Unusual presentation for small lymphocytic lymphoma: Case report of a man with bilateral ear involvement and review of the literature.

INTRODUCTION: Ear involvement by non-Hodgkin lymphoma is quite rare and can be mistaken for other common lesions encountered in otolaryngology. The literature on this subject is also limited. CASE SUMMARY: A 45-year-old man with bilateral ear nodules that progressed over two years. Biopsy of the right ear revealed a B-cell small lymphocytic lymphoma (SLL). The patient responded to radiotherapy well. He received an additional dose two months after the initial treatment because of a remaining nodularity on the right earlobe. After several months, he presented a new lesion on his nasal tip, for which a biopsy confirmed a lymphoma relapse. The patient was managed with oral prednisone and low-dose radiation with a favourable response. DISCUSSION: This case highlights the importance of including lymphoma in the differential diagnosis of ear lesions from an otolaryngology perspective. A biopsy of any lesion or nodule with an atypical course should be considered for appropriate diagnosis and management.

Prevalence of lung function impairment in cured pulmonary tuberculosis patients in Cotonou, Benin.

SETTING: National teaching hospital for the management of respiratory diseases, Cotonou, Benin. OBJECTIVE: 1) To estimate the prevalence of lung function impairment (LFI) and associated factors in patients cured of pulmonary tuberculosis (PTB); and 2) to determine the link between human immunodeficiency virus (HIV) infection and LFI occurrence. DESIGN: We performed a cross-sectional study in cured patients with smear-positive TB (PTB+) treated between 2012 and 2015. We recruited two control groups of 70 HIV-infected (HIV+/TB-) and 70 HIV-negative participants without TB (HIV-/TB-). We performed spirometry in all participants to identify LFI (obstructive, restrictive or mixed) and the 6-min walk test (6-MWT) in PTB+ participants. We assessed the factors associated with LFI using logistic regression. RESULTS: Of 4711 subjects with PTB, 241 were contacted and 189 were included. The median age was 37 years; 128 (68.0%) were male. Overall, 85 cured PTB+ patients had LFI (45.0%). Extent of initial radiological lesions, time between symptom onset and treatment, and female sex were independently associated with LFI. Fifty-five (29.1%) cured PTB+ patients had an abnormal 6-MWT; those with LFI had a higher risk of poor exercise tolerance (OR 2.23; interquartile range 1.16-4.30). We did not find any association between HIV infection and LFI. CONCLUSION: LFI is very common in cured PTB+ patients from Benin and significantly impacts exercise tolerance.

Describing and expanding the clinical phenotype of anti-MDA5-associated rapidly progressive interstitial lung disease: case series of nine Canadian patients and literature review.

OBJECTIVE: To describe and expand the phenotype of anti-MDA5-associated rapidly progressive interstitial lung disease (MDA5-RPILD) in Canadian patients. METHOD: All proven cases of MDA5-RPILD hospitalized in the University of Montreal's affiliated centres from 2004 to 2015 were selected for inclusion. RESULTS: Of nine consecutive patients, RPILD was the presenting manifestation in seven, whereas two patients developed RPILD 2 years after the onset of arthritis and of chronic interstitial lung disease. In the case with arthritis, RPILD was probably triggered by initiation of tumour necrosis factor-α-inhibitor therapy. In most patients (89%), RPILD was accompanied by concomitant onset of palmar/lateral finger papules, skin ulcerations, and/or mechanic's hands. All patients experienced profound weight loss over 1-2 months (mean ± SD 10.2 ± 4.8 kg). All had arthralgias and/or arthritis. Six patients were clinically amyopathic; only one patient had creatine kinase (CK) levels > 500 U/L. Initial ferritin and transaminase levels were elevated in 86% and 67% of patients, respectively. The antinuclear antibody (ANA) test was negative for nuclear and cytoplasmic staining; antisynthetase autoantibodies were negative. Three patients died; time from initial symptoms to death ranged from 7 to 15 weeks. All six survivors received mycophenolate mofetil and/or tacrolimus as part of induction and/or maintenance therapy. CONCLUSION: In an inpatient setting, RPILD associated with characteristic skin rashes, profound weight loss, articular symptoms, normal or low CK with elevated ferritin, and absent fluorescence on ANA testing should alert the clinician to the possibility of MDA5-RPILD. T-cell-mediated therapies may play a role in this highly lethal condition.

Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation.

The frequency of poor outcomes in relapsed leukemia patients underscores the need for novel therapeutic approaches. The Food and Drug Administration-approved immunosuppressant FTY720 limits leukemia progression by activating protein phosphatase 2A and restricting nutrient access. Unfortunately, FTY720 cannot be re-purposed for use in cancer patients due to on-target toxicity associated with S1P receptor activation at the elevated, anti-neoplastic dose. Here we show that the constrained azacyclic FTY720 analog SH-RF-177 lacks S1P receptor activity but maintains anti-leukemic activity in vitro and in vivo. SH-RF-177 was not only more potent than FTY720, but killed via a distinct mechanism. Phosphorylation is dispensable for FTY720's anti-leukemic actions. However, chemical biology and genetic approaches demonstrated that the sphingosine kinase 2 (SPHK2)-mediated phosphorylation of SH-RF-177 led to engagement of a pro-apoptotic target and increased potency. The cytotoxicity of membrane-permeant FTY720 phosphonate esters suggests that the enhanced potency of SH-RF-177 stems from its more efficient phosphorylation. The tight inverse correlation between SH-RF-177 IC50 and SPHK2 mRNA expression suggests a useful biomarker for SH-RF-177 sensitivity. In summary, these studies indicate that FTY720 analogs that are efficiently phosphorylated but fail to activate S1P receptors may be superior anti-leukemic agents compared to compounds that avoid cardiotoxicity by eliminating phosphorylation.

Respiratory effects in children from passive smoking of cigarettes and narghile: ISAAC Phase Three in Syria.

BACKGROUND: The association between environmental tobacco smoke (ETS) and asthma symptoms is well documented, but a causal relationship is inconclusive. International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three was the first to report a dose-response relationship between current wheezing and exposure to parental cigarette smoke. As exposure of children to water pipe (narghile) smoke is of concern in Syria, in the ISAAC Phase Three Tartous Centre we also examined the role of parental smoking of the narghile. METHODS: Parents of children aged 6-7 years completed core written questionnaires about the prevalence of symptoms, and an environmental questionnaire for other risk factors, including parental cigarette smoking. We added questions about narghile to the questionnaire. RESULTS: Among 2 734 pupils (49% females) surveyed, we found an association between exposure to ETS of the mother smoking cigarette or narghile and ever wheezing, nocturnal cough and severe wheeze; however, the strongest association was found when the mother smoked narghile. Mother smoking narghile was also associated with exercise wheeze. Father smoking narghile, but not cigarettes, was associated with nocturnal cough, severe wheeze and exercise wheeze. The association with current wheeze became significant when mother smoked both cigarettes and narghile; however, the effect was addititive and not synergic. CONCLUSION: We recommend that international studies investigating ETS include questions on narghile smoking.

The French-Canadian validation of a disease-specific, patient-reported outcome measure for lupus.

OBJECTIVES: The objective of this paper is to perform the cross-cultural validation of the French version of the LupusPRO, a disease-targeted patient-reported outcome measure, among systemic lupus erythematosus (SLE) patients in Canada. METHODS: The French version of the LupusPRO and the MOS SF-36 were administered; demographic, clinical and serological characteristics were obtained. Disease activity (SELENA-SLEDAI and the Lupus Foundation of America definition of flare) and damage (SLICC/ACR SDI) were assessed. Physician disease activity and damage assessments were ascertained using visual analog scales. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent and discriminant validity (against corresponding domains of the SF-36), criterion validity (against disease activity, damage or health status) and known group validity were tested. RESULTS: A total of 99 French-Canadian SLE patients participated (97% women, mean (SD) age 45.2 (14.5) years). The median (IQR) SELENA-SLEDAI and SDI were 3.5 (6.0) and 1.0 (2.0), respectively. The ICR of the LupusPRO domains ranged from 0.81 to 0.93 (except for lupus symptoms, procreation and coping), while TRT ranged from 0.72 to 0.95. Convergent and discriminant validity, criterion validity and known group validity against disease activity, damage and health status measures were observed. Confirmatory factor analysis showed a good fit. CONCLUSION: The LupusPRO has fair psychometric properties among French-Canadian patients with SLE.

