Publications by authors named "Martina Mittlboeck"

30 Publications

  • Page 1 of 1

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study.

Oral Oncol 2022 Jan 26;124:105634. Epub 2021 Nov 26.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, Vienna A-1090, Austria.

Background: Taxane-based checkpoint inhibitor combination therapy might improve the outcome in recurrent/metastatic (R/M) head and neck cancer (HNSCC) patients. Thus, we investigated the efficacy and safety of docetaxel (DTX) plus pembrolizumab (P) in a prospective phase I/II trial.

Methods: Platinum-resistant R/M HNSCC patients received DTX 75 mg/m^ plus P 200 mg for up to six cycles followed by P maintenance therapy. The primary endpoint was overall response rate (ORR) and safety. Secondary endpoints comprised disease control rate (DCR), overall survival (OS) and progression free survival (PFS).

Results: Twenty-two patients were enrolled. Nine patients (40.9%) had a primary tumor in the oropharynx, 8 (36.4%) in the oral cavity, 3 (13.6%) in the hypopharynx and 2 (9.1%) in the larynx. The ORR was 22.7% (95% CI 10.1%-43.4%) and one (4.5%) complete response was achieved. The DCR was 54.6% (95% 34.7%-73.1%). The median PFS was 5.8 months (95% CI 2.7-11.6) and the median OS 21.3 months (95% CI 6.3-31.1). The 1-year PFS and OS rates were 27.3% and 68.2%, respectively. While the most frequent adverse event (AE) was myelosuppression, which was reported in all 22 patients, 3 (13.6%) patients experienced grade 3 febrile neutropenia. The most common immune-related AEs were grade skin rash (40.9%) and hypothyroidism (40.9%). One patient (4.5%) experienced grade 5 immune thrombocytopenia.

Conclusion: DXT in combination with P shows promising activity accompanied with a manageable side effect profile in pre-treated R/M HNSCC patients.
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January 2022

The Immune Phenotype of Isolated Lymphoid Structures in Non-Tumorous Colon Mucosa Encrypts the Information on Pathobiology of Metastatic Colorectal Cancer.

Cancers (Basel) 2020 Oct 25;12(11). Epub 2020 Oct 25.

Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna 1090, Austria.

The gut-associated lymphoid tissue represents an integral part of the immune system. Among the powerful players of the mucosa-associated lymphoid tissue are isolated lymphoid structures (ILSs), which as information centers, drive the local (and systemic) adaptive immune responses. Germinal center reactions, taking place within ILSs, involve the coordinated action of various immune cell types with a central role given to B cells. In the current study, we aimed at dissecting the impact of ILSs within non-tumorous colon tissue (NT) on the pathobiology of colorectal cancer (CRC) with metastasis in the liver (CRCLM). In particular, we focused on the immune phenotypes of ILSs and ectopic lymphoid structures (ELSs), built up at matching primary and metastatic tumor sites. We implemented an integrative analysis strategy on the basis of tissue image cytometry and clonality assessment to explore the immune phenotype of ILS/ELS at three tissue entities: NT, CRC, and CRCLM (69 specimens in total). Applying a panel of lineage markers used for immunostaining, we characterized and compared the anatomical features, the cellular composition, the activation, and proliferation status of ILSs and ELSs, and assessed the clinical relevance of staining-derived data sets. Our major discovery was that ILS characteristics at the NT site predefine the immune phenotype of ELSs at CRC and CRCLM. Thereby, B-cell-enriched (CD20) and highly proliferative (Ki67) ILSs and ELSs were found to be associated with improved clinical outcome in terms of survival and enabled patient stratification into risk groups. Moreover, the data revealed a linkage between B-cell clonality at the NT site and the metastatic characteristics of the tumor in the distant liver tissue. Consolidation of immunostaining-based findings with the results of compendium-wide transcriptomic analysis furthermore proposed CD27 as a novel marker of T follicular helper cells within lymphoid structures. Overall, the study nominates the ILS immune phenotype as a novel prognostic marker for patients with metastatic CRC.
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October 2020

Plasma homocysteine after laparoscopic Roux-en-Y gastric bypass increases in the early postoperative phase but decreases in the long-term follow-up. A retrospective analysis.

Surg Obes Relat Dis 2020 Mar 9;16(3):372-380. Epub 2019 Dec 9.

Department of Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

Background: Homocysteine is an important independent risk factor for predicting cardiovascular disease (CVD). However, changes in the homocysteine levels after bariatric surgery remain controversial.

Objectives: Modeling differences in homocysteine after bariatric surgery.

Setting: University Hospital, Austria.

Methods: Seven hundred eight consecutive bariatric surgery patients (78% female, 22% male, mean body mass index 41 kg/m preoperatively) underwent laparoscopic long-limb Roux-en-Y gastric bypass in a 6-year period and were retrospectively evaluated for changes in their preoperative homocysteine levels, at 3, 6, 9, 12, 18, 24, 36, 48, 60, and 72 months postoperatively. Furthermore, a postal and telephone screening for postoperative CVD with a follow-up of 71% was conducted.

