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Biomedical subjects

J C Chan

Publications and source records attributed to J C Chan.

At least 199 records · Page 11Linked to original sources

Impact of uraemia on food efficiency and the pulsatile mode of growth hormone secretion in rats.

In view of the profound growth failure resulting from renal insufficiency and uraemia, the present studies were designed to specifically investigate food efficiency and the pattern of GH secretion under these conditions. Animals were made uraemic by 5/6 nephrectomy (Nx) and feeding a high-protein diet. Three groups of animals were studied: uraemic (Ur); sham-operated, fed ad libitum (Sh); and sham-operated pair-fed with the uraemics (PF). Food intake per 100 g body weight and food efficiency (g weight gained per g food consumed) were calculated. Fourteen days after 5/6 Nx, blood samples were taken via intra-atrial catheters at 10-min intervals over a period of 6 h. GH was measured in plasma by radioimmunoassay. GH pulsatility was analysed by multiple parameter deconvolution. The growth rate of Ur animals was significantly lower than that of Sh. The body weights of the Ur animals were also lower than PF due to an initial period of weight loss. Both Sh and PF animals showed the typical negative slope of food intake as body weight increased. In contrast, the Ur animals showed a positive slope of food intake. The lower rate of growth and the elevated food intake corresponded to a decreased food efficiency for the Ur group. Deconvolution analysis of pulsatile GH release demonstrated a significant increase in GH half-life in the Ur animals. The amplitude and mass of GH secretory pulses were decreased, whereas the number of detectable secretory bursts was increased. These changes were specific to uraemia with respect to half-life and number of pulses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗

The relationship between calcium, phosphorus, and sodium intake, race, and blood pressure in children with renal insufficiency: a report of the Growth Failure in Children with Renal Diseases (GFRD) Study.

Nutritional data compiled during the Growth Failure in Children with Renal Diseases Clinical Trial were analyzed to determine the relationship between the dietary intake of divalent minerals and sodium, nutritional status, and serum calcium, phosphorus, and parathyroid hormone (PTH) concentrations and blood pressure in black versus white children. One hundred eighteen patients are included in this report; 25 were black (21%) and 93 were white (79%). Although more of the blacks were male, the age distribution, midarm circumference, midarm muscle circumference, blood pressure, and serum calcium, phosphorus, and PTH concentrations were comparable in the two groups. Phosphorus intake was within the recommended daily allowance in both groups; in contrast, calcium intake was inadequate in all patients: 81% of the recommended daily allowance in whites, and 74% in blacks. Sixteen children were noted to be hypertensive during the observation period; six patients were receiving a variety of antihypertensive medications, including diuretics in two children. Linear regression analysis revealed that systolic and diastolic blood pressures were directly related to calcium and phosphorus intake in black patients. In white children, only dietary phosphorus intake and diastolic blood pressure were directly related. There was no relationship between sodium intake or GFR and blood pressure in the white or black children. PTH levels were directly correlated with systolic and diastolic blood pressure in all children. The correlations between PTH and blood pressure were stronger in white versus black patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Black People↗

Factors determining the blood pressure response to enalapril and nifedipine in hypertension associated with NIDDM.

OBJECTIVE: To examine the factors that determine the blood pressure response to enalapril and nifedipine monotherapy in the treatment of hypertension associated with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: After a 6-week placebo baseline period, 102 hypertensive NIDDM patients were randomly assigned, double-blindly, to treatment with nifedipine retard (slow release) (n = 52) or enalapril (n = 50). The daily dosage of enalapril was increased, if required, from 10 to 20 to 40 mg and that of nifedipine from 40 to 60 to 80 mg at 4-week intervals during the 12-week titration period. Blood pressure, 24-h urinary albumin excretion (UAE), biochemical data, and serum angiotensin-converting enzyme (ACE) activity were measured at weeks -6, -4, 0, 4, 8, and 12. At week 0, venous blood was also sampled for baseline plasma atrial natriuretic peptide, renin, aldosterone, and serum insulin concentrations. RESULTS: At week 12, the mean daily dose of enalapril was 35 +/- 11.4 mg, and 27 (57%) patients were receiving the maximum daily dose of 40 mg. In the nifedipine group, the mean daily drug dose was 50 +/- 12.9 mg, and 4 (8%) were receiving the maximum daily dose of 80 mg. Despite a dose-dependent fall in the serum ACE activity in the enalapril group, the mean arterial pressure (MAP) was reduced by only 8 mmHg throughout the 12-week titration period compared to a decline of 15, 18, and 19 mmHg at weeks 0, 4, and 12, respectively, in the nifedipine group (P = 0.01 between groups). In the enalapril group, changes in MAP between weeks 0 and 12 correlated significantly with baseline plasma glucose (r = 0.45, P = 0.001) and aldosterone concentrations (r = -0.32, P = 0.02) and UAE (r = 0.3, P = 0.04). There was no statistically significant correlation between the changes in MAP and baseline plasma renin concentration. On multivariate analysis, the baseline renal function, glycemic control, and plasma aldosterone and serum insulin concentrations were all independently related to the changes in blood pressure in the enalapril-treated patients. No such statistical associations were observed in the nifedipine group. CONCLUSIONS: In hypertensive NIDDM patients, the activity of the renin-angiotensin-aldosterone system, the level of serum insulin, glycemic control, renal function, and proteinuria may be important determinants of the blood pressure response to ACE inhibition. Good glycemic control may optimize the antihypertensive efficacy of concomitant ACE inhibitor therapy.