The effect of diabetic neuropathy on foot bones: a systematic review and meta-analysis.

AIMS: It is proposed that diabetic neuropathy may affect peripheral bone. Direct innervation of bone as well as neural control over its vascular supply and muscular influences may be affected by diabetes-induced peripheral neuropathies. Associated changes to bone may contribute to the occurrence of foot bone pathology in this population. This systematic review aims to examine the literature related to the effect of diabetic neuropathy on foot bones. METHODS: Studies examining relationships between neuropathy and indicators of bone health (e.g. bone mineral density) in populations with diabetes were sought. Relevant publications were obtained from searches in MEDLINE, CINAHL and Embase in the period up to March 2013. Meta-analysis was performed using a random effects model in the statistical package Stata version 12.1. RESULTS: Ten studies met the inclusion criteria and were included in the narrative synthesis. All studies were cross-sectional or case-control in design. Four of the 10 included studies found results indicating poorer bone health in those with diabetes and neuropathy compared with those with diabetes without neuropathy. Seven of the 10 studies were able to be included in a meta-analysis. The mean pooled effect was -0.36 (95% CI -0.76 to 0.04; P = 0.08), indicating a non-significant trend towards poorer bone health in those with diabetic neuropathy. CONCLUSIONS: We did not find a significant relationship between presence of neuropathy in those with diabetes and poorer peripheral bone health. However, methodological limitations of the included studies mean further research is required to investigate this theoretical relationship.

Dyspnea: a strong independent factor for long-term mortality in the elderly.

OBJECTIVE: To determine the association between dyspnea at entry into the PAQUID cohort and 13-year mortality, taking into consideration BMI and other mortality-related factors. DESIGN: Longitudinal study. SETTING: In Dordogne and Gironde, South Western France. SUBJECTS: A total of 3646 French community dwellers aged 65 years old and over from the PAQUID study were included. MAIN OUTCOME MEASURES: dyspnea measured on 5-grades scale, mortality measured over 13 years of follow-up. Adjustment variables: age, gender, BMI (kg/m²), antecedent of ischemic heart disease, antecedent of stroke, hypertension, smoking history and diabetes. RESULTS: The study sample included 3646 subjects out of whom 54.11% died at 13 years of follow-up, 57.3% of participants were women and mean age was 75.3 (SD 6.8) years. Univariate analysis showed that dyspnea was associated with 13-year mortality. Death occurred in 45.6% of non-dyspneic subjects , 51.8% in those with level 1 of dyspnea, 65.6% in level 2 and 80.6% in level 3 and 4 (P<10⁻4). The median survival was at 13.26 (SD 0.20) years for level-0 of dyspnea, 12.33 (SD 0.31) years for level-1 of dyspnea, 9.28 (SD 0.44) years for level-2 and 6.43 (SD 0.45) years for level-3 and 4 (P=10⁻³). In the multivariate analysis, the risk of mortality for level1 compared to level-0 was HR=1.13 (CI95%=[1.01-1.26]); this risk increases to HR=1.42 (CI95%=[1.25-1.63]) for level-2 and to HR=1.90 (CI95%=[1.61-2.25]) for level-3 and 4. CONCLUSION: These findings suggest that the relationship between long-term mortality and dyspnea is strong, consistent and independent of other covariates in the elderly.

Characterization of a changing relationship between milk production and liveweight for dairy goats undergoing extended lactation.