Results: Hyperhomocysteinemia was present in 11.8% preoperatively (normal range: <15 μmol/L). The median plasma homocysteine level was 10.4 preoperatively, 12.1 at 3, 11.2 at 6, 10.0 at 9, 9.8 at 12, 8.9 at 18, 8.7 at 24, 8.6 at 36, 9.1 at 48, 9.8 at 60, and 10.0 μmol/L at 72 months postoperatively. After subdividing the study population in morbidly obese (n = 509, body mass index 40-50 kg/m) and super-obese (n = 199, body mass index >50 kg/m) patients, the short-term increase into homocysteine levels remained. Overall, newly onset CVD risk was 4.2%. After subdividing the CVD risk into risk for myocardial infarction, stroke, and risk for deep vein thrombosis/pulmonary embolism the distribution was as follows: .2% myocardial infarction, .59% stroke, and 2.97% deep vein thrombosis/pulmonary embolism (median 36 [interquartile range 36-48] mo postoperatively).

Conclusion: Laparoscopic Roux-en-Y gastric bypass leads to increased homocysteine levels in the early postoperative period. However, there was no relationship between increased homocysteine levels and CVD event onset.
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March 2020

Re: Comment on "Incidence of risk factors for bloodstream infections in patients with major burns receiving intensive care: A retrospective single-center cohort study".

Burns 2019 05 24;45(3):744-745. Epub 2018 Dec 24.

Medical University of Vienna, Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Vienna, Austria; Jena University Hospital, Institute of Infectious Diseases and Infection Control, Jena, Germany. Electronic address:

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May 2019

Contribution to the discussion of "When should meta-analysis avoid making hidden normality assumptions?"

Biom J 2018 11 1;60(6):1085-1086. Epub 2018 Aug 1.

Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.

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November 2018

Visualizing the quantile survival time difference curve.

J Eval Clin Pract 2018 08 23;24(4):708-712. Epub 2018 May 23.

Section for Clinical Biometrics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.

The difference between the pth quantiles of 2 survival functions can be used to compare patients' survival between 2 therapies. Setting p = 0.5 yields the median survival time difference. Varying p between 0 and 1 defines the quantile survival time difference curve which can be straightforwardly estimated by the horizontal differences between 2 Kaplan-Meier curves. The estimate's variability can be visualized by adding either a bundle of resampled bootstrap step functions or, alternatively, approximate bootstrap confidence bands. The user-friendly SAS software macro %kmdiff enables the straightforward application of this exploratory graphical approach. The macro is described, and its application is exemplified with breast cancer data. The advantages and limitations of the approach are discussed.
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August 2018

Incidence of risk factors for bloodstream infections in patients with major burns receiving intensive care: A retrospective single-center cohort study.

Burns 2018 06 1;44(4):784-792. Epub 2018 Feb 1.

Medical University of Vienna, Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Vienna, Austria; Jena University Hospital, Center of Infectious Diseases and Infection Control, Jena, Germany. Electronic address:

Objectives: The objective was primarily to identify risk factors for bloodstream infections (BSI) caused by different pathogens.

Methods: A retrospective single-center cohort study was performed on 472 burn patients with an abbreviated burn severity index (ABSI)≥3, a total burn surface area (TBSA)≥10%, and an ICU stay of at least 24h. Risk factors for different BSI pathogens were analyzed by competing risks regression model of Fine and Gray.

Results: A total of 114 burn patients developed 171 episodes of BSIs caused by gram-negative bacteria (n=78;46%), gram-positive bacteria (n=69;40%), and fungi (n=24;14%) median after 14days (range, 1-164), 16days (range, 1-170), and 16days (range, 0-89), respectively. A total of 24/114 patients (21%) had fatal outcomes. Isolation of the most common bloodstream isolates Enterococcus sp. (n=26), followed by Candida sp. and Pseudomonas sp. (n=22 for both) was significantly associated with increased TBSA (p≤0.006) and ABSI (p<0.0001) and need for fasciotomy (p<0.01). The death risk of patients with MDR gram-negative bacteremia was significantly increased by a hazard ratio of 12.6 (95% CI:4.8-32.8; p<0.0001).

Conclusions: A greater TBSA and ABSI were associated with a significantly higher incidence of BSIs caused by Pseudomonas sp., Enterococcus sp. and Candida sp.
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June 2018

A 5‑year update of patients with HPV positive versus negative oropharyngeal cancer after radiochemotherapy in Austria.

Wien Klin Wochenschr 2017 Jun 15;129(11-12):398-403. Epub 2017 Feb 15.

Department of Otorhinolaryngology, Medical University of Graz, Graz, Austria.

Background: After publishing promising results for the treatment of patients with human papilloma virus (HPV) positive oropharyngeal cancer with radiochemotherapy regarding 2‑year survival, we present an update of the disease-specific and disease-free survival after 5 years.

Patients And Methods: A total of 29 patients of which 18 were HPV negative and 11 HPV positive with squamous cell carcinoma of the oropharynx received radiation therapy with or without chemotherapy (cisplatin) or immunotherapy (cetuximab) between 2007 and 2009. At time of the present analysis, six patients are still alive including four with HPV positive and two with HPV negative oropharyngeal carcinoma, while 15 out of 16 patients with HPV negative tumors died and 1 died of another cause with evidence of disease.

