Molecular, serological, and clinical features of 16 consecutive cases of invasive streptococcal disease. Southeastern Minnesota Streptococcal Working Group.

We performed a comprehensive analysis of the molecular, serological, and clinical features of 16 consecutive cases of invasive streptococcal disease (ISD). The majority of cases were linked to two group A streptococcus (GAS) clones closely related by pulsed-field gel electrophoresis (PFGE) and designated as PFGE-1 and PFGE-1.1. These clones, serotyped as M-3, T-3/B3264, carried an allelic variant of the gene that encodes pyrogenic exotoxin A (speA3) and the gene that encodes streptococcal superantigen (SSA) but different emm alleles that encode M-protein. The characteristics and clinical features of patients were similar to those described in previous reports, regardless of the responsible GAS clone. However, worse clinical outcomes (shock and death) were more frequent when patients infected with PFGE1/1.1 clones were considered as a group and compared with all other patients as a group. One striking feature in some patients with deep tissue infection was a lack of inflammatory cells despite the presence of numerous streptococci. An evaluation of PFGE profiles of GAS isolated elsewhere demonstrated that the PFGE-1 clone has caused invasive disease in other locations in the United States and in Japan.

The fate of renal transplants in patients with IgA nephropathy.

BACKGROUND: IgA Nephropathy (IgA N) is one of the most common glomerulopathies and may lead to renal failure in 10-20% of cases. After renal transplantation, IgA N has a strong tendency to recur in the graft. Initially considered a benign condition, graft losses from recurrent IgA N have been reported over the last 20 yr, casting doubt on the initial premise. Since large single-center studies of the fate of renal allografts in IgA N are rare and the Mayo Clinic transplant experience for IgA N is extensive (dating back to 1970), a review of these issues appeared worthwhile. METHODS: A retrospective study was done of all renal transplant patients who had had biopsy-proven IgA N as underlying disorder. We extracted data on the underlying disease, history leading to renal transplantation, factors affecting transplant outcome, and on the course after transplantation with special attention to rejection activity and recurrence of the primary disease. Standard statistical methods were employed. RESULTS: 53 renal allografts were transplanted to 51 biopsy-proven IgA N patients: 12 were cadaveric (CAD) grafts, 3 HLA-mismatched living related donor (LRD) kidneys, 29 one haplotype-matched LRD and 9 HLA-identical LRD organs. Five-year actuarial graft survival was 100% in HLA-identical LRD, 88% in one haplotype-matched LRD, and 74% in CAD grafts. All three HLA-mismatched LRD kidneys were functioning up to 1.6 yr (longest follow-up). Only one patient died after acute rejection of the CAD graft. There were 3 early graft losses from acute rejection and 4 late losses. IgA N recurred in 26% of allograft and led to significant loss of graft function in 10 of the 14 patients (71%) over a long period of observation. Three of four late graft losses were in patients with recurrent IgA N. Recurrence was not related to the type of graft, i.e. CAD vs. LRD, nor to the extent of HLA-matching in LRD transplantation. CONCLUSION: Renal transplantation in patients with IgA N has excellent patient and graft survival. There is a high rate of recurrence of the primary glomerulopathy in the renal allograft, and this event is by no means inconsequential. Loss of renal function and even graft loss occur over prolonged periods of time. There is no disadvantage getting a well matched LRD in regard to incidence of recurrent IgA N. Thus, we encourage LRD transplantation in IgA N.

SLE nephropathy in a patient with HIV infection: case report and review of the literature.

We describe a 39-year-old bisexual man with clinical category B2 human immunodeficiency virus (HIV) infection who subsequently developed systemic lupus erythematosus (SLE). SLE was diagnosed on the basis of a clinical presentation of malar rash, polyarthritis, membranous glomerulonephritis, and characteristic serology. To our knowledge, this is the fourth reported case of a patient with HIV infection to develop SLE and the second adult patient with HIV and coexistent SLE nephropathy.

Reversible membranous nephropathy associated with the use of nonsteroidal anti-inflammatory drugs.

