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Biomedical subjects

J W Ward

Publications and source records attributed to J W Ward.

At least 19 recordsLinked to original sources

Programming placental nutrient transport capacity.

Many animal studies and human epidemiological findings have shown that impaired growth in utero is associated with physiological abnormalities in later life and have linked this to tissue programming during suboptimal intrauterine conditions at critical periods of development. However, few of these studies have considered the contribution of the placenta to the ensuing adult phenotype. In mammals, the major determinant of intrauterine growth is the placental nutrient supply, which, in turn, depends on the size, morphology, blood supply and transporter abundance of the placenta and on synthesis and metabolism of nutrients and hormones by the uteroplacental tissues. This review examines the regulation of placental nutrient transfer capacity and the potential programming effects of nutrition and glucocorticoid over-exposure on placental phenotype with particular emphasis on the role of the Igf2 gene in these processes.

Aging↗

Factors affecting targeting using the computer assisted orthopaedic surgery system (CAOSS).

An advantage of CAOS over traditional surgery is improved precision of implant position and trajectories in 3D space. However, the implementation of these trajectories often adds an extra step to the operation that increases operative time and requires extra training. This paper reports a study of variation in time-to-task and learning curve in performing a standard task of targeting in 3D space using Hull's CAOSS. It shows that time-to-task can be reduced by replacing a 3D targeting task with multiple independent 2D targeting tasks whilst potentially reducing targeting error. Based on this better understanding of targeting a novel jig was developed for performing dynamic hip Screw (DHS) insertion using CAOSS that would provide improved targeting performance by the surgeon.

Hip↗

Functional significance and cortisol dependence of the gross morphology of ovine placentomes during late gestation.

The gross morphological appearance of ovine placentomes is known to alter in response to adverse intrauterine conditions that increase fetal cortisol exposure. The direct effects of fetal cortisol on the placentome morphology, however, remain unknown, nor is the functional significance of the different placentome types clear. The present study investigated the gross morphology of ovine placentomes in relation to placental nutrient delivery to sheep fetuses during late gestation and after experimental manipulation of the fetal cortisol concentration. As fetal cortisol levels rose naturally toward term, a significant decrease was observed in the proportion of the D-type placentomes that had the hemophagous zone everted over the bulk of the placentomal tissue. When the prepartum cortisol surge was prevented by fetal adrenalectomy, there were proportionately more everted C- and D-type placentomes and fewer A-type placentomes with the hemophagous zone inverted into the placentome compared with those of intact fetuses at term. Raising cortisol concentrations by infusion before term reduced the incidence of D-type placentomes and lowered the proportion of individually tagged placentomes that became more everted during the 10- to 15-day period between tagging and delivery. Cortisol, therefore, appears to prevent hemophagous zone eversion in ovine placentomes during late gestation. The distribution of placentome types appeared to have no effect on the net rates of placental delivery of glucose and oxygen to the fetus under normal conditions. When fetal cortisol levels were raised by exogenous infusion, however, placental delivery of glucose, but not oxygen, to the fetus, measured as umbilical uptake, was reduced to a greater extent in fetuses with a higher proportion of C- and D-type placentomes. The gross morphology of the ovine placentomes is, therefore, determined, at least in part, by the fetal cortisol concentration and may influence placental nutrient transfer when fetal cortisol concentrations are high during late gestation. These findings have important implications for the placental control of fetal growth and development, particularly during adverse intrauterine conditions.

Animals↗

Ovine feto-placental metabolism.

Fetal growth depends on the transplacental nutrient supply, which, in turn, is determined partially by the consumption and production of nutrients by the uteroplacental tissues. In fetal sheep, the rates of growth and umbilical glucose uptake decline coincidently towards term in parallel with the normal prepartum rise in plasma cortisol. While cortisol is known to reduce growth in fetal sheep, its effects on the uteroplacental handling and delivery of nutrients remain unknown. Hence, this study, quantified the rates of umbilical uptake and uteroplacental consumption of nutrients in preterm fetuses infused with cortisol for 5 days to mimic the prepartum cortisol surge. Umbilical uptakes of glucose and lactate, but not oxygen, were significantly lower in cortisol- than saline-infused fetuses, irrespective of whether values were expressed as absolute or weight-specific rates. The rate of uteroplacental consumption of glucose, but not oxygen, was significantly higher in cortisol- than saline-infused animals. Absolute rates of uteroplacental lactate production were lower in cortisol-infused animals. When all data were combined, fetal plasma cortisol levels were positively correlated to uteroplacental glucose consumption and inversely related to umbilical glucose uptake. Cortisol treatment had no apparent effect on placental mRNA expression for the glucose transporters, GLUT-1 and GLUT-3. The results demonstrate that cortisol is physiological regulator of uteroplacental metabolism and nutrient delivery to the sheep fetus. These observations have important implications for fetal growth both in late gestation and during adverse intrauterine conditions, which raise fetal cortisol levels earlier in gestation.