Results: Since the 2‑year disease-specific survival of patients with HPV positive cancer of the oropharynx was published with 100% versus 30.4% in HPV negative tumors, we now present the 5‑year disease-specific survival after treatment, which was 85.7% in HPV positive versus 11.1% in HPV negative patients.

Conclusion: We present the results of patients receiving radiochemo(immuno)therapy for oropharyngeal cancer regarding the HPV status, which is still promising.
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June 2017

Percutaneous tibial nerve stimulation versus tolterodine for overactive bladder in women: a randomised controlled trial.

Eur J Obstet Gynecol Reprod Biol 2015 Aug 3;191:51-6. Epub 2015 Jun 3.

Medical University of Vienna, Department of Obstetrics & Gynaecology, Division of General Gynaecology and Gynaecologic Oncology, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

Objective: We performed a randomised controlled trial of percutaneous tibial nerve stimulation (PTNS) versus tolterodine for treating treatment naïve women with overactive bladder (OAB).

Study Design: 36 patients with symptoms of OAB were randomised to 3 months of treatment with weekly PTNS or tolterodine (2mg bid p.o.). The primary outcome measure was the difference of micturitions per 24h. The secondary outcome measure was the impact on quality of life (QoL) measured with a visual analogue scale (VAS) between baseline and after 3 months of therapy.

Results: Micturition frequencies did not decline significantly (p=0.13) over time and there were no significant treatment differences (p=0.96). QoL was significantly dependent from its level at baseline (p=0.002) and showed improvement over time compared to baseline measurements but no significant differences between both treatment groups (p=0.07). Incontinence episodes per 24h depended significantly on the level at baseline (p=0.0001) and declined significantly (p=0.03) during 3 months of therapy in both therapy groups. However no significant treatment differences on the reduction of incontinence episodes in 24h could be shown between both therapy groups (p=0.89). PTNS had fewer side effects than tolterodine (p=0.04).

Conclusion: PTNS and tolterodine were both effective in reducing incontinence episodes and improving QoL in patients with OAB but not micturition frequencies. PTNS had fewer side effects.
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August 2015

B cells and ectopic follicular structures: novel players in anti-tumor programming with prognostic power for patients with metastatic colorectal cancer.

PLoS One 2014 6;9(6):e99008. Epub 2014 Jun 6.

Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

Remarkably limited information is available about biological mechanisms that determine the disease entity of metastatic colorectal cancer in the liver (CRCLM) with no good clinical parameters to estimate prognosis. For the last few years, understanding the relationship between tumor characteristics and local immune response has gained increasing attention. Given the multifaceted roles of B-cell-driven responses, we aimed to elucidate the immunological imprint of B lymphocytes at the metastatic site, the interrelation with macrophages, and their prognostic relevance. Here we present novel algorithm allowing to assess a link between the local patient-specific immunological capacity and clinical outcome. The microscopy-based imaging platform was used for automated scanning of large-scale tissue sections and subsequent qualitative and quantitative analyses of immune cell subtypes using lineage markers and single-cell recognition strategy. Results indicate massive infiltration of CD45-positive leukocytes confined to the metastatic border. We report for the first time the accumulation of CD20-positive B lymphocytes at the tumor-liver interface comprising the major population within the large CD45-positive aggregates. Strikingly, functionally active, activation-induced cytidine deaminase (AID)-positive ectopic lymphoid structures were found to be assembled within the metastatic margin. Furthermore, the CD20-based data set revealed a strong prognostic power: patients with high CD20 content and/or ectopic follicles had significantly lower risk for disease recurrence as revealed by univariate analysis (p<0.001 for both) and in models adjusted for clinicopathological variables (p<0.001 and p = 0.01, respectively), and showed prolonged overall survival. In contrast, CD68 staining-derived data set did not show an association with clinical outcome. Taken together, we nominate the magnitude of B lymphocytes, including those organized in ectopic follicles, as novel prognostic marker which is superior to clinicopathological parameters. Findings emphasize anti-tumoral role of B cell-driven mechanism(s) and thus indicate a new way of thinking about potential treatment strategies for CRCLM patients.
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January 2015

A liquid-film forming acrylate cream for the treatment of anal pruritus.

Br J Nurs 2012 Jan 26-Feb 8;21(2):98, 100-2

Department of Dermatology, Federal University Teaching Hospital, Feldkirch, Austria.

Pruritus ani is a hidden but frequently occurring clinical condition, with a large impact on patients' quality of life. Currently, therapeutic options are scarce, offering mainly limited success. The authors performed a prospective, open-label, two-centre pilot study to analyse the efficacy and safety of a liquid-film forming acrylate cream for the treatment of pruritus ani and peri-anal skin irritation. A total of 28 patients were included and applied the cream to the cleansed anal and peri-anal skin once daily for a study period of 3-4 weeks. The primary outcome measure was the reduction of pruritis ani, comparing day 0 to day 28 results. For this purpose, a visual analog scale (VAS) was used. Secondary parameters included the physician global assessment score (PGA) of peri-anal skin condition, assessment of patients' quality of life using a specifically designed quality of life scoring tool, and patient satisfaction with the treatment regimen. The application of the acrylate skin protection cream resulted in a fast and substantial improvement of all study parameters, with a high score for patient satisfaction. The cream was well tolerated without any adverse events noted during the study period. The authors' pilot study has generated initial evidence that the acrylate skin protection cream may be effective for the treatment of pruritus ani. However, further randomized controlled studies are needed to confirm the authors' findings.
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April 2012

Neoadjuvant chemotherapy increases the rate of breast conservation in lobular-type breast cancer patients.

