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Biomedical subjects

I J Lauder

Publications and source records attributed to I J Lauder.

At least 55 records · Page 3Linked to original sources

An audit of antiasthmatic drug inhalation technique and understanding.

Inhaled rather than oral antiasthmatic therapy is accepted as more advantageous but depends on patient technique and understanding. In 74 asthmatic outpatients, technique using metered-dose inhaler (MDI) was poor; in 56 patients inhaling beta-agonist, the mean peak expiratory flow rate (PEFR) increase was only 15 L/min (6%) greater than in 18 controls, p < 0.05, 95% confidence intervals 2-27 L/min or 2-11%. Tilting the head back and actuation "stopping" inspiration produced the least favorable PEFR responses; taken together, regression analysis yielded a statistically significant negative correlation with absolute or percentage PEFR change (R2 = 0.15; p < 0.02). Patients were unclear about which drugs to inhale as required or regularly. Among 19 patients reassessed inhaling beta-agonist, only 8 had baseline PEFR values within 10% of each other during both assessments. In the latter, the mean postinhalation PEFR increase was 36 L/min (or 13%) greater than the corresponding increase (or % change) at first assessment, p = 0.05 (0.08), 95% confidence intervals 0-73 L/min (-2 to 29%). Thus, MDI users should avoid tilting the head back, actuation stopping inhalation, and be more aware of prophylactic (steroid) versus symptomatic (beta-agonist) treatment.

Administration, Inhalation↗

A controlled trial of interferon with or without prednisone priming for chronic hepatitis B.

In a randomized, controlled trial of recombinant interferon alfa-2b with or without prednisone priming in Chinese adults with chronic hepatitis B virus infection, stratified randomization for pretreatment serum alanine aminotransferase levels was done. Partial or complete antiviral responses were achieved in 17 (21.5%) of 79 treated patients and 3 (8.3%) of 36 controls (P = 0.14). The response to interferon treatment was significantly better in those who had elevated pretreatment transaminase levels and comparable to that reported in white patients [15 (38.5%) of 39 patients compared with 2 (5%) of 40 who had normal pretreatment transaminase levels (P = 0.0005)]. The spontaneous seroconversion rate was also higher among the controls with elevated transaminase levels [3 (18.8%) of 16 compared with 0 of 20 with normal transaminase levels], but this difference was not statistically significant (P = 0.16). Among the interferon-treated patients, prednisone priming appeared to have a marginal benefit over treatment with interferon alone in patients with elevated transaminase levels (43% vs. 33%), but not in those with normal transaminase levels (0% vs. 9.5%). It was confirmed that Chinese patients with normal transaminase levels respond very poorly to interferon alfa therapy. However, the response was significantly better in patients with elevated transaminase levels.

Adult↗

Histologic changes in Chinese patients with chronic hepatitis B virus infection after interferon-alpha therapy.

To evaluate the histologic effects of interferon-alpha (IFN alpha) therapy on chronic hepatitis B virus (HBV) infection, a semiquantitative study using a modified Knodell's numeric histologic scoring system was performed on paired pre- and post-treatment liver biopsy specimens from 127 adult Chinese patients from two trials of IFN alpha therapy (IFN alpha, n = 86; control, n = 41). The effects of IFN alpha therapy on the hepatic expression of HBV antigens were also determined using immunohistochemical analysis. Serologic response with clearance of HBV e antigen (n = 18) was associated with reduction in lobular activity, periportal piecemeal necrosis, portal inflammation, and total histologic scores. Loss of HBV e antigen also was associated with a reduction in the amount of HBV core antigen in the hepatocytes. In contrast, there was an increase in hepatic expression of HBV surface antigen after IFN alpha therapy. Patients who lost HBV e antigen with IFN alpha therapy were characterized by more severe initial periportal piecemeal necrosis before treatment. These data indicate that (1) serologic response is associated with a reduction in hepatic HBV replication and an improvement in hepatic histology, and (2) patients with severe periportal piecemeal necrosis respond more favorably to IFN alpha therapy.

