Cefamandole kinetics in uremic patients undergoing hemodialysis.

A single intravenous 15 mg/kg dose of cefamandole was given to 6 patients in chronic renal failure before hemodialysis, and 3 were examined during an interdialysis period. Mean cefamandole clearance by hemodialysis was 24 +/- 12 ml/min; 35 +/- 15% of the dose was recovered in the dialysate. The cefamandole half-life (1 1/2) on dialysis was 4.0 +/- 0.29 hr; off dialysis it was 13.9 +/- 4.2 hr. High urine concentrations of cefamandole in these patients suggests usefulness in urinary tract infection.

Acute massive chloral hydrate intoxication treated with hemodialysis: a clinical pharmacokinetic analysis.

A 38-year-old female became comatose and exhibited signs of cardiac toxicity 2 hours after ingestion of approximately 38 Gm chloral hydrate. Hemodialysis was initiated 21 hours after ingestion, using twin coils in series, and was continued for 4.5 hours. Trichloroethanol, the active metabolite of chloral hydrate, was measured in plasma and dialysate. Two hours after ingestion, the plasma level was 330 micrograms/ml (average therapeutic level is 12 micrograms/ml or less). The predialysis level was 216 micrograms/ml and after dialysis declined to 141 micrograms/ml. The pre- and post-plasma half-life values were 35 hours, while on dialysis the half-life was only 6 hours. The average dialysis clearance was 120 ml/minute, and the amount of chloral hydrate removed by dialysis was 5.79 Gm. By the end of dialysis, the patient could respond to verbal commands and was ambulatory 36 hours later. In conclusion, hemodialysis can be a clinically important method of treating chloral hydrate overdose.

The heart in diabetes.

Since the introduction of insulin, heart disease has become a major impediment to survival in persons with diabetes mellitus. Coronary disease has increased severity and accelerated development in diabetic persons compared with an age- and sex-matched nondiabetic population. A peculiar vulnerability of women to the influence of diabetes with loss of premenopausal coronary disease protection has been found. The symptomatology of coronary events may differ and coronary care data show a higher incidence of sudden death in diabetic patients who have a myocardial infarction than in their non-diabetic counterparts. Insulin may play a role in the myocardial adjustment to an ischemic insult by enhancing glucose intake and suppressing lipolysis and ketogenesis. Carbohydrate intolerance in dogs, rhesus monkeys and humans appears associated with similar histologic and compositional changes in the myocardium. Abnormalities in diastolic ventricular function not attributable to large- or small-vessel coronary disease have been found in the diabetic subjects of each species. Studies in humans who have diabetes have assessed single pressure-volume relationships and more exacting measures of ventricular compliance are needed. Abnormalities of myocardial function in patients with diabetes have been found using echo and radionuclide techniques. Many of these findings need to be correlated with invasive data or confirmed in larger populations. Autonomic dysfunction is common in diabetic persons and may imply an associated poor prognosis. Reflex abnormalities in parasympathetic function are most prevalent and occur before sympathetic dysfunction.

Crescentic glomerulonephritis associated with nonrenal malignancies.

A review of 80 patients with the renal biopsy diagnosis of idiopathic glomerulonephritis with extracapillary proliferation (crescentic GN) disclosed 7 cases with a coexistent nonrenal malignancy; 6 carcinomas and 1 lymphoma. In a control group of 80 patients with the renal biopsy diagnosis of minimal change or focal segmental glomerulosclerosis, only 1 case of coexistent malignancy was found (chi-square = 4.74, p less than 0.05). All of the malignancies occurred in patients older than 40 years of age and the prevalence of malignancy in patients with crescentic GN over the age of 40 was 20%. Light microscopy, immunofluorescence, and electron microscopy revealed fibrin deposition in all cases and no evidence of anti-GBM or immune complex disease. 3 patients experienced a rapidly progressive course while renal function improved in 4 patients following treatment of the underlying malignancy. The pathogenic mechanisms leading to crescentic GN in patients with malignancy are unknown; however, the high prevalence of malignancy in crescentic GN patients older than 40 along with the improvement during the treatment of the underlying malignancy suggests an etiological relationship.

Fasting: the history, pathophysiology and complications.

An appreciation of the physiology of fasting is essential to the understanding of therapeutic dietary interventions and the effect of food deprivation in various diseases. The practice of prolonged fasting for political or religious purposes is increasing, and a physician is likely to encounter such circumstances. Early in fasting weight loss is rapid, averaging 0.9 kg per day during the first week and slowing to 0.3 kg per day by the third week; early rapid weight loss is primarily due to negative sodium balance. Metabolically, early fasting is characterized by a high rate of gluconeogenesis with amino acids as the primary substrates. As fasting continues, progressive ketosis develops due to the mobilization and oxidation of fatty acids. As ketone levels rise they replace glucose as the primary energy source in the central nervous system, thereby decreasing the need for gluconeogenesis and sparing protein catabolism. Several hormonal changes occur during fasting, including a fall in insulin and T(3) levels and a rise in glucagon and reverse T(3) levels. Most studies of fasting have used obese persons and results may not always apply to lean persons. Medical complications seen in fasting include gout and urate nephrolithiasis, postural hypotension and cardiac arrhythmias.