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Biomedical subjects

M Walker

Publications and source records attributed to M Walker.

At least 613 records · Page 34Linked to original sources
PubMedDate not supplied

Lifestyle and 15-year survival free of heart attack, stroke, and diabetes in middle-aged British men.

BACKGROUND: To examine the relationship between modifiable lifestyle factors (smoking, physical activity, alcohol intake, and body mass index [BMI]) and the likelihood of 15-year survival free of major cardiovascular end points and diabetes in middle-aged men. METHODS: A prospective study of 7142 men aged 40 to 59 years at screening with no history of coronary heart disease, diabetes, and stroke drawn from 1 general practice in each of 24 British towns and followed up for 15 years. MAIN OUTCOME MEASURES: Death from any cause and a combined end point, including survival free of heart attacks or stroke or the development of diabetes over a follow-up of 15 years for each man. RESULTS: During the 15-year follow-up, there were 1064 deaths from all causes, 770 major heart attacks (fatal and nonfatal), 247 stroke events (fatal and nonfatal), and 252 cases of diabetes among the 7142 men. After adjustment for age and each of the other modifiable lifestyle factors, the risk of the combined end point (death or having a heart attack, stroke, or diabetes) went up significantly with increasing smoking levels and from BMI levels of 26 kg/m2 or higher, and decreased significantly with increasing levels of physical activity up to levels of moderate activity with no further benefit thereafter (heavy smoking vs never: relative risk [RR] [odds], 2.50; 95% confidence interval [CI], 2.12-2.94; BMI > or = 30 vs 20-21.9 kg/m2: RR, 2.11; 95% CI, 1.71-2.62; moderate vs inactive: RR, 0.60; 95% CI, 0.50-0.72). Light drinking (vs occasional) showed a relatively small but significant reduction in risk (RR, 0.84; 95% CI, 0.74-0.96). Using Cox predictive survival models, the estimated probability of surviving 15 years free of cardiovascular events and diabetes in a man aged 50 years ranged from 89% in a moderately active man at BMI levels of 20 to 24.0 kg/m2 who had never smoked to 42% in an inactive smoker with BMI level of 30 kg/m2 or higher. CONCLUSIONS: Modifiable lifestyles (smoking, physical activity, and BMI) in middle-aged men play an important role in long-term survival free of cardiovascular disease and diabetes. These findings should provide encouragement for public health promotion directed toward middle-aged men.

Adult↗
PubMedDate not supplied

Individual differences in hypothalamic-pituitary-adrenal activity in later life and hippocampal aging.

Variation in magnitude of cognitive decline in later life is a central feature of human aging. The more severe forms of dementias, such as Alzheimer's disease, clearly define one end of the spectrum. However, among those showing no obvious signs of clinical dementia there are considerable individual differences. Thus, although evidence for learning, memory, and language loss appears in some individuals as early as 50-55 years of age, many people continue to function alertly well into their 90s. These individuals exemplify what Rowe and Kahn (1987) have termed "successful" aging. The wide variability in CNS aging, often a nuisance factor in studies, are becoming a major focus for brain aging research (e.g., Gage et al., 1984;Gallager and Pelleymounter, 1988; Aitken and Meaney, 1990; Issa et al., 1990). Our studies over the past few years have added support to the idea that individual differences in hypothalamic-pituitary-adrenal (HPA) activity can account for part of the variation seen in neurological function among the elderly. In this article we discuss the evidence for the idea that adrenal glucocorticoids can compromise hippocampal function and, thus, produce cognitive impairments, as well as the potential mechanisms for these effects.

Aged↗
PubMedDate not supplied

TGF-beta: upregulator of HIV replication in macrophages.

TGF-beta at physiological concentrations, when added to monocyte-derived macrophages following HIV1 infection, has an enhancing effect upon the rate of virus production. This effect is observed with the monocytotropic isolate ADA, as well as with HIV1 IIIB, which poorly replicates in macrophages.

Cell Differentiation↗
PubMedDate not supplied

Antidepressants restore hypothalamic-pituitary-adrenal feedback function in aged, cognitively-impaired rats.

