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Biomedical subjects

C C Tan

Publications and source records attributed to C C Tan.

At least 55 records · Page 3Linked to original sources

The effect of polyunsaturated phosphatidyl choline in the treatment of acute viral hepatitis.

BACKGROUND: Polyunsaturated phosphatidyl choline is a preparation often advocated for diseases of the liver. METHODS: In a randomized open controlled trial, a preparation of polyunsaturated phosphatidyl choline, at a dose of 900 mg orally daily, was given to 22 patients with acute viral hepatitis. A control group of 25 patients was not treated. RESULTS: Serial serum bilirubin and alanine amino transferase levels were measured up to 12 weeks. The falls in their levels after 2 and 5 weeks, and the lengths of time to their normalization, were not significantly different in the treated group compared to the control group. CONCLUSION: The results indicated that polyunsaturated phosphatidyl choline had no beneficial effect on the course of acute viral hepatitis.

Acute Disease↗

Zidovudine is beneficial in human immunodeficiency virus associated nephropathy.

Human immunodeficiency virus associated nephropathy (Hivan) is a distinct renal disease described in patients infected with the human immunodeficiency virus (HIV). Hivan is characterized by a nephrotic syndrome, enlarged kidneys, a histologic finding of focal and segmental glomerulosclerosis, and a very rapid progression to end-stage renal disease (ESRD). No therapeutic intervention has been shown, in a prospective evaluation, to either alter the course of established Hivan or to influence the emergence of Hivan in HIV-infected patients. We conducted a prospective study on 23 consecutively selected patients seen between 1989 and 1992 who were infected with the HIV, 14 (61%) of whom had significant proteinuria (> or = 2+). Percutaneous kidney biopsy was performed in 5 (36%) of the 14 subjects who had significant proteinuria, and histologic examination of the kidney tissue revealed focal and segmental glomerulosclerosis in all 5 cases. Of the 14 subjects with proteinuria, 8 (57%) also had azotemia (serum creatinine level > or = 1.3 mg/dl). Nine (39%) of 23 subjects admitted intravenous drug use, while 9 (39%) of 23 subjects have had an opportunistic infection before enrollment in the study. The known duration of HIV infection before initiation of zidovudine therapy was 10.3 +/- (SD) 8 months. The mean CD4 count before zidovudine therapy was 195.9 +/- 117 (range 21-654) cells/mm3. The mean dose of zidovudine administered was 543 +/- 117 (range 400-800) mg daily for a period of 20.4 +/- 11 (range 6-38) months.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Associated Nephropathy↗

Production of erythropoietin by liver cells in vivo and in vitro.

Several lines of evidence indicate that the liver is the predominant production site for EPO during the early stages of development. Moreover, in adults, it may contribute significantly to EPO production in some species. Independent of age hepatocytes are the major cellular sites of EPO gene expression in the liver, but quantitatively less significant expression also occurs in at least one additional type of nonparenchymal cell. Although some indirect evidence suggests that these nonparenchymal cells producing EPO may be Kupffer cells, their identity remains to be clarified. Regarding the mechanisms of the adaptation of hepatic EPO production to changes in oxygen availability in the organism, experiments with isolated perfused livers, mixed liver cell cultures, hepatoma cells, and, more recently, isolated hepatocytes have provided evidence that inherent cellular oxygen-sensing mechanisms exist and that external factors are not essential. The use of hepatoma cells has allowed investigation of these cellular mechanisms of oxygen-dependent gene control, and further studies in nontransformed hepatocytes may complement these studies.

Aging↗

Dismal rehabilitation in geriatric inner-city hemodialysis patients.

