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Biomedical subjects

W Smith

Publications and source records attributed to W Smith.

At least 163 records · Page 9Linked to original sources

Chronic nonpulsatile blood flow. II. Hemodynamic responses to progressive exercise in calves with chronic nonpulsatile biventricular bypass.

We investigated the effects of stepwise treadmill exercise on animal (calf) hemodynamic variables during chronic nonpulsatile biventricular bypass with ventricular fibrillation. Seven days was allowed for recovery from the effects of anesthesia and surgery; each animal's natural heart was then fibrillated. The pump flows were maintained at nominal rates of 90, 100, and 120 ml.kg-1.min-1 for 1 week each, with the order varying from experiment to experiment. A total of 30 incremental exercise tests were performed on five animals. No significant changes in mean aortic pressure were observed during nonpulsatile perfusion at the three nominal flow rates of nonpulsatile flow either before or during exercise. The systemic vascular resistance decreased significantly during exercise (from 705 +/- 22 to 547 +/- 81 dyne.sec.cm-5, p < 0.01, and from 604 +/- 25 to 510 +/- 15 dyne.sec.cm-5, p < 0.05, at nominal flow rates of 100 and 120 ml.kg-1.min-1, respectively). There were also significant (analysis of variance, Scheffe test, p < 0.05) differences in systemic vascular resistance among three nominal flow rates both before and during exercise. These results suggest that the autonomic nerve reflex control of the cardiovascular system in physical exercise was functioning normally in animals with chronic nonpulsatile blood flow.

Animals↗

Chronic nonpulsatile blood flow. III. Effects of pump flow rate on oxygen transport and utilization in chronic nonpulsatile biventricular bypass.

The relationship between blood flow and oxygen transport was studied in five calves with chronic nonpulsatile biventricular bypass. Seven days was allowed for recovery from the effects of anesthesia and operation; the natural heart was then fibrillated. Pump flows were maintained at nominal rates of 90, 100, or 120 ml.kg-1.min for 1 week each, with the sequence varied from experiment to experiment. Venous and arterial blood samples were taken at rest for blood gas analysis. Serum lactate analysis was done twice a week, on the third and seventh days after each pump flow change. Serum catecholamine levels were assayed on the seventh day of each flow rate. Progressive exercise tests were also conducted during each test segment. Basal oxygen consumption of a 4-month-old calf was 6.3 +/- 0.3 ml.kg-1.min-1. The mixed venous oxygen tension decreased when pump flow rate was reduced (29.6 +/- 1.0, 28.3 +/- 1.2, and 23.8 +/- 0.9 mm Hg at 120, 100, and 90 ml.kg-1.min-1 of pump flow, respectively), and oxygen extraction increased linearly when pump flow rate was reduced. Hemoglobin concentration significantly affected oxygen extraction rate. Serum lactate concentration increased significantly at a 90 ml.kg-1.min-1 perfusion compared with concentrations at other pump flow rates (7.81 +/- 2.42 mEq/L at 90 ml.kg-1.min-1 vs 0.71 +/- 0.19 and 0.73 +/- 0.81 mEq/L at 100 and 120 ml.kg-1.min-1, respectively; p < 0.01, analysis of variance, Scheffe F test). Maximum oxygen extraction during exercise was 78%. These results suggest that a critical flow level between 90 and 100 ml.kg-1.min-1 maintains oxidative metabolism in the calf with chronic nonpulsatile flow. The resulting oxygen delivery was slightly higher than that indicated in the literature. Maximal oxygen extraction was normal.

Animals↗

Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study.

