[Security of supply: Getting to know more about the organization of suppliers]. / Sécurité d'approvisionnement : mieux connaître l'organisation des fournisseurs.

OBJECTIVES: The worsening pharmaceutical products shortage required the central purchasing structure of AP-HP to include a new criterion on supply safety in the tenders' procedures. Each provider answering to the tender needs to complete a dedicated form. The aim is to review the collected information and assess its relevance. METHODS: This study is based on a retrospective analysis conducted on the last 2 tenders' procedures forms (one started in September 2019 and the other in February 2020). RESULTS: These 2 tenders' procedures were composed of 155 lots. The form response rate was 81,4%. The average rating on 20 was 10,9±3,8. The rates could be very variable depending on the lots. Regarding the 2020s tenders procedures, 57.8% of specialties were classified as drugs of major therapeutic interest. A shortage management plan exists for 24.0% of them. Providers indicated several sources of raw materials (36,1%) and several factories (35,5%). The average advanced stock was 4.1±3.8 months in France and 2.3±2.6 months in Europe. The information system implemented by suppliers scored an average of 15 out of 20. CONCLUSIONS: This study allowed us to know better the suppliers' organisation. The concerning points are the low stocks and the discrepancies in the suppliers' drugs of major therapeutic interest classification of a same product and the existence of a shortage management plan. This form will be maintained with more specific questions. An assessment will be done to determine the relevance of this form to prevent disruptions.

[Impact of the expiry of the patent on quality and price of medicines at hospital: Study of five anticancer drugs from 2008 to 2015 at the Assistance publique-Hôpitaux de Paris]. / Impact de la chute des brevets sur le critère « qualité ¼ et sur le prix des médicaments à l'hôpital : étude sur cinq anticancéreux entre 2008 et 2015 à l'Assistance publique­Hôpitaux de Paris.

OBJECTIVES: Anticancer drugs were in 2005 the first expenditure item of the hospital drugs. Ten years later, it is noted that the placing on the market of generic drugs has led to a strong decrease of their price. To determine whether this decrease comes at the expense of product quality, a price-quality ratio trend study of five anticancer drugs was performed at AP-HP. METHOD: This work concerns docetaxel, oxaliplatin, gemcitabine, irinotecan and paclitaxel, and focus on the transition period between monopoly conditions and competitive situation (2008 to 2015). The price is set by calculating the cost per milligram of each specialty. Quality is evaluated by the average of quality marks obtained during the analysis of the tenders received in the purchasing procedures on four assessment criteria: ready for use form, stability of the solution after dilution, safety use and labeling. RESULTS: Between 2008 and 2015, the price per milligram of these anticancer drugs decreases, following the placing on the market of generic drugs. The quality of the tenders is maintained and even improved in many cases. On average, generic rating quality, lower than that of the originators in 2008, are now the highest. CONCLUSION: This study allows an objective basis of the effects of the drop in patent originator medicines. The placing on the market of generic drugs has a double positive result for the buyer: strong price cuts, parallel to the quality improvement, through the example of five anticancer drugs studied.

[Pharmaco-therapeutic evaluation of medical treatments of adult autistics and multi-handicapped patients in a public mental health unit]. / Les traitements psychotropes prescrits dans un établissement public de santé mentale accueillant des personnes atteintes d'autisme et des polyhandicapés.