Antigens, Viral↗

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

BACKGROUND AND PURPOSE: Hitherto, treatment of acute cerebral hemorrhage with intravenous glycerol has not been evaluated in rigorous clinical studies with sufficient patient numbers. METHODS: We undertook a double-blind, stratified and randomized, placebo-controlled clinical trial. Only patients with a first stroke admitted to the hospital within 24 hours after onset of symptoms were recruited, provided computed tomography confirmed hemorrhage and informed consent was obtained. After stratification into alert, semicoma, and coma subgroups using the Glasgow Coma Scale, 107 patients received active treatment (500 ml of 10% glycerol in saline by intravenous infusion over 4 hours on 6 consecutive days) and 109 were given corresponding saline treatment. Using a variety of objective scoring systems, patients were followed up for up to 6 months. RESULTS: At follow-up, all measures of outcome in the treated and control groups were very similar. At 6 months, respective mortality rates were 37 of 107 and 33 of 109. Corresponding mean +/- SD improvements in Scandinavian Stroke Study Group scores were 8.35 +/- 16.9 versus 11.55 +/- 15.6 (long-term) and 0.64 +/- 7.3 versus 2.40 +/- 6.9 (prognostic), and improvements in the Barthel Index ratings were 10.72 +/- 24.7 versus 13.95 +/- 23.3, respectively. Glasgow Coma Scale score improvements in the survivors were 0.81 +/- 1.5 and 1.16 +/- 1.7 in the treated and control groups, respectively. Hemolysis (generally subclinical) was the only adverse effect of glycerol noted. CONCLUSIONS: In the absence of any clinically or statistically significant difference in outcome between the treated and control groups, this trial provides no justification for glycerol therapy following acute cerebral hemorrhage.

Acute Disease↗

Prediction of persistent carbohydrate intolerance in patients with gestational diabetes.

A 12-month prospective study was carried out in 120 Chinese patients with gestational diabetes who were found to have persistent carbohydrate intolerance at 6 weeks postpartum. The 75 g OGTT and WHO diagnostic criteria were employed for both antepartum and postpartum assessment. By 12 months, persistent carbohydrate intolerance was found in 13.3% of the patients only, 6 patients were diabetic while 10 had impaired glucose tolerance. Of those whose carbohydrate tolerance reverted to normal, 85% did so within the first 6 months. The clinical variables were analysed by multiple discriminant analysis using the logistic model. Five prognostic variables which were predictive of persistent carbohydrate intolerance at 12 months were identified. In order of decreasing predictive value, these included a high fasting glucose during pregnancy and at the first postnatal visit, a high antepartum 2 h blood glucose, the requirement of insulin during pregnancy, and a high postpartum 2 h blood glucose. Macrosomia, gestational age at diagnosis and a family history of diabetes were not predictive of persistent carbohydrate intolerance. Multiparity, maternal age and body mass index were of marginal significance only. The fitted logistic model provides a mechanism to estimate the probability of persistent carbohydrate intolerance. Such information will be helpful in patient counselling and in the efficient planning of postpartum medical follow-up.

Adult↗

Application of hepatitis B virus (HBV) DNA sequence polymorphisms to the study of HBV transmission.

Short sequences in hypervariable regions of the hepatitis B virus (HBV) genome can be used to identify different strains, providing a novel approach to the study of HBV transmission. The nucleotide sequence in positions 2551-2650 (1:EcoRI site) was determined for serum HBV DNA from 96 Chinese children living in Hong Kong and from 38 of their parents. HBV DNA was extracted and sequenced after amplification with the polymerase chain reaction, using as primers oligonucleotides corresponding to two conserved sequences. Among 82 unrelated children, 32 HBV DNA variants were present. One sequence was present in 33 children and 31 variants were found among the other 49. Siblings within each of nine families had the same variant; in three families siblings had different variants. Six of the eight fathers and 28 of the 30 mothers had HBV DNA sequences identical to those of their offspring. A total of 34 variants were found among the 134 individuals. The hypothesis of random assortment of sequences in parents and children was rejected (P less than .00005). Thus, this new approach proves the occurrence of intrafamilial transmission of HBV among Chinese.

Adult↗

Evidence for intrafamilial transmission of hepatitis B virus from sequence analysis of mutant HBV DNAs in two Chinese families.

