Computed Analysis of Retinal Vascular Growth After Bevacizumab Treatment of Retinopathy of Prematurity Until Age 3 Years.

PURPOSE: Premature infants, after anti-vascular endothelial growth factor injections for retinopathy of prematurity, have persistent peripheral avascular retina (PAR). PAR is ablated with laser; however, physiologic growth of the retinal vasculature in the long term has not been measured. The purposes of this study were to measure retinal vessel growth after treatment with intravitreal bevacizumab (IVB) for retinopathy of prematurity, using serial fluorescein angiography (FA), until age 3 years, and to assess the timing for providing laser ablation in PAR. METHODS: Data from an observational, longitudinal clinical study were collected. Angiographic images of eyes treated with IVB were included; imaging data from laser photocoagulation were excluded. All eyes underwent initial examination under general anesthesia with FA and photographic imaging. The retinal vessel length was measured from the temporal margin of the optic disc passing through the foveal center, and the lengths at subsequent FA were compared. To compare the changes in retinal vessel length over time in individual eyes, a paired-sample t test was performed. FINDINGS: FA images from 70 eyes (35 infants) treated with IVB were available. A total of 150 FA images were available for review; data from 125 images of good quality were used for analysis. The mean postmenstrual ages (PMAs) at first, second, third, and fourth FA were 66.2, 100.9, 135.1, and 180.7 weeks, respectively. The mean retinal vessel length was 14.177 mm at first FA and 13.199 mm at fourth FA (PMA range, 42...234 weeks). Retinal vascular lengths of individual eyes compared over time showed no statistically significant growth from the first FA to age 3 years. The changes in retinal vessel length from first to second FA were -0.117 ± 0.79 mm (p = 0.42; n = 30); from first to third FA, +0.060 ± 0.85 mm (p = 0.79; n = 15); and first to fourth FA, -0.404 ± 1.32 mm (p = 0.45; n = 7). IMPLICATIONS: Beyond 65 weeks' PMA, no meaningful retinal vascular growth occurred after IVB up to age 3 years, guiding the timing for physicians if laser photocoagulation is being considered. Future studies are needed to address retinal growth changes in the growing eyes of infants.

Lower serum adiponectin level is associated with lipodystrophy among HIV-infected men in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) study.

OBJECTIVES: Adiponectin levels are inversely related to cardiovascular risk and are low in diabetics and obese persons. We examined the association between adiponectin concentration and HIV-associated lipodystrophy, which remains unclear. METHODS: The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) was a prospective cohort study of HIV-infected adults conducted in four US cities. Lean body and fat masses were assessed using dual-energy X-ray absorptiometry scans. Using baseline data from 2004 to 2006, we defined lipodystrophy using a sex-specific fat mass ratio and performed cross-sectional analyses of associated risks using multivariable logistic regression. RESULTS: Among 440 male participants (median age 42 years; 68% non-Hispanic white; 88% prescribed combination antiretroviral therapy; median CD4 lymphocyte count 468 cells/µL; 76% with viral load < 400 HIV-1 RNA copies/mL; 5% diabetic; median body mass index 25 kg/m2 ), median concentrations of leptin and adiponectin were 3.04 ng/L [interquartile range (IQR) 1.77-5.43 ng/L] and 8005 µg/mL (IQR 4950-11 935 µg/mL), respectively. The prevalence of lipodystrophy was 14%. Lipodystrophy was significantly associated with increasing age [prevalence ratio (PR) 1.50; 95% confidence interval (CI) 1.10-2.06, per 10 years], adiponectin < 8005 µg/mL (PR 5.02; 95% CI 2.53-9.95), ever stavudine use (PR 2.26; 95% CI 1.36-3.75), CD4 cell count > 500 cells/µL (PR 2.59; 95% CI 1.46-4.61), viral load < 400 copies/mL (PR 3.98; 95% CI 1.25-12.6), highly sensitive C-reactive protein < 1.61 mg/L (PR 1.91; 95% CI 1.11-3.28) and smoking (PR 0.42; 95% CI 0.22-0.78). CONCLUSIONS: Among men in this HIV-infected cohort, the prevalence of lipodystrophy was similar to previous estimates for persons living with HIV, and was associated with lower adiponectin levels, potentially indicating increased cardiovascular disease risk.

