Spitzoid melanoma with histopathological features of ALK gene rearrangement exhibiting ALK copy number gain: a novel mechanism of ALK activation in spitzoid neoplasia.

Spitzoid neoplasms pose diagnostic difficulties because their morphology is not consistently predictive of their biological potential. Recent advances in the molecular characterization of these tumours provides a framework by which they can now begin to be categorized. In particular, spitzoid lesions with ALK rearrangement have been specifically associated with a characteristic plexiform growth pattern of intersecting fascicles of amelanotic spindled melanocytes. We report the case of an 87-year-old man with a 3-cm nodule on his mid-upper back comprised of an intradermal proliferation of fusiform amelanotic melanocytes arranged in intersecting fascicles with occasional peritumoral clefts. Immunohistochemical studies demonstrated diffuse, strong expression of SOX10 and S100 by the tumour cells and diffuse, weak-to-moderate cytoplasmic positivity for anaplastic lymphoma kinase (ALK), suggestive of ALK rearrangement. Fluorescence in situ hybridization revealed no ALK rearrangements but instead revealed at least three intact ALK signals in 36% of the tumour cells, confirming ALK copy number gain. To our knowledge, this is the first reported case of a plexiform spitzoid neoplasm exhibiting ALK copy number gain instead of ALK rearrangement. This case suggests that ALK copy number gain is a novel mechanism of ALK activation but with the same characteristic histopathological growth pattern seen among ALK-rearranged spitzoid neoplasms.

Incidence of cephalosporin-induced anaphylaxis and clinical efficacy of screening intradermal tests with cephalosporins: A large multicenter retrospective cohort study.

BACKGROUND: Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests. METHODS: In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins. RESULTS: We identified 76 cases of cephalosporin-induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06). CONCLUSIONS: The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Screening IDT showed no clinical efficacy at a population level.

Staphylococcal enterotoxin IgE sensitization in late-onset severe eosinophilic asthma in the elderly.

BACKGROUND: Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late-onset asthma. Recent studies suggest staphylococcal enterotoxin IgE (SE-IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late-onset elderly asthma. OBJECTIVE: We aimed to examine the associations of SE-IgE sensitization with late-onset asthma in the elderly, using a database of elderly asthma cohort study. METHODS: A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE-IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12-month follow-up period. RESULTS: At baseline, serum SE-IgE concentrations were significantly higher in patients with asthma than in controls [median 0.16 (interquartile range 0.04-0.53) vs. 0.10 (0.01-0.19), P < 0.001]. Elderly asthma patients with high SE-IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE-IgE levels. In multivariate logistic regression analyses, the associations between serum SE-IgE concentrations and severe asthma were significant, independently of covariables [SE-IgE-high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86-30.03, P = 0.005]. Multiple correspondence analyses also showed that high serum SE-IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first report on the significant associations of SE-IgE sensitization with late-onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late-onset eosinophilic asthma in the elderly.

Healthcare use and prescription patterns associated with adult asthma in Korea: analysis of the NHI claims database.

BACKGROUND: National Health Insurance (NHI) claim records could provide valuable data for epidemiological studies of asthma in Korea. The aim of this study is to estimate the prevalence of adult asthma and to investigate asthma-related healthcare use and prescription patterns in Korea over 5 years. METHODS: National Health Insurance claim records from January 1, 2006 to December 31, 2010 were analyzed in a retrospective, population-based study. Outcome measures included asthma prevalence, healthcare use, and prescription patterns over time, by type of hospital, and by medical specialty. Additionally, we assessed differences in healthcare use between newly diagnosed and previously diagnosed patients in 2009. RESULTS: Over 5 years, the prevalence of asthma among Korean adults increased from 4944 to 5707 cases per 100,000 population (from 3760 to 4445 in men and from 6108 to 6951 in women). Asthma-related outpatient visits decreased from 4.82 ± 8.02 to 3.44 ± 5.50. Approximately 3% of all patients were hospitalized and 2.4% received asthma-related emergency treatment each year. Pulmonary function tests were performed in 10-11% of patients an average of 1.3 times per year. Newly diagnosed patients experienced fewer asthma-related hospitalizations (1.78% vs 4.35%) and emergency department visits (0.80% vs 2.11%) than the previously diagnosed group. Prescriptions of inhaled corticosteroids-based inhalers were maintained with about 20% of average of all types of hospitals. CONCLUSIONS: The prevalence of asthma in Korea has increased over a recent 5-year period, and asthma is still suboptimally controlled. Public health strategies are needed to improve the management of asthma in adults.

