Are obesity and asthma in school-age children still strongly related to breastfeeding in infancy? - A real-life study.

OBJECTIVE: Although breastfeeding has been suggested as a candidate for the prevention of obesity and allergies, recent studies have reported mixed results. The aim of the study was (1) to assess breastfeeding length in obese children or children with allergic diseases compared to healthy children; (2) to evaluate the impact of the duration of breastfeeding on the incidence of obesity, allergy rhinitis and asthma. PATIENTS AND METHODS: 408 children were evaluated (mean age 11.9±3.7 years; M/F 220/188) and divided into three groups (Obesity, n=103; Allergy, n=163; and Healthy, n=142). Breastfeeding history was collected during an interview. Physical examination, anthropometry, allergy (skin prick test with aeroallergens; Allergopharma) and a spirometry (Jaeger) assessment were performed in each participant. RESULTS: Most of the children (75%) were breastfed with a mean duration of 7.5 months (range 0-36; SD=7.9 months). The time of breastfeeding was longer in the healthy compared to the obese and allergic groups (p=0.003) and was correlated with BMI centile in all groups of subjects (R Spearman = -0.2, p<0.05). There was a higher number of subjects with hypersensitivity to the allergen of house dust mites and animals in the non-breastfed compared to the breastfed children (p<0.003, p<0.000, respectively). Non-breastfed children compared to the breastfed presented more often asthma (chi2=3.6 df=1 p=0.05), but not allergic rhinitis (chi2=9.0 df=1 p=0.002). Non-breastfed asthmatics, compared to the breastfed asthmatics, presented a significantly higher severity of asthma (OR=0.43; p=0.008). In multivariate regression models, a short breastfeeding time was associated with a higher risk of both obesity and asthma. CONCLUSIONS: School-age children with obesity and asthma were breastfed less often and for a shorter duration than their healthy peers. Longer breastfeeding may result in a reduced number of children with obesity, asthma, and allergy to house dust mites, but further investigation is needed on a larger population of school-age children.

COPD in Germany: Use of Diagnostic Measures Including Blood Eosinophil Counts in Daily Practice.

BACKGROUND: Accumulating evidence on the role of blood eosinophils as a biomarker prompted the Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee to refine the existing treatment algorithm by incorporating eosinophil counts into treatment recommendations. However, there is a lack of data on when, why and how frequently such blood tests and other measures are being performed by German private respiratory specialists. METHODS: A questionnaire evaluating doctors' opinions on the use of diagnostic measures at initial diagnosis and during follow-up, including blood eosinophil count in patients with COPD, was completed by 27 respiratory specialists. Medical records from the past 12 months of 251 patients treated by the same physicians were reviewed retrospectively to investigate the use of these measures. RESULTS: Body plethysmography (100 % of doctors) and chest X-ray (96.3 %) were the most commonly used measures according to the doctor's questionnaire; other measures were COPD assessment test (CAT; 85.2 %) and blood eosinophil count (81.5 %). The evaluation of patients' medical records revealed that body plethysmography was performed in 72.7 %, the CAT in 61.8 % and chest X-ray in 40.6 % of patients. Blood eosinophil count was measured in 7.2 %. CONCLUSIONS: In line with the GOLD recommendations, these results confirm that lung function, imaging and patient-reported outcome questionnaires play a crucial role in managing COPD. Our analyses reveal that measurement of the blood eosinophil count gained importance due to physicians' increased awareness of these cells as a useful biomarker. However, this test seems to be performed mainly for initial diagnosis and not on a regular basis.

[Intravesical salpingiosis: case report and review of the literature]. / Intravesikale Salpingiose ­ Fallbericht und Literaturüberblick.

Endosalpingiosis of the urinary bladder is a rare benign condition characterised by the presence of ectopic endosalpingeal tissue in the bladder. If histology shows two or more Müllerian-derived components, this condition is referred to as Müllerianosis.To our knowledge less than 20 cases of Müllerianosis and 5 cases of endosalpingiosis have been documented in the literature.Although the pathogenesis remains unclear, two theories exist. The implantation theory assumes that Müllerian-derived tissue gets implanted in the wall of the urinary bladder during pelvic surgery. The second theory proposes a metaplastic origin of the disease.Patients suffering from endosalpingiosis or Müllerianosis may present with symptoms such as suprapubic pain, frequent urination, dysuria or gross haematuria, possibly with a cyclical appearance.We present the case of a 40-year-old female patient, who primarily presented with painful haematuria and was diagnosed with endosalpingiosis and treated by transurethral resection. Also we review the current literature.

