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Biomedical subjects

D Chavez

Publications and source records attributed to D Chavez.

17 recordsLinked to original sources

Menopausal symptoms and associated risk factors among postmenopausal women screened for the metabolic syndrome.

BACKGROUND: Although the frequency of menopausal symptoms may vary according to the studied population, in general severe intensity has been related to lower quality of life. OBJECTIVE: To assess the frequency of menopausal symptoms and involved risk factors in an Ecuadorian postmenopausal population. METHODS: Postmenopausal women that participated in a metabolic syndrome screening program were interviewed with the Menopause-specific quality of life questionnaire (MENQOL) in order to determine the most frequently presenting menopausal symptoms and correlate these symptoms with socio-demographic data and the main results of the screening program. RESULTS: Three hundred and twenty-five postmenopausal women (n = 325) were surveyed with the MENQOL. Mean age of participants was 55.9 +/- 8.1 years (median: 54 years). The most frequently presenting symptoms were: hot flushes (53.3%), sweating (49.2%), poor memory (80.6%), feeling depressed (67.4%), aching in muscles and joints (84%), drying of their skin (85.5%), avoiding intimacy (76.2%) and change in their sexual desire (76.5%). Multivariate analysis determined that abdominal obesity was a significant risk factor for presenting hot flushes, depression and muscle and joint pain. High triglyceride levels were associated to higher rates of sweating and depression. While women with basal hyperglycemia were associated to dry skin and changes in sexual desire in a higher proportion, those who were older and with more years of menopause onset were related less frequently to vasomotor symptoms. Older age was also significantly associated in a higher rate to dry skin. CONCLUSION: In this postmenopausal Ecuadorian population, the frequency of menopausal symptoms, as assessed with the MENQOL, was found to be relatively similar to other Latin and non-Latin American populations and associated to age, hormonal status and related metabolic conditions.

Adult↗

Oculo-palatal-cerebral syndrome: a second case.

Oculo-palato-cerebral syndrome is an extremely rare disorder consisting of low birth weight, microcephaly, short stature, persistent hyperplastic primary vitreous, microphthalmia, large ears, small hands and feet, cleft palate, joint hypermobility, developmental delay, and cerebral atrophy. There has been one report of a consanguineous family with three affected children, suggesting autosomal recessive inheritance. We report on the second case of this disorder. Our patient, a 2-year-old boy, had growth delay, microcephaly, bilateral persistent hyperplastic primary vitreous with right microphthalmia, long ears with thickened helices, small hands and feet, highly arched palate, joint hypermobility, hypoplastic nails, frontal cerebral atrophy and thinning of the corpus callosum on brain magnetic resonance imaging, and mild developmental delay. He has much milder features than those seen in the previously reported cases.

Abnormalities, Multiple↗

GB virus B as a model for hepatitis C virus.

GB viruses A and B (GBV-A and GBV-B) are members of the Flaviviridae family and are isolated from tamarins injected with serum from a human hepatitis patient. Along with a related human virus, GB virus C, or alternatively, hepatitis G virus (GBV-C/HGV), the three viruses represent the GB agents. Of the three viruses, GBV-B has been proposed as a potential surrogate model for the study of hepatitis C virus (HCV) infections of humans. GBV-B is phylogenetically most closely related to HCV and causes an acute, self-resolving hepatitis in tamarins as indicated by an increase in alanine aminotransferase and changes in liver histology. Similarities between GBV-B and HCV are found at the nucleotide sequence level with the two viruses sharing 28% amino acid homology over the lengths of their open reading frames. Short regions have even higher levels of homology that are functionally significant as shown by the ability of the GBV-B NS3 protease to cleave recombinant HCV polyprotein substrates. The shared protease substrate specificities suggest that GBV-B may be useful in testing antiviral compounds for activity against HCV. Although there are numerous similarities between GBV-B and HCV, there are important differences in that HCV frequently causes chronic infections in people, whereas GBV-B appears to cause only acute infections. The acute versus chronic course of infection may point to important differences between the two viruses that, along with the numerous similarities, will make GBV-B in tamarins a good surrogate model for HCV.