Validation of the cephalosporin intradermal skin test for predicting immediate hypersensitivity: a prospective study with drug challenge.

BACKGROUND: Cephalosporin is a major offending agent in terms of drug hypersensitivity along with penicillin. Cephalosporin intradermal skin tests (IDTs) have been widely used; however, their validity for predicting immediate hypersensitivity has not been studied. This study aimed to determine the predictive value of cephalosporin intradermal skin testing before administration of the drug. METHODS: We prospectively conducted IDTs with four cephalosporins, one each of selected first-, second-, third-, or fourth-generation cephalosporins: ceftezol; cefotetan or cefamandole; ceftriaxone or cefotaxime; and flomoxef, respectively, as well as with penicillin G. After the skin test, whatever the result, one of the tested cephalosporins was administered intravenously and the patient was carefully observed. RESULTS: We recruited 1421 patients who required preoperative cephalosporins. Seventy-four patients (74/1421, 5.2%) were positive to at least one cephalosporin. However, none of responders had immediate hypersensitivity reactions after a challenge dose of the same or different cephalosporin, which were positive in the skin test. Four patients who suffered generalized urticaria and itching after challenge gave negative skin tests for the corresponding drug. The IDT for cephalosporin had a sensitivity of 0%, a specificity of 97.5%, a negative predictive value of 99.7%, and a positive predictive value (PPV) of 0%, when challenged with the same drugs that were positive in the skin test. CONCLUSION: Routine skin testing with a cephalosporin before its administration is not useful for predicting immediate hypersensitivity because of the extremely low sensitivity and PPV of the skin test (CRIS registration no. KCT0000455).

Lessons from two cases of anaphylaxis to proton pump inhibitors.

WHAT IS KNOWN AND OBJECTIVE: Proton pump inhibitors (PPIs), which are widely used for the treatment of peptic ulcers and gastroesophageal diseases, reduce both basal and stimulated gastric acid secretion by inhibiting the parietal cell enzyme H(+)-K(+)-adenosine triphosphatase. There have been several reports of hypersensitivity reactions to PPIs but anaphylaxis is very rare. We report on two cases of anaphylaxis to PPIs. CASE SUMMARY: Our two interesting and instructive cases of anaphylaxis to PPIs relate to the orally disintegrating form of lansoprazole and omeprazole. The first patient had taken esomeprazole 20 mg/day for 1 month without any side effects before experiencing anaphylaxis to lansoprazole. To our knowledge, this is the first report of anaphylaxis to the orally disintegrating form of lansoprazole. In the second case, the patient was misdiagnosed with penicillin allergy which she suffered from earlier. WHAT IS NEW AND CONCLUSION: Physicians need to be more aware of the possibility of hypersensitivity to PPIs.

Clinical Experience of 1-Minute Brain MRI Using a Multicontrast EPI Sequence in a Different Scan Environment.