Animals↗

Stereo visualization of 3D trabecular bone structures produced by bone remodelling simulation.

Adult human bone is constantly being renewed by a process known as remodelling. For cancellous bone this renewal process occurs at the interface between bone and marrow where bone is depleted by osteoclasts and rebuilt by osteoblasts. This remodelling process allows bone to repair itself. Software simulators for bone remodelling provide insight into the bone remodelling process; they allow investigation into bone form and structural properties, and they also allow the emulation of bone diseases and possible treatments for these diseases over long periods of time. BONESIM is a software that simulates bone remodelling in terms of Basic Multi-cellular Units (BMUs). 3D visualization of trabecular bone and its attributes is an essential tool in understanding this remodelling process for cancellous bone. It enables the bone researcher to quickly understand the dynamic behaviour of remodelling, the resulting geometry of the bone structure and it allows alternative remodelling scenarios to be compared. This paper presents the volume visualization technique that has been developed to provide this visualization tool.

Adult↗

The effect of a reversible period of adverse intrauterine conditions during late gestation on fetal and placental weight and placentome distribution in sheep.

Adverse intrauterine conditions occurring during early to mid-gestation or throughout the whole of gestation influence placental weight and the distribution of placentome types in sheep. However, no study to date has investigated the effect of a reversible period of adverse intrauterine conditions during late gestation upon fetal and placental weight and placentome distribution in sheep. Twenty-two sheep fetuses were chronically instrumented with an inflatable cord occluder, amniotic and vascular catheters and with a Transonic flow probe around an umbilical artery. At 125 days (term isca.145 days) the occluder was inflated to reduce umbilical blood flow by ca.30 per cent for 3d in 12 fetuses (umbilical cord compressed, UCC). The occluder was then deflated and umbilical blood flow allowed to return to baseline. The remaining 10 fetuses acted as sham-operated controls in which the occluder remained deflated at all times. At 135-137dGA ewes were humanely killed and tissues collected, weighed and placentomes classified. A reduction in umbilical blood flow by approximately 30 per cent from baseline for 3 days in UCC fetuses led to mild fetal asphyxia throughout the period of cord-compression. After deflation of the occluder cuff, umbilical blood flow returned to a level that was significantly greater than that measured during baseline. Umbilical cord compression had no effect on fetal body weight but significantly increased fetal adrenal weight relative to body weight. While the total number of placentomes was not altered by cord-compression, total placentome weight and the total weight of C/D-type placentomes were both reduced in UCC relative to control placentae. In addition, the mean weight of placentomes, and of C/D-type placentomes specifically, was significantly lower in UCC relative to control placentae. When expressed as a percentage of the total number of placentomes in the placenta, there was a significantly lower percentage of C/D-type placentomes in UCC relative to control placentae. In addition, there was a significant relationship between the total number of placentomes and the percentage C/D-type placentomes in control, but not UCC, placentae. The data suggest that a temporary, reversible period of adverse intrauterine conditions occurring late in gestation in sheep has persisting effects upon the placenta, mean placentome weight and placentome distribution.

Adrenal Glands↗

The effects of cortisol on the binucleate cell population in the ovine placenta during late gestation.

