Biomedical subjects

D W Smith

Publications and source records attributed to D W Smith.

At least 127 records · Page 7Linked to original sources

PubMed1995

Evolution of longevity in mammals.

Maximum life span is a characteristic of each species, and a diversity of maximum species life spans is seen in each mammalian order. It is argued here that different clusters of related long-lived species evolved independently. A variety of genes could have been involved such as genes for somatic maintenance and genes for resistance to causes of death, including fatal diseases. There are explanations based on natural selection for the long maximum human life span, half of which is post-reproductive.

Animals↗

PubMed1995

beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity.

In several pedigrees of early onset familial Alzheimer's disease (FAD), point mutations in the beta-amyloid precursor protein (APP) gene are genetically linked to the disease. This finding implicates APP in the pathogenesis of Alzheimer's disease in these individuals. To understand the in vivo function of APP and its processing, we have generated an APP-null mutation in mice. Homozygous APP-deficient mice were viable and fertile. However, the mutant animals weighed 15%-20% less than age-matched wild-type controls. Neurological evaluation showed that the APP-deficient mice exhibited a decreased locomotor activity and forelimb grip strength, indicating a compromised neuronal or muscular function. In addition, four out of six homozygous mice showed reactive gliosis at 14 weeks of age, suggesting an impaired neuronal function as a result of the APP-null mutation.

Amyloid beta-Protein Precursor↗

PubMed1995

An outbreak of Barmah Forest virus disease in the south-west of Western Australia.

OBJECTIVES: To describe the first reported outbreak of Barmah Forest (BF) virus disease in the south-west of Western Australia. DESIGN: Case series correlated with results of arbovirus surveillance. All patients with clinically suspected Ross River (RR) virus infection were serologically tested for antibodies to BF and RR viruses. Home address and date of presentation of patients with serologically confirmed recent infection were recorded. Mosquitoes collected from the districts before and during the BF virus outbreak were identified to species level and tested for virus. RESULTS: Twenty-two cases of BF disease were reported from the region between August 1992 and March 1994. Most occurred in the Peel region in the spring and early summer of 1993. Eighteen isolates of BF virus were obtained from three different species of mosquito trapped between January and October 1993. Fifteen were from mosquitoes in the Peel region and a single isolate was from the Perth metropolitan area. No isolates were obtained from the region before 1993. RR virus was not isolated from mosquitoes trapped in the region during the BF virus outbreak. CONCLUSIONS: Most BF infections were acquired in the Peel region during spring and early summer of 1993. Aedes camptorhynchus mosquitoes were probably the main vectors. The lack of isolations from mosquitoes before 1993 suggests that the virus may have only recently been introduced (or reintroduced) to the region. It was transmitted under conditions that were apparently not conducive to transmission of RR virus.

Adolescent↗

PubMed1995

Venous catheter thrombus formation and pulmonary embolism in children.

Central venous catheter (CVC)-related thrombus formation has been increasingly recognized as a complication in adults and somewhat less frequently in children and neonates. However, the association of CVC thrombus and pulmonary embolism (PE) has rarely been reported in infants or children, and the few existing reports primarily involve chronic, indwelling CVCs such as Broviac or Hickman catheters. During an 18-month-period of autopsy review, we found that 5 of our pediatric intensive care unit patients had autopsy-proven CVC thrombus and pulmonary embolism. All of them had prolonged mechanical ventilation for respiratory failure and required insertion of one or more short-term, temporary CVCs during the course of routine critical care management. In retrospect, signs related to CVC thrombus were present in 4 patients (3 had positive blood cultures and 1 had persistent hypertension). PE was not diagnosed until autopsy in every case. The diagnosis may have been missed because the symptoms of PE are the same as those of severe lung disease. We, therefore, advocate a heightened suspicion of CVC thrombus formation and PE in critically ill children with respiratory failure and temporary CVCs and recommend early diagnostic ultrasound to confirm the diagnosis. Once a CVC thrombus is found, subsequent pulmonary deterioration may necessitate evaluation for acute PE.

Catheterization, Central Venous↗

PubMed1995

Personality characteristics of father/perpetrators and nonoffending mothers in incest families: individual and dyadic analyses.