Ann Surg Oncol 2012 Feb 9;19(2):519-26. Epub 2011 Jul 9.

Department of Surgery, Breast Health Care Center, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.

Introduction: Our study aims to determine whether patients with lobular-type breast cancer have significantly improved rates of breast conservation (BCT) after neoadjuvant chemotherapy (nCT).

Methods: Patients who received nCT and surgery within three prospective trials between 1995 and 2007 at the Medical University of Vienna were retrospectively analyzed.

Results: 325 patients had median follow-up of 53 months; 21% had lobular cancer, and 70% of these women were initially scheduled for mastectomy (MX). Twenty-one finally received BCT, yielding a MX-BCT turnover rate of 45%. Of patients primarily scheduled for BCT, 20% had to finally undergo MX in lobular cancer. The 256 patients with ductal-type breast cancer finally had a MX-BCT turnover rate of 52% (p = 0.561 versus lobular) and a BCT-MX turnover rate of 15% (p = 0.933 versus lobular). Secondary MX after initial BCT was necessary in 2% (ductal) and 10% (lobular, p = 0.110). There was no difference in local recurrence in lobular- as compared with ductal-type breast cancer patients after BCT (2.7% versus 10%, p = 0.135), nor was a difference seen in lobular breast cancer patients when comparing BCT with MX (2.7% versus 3.4%, p = 0.795). Tumor type was not an independent predictor for either BCT or local recurrence.

Conclusion: We do not suggest excluding patients with lobular-type breast cancer who are primarily scheduled for MX from nCT, since BCT rates may still increase by 45% without influencing the oncologic outcome.
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February 2012

Survival of patients with HPV-positive oropharyngeal cancer after radiochemotherapy is significantly enhanced.

Wien Klin Wochenschr 2011 Apr 30;123(7-8):215-21. Epub 2011 Mar 30.

Department of Otorhinolaryngology, Medical University of Vienna, Austria.

Background: The purpose of this study was to evaluate the incidence and clinical significance of HPV (Human papilloma virus) infection in patients with head and neck cancer who had received radiotherapy in Eastern Austria.

Patients And Methods: 88 patients with head and neck cancer including 26 patients with oral cavity cancer, 45 patients with oropharyngeal cancer, seven patients with laryngeal carcinoma and ten patients with carcinoma of the hypopharynx were screened for high risk HPV by immunohistochemistry, PCR (Polymerase Chain Reaction) and in-situ hybridization. 29 out of 45 patients with a squamous cell carcinoma of the oropharynx received radiotherapy alone, radiotherapy in combination with cisplatin or cetuximab.

Results: Of the investigated 29 patients with oropharyngeal cancer receiving conservative treatment, 11 had a HPV-positive and 18 a HPV-negative tumor. Patients received radiation ± cisplatin or cetuximab, where the HPV-positive patients had a significant better response to treatment and overall survival (p = 0.015) as well as disease-free survival (p = 0.001) after therapy.

Conclusion: Patients with oropharyngeal carcinoma and a positive HPV status respond considerably better to radiochemotherapy than patients with HPV-negative tumors. HPV screening is a simple procedure and can easily be implemented in routine pathology investigations and should be included in standard operational procedures for the diagnosis and therapy of head and neck cancer patients.
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April 2011

Antitumor activity of SNX-2112, a synthetic heat shock protein-90 inhibitor, in MET-amplified tumor cells with or without resistance to selective MET Inhibition.

Clin Cancer Res 2011 Jan;17(1):122-33

Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.

Purpose: Heat shock protein-90 (HSP-90), a molecular chaperone required by numerous oncogenic kinases [e.g., HER-2, epidermal growth factor receptor (EGFR), Raf-1, v-Src, and AKT] for conformational stability, has attracted wide interest as a novel target for cancer therapy. HSP-90 inhibition induces degradation of HSP-90 client proteins, leading to a combinatorial inhibition of multiple oncogenic signaling pathways with consecutive growth arrest and apoptosis. MET, a tyrosine kinase that is constitutively active in tumor cells with MET oncogene amplification, has recently been identified as another HSP-90 client.

Experimental Design: The aim of our study was to assess the efficacy of SNX-2112, a synthetic HSP-90 inhibitor, in 3 different MET-amplified tumor cell lines (GTL-16, MKN-45, and EBC-1) as well as PR-GTL-16 cells, a GTL-16 subline selected for resistance to the highly selective MET kinase inhibitor PHA-665752.

