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Biomedical subjects

I J Lauder

Publications and source records attributed to I J Lauder.

At least 37 records · Page 2Linked to original sources

Changes in hepatic portal resistance and in liver morphology during regeneration: in vitro study in rats.

OBJECTIVE: To study the effects of liver regeneration on hepatic portal resistance and on the morphology of liver sinusoids. DESIGN: Experimental in vitro study. SETTING: University laboratory, Hong Kong. ANIMALS: 10 Groups of 6 male Sprague Dawley rats each. INTERVENTIONS: Two thirds hepatectomy, with subsequent re-hepatectomy for measurements 0, 1, 3, 7, 21 and 56 days later. Perfusion of isolated livers and histomorphometry. MAIN OUTCOME MEASURES: Hepatic portal resistance and measurement of width and length of sinusoids. RESULTS: Liver weight was restored within 7 days of hepatectomy. Hepatic portal resistance/g of liver increased, reaching a maximum at 3 and 7 days of hepatectomy, and subsequently returned to initial values after 56 days. Width of sinusoids decreased to a minimum within 3 to 7 days of hepatectomy, and subsequently returned close to initial values within 56 days of hepatectomy. The changes in hepatic portal resistance occurred in phase with the changes in the width of liver sinusoids. CONCLUSIONS: There is a transient increase in hepatic portal resistance/g of liver during regeneration; transient narrowing of sinusoids may contribute to this change.

Animals↗

Kernel density analysis of variable and conserved regions of the envelope proteins of human immunodeficiency virus type 1 and associated epitopes.

A new statistical approach to the study of conservation of amino acid and nucleotide sequences based on kernel density analysis is described that enables analysis of both conserved and highly variable HIV-1 protein sequences. The amino acid sequences of HIV-1 env proteins in 63 isolates were analysed to determine, first, whether the designations of regions identified in 1987 as conserved (C1-C6) or variable (V1-V5) were still valid. Even though the data base used was nine times larger, the designations that were based on seven isolates from five patients remain correct. Second, the new approach enabled the quantifications of the degree of conservation in reported B or T cell epitopes. Using this approach, highly conserved epitopes located in both gp41 and gp120 were identified.

Amino Acid Sequence↗

Apolipoprotein (a) levels and phenotypes in NIDDM patients with microalbuminuria and albuminuria.

This study was conducted to determine whether circulating levels of lipoprotein (a), an independent risk factor of macrovascular disease, are increased in non-insulin-dependent diabetes mellitus (NIDDM) patients with microalbuminuria who have an increased risk of cardiovascular mortality. Apolipoprotein (a) [apo(a)] levels and phenotypes, and other circulating lipid levels were determined in 227 Chinese NIDDM patients with varying stages of diabetic nephropathy. None was on lipid-lowering therapy. Apo(a) levels in normoalbuminuric (geometric mean 166 U/L; 95% confidence intervals 137, 200; n = 105) and microalbuminuric patients (162; 132, 209; n = 77) were similar to values in controls (166; 143, 193, n = 168). Albuminuric patients, however, had higher apo(a) levels than both normoalbuminuric patients and controls (242; 184, 317; n = 45; P < 0.05). The overall size range of the apo(a) phenotypes and the frequency of having at least one small isoform, i.e. < 700 kDa, were similar among the four groups of subjects. A positive correlation was found between log apo(a) and log plasma creatinine levels (P < 0.01). Compared to normoalbuminuric patients, both microalbuminuric and albuminuric patients were older (P < 0.01) and had higher HbA1c (P < 0.01), greater BMI (P < 0.05) and longer disease duration (P < 0.05) compared to normoalbuminuric patients. Nevertheless, using multiple linear regression analysis, it was found that the presence of nephropathy conferred an independent influence on increasing total cholesterol (P < 0.001), triglyceride (P < 0.001) and apoB (P < 0.01), and decreasing HDL cholesterol (P < 0.05) levels even when only the normoalbuminuric and microalbuminuric groups were analysed. The prevalence of macrovascular disease was significantly increased in microalbuminuric and albuminuric patients (45.1 and 48.7% respectively vs 20.2% in normoalbuminuric patients, P < 0.01). It is concluded that circulating apo(a) levels were not increased in Chinese NIDDM patients with microalbuminuria. However, atherogenic changes in other lipid and lipoprotein levels may contribute to an increased risk of macrovascular disease in these patients.

Adult↗

Hospital antibiotic prescribing successfully modified by 'immediate concurrent feedback'.

