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Biomedical subjects

M J Gardner

Publications and source records attributed to M J Gardner.

At least 181 records · Page 10Linked to original sources
PubMed1984

Cimetidine-methylprednisolone-theophylline metabolic interaction.

The pharmacokinetics of theophylline and methylprednisolone were examined before and during cimetidine treatment in an asthmatic woman who required long-term administration of these drugs. Cimetidine reduced theophylline plasma clearance by 30 percent, and measurement of urinary metabolites showed that 3-methylxanthine formation was inhibited more strongly than that of the methylated uric acid metabolites. Assessment of methylprednisolone disposition following oral and intravenous doses revealed no effect of cimetidine on the bioavailability (74 to 81 percent absorption) or plasma clearance (22 to 24 liters per hour) of the steroid. Thus, cimetidine exhibits variable and selective effects on the biotransformation pathways of drugs important in asthma therapy.

Adult↗
PubMed1984

Effects of cell volume on insulin binding, internalization and degradation in rat adipocytes.

Adipocytes from old rats (greater than 450 g) were separated into 2 populations with mean cell volumes of 201 +/- 14 and 813 +/- 41 pl (mean +/- SEM, 20 observations) by filtering through nylon mesh (64 microns diameter) and compared with adipocytes from young rats (less than 150 g) with a mean adipocyte volume of 154 +/- 20 pl (14 observations). Large adipocytes had more insulin receptors per cell but less per unit of surface area. They internalized greater amounts of insulin than small cells in the presence or absence of bacitracin and chloroquine, although the proportion of bound hormone which was internalized was similar in all 3 groups. Down-regulation of the insulin receptor was evident in large and small adipocytes after incubation in the presence of 10(-7)M insulin. Large cells degraded insulin (extracellularly and intracellularly) at significantly greater rates than small cells whether expressed per cell or per unit of surface area. Small cells from old rats had essentially identical properties to small cells from young rats in all parameters examined. The results suggest that the decreased surface density of insulin receptors observed in large adipocytes from old rats is due to size rather than age and that the decreased insulin sensitivity of large adipocytes is not due to an inability to internalize insulin or down-regulate its receptors but may be due to increased rates of insulin degradation.

Adipose Tissue↗
PubMed1984

Temporal evolution of body surface map patterns following acute inferior myocardial infarction.

We studied the evolution of body-surface potential map (BSPM) patterns in 32 patients following first acute inferior myocardial infarction. Initial BSPMs were obtained at a mean of 79 hours post-infarction; follow-up BSPMs, a mean of eight months post-infarction. Temporal area-of-difference maps, constructed by subtracting initial from follow-up group-mean BSPMs, revealed reciprocal changes over the superior and inferior torso for both Q-zone and ST-segment time-integral distributions. The temporal changes in Q-zone patterns were small but definite: over the inferior torso there was a relative gain in Q-zone values and, over the superior torso, a relative decrease. In contrast, there were marked spatial and quantitative changes of ST-segment distributions during the follow-up period. Over the superior torso, particularly anteriorly, there was a gain in ST-segment values; over the inferior torso, a decrease. With the small temporal changes in Q-zone time-integral distributions, individual Q-zone maps continued to reflect a pattern of inferior myocardial infarction at follow-up. In contrast, the marked temporal changes in ST-segment time-integral distributions resulted in individual map patterns at follow-up that were nearly indistinguishable from normal ST-segment maps. The relatively small changes in depolarization time-integral patterns during the early post-infarction period suggest that the Q-zone patterns of the acute phase of myocardial infarction reflect near-irreversible or completed myocardial damage. The marked normalization of repolarization time-integral patterns during the recovery phase suggests, however, that there are also considerable areas of myocardium-at-risk during the early phase of the infarction process which stabilize with time.

Adult↗
PubMed1984

Refractory paroxysmal sinus tachycardia: management by subtotal right atrial exclusion.

A 27 year old woman presented with recurrent episodes of disabling paroxysmal sinus tachycardia (150 to 180 beats/min) in the absence of identifiable organic disease. Tachycardia was resistant to all drug therapy. Programmed stimulation could not induce the tachycardia but high dose propranolol therapy failed to suppress sinus tachycardia in response to isoproterenol infusion. Because of the disability resulting from refractory tachycardia, the patient underwent a new operative procedure to create exit block around the region of abnormal impulse formation. This resulted in the appearance of a stable junctional escape rhythm at 60 beats/min. No adverse effects occurred and the patient has remained free of symptoms after a follow-up period of 10 months.