Results: In all cell lines, SNX-2112 led to degradation of MET, HER-2, EGFR, and AKT, as well as abrogation of Ras/Raf/MEK/MAPK and PI3K/AKT signaling, followed by complete cell cycle arrest. SNX-5542, an orally bioavailable prodrug of SNX-2112, displayed significant antitumor efficacy in vivo in nude mice bearing MET-amplified tumor xenografts. Importantly, HSP-90 inhibition maintained its antitumor efficacy in PR-GTL-16 cells both in vitro and in vivo, suggesting that HSP-90 inhibition could be a particularly valuable strategy in MET-amplified tumors that have acquired resistance to MET kinase inhibition.

Conclusions: Our study provides evidence for the efficacy of HSP-90 inhibition in MET-amplified cancer cells, particularly when MET kinase inhibitor resistance has emerged.
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January 2011

Mesh graft infection following abdominal hernia repair: risk factor evaluation and strategies of mesh graft preservation. A retrospective analysis of 476 operations.

World J Surg 2010 Jul;34(7):1702-9

Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Background: Mesh graft infection after prosthetic hernia repair is a challenging complication usually treated by mesh removal. The aim of this study was to identify risk factors associated with mesh infection and to assess the efficacy of conservative wound therapy in preserving an infected mesh.

Methods: We performed a retrospective analysis of 476 consecutive patients with incisional hernia who received mesh graft repair between February 1, 2000 and February 28, 2005 at our institution using chart review and clinical investigation.

Results: Thirty-one of 476 (6.5%) patients developed a deep surgical site infection involving the implanted mesh graft. Upon multivariate analysis, operation time was the only significant risk factor associated with mesh infection (p = 0.0038). Seventeen (55%) of 31 infected mesh grafts were preserved by conservative means. There was a significant association between the type of mesh graft used and the probability of mesh preservation in case of infection: While conservative therapy led to preservation of 100% of infected polyglactin/polypropylene meshes, only 20% of infected polypropylene and 23% of infected PTFE/polypropylene meshes could be salvaged using conservative means (p < 0.0001). In none of the patients with preserved mesh graft was hernia recurrence at the former site of infection observed.

Conclusions: Operation time is the only significant risk factor associated with mesh graft infection following incisional hernia repair. Conservative treatment should be applied in case of infection of absorbable mesh grafts such as polypropylene/polyglactin, while nonabsorbable meshes such as PTFE/polypropylene or pure polypropylene are much less amenable to conservative treatment, usually requiring early surgical removal.
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July 2010

School children sufficiently apply life supporting first aid: a prospective investigation.

Crit Care 2009 31;13(4):R127. Epub 2009 Jul 31.

Department of Emergency Medicine, Medical University of Vienna, Währinger Gürtel, Wien, 1090, Austria.

Introduction: The usefulness of CPR training in schools has been questioned because young students may not have the physical and cognitive skills needed to correctly perform such complex tasks correctly.

Methods: In pupils, who received six hours of CPR training from their teachers during a standard school semester at four months post training the following outcome parameters were assessed: CPR effectiveness, AED deployment, accuracy in checking vital signs, correctness of recovery position, and whether the ambulance service was effectively notified. Possible correlations of age, gender, body mass index (BMI), and outcome parameters were calculated.

Results: Of 147 students (mean age 13 +/- 2 years), 86% performed CPR correctly. Median depth of chest compressions was 35 mm (inter quartile range (IQR) 31 to 41), and the median number of compressions per minute was 129 bpm (IQR 108 to 143). Sixty nine percent of the students tilted the mannequin head sufficiently for mouth to mouth resuscitation, and the median air volume delivered was 540 ml (IQR 0 to 750). Scores on other life supporting techniques were at least 80% or higher. Depth of chest compressions showed a correlation with BMI (r = 0.35; P < 0.0001), body weight (r = 0.38; P < 0.0001), and body height (r = 0.31; P = 0.0002) but not with age. All other outcomes were found to be unrelated to gender, age, or BMI.

Conclusions: Students as young as 9 years are able to successfully and effectively learn basic life support skills including AED deployment, correct recovery position and emergency calling. As in adults, physical strength may limit depth of chest compressions and ventilation volumes but skill retention is good.
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January 2010

Cardiopulmonary resuscitation and the 2005 universal algorithm: has the quality of CPR improved?

Wien Klin Wochenschr 2009 ;121(1-2):41-6

Department of Anesthesia and General Intensive Care, Medical University of Vienna, Vienna, Austria.

Background And Aim: Chest compressions are crucial in cardiopulmonary resuscitation (CPR), although the optimal number, rate and sequence are unknown. The 2005 CPR guidelines of the European Resuscitation Council (ERC) brought major changes to the basic life support algorithm. One of the major aims of the ERC was to decrease hands-off time in order to improve perfusion of the coronary vessels and the brain. Using a manikin model of basic life support in simulated cardiac arrest, we compared hands-off time and total number of chest compressions according to the guidelines of 2000 and those of 2005.

Methods: A total of 50 volunteers performed CPR according to the guidelines of 2000 (Group 2000) and 2005 (Group 2005) in a randomized unblinded cross-over study. Volunteers received 10 min of standardized teaching and 10 min of training, including corrective feedback, for each set of guidelines before performing 5 min of basic life support on a manikin. We compared hands-off time as the primary outcome parameter and the total number of chest compressions as the secondary outcome parameter.

