International validation of the Bullous Pemphigoid Disease Area Index severity score and calculation of cut-off values for defining mild, moderate and severe types of bullous pemphigoid.

BACKGROUND: The Bullous Pemphigoid Disease Area Index (BPDAI) score has been proposed to provide an objective measure of bullous pemphigoid (BP) activity. OBJECTIVES: The objective of this study was to calculate BPDAI cut-off values defining mild, moderate and severe BP. We also aimed to assess the interrater reliability and correlation with the number of daily new blisters, and anti-BP180 and anti-BP230 antibodies. METHODS: Severity scores were recorded by two blinded investigators. Anti-BP180 and anti-BP230 antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Cut-off values defining mild, moderate and severe subgroups were calculated based on the 25th and 75th percentiles of the BPDAI score. RESULTS: In total, 285 patients with BP were enrolled from 50 dermatology departments in Europe. Median BPDAI activity was 37·5 points (range 0-164). Cut-off values corresponding to the first and third quartiles of the BPDAI score were 20 and 57, respectively; thus, these values were used to define mild (≤ 19), moderate (≥ 20 and ≤ 56) and severe (≥ 57) BP. The median BPDAI score for patients with ≤ 10 daily new blisters was 26 [interquartile range (IQR) 17-45], and for patients with > 10 daily new blisters the median score was 55 (IQR 39-82). The BPDAI intraclass correlation coefficient measured at baseline was 0·97 and remained higher than 0·90 up to month 6. The improvement in the BPDAI score was correlated with the absolute decrease in anti-BP180 ELISA value (Spearman's rank r = 0·34, P < 0·004), but not with anti-BP230 antibodies (r = 0·17, P = 0·15). CONCLUSIONS: This study suggests cut-off values of 20-57 for BPDAI to distinguish mild, moderate and severe BP, and confirms that it is a robust tool to assess BP severity precisely.

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.

Subtraction of subcutaneous fat to improve the prediction of visceral adiposity: exploring a new anthropometric track in overweight and obese youth.

BACKGROUND: The efficiency of traditional anthropometric measurements such as body mass index (BMI) or waist circumference (Waist C) used to replace biomedical imaging for assessing visceral adipose tissue (VAT) is still highly controversial in youth. HYPOTHESIS AND OBJECTIVES: We evaluated the most accurate model predicting VAT in overweight/obese youth, using various anthropometric measurements and their correlation with different body fat compartments, especially by testing, for the first time in youth, the hypothesis that subtracting the anthropometric measurement the most highly correlated with subcutaneous abdominal adipose tissue (SAAT) and less correlated possible with VAT from an anthropometric abdominal measurement highly correlated with visceral and total abdominal adipose tissue (TAAT), predicts VAT with higher accuracy. SUBJECTS AND METHODS: VAT and SAAT data resulted from magnetic resonance imaging (MRI) analysis performed on 181 boys and girls (7-17 y) from Diabetes & Endocrinology Care Paediatrics Clinic in Luxembourg. Height, weight, abdominal diameters, waist, hip, and thigh circumferences were measured with a view to developing the anthropometric VAT predictive algorithms. RESULTS: In girls, subtracting proximal thigh circumference (Proximal Thigh C), the most closely correlated anthropometric measurement with SAAT, from Waist C, the most closely correlated anthropometric measurement with VAT was instrumental in improving VAT prediction, in comparison with the most accurate single VAT anthropometric surrogate. [Formula: see text] Residual analysis showed a negligible estimation error (5 cm2 ). In boys, Waist C was the best VAT predictor. CONCLUSIONS: Subtraction of abdominal subcutaneous fat is important to predict VAT in overweight/obese girls.

Lifestyle counseling in patients with carotid arteriosclerosis from Luxemburg should focus more on the reduction of sugar, sodium and saturated fat consumption.

