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Biomedical subjects

G Howard

Publications and source records attributed to G Howard.

At least 109 records · Page 6Linked to original sources

A prospective reevaluation of transient ischemic attacks as a risk factor for death and fatal or nonfatal cardiovascular events.

BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) is generally considered a risk factor for death and cardiovascular events. This assumption is based on comparisons of the survival of the TIA population with that of the general population. Such comparisons may provide biased estimates of the risk associated with TIA because the general population is usually more healthy than TIA patients. METHODS: Using a prospective case-control study design, we report the comparison of a TIA population (n = 280) and a control group (n = 399) with a comparable cardiovascular risk factor burden. Proportional hazards analysis was used to compare survival time and time to fatal or nonfatal stroke and/or myocardial infarction for the two study groups. Comparisons were made without adjustment for risk factors and after adjustment for age, race, sex, and major cardiovascular risk factors. RESULTS: Before adjustment for age-race-sex or risk factors, TIA proved to be a risk factor for early mortality, stroke, and myocardial infarction (P < .05). Adjustment for age-race-sex disparities between the case and control groups explained much of the differences in mortality, as the hazard ratio was reduced from 2.2 to 1.4. However, adjustment for age-race-sex or age-race-sex and risk factors did not markedly reduce the role of TIA as a risk factor for stroke or myocardial infarction. CONCLUSIONS: Although TIA proved to be a risk factor for stroke or myocardial infarction, it apparently plays a smaller role in the risk of death.

Age Factors↗

Relations of intimal-medial thickness among sites within the carotid artery as evaluated by B-mode ultrasound. ARIC Investigators. Atherosclerosis Risk in Communities.

BACKGROUND AND PURPOSE: B-mode ultrasound is a widely used technique for the clinical and epidemiological assessment of carotid atherosclerosis. This article describes the relation between arterial intimal-medial thickness (IMT) at different sites within the extracranial carotid artery. METHODS: IMT was measured by B-mode real-time ultrasound as an index of atherosclerotic involvement in the extracranial carotid arteries as part of the population-based Atherosclerosis Risk in Communities (ARIC) study. The relation between IMT at different sites was described by correlation coefficients and percentile regression techniques based on between 4034 and 9386 pairs of measurements (variation in sample size depending on the paired sites). RESULTS: Increased IMT at one site was associated with increased IMT at other sites. The correlation between right and left IMT at the same anatomic location in the carotid artery ranged from .34 to .49; the correlation at different anatomic locations in the carotid artery on the same side ranged from .25 to .43. The distribution of IMT, described by the percentiles of IMT at the inference site as a function of IMT at the index site, showed constricted percentiles of IMT at the inference site for small IMT at the index site and an increase in the spread of percentiles with increasing IMT. CONCLUSIONS: Although increased carotid IMT at one site is positively associated with thickened walls at other carotid sites, the ability to accurately predict wall thickness at a site given the wall thickness at other sites is modest. The general association between sites supports the systemic nature of atherosclerosis, while the lack of tight agreement between sites supports the focal nature of the atherosclerotic process.

Arteriosclerosis↗

Spatial distribution of carotid intimal-medial thickness as measured by B-mode ultrasonography.

BACKGROUND AND PURPOSE: Measurements of intimal-medial thickness (IMT) of the carotid artery by B-mode ultrasonography are widely used as markers of atherosclerosis. This report describes empirical features of these measurements to characterize their distribution within arterial wall segments, to explore their potential as study outcome measures, and to examine their links with traditional risk factors for cardiovascular disease. METHODS: Sequential transverse measurements of IMT in the carotid arteries were made in 899 participants from the Asymptomatic Carotid Artery Progression Study (ACAPS) at baseline. Data from 17 intrasegment sites in each of 12 arterial wall segments were used to describe patterns of thickness and visualization and to characterize cross-sectional area, severity, and roughness/irregularity by the intrasegment averages, maxima, and SDs of IMT, respectively. RESULTS: Serial correlations of IMT measurements indicated localized and diffuse features of disease. The spatial distribution of IMT had two dominant features: overall mass and mass relative to roughness. The validity of these features was demonstrated by their correlation to known risk factors for carotid atherosclerosis: body mass index, age, high-density lipoprotein cholesterol, systolic blood pressure, smoking, and sex. CONCLUSIONS: Both the mean and maxima of intrasegment measurements appear to be good candidates for use in clinical studies. B-mode ultrasonography has validity for the description of IMT roughness and shape. Both of these features are linked to cardiovascular risk factors, which supports the multifaceted nature of atherosclerosis.

Adult↗

Galanin: a novel intraovarian regulatory peptide.