Clinical reports suggest that mothers and fathers in incestuous families exhibit characteristic personality traits. Typically the father/perpetrator is described as powerful and domineering, the mother weak and submissive. The present study examined individual personality characteristics of 65 nonoffending mothers and 94 father/perpetrators, and used canonical correlations and multiple regression analyses to examine patterns of personality traits occurring in 63 pairs of fathers and mothers in which there was acknowledged child sexual abuse by the fathers. At the individual level, a minority of both mothers and offenders differed from norms on traits reflecting social inadequacy, but no personality deviations were prototypical in either group. At the dyadic level, no evidence for a pervasive "dominant-submissive" pairing was found. Results indicated that father/perpetrator traits tended to be similar to traits of nonoffending mothers. Forensic, clinical, and research implications of the findings are discussed.

Adolescent↗

PubMed1995

Microminiature molding techniques for cochlear electrode arrays.

We provide a general method for producing a variety of small, complex electrode arrays based on injection molds produced using computer-aided drafting and machining (CAD-CAM) procedures and a novel method for connecting to the very fine electrical leads associated with the individual contacts of such arrays. Cat-sized cochlear electrode arrays with up to eight contacts were built according to these methods and their electrical contacts were characterized in vitro by impedance spectroscopy and in vivo by monitoring impedance for over 1 year of intermittent stimulation in chronically instrumented animals.

Animals↗

PubMed1995

Three-dimensional quantitative autoradiography by disparity analysis: theory and application to image averaging of local cerebral glucose utilization.

Traditional autoradiographic image analysis has been restricted to the two-dimensional assessment of local cerebral glucose utilization (LCMRglc) or blood flow in individual brains. It is advantageous, however, to generate an entire three-dimensional (3D) data set and to develop the ability to map replicate images derived from multiple studies into the same 3D space, so as to generate average and standard deviation images for the entire series. We have developed a novel method, termed "disparity analysis," for the alignment and mapping of autoradiographic images. We present the theory of this method, which is based upon a linear affine model, to analyze point-to-point disparities in two images. The method is a direct one that estimates scaling, translation, and rotation parameters simultaneously. Disparity analysis is general and flexible and deals well with damaged or asymmetric sections. We applied this method to study LCMRglc in nine awake male Wistar rats by the [14C]2-deoxyglucose method. Brains were physically aligned in the anteroposterior axis and were sectioned subserially at 100-microns intervals. For each brain, coronal sections were aligned by disparity analysis. The nine brains were then registered in the z-axis with respect to a common coronal reference level (bregma + 0.7 mm). Eight of the nine brains were mapped into the remaining brain, which was designated the "template," and aggregate 3D data sets were generated of the mean and standard deviation for the entire series. The averaged images retained the major anatomic features apparent in individual brains but with some defocusing. Internal anatomic features of the averaged brain were smooth, continuous, and readily identifiable on sections through the 3D stack. The fidelity of the internal architecture of the averaged brain was compared with that of individual brains by analysis of line scans at four representative levels. Line scan comparisons between corresponding sections and their template showed a high degree of correlation, as did similar comparisons performed on entire sections. Fourier analysis of line scan data showed retention of low-frequency information with the expected attenuation of high-frequency components produced by averaging. Region-of-interest (ROI) analysis of the averaged brain yielded LCMRglc values virtually identical to those derived from measurements and subsequent averaging of data from individual brains.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1995

Improving residents' knowledge of cancer prevention: are physicians prepared for prevention?

BACKGROUND: Primary care physicians recognize the goal of integrating cancer-prevention strategies into clinical practice. However, there is little formal training in cancer prevention and early detection. This study describes the effectiveness of a cancer-prevention curriculum called "Recommendations for Cancer Prevention (ReCaP) for Residents" for primary care residency programs. METHODS: The ReCaP for Residents curriculum was organized into eight instructional modules by organ site-specific areas for which there are established primary and secondary cancer-prevention recommendations. The modules include content outlines, learning objectives, slides, and case studies. In-house faculty and 21 residents of two family practice programs participated in an intervention comprising seven one-hour modular presentations during their regular summer teaching program. An established cancer-prevention knowledge test with 100 test items was used to test the residents' knowledge before and after the intervention; the data were analyzed by factor analysis with principal-component extraction and varimax rotation. RESULTS: The residents knew significantly more about cancer prevention after the ReCaP for Residents program. The mean overall prevention knowledge increased significantly (p < .05), and the scores of six of eight specific organ-site areas also increased. CONCLUSION: This study provided evidence that ReCaP for Residents was an effective curriculum for increasing residents' knowledge of cancer prevention. The authors recommend that more extensive programs of this type be implemented.

