Survival and risk of cholangiocarcinoma in patients with primary sclerosing cholangitis. A population-based study

BACKGROUND: Endoscopic retrograde cholangiopancreatography was introduced in the early 1970s, making a more reliable diagnosis of primary sclerosing cholangitis (PSC) possible. Since then decreased survival and increased risk of cholangiocarcinoma have been reported. However, no population-based studies have quantified these outcomes. METHODS: A population-based cohort of 125 patients with a verified PSC diagnosis was followed up through linkage to the Swedish Death Registry and the Swedish Cancer Registry for occurrence of death and cholangiocarcinoma. RESULTS: The diagnosis of PSC was associated with a substantially decreased survival, with an overall 10-year survival of 68.8%. Patients with a diagnosis of inflammatory bowel disease (IBD) had a somewhat better prognosis, 71.8%, compared with 60% for patients without. Fourteen subsequent cholangiocarcinomas yielded a cumulative risk of 11.2% 10 years after diagnosis. Sex, duration of IBD, and colectomy influenced neither the survival nor the cholangiocarcinoma risk. CONCLUSION: Patients with PSC have a substantially decreased survival, which is most pronounced among patients without IBD.     

HLA-identity--long-term renal graft survival, acute vascular, chronic vascular, and acute interstitial rejection

The object is analysis of the impact of acute and chronic rejection on long-term function in HLA-identical renal transplants performed from 1967 to 1995 by the Saskatchewan Renal Transplant Unit. Forty-eight grafts in 46 patients were studied, of which 39 were first and nine second grafts. Forty-two were for primary and six for secondary renal disease. Thirty-five received azathioprine/prednisone prophylaxis, and 13 received cyclosporine/prednisone with/without azathioprine. Ten-year all graft actuarial survival was 84%, 10-year actuarial graft survival in patients with primary renal disease 90%, and with subsequent graft after first HLA graft failed 97.5%, for age-matched population 98.5% (P=NS). Overall death rate was 8.7% (4/46); in secondary renal disease patients 50% (3/6); in primary renal disease patients 2.5% (1/40, P=0.004). All (9/9) HLA-identical second grafts functioned. Acute rejection with azathioprine/prednisone prophylaxis occurred in 55% (9/17) of grafts treated with <6 pre-graft blood transfusions, with the same prophylaxis but >5 units in 12% (2/16, P=0.015), and with cyclosporine prophylaxis in 13% (2/15, P=0.021). Pulse steroids alone reversed all acute rejection. Grafts failed in 6.2% (3/48), all in primary renal disease patients and one from technical one noncompliance, and one chronic rejection. Graft cost/patient/year amortized over 9 years is $3,855 and comparable dialysis cost would be $35,650; cost for all patients on dialysis for 9 years would be $11,293,320 while comparable graft cost was 1,221,418, a savings of 89.2%. Our conclusions are that HLA-identity associates with the following: (1) a 10-year actuarial survival in primary renal disease that equals that of the age-matched population, (2) uniform success in repeat grafts, (3) virtual absence of chronic rejection despite a high incidence of acute rejection in azathioprine/prednisone grafts that (4) always reversed on pulse steroids, and (5) a cost reduction for grafting of 93.2% compared with dialysis therapy.     

Liver transplantation: experiences and results of a program at the University of Liege

The orthotopic liver transplantation (OLT) program of the University of Liège was initiated in 1986. Between 1986 and December 1998, 150 adult OLT have been performed in our institution, including 18 liver retransplantations, 1 combined heart and liver transplantation and 3 combined liver and kidney transplantations. The aim of this study was to report the last 3 years of our experience. From January 1996 to November 1998, we performed 50 OLT on 49 patients. Three were retransplantations and two were combined liver and kidney transplantations. Fourty-three patients were transplanted for chronic liver disease and 6 for acute or subacute hepatopathy. Mean waiting time on the list was 4 weeks. Immunosuppression was based on triple therapy (cyclosporin A/tacrolimus, steroids, azathioprine), with steroid and azathioprine withdrawal in most of the patients after 3 months. In the chronic liver disease group, operative (< 30 days) survival was 95% (peroperative myocardial infarction in 2 patients). In the acute liver disease group, postoperative survival was 66%. No perioperative death occurred in 1997 and 1998. Actuarial one year survival was 87%. In our experience, OLT has become a safe procedure.     

