Opdam F.L.,Leiden University |
Dezentje V.O.,Leiden University |
Den Hartigh J.,Leiden University |
Modak A.S.,Cambridge Isotope Laboratories Inc. andover |
And 5 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2013
Purpose: Adjuvant therapy with tamoxifen significantly reduces breast cancer recurrence and mortality in estrogen receptor positive disease. CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Endoxifen is thought to be a main determinant for clinical efficacy in breast cancer patients using tamoxifen. As the large interindividual variation in endoxifen levels is only partly explained by CYP2D6 genotype, we explored the use of the 13C-dextromethorphan breath test (DM-BT) for phenotyping CYP2D6 and to predict serum steady-state endoxifen levels as a marker for clinical outcome in breast cancer patients using tamoxifen. Methods: In 65 patients with early breast cancer using tamoxifen, CYP2D6 phenotype was assessed by DM-BT. CYP2D6 genotype using Amplichip and serum steady-state levels of endoxifen were determined. Genotype was translated into the gene activity score and into ultrarapid, extensive, heterozygous extensive, intermediate or poor metabolizer CYP2D6 predicted phenotype. Results: CYP2D6 phenotype determined by the DM-BT explained variation in serum steady-state endoxifen levels for 47.5 % (R 2 = 0.475, p < 0.001). Positive and negative predictive values for a recently suggested threshold serum level of endoxifen (5.97 ng/mL) for breast cancer recurrence rate were 100 and 90 %, respectively, for both CYP2D6 phenotype by DM-BT (delta-over-baseline at t = 50 min (DOB50) values of 0.7-0.9) and genotype (CYP2D6 gene activity score of 1.0). Conclusion: DM-BT might be, along with CYP2D6 genotyping, of value in selection of individualized endocrine therapy in patients with early breast cancer, especially when concomitant use of CYP2D6 inhibiting medication alters the phenotype. © 2012 Springer-Verlag Berlin Heidelberg.
Lerner S.,Surgery |
Vidal C.,Mount Sinai School of Medicine
Transplant Infectious Disease | Year: 2011
Dematiaceous fungi are an opportunistic pathogen seen in solid organ transplant recipients. We report 2 cases of Exophiala infection and review the medical literature to summarize the spectrum of disease this pathogen can cause in this patient population. © 2010 John Wiley & Sons A/S.
Nanninga G.L.,Surgery |
de Leur K.,Surgery |
Panneman M.J.M.,Consumer and Safety Institute |
van der Elst M.,Surgery |
Age and Ageing | Year: 2014
Background: age-related issues are expected to rise in the coming decades. Osteoporosis, falls and fractures are major public health issues among elderly. Pelvic fractures are associated with a serious morbidity and hospitalisation rate. We therefore performed a study to determine trends in incidence and age-specific rates of pelvic fracture-related hospitalisations among elderly (≥65 years).Methods: a secular trend analysis of all hospitalisations due to a pelvic fracture among older adults, using the National Medical Registration, 1986-2011, The Netherlands.Results: the total number of hospitalisations due to a pelvic fracture increased from 887 in 1986 to 2,013 admissions in 2011 (127% increase). The overall age-adjusted incidence rate increased from 5.19 in 1986 to 7.14 per 10,000 population in 2011 (37.5% increase). The incidence rate increased with age and was higher for females. The Percentual Annual Change was 1.2% (95% CI: 0.9;1.5) for older males, and 1.0% (95% CI: 0.9;1.2) for females, respectively. The mean length of hospital stay decreased between 1991 and 2011 to 12.0 days (53.4% decrease). The total number of hospital-bed-days decreased from 29,002 days in 1991 to 17,283 days in 2011 (40.4% decrease), despite an increase in absolute number of admissions.Conclusion: absolute numbers and incidence rates of pelvic fractures are increasing among the older Dutch population. Considering the fact the general population is growing older, an increasing number of elderly suffer from pelvic fractures. Attention on osteoporosis screening and prevention of falls in elderly remains important, in order to limit-related healthcare costs in the future. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.
