Richard C. Graham

Effect of corticosteroid therapy on human immunodeficiency virus-associated nephropathy

PURPOSE Human immunodeficiency virus-associated nephropathy (HIV-AN) occurs predominantly in blacks and is characterized histologically by focal segmental glomerulosclerosis or mesangial proliferation and a lymphohistiocytic tubulointerstitial infiltrate. Patients manifest heavy proteinuria and, once azotemia occurs, progress rapidly to end-stage renal disease within 2 to 6 months. No treatment has been shown to be useful for HIV-AN. The purpose of this study was to determine the effect of corticosteroid agents on the progression of HIV-AN. PATIENTS AND METHODS Four consecutive HIV-infected adults with fewer than 200 CD4 cells/microL, moderate to severe renal insufficiency, proteinuria greater than 2 g per 24 hours, and HIV-AN demonstrated by renal biopsy were treated with 60 mg of prednisone daily for 2 to 6 weeks. Patients were followed with respect to serum creatinine level, 24-hour protein excretion, adverse drug reactions, and the occurrence of opportunistic infections. RESULTS CD4 counts ranged from 30 to 80 cells/microL before therapy with steroids. The mean (+/- SD) pretreatment serum creatine concentration was 9.1 +/- 5.7 mg/dL and decreased to 3.3 +/- 1.8 mg/dL (P < 0.05) after 2 to 6 weeks of corticosteroid therapy. Twenty-four hour protein excretion did not change (5.2 +/- 2.4 g pretreatment versus 4.6 +/- 4.1 g posttreatment). One patient was able to discontinue dialysis after 10 days. Two patients developed Mycobacterium avium-complex infections and steroid-associated psychosis. One of these patients developed a recurrence of genital herpes, and the other developed dermatomal zoster. None of the four required dialysis during a 1.5- to 5.5-month period of follow-up after cessation of steroid treatment. CONCLUSION In selected patients with HIV-AN, short-term treatment with corticosteroid agents improves renal function and prevents the development of end-stage renal disease during a 1.5- to 5.5-month period of observation, but may be associated with an increased risk of opportunistic infection.

BOVINE LACTOPEROXIDASE AS A CYTOCHEMICAL PROTEIN TRACER FOR ELECTRON MICROSCOPY

beimmg analyzed (see Burks. op. cit.). When reaction product is studies, the emizyme acts as a multiplier for depositimig relatively large amounts of element in the tissume. Although a possible application of probe analysis, temporal displays of accumulatimig react ion product to evaluate kinetics of the histochemical reaction were not done iii this study. Ability to detect elemental precipitates with the electron probe cant reduce the number of steps in mammy histochemical reactions, as iii the onie described, thereby lessening the danger of false localizatiomi. Of perhaps greater importamice is that development of new histochemical reactions with otherwise imivisible elements in the reactiomi products is now possible. Acknowledgment. Mr. Guy Cnmnmningham performed the histochemical techniques.

Predisposing factors of systemic fungal infections of the genitourinary tract

We reviewed 50 patients with genitourinary fungal infections between 1982 and 1992. Infections were classified as simple--localized to the bladder and complex--demonstrated evidence of upper tract and/or systemic infection. Predisposing factors of fungal infections, including diabetes mellitus, prolonged Foley catheter drainage and corticosteroid use, were not significantly different. The incidence of obstructive uropathy (88% versus 20%), malnutrition (88% versus 48%), neoplasia (56% versus 16%), renal failure (24% versus 8%) and prolonged antibiotic use (60% versus 32%) were significantly greater in patients with complex infections. The incidence of fungemia in patients with complex infections was 81% with an associated mortality rate of 36%. Of the patients with complex infections 56% required urological intervention. Given the high incidence of obstructive uropathy with complex fungal infections, upper tract imaging is essential.

Fibrinogen Cleveland II AN ABNORMAL FIBRINOGEN WITH DEFECTIVE RELEASE OF FIBRINOPEPTIDE A

An abnormal fibrinogen (fibrinogen Cleveland II) was detected in the plasma of a 23-yr-old white man with a mild bleeding diathesis. The one-stage prothrombin time, thrombin time, and Reptilase time were all prolonged. 16 of 24 tested relatives had the defect, which appeared to be transmitted as an autosomal dominant characteristic. The thrombin time of normal plasma was slightly inhibited by the probands plasma. The abnormally long thrombin time of fibrinogen Cleveland II was partially corrected by addition of calcium ions. Fibrinogen Cleveland II was indistinguishable from normal fibrinogen by immunoelectrophoresis, DEAE-cellulose column chromatography, or polyacrylamide gel electrophoresis of reduced fibrinogen in sodium dodecyl sulfate. The major defect detected appeared to be impaired release of fibrinopeptide A when fibrinogen Cleveland II was incubated with thrombin. This defect was localized to the NH(2)-terminal disulfide knot portion of the molecule. An abnormality of polymerization of fibrin monomers was also present, but the abnormal fibrin demonstrated relatively normal crosslinking. Despite these defects, fibrinogen Cleveland II achieved a degree of coagulability similar to normal fibrinogen and appeared to incorporate some molecules of fibrin with intact fibrinopeptide A into the clot. The fibrin clot that was formed appeared to be abnormal by electron microscopy. These functional defects and other descriptive characteristics appear to distinguish fibrinogen Cleveland II from other inherited abnormal fibrinogens.

