Association of a common vitamin D-binding protein polymorphism with inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel diseases (IBDs), Crohn's disease, and ulcerative colitis (UC), are multifactorial disorders, characterized by chronic inflammation of the intestine. A number of genetic components have been proposed to contribute to IBD pathogenesis. In this case-control study, we investigated the association between two common vitamin D-binding protein (DBP) genetic variants and IBD susceptibility. These two single nucleotide polymorphisms (SNPs) in exon 11 of the DBP gene, at codons 416 (GAT>GAG; Asp>Glu) and 420 (ACG>AAG; Thr>Lys), have been previously suggested to play roles in the etiology of other autoimmune diseases. METHODS: Using TaqMan SNP technology, we have genotyped 884 individuals (636 IBD cases and 248 non-IBD controls) for the two DBP variants. RESULTS: On statistical analysis, we observed that the DBP 420 variant Lys is less frequent in IBD cases than in non-IBD controls (allele frequencies, P=0.034; homozygous carrier genotype frequencies, P=0.006). This inverse association between the DBP 420 Lys and the disease remained significant, when non-IBD participants were compared with UC (homozygous carrier genotype frequencies, P=0.022) or Crohn's disease (homozygous carrier genotype frequencies, P=0.016) patients separately. Although the DBP position 416 alone was not found to be significantly associated with IBD, the haplotype DBP_2, consisting of 416 Asp and 420 Lys, was more frequent in the non-IBD population, particularly notably when compared with the UC group (Odds ratio, 4.390). CONCLUSION: Our study adds DBP to the list of potential genes that contribute to the complex genetic etiology of IBD, and further emphasizes the association between vitamin D homeostasis and intestinal inflammation.

Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients.

OBJECTIVE: To evaluate the efficacy and safety of intravenous fluconazole for the prevention of intra-abdominal Candida infections in high-risk surgical patients. DESIGN: Randomized, prospective, double-blind, placebo-controlled study. SETTING: Two university-affiliated hospitals in Switzerland. PATIENTS: Forty-nine surgical patients with recurrent gastrointestinal perforations or anastomotic leakages. INTERVENTIONS: Prophylaxis with intravenous fluconazole (400 mg per day) or placebo continued until resolution of the underlying surgical condition. MEASUREMENTS AND MAIN RESULTS: Patients were evaluated daily, and specimens for culture were obtained three times per week during prophylaxis. The primary study end points were the frequency of and the time to intra-abdominal Candida infections. Secondary end points were the frequency of candidiasis (intra-abdominal and extra-abdominal) and the emergence or persistence of Candida colonization. Among patients who were not colonized at study entry, Candida was isolated from surveillance cultures during prophylaxis in 15% of the patients in the fluconazole group and in 62% of the patients in the placebo group (relative risk, 0.25; 95% confidence interval, 0.07 to 0.96; p = .04). Candida peritonitis occurred in one of 23 patients (4%) who received fluconazole and in seven of 20 patients (35%) who received placebo (relative risk, 0.12; 95% confidence interval, 0.02 to 0.93; p = .02). In addition, one catheter-related Candida albicans sepsis occurred in a fluconazole-treated patient. Thus, overall, candidiasis developed in two fluconazole patients and seven placebo patients (relative risk, 0.25; 95% confidence interval, 0.06 to 1.06; p = .06). C. albicans accounted for 87% of the Candida species isolated before or during prophylaxis, and all C. albicans strains were susceptible to fluconazole. Fluconazole was well tolerated, and adverse events occurred at similar frequencies in both treatment groups. CONCLUSIONS: Fluconazole prophylaxis prevents colonization and invasive intra-abdominal Candida infections in high-risk surgical patients.

Neuropeptide Y secretion from a human insulinoma.