OBJECTIVE: To investigate the frequency of membranous nephropathy associated with nonsteroidal anti-inflammatory drug (NSAID) use and identify associated clinical characteristics. DESIGN: Retrospective chart review. SETTING: A large group practice that staffs 2 large teaching hospitals. PATIENTS: All patients diagnosed as having stage I or early stage II membranous nephropathy by renal biopsy between January 1975 and May 1995. MAIN OUTCOME MEASURES: Nephrotic syndrome was said to be associated with NSAID use if patients developed nephrotic syndrome while taking an NSAID and if other causes of membranous nephropathy were excluded and a rapid remission of the nephrotic syndrome followed withdrawal of the drug. RESULTS: Of 125 patients identified with early membranous nephropathy, 29 were taking NSAIDs at the time symptoms of nephrotic syndrome developed. Thirteen of these patients met the criteria for NSAID-associated membranous nephropathy. None of these patients had any evidence of renal insufficiency or significant proteinuria after follow-up periods ranging from 5 months to 13 years. In addition to diclofenac and fenoprofen, which have previously been implicated, ibuprofen, nabumetone, naproxen, and tolmetin were found to be associated. CONCLUSIONS: Nephrotic syndrome due to membranous nephropathy should be recognized as an idiosyncratic drug reaction to many NSAIDS. Because withdrawal of the drug may result in prompt and complete recovery of normal renal function, a history of NSAID intake should be sought in patients with membranous nephropathy.

Prognostic determinants in lupus nephritis: a long-term clinicopathologic study.

Over the past 50 years, survival has improved in patients with systemic lupus erythematosus and associated nephritis. Yet, there are few long-term outcome studies in patients with well-defined nephropathy. We examined the outcome of 439 patients with lupus nephritis who were seen at the Mayo Clinic between 1964 and 1986 in whom renal biopsies were assessed using the World Health Organization (WHO) classification. There were 341 women and 98 men (mean +/- s.d., age 33.5 +/- 14 years); 200 (46%) patients were hypertensive and 249 (57%) had impaired renal function at renal biopsy. All WHO morphologic classes were represented and 339 (77%) patients had class III, IV and V (the more severe forms of nephritis). Follow-up averaged 10.2 years per patient. At last contact, 286 (65%) patients were alive and 153 (35%) were dead. Overall patient survival was 80%, 69% and 53% at 5, 10 and 20 years after biopsy that was significantly worse than expected survival (P < 0.001). Ten-year cumulative patient survival improved comparing earlier to more recent time spans: 64% in 231 patients seen during 1964-75; 76% in 2089 patients studied during 1976-86 (P = 0.03). Survival free of renal failure was 83%, 74% and 64% at 5, 10 and 20 years, and survival was unfavorably influenced by progressive WHO class, hypertension, impaired renal function, nephrotic range proteinuria, hypoalbuminemia and anemia. Multivariate analysis found impaired renal function, increased urine protein, anemia and younger age to be independent predictors of renal failure. WHO class was not a significant predictor when adjusted for these four factors. Cardiovascular events accounted for 48% of the known deaths and were equally distributed across all WHO classes, followed by infections, renal failure, malignancy, respiratory failure and gastrointestinal bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group.

BACKGROUND: The n-3 fatty acids in fish oil affect eicosanoid and cytokine production and therefore have the potential to alter renal hemodynamics and inflammation. The effects of fish oil could prevent immunologic renal injury in patients with IgA nephropathy. METHODS: In a multicenter, placebo-controlled, randomized trial we tested the efficacy of fish oil in patients with IgA nephropathy who had persistent proteinuria. The daily dose of fish oil was 12 g; the placebo was a similar dose of olive oil. Serum creatinine concentrations, elevated in 68 percent of the patients at base line, and creatinine clearance were measured for two years. The primary end point was an increase of 50 percent or more in the serum creatinine concentration at the end of the study. RESULTS: Fifty-five patients were assigned to receive fish oil, and 51 to receive placebo. According to Kaplan-Meier estimation, 3 patients (6 percent) in the fish-oil group and 14 (33 percent) in the placebo group had increases of 50 percent or more in their serum creatinine concentrations during treatment (P = 0.002). The annual median changes in the serum creatinine concentrations were 0.03 mg per deciliter (2.7 mumol per liter) in the fish-oil group and 0.14 mg per deciliter (12.4 mumol per liter) in the placebo group. Proteinuria was slightly reduced and hypertension was controlled to a comparable degree in both groups. The cumulative percentage of patients who died or had end-stage renal disease was 40 percent in the placebo group after four years and 10 percent in the fish-oil group (P = 0.006). No patient discontinued fish-oil treatment because of adverse effects. CONCLUSIONS: In patients with IgA nephropathy, treatment with fish oil for two years retards the rate at which renal function is lost.

