Lasker's coefficient of isonymy between and within 16 Sardinian villages in the periods 1825-1849, 1875-1899, and 1925-1949.

Coefficients of relationship by isonymy, based on the frequency of common surnames, were used to estimate the biological affinity between (R(ib)) and within (R(iw)) 16 Sardinian villages in the periods 1825-1849, 1875-1899, and 1925-1949. The database for the surname analysis consisted of 13,515 marriages registered in the parishes of villages, all belonging to the Sardinian linguistic area. The values of R(ib) and R(iw) tend to decrease in time. In all three periods, the R(ib) values generally decrease as the geographical distance between villages increases. The negative values of the Bravais-Pearson coefficient of correlation between the matrix of R(ib) values and the matrices of geographical distances (calculated both in a straight line and from road distances) are significant for each period (modified Mantel test), with slightly higher correlation coefficients for road distances. Moreover, the plots of isonymic relationships obtained by nonmetric multidimensional scaling for 1825-1849 and 1925-1949 show that the biological relationships between neighboring villages increase in the latter period. The positive values of the Bravais-Pearson coefficients of correlation between R(iw) and altitude are significant in all three periods, while the correlation between R(iw) and population size is not significant, even when altitude is controlled for. Since altitude is considered an indicator of isolation, the results obtained with the coefficient of relationship by isonymy within villages also support the isolation-by-distance model. R(ib) values provided a reliable picture of the biological relationships between 16 Sardinian villages, while R(iw) values illustrated the biological affinity within the communities for a period of 100 years, from 1825-1849 to 1925-1949.     

Increase in meso‐prefrontal dopaminergic activity after stimulation of CB1 receptors by cannabinoids

The intravenous administration of the psychoactive constituent of marijuana, Δ⁹-tetrahydrocannabinol (Δ⁹-THC) (62.5–1000 μg/kg), and the synthetic cannabinoid agonist WIN 55212,2 (WIN) (62.5–500 μg/kg), produced a dose-related increase in the firing rate and burst firing in the majority of antidromically identified meso-prefrontal dopaminergic neurons. In a restricted number of neurons (n = 4), WIN administration did not increase firing rate but produced an increment of bursting activity. These effects of the cannabinoids were reversed by the intravenous administration of SR 141716 A, a selective cannabinoid antagonist (1 mg/kg), per se ineffective to modify the electrical activity of dopaminergic neurons. The results indicate that stimulation of cannabinoid CB1 receptors produces an activation of meso-prefrontal dopaminergic transmission. Considering that supranormal stimulation of D1 dopamine receptors in the prefrontal cortex has been shown to impair working memory, the present results suggest that the negative effects of cannabinoids on cognitive processes might be related to the activation of dopaminergic transmission in the prefrontal cortex.     

Beta-endorphin in amniotic fluid in normal and hypertensive gestations: relationship with maternal blood pressure parameters.

beta-Endorphin (beta-E) immunoreactivity was measured in the amniotic compartment of 52 normotensive and 45 hypertensive gestations. All the fetuses of the normal group were healthy and showed appropriate intrauterine growth, whereas only suffering and growth-retarded fetuses were included in the pathological group. As expected, amniotic beta-E concentration was found to be significantly higher in hypertensive than in normotensive pregnancies (mean +/- SEM: 129.1 +/- 8.15 vs. 59.1 +/- 2.68 pg/ml; p < or = 0.005). A positive correlation between the hormone levels and the diastolic as well as the mean maternal blood pressure (r: 0.554; p < or = 0.05 and r: 0.525; p < or = 0.05, respectively) was present only in pregnancies complicated by hypertension. Furthermore, a negative correlation (r: -0.555; p < or = 0.05) linked amniotic beta-E and the pulse pressure in normal but not in complicated pregnancies. Unless beta-E in the amniotic compartment is also of amniochorial origin, our results suggest that the fetal endorphinergic tone is either activated by elevated diastolic and mean maternal pressure levels or lowered by increased pulse pressure values in normally elapsing pregnancies.     

Beta-Thalassaemia types in southern Sardinia.

In this study the prevalence of the different beta-thalassaemia types in southern Sardinia was investigated by cellulose acetate and agar gel electrophoresis or globin chain synthesis analysis on column chromatography or both in (1) all the patients (347) presenting with thalassaemia major or intermedia at our haematology service from 1976 to 1979, and (2) a group of 82 patients with transfusion-dependent thalassaemia major randomly chosen from 236 under our care. Apart from six subjects with delta(beta)0/beta+-thalassaemia genotype and eight with beta0/beta+ or less probably beta+/beta/-thalassaemia, all thalassaemia major and intermedia patients studied were beta0-thalassaemia homozygotes. Globin chain synthesis on peripheral blood cells from these patients, performed at different intervals from blood transfusion, showed no incorporation of radioactive leucine into beta-globin peak, the same as before the transfusion. No correlation between kappa/gamma ratios and clinical severity or hypersplenism was found. Globin chain synthesis analysis carried out at birth in three infants later found to have homozygous beta0-thalassaemia demonstrated imbalanced or borderline kappa/gamma ratios.     

