The 35% CO2 hyperreactivity and clinical symptomatology in patients with panic disorder after 1 week of treatment with citalopram: an open study.

The effect of a short treatment (7 days) with citalopram on the reactivity to inhalations of 35% CO2 and 65% oxygen and on clinical symptomatology was investigated in 15 patients with panic disorder who had a positive response to 35% CO2 inhalation. An open study design was applied. On day 0, before starting drug treatment, and after 1 week of treatment, each patient underwent the 35% CO2 challenge, and clinical symptomatology was evaluated with psychometric scales. The results showed a significant reduction of CO2 reactivity and of scores on the anticipatory anxiety subscale of Panic Associated Symptoms Scale. These results confirm that the serotonergic system plays an important role in the modulation of CO2 hyperreactivity and suggest an early anxiolytic effect of citalopram in patients who have panic disorder and are hyperreactive to CO2.

Dopamine function in obsessive compulsive disorder: cortisol response to acute apomorphine stimulation.

Central dopaminergic dysfunction has been suggested to be involved in the pathogenesis of obsessive compulsive disorder (OCD). In 15 patients with OCD and in 15 age-sex matched controls we evaluated the dopamine (DA) function by measuring the cortisol (CORT) responses to stimulation with the DA agonist apomorphine (APO). The CORT response to acute saline administration was also measured, to exclude the existence of a pathology of the circadian secretion of the hormone which could obscure the significance of the CORT response to APO stimulation. Basal levels of CORT were the same in patients and controls, but the values after saline administration were significantly higher in patients than in controls. APO stimulation-induced CORT rises were significantly higher in patients than in controls, but when the data after APO were corrected for those after saline, there were no significant difference between the two groups of subjects. Our data suggest that there are no alterations of the central dopaminergic function connected with the regulation of the hypothalamo-pituitary-adrenal axis in OCD.

Artificial neural networks: a study in clinical psychopharmacology

Controlled trials in clinical psychopharmacology may fail to provide reliable information about the benefit of treatment when the patient is viewed in a real-life setting rather than as part of a well-defined sampling procedure. A viewpoint, rooted in systems theory, is proposed based on the identification of complex relationships among such dimensions as clinician's reasoning, drug properties, and patient's condition. Artificial Neural Network (ANN) technology provides efficient tools for data analysis within a systems-oriented approach. This study proposes a way to predict the outcome of psychopharmacological treatment. Analysis was conducted on retrospective data from clinical records of psychiatric patients treated with moclobemide. Twelve pharmacological, diagnostic, and topological variables were identified as the decisional items considered by six clinicians: age at onset, sex, previous treatment, duration and dose of moclobemide treatment, other drugs, psychiatric diagnosis and other clinical features. Data were binarily coded and transformed into observed frequencies in the sampling space; treatment outcome was binarily scored as the model's target. A Back-Propagation ANN based on the Delta rule with logistic transfer function was used. ANN correctly classified all cases of successful treatment (n = 51, 100%) but only half of the unsuccessful cases (n = 14, 52%). Patterns of response and areas of uncertainty were analyzed in a topological approach.

Sensitivity to 35% carbon dioxide in patients with generalized anxiety disorder.

BACKGROUND: Panic disorder and generalized anxiety disorder (GAD) are both characterized by severe anxiety, but there is evidence that indicates a qualitative difference between these 2 anxiety disorders. To investigate the specificity of the association between carbon dioxide (CO2) hypersensitivity and panic disorder and the possible relationships between panic disorder and GAD, the responses to inhalation of a gas mixture of 35% CO2 and 65% oxygen (O2) were assessed. METHOD: Fifteen patients with panic disorder, 13 patients with GAD, and 10 patients with comorbid GAD and panic disorder according to a consensus diagnosis using Diagnostic Interview Schedule Version III-R (DIS-R) and DSM-IV criteria, and 12 healthy controls inhaled 2 vital capacities: 1 of 35% CO2 and 1 of compressed air. A double-blind, randomized, crossover design was used. RESULTS: GAD patients showed reactions to 35% CO2 that were similar to those of healthy controls and significantly weaker than that of panic disorder patients. Patients with comorbid panic disorder and GAD had anxiogenic reactions similar to those of subjects with panic disorder. CONCLUSION: The results of the present study support the idea that panic disorder and GAD are separate disorders that have at least some differences in pathogenetic mechanisms and suggest that the 35% CO2 test might be a valid tool for discriminating between these 2 disorders.