Effect of sodium chloride, enalapril, and losartan on the development of polycystic kidney disease in Han:SPRD rats.

We found that the administration of an angiotensin I-converting enzyme inhibitor and sodium chloride loading lessen the development of renal cystic disease induced by 2-amino-4-5-diphenylthiazole in rats. To determine whether similar effects could be observed in an autosomal dominant model of polycystic kidney disease, heterozygous cystic (Cy/+) and homozygous normal (+/+) Han:SPRD rats were divided into experimental groups at 3 weeks of age. The first study included four groups receiving enalapril (50 mg/L), losartan (400 mg/L), hydralazine (80 mg/L), or no drug in their drinking water. The second study included four groups fed a sodium-deficient diet or the same diet supplemented with 0.25%, 0.6%, or 3.3% sodium chloride. The Cy/+ rats receiving enalapril had lower kidney weights and histologic scores than those in the control group, and lower kidney weights, plasma creatinines, and histologic scores than those in the hydralazine group. The Cy/+ rats receiving losartan had lower plasma creatinines and histologic scores than those in the control and hydralazine treatment groups. A sodium-deficient diet markedly blunted the growth of the animals and the development of cystic disease. Increases in the sodium content of the diet in the other three groups were accompanied by higher relative kidney weights and histology scores, while the levels of plasma creatinine were not significantly different. Regression of the cystic disease was observed between 3 and 4 months of age. These results indicate that the development of autosomal dominant polycystic kidney disease in the rat can be modulated by pharmacologic and nutritional factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and histopathologic associations with impaired renal function in IgA nephropathy. Mayo Nephrology Collaborative Group.

A multicenter, double-blind, placebo-controlled, randomized trial of fish oil in proteinuric patients with IgA nephropathy is being conducted by the Mayo Nephrology Collaborative Group. We completed enrollment of 106 patients into the trial in December 1991. The treatment period is for two years. Hypertension is being managed in all patients with enalapril maleate (Vasotec). We evaluated the associations between a variety of clinical and renal morphologic features and renal function at the entry of all enrolled patients. Among 78 males and 28 females [age(mean +/- SD) 36 +/- 14 years], older age at treatment randomization, hypertension, at disease discovery as well as at study entry, increased fractional excretion of albumin, increased serum triglyceride levels, and more severe tubulointerstitial, vascular, and combined glomerular and tubulointerstitial histologic lesions were all univariately associated (p < or = 0.01) with poorer renal function measured by reciprocal serum creatinine and creatinine clearance levels. In a multiple regression analysis used to predict baseline reciprocal creatinine, the best final model (R2 = 0.48) included male sex (p < .001), hypertension at treatment randomization (p = .001), decreased peripheral blood erythrocytes (p = .001), increased tubulointerstitial score (p = .004), and increased fractional excretion of albumin (p = .025) as independent predictors of decreased kidney function. These associations are similar to those seen in the high-risk subset of patients with IgA nephropathy who develop end-stage renal disease. In the eventual outcome analysis of the clinical trial, we will examine the effects of treatment on the two potentially modifiable risk factors, hypertension and proteinuria, on renal function.

Prospective study of anti-neutrophil cytoplasmic autoantibody tests in the diagnosis of idiopathic necrotizing-crescentic glomerulonephritis and renal vasculitis.

We prospectively assessed the value of anti-neurtrophil cytoplasmic autoantibodies (ANCA) and nuclear or perinuclear anti-neutrophil autoantibodies measured by indirect immunofluorescence microscopy and antimyeloperoxidase autoantibodies measured by a solid-phase assay in the diagnosis of idiopathic (pauci-immune) necrotizing-crescentic glomerulonephritis (NCGN) and renal vasculitis at our institution. A diagnosis was established on the basis of clinical and renal biopsy findings, and follow-up continued for at least 6 months. ANCA were measured at the conclusion of the study. Of the 111 study patients, 28 had NCGN and renal vasculitis. The immunofluorescence assay had 50% sensitivity and 79% specificity. The combination of the enzyme-linked immunosorbent assay for antimyeloperoxidase autoantibodies and the immunofluorescence assay for cytoplasmic ANCA had 78% sensitivity and 84% specificity. A firm diagnosis was established before the determination of ANCA in 26 of the 28 patients with NCGN and renal vasculitis. The antimyeloperoxidase autoantibody values would have suggested the diagnosis in the other two patients. Of these 28 patients, 5 had negative ANCA results. High antimyeloperoxidase autoantibody values were detected in patients with NCGN and renal vasculitis, whereas lower values were less specific and were detected mainly in patients with anti-glomerular basement membrane antibody disease and lupus glomerulonephritis.