Perez-Mora N.,Medical Science Research |
Goren A.,University Of Rome rconi |
Velasco C.,Surgery |
Bermudez F.,Business Development
Dermatologic Therapy | Year: 2014
Acute telogen effluvium (ATE) is often associated with female androgenetic alopecia (FAA), but predictive factors of ATE-FAA association and clinical factors or therapies that may influence the progression of ATE to chronic telogen effluvium (CTE) have not been reported. We have identified predictive factors of ATE-FAA association and retrospectively evaluated the impact of therapies on the progression to CTE. Conclusions are as follows: (i) Triggering cause is a significant independent factor that predicts association of ATE with FAA. (ii) Triggering causes with higher risk of concurrent FAA are severe diet, iron deficiency, and thyroid dysfunction. (iii) Patients suffering ATE may benefit from different therapeutic approaches (depending on which is the triggering cause) to prevent or treat the association with FAA. (iv) Minoxidil use shows a trend to lower the percentage of progression to CTE. (v) Apart from treating the precipitating cause, the different additional oral treatments used have not shown any correlation with progression to CTE. © 2013 Wiley Periodicals, Inc.
Krueger D.,TU Munich |
Michel K.,TU Munich |
Zeller F.,Surgery |
Demir I.E.,TU Munich |
And 3 more authors.
Journal of Physiology | Year: 2016
Knowledge on basic features of epithelial functions in the human intestine is scarce. We used Ussing chamber techniques to record basal tissue resistance (R-basal) and short circuit currents (ISC; secretion) under basal conditions (ISC-basal) and after electrical field stimulation (ISC-EFS) of nerves in 2221 resectates from 435 patients. ISC-EFS was TTX-sensitive and of comparable magnitude in the small and large intestine. ISC-EFS or R-basal were not influenced by the patients' age, sex or disease pathologies (cancer, polyps, diverticulitis). Ion substitution, bumetanide or adenylate cyclase inhibition studies suggested that ISC-EFS depended on epithelial cAMP-driven chloride and bicarbonate secretion but not on amiloride-sensitive sodium absorption. Although atropine-sensitive cholinergic components prevailed for ISC-EFS of the duodenum, jejunum and ileum, PG97-269-sensitive [vasoactive intestinal peptide (VIP) receptor1 antagonist] VIPergic together with l-NAME-sensitive nitrergic components dominated the ISC-EFS in colonic preparations. Differences in numbers of cholinergic or VIPergic neurons, sensitivity of epithelial muscarinic or VIP receptors, or stimulus frequency-dependent transmitter release were not responsible for the region-specific transmitter contribution to ISC-EFS. Instead, the low atropine-sensitivity of ISC-EFS in the colon was the result of high cholinesterase activity because neostigmine revealed cholinergic components. Colonic ISC-EFS remained unchanged after tachykinin, P2X, P2Y or A1 and A2 receptor blockade. R-basal was smaller and ISC-basal was higher in the small intestine. TTX and bumetanide decreased ISC-basal in all regions, suggesting nerve-dependent secretory tone. ISC-basal was atropine-sensitive in the small intestine and PG97-269-sensitive in the large intestine. This comprehensive study reveals novel insights into region-specific nerve-mediated secretion in the human small and large intestine. © 2016 The Physiological Society.
Schemann M.,TU Munich |
Hafsi N.,TU Munich |
Michel K.,TU Munich |
Kober O.I.,Glaxosmithkline |
And 7 more authors.
Gastroenterology | Year: 2010
Background & Aims: β3 Adrenoceptor (β3-AR) is expressed on adipocytes and enteric neurons. GW427353 is a human selective β3-AR agonist with visceral analgesic effects. Some of its effects may involve release of somatostatin (SST) and actions on enteric neurons. The aim of this study was to investigate the mode of action of GW427353 in human submucous neurons. Methods: Voltage sensitive dye imaging was used to record from human submucous neurons. SST release from human primary adipocytes was measured with enzyme-linked immunoabsorbent assay. Immunohistochemistry was used to detect adiponectin, β3-AR, SST, SST2 receptors, tyrosine hydroxylase (TH), and protein gene product 9.5. Results: Confocal imaging showed cytoplasmic β3-AR labeling in somata of submucous neurons and nerve varicosities. GW427353 had no direct postsynaptic actions but decreased fast synaptic input to submucous neurons. Tissue perfusion with GW427353 reduced nicotine-evoked neuronal spike frequency, an effect prevented by the β3-AR antagonist SR-59230 and the SST2-receptor antagonist CYN154806 and mimicked by the SST2 receptor agonist octreotide. Adipocytes expressed adiponectin, β3-AR, and SST. TH-positive fibers were in close proximity to adipocytes. Submucous neurons expressed SST2 receptors. Human primary adipocytes released SST in response to GW427353 in a concentration-dependent manner, an effect abolished by SR-59230. Conclusions: Inhibitory action of GW427353 involves release of SST which stimulates inhibitory SST2 receptors on human submucous neurons. Adipocytes are a potential source for SST. β3-AR activation may be a promising approach to reduce enteric neuron hyperexcitability. The action of GW427353 may be the neurophysiologic correlate of its beneficial effect in patients with irritable bowel syndrome. © 2010 AGA Institute.