INTRODUCTION: This paper presents a survey conducted on a population of multi-handicapped patients and autistic adults hospitalised long term in the Paul Guiraud mental health Hospital in Villejuif France. OBJECTIVE: The aim of the survey is to deepen the knowledge of the treatments for this specific population. METHODS: A preliminary medical investigation was conducted on the population in order to target different groups of patients. Once patients had listed and defined their medical needs, prescriptions were analysed to assess whether clinical characteristics had an impact. Thus, the analysis of treatments was carried out for the 57 patients (14% of the hospital population) and compared to other investigations conducted on the population commonly hospitalised in Psychiatry. The evaluation of the treatments was obtained through a questionnaire which enabled us to target the therapeutical goals and to obtain additional clinical information. The drugs with a high rate of prescription were compared between the autistic group and the multi-handicapped group. The important comorbidity and the multi-symptomatology of autism often involves the polymedication of these patients (8+/-0.8 drugs per patient). RESULTS: Fifty per cent of the treatments are referred to as somatic treatments. The average length of stay (22.3 years) and the high average age are aggravating factors for polymedication. The average number of psychotropic molecules also appears higher than in the populations studied in the literature. The heterogeneity of clinical forms of autism and polyhandicap encourages prescribers to multidrug therapy. The prescriptions usually remain stable (17.5% of psychiatric treatment is adapted and only 7% of somatic treatment). Epilepsy and constipation are the main treated somatic disorders. In psychiatry, the oral route is the privileged route of administration (81% of treatments) with, more specifically, the use of drinkable solutions for the psychiatric treatment. Neuroleptic drugs are the basic treatment of these patients (82% of prescriptions). The aim of the prescription of neuroleptics is essentially to obtain behavioural or antipsychotic sedation. Cyamemazin is the most prescribed drug (46% of neuroleptic prescriptions), mainly for its anxiolytic effects. Co-prescription is frequent (55.3%) and corresponds to 53% of co-prescriptions of an association of phenothiazine and butyrophenone. Doses are high, which implies the prescription of treatments against the neuroleptics side-effects (86% of patients have such a prescription). The rate of prescriptions of the other psychotropic drugs (hypnotics, anxiolytics, etc.) is approximately equivalent between our population and the "classical" hospitalised psychiatric population, except for antidepressants (7% of prescriptions) because the differential diagnosis is difficult in these patients. Nearly 60% of patients have prescriptions of hypnotic drugs. However, this figure is tempered by prescriptions of drugs "if necessary" in two-thirds of the cases. Finally, only 30% of patients have systematic hypnotic prescriptions. CONCLUSION: Although autistics are clinically different from multi-handicapped patients, no statistically significant difference was demonstrated in their prescriptions, which implies a similar pharmacological management. It is difficult to clearly distinguish these two populations only according to the type of drugs used and the doses prescribed.

Screening for germ line p53 mutations in children with malignant tumors and a family history of cancer.

We have undertaken a routine investigation of the p53 status for all the children treated at our institution either affected by multiple tumors or whose family displays at least one second degree relative or less, affected by cancer before the age of 45 years. We report here on the first set of ten such families, eight of which were identified through a proband with sarcoma. p53 exons 5 to 8 have been sequenced following polymerase chain reaction amplification performed on DNA isolated from total blood. A missense mutation affecting codons 248, 273, and 282 was identified in three families. The mutation was inherited in these three families and was detected in unaffected members. In seven families no mutation was detected in exons 5 to 8.

Genetic polymorphism of induction of CYP1A1 (EROD) activity.

CYP1A1 is a cytochrome P450 which is inducible by polycyclic aromatic hydrocarbons (PAH). This induction is mediated via the Ahr locus which encodes the cytosolic Aryl hydrocarbon receptor. The induced activity of CYP1A1 can be measured in vitro by the ethoxyresorufin-O-deethylase (EROD) activity in lymphocytes after induction by benz(a)anthracene (B(a)A). Our purpose was to determine, using this assay, the genetic polymorphism of CYP1A1 induction. With this aim, a population and family study was undertaken. Using the statistical SKUMIX method, a bimodal distribution (two peaks) of the induced EROD activity among 102 unrelated individuals was obtained. We were unable to discriminate three classes of CYP1A1 induction phenotype since a trimodal distribution did not significantly improve the fit to the data (chi 2(1) = 0.37, p > 0.9). Segregation analysis performed on 57 nuclear families gave evidence of a major gene effect together with a polygenic component. The frequency of the high induction allele is equal to 0.11 with dominance on the low induction allele. This is an accordance with two distributions, with individuals showing low and high CYP1A1 induction phenotypes in proportions of 89% and 21% respectively. However, some degree of overlap between the two distributions prevented a clear genotype classification on the basis of the phenotype measured with the EROD assay. Further analyses should not be made with a dichotomized phenotype (low and high inducers) but should use quantitative measurements.

