Therapeutic drug monitoring of posaconazole in patients with acute myeloid leukemia or myelodysplastic syndrome.

Posaconazole is a broad-spectrum triazole antifungal available as an oral suspension. Pharmacokinetic data showed a high variability of plasma posaconazole concentrations (PPCs) in patients, suggesting a potential interest in drug monitoring. The aim of our prospective study was to measure the PPCs in prophylactically treated patients to evaluate the impact of different factors on these concentrations. In 40 patients treated prophylactically with posaconazole for acute myeloid leukemia or myelodysplastic syndrome between February 2009 and August 2010, PPCs were measured at day 7 of treatment and then twice weekly. Demographic data, clinical data (including gastrointestinal disorders, comedications, and treatment compliance), caloric and fat intake, and biological data were collected and evaluated. We obtained 275 measurements of PPCs, with a median of 430 ng/ml. PPCs were significantly lower in patients with mucositis (P < 0.001), nausea (P = 0.03), diarrhea (P = 0.03), or vomiting (P = 0.05). PPCs were higher in patients with a higher caloric intake (P = 0.02), while the proportion of fat intake had no influence on PPCs (P = 0.84). The concomitant use of proton pump inhibitors decreased the PPCs (P = 0.02), while the use of tacrolimus increased the PPC (P = 0.03). In the multivariate analysis, the factors influencing the PPCs independently were the concomitant use of tacrolimus (P < 0.001), the presence of mucositis (P = 0.01), and food intake (P = 0.02). Our study confirmed the high variability of posaconazole bioavailability and showed the significant influence of gastrointestinal disorders, food intake, and concomitant medication on the PPCs. However, the optimal PPCs still remain to be defined and correlated with clinical efficacy.

Subthalamic nucleus stimulation in Parkinson disease induces apathy: a PET study.

OBJECTIVE: Apathy may be induced by subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease (PD). We therefore wished to test the hypothesis that apathy induced by STN-DBS correlates with changes in glucose metabolism, using (18)FDG-PET. METHODS: Twelve patients with PD were assessed 3 months before (M-3) and 3 months after (M+3) STN-DBS with (18)FDG-PET and the Apathy Evaluation Scale. RESULTS: Apathy had significantly worsened at M+3 after STN-DBS. Positive correlations were observed between this variation in apathy scores and changes in glucose metabolism, especially in the right frontal middle gyrus (Brodmann area [BA] 10) and right inferior frontal gyrus (BA 46 and BA 47). Negative correlations between the two were observed in the right posterior cingulate gyrus (BA 31) and left medial frontal lobe (BA 9). CONCLUSION: These preliminary results confirm the role of the subthalamic nucleus in associative and limbic circuitry in humans and suggest that it is a key basal ganglia structure in motivation circuitry.

Emotion recognition impairment and apathy after subthalamic nucleus stimulation in Parkinson's disease have separate neural substrates.

OBJECTIVE: To test the hypothesis that emotion recognition and apathy share the same functional circuit involving the subthalamic nucleus (STN). METHODS: A consecutive series of 17 patients with advanced Parkinson's disease (PD) was assessed 3 months before (M-3) and 3 months (M+3) after STN deep brain stimulation (DBS). Mean (+/-S.D.) age at surgery was 56.9 (8.7) years. Mean disease duration at surgery was 11.8 (2.6) years. Apathy was measured using the Apathy Evaluation Scale (AES) at both M-3 and M3. Patients were also assessed using a computerised paradigm of facial emotion recognition [Ekman, P., & Friesen, W. V. (1976). Pictures of facial affect. Palo Alto: Consulting Psychologist Press] before and after STN DBS. Prior to this, the Benton Facial Recognition Test was used to check that the ability to perceive faces was intact. RESULTS: Apathy had significantly worsened at M3 (42.5+/-8.9, p=0.006) after STN-DBS, in relation to the preoperative assessment (37.2+/-5.5). There was also a significant reduction in recognition percentages for facial expressions of fear (43.1%+/-22.9 vs. 61.6%+/-21.4, p=0.022) and sadness (52.7%+/-19.1 vs. 67.6%+/-22.8, p=0.031) after STN DBS. However, the postoperative worsening of apathy and emotion recognition impairment were not correlated. CONCLUSIONS: Our results confirm that the STN is involved in both the apathy and emotion recognition networks. However, the absence of any correlation between apathy and emotion recognition impairment suggests that the worsening of apathy following surgery could not be explained by a lack of facial emotion recognition and that its behavioural and cognitive components should therefore also be taken into consideration.

Genetic abortion: considerations for patient care.

Women who receive abnormal prenatal diagnosis results potentially face two emotionally difficult decisions. In this article, the first decision--whether or not to terminate the pregnancy--is presented with a discussion of the factors that may influence a women's choice. Women who choose to terminate the pregnancy face a second decision when more than one type of abortion procedure is available. Two second trimester abortion procedures--dilation and evacuation and labor induction--are compared and contrasted to delineate potential advantages and disadvantages of each. The decision-making process is examined, emphasizing the individual ways in which women may weigh this information to make a fully informed decision. In addition, a number of recommendations are offered to health care providers in the role of discussing options and supporting women in their choices.

A prospective, randomized study of pefloxacin versus teicoplanin in the treatment of gram-positive coccal infections in cancer patients: early termination due to emergence of resistance to fluoroquinolones.