BACKGROUND AND PURPOSE: The long scan time of MR imaging is a major drawback limiting its clinical use in neuroimaging; therefore, we aimed to investigate the clinical feasibility of a 1-minute full-brain MR imaging using a multicontrast EPI sequence on a different MR imaging scanner than the ones previously reported. MATERIALS AND METHODS: We retrospectively reviewed the records of 146 patients who underwent a multicontrast EPI sequence, including T1-FLAIR, T2-FLAIR, T2WI, DWI, and T2*WI sequences. Two attending neuroradiologists assessed the image quality of each sequence to compare the multicontrast EPI sequence with routine MR imaging protocols. We used the Wilcoxon signed rank test and McNemar test to compare the 2 MR imaging protocols. RESULTS: The multicontrast EPI sequence generally showed sufficient image quality of >2 points using a 4-point assessment scale. Regarding image quality and susceptibility artifacts, there was no significant difference between the multicontrast EPI sequence DWI and routine DWI (P > .05), attesting to noninferiority of the multicontrast EPI, whereas there were significant differences in the other 4 sequences between the 2 MR imaging protocols. CONCLUSIONS: The multicontrast EPI sequence showed sufficient image quality for clinical use with a shorter scan time; however, it was limited by inferior image quality and frequent susceptibility artifacts compared with routine brain MR imaging. Therefore, the multicontrast EPI sequence cannot completely replace the routine MR imaging protocol at present; however, it may be a feasible option in specific clinical situations such as screening, time-critical diseases or for use with patients prone to motion.

Additive role of tiotropium in severe asthmatics and Arg16Gly in ADRB2 as a potential marker to predict response.

BACKGROUND: Recent findings have raised new interests about the use of anticholinergics, especially tiotropium, for the treatment of asthma. This study was performed to determine whether an additional improvement in lung function is obtained when tiotropium is administrated in addition to conventional therapies in severe asthmatics, and to identify factors capable of predicting the response to tiotropium, using a pharmacogenetic approach. METHODS: A total of 138 severe asthmatics on conventional medications and with decreased lung function were randomly recruited. Tiotropium 18 microg was added once a day and lung functions were measured every 4 weeks. Responders were defined as those with an improvement of > or = 15% (or 200 ml) in the forced expiratory volume in 1 s (FEV1) that was maintained for at least 8 successive weeks. Eleven single nucleotide polymorphisms (SNPs) in CHRM1-3 (coding muscarinic receptors one to three) which were identified by re-sequencing, and Arg16Gly and Gln27Glu in ADRB2 (coding beta(2) adrenoreceptor) were scored in 80 of the 138 asthmatics. RESULTS: Forty-six of the 138 asthmatics (33.3%) responded to tiotropium treatment. Logistic regression analyses (controlled for age, gender, and smoking status) showed that Arg16Gly in ADRB2 [P = 0.003, OR (95% CI) = 0.21 (0.07-0.59) in a minor allele-dominant model] was significantly associated with response to tiotropium. CONCLUSIONS: As many as 30% of severe asthmatics on conventional medications with reduced lung function were found to respond to adjuvant tiotropium. The presence of Arg16Gly in ADRB2 may predict response to tiotropium.

Do dietary patterns in older men influence change in homocysteine through folate fortification? The Normative Aging Study.

OBJECTIVE: We aimed to describe the difference in B-vitamin intake and in plasma B-vitamin and homocysteine concentrations before and after folic acid fortification, in relation to dietary patterns. DESIGN: The Normative Aging Study (NAS) is a longitudinal study on ageing. Between 1961 and 1970, 2280 male volunteers aged 21-80 years (mean 42 years) were recruited. Dietary intake data have been collected since 1987 and assessment of plasma B vitamins and homocysteine was added in 1993. SETTING: Boston, Massachusetts, USA. SUBJECTS: In the present study, 354 men who had completed at least one FFQ and one measurement of homocysteine, both before and after the fortification period, were included. RESULTS: Three dietary patterns were identified by cluster analysis: (i) a prudent pattern, with relatively high intakes of fruit, vegetables, low-fat milk and breakfast cereals; (ii) an unhealthy pattern, with high intakes of baked products, sweets and added fats; and (iii) a low fruit and vegetable but relatively high alcohol intake pattern. Dietary intake and plasma concentrations of folate increased significantly (P < 0.05) among all dietary patterns after the fortification period. Homocysteine tended to decrease in supplement non-users and in subjects in the high alcohol, low fruit and vegetable dietary pattern (both P = 0.08). CONCLUSIONS: After fortification with folic acid, folate intake and plasma folate concentration increased significantly in all dietary patterns. There was a trend towards greatest homocysteine lowering in the high alcohol, low fruit and vegetable group.