BACKGROUND: Healthy diet and physical activity improve risk factors for cerebrovascular disease. It is unclear whether patients with carotid artery disease from Luxemburg meet common guideline criteria and whether systematic counseling has a sustained effect. METHODS: We assessed anthropometric data, eating habits and physical activity habits in 53 patients with carotid atherosclerosis at baseline, after 4 and 20 weeks, and advised them five times for 30 min to follow a modified Mediterranean diet and to perform moderate physical exercise at least during 30 min/day. RESULTS: The patients had a mildly increased BMI (mean 27.6, recommended below 25), they already ate enough vegetables and fruits (mean 485 g daily, recommended at least 400 g), they ate too much sugar (mean 74 g daily) and sodium (mean 2710 mg daily, recommended less than 1500), they consumed 13% of calories from saturated fatty acids (recommended less than 10%), and they already moved sufficiently (62 min daily of moderate and intense physical activity, recommended at least 30 min of moderate physical activity). Lifestyle counseling had a sustained effect on weight, reduction of global caloric intake, carbohydrate and cholesterol intake and on an increase in consumption of poly-unsaturated fatty acids, vegetables and fibres. There was no sustained effect on the consumption of sugar, sodium, and saturated fat. CONCLUSIONS: The reduction of sugar, sodium and saturated fat consumption should be stressed more in counselling of this patient group.

Taste preference and psychopathology.

OBJECTIVE: Excessive food intake has been linked to many factors including taste preference and the presence of psychopathology. The purpose of this study was to investigate the association between sweet and salty taste preference and psychopathology in patients with severe obesity. METHODS: A consecutive series of patients applying for bariatric surgery was recruited for the study. Taste preference was self-reported. Psychopathology was assessed using the revised version of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). 190 patients were included in the study. RESULTS: In comparison with patients who had salty taste preference, patients with sweet taste preference had significantly higher elevations on the depression (OD: 4.090, p = 0.010) and the hysteria (OD: 2.951, p = 0.026) clinical scales of the MMPI-2. CONCLUSION: The results suggest the presence of an association between taste preference and psychopathology. The findings may be of interest for clinicians who are involved in the treatment of obesity. In particular, they may wish to pay increased attention to patients with sweet taste preference or who have a strong attraction for both sweet and salty foods, in order to detect psychopathology and to adapt the treatment.

Effect of artesunate and mefloquine in combination on the Fridericia corrected QT intervals in Plasmodium falciparum infected adults from Thailand.

OBJECTIVE: To ascertain whether mefloquine (MQ) produces electrocardiogram (ECG) changes that could be a risk for Torsades de Pointe (TdP), a potentially malignant, ventricular tachyarrhythmia. METHODS: We measured the Fridericia corrected QT (QTcF) intervals on 12 lead ECGs on days (D) 0, 3, 7 in Plasmodium falciparum infected adults, treated with oral artesunate (AS) and MQ as a new fixed dose (n = 25) combination or loose tablets (n = 25) over 3 days. Target total doses were 12 mg/kg of AS and 24-25 mg/kg of MQ. MQ concentrations ([MQ]) were measured by HPLC. RESULTS: All ECG intervals were similar between drug arms and were combined for analysis. Mean QTcF values were 389 (D0), 407 (D3) and 399 (D7) ms (Ps < 0.003 vs. D0); corresponding heart rates and [MQ]s were 83, 67 and 73 beats/minute (Ps ≤ 0.0003 vs. D0) and 0, 3095 and 1721 ng/ml. One male patient (loose arm) had a D3 QTcF 504 ms (D0 406 ms, D7 433 ms). In the modelling of QTcF and JTcF from D0 to D7, significant effects were observed individually for [MQ], temperature and heart rate (HR). The MQ AUC(0-∞) was not a significant factor. Using a manual descending, model building approach to select variables, the HR was the only significant variable (P = 0.001) over time in the model that best explained the changes in the QTcF and JTcF intervals. CONCLUSIONS: In this small group of patients, slowing heart rates due to malaria resolution best explained the observed increases in the QTcF intervals.