Long-term renal function in heart transplant recipients receiving cyclosporine therapy

BACKGROUND: Immunosuppression with cyclosporine has improved allograft function and reduced both morbidity and mortality in organ transplantation. However, cyclosporine-induced nephrotoxicity still is a concern. The purpose of our study was to evaluate the effects of cyclosporine on renal function in orthotopic heart transplant recipients. METHODS: Thirty-nine patients who received transplants from 1985 to 1991 and had at least three yearly glomerular filtration rate measurements posttransplantation by 125I-iothalamate clearance method were included in the study. In addition, serum creatinine (before and after transplantation) and cyclosporine doses were analyzed. RESULTS: Maintenance immunosuppression at 1 year consisted of prednisone (0.1 mg/kg/day), azathioprine (2 mg/kg/day), and cyclosporine (12-hour trough level 100 to 150 ng/ml by fluorescence polarization immunoassay). The mean serum creatinine at 1 year was significantly higher than the mean pretransplantation serum creatinine (1.51 +/- 0.32 versus 1.28 +/- 0.38, p < 0.05) and stabilized after the first year. The mean glomerular filtration rate by 125I-iothalamate clearance method was 70.6 +/- 20.3 ml/min/1.73 m2 (range 32 to 105) at 1 year and remained relatively stable during the follow-up period of up to 7 years. Creatinine clearance calculated by the Cockcroft and Gault formula overestimated the true glomerular filtration rate after the third year. The mean cyclosporine dosage was significantly lower after the first-year dose of 3.9 +/- 1.8 mg/kg/day (p < 0.05). Three patients in 39 started hemodialysis at 5, 7, and 10 years after transplantation. CONCLUSION: Our data indicate that the adequacy of renal function is preserved with long-term cyclosporine therapy in heart transplant recipients.     

Heart transplantation in patients with treated breast carcinoma

Since 1987, five women with end-stage cardiomyopathy and a history of treated breast carcinoma have undergone transplantation at our institution. All patients underwent extensive multidisciplinary pretransplantation evaluation to rule out metastatic disease. Disease-free interval before heart transplantation ranged from 5 to 11 years (mean, 7.6 years). All patients received immunosuppression in accordance with a standard protocol of rabbit antithymocyte globulin, cyclosporine, prednisone, and azathioprine. Mean postoperative follow-up is 49 months. All patients are alive and have no symptoms 18 to 73 months after transplantation. In carefully selected patients with a history of breast carcinoma, heart transplantation can be performed with good functional results and satisfactory late survival.     

What is the association of primary sclerosing cholangitis with sex and inflammatory bowel disease in Turkish patients?

BACKGROUND/AIMS: In the Western world, primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that is associated with inflammatory bowel disease (IBD), particularly chronic ulcerative colitis and, to a lesser degree, Crohn's disease. The goal of this study was to determine the prevalence of PSC in Turkish patients with IBD and chronic amebic colitis, a disease that is endemic in Turkey. METHODOLOGY: During a 10-year period, between 1986 and 1996, a total of 81 IBD (64 ulcerative colitis and 17 Crohn's disease) patients and 127 patients with chronic amebic colitis were seen and evaluated with radiologic, serologic, immunologic and pathologic tests. Whenever a clinical or biochemical finding suggested the presence of co-existent hepatic and/or biliary disease, the patient was further evaluated by liver biopsy, auto-antibodies and endoscopic retrograde cholangiopancreatography (ERCP) to determine whether they also had PSC or some other form of liver disease. As a disease control group, a total of 752 patients with clinical and/or laboratory evidence of pancreaticobiliary disease were also studied. In 86 of these 752 patients (10%), a primary disorder of the biliary tree was diagnosed by ultrasonography, computed tomography, peritoneoscopy, liver biopsy, ERCP and abdominal laparotomy. In addition, all 86 patients of the control group were evaluated endoscopically in order to determine whether they had any associated gastrointestinal condition of the upper or lower gastrointestinal tracts. After establishing final diagnoses of IBD, amebic colitis and PSC, these patients were evaluated with respect to their socio-economic status. A high protein diet (1.8 gram/kg/day) was administered to those patients with chronic amebic colitis and IBD during the active period of the disease. RESULTS: Of the 208 patients (81 with IBD and 127 with chronic amebic colitis), no cases of PSC were identified. Of the 86 patients in the control group with primary biliary tract disease, 45 had a biliary system malignancy, 14 had primary biliary cirrhosis (PBC), 16 had PSC, 3 had Caroli's disease, 6 had a common bile duct cyst, and 2 had gallbladder adenomatosis. All but 1 of the 16 patients with PSC were female. CONCLUSIONS: These data suggest that, in contrast to findings in Western Europe and the USA, in Turkey: 1) PSC is not regularly associated with idiopathic IBD; 2) most patients with PSC are female; 3) PSC accounts for only 18% of patients with a primary disorder of the biliary tree; 4) the incidence of small-duct primary sclerosing cholangitis is greater than that reported in the literature; and, 5) the incidence of IBD and PSC in Turkey is relatively lower than in other countries.     