Curriculum↗

PubMed1995

Opinions of rural Texas parents concerning elementary school health education.

Parents of elementary school children in rural east-central Texas were surveyed about their attitudes toward and knowledge of Comprehensive School Health Education. Data indicated widespread support for health education compared to other subject areas. Parents felt alcohol and other drugs, nutrition, and first aid were the most important topics to be covered in elementary school, while sexuality, cancer, and stress were the least important. Parents were most comfortable discussing alcohol and other drugs, family life, and growth and development with their children and least comfortable discussing exercise, cancer, and sexuality. Implications for school health programs are discussed.

Attitude↗

PubMed1995

Behavioral auditory thresholds for sinusoidal electrical stimuli in the cat.

Behavioral thresholds were measured in four cats by training them to respond behaviorally to acoustic auditory stimuli using food as a reward in an operant reinforcement paradigm. Following training, the subjects were implanted unilaterally with either a scaled-UCSF electrode containing four contacts or an electrode array containing eight intracochlear contacts and one extracochlear contact under temporalis muscle. Behavioral thresholds for electrical stimuli were obtained as a function of sinusoidal frequency, duration, and electrode configuration. Threshold functions for both electrode types and all animals had minima between 48 and 125 Hz and, in general, were relatively flat below this minima; functions increased at 3-6 dB/octave from 96 Hz to 1 kHz. Threshold varied predictably as a function of electrode configuration, with thresholds decreasing as much as 20 dB as electrode spacing was widened from a radial bipolar (200-microns separation) to a monopolar configuration (apical stimulating and temporalis return). With long-duration stimuli, increasing the electrode separation systematically increased the slope of the threshold-versus-frequency contours in all animals. Irrespective of electrode type or configuration, charge/phase thresholds for single-cycle sinusoids were relatively flat for stimulus periods up to 1-5 ms, approximating a constant charge/phase determination of threshold. At phase durations greater than 5 ms, charge thresholds increased at a rate slightly above 6 dB/octave (constant peak current), which was suggestive of neural accommodation. Thresholds for the cat share many features with those reported for implanted humans and monkeys.

Acoustic Stimulation↗

PubMed1995

Rat vasopressin cell responses to simulated hemorrhage: stimulus-dependent role for A1 noradrenergic neurons.

c-fos expression mapping and electrophysiological recording experiments were done to clarify the role of the A1 noradrenergic cell group in the vasopressin response to hypotensive hemorrhage. In pentobarbital-anesthetized rats, moderate and severe hypotensive hemorrhages were simulated by brief occlusion of the inferior vena cava sufficient to reduce mean arterial pressure to approximately 50 or 30 mmHg, respectively. Both stimuli significantly increased the number of A1 region catecholamine cells displaying Fos-like immunoreactivity, this effect being most prominent at the level of the area postrema. Both stimuli also increased the number of supraoptic nucleus vasopressin cells displaying Fos-like immunoreactivity. Accordingly, electrophysiological studies involving separate animals confirmed that both moderate and severe caval occlusion significantly increased the firing of functionally identified vasopressin cells recorded in the supraoptic nucleus. However, although interruption of A1 region neuronal function by injection of gamma-aminobutyric acid at the level of the area postrema eliminated the increase in vasopressin cell firing elicited by moderate caval occlusion, it did not block the response to severe caval occlusion. These findings suggest that, in the rat, the vasopressin response to an acute reduction in central blood volume, such as that produced by hemorrhage, depends on the A1 projection only if the stimulus is of moderate intensity. Severe stimuli appear to involve activation of both the A1 projection and an additional vasopressin-stimulatory pathway that bypasses the A1 region.

