Testing a new health indicator: Using avoidable causes of death and life expectancy for Spain between 1975–1986

The concept of avoidable cause of death serves as the basis for measuring the quality and diversity of a health care system. In this study the authors propose a new way to use this kind of mortality by combining with the concept of life expectancy to obtain what they call life expectancy free of avoidable mortality (LEFAM).This indicator was 76.9 in 1986 in Spain while life expectancy was 75.83. If these deaths were avoidable there would be a gain of 1.09 years per person born. There is an important difference between the would-be male gain of 1.76 years and the would-be female gain of 0.6. In the ecological study, LEFAM would better explain the year to year changes of the resources in the health sector, measured in terms of the human resources (R = 0.96), the hospital beds per thousand persons (R = –0.86), and would also increase the relation with other health indicators such as infant mortality rate (R = –0.98) and mortality rate (R = 0.59) as compared with life expectancy alone.     

Recall strategies and memory for health-care visits

Complex questions in health surveys place heavy cognitive demands on respondents, prompting researchers to appraise how specific cognitive interventions may improve the accuracy of people's answers. Investigators in one experiment asked participants to recall visits to medical providers in forward, backward, or no particular order, and matched results with providers' records. "Free" recall proved marginally superior to forward or backward ordering, although overall respondents underreported the number of visits by 20 percent; participants' gender and self-reported health status, among other factors, also affected quality of recall. The experiment lends support to contentions that the methods of cognitive science applied to survey research better the accuracy of population survey data.     

Influence of aging on thromboxane A2 and prostacyclin levels in rat hippocampal brain slices

We have investigated the influence of age (3, 18, 24 months) on Thromboxane A₂ (TXA₂) and Prostacyclin (PGI₂) levels in hippocampal slices from F344/NHSD rats. A significant increase in TXA₂ and PGI₂ levels was observed in 18 and 24 months old compared to 3 months old animals. A significant reduction in the ratio TXA₂/PGI₂ produced by a higher increase in PGI₂ was observed in 24 month old animals. The reduction in the TXA₂/PGI₂ ratio has been related to vasodilatory and antiaggregating effects that may contribute to protect the brain against neuronal damage.     

Penicillium peritonitis in an adolescent receiving chronic peritoneal dialysis

A 19-year-old female on chronic peritoneal dialysis developed acute peritonitis; multiple peritoneal fluid and catheter tip cultures yielded Penicillium species. She promptly responded to catheter removal and intravenous amphotericin B, followed by oral fluconazole, without further recurrences 1 year later. This is the first reported case of Penicillium peritonitis in the pediatric population. We review the microbiology and clinical spectrum of this disease, as well as the few previous reported cases in adults. Received: 2 November 1998 / Revised: 1 February 1999 / Accepted: 4 February 1999     

Selective inhibitors of glial GABA uptake: synthesis, absolute stereochemistry, and pharmacology of the enantiomers of 3-hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole (exo-THPO) and analogues

3-Methoxy-4,5,6,7-tetrahydro-1,2-benzisoxazol-4-one (20a), or the corresponding 3-ethoxy analogue (20b), and 3-chloro-4,5,6, 7-tetrahydro-1,2-benzisothiazol-4-one (51) were synthesized by regioselective chromic acid oxidation of the respective bicyclic tetrahydrobenzenes 19a,b and 50, and they were used as key intermediates for the syntheses of the target zwitterionic 3-isoxazolols 8-15 and 3-isothiazolols 16 and 17, respectively. These reaction sequences involved different reductive processes. Whereas (RS)-4-amino-3-hydroxy-4,5,6,7-tetrahydro-1,2-benzisoxazole (8, exo-THPO) was synthesized via aluminum amalgam reduction of oxime 22a or 22b, compounds 9, 11-13, and 15-17 were obtained via reductive aminations. Compound 10 was synthesized via N-ethylation of the N-Boc-protected primary amine 25. The enantiomers of 8 were obtained in high enantiomeric purities (ee >/= 99.1%) via the diastereomeric amides 32 and 33, synthesized from the primary amine 23b and (R)-alpha-methoxyphenylacetyl chloride and subsequent separation by preparative HPLC. The enantiomers of 9 were prepared analogously from the secondary amine 27. On the basis of X-ray crystallographic analyses, the configuration of oxime 22a was shown to be E and the absolute configurations of (-)-8 x HCl and (+)-9 x HBr were established to be R. The effects of the target compounds on GABA uptake mechanisms in vitro were measured using a rat brain synaptosomal preparation and primary cultures of mouse cortical neurons and glia cells (astrocytes). Whereas the classical GABA uptake inhibitor, (R)-nipecotic acid (2), nonselectively inhibits neuronal (IC(50) = 12 microM) and glial (IC(50) = 16 microM) GABA uptake and 4,5,6,7-tetrahydroisoxazolo?4,5-cpyridin-3-ol (1, THPO) shows some selectivity for glial (IC(50) = 268 microM) versus neuronal (IC(50) = 530 microM) GABA uptake, exo-THPO (8) was shown to be more potent as an inhibitor of glial (IC(50) = 200 microM) rather than neuronal (IC(50) = 900 microM) GABA uptake. This selectivity was more pronounced for 9, which showed IC(50) values of 40 and 500 microM as an inhibitor of glial and neuronal GABA uptake, respectively. These effects of 8 and 9 proved to be enantioselective, (R)-(-)-8 and (R)-(+)-9 being the active inhibitors of both uptake systems. The selectivity of 9 as a glial GABA uptake inhibitor was largely lost by replacing the N-methyl group of 9 by an ethyl group, compound 10 being an almost equipotent inhibitor of glial (IC(50) = 280 microM) and neuronal (IC(50) = 400 microM) GABA uptake. The remaining target compounds, 11-17, were very weak or inactive as inhibitors of both uptake systems. Compounds 9-13 and 15 were shown to be essentially inactive against isoniazide-induced convulsions in mice after subcutaneous administration. The isomeric pivaloyloxymethyl derivatives of 9, compounds 43 and 44, were synthesized and tested as potential prodrugs in the isoniazide animal model. Both 43 (ED(50) = 150 micromol/kg) and 44 (ED(50) = 220 micromol/kg) showed anticonvulsant effects, and this effect of 43 was shown to reside in the (R)-(+)-enantiomer, 45 (ED(50) = 44 micromol/kg). Compound 9 also showed anticonvulsant activity when administered intracerebroventricularly (ED(50) = 59 nmol).