Acute Disease↗

Ribavirin induces error-prone replication of GB virus B in primary tamarin hepatocytes.

GB virus B (GBV-B) is the closest relative of hepatitis C virus (HCV) and is an attractive surrogate model for HCV antiviral studies. GBV-B induces an acute, resolving hepatitis in tamarins. Utilizing primary cultures of tamarin hepatocytes, we have previously developed a tissue culture system that exhibits high levels of GBV-B replication. In this report, we have extended the utility of this system for testing antiviral compounds. Treatment with human interferon provided only a marginal antiviral effect, while poly(I-C) yielded >3 and 4 log units of reduction of cell-associated and secreted viral RNA, respectively. Interestingly, treatment of GBV-B-infected hepatocytes with ribavirin resulted in an approximately 4-log decrease in viral RNA levels. Guanosine blocked the antiviral effect of ribavirin, suggesting that inhibition of IMP dehydrogenase (IMPDH) and reduction of intracellular GTP levels were essential for the antiviral effect. However, mycophenolic acid, another IMPDH inhibitor, had no antiviral effect. Virions harvested from ribavirin-treated cultures exhibited a dramatically reduced specific infectivity. These data suggest that incorporation of ribavirin triphosphate induces error-prone replication with concomitant reduction in infectivity and that reduction of GTP pools may be required for incorporation of ribavirin triphosphate. In contrast to the in vitro studies, no significant reduction in viremia was observed in vivo following treatment of tamarins with ribavirin during acute infection with GBV-B. These findings are consistent with the observation that ribavirin monotherapy for HCV infection decreases liver disease without a significant reduction in viremia. Our data suggest that nucleoside analogues that induce error-prone replication could be an attractive approach for the treatment of HCV infection if administered at sufficient levels to result in efficient incorporation by the viral polymerase.

Animals↗

Development of a primary tamarin hepatocyte culture system for GB virus-B: a surrogate model for hepatitis C virus.

GB virus-B (GBV-B) causes an acute hepatitis in tamarins characterized by increased alanine transaminase levels that quickly return to normal as the virus is cleared. Phylogenetically, GBV-B is the closest relative to hepatitis C virus (HCV), and thus GBV-B infection of tamarins represents a powerful surrogate model system for the study of HCV. In this study, the course of infection of GBV-B in tamarins was followed using a real-time 5' exonuclease (TaqMan) reverse transcription-PCR assay to determine the level of GBV-B in the serum. Peak viremia levels exceeded 10(9) genome equivalents/ml, followed by viral clearance within 14 to 16 weeks. Rechallenge of animals that had cleared infection resulted in viremia that was limited to 1 week, suggestive of a strong protective immune response. A robust tissue culture system for GBV-B was developed using primary cultures of tamarin hepatocytes. Hepatocytes obtained from a GBV-B-infected animal maintained high levels of cell-associated viral RNA and virion secretion for 42 days of culture. In vitro infection of normal hepatocytes resulted in rapid amplification of cell-associated viral RNA and secretion of up to 10(7) genome equivalents/ml of culture supernatant. In addition, infection could be monitored by immunofluorescence staining for GBV-B nonstructural NS3 protein. This model system overcomes many of the current obstacles to HCV research, including low levels of viral replication, lack of a small primate animal model, and lack of a reproducible tissue culture system.

Animals↗

Hepadnavirus infection in captive gibbons.

The recent isolation of a nonhuman primate hepadnavirus from woolly monkeys prompted an examination of other primates for potentially new hepadnaviruses. A serological analysis of 30 captive gibbons revealed that 47% were positive for at least one marker of ongoing or previous infection with a hepatitis B virus (HBV). The amino acid sequences of the core and surface genes of human and gibbon virus isolates were very similar. Phylogenetic analysis indicated that the gibbon isolates lie within the human HBV family, indicating that these HBV isolates most likely stem from infection of gibbons from a human source.