Albuminuria↗

Abnormal albuminuria as a predictor of mortality and renal impairment in Chinese patients with NIDDM.

OBJECTIVE: Microalbuminuria predicts mortality in non-insulin-dependent diabetes mellitus (NIDDM), but its association with deterioration of renal function remains more controversial than in insulin-dependent diabetes mellitus (IDDM). Using albumin-to-creatinine ratios (ACRs) in random spot urine samples is a convenient method for evaluating albuminuria. We studied prospectively the predictive values of albuminuria in NIDDM when assessed by this urine measurement. RESEARCH DESIGN AND METHODS: Between 1991 and 1992, we restudied the clinical and biochemical status of 403 Chinese NIDDM patients recruited in 1989 after a follow-up period of 26.6 +/- 3.2 months (mean +/- SD). Spot urine ACR was measured on two occasions and microalbuminuria was defined as a mean ACR between 5.6 and 38 mg/mmol. RESULTS: From the original cohort, 29 patients had died mostly because of cardiovascular events with or without renal failure. The overall relative risk of death in patients with abnormal albuminuria was 7.1 (P < 0.001) (microalbuminuria: 3.7, P = 0.04; macroalbuminuria: 11, P < 0.001). On multivariate analysis, the independent predictive factors for mortality were plasma creatinine (wald = 12.1, P < 0.001) and glucose concentrations (wald = 10.4, P < 0.001) in the normo- and microalbuminuric patients (n = 11) and age (wald = 4.4, P = 0.03) and plasma creatinine (wald = 8.2, P < 0.01) in the macroalbuminuric group (n = 18). In the survivors (n = 374), baseline spot urine ACR was independently associated with 2-year spot urine ACR in the normo- (P < 0.001), micro- (P < 0.01), and macroalbuminuric groups (P = 0.01). In addition, baseline spot urine ACR was independently related to 2-year plasma creatinine (P = 0.01) in the macroalbuminuric group. The rates of change of the reciprocal of plasma creatinine ( delta [Cr]-1) were -27.3 +/- 62.5, -43.4 +/- 68.6, and -108.8 +/- 98.81.mumol01.month-1 in the normo-, micro-, and macroalbuminuric groups, respectively (P < 0.001). The delta [Cr]-1 was independently and inversely related to the baseline spot urine ACR (P < 0.001) and 2-year systolic blood pressure (P < 0.001). CONCLUSIONS: Abnormal albuminuria as indicated by a random spot urine ACR > 5.6 mg/mmol predicts increased mortality and is associated with the progression of albuminuria and deterioration of renal function in Chinese NIDDM patients.

Aged↗

Acute tubular necrosis following endosulphan insecticide poisoning.

Endosulphan is a chlorinated hydrocarbon insecticide with potential toxicity for the respiratory and central nervous systems. Renal toxicity has been rarely reported. We describe a man who developed renal failure due to acute tubular necrosis following a suicidal attempt with endosulphan in the absence of significant hypotension or sepsis.

Aged↗

The knowledge and attitude of Hong Kong secondary school teachers and students towards HIV infection and dentistry.