Results: Fifty volunteers were enrolled in the study, one individual dropped out after randomization. In Group 2005, hands-off time was significantly lower (mean 107 +/- 19 [SD] s vs. 139 +/- 15 s in Group 2000 (P < 0.0001) and the total number of chest compressions was significantly higher (347 +/- 64 compressions vs. 233 +/- 51 compressions; P < 0.0001).

Conclusion: In this manikin setting, both hands-off time and the total number of chest compressions improved with basic life support performed according to the ERC guidelines of 2005.
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March 2009

Breast-conserving therapy for centrally located breast cancer.

Ann Surg 2008 Mar;247(3):470-6

Department of Surgery, Medical University of Vienna, Austria.

Objective: To analyze whether breast-conserving therapy (BCT) may be an oncologically safe approach and result in a good cosmesis in patients with centrally located breast cancer (CLBC).

Summary Background Data: Only underpowered, retrospective, single-arm studies have suggested that oncoplastic BCT for CLBC may be oncologically safe and may result in a good cosmesis.

Methods: The authors retrospectively analyzed the overall and recurrence-free survival in 1485 patients with breast cancer undergoing BCT comparing CLBC with non-CLBC. Moreover, the authors described 4 different oncoplastic techniques for BCT in patients with CLBC and compared the cosmetic results with simple lumpectomy according to a recently elaborated objective cosmetic evaluation system, the Breast Symmetry Index.

Results: Kaplan-Meier curves show no significant difference in a 5-year overall, local, or distant recurrence-free survival between patients with CLBC and non-CLBC after BCT (94% vs. 96%; 100% vs. 98%; 92% vs. 90%; median follow-up, 35.3 months). The cosmetic outcome after oncoplastic BCT compared with simple lumpectomy differed significantly (Breast Symmetry Index: 22 +/- 6%d vs. 44 +/- 12%d; P < 0.05).

Conclusions: The results demonstrate that BCT for CLBC is oncologically safe and that oncoplastic techniques improve cosmesis.
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March 2008

Statistical problems caused by missing data resulting from neodymium:YAG laser capsulotomies in long-term posterior capsule opacification studies: problem identification and possible solutions.

J Cataract Refract Surg 2008 Feb;34(2):268-73

Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.

Purpose: To describe a way to eliminate the problem caused by missing data due to neodymium:YAG (Nd:YAG) laser capsulotomies before statistical analysis, which leads to incomplete data in long-term studies of posterior capsule opacification (PCO).

Setting: Medical University of Vienna, Vienna, Austria.

Methods: To demonstrate the problem, an existing long-term study comparing PCO development in eyes with round-edged and sharp-edged intraocular lenses (IOLs) was analyzed. In the study, several Nd:YAG capsulotomies led to dropouts in the round-edged IOL group. To solve the resulting missing value problem, the missing values were replaced by estimated PCO values in various scenarios; that is, different assumptions were made of how PCO would have developed without a capsulotomy. Standard statistical analyses that included the estimated PCO values rather than excluding the incomplete cases were then performed.

Results: The analysis of all cases (including the estimated PCO scores) showed a highly significant difference between the round-edged group and the sharp-edged group. Sensitivity analyses confirmed that the difference between the 2 groups remained significant up to highly implausible values chosen for the missing PCO scores, thus proving the correctness of the analysis.

Conclusions: This study showed it is possible to perform statistical analyses without excluding incomplete cases. This approach is recommended for all studies with Nd:YAG dropouts as it increases the statistical power. Excluding incomplete cases may lead to biased or wrong study conclusions.
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February 2008

Results from Austria's nationwide public access defibrillation (ANPAD) programme collected over 2 years.

Resuscitation 2008 May 31;77(2):195-200. Epub 2008 Jan 31.

Medical University of Vienna, Department of Emergency Medicine, Vienna, Austria.

Aim Of The Study: To analyse 2 years of experience after introducing automated external defibrillators (AED) all over Austria.

Materials And Methods: This observational study evaluated the number of privately purchased devices and the rate of local bystander-triggered AED deployments from November 2002 to December 2004. As outcome measurements, the hospital discharge rate and neurological condition were recorded. Arrival times of the emergency medical service (EMS) on scene and the time intervals until shock decisions were made were calculated. Shock decisions were verified according to ECG downloads. Results were compared with historical data if applicable.

Results: During the study period, 1865 devices were installed. Seventy-three AED deployments were recorded. Eleven cases were excluded from the study because bystanders were part of the local EMS. Seventeen out of the remaining 62 (27%) compared to a historical 27 out of 623 (4.3%) individuals were discharged alive from hospital. Fourteen out of 26 (54%) patients who were found with a shockable rhythm survived to hospital discharge. Fifteen of our patients survived in good neurological condition (CPC I and II), two suffered from severe neurological deficit (CPC III and IV) and 45 people died. The median "call-to-AED advice interval" was 3.5 min (IQR 2-6 min; N=24). In two cases, the AED made inappropriate decisions because of artefacts.

Conclusions: Compared to historical data, short 'intervals to shock' delivery and the frequent start of basic life support resulted in an increased hospital discharge rate in good neurological condition. Despite the relatively high number of installed devices, the number of patients reached remained small.
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May 2008

Sagittal and vertical load-deflection and permanent deformation of transpalatal arches connected with palatal implants: an in-vitro study.