A population and family study of N-acetyltransferase using caffeine urinary metabolites.

Population and family studies were undertaken to validate caffeine as a probe drug to establish the genetic status of rapid acetylators and slow acetylators. The acetylator status was established from the urinary metabolic ratio of 5-acetylamino-6-formylamino-3-methyluracil to 1-methylxanthine (AFMU/1X) after oral administration of caffeine. We confirmed a bimodal distribution (chi 2(1) = 229.48; p << 10(-9)) of the AFMU/1X ratio in 245 unrelated subjects. A third distribution did not significantly improve the fit to the data (chi 2(1) = 0.04; p = 0.84). Complex segregation analysis of 76 nuclear families confirmed the monogenic inheritance of N-acetyltransferase, with incomplete dominance of the rapid allele over the slow one. We observed a slight shift between the mean activities of heterozygous and homozygous rapid acetylators (t = 2.89; p < 0.01). However, the 30 obligate heterozygotes belonging to the 76 families were evenly distributed among the rapid acetylators and never located in a hypothetic intermediary group between slow acetylators and rapid acetylators.

Cancers in relatives of children with non-Hodgkin's lymphoma.

We undertook a family study of children treated at the Institute Gustave-Roussy in France to investigate a familial aggregation of cancer in the families of children with non-Hodgkin's lymphoma (NHL). We obtained family dat for 284 children with NHL. Using the Standardized Incidence Ratio, we compared the observed and expected number of families with at least one proband relative affected by cancer at a young age (before 46 years). We found a small but non-significant excess of all tumors in first-degree relatives (SIR = 1.3, 95% CI = 0.7-2.3) explained by a small but non-significant excess of hematological malignancies (SIR = 1.5, 95% CI = 0.2-5.5), particularly Hodgkin's disease and leukemia, and of osteosarcoma (SIR = 7.5, 95% CI = 0.1-41.4). This is probably a lower bound of the SIR, because the expected number of families was estimated from cancer incidence in France between 1978 and 1982, whereas most cancers occurred before this period. Other tumors were not in excess in first-degree relatives.

[Collection of familial data in pharmacogenetics. Methodological problems]. / Recueil de données familiales en pharmacogénétique. Problèmes méthodologiques.

The purpose of this paper is to show the problems with family data collection in a pharmacogenetic study, the aim of which was to study the genetic polymorphism of inducibility of cytochromes P4501A by polycyclic aromatic hydrocarbon (PAH). Data were collected from 76 smoker nuclear families (315 volunteers). A caffeine test, a blood sample and answers to a questionnaire were obtained from each healthy volunteer. It was a crucial problem to recruit nuclear families with healthy smoker father and/or mother and 2 smoker children. On 127 answers, 22 families were not eligible, 27 refused and 10 had a single child, that meant secondary refusals. Problems differed with origin of the recruitment. Included were 40 families obtained from 3 antismoking outpatient departments, 29 from general practitioners but 6 only from students. The family rates with 2 parents/2 children were significantly higher with general practitioners (p < 0.01). This emphasized their part in epidemiologic studies. Problems with the use of methodology were bound to acceptability of the tests which were better in females (p < 0.05), and a change in caffeine form could improve this acceptability. Lastly, difficulties with laboratories constraints required a very good coordination between families, nurses and laboratories.

[Clinical follow-up -- EEG -- serum determinations: therapeutic experience with clozapine]. / Suivi clinique--EEG--dosages sériques: expérience thérapeutique de la clozapine.

The effects of clozapine were studied during 5 years at the Villejuif psychiatric hospital in outside and inside patients. Among the results obtained in 114 cases treated, we report here the results obtained in a group of 18 patients in which the longitudinal therapeutic data given by EEG recordings were confronted with those obtained for the plasma levels of the drug and it demethyl metabolite. This study shows on one side that EEG abnormal activities are frequent and need to be taken in account. On another hand we found an important inter as well as intra-variability of the plasma concentrations. For the intra-individual variations a large number of responsible factors was found. The interest to perform the demethyl metabolite dosage is discussed.

