The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis.

The frequency with which florid duct lesions are seen in needle-biopsy specimens of the liver was assessed in patients with primary biliary cirrhosis (PBC) enrolled in a 2-year randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) versus placebo. Paired biopsy specimens obtained at entry and after 2 years on medication were reviewed blindly and mostly simultaneously by a panel of 5 hepatopathologists who, earlier, had characterized the florid duct lesion, which has been well described in the pathology literature. Florid duct lesions at entry were identified in approximately 36%. Patients with earlier disease showed florid duct lesions much more frequently than those with more advanced disease. The prevalence of florid duct lesions in 60 patients receiving placebo medication fell from 38.3% to 21.7%, P =. 025, over the period of 2 years. The prevalence of florid duct lesions also decreased in the 55 patients receiving UDCA, from 32.7% to 18.2%, P =.046. The prevalences of these lesions in the placebo and UDCA patients at entry and at 2 years were not significantly different from each other. The findings suggest that UDCA does not prevent ongoing bile duct destruction in patients with PBC. Instead, they support the impression that UDCA exerts its beneficial effects by protecting against the consequences of bile duct destruction.

Histologic similarity of murine colonic graft-versus-host disease (GVHD) to human colonic GVHD and inflammatory bowel disease.

In a study designed to determine which T-cell subsets are involved in the development of murine graft-versus-host disease (GVHD), a prospective histologic analysis of gastrointestinal involvement was performed. In C57BL/6JXDBA/2F1 (B6D2F1) recipients of DBA/2 donor spleen and bone marrow cells, the colonic histologic findings were found to be similar in many respects to the histologic findings reported in human colonic GVHD and were much more severe and diffuse than were the abnormalities of the small intestine. Host irradiation before transplantation was found to play an additive or synergistic role in the development of GVHD. Furthermore the histologic features noted in DBA/2----B6D2F1 murine colonic GVHD suggest that bone marrow and spleen cell transplantation in this strain combination may be a useful model for studying the immunologic mechanisms involved in human inflammatory bowel disease. Thus severe colonic disease noted during the course of DBA/2----B6D2F1 murine GVHD was found to have significant histopathologic similarities to both human GVHD enteropathy and other inflammatory diseases of the human colon.

Liver histopathologic findings in women with sickle cell disease given prophylactic transfusion during pregnancy.

Forty women with a major sickle hemoglobinopathy (hemoglobin SS, SC, or S-beta-thalassemia) were given red blood cell transfusions prophylactically during pregnancy. A mean of 13.6 units of erythrocytes per woman was given and none received more than 28 units. Direct-vision needle biopsy of the liver was performed in conjunction with cesarean section or puerperal sterilization. Although iron deposition in hepatocytes and Kupffer cells was identified commonly, neither cirrhosis nor widespread hepatocellular necrosis was found. We conclude that the risk of irreversible hepatic damage is negligible in women with sickle hemoglobinopathies who are given erythrocytes prophylactically during one pregnancy.

Intestinal graft-versus-host disease is initiated by donor T cells distinct from classic cytotoxic T lymphocytes.

In these studies, the role of T helper and T cytotoxic cells in generating intestinal graft-vs.-host disease (GVHD) was examined. Treatment of C57BL/6J (B6) splenocytes with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes natural killer cells, cytotoxic T lymphocyte (CTL) precursors, and the capacity to cause lethal GVHD in irradiated B6xDBA/2 F1 (B6D2F1) mice while preserving T helper cell function. Neither control nor Leu-Leu-OMe-treated DBA/2 donor spleen and bone marrow cells were found to induce lethal GVHD in B6D2F1 recipients. However, extensive colonic GVHD developed in B6D2F1 recipients of DBA/2 bone marrow and spleen cells. Enteropathic GVHD in DBA/2----B6D2F1 mice was reduced in severity after anti-L3T4 + C treatment of donor cells, and was eliminated by anti-Thy1.2 + C or the combination of anti-L3T4 and anti-Lyt2 + C treatment of the donor cell inoculum. However, neither anti-Lyt2 + C, Leu-Leu-OMe, nor anti-Lyt2 + C and Leu-Leu-OMe treatment of donor cells significantly decreased severity of gut GVHD. Leu-Leu-OMe treatment of DBA/2 or B6 SpC was comparably effective in preventing in vitro or in vivo generation of B6D2F1-specific CTL. These findings, therefore, demonstrate that histologically severe enteropathic GVHD does not require participation of CTL and is not always associated with high mortality rates.

