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Biomedical subjects

Richard Ward

Publications and source records attributed to Richard Ward.

11 recordsLinked to original sources

Effect of rotavirus strain on the murine model of biliary atresia.

Biliary atresia is a devastating disorder of the newborn in which afflicted infants develop inflammation and fibrosis of the extrahepatic biliary tract, resulting in cirrhosis and end-stage liver disease. Infection with a virus is thought to be a contributing factor in the etiology of biliary atresia. In the murine model of biliary atresia, perinatal exposure to rhesus rotavirus (RRV) results in biliary epithelial cell infection causing bile duct obstruction. The purpose of this study was to determine if tropism for the biliary epithelial cell was unique to RRV. Newborn mice underwent intraperitoneal injection with five strains of rotavirus: RRV (simian), SA11-FM (simian/bovine), SA11-SM (simian), EDIM (murine), and Wa (human). RRV and SA11-FM caused clinical manifestations of bile duct obstruction and high mortality. SA11-SM caused clinical signs of hepatobiliary injury but the mortality was markedly reduced. EDIM and Wa caused no sign of hepatobiliary disease. The systemic and temporal distribution of viral protein and live virus varied according to the injected strain. Immunohistochemistry revealed that RRV and SA11-FM targeted the biliary epithelial cells. In contrast, SA11-SM was found in the liver but in not in the biliary epithelium. These results indicate that strain-specific characteristics dictate tropism for cells of hepatobiliary origin which in turn impact the ability to induce the murine model of biliary atresia.

Animals↗

Rhesus rotavirus vaccine effectiveness and factors associated with receipt of vaccine.

BACKGROUND: The rhesus rotavirus tetravalent vaccine (RotaShield) had an efficacy of 75%-100% in preventing severe rotavirus disease in prelicensure clinical trials. Before RotaShield's withdrawal because of reports of intussusception, there was an opportunity to evaluate the postlicensure effectiveness of the vaccine. The objective of this study was to determine the effectiveness of the RotaShield vaccine against rotavirus gastroenteritis requiring hospitalization and to evaluate factors associated with vaccine receipt. METHODS: Rotavirus cases were identified through active hospital-based rotavirus surveillance at 3 children's hospitals in Cincinnati, New Orleans and Providence. Cases were selected if they had been eligible for vaccine during the 10-month period when vaccine was available. Controls were matched to cases by date and county or state of birth. Immunization records were obtained from cases and controls to document receipt of RotaShield. Vaccine effectiveness (VE) was calculated for 1, 2, and 3 doses of vaccine with 95% confidence intervals (CI). RESULTS: For the 10-month period, 136 cases and 440 controls were enrolled. For 3 versus 0 doses of RotaShield, the VE was 100% (CI: 75%, 100%); for 2 versus 0 doses, the VE was 100% (CI: 62%, 100%), and for 1 versus 0 doses the VE was 89% (CI: 49%, 97%). RotaShield receipt was associated with white race, having more than 1 adult in the household, having insurance and having an older, more educated mother. CONCLUSIONS: This postlicensure study of RotaShield effectiveness found the vaccine to be highly effective in preventing rotavirus disease requiring hospitalization.

Animals↗

A case-control study to determine risk factors for hospitalization for rotavirus gastroenteritis in U.S. children.