Amino Acid Sequence↗

Attaining health for all through community partnerships: principles of the census-based, impact-oriented (CBIO) approach to primary health care developed in Bolivia, South America.

This article describes a flexible primary health care methodology which was developed by Andean Rural Health Care and its colleagues in Bolivia, South America. This methodology, the census-based, impact-oriented (CBIO) approach to primary health care, involves determining local health priorities as defined both by locally acquired epidemiologic information and by the local people themselves. The CBIO approach to primary health care is now functioning successfully at seven program sites in Bolivia, which together serve 75,000 people in urban and rural communities in three distinct cultural and ecological regions of the country. High levels of coverage of basic health services can be achieved through a system of 'epidemographic' surveillance of all families and through home delivery, when needed, of priority services to those at risk. When the services provided are based on local health priorities, when they are provided in a technically effective manner, and when the community has a strong partnership in planning, implementation and evaluation, then the CBIO approach to primary health care will lead to measurable health improvements as defined by changes in population-based rates of mortality and illness in the community. On the basis of our experience, we believe that the CBIO approach offers great potential for strengthening the effectiveness of local health programs in impoverished communities around the world in a way which fosters community ownership and, hence, long-term sustainability.

Bolivia↗

Diarrhoea prevention in Bolivia through point-of-use water treatment and safe storage: a promising new strategy.

A novel water quality intervention that consists of point-of-use water disinfection, safe storage and community education was field tested in Bolivia. A total of 127 households in two periurban communities were randomized into intervention and control groups, surveyed and the intervention was distributed. Monthly water quality testing and weekly diarrhoea surveillance were conducted. Over a 5-month period, intervention households had 44% fewer diarrhoea episodes than control households (P = 0.002). Infants < 1 year old (P = 0.05) and children 5-14 years old (P = 0.01) in intervention households had significantly less diarrhoea than control children. Campylobacter was less commonly isolated from intervention than control patients (P = 0.02). Stored water in intervention households was less contaminated with Escherichia coli than stored water in control households (P < 0.0001). Intervention households exhibited less E. coli contamination of stored water and less diarrhoea than control households. This promising new strategy may have broad applicability for waterborne disease prevention.

Adolescent↗

Academic models for practice relief, recruitment, and retention at the University of New Mexico Medical Center and East Carolina University School of Medicine.

Locum tenens programs were independently developed by the University of New Mexico Health Sciences Center and East Carolina University School of Medicine to address health care needs within their states. The programs represent distinct models to provide locum tenens services for practices in rural and medically underserved regions through collaboration with stage government representatives and agencies. Differences between programs include years of operation, days of coverage provided, types of learners and providers involved, sources of funding, costs of the programs, and extent of institutional support. Common beneficial outcomes of the programs include coverage for struggling practices, training in rural medicine for locum tenens providers, recruitment of physicians to rural practice sites, and improved relationships with program partners. Adequate funding and institutional support are essential for success of locum tenens programs.

Career Choice↗

Isolation of a hepadnavirus from the woolly monkey, a New World primate.

Hepatitis B virus (HBV) infections are a major worldwide health problem with chronic infections leading to cirrhosis and liver cancer. Viruses related to human HBV have been isolated from birds and rodents, but despite efforts to find hepadnaviruses that infect species intermediate in evolution between rodents and humans, none have been described. We recently isolated a hepadnavirus from a woolly monkey (Lagothrix lagotricha) that was suffering from fulminant hepatitis. Phylogenetic analysis of the nucleotide sequences of the core and surface genes indicated that the virus was distinct from the human HBV family, and because it is basal (ancestral) to the human monophyletic group, it probably represents a progenitor of the human viruses. This virus was designated woolly monkey hepatitis B virus (WMHBV). Analysis of woolly monkey colonies at five zoos indicated that WMHBV infections occurred in most of the animals at the Louisville zoo but not at four other zoos in the United States. The host range of WMHBV was examined by inoculation of one chimpanzee and two black-handed spider monkeys (Ateles geoffroyi), the closest nonendangered relative of the woolly monkey. The data suggest that spider monkeys are susceptible to infection with WMHBV and that minimal replication was observed in a chimpanzee. Thus, we have isolated a hepadnavirus with a host intermediate between humans and rodents and establishes a new animal model for evaluation of antiviral therapies for treating HBV chronic infections.

