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Biomedical subjects

E Chan

Publications and source records attributed to E Chan.

At least 91 records · Page 5Linked to original sources
PubMed1995

Diarrhoeal diseases in the White Mountain Apaches: clinical studies.

Acute diarrhoeal diseases continue to be a major health problem in certain underprivileged populations in the United States, including native Americans living in reservations. To describe the features of patients with diarrhoeal diseases requiring medical care, those attending the medical facilities of the Fort Apache Indian Reservation, Whiteriver, Arizona, were studied during 1981-1985. Clinical and aetiological information was obtained on 535 patients which constitute a 20% sample of those attending the outpatient clinic and all 386 patients who required 550 hospitalizations. Rotavirus, enterotoxigenic Escherichia coli, and Shigella were the most common aetiologic agents, a pattern similar to that seen in the developing countries. The clinical features of diarrhoeal illness and the frequent associated occurrence of acute respiratory symptoms, however, were remarkably similar, regardless of aetiology.

Acute Disease↗
PubMed1995

Diarrhoeal diseases in the White Mountain Apaches: epidemiologic studies.

Acute diarrhoeal disease in children is known to be a major public health problem among native Americans living in reservations in the southwestern part of the United States. This study was undertaken to describe the epidemiology and causative agents of diarrhoea more completely, with the expectation that this information may help in the ultimate control of the disease in this population. Three interrelated epidemiologic studies were carried out in the White Mountain Apache Tribe, Whiteriver, Arizona, during 1981-1985: a three-year longitudinal study on a cohort of 112 newborns, a longitudinal two-year study in a cohort of 200 families, and a case-control study on 1,072 children with diarrhoea attending a medical facility. Both epidemiologic and microbiological patterns of diarrhoeal disease were found to be very similar to those seen in developing countries, indicating the need for basic improvements in sanitation and hygiene in this population.

Acute Disease↗
PubMed1994

[Anaphylaxis caused by chlorhexidine following cystoscopy or urethral catheterization].

Since 1983 the Netherlands Centre for Monitoring of Adverse Reactions to Drugs received 6 reports of anaphylaxis due to a chlorhexidine-containing lubricant used during cystoscopy or urinary catheterization. One case was described earlier. An accidental rechallenge in two patients was positive. In 5 cases, the causal relationship with chlorhexidine was confirmed by a positive reaction to intracutaneous testing. Although this adverse reaction is probably rare, medical practitioners should be aware of the possibility that a severe anaphylactic reaction may occur during use of these products.

Adrenal Cortex Hormones↗
PubMed1994

Stability of ganciclovir sodium and amino acids in parenteral nutrient solutions.

The stability of ganciclovir sodium and amino acids in parenteral nutrient solutions was studied. Three admixtures of ganciclovir sodium plus parenteral nutrient solution were prepared, one containing ganciclovir sodium 0.83 mg/mL, 1% amino acids, and 10% dextrose injection; one containing ganciclovir sodium 1.4 mg/mL, 2.5% amino acids, and 10% dextrose injection; and one containing ganciclovir sodium 1.4 mg/mL, 5% amino acids, and 25% dextrose injection. The solutions were visually inspected for precipitates, color change, and gas formation and were tested for pH. High-performance liquid chromatography was used to measure the concentration of ganciclovir and 16 amino acids in each admixture immediately and one, two, and three hours after preparation. There was no evidence of visual incompatibility in any of the admixtures, and pH did not vary appreciably during the study. The mean ganciclovir sodium concentration remaining was greater than 100% of the initial concentration for all the admixtures at one, two, and three hours. The mean amino acid concentration remaining in the admixtures with 2.5% or 5.0% amino acids was greater than 90% of the initial concentration for each amino acid at one, two, and three hours. The mean amino acid concentration remaining in the admixture with 1% amino acids was greater than 90% of the initial level at one and two hours. Ganciclovir sodium 0.83 mg/mL was stable for at least three hours in parenteral nutrient solution with 1% amino acids, and ganciclovir sodium 1.4 mg/mL was stable for at least three hours in admixtures with 2.5% or 5% amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1994

Glipizide-induced prevention of diabetes and autoimmune events in the BB rat.