New fixed-dose artesunate-mefloquine formulation against multidrug-resistant Plasmodium falciparum in adults: a comparative phase IIb safety and pharmacokinetic study with standard-dose nonfixed artesunate plus mefloquine.

A new fixed-dose artesunate (AS)-mefloquine (MQ) was assessed in adults hospitalized for 28 days with uncomplicated drug-resistant falciparum malaria. The patients (n = 25/arm) were treated with (i) two fixed-dose tablets (AS-MQ arm; 100 mg AS-200 mg MQ/tablet) daily for 3 days (days 0, 1, and 2) or (ii) nonfixed AS (AS-plus-MQ arm; 4 mg/kg of body weight/day for 3 days) plus MQ (15 mg/kg on day 1 and 10 mg/kg on day 2), dosed by weight. Clinical laboratory electrocardiogram (ECG), adverse events (AEs), efficacy, and pharmacokinetic parameters were assessed over 28 days. Both regimens were well tolerated. No AEs were drug related. Two serious AEs of malaria-induced hypotension occurring in the AS-MQ arm necessitated rescue treatment. There were no significant changes in hematology, biochemistry, or PR and QRS intervals. For all patients, mean Fridericia-corrected QT intervals were significantly (P < or = 0.0027) prolonged on day 3 (407 ms) and day 7 (399 ms) versus day 0 (389 ms), in parallel with significant (P < or = 0.0003) falls in heart rates (67 [day 3], 73 [day 7], and 83 [day 0] beats/minute). Fixed-nonfixed formulations were bioequivalent for MQ, but not for AS and dihydroartemisinin (DHA). One AS-MQ patient developed a new infection on day 28; his day 28 plasma MQ concentration was 503.8 ng/ml. Fixed-dose AS-MQ was well tolerated, had pharmacokinetic (PK) profiles broadly similar to those of nonfixed AS plus MQ, and is a suitable replacement.

Is there an optimal sampling time and number of samples for assessing exposure to fast elimination endocrine disruptors with urinary biomarkers?

In studies investigating the effects of endocrine disruptors (ED) such as phthalates, bisphenols and some pesticides on human health, exposure is usually characterized with urinary metabolites. The variability of biomarkers concentration, due to rapid elimination from the body combined with frequent exposure is however pointed out as a major limitation to exposure assessment. This study was conducted to assess variability of urinary metabolites of ED, and to investigate how sampling time and number of samples analyzed impacts exposure assessment. Urine samples were collected over 6 months from 16 volunteers according to a random sampling design, and analyzed for 16 phthalate metabolites, 9 pesticide metabolites and 4 bisphenols. The amount of biomarkers excreted in urine at different times of the day were compared. In parallel, 2 algorithms were developed to investigate the effect of the number of urine samples analyzed per subject on exposure assessment reliability. In the 805 urine samples collected from the participants, all the biomarkers tested were detected, and 18 were present in >90% of the samples. Biomarkers variability was highlighted by the low intraclass correlation coefficients (ICC) ranging from 0.09 to 0.51. Comparing the amount of biomarkers excreted in urine at different time did not allow to identify a preferred moment for urine collection between first day urine, morning, afternoon and evening. Algorithms demonstrated that between 10 (for monobenzyl (MBzP) phthalate) and 31 (for bisphenol S) samples were necessary to correctly classify 87.5% of the subjects into quartiles according to their level of exposure. The results illustrate the high variability of urinary biomarkers of ED over time and the impossibility to reliably classify subjects based on a single urine sample (or a limited number). Results showed that classifying individuals based on urinary biomarkers requires several samples per subject, and this number is highly different for different biomarkers.

Dosing accuracy of artesunate and amodiaquine as treatment for falciparum malaria in Casamance, Senegal.

