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Biomedical subjects

J A Light

Publications and source records attributed to J A Light.

At least 73 records · Page 4Linked to original sources
PubMed1989

Quadruple immunosuppression: comparison of OKT3 and Minnesota antilymphocyte globulin.

From May 1977 to June 1988, 110 patients receiving cadaveric kidney transplants were selected to receive Orthoclone (OKT3; Ortho Pharmaceutical Corporation, Raritan, NJ; 5 mg intravenous bolus) (n = 43) or Minnesota antilymphocyte globulin (MAG; 20 mg/kg/day) (n = 67) as the induction phase of a quadruple immunosuppressive protocol. The duration of treatment ranged from 5 to 16 days for OKT3 (mean, 8 days) and 7 to 14 days for MAG (mean, 9 days) as dictated by the postoperative recovery of renal function. All patients were followed-up for at least 3 months (maximum, 18 months; mean, 10 months). Of the 43 patients receiving OKT3, 11 (26%) had rejection episodes that were reversed and did not reoccur. Two patients had episodes that could not be reversed, resulting in graft loss. Of the 67 patients receiving MAG, 38 (57%) experienced a first rejection episode within the follow-up period; 16 of these had repeat rejections. Renal function was significantly better in the OKT3 group. Although both OKT3 and MAG were associated with excellent patient (98%) and graft (92%) survival, OKT3 was easier to administer with fewer rejection episodes. It was concluded that OKT3 is superior to MAG as perioperative cytoreductive therapy following cadaveric kidney transplantation.

Adult↗
PubMed1989

Comparison of Minnesota antilymphocyte globulin and OKT3 for induction of immunosuppression in renal transplant patients.

From May 1977 to April 1988, 88 patients receiving cadaveric kidney transplants were selected to receive Orthoclone (OKT3; 5 mg intravenous bolus) (n = 28) or Minnesota antilymphocyte globulin (MAG; 20 mg/kg/day) (n = 60) as the induction phase of a quadruple immunosuppressive protocol. The duration of treatment ranged from 5-16 days for OKT3 (mean, eight days) and 7-14 days for MAG (mean, nine days), as dictated by the post-operative recovery of renal function. All patients were followed for at least four months (maximum 16 months, mean 10 months). Of the 28 patients receiving OKT3, six (21%) had rejection episodes which wre reversed and did not reoccur. Two patients developed OKT3 antibody. Only one graft was lost to rejection. Of the 60 patients receiving MAG, 30 (50%) experienced a first rejection episode within the follow-up period; 15 of these had repeat rejections. Three allografts were subsequently lost in the MAG group. Renal function was significantly better in the OKT3 group. While both OKT3 and MAG were associated with excellent patient (98%) and graft (92%) survival, OKT3 was easier to administer with fewer rejection episodes. We conclude that OKT3 is superior to MAG as perioperative cytoreductive therapy following cadaveric kidney transplantation.

Adult↗
PubMed1988

The utility of cytodiagnostic urinalysis for monitoring renal allograft injury. A clinicopathological analysis of 87 patients and over 1,000 urine specimens.

Cytodiagnostic urinalysis was tested to determine its utility in the evaluation of allograft dysfunction in renal transplant patients. Specimens were prepared using the Papanicolaou stain on cytocentrifuge preparations of standardized quantities of urine. Differential counts of blood cells (neutrophils, lymphocytes, red cells), renal tubule cells (convoluted, collecting duct, necrotic), and casts (i.e. hemoglobin, renal tubule cell) were included in the sediment evaluation. Receiver operating characteristic curves demonstrated collecting duct cell exfoliation at 20 per 10 hpf to be a more sensitive and specific reflector of acute rejection than lymphocytes at their optimum decision point of 13 per 10 hpf. Sixty-four percent of cytodiagnostic urinalysis diagnoses preceded the clinical diagnoses. Ciclosporin nephrotoxicity was differentiated by the exfoliation of renal tubule convoluted cells in excess of collecting duct cells. The advantages of this technique over membrane-filter or phase-microscopic techniques for examining urine sediment of both transplant and nephrology patients include improved sensitivity and specificity in identification of sediment elements and reliable quantitative data for use in detecting renal disease and for monitoring therapy.