Although human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) are firmly entrenched in Hong Kong no data are available on the knowledge and attitudes of Hong Kong secondary school teachers and teenage children towards this infection, and their perception of infection control measures currently undertaken by the dental profession to prevent such infectious diseases. Hence a postal questionnaire survey of a total of 2,886 teenagers and 372 school teachers of 21 secondary schools in Hong Kong was conducted. The questionnaire comprised a total of 13 questions divided into two categories; the first, aimed at assessing the respondents' general knowledge and attitudes towards AIDS, and the second related to AIDS, dentistry and infection control. More than half of the students and one quarter of the teachers surmised that HIV infection is equivalent to developing AIDS. Although the great majority of the respondents (85-97 per cent) were aware that HIV can not be transmitted through sharing combs and meals, one in two teachers and one in three students thought that the virus could be transmitted through saliva. A large majority of respondents believed television to be the most, and dentists the least, informative source on AIDS out of a list of eight options. Approximately one half of both groups were concerned about contracting HIV infection during dental treatment and 65 per cent of students and 57 per cent of teachers thought that dentists did not have sufficient knowledge to identify AIDS patients. Finally, more than three quarters of the respondents thought that it would be ill-advised to visit a dentist treating HIV-infected patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Evenoming by Bungarus multicinctus (many-banded krait) in Hong Kong.

We describe the clinical course of two cases of envenoming by the many-banded krait (Bungarus multicinctus). A man developed generalized paralysis and respiratory failure with transient hypertension. Nerve conduction studies revealed normal motor and sensory conduction velocities with reduced motor unit action potential amplitudes consistent with neuromuscular blockade. He showed a slight transient response to the banded krait (B. fasciatus) antivenom but required ventilatory support for 8 days. After the fourth day, there was some response to treatment with anticholinesterase. Another man developed diplopia, dysphagia and leg weakness but recovered spontaneously after 48 hours.

Adult↗

Randomised, double-blind, parallel study of the anti-hypertensive efficacy and safety of losartan potassium compared with felodipine ER in elderly patients with mild to moderate hypertension.

This study investigated the anti-hypertensive efficacy and tolerability of once-daily losartan potassium (50 mg titrated to 100 mg), an angiotensin II receptor antagonist, compared with once daily felodipine extended release (ER) (5 mg titrated to 10 mg), a calcium channel blocker, after 12 weeks of therapy in elderly hypertensive patients. Following a 4-week, single-blind, placebo baseline period, qualifying patients were randomly allocated to 12 weeks of double-blind treatment with losartan potassium or felodipine ER. After 6 weeks, patients with a 24 h post-dose sitting diastolic blood pressure > or = 90 mm Hg had their dose doubled for the remaining 6 weeks. At 6 weeks, there was a greater BP response for felodipine ER than losartan potassium in elderly patients with mild to moderate hypertension. However, after 12 weeks of therapy, losartan potassium reduced BP as effectively as felodipine ER with no differences in mean BP reduction or anti-hypertensive response category between treatment groups. In this study, both treatments were well tolerated; felodipine ER was associated with a numerically higher incidence of headache and oedema while the incidence of asthenia was numerically higher in losartan-treated patients.

Aged↗

Comparative tumor localization of whole immunoglobulin G anticarcinoembryonic antigen monoclonal antibodies IMMU-4 and IMMU-4 F(ab')2 in colorectal cancer patients.

BACKGROUND: Previous studies in the literature have suggested that radiolabeled F(ab')2 fragments might be superior to whole immunoglobulin G (IgG) for imaging and therapy of cancer because of their greater penetration in tumors. To test this hypothesis, the authors compared tumor and normal tissue uptake along with plasma clearance of 125I-labeled monoclonal antibody (MoAb) IMMU-4 whole IgG with its 131I-labeled F(ab')2 fragment. METHODS: Five patients with either liver metastases from colorectal cancer (n = 4) or intact primary tumors (n = 1) received a combination of 125I-IMMU-4 IgG (2 mCi/1 mg) plus 131I-IMMU-4 F(ab')2 (10 mCi/1 mg) as a single 1-hour intravenous infusion on day 1. Serial blood samples were taken for up to 72 hours postinfusion to determine plasma clearance of each MoAb. On days 3-9, patients underwent exploratory laparotomy in which biopsies of tumor as well as normal tissues (liver, normal colon, lymph node, and blood) were obtained. Tissues were weighed and counted in a gamma counter, and the percent of injected dose per kilogram (%ID/kg) of each antibody, along with the radiolocalization index (RI), was computed (RI = %ID/kg tumor.%ID/kg normal tissue). RESULTS: Tumor uptake of both antibodies (2.3 +/- 0.53 %ID/kg) was significantly higher than that of normal tissues (0.56 +/- 0.12; P < 0.001), except for blood (2.8 +/- 0.83), resulting in an RI > or = 3. There were no significant differences in uptake (%ID/g) between F(ab')2 and IgG (F[ab']2 = 2.0 +/- 0.57; IgG = 2.6 +/- 0.94). The mean +/- SD of plasma T1/2 was slightly shorter for F(ab')2 (28.8 +/- 7.2 hours) than for IgG (45.9 +/- 16.7; P = 0.08). CONCLUSION: In short, the biodistribution and pharmacokinetics of IMMU-4 F(ab')2 were comparable to those of IMMU-4-IgG.