To study the heterogeneity of hepatitis B virus (HBV) DNAs in Hong Kong, where HBV infection is endemic, serum specimens from 90 HBsAg carrier children were systematically tested with nine oligonucleotide probes representing conserved sequences in the viral genome. In a pair of twins and their cousin (belonging to family H) and an unrelated child (family Y) serum HBV DNA annealed to all but one probe, a sequence located between the core and pre-S regions of the viral genome (positions 2723-2738; EcoRI site 1). Serum from the H twins' aunt and the father and paternal grandparents in the Y family were also HBV DNA-positive. The nucleotide sequences in positions 2701-2800 were analysed. The same point mutation, C to T in position 2735, was present in the HBV DNAs from 7 individuals in the two families. All 4 H family members had the same HBV DNA sequence. The HBV DNA sequences found in the Y daughter, father, and grandfather were identical and they were different from the H family mutant. These results provided evidence at the DNA level of intrafamilial transmission within these Chinese families.

Adolescent↗

Lack of association between slow acetylator status and spontaneous lupus erythematosus.

The Chinese in Southeast Asia are recognized as a population group that has a relatively high prevalence of rapid "acetylators" and a relatively high incidence of systemic lupus erythematosus. This study was designed to evaluate the possibility that there were environmental lupus erythematosus provocative substances eliminated by acetylation that resulted in a preponderance of slow acetylators among patients with the disease. We compared acetylator status in 36 Chinese women with mild, stable, and confirmed lupus erythematosus and 36 healthy control subjects matched for age, sex, and ethnic origin. Acetylator status was determined by use of HPLC to assay 5-acetylamino-6-formylamino-3-methyluracil/methylxanthine (AFMU/MX) and AFMU/(AFMU + MX) ratios in urine 1 to 4 hours after drinking a strong cup of coffee (caffeine). By use of parametric and nonparametric methods of analysis, the frequency distribution of AFMU/MX and AFMU/(AFMU + MX) ratios in both the patients and control subjects were determined to be very similar. Thus there was no association between slow acetylator status and lupus erythematosus in the study subjects.

Acetylation↗

Investigation of intravascular haemolysis during treatment of acute stroke with intravenous glycerol.

1. In patients with acute strokes entering a large ongoing randomised double-blind controlled trial of intravenous glycerol therapy, the extent and pathogenesis of any ensuing haemolysis were evaluated using standard clinical investigations and in vitro techniques. 2. Twenty patients received 10% glycerol in saline (500 ml over 4 h on 6 consecutive days) and 15 received corresponding control treatment with saline. 3. Intravascular haemolysis was evident after the first infusion; compared with the controls the glycerol group had i) a greater mean reduction in serum haptoglobin concentration (P less than .05), and ii) a greater proportion exhibiting haemoglobinaemia (P = 0.03). 4. After 6 days of glycerol treatment, the mean reduction in haemoglobin concentration was only 0.8 g more than in controls; this difference being neither clinically nor statistically significant. 5. Glycerol therapy was not associated with haemoglobinuria, renal insufficiency or disseminated intravascular coagulation. 6. Exposure of red blood cells to 1-10% glycerol in vitro did not induce haemolysis per se; on re-exposure to lower concentrations lysis ensued provided a minimum osmotic gradient was present. 7. Whilst taking standard dosage regimes of glycerol, the stroke patients we studied manifested a degree of intravascular haemolysis but its consequences were not clinically significant; lysis probably ensued after venous blood acquiring high glycerol concentrations mixed with blood containing little or no glycerol.

Acute Disease↗

Differences in diazepam pharmacokinetics in Chinese and white Caucasians--relation to body lipid stores.

We have compared diazepam pharmacokinetics in 16 Chinese and 18 white Caucasian healthy male volunteers, resident in Hong Kong and have correlated them with physical attributes. Serum concentrations of diazepam and desmethyldiazepam were measured in venous blood by an enzyme-linked immunoassay (0-3 h samples) and HPLC (3-72 h samples). Pharmacokinetic parameters were derived assuming a two compartment model, distribution phase less than 6 h, and 100% oral systemic availability. Compared with the Chinese the white Caucasians were older, heavier, taller, and fatter, as judged by skin fold thickness (SFT) and total body weight to 'Ideal' body weight (TBW/IBW) ratio; respective mean differences being 16%, 27%, 4%, 26%, and 15% (p less than 0.05). Mean diazepam apparent volume of distribution (V) and V/IBW were larger in the white Caucasians (52% & 39% respectively, p = 0.002). SFT and TBW/IBW ratio yielded the best correlations with V, V/TBW and V/IBW (0.50-0.75, p less than 0.05). Obesity indices contributed most to the overall regressions (R2 up to 0.52), and for V there was a further small effect (2%, partial F test) due to ethnic group, possibly reflecting stature. Mean peak diazepam concentration (Cmax) was similar in both ethnic groups. Time to Cmax (tmax) was more often prolonged in the Chinese (chi 2 test, p = 0.01). Body fat and stature may thus account for these inter-ethnic differences in the apparent volume of distribution of diazepam, a highly lipid-soluble drug.