Neuropeptide Y (NPY) is a 36 aminoacid peptide known to inhibit glucose-stimulated insulin secretion. NPY has been shown to be synthesized and secreted by rat islets of Langerhans. More recently, we described the presence on NPY within human islets of Langerhans and in several pancreatic endocrine tumors. In this report, we describe the case of a patient presenting with an insulinoma who underwent the surgical resection of the tumor and was studied in vivo and in vitro for NPY production. Using a highly specific and sensitive two-site amplified enzyme-linked immunosorbent assay, we detected high plasma NPY levels in the patient prior to the surgical resection of the tumor which returned to normal after surgery. NPY was secreted from the tumor when kept in primary cell culture. Furthermore, immunohistochemistry of the insulinoma revealed the presence of NPY and its C-flanking peptide together with insulin, chromogranin and neuron specific enolase. It is concluded that elevated circulating NPY levels observed in this patient with an insulinoma reflected in vivo secretion by the tumor and it is hypothesized that NPY could potentially be used as an endocrine marker in patients with suspected insulinoma.

Transapical aortic 'valve-in-valve' procedure for degenerated stented bioprosthesis.

Standard surgical aortic valve replacement with a biological prosthesis remains the treatment of choice for low- and mid-risk elderly patients (traditionally >65 years of age) suffering from severe symptomatic aortic valve stenosis or insufficiency, and for young patients with formal contraindications to long-lasting anticoagulation. Unfortunately, despite the fact that several technical improvements have noticeably improved the resistance of pericardial and bovine bioprostheses to leaflet calcifications and ruptures, the risk of early valve failure with rapid degeneration still exists, especially for patients under haemodialysis and for patients <60 years of age at the time of surgery. Until now, redo open heart surgery under cardiopulmonary bypass and on cardioplegic arrest was the only available therapeutic option in case of bioprosthesis degeneration, but it carried a higher surgical risk when elderly patients with severe concomitant comorbidities were concerned. Since a few years, the advent of new transcatheter aortic valve procedures has opened new horizons in cardiac surgery and, in particular, the possibility of implanting stented valves within the degenerated stented bioprosthesis, the so-called 'valve-in-valve' (VinV) concept, has become a clinical practice in experienced cardiac centres. The VinV procedure represents a minimally invasive approach dedicated to high-risk redo patients, and published preliminary reports have shown a success rate of 100% with absence of significant valvular leaks, acceptable transvalvular gradients and low complication rate. However, this procedure is not riskless and the most important concerns are about the size mismatch and the right positioning within the degenerated bioprosthesis. In this article, we review the limited available literature about VinV procedures, underline important technical details for the positioning and provide guidelines to prevent valve-prosthesis mismatch comparing the three sizes of the only commercially available transapical device, the Edwards Sapien, with the inner diameter of three of the most commonly used stented bioprostheses.

Family physician involvement in cancer care follow-up: the experience of a cohort of patients with lung cancer.

PURPOSE There has been little research describing the involvement of family physicians in the follow up of patients with cancer especially during the primary treatment phase We undertook a prospective longitudinal study of patients with lung cancer to assess their family physician s involvement in their follow up at the different phases of cancer METHODS In 5 hospitals in the province of Quebec Canada patients with a recent diagnosis of lung cancer were surveyed every 3 to 6 months whether they had metastasis or not, for a maximum of 18 months to assess aspects of their family physician s involvement in cancer care RESULTS Of the 395 participating patients 92% had a regular family physician but only 60% had been referred to a specialist by him/her or a colleague for the diagnosis of their lung cancer A majority of patients identified the oncology team or oncologists as mainly responsible for their cancer care throughout their cancer journey except at the advanced phase where a majority attributed this role to their family physician At baseline only 16% of patients perceived a shared care pattern between their family physician and oncologists but this pro portion increased with cancer progression Most patients would have liked their family physician to be more involved in all aspects of cancer care CONCLUSIONS Although patients perceive that the oncology team is the main party responsible for the follow up of their lung cancer they also wish their family physicians to be involved Better communication and collaboration between family physicians and the oncology team are needed to facilitate shared care in cancer follow up

Effective temporary analgesia for severe painful blind eye.

There are various methods of providing pain relief for painful blind eyes. We wish to recommend this effective method of providing temporary analgesia in patients suffering from a severe painful blind eye before undergoing enucleation.

The spiritual distress assessment tool: an instrument to assess spiritual distress in hospitalised elderly persons.