Aged, cognitively-impaired rats (and humans) show hypothalamic-pituitary-adrenal (HPA) hyperactivity that correlates with hippocampal damage. The resultant increase in plasma glucocorticoid exposure is thought to contribute to impaired hippocampal function and to potentiate hippocampal neuron death. In young, adult rats antidepressant drugs increase corticosteroid receptor expression in brain regions known to regulate the HPA axis, leading to increased negative-feedback control and decreased HPA activity. In the present study we examined basal levels of plasma adrenocorticotropin hormone (ACTH) and corticosterone in aged, cognitively-impaired (AI), aged, cognitively-unimpaired (AU) and young, adult (Yg) rats. Plasma ACTH and corticosterone levels were significantly elevated in the AI rats, but only in samples obtained during the diurnal peak. Five weeks of treatment with desipramine (15 mg/kg) significantly reduced evening levels of both ACTH and corticosterone in all groups, and eliminated the group differences. We then examined delayed, glucocorticoid negative feedback in these animals. Among vehicle-treated animals, a bolus injection of corticosterone (10 mg/kg), administered 3 hours prior to testing, completely inhibited the plasma ACTH response to restraint in AU and Yg, but not AI animals. In contrast, plasma ACTH responses to restraint were completely inhibited in AI rats following chronic treatment with desipramine. These findings indicate that the antidepressant, desipramine, decreases HPA activity and increases glucocorticoid negative-feedback sensitivity in AI rats, suggesting that antidepressant drugs may form a useful therapeutic approach to HPA dysfunction in elderly human populations.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Vascular anatomy anterior to lumbosacral transitional vertebrae and implications for anterior lumbar interbody fusion.

BACKGROUND CONTEXT: Anterior approaches to the lumbosacral spine afford the ideal window to the disc for interbody fusion. Vascular injuries represent the most feared complications of such approaches. Unfortunately, the combination of more procedures being performed, more surgeons at the beginning of the learning curve and less invasive techniques of approach combine to increase the risk of vascular injury in the face of altered vascular anatomy. PURPOSE: To assess cases in which vascular anatomy significantly altered the surgical approach to the lumbosacral junction. STUDY DESIGN/SETTING: Chart review of operative reports. PATIENT SAMPLE: All patients undergoing anterior lumbar interbody fusion between 1994 and 1997 at one large center. METHODS: We reviewed all cases of anterior lumbar interbody fusion performed between 1994 and 1997 to discover cases requiring significant alteration in approach because of vascular variation. RESULTS: One hundred seven consecutive cases were reviewed. Of these, 11 required significant alteration of the approach secondary to vascular variation. All 11 were in cases at the functional lumbosacral junction above a fixed transitional level. In only one case of transition was a usual approach able to be used. CONCLUSIONS: A consistent pattern of altered vascular anatomy anterior to the functional lumbosacral junction was found. This pattern is depicted and the surgical alterations required discussed. Such alteration in surgical approach was required in nearly all cases with transitional vertebrae and represented about 10% of cases overall. If anterior lumbar surgery is to be performed at the functional lumbosacral junction in the presence of transitional vertebrae, it is vital that close attention be paid to the vascular anatomy and more open techniques of approach should be considered.

Humans↗
PubMedDate not supplied

Significance of meconium-stained amniotic fluid in the preterm population.

OBJECTIVE: Numerous studies have assessed the significance of meconium-stained amniotic fluid (MSAF) at term. However, to date, there has been very little documentation on the incidence and significance of meconium in the preterm population. Our objective was to define the incidence of MSAF in patients delivering prematurely (<37 weeks) and examine its association with underlying fetal acidosis, Apgars and admission to the neonatal intensive care unit (NICU). METHOD: All patients delivering at a single tertiary care center between June 1994 and September 1997 were reviewed for the presence of meconium and gestational age <37 weeks at delivery. Maternal demographics and birth outcomes including cord gases, Apgar scores and admission to the NICU were collected. Exclusion criteria included multiple gestations, breech presentations, fetal anomalies and patients not in labor. RESULTS: Out of a total of 9570 patients there were 506 (5.3%) preterm births meeting the inclusion criteria, of whom 24 (4.8%) had MSAF noted either during labor or at delivery. Comparing the preterm group with and without meconium, there were no differences in maternal age, gravidity, rate of Cesarean section, or gestational age at delivery. Cord pH (7.27 meconium vs. 7.29 no meconium) and base excess (-5.1 meconium vs. -4.0 no meconium) were similar in both groups. There were no clinically significant differences in mean Apgar scores at 1 and 5 minutes. However, an increased number of NICU admissions were noted in the group with meconium (75% vs. 53%, p=0.04). CONCLUSION: The incidence of meconium staining of the amniotic fluid in labor in the preterm population is less than 5% and by itself is not a significant marker of fetal acidosis.