1. To determine the effectiveness of ongoing immediate concurrent feedback (ICF) in minimizing 'inappropriate' sultamicillin or co-amoxiclav prescribing via the parenteral route (i.e. when the oral route was accessible and not contraindicated), a prospective controlled audit was carried out on hospital inpatients over a 20 month period. 2. After an education programme to promote oral rather than unnecessary intravenous (i.v.) use of sultamicillin, co-amoxiclav and certain other drugs, an ongoing ICF strategy was instituted. 3. ICF entailed issue of memos on the following day to prescribers of i.v. sultamicillin or co-amoxiclav for inpatients in whom this route was deemed 'inappropriate', by a specially trained nurse using strict objective criteria. The memos recommended oral prescribing (particularly of co-amoxiclav, currently the less expensive alternative). 4. After starting ICF, there were consistent, clinically and statistically significant reductions in the monthly proportions of (i) admissions prescribed i.v. sultamicillin or co-amoxiclav (38% P < 0.001), (ii) those in whom the route was 'inappropriate' (75%, P < 0.001), and (iii) corresponding ratios of i.v./oral usage and expenditure, oral sultamicillin/co-amoxiclav usage and expenditure, as well as total and per admission expenditure on i.v. forms (> or = 43%, P < 0.01). 5. For i.v. cefuroxime (for which there was no ICF) and its oral counterpart cefuroxime-axetil, there were no comparable changes in usage or expenditure. 6. This simple, ongoing ICF strategy was effective and well accepted; estimated net monthly savings being HK$26-30,000.

Anti-Bacterial Agents↗

Long-term survival after gastrectomy for advanced bleeding or perforated gastric carcinoma.

OBJECTIVE: To find out whether massive bleeding or free perforation of advanced gastric carcinoma affect long term survival after gastrectomy. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Teaching hospital, Hong Kong. INTERVENTIONS: Gastrectomy. MAIN OUTCOME MEASURES: Long term survival. RESULTS: Data of 50 patients with gastric carcinoma that had penetrated the serosa (pT3) and who were operated on between 1985 and 1990 were analysed. A total of 17 patients with tumour free perforation and 10 with massive bleeding underwent emergency gastrectomy, and 23 patients with comparable uncomplicated tumours had elective gastrectomy. Twelve variables that could have influenced survival including malignant perforation, bleeding, or the absence of complications were analysed using the Cox's proportional hazards model. Survival was influenced only by proliferative cell nuclear antigen (PCNA) index and not by perforation, bleeding, or the uncomplicated nature of the tumour. CONCLUSIONS: These findings suggest that perforation or bleeding from advanced gastric carcinomas do not significantly affect long term survival after gastrectomy.

Aged↗

Prognostic significance of serum tumour markers in carcinoma of the cervix.

PURPOSE: The purpose was to evaluate the prognostic significance of serum tumour markers and other potential prognostic factors in cervical cancer. MATERIALS AND METHODS: Five hundred and thirty-one patients with cervical cancer were studied. The pre-treatment levels of SCC (squamous cell carcinoma antigen), TPA (tissue polypeptide antigen), CEA (carcinoembryonic antigen), CA125 and hCG (human chorionic gonadotrophin) were assayed in these patients. Possible association between raised tumour markers and potential prognostic factors and their prognostic significance were sought by univariate and multivariate Cox analysis. RESULTS: SCC was raised in 65% of squamous cell carcinoma of the cervix and TPA was raised in 50%. Other markers were raised in less than 25%. No tumour markers were raised more than 30% in adenocarcinoma of the cervix. Raised SCC and TPA were related to advancing age, stage and grade of differentiation. Univariate analysis showed that age, stage, grade, raised SCC and TPA were significant prognostic factors on survival. Multivariate Cox analysis showed that stage was the most significant factor. CONCLUSION: Stage, age, grade of differentiation, raised pre-treatment levels of SCC and TPA were significant prognostic factors in cervical cancer using univariate analysis. However, only stage remains the most important independent prognostic factor in multivariate analysis. The prognostic value of these other factors in early stage disease needs further exploration.

Adenocarcinoma↗

Free perforation of gastric carcinoma. Results of surgical treatment.

