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Biomedical subjects

R Ward

Publications and source records attributed to R Ward.

At least 145 records · Page 8Linked to original sources

A population-based study of congenital diaphragmatic hernia in Utah: 1988-1994.

OBJECTIVE: To define the natural history of congenital diaphragmatic hernia and to determine the potential impact of fetal therapy. METHODS: This retrospective case series consisted of all fetuses and neonates with congenital diaphragmatic hernia born between 1988 and 1994 in the state of Utah that could be identified through genetic counseling referrals, delivery logs, and neonatal intensive care unit discharge diagnosis records. Maternal and neonatal hospital records were reviewed for antepartum, intrapartum, and postpartum variables. Based on existing recommendations, fetuses who might have benefited from fetal therapy were identified. RESULTS: Ninety-six cases were identified, for a frequency of one case in 2710 live births per year. Five pregnancies were terminated before 21 weeks' gestation. The overall survival rate excluding these five cases was 58.2%. Among the remaining 91 cases, survival was significantly better for infants diagnosed in the neonatal period than for those diagnosed prenatally (78% versus 35%; P < .001). The frequency of associated anomalies was similar for antepartum and postpartum cases. Sixty-two percent of nonsurvivors had some type of other anomaly, but no pattern was apparent. There were no accurate prenatal predictors for lethal pulmonary hypoplasia, but preterm birth and the presence of severe cardiac anomalies were predictors of neonatal death. Only two of 96 fetuses would have potentially benefited from fetal therapy. CONCLUSION: The outcome of infants with congenital diaphragmatic hernia is worse with preterm birth and if diagnosed prenatally. The survival rate we found was better than that reported in earlier studies, suggesting improved perinatal and neonatal management. Fetal therapy based on current eligibility criteria would have a minimal impact on survival of fetuses with congenital diaphragmatic hernia.

Congenital Abnormalities↗

Factors associated with early failure of arteriovenous fistulae for haemodialysis access.

The radiocephalic arteriovenous fistula remains the method of choice for haemodialysis access. In order to assess their suitability for fistula formation, the radial arteries and cephalic veins were examined preoperatively by ultrasound colour flow scanner in conjunction with a pulse-generated run-off system. Intraoperative blood flow was measured after construction of the fistulae. Post-operative follow-up was performed at various intervals to monitor the development of the fistulae. Radial artery and cephalic vein diameter less than 1.6 mm was associated with early fistula failure. The intraoperative fistula blood flow did not correlate with the outcome of the operation probably due to vessel spasm from manipulation. However, blood flow velocities measured non-invasively 1 day after the operation were significantly lower in fistulae that failed early compared with those that were adequate for haemodialysis. Most of the increase in fistula diameter and blood flow occur within the first 2 weeks of surgery.

Arm↗

Protective mucosal immunity elicited by targeted iliac lymph node immunization with a subunit SIV envelope and core vaccine in macaques.

Prevention of sexually transmitted HIV infection was investigated in macaques by immunization with a recombinant SIV (simian immunodeficiency virus) envelope gp 120 and core p27 vaccine. In two independent series of experiments, we used the novel targeted iliac lymph node (TILN) route of immunization, aiming close to the iliac lymph nodes draining the genitorectal mucosa. Rectal challenge with the SIVmac 32H J5 molecular clone in two series induced total protection in four out of seven macaques immunized by TILN, compared with infection in 13 of 14 unimmunized macaques or immunized by other routes (P = 0.025). The remaining three macaques showed either a decrease in viral load ( > 90%) or transient viremia, indicating that all seven TILN-immunized macaques showed total or partial protection (P = 0.001). Protection was associated with significant increase in the iliac lymph nodes of IgA antibody-secreting cells to p27 (P < 0.02), CD8-suppressor factor (P < 0.01), and the chemokines RANTES and MIP-1 beta (P < 0.01).

Animals↗

Soluble TNF alpha receptors are increased in chronic renal insufficiency and hemodialysis and inhibit neutrophil priming by TNF alpha.