To determine whether glipizide, a sulfonylurea, can prevent diabetes in the diabetic-prone BB rat model, rats were studied from 35 to 240 days of age. Treated animals received oral glipizide (10 or 100 mg/kg/day) from 35 to 200 days of age, and control rats received oral placebo. From 80 to 135 days of age at both drug doses, glipizide decreased the incidence of diabetes, thus delaying disease onset (P < 0.02). At the higher dose of glipizide, a diabetes preventive effect was observed (P < 0.025). There were no significant differences in body weights between the treated and control groups. At 240 days, i.e. 40 days after stopping glipizide and placebo treatments, diabetes incidence remained stable in the two groups; thus the effect of glipizide persisted after discontinuation of the drug. Serum glucose and insulin levels measured at 90 and 200 days did not reveal differences between the glipizide treated and control groups. To determine whether the sulfonylurea affected autoimmune events, the prevalence and severity of islet inflammation were examined. In glipizide-treated BB rats at 240 days, only 44% of rats had islet inflammation compared to 86% in the control group (P < 0.01). At both 90 and 240 days the severity of islet inflammation was decreased in the glipizide treatment groups compared with the control groups (P < 0.01). These data indicate that glipizide (a) prevents diabetes in the diabetic-prone BB rat strain, (b) decreases the prevalence and severity of islet inflammation even after drug withdrawal and (c) may dampen autoimmune events leading to diabetes onset.

Age Factors↗
PubMed1994

In situ islet cytokine gene expression during development of type I diabetes in the non-obese diabetic mouse.

Expression of cytokine genes in the islets of non-obese diabetic (NOD) female mice was examined. RNA samples were prepared from the islets and spleens of NOD mice at different time points at prediabetic stages during the natural disease process. Cytofluorometric analyses showed that the majority of lymphocyte infiltrates in the islets at 14 weeks of age consisted of T cells (68%). Of these, 80% of Thy1.2+ cells were CD4+ T cells. Less than 1% of in situ islet immune cells expressed a cell surface marker specific for the macrophage (Mac-1). Results of polymerase chain reaction using RNA (RT-PCR) prepared from spleens, and isolated and purified islets demonstrated that IFN-gamma message was detectable in the islets at 7 weeks of age (an early stage of insulitis). No message for this gene was detected in the spleen at any stage studied (7, 14 and 16 weeks of age). In contrast, TNF-alpha message was detected in both spleen and the islets at all stages, although the level of expression of TNF-alpha in the islets was much higher than that in the spleen. These results suggest that both cytokines are produced by in situ islet T cells, possibly activated T cells, which may be responsible for initiating or perpetuating autoimmune reactions in the islets.

Animals↗
PubMed1994

Stereochemical aspects of warfarin drug interactions: use of a combined pharmacokinetic-pharmacodynamic model.

OBJECTIVE: To apply a combined pharmacokinetic-pharmacodynamic model to data from warfarin drug interaction studies. METHODS: The pharmacokinetic model for warfarin enantiomers combined a common first-order absorption process with individual clearance and volume of distribution values and is based on unbound drug. The complete pharmacodynamic model comprised two components: that involving inhibition of prothrombin complex activity (PCA) synthesis described by a sigmoid maximum effect (Emax) model and that relating temporal changes in PCA to synthesis and degradation. The combined model was applied to prothrombin time and plasma concentration-time data obtained after oral administration of single doses of racemic warfarin to healthy subjects either alone or during multiple dosing with the metabolic enzyme inhibitor phenylbutazone or the inducer secobarbital. RESULTS: The five parameters associated with the complete pharmacodynamic model were kd (0.054 +/- 0.014 hr-1), the degradation rate constant of PCA; Cu50,S (0.0026 +/- 0.0015 mg.L-1) and Cu50,R (3.45 +/- 4.20 mg.L-1), the unbound concentrations of (S)- and (R)-warfarin required to produce a 50% reduction in PCA synthesis if administered individually; gamma (0.90 +/- 0.23), the slope parameter in the sigmoid Emax model; and td (8.2 +/- 0.3 hours), the observed delay in the onset of warfarin anticoagulant response. CONCLUSIONS: These findings qualitatively confirm the known potency difference between warfarin enantiomers. Furthermore, although phenylbutazone and secobarbital altered the pharmacokinetics of warfarin, these compounds do not appear to influence its pharmacodynamics. Simulation studies indicate that, after racemate administration, the continual presence of the more potent (S)-enantiomer precludes accurate assessment of Cu50,R. Analysis indicates that use of racemic (rather than enantiomer) warfarin concentration data in drug interaction studies may lead to misinterpretation of pharmacodynamic data.