Animals↗

The census-based, impact-oriented approach: its effectiveness in promoting child health in Bolivia.

This paper describes the effectiveness for child health of a primary health care approach developed in Bolivia by Andean Rural Health Care and its colleagues, the census-based, impact-oriented (CBIO) approach. Here, we describe selected achievements, including child survival service coverage, mortality impact, and the level of resources required to attain these results. As a result of first identifying the entire programme population through visits at least biannually to all homes and then targeting selected high-impact services to those at highest risk of death, the mortality levels of children under five years of age in the established programme areas was one-third to one-half of mortality levels in comparison areas. Card-documented coverage for the complete series of all the standard six childhood immunizations among children 12-23 months of age was 78%, and card-documented coverage for three nutritional monitorings during the previous 12 months among the same group of children was 80%. Coverage rates in comparison areas for similar services was less than 21%. The local annual recurring cost of this approach was US $8.57 for each person (of all ages) in the programme population. This cost includes the provision of primary care services for all age groups as well as targeted child survival services. This cost is well within the affordable range for many, if not most, developing countries. Manpower costs for field staff in Bolivia are relatively high, so in countries with lower salary scales, the overall recurring cost could be substantially less. An Expert Review Panel reviewed the CBIO approach and found it to be worthy of replication, particularly if stronger community involvement and greater reliance on volunteer or minimally paid staff could be attained. The results of this approach are sufficiently promising to merit implementation and evaluation in other sites, including sites beyond Bolivia.

Bolivia↗

Noninvasive comprehensive characterization of renal artery stenosis by combination of STAR angiography and EPISTAR perfusion imaging.

In a small fraction of patients with hypertension, the cause is stenosis of the renal artery. To date, there is no established noninvasive screening technique available to identify this population, for whom treatment with a surgical procedure or percutaneous transluminal angioplasty is often possible. In this study, the sensitivity and specificity of STAR angiography and EPISTAR perfusion imaging in characterizing renal artery stenosis were evaluated in an animal model. Qualitatively, STAR provided projection angiograms that were comparably sensitive to x-ray angiograms but obtained noninvasively. The sensitivity for detecting the stenosis was 100%. The specificity varied according to the definition of the threshold for significance, which varied 78-94%, depending on whether > 70% or > 50% diameter reduction was considered. Improvements in specificity will depend upon use of shorter echo times and higher spatial resolution. Our preliminary data indicate that EPISTAR provides sensitivity and specificity of 100% for characterizing stenosis with diameter reductions of > 70%.

Animals↗

Lack of susceptibility of baboons to infection with hepatitis B virus.

Historically, hepatitis B virus (HBV) has been considered species specific and unable to infect baboons. Based on this premise, two patients with HBV endstage liver disease underwent baboon liver xenotransplantation. To study whether baboons are susceptible to HBV infection, four baboons (two receiving immunosuppressive therapy) were inoculated with HBV. Animals were followed for 6 months: clinical examinations and biochemical studies were normal, hepatitis B surface antigen and hepatitis B core antigen staining of biopsies was negative, and HBV serology remained negative. HBV polymerase chain reaction was transiently positive in one animal, which most likely reflects the initial inoculation. This pilot study corroborates historical evidence and beliefs that baboons are resistant to HBV.

Animals↗

Persistence of extrahepatic hepatitis B virus DNA in the absence of detectable hepatic replication in patients with baboon liver transplants.