Adrenergic beta-Antagonists↗
PubMed1984

Relationship of serum thiocyanate concentrations to smoking characteristics.

Thiocyanate (SCN) concentrations were determined in serum samples from 130 young healthy persons (60 smokers) and related to their smoking and physiologic characteristics. Serum thiocyanate correlated strongly and approximately equally with the number of cigarettes/d X kg of ideal body weight (IBW) (r = 0.748), total nicotine intake in mg/d X kg IBW (r = 0.735), and total tar intake in mg/d X kg IBW (r = 0.731). Multiple linear regression analysis that included these factors as well as sex, marijuana use, menthol, and degree of inhalation only increased the multiple r to 0.803. A more sensitive statistical method (NYBAID) was also used to determine the most significant influences of these variables on serum SCN. The association with depth of inhalation (i.e., smoking versus nonsmoking) was dominant among the relationships considered. The highest SCN levels were exhibited in heavy nicotine users (8.58 +/- 3.00 mg/l), while average users had slightly lower concentrations (6.49 +/- 2.37 mg/l) (p less than 0.03). In nontobacco smokers, those who smoked marijuana several times weekly had higher SCN levels (4.66 +/- 2.16 mg/l) than noncannabis users (2.38 +/- 1.38 mg/l) (p less than 0.03). These studies confirm the utility of serum SCN as an index of smoking rate and demonstrate the role of secondary variables in accounting for the chemical in serum.

Adult↗
PubMed1984

Cancer in a factory using amosite asbestos.

The paper describes the mortality experience of 5969 men employed in a factory where insulation board was manufactured using amosite asbestos from 1947 to 1979. 422 (7%) of the men were known to have died by the end of 1980. Among the 4820 men engaged in the manufacture of insulation board a doubling of the risk of lung cancer has occurred (57 deaths observed; 29 deaths expected). An excess is present both in men who entered the factory before and after 1960. Among the 2461 for whom smoking information is available a detectable excess risk is limited to current smokers exposed to higher levels of asbestos. Apart from five deaths from mesothelioma no statistically large or significant excesses of mortality from cancers of other sites have occurred, but further follow-up of the cohort is in progress. Nine deaths from asbestosis have been recorded. The results are discussed in the light of other studies of the effects of exposure to amosite asbestos.

Adult↗
PubMed1984

Mapping small area cancer mortality: a residential coding story.

During the compilation of an atlas of cancer mortality in England and Wales on a small area scale, one rural district was found to have raised death rates for most sites of cancer. On investigation this proved to be related to the opening in that district of a home for patients terminally ill with cancer. Deaths occurring in the home to patients from outside areas were not consistently transferred back to the deceased's area of residence. The effect of the transferability status of the home on the district's cancer rates is described. The Office of Population Censuses and Surveys is now reviewing the procedure for coding the area of residence of deaths in long stay institutions.

Aged↗
PubMed1984

Mortality and incidence of cancer of workers in the man made vitreous fibres producing industry: an international investigation at 13 European plants.

A total of 25 146 workers at 13 plants producing man made mineral fibres (MMMF) in seven European countries (Denmark, Finland, Federal Republic of Germany, Italy, Norway, Sweden, and United Kingdom) were studied in a historical cohort investigation. At 12 of the 13 plants an environmental survey was carried out to determine present day concentrations of airborne man made mineral fibres that showed levels of respirable fibres usually below 1 f/ml and most commonly in the range 0.01 to 0.1 f/ml. Workers were entered into the cohort at the moment of their first employment at one of the 13 factories (which started to operate between 1900 and 1955), and were followed up to at least 31 December 1977. Three per cent of the workers were lost to follow up. National death rates and national cancer incidence rates, where applicable, were used for each of the seven countries for comparison with the workers' cohort. A single death from mesothelioma was reported out of a total of 309 353 person-years of observation. No consistent differences (within and between plants) were noted between observed and expected numbers concerning individual causes of death or individual cancer sites, apart from lung cancer. For this cause a tendency was observed for the standardised mortality ratio (SMR) to increase with time from first employment. When the data from all the plants were pooled a statistically significant raised SMR of 192 (17 observed, 8.9 expected; 95% confidence interval 117-307) appeared in the group with 30 years or more since first employment. The relevance of this finding, to which different factors including uncontrolled confounders such as smoking habits may have contributed, cannot be established at present. The result is suggestive, however, of an increased risk associated with the man made mineral fibres working environment of 30 or more years ago.