PURPOSE: The purpose of this study was to determine the prevalence of open-angle glaucoma and ocular hypertension in an Australian community whose residents are 49 years of age or older. SUBJECTS: There were 3654 persons, representing 82.4% of permanent residents from an area west of Sydney, Australia, who were examined. The population was identified by a door-to-door census of all dwellings and by closely matched findings from the national census. METHODS: All participants received a detailed eye examination, including applanation tonometry, suprathreshold automated perimetry (Humphrey 76-point test), and Zeiss stereoscopic optic disc photography. Glaucoma suspects were asked to return for full threshold fields (Humphrey 30-2 test), gonioscopy, and repeat tonometry. RESULTS: A 5-point hemifield difference on the 76-point test was found in 616 persons (19% of people tested). Humphrey 30-2 tests were performed on 336 glaucoma suspects (9.2% of population), of whom 125 had typical glaucomatous field defects. Two hundred three persons had enlarged or asymmetric cup-disc ratios (> or = 0.7 in 1 or both eyes or a cup-disc ratio difference of > or = 0.3). Open-angle glaucoma was diagnosed when glaucomatous defects on the 30-2 test matched the optic disc changes, without regard to the intraocular pressure level. This congruence was found in 87 participants (2.4%), whereas an additional 21 persons (0.6%) had clinical signs of open-angle glaucoma but incomplete examination findings. Open-angle glaucoma was thus found in 108 persons, a prevalence of 3.0% (95% confidence interval [CI], 2.5-3.6), of whom 49% were diagnosed previously. An exponential rise in prevalence was observed with increasing age. Ocular hypertension, defined as an intraocular pressure in either eye greater than 21 mmHg, without matching disc and field changes, was present in 3.7% of this population (95% CI, 3.1-4.3), but there was no significant age-related increase in prevalence. The prevalence of glaucoma was higher in women after adjusting for age (odds ratio, 1.5; CI, 1.0-2.2). There was no sex difference in the age-adjusted prevalence of ocular hypertension. CONCLUSIONS: These data provide detailed age and sex-specific prevalence rates for open-angle glaucoma and ocular hypertension in an older Australian population.

Age Distribution↗

Visual acuity and the causes of visual loss in Australia. The Blue Mountains Eye Study.

BACKGROUND: The Blue Mountains Eye Study is a population-based study of vision and the causes of visual impairment and blindness in a well-defined urban, Australian population 49 years of age and older. METHODS: The logarithm of the minimum angle of resolution (logMAR) visual acuity was measured before and after refraction in 3647 persons, representing an 88% response rate in two postcode areas in the Blue Mountains area, west of Sydney. RESULTS: Refraction improved visual acuity by one or more lines in 45% of participants and by three or more lines in 13%. Visual impairment (visual acuity 20/40 or worse in the better eye) was found in 170 participants (4.7%). Mild visual impairment (Snellen equivalent 20/40 to 20/60 in the better eye) was found in 3.4% moderate visual impairment (20/80 to 20/160 in the better eye) in 0.6%, and severe visual impairment or blindness (20/200 or worse in the better eye) in 0.7%. Visual impairment increased with age from 0.8% of persons 49 to 54 years of age to 42% of persons 85 years of age or older. Visual impairment was significantly more frequent in females at all ages. Among persons with severe visual impairment, 79% were female. After adjusting for age, females were less likely to achieve 20/20 best-corrected visual acuity than males (odds ratio, 0.57; confidence interval, 0.48-0.66). After adjusting for age and sex, no association was found between visual acuity and socioeconomic status. Age-related macular degeneration was the cause of blindness in 21 of the 24 persons with corrected visual acuity of 20/200 or worse. CONCLUSION: Increasing age and female sex were independent predictors of visual impairment.

Adult↗

DL_POLY_2.0: a general-purpose parallel molecular dynamics simulation package.

DL_POLY_2.0 is a general-purpose parallel molecular dynamics simulation package developed at Daresbury Laboratory under the auspices of the Council for the Central Laboratory of the Research Councils. Written to support academic research, it has a wide range of applications and is designed to run on a wide range of computers: from single processor workstations to parallel supercomputers. Its structure, functionality, performance, and availability are described.

Computer Simulation↗

Disturbed development of the preimplantation embryo in the insulin-dependent diabetic BB/E rat.

