Prospective trial of warfarin and dipyridamole in patients with membranoproliferative glomerulonephritis.

A prospective trial of warfarin and dipyridamole was performed in patients with membranoproliferative glomerulonephritis. Eighteen completed either a control or treatment year, and 13 completed both a control and treatment year. To obviate the bias of excluding control patients who had renal failure after one year, both an unpaired and a paired analysis were performed. The unpaired analysis compared 10 patients followed for an initial control year with eight patients receiving treatment first. Renal function remained stable over the year in the treated group, but worsened in the control group. Slopes of regression lines for reciprocal serum creatinine values were significantly different between groups (p less than 0.025). Urine protein excretion also decreased in the treated group. Four of 10 control patients had a two-fold increase in serum creatinine levels, but no treatment patient did. In the paired crossover analysis, significant differences in renal function were detected between control and treatment years in six patients whose renal function significantly changed over one of the years. In every instance, there was better preservation of renal function in the treatment year. Urinary protein also decreased significantly over the treatment year compared with the control year. Bleeding was the most frequent complication. These data suggest that warfarin and dipyridamole have a beneficial effect on renal function in membranoproliferative glomerulonephritis.

Effects of 13-CIS retinoids on premalignant and malignant cells of lung origin.

Deficiency of vitamin A has been shown to cause squamous metaplasia of the epithelium of the tracheobronchial tree. Vitamin A analogues, such as retinoid acid, have been shown to be effective in the treatment of various skin disorders in humans; these compounds have also caused a reduction in the incidence of carcinogen-induced tumors in experimental animals. For these reasons, a clinical trial with orally administered 13-CIS retinoic acid was conducted in 26 patients with varying degrees of cytologic abnormalities in sputum, ranging from moderately atypical metaplasia to overt carcinoma. The drug was administered in daily doses from 1 to 2.5 mg/kg or until toxicity was observed. The cytologic effects of the drug were monitored in sputum. The treatment did not affect the quantitative aspects of sputum cytology. However, degenerative alterations were observed in many of the abnormal cells. Although the experience with 13-CIS retinoic acid reported in this paper is too small for statistical analysis, the cytotoxic effects observed are sufficiently intriguing to suggest further studies in humans and experimental animals.

Hyperchloremia associated with membranoproliferative glomerulonephritis.

16 patients with membranoproliferative glomerulonephritis had a mean serum chloride level significantly higher than that in normal subjects or in comparable groups of patients with nephrotic syndrome secondary to either systemic lupus erythematosus or to other primary nephrotic glomerular diseases. Differences in the severity of histologic alterations of the renal interstitium did not correlate with the different levels of serum chloride seen in these groups. The increased chloride concentration may be partially explained as a compensating reaction for a decrease in protein anions. However, a renal tubular acidifying defect demonstrated in one of our patients may also contribute to the hyperchloremia in some cases.

Nephropathy and mixed cryoglobulinemia: evidence for an immune complex pathogenesis.

Mixed IgM-IgG cryoglobulins were present in the serum of a patient with the nephrotic syndrome, recurrent purpura, chronic active hepatitis and ascites. A renal biopsy demonstrated deposition of IgM, IgG, and complement components C3 and C4 in intracapillary 'coagula' and glomerular capillary walls. No glomerular deposition of alternate complement pathway components was noted. Serum levels of C3 and C1q were depressed, and the cryoprecipitate which contained monoclonal chi-type IgM and polyclonal IgG, behaved as an immune complex by in vitro C3 conversion tests. It is suggested that the renal disease resulted from entrapment of circulating cryoglobulin 'aggregates' having immunopathologic effects similar to those of immune complexes.

Dialysis-induced muscle cramps: treatment with hypertonic saline and theory as to etiology.

We postulate that plasma or muscle cell hypo-osmolality may be the major factor or co-factor causing muscle cramps during dialysis, rather than plasma volume contraction alone. The transient hyperosmolality induced with hypertonic saline is therapeutic because it reverses this abnormal state. We feel that the bolus administration of hypertonic saline is of great value in the therapy of dialysis-induced cramps and may be the treatment of choice. It is a rapid and effective means of relieving cramps at no risk to the patient, and without compromising ultrafiltration.