A multicentre, randomized, single-blind, parallel-group study comparing the efficacy and tolerability of benzoyl peroxide 3%/clindamycin 1% with azelaic acid 20% in the topical treatment of mild-to-moderate acne vulgaris.

BACKGROUND: Mild-to-moderate acne vulgaris is treated with a range of mono- and combination therapies; however, clinical evidence is still required to optimize treatment recommendations. OBJECTIVE: To compare the efficacy, tolerability and safety of a combination of benzoyl peroxide 3% and clindamycin 1% (BPO + CLN) with azelaic acid 20% (AzA) for the topical treatment of mild-to-moderate acne vulgaris. METHOD: This was a randomized, assessor-blinded, parallel-group, multicentre study conducted in Germany. Patients with a confirmed diagnosis of acne vulgaris, aged 12-45 years, were randomized 1 : 1 to once-daily BPO + CLN gel or twice-daily AzA cream for up to 12 weeks. The primary endpoint was the percentage change in inflammatory lesions from baseline at Week 4. Secondary endpoints included total and inflammatory lesion counts and tolerability assessments. For selected secondary endpoints, inductive statistical analysis was performed post hoc. Patient safety was assessed by adverse event (AE) monitoring. RESULTS: Efficacy was assessed in the modified intent-to-treat (mITT) population [patients using ≥1 dose of study medication (ITT), plus baseline and ≥1 post-baseline lesion count (n = 215)]. There was a statistically significant difference in the primary endpoint, with a median decrease of -52.6% for BPO + CLN (n = 107) vs.-38.8% for AzA (n = 108; P = 0.0004). There was also a greater difference in secondary lesion endpoints at Week 12, with a median decrease in inflammatory lesions of -78.8% and -65.3% and total lesions of -69.0% and -53.9% with BPO + CLN and AzA, respectively (both P < 0.0001). Tolerability was acceptable for both treatments. Overall, 55.6% (BPO + CLN) and 69.7% (AzA) of patients reported treatment-emergent AEs, and 15.7% and 35.8% of patients experienced application site reactions with BPO + CLN (24 events; 17 patients) and AzA (60 events; 39 patients) treatment, respectively (ITT population). CONCLUSION: BPO + CLN demonstrated greater efficacy than AzA in the treatment of mild-to-moderate acne vulgaris and has a positive tolerability and safety profile.

[Selective and non-invasive monitoring of the posterior columns and pyramidal tract during surgery of the spine and spinal cord]. / Monitorage non invasif et sélectif des cordons postérieurs et de la voie pyramidale pendant les chirurgies du rachis et de la moelle épinière.

For intra-operative neurophysiological monitoring during spine and spinal cord surgery, the challenge is to detect, in real-time, the occurrence of neurological impairment at onset in order to remedy the problem as quickly as possible before it becomes definitely acquired and irreversible. The past three decades were marked by considerable technical progress. Feasibility and reliability have now reached a very high level. A multimodal approach combining simultaneous monitoring of somatosensory and motor pathways has enabled a considerable decline in the rate of false negatives reported in the 80s when somatosensory evoked potentials (SSEP) were monitored alone. Several methods of monitoring are described in the literature. Combining transcranial electric stimulation of muscle motor evoked potentials (mMEP) and cortical SSEP allows non-invasive and selective monitoring of the posterior columns and pyramidal tract. One of the most widely used techniques internationally backed by a broad consensus within the International Society of Intra-operative Neurophysiology (ISIN), this technique remains exceptional in French-speaking countries. We expose here the methodological aspects for the readers of La Revue Neurologique.

Everolimus improves experimental autoimmune uveoretinitis.