Blood Coagulation↗
PubMed1994

Association between calcium regulatory hormones and other factors and bone mineral density in elderly Chinese men and women.

BACKGROUND: The purpose of the study was to determine if bone mineral density (BMD) in elderly Chinese subjects was associated with indices of calcium metabolism (parathyroid hormone, vitamin D), osteocalcin, and other nonbiochemical factors. METHOD: 104 men (mean age 74 +/- 6 yrs) and 213 women (mean age 76 +/- 8 yrs) with no previous history of fractures were recruited from old age hostels and community centers. BMD was measured with dual energy X-ray absorptiometry. RESULTS: BMD in both sexes was associated with body mass index (BMI), arm circumference, and skinfold thicknesses. Additionally, in women there was a positive association with grip strength and load-bearing activities, a negative association with age in all sites except for the lumbar spine, and negative associations with indices of bone turnover (osteocalcin, urinary hydroxyproline/creatinine and calcium/creatinine ratios). After adjusting for BMI, women with hypertension or taking antihypertensive drugs had higher mean BMD at the lumbar spine. Multivariate analyses showed that only BMI predicted BMD in men, while age, BMI, and arm circumference were predictors of BMD in women. CONCLUSION: Indices of calcium metabolism were not correlated with BMD in this elderly Chinese population, suggesting that the age-related rise in parathyroid hormone and reduced intestinal absorption of calcium may not be important factors in determining BMD in elderly Chinese men and women.

25-Hydroxyvitamin D 2↗
PubMed1994

Disposition of warfarin enantiomers and metabolites in patients during multiple dosing with rac-warfarin.

1. The disposition of warfarin enantiomers and metabolites has been studied in 36 patients receiving chronic rac-warfarin therapy, titrated to approximately the same anticoagulant response. 2. A stereoselective h.p.l.c. assay was employed to determine the concentrations of (R)- and (S)-warfarin, (R,S)-warfarin alcohol and (S)-7-hydroxywarfarin in plasma and 24 h urine samples. The concentrations of (R)-7-hydroxywarfarin, (S,S)-warfarin alcohol and (R)-6- and (S)-6-hydroxywarfarin were also determined in urine samples. The fractions unbound of warfarin enantiomers were determined using equilibrium dialysis. 3. Wide variability was observed in daily dose requirements (mean 6.1 mg; range: 2.5-12 mg), in plasma concentrations of (S)-warfarin (0.48 mg l(-1); 0.11-1.02 mg l(-1)), (R)-warfarin (0.87 mg l(-1); 0.29-1.82 mg l(-1)), (R,S)-warfarin alcohol (0.31 mg l(-1); 0.02-0.72 mg l(-1)) and (S)-7-hydroxywarfarin (0.25 mg l(-1); 0.07-0.37 mg l(-1)) and the percentage unbound of (S)-warfarin (0.53%; 0.29%-0.82%) and (R)-warfarin (0.54%; 0.26%-0.96%). 4. The mean plasma clearances of warfarin enantiomers were 7.5 1 day-1 per 70 kg (2.5-22.1) for (S)-warfarin and 3.6 1 day-1 per 70 kg (1.6-8.8) for (R)-warfarin. There was a significant correlation between the estimated formation clearance of (S)-7-hydroxywarfarin and the clearance of (S)-warfarin, which accounted for much of the variability in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Spirometric impairments in long-term insulators. Relationships to duration of exposure, smoking, and radiographic abnormalities.