OBJECTIVES: Several products of artesunate plus amodiaquine (AS + AQ) are being deployed in malaria-endemic countries for treating uncomplicated falciparum malaria but dosing accuracy and consequential effects on efficacy and tolerability have not been examined. METHODS: Patients with parasitologically confirmed, uncomplicated falciparum malaria were treated and followed by research teams or local health centre staff in Casamance, Senegal. AS + AQ was given as: (i) loose combination (AS 50 mg, AQ 200 mg), dosed on body weight, or (ii) co-blistered product (AS 50 mg, AQ 153 mg) dosed by weight or age. Target doses were: (i) AS 4 (2-10) mg/kg/day and (ii) AQ 10 (7.5-15) mg/kg/day. Patients receiving therapeutic doses defined dosing accuracy. Treatment-emergent signs and symptoms (TESS) were recorded. RESULTS: A total of 3277 patients were treated with loose (n = 1972, weight-dosed) or co-blistered (n = 1305, 962 age-dosed, 343 weight-dosed) AS + AQ by the research team (n = 966) or clinic staff (n = 2311). AS was dosed correctly in >99% with all regimens. Loose AQ by weight was 98% correct. The co-blister AQ overdosed 18% of patients when dosed by age and underdosed 13% by weight. Low weight was an independent risk factor for overdosing. The co-blister had significantly more TESS than the loose product [117/1305 (9%) vs. 41/1972 (2%), relative risk = 4.3 (95% CI: 3.0-6.1, P < 0.0001)]. Age-based dosing accounted for the difference. TESS occurred mostly within one day (72%) and were mild or moderate (75%). CONCLUSION: Artesunate is easier to dose than AQ. Currently available age-dosed, co-blistered AS + AQ tends to overdose AQ and is less well tolerated than loose tablets. It is not the optimal presentation of AS + AQ.

Slow wave sleep and dopaminergic treatment in Parkinson's disease: a polysomnographic study.

BACKGROUND: In Parkinson's disease (PD), there is entanglement of disease-inherent and treatment-induced sleep abnormalities. So far, there has been no study specifically investigating the influence of diurnal dopaminergic medication (DM) on nocturnal slow wave sleep (SWS). METHODS: Polysomnographic analysis in 62 PD patients. RESULTS: PD patients had a sleep efficiency of 70 +/- 17% and an SWS amount of 16 +/- 11%. Linear regression analysis showed no significant correlation between the amounts of SWS and DM. However, patients with a medium DM dosage (300-600 mg of levodopa equivalents) preserved a SWS percentage >25% (p = 0.035, chi(2) test) more frequently than patients with higher or smaller DM. The DM dosage had no effect on other main sleep parameters. Psychotropic comedication had no effect on SWS percentage. In contrast, SWS amount was inversely correlated with both disease duration and age. It was independent of rapid eye movement sleep amount. The natural female bonus effect on SWS amount was absent in women with PD. CONCLUSION: Diurnal dopaminergic treatment has no major impact on SWS in PD, which, however, decreases with disease duration. Disease-dependent, but treatment-independent decrease in SWS suggests primary degeneration of sleep-regulating systems in PD.

Two distinct mechanisms control the accumulation of cyclin B1 and Mos in Xenopus oocytes in response to progesterone.

Progesterone-induced meiotic maturation of Xenopus oocytes requires the synthesis of new proteins, such as Mos and cyclin B. Synthesis of Mos is thought to be necessary and sufficient for meiotic maturation; however, it has recently been proposed that newly synthesized proteins binding to p34(cdc2) could be involved in a signaling pathway that triggers the activation of maturation-promoting factor. We focused our attention on cyclin B proteins because they are synthesized in response to progesterone, they bind to p34(cdc2), and their microinjection into resting oocytes induces meiotic maturation. We investigated cyclin B accumulation in response to progesterone in the absence of maturation-promoting factor-induced feedback. We report here that the cdk inhibitor p21(cip1), when microinjected into immature Xenopus oocytes, blocks germinal vesicle breakdown induced by progesterone, by maturation-promoting factor transfer, or by injection of okadaic acid. After microinjection of p21(cip1), progesterone fails to induce the activation of MAPK or p34(cdc2), and Mos does not accumulate. In contrast, the level of cyclin B1 increases normally in a manner dependent on down-regulation of cAMP-dependent protein kinase but independent of cap-ribose methylation of mRNA.