Hemolytic uremic syndrome after bone marrow transplantation without total body irradiation.

The cause of hemolytic uremic syndrome after bone marrow transplantation is unknown. Investigators have implicated multiple causes, including cyclosporin A, graft versus host disease, cytomegalovirus infection, and total body irradiation. We report a case of biopsy-supported hemolytic uremic syndrome in a recipient of an autologous bone marrow transplant who did not receive total body irradiation or cyclosporin A and did not have clinical evidence of cytomegalovirus infection. This case casts doubt on the hypothesis that irradiation or any of these factors is the sole and universal cause of hemolytic uremic syndrome in patients receiving bone marrow transplants.

Lupus anticoagulant in systemic lupus erythematosus: a clinical and renal pathological study.

Circulating lupus anticoagulant (LA) is associated with thrombosis in large and small vessels. To determine how often the presence of LA is associated with thrombosis within the renal microcirculation, 33 patients with systemic lupus erythematosus (SLE), renal dysfunction, and LA were identified over a 25-year period (LA group) and 32 patients with renal SLE but with normal gross coagulation screen were matched for age, sex, and biopsy timing (C group). Prevalences of serositis, neuropsychiatric illness, leukopenia, thrombocytopenia, hemolysis, anti-DS-DNA elevation, and complement reduction were similar. Arthritis was less and biologic false-positive (BFP) syphilis serology more common in LA. More LA patients had thrombotic events (LA 39% v C 13%; P = 0.014); bleeding episodes, including postbiopsy, were similar. At biopsy, hypertension (LA 55%, C 41%), serum creatinine (mean +/- SD: LA 186 +/- 168 mumol/L [2.1 +/- 1.9 mg/dL] v C 150 +/- 168 mumol/L [1.7 +/- 1.9 mg/dL]) and proteinuria (LA 2.6 +/- 3.1 g/24 h v C 3.1 +/- 2.7) were similar. Lesions by World Health Organization (WHO) class, activity, and chronicity indices, as well as immunofluorescence (IF) and electron microscopy (EM) findings, were not significantly different. Occlusive glomerular, arteriolar, and arterial fibrin thrombi, along with varying degrees of renal thrombotic microangiopathy, were seen in five of 33 patients with LA, but zero of 32 C patients (P = 0.053); three of these five patients died soon after biopsy. Overall, mortality was not different between LA and C. We conclude that the majority of patients with SLE, renal dysfunction, and LA exhibit renal morphologic findings indistinguishable from patients without LA. However, a significant minority of LA patients have thrombotic microangiopathy in their biopsy, which is accompanied by a worse prognosis.

Synthesis of renin by tubulocystic epithelium in autosomal-dominant polycystic kidney disease.

Evidence suggests an important role for the renin-angiotensin system in the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD). Therefore, we studied the presence of immunoreactive renin in renal biopsies and measured the concentrations of renin in cyst fluids. Normal kidneys and kidneys with renal artery stenosis were used for comparison. In ADPKD, immunoreactive renin was present in juxtaglomerular apparatus, associated arterioles, and in some cells within the connective tissue surrounding the cysts. Vascular immunoreactive renin was less prominent than in renal artery stenosis. Increased amounts of tubular immunoreactive renin were noted in polycystic kidneys, as compared to normal kidneys and kidneys with renal artery stenosis. Cyst fluids contained renin detected by Western analysis and enzymatic activity; concentrations were greater in gradient cysts than in nongradient cysts. Seventy-four percent of the renin in gradient cysts was active as compared to 23% in nongradient cysts and 15% in plasma. To determine whether cyst epithelial cells are capable of synthesizing renin, these cells were isolated in tissue culture. Enzymatic assay of extracts from these cells revealed the presence of renin-like enzymatic activity (1.3 +/- 0.8 ng AI/mg protein/hr). The synthesis of renin by tubulocystic epithelium was confirmed by [35S]-methionine radiolabeling of cyst-derived cells, followed by immunoprecipitation and SDS-PAGE and by detection of renin mRNA by the polymerase chain reaction. These results indicate that the tubulocystic epithelium has the potential to synthesize renin. Elevated levels of active renin in renal cysts may be linked to the pathogenesis of hypertension in ADPKD. The occurrence of renin in the lining epithelium of cyst walls raises the possibility that abnormal expression of the renin-angiotensin system may, by a paracrine or autocrine mechanism, regulate epithelial hyperplasia in growing renal cysts.