A long-term prospective evaluation of first-degree relatives of panic patients who underwent the 35% CO2 challenge.

BACKGROUND: This follow-up study investigated the potential priming effect of the 35% CO2 challenge on the development of anxiety disorders and/or panic attacks in healthy first-degree relatives of panic patients across a period of 3-4 years subsequent to the challenge. METHODS: Thirty-one relatives who underwent the 35% CO2 challenge 3-4 years before and 14 relatives, free from psychiatric diagnoses in the same period, were directly reevaluated for the presence of anxiety disorders and panic attacks. RESULTS: None developed anxiety disorders and only 1, among relatives previously tested with the 35% CO2 challenge, reported sporadic panic attacks. CONCLUSIONS: The 35% CO2 challenge is a safe research paradigm in the investigation of healthy subjects with a familial vulnerability to panic, and CO2 hypersensitivity might be considered a trait marker of an underlying familial vulnerability to panic disorder.

Primary care pediatrics in Italy: eighteen years of clinical care, research, and teaching under a national health service system.

This article reviews how Italian National Health Service (NHS) pediatricians have tried to fulfill the obligations of modern primary care providers in a managed care environment, with special reference to the experience of the Veneto region in Italy and compares this situation with the present changes of the health system in the United States. Italian NHS primary care pediatricians work independently in their offices, providing acute and chronic patients to all children 0 to 14 years old: NHS primary care physicians, including 7000 pediatricians, contract directly with the government for the care of patients through a capitated reimbursement system. Twenty-nine independent associations of community pediatricians have been formed with the primary goal to pursue research and education in primary care pediatrics, in addition to traditional care. Several multicenter collaborative research studies at the national level have been organized and four university residency programs are training their residents in community-based pediatricians' offices also, giving priority to activities specific to ambulatory practice and follow the suggestion of an Italian work group on ambulatory pediatric training. The NHS has allowed the Italian pediatrician to focus on patient care and education rather than business. Computerization has been applied to the practice of medicine through the development of electronic medical records, particularly in the Veneto region. This technology allows combining effective clinical care with outcome researches and facilitates continuing medical education and residents' training programs. Italian primary care NHS pediatricians have tried to identify and address patient's needs as well as the needs of a primary care provider in a managed care system. Recent and possible future modifications in the health system in the United States and in Italy need to be examined to learn from similarities and differences.

Toxicological evaluation of u-hEGF.

The toxicological evaluation of urinary human epidermal growth factor (u-hEGF) included mutagenicity, single and repeated dose general toxicity, and teratogenicity studies in various animal species. The mutagenic potential of u-hEGF was tested in vitro (Ames test, chromosome aberration in human lymphocytes, unscheduled DNA synthesis in HeLa cells) and in vivo (chromosome aberration in Chinese hamster bone marrow and micronucleus test in rat bone marrow). No mutagenic or clastogenic effects were found. The acute toxicity of u-hEGF was evaluated in mice and rats, using single subcutaneous (sc) or intravenous (i.v.) injection of 15 mg/kg. No toxic effects were observed Four-week i.v. daily administration of u-hEGF at the doses of 0.3, o.9, and 3 mg/kg in the SD rat followed by 2 wk of compound withdrawal induced pronounced and generally dose-related effects (i.e., epithelial hyperplasia) in a wide range of tissues and organs, at all doses. However, these effects were not apparently detrimental to the general health of the rats. The repeated sc administration of u-hEGF to cynomolgus monkeys for 4 wk at the same doses as used in the rat study resulted in lethality after about 7 days of treatment in the 2 higher dose groups or after 14 days at the lowest dose. The main clinical signs observed were gastrointestinal effects, respiratory distress, sedation, marked loss of body weight, and cutaneous desquamation. At histology, hyperplasia of most epithelia was seen in all groups. In addition, atrophy of the ovarian follicles and necrosis of the uterine endometrium were noted. Changes considered secondary to physical distress were atrophy of the hemopoietic and lymphatic system and hepatic steatosis. The embryofetal toxicity and teratogenicity of u-hEGF was tested, using the i.v. route in the SD rat and the i.v. and sc routes in the New Zealand White rabbit. In both species, the compound was administered at the doses of 0, 0.3, 0.9, and 3 mg/kg/day, from day 6 to 15 of pregnancy in rats and 6-18 in rabbits. In the rat, an increase in body weight was noted in the dams and fetuses at the 2 high doses. No embryotoxic or teratogenic effects were observed. In the rabbit studies, mortality and severe clinical signs involving various systems, with marked effects on the eyes, were observed at all doses tested during the first days of treatment by both routes. From the reproductive point of view, most of the surviving treated gravid females showed only resorptions.