Adult↗

Hepatitis B surface antigen, hepatocellular carcinoma and cirrhosis in hong kong: a necropsy study: 1963-1976.

Hepatitis B surface antigen (HBsAg) was stained in liver tissue in 71% of 496 cases of cirrhosis with and without hepatocellular carcinoma (HCC) in Chinese coming to necropsy in Hong Kong from 1963-1976. Male cases numbered 417; HBsAg was positive in 83% of those in which HCC was combined with cirrhosis and in 62% of those with cirrhosis alone. Of 39 additional male cases of HCC without cirrhosis, 38% were HBsAg+. Similar proportions were recorded in the famale cases. This progression suggests a cumulative carcinogenic effect of persistent hepatitis B virus (HBV) fully expressed in the presence of cirrhosis. The approximate risk factors for males in Hong Kong who are HBsAg+ at the time of death, compared with HBsAg- males, are 6:1 for HCC alone, 16:1 for cirrhosis alone and 50:1 for HCC combined with cirrhosis. The frequency of HBsAg+ tests is much higher in Hong Kong than in the United Kingdom, and cirrhosis is calculated to be 2.8 times and HCC 11 times commoner. The high incidence of HCC in Hong Kong is not attributable solely to the high incidence of cirrhosis, but can be related to the high incidence of cirrhosis accompanied by persistent HBV.

Carcinoma, Hepatocellular↗

Factors associated with mortality in older people.

A random sample of older people from Edinburgh (215 men and 272 women aged 62--90 years) was examined clinically and by a questionnaire. Various measurements were made. Five years later, mean values of measurements were compared in those who had died and in survivors. Where significant differences occurred, regression techniques were used to separate age and mortality effects. Variables in which death was the predominant independent variable in the regressions were body weight, bi-iliac diameter, FEV1.0, transverse chest diameter, index of kyphosis, leucocyte ascorbic acid and some nutrient intakes in men plus transverse cardiac diameter and leucocyte ascorbic acid in women. Apart from index of kyphosis in men and cardiac diameter in women, mean values were significantly larger in survivors. Dichotomous variables from questionnaire and examination significantly related to mortality were 'possible' ischaemic heart disease in women, diastolic hypertension in men, persistent cough in men and dyspnoea worse than grade 2 in men and women. Cigarette smoking had no mortality effects in this study.

Age Factors↗

Automated measurements on human C-bands in family studies.

An automated system providing quantitative measurements of C-band size has been used, in conjunction with statistical methodology developed for the purpose, in a family study to demonstrate its potential in determining the mode of transmission of C-bands from parent to offspring, and to test the assumption of Mendelian inheritance. The most serious obstacle encountered was the high within-person variance of the normalized band sizes, the large within-slide variance being increased by technical variation between different preparations. Attempts to reduce variance by developing more effective normalization techniques did not prove fruitful. Nevertheless, the ability of the present system to perform a trace using a reasonable number of cells has been demonstrated in an example. In the two families studied we saw no evidence that band size was not transmitted and changes in band size, if any, were less than about 5 micrometer2 X 10(-2) (compared to a typical medium-category band size of about 65 mcirometer2 X 10(-2)).

Automation↗

The relationship of kyphosis to the shape of vertebral bodies.

An index which measures the wedge deformity of vertebral bodies in lateral chest radiographs in older people was calculated by dividing the sum of the vertical anterior heights of the lower six thoracic vertebral bodies and discs by the corresponding sum of vertical posterior heights. This index increased with increasing age in a similar manner in men and in women, in contradistinction to an index measuring kyphosis in which the age effect was greater in women. The index of wedging explained 42 per cent and 48 per cent of the variation in kyphosis in men and in women respectively. Additional effects due to age, detected in women only, added a further 4 per cent to the explained variation and may be due to ageing of soft tissues.

Aged↗