Epidemiology and cost analysis of varicella in Italy: results of a sentinel study in the pediatric practice. Italian Sentinel Group on Pediatric Infectious Diseases.

BACKGROUND: Describing the epidemiology of varicella is relevant to the development of specific prevention strategies and to building up of economic models evaluating the cost:efficiency ratios of these strategies. AIM: Our study was designed to describe the epidemiology of chickenpox among Italian children and to assess the resulting economic and health burden on the country. METHODS: Thirty-nine Italian pediatricians participated in a sentinel network on pediatric infectious diseases representing a total pediatric population of 30 168 children. Each case of varicella observed from January through December, 1997, was recorded. Economic analysis was conducted from the societal point of view. All costs were broken down into two groups: direct and indirect costs. RESULTS: A total of 1599 cases of varicella were reported among children 0 to 14 years old. There were 1266 primary cases (mean age, 4.5 +/- 2 years) and 333 secondary cases (mean age, 3.6 +/- 3.2 years). The global incidence of chickenpox was 51.01/1000/year. Complications were seen in 56 cases (3.5%). Drugs were prescribed in 672 cases. A group of adults (364 susceptible and 193 with uncertain status) were exposed to primary cases. Seventy (12.5%) were eventually infected among whom there were 4 pregnant women. For pediatric patients an average cost of $146.90 (250 400 lire) was estimated; this is largely accounted for by indirect costs. CONCLUSIONS: The epidemiology of varicella in Italy is consistent with that found in previous studies in industrialized countries. Severe complications did not occur in our population. We believe that the health arguments in favor of universal vaccination of children > 18 months of age do not differ in our own country from those of other industrialized nations. Our data could now be incorporated into pharmacoeconomic models to establish cost-efficient strategies for Italy.

Kinetics of distribution of amphetamine in cats.

The distribution and metabolic fate of amphetamine were studied in cats. In the brain, high levels of drug were detected in the grey matter structures at short intervals after administration, while at longer intervals distribution between white and grey matter areas was more uniform. In peripheral tissues the greatest concentration of the drug was seen in the highly vascularized organs. Para-hydroxy-amphetamine was found in minimal amounts in the liver and kidneys and only at trace quantities in the brain.

Pharmacokinetics of pinazepam in healthy volunteers.

The kinetics of pinazepam were studied in six healthy male volunteers aged between 26 and 31 years. The drug was administered in a single oral dose (10 mg). The concentrations of the parent compound and metabolites were measured in the plasma and urine by gas-chromatographic analysis. Plasma levels of pinazepam were fitted to a two-compartment open model with first order absorption rate using a three-exponential equation. Absorption rate constant and peak plasma levels of pinazepam were 1.36 +/- 0.15 h-1 and 36.8 +/- 5.1 ng/ml respectively. Plasma decay of the drug consisted of an initial rapid elimination phase (alpha = 0.46 +/- 0.06 h-1) followed by a slow one (beta = 0.046 +/- 0.004 h-1). N-desmethyldiazepam was the only metabolite detected in the plasma. Its plasma concentrations were higher than those of the parent compound shortly after administration. Urine was collected for 72 h after dosing. Those specimens contained unconjugate pinazepam and N-desmethyldiazepam and glucuronated oxazepam and 3-OH-pinazepam. Only 0.016% of the pinazepam administered was recovered as unchanged compound in the urine.

Localization of S-[methyl-14 C]adenosyl-L-methionine in pregnant mice and fetuses as determined by autoradiography.

The distribution of S-[methyl-14C]Adenosyl-L-methionine has been examined in pregnant mice using an autoradiographic technique. The results indicate that the compound crosses the placental barrier quite slowly and accumulates in some fetal tissues such as intestine, liver, kidney, eye and lung. The highest concentration is reached 12 hours after i.v. administration of the compound. In the placenta the labelling can be detected for a long time after administering the radioactive compound.

Elimination kinetics of desmethyldiazepam in two young and two elderly subjects.

Pinazepam (P) (10 mg) was orally administered to two young (22-23 years) and two elderly (74-80 years) healthy volunteers. Also, desmethyldiazepam (DD) (10 mg) was orally administered to the same young volunteers on a separate occasion. P was almost completely converted into DD 24 h after administration. Plasma levels of DD were measured in all subjects. In all cases, the DD concentration-time curve showed a biphasic decay (a first slow decay was followed by a fast one) which closely fitted by a Michaelis-Menten equation. Vmax and km constant were computed for all subjects. The kinetic analysis relative to the young subjects showed that T 1/2 of both the slow and fast decay as well as the area under the curve (AUC) were reduced when P was administered instead of DD. Comparison of DD kinetics between young and elderly subjects showed an increase of half-life in the elderly, while AUC was found unchanged.

Evaluation of the central dopaminergic activity in gestational hyperprolactinaemia by means of the electroretinographic technique.

