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Biomedical subjects

J Osorio

Publications and source records attributed to J Osorio.

At least 19 recordsLinked to original sources

Better maintained adherence on switching from twice-daily to once-daily therapy for HIV: a 24-week randomized trial of treatment simplification using stavudine prolonged-release capsules.

BACKGROUND: Adherence to antiretroviral therapy is critical to treatment outcomes. Adherence studies in other therapeutic areas of medicine suggest that once-daily regimens support improved adherence when compared to twice-daily therapy. An expansion in the range of once-daily antiretrovirals is making once-daily therapy possible for persons with HIV infection. METHODS: A 24-week randomized open-label simplification study of twice-daily regimens based on stavudine immediate release or zidovudine to an all once-daily regimen based on the stavudine prolonged-release capsule (PRC), in persons with complete virological suppression on regimens also including efavirenz and lamivudine, was carried out. Subjects were assessed for adherence [using the Medication Event Monitoring System (MEMS) cap; Aardex Corporation, Union City, CA, USA], quality of life, tolerability and efficacy. RESULTS: Forty-three patients were randomly assigned: 21 remained on their original regimen and 22 switched to once-daily therapy with stavudine PRC. Although high levels of adherence and good quality of life were present at study enrollment, adherence declined to a significantly lesser extent at week 24 in the group that switched to once-daily therapy. Efficacy was maintained in both groups and there were no differences in tolerability or toxicity. CONCLUSIONS: Subjects switching from twice-daily therapy to once-daily therapy demonstrate less of a decline in adherence over 24 weeks. A once-daily regimen including stavudine PRC is as effective and tolerable as a regimen containing the twice-daily formulation.

Adult↗

A family based study shows no association between rheumatoid arthritis and the PADI4 gene in a white French population.

BACKGROUND: Autoantibodies to citrullinated proteins (ACPA) are considered a specific marker for rheumatoid arthritis. Peptidylarginine deiminase (PAD) is the enzyme that converts arginyl into citrullyl residues; different isoforms of the enzyme are expressed in mammals. It has been suggested that the PADI4 gene may contribute to genetic susceptibility to rheumatoid arthritis, but conflicting results have been obtained in different populations. OBJECTIVE: To test the hypothesis that the PADI4 gene may confer susceptibility to rheumatoid arthritis in a white French population, using powerful and highly reliable family based association tests. METHODS: DNA samples were analysed from 100 families where one member was affected by rheumatoid arthritis and both parents were available for sampling. Five single nucleotide polymorphisms, located within the PADI4 gene and in its close proximity, were genotyped by restriction fragment length polymorphism, and haplotypes were constructed. The analysis involved use of the transmission disequilibrium test and genotype relative risk. ACPA were detected by ELISA on cyclic citrullinated peptides and on human deiminated fibrinogen. RESULTS: No single SNP or haplotype was associated with the disease, or was preferentially transmitted. No association was found when patients were partitioned according to ACPA positivity. CONCLUSIONS: No PADI4 haplotype is associated with rheumatoid arthritis in a white French population. The role of genes encoding the other PAD isoforms, or modulating tissue expression or enzyme activity, remains to be elucidated.

Adult↗

Epidermal powder immunization with a recombinant HIV gp120 targets Langerhans cells and induces enhanced immune responses.

The recombinant envelope gp120 (rgp120) of human immunodeficiency virus (HIV) is a weak immunogen when administered by intramuscular (IM) injection. In the present study, we report that epidermal powder immunization (EPI) elicits robust antibody responses to the rgp120. EPI of mice with a dose 0.2-5 microg of rgp120 protein elicited geometric mean antibody titers that were 18- to 240-fold higher than that elicited by IM injection using a 5.0 microg dose. Targeting antigen to and mobilization of Langerhans cells (LCs) by EPI may explain the enhanced immunogenicity of the rgp120. EPI with rgp120 using sugar and gold particles as carrier resulted in differential antigen entry into the LCs and differential IgG subclass antibody and cellular immune responses. EPI may serve as a useful tool to evaluate vaccine potential of the rgp120 protein.

AIDS Vaccines↗

Circadian patterns in men acclimatized to intermittent hypoxia.

Six men, normally working shifts of 7 days at high altitude (HA, 3800 m, approximately 480 mm Hg barometric pressure) followed by 7 days of rest at sea level (SL), were studied during the last days of their HA and SL shifts with a 24-h constant routine protocol of sustained wakefulness and minimal activity. The amplitude of the circadian oscillations of oxygen consumption, breathing rate, thoracic skin temperature and diastolic pressure did not differ between HA and SL. At HA, the amplitude of the tympanic and calf temperature oscillations, were, respectively, lower and higher than at SL. End-tidal P(CO2) and systolic pressure had larger amplitude oscillations at HA than at SL. Hence, also in humans, as previously shown in animals, hypoxia can affect some circadian patterns, including those involved in thermoregulation. These effects of hypoxia could contribute to sleep disturbances at HA and in patients with cardiorespiratory diseases.