The oxidative burst of neutrophils from azotemic patients is refractory to priming by tumor necrosis factor-alpha (TNF alpha). Soluble TNF alpha binding protiens (sTNFR) accumulate in the plasma of azotemic patients. To test the hypothesis that these increased sTNFR concentrations inhibit TNF alpha priming of oxidative burst activity, we measured plasma sTNFR concentrations in nondialyzed azotemic patients, hemodialysis patients, and normal subjects, and determined TNF alpha priming of fMet-Leu-Phe-stimulated superoxide production in neutrophils incubated in plasma with differing levels of sT-NFR. These sTNFR concentrations increased significantly as creatinine clearance decreased and were significantly greater in hemodialysis patients than could be accounted for by loss of renal function alone. TNF alpha primed superoxide production by normal neutrophils in normal plasma, but this effect was significantly reduced in plasma with increased concentrations of sTNFR. Neutrophils from azotemic and hemodialysis patients were refractory to priming by TNF alpha in autologous plasma, and incubation in normal plasma only partially corrected this defect. We conclude that sTNFR accumulate as a result of the loss of renal function and hemodialysis and inhibit TNF alpha priming of neutrophils in azotemic and hemodialysis patients, but that these cells also have an intrinsic functional defect.

Adult↗

Asthma, airways responsiveness and air pollution in two contrasting districts of northern England.

BACKGROUND: To assess the possible magnitude of differences between normal populations an epidemiological investigation of asthma was conducted in two strongly contrasting districts of northern England--rural West Cumbria on the west coast and urban Newcastle upon Tyne on the east coast. METHODS: A cross sectional survey of randomly identified men aged 20-44 years was conducted in two phases: phase 1, a postal survey of respiratory symptoms and asthma medication in 3000 men from each district; and phase 2, a clinical assessment of 300 men from each district comprising investigator administered questionnaires, skin prick tests, spirometry, and methacholine challenge tests. RESULTS: The phase 1 (but not phase 2) study showed a small excess of "ever wheezed" in Newcastle (44% versus 40%), but neither phase showed differences between the two districts for recent wheeze or for other symptoms characteristic of asthma. There were also no differences with regard to diagnosed asthma, current asthma medication, spirometric parameters, or airways responsiveness. The prevalence of quantifiable airways responsiveness (PD20 < or = 6400 micrograms) was 27.7% in West Cumbria and 28.2% in Newcastle. Regression analyses showed that PD20 was negatively associated with atopy and positively with forced expiratory volume in one second (FEV1); that an association between PD20 and current smoking could be explained by diminished FEV1; and that PD20 was not related to geographical site of residence. CONCLUSIONS: Neither airways responsiveness nor the other parameters of diagnostic relevance to asthma varied much between the two study populations, despite the apparent environmental differences. The most obvious of these were the levels of outdoor air pollution attributable to vehicle exhaust emissions, the ambient levels of which were 2-10 fold greater in Newcastle. Our findings consequently shed some doubt over the role of such pollution in perceived recent increases in asthma prevalence. It is possible, however, that an air pollution effect in Newcastle has been balanced by asthmagenic effects of other agents in West Cumbria.

Adult↗

Polymorphisms of renin-angiotensin genes among Nigerians, Jamaicans, and African Americans.

Within the context of an international collaborative study of the evolution of hypertension in the black diaspora, we determined the allelic distribution of hypertension candidate genes for the renin-angiotensin system in three populations of African origin. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) and the M235T and T174M variants of the angiotensinogen (AGT) gene were examined in individuals from Nigeria, Jamaica, and the United States. Large differences in the prevalence of hypertension were recorded in door-to-door surveys, ranging from 16% in Nigeria to 33% in the United States. The frequency of the D allele was similar in all groups (54%, 59%, and 63% in Nigeria, Jamaica, and the United States, respectively). The 235T allele of the AGT gene was found in 81% of US and Jamaican blacks and 91% of Nigerians; very little variation was seen for the T174M marker. Despite large differences in hypertension rates, genetic variation at the index loci among these groups was modest. Overall, the frequency of the ACE*D allele was only slightly higher than that reported for European and Japanese populations, whereas the AGT 235T allele was twice as common. Compared with blacks in the western hemisphere, Nigerians had a higher frequency of the 235T allele, which is consistent with 25% European admixture in Jamaica and the United States. The results indicate the potential for etiologic heterogeneity in genetic factors related to hypertension across ethnic groups while suggesting that environmental exposures most likely explain the gradient in risk in the comparison among black populations.