Large granulated binucleate cells (BNCs) producing placental lactogen (PL) and pregnancy-associated glycoproteins (PAG) are present in all ruminant placentae throughout pregnancy. These BNC account for 15-20% of the cells in ovine trophectoderm for most of gestation but decrease in number close to term at the same time that fetal cortisol levels rise. The present study investigated the effects of cortisol on the BNC population using immunohistochemistry to count BNCs in ovine placentomes during late gestation and after experimental manipulation of the fetal cortisol level by fetal adrenalectomy and exogenous cortisol infusion. Abolition of the prepartum rise in fetal cortisol prevented the normal decline in BNC numbers towards term. Conversely, raising cortisol levels in immature fetuses to prepartum values prematurely reduced placental BNC numbers. However, a small population of BNC remained, even at the highest cortisol concentrations. When all the data were combined irrespective of treatment or gestational age, there was a significant inverse correlation between fetal plasma cortisol and the number of BNCs in the ovine placenta. These findings show that cortisol regulates the BNC population in ovine placenta during late gestation. They also have important implications for the production of PL and PAG during ovine pregnancy.

Adrenal Glands↗

Regulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity in ovine placenta by fetal cortisol.

The effect of fetal cortisol on the activity of the type 2 isoform of the enzyme, 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD2), was examined in ovine placenta and fetal kidney by measuring tissue 11 beta-HSD2 activity during late gestation when endogenous fetal cortisol levels rise and after exogenous cortisol administration to immature fetuses before the prepartum cortisol surge. Placental 11 beta-HSD2 activity decreased between 128-132 days and term (approximately 145 days of gestation) in association with the normal prepartum increase in fetal plasma cortisol. Raising fetal cortisol levels to prepartum values in the immature fetus at 128--132 days of gestation reduced placental 11 beta-HSD2 activity to term values. In contrast, 11 beta-HSD2 activity in the fetal renal cortex was unaffected by gestational age or cortisol infusion. When all the data were combined, there was an inverse correlation between the log fetal plasma cortisol level at delivery and placental 11 beta-HSD2 activity, expressed both on a weight-specific basis and per mg placental protein. Fetal cortisol therefore appears to be a physiological regulator of placental, but not renal, 11 beta-HSD2 activity in fetal sheep during late gestation. These findings have important implications, not only for glucocorticoid exposure in utero, but also for the local actions of cortisol within the placental tissues that are involved in initiating parturition in the sheep.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

Pneumococcal disease among human immunodeficiency virus-infected persons: incidence, risk factors, and impact of vaccination.

To determine the factors associated with pneumococcal disease (pneumococcal pneumonia or invasive disease) and the impact of pneumococcal vaccine in HIV-infected persons, we analyzed patient data collected by the Adult and Adolescent Spectrum of HIV Disease Project for person-time between January 1990 and December 1998. Among 39,086 persons with 71,116 person-years (py) of observation, 585 episodes of pneumococcal disease were diagnosed (incidence, 8.2 episodes per 1000 py). Factors associated with an increased risk for pneumococcal disease (P < .05) included injection drug use (adjusted relative risk [RR], 1.5) and blood transfusion (RR, 2.0) as the mode of HIV transmission (referent, male-male sex); black race/ethnicity (RR, 1.5; referent, white race); history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic illness (RR, 2.1); a CD4(+) cell count of 200-499 cells/microL (RR, 2.5) or < 200 cells/microL (RR, 3.7; referent, CD4(+) cell count of > or = 500 cells/microL); and alcoholism (RR, 2.0). Factors associated with a decreased risk included prescription of antiretroviral therapy (RR for monotherapy, 0.6; for dual therapy, 0.7; for triple therapy, 0.5) and pneumococcal vaccination (RR for persons vaccinated at a CD4(+) cell count of > or = 500 cells/microL, 0.5). We recommend that pneumococcal vaccine be given to HIV-infected persons before profound immunosuppression has occurred.

AIDS-Related Opportunistic Infections↗

The completeness, validity, and timeliness of AIDS surveillance data.

PURPOSE: To assess the completeness, validity, and timeliness of the AIDS surveillance system after the 1993 change in the surveillance case definition. METHODS: To assess completeness of AIDS case reporting, three study sites conducted a comparison of their AIDS surveillance registries with an independent source of information. To evaluate validity, the same sites conducted record reviews on a sample of reported AIDS cases, we then compared agreement between the original report and the record review for sex, race, and mode of transmission. To evaluate timeliness, we calculated the median delay from time of diagnosis to case report, before and after the change in case definition, in each of the three study sites. RESULTS: After expansion of the case definition, completeness of AIDS case reporting in hospitals (> or = 93%) and outpatient settings (> or = 90%) was high. Agreement between the information provided on the original case report and the medical record was > 98% for sex, > 83% for each race/ethnicity group; and > 67% for each risk group. The median reporting delay after the change was four months, but varied by site from three to six months. CONCLUSIONS: The completeness, validity, and timeliness of the AIDS surveillance system remains high after the 1993 change in the surveillance case definition. These findings might be useful for programs implementing integrated HIV and AIDS surveillance systems.