BACKGROUND: Although spirituality is usually considered a positive resource for coping with illness, spiritual distress may have a negative influence on health outcomes. Tools are needed to identify spiritual distress in clinical practice and subsequently address identified needs. This study describes the first steps in the development of a clinically acceptable instrument to assess spiritual distress in hospitalized elderly patients. METHODS: A three-step process was used to develop the Spiritual Distress Assessment Tool (SDAT): 1) Conceptualisation by a multidisciplinary group of a model (Spiritual Needs Model) to define the different dimensions characterizing a patient's spirituality and their corresponding needs; 2) Operationalisation of the Spiritual Needs Model within geriatric hospital care leading to a set of questions (SDAT) investigating needs related to each of the defined dimensions; 3) Qualitative assessment of the instrument's acceptability and face validity in hospital chaplains. RESULTS: Four dimensions of spirituality (Meaning, Transcendence, Values, and Psychosocial Identity) and their corresponding needs were defined. A formalised assessment procedure to both identify and subsequently score unmet spiritual needs and spiritual distress was developed. Face validity and acceptability in clinical practice were confirmed by chaplains involved in the focus groups. CONCLUSIONS: The SDAT appears to be a clinically acceptable instrument to assess spiritual distress in elderly hospitalised persons. Studies are ongoing to investigate the psychometric properties of the instrument and to assess its potential to serve as a basis for integrating the spiritual dimension in the patient's plan of care.

Intérêt du bleu de méthylène dans la chirurgie de l'hyperparathyroïdism primaire [Methylene blue in surgery of primary hyperparathyroidism]

Is surgery for primary hyperparathyroidism easier when methylene blue (MB) is given preoperatively? This retrospective study compares the durations of interventions for primary hyperparathyroidism carried out after i.v. MB administration to those when no MB was given. Over a period of 20 years (June 1976 to December 1996), 175 consecutive patients (56 men and 119 women, with ages ranging from 16 to 92, mean 59.6) were operated upon for primary hyperparathyrodism; 55 were operated before February 1986--the period when BM was introduced routinely, and 120 after. Thirty-two other patients were excluded from the study: 14 had had a previous cervicotomy and 18 another procedure in addition to the parathyroidectomy (usually on the thyroid gland), two conditions which prolonged the time devoted to parathyroid identification and excision. Preoperative calcemia averaged 2.97 mmol/L (2.34 to 4.59) and mean preoperative PTH was equal to 2.6 times the upper normal limit (0.5 to 24.1). Both groups were similar for as age, sex, preoperative calcium and PTH, and histologies. Methylene blue was administered intravenously (5 mg/kg diluted in 500 cc of 5% glucose) over a period of time of one hour starting two hours prior to surgery. All 175 procedures were performed by two surgeons and duration of surgery was recorded from the anesthesiologist's notes. There were 149 adenomas (85%), 24 hyperplasias (14%), a combination of both in two, and unspecified in two others. Except for a case of acute lower back pain synchronous to the injection of the dye (which was immediately stopped), MB was well tolerated. Mean duration for the 55 interventions performed without MB was 68 minutes (35 to 140, median 60), compared to 49 minutes for the 120 procedures carried out after MB had been given (20 to 155, median 45). Differences in operative, times were highly significant (p < 10(-6) and represented a gain of time of 27%. Surgery for primary hyperparathyroidism was significantly shorter when it was preceded by the administration of MB, a dye which facilitates the identification of pathologic parathyroid gland(s).

Automatic classification of MR scans in Alzheimer's disease.