Alleles↗

Performance of carotid ultrasound in evaluating candidates for carotid endarterectomy is optimized by an approach based on clinical outcome rather than accuracy.

BACKGROUND AND PURPOSE: The best method of selecting endarterectomy candidates for cerebral angiography is controversial. Carotid duplex ultrasound (CDUS) is widely used, but its performance varies across institutions. The clinical utility of CDUS could be improved with test criteria based on patient outcome rather than test accuracy. METHODS: In 155 carotid bifurcations studied by CDUS and cerebral angiography, the degree of angiographic stenosis was measured by a reader, blinded to CDUS, using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method. We calculated accuracy, sensitivity, and specificity for predicting > or = 70% angiographic carotid stenosis of different peak systolic frequencies (PSF) measured by CDUS and generated a receiver operator characteristic (ROC) curve. We used NASCET outcome data and published data on angiographic complications to define relative "costs" of false-positive and false-negative CDUS, and we determined the point on the ROC curve representing the CDUS criterion with the highest clinical utility. We compared projected morbidity and mortality rates for 1000 hypothetical endarterectomy candidates resulting from the use of the most accurate CDUS criterion versus the CDUS criterion with the highest clinical utility by ROC analysis. RESULTS: While PSF > or = 8 kHz had the highest CDUS accuracy (93%), its projected stroke and death rate due to CDUS error was 10.4/1000. On the other hand, PSF > or = 7 kHz, defined by ROC analysis to have the highest clinical utility, had a lower morbidity and mortality rate of 6.8/1000. CONCLUSIONS: The use of ROC analysis and available outcome data can improve the performance of CDUS in selecting endarterectomy candidates for cerebral angiography.

Algorithms↗

Role of bronchoalveolar lavage in hospitalized pediatric patients.

Bronchoalveolar lavage (BAL) has been shown to be a rapid, relatively safe, and relatively noninvasive diagnostic procedure. Theoretically, BAL can be performed on all children hospitalized for pneumonia resistant to oral antibiotics, though practically and economically, this is not feasible. A 1-year retrospective review was conducted to define a cost-effective role for BAL in the management of hospitalized children with resistant pneumonia. The data revealed identification of at least one pathogen in 87% of sputum samples and in 95% of BAL specimens. Sputum samples provided the same information as the more invasive BAL technique in 60% of patients who had both sputum and BAL obtained for culture. Recommendations are made for the use of BAL as a diagnostic tool in the hospitalized child with resistant pneumonia.

Adolescent↗

Improving the management of patients with schizophrenia in primary care: assessing learning needs as a first step.

OBJECTIVE: To assess family physician learning needs related to the care of patients with schizophrenia. METHODS: Questionnaires were mailed to all family physicians and general practitioners practising in southern Alberta. Physicians were asked to indicate the number of patients with schizophrenia cared for, their interest in improving the care the provided, their preferred learning methods, and the content they wished to learn. RESULTS: A total of 539 surveys were returned for a return rate of 43.8%. Over half of the physicians (53.5%) indicated that they saw 1 to 2 patients with schizophrenia each month. Almost half (48.5%) indicated they were somewhat or very interested in increasing the care provided. Primary learning needs included increasing their knowledge of psychopharmacologic agents and monitoring and adjusting medications. Lectures and half-day workshops were the preferred learning methods. CONCLUSION: Our study was helpful in identifying the types of education that physicians wanted as well as the duration of the programming prior to the development of teaching interventions.

