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Biomedical subjects

M J Gardner

Publications and source records attributed to M J Gardner.

At least 145 records · Page 8Linked to original sources
PubMed1989

Inhibition of neonatal rat growth and circulating concentrations of insulin-like growth factor-I using an antiserum to rat growth hormone.

Treatment of rats for 24 h on day 2, 10 or 20 of age with a specific antiserum to rGH (anti-(rGH], GH, bromocriptine (CB-154) or prolactin failed to influence body weight gain or serum concentrations of insulin-like growth factor-I (IGF-I). On day 28 of age, however, anti-(rGH) completely inhibited body weight gain and markedly reduced circulating IGF-I concentrations, effects which were completely prevented by exogenous ovine GH (oGH). When administered to control rats on day 28 oGH caused supranormal weight gain and serum IGF-I concentrations. These results suggested that GH does not play a significant role in growth or regulation of serum IGF-I until after day 20 of age. By contrast, when anti-(rGH) was given for 4 consecutive days beginning on day 2 of life, body weight gain was reduced within 48 h and remained so until at least 28 days of age. Tail length was also significantly reduced. The effect was due to inhibition of GH effects since serum GH concentrations were low and exogenous GH prevented the effect. Inhibition of growth during the first 14 days of life occurred in the absence of any effect on serum IGF-I although by 21 days of age serum IGF-I was considerably lower than in control rats. The prolonged reduction in growth after treatment has stopped appeared to be due to a cytotoxic effect on the pituitary gland since pituitary weight and GH but not prolactin content were significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects on health of non-occupational exposure to airborne mineral fibres.

The most prominent potential marker of disease-related non-occupational exposure to mineral fibres is mesothelioma. Although many cases of mesothelioma have resulted from occupational exposure to asbestos, some have been associated with para-occupational domestic and/or neighbourhood exposure and have been reported in case series, case-control studies and a cohort study among non-occupationally exposed subjects. However, little information is available on mesothelioma as a direct consequence of general environmental asbestos exposure. Such cases of mesothelioma related to non-occupational exposure to asbestos as have occurred to date are likely to have resulted from past exposures much higher than those prevailing at the present time (in the developed countries); numbers will therefore probably decrease in the future. Very high rates of mesothelioma have been reported as a result of exposure to erionite. No studies are available on the effects of non-occupational exposure to man-made mineral fibres but, among occupationally exposed workers, a risk of mesothelioma is not apparent. There are suggestions of raised lung cancer rates among household contacts of asbestos workers and among individuals exposed to erionite. Non-malignant parenchymal and pleural abnormalities have been observed in subjects exposed non-occupationally to asbestos and erionite, but these are not necessarily associated with malignant lesions. Quantitative risk estimates of adverse effects on health have not been derived from these studies, essentially because of the absence of fibre exposure measurements.

Air Pollutants↗
PubMed1988

Body surface potential maps with low-level exercise in isolated left anterior descending coronary artery disease.

One hundred and twenty-lead body surface potential maps (BSPMs) were recorded at rest, at immediate cessation of exercise and after 1 (early) and 5 minutes (late) of recovery in 14 patients with isolated, critical, left anterior descending (LAD) coronary artery stenosis. Exercise endpoints, at an average peak rate of 98 +/- 13, were usual pain worsening in 13 LAD patients, and diagnostic ST depression in lead V5 in 1 patient. Twelve patients also had positive thallium scans. BSPMs were also recorded in 8 normal subjects who exercised to peak heart rates similar to those of the LAD subjects. Spatially, there were similar exercise changes in QRS and ST-segment integral patterns over the precordium and inferior torso in both groups. These were transient in the control group but persisted to late recovery in the LAD group, particularly for ST integral. Quantitatively, multivariate analysis revealed significant temporal differences between the 2 groups. However, the only independent BSPM variable was the sum of ST integral decrease, averaging --2,323 +/- 1,809 microV.s for normal patients between rest and immediate cessation of exercise, compared with -3,828 +/- 2,329 microV.s for the LAD patients (p less than 0.05). Late recovery minus rest difference averaged -1,264 +/- 1,080 microV.s for normal subjects and -2,575 +/- 1,844 microV.s for LAD patients (p less than 0.01). To control for the physiologic changes of exercise, the ST integral temporal differential maps of the normal subjects were subtracted from those of the LAD patients and the sum of negative intergroup differences was assumed to reflect only ischemia. Correlation of ST integral ischemia values at immediate cessation of exercise and late recovery was high (r = 0.88); however, intertechnique correlations of the BSPM variables with quantitative angiographic scores and thallium perfusion scan scores revealed generally low r values (range 0 to 0.52). These data demonstrate that ischemic repolarization changes are detectable and quantifiable by BSPM at low levels of cardiac stress in patients with 1-vessel disease when the usual electrocardiographic criteria of myocardial ischemia are frequently absent. The data further suggest that ST integral changes reflective of myocardial ischemia persist well after the exercise recovery period and that they are complementary to, rather than substitutionary for, other indirect measures of myocardial ischemia.