Long-term follow-up and response to chemotherapy in patients with light-chain deposition disease.

Nineteen patients with light-chain deposition disease (LCDD) were studied retrospectively. This report presents data on long-term patient and renal survival and the response to intermittent administration of melphalan and prednisone. Immunoelectrophoresis or immunofixation demonstrated a monoclonal protein in the serum of 78% and in the urine of 84% of the patients; 16% had no demonstrable monoclonal protein in serum or urine. The median age at presentation was 51 years (range, 37 to 77 years). Twelve (63%) of the patients had a monoclonal protein of undetermined significance without evidence of myeloma. The typical glomerular lesion was a diffuse mesangial nodular lesion that was positive for periodic acid-Schiff (PAS) stain with acute and chronic tubulointerstitial changes. Fifteen patients had kappa light-chain deposition and four had lambda light-chain deposition. Five-year actuarial patient survival and survival free of end-stage renal disease were 70% and 37%, respectively. Seventeen patients received melphalan and prednisone, and one patient received chlorambucil and prednisone. All of the patients had some impairment of renal function at presentation, and 58% had a serum creatinine concentration greater than 354 mumol/L (4.0 mg/dL). There was either stabilization or improvement in renal function after chemotherapy in five of eight patients who had a serum creatinine concentration less than 354 mumol/L (4.0 mg/dL) at the initiation of therapy. Of the 11 patients with a high serum creatinine concentration (greater than 354 mumol/dL [4.0 mg/dL]), 82% progressed to end-stage renal disease despite therapy. Follow-up urine protein studies demonstrated at least a 50% decrease in urine protein excretion in five of 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis of cytomegalovirus hepatitis by histopathology and in situ hybridization in liver transplantation.

Hematoxylin-eosin staining (H&E) of cytomegalovirus (CMV) inclusion bodies was compared with in situ hybridization using a biotinylated DNA probe for the detection of CMV. Of 29 biopsy specimens selected from 23 patients with clinical CMV hepatitis and typical CMV inclusions on histopathologic examination, 23 (79%) were positive by DNA probe and 17 (59%) were detected in cell cultures. The mean number of CMV foci per tissue section was higher by DNA probe (12) compared with H&E (5). We do not recommend in situ hybridization in microbiology laboratories as a replacement for histopathology for the diagnosis of CMV in tissue specimens.

Laboratory investigation of deaths due to anaphylaxis.

To establish a useful laboratory protocol to investigate possible cases of fatal anaphylaxis, we measured mast-cell-derived tryptase levels and allergen-specific immunoglobulin E (IgE) antibody levels in sera obtained prior to or within 24 h after death from 19 anaphylaxis victims. Elevated serum tryptase levels (range = 12 ng/mL to 150 micrograms/mL) were found in nine of nine Hymenoptera sting fatalities, six of eight food-induced fatalities, and two of two reactions to diagnostic therapeutic agents. Tryptase levels were normal (less than 10 ng/mL) in 57 sequential sera obtained postmortem from six control patients. Tryptase could not be measured in pleural or pericardial fluids for technical reasons. Serum IgE antibodies were elevated in five of the nine Hymenoptera sting fatalities and in eight of the eight fatal food reactions; assays were unavailable for the two diagnostic/therapeutic agents. If elevated, the victim's serum IgE antibodies to food could be used to identify allergens in uneaten portions of foods consumed shortly before the anaphylactic event. IgE antibodies were moderately stable during storage in a variety of anticoagulants at room temperature for up to 11 weeks. Elevated mast-cell-derived tryptase levels in postmortem sera reflect antemortem mast cell activation and may be used as a marker for fatal anaphylaxis. If assays are available for IgE antibodies to relevant allergens, such assays provide evidence for antemortem sensitization; these assays may be modified to identify allergens in foods consumed by victims of food-induced anaphylaxis.