Polymorphisms in the neurokinin-2 receptor gene are associated with angiotensin-converting enzyme inhibitor-induced cough.

BACKGROUND AND OBJECTIVE: Treatment with angiotensin-converting enzyme (ACE) inhibitors can induce chronic cough in many patients. Genetic variations in the neurokinin 2 receptor gene (NK2R) are significantly associated with cough sensitivity to capsaicin. METHODS: This study assessed the relationship between genetic polymorphisms in the NK2R gene and chronic cough in 91 patients taking ACE inhibitors. Patients included in the study did not have chest abnormalities, postnasal drip, gastroesophageal reflux or a recent history of upper respiratory infection. RESULTS: We detected two single nucleotide polymorphisms in the NK2R gene (i.e., Gly231Glu and Arg375His). The allelic frequencies at amino acid 231 were 36.3% for Gly/Gly, 49.5% for Gly/Glu and 14.3% for Glu/Glu. The allelic frequencies at amino acid 375 were 74.7% for Arg/Arg, 24.2% for Arg/His and 1.1% for His/His. The prevalence of chronic cough in patients with the amino acid 231 genotype was 33.3% in Gly/Gly homozygotes, 24.4% in Gly/Glu heterozygotes and 0% in Glu/Glu homozygotes. There was a statistically significant association between chronic cough and the Glu/Glu allele (P = 0.028) when the data were analyzed with a recessive model. In addition, there was a significant inverse linear association between the number of Glu231 alleles and ACE inhibitor-related cough (P = 0.026). The prevalence of chronic cough in patients with the amino acid 375 genotype was 22.1% in Arg/Arg homozygotes, 31.8% in Arg/His heterozygotes and 0% in His/His homozygotes, although none of these association were statistically significant. CONCLUSION: Our findings indicate that the Gly231Glu polymorphism is associated with a lower prevalence of ACE inhibitor-related cough.

Second to fourth digit ratio and lung function (forced vital capacity): predictors of maximum urinary flow rate after holmium laser enucleation of the prostate.

BACKGROUND: Maximum urinary flow rate (Qmax) is usually increased after holmium laser enucleation of the prostate (HoLEP). However, improvements vary between patients and results regarding potential predictors of Qmax after HoLEP are inconsistent. Thus, we investigated pre-operative variables including second to fourth digit ratio (digit ratio) and pulmonary function test (PFT) findings as potential predictors of Qmax after HoLEP. METHODS: One hundred and ninety-five consecutive patients with benign prostatic hyperplasia (BPH) who underwent HoLEP were enrolled. Before HoLEP, PFTs were performed and lengths of second and fourth digits of right hands were measured by a single investigator using a digital vernier caliper. To identify independent predictors of Qmax after HoLEP, univariate and multivariate analyses were performed using linear regression models. RESULTS: Mean age and total prostate volume for all 195 study subjects were 69.4 years and 63.3 mL respectively. Mean pre-operative and post-operative Qmax values were 8.7 and 26.2 mL/sec respectively. Univariate analysis showed age (r = -0.181, p = 0.014), digit ratio (r = 0.213, p = 0.004), lung function (forced vital capacity (FVC): r = 0.218, p = 0.005; forced expiratory volume in 1 sec (FEV1): r = 0.166, p = 0.034), pre-operative Qmax (r = 0.264, p = 0.000), pre-operative voided volume (VV) (r = 0.158, p = 0.033), and post-operative VV (r = 0.311, p = 0.000) were associated with post-operative Qmax, whereas multivariate analysis showed that digit ratio (ß = 0.285, p = 0.001), FVC (ß = 0.340, p = 0.039), and post-operative VV (ß = 0.301, p = 0.000) independently predicted post-operative Qmax. CONCLUSIONS: The independent predictors of Qmax after HoLEP were digit ratio and lung function (FVC) as well as post-operative VV. This means that the higher a man's digit ratio and lung function (FVC), the higher his Qmax after HoLEP.

