Geneviève Chamba

Quality of asthma care: results from a community pharmacy based survey

Background:  Optimal control is a major objective of disease management of asthma. The aim of the present study was to provide descriptive data on disease management in asthma patients, including medical resource utilization.

Missense mutation in exon 11 (codon 378) of the presenilin-1 gene in a French family with early-onset Alzheimer's disease and transmission study by mismatch enhanced allele specific amplification

Mutations in the presenilin‐1 (PS1) gene account for the majority of familial early‐onset Alzheimers disease (EOAD) cases. We screened the coding part of the PS1 gene for the presence of mutations in a French family with EOAD, using single strand conformation polymorphism (SSCP) analysis. Patients in the pedigree showed a missense mutation in exon 11 of the PS1 gene involving a transition of G to A, altering glycine to glutamate at codon 378. The cosegregation of the mutation with EOAD in the family was studied by allele specific amplification, enhanced by the introduction of a mismatch at the penultimate position near the 3′ primer end. The mutation has not been described before and is located within the third large cytoplasmic loop and may lead to the appearance of a short additional a‐helix. Hum Mutat 11:481, 1998.

Comparative Microdistribution of the Activity of Catecholamine‐Synthesizing Enzymes in Horizontal Sections of the Rat Lower Brainstem

Abstract: The activities of the three major catecholamine‐synthesizing enzymes were determined in brain tissue pellets dissected from 500‐μm thick horizontal sections of rat lower brainstem. The rostrocaudal distributions of the three enzymatic activities were generally not parallel, suggesting differences in the respective localization of the noradrenergic and adrenergic neurons. The difference was most important in the A2‐C2 region where the maximal activity of phenylethanolarnine‐N‐methyltransferase (EC 2.1.1.28) was located 1.5 mm more rostrally than the maximal activities of the tyrosine hydroxylase (EC 1.14.16.2) and dopamine β‐hydroxylase (EC 1.14.17.1). This result indicates that a more specific dissection of the adrenergic and noradrenergic neurons could be performed in the A2‐C2 area of the rat brainstem.

Biological parameters in major depression: effects of paroxetine, viloxazine, moclobemide, and electroconvulsive therapy. Relation to early clinical outcome

BACKGROUND Clinical and pharmacologic studies report a relative or absolute serotonergic deficiency in major depression; however, the variability of clinical characteristics of illness has led to controversial results. In the present work, we looked for a possible relationship between i) biochemical values that indirectly reflect aminergic neurons activity and clinical characteristics and ii) their evolution and the early clinical outcome under antidepressive therapies (ATs). METHODS Platelet serotonin content, platelet monoamine oxydase activity, and urinary biopterins were measured in 27 depressed patients before and during four different ATs (paroxetine, viloxazine, moclobemide, or electroconvulsive therapy). Depressive symptomatology and its evolution under ATs were quantified using three clinical rating scales. RESULTS A severe symptomatology, high serotonin (5-HT) platelet content, and high or low urinary B could represent risk factors leading to a smaller or delayed response to an AT. Furthermore, the early improvement under ATs was negatively correlated to pretreatment 5-HT platelet content. CONCLUSIONS Determination of 5-HT level could be useful in the choice of an AT.

Relative exposure to controller therapy and asthma exacerbations: a validation study in community pharmacies

“Controllers‐to‐total asthma drug” ratios computed from claims data identify asthmatics at risk of exacerbations. Direct link of ratios to data obtained from patients, such as control and recent outcomes, would facilitate their interpretation. We studied the relationship between R1 ratio (inhaled corticosteroids (ICS)/total anti‐asthma drug ratio) and the Asthma Control Test. Comparisons were also conducted for secondary outcomes (asthma‐related hospital contacts, monthly medical contacts, use of oral corticosteroids, and perception of disease burden). Results with R1 ratio were compared with those obtained with a second ratio, “ICS‐plus‐leukotriene receptor antagonist/total asthma drug” (R2 = ICS + leukotriene receptor antagonist/total anti‐asthma drugs).

Changes in tyrosine hydroxylase and dopamine-beta-hydroxylase activities but not in phenylethanolamine-N-methyltransferase activity within central adrenaline neurons after 6-hydroxydopamine administration

By using a new microdissection procedure allowing the noradrenaline (NA) and adrenaline (A) cell groups of the A2-C2 region to be sampled preferentially, it was possible to study the biochemical response of these two neuronal populations after 6-hydroxydopamine (6-OHDA) administration. Five days after an intraventricular 6-OHDA injection, tyrosine hydroxylase (TH) activity increased (+104%, P less than 0.01) in the adrenergic C2 region, in the locus coeruleus (LC) and in the A1-C1 region, while the NA A2 region exhibited no significant increase. Twenty-one days after 6-OHDA administration, dopamine-beta-hydroxylase (DBH) activity had decreased in both the noradrenergic regions (LC, A1-C1 and A2 regions) and in the C2 adrenergic region. Conversely, phenylethanolamine-N-methyltransferase (PNMT) activity was not modified either in the cell bodies or in the terminals located in the tractus intermediolateralis of the spinal cord and in the hypothalamic nuclei. These data suggest: (i) that adrenaline-containing neurons could be sensitive to the neurotoxic action of 6-OHDA since they exhibit changes in TH and DBH activities; and (ii) that the determination of PNMT activity may not be sensitive enough to estimate the functional integrity of the A cell bodies or terminals.