Adult↗
PubMed1988

Mitochondrial DNA of the human malarial parasite Plasmodium falciparum.

Covalently closed circular DNA molecules were isolated from Plasmodium falciparum total DNA by isopycnic centrifugation in CsCl gradients containing either ethidium bromide or 2',6-diamidino-2-phenylindole. The circular molecules had an average contour length of 11.1 +/- 0.5 micron, similar to the analogous molecules previously isolated from the simian malaria parasite P. knowlesi. Both circular molecules shared considerable sequence homology and conserved restriction sites. The nucleotide sequence of one 936 bp fragment of the P. falciparum molecule was determined and identified, by a data base homology search, as part of a mitochondrial small rRNA subunit, thus confirming the mitochondrial origin of the circular DNAs of both malarial species.

Animals↗
PubMed1988

Pharmacokinetics of single and multiple doses of ethinyl estradiol and levonorgestrel in relation to smoking.

The effects of tobacco and oral contraceptive (OC) use (Ovral) on the pharmacokinetics of levonorgestrel (0.25 mg) and ethinyl estradiol (50 micrograms) were examined. Young women (n = 27) were grouped as follows: I: non-OC users/nonsmokers; II: OC users/nonsmokers; III: non-OC users/smokers; and IV: OC users/smokers. The apparent clearance of levonorgestrel in group I was 80.9 +/- 15.6 ml/hr/kg and the half-life was 19.3 hours. A significant decrease in levonorgestrel clearance was seen in the chronic OC users (groups II and IV). The apparent oral clearance of ethinyl estradiol was 1002 +/- 398 ml/hr/kg in group I and the half-life averaged 7.7 hours. Groups II and III showed decreased (not significant) clearance of ethinyl estradiol. Tobacco use had no effect on steroid pharmacokinetics in the non-OC users. Although chronic OC use did not affect ethinyl estradiol clearance, a joint effect of tobacco/OC use on enhancing clearance of ethinyl estradiol appeared to occur. A linear relationship was found between 24-hour trough serum concentrations and AUC values of both steroids that may facilitate population monitoring studies of OC exposure.

Adult↗
PubMed1988

Lung cancer among glass fibre production workers: a case-control study.

A cohort study among 4734 employees at an English glass fibre plant previously reported no excess of lung cancer mortality either overall or when examined in broad occupational groups. To investigate occupation in more detail, and to test the hypothesis that processes producing or using finer (respirable) fibres may be related to a higher risk of lung cancer, a nested case-control study has now been carried out. Included are 73 cases of lung cancer and 506 matched controls, for whom jobs held and processes worked on have been blindly recorded in more detail than for the cohort study. Workers known to have been employed on processes containing respirable fibres had a relative risk of lung cancer of 1.2 (95% confidence interval 0.7-2.0) compared with other workers. There was no evidence of a relationship of lung cancer to fibre diameter, duration of exposure, or time since first exposure. The results by broad occupational group were similar to those of the cohort study, and although some of the many detailed occupational categories examined had significantly raised relative risks, these did not appear to be related to exposure to respirable glass fibre. Although the study has not indicated a differential risk of lung cancer among workers exposed to finer diameter glass fibres, the exposure levels were low and the number of cases small.

Chemical Industry↗
PubMed1987

Follow up study of children born elsewhere but attending schools in Seascale, West Cumbria (schools cohort).

Records on 1546 children who were identified as having attended schools in Seascale up to November 1984 and were born since 1950 but not in the civil parish were studied. These children lived in or near Seascale for a period of time while they were attending one or more of three local schools and are an additional group to the 1068 children who were identified as born to mothers resident in Seascale in an accompanying study. Even though some of the schoolchildren apparently remained in the village for a short period only all but 7% were followed up through the National Health Service Central Register. Mortality among these children to 30 June 1986 is comparable to that expected at national rates. From all causes there were 10 observed deaths compared with 12.69 expected--a ratio of 0.79 (95% confidence interval 0.38 to 1.45)--and from cancer one observed death compared with 2.04 expected--a ratio of 0.49 (95% CI 0.01 to 2.73). No deaths from leukaemia or lymphoma were reported, but only 0.83 was expected. Since 1971 (the year when cases of cancer were first notified to the NHS Central Register) three non-fatal cases of cancer were reported, including two lymphomas, compared with 2.04 expected and two cases of carcinoma in situ of the cervix compared with 1.79 expected. In addition, there was a case of leukaemia among the schoolchildren which was known previously and had been diagnosed in 1968. There is an interesting difference between the results of this study and the results of the study of children born to mothers who were resident in Seascale. In the latter study there was an excess of leukaemia and of other cancers, but a similar finding is not apparent among children who spent some time at schools in Seascale but were born elsewhere. This raises the question of whether one or more aetiological factors in childhood cancer were acting on a locality specific basis before birth or early in life. This cannot be answered from these cohort studies, but it is hoped that the case-control study that is under way in West Cumbria will provide relevant information.