Chronic sclerosing glomerulopathy (heroin-associated nephropathy) in intravenous T's and Blues abusers.

The intravenous (IV) use of pentazocine (Talwin) and tripelennamine (pyribenzamine) has become a major form of drug abuse seen in the midwestern United States. Complications of this abuse have included psychotic reactions, acute pulmonary insufficiency, convulsions, and various infections. We have observed three patients in whom the IV use of these agents was associated with the nephrotic syndrome and renal histopathologic findings similar to that reported in heroin addicts with the so-called "heroin-associated nephropathy." Percutaneous renal biopsy demonstrated focal to diffuse segmental or global glomerulosclerosis by light microscopy. Electron microscopy revealed glomerular visceral epithelial cell foot process effacement and microvillus formation. Immunofluorescent studies were negative in the two patients studied. One patient presented in renal failure, and two others progressed to renal failure within 3 years of diagnosis. We suggest the term opiate nephropathy for this lesion in narcotics users, indicating its potential occurrence in non-heroin-using drug addicts.

An ultrastructural study of the renal juxtaglomerular apparatus and extraglomerular mesangium in patients with systemic lupus erythematosus.

Experimental studies have indicated that the glomerular mesangium may function by phagocytosis of various circulating substances which are then processed and flow to the juxtaglomerular apparatus (JGA) region and into the intercellular spaces of the macula densa. An electron-micrographic study of the juxtaglomerular apparatus and extramesangial region in systemic lupus erythematosus (SLE) was undertaken. In only five of 39 cases (13%) of SLE were discrete electron-dense "immune-type" deposits noted in the JGA region. In four of those patients, there were also a large number of variously-sized electron-dense deposits in the glomerular mesangial and capillary wall regions, Bowman's capsule, tubular basement membranes, renal interstitium, or in the nearby periglomerular arterioles. The paucity of demonstrable discrete electron-dense deposits in the JGA regions in this study suggests that the deposits noted in SLE in humans may not be commonly processed in this fashion, or alternatively, that the discrete electron-dense deposits are processed and undergo lysis within the glomerular mesangial regions before they are transported to the extraglomerular mesangial regions of the JGA.

Cat scratch disease. Report of a case with hepatic lesions and a brief review of the literature.

An unusual case of cat scratch disease with large hepatic defects is presented. We describe a previously healthy 16-yr-old black man presenting with a neck mass, hepatosplenomegaly, and systemic symptoms. Pathology of the neck mass revealed a lymph node with chronic inflammation and focal necrosis. An abnormal computed tomography scan showed large hepatic defects which were confirmed at peritoneoscopy; biopsy specimens are described. Routine and special stains for bacteria and fungi were all negative. Serologic studies were unremarkable but a cat scratch skin test was positive. Follow-up examinations revealed resolution of all findings. Cat scratch disease should be considered in the differential diagnosis of diseases causing lymphadenopathy, systemic symptoms, and hepatic (and splenic) defects.

Interstitial nephritis caused by methicillin. Studies in a case complicating staphylococcal sepsis with acute glomerulonephritis.

