Liposomally-entrapped ganciclovir for the treatment of cytomegalovirus retinitis in AIDS patients

Treatment of retinitis by cytomegalovirus (CMV) in AIDS patients requires frequent repetitive injections of intravitreal ganciclovir (GCV). This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped GCV could prolong intraocular therapeutic levels when compared with the intravitreal injection of free GCV, and the clinical effectiveness of this approach in AIDS patients. Intraocular concentration of GCV was determined by means of an ELISA test in rabbit vitreous 2, 3, 7, and 14 days after a single intravitreal injection of either different doses of the free drug (0.2–20 mg) or 1 mg of liposomally-entrapped GCV. After 72 h, only the vitreous of rabbits injected with doses of free GCV greater than or equal to 5 mg showed therapeutic levels of the drug; no GCV was detected after 72 h with any of the doses applied. Moreover, the microscopic study revealed GCV-induced damage in retinal structures in the animals injected with a free GCV dose greater than or equal to 15 mg. Intravitreal injection to rabbits of 1 mg of liposomally-encapsulated GCV showed no retinal toxicity at any of the time points studied, and therapeutic levels were detected up to 14 days after injection (4.67 ± 0.39 g/ml). Five AIDS patients suffering CMV retinitis were injected with 0.5 mg of liposomally-entrapped GCV (2 mg of lecithin). Complete remission of the CMV retinitis was observed already at the third injection of 0.5 mg GCV (one per week) and relapse did not occur during the 2–4 month follow-up of the patients. In view of the results presented, it can be concluded that intravitreal injection of liposomally-encapsulated GCV increases the time period required for reinjections in the treatemnt of CMV retinitis.Abbreviations AIDS acquired immunodeficiency syndrome - AZT zidovudine - CMV cytomegalovirus - GCV ganciclovir     

Results of surgical treatment of hepatic hydatidosis: Current therapeutic modifications

Hepatic hydatidosis is an endemic disease that affects vast segments of the populations of various countries in the Mediterranean region, South America, the Pacific, and temperate zone nations that possess large numbers of sheep. Four hundred and ten patients bearing 561 hydatid cysts were treated at 2 major hospitals in Madrid, Spain in the period 1974–1989. In order to establish the modifications in diagnostic and therapeutic management introduced as a result of modernization of our clinical facilities and improved technological standards, they were divided into 2 groups: group A corresponded to the period 1974–1984, and group B, corresponded to the period 1985–1989. Since no effective parasiticide agent is available, hepatic hydatidosis must be treated surgically. Today's better knowledge and advancements in liver surgery have made it possible to extirpate the cyst completely with little risk and improved results; hepatic resection should only be considered in exceptional cases; aspiration, drainage procedures, or partial resections of the cyst yield inferior results. We have had no relapse of the hydatid disease in the liver or in any other abdominal site.

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Resumen La hidatidosis hepática es una enfermedad endémica que afecta a vastos segmentas de las poblaciones de diversos países de la región mediterránea, Sur América, el Pacífico, y las naciones de las zonas templadas que mantienen grandes rebanos de ovejas. Cuatrocientos diez pacientes con 561 quistes hidatídicos fueron tratados en 2 grandes hospitales de Madrid, España en el período 1974–1989. Con el propósito de establecer las modificaciones en el manejo diagnóstico y terapéutico ocurridas como resultado de la modernización de nuestras facilidades clínicas y de superiores estándares tecnológicos, dividimos la población total de estos pacientes en 2 grandes grupos: grupo A, correspondiente al período 1974–1984, y grupo B, correspondiente al período 1985–1989. Puesto que no existe un agente parasitocida efectivo, la hidatidosis hepática debe ser tratada quirúrgicamente. El mejor conocimiento actual y el avance en la cirugía hepática han hecho posible la extirpatión completa del quiste con bajo riesgo y mejores resultados; la resection hepática debe ser considerada sólo en casos excepcionales; la aspiración, los procedimientos de drenaje o las resecciones parciales del quiste se asocian con malos resultados. En nuestra experiencia no hemos tenido recurrencia de la enfermedad ni en el hígado ni en otros órganos.

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Résumé Le kyste hydatique du foie est une maladie endémique qui touche une partie importante de la population dans différents pays de la région méditerranéenne, en Amérique du Sud, dans le Pacifique, et dans les pays de la zone tempérée qui ont beaucoup de moutons. Quatre cent dix patients porteurs de 561 kystes hydatiques ont été traités dans les deux plus grands hôpitaux de Madrid en Espagne de 1974 à 1989. Pour mesurer les progrès dans le diagnostic et le traitement dus à la modernisation de notre équipement médical et à une meilleure technologie, les patients ont été divisés en 2 groupes chronologiques: groupe A de 1974 à 1984 et groupe B de 1985 à 1989. Comme il n'y a pas actuellement de médicament efficace contre ce parasite, on doit traiter par la chirurgie le kyste hydatique. Aujourd'hui, les connaissances plus étendues et les progrès dans la chirurgie du foie permettent d'enlever complètement le kyste avec peu de risques et avec de meilleurs résultats; la résection du foie ne doit être envisagée que dans de rares cas. Les procédés d'aspiration ou de drainage ou les résections partielles du kyste donne des résultats moins bons. Nous n'avons pas eu de récidive du kyste hydatique, ni au foie ni dans une autre localisation péritonéale.