Pseudo cluster randomization: a treatment allocation method to minimize contamination and selection bias

In some clinical trials, treatment allocation on a patient level is not feasible, and whole groups or clusters of patients are allocated to the same treatment. If, for example, a clinical trial is investigating the efficacy of various patient coaching methods and randomization is done on a patient level, then patients who are receiving different methods may come into contact with each other and influence each other. This would create contamination of the treatment effects. Such bias might be prevented by randomization on the coaches level. The patients of a coach constitute a cluster and all the subjects in that cluster receive the same treatment. Disadvantages of this approach may be reduced statistical efficiency and recruitment bias, as the treatment that a subject will receive is known in advance. Pseudo cluster randomization avoids this, because in pseudo cluster randomization, not everybody in a certain cluster receives the same treatment, just the majority. There are two groups of clusters: in one group the majority of subjects receive treatment A, while a limited number receive treatment B. In the other group of clusters the proportions are reversed. The statistical properties of this method are described. When contamination is present, the method appears to be more efficient than randomization on a patient level or on a cluster level.     

Pressure pain threshold of the lateral pterygoid muscles in TMD patients and controls

OBJECTIVES: The aim of this experiment was to detect pressure pain threshold (PPT) differences on intra-oral palpation of the lateral pterygoid muscle (LPM) between subjects diagnosed with temporomandibular disorders (TMD) and controls. METHODS: Thirty-one consecutive female TMD patients and 31 age and gender matched controls underwent palpation of the LPM using an algometer made with a queue-tip connected to a digital scale, and PPT was measured. RESULTS: Mean PPTs of the right and left LPM of the controls were respectively 191g (49KPa) and 200g (51KPa), and mean PPTs of the right and left LPM of TMD patients were respectively 245g (62KPa) and 256g (63KPa). ANOVA between the four PPT measurements showed significant difference only between the PPT readings of the right LPM of the controls and the left LPM of the patients (p<0.05). CONCLUSIONS: The findings of this study suggest that PPT measured by means of the described algometer is not decreased in TMD patients as compared to control subjects.     

PD-168077, a selective dopamine D4 receptor agonist, induces penile erection when injected into the paraventricular nucleus of male rats

The effect of PD-168077 (N-methyl-4-(2-cyanophenyl)piperazynil-3-methylbenzamide maleate), a selective D4 dopamine receptor agonist, injected into the paraventricular nucleus of the hypothalamus on penile erection was studied in male rats. PD-168077 (1-200 ng) induced penile erection in a dose-dependent manner. The minimal effective dose was 50 ng, while the maximal response was found with 200 ng of the compound, which increased penile erection episodes from 0.3+/-0.03 to 1.7+/-0.21. The proerectile effect of PD-168077 was reduced almost completely by L-745,870 (3-(4-[chlorophenyl]piperazin-1-yl)-methyl-1H-pyrrolo[2,3-B]pyridine trihydrochloride), a selective D4 dopamine receptor antagonist, (1 microg) given into the paraventricular nucleus before the D4 dopamine agonist, and by other nonselective dopamine receptor antagonists, such as haloperidol (1 microg) and clozapine (1 microg), which block all dopamine receptor subtypes. The pro-erectile effect of PD-168077 was also reduced by the NO synthase inhibitor NG-nitro-L-arginine methylester (25 microg), but not by the oxytocin receptor antagonist d(CH2)5Tyr(Me)2-Orn8-vasotocin (1 microg), when given into the paraventricular nucleus. In spite of its inability to prevent the pro-erectile effect of PD-168077 when given in the paraventricular nucleus, d(CH2)5Tyr(Me)2-Orn8-vasotocin (1 microg) reduced almost completely PD-168077-induced penile erection when given into the lateral ventricles. The present results show that D4 dopamine receptors present in the paraventricular nucleus may influence penile erection by modulating the activity of paraventricular oxytocinergic neurons mediating erectile function.     

Abnormal uterine bleeding: medical treatment with vaginal danazol and five-year follow-up

STUDY OBJECTIVE: To evaluate the clinical efficacy and patient satisfaction of long-term danazol delivered vaginally as treatment for heavy menstrual bleeding. DESIGN: Prospective study (Canadian Task Force classification II-3). SETTING: University hospital. PATIENTS: Twenty premenopausal women with endometrial hyperplasia or endometrial polyps. INTERVENTION: After curettage or hysteroscopic-directed biopsies, women used one 200-mg tablet of danazol vaginally every day, continuing the therapy as long as they were totally satisfied with it. MEASUREMENTS AND MAIN RESULTS: Women were instructed to keep a diary of menstrual bleeding and to rate blood loss on a visual analog scale from zero (no blood loss) to 10 (gushing-type bleeding). They were seen every month for 3 months, then every 3 months for 9 months, and then every 6 months for 4 years for Papanicolau smear, pelvic examination, and transvaginal ultrasonography. They were asked to bring their diary of menstrual bleeding. They were asked about side effects and their satisfaction with the therapy. Peripheral blood was drawn for blood count and serum chemistries. Hysteroscopic-directed biopsies were repeated after 3 months of therapy in women with endometrial hyperplasia. The severity of blood loss was significantly reduced in all women after 3 months of treatment. All women with endometrial hyperplasia had regression of hyperplastic endometrium. None of the women with endometrial polyps had sonographic signs of recurrence during therapy. Only 10 women (50%) completed 1-year follow-up, and only 5 women (25%) completed 5-year follow-up. CONCLUSION: These results suggest that long-term administration of vaginal danazol after curettage or hysteroscopic-directed biopsy is both efficacious and safe in women with heavy menstrual bleeding, but the rate of discontinuance is high.