Europe↗
PubMed1984

Extensions to a technique for relating mortality and environment--exemplified by nasal cancer and industry.

The use of geographic data to interrelate mortality rates and environmental variables is an important approach to determining reasons for the variations in disease frequency. An alternative methodology to standard regression analysis was recently suggested, which is particularly useful when there are a large number of geographic areas and relatively few deaths. An extension of this technique is described, which includes a modified regression approach using areas aggregated according to their level of the environmental factor. An example is given relating nasal cancer mortality to the distribution of industry in England and Wales. The known hazards in the furniture and leather industries are indicated and other potential risk industries, including tailoring, are suggested.

England↗
PubMed1983

Is the statistical assessment of papers submitted to the "British Medical Journal" effective?

A study was performed to judge the effectiveness of the statistical assessment scheme for papers submitted to the "British Medical Journal." Statistical criticism of the content of 200 submitted papers which had already been seen by a subject referee led directly or indirectly to 73 (37%) being rejected for publication. In most cases (53 out of 73) serious problems requiring more than minor revision were identified. A comparison of reports on subsequently unpublished and published papers showed that adverse statistical assessments--suggesting major problems--were more common in the papers that were not accepted for publication. Moderate, or less, revision was recommended for 63% of published papers but 39% of the remainder. A checklist of relevant questions was used in making a detailed comparison of 12 published papers, six of which had been statistically assessed and six of which had not. This comparison yielded little evidence that the papers that had been assessed were statistically more acceptable than those that had not been assessed but re-emphasised the subjectivity of refereeing and assessment.

Periodicals as Topic↗
PubMed1983

Zn(II)-theophylline-ethylenediamine: structure and pH stability.

A zinc-containing salt of theophylline, Zn(II)-aminophylline, was synthesized and its structure determined by X-ray diffraction techniques. The zinc ion is coordinated to two theophylline anions and a molecule of ethylenediamine in a tetrahedral arrangement. The solubility of the compound in water at 30 degrees (0.047 mg/ml) is 180-fold lower than that of theophylline (8.40 mg/ml). The complex is relatively stable in the alkaline pH range, but it hydrolyzes, releasing theophylline in acidic environments. The rate of theophylline release is pH dependent. These properties are useful in formulating chewable tablets and liquid suspension dosage forms that overcome the characteristic bitter taste of theophylline, yet provide for efficacious treatment of diseases involving the respiratory tract.

Drug Stability↗
PubMed1983

Effects of tobacco smoking and oral contraceptive use on theophylline disposition.

The independent as well as interactive effects of chronic (greater than 6 months) oral contraceptive (OC) use and cigarette smoking on single-dose (4 mg/kg) theophylline disposition were assessed in 49 young, healthy women. Significant elevations (40%) in theophylline plasma clearance were found in women who smoked. OC use resulted in decreases in clearance of a similar magnitude (28%). These factors do not appear to interact with respect to theophylline disposition. The combination of main effects tended to cancel one another (clearance of 49.1 ml h-1 kg-1 ideal body weight for OC non-user, non-smoker, vs 49.7 ml h-1 kg-1 for OC user-smoker). Single dose exposure to OC in non-users did not significantly alter theophylline pharmacokinetics for the group as a whole. However, in the subgroup of smoking subjects, significant decreases in clearance were evident (P less than 0.05). Analogous results were found for half-life. Volume of distribution was slightly diminished in smokers, but was unaffected in OC users. Areas under the serum concentration-time (AUC) profiles of norgestrel and ethinyloestradiol were examined in 27 women as indices of OC exposure. The smallest values of theophylline clearance were found in the subjects with largest AUC of both OC steroids. Appropriate statistical analyses of data which are influenced by multiple factors are discussed. Special concern is needed when the factor partitioning process yields subgroups of unequal sizes.

Adult↗
PubMed1983

Interpretation of disease time trends: is cancer on the increase? A simple cohort technique and its relationship to more advanced models.

Analysis of trends in mortality from respiratory cancer among women shows that, contrary to previous interpretation, there is no suggestion of any increase over time which might be due to recent increases in exposures to carcinogens. Although there are upward trends in the number of deaths, the crude death rate, and the age standardised rate, these are shown to be related to the aging of earlier cohorts of women who have experienced high mortality rates. More recent cohorts, born since the middle 1920s, show a decline. A simple technique to identify trends in different cohorts is described, and it is shown to be linked to the age-period-cohort modelling approach to investigating time trends. Dangers inherent in ignoring either period or cohort effects when describing one of these factors are discussed.

Adult↗