Am J Orthod Dentofacial Orthop 2007 Jun;131(6):742-52

Department of Orthodontics, School of Dentistry, Medical University of Vienna, Vienna, Austria.

Introduction: The purposes of this laboratory investigation were to (1) measure the sagittal and vertical deflection of loaded transpalatal arches (TPAs) connected to a palatal implant, (2) measure the extent of permanent deformation of the connecting TPA in the sagittal and vertical directions, (3) test various wire dimensions in terms of deflection behavior, and (4) evaluate soldering vs laser welding vs adhesive bonding of TPAs in terms of load deflection behavior.

Methods: Stainless steel wires of 6 dimensions were tested: 0.8 x 0.8, 0.9, 1, 1.1, 1.2, and 1.2 x 1.2 mm. For each dimension, 10 specimens were soldered to the palatal implant abutment, 10 were laser welded, and 10 were adhesively bonded to the implant abutment (total, 180 specimens). The measuring device applied increments of force of 50 cN, from 0 to 500 cN. Then the specimens were unloaded. The values were statistically described and analyzed with ANOVA and Wilcoxon rank sum tests.

Results And Conclusions: Absolute orthodontic anchorage without deformation of TPAs was not observed with the wire dimensions tested. To prevent loss of anchorage greater than 370 mum (sagittal deflection of 1.2 x 1.2 mm adhesively bonded TPA at 500 cN force level), wires thicker than 1.2 x 1.2 mm or cast anchorage elements must be considered for clinical practice. However, larger cross sections might cause more patient discomfort, and laboratory procedures increase costs.
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June 2007

Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group.

J Clin Oncol 2007 Mar 11;25(7):820-8. Epub 2006 Dec 11.

Department of Surgery, General Hospital, Medical University of Vienna, Vienna, Austria.

Purpose: Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients.

Patients And Methods: This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) +/- zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin +/- zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months.

Results: Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, -14.4% after 36 months; mean T score reduction, -1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, -17.3%; mean T score reduction, -2.6) compared with patients receiving tamoxifen/goserelin (BMD, -11.6%; mean T score reduction, -1.1). In contrast, BMD remained stable in zoledronic acid-treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted.

Conclusion: Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.
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March 2007

Automated external defibrillators do not recommend false positive shocks under the influence of electromagnetic fields present at public locations.

Anesth Analg 2006 Dec;103(6):1485-8

Research Institute, Vienna Red Cross, Vienna, Austria.

Electromagnetic fields (EMF) reduce the signal quality of electrocardiograms and may lead to the misinterpretation by automated external defibrillators (AED). We designed this investigation as a prospective study, with a randomized sequence of AED applications on healthy volunteers. We chose busy public places where public access defibrillation was possible as test locations. Strong EMF were sought and found at train stations next to accelerating and decelerating trains. The primary outcome variable was the absolute number of shocks advised in the presence of sinus rhythm by five commonly used AED in Austria. For data analysis, the statistician was blinded in regard to the AED models tested. Data analysis was based on a per protocol evaluation. Of 390 tests run, 0 cases of false positive results occurred (95% CI: 0-0.77). AED can be regarded as safe, even with the interference of EMF present at train stations.
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December 2006

Reaching the public via a multi media campaign as a first step to nationwide public access defibrillation.

Resuscitation 2006 May 24;69(2):269-75. Epub 2006 Apr 24.

Research Institute of the Vienna Red Cross, Vienna, Austria.

Public access defibrillation (PAD) is a promising strategy to fight sudden cardiac death. The Austrian Red Cross provided automated external defibrillators (AEDs) and basic life support (BLS) training as an "all inclusive package" combined with on site consultation and maintenance with annual retraining as a part of a nationwide PAD programme. A multi media campaign was started to promote the package and to increase awareness about sudden cardiac death. Data about the campaign, its recognition by the public in Austria and the number of packages were recorded. Sixty-eight percent of the Austrian public above the age of 15 years were able to recall the multi media campaign. Comparing the periods before and after the campaign, the number of website hits climbed significantly from 2,931 hits/month (1,866-6,168) to 4,812 hits/month (3,432-13,434) (p=0.0276). The number of AED services implemented before the campaign increased significantly (p=0.0026) in the time after the campaign. Therefore, we conclude that a multi media campaign is useful to stimulate public discussion and it encourages companies to buy "all inclusive packages" containing AEDs, BLS training, on site consultation and maintenance. These measures represent a possible first step in introducing PAD but it seems that they have to be continued on a constant basis.
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May 2006

Influence of electromagnetic fields on function of automated external defibrillators.

Acad Emerg Med 2006 Jan 19;13(1):1-6. Epub 2005 Dec 19.

Department of Emergency Medicine, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

Objectives: In this study, the authors tested whether electromagnetic interference (EMI) is able to impair correct electrocardiogram analysis and produce false-positive shock advice from automated external defibrillators (AEDs) when the true rhythm is sinus.

Methods: Nineteen healthy subjects were used to test five AEDs available on the Austrian market in a prospective, open, and sequence-randomized study. The primary outcome variable was the absolute number of shocks advised in the presence of EMI. The secondary outcome was the number of impaired analyses caused by incorrectly detected patient movements or electrode failure.