     

Binding of cadmium by cyanobacterial growth media: Free ion concentration as a toxicity index to the cyanobacteriumNostoc UAM 208

A quantitative study of cadmium binding to three different growth media for nitrogen-fixing cyanobacteria was done with the aid of a solid state ion-specific electrode. Kratz and Myers modified medium and Arnon medium bound large amounts of Cd²⁺, BG11₀ medium had less binding capacity. Of the media components, phosphate ion showed the greatest ability to bind Cd²⁺. Different pHs, the size of cell inoculum and two buffers (Tricine and HEPES, 25 mM) also changed the availability of free cadmium ion in solution.The effect of free Cd²⁺ ion towards the cyanobacteriumNostoc UAM 208, isolated from a heavy metal polluted environment, also was tested. The effective concentration affecting 50% of population (EC₅₀), at 120 h of exposure, was less for nitrogenase activity (0.26 g/mL) than for growth (0.55 g/mL), suggesting that this enzyme activity is more sensitive to cadmium than growth. Furthermore, cadmium toxicity was influenced by the addition of buffers to the growth medium. In the presence of buffer, Tricine (25 mM), growth and nitrogenase activity was reduced by 50% at a total cadmium concentration of about 115 g/mL, although no free ion was detected in this case.These results suggest that although generally cadmium toxicity is a function of free metal ion concentration, this can also vary in the presence of complexing agents.     

The organization of health services: the comparison as contribution

This article discusses about a recent procedure in health care studies, the comparison as a methodology of analysis. The different analytical currents refer to a particular method of understanding health-disease process. They are: functionalism, the historical-materialism and the new currents. Their phylosophical and sociological basis, concepts, analysis instruments and purposes are showed here by a review of the principal works from representative authors as Navarro, Terris, Roemer, Fry, Illich, Capra and others. The paper suggests that comparative analysis can take two directions: the first is a operational approach for analysing the concrete situations of health's service organization, the second, a more conceptual one, aimed at identifying critical questions and international tendencies in health's systems. The recent discussion search for the overcoming of these dichotomies toward the progress of the production of knowledge and its effects in health's services organization.     

A new approach to public health. Strategies for its implementation]

Public Health System accepts "New Public Health" only in a theoretical way, since in the practice essential modifications to get "Health For All-2000" aims are not implemented. It is necessary to look "bridge-heads" that permit to introduce changes gradually to reorganize Health Services. In the present article, different alternatives are analyzed, all of them giving priority to the programmes that consider Health as a natural resource. These programmes can be "Governmental Programmes" so Health policies coming from the Health Department can be assumed by the others Public Administration Departments.     

Aristolochic acids in Aristolochia chilensis

The major components of the acid fraction of the leaves and tender stems of Aristolochia chilensis Miers are aristolochic acids I and Ia. Aristolochic acid Ia has been isolated from plant material for the f?rst time, and its PMR spectrum is discussed.     

Release of noradrenaline by the ionophore X537A from normal and reserpinized guinea-pig atrium

Summary The effects of ionophore X537A on the release of ³H-noradrenaline and its metabolites from the superfused guinea-pig left atrium were investigated. Concentrations of ionophore of 10 and 30 M greatly increased the release of tritium. Of the total increase in radioactivity elicited by X537A 44% was accounted for as noradrenaline and 50% was due to deaminated metabolites. The ionophore-evoked release of tritium was independent of the extracellular calcium ions and was not affected by agents which modify calcium movements such as verapamil, ryanodine, ruthenium red and tetracaine. X537A released ³H-noradrenaline from extragranular sites in MAO-inhibited atria from reserpine-treated animals and this release was also calcium independent. It is concluded that the ability of X537A to release noradrenaline from vesicular or cytoplasmic sites is not related to its ability to couple with and transport calcium ions through membranes. The ionophore might modify the ionic distribution outside and inside the neuronal membrane which would lead to leakage of the transmitter.     

A pharmacological study of the angiotensin receptor and tachyphylaxis in smooth muscle.

The interaction of angiotensin with its receptor has been studied on the basis of the tachyphylaxis shown by the rat uterus towards angiotensin II when pH and Ca2+ concentration are below physiological levels. 14C-Angiotensin binding and 45Ca2+-uptake investigations suggest tachyphylaxis to be due to increased binding at low pH and Ca2+ concentration. Studies with alkylating (affinity labeled) angiotensin derivatives containing the N-mustard chlorambucil suggest a "Charnière type" inhibition at the Ca-binding site of receptor and an irreversible inhibition at an anionic site. Angiotensin inhibitors containing chlorambucil do not alkylate tissue but are competitive inhibitors suggesting that the aromatic side chain in angiotensin may induce conformational changes in the receptor. The results obtained lead to a logical model for the angiotensin receptor allowing for normal activation by the hormone as well as for production of tachyphylaxis.     

Income differences in persons seeking outpatient treatment for mental disorders: a comparison of the United States with Ontario and The Netherlands

BACKGROUND: Variations in the relationships among income, use of mental health services, and sector of care are examined by comparing data from 3 countries that differ in the organization and financing of mental health services. METHODS: Data come from the 1990-1992 National Comorbidity Survey (n = 5,384), the 1990-1991 Mental Health Supplement to the Ontario Health Survey (n = 6,321), and the 1996 Netherlands Mental Health Survey and Incidence Study (n = 6031). Analysis of the association between income and use of mental health services was carried out for the population that was between ages 18 and 54 years. Differential use of mental health treatment was examined in 3 sectors: the general medical sector, the specialty sector, and the human services sector. RESULTS: No significant association between income and probability of any mental health treatment was observed for persons with psychiatric disorders in any of the 3 countries. However, there were significant differences among countries in the association between income and sector of mental health care treatment. In the United States, income is positively related to treatment being received in the specialty sector and negatively related to treatment being received in the human services sector. In the Netherlands, patients in the middle-income bracket are less likely to receive specialty care, while those in the high-income bracket are less likely to be seen in the human service sector. Income is unrelated to the sector of care for patients in Ontario. CONCLUSIONS: Future research should examine whether differential access to the specialty sector for low-income people in the United States is associated with worse mental health outcomes.