Clinical Feasibility of Zero TE Skull MRI in Patients with Head Trauma in Comparison with CT: A Single-Center Study.

BACKGROUND AND PURPOSE: Conventional MR imaging techniques cannot produce optimal images of bone structures because bone has little water and a very short T2 life span. The aim of this study was to investigate the clinical feasibility of skull MR imaging using the zero TE sequence in patients with head trauma by assessing its diagnostic image quality and quantitative measurement compared with CT images. MATERIALS AND METHODS: Thirteen enrolled patients with head trauma were assessed using brain CT and skull MR imaging. Image quality was graded on a 5-point Likert scale to compare the 2 modalities. To evaluate quantitative analyses between the 2 imaging modalities, we measured skull thickness and normalized bone tissue signal. Interobserver reliability was assessed using weighted κ statistics and the intraclass correlation coefficient. RESULTS: Both imaging techniques clearly depicted skull fractures in all 13 patients. The mean scores for skull MR imaging and CT were 4.65 ± 0.56 and 4.73 ± 0.45 (P = .157), respectively, with substantial interobserver agreement (P < .05). The 2 imaging modalities showed no difference in skull thickness (P = .092) and had good correlation (r 2 = 0.997). The mean value of normalized bone tissue signal among the 3 layers of the skull was relatively consistent (P = .401) with high interobserver agreement (P < .001). CONCLUSIONS: Zero TE skull MR imaging has diagnostic image quality comparable with that of CT images. It also provides consistent results on the quantitative measurement of cortical bone with CT images.

Multiscale analyses reveal native-like lamellar bone repair and near perfect bone-contact with porous strontium-loaded bioactive glass.

The efficient healing of critical-sized bone defects using synthetic biomaterial-based strategies is promising but remains challenging as it requires the development of biomaterials that combine a 3D porous architecture and a robust biological activity. Bioactive glasses (BGs) are attractive candidates as they stimulate a biological response that favors osteogenesis and vascularization, but amorphous 3D porous BGs are difficult to produce because conventional compositions crystallize during processing. Here, we rationally designed a porous, strontium-releasing, bioactive glass-based scaffold (pSrBG) whose composition was tailored to deliver strontium and whose properties were optimized to retain an amorphous phase, induce tissue infiltration and encourage bone formation. The hypothesis was that it would allow the repair of a critical-sized defect in an ovine model with newly-formed bone exhibiting physiological matrix composition and structural architecture. Histological and histomorphometric analyses combined with indentation testing showed pSrBG encouraged near perfect bone-to-material contact and the formation of well-organized lamellar bone. Analysis of bone quality by a combination of Raman spectral imaging, small-angle X-ray scattering, X-ray fluorescence and focused ion beam-scanning electron microscopy demonstrated that the repaired tissue was akin to that of normal, healthy bone, and incorporated small amounts of strontium in the newly formed bone mineral. These data show the potential of pSrBG to induce an efficient repair of critical-sized bone defects and establish the importance of thorough multi-scale characterization in assessing biomaterial outcomes in large animal models.

Body weight changes in elderly psychogeriatric nursing home residents.