OBJECTIVE: To assess the extent of functional and vocational rehabilitation achieved by elderly inner-city patients sustained on maintenance hemodialysis. DESIGN: Inception cohort study of elderly patients who have end-stage renal disease using a modified Karnofsky rating system. The need for a wheelchair, participation in household activities, and effect of comorbid conditions were noted. Current status was compared with patient's recollection of functional activity level 2 years before commencing maintenance hemodialysis. SETTING: Seven outpatient, hospital-affiliated and private hemodialysis units in Brooklyn, NY. PATIENTS: One hundred four patients aged 65 years or older who were receiving maintenance hemodialysis for at least 6 months. MAIN OUTCOME MEASURES: A score of 76 or greater on a modified Karnofsky scale indicated independent function at a level that permitted participation in activities beyond those mandated by the hemodialysis regimen. A comorbidity score 6 or greater on a newly constructed index correlated with severe debility. Employment status was also recorded. RESULTS: Present functional activity had deteriorated to a modified Karnofsky score of 66 +/- 12.3 (+/- SD) compared with patients' recollection of a mean score of 84 +/- 14.3 (P < .001) 2 years before initiation of hemodialysis. Diabetic patients had a lower score than nondiabetic patients. The mean comorbidity index of the entire study group was 7.8 +/- 2.9 (mean +/- SD). Within the diabetic subset, severe debility constrained 71 patients (68%) to limit all activity to their residence with the exception of travel to and from their dialysis facility. By contrast, 2 years prior to commencing dialytic therapy, 81 diabetic patients (78%) had interests and activities that took them outside their homes (P < .001). Generalized weakness was the most common explanation given for the lack of outside activity by nine patients (9%) who were wheelchair bound. Erythropoietin, though regularly administered to 87 patients (84%) in the study group, was unsuccessful in raising mean hematocrit reading above 0.28 +/- 0.05 (mean +/- SD). CONCLUSIONS: Maintenance hemodialysis does not return inner-city elderly patients to their predialysis level of functioning. Few elderly, diabetic hemodialysis patients conduct any substantive portion of their lives outside their homes. For nondiabetic patients, the modified Karnofsky score of whites (70.4 +/- 11.9) and blacks (66.5 +/- 15.3), though low, was equivalent (P < .4).

Activities of Daily Living↗

Gouty arthritis in end-stage renal disease: clinical course and rarity of new cases.

We studied 201 end-stage renal disease (ESRD) patients sustained on maintenance hemodialysis (MD) (n = 164) and chronic ambulatory peritoneal dialysis (CAPD) (n = 37) to determine (1) the frequency of acute attacks of gouty arthritis (GA) in those ESRD patients who had GA before dialytic therapy, and (2) the incidence of new-onset GA in hyperuricemic long-term (> 12 years) ESRD patients on MD. The 2-month mean of predialysis serum uric acid levels was calculated for each subject and the prevalence of hyperuricemia ascertained. There were 25 patients on MD for more than 12 years, and this group was evaluated and analyzed separately from those patients on dialytic therapy for less than 12 years; the mean of each of their predialysis uric acid values was calculated for each subject for at least 60% of the time they have been on dialysis. Patients who had GA before or after initiation of dialytic therapy were identified, and the frequency of acute attacks of GA determined. The presence of treated hypertension in each subject was noted. Thirteen of 201 patients had clinically active GA before commencing dialytic therapy, and each recalled a minimum of two painful attacks of GA per year before the initiation of ESRD therapy. Mean duration of ESRD for these 13 patients was 25 +/- 3.8 months; painful attacks of GA have not recurred in nine patients (70%), and the frequency of attacks declined by 50% in the remaining four patients (30%), despite persistent hyperuricemia in all 13.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Closure of a benign gastrocolic fistula on medical management.

Gastrocolic fistulae secondary to un-operated benign gastric ulcers are rare. We report a case of a large benign gastrocolic fistula diagnosed by colonoscopy, which was found to have healed over a short period of 3 weeks, while the patient was being prepared for surgery. He was on parenteral nutrition and intravenous cimetidine. The available literature is reviewed and an attempt is made to explain the closure of the fistula on medical treatment. A trial of medical management may be justified in patients with benign gastrocolic fistulae who are poor surgical risks.

Cimetidine↗

Dermal mast cell density and pruritus in end-stage renal failure.