OBJECTIVE: To define by actual standards the results of treatment of free perforation of gastric carcinoma in a consecutive number of patients treated at one institution. DESIGN: Case series of patients with perforated adenocarcinoma of the stomach treated in Hong Kong between 1984 and 1992. SETTING: Urban academic medical center. PATIENTS: Thirty-four Chinese patients who were operated on for perforated gastric carcinoma. A risk scoring system was used to predict postoperative mortality. Factors with a possible influence on postoperative mortality and long-term survival were studied using univariate and multivariate analysis. INTERVENTION: All patients underwent laparotomy, which was performed for closure of the perforation in four patients and for gastrectomy in 30. MAIN OUTCOME MEASURES: Thirty-day mortality and survival times. RESULTS: The 30-day mortality rate was 20%, and the median survival time was 10 months (range, 2 to 92 months). The risk score was the only significant predictor of 30-day mortality, and the pathologic TNM staging, of long-term survival. CONCLUSIONS: A significant proportion of patients can be saved and offered good palliation with emergency gastrectomy; those likely to die can be identified before surgery.

Adenocarcinoma↗

Molecular evolution of the hepatitis B virus genome.

The hepatitis B virus (HBV) has a circular DNA genome of about 3,200 base pairs. Economical use of the genome with overlapping reading frames may have led to severe constraints on nucleotide substitutions along the genome and to highly variable rates of substitution among nucleotide sites. Nucleotide sequences from 13 complete HBV genomes were compared to examine such variability of substitution rates among sites and to examine the phylogenetic relationships among the HBV variants. The maximum likelihood method was employed to fit models of DNA sequence evolution that can account for the complexity of the pattern of nucleotide substitution. Comparison of the models suggests that the rates of substitution are different in different genes and codon positions; for example, the third codon position changes at a rate over ten times higher than the second position. Furthermore, substantial variation of substitution rates was detected even after the effects of genes and codon positions were corrected; that is, rates are different at different sites of the same gene or at the same codon position. Such rates after the correction were also found to be positively correlated at adjacent sites, which indicated the existence of conserved and variable domains in the proteins encoded by the viral genome. A multiparameter model validates the earlier finding that the variation in nucleotide conservation is not random around the HBV genome. The test for the existence of a molecular clock suggests that substitution rates are more or less constant among lineages. The phylogenetic relationships among the viral variants were examined. Although the data do not seem to contain sufficient information to resolve the details of the phylogeny, it appears quite certain that the serotypes of the viral variants do not reflect their genetic relatedness.

Codon↗

A pill for every ill?

Many doctors believe that Chinese expect a pill for every ill but this has never been validated by research data. The aim of our study was to find out what Chinese really expect from medications when they are ill. We interviewed a random sample of the 1068 Chinese in Hong Kong by telephone with a structured questionnaire. Only 40% thought illnesses always needed drug treatment but 76% always expected a prescription from a consultation. Nearly 100% of their last consultations resulted in a prescription. Eighty-five per cent of the prescriptions consisted of three drugs or more. Seven per cent of them thought too many drugs were given. Less than half of the people finished all the medications last prescribed. Those who thought too many drugs were given were less likely to have finished them. Younger age and more education were associated with less likelihood of thinking illnesses always needed drug treatment, consulting doctors for their last illnesses and expecting a prescription for every consultation. We conclude that Chinese do not expect a pill for every ill but doctors prescribe in nearly 100% of the consultations. Doctors may have over-estimated Chinese patients' expectation for medications. They may even have created a high expectation for a prescription in every consultation through their own prescribing habit. More open discussion on the need and expectation for drugs between patients and doctors may help to make prescribing for Chinese patients more rational.

Adolescent↗

Single-strand conformation polymorphism study of human immunodeficiency virus type 1 RNA and DNA in plasma, peripheral blood mononuclear cells, and their virologic cultures.

Single-strand conformation polymorphism (SSCP) analysis was applied to human immunodeficiency virus type 1 (HIV-1) nucleic acids in plasma and peripheral blood mononuclear cells (PBMC) from 16 patients and to 15 PBMC cocultures and 6 plasma cultures prepared from the specimens. Two hypervariable regions were analyzed: in the gag gene and part of the V3 loop. Random paired matching of SSCP patterns between HIV-1 RNA and provirus DNA was tested, from plasma and PBMC from the same blood specimen, supernatant and PBMC from the same PBMC coculture, supernatant and PBMC from the same plasma culture, provirus DNA in cocultured PBMC and the PBMC inoculum, and HIV-1 RNA in a plasma culture supernatant and in the plasma inoculum. Paired matching was nonrandom for both regions in the first three situations and for gag in the fourth, with P < or = .01; matching was random for gag in the last situation. The HIV-1 env target region produced in culture diverged from that in the inoculum in 18 of 21 instances.

Base Sequence↗

Self-medication among Hong Kong Chinese.