Alberta↗

Topography of the NADPH-diaphorase system in the chameleon brain.

The NADPH-diaphorase histochemical technique, which reflects the activity of nitric oxide synthase was used in order to map the corresponding chameleon brain structures. In the forebrain, stained neurons were found particularly in the dorsal ventricular ridge and the ventral telencephalon, but no stained somata were observed in the cortical areas nor in the septum. In the midbrain, few NADPH-stained structures were seen. The stained cells were confined in the nucleus dorsomedialis, the nucleus geniculatus lateralis dorsalis, and the ventromedial hypothalamus. More caudally, some stained neurons were observed in the nucleus opticus mediodorsalis hypothalami posterior. In the brainstem, NADPH-stained cells were located in the optic tectum, the torus semicircularis, the substantia nigra, the ventral tegmental area, and all motor nuclei of the cranial nerves. The present results showed some striking differences and similarities with birds and mammals. Moreover, the presence of NADPH-staining in most of retinofugal, retinopetal and oculomotor nuclei suggests that nitric oxide system plays a prominent role in the visual and oculomotor functions.

Animals↗

A quantitative study of the effects of microphthalmia on the organisation of the primary visual system of the mouse.

The retinal projections of C57BL/Orl mice homozygous for the mutation microphthalmic-white (Miwh) were investigated by autoradiographic and HRP tracing techniques, and compared to those of heterozygous and normal mice of the same inbred strain; the anatomy of the eyes and optic nerves of the three genotypes were also examined. The eye of homozygous mutant mice is considerably reduced in size; the optic nerve shows a decrease in the number of myelinated fibres which is partially compensated by an increase in the proportion of unmyelinated axons. All primary visual centres that are labelled in normal mice receive retinal projections in mutant mice, although these centres are reduced in size in mutants. The reduction is most evident for those centres forming the thalamic relays of the retino-telencephalic pathway, to a lesser extent for the retino-collicular pathway and least of all for the retino-hypothalamic projections. These findings are compared to those obtained in naturally microphthalmic rodent species, and also to the effects of another mutation at the mi locus, maintained on a different background.

Animals↗

Psychodemographic profile of stockpeople working on independent and integrated swine breeding farms in Quebec.

As a part of a larger study, the psychodemographic profile of Quebec pig stockpeople was described based on a sample of 48 persons working on independent farms randomly selected in the Richelieu-Saint-Hyacinthe region, and on a convenience sample of 38 others employed by 5 organizations of integrated swine production chosen among the largest ones in Québec. The 2 groups of stockpeople were described separately because of the differences between the 2 types of production. Demographic data (age, sex, level of education, training and experience in swine production, seniority on the farm) were obtained through a face-to-face interview. The personality profile was assessed using a standard personality test (French translation of the Sixteen Personality Factor Questionnaire). Both the stockpersons on independent farms and those employed by the organizations were more reserved, emotionally stable, serious, conscientious, unsentimental, controlled, introverted, and less anxious than the average person in the general population. However, multivariate analyses revealed some differences between these two groups of stock-persons (P = 0.021) as well as between the employees of the different organizations (P = 0.0038). These differences in personality profiles may reflect differences in working conditions, particularly regarding the human relationships, and in corporate cultures of the organizations.

Animal Husbandry↗

Different patterns of dendritic branching of posterior collicular neurons in two mouse strains are associated with a difference in audiogenic seizure susceptibility.

Golgi preparations of the superficial layers of the posterior colliculus of two inbred strains of mice, differing in susceptibility to audigenic seizure, were examined. The cell bodies of neurons observed in DBA/2J mice were found to be, on average, significantly larger than those observed C57BL/6J mice. Both the spatial extent of dendritic arborisations and the complexity of dendritic branching were also found to be greater in DBA/2J mice. While these differences are associated with the difference in susceptibility to audiogenic seizure between these two strains, further investigations are called for before it can be asserted that this behavioral difference is causally related to the morphological differences that we describe.

