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Biomedical subjects

H Ward

Publications and source records attributed to H Ward.

At least 73 records · Page 4Linked to original sources

Recruitment experience in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

Several approaches for recruitment of African American adults with renal insufficiency due to hypertension (glomerular filtration rate between 25 and 70 ml/min/1.73 m2) were explored in the Pilot Study for the African American Study of Kidney Disease and Hypertension (AASK). Over a period of 42 weeks, prescreening information was obtained on 2880 individuals, of whom 498 (17%) were evaluated at a screening visit. Two hundred and twenty-five (8%) had an 125I-iothalamate assessment of glomerular filtration rate. Ninety-four of 97 participants who met all the study eligibility criteria were enrolled in the trial. The most common reasons for ineligibility during screening were absence of renal insufficiency or hypertension, presence of diabetes mellitus, and a body mass index above the acceptable level. Overall, an average of 31 prescreen contacts and 8 screening visits were conducted for every randomization (3.3% yield from prescreening to randomization). Screening in clinical practice was the most efficient method for recruitment (12.6% yield from prescreen contact to randomization compared to 1.1% from mass mailing campaigns, 1.3% from mass media campaigns, and 1.7% from referrals by patients with end-stage renal disease). Randomization yields increased with progressively higher age ranges (2.4%, 3.3%, and 6.0% prescreen to randomization yields for those aged < or = 50, 51-60, and 61-70, respectively). A slight majority (51%) of the prescreen contacts were women, but 75% of the randomized participants were men. Our results suggest that clinic-based screening is an effective approach for recruitment of African Americans with hypertension and renal insufficiency into clinical trials. They also suggest that enrollment of African American women in such studies is a special challenge.

Adult↗

Temporal changes in function and regional glucose uptake within stunned porcine myocardium.

UNLABELLED: This study compared the effects of porcine myocardial stunning on the uptake of [18F]-fluorodeoxyglucose (FDG) at 24 hr and 7 days after reperfusion. Prior studies in animals subjected to severe myocardial ischemia have shown a sustained increase in FDG uptake relative to perfusion (FDG/MBF). The time course of recovery of FDG/MBF relative to function poststunning, however, has not been well characterized. METHODS: Stunning was induced in eight swine by partially occluding the LAD artery for 20 min. At 1 and 7 days postreperfusion, function was assessed by two-dimensional echocardiography and PET studies were obtained with FDG and either 15O-water or 13N-ammonia. Blood flow by microspheres was determined at baseline, during ischemia and after stunning. Myocardial uptake of FDG relative to blood flow on matching images (FDG/MBF) was calculated for all ROIs and expressed as a ratio of LAD to non-LAD areas. RESULTS: After stunning, left ventricular ejection fraction (LVEF) increased from 42% +/- 10% on Day 1 to 52% +/- 6% on Day 7 (p < 0.05). At Day 1, myocardial blood flow was 0.60 +/- 0.10 ml/min/g in LAD and 0.67 +/- 0.16 in non-LAD regions and neither differed at Day 7. The magnitude of FDG/MBF in the LAD region when normalized to the non-LAD region was 1.29 +/- 0.16 on Day 1 and 1.09 +/- 0.08 on Day 7 (p < 0.05) and was inversely proportional to global measures of LVEF (r2 = 0.61; p < 0.005). CONCLUSION: The severity of postischemic LV dysfunction at 1 and 7 days after stunning correlates with the degree of enhanced regional glucose uptake as estimated by PET. Both normalize within 7 days, suggesting that metabolic and functional abnormalities within completely reperfused myocardium recover in parallel.

Animals↗

Cryptosporidia--who is at risk?

Cryptosporidium parvum is a coccidian parasite originally described a century ago and, until recently, not considered to be a human pathogen. It has a complex life cycle, including both sexual and asexual reproduction, an auto-infectious cycle, and the ability to complete its development within a single host. The transmission form is a robust, environmentally resistant oocyst, excreted in the stool, which can exist for long periods of time in the environment. Because animals, in particular domesticated livestock, are its primary host, human infection is usually zoonotic. Oocysts often find their way into water supplies, and it resists chlorination and is incompletely filtered from processed drinking water supplies, even when filtration is working optimally. Transmission via ingestion of fecally contaminated swimming pool water, food, fomites, and sexual activities facilitating fecal-oral inoculation have been demonstrated. The major target of C. parvum in the host is the intestinal epithelial cell, resulting in diarrhea, sometimes profuse and persistent, although it may also infect other organs such as the gall bladder and lungs. Pathogenesis involves attachment, probably via a sporozoite lectin, invasion, probably involving apical organelles, replication within a parasitophorous vacuole with the host cell membrane, causing cellular dysfunction. Diagnosis is generally made by visualization of the oocyst form in stool by staining methods, the best of which appears to be auramine and fluorescence microscopy. Those at greatest risk are immunocompromised adults and children, especially those with AIDS, children in day care, travelers to endemic regions, dairy or cattle farm workers of their families or contacts, household contacts of cases or carriers, and possibly owners of infected dogs or cats or their neighbors. There is no specific therapy available, however in the immunocompetent host the illness is self-limited, lasting from a few days to 3 weeks, and long term carriage is uncommon. In the immunocompromised host, infection is prolonged, sometimes asymptomatic, but may result in chronic debilitating diarrhea with dehydration, malabsorption and wasting. Public health measures to reduce contamination of water supplies and vigilant surveillance will reduce the risk to populations. Reducing behaviors favoring fecal-oral transmission, such as certain sexual activities, and scrupulous hygiene in the day care setting would also reduce the likelihood of transmission but not eliminate it. Given our lack of knowledge about Cryptosporidium biology and pathogenesis, high priority should be given to research designed to increase our understanding of the organism and improve the chance of developing useful therapeutic or preventative drugs or strategies.

