New perspectives in the management of public health systems

The following pages try to offer some ways of arguing against pesimism in our health administration culture. In fact, the review of a wide range of feasible reforms of our health system undertaken in this paper gives some clues for a better implementation of the a priori advantages of public health systems. These advantages are not achieved today because of some dysfunctionalities of daily management. To rationalize resources distribution, to evaluate the results, to eliminate unnecessary administrative control, to coordinate responsibility and budgeting centers, to introduce free choice as a response to public demand, and to simulate marketing by private production of public services are elements suggested in this paper to improve public health services management.     

In vitro metabolism and toxicity assessment of toxin T-514 (Peroxisomicine A1) of Karwinskia humboldtiana in microsomes and primary cultured hepatocytes.

T-514 (Peroxisomicine A(1)) from Karwinskia humboldtiana is a dimeric hydroxyanthracenone with a highly selective cytotoxic effect on tumor cells. We evaluated the metabolism of this compound in two in vitro systems (liver microsomes and hepatocytes) and assessed the cytotoxicity of its metabolites on normal and tumor cells. Microsomes (12.5, 125 and 250 microg of protein/ml) and hepatocytes (1 x 10(6) cells/ml) were incubated with the toxin (25 microM) for 0.5, 1, 3, 6, 9, 12 and 24 h and the samples were examined using chromatographic analysis and UV spectra. Two metabolites (M1 and M2) were detected in the rat microsomes and one (M1) in the monkey microsomes. The retention times and UV spectra of the peaks were very similar to those of the toxin T-514. M1 was isolated and identified as a mixture of two isomers. The cytotoxicity of the metabolites was evaluated in Chang liver and Hep G2 cells but they did not show the selective cytotoxic effect on tumor cells seen in the original compound.     

Über die Entstehung und die Bedeutung der Bogenförmigen ST-Strecke,Sowie der Sog. Zwischenzacke und Ihren Zusammenhang mit der S-Achse

Zusammenfassung Die bogenförmige ST-Strecke kommt häufig, in etwa 12%der Fälle, und die Zwischenzacke selten, in 5der Fälle eines nichtausgewählten Krankenmaterials, vor. Sowohl die Entstehungsursache der bogenförmigen ST-Strecke als der Kischschen Zwischenzacke liegt in der stärkeren oder schwächeren Rechts- oder Linksdeviation der S-Achse. Die Richtung und der Grad der S-Achsendeviation wird es also bestimmen, in wie vielen und welcher Einthovenschen Ableitung die bogenförmige ST-Strecke bzw. die Zwischenzacke notwendigerweise auftreten muß. Bei S-Achsenstellungen zwischen –90°und –30°wird die ST-Strecke in Ableitung I, bei S-Achsenstellungen zwischen –30°und +30°in der I. und II., zwischen +30°und +90°in der I., II., III., zwischen +90°und +150°in der II., III. und bei den Achsenstellungen zwischen +150°und –150°in der III. Einthovenschen Ableitung bogenförmig sein. Die klinische Bedeutung der bogenförmigen ST-Strecke ist gleich mit der klinischen Bedeutung der S-Achsendeviation. Bei dem Vergleich des Herzbefundes der Kranken mit der elektrischen S-Achsenstellung können folgende Feststellungen gemacht werden: Geringergradige Linksdeviation der S-Achse, d. h. bogenförmiges ST _I sowie geringergradige Rechtsdeviation der S-Achse, d. h. ST_III kann praktisch bei pathologischem Herzbefund nicht verwertet werden. Stärkere Links- bzw. Rechtsdeviation der S-Achse, d. h. ST_I und_II bzw. ST_II und_III können im allgemeinen ebenfalls nicht verwertet werden, es ist jedoch wahrscheinlich, daß sie schon einen Übergang zu den pathologischen Befunden bilden. Während jene starken S-Achsendeviationen, wo schon in allen drei Ableitungen bogenförmiges ST besteht, meistens für das Zeichen der myokardialen Läsion betrachtet werden sollen, und zwar in erster Linie dann, wenn die positive S-Zacke in oder neben dem absteigenden Schenkel der R-Zacke gut wahrnehmbar ist.     

Adipose tissue and liver lipid metabolism in obese children: role of the body mass index and the presence of acanthosis nigricans.