Nomenclature and classification of the rheumatic diseases

BACKGROUND: A pilot study was performed to prospectively evaluate the safety and efficacy of "low-dose" OKT3 induction after liver transplantation. METHODS: Sixteen patients received a 5- to 10-day course of OKT3 (2.5 mg i.v. daily) along with azathioprine, prednisone, and the delayed introduction of cyclosporine (Neoral). RESULTS: Patient and graft survival rates at 1 year were 88% and 82%. Five patients (31%) had biopsy-proven rejection; all five were treated successfully with steroids. There were 15 infections in 12 patients, including 5 cytomegalovirus infections. Adverse events attributed to OKT3 consisted of low-grade fever (five patients), transient hypoxemia (three patients), and transient hypotension (two patients). Pharmacy acquisition costs for OKT3 averaged $2,139 less as compared to a group of historical controls receiving full-dose therapy. CONCLUSIONS: Low-dose OKT3 induction appears to be a safe and useful method of postoperative immunosuppression after liver transplantation. Its ultimate clinical, immunologic, and economic efficacy awaits determination by randomized trial.     

Liver transplantation using grafts from donors over 65

OBJECTIVE: Donors age 50 years was an exclusion criteria in past decades. The increase of patients in the waiting list has determined the acceptance of older donors (over 65 years old). We analyze our results in liver transplantation using donors over 65 years. PATIENTS: From 1986 to may 1994, we performed 381 OLT. In five cases (1.3%) the OLT was performed using donors over 65 years of age (66, 67, 68, 70 and 71). The selection criteria for donors and recipients were similar to the other transplanted patients. Immunosuppression included cyclosporine or FK-506, prednisone and azathioprine. RESULTS: There were no primary graft failures and preservation damage, biochemical and clinical evolution were not different to the procedures using younger donors. Three grafts presented non-corticoresistant acute rejection. After a follow-up of 11.6 mo (range 4-37 mo) only one graft was lost (Kaposi's sarcoma in the liver). Four grafts and four patients are in excellent biochemical and clinical condition. CONCLUSIONS: Donor age should not be an exclusion criteria. Grafts from older donors (over 65 years old) may be considered safe and will permit to increase the number of OLT.     

Hyperlipidaemia in renal transplant patients

OBJECTIVES: The aim of study was to assess the prevalence and severity of hyperlipidaemia in renal transplant patients in a Nordic country. DESIGN: Multicentre, cross-sectional study. SETTING: Outpatients and ward inpatients registered from 23 hospitals covering all regions of the country. SUBJECTS: Renal transplant patients with a functioning graft were registered: 406 patients in all; that is, 43% of the national renal transplant population. All patients used prednisolone, 71% used cyclosporine, either with (51%) or without (20%) azathioprine. Total cholesterol values from general population were obtained from a national survey. MAIN OUTCOME MEASURES: Blood lipids and their relation to clinical parameters. RESULTS: Total cholesterol was significantly higher in transplant patients than in the general population for both genders and all age groups (P < 0.01). Female patients had higher total cholesterol (mean +/- SD: 7.49 +/- 1.61 mmol L(-1)) than males (7.01 +/- 1.55 mmol L(-1); P < 0.001), and also higher HDL cholesterol (1.55 +/- 0.43 vs. males: 1.32 +/- 0.46 mmol L(-1); P < 0.001). Triglycerides were equally elevated in both genders, and 33% had values above 2.2 mmol L(-1). Reduced creatinine clearance, a high body-mass index, female gender, hypertension, and coronary artery disease were independently associated with higher total cholesterol. Beta blockers were associated with lower HDL cholesterol and higher triglycerides, and diuretics with higher triglycerides. Blood lipid levels were not associated with cyclosporine immunosuppression. CONCLUSION: Hyperlipidaemia is prevalent after renal transplantation, and is associated with impaired graft function, hypertension, and with the use of beta blockers and diuretics, but not with the use of cyclosporine.     