Sung J.,Surgery |
Pediatric Nephrology | Year: 2012
Vesicoureteral reflux (VUR) is the most common uropathy affecting children. Compared to children without VUR, those with VUR have a higher rate of pyelonephritis and renal scarring following urinary tract infection (UTI). Options for treatment include observation with or without antibiotic prophylaxis and surgical repair. Surgical intervention may be necessary in patients with persistent reflux, renal scarring, and recurrent or breakthrough febrile UTI. Both open and endoscopic approaches to reflux correction are successful and reduce the occurrence of febrile UTI. Estimated success rates of open and endoscopic reflux correction are 98.1% (95% CI 95.1, 99.1) and 83.0% (95% CI 69.1, 91.4), respectively. Factors that affect the success of endoscopic injection include pre-operative reflux grade and presence of functional or anatomic bladder abnormalities including voiding dysfunction and duplicated collecting systems. Few studies have evaluated the long-term outcomes of endoscopic injection, and with variable results. In patients treated endoscopically, recurrent febrile UTI occurred in 0-21%, new renal damage in 9-12%, and recurrent reflux in 17-47.6% of treated ureters with at least 1 year follow-up. These studies highlight the need for standardized outcome reporting and longer follow-up after endoscopic treatment. © IPNA 2011.
Education for Primary Care | Year: 2010
This small study in Essex has shown that MSF is seen as a tool with the potential to identify learning needs and help participants change their behaviour. However, while it is seen as a tool with potential it has not been shown to have significant educational impact on established GPs. Trainees have been able to take advantage of a clear-cut system; a well-researched and designed tool and an opportunity to discuss findings, educational needs and plans with another doctor who has observed their work. Even so, the process does not appear to be good at identifying and encouraging changes in clinical behaviour. This suggests that the nMRCGP tool may need to be revised. Established GPs will need to develop a trusted tool and a recognised pathway to encourage them to make best use of the MSF process.
Journal of Arthroplasty | Year: 2012
The purpose of this multicenter study is to determine the utility of the erythrocyte sedimentation rate, C-reactive protein, and synovial fluid white blood cell (WBC) count and differential for evaluating periprosthetic joint infection (PJI) in patients with a failed unicompartmental knee arthroplasty (UKA). A total of 259 patients undergoing revision of a failed UKA were reviewed; 28 (10.8%) met the study criteria for PJI. The optimal cutoff values were 27 mm/h for the erythrocyte sedimentation rate, 14 mg/L for the C-reactive protein, 6200/. μL for the synovial fluid WBC count, and 60% for the differential. These tests are useful for diagnosing PJI after UKA with optimal cutoff values that are similar to those used for total knee arthroplasty; however, the optimal synovial WBC count was found to be somewhat higher, which may be related to the unresurfaced compartments. In addition, we found that nearly half of patients had suboptimal evaluation for PJI. © 2012 Elsevier Inc..
Lopater J.,Surgery |
Hartung O.,Surgery |
Bretelle F.,Surgery |
Obstetrics and Gynecology | Year: 2011
Background: Angiomyolipoma can worsen during pregnancy. Inferior vena cava thrombus of renal angiomyolipoma during pregnancy is rare, and threatens to cause massive emboli. We report a case of vena cava tumor thrombectomy during the second trimester of pregnancy with delayed renal tumorectomy. Case: A 34-year-old woman with bilateral known angiomyolipomas presented asymptomatic at 30 weeks of gestation with an inferior vena cava thrombus at renal follow-up ultrasonography. Retro-hepatic thrombus had fatty signal on magnetic resonance imaging (MRI). The woman had renal vein and vena cava tumor initial thrombectomy, and had normal cesarean delivery at 39 weeks of gestation. The tumor was treated by postpartum right partial nephrectomy. Conclusion: Successful angiomyolipoma isolated thrombectomy during pregnancy with delayed partial nephrectomy is possible. Angiomyolipoma needs follow-up during pregnancy with repeated renal ultrasonography. © 2011 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.