AIMS: The aims of our study were to determine if insulin resistance is associated with increased plasma levels of non-esterified fatty acids (NEFA), glycerol, 3-hydroxybutyrate and triglycerides in obese children. We also studied whether the presence of acanthosis nigricans (AN) led to further alterations in the above parameters. METHODS: A total of 101 children were studied on their first visit to the paediatric endocrine clinic. Seventy-four were obese, 30 of them with AN. The remaining 27 were non-obese healthy children (control group). NEFAs, glycerol, triglycerides, 3-hydroxybutyrate, insulin, leptin, adiponectin and glucose were determined in blood samples obtained after overnight fasting. The insulin resistance index (IRI) was calculated following the homeostasis model assessment (HOMA). Data from the three groups were compared using appropriate statistical tests. RESULTS: No differences in age, sex ratio and pubertal stage were observed among the three groups. The group of children with the highest body mass index (BMI) showed higher plasma levels of insulin and leptin, higher IRI and lower plasma levels of adiponectin. As insulin and IRI increased, NEFA and 3-hydroxybutyrate decreased and triglycerides increased. When obese children were categorized by BMI, the presence of AN further exacerbated these differences. CONCLUSIONS: In obese children, insulin resistance is associated with plasma lipid alterations suggestive of both decreased adipose tissue lipolysis and hepatic beta-oxidation and increased hepatic synthesis of triglycerides. Such a metabolic condition may facilitate fat storage and hinder weight loss.     

Hepatic encephalopathy secondary to porto-systemic shunt satisfactorily treated with interventionist radiology

Hepatic encephalopathy is a reversible state of altered cognition that may occur in patients with acute or chronic liver disease or porto-systemic shunt, and in which known neurological or psychiatric signs may develop. Nitrogenated substances from intestinal digestion reach the brain without being cleared by their passage through the liver due to the presence of porto-systemic shunt. We report two cases of patients with porto-systemic shunt diagnosed with recurrent chronic hepatic encephalopathy refractory to conventional medical treatment. They were satisfactorily treated with shunt embolization using interventionist radiology techniques.     

The R7 subfamily of RGS proteins assists tachyphylaxis and acute tolerance at mu-opioid receptors.

Members of the R7 subfamily of regulators of G-protein signaling (RGS) proteins (RGS6, RGS7, RGS9-2, and RGS11) are found in the mouse CNS. The expression of these proteins was effectively reduced in different neural structures by blocking their mRNA with antisense oligodeoxynucleotides (ODNs). This was achieved without noticeable changes in the binding characteristics of labeled beta-endorphin to opioid receptors. Knockdown of R7 proteins enhanced the potency of antinociception promoted by morphine and [D-Ala(2), N-MePhe(4), Gly-ol(5)]-enkephalin (DAMGO)-both agonists at mu-opioid receptors. The duration of morphine analgesia was greatly increased in RGS9-2 and in RGS11 knockdown mice. The impairment of R7 proteins brought about different changes in the analgesic activity of selective delta agonists. Knockdown of RGS11 reduced [D-Ala(2)]deltorphin II analgesic effects. Those of RGS6 and RGS9-2 proteins caused [D-Ala(2)]deltorphin II to produce a smoothened time-course curve-the peak effect blunted and analgesia extended during the declining phase. RGS9-2 impairment also promoted a similar pattern of change for [D-Pen(2,5)]-enkephalin (DPDPE). RGS7-deficient mice showed an increased response to both [D-Ala(2)]deltorphin II and DPDPE analgesic effects. A single intracerebroventricular (i.c.v.) ED(80) analgesic dose of morphine gave rise to acute tolerance in control mice, but did not promote tolerance in RGS6, RGS7, RGS9-2, or RGS11 knockdown animals. Thus, R7 proteins play a critical role in agonist tachyphylaxis and acute tolerance at mu-opioid receptors, and show differences in their modulation of delta-opioid receptors.     

Preparation of bupivacaine-loaded poly(epsilon-caprolactone) microspheres by spray drying: drug release studies and biocompatibility.

Poly(epsilon-caprolactone) microspheres containing bupivacaine were prepared by the spray-drying process. The average size of drug loaded microspheres was less than 3 microm in diameter, and the percentage of entrapment efficiency was 91 +/- 3%. In vitro drug release kinetic in phosphate buffer at 37 degrees C showed a hyperbolic profile, with a burst-effect during the first hour. Subcutaneous injection of bupivacaine-loaded microspheres in the back of rats caused an increase in drug concentration in plasma. Maximum bupivacaine concentration in plasma was 237 +/- 58 ng/ml at 105 h, and drug was detected in plasma for 16 days. The half-life time of the drug was increased by more than 125 times with regard to that of the drug administered in a solution by intraperitoneal injection. After 30 days of injection, a mass formed by microspheres surrounded by a thin fibrous capsule was observed. Small blood vessels and multinucleate foreign body giant cells with macrophagic function around microspheres were detected. After 60 days of injection a subcutaneous mass was also observed, which was formed of more degraded dispersed microspheres in conjunctive tissue, which had a normal structure. Thus, bupivacaine-loaded poly(epsilon-caprolactone) microspheres could be considered as a device to be used in the treatment of severe pain that is not responsive to opioids for example in cancer-related syndromes or in intractable herpetic neuralgia.