A randomized telephone survey on the practice of self-medication in the preceding 2 weeks was carried out from October 1989 to April 1990 among Chinese living in Hong Kong. 1068 people were interviewed. Self-medication was a common and universal practice by Hong Kong Chinese with a prevalence of 32.5% in 2 weeks. Those who reported illness were significantly more likely than those who did not use self-medication (65 vs 18.2%) and to have used more than one item of medications (39 vs 20%). Chinese tonics were the most frequently used self-medications although they were the least known. Chinese medicines were used as often as Western medicines in the self-treatment of illnesses. People used self-medication mainly because they felt that they knew what to do. About 80% of the Western and Chinese medicines were perceived to be effective but only 49% of the tonics were reported so. Side effects were reported from all types of medications with an overall prevalence of 6.4%. There was a lack of knowledge of the possible side effects in over 96% of the self-medications which is an area for patient education. The popularity but the relative lack of knowledge of Chinese tonics call for more scientific research and better regulation on their sales.

Adolescent↗

Can the Dartmouth COOP/WONCA charts be used to assess the functional status of Chinese patients?

This is the first study on the use of the Dartmouth functional health assessment charts COOP/WONCA in the assessment of the functional status of Chinese patients. The Chinese are the world's largest ethnic group and make up more than one-fifth of the world's population. We have developed a Chinese translation of the Dartmouth COOP/WONCA charts that satisfies the two minimal and one intermediate criteria on translation of scales and instruments set by the European Research Group in Health Outcome (ERGHO). We tested the charts on 84 Chinese patients with previous strokes when they attended follow-up at the General Practice Unit of the University of Hong Kong from 1 August to 30 November 1992. We found that the Dartmouth COOP/WONCA charts in Chinese were easy to administer and were well accepted by our patients. All but one patient understood all the charts. There was good face validity in the results obtained by the charts. The consulting doctors found that the information detected by the charts was moderately useful in 64% of the patients and was very useful in 5% of the patients. Our translation can be applied to other Chinese in Hong Kong as well as other countries, because there is only one written Chinese language. It is hoped that our pilot study will stimulate further research to establish the reliability, validity and clinical application of the COOP/WONCA charts in Chinese.

Activities of Daily Living↗

Investigation of nimodipine pharmacokinetics in Chinese patients with acute subarachnoid haemorrhage.

Nimodipine pharmacokinetics was investigated in 12 Chinese patients with acute subarachnoid haemorrhage receiving an IV infusion of 1.6 or 2 mg/h (based on estimated body weight) for 10 days. Peripheral venous blood samples were collected for up to 4 days and plasma nimodipine was assayed by GC/ECD. The mean value was taken as the steady state concentration (Css) and Clearance (CL) (hourly dose/Css) was calculated. Eight survivors were given oral nimodipine (60 or 90 mg) every 6h (based on body weight), blood was sampled over 6 h and the plasma nimodipine level determined. The values for Css, CL and CL.kg-1 were 33.5 micrograms.l-1, 58 l.h-1 and 1.0 l.h-1 x kg-1 respectively; in survivors receiving the drug orally, bioavailability of the 30 mg tablet was 9%. In one very sick patient given crushed tablets by naso-gastric tube, the AUC was very low; in vitro studies indicated that adsorption of nimodipine by the tubing was unlikely to have been the cause. The pharmacokinetic findings in Chinese patients are comparable to previously reported values in Caucasians.

Acute Disease↗

The hepatitis C virus genome: a guide to its conserved sequences and candidate epitopes.

A comprehensive analysis of reported hepatitis C virus genomic sequences comprising 151 partial or complete nucleotide sequences and 159 partial or complete amino acid sequences revealed an irregular composition of conserved and variable regions. There were but eight conserved nucleotide sequences, none outside the 5' noncoding and structural regions. A search among conserved amino acid sequences revealed 14 candidate B-cell epitopes, which were chosen mainly on the basis of their hydrophilicity profiles. Twenty five candidate T-cell epitopes were selected according to the criteria of absolute conservation of amino acid sequence, together with characteristic sequence motifs, amphipathic helical structure, or both. Conserved peptide sequences, with the characteristics of both B- and T-cell epitopes, were identified in the nonstructural 5 (NS5) region of the genome.

Amino Acid Sequence↗

The variability of the hepatitis B virus genome: statistical analysis and biological implications.

A statistical analysis of the nucleotide sequence variability in 14 published hepatitis B virus (HBV) genomes was carried out using parametric and nonparametric methods. A parametric statistical model revealed that the different regions of the genome differed significantly in their variability. The conclusion was supported by a nonparametric kernel-density model of the HBV genome. Genes S, C, and P, region X, the precore region, and the pre-S2/pre-S1 regions were ranked in order of increasing variability. In many instances, conserved regions of the genome identified with sequences of known function in HBV biology. However, other characterized regions (such as pre-S) showed much variability despite the involvement of their encoded peptides in specific functions. Point mutations that may result in the formation of stop codons and amino acid changes may affect the clinical picture of HBV infection and may be reflected in atypical serological patterns.