Animals↗

PubMed1995

Power and spirituality in polio survivors: a study based on Rogers' science.

Rogers' model was used to study patterns of power and spirituality in polio survivors (n = 172) and people who have not had polio (n = 80). Participants completed the Power as Knowing Participation in Change Test and the Spiritual Orientation Inventory. Power was positively related to spirituality (r = .34, p < .005). Polio survivors manifested the same power (t = .44, df = 250, p = .33) and greater spirituality than people who had not experienced polio (t = 3.79, df = 250, p < .001), indicating that patterns of human field change are related to surviving polio. Recommendations include replicating this study with other populations and continuing to develop a theory of spirituality within Rogers' framework.

Adaptation, Psychological↗

PubMed1995

High sun protection factor sunscreens in the suppression of actinic neoplasia.

BACKGROUND AND DESIGN: A controlled trial was undertaken from December 1987 to December 1990 to test the hypothesis that a strong sunscreen can reduce the number of cancerous and precancerous skin lesions. Candidates were selected from a high-risk population attending either a university- or Veterans Affairs-based dermatology practice in Lubbock, Tex, for a prospective, double-blind, controlled trial of daily application of sunscreen vs placebo over a 2-year period. Participants were asked to volunteer if they had demonstrated premalignant changes (actinic keratoses) or nonmelanoma skin cancer (basal cell carcinoma or squamous cell carcinoma), had continuing sun exposure, and were not using sunscreen on a regular basis. Fifty-three volunteers were initially enrolled in the study, and 37 came for the final 24-month visit. RESULTS: The rate of appearance of new precancerous skin lesions was less for the treatment group than for control subjects. People with darker skin had fewer actinic keratoses, women had fewer lesions than men, and people with fewer lesions at enrollment had fewer lesions during the study. The numbers of new nonmelanoma skin cancers appearing during the study period were too small for statistical analysis. CONCLUSIONS: The regular use of sunscreens can significantly reduce cutaneous neoplasia, as indicated by its suppression of precancerous lesions. A longer and/or larger study would be necessary to demonstrate an effect on malignant lesions.

Adult↗

PubMed1995

Role of ventrolateral medulla catecholamine cells in hypothalamic neuroendocrine cell responses to systemic hypoxia.

Systemic hypoxia stimulates the release of vasopressin (VP) and adrenocorticotropin hormone (ACTH). To examine the involvement of catecholamine cell groups of the ventrolateral medulla (VLM) in the neuroendocrine responses, we have used the c-fos activity mapping technique to compare the effects of hypoxia on VLM catecholamine cells to those on neurosecretory VP and putative corticotropin releasing factor (CRF) containing cells. A limited degree of catecholamine cell activation was evident at predominantly mid-VLM levels at 12% oxygen in the inspired air. Further reduction in inpsirate oxygen levels enhanced recruitment of caudally located VLM catecholamine cells considered to form part of the A1 noradrenergic cell group. Threshold for activation of VP and putative CRF cells occurred at the 10% oxygen level. Unexpectedly, this stimulus also activated neurosecretory oxytocin (OT) cells. With increasing hypoxic severity the number of activated supraoptic VP and OT cells was not significantly different to that observed at the 10% level. However, paraventricular neuroendocrine responses continued to increase with putative CRF containing cells of the medial parvocellular zone having nearly double the level of activity (as measured by the number of cells within this region displaying Fos-like immunoreactivity; FLI) at 6% compared to that apparent to the 10% level of hypoxia. Paraventricular VP cells displaying FLI were also increased at the most severe levels of hypoxia but this effect was much less marked than the medial parvocellular response. Consistent with a role for VLM catecholamine cells in generation of neuroendocrine cell responses to hypoxia, unilateral VLM lesions, restricted to the caudal two thirds of the catecholamine cell column, resulted in significant reductions in the responses of all three cell types. These results, in addition to establishing a role for VLM catecholamine cells in neuroendocrine cell responses to systemic hypoxia, have important general implications for catecholamine cell group involvement in neuroendocrine regulation.

Animals↗

PubMed1994

Rapid, reversible elimination of medial olivocochlear efferent function following single injections of gentamicin in the guinea pig.