Although improved regulation of maternal IDDM during pregnancy has resulted in a major fall in the stillbirth rate, the rates for other problems, such as spontaneous preterm labor, fetuses small for gestational age, congenital malformation, and the incidence of large placentas, remain raised. This has suggested the possibility that the damaging effect of conventionally treated but poorly regulated IDDM may operate primarily at the earliest stages of gestation, even before the diagnosis of pregnancy has been made. This study shows that spontaneous autoimmune IDDM in the Bio Breeding/Edinburgh (BB/E) rat is associated with severe disturbance in the development of the preimplantation embryo in a majority of pregnancies, as indicated by a fivefold increase in the incidence of degenerate fragmented embryos and a 33% reduction in the number of expanded blastocysts and in those blastocysts that reach the expanded stage a 20% cellular deficit in the inner-cell mass without any change in trophectoderm cell number. In addition, we find that blastocysts removed from diabetic rats and cultured in vitro for 24 h show no sign of "catch-up" growth of the inner-cell mass, although under these conditions, the trophectoderm exhibits a 25% cellular accretion. It is tempting to speculate that these phenomena are a presage of the characteristic combination of fetal growth retardation and large placentas, which are a feature of both BB/E rat and human IDDM pregnancy.

Animals↗

A pharmacoeconomic study of the management of major depression: patients in a TennCare HMO.

The purpose of this study was to evaluate the direct medical costs of treating patients diagnosed with major depression in a TennCare managed care setting. This retrospective analysis was conducted on paid-claims data (including a 10-month lag) from January through December 1994 for patients who met criteria for major depressive disorder and were receiving tricyclic antidepressants (TCAs) or selective serotonin-reuptake inhibitors (SSRIs), for at least three consecutive months. Expenditures measured included office visits, hospital charges, emergency room charges, and drug costs. A total of 976 HMO beneficiaries were identified, and 76 randomly selected patients who were receiving TCAs were compared with 76 randomly selected patients who were receiving SSRIs to evaluate total cost of therapy associated with these two classes of antidepressants. The results of this analysis indicate that the total cost of treatment for Medicaid patients suffering major depression is similar between these two classes of antidepressants. Also, among the three SSRIs, the average daily dose was lowest for paroxetine (21.1 mg/day) and highest with sertraline (81.3 mg/day) and concomitant antidepressant therapy highest with fluoxetine (7.4%).

Adolescent↗

Client self-determination and professional intervention: striking a balance.

Social workers find themselves caught in the cross fire between two imperatives: (1) outcome-oriented and competency-based practice requisites and (2) the principle of client self-determination. In this context, the authors hypothesize that social workers use a wide range of gradations along a continuum of practice directiveness. Furthermore, there is ethical justification for this diverse role repertoire. Directiveness modalities are influenced by specific conditional factors that guide practitioner behavior. A study is described that empirically explores and amplifies these hypotheses.

Adult↗

Magnetic resonance imaging of peripartum rupture of the symphysis pubis.

BACKGROUND: Peripartum pubic symphyseal rupture is diagnosed on clinical grounds. Although the diagnosis may be supported by radiography, which shows diastasis of the pubic rami, magnetic resonance imaging (MRI) can visualize the nature of the soft tissue injury. CASE: Two puerperas thought clinically to have pubic symphyseal rupture were imaged with MRI. In addition to diastasis of the pubic rami, clefts were seen within the symphyseal cartilage, extending the entire breadth of the joint. The clefts were filled with fluid or hemorrhage, seen in T1- and T2-weighted images. The fluid was encapsulated within the joint by the surrounding ligaments. Four control normal puerperas, who had vaginal deliveries but were asymptomatic, showed none of the aforementioned findings. CONCLUSION: MRI can visualize the soft tissue injury seen in pubic symphyseal rupture and may be used to confirm the clinical diagnosis.

Adult↗

The use of synthetic Cecropin (D5C) in disinfecting contact lens solutions.