Bone disease in children and adolescents undergoing successful renal transplantation

Little is known about the extent and severity of bone disease in children undergoing successful renal transplantation. To address this issue, 47 patients with stable renal function 3.2 +/- 1.7 years after transplantation (Tx) underwent iliac crest bone biopsy. The mean age of patients was 12 +/- 2.0 years; 36 had received cadaveric renal grafts, whereas 11 had undergone living-related Tx. Immunosuppressive drugs included cyclosporine 0.17 +/- 0.4 mg/kg/day, prednisone 7.5 +/- 2.1 mg/kg/day, and either azathioprine 1.6 +/- 0.9 mg/kg/day or mycophenolate mofetil 30 +/- 3 mg/kg/day. In addition to quantitative bone histomorphometry, the bone mineral content (BMC) of the lumbar spine was measured by dual energy X-ray absorptiometry (DXA) in 24/47 patients. Thirty-one transplant recipients had normal bone formation (N-Bfr), 11 had mild hyperparathyroidism (HPT) and 5 had adynamic skeletal lesions (AD). The interval since Tx, duration of dialysis before Tx and cumulative prednisone dose did not differ among groups. Trabecular bone area was highest in subjects with HPT. Unexpectedly, eroded bone perimeter exceeded normal reference values both in patients with AD and in those with N-Bfr; the osteoid area and osteoid perimeter were also elevated in these two groups. Hyperparathyroidism improved or resolved after Tx in all 14 subjects with this skeletal lesion prior to Tx, but one patient developed AD after Tx. Bone histology did not change after Tx in those with N-Bfr during regular dialysis, but bone formation increased after Tx in two of three patients with AD during regular dialysis. Z-scores for height in pre-pubertal patients after Tx were below age-appropriate values in each histologic subgroup, but values did not differ among groups. Z-scores for bone mineral content at the lumbar spine were also less than age-predicted values, -0.67 +/- 1.2. After adjusting for the degree of growth retardation, height-adjusted z-scores for lumbar spine BMC after Tx were above normal in all three histologic groups (0.68 +/- 1.0). The results suggest that reductions in bone mass and post-transplant osteoporosis are not prominent findings in pediatric renal transplant recipients when the influence of growth retardation on bone mass measurements by DXA is carefully considered.     

Mycophenolate mofetil. A useful immunosuppressive in inflammatory eye disease

OBJECTIVE: To assess the usefulness of mycophenolate mofetil (MMF) (Cellcept, Roche), a potent selective uncompetitive and reversible inhibitor of ionisine monophosphate dehydrogenase involved in purine synthesis, as an immunosuppressive and steroid-sparing agent in the management of ocular inflammatory disease. DESIGN: Open-label, prospective, uncontrolled pilot study. PARTICIPANTS: Eleven patients with uncontrolled ocular inflammation. INTERVENTION: Mycophenolate mofetil, at a dosage of 1 g twice daily, was given in conjunction with steroids, as a steroid-sparing agent, or as an additional agent with cyclosporine (CsA), or instead of CsA or azathioprine. MAIN OUTCOME MEASURES: The inflammatory response, side effects, and toxicity were monitored. RESULTS: The addition of MMF to immunosuppressive regimens led to the improvement in symptoms and the ability to reduce the dose of prednisone in most patients. Ten of 11 patients showed a favorable response to MMF, with few side effects noted. CONCLUSION: These findings suggest that MMF is a useful immunosuppressive drug for controlling ocular inflammation with minimal side effects.     

Surgical wound infection in renal transplantation: outcome data in 102 consecutive patients without perioperative systemic antibiotic coverage