The presence of hepatitis B virus (HBV) DNA in extrahepatic tissues has been well documented. Whether HBV DNA can persist in extrahepatic tissues for long periods of time in the absence of replication in the liver has not been determined previously. Recently, two patients with end-stage liver disease secondary to chronic active HBV were treated with baboon liver xenotransplants as these animals are felt to be resistant to HBV infection. Multiple tissues from these two patients were examined for HBV DNA using polymerase chain reaction (PCR). HBV DNA was not detectable in four of five samples of the liver xenografts. A positive signal was observed in a single assay for one sample, but this sample was not positive in subsequent assays. HBV DNA was detected in peripheral blood lymphocytes, spleen, kidney, bone marrow, pancreas, lymph node, heart and small intestine. The level of HBV DNA in these tissues was too low for the detection of HBV DNA replicative intermediates by Southern hybridization; thus, it could not be determined whether the HBV DNA in these tissues represented actively replicating HBV in extrahepatic sites, integrated HBV sequences, HBV in infiltrating lymphocytes, or deposition of HBV immune complexes originating from the plasma. However, it is clear from this study that HBV DNA persisted in multiple tissues for 70 days after replication in the liver had ceased or at least was below the level of detection by PCR.

Adult↗

Lack of detection of negative-strand hepatitis C virus RNA in peripheral blood mononuclear cells and other extrahepatic tissues by the highly strand-specific rTth reverse transcriptase PCR.

To further explore the controversial potential for extrahepatic replication of hepatitis C virus (HCV), the highly strand-specific rTth method of reverse transcriptase PCR was used to examine sera, liver, peripheral blood mononuclear cells, and other extrahepatic tissues from HCV-infected chimpanzees and humans. Positive-strand HCV RNA was present in the liver at approximately 10-fold-higher levels than negative-strand HCV RNA. No negative-strand RNA was detected in peripheral blood mononuclear cells or other extrahepatic tissues despite the presence of abundant positive-strand RNA. These data demonstrate that within the limits of sensitivity of this highly strand-specific reverse transcriptase PCR method, no extrahepatic replication of HCV was detected.

Animals↗

Analysis of hepatitis C virus capsid, E1, and E2/NS1 proteins expressed in insect cells.

The baculovirus/insect cell expression system was used to express the capsid protein and glycoproteins (e1 and e2/NS1) of the hepatitis C virus (HCV). Each polypeptide domain was expressed individually using two different constructs varying at their carboxy termini in order to retain or delete hydrophobic domains that may be involved in membrane association. The capsid proteins were transported to the nucleus where they formed a single large crystal-like inclusion. The capsid proteins were phosphorylated in insect cells. The e1 and e2 polypeptides were present in both the soluble and insoluble cellular fractions. Deletion of a hydrophobic domain in the carboxy terminus of e2 resulted in the polypeptide becoming soluble but not secreted. Deletion of the carboxy terminus of e1 had no effect on solubility. Both e1 and e2 were glycosylated, with variable glycosylation of e1 giving rise to a series of polypeptides varying in apparent molecular weight. Co-infection of insect cells with viruses expressing e1 and e2 resulted in a complex that permitted the coimmunoprecipitation of e1 with antibodies to e2 and vice versa. Immunofluorescence staining of insect cells expressing e1 and e2 indicated that reactivity to e2 was more prevalent in anti-HCV positive human sera.

Animals↗

Magnetic resonance urography by breath-hold contrast-enhanced three-dimensional FISP.

The purpose of this study was to present our initial experience with contrast-enhanced MR urography with a breath-hold three-dimensional imaging technique. We performed MR urographic studies in two pigs (four studies) and five human subjects using gadopentetate dimeglumine. The FISP sequence we used was the same as the one used for contrast-enhanced three-dimensional breath-hold angiography. MR three-dimensional urograms were obtained 7-24 minutes after the contrast injection with a dose as low as .03 mmol/kg. The calyces, renal pelves, and ureters were very well visualized. Three-dimensional MR urography can be acquired within a single breath-hold after administration of gadolinium chelates. This technique could become part of a protocol that could potentially lead to a single comprehensive diagnostic workup for suspected ureteral obstruction and gross hematuria.

Adult↗