Re-irradiation of recurrent glioblastoma as part of a sequential multimodality treatment concept.

PURPOSE: The aim of this retrospective study was to evaluate survival outcomes in well-performing, mainly, young patients receiving a sequence of all available therapeutic options for relapsed glioblastoma, including re-irradiation. METHODS: We performed a retrospective analysis of 27 patients irradiated twice for glioblastoma between 2008 and 2016. In the first line, all had surgical treatment of the tumor followed by radiotherapy with a total dose of 60 Gy and temozolomide. All re-irradiated patients were treated with a total dose of 36 Gy in 12 fractions. The endpoints were death from glioblastoma or any cause, and toxicity after re-irradiation. RESULTS: The median follow-up of survivors was 35.6 months. At the time of analysis, 25 patients had died. The median time between first and second radiotherapy was 18.9 months (6.1-58.4). Re-irradiation was performed at different time points of first, second and third progression. The median overall survival after first diagnosis was 39.2 months. Five years after first surgery, nearly 20% of the patients were alive. CONCLUSION: Carefully planned re-irradiation of the brain is a safe therapy for recurrent glioblastoma. Younger and well-performing patients benefit from all available therapy options. Every patient should be discussed in a multidisciplinary setting at each time point of tumor progression. Further prospective studies are needed to define the optimal time, dose and volume of re-irradiation.

TGF-ß1 alters esophageal epithelial barrier function by attenuation of claudin-7 in eosinophilic esophagitis.

Barrier dysfunction has been implicated in the pathophysiology of eosinophilic esophagitis (EoE). Transforming growth factor-ß1 (TGF-ß1), a potent pleiotropic molecule, is increased in EoE; however, no study has evaluated its influence on esophageal epithelial barrier. We hypothesized that TGF-ß1 regulates barrier dysfunction in EoE. We aimed to determine the role of TGF-ß1 in the epithelial barrier in models of EoE. To examine the impact of TGF-ß1 on esophageal barrier, immortalized human esophageal epithelial (EPC2-hTERT) cells were exposed to TGF-ß1 during the three-dimensional air-liquid interface (3D-ALI) model in vitro. TGF-ß1 exposure diminished EPC2-hTERT barrier function as measured by transepithelial electrical resistance (TEER) and 3 kDa Fluorescein isothiocyanate dextran paracellular flux (FITC Flux), and hematoxylin and eosin (H&E) assessment revealed prominent cellular separation. In analysis of epithelial barrier molecules, TGF-ß1 led to the specific reduction in expression of the tight-junction molecule, claudin-7 (CLDN7), and this was prevented by TGF-ß-receptor I inhibitor. Short hairpin ribonucleic acid (shRNA)-mediated CLDN7 knockdown diminished epithelial barrier function, whereas CLDN7 overexpression resulted in protection from TGF-ß1-mediated barrier dysfunction. In pediatric EoE biopsies CLDN7 expression was decreased and altered localization was observed with immunofluorescence analysis, and the TGF-ß1 downstream transcription factor, phosphorylated SMAD2/3 (pSMAD2/3), was increased. Our data suggest that TGF-ß1 participates in esophageal epithelial barrier dysfunction through CLDN7 dysregulation.

Targeting granulocyte-macrophage colony-stimulating factor in epithelial and vascular remodeling in experimental eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic antigen-mediated clinicopathologic disease of the esophagus characterized by an eosinophil-predominant inflammatory infiltrate. A clinical hallmark is extensive tissue remodeling including basal zone hyperplasia, fibrosis, and angiogenesis. However, the cellular mechanisms responsible for these processes are not fully defined. We hypothesized that targeting granulocyte-macrophage colony-stimulating factor (GM-CSF; an agonist cytokine linked with eosinophil survival and activation) would be protective in a preclinical model of EoE. METHODS: Eosinophilic esophagitis-like esophageal inflammation was induced in the L2-IL5OXA EoE mouse model, and GM-CSF production was assessed by mRNA and protein analyses. Granulocyte-macrophage colony-stimulating factor-receptor-alpha expression patterns were examined by flow cytometric and immunofluorescence analysis. L2-IL5OXA EoE mice were treated with anti-GM-CSF neutralizing antibody or isotype control and assessed for histopathological indices of eosinophilia, epithelial hyperplasia, and angiogenesis by immunohistochemistry and RT-PCR. RESULTS: Significantly increased levels of esophageal GM-CSF expression was detected in the L2-IL5OXA mouse EoE model during active inflammation. Granulocyte-macrophage colony-stimulating factor-receptor-alpha was predominantly expressed on esophageal eosinophils during EoE, in addition to select cells within the lamina propria. Anti-GM-CSF neutralization in L2-IL5OXA EoE mice resulted in a significant diminution of epithelial eosinophilia in addition to basal cell hyperplasia and vascular remodeling. This treatment response was independent of effects on esophageal eosinophil maturation or activation. CONCLUSION: Granulocyte-macrophage colony-stimulating factor is a potential therapeutic target to reduce esophageal eosinophilia and remodeling.