Acclimatization↗

Artificial liver support devices for fulminant liver failure.

Artificial liver-support devices attempt to bridge patients with fulminant hepatic failure until either a suitable liver allograft is obtained for transplantation or the patient's own liver regenerates sufficiently to resume normal function. It is thought that toxins contribute to the clinical picture of fulminant hepatic failure. The earliest reports of successful toxin removal were blood- and plasma-exchange transfusions. Given these successful case reports, mechanical liver-support devices were designed to filter toxins. These mechanical devices used hemodialysis, charcoal hemoperfusion, hemoperfusion through cation-exchange resins, hemodiabsorption, and combinations of all of these techniques as in the MARS liver-support device. Despite promising case reports and small series, no controlled studies of mechanical devices have ever showed a long-term survival benefit. Thus, the removal of presumed toxins seems to be insufficient to support patients with fulminant hepatic failure, and the biologic function of the liver must also be replaced. Attempts at replacing the biologic function have included extracorporeal liver perfusion, cross-circulation, and hepatocyte transplantation. Current technologies have combined mechanical and biologic support systems in hybrid liver-support devices. The mechanical component of these hybrid devices serves both to remove toxins and to create a barrier between the patient's serum and the biologic component of the liver-support device. The biologic component of these hybrid liver support devices may consist of liver slices, granulated liver, or hepatocytes from low-grade tumor cells or porcine hepatocytes. These biologic components are housed within bioreactors. Currently the most clinically studied bioreactors are those that use capillary hollow-fiber systems. Both the bioartificial liver by Demetrious and the extracorporeal liver-assist device by Sussman and Kelly are in clinical trials. Although the trials seemed to have yielded good survival data when the devices are used as a bridge to transplantation, the type and degree of liver support provided by these devices remains uncertain. Thus, despite decades of great progress in the field of artificial liver support, no one technique alone yet provides sufficient liver support. A hybrid system seems to be the best option at present. Still to be determined is the best tissue to use, how much liver tissue should be used, and the optimal design of the bioreactor.

Cell Transplantation↗

Epidermal powder immunization induces both cytotoxic T-lymphocyte and antibody responses to protein antigens of influenza and hepatitis B viruses.

Cytotoxic T lymphocytes (CTL) play a vital role in host defense against viral and intracellular bacterial infections. However, nonreplicating vaccines administered by intramuscular injection using a syringe and needle elicit predominantly humoral responses and not CTL responses. Here we report that epidermal powder immunization (EPI), a technology that delivers antigens on 1.5- to 2.5-microm gold particles to the epidermis using a needle-free powder delivery system, elicits CTL responses to nonreplicating antigens. Following EPI, a majority of the antigen-coated gold particles were found in the viable epidermis in the histological sections of the target skin. Further studies using transmission electron microscopy revealed the intracellular localization of the gold particles. Many Langerhans cells (LCs) at the vaccination site contained antigen-coated particles, as revealed by two-color immunofluorescence microscopy, and these cells were found in the draining lymph nodes 20 h later. Immune responses to several viral protein antigens after EPI were studied in mice. EPI with hepatitis B surface antigen (HBsAg) and a synthetic peptide of influenza virus nucleoprotein (NP peptide) elicited antigen-specific CTL responses as well as antibody responses. In an in vitro cell depletion experiment, we demonstrated that the CTL activity against HBsAg elicited by EPI was attributed to CD8(+), not CD4(+), T cells. As controls, needle injections of HBsAg or the NP peptide into deeper tissues elicited solely antibody, not CTL, responses. We further demonstrated that EPI with inactivated A/Aichi/68 (H3N2) or A/Sydney/97 (H3N2) influenza virus elicited complete protection against a mouse-adapted A/Aichi/68 virus. In summary, EPI directly delivers protein antigens to the cytosol of the LCs in the skin and elicits both cellular and antibody responses.

Animals↗

Comparative analysis of the promoter structure and genomic organization of the human and mouse ABCA7 gene encoding a novel ABCA transporter.