The efficacy and action mechanism of everolimus in the treatment of experimental autoimmune uveoretinitis (EAU) was analyzed. Disease was induced in B10.RIII mice by immunization with human interphotoreceptor-retinoid-binding protein peptide 161-180 (hIRBPp161-180). Everolimus was administered by oral gavage (5 mg/kg/d) beginning either two days before or 14 days after immunization. Everolimus significantly reduced the histopathological uveitis score compared to sham-treated mice. To examine the effect on the antigen-specific immune response, proliferation ([(3)H]-thymidine test) and delayed-type hypersensitivity (DTH) response were measured. Furthermore, content of T-helper-1, -2, and -17 cytokines were analyzed intraocularly (Bead Array) and in cell culture supernatants from splenocytes (sandwich ELISA). To study the effect on the humoral immune response the presence of antigen-specific serum antibodies was tested (indirect ELISA). The DTH, the humoral immune response, the proliferation of splenocytes and the intraocular Th1, Th2, Th17 cytokine content and in vitro production of Th1 and Th17 cytokines were impaired after everolimus treatment. The study of CD4+CD25+FoxP3+ regulatory T cells (T(reg)) in peripheral blood, draining lymph nodes, and spleen by flow cytometry showed an increased number of splenic T(reg) in mice of the everolimus therapy group. Furthermore the T(reg) of these mice had a higher suppressive capacity than cells from sham-treated mice. These results indicate that the immunosuppressive effect of everolimus on EAU was associated with the suppression of pathogenic effector responses and induction of regulatory T cells.

Transport, separation, and accumulation of proteins on supported lipid bilayers.

Transport, separation, and accumulation of proteins in their natural environment are central goals in protein biotechnology. Miniaturized assays of supported lipid bilayers (SLBs) have been proposed as promising candidates to realize such technology on a chip, but a modular system for the controlled transport of membrane proteins does not exist. In this letter, we demonstrate that standing surface acoustic waves drive the in-plane redistribution of proteins on planar SLBs over macroscopic distances (3.5 mm). Accumulation of proteins in periodic patterns of about 10-fold protein concentration difference is accomplished and shown to relax into the homogeneous state by diffusion. Different proteins separate in individual fractions from a homogeneous distribution and are transported and accumulated into clusters using beats. The modular planar setup has the potential of integrating other lab-on-a-chip tools, for monitoring the membrane-protein integrity or adding microfluidic features for blood screening or DNA analysis.

Comparison of zirconia and titanium implants after a short healing period. A pilot study in minipigs.

The aim of this animal study was to investigate and compare the osseointegration of zirconia and titanium dental implants. 14 one-piece zirconia implants and 7 titanium implants were inserted into the mandibles of 7 minipigs. The zirconia implants were alternately placed submerged and non-submerged. To enable submerged healing, the supraosseous part was removed, using a diamond saw. The titanium implants were all placed submerged. After a healing period of 4 weeks, a histological analysis of the soft and hard tissue and a histomorphometric analysis of the bone-implant contact (BIC) and relative peri-implant bone-volume density (rBVD; relation to bone-volume density of the host bone) was performed. Two zirconia implants were found to be loose. All other implants were available for evaluation. For submerged zirconia and titanium implants, the implant surface showed an intimate connection to the neighbouring bone, with both types achieving a BIC of 53%. For the non-submerged zirconia implants, some crestal epithelial downgrowth could be detected, with a resultant BIC of 48%. Highest rBVD values were found for submerged zirconia (80%), followed by titanium (74%) and non-submerged zirconia (63%). The results suggest that unloaded zirconia and titanium implants osseointegrate comparably, within the healing period studied.

Co-expression of KLK6 and KLK10 as prognostic factors for survival in pancreatic ductal adenocarcinoma.