Animals↗

Carcinoembryonic antigen in human colonic aberrant crypt foci.

BACKGROUND/AIMS: Aberrant crypt foci are putative preneoplastic lesions that, by definition, are identified microscopically in whole-mount preparations of colonic mucosa. Because the identification of hexosaminidase as a marker for rat aberrant crypt foci in histological sections facilitated their characterization, a similar marker for human foci in histological sections was sought. METHODS: Human aberrant crypt foci were marked in whole-mount preparations, embedded in paraffin, and evaluated for their expression of carcinoembryonic antigen with two monoclonal antibodies. RESULTS: Elevated expression of carcinoembryonic antigen was detected in 39 of 42 (93%) aberrant crypt foci from 15 patients. The expression of carcinoembryonic antigen assisted in the evaluation of longitudinal sections of foci, where dysplasia is more readily detected in these small lesions. The expression of carcinoembryonic antigen was related to the sizes of the foci (P = 0.0085, generalized Fisher's Exact Test) but not to the presence or degree of dysplasia. CONCLUSIONS: The overexpression of immunohistochemically demonstrable carcinoembryonic antigen is, to date, the only described alteration in most of these putative precursors of human colon cancer that differs from the expression in contiguous, normal crypts at the histological level and thus facilitates the identification of aberrant crypts in histological sections for further characterization.

Adult↗

Simulation of free-field sound sources and its application to studies of cortical mechanisms of sound localization in the cat.

We synthesized a set of signals (clicks) for earphone delivery whose waveforms and amplitude spectra, measured at the eardrum, mimic those of sounds arriving from a free-field source. The complete stimulus set represents 1816 sound-source directions, which together surround the head to form a 'virtual acoustic space' for the cat. Virtual-space stimuli were delivered via calibrated earphones sealed into the external meatus in cats under barbiturate anesthesia. Neurons recorded in AI cortex exhibited sensitivity to the direction of sound in virtual acoustic space. The aggregation of effective sound directions formed a virtual space receptive field (VSRF). At 20 dB above minimal threshold, VSRFs fell into one of several categories based on spatial dimension and location. Most VSRFs were confined to either the contralateral (59%) or ipsilateral (10%) sound hemifield. Seven percent spanned the frontal quadrants and 16% were omnidirectional. Eight percent fit into no clear category and were termed 'complex'. The size, shape, and location of VSRFs remained stable over many hours of recording. The results are in essential agreement with free-field studies. VSRFs were found to be shaped by excitatory and inhibitory interactions of activity arriving from the two ears. Some cortical neurons were found to preserve the spectral information in the free-field sound which was generated by the acoustical properties of the head and pinna, filtered by the cochlea and transmitted by auditory nerve fibers.

Acoustic Stimulation↗

A prospective, double-blind study of growth failure in children with chronic renal insufficiency and the effectiveness of treatment with calcitriol versus dihydrotachysterol. The Growth Failure in Children with Renal Diseases Investigators.