Cyclosporins↗
PubMed1985

External ureteroneocystostomy in renal transplantation.

The urologic complications of 184 consecutive renal transplants (68 living-related and 116 cadaveric) performed at Walter Reed Army Medical Center are reviewed. An anterior extravesical technique modified from Witzel, Sampson, and Lich was used to reimplant the ureter. Urologic complications occurred in 11 patients (6%): urine leak (4), obstruction (3), stricture (3), and total ureteral necrosis (1). These complications occurred in the first 115 patients; no complications have been documented in the last 69 patients. The several advantages of extravesical ureteroneocystostomy include: less operative time, avoidance of a separate cystotomy, virtually no hematuria, ability to use short ureters, no need for splints or stents, shortened Foley catheter drainage, and no interference with native ureteral function. Complications are few and become uncommon with practice.

Humans↗
PubMed1985

Lack of influence of donor-recipient differences in subtypic HLA-A,B antigens (splits) on the outcome of cadaver renal transplantation.

Data collected prospectively on 3811 cadaver renal transplants performed between June 1977 and July 1982 by the 42 member institutions of the South-Eastern Organ Procurement Foundation (SEOPF) were analyzed to determine whether donor-recipient differences in sub-typic HLA-A,B specialties (splits) influenced outcome. The number of HLA-A,B antigens matched and mismatched between each donor and recipient was calculated in three ways: (1) considering all antigens and splits as distinct (not matched); (2) considering all splits as only matched with their corresponding typic antigen (but not with each other); and (3) considering all splits as matched with both their corresponding typic antigen as well as each other. Overall graft survival, graft loss from irreversible rejection, and patient survival stratified by the level of HLA match were the same using all three methods. In addition, using multivariate Cox regression analysis, the strong association between good HLA matching and increased graft survival was the same using all three methods of matching. Patients with a given number of mismatched antigens had no significant decrease in survival when additional splits were considered mismatched with each other or their corresponding typic antigen. These results suggest that matching of typic HLA-A,B antigens plays a highly significant role in reducing graft rejection but that donor-recipient differences in splits have a negligible effect on graft outcome.

Graft Survival↗
PubMed1985

Human apolipoprotein A-I isoprotein metabolism: proapoA-I conversion to mature apoA-I.

ProapoA-I (apoA-i+2 isoform) is the major apoA-I isoprotein secreted by the liver and intestine; however, it is a minor isoprotein in plasma and lymph where the major A-I apo-lipoprotein is mature apoA-I (apoA-I0, apoA-I-1, and apoA-I-2 isoforms). In the present report we provide evidence that apoA-I is rapidly and quantitatively converted to mature apoA-I, and the mature apoA-I isoforms are catabolized at equal rates. In these studies, human proapoA-I was isolated from thoracic duct chylomicrons collected during active fat absorption and mature apoA-I was isolated from plasma high density lipoproteins. The isolated lipoproteins were delipidated, fractionated by gel permeation chromatography, and the individual apoA-I isoforms were separated by preparative isoelectrofocusing. The metabolism of apoA-I isoproteins was studied in normal volunteers (N = 6) in a metabolic ward. In the first study proapoA-I and mature apoA-I (apoA-I0 isoform) were injected simultaneously into two normal subjects and the conversion of proapoA-I to mature apoA-I and the decay of radioactivity were followed in plasma and HDL over a 14-day period. ProapoA-I was rapidly and completely converted to mature apoA-I with a fractional rate of conversion of 4.0 pools/day. The average residence times of proapoA-I and mature apoA-I were 0.23 and 6.5 days, respectively. The mature apoA-I derived from proapoA-I had a residence time which was the same as the injected mature apoA-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Benefits of HLA-A and HLA-B matching on graft and patient outcome after cadaveric-donor renal transplantation.

