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Biomedical subjects

S C Wood

Publications and source records attributed to S C Wood.

At least 19 recordsLinked to original sources

Transforming growth factor beta-induced connective tissue growth factor and chronic allograft rejection.

Late loss of allograft function is primarily attributed to chronic rejection (CR). There are no effective treatments for CR and the underlying cause of the disease is unknown. This study compared events that occurred within cardiac allografts placed in mice that received either anti-CD4 therapy and develop CR or anti-CD40L therapy and do not develop CR. Both TGFbeta and connective tissue growth factor (CTGF), which is induced by TGFbeta, were expressed in grafts with CR but were not expressed in grafts without CR. TGFbeta transfection of allografts in anti-CD40L-treated recipients resulted in CTGF expression and CR. However, TGFbeta transfection of syngeneic grafts did not result in CTGF expression or CR. These data indicate that TGFbeta alone is insufficient to induce CR and that CTGF is required. Further, antigenic stimulation is required for TGFbeta induction of CTGF. Thus, CTGF may serve as a therapeutic target for CR.

Animals↗

A field based evaluation of household arsenic removal technologies for the treatment of drinking water.

Seven household treatment technologies for the removal of arsenic (Alcan, BUET, DPHE/DANIDA, Garnet, Sono, Stevens, Tetrahedron) were each evaluated using water from 63 different tube wells taken from 3 different regions of Bangladesh. The technologies that were evaluated were chosen from those that appeared user friendly, readily available and whose promoters were open to participate in the study. Arsenic concentrations in feed and treated waters were analysed by the PeCo 75 arsenic field test kit, AA-hydride generation and ICP-AES. Feed water arsenic concentrations were found to be up to 600 microg l(-1). The more advanced treatment methods using: activated alumina (Alcan, BUET); metallic iron (Sono); anionic exchange resin (Tetrahedron) and iron coagulation (Stevens) were found to be most easily used and efficiently reduced arsenic concentrations to below the Bangladesh drinking water standard (0.05 mg As l(-1)). The use of aluminium sulphate coagulants and permanganate oxidants in the DPHE/DANIDA technology introduced unacceptably high concentrations of aluminium and manganese into the treated waters and are not recommended in household water treatment applications. While arseric concentrations were initially considered to be of paramount importance, it became clear that such technologies can increase the risk of bacterial contamination in the treated water and this needs serious consideration as this could create a hazard much greater than the arsenic contained in the water. Ground waters sampled during the course of this study were mostly found to be bacteria free. To minimize any risks relating to bacterial contamination the addition of hypochlorite or the boiling of water is necessary.

Aluminum Oxide↗

Cost-effectiveness of influenza vaccination in high-risk children in Argentina.

OBJECTIVES: our study aimed to evaluate the cost-effectiveness of influenza vaccination in high-risk children in Argentina. METHODS: a decision analysis model was performed, using data from published and unpublished sources, to compare two strategies--to vaccinate or not to vaccinate. We simulated the expected consequences of vaccination on direct medical costs, related to disease management and indirect costs, related to lost parental working days (absenteeism). RESULTS: Using base-case assumptions vaccination of high-risk children aged 6 months to 15 years old, in Argentina (estimated cohort of 1184748) would prevent 207331 cases of influenza, resulting in a reduction of 58052 days of hospitalization and 207331 outpatient visits. Vaccination would lead to net savings of US$ 11894870 per vaccinated cohort (US$ 10.04 per vaccinated child). CONCLUSION: our economic analysis shows that in Argentina, routine vaccination of high-risk children against influenza would be cost saving for society.

Adolescent↗

Role of airway receptors in altitude-induced dyspnea.

PURPOSE: The purpose of this study was to examine the role of airway receptors in respiratory-related sensations after ascent to altitude. METHODS: Ratings of respiratory-related sensations, perceived exertion and acute mountain sickness, heart rate, and peripheral oxygen saturation were recorded at rest and exercise in male and female subjects who had inhaled either aerosolized saline or saline with tetracaine after acute ascent to an altitude of 3500 m and after prolonged acclimatization of 18 d at altitudes between 4000 and 5000 m. RESULTS: Tetracaine had no effect on respiratory-related sensations at altitude either at rest or during exercise, and male and female subjects experienced similar respiratory-related sensations. Sensations of rapid breathing were experienced at rest after acute exposure to 3500 m as compared with sea level, but not after acclimatization to 5000 m. Sensations of rapid breathing, air hunger, and heavy breathing were experienced during exercise after acute and prolonged altitude exposure as compared with sea level, with a sensation of chest tightness experienced at 3500 m and a sensation of gasping experienced at 5000 m. CONCLUSION: These results suggest that airway afferents play no role in the respiratory-related sensations experienced by male and female subjects either during acute ascent to altitude or after prolonged acclimatization at altitude.