This study aimed to characterize the time-profile of extended lactation (EL) for dairy goats, and the relationships between milk production, liveweight, and intake that are associated with this profile. For this, 20 nonpregnant multiparous dairy goats were monitored daily for about 90 d from the onset of EL [i.e., when an increase in milk yield (MY) was observed]. These 20 individual profiles were pooled to create a group average profile at the onset of EL for the purpose of parameterizing a simple compartmental model. Moreover, 9 of the 20 EL goats were kept to compare their 24-mo profiles of body weight and milk production with those observed during 2 successive normal lactations (NL). Despite being kept in the same environment and on the same feed, a clear change from decreasing to increasing MY was identified (time of change, Tchange) for all of the 20 EL goats around 330 d in milk. During the whole 24-mo period, EL goats produced as much milk as NL goats but this total milk production was unequally split before (56%) and after (44%) Tchange. In terms of body weight, the most striking difference between EL and NL goats was the rapid and very high increase (+9.3 kg with an average daily gain of 60.4 g/d) that was observed concurrently with the increase in MY. Model parameterization with the group average profile does not support that the rise in MY drives the increase in resource acquisition as is generally assumed at the onset of an NL. Rather, it demonstrates that the transfer of energy from feed to milk is delayed at the onset of EL. Moreover, assessing the model ability to fit the range of individual profiles showed that the performances over the first 90 d of EL are largely predetermined by the animal state at Tchange. The analysis of individual variability in EL efficiency showed that it depends both on an increase in resource acquisition and on the potential of goats to partition energy from the diet toward milk production instead of to body tissue gain. Finally, predicting the suitability for EL requires the consideration of more than just milk production for 300 d in milk.

Features associated with cardiac abnormalities in systemic lupus erythematosus.

OBJECTIVES: To determine the prevalence of echocardiographic abnormalities and identify associated clinical and laboratory features in a large systemic lupus erythematosus (SLE) cohort. METHODS: Patients fulfilling ACR criteria for SLE underwent a transthoracic echocardiogram (TTE) between January 2005 and June 2006. Variables used as potential correlates included age, sex, ethnicity, lupus duration, lupus disease activity (SLEDAI), cumulative damage (SLICC/ACR damage index (DI)), arterial hypertension, diabetes, current smoking, medication use and laboratory data. Multivariate logistic regression was used to examine the association between TTE abnormalities and potential determinants. RESULTS: For the 217 subjects with a TTE performed during the study, the main abnormalities were of the mitral valve (37.3%) and included thickening (25.4%) and insufficiency (25.8%). Other findings included pulmonary artery pressure (PAP) ≥ 30( )mm( )Hg (10.1%), pericardial effusion (4.6%), hypokinesis (2.8%), and aortic insufficiency (3.7%). In multivariate analysis, mitral insufficiency was associated with the use of corticosteroids (OR 2.90; 95%CI 1.42-5.94) and hypokinesis with angiotensin-converting enzyme inhibitors (12.89; 1.06-157.18). Elevated PAP was associated with age (1.04; 1.01-1.07) and with DI (1.20; 1.01-1.42). CONCLUSION: Valvular abnormalities are frequent in patients with SLE, with mitral valve lesions occurring in over one third. TTE screening may be indicated in patients with SLE, especially for those with identified risk factors such as corticosteroid use.

Comparison of dynamic contrast-enhanced MRI and dynamic contrast-enhanced CT biomarkers in bladder cancer.