Phenotyping of subjects for large scale studies on patients with IBS.

BACKGROUND: Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. PURPOSE: The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu).

[Novel uses of afterbirth tissues in regenerative medicine]. / Neue Verwendungsmöglichkeiten von Nachgeburtsgewebe für die Regenerative Medizin.

INTRODUCTION: Afterbirth tissues, which include the umbilical cord, placenta, amnion, and cord blood, are usually discarded. Recent progress in regenerative medicine suggests that we re-evaluate these tissues and assess their therapeutic potential. METHODS: Firstly the unique properties of afterbirth tissues and their current use in regenerative medicine are summarised. Then we introduce the cooperation of our institutions and our experiences regarding the collection and utilisation of afterbirth tissues. RESULTS: A literature survey suggests that besides the well-known transplantation of hematopoietic stem cells from cord blood, afterbirth tissues were also used as a source of stem cells, progenitor cells, differentiated cells, and blood vessels for tissue engineering purposes. According to our own experience, the two participating OB/GYN departments and the blood donation service were able to organise a sufficient supply of umbilical cords for research purposes. The yield correlated with incentives for the midwives. A total of more than 4,300 cords was collected for experiments designed to create small caliber vessel grafts. The contamination rate was low. Birth mode significantly affected umbilical vein function, whereas ischaemia for up to 40 h did not have any deleterious effects. Umbilical veins were cryopreserved with a moderate loss of function. Fresh umbilical veins were endothelium-denuded and reseeded with endothelial cells harvested from coronary artery disease patients to generate an autologous surface. CONCLUSIONS: Afterbirth tissues have unique properties which make them ideally suited for regenerative medicine. These tissues can be procured and utilised in research facilities even in the absence of an in-house birthing centre.

CD4+ T cells from HIV-1-infected patients recognize wild-type and mutant human immunodeficiency virus-1 protease epitopes.

Human immunodeficiency virus (HIV)-1 protease is a known target of CD8+ T cell responses, but it is the only HIV-1 protein in which no fully characterized HIV-1 protease CD4 epitopes have been identified to date. We investigated the recognition of HIV-1 protease by CD4+ T cells from 75 HIV-1-infected, protease inhibitor (PI)-treated patients, using the 5,6-carboxyfluorescein diacetate succinimidyl ester-based proliferation assay. In order to identify putative promiscuous CD4+ T cell epitopes, we used the TEPITOPE algorithm to scan the sequence of the HXB2 HIV-1 protease. Protease regions 4-23, 45-64 and 73-95 were identified; 32 sequence variants of the mentioned regions, encoding frequent PI-induced mutations and polymorphisms, were also tested. On average, each peptide bound to five of 15 tested common human leucocyte antigen D-related (HLA-DR) molecules. More than 80% of the patients displayed CD4+ as well as CD8+ T cell recognition of at least one of the protease peptides. All 35 peptides were recognized. The response was not associated with particular HLA-DR or -DQ alleles. Our results thus indicate that protease is a frequent target of CD4+ along with CD8+ proliferative T cell responses by the majority of HIV-1-infected patients under PI therapy. The frequent finding of matching CD4(+) and CD8+ T cell responses to the same peptides may indicate that CD4+ T cells provide cognate T cell help for the maintenance of long-living protease-specific functional CD8+ T cells.

Factors associated with prevalent abnormal anal cytology in a large cohort of HIV-infected adults in the United States.

