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Biomedical subjects

A J Fabrega

Publications and source records attributed to A J Fabrega.

At least 19 recordsLinked to original sources

Embolization of a mesenteric arteriovenous fistula following pancreatic allograft: the steal effect.

The first pancreatic transplant was performed in 1966 by Kelly and Lillehei at the University of Minnesota (1, 2). Nearly 30 years later, Ozaki et al., published the first occurrence of an arteriovenous fistula (AVF) in a transplanted allograft bundle (3). From its early days as a radical and experimental procedure in the treatment of insulin-dependent diabetes mellitus, this operation has progressed to become routine in many major medical centers. However, the incidence of technical complications remains relatively high, ranging from 10 to 40% (1). The list of potential complications includes allograft pancreatitis, vascular thrombosis, hemorrhage, pseudoaneurysm formation, anastomotic leaks, intra-abdominal infections, and, al. though rare, AVF. Lowell et al., in 1993, reported this last complication in 3 of 90 consecutive pancreatic recipients (4). These same authors promoted the theory that AVF formation was directly related to procurement technique: a nonspecific "blind ligation" of mesenteric vessels along the inferior pancreatic border. However, this approach continues to be used commonly. We have identified the occurrence of an allograft superior mesenteric artery-superior mesenteric vein (SMA-SMV) AVF in a pancreas-after-kidney (PAK) transplant recipient.

Adult↗

Cationic lipid-mediated transfer of the hIL-10 gene prolongs survival of allogeneic hepatocytes in Nagase analbuminemic rats.

Gene transfer techniques can be used as a drug delivery system to achieve local immunosuppression. We performed a series of experiments to identify the cationic lipid that most efficiently transfects isolated, cultured, rat hepatocytes; to optimize conditions for efficient transfection; to determine the duration of gene expression in vitro; and finally, to determine the survival of allogeneic hepatocytes transplanted into Nagase rats. Our results suggest that DOTAP is the best cationic lipid for transfection of cultured rat hepatocytes. In addition, the following conditions appear to optimize transfection efficiency: a DNA:DOTAP ratio of 1:6; a 24 exposure time of the hepatocytes to the DNA-DOTAP complex; a DNA dose of 4 microg/35 mm culture plate seeded with 2.5x10(5) rat hepatocytes. When transfected as described above, cultured hepatocytes expressed the hIL-10 gene for approximately 14 days. Accordingly, Nagase rats transplanted with 4x10(7) DOTAP-hIL-10 transfected, allogeneic hepatocytes had an abrupt rise in serum albumin levels that peaked within 7 days of the transplant, decreased abruptly after 15 days, and approached baseline by day 40. In contrast, control animals had a smaller albumin peak that returned to baseline within 10 days (P<0.01). In all animals, serum hIL-10 levels were undetectable when tested. We conclude that DOTAP is the best cationic lipid for transfection of cultured rat hepatocytes. Furthermore, hIL-10 transfected hepatocytes have a prolonged survival in an allogeneic host which is probably limited by loss of gene expression. Further studies using other vectors capable of prolonged gene expression will help determine if indefinite hIL-10 gene expression leads to indefinite graft survival.

Animals↗

Gastrointestinal problems in the immunocompromised host. A review for surgeons.

As the immunocompromised patient population grows, the gastrointestinal surgeon is increasingly called upon to make complex diagnostic and therapeutic decisions. The surgeon should first identify the patient as immunocompromised and then categorize the probable degree of immunocompromise as mild, moderate, or severe. Mildly immunocompromised patients tend to present late and with minimal symptoms, but the disease entities are the same ones seen in the general population. Moderately and severely immunocompromised patients may also develop the usual surgical problems, but the differential diagnosis is expanded to include complications of the immunocompromised state or complications of the underlying problem which caused the immune compromise. The expanded differential diagnosis includes infections with atypical organisms, opportunistic neoplasms, neutropenic enterocolitis, complications of medications, and forms of biliary tract disease not seen in the general population. Advances in oncology, transplantation, and the treatment of AIDS, have extended the life expectancy of these patients and increased the immunocompromised population. Prompt appropriate operative therapy may be lifesaving when surgical complications develop.