[Value of trimeprazine among hypnotics in a psychiatric facility]. / Place de l'alimémazine parmi les hypnotiques dans un établissement de soins psychiatriques.

Trimeprazine (TPZ) has been marketed in France since 1959, as tablets and solution containing respectively 5 mg and 40 mg/ml. TPZ is a phenothiazine derivative with known antihistaminic and sedative effects. The first approved indication for TPZ is in the treatment of allergy. However, its frequent sedative effects are undesirable in this indication. The second approved indication is in the treatment of insomnia (5-20 mg/day) and TPZ is an alternative to conventional hypnotics as diazepam, flunitrazepam, zolpidem, butobarbital... Due to the prescription frequency of this medicine in our hospital, we analyzed the naturalistic prescriptions mode and the clinical end point in patients hospitalized for mental illness. On the one hand, using the hospital prescription software, we analyzed: prescriptions frequency, dose regimen and drug associations with hypnotics, anxiolytics and sedative antipsychotics. On the other hand, we came into contact with physicians in order to know their opinion on TPZ and the whole point of that indication. The results showed a very high prescription frequency (139/400 patients; 35%), a marked increase in dose compared to those approved by the French Drug Administration (5-20 mg/day: 5%; 20-200 mg/day: 95%) and main drug association with hypnotics, tranquilizers or antipsychotics, respectively 38%, 65% and 91%. Clinical end points are: non addictive properties and an easily adequation of posology for the drinkable drop form in contrast with tablets. Thus, TPZ appears as a first-line hypnotic in spite of its adverse effects common to phenothiazine (atropinic and antidopaminergic effects) and is a usefull medicine for the treatment of insomnia in psychotic patients.

[Chemotherapy in Alzheimer's disease. Retrospective study in a specialized hospital center]. / Chimiothérapie dans la maladie d'Alzheimer. Etude rétrospective dans un Centre Hospitalier Spécialisé.

In this study, our aim was to analyse the prescriptions of drugs used to improve Alzheimer's disease at CHS Paul Guiraud. This study was carried out a posteriori on 16 hospitalized patients. We have seen that for our patients there is no general rule, nor therapeutic scheme but the choice of treatment is carried out according to the professional experience of the physician. The treatment therefore is composed of symptomatic drugs alone or associated with etiologic drugs. Eleven anxiolytic or hypnotic drugs were prescribed. Alimemazine is the most prescribed in the sixteen cases. The preferential use of this drug can be explained by its presentation in the form of drops. In two cases, behavioural improvements were noted, in two other cases, we noted accentuation of dementia. Meprobamate used in seven cases of the sixteen, was never used alone. We find neuroleptics in fifteen of the sixteen cases studied: In seven cases they were administered from the beginning of the hospitalisation; for the others they were introduced later during a phase of agitation or delirium. On the whole, they were effective on aggressive agitation, in particular thioridazine. Eight of the patients, were treated with halopéridol. In two cases, the behaviour disorders were not stopped; in four cases, there was a worsening of dementia. We noted depression in 6 cases from the beginning of hospitalization, and two cases during hospitalization. The anti-depressive drugs besides their main effect, reduce also anxiety. In two cases, we observed an aggravation of disorientation and confusion following of the prescription of amitryptiline and mianserine.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensitivity of transmission probabilities to paternity exclusion in segregation analysis.

Paternity exclusions are known to be common in Western countries and are yet neglected in segregation analysis because it is almost impossible to check it systematically on a large family sample. We had the opportunity of observing the sensitivity of segregation analysis parameters to a paternity exclusion in analyzing 34 families for a simple Mendelian trait, the acetylator phenotype. We found that only one family, with proven paternity exclusion, was responsible for a strong rejection of Mendelian transmission probabilities (P much much less than 0.001).

[Tuberculosis in France. Current epidemiologic status and evolution over the last 10 years]. / La tuberculose en France. Situation épidémiologique actuelle et évolution au cours des 10 dernières années.