Because controlled trials in adults have shown accelerated deterioration of renal function in a small number of patients receiving calcitriol for renal osteodystrophy, we initiated a prospective, randomized, double-blind study of the use of calcitriol versus dihydrotachysterol in children with chronic renal insufficiency. We studied children aged 1 1/2 through 10 years, with a calculated glomerular filtration rate between 20 and 75 ml/min per 1.73 m2, and with elevated serum parathyroid hormone concentrations. Ninety-four patients completed a mean of 8.0 months of control observations and were randomly assigned to a treatment period; 82 completed the treatment period of at least 6 months while receiving a calcitriol dosage (mean +/- SD) of 17.1 +/- 5.9 ng/kg per day or a dihydrotachysterol dosage of 13.8 +/- 3.3 micrograms/kg per day. With treatment the height z scores for both calcitriol- and dihydrotachysterol-treated groups showed no differences between the two groups. In relation to cumulative dose, there was a significant decrease in glomerular filtration rate for both calcitriol and dihydrotachysterol; for calcitriol the rate of decline was significantly steeper (p = 0.0026). The treatment groups did not differ significantly with respect to the incidence of hypercalcemia (serum calcium concentration > 2.7 mmol/L (> 11 mg/dl)). We conclude that careful follow-up of renal function is mandatory during the use of either calcitriol or dihydrotachysterol because both agents were associated with significant declines in renal function. There was no significant difference between calcitriol and dihydrotachysterol in promoting linear growth or causing hypercalcemia in children with chronic renal insufficiency. Dihydrotachysterol, the less costly agent, can be used with equal efficacy.

Calcitriol↗

Post-transcriptional regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol 7 alpha-hydroxylase in rats with subtotal nephrectomy.

Chronic renal failure is associated with hyperlipidemia and atherosclerosis. The mechanism responsible for the observed increase of serum cholesterol in chronic renal disease is not certain. The objective of the present study was to characterize the effect of induced renal failure on 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) and cholesterol 7 alpha-hydroxylase, the two rate determining enzymes of the cholesterol and bile acid biosynthetic pathways, respectively. Studies were carried out in rats with subtotal (75%) nephrectomy, which resulted in a marked elevation of blood urea nitrogen (371 +/- 44% of control, P < 0.001), and was accompanied by significant increases in the levels of serum cholesterol (133 +/- 7%, P < 0.005) and triglycerides (185 +/- 25, P < 0.01). In nephrectomized rats, an increase in the specific activity of HMG-CoA reductase (219 +/- 30% above control levels, P < 0.02) was observed. This increase occurred in the presence of elevated hepatic microsomal cholesterol concentrations (150 +/- 13% of controls, P < 0.01). Surprisingly, the increase in HMG-CoA reductase specific activity was not associated with parallel increases in HMG-CoA reductase steady-state mRNA levels and gene transcriptional activity. These uremic rats also exhibited a marked increase in the specific activity of cholesterol 7 alpha-hydroxylase (240 +/- 559% of controls, P < 0.05). There was no concomitant increase in cholesterol 7 alpha-hydroxylase steady-state mRNA levels or gene transcriptional activity. The factors responsible for the observed increases in HMG-CoA reductase and cholesterol 7 alpha-hydroxylase specific activity in renal failure remain to be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Piperacillin/tazobactam compared with ticarcillin/clavulanate in community-acquired bacterial lower respiratory tract infection.

The efficacy and safety of a new combination parenteral antibiotic, piperacillin/tazobactam, was compared with that of parenteral ticarcillin/clavulanate in the treatment of adult patients with community-acquired lower respiratory tract infections. A total of 299 patients were enrolled in this multicentre, double-blind, comparative study; 177 received piperacillin/tazobactam and 122 received ticarcillin/clavulanate. Of these, 119 met the evaluability criteria (69, piperacillin/tazobactam and 50, ticarcillin/clavulanate). The study drugs (piperacillin/tazobactam 3 g/375 mg or ticarcillin/clavulanate 3 g/100 mg) were given every 6 h by slow iv infusion for a minimum of 5 days. The favourable clinical response (cured and improved) rates of evaluable patients were 84% and 64% at endpoint (P < 0.01) for piperacillin/tazobactam and ticarcillin/clavulanate, respectively. The favourable bacteriological response at the early follow-up (eradicated and presumed eradicated) were 91% and 67% for piperacillin/tazobactam and ticarcillin/clavulanate, respectively (P < 0.01). At endpoint, 84% and 64%, respectively (P = 0.02) had a favourable response. The most common adverse experiences involved the gastrointestinal tract and occurred in 31.6% of the piperacillin/tazobactam group compared with 20.5% in the ticarcillin/clavulanate group (P = 0.02). These events were mild and generally did not affect therapy. Piperacillin/tazobactam appears to be more effective than ticarcillin/clavulanate in this patient population and is generally well tolerated.

Adolescent↗