Kallikreins play an important role in tumour microenvironment and as cancer biomarkers in different cancer entities. Previous studies suggested an upregulation of KLK10 and KLK6 in pancreatic ductal adenocarcinoma (PDAC). Therefore, we evaluated the clinicopathological role of these kallikreins and their value as biomarkers in PDAC.Differential expression was validated by DNA-microarrays and immunohistochemistry in normal and malignant pancreatic tissues. Sera concentrations of both kallikreins were evaluated using ELISA. In silico analysis of possible protein interactions and gene silencing of KLK10 in vitro using siRNAs gave further insights in the pathomechanisms.Gene expression analysis and immunohistochemistry demonstrated a strong expression for KLK10 and KLK6 in PDAC. Statistical analysis showed that co-expression of these kallikreins correlated with an R1-resection status (P=0.017) and worse outcome for overall survival (P=0.031). Multivariate analysis proofed that co-expression is an independent prognostic factor for survival (P=0.043). Importantly, KLK10 knockdown in AsPC-1 cells significantly reduced cell migration, whereas computational analysis suggested interaction of KLK6 with angiogenetic factors as an important mechanism.Co-expression of KLK10 and KLK6 plays an unfavourable role in PDAC. Our results suggest that this effect is likely mediated by an interaction with the factors of the extracellular matrix and enhancement of cancer cell motility.

Visualisation of metastatic oesophageal and gastric cancer and prediction of clinical response to palliative chemotherapy using 18FDG PET.

AIM: This study assessed the value of (18)F-deoxyglucose positron emission tomography (FDG-PET) for visualisation and early metabolic response assessment in metastatic gastro-oesophageal cancer. PATIENTS, METHODS: Twenty-six patients who were treated for metastatic disease (20 adenocarcinomas, 6 squamous cell cancers) underwent FDG-PET before and two weeks after the onset of palliative chemotherapy with either oxaliplatin + 5-FU/LV or with docetaxel + capecitabine. PET results were validated according to clinical response based on RECIST criteria. RESULTS: Twenty-four tumours (92%) could be visualised by FDG-PET and were also assessable by a second PET scan at 2 weeks. The 2 tumours that were not detectable by PET were both gastric cancers belonging to the non-intestinal subtype according to Lauren. Median time to progression and overall survival were not significantly different for metabolic responders and non-responders (6.3 vs 5.3 months and 14.1 vs 12.5 months, respectively). CONCLUSION: In this heterogeneous study population, FDG-PET had a limited accuracy in predicting clinical response. However, the metabolic response prediction was particularly good in the subgroup of patients with oesophageal squamous cell cancer. Therefore, FDG-PET and assessment of cancer therapy clearly merits further investigation in circumscribed patient populations with metastatic disease.

Cardiac index monitoring by pulse contour analysis and thermodilution after pediatric cardiac surgery.

OBJECTIVES: To validate a new device (PiCCO system; Pulsion Medical Systems, Munich, Germany), we compared cardiac index derived from transpulmonary thermodilution and from pulse contour analysis in pediatric patients after surgery for congenital heart disease. We performed a prospective clinical study in a pediatric cardiac intensive care unit of a university hospital. METHODS: Twenty-four patients who had had cardiac surgery for congenital heart disease (median age 4.2 years, range 1.4-15.2 years) were investigated in the first 24 hours after admission to the intensive care unit. A 3F thermodilution catheter was inserted in the femoral artery. Intracardiac shunts were excluded by echocardiography intraoperatively or postoperatively. Cardiac index derived from pulse contour analysis was documented in each patient 1, 4, 8, 12, 16, 20, and 24 hours after admission to the intensive care unit. Subsequently, a set of three measurements of thermodilution cardiac indices derived by injections into a central venous line was performed and calculated by the PiCCO system. RESULTS: The mean bias between cardiac indices derived by thermodilution and those derived by pulse contour analysis over all data points was 0.05 (SD 0.4) L x min x m(-2) (95% confidence interval 0.01-0.10). A strong correlation between thermodilution and contour analysis cardiac indices was calculated (Pearson correlation coefficient r = 0.93; coefficient of determination r2 = 0.86). CONCLUSIONS: Pulse contour analysis is a suitable method to monitor cardiac index over a wide range of indices after surgery for congenital heart disease in pediatric patients. Pulse contour analysis allows online monitoring of cardiac index. The PiCCO device can be recalibrated with the integrated transpulmonary thermodilution within a short time frame.

Acceleration of AMPA receptor kinetics underlies temperature-dependent changes in synaptic strength at the rat calyx of Held.