PURPOSE: Microbial keratitis caused by Pseudomonas aeruginosa is the most common contact lens associated corneal infection. Cecropins are microbicidal peptides isolated from the hemolymph of the Cecropia moth. Previous in vitro studies have demonstrated their efficacy against a broad spectrum of ocular pathogens. This study was designed: a) to evaluate the antimicrobial potency of three different contact lens solutions (Renu, Complete, and Opti-Free) against P. aeruginosa, and b) to evaluate the activity of the same contact lens solutions in combination with a synthetic cecropin analog, D5C, against the challenge organism in the presence of a soft contact lens. METHODS: A virulent strain of P.aeruginosa isolated from a case of ulcerative keratitis was used in the study. Three different concentrations of bacteria (10(3), 10(5) and 10(7) CFU/mL) were inoculated into the contact lens solutions and into buffered saline, which was employed as a control. The samples were incubated at 27 degrees C, and at time 0, 30, and 90 minutes, 24, 48, and 72 hours, and aliquots of the test solutions were plated and subcultured on nutrient agar. After 24 hours of incubation at 37 degrees C, colonies observed on the nutrient agar plates were counted. To study the antimicrobial efficacy of D5C (100 micrograms/mL), we used the identical test series and assay, adding a soft contact lens to the solutions and a larger inoculum of bacteria (10(9) CFU/mL). RESULTS: After 72 hours, all of the contact lens solutions tested sterilized 10(3) CFU/mL of P. aeruginosa. At 10(7) CFU/mL, they yielded greater than 2 logs of killing of the bacteria, but the solutions were not sterilized. The addition of D5C (100 micrograms/mL) to the contact lens solutions yielded greater than 3 logs of killing with a larger inoculum of bacteria in the presence of the soft contact lens. CONCLUSION: The contact lens solutions tested were effective against P. aeruginosa at 27 degrees C for up to 72 hours with an inoculum of 10(3) CFU/mL. The addition of D5C augmented their antimicrobial activity in the presence of the contact lens.

Colony-Forming Units Assay↗

Pain in pediatric human immunodeficiency virus infection: incidence and characteristics in a single-institution pilot study.

OBJECTIVE: Children with human immunodeficiency virus (HIV) infection have multiple complications associated with the disease process. Many of these complications are potentially painful and could affect the patient's quality of life. We examined the incidence and characteristics of the perception of pain in a cohort of families with children with HIV infection. METHODOLOGY: A questionnaire was developed and validated with a cohort of families with children with cancer. In a survey of families at the Pediatric Branch of the National Cancer Institute, 61 children with HIV infection and their care givers, along with 19 children with cancer and their care givers, were interviewed to determine the incidence and impact of pain. RESULTS: Fifty-nine percent of the HIV-infected children and 55% of their care givers described pain as a component of their illness that impacted on their lives. Younger children and girls tended to report more pain. There was also a tendency for biological parents to expect and to treat more pain than foster parents, although there was no difference in the incidence of pain that biological and foster parents reported for their children. No differences were found between parents who were HIV positive and those who were not. In addition, no correlations were noted in incidence, expectation, or impact of pain with disease progression or surrogate markers such as CD4 counts. Pain in HIV-infected patients tended to be either in the gastrointestinal tract or limbs and usually responded to nonsteroidal anti-inflammatory therapy. The patients with cancer reported an incidence (47%) and impact of pain similar to those of previously reported studies on pediatric patients with cancer. CONCLUSION: Pain is common among children infected with HIV and can adversely impact on their lives, and its management should be a component of the general care of these patients.

Adolescent↗

An exact McNemar test for paired binary Markov chains.

A straightforward extension of the McNemar test for paired binary data yields an exact test for the equality of the limiting marginal distributions for bivariate binary Markov chains. The exact distribution of the test statistics under the null hypothesis of equal marginals depends on the classical cell occupancy statistics for the Bose-Einstein model. Exact p-values are computed for the one-sided test, and the mean and variance of the test statistic are found. The power of the Markov-McNemar test is found to be close to the power of the classical McNemar test for independent paired observations when the independence assumption holds. The method is applied to the comparison of ribosomal DNA sequences.

Animals↗

The expression of neuronal voltage-dependent calcium channels in human cerebellum.