Early diagnosis of cytomegalovirus hepatitis in liver transplant recipients: role of immunostaining, DNA hybridization and culture of hepatic tissue.

Immunostaining techniques that use a monoclonal antibody against an early cytomegalovirus antigen or a polyclonal antibody, in situ DNA hybridization and inoculation of cell cultures for the detection of cytomegalovirus from liver biopsy specimens were studied in 20 liver transplant patients with cytomegalovirus hepatitis, as defined by histological criteria. A total of 108 liver biopsy specimens from 20 patients with a diagnosis of cytomegalovirus hepatitis (obtained per protocol at 7, 21, 90, and 180 days or whenever liver dysfunction occurred), which had previously been examined histologically and in cell culture, were again studied by recutting the liver tissue for histological examination, DNA hybridization and immunostaining with monoclonal or polyclonal antibodies to cytomegalovirus. In 5 of 20 patients, the diagnosis of cytomegalovirus hepatitis could have been made earlier (mean = 9.6 days) by immunostaining with a monoclonal antibody. Of 47 biopsy specimens with cytomegalovirus inclusion bodies, the sensitivity and specificity of the diagnostic procedures were immunostaining with monoclonal antibody (84% and 90%) and polyclonal antibody (72% and 97%), in situ DNA hybridization (72% and 100%) and cell culture detection (52% and 95%), respectively. Immunostaining with a monoclonal antibody against an early CMV antigen frequently detected cytomegalovirus infection in the liver allograft earlier than identification of typical histological inclusion bodies. DNA in situ hybridization was less sensitive than other techniques but highly specific; cytomegalovirus cell culture lacked sensitivity compared with the other procedures.

Pulmonary fibrosis as an unusual clinical manifestation of a pulmonary-renal vasculitis in elderly patients.

Between 1978 and 1988, three patients at our institution had an initial diagnosis of idiopathic pulmonary fibrosis but later were correctly diagnosed as having pulmonary-renal syndrome and microscopic polyarteritis. These cases involved elderly patients with progressive dyspnea and nonproductive cough, bilateral dry crackling rales, bilateral interstitial infiltrates evident on a chest roentgenogram, and restrictive findings on pulmonary function testing. In two patients, lung biopsy specimens were obtained, and an initial diagnosis of nonspecific pulmonary fibrosis was made. All three patients eventually had microhematuria and renal insufficiency. A revised diagnosis of small-vessel pulmonary-renal vasculitis was based on the demonstration of segmental necrotizing glomerulonephritis in renal biopsy specimens in two patients, thrombotic microangiopathy consistent with healed vasculitis on postmortem examination of the kidney in one patient, and subsequent detection of small-vessel vasculitis on review of the two lung biopsy specimens. Anti-neutrophil cytoplasmic antibodies with perinuclear staining on indirect immunofluorescence microscopy were positive in the two patients in whom determinations were performed. The clinical manifestations of vasculitis were notably scarce--no involvement of the skin, nervous system, or gastrointestinal tract; no episodes of fever; and minimal or absent musculoskeletal symptoms. These cases illustrate the importance of a high index of suspicion for the diagnosis of systemic vasculitis in elderly patients and the need to consider a vasculitis in the differential diagnosis of idiopathic pulmonary fibrosis, especially if an active urinary sediment is present.

Augmentation cystoplasty utilizing de-epithelialized sigmoid colon: a preliminary study.

The use of bowel segments for bladder replacement or augmentation has been associated with metabolic complications and obstruction due to mucus production. Establishment of a transitional epithelium over the de-epithelialized surface of a segment of intestine might alleviate these complications. Twenty Holstein bull calves underwent sigmoidocystoplasty. Fourteen experimental animals had the epithelium of the sigmoid removed before augmentation. Six calves with intact mucosa served as controls. Fifteen calves survived the study: 11 experimentals and four controls. Cystectomies were performed at four, six, eight, or 12 weeks. Ninety-one percent (10/11) of the experimental calves had almost complete epithelialization of the de-epithelialized graft. All experimental animals had residual colonic mucosa or mucoceles. Nine of 11 experimental calves (82%) had greater than 25% contracture of the sigmoid graft. Two animals had less than 25% graft contracture (1) or formed a wide-mouthed true diverticulum (1) in the grafted segment. All control animals formed a wide-mouthed true diverticulum and had no graft contracture.