[Quality of life of patients with total cavopulmonary anastomosis]. / Qualité de vie des patients avec une dérivation cavo-pulmonaire totale.

INTRODUCTION: Total cavo-pulmonary connection (TCPC) represents the current surgery standard for congenital univentricular heart disease (CUHD) patients. We studied the health related quality of life (HRQOL) expressed by TCPC operated patients. PATIENTS AND METHODS: This transversal study is based on 24 children and 10 adult TCPC patients aged from 5 to 41 years old. The HRQOL evaluation relies on generic self report instruments such as the PedsQL 4.0 for the children and their parents, and the Duke Health profile for the adult patients. Additional questions were specifically designed for this study as well. RESULTS AND DISCUSSION: The estimated HRQOL is 68.15 for the children and 68.71 for their parents. In these young cases, the global HRQOL or some specific score are altered when any comorbidity or scholar difficulties are present, or when TCPC was performed more than 10 years ago. The estimated HRQOL is 74.67 in adulthood. In these patients, the young age, the lifestyle, the onset of more than 2 early complications ans the necessity of anti-arrhythmia therapy decrease various HRQOL scores. The physical handicap is considered as the major limitation for children and adult patients. Thanks to adaptative and cognitive compensatory mechanisms, such as resilience, both groups express a satisfying HRQOL assessment. CONCLUSION: Our study indicates that TCPC provides a good HRQOL in CUHD patients despite the complex management and follow-up of these diseases, the risk of complication onset and the physical handicap usually observed.

[Heart murmurs in asymptomatic children: When should you refer?]. / Souffle cardiaque chez l'enfant asymptomatique : quand demander un avis cardiologique ?

Heart murmurs are common in children and adolescents. Although most are innocent, an isolated heart murmur in asymptomatic children may be the sole finding indicating serious heart disease. Historical elements of familial heart disease, cardiovascular symptoms and a well-conducted medical examination can identify children with an increased risk of heart disease. The distinction between an innocent heart murmur and a pathologic heart murmur is not always easy for primary care physicians because most of them have little experience with auscultation searching for congenital heart malformation. Echocardiography provides a definitive diagnosis of heart disease but is not required in case of innocent murmur. Inappropriate pediatric cardiologist and echocardiographic referral leads to useless and expensive examinations, resulting in a work overload for pediatric cardiologists. The objective of this review is to provide the keys to differentiate innocent and pathologic murmurs, and to help physicians decide on the optimal diagnostic strategy.

Comparison of passive-beam proton therapy, helical tomotherapy and 3D conformal radiation therapy in Hodgkin's lymphoma female patients receiving involved-field or involved site radiation therapy.