Little is known about the comparative distribution of voltage-dependent calcium channel subtypes in normal human brain. Previous studies in experimental animals have predominantly focused on the regional expression of single alpha 1 genes. We describe the preparation of riboprobes and antisera specific for human alpha 1A, alpha 1B and alpha 1E subunits and their application in comprehensive mapping studies of the human cerebellum. Within the cerebellar cortex, these pore forming proteins were found to have differential localisations when examined in adjacent sections. The alpha 1A and alpha 1B subunits broadly colocalised and were both present, though at apparently different levels, in the molecular, Purkinje and granule cell layers whilst alpha 1E was predominantly expressed in Purkinje cells. In the dentate nucleus, an area which has received little attention in previous studies, alpha 1A was highly expressed in regions in which Purkinje cell nerve terminals form synapses with deep cerebellar neurones.

Aged↗

Affinity purification of rat cortical and chicken forebrain synaptosomes using a biotinylated derivative of omega-CgTx GVIA.

We describe a magnetophoretic method for the affinity purification of synaptosomes expressing omega-CgTx GVIA-sensitive, N-type voltage-sensitive calcium channels (VSCCs). The method utilizes a biotinylated derivative of omega-CgTx GVIA which retains its ability to displace [125I] omega-CgTx GVIA from its binding sites on rat synaptic membranes. When coupled to streptavidin coated magnetizable beads, the hexanoyl spacer between omega-CgTx GVIA and the biotin:streptavidin bead complex is sufficiently long to allow flexibility of the toxin to bind to its receptor on synaptosomes. We have used this ligand successfully to isolate deaggregated synaptosomes from the parent fractions of chicken forebrain and rat cortex. In the chicken synaptosome parent fraction, omega-CgTx GVIA (1 nM-1 microM) produced a concentration-dependent block of the KCl-induced intracellular free Ca2+, [Ca2+]i, elevation with an IC50 of 28 nM. After affinity magnetophoresis no increase in [Ca2+]i elevation was observed in either the bound or unbound fractions. In the rat synaptosome parent fraction, the KCl-induced increase in free intracellular Ca2+ ([Ca2+]i) elevation was partially blocked by omega-CgTx GVIA (17 +/- 2% / 1 microM) and to a greater extent by omega-Aga IVA (55 +/- / 1 microM): a combination of the two toxins was additive (72 +/- 4% / 1 microM). The block obtained by omega-CgTx GVIA (1 microM) in the unbound fraction was reduced to 3 +/- 2%, whereas that by omega-Aga IVA (1 microM) increased to 82 +/- 3%. The block obtained by a combination of both toxins (83 +/- 2%) was the same as that with omega-Aga IVA alone (82 +/- 3%). No increase in free [Ca2+]i elevation was observed in the bound fraction although single synaptosome-like structures, displaying synaptophysin immunoreactivity, were detected on the beads. We conclude that omega-CgTx GVIA-sensitive N-type calcium channels are present on all chicken forebrain synaptosomes but only a subset of rat cortical synaptosomes.

Animals↗

Measurement of the proportion of free to total prostate-specific antigen improves diagnostic performance of prostate-specific antigen in the diagnostic gray zone of total prostate-specific antigen.

OBJECTIVES: This study examined the clinical significance of non-complexed (free) prostate-specific antigen (PSA) in the differential diagnosis of prostate cancer with an emphasis on patients with total PSA values between 4.0 and 10.0 ng/mL (the diagnostic gray zone). METHODS: Serum samples were obtained from three specimen banks. Patient samples consisted of 55 untreated histologically confirmed primary cancer, 62 men with untreated benign prostatic disease histologically confirmed by 6 negative sextant biopsies, and 64 asymptomatic healthy male controls with normal digital rectal examinations and PSA values less than 4.0 ng/mL. All patients were between the ages of 50 and 75 years. Total PSA levels were determined using the PA immunoassay performed on the TOSOH AIA-1200 automated immunoassay instrument. Free PSA levels were determined using a monoclonal-polyclonal antibody sandwich radioimmunoassay. The proportion of free to total PSA was calculated by dividing the patient's free PSA value by the total PSA value. RESULTS: When all subjects were included, both total PSA and the proportion of free to total PSA significantly differentiated between patients with prostate cancer and patients with benign histologic conditions (P < 0.0001). However, in men with total PSA values between 4.0 and 10.0 ng/mL, the proportion of free to total PSA significantly differentiated between patients with benign and malignant histologic conditions (P = 0.0004), whereas the total PSA did not (P = 0.13). Among this subgroup of patients, the analysis of sensitivity and specificity showed that the proportion of free to total PSA had a clearly higher specificity compared with that of the total PSA at the same level of sensitivity. CONCLUSIONS: Measurement of the free PSA level in a patient's serum and calculation of the proportion of free to total PSA enhances the ability to distinguish benign histologic conditions from cancer while retaining high sensitivity for detecting cancer in men who present with total PSA levels between 4.0 and 10.0 ng/mL. A large-scale population-based study is currently in progress to confirm this preliminary finding.