A study of 2,611 long-term asbestos insulators was well suited to provide information on (1) the prevalence of spirometric impairments in a large, well-defined population and (2) the effects of cigarette smoking, radiographic abnormalities, and duration from onset of exposure on pulmonary function. Prevalences are reported by a mutually exclusive classification of impairments (normal, restrictive, obstructive, small airways, and combined) as well as by abnormality of specific spirometric tests (FVC, FEV1/FVC, and midexpiratory time). Only 3 percent of nonsmokers (NS) had obstruction and 6 percent a decreased FEV1/FVC. Frequency of restriction did not vary by smoking history; it was 31 percent in NS and current smokers (CS) and 34 percent in ex-smokers (XS). Obstruction (present in 17 percent) and combined impairment (in 18 percent) were most common in CS. The FEV1/FVC was decreased in 35 percent of CS and 18 percent of XS. The FVC was decreased in 49 percent of CS, 44 percent of XS, and 33 percent of NS. Normal spirometry was most common when the radiograph was normal (almost half the workers with normal radiographs had normal spirometry). Nevertheless, FVC was reduced in 27 percent of those with normal radiographs and a normal radiograph was seen in 11 percent of workers with restriction. Restrictive and combined impairments were most frequent when both parenchyma and pleura were abnormal. Restriction was more frequent in isolated pleural disease (seen in 34 percent such subjects) than in isolated parenchymal disease (22 percent). The contribution of pleural fibrosis to reduced FVC and of asbestos exposure and smoking both to reduced FVC and to reduced FEV1/FVC was confirmed by regression analysis. That reduced FVC and reduced FEV1/FVC are both more frequent in insulators who have smoked (compared with NS insulators or smokers in the general population) suggests an interaction between asbestos and smoking in producing both these physiologic abnormalities.

Asbestosis↗
PubMed1994

Insulin antibody responses after long-term intraperitoneal insulin administration via implantable programmable insulin delivery systems.

OBJECTIVE: To determine whether insulin antibodies are generated in diabetic patients after short- and long-term intraperitoneal insulin use and, if so, whether they are of potential clinical interest. Insulin antibodies commonly develop in diabetic patients who use subcutaneous human insulin, although their clinical significance remains controversial. Few data are available regarding insulin antibody responses to intraperitoneal insulin. RESEARCH DESIGN AND METHODS: We studied insulin antibody levels and clinical diabetes control in 25 type 1 diabetic patients treated for 3-6 years with intraperitoneal surfactant-stabilized porcine modified human insulin delivered by implantable programmable insulin delivery systems. RESULTS: All patients had preimplantation insulin antibody levels < 20 microU/ml, with a mean value of 2 +/- 2 microU/ml (1 SD). Mean antibody levels increased throughout the study period to a mean maximum of 197 +/- 326 microU/ml (P < 0.02) with 11 of 25 (44%) patients' levels exceeding 20 microU/ml (insulin responders). The mean time to significant antibody development was 21.8 +/- 4.4 months. Of the 11 responder patients, 4 had clinical syndromes that consisted of increasing daily insulin requirements and/or nocturnal hypoglycemia despite minimal nighttime basal insulin infusion rates associated with peak antibody levels > 200 microU/ml. None of the nonresponder patients (antibody levels < 20 microU/ml) had these clinical findings. CONCLUSIONS: Our results indicate that insulin antibody levels observed during intraperitoneal administration of human insulin are 1) similar to those reported during subcutaneous administration; although the rise in antibody level may be delayed compared with subcutaneous human insulin, 2) associated with a patient subset who are insulin antibody responders after switching from subcutaneous to intraperitoneal human insulin, 3) associated with a decrease in levels among responder patients regardless of whether they discontinue or continue pump use, and 4) associated with increased insulin needs and/or nocturnal hypoglycemia despite minimal basal rate insulin infusion at nighttime when antibody levels exceed 200 microU/ml.