PURPOSE: Second cancers and cardiovascular toxicities are long term radiation toxicity in locally advanced Hodgkin's lymphomas. In this study, we evaluate the potential reduction of dose to normal tissue with helical tomotherapy and proton therapy for Hodgkin's lymphoma involved-field or involved-site irradiation compared to standard 3D conformal radiation therapy. PATIENTS AND METHODS: Fourteen female patients with supradiaphragmatic Hodgkin's lymphoma were treated at our institution with 3D conformal radiation therapy or helical tomotherapy to a dose of 30Gy in 15 fractions. A planning comparison was achieved including proton therapy with anterior/posterior passive scattered beams weighted 20Gy/10Gy. RESULTS: Mean doses to breasts, lung tissue and heart with proton therapy were significantly lower compared to helical tomotherapy and to 3D conformal radiation therapy. Helical tomotherapy assured the best protection of lungs from doses above 15Gy with the V20Gy equal to 16.4%, compared to 19.7% for proton therapy (P=0.01) or 22.4% with 3D conformal radiation therapy (P<0.01). Volumes of lung receiving doses below 15Gy were significantly larger for helical tomotherapy than for proton therapy or 3D conformal radiation therapy, with respective lung doses V10Gy=37.2%, 24.6% and 27.4%. Also, in the domain of low doses, the volumes of breast that received more than 10Gy or more than 4Gy with helical tomotherapy were double the corresponding volumes for proton therapy, with V4Gy representing more than a third of one breast volume with helical tomotherapy. CONCLUSIONS: Helical tomotherapy achieved a better protection to the lungs for doses above 15Gy than passive proton therapy or 3D conformal radiation therapy. However, dose distributions could generally be improved by using protons even with our current passive-beam technology, especially allowing less low dose spreading and better breast tissue sparing, which is an important factor to consider when treating Hodgkin's lymphomas in female patients. Prospective clinical study is needed to evaluate the tolerance and confirm these findings.

Self-defined residential neighbourhoods: size variations and correlates across five European urban regions.

The neighbourhood is recognized as an important unit of analysis in research on the relation between obesogenic environments and development of obesity. One important challenge is to define the limits of the residential neighbourhood, as perceived by study participants themselves, in order to improve our understanding of the interaction between contextual features and patterns of obesity. An innovative tool was developed in the framework of the SPOTLIGHT project to identify the boundaries of neighbourhoods as defined by participants in five European urban regions. The aims of this study were (i) to describe self-defined neighbourhood (size and overlap with predefined residential area) according to the characteristics of the sampling administrative neighbourhoods (residential density and socioeconomic status) within the five study regions and (ii) to determine which individual or/and environmental factors are associated with variations in size of self-defined neighbourhoods. Self-defined neighbourhood size varies according to both individual factors (age, educational level, length of residence and attachment to neighbourhood) and contextual factors. These findings have consequences for how residential neighbourhoods are defined and operationalized and can inform how self-defined neighbourhoods may be used in research on associations between contextual characteristics and health outcomes such as obesity.

Membrane-anchored cyclin A2 triggers Cdc2 activation in Xenopus oocyte.

In Xenopus oocyte, the formation of complexes between neosynthesized cyclins and Cdc2 contributes to Cdc2 kinase activation that triggers meiotic divisions. It has been proposed that cytoplasmic membranes could be involved in this process. To investigate this possibility, we have injected in the oocyte two undegradable human cyclin A2 mutants anchored to the endoplasmic reticulum (ER) membrane. They encode fusion proteins between the truncated cyclin A2-Delta152 and a viral or cellular ER-targeting domain. We show that both mutants are fully functional as mitotic cyclins when expressed in Xenopus oocytes, bind Cdc2 and activate M-phase promoting factor.

Immune responses against Plasmodium falciparum asexual blood-stage antigens and disease susceptibility in Gabonese and Cameroonian children.

The frequency and level of cellular and humoral responses to seven synthetic peptides from asexual blood stages of Plasmodium falciparum were measured in two cohorts of children living in areas highly endemic for malaria in Gabon and Cameroon. A prospective longitudinal study was conducted for one year in these sites to examine the relationship between specific in vitro immune responses and susceptibility to clinical malaria. Clinical protection was related to high proliferative responses (merozoite surface antigen-1 [MSA-1] and MSA-2 peptides) as well as to elevated antibody levels (schizont extract, MSA-2, and rhoptry-associated protein-1 [RAP-1] peptides) in the village of Dienga, Gabon. Higher response rates of interferon-gamma but lower response rates of tumor necrosis factor-alpha to four and six peptides, respectively, were observed in Dienga than in Pouma that were independent of the older age of the Gabonese children. Age accounted only for the higher prevalence rate in Dienga of the antibody responders to the peptide from Pf155/ring-infected erythrocyte surface antigen (RESA). Our results support the inclusion of epitopes from MSA-1, MSA-2, RAP-1, and Pf155/RESA antigens in a subunit vaccine against malaria, but show that a longitudinal clinical, parasitologic, and immunologic study conducted according to identical criteria in two separate areas may lead to contrasting observations, demonstrating the geographic limitation of the interpretation of such results.