A randomized prospective study comparing pefloxacin to teicoplanin in the treatment of gram-positive infections in cancer patients was prematurely terminated because of the emergence of pefloxacin resistance associated with oxacillin resistance in Staphylococcus aureus and coagulase-negative staphylococci. Among 56 patients evaluated for efficacy (26 pefloxacin and 30 teicoplanin) and infected with bacteria susceptible to both antibiotics, the clinical cure and eradication rates were similar for pefloxacin (80.5% and 77.3% respectively) and teicoplanin (66.6% and 52.2% respectively). The relapse rates (15% and 10% for pefloxacin and teicoplanin respectively) and the overall mortalities within 1 month (42% and 31%) were similar.

[Study of mortality under 30 years of age in families of psychotic patients]. / Etude de la mortalité avant 30 ans dans les familles de psychotiques.

After O. Bourguignon's studies (1984), the authors made the following assumption: there is an higher mortality rate before 30 years in families including at least one psychotic. This assumption is confirmed, as far as brothers, sisters and children are concerned, for 101 psychotics compared to 101 control-subjects. This higher death-rate in young subjects is associated in these psychotics' families with greater psychiatric morbidity, with higher rates of celibacy and break-ups of couples. It is the opinion of the authors that these phenomena should be interpreted as portent of a possible extinction of the lineage.

Ceftazidime combined with mecillinam: serum bactericidal titres compared with in-vitro synergy against gram-negative bacilli.

In a study of the possible interaction between mecillinam and ceftazidime against Gram-negative bacilli, ten volunteers received on separate days: ceftazidime 20 mg/kg iv in 15 min, mecillinam 10 mg/kg iv in 15 min, or the combination. Blood samples were obtained before and 1 and 6 h after the end of the infusion. Ten strains each of Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, Salmonella spp. and Yersinia spp. and nine strains each of Acinetobacter spp., and Pseudomonas aeruginosa were selected. Most of the strains were resistant to ampicillin and cefazolin. Serum levels of ceftazidime and mecillinam were measured by bioassay. Serum bacteriostatic (SBS) and bactericidal (SBA) titration was done in microtitre plates in cation supplemented Mueller-Hinton broth and 50% human serum. Chequerboard titration was also studied to assess in-vitro synergy between ceftazidime and mecillinam in Mueller-Hinton broth with or without 50% serum. The mean serum concentrations (SD) were for mecillinam: 6.1 (1.7) at 1 h, and less than 0.3 at 6 h and for ceftazidime: 36.3 (5.5) at 1 h and less than 5 at 6 h. Identical concentrations were measured for the combination. By chequerboard titration, no synergy occurred for Acinetobacter spp. and Ps. aeruginosa, whereas it was observed in 37/60 (FIC) and 33/60 (FBC) of the strains of other species in Mueller-Hinton; from the strains showing synergy, 28/37 (FIC) and 30/33 (FBC) showed also synergy in Mueller-Hinton with 50% human serum. In SBS and SBA, on the other hand, the combination of mecillinam with ceftazidime showed an additive effect against most Enterobacteriaceae tested, synergy being shown for only 10-35% of tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence and significance of Clostridium difficile in hospitalized cancer patients.

The aim of the study was to assess the incidence and clinical significance of Clostridium difficile in patients in our cancer center. Over a period of seven consecutive months, 557 stools samples obtained from 156 hospitalized cancer patients (37 leukemic patients receiving oral antimicrobial prophylaxis and 119 patients from whom a stool sample was sent to the laboratory) were analyzed for the presence of Clostridium difficile. Clostridium difficile and/or its toxin was recovered from 13 (35%) of the 37 patients receiving oral antimicrobial prophylaxis, and from 15 (12%) of the other 119 patients (p less than 0.05). Isolation of Clostridium difficile was associated with diarrhoea in 13 (46%) of 28 patients but specific treatment was initiated only in 7 (25%) of the 28 patients in whom Clostridium difficile was isolated. The wide distribution of the serotypes identified in our patients does not suggest an epidemic situation in our hospital.

[First relations between mother and child in Algeria]. / Les premières relations entre la mère et l'enfant en milieu algérois.

This is a study of mother-child relationships (from birth to 18 months), using a homogeneous sample of 15 babies born in the same month. Mothers and babies lived in Algiers. The study is based on direct observation, in the family setting, of the behavior of women and children, mother-child interactions and child rearing techniques. It is also based on the analysis of semi-directed interviews (in arabic and french) with the mothers as well as on psychometric tests of the children (the Brunet-Lézine baby-test). The authors highlight the difficulties for the mother and for the child which are a result of the conflict between traditional and western culture.

[Objective and subjective needs of mental patients 1 year after their discharge from a sectorized service]. / Les besoins objectifs et subjectifs des malades mentaux un an après leur sortie d'un service sectorisé.

The present paper is based on a study of 50 non-randomized psychiatric patients who had left the hospital one year before. A semi-structured interview was used to acquire the data. Two types of data have been collected: objective and subjective. Objective data concern the diagnosis, marital status, living conditions, economic situation, educational and professional levels and medical care after hospitalization. As a whole living conditions were found to be very poor. Subjective data concern patients complaints, financial difficulties, their needs and their desire to get in contact with the community health center during hospitalisation. Most patients were in favour of starting after care just prior to discharge. All data are discussed. The most interesting finding is, that despite the many socio-economic hardships, the primary need expressed by the patients is a valuable personal relationship.

[Trial of onager oil in the treatment of schizophrenia in connection with the prostaglandin deficiency hypothesis]. / Essai de l'huile d'onagre dans le traitement de la schizophrénie en rapport avec l'hypothèse d'un déficit en prostaglandine.

Ten schizophrenic patients were treated with onager oil. It was hypothesized that E1 prostaglandin deficiency underlies the different biological disorders of schizophrenia. The clinical and biological results were disappointing. However the fact that the patients had been severely ill for a long time might have to be taken into account. Moreover, the blood level of gamma-linolenic acid was normal, at the start, in all the patients.