BACKGROUND: The prevalence of and risk factors for abnormal anal cytology among men and women with human immunodeficiency virus (HIV) infection have not been extensively investigated. METHODS: The Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN study) is a prospective cohort study of HIV-infected patients in 4 US cities. Baseline questionnaires were administered and anal samples for cytology and human papillomavirus (HPV) detection and genotyping were collected. RESULTS: Among 471 men and 150 women (median age, 41 years), 78% of participants were receiving combination antiretroviral therapy, 41% had a CD4(+) cell count of ≥500 cells/µL, and 71% had an HIV RNA viral load of <400 copies/mL. The anal cytology results were as follows: 336 participants (54%) had negative results, 96 participants (15%) had atypical squamous cells, 149 participants (24%) had low-grade squamous intraepithelial lesions, and 40 participants (6%) had high-grade squamous intraepithelial lesions. In a multivariate analysis, abnormal anal cytology was associated with number of high-risk and low-risk HPV types (adjusted odds ratio [AOR] for both, 1.28; P < .001), nadir CD4(+) cell count of <50 cells/µL (AOR, 2.38; P = .001), baseline CD4(+) cell count of <500 cells/µL (AOR, 1.75; P = .004), and ever having receptive anal intercourse (AOR, 2.51; P < .001). CONCLUSION: HIV-infected persons with multiple anal HPV types or a nadir CD4(+) cell count of <50 cells/µL have an increased risk for abnormal anal cytology.

Implementation of the scientific evidence into daily practice--example from fast-track colonic cancer surgery.

OBJECTIVE: To report the implementation and results of fast-track surgery for colonic cancer in the daily routine. METHOD: A total of 131 consecutive patients scheduled for elective colonic cancer resections entered a fast-track perioperative course after thorough information. The regimen contained: no preoperative bowel cleansing, transverse and small abdominal incisions, no drains nor tubes, mobilization and normal meal the evening on the day of surgery, epidural analgesia, oral laxatives, and a planned discharge on postoperative day 3. RESULTS: Median number of days postoperative in hospital were 4 days (range 1-46). Eighty-nine per cent experienced an uncomplicated course, 3% were readmitted within 30 days, and the 30-day mortality was 3.8%. CONCLUSION: Fast-track surgery is feasible in an unselected patient population scheduled for elective colon cancer resections without compromising quality.

Pulmonary function following completion of Minimally Invasive Repair for Pectus Excavatum (MIRPE).

UNLABELLED: Pulmonary function testing remains part of the routine preoperative investigations in patients with pectus excavatum, although there is evidence that reduced exercise capacity is predominantly due to impaired cardiovascular performance rather than ventilatory limitation. AIM OF THE STUDY: To evaluate the change of pulmonary function in patients after completion (metal bar removal) of minimally invasive repair for pectus excavatum compared to the preoperative functional results. PATIENTS AND METHODS: All patients who underwent minimally invasive repair for pectus excavatum (MIRPE) between February 2000 and June 2006 and subsequently had their metal bars removed were examined. Pulmonary function tests were performed as part of the routine pre- and postoperative protocol. Vital capacity (VC), forced expiratory volume in one second (FEV1), total lung capacity (TLC), residual volume (RV) and maximal expiratory flow rate at 25 % (MEF25) were evaluated. In addition, comparisons were made between patients with a low ( 6) pectus severity index (PSI) to establish the relative pre- to postoperative change of the above-mentioned lung function parameters. RESULTS: Fifteen patients were included in the study (14 males, 1 female). The median age at surgery was 15.9 years. The metal bar(s) were removed after a median of 37 months following the initial operation. Lung function tests were performed at a median of 32 days preoperatively and 129 days after completion of the procedure. Preoperative lung function values lay below population averages. The majority of patients had either a restrictive, obstructive or combined pulmonary disorder. Improvement was observed in all lung function parameters after metal bar removal compared to preoperative values and was significant for VC, FEV1 and the RV/TLC ratios. With regard to the severity of the deformity, although not statistically significant, patients with a higher PSI (> 6) appeared to benefit particularly from the operation. CONCLUSION: Our findings indicate that pulmonary function improves in patients after completion of minimally invasive repair of pectus excavatum. However, a review of the literature suggests that, in all probability, following surgery, patients benefit more with regard to enhanced cardiovascular performance than from improved pulmonary limitations. The value of routine testing of pre- and postoperative lung function in patients with pectus excavatum is questionable.