Acoustic Stimulation↗

Fine structure of the dorsal lateral geniculate nucleus of the turtle, Emys orbicularis: a Golgi, combined HRP tracing and GABA immunocytochemical study.

The afferent and efferent cortical projections of the dorsal lateral geniculate nucleus (GLD) of adult specimens of the turtle Emys orbicularis were investigated after intraocular or intracortical injections of horseradish peroxidase (HRP), and the distribution of gamma aminobutyric acid (GABA) immunoreactivity in the nucleus was carried out by immunocytochemical techniques, both techniques being combined with light and electron microscopy. In addition, some specimens were prepared for double-labeling of HRP and GABA immunoreactivity, and additional samples impregnated by a rapid Golgi technique. On purely morphological grounds, four types of neurons can be distinguished by light microscopy: two types of large cells in the cell plate which project to the cortex, and two types of smaller cells in the neuropil and optic tract which do not. The small cells are consistently GABA-immunoreactive, while the former are, with extremely rare exceptions, immunonegative for GABA. The supposition that the small neurons of the neuropil are interneurons is supported by electron microscopic observations; these strongly GABA-immunoreactive cells have large plicated nuclei surrounded by a thin layer of cytoplasm poorly endowed with organelles. The dendrites of these cells may contain pleomorphic synaptic vesicles (DCSVs) and appear to be presynaptic to other dendritic profiles. These DCSVs are occasionally contacted by GABA-immunoreactive axon terminals, and more frequently by retinal terminals consistently immunonegative for GABA. The latter, frequently organized in glomeruli, also make synaptic contacts with immunonegative dendrites arising from corticopetal neurons of the cell plate. Two major categories of GABA-immunoreactive axon terminals can be distinguished, and we are led to the conclusion that one of these represents an intrinsic GABAergic innervation of the GLD, while the second is tentatively interpreted as an extrinsic source of GABA to the nucleus, possibly from ventral thalamic structures. The fine structure of the dorsal lateral geniculate nucleus of Emys orbicularis thus shows many similarities with that of mammals.

Afferent Pathways↗

Cytokeratin expression in human respiratory epithelium of nasal polyps and turbinates.

The cytokertatins in respiratory epithelial cells (REC) of human nasal polyps and turbinates were analyzed by immunohistochemistry. Cytokeratin 19 (CK19) was present in all REC, CK5 and 14 were expressed primarily in basal cells, and CK7, 8, and 18 were found in suprabasal cells. Differences in cytoplasmic locations were also apparent among the individual cytokeratins. CK13 was not detected in any REC of these tissues. The results indicate the profile of cytokeratins in REC of human nasal polyps and turbinates is essentially identical to that of REC in the more distal respiratory tract.

Antibodies, Monoclonal↗

Gender differences in physiological reactions to thermal stress.

Following an extensive anthropometric evaluation, thermoregulatory responses were studied in nine men and nine women who performed immersed exercise with post-exercise rest in 28 degrees C water. During the post-exercise period esophageal temperature (Tes), oxygen consumption, heat flux and skin blood perfusion were monitored at 10 s intervals, with average minute values used for calculations. The delta Tes (relative to resting Tes) at which sweating abated and shivering commenced were defined as the delta Tes thresholds for the cessation of sweating and onset of shivering, respectively. No significant gender differences were evident in the sweating and shivering threshold delta Tes values, or the magnitude of the null-zone. Using z-tests for parallelism the rates of core cooling across the null-zone were not found to differ significantly between genders, nor were the slopes of the perfusion: delta Tes responses across the null-zone or the post-threshold shivering responses (ml.kg-1.min-1.degrees C-1). The slope of the sweating response (measured from immersion until sweat cessation; g.m-2.min-1 degree C-1) was, however, significantly lower in the female than in the male samples (z = 3.93; P < 0.01). Despite the gender-related dimorphic distribution of adipose tissue, both men and women lost equal proportions of their total heat flux from central and peripheral measurement sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