By evaluating the statistics of the cause of death, the current reports of antituberculous clinics and the information gathered from the tuberculosis registers of certain departments, an epidemiological survey in France shows that there were 2,048 deaths due to tuberculosis in 1981 (3.8 per 100,000). The level is steadily falling; these were 8.2/100,000 in 1970. It is the same for morbidity, the incidence of all forms of tuberculosis was 54 0/0000 in 1972 and 26.9 in 1980. In the register in the Bas-Rhin the level fell from 70.5 to 30.4, in the Rhône from 41.6 to 14.4 and in the Hautes Pyrénées from 22.2 (in 1973) to 15.3. In the Bas-Rhin the prevalence has fallen steadily: 233.3 in 1972 to 97.7 in 1979. Foreigners are five times more affected than the French by respiratory forms and 8 times more for extra-respiratory tuberculosis. Those who came from Black Africa are the most affected.

Treatment compliance and self-medication in asthma in France.

A study was carried out among asthmatic patients in order to determine their compliance to treatment and self-medication. Data collection used a self-administered postal questionnaire as tested in a previous study. The population under study included 450 asthmatic patients; 370 answered; their mean age was 47 +/- 16 yrs and 44% were men. An aerosol was the preferred route of administration (41%). Eighty two percent of the patients tended to reduce the doses following improvement; 80% claimed to know treatment for attacks; 90% had already been using an inhaler, although only 62% had been shown how to use one. Forty eight percent had already bought drugs without prescription, especially patients within the 25-34 yrs age group. This study is consistent with similar surveys performed in other populations. Improved quality of information about treatments and how to use drugs is higher in patients with chronic forms of asthma involving unpredictable acute attacks.

A population and family study of CYP1A2 using caffeine urinary metabolites.

CYP1A2 is a cytochrome P450 which is inducible by polycyclic aromatic hydrocarbons. This induction could be mediated via the Ah locus, which encodes a cytosolic receptor responsible for the regulation of the CYP1A1 gene. Enzyme activity in vivo can be measured by the urinary caffeine metabolite ratio (AFMU + 1X + 1U)/17U. Our goal was to determine, using this ratio, the possible existence of a genetic polymorphism in CYP1A2 induction. For this purpose, a population and family study, including smokers, were undertaken. In a first step, we investigated factors influencing enzyme activity in a population of 245 unrelated individuals. The induction effect of smoking and inhibiting effect of oral contraceptive use were confirmed. None of the other factors examined (age, sex, level of cigarette consumption, nicotine or tar amounts, filter, inhalation) accounted for the interindividual variability in the metabolic ratio. Using the statistical SKUMIX method, a unimodal (one peak) distribution of the ratio was concluded in 164 unrelated smokers, since a second distribution did not significantly improve the fit to the data (chi 2(1) = 1.39, P > 0.2). Segregation analysis was performed on 68 nuclear families and no major gene effect could be shown. Furthermore, the polygenic model did not provide a higher likelihood than the sporadic one, which argues against the existence of any familial resemblance. Although we cannot rule out the possibility that some environmental factors could obscure the phenotypes and occult a genetic determinism, we conclude that genetic factors are probably negligible in the determination of CYP1A2 activity measured by this method.(ABSTRACT TRUNCATED AT 250 WORDS)

[Changes in pharmacists practices (1996 - 2000) related to harm reduction policy (condoms, injecting equipment, methylmorphine) and maintenance therapy delivery (buprenorphine, methadone)]. / Evolution de l'implication du pharmacien d'officine dans la prévention des dommages liés à l'usage de drogues et la dispensation des traitements de substitution.