Electroretinography, a simple, bloodless technique commonly used in ophthalmological diagnostic practice, seems to give important informations on the level of activity of the retinal and/or other central dopaminergic systems. The Authors have employed this technique in a group of 30 normal pregnant women in the ninth month of gestation, in order to evaluate the dopaminergic activity in a condition of physiological hyperprolactinemia, such as pregnancy, and in a group of 25 normal nonpregnant control women. The b wave amplitude of the electroretinographic traces was significantly higher in pregnant women than in controls, suggesting an over-activity of dopaminergic systems in late pregnancy. The possible interpretations of these data are discussed.

High incidence of goiter in patients treated with lithium carbonate.

The effects of lithium carbonate on thyroid was evaluated in 40 consecutive psychiatric patients on long-term treatment with this drug. Five patients had clinical and/or biochemical hypothyroidism. Twenty four (60%) subjects showed goiter of different size, including very large glands. A very high prevalence of goiter (87%) was observed in the 15 patients coming from a moderate endemic area. A lower incidence of goiter (44%) was found in subjects coming from non endemic areas. Goiter was associated with significantly elevated serum thyroglobulin concentration similar to that reported in endemic or sporadic nontoxic goiter. None of 25 psychiatric patients not receiving lithium therapy was hypothyroid and only three (12.5%) of them showed a small size goiter. These data indicate a very high prevalence of thyroid enlargement in patients on lithium therapy and suggest the opportunity to institute a prophylactic thyroid hormone treatment at least in subjects coming from endemic areas.

Lifetime co-morbidity with different subtypes of eating disorders in 148 females with bipolar disorders.

OBJECTIVES: To evaluate the impact of Eating Disorders (EDs) lifetime co-morbidity among female with Bipolar Disorders (BDs) and to compare clinical and cognitive features among EDs subgroups. METHOD: A hundred and forty eight women with a lifetime history of Diagnostic and Statistical Manual, Fourth Edition (DSM-IV)-defined Bipolar-I, Bipolar-II and/or Cyclothymia, were consecutively enrolled to determinate the prevalence of co-morbid DSM-IV-defined Anorexia Nervosa [AN], Bulimia Nervosa [BN] or Binge Eating Disorder [BED]. Measures included the Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID-I), the Clinical Global Impression (CGI) rating scale, the Eating Disorder Examination Questionnaire (EDE-Q) and BMI record. RESULTS: Forty six patients (31%) reported lifetime history of at least one ED: AN was the most common ED (n=23, 15.5%), followed by BED (n=21, 14.2%), and BN (n=8, 5.4%); 6 patients (4.1%) reported multiple lifetime EDs. As expected, BMI was highest in BED patients and lowest in those with AN. Clinical characteristics were similar in the 3 groups, while rapid cycling and co-morbid drug abuse were more common in BED compared to AN or No-ED group. As expected cognitive eating symptoms assessed by the EDE-Q were all more represented in AN than in No-ED patients. AN and BED only differed in restricting behavior and weight concerns. CONCLUSIONS: Our results prompt for the recognition of co-morbid EDs among bipolar patients, indicating that BED, along with other EDs, may influence in different ways both clinical characteristics and course of the illness. Further perspective studies are necessary to better define the relationships between different EDs and Bipolar Spectrum disorders.

Electroretinographic effects induced in humans by psychopharmacologic agents.

We studied the effects of single doses of different dopamine agonists and antagonists on the electroretinogram of a group of healthy volunteers. The results demonstrated significant b-wave amplitude changes after drug administration, suggesting that electroretinograms can be employed to evaluate the effects on retinal dopaminergic activity induced by psychotropic drugs and that the study of the electroretinographic effects of psychopharmacologic agents can provide new insights into the relationship between retinal dopaminergic mechanisms and the electroretinogram b-wave origin.

[The dexamethasone test and the choice of treatment and drug in depression]. / Il test al desametazone e la scelta del trattamento e del farmaco nella depressione.

A large body of literature data have indicated that the dexamethasone suppression test (DST) may be useful in diagnosing depression. It has been also hypothesized that depressed patients showing an abnormal response to dexamethasone administration ("DST-non suppressors") are responsive to the treatment with psychopharmacological agents whereas the "DST-suppressors" subjects are often "placebo-responders". Moreover, on the basis of considerations concerning the inhibitory role of noradrenaline in the control of both the activity of the hypothalamic-pituitary-adrenal axis and mood, it has been claimed that the "DST-non suppressors" subjects respond to the treatment with antidepressant drugs potentiating the noradrenergic activity at level of the central nervous system. The present review of the main data on the topic leads to conclude that the DST may be useful in selecting the most appropriate treatment for depressed patients; the test, however, does not make it possible to choose the antidepressant drug on the basis of its neurochemical profile.

Distribution of 14C-bis-(p-acetoxyphenyl)-cyclohexylidenemethane (F 6066) in mice.

The distribution of 14C-bis-(p-acetoxyphenyl)-cyclohexylidenemethane (14C-F 60666, cyclofenil) in mice was studied by means of an autoradiographic technique and organ radioassay. High concentration of radioactivity was found in liver, pancreas, hypophysis, lung, salivary glands, myocardium, blood, skeletal muscles and brain in decreasing order at various times after the administration. The drug penetrated very easily the blood-brain barrier and the highest concentration in the brain was detected in the hypophysis. The radiochemical studies confirm the autoradiographic data. 14C-F 6066 crossed the placental barrier and traces of radioactivity were seen in the foetuses.

