L-forms: evolution or revolution?
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Biomedical subjects
Publications and source records attributed to A M Paton.
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The pharmacokinetics of ceftazidime, a new injectable broad-spectrum cephalosporin with high anti-pseudomonal activity, were studied in 50 preterm, full-term and young infants after an intravenous bolus dose of 30 mg/kg. The serum concentrations of ceftazidime were higher in the younger babies, both premature and full-term. In infants over 2 months of age blood levels were similar to those of adult volunteer subjects. No untoward effects were encountered. Considering the in vitro activity of ceftazidime against a wide spectrum of pathogenic bacteria, the present dose schedules, 25-50 mg/kg/d for babies less than 2 months of age and 50-100 mg/kg/d for those 2-12 months of age, appear to be appropriate. Until more experience is gained with ceftazidime in neonates, monitoring of trough levels to ensure adequate blood concentrations would be ideal.
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Fifty neonates and infants with suspected or proven bacterial infection were given 30 mg/kg of ceftazidime as a single intravenous dose to investigate the pharmacokinetics of ceftazidime. The mean serum half-lives for babies aged less than 2 months was 4.18 +/- 1.60 h and for those aged 2 to 12 months 2.00 +/- 0.64 h. Dose bands of 25 to 50 mg/kg/day for those less than two months and 50-100 mg/kg/day for those aged 2 to 12 months are recommended for the treatment of suitable bacterial infections.
The pharmacokinetic behavior of ceftazidime was assessed after single bolus intravenous injections of 1 g to 12 male and 12 female volunteers. The kinetic handling of the drug was essentially identical in the two sexes, exhibiting two-compartment model characteristics. However, the peripheral compartment volume of distribution of ceftazidime was smaller in the females (mean 3.95 liters, compared with 6.15 liters), and this was attributed to a smaller extracellular fluid volume. Eight volunteers in each group also received single 1-g doses of ceftazidime into the vastus lateralis and gluteus maximus muscles. The time to peak concentration was longer in the women, and it was longer after injection into the gluteus maximus in both sexes, presumably because of differences in local blood flow. The bioavailability of ceftazidime may have been slightly reduced by delays in absorption. Again, body and renal clearances were similar for both sexes when allowance was made for differences in distribution volume.
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One hundred and seven consecutive cadaver kidney transplants have been followed for up to 6 years. The beneficial effect of HLA matching, shown in previous studies, has been confirmed. The 2-year failure rate from rejection was 29% for grafts with less than two incompatibilities, in comparison with a figure of 52% where there were two or more incompatibilities. In contrast to some reports, the presence of HLA antibodies did not have an adverse effect on the survival of first grafts. Patients not transfused prior to transplantation had a much higher 1-year graft failure rate (72%) than those given either frozen-thawed red cells (29%) or whole blood (23%). This apparently beneficial effect of blood transfusion was no greater in patients transfused with more than five units compared with those given less than five units. We believe that blood transfusion has an important influence on the outcome of renal transplantation.
Bilateral nephrectomy was performed in 53 patients on regular haemodialysis. The indications were pyelonephritis in 30, polycystic kidneys in 6, glomerulnephritis in 7, uncontrollable hypertension in 9 and horseshoe kidney in 1. In 87 per cent of cases the operation was carried out as a separate procedure prior to transplantation. The mortality was 9 per cent and the postoperative complications included hypotension, clotting of arteriovenous shunts, pneumonia and subphrenic abscess. As a result of our experience we have revised our indications for bilateral nephrectomy which now are pyelonephritis only when associated with persistent bacteriuria or ureteric reflux, polycystic kidneys and uncontrollable hypertension.
Ultrasound examinations of the pelvis and kidney have been carried out following 68 renal transplants. In 16 patients moderate sized or large perirenal or pelvic fluid collections were demonstrated. The composition of the fluid was lymph in seven cases, pus in four, blood in three and urine in two. Ten of these 16 patients had clinical features compatible with a pelvic fulid collection while six had no such localising features. We have found ultrasound to be extremely valuable in the diagnosis and precise localisation of pelvic fulid collections following transplantation, often at a stage before pressure effects and symptoms have appeared. It also provides a rapid and reliable means of excluding a pelvic or perirenal abscess in the pyrexial patient.
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Plasma concentrations of angiotensin II, renin, renin-substrate and aldosterone were measured in cases of acute renal failure. Angiotensin II, and renin levels were abnormally high on at least one occasion in nearly all patients. Mean angiotensin II and renin levels were highest in the first ten days of the disease. There was a highly significant positive correlation between concurrent estimations of renin and angiotensin II. Renin-substrate was also frequently elevated, but the correlations with renin and angiotensin II were not statistically significant. Despite the frequently marked elevation of plasma angiotensin II, only 2 of 17 measurements of plasma aldosterone were abnormally high. There was no significant relationship between aldosterone and plasma concentrations of angiotensin II, renin, sodium or potassium. The data are discussed in relation to current hypotheses implicating renin and angiotensin in the pathogenesis of acute circulatory renal failure.
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Explore the source record for details and available documents.
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Circulating levels of renin, angiotensin I, and angiotensin II were increased in six patients with chronic renal failure and hypertension uncontrolled by dialysis and hypotensive drugs. Lower and often normal levels were found in 10 patients whose blood pressure was controlled by dialysis treatment. For a variety of reasons all patients were subjected to bilateral nephrectomy. The logarithm of the decrease in plasma concentrations of renin and angiotensin II was significantly related to the fall of blood pressure after operation. Plasma renin concentration correlated significantly with blood angiotensin I concentration and with plasma angiotensin II in samples taken before and after nephrectomy. Renin, angiotensin I, and angiotensin II were measurable in samples of blood taken 48 hours or more after the operation.
The occurrence of an outbreak of influenza in a renal transplant unit is described. Five patients had a proved episode of infection, confirmed by a rise in the complement fixation titre to influenza virus A, and this coincided in three of the patients with episodes of acute rejection. It seems likely that the virus infection was responsible for the rejection, possibly through a stimulating effect of the virus on the host's immune response.