Abdomen, Acute↗

Antibody-mediated hemolytic anemia following ABO-mismatched organ transplantation: contributory role of HLA matching and polyclonal antilymphocyte globulin.

We report three instances of antibody-mediated hemolytic anemia following ABO-mismatched, but compatible, renal (n = 2) and simultaneous pancreas-kidney (n = 1) transplantation. The two renal allograft recipients had received a 6-antigen matched transplant; one received polyclonal antilymphocyte globulin to treat an early rejection episode. The simultaneous pancreas-kidney transplant received polyclonal antilymphocyte globulin (ALG) as part of a quadruple therapy induction regimen. All three patients developed severe, but self-limited, antibody-mediated hemolytic anemia within two weeks of their transplants. Serologic testing demonstrated the hemolysis to be antibody mediated; furthermore, testing of the ALG lots demonstrated high titers of anti-red blood cell antibodies. The possible contribution of ALG and HLA matching to the hemolysis seen in these patients after ABO mismatched organ transplantation is discussed.

ABO Blood-Group System↗

Hepatitis C infection in potential recipients with normal liver biochemistry does not preclude renal transplantation.

The hepatitis C virus (HCV) may be an important cause of chronic liver disease in renal transplant recipients. We investigated retrospectively the incidence and outcome of HCV infection in long-term renal transplant recipients and patients on hemodialysis. Stored, pretransplant sera of transplant recipients with normal liver biochemistry at surgery were tested for hepatitis C by a second-generation enzyme immunoassay. Hemodialysis patients were tested by a first-generation enzyme-linked immunosorbent assay (ELISA) against c100-3. We studied 252 renal transplant recipients and 58 hemodialysis patients followed for 65 +/- 10 months and 26 +/- 6 months, respectively. Fifteen percent (38/252) of the transplant recipients were HCV positive as were 3/58 (5%) of the hemodialysis patients. Overt liver disease occurred in 22/252 (8.7%) transplant recipients and none in the hemodialysis group. Thirty-six percent (8/22) of transplant recipients with overt liver disease were HCV positive. No HCV-positive patients died of liver failure. Of six biopsies in the HCV-positive transplant group, two had histological evidence of CAH. CAH was seen in six of eight biopsies in the HCV-negative transplants and two of these latter patients progressed to cirrhosis. No hemodialysis patients had clinical or histological evidence of chronic liver disease. Two HCV-negative transplant patients died of liver failure, while no deaths related to liver disease occurred in hemodialysis patients regardless of HCV status. We conclude that hepatitis C may cause chronic hepatitis in renal transplant patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of steroid withdrawal on long-term renal allograft recipients with posttransplantation diabetes mellitus.

BACKGROUND: Posttransplantation diabetes mellitus (PTDM), a common complication of current immunosuppressive regimens, has been attributed to the diabetogenic effects of prednisone and cyclosporine. We report our experience with steroid withdrawal (SW) in renal allograft recipients with PTDM. METHODS: SW was attempted on 12 selected renal allograft recipients with PTDM, and its effects on various clinical parameters were recorded before and more than 3 months after SW. RESULTS: Patient and graft survival was 100%, and all patients had a stable serum creatinine level and remained steroid free 15.4 +/- 5 months after SW. Ten patients had a significant improvement in their diabetic management. Glycosylated hemoglobin decreased from 13.6% +/- 2.3% to 9.2% +/- 2.9% (p = 0.0002); body weight decreased from 92 +/- 21 kg to 86 +/- 21 kg (p = 0.0134), and management of hypertension improved in eight of nine (89%) recipients with hypertension. The total cholesterol level decreased from 253 +/- 57 mg/dl to 208 +/- 40 mg/dl (p = 0.0041), but the high-density lipoprotein cholesterol also decreased from 46 +/- 8.9 mg/dl to 39.7 +/- 10.9 mg/dl (p = 0.073), so that the total cholesterol/high-density lipoprotein ratio was not significantly affected (p = 0.775). CONCLUSIONS: SW in selected, stable, long-term renal allograft recipients with PTDM has a favorable effect on glucose homeostasis, body weight, and management of hypertension; its effect on lipid metabolism and subsequent cardiovascular risk factors warrant further study.

Adrenal Cortex Hormones↗