BACKGROUND: The incidence of surgical wound infection in the presence of immunosuppression has been reported in the literature to approach 7%. Perioperative systemic antibiotic therapy is routinely used to reduce the occurrence of wound infections. This therapy is not without complications, including adverse effects and development of resistant strains. DESIGN: Surgical wound infection rates during the first 100 days after renal transplantation were studied in 102 consecutive patients. Eighty-one patients underwent cadaveric transplantation and 21 patients underwent living-related donor transplantation from February 1, 1991, to January 1, 1992. No systemic perioperative antibiotic coverage was used, but local antibiotic irrigation was part of the perioperative protocol. SETTING: Hahnemann University Hospital, Philadelphia, Pa, is a large, tertiary care center. Patients were initially hospitalized and were discharged during the 100-day follow-up period based on clinical status and improvement in renal function. PATIENTS: Twenty-seven (25%) of 102 patients had diabetes mellitus. INTERVENTIONS: Induction immunosuppression consisted of azathioprine, prednisone, and anitlymphocyte globulin, while maintenance immunosuppression consisted of azathioprine, prednisone, and cyclosporine. Acute allograft rejection episodes were treated with steroids and/or OKT3 (Ortho Pharmaceutical Group, Raritan, NJ). RESULTS: Two surgical wound infections (2%) occurred. In both, infection was superficial, resolving with wound drainage and intravenous antibiotics. The surgical wound infection rate was not significantly affected by age, sex, allograft source, or presence of diabetes mellitus. CONCLUSIONS: Despite immunosuppression, the incidence of surgical wound infection was minimal, comparing favorably to rates reported for renal transplantation with the use of systemic antibiotics. Possible explanations for the low incidence of surgical wound infections include local wound irrigation, meticulous hemostasis, improved organ procurement techniques, and continuity in perioperative care.     

Relationship between myocardial collagen and echo amplitude in non-fibrotic hearts

The aim of the study was to investigate the relationship between myocardial collagen and regional echo amplitude in humans with non-fibrotic myocardium. The ratio of myocardial collagen to total myocardial protein was determined as the hydroxyproline/leucine ratio in endomyocardial biopsies obtained from the right ventricular side of the interventricular septum in orthotopically transplanted hearts. Regional echo amplitude was measured in the interventricular septum. Patients were studied prospectively. Twenty-five patients (five female, 20 male) who had undergone orthotopic cardiac transplantation were studied 355 to 2939 days (1009 +/- 718, mean +/- SD) post-transplantation at the time of annual cardiac catheterization and endomyocardial biopsy. Patient ages varied from 22 to 62 years (46 +/- 11). Donor ages were 14 to 47 years (25 +/- 8) and the ischaemic time, 90 to 245 min (151 +/- 42). Cardiac transplantation was performed for end-stage cardiac failure in all patients. The aetiology of cardiac failure was valvular heart disease in three, dilated cardiomyopathy in eight and ischaemic heart disease in the remainder. Echo amplitude studies were performed within 24 h of endomyocardial biopsy. All but one patient were on an immunosuppressive regime consisting of cyclosporine A and azathioprine with additional steroids in three. The remaining patient, who was the longest surviving patient in the study group, had never been treated with cyclosporine. This patient was maintained on steroids and azathioprine alone. No patient had clinical or histological evidence for acute cardiac rejection and all were clinically well. Five patients had angiographic evidence of coronary artery disease. All subject studies were performed at Harefield Hospital.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genomic organization and chromosomal localization of the Itm2a gene

BACKGROUND: Pemphigus vulgaris is a potentially life-threatening autoimmune disease. Although combination therapies with prednisone and azathioprine are usually effective in controlling the disease, some patients either do not respond to this treatment or show early relapses. OBJECTIVE: To find out whether mycophenolate mofetil would be an effective drug in controlling pemphigus vulgaris in patients who failed initial treatment with azathioprine and prednisone. RESULTS: Twelve patients who were initially diagnosed as having pemphigus vulgaris and had relapsed while undergoing treatment with azathioprine (1.5-2 mg/kg of body weight) and prednisolone (2 mg/kg of body weight) subsequently received combination therapy with mycophenolate mofetil (2 x 1 g/d) and prednisolone (2 mg/kg of body weight per day). Eleven of the 12 patients responded to therapy and showed no relapse of their disease even after tapering of the steroid dose. One patient did not respond. Toxic effects were low with only mild gastrointestinal symptoms in 5 patients and mild lymphopenia (World Health Organization grade I) in 9 patients. During the 9- to 12-month follow-up, none of the 11 patients showed reappearance of pemphigus lesions. CONCLUSION: Treatment of pemphigus vulgaris with mycophenolate is a safe and effective treatment.     