We report here the genomic and transcriptional characterization in mouse and man of a novel transporter of the ABCA subclass, named ABCA7. As it is the case for other ABCA genes, the predicted protein encoded by ABCA7 is a full symmetric transporter, highly conserved across species. The ABCA7 gene maps to human chromosome 19 and to the homologous region at band B4-C1 on mouse chromosome 10. The preferential expression of ABCA7 in the spleen, thymus, and fetal liver is consistent with the finding, in both human and mouse promoter, of sites targeted by lymphomyeloid-specific transcription factors. This suggests that ABCA7 may play a pivotal role in the developmental specification of hematopoietic cell lineages.

ATP-Binding Cassette Transporters↗

[Acute mountain sickness at 3500 and 4250 m. A study of symptom, incidence and severity].

BACKGROUND: Acute Mountain Sickness (AMS) refers to signs and symptoms associated with hypobaric hypoxia. Its reported incidence is highly variable. AIM: To determine the incidence of AMS symptoms and severity at 3,500 and 4,250 m above sea level. SUBJECTS AND METHODS: A population of 362 soldiers without former exposure to altitude was studied. AMS symptoms, were assessed by an extensively used standard questionnaire (Lake Louise), applied 36-72 hours after exposure to high altitude. RESULTS: A group of 200 recruits ascended to Putre (3,500 m) and a second group (162) ascended to Alto Pacollo (4,250 m). The incidence of AMS was 28% and 60% respectively (p < 0.05). Headaches and sleeping difficulties were the most frequent symptoms at both altitudes. Furthermore, severe digestive problems and dizziness were described in a high proportion of individuals at both 3,500 and 4,250 m. CONCLUSIONS: The prevalence of AMS in this study is similar to that reported elsewhere at equivalent altitudes.

Acute Disease↗

Complete genomic sequence of the human ABCA1 gene: analysis of the human and mouse ATP-binding cassette A promoter.

The ABCA1 gene, a member of the ATP-binding cassette A (ABCA1) transporter superfamily, encodes a membrane protein that facilitates the cellular efflux of cholesterol and phospholipids. Mutations in ABCA1 lead to familial high density lipoprotein deficiency and Tangier disease. We report the complete human ABCA1 gene sequence, including 1,453 bp of the promoter, 146,581 bp of introns and exons, and 1 kb of the 3' flanking region. The ABCA1 gene spans 149 kb and comprises 50 exons. Sixty-two repetitive Alu sequences were identified in introns 1-49. The transcription start site is 315 bp upstream of a newly identified initiation methionine codon and encodes an ORF of 6,783 bp. Thus, the ABCA1 protein is comprised of 2,261 aa. Analysis of the 1,453 bp 5' upstream of the transcriptional start site reveals multiple binding sites for transcription factors with roles in lipid metabolism. Comparative analysis of the mouse and human ABCA1 promoter sequences identified specific regulatory elements, which are evolutionarily conserved. The human ABCA1 promoter fragment -200 to -80 bp that contains binding motifs for SP1, SP3, E-box, and AP1 modulates cellular cholesterol and cAMP regulation of ABCA1 gene expression. These combined findings provide insights into ABCA1-mediated regulation of cellular cholesterol metabolism and will facilitate the identification of new pharmacologic agents for the treatment of atherosclerosis in humans.

ATP Binding Cassette Transporter 1↗

Sequelae after nasal septum injuries in children.

OBJECTIVE: To study the results of surgical treatment and sequelae in nasal septum injuries in children. METHODS: Between January 1990 and December 1997, 16 pediatric patients with septal haematoma and/or abscess were treated. Mean age was 5 years (range: 2-14 years). Thirteen were male (81.2%), and three were female (18.8%). In nine cases (56.2%) the disease was a consequence of a minor trauma. Only two children had nasal fracture associated (12.5%). Minimum follow-up after the first visit was 10 months (mean, 3 years). RESULTS: All cases were surgically treated. Minor sequelae were observed in six cases (37.5%), and major ones in ten patients (62.5%). In this latter group, multiple reconstructive procedures were needed. CONCLUSIONS: It is necessary to be aware of the possibility of haematoma and abscess of the nasal septum. Major sequelae can be also expected after cases following minor traumas.

Abscess↗

Cocaine-induced mesenteric ischaemia.

We report a 33-year-old man with distal ileum infarction after intravenous abuse of cocaine. He underwent resection of a gangrenous bowel segment and survived. We review the literature regarding intestinal ischaemia related to cocaine. To date, 19 cases have been published. Like most previously reported cases, our patient was young and had no previous history of arteriosclerosis. He suffered cocaine-induced rhabdomyolysis and acute renal failure. Mesenteric ischaemia should be considered in the differential diagnosis of acute or chronic abdominal pain in cocaine consumers.

Adult↗

Ideal gingival form with computer-generated permanent healing abutments.