Proximal humerus fractures: a comparative biomechanical analysis of intra and extramedullary implants.

INTRODUCTION: The biomechanical stability of a newly developed humerus nail (Sirustrade mark) for the treatment of fractures of the proximal humerus was analyzed in comparison to established systems. In total, three randomized groups were formed (n = 4 pairs) from 12 matched pairs of human cadaver humeri. MATERIALS AND METHODS: All intact bones were mechanically characterized by five subsequent load cycles under bending and torsional loading. The bending moment at the osteotomy was 7.5 N m the torsional moment was 8.3 N m over the hole specimen length. Loading was consistently initiated at the distal epiphysis and the deformation at the distal epiphysis was continuously recorded. Prior to implant reinforcement, a defect of 5 mm was created to simulate an unstable subcapital humerus fracture. For paired comparison, one humerus of each pair was stabilized with the Sirus proximal humerus nail while the counterpart was stabilized by a reference implant. In detail, the following groups were created: Sirus versus Proximal humerus nail (PHN) with spiral blade (group I); Sirus versus PHILOS plate (group II); Sirus versus 4.5 mm AO T-plate (group III). RESULTS: The Sirus nail demonstrated significantly higher stiffness values compared to the reference implants for both bending and torsional loading. The following distal epiphyseal displacements were recorded for a bending moment of 7.5 N m at the osteotomy: Sirus I: 8.8 mm, II: 8.4 mm, III: 7.7 mm (range 6.9-10.9), PHN 21.1 mm (range 15.7-25.2) (P = 0.005), PHILOS plate 27.5 mm (range 21.6-35.8) (P < 0.001), 4.5 AO T-plate 26.3 mm (range 24.3-33.9) (P = 0.01). The rotations corresponding to 8.3 N m torsional moment were: Sirus I: 9.1 degrees , II: 9.3 degrees , III: 10.6 degrees (range 7.5-12.2), PHN 13.5 degrees (range 10.3-15.6) (P = 0.158), PHILOS plate 15.6 degrees (range 13.7-20.8) (P = 0.007), 4.5 AO T-Platte 14.1 degrees (range 11.5-19.7) (P = 0.158). CONCLUSION: The intramedullary load carriers were biomechanically superior when compared to the plating systems in the fracture model presented here. Supplementary, the Sirus Nail showed higher stiffness values than the PHN. However, the latter are gaining in importance due to the possibility of minimal invasive implantation. Whether this will be associated with functional advantages requires further clinical investigation.

Cystic fibrosis and intrauterine death.

Fetal death is not commonly associated with cystic fibrosis (CF). We report a case of late intrauterine death attributed to cardiovascular failure and shock consequent to malrotation and intestinal volvulus in a fetus affected with CF. An argument is made that CF promoted this deleterious incident. Whole blood or cell-rich tissue specimens should be preserved and genetic testing for CF considered in stillbirths with intestinal complications.

The effect of caudal block on functional residual capacity and ventilation homogeneity in healthy children.

Caudal block results in a motor blockade that can reduce abdominal wall tension. This could interact with the balance between chest wall and lung recoil pressure and tension of the diaphragm, which determines the static resting volume of the lung. On this rationale, we hypothesised that caudal block causes an increase in functional residual capacity and ventilation distribution in anaesthetised children. Fifty-two healthy children (15-30 kg, 3-8 years of age) undergoing elective surgery with general anaesthesia and caudal block were studied and randomly allocated to two groups: caudal block or control. Following induction of anaesthesia, the first measurement was obtained in the supine position (baseline). All children were then turned to the left lateral position and patients in the caudal block group received a caudal block with bupivacaine. No intervention took place in the control group. After 15 min in the supine position, the second assessment was performed. Functional residual capacity and parameters of ventilation distribution were calculated by a blinded reviewer. Functional residual capacity was similar at baseline in both groups. In the caudal block group, the capacity increased significantly (p < 0.0001) following caudal block, while in the control group, it remained unchanged. In both groups, parameters of ventilation distribution were consistent with the changes in functional residual capacity. Caudal block resulted in a significant increase in functional residual capacity and improvement in ventilation homogeneity in comparison with the control group. This indicates that caudal block might have a beneficial effect on gas exchange in anaesthetised, spontaneously breathing preschool-aged children with healthy lungs.