Adolescent↗
PubMed1987

Follow up study of children born to mothers resident in Seascale, West Cumbria (birth cohort).

Records on 1068 children who were born to mothers resident in Seascale Civil Parish during 1950-83 were studied. There was a large degree of mobility among the families, and nearly half of the children did not subsequently attend the main local school. Use of the National Health Service Central Register, however, enabled us to follow up the children's records regardless of place of residence. The excess of leukaemia among Seascale children first supported from the analysis of geographical areas is confirmed. There were five deaths from leukaemia identified to 30 June 1986 compared with 0.53 expected at national rates--a ratio of 9.36 (95% confidence interval 3.04 to 21.84). One of these deaths occurred after the child had left Seascale. There were four deaths from other cancers compared with 1.06 expected--a ratio of 3.76 (95% CI 1.02 to 9.63). In addition, three further cases of cancer, apart from the deaths, were reported compared with 1.19 expected since 1971--a ratio of 2.53 (95% CI 0.52 to 7.40). For other causes of death, including stillbirths and infant mortality, there was a reported deficit compared with national rates, some of which at least was to be expected on the basis of the social class composition of the population of Seascale. In view of the importance of this cohort of births continued follow up is planned, with the possibility of extending it to include births since 1983, and the methods available for this type of study will be examined further.

Adolescent↗
PubMed1987

Longitudinal effects of pregnancy on the pharmacokinetics of theophylline.

The effects of pregnancy on the disposition of theophylline were assessed in 10 patients throughout pregnancy and post-partum. The clearance relative to total theophylline concentrations was only slightly affected during the first two trimesters (2.61 +/- 0.63 l/h and 2.85 +/- 1.05 l/h), while a statistically significant reduction was evident late in pregnancy (2.05 +/- 0.49 l/h). Post-partum clearance values (2.16 +/- 2.81 l/h) suggest an ongoing suppression relative to pre-pregnancy levels. A similar pattern was evident with clearance values based on free theophylline plasma concentrations (p = 0.12). Absolute volume of distribution increased in concert with gestation, suggesting that theophylline partitions into the enlarged tissue spaces. In addition, theophylline binding to plasma proteins decreased, albeit insignificantly, during the second (fraction bound = 29%) and third (32%) trimesters compared to post-partum values (41%). Increases in half-life during the third trimester (13.00 +/- 2.31 h vs 9.53 +/- 3.53 h post-partum) were highly significant. This change reflects the net effect of reduced clearance and increased distribution. Breast feeding had no effect on the disposition of theophylline, although the transfer of this compound into breast milk was confirmed.

Asthma↗
PubMed1987

Perioperative myocardial infarction with coronary artery surgery: diagnosis, incidence and consequences.

Perioperative myocardial infarction is a potential consequence of coronary artery bypass surgery. The diagnosis is difficult due to multiple factors including postoperative chest discomfort, serum enzyme elevations and nonspecific electrocardiographic changes. No one test is reliable, but a combination of electrocardiogram, MBCK serum enzyme analysis and technetium pyrophosphate scanning should increase the probability of correct diagnosis. Using this method, the incidence of perioperative myocardial infarction in this study was six out of 100. Left ventricular function in the early postoperative period was adversely affected by perioperative myocardial infarction with a reduction in left ventricular ejection fraction (63 +/- 9% preoperative to 54 +/- 12% postoperative; P less than 0.05), whereas left ventricular ejection fraction was unchanged in the absence of perioperative myocardial infarction. The long term left ventricular function, however, appears to recover, and at two years after surgery there was no difference in rest or exercise left ventricular function between patients who suffered perioperative myocardial infarction versus those who did not. All patients with perioperative myocardial infarction survived to be discharged from hospital, and all returned for follow-up at two years. Their functional and work status was no different from those without perioperative myocardial infarction. This would suggest that, if patients survive a perioperative myocardial infarction, their long term functional status is no different from those patients without perioperative myocardial infarction.

Adult↗