OBJECTIVE: The objective of this case-control study nested within a surveillance study conducted at 3 hospitals (Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's Hospital of New Orleans, New Orleans, LA; and Hasbro Children's Hospital, Providence, RI) was to identify risk factors for rotavirus gastroenteritis requiring hospitalization. PATIENTS: Cases were children < or =59 months of age who were admitted with acute gastroenteritis (AGE) and found to have rotavirus infection. Controls were selected from a birth certificate registry (Cincinnati and Providence) or a registry of patients from a large practice consortium in 11 locations (New Orleans). RESULTS: Three hundred forty-nine rotavirus-infected cases and 1242 control subjects were enrolled. Breast feeding was protective against hospitalization for rotavirus AGE for infants <6 months of age. (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.2-13.2). Low-birth-weight (<2500 g) infants had increased risk for hospitalization even beyond the first few months of life (OR, 2.8; 95% CI, 1.6-5.0). Children in child care were more likely to be hospitalized for rotavirus AGE than those cared for at home, particularly those > or =24 months of age (OR, 3.0; 95% CI, 1.8-5.3). Other characteristics associated with rotavirus AGE hospitalization were children <24 months of age covered by Medicaid or without insurance (OR, 2.1; 95% CI, 1.4-3.2) and having another child in the house <24 months of age (OR, 1.6; 95% CI, 1.1-2.3). The data suggest that maternal age <25 years (OR, 1.4; 95% CI, 1.0-2.0) and a mother with less than a high school education (OR, 1.5; 95% CI, 1.0-2.3) may also increase risk of rotavirus hospitalization. CONCLUSION: There are socioeconomic and environmental factors and aspects of the child's medical and dietary history that identify children at risk for hospitalization with rotavirus AGE.

Age Factors↗

Purification and characterization of two xylanases from alkalophilic and thermophilic Bacillus licheniformis 77-2.

The alkalophilic bacteria Bacillus licheniformis 77-2 produces significant quantities of thermostable cellulase-free xylanases. The crude xylanase was purified to apparent homogeneity by gel filtration (G-75) and ionic exchange chromatography (carboxymethyl sephadex, Q sepharose, and Mono Q), resulting in the isolation of two xylanases. The molecular masses of the enzymes were estimated to be 17 kDa (X-I) and 40 kDa (X-II), as determined by SDS-PAGE. The Km and V(max) values were 1.8 mg/mL and 7.05 U/mg protein (X-I), and 1.05 mg/mL and 9.1 U/mg protein (X-II). The xylanases demonstrated optimum activity at pH 7.0 and 8.0-10.0 for xylanase X-I and X-II, respectively, and, retained more than 75% of hydrolytic activity up to pH 11.0. The purified enzymes were most active at 70 and 75 degrees C for X-I and X-II, respectively, and, retained more than 90% of hydrolytic activity after 1 h of heating at 50 degrees C and 60 degrees C for X-I and X-II, respectively. The predominant products of xylan hydrolysates indicated that these enzymes were endoxylanases.

Bacillus↗

Twelve tips for effective short course design.

Short courses are commonly used by physicians to stay up-to-date and acquire new skills for practice. Unfortunately, many short courses are not designed to maximize their impact on practice as they fail to acknowledge how people learn and change. Designers of effective short course planning should pay attention to writing outcomes based objectives; conducting needs assessments; determining the optimal content, resources, speakers and format; preparing ancillary materials (handouts and pre- and post-course assessments); and preparing speakers and evaluation. This paper discusses how each of the components of the curriculum design can be used to enhance the learning experience and obtain the desired course outcomes.

Canada↗

Linking human anatomy to knowledge bases: a visual front end for electronic medical records.

A new concept of a visual electronic medical record is presented based on developments ongoing in the Defense Advanced Research Projects Agency Virtual Soldier Project. This new concept is based on the holographic medical electronic representation (Holomer) and on data formats being developed to support this. The Holomer is being developed in two different visualization environments, one of which is suitable for prototyping the visual electronic medical record. The advantages of a visual approach as a front end for electronic medical records are discussed and specific implementations are presented.

Humans↗

Phe120 contributes to the regiospecificity of cytochrome P450 2D6: mutation leads to the formation of a novel dextromethorphan metabolite.

Although the residues that determine the preference of CYP2D6 (cytochrome P450 2D6) for compounds containing a basic nitrogen are well characterized, the contribution of other active site residues to substrate binding and orientation is less well understood. Our structural model of CYP2D6 identifies the aromatic residue Phe120 as a likely major feature of the active site. To examine the role of Phe120, mutants of CYP2D6 in which this residue has been substituted by alanine, leucine, tyrosine, serine, histidine, tryptophan or methionine residues have been prepared in bacterial membranes co-expressing human cytochrome NADPH cytochrome P450 oxidoreductase. The mutants have been characterized using the prototypical bufuralol 1' hydroxylase and dextromethorphan O- and N-demethylase activities of CYP2D6. Larger effects on K(m) values are observed for dextromethorphan O-demethylation than for bufuralol 1' hydroxylation, indicating that the Phe120 side chain is more important in dextromethorphan than in bufuralol binding. A role for this side chain in determining the regiospecificity of substrate oxidation was indicated by changes in the relative rates of O- and N-demethylation of dextromethorphan and, notably, by the formation of 7-hydroxy dextromethrophan, a novel dextromethorphan metabolite, in mutants in which it had been substituted. Computational studies of dextromethorphan binding to the active site of the Phe120-->Ala mutant were carried out to throw light on the way in which the removal of this side chain leads to different modes of ligand binding.

