 9 days of treatment, but returned to normal by the 15th day.

Animals↗

Gentamicin binding to serum and plasma proteins.

Gentamicin binding to serum proteins was studied by equilibrium dialysis at 37 degrees C and pH 7.4 in the presence of both physiologic and adjusted concentrations of ionized calcium and magnesium. The percentage of bound drug was inversely related to the concentration of these two divalent cations, raning from 27% bound with no calcium and magnesium present to 17% bound in the presence of four times physiologic concentrations. No significant difference in the extent of drug-protein binding was noted in a comparison of sera from healthy and uremic subjects. Heparin also was found to affect gentamicin binding. Increasing heparin concentration in serum increased apparent gentamicin-protein binding to 34% in the presence of physiologic amounts of calcium and magnesium. Buffered heparin solutions without plasma proteins bound up to 65% of total drug concentration. Gentamicin-protein binding may have implications regarding pharmacokinetics and renal cortical uptake.

Blood Proteins↗

Natural history of asymptomatic coronary arteriographic lesions in diabetic patients with end-stage renal disease.

Arteriosclerotic heart disease is a major cause of death in insulin-requiring juvenile diabetic patients treated for end-stage renal disease. Eleven consecutive diabetic patients without clinical evidence of coronary artery disease underwent complete cardiac evaluations, including coronary arteriography, as part of transplant recipient work-ups. Seven were women and four were men; their mean age was 32 (21 to 50 years). Angiographically, every patient had multifocal atherosclerotic coronary disease. Four of seven patients tested had positive-stress electrocardiograms. In this group of patients followed for a mean of 19.8 months, eight died. Of these deaths, six were due to coronary heart disease and another due to a stroke. In two patients who became clinically symptomatic, serial angiograms revealed progressive disease of the coronary circulation; in one case, despite normal renal allograft function and serum lipid levels. The mode of end-stage renal disease treatment, serum lipids or blood pressure control could not be linked to mortality. It is concluded that arteriosclerotic heart disease is common in diabetic patients with end-stage renal disease even when angina is absent. The natural history in this high risk population is an important consideration in the selection of patients for end-stage renal disease treatment.

Adult↗

Primary cadaver kidney transplantation in older patients: survival equal to dialysis.

In our experience, primary cadaver kidney transplantation is a reasonable alternative to dialysis in the older patient with ESRD. The probability for a transplant success is no different from that of other age groups receiving their first grafts from cadaver donors and the quality of life after transplantation is equal to or exceeds that obtained with chronic dialysis.

Aging↗

Myeloid bodies in the renal tubules of humans: relationship to gentamicin therapy.

Ultrastructural changes in renal proximal tubule lysosomes, including the formation of myeloid bodies, occur reliably with gentamicin administration in experimental animals. The present study reviewed the electron microscopic tubular morphology of renal biopsies and nephrectomies performed in our institution over a 2-year period. The frequency of myeloid bodies and their relation to drug therapy and selected clinical features were determined. Myeloid bodies were found in the proximal tubules of 19 of 109 cases that were judged adequate for study. On review of the drug histories of these 19 patients, 15 had received gentamicin within 6 weeks of biopsy or nephrectomy. None of the 90 patients without myeloid bodies had received the drug within 6 weeks of tissue examination. Of 4 patients with myeloid bodies who had not received gentamicin, 1 had received chloroquin and 3 had received drugs with no known or suspected capacity to induce myeloid bodies. The presence of myeloid bodies in proximal tubules did not appear to be related to the total dose of gentamicin, duration of therapy, or serum drug concentration. Clinical evidence of gentamicin nephrotoxicity was present in only 1 case.

Adolescent↗

Drug-related syndromes in clinical nephrology.

The major clinical presentations of disease to a nephrologist can be grouped into six general areas: acute renal failure, chronic renal failure, nephrotic syndrome, fluid-electrolyte disorders, acid-base disturbances, and the uremic symptom-complex. Each of these major clinical syndromes can be caused by, or related to, drugs or environmental toxins. Prototype drugs can be used to highlight the features of each drug-related syndrome. Although it is preventable, drug-related disease may present opportunities to learn about general pathophysiologic mechanisms in clinical nephrology.

Acute Kidney Injury↗

Do diuretics have antihypertensive properties independent of natriuresis?

To ascertain whether diuretics have an antihypertensive effect independent of natriuresis, 12 stable patients on maintenance hemodialysis underwent a crossover evaluation with hydrochlorothiazide, 50 mg daily, metolazone, 5 mg daily, or placebo in 4-wk treatment periods for 6 mo. Compliance was assured by pill counts and serum drug concentrations. All patients had daily urine less than 100 ml. Pre- and postdialysis blood pressure, body weight, plasma volume, and plasma renin activity were monitored. Over the 6-mo study period there were no statistically significant changes in any parameter related to diuretic therapy. It is concluded that a functioning kidney with the ability to respond to diuretics with a natriuresis is necessary for the antihypertensive action of diuretics. Direct vascular effects of diuretics to lower peripheral resistance could not be demonstrated in this unique patient population.

Adult↗

Ultrasound monitoring of fetal movements. A method for assessing fetal development?

Human fetal movements in utero have been analysed by conventional compound B-scan ultrasound techniques. With practice, movements of specific parts of the fetus can be readily recognised, and even as early as the 6th week after conception gross movements of the whole embryo are visible. Monitoring of fetal movements as an indication of normal or abnormal fetal development appears to have been neglected, and future studies in this important area of antenatal paediatrics are suggested.

Arm↗