Increased tyrosine hydroxylase activity in central adrenaline neurons after reserpine treatment

By using preferential microdissection of the adrenaline (A) and noradrenaline (NA) neurons within the A2-C2 region of the rat medulla oblongata, it was possible to study the biochemical response of these two neuronal populations to reserpine administration. Three days after reserpine injections (10 mg/kg s.c., per day for 3 days), tyrosine hydroxylase (TH) activity was increased in the adrenergic C2 region whilst no change was observed in the noradrenergic A2 region. The response of the A neurons to reserpine was of lesser magnitude than the increase in TH activity observed under the same conditions in the NA neurons of the locus coeruleus and of the A5 region, and was likely to have originated in the A cell bodies. In contrast with previous studies, this work suggests that the A-containing neurons are responsive to reserpine administration, despite the lack of change in phenylethanolamine-N-methyltransferase activity.

Factors influencing dispensing of psychotropic medications to patients with asthma: a community pharmacy-based survey.

BACKGROUND To our knowledge, the use of psychotropic medications (antidepressant, anxiolytic, and hypnotic agents) in patients with asthma has not been extensively explored. OBJECTIVE To identify factors associated with the use of these medications in patients with asthma. METHODS Regular customers (aged 18-50 years) of 348 pharmacies in 9 French regions were consecutively recruited from November 2003 to June 2004. Patients with a prescription for an asthma medication were included. Patients completed a questionnaire, complemented by the computerized records of their therapy dispensed in the past 12 months. Asthma control was measured with the Asthma Control Test. RESULTS Among 886 patients (mean age, 37.4 years; 55.0% female), during the 12 months before the survey, the proportions who received at least 1 U of anxiolytic, antidepressant, and hypnotic agents were 25.6%, 13.7%, and 13.0%, respectively. Higher dispensing levels of antidepressant, anxiolytic, and hypnotic agents were observed with decreasing asthma control (P < .001 for each drug class). Other correlates of receiving any of these classes included older age, female sex, smoking status, and dispensing of antireflux treatment (P < .001 for all). These results were confirmed in multivariate analyses. CONCLUSIONS Psychotropic drugs were commonly dispensed to patients with asthma, and correlates of receiving these drugs were identified in this population. The high use of psychotropic medication, particularly in patients with poorly controlled asthma, is of concern.

Biochemical evidence that brainstem adrenaline-containing neurons are activated during clonidine withdrawal in the spontaneously hypertensive rat.

SummaryWe have investigated the effects of prolonged treatment with clonidine (delivered intravenously via osmotic minipumps, 0.1 mg/kg/day for 7 or 10 days) and of withdrawal of such treatment on brainstem noradrenaline and adrenaline metabolism in the adult spontaneously hypertensive rat (SHR). After a seven day treatment with clonidine, noradrenaline and adrenaline turnovers were unchanged both in the A2-C2 and A1-C1 regions. During withdrawal, the noradrenaline turnover was also unchanged in these regions. However, the adrenaline turnover was significantly increased 16 h after withdrawal (p < 0.01) in the A2-C2 region and 16 h (p < 0.01) and 40 h (p < 0.05) after withdrawal in the A1-C1 region. These results show that noradrenaline metabolism is unchanged both during clonidine treatment and during its withdrawal in the brainstem catecholaminergic regions analyzed. In contrast, the increases in adrenaline turnover found in the A2-C2 and A1-C1 regions suggest that the adrenergic neurons of the brainstem could be activated during clonidine withdrawal. As the adrenergic CI neurons are a key element of the sympathetic vasopressor system, the increase in adrenaline turnover observed during withdrawal could be at the origin of the sympathetic hyperactivity found after cessation of prolonged treatment with clonidine.

Prise en charge de la migraine: enquête en pharmacie

AIM To describe the characteristics and the management of migraine. METHOD Data on headaches, drug consumption and life habits of 762 patients were collected using questionnaires and pharmacy records. RESULTS The migraine attack was characterized by a severe pain for more than 80% of the patients. The frequency was more than 2 attacks a week in 16% of the cases. Eighty four per cent of the patients had triptans and 45% had a long-term migraine treatment. Nonspecific analgesics were prescribed for 55%. The frequency of over-consumption of treatments of migraine attacks was 46%. CONCLUSION The management of migraine still remains inadequate. The pharmacist could contribute to its improvement.