Reproductive toxicology of the new antitussive moguisteine.

Moguisteine (R,S(+/-)-2-(2-methoxyphenoxy)-methyl-3-ethoxycarbonylacetyl- 1,3-thiazolidine, CAS 119637-67-1), a new oral non narcotic peripherally acting antitussive drug, was examined for effects in the rat on general reproductive performance (at 0, 50, 212, 900 mg/kg/d,) for embryotoxicity (at 0, 25, 75, 225, 900 mg/kg/d) and for peri-postnatal toxicity (at 0, 62.5, 250, 1000 mg/kg/d). Embryotoxicity (at 0, 75, 225, 900 mg/kg/d) was also examined in the New Zealand White rabbit. In all the studies, moguisteine was administered orally as a suspension by gavage. At the tested doses, moguisteine did not interfere with general reproductive performance, either in the F0 or in the F1 generation. The drug did not show any toxic effect on the dams and their fetuses, nor did it have any teratogenic effect in either of the tested species. Finally, moguisteine had no adverse effects, either on parturition or on peri-and postnatal survival and/or development of the offspring.

Toxicological evaluation of pidotimod.

This paper reports the toxicological evaluation of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6). Its acute toxicity in mice, rats and dogs was very low after oral, i.v., i.m. and i.p. administration. The repeated administration studies in rats were performed for 4 months via the i.p. route and for 12 months via the oral route. Pidotimod did not show toxic effects at dosages up to 200 mg/kg i.p. and 800 mg/kg p.o. These dosages correspond to 32.5 times the maximum dosage intended for clinical use. The repeated administration studies in dogs were performed for 26 weeks via the i.m. route and for 52 weeks via the oral route. Pidotimod did not show toxic effects at dosages up to 300 mg/kg i.m. and 600 mg/kg p.o.. It did not affect male or female rat fertility at dosages up to 600 mg/kg by oral and 500 mg/kg by i.v. route. The compound was not teratogenic in rats (600 mg/kg p.o. and 1000 mg/kg i.v.), with no effects on subsequent embryofoetal development at dosages up to 1000 mg/kg/day, and in rabbits (300 mg/kg p.o. and 500 mg/kg. i.v.). There were no peri- and postnatal toxic effects in rats (600 mg/kg p.o. and 500 mg/kg i.v.). Local tolerability of pidotimod after i.m. administration was very good. In conclusion pidotimod is characterized by a high safety margin in all animal species.

Prevención farmacológica de la otitis media aguda recurrente / Pharmacological prevention of the recurrent acute otitis media

El presente trabajo se de sarrolló en dos fases: en la primera los pdiatras respondieron a preguntas de un cuestionario, para poner en evidencia los tratamientos personales practicados en caso de Otitis Media Aguda (OMA) así como otitis media concaracter recurrente (ver cuadro 1). La segunda fase del trabajo consiste en evaluar críticamente cada uno de los estudios clínicos publicados sobre prevención farmacológica de OMAR y discutirlos en encuentros formales, de caracter colegial

Effects of continuous low-level exposure to radiofrequency radiation on intrauterine development in rats.

To assess the effect of low-level radiofrequency radiation on pregnant rats, gravid dams were exposed continuously to 0.1 mW cm-2 at 27.12 MHz during different periods of pregnancy. Biological assays consisted of determining pre- and post-implantation losses and the effects on maternal body weight increase. Fetal parameters monitored included sex, mean viable fetal weight on Day 20 of gestation, external, skeletal and visceral fetal malformations, anomalies and variations. Dosimetric evaluations were made in terms of average specific absorption rate (SAR) and basal metabolic rate (BMR). Findings included a considerable increase in the percentage of total resorptions, reduced body weight increase in the exposed dams and incomplete cranial ossification in their fetuses. Results obtained were compared with those shown by other authors. It seems possible to ascribe some of the effects to a specific action of the radiofrequency radiation occurring independently of the rise in temperature. The hypothesis the exposure time, together with SAR, plays an important role in inducing specific exposure effects due to radiofrequency radiation is presented.