Acidosis↗
PubMedDate not supplied

Chloroform: exposure estimation, hazard characterization, and exposure-response analysis.

Chloroform has been assessed as a Priority Substance under the Canadian Environmental Protection Act. The general population in Canada is exposed to chloroform principally through inhalation of indoor air, particularly during showering, and through ingestion of tap water. Data on concentrations of chloroform in various media were sufficient to serve as the basis for development of deterministic and probabilistic estimates of exposure for the general population in Canada. On the basis of data acquired principally in studies in experimental animals, chloroform causes hepatic and renal tumors in mice and renal tumors in rats. The weight of evidence indicates that chloroform is likely carcinogenic only at concentrations that induce the obligatory precursor lesions of cytotoxicity and proliferative regenerative response. Since this cytotoxicity is primarily related to rates of formation of reactive, oxidative metabolites, dose response has been characterized in the context of rates of formation of reactive metabolites in the target tissue. Results presented here are from a "hybrid" physiologically based pharmacokinetic (PBPK) animal model that was revised to permit its extension to humans. The relevant measure of exposure response, namely, the mean rate of metabolism in humans associated with a 5% increase in tumor risk (TC05), was estimated on the basis of this PBPK model and compared with tissue dose measures resulting from 24-h multimedia exposure scenarios for Canadians based on midpoint and 95th percentiles for concentrations in outdoor air, indoor air, air in the shower compartment, air in the bathroom after showering, tap water, and food. Nonneoplastic effects observed most consistently at lowest concentrations or doses following repeated exposures of rats and mice to chloroform are cytotoxicity and regenerative proliferation. As for cancer, target organs are the liver and kidney. In addition, chloroform has induced nasal lesions in rats and mice exposed by both inhalation and ingestion at lowest concentrations or doses. The mean rate of metabolism associated with a 5% increase in fatty cysts estimated on the basis of the PBPK model was compared with tissue dose measures resulting from the scenarios already described, and lowest concentrations reported to induce cellular proliferation in the nasal cavities of rats and mice were compared directly with midpoint and 95th percentile estimates of concentrations of chloroform in indoor air in Canada. The degree of confidence in the underlying database and uncertainties in estimates of exposure and in characterization of hazard and dose response are delineated.

Air Pollutants↗
PubMedDate not supplied

1,3-Butadiene: exposure estimation, hazard characterization, and exposure-response analysis.

1,3-Butadiene has been assessed as a Priority Substance under the Canadian Environmental Protection Act. The general population in Canada is exposed to 1,3-butadiene primarily through ambient air. Inhaled 1,3-butadiene is carcinogenic in both mice and rats, inducing tumors at multiple sites at all concentrations tested in all identified studies. In addition, 1,3-butadiene is genotoxic in both somatic and germ cells of rodents. It also induces adverse effects in the reproductive organs of female mice at relatively low concentrations. The greater sensitivity in mice than in rats to induction of these effects by 1,3-butadiene is likely related to species differences in metabolism to active epoxide metabolites. Exposure to 1,3-butadiene in the occupational environment has been associated with the induction of leukemia; there is also some limited evidence that 1,3-butadiene is genotoxic in exposed workers. Therefore, in view of the weight of evidence of available epidemiological and toxicological data, 1,3-butadiene is considered highly likely to be carcinogenic, and likely to be genotoxic, in humans. Estimates of the potency of butadiene to induce cancer have been derived on the basis of both epidemiological investigation and bioassays in mice and rats. Potencies to induce ovarian effects have been estimated on the basis of studies in mice. Uncertainties have been delineated, and, while there are clear species differences in metabolism, estimates of potency to induce effects are considered justifiably conservative in view of the likely variability in metabolism across the population related to genetic polymorphism for enzymes for the critical metabolic pathway.