Dynamic contrast-enhanced MRI (DCE-MRI) is frequently used to provide response biomarkers in clinical trials of novel cancer therapeutics but assessment of their physiological accuracy is difficult. DCE-CT provides an independent probe of similar pharmacokinetic processes and may be modeled in the same way as DCE-MRI to provide purportedly equivalent physiological parameters. In this study, DCE-MRI and DCE-CT were directly compared in subjects with primary bladder cancer to assess the degree to which the model parameters report modeled physiology rather than artefacts of the measurement technique and to determine the interchangeability of the techniques in a clinical trial setting. The biomarker K(trans) obtained by fitting an extended version of the Kety model voxelwise to both DCE-MRI and DCE-CT data was in excellent agreement (mean across subjects was 0.085 ± 0.030 min(-1) for DCE-MRI and 0.087 ± 0.033 min(-1) for DCE-CT, intermodality coefficient of variation 9%). The parameter v(p) derived from DCE-CT was significantly greater than that derived from DCE-MRI (0.018 ± 0.006 compared to 0.009 ± 0.008, P = 0.0007) and v(e) was in reasonable agreement only for low values. The study provides evidence that the biomarker K(trans) is a robust parameter indicative of the underlying physiology and relatively independent of the method of measurement.

A two-part phase II study of cediranib in patients with advanced solid tumours: the effect of food on single-dose pharmacokinetics and an evaluation of safety, efficacy and imaging pharmacodynamics.

BACKGROUND: Cediranib (RECENTIN™) is an oral, highly potent VEGF inhibitor. This study evaluated the effect of food on the pharmacokinetics of cediranib and compared the administration of continual cediranib via two dosing strategies using this as a platform to investigate pharmacodynamic imaging biomarkers. METHODS: Sixty patients were randomised to receive two single doses of cediranib in either fed/fasted or fasted/fed state (Part A). In continual dosage phase (Part B), patients were randomised to a fixed-dose or dose-escalation arm. Exploratory pharmacodynamic assessments were performed using DCE-MRI and CT enhancing fraction (EnF). RESULTS: In part A, plasma AUC and C (max) of cediranib were lower in the presence of food by a mean of 24 and 33%, respectively (94% CI: AUC, 12-34% and C (max), 20-43%), indicating food reduces cediranib plasma exposure. In part B, cediranib 30 mg/day appeared to be the most sustainable for chronic dosing. Continuous cediranib therapy was associated with sustained antivascular effects up to 16 weeks, with significant reductions in DCE-MRI parameters and CT EnF. CONCLUSIONS: It is recommended that cediranib be administered at least 1 h before or 2 h after food. Evidence of antitumour activity was observed, with significant sustained effects upon imaging vascular parameters.

Spa therapy in the treatment of knee osteoarthritis: a large randomised multicentre trial.

OBJECTIVE: To determine whether spa therapy, plus home exercises and usual medical treatment provides any benefit over exercises and usual treatment, in the management of knee osteoarthritis. METHODS: Large multicentre randomised prospective clinical trial of patients with knee osteoarthritis according to the American College of Rheumatology criteria, attending French spa resorts as outpatients between June 2006 and April 2007. Zelen randomisation was used so patients were ignorant of the other group and spa personnel were not told which patients were participating. The main endpoint criteria were patient self-assessed. All patients continued usual treatments and performed daily standardised home exercises. The spa therapy group also received 18 days of spa therapy (massages, showers, mud and pool sessions). MAIN ENDPOINT: The number of patients achieving minimal clinically important improvement (MCII) at 6 months, defined as > or =19.9 mm on the visual analogue pain scale and/or > or =9.1 points in a normalised Western Ontario and McMaster Universities osteoarthritis index function score and no knee surgery. RESULTS: The intention to treat analysis included 187 controls and 195 spa therapy patients. At 6 months, 99/195 (50.8%) spa group patients had MCII and 68/187 (36.4%) controls (chi(2)=8.05; df=1; p=0.005). However, no improvement in quality of life (Short Form 36) or patient acceptable symptom state was observed at 6 months. CONCLUSION: For patients with knee osteoarthritis a 3-week course of spa therapy together with home exercises and usual pharmacological treatments offers benefit after 6 months compared with exercises and usual treatment alone, and is well tolerated.

Disseminated Histoplasma capsulatum infection presenting with panniculitis and focal myositis in rheumatoid arthritis treated with etanercept.