Pityriasis rubra pilaris : An unusual cutaneous complication of AIDS

Pityriasis rubra pilaris is an uncommon hyperkeratotic, papulosquamous disorder that has been reported in patients infected by HIV. We recount a case of pityriasis rubra pilaris in an HIV-seropositive man. A 36-year-old man with a history of ulcerative colitis and recurrent otitis externa had diffuse psoriaform erythroderma. He was treated initially with methotrexate and isoretinoin without clinical improvement. Skin examination showed large, erythematous, orange, scaly patches on the upper extremities and thickening of the nail beds. The palms and soles were hyperkeratotic. Skin biopsy revealed changes that were consistent with pityriasis rubra pilaris. Six months before the onset of symptoms, results of an enzyme-linked immunosorbent assay (ELISA) and Western Blot assay for HIV were negative. Six months after symptoms, results of repeat enzyme-linked immunosorbent assay and Western blots for HIV were positive (CD4+ T-cell count = 200 cells/ mm3). Clinical course had been complicated by episodes of Staphylococcus aureus bacteremia, mucocutaneous candidiasis, and development of localized squamous cell carcinoma of the skin. The increased severity of pityriasis rubra pilaris should prompt clinicians to consider coinfection with HIV in patients who have disease that is refractory to treatment. Clinicians also should remain vigilant for the development of squamous cell carcinoma.

Young Investigator Award. In vivo treatment of infected prosthetic graft material with urokinase: an animal model.

PURPOSE Pyogenic infection of vascular grafts represents a serious complication that may necessitate graft removal. If better treatment methods could be developed, perhaps some infected grafts could be salvaged and not removed. This study reports an animal model that evaluates the sterilization of contaminated vascular graft material implants with urokinase and antibiotics. MATERIALS AND METHODS Polytetrafluoroethylene (PTFE) implants were incubated overnight in a known concentration of bacteria (Staphylococcus epidermidis) and were then implanted subcutaneously into four groups of anesthetized hamsters. The first group (control) received no treatment. The second group received urokinase injections twice daily into each abscess. The third group received intraabscess urokinase and systemic gentamicin twice daily. The fourth group received only systemic gentamicin. The hamsters were killed after 1 week. The graft implants and surrounding tissues were excised and submitted for quantitative cultures. RESULTS With use of a cutoff value of 100 organisms per milliliter, below which the abscesses were considered noninfected, the following rates of noninfectivity were observed: group 1 (control), 5% noninfected; group 2 (urokinase only), 19.4%; group 3 (urokinase and gentamicin), 63.2%; and group 4 (gentamicin only), 32.5%. The noninfectivity rate of group 3 was significantly higher than that of all other groups combined (P < .001) and was significantly better than that of group 4 alone (P = .013). CONCLUSION The combination of intraabscess urokinase and systemic gentamicin is very synergistic in graft sterilization. Urokinase may assist in the degradation of both fibrin and the biofilm produced by S epidermidis, thus improving penetration of antibiotics and local host defense mechanisms.

Erythrocyte lipids and vitamin E in Type II congenital dyserythropoietic anemia

An 8-year-old girl with Type II congenital dyserythropoietic anemia, characterized by morphologic abnormalities of erythroid precursors, immunologic alterations, hyperbilirubinemia, and chronic anemia, was found to be vitamin E deficient. Nutritional history and vitamin E absorption studies indicated that neither dietary lack nor intenstinal malabsorption was the cause of the deficiency. Striking changes in the patients hematologic status following administration of vitamin E included rise in hemoglobin, decrease in bilirubin and reticulocyte count, and a marked increase in red blood cell survival. Erythrocyte phospholipids, altered while the patient was vitamin E deficient, returned to normal levesl during therapy. However, hematologic improvement was not complete, immunolotic abnormalities persisted, and morphologic aberrations in erythrocyte precursors actually increased during vitamin E therapy. It is therefore concluded that vitamin E deficiency played a secondary role in the production of the childs hematologic disorder and may have been a result of the increased utilization of the vitamin in stabilization of defective cellular membranes.