Adult↗

Safety and immunogenicity of a pediatric formulation of inactivated hepatitis A vaccine in Argentinean children.

BACKGROUND: Children are a reservoir of hepatitis A virus and must be considered as primary targets of any immunization strategy. The safety and immunogenicity were evaluated for a new formulation of an inactivated hepatitis A vaccine, Avaxim 80 units, containing one-half the antigen dose of the adult formulation. METHODS: The safety of two doses of this vaccine given 6 months apart was evaluated in an open study in 537 Argentinean children 12 months to 15 years old. Immunogenicity was evaluated at Weeks 0, 2, 24 and 27 in a subgroup of 120 subjects. RESULTS: Two weeks after the first vaccine dose, >99% of initially seronegative children had seroconverted (titers > or =20 mIU/ml), with a geometric mean titer of 98.5 mIU/ml. Before booster at 24 weeks all subjects had seroconverted. A strong anamnestic response was observed after the second dose at which time the geometric mean titer had increased >35-fold, and antibody titers were consistent with long term protection. Immediate adverse reactions were observed in 3 of 537 (0.6%) subjects after the first dose. Local reactions were mild and transient and did not increase with subsequent doses. Among the systemic events reported during the 7-day follow-up period, 37 cases of fever after the first dose and 22 cases after the second dose were reported. Only 3 cases of fever were clearly related to vaccination (< or =38.2 degrees C) after the first injection, all of which subsided in less than 1 day. CONCLUSIONS: This study demonstrated the safety and immunogenicity of a pediatric formulation of hepatitis A vaccine in children ages 12 months to 15 years in healthy children ages 12 to 47 months.

Adolescent↗

Immunogenicity and effectiveness of post-exposure rabies prophylaxis with a new chromatographically purified Vero-cell rabies vaccine (CPRV): a two-stage randomised clinical trial in the Philippines.

Recent improvements in chromatographic purification procedures have made it possible to develop a new chromatographically purified rabies vaccine (CPRV) by further purifying the current rabies vaccine prepared from Vero-cell culture (PVRV) (Verorab; Pasteur Merieux Connaught). The immunogenicity and effectiveness of post-exposure rabies prophylaxis with this new vaccine were evaluated in a two-stage clinical trial conducted in the Philippines. In both study stages. post-exposure treatment consisted of five injections of vaccine [(D)ays 0, 3, 7, 14, 28], together with a dose of rabies immunoglobulin (RIG) of equine or human origin on D0. In stage 1, 231 subjects with low-risk rabies exposure (WHO category I or II), and who had a negative ERIG skin test, were treated with either CPRV (n = 114) or PVRV (n = 117). By D14, all subjects in each group had achieved rabies antibody titres over ten times that recommended by the WHO as indicating seroconversion (> or = 0.5 IU/ml). The kinetics of the immune response to vaccination were very similar in the two groups, and at D28, the immunogenicity of CPRV was equivalent to that of PVRV (one-sided equivalence test). Following these positive results, 132 subjects with severe rabies exposure were included in the second stage of this trial. All were scheduled to receive four vaccine doses with CPRV. After D14, only those 57 patients with confirmed rabies exposure (animal with positive FA test) and seven patients for whom rabies exposure could not be excluded (animal lost or not tested) completed the treatment and were followed for one year to assess survival. After 1 year, 62 patients treated for confirmed or possible severe rabies exposure had been examined and were still alive. Two patients contacted by letter and telephone confirmed good health 7 and 16 months after exposure. No severe local or systemic reactions were reported in either stage of the study, and no treatment-related serious adverse event occurred. This two-stage clinical trial attests to the safety and satisfactory immunogenicity of CPRV in post-exposure rabies treatment, and confirms the effectiveness of a new rabies vaccine in patients with severe confirmed exposure.

Adolescent↗

Role of adenosine in the hypoxia-induced hypothermia of toads.