Autoradiographic distribution study of 14C-2-phenyl-6-sulfonamido-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone (fenquizone) in mice.

The distribution of 2-phenyl-6-sulfonamido-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone (fenquizone, M.G. 13054) labelled with 14C in mice was studied by means of an autoradiographic technique. High concentration of radioactivity was found in the intestine, liver, kidney, blood, myocardium and skeletal muscles in decreasing order at various times after oral administration. The drug was easily absorbed in the intestine reaching the highest concentration between 2 and 4 hr. The labelled compound did not cross the blood-brain barrier.

Patients with mood depression have a high prevalence of seborrhoeic dermatitis.

Prevalence and severity of seborrhoeic dermatitis were studied in 150 patients with psychiatric disorders, including schizophrenia, mood disorders, anxiety and organic mental illness. As a control group, we examined 150 patients waiting for surgery and regarded as obviously anxious. Thirty-eight psychiatric patients were found to have seborrhoeic dermatitis, versus 13 in the surgery group. This statistically significant difference was entirely ascribable to patients with depression.

A double-blind clinical trial of nomifensine vs. amitriptyline in depressed patients.

This article describes a controlled clinical trial comparing nomifensine and amitriptyline in endogenously depressed inpatients. It is also the first trial of the ICPP-BLIPS, a computer based clinical trial data documentation system. Using strict methodological criteria, careful quality control and comprehensive and systematic data display and data analysis, we have been able to show clearcut efficacy differences between nomifensine and amitriptyline (favouring the later) and clearcut differences in the profile of side effects between these drugs. Future studies utilizing this methodology are recommended were definitive and documented results of clinical trials are desired.

Pinazepam: a precursor of N-desmethyldiazepam.

The plasma profile of a single oral dose of pinazepam 10 mg was studied in 6 healthy male volunteers, aged 26 to 31 years. The concentrations of the parent compound and of its metabolite in plasma were measured by gas-chromatography. The peak plasma levels of pinazepam was 36.8 +/- 5.1 ng/ml and of N-desmethyldiazepam 150 +/- 13.3 ng/ml. The plasma concentration of the metabolite become higher than that of the parent compound shortly after administration, suggesting that pinazepam acts as a prodrug.

Autoradiographic distribution study of 14C-DOPA in cat brain.

The penetration and distribution in various areas of cat brain of 14C-DL-DOPA and/or its derivatives was studied by the autoradiographic technique. The highest activity was found, 1 hr after administration, in the caudate nucleus, putamen and n. accumbens, while hypothalamus, substantia nigra, substantia grisea pericentralis, tuberculum olfactorium, raphe nuclei and nucleus interpeduncolaris showed lower levels of labelling. Very low activity was detected in the cerebral cortex and in the other gray and white matter structures of brain. After pretreatment with a peripheral DOPA-decarboxylase inhibitor or high dosage of cold DOPA, the distribution pattern was not modified but the levels of radioactivity were greatly enhanced. The localization of the drug in dopaminergic structures and other areas of the brain is discussed.

Placental transfer of pinazepam and its metabolite N-desmethyldiazepam in women at term.

Placental transfer of pinazepam and its metabolite N-desmethyldiazepam was investigated in 25 pregnant women at term. Pinazepam was administered orally as a single (10 mg) dose to 13 women, or in multiple doses of 5 mg daily to 12 women. The dose-delivery interval ranged between 1 and 26 h for the single dose, and the period between the last of the multiple doses and delivery was 1.4 to 24 h. Pinazepam and N-desmethyldiazepam were measured in plasma obtained from the umbilical vein and from the mother, at delivery. Pinazepam was only detectable in plasma after the 10 mg dose. The drug did not reach an apparent equilibrium between fetal and maternal plasma. The average (+/- SEM) cord/maternal ratio of plasma pinazepam concentrations was 0.64 +/- 0.07. N-desmethyldiazepam was detectable on each occasion. Its concentration in the plasma from the cord vein became higher than that in the maternal specimens 1-2 h after administration of the parent drug. Little N-desmethyldiazepam was excreted in breast milk.

A cantilever array-based artificial nose

We present quantitative and qualitative detection of analyte vapors using a microfabricated silicon cantilever array. To observe transduction of physical and chemical processes into nanomechanical motion of the cantilever, swelling of a polymer layer on the cantilever is monitored during exposure to the analyte. This motion is tracked by a beam-deflection technique using a time multiplexing scheme. The response pattern of eight cantilevers is analyzed via principal component analysis (PCA) and artificial neural network (ANN) techniques, which facilitates the application of the device as an artificial chemical nose. Analytes tested comprise chemical solvents, a homologous series of primary alcohols, and natural flavors. First differential measurements of surface stress change due to protein adsorption on a cantilever array are shown using a liquid cell.