Adult↗
PubMed1994

Kv3.3b: a novel Shaw type potassium channel expressed in terminally differentiated cerebellar Purkinje cells and deep cerebellar nuclei.

A two-step hybridization/subtraction procedure was employed to isolate markers for the later stages of Purkinje cell differentiation. From this screen, a novel Shaw potassium channel cDNA (Kv3.3b) was identified that is developmentally regulated. Expression of this channel is highly enriched in the brain, particularly in the cerebellum, where its expression is confined to Purkinje cells and deep cerebellar nuclei. Sequence analysis revealed that it is an alternatively spliced form of the mouse Kv3.3 gene, and that the previously reported Kv3.3 mRNA (Ghanshani et al., 1992) is not expressed in cerebellum. Expression of the Kv3.3b mRNA begins in cerebellar Purkinje cells between postnatal day 8 (P8) and P10 and continues through adulthood, coinciding with elaboration of the mature Purkinje cell dendritic arbor. The timing of expression of Kv3.3b mRNA is maintained in mixed, dissociated primary cerebellar cell culture. These results suggest that the Kv3.3b K+ channel function is restricted to terminally differentiated Purkinje cells, and that analysis of the mechanisms governing its expression in vivo and in vitro can reveal molecular mechanisms governing Purkinje cell differentiation.

Amino Acid Sequence↗
PubMed1993

Poor survival of black patients in carcinoma of the endometrium.

PURPOSE: To compare the prognostic factors and survivals of black and white patients with endometrial carcinoma. METHODS AND MATERIALS: A retrospective study was undertaken of a total of 290 patients with endometrial carcinoma who were treated similarly at the Health Science Center at Brooklyn and Kings County Hospital Center from 1975 and 1990. One hundred and thirty-six of 290 (47.2%) were black and 135/290 (46.9%) were white. Well-known prognostic factors affecting endometrial carcinoma were studied in black and white group of patients. Their overall survival and comparison of survival in each prognostic group were also estimated using multi-variate analysis. RESULTS: Fifty-four percent of white patients had Stage I disease, compared to 45.9% in black patients. In Stage II, 51.6% were white and 48.4% were black, and in Stage III, 88.89% were black and 11.1% were white patients (p = 0.034). Fifty six percent Grade 1 patients were white and 44% were black. In Grade 2, 53.3% were white and 46.7% were black and in Grade 3 disease, 70.5% were black and 29.5% were white (p = 0.008). Up to the inner third of myometrial invasion had occurred in 60.6% of white patients and 39.4% in black patients. The middle third of the myometrium was invaded in 60.7% of white patients, and 39.3% of black patients. Thirty-seven percent of outer third of myometrial invasion was found in white patients and 63% in black patients (p = 0.038). Seventy-two percent of positive lymph nodes were found in black patients and 28.0% in white patients (p = 0.01). Sixty-one percent of patients with positive peritoneal cytology were black as compared to 38.7% in white patients (p = 0.017). The overall ten-year corrected survival for white and black patients was 72% and 40%, respectively (p = 0.0003). Survivals comparisons, when stratified by race and each prognostic group, showed statistically significant overall survival differences in favor of white patients. CONCLUSION: Black patients with endometrial carcinoma have poor survival. Low socio-economic status (SES) would not explain these findings. More research is required to determine the cause of poor survival in black patients with endometrial carcinoma.

Adult↗
PubMed1993

Comparison of HLA class II genes in Caucasoid, Chinese, and Japanese patients with primary Sjögren's syndrome.