The concept that hypoxia elicits a drop in body temperature (T(b)) in a wide variety of animals is not new, but the mechanisms remain unclear. We tested the hypothesis that adenosine mediates hypoxia-induced hypothermia in toads. Measurements of selected T(b) were performed using a thermal gradient. Animals were injected (into the lymph sac or intracerebroventricularly) with aminophylline (an adenosine receptor antagonist) followed by an 11-h period of hypoxia (7% O(2)) or normoxia exposure. Control animals received saline injections. Hypoxia elicited a drop in T(b) from 24.8 +/- 0.3 to 19. 5 +/- 1.1 degrees C (P < 0.05). Systemically applied aminophylline (25 mg/kg) did not change T(b) during normoxia, indicating that adenosine does not alter normal thermoregulatory function. However, aminophylline (25 mg/kg) significantly blunted hypoxia-induced hypothermia (P < 0.05). To assess the role of central thermoregulatory mechanisms, a smaller dose of aminophylline (0.25 mg/kg), which did not alter hypoxia-induced hypothermia systemically, was injected into the fourth cerebral ventricle. Intracerebroventricular injection of aminophylline (0.25 mg/kg) caused no significant change in T(b) under normoxia, but it abolished hypoxia-induced hypothermia. The present data indicate that adenosine is a central and possibly peripheral mediator of hypoxia-induced hypothermia.

Adenosine↗

The effect of graded hypoxia on the metabolic rate and buccal activity of a lungless salamander (Desmognathus fuscus).

The hypothesis that the lungless salamander Desmognathus fuscus responds actively to hypoxia was tested. Patterns of buccal movements [apneic period duration, the duration (min h(-)(1)) of buccal pumping and buccal pumping frequency], heart rate and metabolic rate (rates of oxygen uptake and carbon dioxide output) were determined during a control period (21 % oxygen), a hypoxic period (2, 5, 6.5, 8 or 10 % oxygen) and a recovery period (21 % oxygen). Hypoxic salamanders maintained their rate of oxygen uptake at control levels until a critical oxygen level between 10 and 8 % oxygen was reached. The rate of carbon dioxide output remained constant across all oxygen levels, except for a significant increase during exposure to 5 % oxygen. The buccal activity of lungless salamanders was responsive to environmental hypoxia, with a significant stimulation during exposure to 6.5 % and 5 % oxygen. Buccal pumping frequency was inhibited at 2 % oxygen. Heart rate was stimulated at all hypoxic levels except 2 % O(2). During recovery, metabolic rate and heart rate returned to control levels within 20 min after all hypoxic exposures. The durations of apneic periods increased significantly compared with the hypoxic value during recovery from exposure to 10 %, 6.5 % and 5 % oxygen. Overall, the animals responded actively to hypoxia by increasing the duration of buccal activity as oxygen levels decreased. The ability of these changes to facilitate oxygen uptake is not known. However, the response of the dusky salamander to low levels of oxygen is analogous to the hypoxic ventilatory response observed in lunged vertebrates.

Animals↗

Economic evaluations of influenza vaccination in healthy working-age adults. Employer and society perspective.

OBJECTIVE: To determine what benefits to the employer and to society are associated with influenza (flu) vaccination in healthy adults. DESIGN AND METHODS: We performed a literature review concerning cost-benefit and cost-effectiveness evaluations of influenza vaccination in healthy, working-age adults. Up to the end of 1999, we found 6 published economic evaluations on the use of influenza vaccine in healthy, working-age adults: 3 prospective studies, 1 retrospective evaluation and 2 model-based simulations. Evaluations were performed from the perspective of an employer or society. Costs were reported in the local currency used in the published evaluation, with conversions into US dollars (when not provided in the article), for comparative purposes only, according to the exchange rates of June 8 1998. MAIN OUTCOME MEASURES AND RESULTS: Estimations of the cost-benefit of vaccination, compared with a no vaccination strategy, varied widely from a net loss of $US106.59 per infection averted in one study to savings of varying sizes in the 5 others (savings ranged from $US2.58 per dollar invested to $US46.85 per vaccinee). Studies differed in the definition of illness and the measurement of costs associated with vaccination or illness. CONCLUSIONS: Decision makers have not yet extended existing vaccine recommendations to cover healthy, working-age adults, partly because of the disparity among economic studies in their methods of estimating costs and measuring effects. However, the published studies seem to suggest that influenza vaccination in the healthy, working adult would be a cost-effective health intervention, at least from the perspective of an employer.

Adult↗

Immunogenicity and safety of purified Vero-cell rabies vaccine in severely rabies-exposed patients in China.