Determinants of late allograft nephrectomy

When loss of graft function occurs more than six months after transplantation, allograft nephrectomy is not routinely performed at the time of graft failure. It is usually performed only on those patients who subsequently develop specific complications. However, little is known about the characteristics that make patients more likely to require allograft nephrectomy. The purpose of our study was to identify risk factors for the subsequent need for allograft nephrectomy in patients with graft failure occurring more than 6 months after transplantation. Forty-one patients were studied. Inclusion criteria were: loss of graft function > or = 6 months after transplantation, resumption of dialysis and initiation of weaning from immunosuppression. Thirty patients were treated with cyclosporine + prednisone +/- azathioprine and 11 with azathioprine + prednisone. Mean follow-up time was 17.8 months, ranging from 6 months to 6.1 years. Recipient age, sex and race, original renal disease, donor, donor source (cadaveric vs living related), HLA compatibility, levels of panel reactive antibodies, occurrence of initial delayed graft function, causes of graft failure and tapering of immunosuppression were similar in patients with and without allograft nephrectomy. Using univariate analysis, allograft nephrectomy was found to be significantly more frequent in patients with a history of 2 or more episodes of acute rejection than in patients with no rejection episode: 83% vs 30% (p = 0.03). In addition, allograft nephrectomy was found to be significantly more frequent if the immunosuppressive regimen included cyclosporine (62% vs 27.3%; p = 0.04). Using multivariate analysis however, the number of previous episodes of rejection was found to be the only significant predictor for allograft nephrectomy. None of the other variables considered in the multivariate analysis, including the type of immunosuppressive therapy, was identified as a significant predictor for the need to perform allograft nephrectomy. In summary, the need for late allograft nephrectomy was correlated with the number of previous episodes of acute rejection. Patients with a history of numerous rejection episodes should thus be considered more likely to require allograft nephrectomy once immunosuppression is withdrawn. Possible interventions to reduce or prevent the need for nephrectomy include more gradual tapering of immunosuppression at the time of graft failure or indefinite low-dose immunosuppressive therapy.     

Bread staling. Simultaneous effect of bacterial alpha-amylase and emulsifier on firmness and pasting properties of bread crumbs++

Late recurrent primary biliary cirrhosis (PBC) following orthotopic liver transplant remains a controversial topic. The first documented case of recurrence occurring in 16 patients transplanted for PBC and followed at the authors' institution for longer than one year is presented. A 54-year-old man transplanted for PBC developed a cholestatic pattern of enzyme elevation on post-transplant day (PTD) 1305. Repeat antimitochondrial antibody was strongly positive (1:300 to 1:400). A liver biopsy revealed severe bile duct damage, lymphocytic cholangitis, focal periductal noncaseating granuloma and minimal endotheliitis. Recurrent PBC was diagnosed. At the time of orthotopic liver transplant this patient received induction immunosuppression with OKT3 crossed over to cyclosporine (CsA), azathioprine (AZA) and prednisone. AZA was discontinued early and maintenance CsA tapered to a target trough level of 150 to 200 ng/mL by PTD 365. Prednisone was withdrawn by PTD 664. CsA levels during PTDs 1225 to 1305 (before elevation of hepatobiliary enzymes) were below target at 114 to 166 ng/mL. Of the 16 patients, all but three were maintained on CsA, AZA and prednisone. One was on CsA (trough levels on target) and AZA; the other two, including the patient with recurrent PBC, were on CsA only. The trough CsA level of the patient without recurrent PBC has been within the target range. The authors speculate that the underlying defect in immunoregulation in PBC persists post-transplant and that in the patient without recurrent PBC this defect was unmasked by lowered maintenance immunosuppression--allowing recurrence of PBC in a previously stable liver allograft.     

Lipid disorder and transplant coronary artery disease in long-term survivors of heart transplantation

BACKGROUND: Transplant coronary artery disease is the major cause of late mortality after heart transplantation. The underlying mechanism probably involves various factors including immunologic and nonimmunologic factors. METHODS: The influence of various risk factors concerning both the development and the progression of transplant coronary artery disease was analyzed. Fifty-two heart transplant patients, who survived at least 2 years after transplantation (24 to 60 months), were included. RESULTS: Of these patients 38.5% had angiographic evidence of transplant coronary artery disease. They had significantly higher values of total cholesterol, low-density lipoprotein cholesterol, and log triglycerides than patients without evidence of the disease (p = 0.037, p = 0.002, and p = 0.015, respectively). In addition, preoperative diagnosis of coronary artery disease was a predictor of the development of transplant coronary artery disease, whereas significant differences were not found corresponding to recipient age, donor age, ischemic time, body mass index, lipoprotein (a) value, high-density lipoprotein cholesterol value, time after transplantation, number of postoperative rejection episodes, or prednisone dosage. A 12-month angiographic follow-up indicated disease progression in 25% of the patients. With respect to the majority of factors analyzed within the study, the differences between patients with and those without progression were comparable to the differences between patients in whom transplant coronary artery disease developed and those in whom it did not. However, patients exhibiting disease progression had a higher prednisone intake dosage (p = 0.006) and had significantly higher lipoprotein (a) values (p = 0.0229) than patients without progression. CONCLUSION: This study clearly shows that in heart transplant patients surviving more than 2 years, lipid disorder is one of the main risk factors of both the development and the progression of transplant coronary artery disease.     