Early European experience with the MammoSite radiation therapy system for partial breast brachytherapy following breast conservation operation in low-risk breast cancer.

Preliminary results of ultrasound studies do exist in the literature on the successful use of the MammoSite Radiation Therapy System (RTS), a new device for delivering brachytherapy following breast-conserving surgery. In Europe, some groups started a prospective multicentre trial to investigate the use of the MammoSite RTS. In this early publication, we analysed the surgical procedure and placement of the MammoSite, treatment planning and radiation delivery complications, and early cosmesis, as well as the comfort of the patients. Between June 2002 and March 2005, a total of 54 low-risk breast cancer patients fulfilling the enrolment criteria were implanted intra- or postoperatively using the MammoSite applicator. After inflating the balloon in the excision cavity, the reference isodose was defined 1cm from the balloon's surface. Twenty-eight patients were treated with primary brachytherapy with a total dose of 34 Gy (2x3.4 Gy) and 16 patients had a boost with a mean dose of 13.3 Gy (range: 7.5-15 Gy; 2x2.5 Gy) combined with external beam radiotherapy (EBRT). Doses ranged between 46 and 50 Gy. We analysed the postimplant anatomic position of the applicator in relation to the skin and chest wall as well as the geometric form of the balloon via ultrasound, computed tomography and X-ray before, during and after the treatment. Forty-four out of 54 patients (81.5%) were eligible for MammoSite RTS brachytherapy. Ten patients were excluded from the trial due to the strict study criteria and received no brachytherapy. Balloon rupture occurred in two cases. We observed seroma in 16 patients (36%); furthermore, an abscess developed in two patients (4.5%) within 3 months of implantation. Postoperative air gaps and haematoma were successfully reduced by draining the operation cavity in one institution. At a mean follow-up of 14 months (range 3-31 months), the skin-related side effects observed were skin discoloration or inflammation in 36 patients (82%) and teleangiectasia in eight patients (18%). The MammoSite RTS is a feasible treatment modality for postoperative partial breast irradiation after breast-conserving surgery for selected low-risk breast cancer patients. The main advantage of the system is the necessity of only one applicator for the delivery of fractionated radiotherapy over a 5-day treatment period. In addition, patient tolerance of the procedure is high. Based on this early experience, the method may serve as a successful alternative to conventional multicatheter brachytherapy for a highly select group of patients, but we have to bear in mind the higher level of acute toxicity.

Impact of elective resection on plasma TIMP-1 levels in patients with colon cancer.

OBJECTIVE: Pre- and post-operative plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) levels have a prognostic impact on patients with colorectal cancer. However, the surgical trauma may play an essential role in regulation of plasma TIMP-1 levels, which in turn may influence subsequent TIMP-1 measurements. PATIENTS AND METHODS: Consecutively, 48 patients with colon cancer (CC) and 12 patients with nonmalignant colonic disease were randomised to undergo elective laparoscopically assisted or open resection followed by fast track recovery. Plasma samples were collected just before and 1, 2 and 6 h after skin incision, and 1, 2, 8 and 30 days after surgery. TIMP-1 was determined concurrently in all samples by a validated ELISA method. RESULTS: Geometric mean preoperative TIMP-1 level was 142 ng/ml (range 54-559 ng/ml) among CC patients compared with 106 ng/ml (range 64-167 ng/ml) among patients with nonmalignant diseases (P<0.0001). TIMP-1 levels were decreased significantly 2 h after skin incision compared to the preoperative levels returning to preoperative levels at 6 h. A highly significant (P<0.0001) maximum level was observed 1 day after surgery and was decreasing to preoperative levels 30 days after surgery. Patients undergoing laparoscopically assisted or open resection had similar TIMP-1 levels at each time point. CONCLUSIONS: Major surgery has considerable impact on plasma TIMP-1 levels. Intra- and post-operative changes of plasma TIMP-1 levels are independent of the surgical approach, and resection for CC does not lead to a significant decrease of plasma TIMP-1 levels within 30 days postoperatively.