Skin mast cell density was determined in two age- and sex-matched groups of patients with end-stage renal failure, one with severe uraemic pruritus (n = 9) and the other without (n = 9). In each group, seven patients were on chronic haemodialysis. In uraemic patients without pruritus, skin mast cell density was similar to that in eight healthy controls (40.1 +/- 10.2 mm2 versus 46.5 +/- 20.6 mm2; P = 0.44), a result also obtained when only the patients on haemodialysis were considered (39.3 +/- 14.7 versus 46.5 +/- 20.6; P = 0.46), showing that haemodialysis per se did not cause mast cell proliferation. In contrast, uraemic patients with itch had significantly higher dermal mast cell counts when compared with those without itch (71.8 +/- 36.4 mm2 versus 40.1 +/- 12.9 mm2; P = 0.01). However, there was no difference in serum parathyroid hormone (PTH) and calcium or phosphate concentrations between the two groups. In addition, there was no significant correlation between dermal mast cell density and serum PTH, calcium or phosphate concentrations. These data suggest that uraemic pruritus may be related to mast cell proliferation in the skin.

Adult↗

[Studies on the molecular evolution of apolipoprotein multigene family].

The apolipoprotein genes represent a large family of genes encoding various binding proteins for plasma lipid transport. Because of their long divergence history, it is not known whether and how these genes have evolved through gene duplication from a common ancestor. To test this possibility and reconstruct a reliable phylogenetic tree, a simple method to evaluate the branch length and its divergence time in unrooted parsimony tree under the condition of non-even evolutionary rate was developed. The tree built from the 26 apolipoprotein sequences by above method clearly shows: (1) The common ancestor of ApoA-I ApoA-II, ApoA-IV, ApoE may appear 460 million years ago in an ordovician vertebrate which may be related with the major apolipoprotein LAL1 and LAL2 in Lamprey from the evidence of sequence alignment; (2) The central role of different selection pressure upon the ancestor gene of apolipoprotein made them evolved into different subgroups; (3) The high evolution rate in rodent ApoE molecules may be related with the existence of a large amount of hidden substitutions and the disruption of synonym codon usage clock in their genome; (4) The evolutionary rate of various branches in parsimony tree is significantly different in which the average UEP of ApoA-I, ApoA-IV is 2.0 MY, ApoA-II 1.7MY, ApoE 2.4MY; (5) The receptor domain in ApoE seems to be more conservative than other fragments. These data suggest a long, complex evolutionary history for apolipoprotein genes in which the gene duplication events of different origins took place.

Amino Acid Sequence↗

Comparison of the human and mouse erythropoietin genes shows extensive homology in the flanking regions.

Considerable insights into important cis regulatory elements in a gene can be gleaned from the identification of sequence homologies among different species. To extend and optimize the sequence comparison between human and mouse erythropoietin (Epo) genes, we have obtained new human sequence from 5,547 to 385 bp upstream of the cap site and extended the 3' flank by 489 bp. In addition, we have obtained new sequence information on the mouse Epo gene extending from within the 3' untranslated region (UTR) to 1,001 bp downstream of the polyadenylation site. Analysis of these additional sequences shows considerable homology between human and mouse Epo genes as far as 4 kb (human) or 3 kb (mouse) upstream of the cap sites, as well as far more homology at the 3' end than was previously realized. In addition, both species were found to have a high frequency of short interspersed (SINE) repetitive sequences that interrupt homologies in both the 5' flank and within the transcription unit.

Amino Acid Sequence↗

Distribution of erythropoietin producing cells in rat kidneys during hypoxic hypoxia.

We have used in situ hybridization to determine the localization and distribution of cells expressing the erythropoietin (EPO) gene in kidneys of rats exposed to reduced oxygen tensions to characterize the control of renal EPO formation during hypoxic hypoxia. Animals were subjected to severe hypoxia (7.5% O2) for 4, 8 and 32 hours to assess changes related to the duration of hypoxic exposure, and additionally to 9% and 11.5% O2 for eight hours to define changes related to the degree of hypoxia. The number of cells containing EPO mRNA were counted on tissue sections and compared to tissue concentrations of EPO mRNA and to the serum hormone concentrations. In situ hybridization revealed expression of the EPO gene exclusively in peritubular cells that were predominantly located in the cortical labyrinth under all conditions tested. After four hours of severe hypoxia (7.5% O2) approximately 170-fold more cells were found to contain EPO mRNA than under normoxic conditions. The number of EPO producing cells did not change significantly between four and eight hours exposure to 7.5% O2, but the amount of EPO mRNA per kidney increased approximately threefold. Further continuation of hypoxia resulted in down-regulation of renal EPO mRNA levels, which was mainly due to a reduction in the number of cells containing EPO mRNA. Comparison of graded degrees of hypoxia applied for eight hours showed an inverse exponential relationship between oxygen tension and the number of EPO producing cells. This recruitment of cells expressing the EPO gene occurred along a gradient extending from the corticomedullary border to the subcapsular tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗

Identification of the renal erythropoietin-producing cells using transgenic mice.