A 16-year-old student was admitted with acute, oliguric renal failure complicating staphylococcal sepsis. During treatment with methicillin drug hypersensitivity was suspected, and antibiotic was changed to vancomycin; by day 19 hemodialysis was discontinued. Renal biopsy showed two pathologic processes: acute exudative glomerulonephritis and widespread tubulointerstitial nephritis. In addition to glomerular immunoglobulin and C'3 deposits, interstitial and focal tubular basement membrane deposits of IgG were seen. Antiserum to DPO (methicillin) haptens localized apparently to the same tubular sites, as did fluorescein-conjugated antibodies from the patient's serum. The data suggest that interstitial nephritis was caused by serum antibodies to methicillin which bound to sites in renal tubules to which methicillin also had fixed. The acute tubulointerstitial nephritis complicated acute oliguric glomerulonephritis of staphylococcal sepsis.

A prospective trial of steroid therapy in severe viral hepatitis. The prognostic significance of bridging necrosis.

A prospective, double-blinded, randomized trial of corticosteroid therapy in patients with severe acute viral hepatitis has been conducted. At the same time, we have examined the prognostic significance of the presence of bridging necrosis in liver biopsies obtained from such patients as well as the predictive value of certain serologic markers. Forty-two of the 77 patients admitted to the trial were shown to have bridging necrosis on their initial biopsies. Two patients progressed to death with massive hepatic necrosis, while 5 patients developed chronic liver disease. A complicated course could not be predicted by the initial biopsy findings nor by any of the serologic markers assessed. We could not identify any clinical or epidemiologic features with prognostic impact. No advantage was demonstrated to be associated with the use of corticosteroids early in the course of severe viral hepatitis.

Etiology of liver disease in renal-transplant patients.

The etiology of 72 episodes of liver disease that developed in 62 of 162 renal-transplant recipients was evaluated. Infection with hepatitis B virus was a minor problem, and none of our patients had evidence of infection with hepatitis A. Cytomegalovirus infection was ubiquitous in the population and probably accounted for many episodes of acute liver disease. This agent's role in causing chronic hepatitis is less secure. Infections with other viruses including Epstein-Barr virus, adenovirus, and the herpes viruses were only rarely associated with hepatic disease. Azathioprine was responsible for some episodes of acute cholestasis but could not be incriminated as a direct cause of chronic disease. A cause could be identified for the majority of episodes of acute hepatic dysfunction, but the cause of most of the chronic hepatitis remains undetermined. It is likely that infection with non-A, non-B hepatitis virus accounts for much of this serious, often fatal, complication of renal transplantation.

Colitis associated with oral clindamycin therapy. A clinical study of 16 patients.

The clinical, radiologic, and histologic features of 16 patients hospitalized with clindamycin-associated colitis are presented. The findings are tabulated and compared to 33 cases reported in the literature. The majority of patients were caucasian females over 40 years of age. The clinical presentation varied from mild persistent diarrhea to acute surgical abdomen. Proctoscopic examination revealed nonspecific colitis in 9 and pseudomembranous colitis in 7 cases. No specific radiologic or histologic fingings for postanitbiotic colitis were found. Therapy was nonspecific and varied according to the severity of the clinical course. Clinically, there appeared to be some benefit from systemic steroid therapy. 4 of the 16 patients died. None of the recovered patients have had spontaneous relapses off medication during follow-up evaluation. The pathogenic mechanism for postantibiotic colitis secondary to clindamycin remains unknown and does not appear dose related. Clindamycin therapy should be limited to disorders with specific indications.

Prognostic significance of subacute hepatic necrosis in acute hepatitis.

A retrospective analysis has been made of 57 patients with subacute hepatic necrosis demonstrated on a liver biopsy obtained during the course of an episode of acute hepatitis. Fourteen patients have been lost to follow-up. One patient died acutely with massive hepatic necrosis, while 8 have developed chronic active liver disease. Two of nine biopsies subsequently performed on patients who had shown complete clinical and biochemical resolution revealed an inactive postnecrotic cirrhosis. The incidence of these complications developing in patients with subacute hepatic necrosis was approximately 30%. These findings add qualitative support to the position that liver biopsy findings bear important prognostic value in patients with acute hepatitis.