Biomedical subjects

R Holton

Publications and source records attributed to R Holton.

5 recordsLinked to original sources

PubMed1995

Correction of congenital indirect hyperbilirubinemia by small intestinal transplantation.

INTRODUCTION: Crigler-Najjar syndrome, type I, is a disease characterized by complete absence of hepatic bilirubin glucuronidation. The congenital indirect hyperbilirubinemia is due to an autosomal recessive deficiency of the enzyme, uridine diphosphate glucuronosyl transferase (UDPGT). The inbred homozygous Gunn rat is also deficient in UDPGT, exhibits unconjugated hyperbilirubinemia, and is an excellent animal model of the Crigler-Najjar syndrome. This study was performed to test the ability of transplanted intestine from normal Wistar rat donors to correct the deficiency in hepatic bilirubin conjugation. MATERIALS AND METHODS: In phase 1, Gunn rats underwent 40-cm heterotopic small-bowel transplants from either Wistar (experimental) or Gunn (control) rats. In phase 2, 15- to 20-cm Wistar-to-Gunn jejunal transplants were placed either heterotopically or orthotopically (in intestinal continuity). All rats were treated with cyclosporin A (CsA), 5 mg/kg per day. Serum bilirubin levels were determined spectrophotometrically at weekly intervals posttransplantation. In phase 2, UDPGT activity was quantitated at 0, 2, 4, and 8 weeks using known quantities of bilirubin as substrate. RESULTS: Total bilirubin levels decreased significantly in the 40-cm heterotopic transplant recipient rats. From the initial values of 7.12 +/- 0.59 mg/dL, levels reached the nadir of 4.23 +/- 0.27 mg/dL. A parallel drop in serum levels of indirect bilirubin was noted (5.04 +/- 0.54 mg/dL to 2.74 +/- 0.23 mg/dL). After 6 weeks, bilirubin levels began to rise toward pretransplant values. In contrast, there was no significant change in bilirubin levels in the control Gunn-to-Gunn rats. Fifteen- to 20-cm heterotopic Wistar-to-Gunn transplants caused a qualitatively similar drop in total and indirect bilirubin levels. Orthotopic (in continuity) Wistar-to-Gunn transplants lowered serum bilirubin levels more rapidly, and the effect was sustained throughout the 8-week study period. By 1 week posttransplantation, total bilirubin levels dropped from 5.11 +/- 0.48 mg/dL to 2.41 +/- 0.16 mg/dL (P < 0.05); data at 8 weeks averaged 1.84 +/- 0.35 mg/dL. Respective data for indirect bilirubin levels were 4.81 +/- 0.45 mg/dL, 2.26 +/- 0.18 mg/dL, and 1.35 +/- 0.39 mg/dL. Wistar rat UDPGT activity in intestine and liver averaged 0.61 +/- 0.05 and 1.88 +/- 0.06 mg bilirubin conjugated/mg tissue per hour, respectively. Enzyme activity in the transplanted intestine persisted throughout the course of the study. CONCLUSION: Transplants of small intestine with known UDPGT activity partially corrected the deficiency in Gunn rats and allayed the hyperbilirubinemia. Since the small intestine is known to contain small but significant amounts of a large number of predominantly hepatic enzymes, bowel transplantation may be an appropriate treatment for this and other similar genetic enzyme deficiencies.

Animals↗

PubMed1993

Does ketorolac tromethamine, a new analgesic, decrease postoperative recovery time, narcotic requirements, nausea and/or vomiting, and unscheduled hospital admissions: a retrospective analysis.

This study retrospectively evaluated patients receiving intramuscular ketorolac for postoperative analgesia as compared to intravenous narcotics. Ninety-eight patients' charts were reviewed. Forty-nine subjects who received ketorolac postoperatively (intramuscularly) when entering the post anesthesia recovery unit, were matched with forty-nine subjects who had had similar diagnoses (operated on during the same eight months) who did not receive ketorolac (groups 1 and 2). All subjects received narcotics (intravenously) when complaining of pain. Variables recorded were type and duration of procedure, patient age, gender, post anesthesia recovery time, unscheduled admissions, ketorolac dose, narcotic requirements and doses, and nausea and/or vomiting. Data for each of the two groups were compared by Wilcoxon signed-rank test. Groups 1 and 2 did not differ in type or duration of surgery, patient age or gender. Procedures ranged from dilatation and curettage to major spinal surgeries. Post anesthesia recovery unit times, narcotic dosages and nausea and/or vomiting were not different between group 1 and 2. The timing of administration for the ketorolac may be a reason for these results; it may be beneficial if administered intraoperatively, or intravenously (when FDA approved in the United States) during the postoperative period.