Adult↗

Myocardial blood flow and FDG retention in acutely stunned porcine myocardium.

UNLABELLED: This study assesses regional differences in myocardial blood flow and 18F-fluorodeoxyglucose (FDG) retention in acutely stunned porcine myocardium. METHODS: Two groups of swine were used for these studies. In Group 1, 15 animals underwent stunning induced by 20 min of myocardial ischemia followed by reperfusion. Regional function was measured with ultrasonic crystals and myocardial blood flows were quantitated with radiolabeled microspheres. Within 2 hr postischemia, myocardial blood flow images were obtained with 15O-water, and FDG uptake was estimated with dynamic scanning. In a second group of five animals, PET scanning was performed 2 hr poststunning and repeated 24 hr later. RESULTS: In Group 1 animals, postischemic reductions were noted in both regional shortening and myocardial oxygen consumption. Myocardial blood flows at baseline were 0.72 +/- 0.05 ml/min/g in the LAD region and 0.83 +/- 0.07 ml/min/g in the non-LAD region; following reperfusion they were 0.70 +/- 0.07 ml/min/g and 0.89 +/- 0.08 ml/min/g, respectively. Within 2 hr of reperfusion, FDG retention was significantly lower in the LAD region compared with remote myocardium. As with Group 1, Group 2 also showed a reduction in FDG uptake in acutely reperfused myocardium relative to remote regions. Twenty-four hours later, FDG uptake within reperfused regions increased to 0.31 +/- 0.04 mumole/min/g and did not differ from remote myocardium. CONCLUSION: FDG uptake in acutely stunned swine myocardium is lower than remote regions at a time when regional myocardial blood flows are not dissimilar. This differs from 24 hr following reperfusion in which enhanced FDG uptake may be observed relative to perfusion. Therefore, the time course of metabolic changes following reperfusion needs to be considered in patients undergoing viability studies with PET.

Animals↗

Evaluation of oncofetal protein-related mRNA transport activity as a potential early cancer marker in dogs with malignant neoplasms.

A 55-kd protein with mRNA transport activity found in fetal rat liver cells and plasma from mice, rats, and human beings with malignant neoplasms has been designated oncofetal protein 55 (OFP55). Monoclonal antibody produced to rat OFP55 cross-reacts with human OFP55. Using this monoclonal antibody in a bioassay measuring mRNA transport stimulated by OFP55, we tested the plasma from 19 dogs with a variety of malignant neoplasms, including carcinomas, sarcomas, lymphomas, and melanomas, and compared the results with plasma from 20 clinically normal dogs without evidence of neoplasia. The mean mRNA transport activity from the group of dogs with malignant neoplasms was 0.43 +/- 0.28%/mg of protein. Mean transport activity from the group of control dogs was 0.04 +/- 0.02%/mg of protein. These means were significantly different (P < 0.0001). The degree of overlap between these 2 groups in their OFP55-related mRNA transport activity was minimal, and measurement of this protein appears to have potential for the early detection of malignant neoplasms in dogs.

Animals↗

FDG uptake within regionally stunned myocardium.

Clinical cardiologists are now aware of several conditions in which myocardial function can be depressed in the absence of overt ischemia or infarction. Myocardial stunning refers to a particular situation in which the contractile state of the myocardium remains depressed after a brief period of ischemia and reperfusion. Positron emission tomography has been shown to be an important tool for identifying viability within stunned myocardium on the basis of enhanced fluorine 18-fluorodeoxyglucose (FDG) uptake relative to perfusion. This image pattern has been referred to as a ¿flow-metabolism mismatch¿ and is predictive of patients who would benefit from reperfusion therapies. This review highlights the importance of considering the time course of altered FDG uptake within regionally stunned myocardium.

Animals↗

An internist joins the surgery service: does comanagement make a difference?