Acquired Immunodeficiency Syndrome↗

Distance learning in nursing.

OBJECTIVES: To inform oncology nurses about distance-learning technologies and to offer suggestions for how nurses can locate, appropriately select, and use distance learning to their benefit. DATA SOURCES: Published articles, research studies, and review articles pertaining to distance education and learning in nursing. CONCLUSIONS: Distance learning offers new opportunities for nurses who are seeking basic or advanced degrees, certificates, or lifelong learning for professional development. IMPLICATIONS FOR NURSING PRACTICE: Oncology nursing practice is a dynamic specialty and requires the nurse to be a lifelong learner. Distance learning facilitates this requirement.

Certification↗

Surgical trainee assessment using a VE knee arthroscopy training system (VE-KATS): experimental results.

Previous work has described the development of a Virtual Environment Knee Arthroscopy Training System (VE-KATS): a collaborative project between the Orthopaedic Department, Hull and East Yorkshire Hospitals NHS Trust, Hull, U.K., and the Department of Computer Science, University of Hull, U.K. This work describes the initial results obtained by Orthopaedic Surgical Trainees using VE-KATS. The results showed that differences between individual trainees could be measured using the scoring system incorporated within VE-KATS. There was a weak correlation with the seniority of the surgical trainees.

Arthroscopy↗

Effect of influenza vaccination on disease progression among HIV-infected persons.

OBJECTIVE: To describe the effect of influenza vaccination on long-term change in CD4 count and HIV RNA level, and on progression to AIDS or death. DESIGN AND SETTING: A longitudinal medical record review set in 113 medical clinics in 10 United States cities. PATIENTS: A total of 36,050 HIV-infected persons aged > or = 13 years in care for HIV infection. MAIN OUTCOME MEASURES: Change in CD4 count and HIV RNA level at follow-up (3-12 months after vaccination); hazard ratios (HR) for association of influenza vaccine with progression from baseline CD4 or HIV RNA level to AIDS and to death. RESULTS: The median CD4 count among all persons decreased 28 cells/year during follow-up, with no difference in change in CD4 count between the 8007 (40%) vaccinated (median = 6 months, vaccine to follow-up CD4 count) and the 11,794 unvaccinated persons. In a viral load subanalysis, median HIV RNA level decreased 90 copies/ml per year among all persons during follow-up; decreases were not different between vaccinated and unvaccinated persons (median = 7 months, vaccine to follow-up HIV RNA level determination). Influenza vaccination was weakly associated with decreased risk of progression to clinical AIDS [HR 0.93; 95% confidence interval (CI), 0.87-0.99], but not associated with time to death (HR, 0.97; CI, 0.93-1.01). CONCLUSIONS: No negative long-term effect of influenza vaccination on CD4 counts, HIV RNA levels, or progression to AIDS or death was found in this HIV-infected population. These data suggest that physicians should not withhold influenza vaccine because of concerns about long-term detrimental effects of increased viral replication.

Acquired Immunodeficiency Syndrome↗

Risk for preventable opportunistic infections in persons with AIDS after antiretroviral therapy increases CD4+ T lymphocyte counts above prophylaxis thresholds.

To determine incidence and risk for preventable opportunistic infections (Pneumocystis carinii pneumonia [PCP] and disseminated Mycobacterium avium-complex [MAC] infection) in persons whose CD4(+) T lymphocyte counts had increased by >/=100 cells/microL to exceed the threshold of risk and in persons whose CD4(+) counts had never dropped below the threshold of risk, we analyzed data collected during the period 1990-1998 in the Adult/Adolescent Spectrum of HIV (Human Immunodeficiency Virus) Disease Project. Using a counting-process formulation of the Cox model, we analyzed observation time in these 2 groups for persons who were prescribed antiretroviral therapy but not prophylaxis. The incidences of the infections were low for patients whose CD4(+) count rose above the threshold of risk (PCP, 0.6 cases per 100 person-years [PY]; MAC, 1. 0 cases per 100 PY) and not higher than in persons whose CD4(+) counts had not decreased below these thresholds, which suggests that discontinuation of primary prophylaxis for opportunistic infections may be considered for some patients.