AIMS: To measure pharmacists involvement in harm reduction programs and in delivery of maintenance therapies in order to estimate their contribution to the new public health policy. METHOD: A longitudinal study was conducted among 327 pharmacies located in the southern suburban area of Paris (28 communities) using a standardized questionnaire. RESULTS: The response rate was 95% in 1996 and 92% in 2000. The number of condoms offered to intravenous drug users (IDU) decreased dramatically from 99% to 24% while delivered units decreased from 857 to 566 per day for needles and from 1200 to 760 per month per pharmacy for methylmorphine tablets (14.93 mg/tablet). Pharmacists delivered injecting equipment to some of their patients under opiate treatment: methylmorphine 19%, buprenorphine 35%, methadone 14%. Their contribution to the local healthcare network on addiction decreased from 38% to 20%. Nevertheless, the pharmacists attitude towards the IDU and public health policy was found to be improving with problems being mentioned for 62% of the cases in 1996 and for 16% in 2000. CONCLUSION: Pharmacists are rapidly and intensively changing their practices and are discovering a new comprehensive relationship with IDU. Better pharmacist involvement is associated with a shift in local healthcare network concentration, reinforcing the general practitioner-pharmacist partnership.

Validity and repeatability of the IUATLD (1984) Bronchial Symptoms Questionnaire: an international comparison.

The International Union against Tuberculosis and Lung Disease (IUATLD) Bronchial Symptoms Questionnaire (1984) was developed for use in studies of asthma and its reliability measured in an earlier survey in England. The association of the symptoms elicited by this questionnaire to bronchial response to histamine has also been described. This paper presents the results of studies of the questionnaire in four clinical centres in Europe. The reliability of the questionnaire and its ability to predict the bronchial response to histamine were compared for English, Finnish, French and German translations of the questionnaire in samples of diagnosed asthmatics and controls in Nottingham, Berlin, Helsinki and Paris. The answers to questions showed good repeatability, especially in Finland and Germany, particularly those questions on asthma and wheeze. The most sensitive symptom for predicting hyperresponsiveness was the question on wheeze, the most specific questions were those on waking at night with shortness of breath (Paris and Nottingham) and morning tightness (Helsinki and Berlin). This study shows that the IUATLD (1984) questionnaire may provide useful, valid and comparable data even in translation but these studies will need to be repeated in representative samples before such a possibility is accepted as fully demonstrated.

Genetic transmission of susceptibility to cancer in families of children with soft tissue sarcomas.

BACKGROUND: This article presents analysis of clinical and family data for 239 patients with childhood soft tissue sarcoma (STS) treated at the Institut Gustave Roussy in Villejuif. METHODS: A molecular study was performed to detect germline p53 mutations in the 44 families in which at least 1 relative developed cancer before the age of 46 or in which the proband had a second neoplasm. Mutations were found in five families. Standardized incidence ratio calculation and segregation analysis were used to study cancer occurrence in 4448 relatives, including first- and second-degree relatives and first cousins. RESULTS: An excess of brain tumors was observed in all relatives, and of breast carcinoma and STS in first-degree relatives of patients with STS. An excess of breast carcinoma was observed only in young mothers of patients with rhabdomyosarcoma. This excess might be mostly linked to the presence of a germline p53 mutation because it was no more significant when excluding families in which such a mutation existed. No association between breast carcinoma in the mother and rhabdomyosarcoma of the genitourinary tract in the proband was observed. This should be kept in mind when developing a screening strategy for breast carcinoma in mothers of patients with STS. Segregation analysis showed evidence for transmission of an autosomal dominant gene with complete penetrance by the age of 84. The genetic component was explained primarily by p53 germline mutations. CONCLUSIONS: These results show that most relatives of patients with STS are at the same risk for cancer as the general population.

Effects of chronic paroxetine treatment on dialysate serotonin in 5-HT1B receptor knockout mice.