The immunogenicity and safety of a purified Vero-cell rabies vaccine (PVRV, VERORAB; Aventis Pasteur, France) were evaluated in 171 patients treated for severe exposure to rabies (WHO category III contacts) at the Shandong Provincial Antiepidemic Station in Jinan and an EPI center in Ping Yin, China. Post-exposure treatment consisted of a single dose of equine rabies immunoglobulin (ERIG, 40 IU/kg body weight) on Day (D) 0, and intra-muscular administration of PVRV on D 0, 3, 7, 14 and 28. Antirabies antibody levels were evaluated on D 0, 7, 14, 28, 90 and 180 using the rapid fluorescent focus inhibition test. By D 14 all subjects had seroconverted (> or = 0.5 IU/ml), with a geometric mean titer of 50.3 IU/ml. Antibody titers remained above the seroprotection threshold in all patients for 3 months, and in 98.2% of subjects for 6 months. All patients were still alive 6 months after the start of treatment. PVRV and ERIG were shown to be well tolerated and no serious adverse events were observed. Following PVRV administration, 12 patients (7.0%) had at least one local reaction (mostly pruritus, erythematous rash and pain). Fourteen patients (8.2%) developed local reactions at the site of ERIG administration. Twelve patients (7.0%) developed systemic reactions following post-exposure treatment, the most frequent of which were pruritus, rash and vertigo. This study demonstrates that PVRV is immunogenic and safe in Chinese patients treated according to WHO recommendations for severe rabies exposure.

Animals↗

New acellular pertussis-containing paediatric combined vaccines.

Combined pediatric vaccines have the advantages of conferring protection against multiple common infectious diseases with a reduced number of injections. Their use should lead to better compliance to recommended vaccination schedules. Diphtheria (D), tetanus (T) and whole-cell pertussis vaccine (P) have been successfully combined, with or without inactivated poliovirus vaccine (IPV) in the same syringe for many years. Recently developed acellular pertussis (aP) Haemophilus influenzae type B (Hib), inactivated poliomyelitis virus and hepatitis B vaccines are ideal candidates for inclusion in current combined vaccines. Nevertheless, the development of new combinations has to face preclinical and clinical issues: the appropriate formulation of the new antigen(s) and other vaccine components needs to be determined to ensure compatibility and guard against potential additive or unexpected adverse reactions; potential immunological interference between antigens and the negative impact of other vaccine components on immunogenicity may occur, and these have to be examined also. Whole-cell pertussis vaccines are highly protective against whooping cough, but the severe adverse reactions that these vaccines sometimes produce have led to hesitation over their use, including the decision of some countries to stop pertussis immunization. To increase the acceptability of pertussis vaccination, Pasteur Mérieux Connaught has developed a combined D, T and a two-component acellular pertussis vaccine (DTaP), composed of purified pertussis toxoid (PT) and filamentous haemagglutinin (FHA), which has been shown to be effective in an efficacy trial conducted in Senegal. Acellular DTaP vaccines are immunogenic and have a better safety profile than DTP vaccines, when given either for the primary series, for the booster vaccination or for both. In order to meet worldwide demands, the combined DTaP-IPV or DTP-IPV has been developed for countries where IPV is recommended. Following the encouragement of the WHO, an H. influenzae type B tetanus-conjugated (Act-HIB) vaccine, has been combined in a full liquid formulation with the whole-cell DTP. This vaccine showed a good safety and immunogenicity profile in infants and in toddlers. A combined DTaP-IPV-PRP-T vaccine (where the Act-HIB vaccine is reconstituted by the full-liquid DTaP-IPV) also has been successfully developed both for the primary series and for booster vaccination; although, a reduced immunogenicity against PRP observed after the primary series, this did not affect vaccine priming. Hepatitis B immunization campaigns targeting high-risk groups have failed to control the disease in areas of low endemicity. In 1992, the WHO recommended that hepatitis B vaccination should be integrated into the EPI in all countries by 1997-1999. For that purpose, hepatitis B vaccine is currently evaluated in pediatric combined vaccines. Developing new combination vaccines is a difficult but essential process for maintaining high immunization rates worldwide against infectious diseases, provided that the costs are acceptable. New combined vaccines including pneumococcal and meningococcal component are under wide-scale development.

Hepatitis B Vaccines↗

Multidose streptozotocin induction of diabetes in BALB/cBy mice induces a T cell proliferation defect in thymocytes which is reversible by interleukin-4.

Thymic T cell function in streptozotocin-treated (STZ) diabetic mice has been examined. STZ administration suppresses thymic T cell proliferation in response to mitogen stimulation in vitro. Secretion of IL-4 was dramatically reduced; however, secretion of IL-2 or IFN-gamma was not significantly inhibited. RT-PCR analysis of thymocyte RNA revealed that levels of IL-4 mRNA were dramatically decreased in STZ-treated mice. Levels of mRNA encoding IFN-gamma were similar, but the appearance was delayed in thymocytes derived from STZ-treated mice, implying differential regulation of IL-4 and IFN-gamma. Defective thymocyte proliferation was partially restored by exposure to IL-2 in vitro; however, IL-4 completely reversed the STZ-induced defect. Administration in vivo of IL-4 before STZ treatment reversed the STZ-induced thymocyte proliferation defect and prevented both pancreatic islet destruction and hyperglycemia. Thymocyte cell surface differentiation markers were not appreciably different from control mice. Collectively these experiments suggest that STZ treatment of mice reduces expression of IL-4 which is associated with development of autoimmune diabetes.