Cytochrome P-450 CYP2D6↗

A high resolution computer model for sound propagation in the human thorax based on the Visible Human data set.

A parallel supercomputer model based on realistic tissue data is developed for sound propagation in the human thorax and the sound propagation behavior is analyzed under various conditions using artificial sound sources. The model uses the Visible Human male data set for a realistic representation of the human thorax. The results were analyzed in time and frequency domains. The analysis suggests that lower frequencies of around 100 Hz are more effectively transmitted through the thorax and that the spatial confinement of sound waves within the thorax results in a resonance effect at around 1500 Hz. The results confirm previous studies that show the size of the thorax plays a significant role in the type of sound generated at the chest wall.

Acoustics↗

Double aortic arch masquerading as asthma for thirty years.

A case of a 30-year-old woman with a double-barrelled aorta misdiagnosed as asthma is presented. The patient was significantly improved after surgical treatment but a degree of airway symptoms persisted. She was further investigated and diagnosed with tracheomalacia. The paediatric experience with managing tracheomalacia is briefly reviewed and recommendations for the treatment of the rare adult cases are made. Our report emphasises the importance of early diagnosis and treatment of aortic arch abnormalities.

Adult↗

Development and Application of a Pediatric Anthropometric Evaluation System.

Children with developmental disabilities are at increased nutritional risk because of feeding problems, abnormal levels of physical activity, and altered weight and growth patterns. Children with physical disabilities are often more difficult to measure because of muscular contractures, spasms, scoliosis, and the presence of splints, braces, or wheelchair accessories. In addition, body weights may be difficult to obtain for heavier children with limited access to wheelchair scales. The purpose of this project was to produce a package of anthropometric measurements easier to use in children with physical disabilities but still applicable to able-bodied children, and computer software to generate growth charts. The project included the development of growth charts for each anthropometric measurement, using data from the Coquitlam Growth Study (921 children aged six to 18) and the Sunny Hill Growth Study (567 children aged one to 5.9). The custom computer software allows serial plotting of a child's measurements on growth charts, permitting comparative assessment of growth and muscle and adipose tissue development. The resultant Sunny Hill Anthropometric Pediatric Evaluation System (SHAPES) provides a tool for nutritional assessment and monitoring after intervention. The use of SHAPES is illustrated with a case study of a child who represented a challenge to traditional nutritional evaluation.

Journal Article↗

Improving outcomes in CKD and ESRD patients: carrying the torch from training to practice.

Practicing nephrologists are spending more time caring for end-stage renal disease (ESRD) and chronic kidney disease (CKD) patients. Despite this focus, and considerable advances in the understanding of those aspects of care that impact on clinical outcomes, morbidity, mortality, and quality of life for these patients has not improved substantially over the past decade. One of the possible explanations for this lack of progress is the structure of current nephrology training programs, where ESRD and CKD patient care is not emphasized. To address this issue, we developed a short preceptorship for second-year nephrology fellows, including didactic lectures and workshops. Of 67 participating fellows, 50% were from programs offering 3 or fewer months of exposure to outpatient hemodialysis, and 25% reported no exposure to peritoneal dialysis. Of more concern, 25% reported no "official rounds" with an attending nephrologist on dialysis patients. If nephrologists are to take their appropriate place as leaders of the care delivery team, nephrology fellowships must be restructured with appropriate emphasis placed on the comprehensive care of ESRD and CKD patients.

Attitude of Health Personnel↗