Adolescent↗

PubMed1983

Thymine salvage, mitochondria, and the evolution of the herpesviruses.

The salvage of thymine is an apparently ubiquitous feature of free-living lifeforms as well as of mitochondria, chloroplasts and most of the large DNA viruses. Assumptions and data are described which explain the evolution of thymine salvage in prokaryotes, animal cells, and large DNA viruses, in terms of deoxythymidine kinase and its relationship to mitochondria. Specifically, it is suggested that regulation of deoxythymidine kinase (by end-product inhibition) has evolved as a means of assuring a constant supply of thymine compounds for the mitochondria and that the degree to which this regulation is present in the deoxythymidine kinases of the various herpesviruses correlates with the degree of dependence of their replicative cycle on the continued health of the mitochondria of their host cells.

Biological Evolution↗

PubMed1975

Chlorinated pesticides and polychorinated biphenyls in marine species, Oregon/Washington Coast, 1972.

Concentrations of chlorinated pesticides and polychlorinated biphenyls (PCB's) were determined in three offshore marine species from the Oregon/Washington coast: pink shrimp, euphausiids, and flatfish; five species of bivalve mollusks from five estuaries along the Oregon coast; several fish species from the Coos Bay and Columbia River estuaries; and a summer run of steelhead from the Rogue River. The compounds p,p'-DDE and PCB's were detected most frequently. Euphausiids and pink shrimp contained approximately 2 ppb (mug/kg) wet-weight DDE and 8 and 25 ppb PCB's, respectively. Offshore flatfish contained an average of 9 ppb DDE and 29 ppb PCB's. DDE residues in estuarine mollusks approximated 0.5 ppb. PCB levels were not detectable (greater than 3 ppb) except in collections from the mouth of the Columbia River where the levels averaged 400 ppb PCB's and 17 ppb DDT. Selected Columbia River where levels averaged 400 ppb PCB's and 17 ppb DDT. Selected Columbia River fish species contained 38 ppb DDE and 480 ppb PCB's; summer-run steel-head in the Rogue River contained 97 ppb DDE and 125 ppb PCB's. PCB chromatograms of most euphausiids closely resembled those of Aroclor 1254. Chromatograms of shrimp and flatfish indicated selective metabolism of two compounds in the Aroclor 1254 formulation. Biphenyls of higher chlorine content were also detected in the shrimp and flatfish.

Animals↗

PubMedDate not supplied

Glycosylated haemoglobin in uraemia.

Glycosylated haemoglobin (GHb) was measured in 71 patients with stable chronic renal failure by the thiobarbituric acid (TBA) reaction and by agar gel electrophoresis. Nineteen patients were diabetic. Of the non-diabetics, 22 were treated conservatively (including 8 children), 15 by maintenance haemodialysis, and 15 by continuous ambulatory peritoneal dialysis. GHb measured by both methods correlated with postprandial blood glucose levels. There was a significant discrepancy between the two methods only in patients with serum urea concentrations greater than 30 mmol/l, mean +/- SD, (6.8 +/- 2.6% vs 8.2 +/- 2.5% for TBA and electrophoresis, respectively). This difference, delta GHb, correlated with serum urea, serum creatinine, and serum bicarbonate, but after logistic regression of results from all 71 patients only serum urea was associated with delta GHb. Lower haemoglobin and GHb and high fetal haemoglobin concentrations in the haemodialysis group suggested increased haemolysis in these patients. Measurement of GHb by the TBA method and by agar gel electrophoresis remain useful indicators of hyperglycaemia in patients with mild, stable chronic renal failure.

Adolescent↗