Implant fixture positioning and inclination problems that result from poor osseous height, width, and ridge configuration have created difficult prosthetic tooth replacement scenarios. Options for ameliorating poor angulation are limited to the use of preangled and custom abutments. Overcoming poor angulation has been simplified by using custom vs preangled abutments because preangled abutments are limited by their standardization to a few random angles. Custom abutments can be more predictably formed to re-create the desired supporting preparation orientation and morphology. This facilitates the formation of anatomical gingival topography and coronal contours for prosthetic replacement. Cast, ceramic, and machine-milled titanium abutments have several advantages and disadvantages. A new custom abutment system that uses computer-guided manufacturing technology to machine mill custom abutments from commercially pure titanium is described. These abutments are anatomically correct, have the proper emergence anatomy, proper spatial design at the cervical margins, necessary occlusal reduction, and the proper axial angulation of ideal tooth preparations. A clinical case that illustrates implementation, with respect to the principle of stage 2 guided tissue healing, is presented.

Anodontia↗

Managed care, school health programs, and adolescent health services: opportunities for health promotion.

The rapid expansion of managed care creates opportunities and dilemmas for those involved in school health and adolescent health promotion. Managed care organizations (MCOs), public health agencies, and school and adolescent health providers share certain common goals and priorities including an emphasis on prevention, cost-effectiveness, and quality of care--and a willingness to explore innovative approaches to health promotion and disease prevention. However, MCOs often face conflicting challenges, balancing the goals of cost containment and investment in prevention. In considering support for school health programs, MCOs will be interested in evidence about the effectiveness of services in improving health and/or reducing medical expenditures. Mechanisms for improving prevention efforts within MCOs include quality assurance systems to monitor the performance of health plans, practice guidelines from professional organizations, and the contracting process between payers and health care providers. Development of partnerships between MCOs and schools will be a challenge given competing priorities, variation in managed care arrangements, structural differences between MCOs and schools, and variability in services provided by school health programs.

Adolescent↗

[Measurement of maximal oxygen uptake in a Chilean population sample].

BACKGROUND: Maximal oxygen uptake is considered by the International Biological Programme as the international standard of cardiorespiratory adequacy and physical condition. AIM: To measure maximal oxygen uptake in normal Chilean subjects, to establish normal reference values. SUBJECTS AND METHODS: Maximal oxygen uptake was measured in 2,203 subjects (451 women) aged 7 to 66 years old, during maximal exercise in a cyclo-ergometer or treadmill. This sample included trained sportsmen. RESULTS: Maximal oxygen uptake in men was 3.4 +/- 0.8 Vmin (range 1.1 to 5.6) or 55.2 +/- 9.2 ml/kg/min (range 23.8 to 83.2). In women, the figures were 2.55 +/- 0.55 l/min (range 0.87 to 3.82) or 47.5 +/- 8.0 ml/kg/min (range 20.8 to 76.3). These values decrease 0.65 ml/kg/min per year of age. CONCLUSIONS: These values can be useful as a normal reference for epidemiological, clinical or sportive purposes.

Adolescent↗

[Evaluation of commercially available reagents for diagnosis of chagas disease in Chilean blood banks. I. Selection of reagents].

Infection with T cruzi through blood transfusion is an important public health problem in Latin America, including Chile. A study on the sensitivity, specificity and applicability of currently applied methods was performed. Ten commercially available products were tested in a panel of 180 blood specimens against the indirect immunofluorescence antibody test (IFAT) and the immunoperoxidase test (IP). Qualitative concordance ranged from 82 to 98%, sensitivity from 64 to 97% and specificity from 93 to 100%. Some commercial products had a low performance and ELISA is recommended for routine use in Chilean blood banks, given its significantly higher sensitivity and specificity when compared to the hemagglutination test. In addition, experience with the use of the ELISA test is widespread in Chile.

Animals↗

[Functional evaluation of a nutritional energy supplement in athletes].

A nutritional caloric supplement as bar in 5 different flavours was evaluated in 9 sportsmen that ate daily 1040 Kcal/100 g extra during 8 weeks. Anthropometric measurements were used for weight, body fat, lean body mass and functional test for VO2 max, anaerobic threshold (AnT) and anaerobic power (AnP). Both tolerance and acceptability were evaluated too. Other similar sportsmen group was employed as control. Positives answers were registered in VO2 max (8.74%) and AnP (p < or = .04), meanwhile the rest of parameters remained without alterations, the same of control group. Test TAT evidence a high preference and a tolerance without deleterious effect. In conclusion, the product evaluated is an excellent ergogenic aid in effort with elevated energetic demand.

Adult↗