It is well established that synaptic transmission declines at temperatures below physiological, but many in vitro studies are conducted at lower temperatures. Recent evidence suggests that temperature-dependent changes in presynaptic mechanisms remain in overall equilibrium and have little effect on transmitter release at low transmission frequencies. Our objective was to examine the postsynaptic effects of temperature. Whole-cell patch-clamp recordings from principal neurons in the medial nucleus of the trapezoid body showed that a rise from 25 degrees C to 35 degrees C increased miniature EPSC (mEPSC) amplitude from -33 +/- 2.3 to -46 +/- 5.7 pA (n=6) and accelerated mEPSC kinetics. Evoked EPSC amplitude increased from -3.14 +/- 0.59 to -4.15 +/- 0.73 nA with the fast decay time constant accelerating from 0.75 +/- 0.09 ms at 25 degrees C to 0.56 +/- 0.08 ms at 35 degrees C. Direct application of glutamate produced currents which similarly increased in amplitude from -0.76 +/- 0.10 nA at 25 degrees C to -1.11 +/- 0.19 nA 35 degrees C. Kinetic modelling of fast AMPA receptors showed that a temperature-dependent scaling of all reaction rate constants by a single multiplicative factor (Q10=2.4) drives AMPA channels with multiple subconductances into the higher-conducting states at higher temperature. Furthermore, Monte Carlo simulation and deconvolution analysis of transmission at the calyx of Held showed that this acceleration of the receptor kinetics explained the temperature dependence of both the mEPSC and evoked EPSC. We propose that acceleration in postsynaptic AMPA receptor kinetics, rather than altered presynaptic release, is the primary mechanism by which temperature changes alter synaptic responses at low frequencies.

Randomized clinical trial of vertical or transverse laparotomy for abdominal aortic aneurysm repair.

BACKGROUND: The objective of this randomized trial was to evaluate the incidence of incisional hernia after transverse or vertical incisions for open aortic aneurysm repair. METHODS: The study group comprised 69 patients who underwent elective aneurysm repair between November 1998 and November 2000 (60 men, nine women; mean age 72.8 (range 56-95) years). Patients were randomized to a transverse (n = 32) or vertical (n = 37) incision for the procedure. Of the 42 patients who were still alive in February 2004, 37 (15 transverse, 22 vertical incisions) attended for review. Laparotomy scars were assessed both clinically and ultrasonographically by the same examiner, to look for incisional hernia. RESULTS: Mean follow-up was 4.4 years. A multivariable logistic regression analysis revealed that the type of incision was the only parameter that significantly influenced the rate of incisional hernia: six of 15 patients with a transverse laparotomy versus 20 of 22 with a vertical laparotomy (P = 0.010). CONCLUSION: The incidence of incisional hernia was high after aortic aneurysm repair, but was lower in patients who had a transverse incision.

Phase II study of weekly oxaliplatin plus infusional fluorouracil and folinic acid (FUFOX regimen) as first-line treatment in metastatic gastric cancer.

Oxaliplatin plus fluorouracil/folinic acid (5-FU/FA) every 2 weeks has shown promising activity in advanced gastric cancer. This study assessed the efficacy and safety of weekly oxaliplatin plus 5-FU/FA (FUFOX regimen) in the metastatic setting. Patients with previously untreated metastatic gastric cancer received oxaliplatin (50 mg m(-2)) plus FA (500 mg m(-2), 2-h infusion) followed by 5-FU (2000 mg m(-2), 24-h infusion) given on days 1, 8, 15 and 22 of a 5-week cycle. The primary end point of this multicentre phase II study was the response rate according to RECIST criteria. A total of 48 patients were enrolled. Median age was 62 years and all patients had metastatic disease, with a median number of three involved organs. The most common treatment-related grade 3/4 adverse events were diarrhoea (17%), deep vein thrombosis (15%), neutropenia (8%), nausea (6%), febrile neutropenia (4%), fatigue (4%), anaemia (4%), tumour bleeding (4%), emesis (2%), cardiac ischaemia (2%) and pneumonia (2%). Grade 1/2 sensory neuropathy occurred in 67% of patients but there were no episodes of grade 3 neuropathy. Intent-to-treat analysis showed a response rate of 54% (95% CI, 39-69%), including two complete responses. At a median follow-up of 18.1 months (range 11.2-26.2 months), median survival is 11.4 months (95% CI, 8.0-14.9 months) and the median time to progression is 6.5 months (95% CI, 3.9-9.2 months). The weekly FUFOX regimen is well tolerated and shows notable activity as first-line treatment in metastatic gastric cancer.

Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic oesophageal cancer: final results of a phase II trial.

Capecitabine and docetaxel have single-agent activity in upper gastrointestinal tumours, and have together demonstrated preclinical synergy and a survival benefit in breast cancer, and high response rates in first-line metastatic gastric cancer. This trial assessed the efficacy, safety and feasibility of capecitabine in combination with docetaxel in patients with metastatic oesophageal cancer. In all, 24 patients with advanced disease (17 squamous cell carcinoma and seven adenocarcinoma) received oral capecitabine (1000 mg m(-2) twice daily on days 1-14) plus intravenous docetaxel (75 mg m(-2) on day 1) every 3 weeks as first- (n = 16) or second-line (n = 8) therapy. Patients received a median of four cycles of treatment (range, 0-6). The median follow-up is 16.5 months (range, 7.9-21.4 months). Intent-to-treat efficacy analysis showed an overall response rate of 46%. Of the 11 responders (one complete and 10 partial), nine of 16 (56%) received first-line and two of eight (25%) received second-line therapy. The median time to progression was 6.1 months (95% confidence interval (CI), 4.5-7.7 months). The median survival was 15.8 months (95% CI, 7.8-23.9 months). Severe adverse events (grade 3/4) reported were: neutropenia (42%, including febrile neutropenia 8%), hand-foot syndrome (29%), diarrhoea (13%), sensory neuropathy (13%), anaemia (8%) and fatigue (8%). Capecitabine plus docetaxel has a manageable adverse event profile and very promising activity in metastatic oesophageal cancer, at least comparable to other doublet regimens. Therefore, the combination merits further investigation in this setting.

[MS registry in Germany--design and first results of the pilot phase]. / MS-Register in Deutschland -- Design und erste Ergebnisse der Pilotphase.

In the summer of 2001, a nationwide epidemiological multiple sclerosis (MS) register was initiated under the auspices of the German MS Society (DMSG). This project aimed at collecting epidemiological data on the number of patients with MS, course of the disease, and their social situation in Germany. During the 2-year pilot phase, five MS centers with various regional differences and treatment methods participated, leading to a representative selection of patients. In December 2003, standardised data sets of 3,458 MS patients were available for evaluation. After examining the quality of the data, 3,223 sets remained for further analysis. The demographics were similar to those obtained from other epidemiological studies: 72% of the patients were female, mean age was 42.9+/-11.2 years, mean disease duration 12.6+/-8.7 years, and 64% suffered from the relapsing-remitting form of the disease. The median EDSS was 3.0, and 69% of patients had an EDSS

Male factors determining the outcome of intracytoplasmic sperm injection with epididymal and testicular spermatozoa.

During a period of 8 years, 1,079 intracytoplasmic sperm injection (ICSI) procedures with aspirated epididymal or testicular spermatozoa were performed. Epididymal spermatozoa were used in 172 cycles and testicular spermatozoa or spermatids in 907 cycles. Multiple biopsies were obtained from at least two different locations in the testes. Retrieved spermatozoa were used after cryopreservation (frozen) or immediately after aspiration (fresh). Three hundred patients had obstructive azoospermia (OA) or ejaculation failure. In 414 cases, azoospermia was caused by impaired spermatogenesis resulting from maldescended testes, chemotherapy/radiotherapy, or by Sertoli-cell-only syndrome, genetic disorders or unknown aetiology. Transfer rates, pregnancy rates and birth rates per ICSI cycle showed no statistically significant differences between testicular and epididymal spermatozoa in men with OA (28% average birth rates in both cases). However, birth rates differed significantly with regard to the status of spermatogenesis. Treatment of men with nonobstructive azoospermia (NOA) resulted in a birth rate of 19% per cycle. In all patient groups, there was no difference in the birth rates achieved with fresh and cryopreserved spermatozoa. While testicular volume, follicle-stimulating hormone level and age of the male patient are no statistically significant prognostic factors, the underlying cause of azoospermia is the most important factor determining the outcome of ICSI with epididymal and testicular spermatozoa. The pregnancy rate is lower in NOA patients than in those with OA.