Consensus Sequence↗

Multivariate analysis of factors affecting pulmonary function in bronchiectasis.

Impaired pulmonary function is of prognostic importance in bronchiectasis. To assess the factors affecting pulmonary function in bronchiectasis, we studied the clinical features, atopic status, bronchial responsiveness, systemic inflammatory indices, and sputum characteristics including volume, purulence, leucocyte count, neutrophil chemotactic activity, elastolytic activity (EA) and bacteriology in 82 Chinese patients. The majority of patients had impaired spirometry with airflow obstruction but normal carbon monoxide diffusing capacity. Multivariate analysis showed that factors significantly associated with worse lung function were: bronchial hyperresponsiveness, concomitant asthma, higher serum globulin, higher peripheral leucocyte count, lower serum albumin, greater sputum volume, diffuse disease and older age. When subjects with clinical asthma were excluded, similar factors were identified, and in addition, longer duration of disease, presence of eosinophils in sputum and higher sputum EA were significantly related to worse spirometry. Most of the identified factors reflect a state of inflammation. Thus the findings suggest that persistent inflammation plays an important role in the deterioration of lung function in bronchiectasis.

Bronchial Provocation Tests↗

Pattern of cerebral atherosclerosis in Hong Kong Chinese. Severity in intracranial and extracranial vessels.

BACKGROUND AND PURPOSE: The clinical pattern of stroke and the angiographic distribution of cerebral atherosclerosis in Chinese are different from those in Caucasians. Pathological data from autopsy studies are lacking. METHODS: The intracranial and extracranial arteries supplying the brains of 114 consecutive Chinese patients undergoing autopsy in a regional general hospital were examined by computer-assisted morphometric analysis under a microscope as well as by macroscopic grading for atherosclerotic narrowing. The severity was correlated with various atherosclerosis-related factors. RESULTS: Atherosclerosis of the intracranial cerebral vessels was more severe than that of the extracranial vessels. The distal branches of the intracranial vessels were also commonly involved. Hypertension and diabetes mellitus were identified as factors associated only with intracranial atherosclerosis (p < 0.001), whereas ischemic heart disease was associated with atherosclerosis in both the intracranial (p < 0.001) and extracranial (p = 0.012) vessels. Smoking was associated with narrowing of the extracranial vessels only (p = 0.0054). CONCLUSIONS: Compared with figures from Caucasian and Japanese populations, the extent of intracranial atherosclerosis is much more severe in Hong Kong Chinese, whereas atherosclerotic narrowing of the extracranial carotid artery is less severe in Hong Kong Chinese than in Caucasians.

Adolescent↗

Treatment of acute cortical infarct with intravenous glycerol. A double-blind, placebo-controlled randomized trial.

BACKGROUND AND PURPOSE: This clinical trial investigates the effectiveness of intravenous glycerol therapy in patients with acute cortical infarction in whom intracerebral hemorrhage was rigorously excluded. METHODS: Within 48 hours of symptoms from their first ischemic stroke, 113 hospital inpatients were randomized into the trial, provided that hemorrhage was excluded by computed tomography and informed consent was obtained. Patients were stratified into alert, semicoma, and coma groups using the Glasgow Coma Scale. Treatment was allocated according to a double-blind, randomized protocol; 56 patients received 500 mL of 10% glycerol in saline over 4 hours on 6 consecutive days, and 57 patients received corresponding placebo treatment with saline. Using a variety of objective scoring systems, patient follow-up was up to 6 months. RESULTS: Corresponding measures of outcome in the glycerol and placebo groups were similar. At 6 months, respective mortality rates were 17 of 56 and 16 of 57, and mean +/- SD improvements in scores were 9.98 +/- 14.40 vs 10.51 +/- 12.68 (long-term), 1.12 +/- 7.20 vs 1.57 +/- 6.30 (prognostic), -1.94 +/- 5.53 vs -2.06 +/- 5.34 (Glasgow Coma Scale), and 21.72 +/- 23.40 vs 11.94 +/- 18.10 (Barthel Index rating in survivors). Hemolysis (generally subclinical) was the only adverse effect. CONCLUSIONS: There was no clinically or statistically significant difference in outcome between the groups; a trend toward greater functional recovery among survivors was evident after treatment with glycerol.

Acute Disease↗