Data collected prospectively on 3811 renal transplantations performed between June 1977 and July 1982 by the 42 member institutions of the South-Eastern Organ Procurement Foundation were analyzed to determine the influence of donor-recipient HLA-A and HLA-B matching on patient and graft outcome. Well-matched recipients were more likely to have received kidneys from outside their own centers, were more highly presensitized, included fewer blacks, and were more likely to have lost an earlier graft. Multivariate Cox regression analysis that included these and six other potential confounding variables revealed a significant association (P less than 0.001) between good HLA-A and B matching and increased graft survival. The difference in mean (+/- S.E.) actuarial graft survival between recipients worst matched and best matched for HLA-A and B antigens increased with time: 55 +/- 2 per cent as compared with 64 +/- 4 per cent at six months and 18 +/- 4 per cent as compared with 44 +/- 7 per cent at four years. Poor HLA matching of donor with recipient provided the greatest relative risk (2.16) of irreversible graft rejection of all the variables examined. Among patients with functioning grafts, well-matched recipients had lower serum creatinine levels and received significantly smaller amounts of glucocorticoids. Our findings indicate that good HLA-A and B matching is highly dependent on a system for sharing organs among institutions, and results in decreased graft rejection, better long-term graft function, and less need for post-transplantation immunosuppression.

Adult↗
PubMed1983

Human plasma proapoA-I: isolation and amino-terminal sequence.

Human apoA-I is synthesized as preproapoA-I, a 267 amino acid precursor apolipoprotein. PreproapoA-I initially undergoes intracellular co-translational proteolytic cleavage into proapoA-I. ProapoA-I is secreted from the cell and was isolated from thoracic duct lymph in the apoA-I1 isoform position. The amino-terminal sequence of proapoA-I isolated from human lymph revealed the presence of 6 additional amino acids, Arg-His-Phe-Trp-Gln-Gln, on the amino-terminal end of apoA-I consistent with the proapoA-I sequence determined by nucleic acid sequence analysis of cloned apoA-I. Our results indicate that proapoA-I is present in human plasma, and undergoes post-translational proteolytic cleavage to mature plasma apoA-I.

Amino Acid Sequence↗
PubMed1983

APUD system neoplasms in renal transplant patients.

Apudomas are uncommon neoplasms composed of neuroendocrine cells. They include carcinoid tumors, islet cell tumors, and small cell lung carcinoma. We found six cases of apudomas in a series of 1028 renal transplants from three medical centers (0.58%). One of these had been reported in 1976. The cases included a carcinoid tumor of a Meckel's diverticulum discovered and removed prior to transplantation, with no evidence of recurrence 9 years later. A small cell lung carcinoma was discovered 40 months after renal transplantation, with a fatal outcome 6 months later. Four clinically occult apudomas were found at autopsy, including one gastric and one bronchial carcinoid tumor, one multicentric pancreatic islet cell neoplasm, and one case of multiple ileal carcinoids. With the exception of the small cell lung cancer, none of the apudomas was clinically significant, and none was associated with carcinoid or other paraneoplastic syndrome. These cases illustrate the difficulty of diagnosis of apudomas in patients with renal failure and the usually benign nature of these tumors despite the administration of potent immunosuppressive agents.

Adenoma↗
PubMed1983

Apolipoprotein A-I isoforms in human lymph: effect of fat absorption.

The effect of fat feeding (100 g of cream) on the apoA-I isoproteins distribution has been analyzed by two-dimensional gel electrophoresis in the chylomicrons, VLDL, LDL, and HDL isolated from the thoracic duct lymph of patients undergoing lymph drainage for immunosuppression, Isoforms apoA-I3 and apoA-I4 are the most abundant apoA-I isoproteins in plasma lipoproteins as well as in lymph lipoproteins collected in the fasting state. Fat feeding, on the other hand, results in a marked change in the apoA-I isoform pattern in lymph chylomicrons and VLDL, with a significant increase in the relative concentration of the apoA-I1 isoform. As a result the total concentration of this isoprotein in the lymph increased. The data indicate that fat feeding is associated with major changes in the distribution of the apoA-I isoforms in the lymph (d less than 1.006 g/ml lipoproteins), which may be of significance in their plasma catabolism.

Apolipoprotein A-I↗