Animals↗
PubMedDate not supplied

Neonatal exposure to potent and environmental oestrogens and abnormalities of the male reproductive system in the rat: evidence for importance of the androgen-oestrogen balance and assessment of the relevance to man.

The effects on reproductive tract development in male rats, of neonatal exposure to potent (reference) oestrogens, diethylstilboestrol (DES) and ethinyl oestradiol (EE), with those of two environmental oestrogens, octylphenol and hisphenol A were systematically compared. Other treatments, such as administration of a gonadotrophin-releasing hormone antagonist (GnRHa) or the anti-oestrogen tamoxifen or the anti-androgen flutamide, were used to aid interpretation of the pathways involved. All treatments were administered in the neonatal period before onset of puberty. The cellular sites of expression of androgen receptors (AR) and of oestrogen receptor-alpha (ERalpha) and ERbeta were also established throughout development of the reproductive system. The main findings were as follows: (i) all cell types that express AR also express one or both ERs at all stages of development; (ii) Sertoli cell expression of ERbeta occurs considerably earlier in development than does expression of AR; (iii) most germ cells, including fetal gonocytes, express ERbeta but not AR; (iv) treatment with high, but not low, doses of potent oestrogens such as DES and EE, induces widespread structural and cellular abnormalities of the testis and reproductive tract before puberty; (v) the latter changes are associated with loss of immunoexpression of AR in all affected tissues and a reduction in Leydig cell volume per testis; (vi) none of the effects in (iv) and (v) can be duplicated by treating with high-dose octylphenol or bisphenol A; (vi) none of the reproductive tract changes in (iv) and (v) can be induced by simply suppressing androgen production (GnRHa treatment) or action (flutamide treatment); and (vii) the adverse changes induced by high-dose DES (iv and v) can be largely prevented by co-administration of testosterone. Thus, it is suggested that many of the adverse changes to the testis and reproductive tract induced by exposure to oestrogens result from a combination of high oestrogen and low androgen action. High oestrogen action or low androgen action on their own are unable to induce the same changes.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Microbicidal properties of a silver-containing hydrofiber dressing against a variety of burn wound pathogens.

Partial-thickness burns are often characterized by microbial contamination and copious exudate produced during the early postburn period. Consequently, topical wound management often relies on the use of antimicrobial agents and absorbent dressings, and an AQUACEL Hydrofiber Dressing containing ionic silver has been designed to meet such needs. To assess the antimicrobial properties of the AQUACEL Hydrofiber dressing, samples were challenged with a wide variety of recognized burn wound pathogens in a simulated wound fluid model. Dressing samples were inoculated with the challenge organisms at time zero and then reinoculated on days 4 and 9 to mimic the worst-case clinical scenario. The dressing was shown to be microbicidal against aerobic and anaerobic bacteria (including antibiotic-resistant strains), yeasts, and filamentous fungi during a 14-day test period. Based on our results, the silver-containing dressing is likely to provide a barrier to infection, in addition to providing proven fluid-handling benefits of the AQUACEL Hydrofiber dressing, in the management of partial-thickness burns.

Anti-Bacterial Agents↗
PubMedDate not supplied

Diabetic neuropathic bladder associated with clinical features of iliofemoral venous thrombosis.

A 60-year-old female diabetic patient with autonomic neuropathy gradually developed a warm swollen left leg over a period of 12 days. She was found to have chronic retention of urine due to a neuropathic bladder. Venography did not reveal thrombus but showed compression of the ipsilateral external iliac vein by the bladder. No other cause for her warm swollen leg was found. Following the introduction of a bladder catheter, her leg gradually returned to normal.

Diabetes Mellitus, Type 1↗
PubMedDate not supplied

Short-bowel syndrome in four dogs.

Short bowel syndrome occurred in four dogs after extensive (74% to 88%) small intestinal resection. Weight loss and diarrhea were the principal clinical signs. Treatment was based on the severity of clinical signs. One dog is alive after 27 months. Three dogs died within 3 months. The prognosis depends on the extent and site of resection, degree of intestinal adaptation, preoperative condition, and postoperative care.

Anastomosis, Surgical↗