The role of serotonin (5-HT)1B receptors in the mechanism of action of selective serotonin re-uptake inhibitors (SSRI) was studied by using intracerebral in vivo microdialysis in conscious, freely moving wild-type and 5-HT1B receptor knockout (KO 5-HT1B) mice in order to compare the effects of chronic administration of paroxetine via osmotic minipumps (1 mg per kg per day for 14 days) on extracellular 5-HT levels ([5-HT]ext) in the medial prefrontal cortex and ventral hippocampus. Basal [5-HT]ext values in the medial prefrontal cortex and ventral hippocampus, approximately 20 h after removing the minipump, were not altered by chronic paroxetine treatment in both genotypes. On day 15, in the ventral hippocampus, an acute paroxetine challenge (1 mg/kg i.p.) induced a larger increase in [5-HT]ext in saline-pretreated mutant than in wild-type mice. This difference between the two genotypes in the effect of the paroxetine challenge persisted following chronic paroxetine treatment. Conversely, in the medial prefrontal cortex, the paroxetine challenge increased [5-HT]ext similarly in saline-pretreated mice of both genotypes. Such a challenge produced a further increase in cortical [5-HT]ext compared with that in saline-pretreated groups of both genotypes, but no differences were found between genotypes following chronic treatment. To avoid the interaction with raphe 5-HT1A autoreceptors, 1 micro m paroxetine was perfused locally through the dialysis probe implanted in the ventral hippocampus; similar increases in hippocampal [5-HT]ext were found in acutely or chronically treated wild-type mice. Systemic administration of the mixed 5-HT1B/1D receptor antagonist GR 127935 (4 mg/kg) in chronically treated wild-type mice potentiated the effect of a paroxetine challenge dose on [5-HT]ext in the ventral hippocampus, whereas systemic administration of the selective 5-HT1A receptor antagonist WAY 100635 did not. By using the zero net flux method of quantitative microdialysis in the medial prefrontal cortex and ventral hippocampus of wild-type and KO 5-HT1B mice, we found that basal [5-HT]ext and the extraction fraction of 5-HT were similar in the medial prefrontal cortex and ventral hippocampus of both genotypes, suggesting that no compensatory response to the constitutive deletion of the 5-HT1B receptor involving changes in 5-HT uptake capacity occurred in vivo. As steady-state brain concentrations of paroxetine at day 14 were similar in both genotypes, it is unlikely that differences in the effects of a paroxetine challenge on hippocampal [5-HT]ext are due to alterations of the drug's pharmacokinetic properties in mutants. These data suggest that there are differences between the ventral hippocampus and medial prefrontal cortex in activation of terminal 5-HT1B autoreceptors and their role in regulating dialysate 5-HT levels. These presynaptic receptors retain their capacity to limit 5-HT release mainly in the ventral hippocampus following chronic paroxetine treatment in mice.

Asymmetric metabolic profile in mesial temporal lobes: localized H-1 MR spectroscopy in healthy right-handed and non-right-handed subjects.

PURPOSE: To determine a possible asymmetric metabolic profile in right- handed and non-right-handed healthy subjects by comparing proton spectra from temporal lobes. MATERIALS AND METHODS: Twenty-eight healthy adults (17 right-handers, 11 non-right-handers) underwent magnetic resonance (MR) imaging and single-voxel MR spectroscopy. N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) peak areas were measured. RESULTS: Volume of hippocampal formations was larger on the right in right-handers (right volume: 4.04 cm3 +/- 0.67 vs left volume: 3.84 cm3 +/- 0.62; P = .00004) and in non-right-handers (right volume: 4.22 cm3 +/- 0.78 vs left volume: 4.05 cm3 +/- 0.80; P = .004). NAA/Cho was significantly higher in the left temporal lobe of right-handers (right lobe: 1.53 +/- 0.18 vs left lobe: 1.89 +/- 0.18; P=.00004) as was NAA/Cr (right lobe: 1.79 +/- 0.36 vs left lobe: 2.45 +/- 0.45; P=.0001). No statistically significant difference was noted for these ratios in non-right-handers: NAA/Cho (right lobe: 1.49 +/- 0.18 vs left lobe: 1.61 +/- 0.35) and NAA/Cr (right lobe: 1.93 +/- 0.45 vs left lobe: 2.40 +/- 0.70). CONCLUSION: A clear metabolic asymmetry observed in right-handers is less clear-cut in non-right-handers. Both tendencies should be considered when assessing the brain metabolism of patients with uni- or bilateral disorders, such as temporal lobe epilepsy.