To better define the genetic factors that predispose to primary Sjögren's syndrome (SS), we have used polymerase chain reaction in combination with oligonucleotide probe hybridization and DNA sequencing to analyze HLA-DRB1, -DQA1, -DQB1, and -DPB1 alleles in Caucasoid (California), Japanese (Tokyo), and Chinese (Shanghai and Beijing) SS patients. In comparison to local controls in each region, we found: 1) increased frequency of the predicted haplotype HLA-DRB1*0301-DRB3*0101-DQA1*0501-DQB1*0201 in Caucasoid patients (p < 0.001); 2) increased frequency of the predicted haplotype HLA-DRB1*0405-DRB4*0101-DQA1*0301-DQB1*0401 in Japanese patients (p < 0.05); 3) increased frequency of the predicted haplotype DRB1*0803-DQA1*0103-DQB1*0601 in Chinese patients (p < 0.05); and 4) no statistically significant association with DPB1 alleles in any group, although an increased number of Caucasoid and Japanese SS patients possessed DPB1*0301. Comparison of DNA sequences for the three disease-associated haplotypes in these ethnic groups revealed a shared region of predicted amino acids from positions 58 to 69 in the first domain of HLA-DQB1. These results extend previous studies by demonstrating that no single class II allele was associated with 1 degree SS in the different ethnic groups. However, a shared amino acid motif in the DQB1 first domain was present in each disease-associated haplotype.

Alleles↗
PubMed1993

Warfarin metabolites: stereochemical aspects of protein binding and displacement by phenylbutazone.

The in vitro human serum albumin binding characteristics of the enantiomers of the major metabolites of warfarin [6-hydroxywarfarin (6-HW), 7-hydroxywarfarin (7-HW), (S)-warfarin alcohols [(S,S)- and (S,R)-WA], and (R,S)-warfarin alcohol [(R,S)-WA]] have been studied, using a stereospecific HPLC assay. Warfarin metabolites are less bound both within plasma and a 40 g/liter solution of human serum albumin than the enantiomers of warfarin. The reduced warfarin metabolites have a lower fraction unbound [1.33% for (S,R)-WA, 2.09% for (S,S)-WA, and 1.04% for (R,S)-WA] than hydroxylated metabolites [3.24% for (R)-6-HW, 4.26% (S)-6-HW, 4.49% for (R)-7-HW and 4.27% for (S)-7-HW] to HSA. Phenylbutazone produced a concentration-dependent increase in the unbound fraction of all metabolites. It was possible to predict the unbound fraction of warfarin metabolites based on the unbound fraction of warfarin enantiomers.

Humans↗
PubMed1993

Quantitative phenotypic and functional analyses of islet immune cells before and after diabetes onset in the BB rat.

Inflammatory cells invading islets are thought to be mediators of islet destruction in spontaneous autoimmune diabetes mellitus. Thus methods were developed to isolate and characterize in situ islet inflammatory cells from 75-95-day-old prediabetic and diabetic BB rats. Islet inflammatory cells were structurally examined using single- and double-colour flow cytometry. Functional studies consisted of cytolytic assays using normal rat islet target cells and in situ islet or spleen effector cells. Structural data reveal natural killer cells to be the major cell population (70%) of total immune cells present in inflamed islets during prediabetes. At diabetes onset, the natural killer cell population remained at a high level (47%), but an increasing population of T cells (40%) was noted also. Analyses of T-cell subsets before and after diabetes onset revealed CD4+ T cells as predominant (50-55% of total T cells) with double-negative (CD4-CD8-) T cells (25-30%) and CD8+ T cells (15-20%) also present in significant quantities. Activated T cells accounted only for a minority of T cells (< 3%). Functional studies indicate that in situ islet-derived cytolytic effector cells are more potent killers (ten-fold) of normal islet target cells than are splenic effector cells. These data suggest that in situ islet inflammatory cells (a) can be quantitatively studied both structurally and functionally; (b) express structural phenotypes differing substantially from splenic mononuclear cell populations; (c) are considerably more cytolytic than splenic effectors; and (d) should prove informative in determining the most significant autoimmune functional events prior to and during islet beta-cell destruction.

Animals↗