We report the case of a patient with rheumatoid arthritis (RA) on etanercept who presented with panniculitis and focal myositis as manifestations of disseminated histoplasmosis. Systematic search of the literature showed 11 additional case reports of disseminated histoplasmosis with tumour necrosis factor-alpha (TNFalpha) blockade therapy (infliximab, n = 8; etanercept, n = 3). Although disseminated histoplasmosis may manifest with classical symptoms of fever and respiratory complaints, it may also present atypically, such as with panniculitis and focal myositis. This review illustrates and emphasizes the importance of being highly suspicious for infection, including by opportunistic organisms, and to exclude such process in patients treated with a TNFalpha inhibitor when faced with unusual complications, even when an alternative aetiology appears plausible.

Effects of AZD2171 and vandetanib (ZD6474, Zactima) on haemodynamic variables in an SW620 human colon tumour model: an investigation using dynamic contrast-enhanced MRI and the rapid clearance blood pool contrast agent, P792 (gadomelitol).

The effect of two novel therapeutic agents on tumour haemodynamics was investigated using a fast dynamic contrast-enhanced (DCE)-MRI protocol (0.5 s/image) sensitive to signal changes in both the vascular input function and tumour during the administration of the macromolecular rapid clearance blood pool agent (MM-RCBPA), gadomelitol (P792, Vistarem). This enabled simultaneous measurement of the tumour blood flow per unit volume of tissue (F/V(T), mL/s/mL), the fractional plasma volume (V(p), %), and the permeability surface area product per unit volume of tissue (PSrho, s(-1)) in subcutaneous SW620 human colorectal tumour xenografts grown in nude rats before and after (at 0 and 22 h; imaging at 24 h) acute treatment with AZD2171 (3 mg/kg) and vandetanib (ZD6474, Zactima; 50 mg/kg), which have inhibitory activity against vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase. MRI was performed at 4.7 T using a single-slice, modified, T(1)-weighted, spoiled gradient-echo technique. Both compounds reduced gadomelitol uptake into the tumour. AZD2171 and vandetanib, respectively, (a) greatly reduced PSrho to 19.7 +/- 9.5% and 28.9 +/- 14.1% of baseline (P = 0.007 and P = 0.02), (b) markedly reduced V(p) to 31.2 +/- 19.1% and 54.8 +/- 21.2% of baseline (P = 0.015 and P = 0.09), and (c) had no significant effect on F/V(T). There was no significant difference between groups treated with AZD2171 and vandetanib when each variable was compared. The reductions in PSrho and V(p) are consistent with inhibition of VEGF signalling. AZD2171 (3 mg/kg) and vandetanib (50 mg/kg) were also found to produce a comparable chronic inhibition of SW620 tumour growth (89% for both). This study shows that DCE-MRI using an MM-RCPBA can be used to distinguish tumour vascular flow, volume, and permeability surface area product in a tumour model, and enables the acute effects of VEGF signalling inhibition to be examined in detail.

[Smoking among journalists in the private and public media in Togo]. / Tabagisme dans les médias publics et privés du Togo.

BACKGROUND: Collaboration with journalists should help to reduce the tobacco epidemic. All over the world, no study assessed the extent of tobacco smoking in the bosom of reporters. OBJECTIVE: To determine the prevalence of tobacco smoking among reporters and to evaluate their attitudes towards tobacco. MATERIALS AND METHODS: A cross-sectional survey using an anonymised questionnaire was conducted among reporters working for both the public and private media in Togo between the 1st May and the 31st June 2005 using the "from door to door" method. Data analysis was performed with Epi-Info 3.3.2. RESULTS: The participation rate was 82.44%. The prevalence of tobacco smoking was 25%. Smoking was more common in men (26.1% versus 19.6%, p=0.03). The average age that subjects had started to smoke was 17.1 years (Range: 6 and 30 years) with all smokers reporting that they smoked tobacco only in the form of cigarettes. 79.3% of smokers thought that they would quit within the next five years. Only 6.2% reporters often talked about smoking while on the microphone. A majority of the reporters approved of anti-smoking initiatives. CONCLUSION: Because of their importance in the diffusion of news, the media must be enrolled in the fight against tobacco.