Galanin is a 29-amino acid peptide that acts as a neuropeptide in many tissues. To date, galanin action and the hormonal regulation of galanin gene expression have not been described in the ovary of any species. To study possible ovarian expression and regulation of galanin, immature gonadotropin-primed rats were given hCG (10 IU), and their ovaries were collected 0, 4, 8, 12, and 20 h after hCG treatment for determination of galanin messenger RNA (mRNA) concentration by solution hybridization. Galanin mRNA levels progressively increased after hCG administration, peaking at 12 h (2.4-fold increase vs. 0 h), with a subsequent return to 0 h levels at 20 h. To determine a possible ovarian role for galanin, rats were killed 48 h after gonadotropin administration, their ovaries were removed, and granulosa cells were harvested. These cells and the ovarian tissue remaining after granulosa cell collection (i.e. "shells") were each cultured for 24 h with increasing concentrations of galanin (0, 10, 100, and 1000 nM) in the presence or absence of LH. The medium was examined for steroid production and metalloproteinase inhibitor activity. In granulosa cell cultures, galanin increased the levels of estradiol by 26% and had no effect on progesterone, but decreased metalloproteinase inhibitor activity by 61% in the conditioned medium. In the shell cultures, galanin increased estradiol, progesterone, and androstenedione in the medium, suggesting that galanin acts on cells other than granulosa cells or that galanin action requires a paracrine interaction between granulosa and thecal cells. Our data demonstrate that galanin message is increased by hCG, and that galanin acts to amplify ovarian steroidogenesis while decreasing metalloproteinase inhibitor activity. These findings establish that ovarian galanin mRNA is hormonally stimulated and that galanin acts as an intraovarian regulatory peptide.

Animals↗

Decline in stroke mortality in North Carolina. Description, predictions, and a possible underlying cause.

Data from the National Center for Health Statistics were used to describe the decline in age-adjusted stroke mortality rates from 1962 to 1987 for North Carolina and for six regions of the state. For the state as a whole, stroke mortality decreased from 0.0050 to 0.0018 (64% decrease) for white males, 0.0039 to 0.0016 (59% decrease) for white females, 0.0072 to 0.0030 (58% decrease) for black males, and 0.0064 to 0.0025 (61% decrease) for black females. Under the hypothesis that the rate of decline in stroke mortality will slow and approach a "floor," a four-parameter logistic model was fit to the data. This model suggests that most of the decline in North Carolina stroke rates had occurred by 1987 and that the rates are now approaching the floor. For example, the estimated 1987 white male stroke mortality rate was 0.00190 and the floor 0.00176, suggesting only a 7% decline in the future. Similar percentage differences between 1987 levels and the floor were estimated for the three other race-gender groups. This analysis also suggested that while the absolute disparity by sex and race decreased between 1962 and 1987, the ratio of black to white mortality rates and the ratio of male to female mortality rates remained relatively constant. Estimates of 1-year case-fatality rates from two surveys of hospitalized stroke patients in a high-mortality five-county region of North Carolina decreased from 51% in 1970 to 38% in 1980. This decrease in stroke fatality rate is sufficient to account for 64% of the decrease in mortality estimated for this region over the same period.

Black People↗

In vitro validation of color velocity imaging and spectral Doppler for velocity determination.

Color velocity imaging (CVI) is a new non-Doppler ultrasound technique for vascular color flow imaging. Using information contained in the two-dimensional B-mode, gray-scale image to determine velocity, CVI offers potential advantages over Doppler color flow imaging methods. In order to be used clinically, velocity determination with CVI must be validated by other current methods. A Doppler string phantom was studied with a Philips CVI ultrasound system. Velocity measurements were obtained by both CVI and duplex Doppler spectral analysis for constant string speeds from 10 to 200 cm/sec, at intervals of 10 cm/sec. Twenty separate estimates were obtained with each method, at each string speed. Linear regression assessed the relationship between estimated and actual string velocities, with CVI and spectral Doppler analysis yielding highly valid results (CVI = -0.713 + 1.000997 x phantom; r 2 = 0.9979). At all string speeds tested, the averaged estimated and the actual velocities for both methods were within the 95% confidence estimates. The range for the CVI 95% confidence limits from the regression line varied from +/-1.07 cm/sec at the lowest speed of 10 cm/sec (11.6%) to +/-7.72 cm/sec at 200 cm/sec (3.87%). Based on in vitro testing, CVI is as accurate as Doppler spectral analysis for the estimation of flow velocity.

Blood Flow Velocity↗

Carotid artery intimal-medial thickness distribution in general populations as evaluated by B-mode ultrasound. ARIC Investigators.