Animals↗

A new Vero cell rabies vaccine: results of a comparative trial with human diploid cell rabies vaccine in children.

We evaluated the immunogenicity and safety of a chromatographically purified rabies vaccine (CPRV) compared with human diploid cell rabies vaccine (HDCV) after pre-exposure immunizations (both primary and booster). Intramuscular doses of either 0.5 mL of CPRV or 1.0 mL of HDCV were given to 400 schoolchildren on days 0, 7, 28, and 365 (booster). Adequate titers of antibody (> or = 0.15 IU/mL, as defined by the Centers for Disease Control and Prevention) were observed in serum samples from all children 14 days after primary immunization with CPRV and HDCV; the antibodies persisted in all but one child up until 1 year. Fourteen days after the primary immunization series (day 42) and 7 days after booster immunization (day 372), all children had antibody titers of > or = 0.5 IU/mL. Local and systemic reactions after primary and booster immunizations occurred significantly less frequently in the CPRV group. A severe allergic reaction (angioedema) was reported in only one child after booster immunization with HDCV. CPRV has adequate immunogenicity for primary and booster pre-exposure immunizations in children and has a better safety profile than does HDCV.

Animals↗

Molecular analysis of ovine prion protein identifies similarities between BSE and an experimental isolate of natural scrapie, CH1641.

New variant Creutzfeldt-Jakob disease (vCJD) and bovine spongiform encephalopathy (BSE) are caused by the same strain of pathogen and, as sheep can develop experimental BSE, this has raised concern that humans may be at risk from eating mutton if BSE has naturally transmitted to sheep. Biochemical typing of abnormal prion proteins (PrPsc) has been suggested to detect BSE in sheep. Although this approach is ingenuous, we can now report biochemical evidence of strain variation in contemporary and archival brain tissue from cases of experimental BSE or experimental and natural scrapie in sheep. Interestingly, we found at least one isolate of natural scrapie (CH 1641) with a very similar, but not identical, PrPsc profile to BSE but which differs from BSE in its transmission characteristics to mice.

Animals↗

Effect of gender on thermoregulation and survival of hypoxic rats.

1. Hypothermia is a documented response to hypoxia but little is known about possible gender differences. Because female rats have a greater hypoxic ventilatory response than males, we hypothesized that females would be more tolerant of hypoxia. We studied 18 female and 18 male Long-Evans rats. 2. Radiotelemetry transmitters for body temperature (Tb) were implanted under general anaesthesia (90 mg/mL ketamine and 10 mg/mL xylazine; 0.1 mL/100 g bodyweight, i.p.). 3. Rats were exposed to 21, 16, 12, 10, 8, 6, 4 and 2% O2 (balance N2) for 30 min each in chambers kept at either 31 degrees C (clamped) or 20 degrees C (hypothermic). Survival was defined as ataxic and unresponsive. 4. Females were more hypoxia tolerant than males, often enduring 2% inspired O2 (13 km altitude). 5. This was correlated with a lower Tb in the hypothermic group, but not in the clamped group. 6. Hypothermia increased 'survival' of rats independent of gender. 7. When Tb was clamped, female rats showed significantly greater survival than males. 8. Thus, separate mechanisms (hypothermia or ventilation) may be acting to increase tolerance of clamped and hypothermic female rats to severe hypoxia.

Animals↗

Effects of racing and gender on viscoelastic properties of horse blood.

Splenic contraction in racing horses increases the hematocrit (hct), thereby increasing blood viscosity. We tested as to whether racing also affects the elastic properties of blood. Mares and geldings were studied for thus purpose. After racing, there was: (i) an increased erythrocyte count independent of gender and race distance (0.32 to 1.7 km): (ii) an increased mean erythrocyte volume in both sexes; (iii) an increased heterogeneity of RBC size in both sexes; (iv) an increased plasma fibrinogen concentration and erythrocyte sedimentation rate in both sexes; and (v) an increased elastic yield stress (EYS). When corrected to a constant hct of 65%, the blood of mares, but not geldings, had increased EYS after racing. Gender differences in fibrinogen response (p = 0.72) did not account for this and the mechanism is not known. Since EYS is analogous to the point at which ketchup starts to flow from a bottle, its increase could be deleterious in vascular beds characterized by pulsatile flow, e.g. the coronary circulation.

Animals↗