Health effects of PM10 air pollution in a low-income country: the case of Algiers.

SETTING: Although there are proven risk factors related to air pollution, the prevalent situation in low-income countries is not well known. OBJECTIVE: To quantify the health impacts associated with particulate air pollution in the city of Algiers. DESIGN: Descriptive study to evaluate a health impact assessment (HIA) approach based on a dose-response curve from the literature. A study area was defined around an air quality monitoring site in Algiers. Daily health data were obtained from a network of physicians practising in out-patient health centres. RESULTS: Over the period studied, the number of consultations for respiratory reasons attributable to PM10 exposure was 439, representing 4.5% of all health events observed. Different scenarios were examined, showing that a reduction in ambient levels of PM10 would be accompanied by important public health gains. CONCLUSION: The study allowed us to test the applicability of the HIA approach in a low-income country and to confirm the interest of the approach. Although the estimation of dose-response functions obeys a complex methodology, the HIA is an alternative that constitutes an important decision-making tool.

[Measuring levels of professionally-related stress in taxi drivers in Fes, Morocco]. / Mesure du stress professionnel des chauffeurs de taxi a Fès, Maroc.

Professional stress is a harmful physical and emotional reaction that can occur when tension exists between the requirements imposed on a person and the level of control that person may, or may not, have on the fulfillment of these requirements (essentially tension between what one is expected to achieve and what one can realistically achieve). At present, traffic accidents are considered to be a major social problem in Morocco. The authors aim to describe stress levels in taxi drivers and to study potential associated factors, in particular the risk of having an accident while driving. A questionnaire was administered in a cross sectional survey to a sample of 338 taxi drivers working in the city of Fes, Morocco. Stress was evaluated by using a standardized scale developed by the French National Institute of Research and Safety (INRS). It allows for the intensity of stress to be quantified according to a set of seven scores. According to the INRS scale, 46.3% of the taxi drivers could be considered as stressed. Moodiness and blood pressure problems were specifically identified as indicators of stress in this population. These results should incite interest in developing prevention measures in order to reduce or eliminate sources of stress at work in order to decrease the number of traffic accidents related to stress, and hence to improve the taxi drivers' working conditions.

NPT2a gene variation in calcium nephrolithiasis with renal phosphate leak.

A decrease in renal phosphate reabsorption with mild hypophosphatemia (phosphate leak) is found in some hypercalciuric stone-formers. The NPT2a gene encodes a sodium-phosphate cotransporter, located in the proximal tubule, responsible for reclaiming most of the filtered phosphate load in a rate-limiting manner. To determine whether genetic variation of the NPT2a gene is associated with phosphate leak and hypercalciuria in a cohort of 98 pedigrees with multiple hypercalciuric stone-formers, we sequenced the entire cDNA coding region of 28 probands, whose tubular reabsorption of phosphate normalized for the glomerular filtration rate (TmP/GFR) was 0.7 mmol/l or lower. We performed genotype/phenotype correlations for each genetic variant in the entire cohort and expressed NPT2a variant RNAs in Xenopus laevis oocytes to test for cotransporter functionality. We identified several variants in the coding region including an in-frame 21 bp deletion truncating the N-terminal cytoplasmic tail of the protein (91del7), as well as other single-nucleotide polymorphisms that were non-synonymous (A133V and H568Y) or synonymous. Levels of TmP/GFR and urine calcium excretion were similar in heterozygote carriers of NPT2a variants compared to the wild-type (wt) homozygotes. The transport activity of the H568Y mutants was identical to the wt, whereas the N-terminal-truncated version and the 91del7 and A133V mutants presented minor kinetic changes and a reduction in the expression level. Although genetic variants of NPT2a are not rare, they do not seem to be associated with clinically significant renal phosphate or calcium handling anomalies in a large cohort of hypercalciuric stone-forming pedigrees.