To be diagnostically useful, structural MRI must reliably distinguish Alzheimer's disease (AD) from normal aging in individual scans. Recent advances in statistical learning theory have led to the application of support vector machines to MRI for detection of a variety of disease states. The aims of this study were to assess how successfully support vector machines assigned individual diagnoses and to determine whether data-sets combined from multiple scanners and different centres could be used to obtain effective classification of scans. We used linear support vector machines to classify the grey matter segment of T1-weighted MR scans from pathologically proven AD patients and cognitively normal elderly individuals obtained from two centres with different scanning equipment. Because the clinical diagnosis of mild AD is difficult we also tested the ability of support vector machines to differentiate control scans from patients without post-mortem confirmation. Finally we sought to use these methods to differentiate scans between patients suffering from AD from those with frontotemporal lobar degeneration. Up to 96% of pathologically verified AD patients were correctly classified using whole brain images. Data from different centres were successfully combined achieving comparable results from the separate analyses. Importantly, data from one centre could be used to train a support vector machine to accurately differentiate AD and normal ageing scans obtained from another centre with different subjects and different scanner equipment. Patients with mild, clinically probable AD and age/sex matched controls were correctly separated in 89% of cases which is compatible with published diagnosis rates in the best clinical centres. This method correctly assigned 89% of patients with post-mortem confirmed diagnosis of either AD or frontotemporal lobar degeneration to their respective group. Our study leads to three conclusions: Firstly, support vector machines successfully separate patients with AD from healthy aging subjects. Secondly, they perform well in the differential diagnosis of two different forms of dementia. Thirdly, the method is robust and can be generalized across different centres. This suggests an important role for computer based diagnostic image analysis for clinical practice.

Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction.

BACKGROUND: Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI. METHODS AND RESULTS: Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from 5 independent community-based cohorts, with replication in 3 additional independent cohorts (n=6032). We examined the top single-nucleotide polymorphisms (SNPs) associated with CAC quantity for association with MI in multiple large genome-wide association studies of MI. Genome-wide significant associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top SNP: rs1333049; P=7.58×10(-19)) and 6p24 (top SNP: rs9349379, within the PHACTR1 gene; P=2.65×10(-11)) replicated for CAC and for MI. Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene). CONCLUSIONS: SNPs in the 9p21 and PHACTR1 gene loci were strongly associated with CAC and MI, and there are suggestive associations with both CAC and MI of SNPs in additional loci. Multiple genetic loci are associated with development of both underlying coronary atherosclerosis and clinical events.

Intravitreal ranibizumab (Lucentis) in the treatment of retinal angiomatous proliferation (RAP).

BACKGROUND: Retinal angiomatous proliferation (RAP) is a distinct variant of neovascular age-related macular degeneration (AMD). The aim of this study is to evaluate the functional and anatomic outcome after intravitreal ranibizumab (Lucentis) treatment in patients with RAP. METHODS: Prospective study of consecutive patients with newly diagnosed or recurrent RAP treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between March 2006 and December 2007. Baseline and monthly follow-up visits included best-corrected visual acuity (BCVA), fundus exam and optical coherence tomography. Fluorescein and indocyanine green angiography were performed at baseline and repeated at least every 3 months. RESULTS: Thirty-one eyes of 31 patients were treated with 0.5 mg of intravitreal ranibizumab for RAP between March 2006 and December 2007. The mean age of the patients was 82.6 years (SD:4.9). The mean number of intravitreal injections administered for each patient was 5 (SD: 2.4, range 3 to 12). The mean follow up was 13.4 months (SD: 3, range 10 to 22). The baseline mean logMAR BCVA was 0.72 (SD: 0.45) (decimal equivalent of 0.2). The mean logMAR BCVA was improved significantly (P < 0.0001) at the last follow-up to 0.45, SD: 0.3 (decimal equivalent 0.35). The visual acuity (VA) improved by a mean of 2.7 lines (SD 2.5). Mean baseline central macular thickness (CMT) was 376 microm, and decreased significantly to a mean of 224 microm (P < 0.001) at the last follow-up. Mean reduction of CMT was 152 microm (SD: 58). An average of 81.5% of the total visual improvement and 85% of the total CMT reduction occurred during the first post-operative month after one intravitreal injection of ranibizumab. During follow-up, an RPE tear occurred in one eye (3.2%) of the study group. No injection complications or systemic drug-related side-effects were noted during the follow-up period. CONCLUSIONS: Intravitreal ranibizumab injections appeared to be an effective and safe treatment for RAP, resulting in visual gain and reduction in macular thickness. Further long-term studies to evaluate the efficacy of intravitreal ranibizumab in RAP are warranted.

First nationwide study on driving under the influence of drugs in Switzerland.

