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.     

C-reactive protein as a predictor of fetal and maternal infective morbidity and fetal mortality

The value of maternal C-reactive protein (CRP) levels as predictors of fetal and maternal infective morbidity and fetal mortality was assessed prospectively over a 6-month period in all cases of premature rupture of the fetal membranes or suspected premature labour. Statistical analysis of results showed that CRP at a level of 1.32 mg/dl is a sensitive marker of infective morbidity in mother and neonate. Furthermore, there was a significant association between raised CRP levels and low-birth-weight babies, suggesting that intra-uterine infection is a major cause of prematurity in the study population.     

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.     

Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study.

HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white matter hyperintensities. METHODS: In the Leukoaraiosis And DISability in the elderly (LADIS) study, we investigated the relationships between DM, hypertension, blood pressure and MTA in 582 subjects, stratified by white matter hyperintensity severity, using multinomial logistic regression. MTA was visually scored for the left and right medial temporal lobe (score 0-4), and meaned. RESULTS: Mean age was 73.5 years (sd 5.1), 54% was female. Of the subjects, 15% had DM, and 70% had a history of hypertension. The likelihood of having MTA score 3 was significantly higher in subjects with DM (OR 2.9; 95% CI: 1.1-7.8) compared with an MTA score of 0 (no atrophy). The odds ratio for MTA score 2 was not significantly increased (OR 1.8; CI: 0.9-4). Systolic and diastolic blood pressure and a history of hypertension were not associated with MTA. There was no interaction between DM and hypertension. Stratification on white matter hyperintensities (WMH) did not alter the associations. CONCLUSION: Our study strengthens the observation that MTA is associated with DM, independently of the amount of small vessel disease as reflected by WMH.     

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.     

Diagnosis of diffuse and localized arrhythmogenic right ventricular dysplasia by gated blood-pool SPECT.

This study aimed to assess the ability of global and local systolic parameters measured with gated blood-pool SPECT (GBPS) to diagnose and characterize the severity of diffuse or localized arrhythmogenic right ventricular dysplasia (ARVD). METHODS: Fifty-nine subjects with symptomatic ventricular arrhythmias were prospectively included in the study. With the International Society and Federation of Cardiology criteria for ARVD as a gold standard, these subjects were classified as subjects without ARVD (21 control subjects) and patients with localized ARVD (16 patients) or diffuse ARVD (22 patients). Right ventricular volumes, right ventricular ejection fractions (EF), the SD of local EF (sigma-EF), and the SD of the local times of end systole (sigma-TES) were computed from GBPS data and compared among the groups in the study population. RESULTS: sigma-EF did not differ between control subjects and patients with diffuse or localized ARVD. Right ventricular EF and volumes differed between patients with diffuse ARVD and control subjects, with similar areas under the receiver-operating-characteristic curves, but right ventricular EF and volumes failed to differentiate patients with localized ARVD. In contrast, sigma-TES differed between patients with diffuse or localized ARVD and control subjects. Regression analysis showed that the systolic parameter most strongly associated with the diagnosis of ARVD was sigma-TES. The probabilities of a randomly chosen patient in the diffuse ARVD group and of a randomly chosen patient in the localized ARVD group having sigma-TES values greater than that of a randomly chosen control subject were 98.5% and 96.7%, respectively. For the diagnosis of localized ARVD, a threshold of 80 ms for sigma-TES corresponded to sensitivity, specificity, and positive and negative predictive values of 100%, 81%, 80%, and 100%, respectively. CONCLUSION: With GBPS, both diffuse ARVD and localized ARVD can be accurately diagnosed by computing sigma-TES for all of the pixels on the surface of the right ventricle.