Measurements were made of the ability of nonsimultaneous, contralaterally presented broadband noise maskers to suppress ipsilaterally-evoked compound action potentials (CAPs) of the auditory nerve to 8-kHz tone pips in guinea pigs. Contralateral acoustic stimuli have been shown to suppress responses to ipsilateral stimuli through the action of the medial olivocochlear efferent bundle. In this study, maximum suppression across subjects ranged from 2-6 dB. The ability of the contralateral noise to suppress ipsilateral CAPs was rapidly reduced beginning within minutes of a single intramuscular injection of the aminoglycoside antibiotic gentamicin (150 mg/kg), and, in general, was completely abolished by 1.5-2 h. Changes in suppression were presumably produced by gentamicin-induced blockade of presynaptic calcium channels on the medial olivocochlear efferents and closely follow the pharmacokinetics of gentamicin in perilymph. Reductions in efferent-mediated suppression were observed in the absence of any measurable change in either CAP thresholds to different frequencies or CAP input/output. Suppression was partially restored in some animals after 24 h, and was fully recovered in all subjects within 96 h postinjection. The present studies suggest that measures of efferent function might form the rational basis for an objective means to assess aminoglycoside insult on the cochlea in the absence of hair cell damage. These results also indicate that single injections of gentamicin offer a reversible, non-invasive model in which medial efferent function can be studied in behavioral animals.

Acoustic Stimulation↗

PubMed1994

Evaluating risk adjustment by partitioning variation in hospital mortality rates.

The variation in mortality rates among hospitals has often been described informally as having three major components: patient severity, quality of care and random variation. These informal concepts are characterized formally by partitioning sums of squares and finding their expected values. The partition relates to commonly used tests for whether individual hospitals have unusual mortality rates. Application of the partition to the hospital mortality reports by the Health Care Financing Administration shows that their models for patient risk account for about one-half the variation among hospital mortality rates. An example using clinical measures of severity accounts for about two-thirds of mortality variation among hospitals.

Confounding Factors, Epidemiologic↗

PubMed1994

The tails of survival curves.

This article focuses on the occasional individuals of many species that live longer than is usual for their populations--here called longevity outliers. They appear to be exceptions to the usual patterns of mortality rates that increase with age. There is no model of survivorship that accommodates all of these individuals. They are less vulnerable to the usual causes of death than most in their populations. There are hints of genetically based mechanisms in the form of life-prolonging genes in invertebrates and genetic resistance to fatal diseases in higher organisms. The reasons why longevity outliers ultimately die are not known. Based on well-established trends, I predict that there will be many more humans reaching very old ages in the next century.

Animals↗

PubMed1994

Small intestinal microcirculatory effects of octreotide.

Somatostatin and its analogue, octreotide acetate, are thought to decrease mesenteric blood flow; however, it is unknown whether the decrease occurs at the central, regional, or microvascular level. We hypothesized that the circulatory effects of octreotide are regulated at the microvascular level. Changes in superior mesentery artery (SMA) flow in response to octreotide were measured with a perivascular ultrasonic flow probe. In separate experiments, the jejunal microcirculatory effects of octreotide were studied using in vivo videomicroscopy. After accrual of baseline hemodynamic and microcirculatory data, animals were randomized to control or treatment (10 micrograms/kg octreotide) iv groups. Measurements were made every 15 min during the infusion and for 90 min after the completion of the infusion. Results are expressed as means +/- SEM. Intravenous infusion of octreotide caused no significant change in arterial pressure, cardiac index, or systemic vascular resistance index in either group in either set of experiments. A statistically significant decrease in heart rate (9%) occurred in the control group of animals undergoing SMA flow measurement. SMA flow did not change significantly with infusion of octreotide. In contrast, jejunal first-order arteriole flow increased to 117.9 +/- 9.7% of baseline (P < 0.05) in the absence of significant changes in microvessel diameters. This was due to an increase in centerline red cell velocity (116 +/- 5% of baseline, P < 0.05). We conclude that octreotide increases jejunal first order arteriole flow by mechanisms that are regulated at the microcirculatory level.

Animals↗