Aged↗

Prevalence of age-related maculopathy in Australia. The Blue Mountains Eye Study.

PURPOSE: To examine the prevalence of age-related maculopathy (drusen and retinal pigmentary abnormalities) and end-stage age-related macular degeneration lesions (neovascular maculopathy or geographic atrophy) in a defined older Australian urban population. SUBJECTS: All noninstitutionalized residents 49 years of age or older who were identified in a door-to-door census of two postcode areas west of Sydney, Australia. METHODS: All participants received a detailed eye examination, including stereoscopic photographs of each macula. Two trained graders used the Wisconsin Age-related Maculopathy Grading System to assess the presence and severity of typical lesions. RESULTS: A marked age-related increase in all typical lesions of age-related maculopathy and macular degeneration was observed. End-stage age-related macular degeneration was present in 1.9% of the population, rising from 0% among people younger than 55 years of age to 18.5% among those 85 years of age or older. Soft drusen were found in 13.3% of people, with distinct drusen more frequent than indistinct soft drusen. Retinal pigmentary abnormalities were found in 12.6% of people. For end-stage lesions and soft drusen, females had higher age-specific prevalence rates than males, whereas retinal pigmentary abnormalities were more frequent in males, although most of these differences were not significant. Prevalence rates for all lesions were lower (statistically significant for retinal pigmentary abnormalities and soft drusen) than for the United States Beaver Dam Eye Study which examined a similar population. CONCLUSIONS: These data provide detailed prevalence rates for most components of ARM in an Australian population and reinforce the Beaver Dam Eye Study findings for the relative age-specific frequency of age-related macular degeneration components.

Age Distribution↗

Effect of a leukotriene B4 receptor antagonist SC-53228 on ozone-induced airway hyperresponsiveness and inflammation in dogs.

The importance of the potent neutrophil chemoattractant leukotriene (LT)B4 in causing ozone-induced bronchoconstriction, airway inflammation, and airway hyperresponsiveness in dogs was studied using the LTB4-receptor antagonist SC-53228. Seven dogs from random sources were studied three times, at least 2 wk apart. On each occasion, acetylcholine (Ach) airway responsiveness was measured before and 1 h after ozone (3 ppm, 30 min) or dry air inhalation, followed by a bronchoalveolar lavage (BAL). On the first day, dogs were treated with SC-53228 (0.4 mg/kg intravenously) followed by a continuous intravenous infusion of 1.2 mg/kg/h before ozone inhalation. On the other two days, diluent was infused followed by ozone or dry air inhalation. Cell counts were measured in BAL and cell activation was measured by spontaneous and by phorbol myristate acetate-stimulated (PMA) (2.4 mumol/L) oxygen radical release, measured from washed BAL cells (4 x 10(6) cells) by lucigenin-enhanced chemiluminescence. Ozone inhalation caused bronchoconstriction and airway hyperresponsiveness. SC-53228 inhibited the ozone-induced airway hyperresponsiveness (p = 0.006), but not the bronchoconstriction. Spontaneous (p = 0.004) and PMA-stimulated (p = 0.04) lucigenin-enhanced chemiluminescence were increased after ozone inhalation. The ozone-induced increases in PMA-stimulated chemiluminescence were significantly attenuated by treatment with SC-53228 (p = 0.04). These results suggest that LTB4 is involved in the pathogenesis of ozone-induced airway hyperresponsiveness, possibly through activation of airway inflammatory cell.

Acetylcholine↗