Acquired Immunodeficiency Syndrome↗

Human immunodeficiency virus (HIV) subtype surveillance of African-born persons at risk for group O and group N HIV infections in the United States.

A population-based surveillance registry was used to identify human immunodeficiency virus (HIV)-infected persons in the United States at increased risk for group O and group N infections (those born in or near African countries where group O infection has been reported). Of 155 eligible subjects, 37 gave samples. By phylogenetic and serologic analysis, 32 were infected with group M (16 with subtype A, 5 with B, 7 with C, and 1 each with subtypes D, F2, G, and recombinant A/J) and 2 with group O but none with group N virus. For 3, samples could not be typed by serology or amplified by polymerase chain reaction using group M-, O-, or N-specific primers. In the United States, group O HIV infection is uncommon; no case of group N infection was found. African-born persons may have HIV strains typical of their birth country. Ongoing subtype surveillance may allow early identification of novel or emerging HIV strains.

Adult↗

Human immunodeficiency virus infection in rural areas and small cities of the southeast: contributions of migration and behavior.

The design of education and prevention strategies to stem the spread of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) in rural areas depends on having accurate patterns of risk behavior and transmission in local areas. Interviews were conducted with people in rural areas and small cities in Delaware, Florida, Georgia and South Carolina who were at least 18 years old and infected with HIV in order to describe demographic characteristics, migration patterns and risk behaviors. Interviews were conducted with 608 people. Most respondents were male (66 percent), black (63 percent of men, 85 percent of women) and had been infected through sexual contact (67 percent of men, 66 percent of women). Most (65 percent) had lived away from a rural area or small city for at least one month; of those, 71 percent had moved from an urban area. Twenty-seven percent of respondents indicated they had been infected locally. People with a history of injection drug use were less likely to have been infected locally than those who had no history of injection drug use (6 percent vs. 26 percent among men, 3 percent vs. 40 percent among women, P < 0.001). Further understanding of the role of socioeconomic factors in HIV transmission in rural areas and small cities is needed. Programs designed to prevent HIV acquisition among people living in rural areas and small cities in the Southeast should focus on sexual behavior.

Adolescent↗

Effects of antiretroviral therapy and opportunistic illness primary chemoprophylaxis on survival after AIDS diagnosis. Adult/Adolescent Spectrum of Disease Group.

OBJECTIVE: To examine the effects of antiretroviral therapy (ART) and opportunistic illness chemoprophylaxis on the survival of persons with AIDS and survival time based on year of AIDS diagnosis. DESIGN: Longitudinal medical record review. SETTING: Ninety-three hospitals and clinics in nine cities in the USA. PATIENTS: We observed 19,565 persons with AIDS from 1990 through January 1998. INTERVENTIONS: Prescribed use of antiretroviral monotherapy, dual- and triple-combination therapies, primary prophylaxis against Pneumocystis carinii pneumonia and Mycobacterium avium complex, and pneumococcal vaccine. MAIN OUTCOME MEASURES: Time from AIDS diagnosis to death in the presence and absence of ART. Survival curves were compared of AIDS cases diagnosed during 1990-1992 and 1993-1995. RESULTS: Triple ART had the greatest effect on the risk of death [relative risk (RR), 0.15; 95% confidence limit (CL), 0.12, 0.17], followed by dual ART (RR, 0.24; 95% CL, 0.22, 0.26), and monotherapy (RR, 0.38; 95% CL, 0.36, 0.40). Risk of death was decreased among persons receiving Pneumocystis carinii pneumonia prophylaxis (RR, 0.79; 95% CL, 0.70, 0.89) and Mycobacterium avium complex prophylaxis (RR, 0.76; 95% CL, 0.68, 0.86). Median survival increased from 31 months [95% confidence interval (CI), 30-32 months] for AIDS cases diagnosed during 1990-1992 to 35 months (95% CI, 35-38 months) for cases diagnosed during 1993-1995. CONCLUSIONS: The risk of death was decreased for persons receiving triple ART compared with persons receiving dual therapy and persons receiving monotherapy. Increased use of ART and improved ART regimens probably contributed to prolonged survival of persons whose diagnosis was made during 1993-1995 compared with persons whose diagnosis was made during 1990-1992.

AIDS-Related Opportunistic Infections↗