Use of continuous positive airway pressure during flexible bronchoscopy in young children.

Young children are at increased risk for hypoxaemia and hypercapnia during flexible bronchoscopy due to the small size and increased collapsibility of their airways. Various strategies are used to prevent hypoventilation and to provide oxygen during the procedure. The aim of this study was to assess the impact of continuous positive airway pressure (CPAP) on ventilation during flexible bronchoscopy in infants and young children. Tidal breathing was measured in 16 spontaneously breathing and deeply sedated children, aged 3-25 months, by ultrasound spirometry via an airway endoscopy mask. Measurements were made with the tip of the bronchoscope positioned in the pharynx with no CPAP, and in mid-trachea with 0, 5 and 10 cmH2O of CPAP. Transition of the bronchoscope through the vocal cords was associated with significant decreases of tidal volumes (5.0+/-0.5 versus 3.4+/-0.5 mL.kg(-1)), peak tidal expiratory flows (78+/-12 versus 52+/-10 mL.s(-1)) and peak tidal inspiratory flows (98+/-15 versus 66+/-12 mL.kg(-1)). CPAP (5-10 cmH2O) induced almost complete reversal of these changes. In conclusion, it is shown here that flexible bronchoscopy in spontaneously breathing young children is associated with significant decreases in tidal volume and respiratory flow. These changes are largely reversible with continuous positive airway pressure.

Identification of paramyosin T cell epitopes associated with human resistance to Schistosoma mansoni reinfection.

Paramyosin, a Schistosoma mansoni myoprotein associated with human resistance to infection and reinfection, is a candidate antigen to compose a subunit vaccine against schistosomiasis. In this study, 11 paramyosin peptides selected by TEPITOPE algorithm as promiscuous epitopes were produced synthetically and tested in proliferation and in vitro human leucocyte antigen (HLA)-DR binding assays. A differential proliferative response was observed in individuals resistant to reinfection compared to individuals susceptible to reinfection in response to Para (210-226) peptide stimulation. In addition, this peptide was able to bind to all HLA-DR molecules tested in HLA-DR binding assays, confirming its promiscuity. Para (6-22) and Para (355-371) were also shown to be promiscuous peptides, because they were able to bind to the six and eight most prevalent HLA-DR alleles used in HLA-DR binding assays, respectively, and were also recognized by T cells of the individuals studied. These results suggest that these paramyosin peptides are promising antigens to compose an anti-schistosomiasis vaccine.

[Partial breast irradiation for early breast cancer with favorable prognostic factors: 3-year results of the German-Austrian phase II-trial]. / Teilbrustbestrahlung beim Mammakarzinom mit günstigen prognostischen Faktoren: 3-Jahres-Ergebnisse der deutsch-österreichischen Phase II-Studie.

PURPOSE: To evaluate perioperative morbidity, toxicity and cosmetic outcome in patients treated with interstitial brachytherapy to the tumor bed as the sole radiation modality after breast conserving surgery. MATERIALS AND METHODS: From 11/2000 to 11/2004, 240 women with early stage breast cancer participated in a protocol of tumor bed irradiation alone using pulsed dose rate (PDR) or high dose rate (HDR) interstitial multi-catheter implants (partial breast irradiation). Perioperative morbidity, acute and late toxicity as well as cosmetic outcome were assessed. Of the first 51 patients treated in this multicenter trial, we present interim findings after a median follow-up of 36 months. RESULTS: Perioperative Morbidity: Bacterial infection of the implant: 2 % (1/51). Acute toxicity: radiodermatitis Grade 1: 4 % (2/51). Late toxicity: breast pain Grade 1: 8 % (4/51), Grade 2: 2 % (1/51); dyspigmentation Grade 1: 8 % (4/51); fibrosis Grade 1: 4 % (2/51), Grade 2: 8 % (4/51); telangiectasia Grade 1: 10 % (5/51), Grade 2: 4 % (2/51). Cosmetic results: Excellent and good in 94 % (48/51) of the patients. CONCLUSION: This analysis indicates that accelerated partial breast irradiation with 192-iridium interstitial multicatheter PDR-/HDR-implants (partial breast irradiation) is feasible with low perioperative morbidity, low acute and mild late toxicity at a median follow-up of 36 months. The cosmetic result is not significantly affected.