Infectious ocular complications in orthotopic liver transplant patients

We report the frequency and type of infectious ocular complications following orthotopic liver transplantation (OLT) and review diagnostic and therapeutic strategies. During the period September 1988 through November 1994, 684 patients underwent OLT at Mount Sinai Hospital (New York). Nine orthotopic liver transplant patients (1.3%) developed ocular infections: Candida albicans endophthalmitis (2), Aspergillus fumigatus endophthalmitis (1), cytomegalovirus retinitis (4), herpes simplex virus keratitis (1), and varicella-zoster virus panophthalmitis (1). The mean time from OLT to ocular symptoms was 42 days for patients with fungal infections and 128 days for patients with viral infections. Blurred vision was the commonest symptom (five of nine cases). The mean duration of follow-up was 2 years (range, 33 days to 5 years). Permanent loss of vision occurred in three patients, five had improvement in visual acuity, and one died of disseminated aspergillosis 33 days after OLT. Infectious ocular complications following OLT may occur as isolated events or with disseminated disease. Fungal infections occur earlier (mean, 42 days after OLT) than viral infections (mean, 4 months after OLT). The clinical presentation may be atypical; aggressive vitreoretinal procedures and serial examinations may be required to establish the diagnosis. Cytomegalovirus retinitis in orthotopic liver transplant patients may not require life-long maintenance therapy with antiviral agents.     

Cyclosporin for the treatment of severe ulcerative colitis

The effect of cyclosporin was evaluated in six patients with severe ulcerative colitis not responding to at least 8 days of standard therapy with intravenous corticosteroids. Cyclosporin (5-7.5 mg/kg/day intravenously) was added while steroid therapy was continued. Five of 6 patients responded after a mean of 7 days and colectomy was not necessary. After 4 weeks three patients achieved clinical remission or had mild symptoms and were weaned from cyclosporin and corticosteroids without exacerbation within the next 7-15 months. Two patients improved and they were put on oral cyclosporin. One of them relapsed after 2 weeks and then responded to high dose corticosteroids. This patient is doing well at 8 months of followup on azathioprine and steroids. One patient stopped oral cyclosporin after 3 months abruptly and then had a relapse. He subsequently improved while refusing any medical therapy. Side effects of cyclosporin occurred in 2 patients but were mild and self limited and did not necessitate discontinuation of the drug. Cyclosporin appears to be effective in a large portion of patients with severe ulcerative colitis who failed to improve on corticosteroids and in whom colectomy would otherwise be considered.     

Pulmonary fibrosis with predominant CD8 lymphocytic alveolitis and anti-Jo-1 antibodies

Interstitial lung disease (ILD) is a complication of polymyositis (PM) and dermatomyositis (DM). It often manifests itself in association with myositis-specific antisynthetase autoantibodies, among which anti-Jo-1 antibodies are the most commonly encountered. In contrast, ILD associated with anti-Jo-1 antibodies without muscle involvement is rare and not well characterized. We report four patients presenting with ILD associated with anti-Jo-1 antibodies. Histological findings of transbronchial biopsies disclosed a pattern consistent with nonspecific interstitial pneumonitis, a CD8+ lymphocytosis was found in bronchoalveolar lavage. Only one of these patients developed an "antisynthetase syndrome" with PM, after nearly 2 yrs of severe ILD. The clinical conditions of all four cases showed stabilization or improvement when cyclosporine was added to their immunosuppressive treatment. These cases confirm that a CD8+ lymphocytic interstitial lung disease may be the first, and sole manifestation of autoimmune disease associated with anti-Jo-1 antibodies. Furthermore, they suggest that this form of interstitial lung disease apparently has a poor response to steroids and cytotoxic drugs, but may respond to moderate doses of cyclosporine and azathioprine in addition to low doses of steroids.