OBJECTIVE: To determine the effect of internist comanagement of cardiothoracic surgical patients on patient outcome and resource utilization. DESIGN: Before/after comparison. SETTING: Tertiary care university-affiliated Veterans Affairs hospital. PATIENTS: 165 patients (86 before the intervention and 79 after the intervention) undergoing cardiothoracic surgery. INTERVENTIONS: All patients were seen preoperatively and at least daily through discharge by a comanaging staff internist who was a full-time member of the surgical team. MAIN OUTCOME MEASURES: Length of stay, in-hospital mortality, and laboratory and radiology utilization. RESULTS: Significant shortening of postoperative length of stay (18.1 days before and 12.1 days after, p = 0.05) and total length of stay (27.2 days before and 19.7 days after, p = 0.03) was noted. The in-hospital mortality rate for the patients undergoing surgery was 8.1% before the intervention versus 2.5% afterward (p = 0.17). There were significant reductions in the total number of x-rays (p = 0.02) and nearly significant reductions in total laboratory test utilization (p = 0.06). Referring physicians and surgeons both believed that the contribution of the internist was important. CONCLUSIONS: The addition of an internist to the cardiothoracic surgery service at a tertiary care teaching center was associated with decreased resource utilization and possible improved outcomes. Before becoming more widely adopted, this intervention deserves further exploration at other sites using stronger study designs.

Hospital Mortality↗

Alteration of copolymer-specific humoral and cell-mediated immune responses by ethanol.

Excessive alcohol consumption represents a major human health threat. The frequency and severity of infections in alcoholics is often pronounced, suggesting impaired immune function in these patients. The precise effect of ethanol on cells of the immune system is poorly understood. We have previously shown that synthetic copolymers of L-amino acids, GT and GAT, are powerful tools for clarifying the role of regulatory T-cells in both cell-mediated and humoral immunity in inbred mouse strains. We asked whether these same antigens would have application to a murine model of ethanol consumption. In this study, female mice were placed on a nutritionally complete liquid diet containing 35% ethanol-derived calories. As control, mice either were placed on a liquid control diet that isocalorically substitutes sucrose for ethanol or remained on a solid diet consisting of standard laboratory chow and water ad libitum. Our data show that the liquid ethanol diet severely inhibits two measures of cell-mediated immunity, the ability of responder B6 mice to make an anti-GAT delayed hypersensitivity and GAT-specific T-cell proliferative responses as compared with pair-fed liquid control diet or solid diet controls. On the contrary, this liquid ethanol diet does not significantly impair humoral immunity; it allows nonresponder C57BL/6 or C3H/HeN mice to respond in vivo to GT immunization. These findings suggested to us that the effect of ethanol may occur prior to antigenic stimulation, and this was confirmed by in vitro immunization.

Alcoholism↗

Reduction in the contraction and intracellular calcium transient of single rat ventricular myocytes by gadolinium and the attenuation of these effects by extracellular NaH2PO4.

Gadolinium (Gd3+) is the most commonly used blocker of stretch-activated channels (SACs). The actions of Gd3+ in unstretched adult heart were investigated by observing its effects on the contraction and intracellular calcium transient of single rat ventricular myocytes. We found that Gd3+ caused a profound reduction in both these parameters at doses typically used to block SACs. However, the actions of Gd3+ were severely attenuated by the presence of 0.33 mM NaH2PO4, which possibly chelates the Gd3+ ion.

Animals↗

Attachment of Cryptosporidium parvum sporozoites to MDCK cells in vitro.

The initial attachment of Cryptosporidium parvum sporozoites to host cells in vivo may be a critical event in the pathogenesis of this infection. The molecular basis of attachment and the conditions influencing this host-parasite interaction have not been studied systematically. Therefore, we have developed a sporozoite attachment model by using paraformaldehyde-fixed Madin-Darby canine kidney (MDCK) cells. Attachment of sporozoites to fixed MDCK cells was quantitated by indirect immunofluorescence and confirmed by transmission electron microscopy. Attachment in this system was time, temperature (37 degrees C), and pH (7.2 to 7.6) dependent. Dose-response studies demonstrated that the attachment of sporozoites to fixed MDCK cells was a saturable process. Attachment was enhanced in the presence of 10 mM manganese, 1 mM calcium, and 1 to 10 mM zinc. Attachment of sporozoites to MDCK cells was inhibited in a dose-dependent manner by polyclonal anti-Cryptosporidium antisera and by purified immunoglobulin G (IgG). This model will be useful for the study of parasite and host cell molecules involved in the initial interaction of C. parvum sporozoites with their target cell.

Adhesiveness↗

Human acoustic neuromas secrete interleukin-6 in cell culture: possible autocrine regulation of cell proliferation.

Interleukin-6 (IL-6) secretion by cell cultures of human acoustic neuromas was examined. Secretory rates varied from 0.02 to 5.4 ng/10(5) cells per 4 days, depending on the tumor. The IL-6 immunoreactivity eluted from a Sephadex G-100 column in a major peak corresponding to an M(r) of 30,000 and a lesser peak corresponding to an M(r) of 50,000. Western blot analysis revealed three IL-6 immunoreactive bands with M(r)s corresponding to 53,000, 29,000, and 24,000. Tumor necrosis factor-alpha, interleukin-1-beta, and cholera toxin all stimulated IL-6 secretion. An antisense phosphorothioate oligonucleotide against IL-6 messenger RNA inhibited both [3H]thymidine uptake and IL-6 secretion by acoustic neuroma cells in culture. In addition, [3H]thymidine uptake was inhibited by a specific polyclonal antibody against IL-6. We conclude that human acoustic neuroma cells produce and secrete IL-6, which may act in an autocrine manner to stimulate cellular proliferation.

Adult↗