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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 METHODS: a decision analysis model was performed, using data from published and unpublished sources, to compare two strategies--to vaccinate or not to vaccinate.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.

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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.

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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.

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Most animals respond to a shortage of oxygen by lowering their body temperature. This response, mediated by behavior and physiological means, reduces oxygen demand via the Q10 effect, and should therefore be adaptive. This article reviews the occurrence of this response within the animal kingdom, the possible mechanisms and mediators of the response, and the physiological significance of hypoxia-induced hypothermia.

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Most animals respond to a shortage of oxygen by lowering their body temperature. This response, mediated by behavior and physiological means, reduces oxygen demand via the Q10 effect, and should therefore be adaptive. This article reviews the occurrence of this response within the animal kingdom, the possible mechanisms and mediators of the response, and the physiological significance of hypoxia-induced hypothermia.

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A novel method is described for the cyclization of peptides--or segments of polypeptides--which requires a free N-terminal alpha-amino group and a distal amino acid residue containing a nucleophilic side chain. The reaction is conducted in two steps, both in the aqueous phase. The first step involves acylation of the N-terminal alpha-amino group with iodoacetic anhydride at pH 6. This acylation reaction has greater than 90% specificity for peptide alpha-amino groups and gives no alkylation of Arg, His, Lys or Met by the iodoacetate side product (R. Wetzel et al., Bioconjugate Chem., 1, 114-122, 1990). In the second step, the acylation reaction mixture or the isolated iodoacetyl-peptide is incubated at room temperature to give the cyclic peptide formed by reaction of the nucleophilic side chain with the iodoacetyl moiety. The pH dependence of the cyclization reaction by Met, Lys, Arg or His is consistent with the pKa of the nucleophilic side chain. Thus, peptides containing Met plus other nucleophilic amino acids should preferentially cyclize via Met at low pH. In this paper, preparation of cyclic peptides containing 3-6 amino acids is described; the full range of ring sizes and sequences which can undergo this cyclization has not been further explored. Preliminary results suggest that this method is also fairly general with respect to the amino acid sequence being cyclized. The reaction appears to be particularly suited for cyclization via Lys and Met side chains. All of the cyclized products are sufficiently stable for many biological applications.(ABSTRACT TRUNCATED AT 250 WORDS)

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The impact of temperature on the chemical control of respiration in the Mexican black iguana Ctenosaura pectinata was examined by measuring ventilatory responses to graded hypoxia with and without 2.9% inspired CO2 at 25, 30, and 35 degrees C. Black iguanas increased pulmonary ventilation in response to hypoxia by increasing both tidal volume and respiratory frequency. Breathing 2.9% CO2 stimulated an increased pulmonary ventilation primarily through increases in tidal volume. The fractional O2 concentration at which ventilation began to increase (hypoxic threshold) varied with temperature, increasing from 0.067 at 25 degrees C to 0.085 at 30 degrees C and 0.112 at 35 degrees C. At 35 degrees C, breathing 2.9% CO2 promoted a further, although statistically insignificant, shift in the ventilatory hypoxic threshold to approximately 0.130 fractional inspired O2 concentration. A "gasping" ventilatory pattern was also observed, the frequency of which increased with progressive hypoxia and increasing temperature. These results suggest that the chemical control of ventilation in this lizard is susceptible to changes in temperature, although the mechanism underlying the temperature sensitivity remains obscure.

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