OBJECTIVE: This study was undertaken to identify predictors of body weight change in nursing home patients with possible to severe dementia. METHODS: For 24 weeks, 108 elderly residents of a nursing home were followed. Body weight was measured every 2 weeks. Other anthropometric characteristics, dietary intake, food behavior restrictions, psychological characteristics, medical status, and use of medicines were measured at baseline. Dietary intake was measured with a combined 3-day food record and by observations during the hot meals. Food behavior restrictions were measured following the classification of Berkhout. Dependency was measured by a questionnaire (Care Index Geriatrics), which measures restrictions in cognitive, physical, and social functioning. A generalized linear mixed effects model was used to investigate weight changes over time. The model was adjusted for age and sex. RESULTS: During the follow-up period, 26% of the participants lost and 22% gained at least 2 kg of body weight. Dependency (beta = -0.11, 95% confidence interval [CI] = -0.21, -0.01) and decreased appetite (beta = -2.17, 95% CI = -4.32, -0.01) were significantly associated with body weight loss, whereas body mass index (beta = 2.25, 95% CI = 1.98, 2.51) and intake of fat (beta = 0.07, 95% CI = 0.01, 0.15) were predictors of weight gain. CONCLUSION: Dependency, body mass index, intake of fat, and decreased appetite are significant predictors of body weight changes.

Assessment of susceptibility of Plasmodium falciparum to chloroquine, quinine, mefloquine, sulfadoxine-pyrimethamine and artemisinin in southern Viet Nam.

Resistance to antimalarial chemotherapy is a major concern for malaria control in Viet Nam. In this study undertaken in 1998, 65 patients with uncomplicated Plasmodium falciparum malaria were monitored for 28 days after completion of a 5-day treatment course with artemisinin. Overall 36.9% (24/65) of patients had recurrent parasitaemia during the surveillance period. P. falciparum isolates were tested for sensitivity in vitro to chloroquine, mefloquine, quinine, sulfadoxine-pyrimethamine and results were compared to those from a similar study in 1995. Increased parasite sensitivity to sulfadoxine-pyrimethamine, chloroquine and quinine was demonstrated, with significantly lower mean EC50 and EC99 values in 1998 compared to 1995. Parasite sensitivity to mefloquine did not differ significantly in the 2 surveys. Isolates were also tested for sensitivity in vitro to artemisinin in the 1998 survey. The mean EC50 was 0.03 mumol/L and the EC99 was 0.94 mumol/L. Parasite sensitivity to artemisinin will need to be monitored in view of its increasing use in Viet Nam.

Resistance of Plasmodium falciparum to antimalarial drugs in a highly endemic area of southern Viet Nam: a study in vivo and in vitro.

To assess the antimalarial sensitivity of Plasmodium falciparum in vivo and in vitro in a highly endemic area of southern Viet Nam, a field study was conducted (in 1999) at a rubber plantation in Binh Phuoc Province north of Ho Chi Minh City. Fifty patients were treated with either artesunate (4 mg/kg on day 0, then 2 mg/kg on day 1 to 4) or mefloquine (10 mg/kg at 0 h, then 5 mg/kg at 6 h), and their progress was followed for 28 days under standard WHO protocols. Blood spots were taken at baseline from all patients, as well as from those who redeveloped parasitaemia during follow-up, for polymerase chain reaction (PCR) determination of parasite genotypes to assist differentiation of re-infection from recrudescence. Both treatments cleared parasites within 5 days. Of the 25 mefloquine-treated patients, 2 (8%) re-presented with probable re-infections. For artesunate, 4 patients (16%) had re-infections and 5 (20%) had recrudescences. Sensitivity tests in vitro of pre-treatment P. falciparum isolates showed geometric mean IC50 values of 29, 38, 209 and 15 nmol/L for chloroquine (n = 32), mefloquine (n = 33), quinine (n = 31) and artemisinin (n = 31), respectively. There were significant correlations between IC50s for artemisinin and mefloquine (r = 0.72, P = 0.004), and chloroquine and quinine (r = 0.44, P = 0.05). These data show that, although mefloquine has been used for 10 years in Binh Phuoc Province, it remains fully effective, perhaps because an artemisinin derivative is commonly given at the same time. The recrudescence rate for artesunate is similar to those reported in other epidemiological contexts. The present in-vitro data imply that quinine remains effective and that reduced drug pressure has been associated with increased sensitivity of local strains of P. falciparum to chloroquine. Although from one hyperendemic area, these results may have implications for antimalarial prophylaxis and treatment strategies for residents and travellers to southern Viet Nam.

Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project.

CONTEXT: Dietary patterns and lifestyle factors are associated with mortality from all causes, coronary heart disease, cardiovascular diseases, and cancer, but few studies have investigated these factors in combination. OBJECTIVE: To investigate the single and combined effect of Mediterranean diet, being physically active, moderate alcohol use, and nonsmoking on all-cause and cause-specific mortality in European elderly individuals. DESIGN, SETTING, AND PARTICIPANTS: The Healthy Ageing: a Longitudinal study in Europe (HALE) population, comprising individuals enrolled in the Survey in Europe on Nutrition and the Elderly: a Concerned Action (SENECA) and the Finland, Italy, the Netherlands, Elderly (FINE) studies, includes 1507 apparently healthy men and 832 women, aged 70 to 90 years in 11 European countries. This cohort study was conducted between 1988 and 2000. MAIN OUTCOME MEASURES: Ten-year mortality from all causes, coronary heart disease, cardiovascular diseases, and cancer. RESULTS: During follow-up, 935 participants died: 371 from cardiovascular diseases, 233 from cancer, and 145 from other causes; for 186, the cause of death was unknown. Adhering to a Mediterranean diet (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.68-0.88), moderate alcohol use (HR, 0.78; 95% CI, 0.67-0.91), physical activity (HR, 0.63; 95% CI, 0.55-0.72), and nonsmoking (HR, 0.65; 95% CI, 0.57-0.75) were associated with a lower risk of all-cause mortality (HRs controlled for age, sex, years of education, body mass index, study, and other factors). Similar results were observed for mortality from coronary heart disease, cardiovascular diseases, and cancer. The combination of 4 low risk factors lowered the all-cause mortality rate to 0.35 (95% CI, 0.28-0.44). In total, lack of adherence to this low-risk pattern was associated with a population attributable risk of 60% of all deaths, 64% of deaths from coronary heart disease, 61% from cardiovascular diseases, and 60% from cancer. CONCLUSION: Among individuals aged 70 to 90 years, adherence to a Mediterranean diet and healthful lifestyle is associated with a more than 50% lower rate of all-causes and cause-specific mortality.

Second to fourth digit ratio: a predictor of adult testicular volume.

It has been suggested that second to fourth digit ratio (digit ratio) may correlate with male reproductive system function or disorders. This hypothesis is based on finding that the Hox genes control finger development and differentiation of the genital bud during embryogenesis. Thus, we investigated the association between digit ratio and adult testicular volume. A total of 172 Korean men (aged 20-69 years) hospitalized for urological surgery were prospectively enrolled. Patients with conditions known to strongly influence testicular volume were excluded. Before determining testicular volume, the lengths of the second and fourth digits of the right hand were measured by a single investigator using a digital vernier calliper. Using orchidometry, the testes were measured by an experienced urologist who had no information about the patient's digit ratio. To identify the independent predictive factors influencing testicular volume, univariate and multivariate analyses were performed using linear regression models. Age, height, serum testosterone and free testosterone level were not correlated with testicular volume. Digit ratio, along with weight, was significantly correlated with testicular volume (right testicular volume: r = -0.185, p = 0.015; left testicular volume: r = -0.193, p = 0.011; total testicular volume: r = -0.198, p = 0.009). Multivariate analysis using linear regression models showed that only digit ratio was the independent factor to predict all (right, left and total) testicular volumes (right testicular volume: ß = -0.174, p = 0.023; left testicular volume: ß = -0.181, p = 0.017; total testicular volume: ß = -0.185, p = 0.014). Our findings demonstrated that digit ratio is negatively associated with adult testicular volume. This means that men with a higher digit ratio may be more likely to have smaller testis compared to those with a lower digit ratio.