In Switzerland, a two-tier system based on impairment by any psychoactive substances which affect the capacity to drive safely and zero tolerance for certain illicit drugs came into force on 1 January 2005. According to the new legislation, the offender is sanctioned if Delta(9)-tetrahydrocannabinol THC is >or=1.5ng/ml or amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), cocaine, free morphine are >or=15ng/ml in whole blood (confidence interval+/-30%). For all other psychoactive substances, impairment must be proven in applying the so-called "three pillars expertise". At the same time the legal blood alcohol concentration (BAC) limit for driving was lowered from 0.80 to 0.50g/kg. The purpose of this study was to analyze the prevalence of drugs in the first year after the introduction of the revision of the Swiss Traffic Law in the population of drivers suspected of driving under the influence of drugs (DUID). A database was developed to collect the data from all DUID cases submitted by the police or the Justice to the eight Swiss authorized laboratories between January and December 2005. Data collected were anonymous and included the age, gender, date and time of the event, the type of vehicle, the circumstances, the sampling time and the results of all the performed toxicological analyses. The focus was explicitly on DUID; cases of drivers who were suspected to be under the influence of ethanol only were not considered. The final study population included 4794 DUID offenders (4243 males, 543 females). The mean age of all drivers was 31+/-12 years (range 14-92 years). One or more psychoactive drugs were detected in 89% of all analyzed blood samples. In 11% (N=530) of the samples, neither alcohol nor drugs were present. The most frequently encountered drugs in whole blood were cannabinoids (48% of total number of cases), ethanol (35%), cocaine (25%), opiates (10%), amphetamines (7%), benzodiazepines (6%) and methadone (5%). Other medicinal drugs such as antidepressants and benzodiazepine-like were detected less frequently. Poly-drug use was prevalent but it may be underestimated because the laboratories do not always analyze all drugs in a blood sample. This first Swiss study points out that DUID is a serious problem on the roads in Switzerland. Further investigations will show if this situation has changed in the following years.

Facteurs de risque fracturaire, nouveaux traitements: comment evolue la prise en charge de l'ostéoporose de la personne agée [Fracture risk, new treatments: how does the management of the osteoporosis of elderly change?]

Osteoporosis of elderly is a growing medical, economic and health-care problem. It is due to the increase of the life expectancy and the number of osteoporotic fractures. With the new Swiss-specific tool FRAX and the development of inpatients fracture trajectory, we can better identify patients with high risk of fracture. An appropriate treatment can be proposed more quickly. The follow-up of bone markers increases the treatment efficiency. With a better identification, treatment and follow-up of osteoporosis of elderly patients, we can ameliorate the patient's quality of life and decrease the number of osteoporotic fractures with a good cost-effectiveness ratio.

Hip fracture incidence in the canton of Vaud, Switzerland, 1986-1991.

The objective of this study was to estimate the incidence of hip fracture in the canton of Vaud, Switzerland (total population 584 000), for the period 1986-1991 using routine hospital discharge data collected by the Cantonal Service of Statistical Research and Information (SCRIS). For the survey period, the estimated average annual crude incidence rate of hip fractures was 167 per 100 000 persons aged 20 or older (241 for women and 84 for men). For the population aged 50 years or older, the crude incidence rate was 388 per 100 000 persons (546 for women and 185 for men). The average annual age-specific rates rose exponentially by successive 5-year age groups. The median age of patients at the time of the fracture was 82 years in women and 74 years in men. There was no significant difference between the total number of cervical and trochanteric fractures. Between the ages of 20 and 84 years, the cumulative risk for a woman to be admitted to hospital with a hip fracture was twice that of a man (15.8% vs 7.8%). From 1986 to 1991, the age- and sex-adjusted incidence, like the ratio of cervical to trochanteric fractures, did not show any significant trend, although it was consistent with an increase in men (p=0.09). However, the annual number of fractures rose from 644 to 776, particularly among very aged men. The mean length of stay in the acute care hospital fell from 38 days in 1986 to 25 days in 1991. Finally, the comparison of these results with those obtained in 1986 for the same population from more exhaustive sources has confirmed the provision of a consistent, although overestimated, assessment of hip fracture incidence by means of these routine hospital statistics in the canton of Vaud, Switzerland.