BACKGROUND AND PURPOSE: B-mode ultrasound is a widely used technique for the clinical and epidemiological assessment of carotid atherosclerosis. This article provides a description of the distribution of carotid atherosclerosis in the general population. METHODS: Intimal-medial arterial wall thickness was measured by B-mode real-time ultrasound as an index of atherosclerotic involvement in the extracranial carotid arteries as part of the population-based Atherosclerosis Risk in Communities (ARIC) study. The distribution was described by race-sex strata, in which 759 to 4952 individuals were imaged depending on strata and location in the carotid system. RESULTS: Median wall thickness ranged between 0.5 and 1 mm at all ages; fewer than 5% of ARIC participants had values exceeding 2 mm. Individuals tended to have a larger wall thickness in the carotid bifurcation than in the common carotid artery. Internal carotid artery values were more variable, with higher proportions of both large and small wall thicknesses than in the common carotid. The proportion of individuals with a large wall thickness was greatest at the bifurcation and smallest at the common carotid artery. Men had uniformly larger wall thickness than women. Cross-sectional analysis suggests that age-related increases in wall thickness average approximately 0.015 mm/y in women and 0.018 mm/y in men in the carotid bifurcation, 0.010 mm/y for women and 0.014 mm/y for men in the internal carotid artery, and 0.010 mm/y in both sexes in the common carotid artery. CONCLUSIONS: Estimates provided for wall thickness percentiles can serve as "nomograms" by age, race, and sex.

Arteriosclerosis↗

MtTW-10 pituitary tumor cells: galanin gene expression and peptide secretion.

The peptide galanin is synthesized within and secreted from specific cell types of the rat anterior pituitary gland. The small size of the rat anterior pituitary gland is somewhat limiting for studying the regulation of galanin gene expression and peptide synthesis/secretion. We examined the mammotropic rat pituitary tumor MtTW-10 as a possible model system to study galanin. The objectives of this study were to 1) determine if galanin is secreted from MtTW-10 cells in vitro in a regulated manner, 2) characterize the molecular forms of immunoreactive galanin secreted by MtTW-10 cells, and 3) assess whether galanin gene expression in MtTW-10 tumors is regulated by estradiol. MtTW-10 pituitary tumors were transplanted to female Wistar-Furth rats that were implanted with estradiol-filled capsules. Cells were harvested from the MtTW-10 tumors and cultured for 4 days. When examined by electron microscopy, the MtTW-10 cells maintained in culture were irregular in shape with microvilli on their surface and contained numerous large secretory granules. Immunoreactive galanin, PRL, and GH were secreted from the cells in a time-dependent fashion during static incubations. LH, ACTH, and TSH were undetectable in the culture medium. Somatostatin (10 and 100 nM) inhibited galanin, PRL, and GH release in a dose-dependent manner. In contrast, dopamine, TRH, LH-releasing hormone, CRH, and GH-releasing hormone at concentrations of 10-100 nM failed to alter hormone secretion. Only high concentrations of dopamine (1 microM) inhibited the secretion of galanin, PRL, and GH. HPLC fractionation of peptides secreted by MtTW-10 cells cultures showed that approximately 84% of the galanin immunoreactivity coeluted with synthetic rat galanin. In tumor-bearing rats, plasma levels of immunoreactive galanin were 10-fold higher after estradiol treatment than levels in ovariectomized controls. Galanin mRNA levels were increased 20-fold by estradiol in MtTW-10 tumors, as determined by solution hybridization, and peptide levels were elevated nearly 100-fold. We conclude that 1) galanin is secreted from MtTW-10 cells in vitro, and its secretion is inhibited by somatostatin; and 2) estradiol increases galanin gene expression and peptide secretion in MtTW-10 tumors in vivo. These data show that MtTW-10 tumors may be useful to study the regulation of pituitary galanin gene expression, peptide synthesis, and secretion.

Animals↗

1993--the year of living safely.

The Employment Bill aims to safeguard the rights of pregnant workers and those victimised at work on the grounds of health and safety. Gillian Howard, a barrister and industrial relations consultant, examines the new regulations.

Female↗

The neuromuscular basis of hereditary kyphoscoliosis in the mouse.

We describe a new neuromuscular disorder in the kyphoscoliotic mouse mutant (ky). Mice were killed at ages from birth to 210 days, and tissues were taken for standard light microscopy, histochemistry, nerve ending studies, and electron microscopy. At birth a few myofibers showed phagocytosis ultrastructurally. Between 6 and 25 days there was prominent necrosis and regeneration in soleus, gracilis, paraspinal, and back muscles. At 47 days, these muscles were atrophic and necrosis and regeneration were rare. At 136 days, all muscle groups, including head muscles, showed some degree of myofiber atrophy and gracilis was fibrotic. Prominent intramuscular axonal sprouting was present from 31 days. Peripheral nerves and anterior horn cells were normal. The findings indicate a neuromuscular basis of hereditary kyphoscoliosis in the mouse. The animal may be useful as a model of human muscle disease and scoliosis.

Animals↗