Relationship between entomological inoculation rate, Plasmodium falciparum prevalence rate, and incidence of malaria attack in rural Gabon.

To assess the relationships between variations of Plasmodium falciparum transmission and those of peripheral parasitaemia prevalence or malaria attack incidence rates in regions with limited fluctuations of transmission, we conducted a follow-up in two Gabonese populations. Entomological surveys were carried out from May 1995 to April 1996 in Dienga, and from May 1998 to April 1999 in Benguia. In Dienga, malaria transmission was seasonal, being not detected during two 3-month periods. Mean entomological inoculation rate (EIR) was 0.28 infective bite/person/night. In Benguia, malaria transmission was perennial with seasonal fluctuations, mean EIR being 0.76 infective bite/person/night. In Dienga, 301 schoolchildren were followed from October 1995 to March 1996. Clinical malaria attack was defined as fever associated with >5000 parasites/microl of blood. P. falciparum prevalence varied from 28 to 42%, and monthly malaria attack incidence from 30 to 169 per thousand. In Benguia, the entire population (122 persons) was followed from November 1998 to April 1999. Prevalence varied from 22 to 50%, and monthly malaria attack incidence from 52 to 179 per thousand. In each area, entomological variations were not related to parasite prevalence, but preceded malaria attack incidence with 1- or 2-month time lag, corresponding to the pre-patency period that differs in the two populations, possibly according to differences in immunity related to parasite transmission.

Measuring the variability of prescription use in patients with HIV infection or AIDS. The contribution of a French hospital longitudinal database.

This study is based on a sample of 937 patients with HIV infection or AIDS who were treated in 5 French hospitals. It sets out to describe the prescription of antiretroviral and prophylactic drugs used in treating such patients and, aims to interpret the various treatment strategies used. The study showed the contribution of longitudinal data in the descriptive analysis of patient follow-up, given the evolving nature of the illness. The Principal Components Analysis method allowed the temporal and quantitative aspects of the data, as well as their combination with qualitative variables, to be taken into account. The results revealed the stability over time of the choice of prescriptions, and allowed joint prescription/substitution phenomena between drugs to be evaluated. At the same time, the study provided evidence for a "site' effect, which showed that the heterogeneity of professional practice is not solely the result of differences in patients or in severity of the illness.

Instillation rate effects of Exosurf on cerebral and cardiovascular haemodynamics in preterm neonates.

The acute effects of surfactant instillation rate on the cerebral and cardiovascular haemodynamics were studied in a randomised trial of 27 preterm neonates with respiratory distress syndrome (RDS). Cerebral blood flow velocity (CBFV), mean arterial blood pressure (MABP), blood gases and electroencephalogram (EEG) were continuously recorded before, during, and for at least 10 minutes after the administration of surfactant. The measurements were repeated one, three, and six hours later. Left ventricular output (LVO) and ductal patency were assessed 10 minutes before and then one, three, and six hours after surfactant administration. Surfactant (Exosurf) was instilled rapidly over five minutes in 13 infants and slowly over 15 minutes in 14 infants. The rapid group showed a significant but transient increase (mean 38%) in CBFV, a rise strongly related to an increase in carbon dioxide tension. No significant change in CBFV was observed in the slow group. There were no significant changes in EEG, MABP, LVO, or ductal shunting in either group. The findings suggest that rapid instillation of Exosurf leads to an increase in CBFV and partial carbon dioxide pressure (PCO2) and requires a close monitoring of blood gases to maintain adequate ventilation. Furthermore, the findings should alert clinicians to the need for slow infusion of Exosurf.