Regulation of erythropoietin production by the kidneys is central to the control of erythropoiesis. Uncertainty about the identity of the renal cells involved has been a major obstacle to understanding this mechanism. We have used sequence from the mouse erythropoietin locus to direct expression of a marker gene, SV40 T antigen, to these cells in transgenic mice. The transgenic constructs contained an oligonucleotide marker (Epo-M) or SV40 sequence (Epo-TAg) in the 5' untranslated region of the mouse erythropoietin gene, flanked on each side by 9 and 7.5 kb of DNA from the mouse erythropoietin locus. Anemia-inducible expression of Epo-M and Epo-TAg was observed in the kidney. In one of thirteen lines, homologous integration of Epo-TAg into the mouse erythropoietin locus occurred. In transgenic mice bearing Epo-TAg at homologous and heterologous insertion sites, renal expression was restricted to a population of cells in the interstitium of the cortex and outer medulla. Immunohistochemical characterization by light and electron microscopy shows that these are the fibroblast-like type I interstitial cells.

Animals↗

Pill-induced esophageal ulcer.

We describe nine cases of esophageal injury associated with the ingestion of prescribed medications. Antibiotics were the most commonly implicated drugs. Odynophagia, retrosternal chest pain and dysphagia were the usual presenting symptoms. The typical endoscopic finding was that of discrete ulcers in the mid-esophagus. All patients recovered uneventfully with discontinuation of the offending drug and symptomatic treatment. Drug induced esophageal injury should be considered in patients presenting acutely with the above mentioned symptoms and having discrete esophageal ulcers on endoscopy.

Administration, Oral↗

Rapid oxygen-dependent changes in erythropoietin mRNA in perfused rat kidneys: evidence against mediation by cAMP.

Erythropoietin (EPO) is mainly produced in the kidneys and is regulated by blood oxygen availability. Studies with isolated perfused kidneys have established that an oxygen-sensing system exists intrarenally but the mechanisms involved are poorly understood. Using a quantitative RNase protection assay, we have demonstrated oxygen-dependent EPO mRNA production in isolated perfused rat kidneys, with EPO mRNA levels increasing 30-fold when perfusate pO2 was reduced from 474 to 25 mm Hg. To determine if the high amplitude changes in EPO mRNA levels in response to hypoxia are mediated by cyclic AMP, four agents, which activate the cyclic AMP system in different ways, were administered to isolated kidneys perfused over a range of perfusate pO2. Salbutamol and N6-ethyl carboxamidoadenosine, which activate adenylate cyclase, dibutyryl cyclic AMP (a cyclic AMP analogue) and forskolin did not augment EPO mRNA production, and no significant differences in the regression of log (EPO mRNA) on perfusate pO2, were found between experimental groups exposed to each of these compounds and controls. We conclude that the rapid increase in EPO mRNA levels in response to hypoxia is not mediated or substantially modulated by a cyclic AMP-dependent mechanism.

Adenosine↗

Prophylactic antibiotics in the insertion of Tenckhoff catheters.

We assessed the efficacy of preoperative antibiotic prophylaxis in a prospective trial for patients undergoing insertion of Tenckhoff catheters for continuous ambulatory peritoneal dialysis (CAPD). The prophylactic regimen was a single dose of cefazolin (500 mg) and gentamicin (80 mg) given intravenously half an hour before surgery. There was no significant difference in the number of exit site infections (8 in the antibiotic group vs. 8 in the controls) and the number of episodes of peritonitis (5 in the antibiotic group vs. 2 in the controls). Our study showed that prophylactic preoperative antibiotics did not reduce the number of exit site infections and peritonitis after the insertion of Tenckhoff catheters.

Adult↗