Results: Of 760 tests run, 18 (2.37%) cases of false-positive results occurred, and two of five AEDs recommended shocks in the presence of sinus rhythm. Of 760 tests run, no electrode failures occurred. There were 27 occurrences (3.55%) of motion detected by an AED in the presence of strong electromagnetic fields.

Conclusions: AED models differ in their response to EMI; it may be useful to consider specific safety requirements for areas with such fields present. Working personnel and emergency medical services staff should be informed about potential risks and the possible need for patient evacuation before AEDs are attached and shock recommendations are followed.
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January 2006

Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial.

Lancet 2005 Aug 6-12;366(9484):455-62

Austrian Breast and Colorectal Cancer Study Group (ABCSG), Vienna Medical University, Vienna General Hospital, Waehringer Guertel 18-20, Vienna A-1090, Austria.

Background: Tamoxifen has been the standard adjuvant treatment for postmenopausal women with hormone-responsive early breast cancer for more than 20 years. However, the third-generation aromatase inhibitor anastrozole has proven efficacy and tolerability benefits compared with tamoxifen when used as initial adjuvant therapy. We investigate whether women who have received a period of adjuvant tamoxifen would benefit from being switched to anastrozole.

Methods: We present a combined analysis of data from two prospective, multicentre, randomised, open-label trials with nearly identical inclusion criteria. Postmenopausal women with hormone-sensitive early breast cancer who had completed 2 years' adjuvant oral tamoxifen (20 or 30 mg daily) were randomised to receive 1 mg oral anastrozole (n=1618) or 20 or 30 mg tamoxifen (n=1606) daily for the remainder of their adjuvant therapy. The primary endpoint was event-free survival, with an event defined as local or distant metastasis, or contralateral breast cancer. Analysis was by intention to treat.

Findings: 3224 patients were included in analyses. At a median follow-up of 28 months, we noted a 40% decrease in the risk for an event in the anastrozole group as compared with the tamoxifen group (67 events with anastrozole vs 110 with tamoxifen, hazard ratio 0.60, 95% CI 0.44-0.81, p=0.0009). Both study treatments were well tolerated. There were significantly more fractures (p=0.015) and significantly fewer thromboses (p=0.034) in patients treated with anastrozole than in those on tamoxifen.

Interpretation: These data lend support to a switch from tamoxifen to anastrozole in patients who have completed 2 years' adjuvant tamoxifen.
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October 2005

Effect of laser perforation on the remodeling of acellular matrix grafts.

J Biomed Mater Res B Appl Biomater 2005 Jul;74(1):495-503

Institute of Biomedical Research, Medical University of Vienna, Austria.

Autologous cells migrate only slightly into acellular matrix grafts. This study was carried out in small-diameter, allogeneic matrix grafts to investigate the effects on cell repopulation and remodeling caused by increased wall porosity induced by laser perforation. Allogeneic ovine carotid arteries were decellularized by dye-mediated photooxidation (Photofix). Matrix grafts (10 cm x 4 mm i.d.) were perforated with holes of 50 microm diameter at a density of 50 holes/cm(2) using a Ti-sapphire laser. The grafts were implanted in the carotid arteries of 10 sheep and were compared to nonperforated grafts implanted contralaterally. The prostheses were retrieved after 6 weeks or 3 or 6 months following implantation and were evaluated by histologic examination, immunohistochemical staining, and scanning electron microscopy. All grafts, except one of the perforated specimens, remained patent. Perforated implants, examined at 6 weeks, showed faster recellularization with endothelial cells than did the corresponding contralateral controls. Perforated grafts, examined at 6 months, showed a significantly thicker neointima and clear signs of neovascularization: endothelial cells, basal lamina, elastic fibers, circular and longitudinally orientated smooth muscle cells in comparison to nonperforated specimens. Repopulation of the decellularized matrix with host cells was higher in the perforated than in the nonperforated prostheses. These results suggest that the increased matrix porosity induced by laser perforation promotes graft remodeling and reconstitution with host cells.
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July 2005

Professional satisfaction of women in surgery: results of a national study.

Arch Surg 2004 Nov;139(11):1208-14

Department of Cardiothoracic Surgery, University of Vienna, Vienna, Austria.

Hypothesis: Individual, group, and organizational factors influence the professional satisfaction of women surgeons in Austria.

Design: Survey on professional and private issues sent out by mail in 2000 and 2001.

Setting: Women surgeons working in hospitals and/or in private practices and those who were retired or on maternity leave.

Participants: All 351 Austrian women surgeons of all core surgical specialties (general, trauma, pediatric, plastic, thoracic, and cardiovascular), certified or in training, were addressed.

Main Outcome Measures: Proportional odds regression models were used to correlate professional satisfaction with objectively measurable prognostic factors such as age, surgical subspecialty, status of training, type of hospital, location of work (federal states vs the capital), status of activity (active vs on maternity leave), profession of private partner, number of children, and subjectively assessed prognostic factors such as operative volume and departmental organization.

Results: The response rate was 58.7% (206/351). One hundred eighty-seven surgeons-active or on maternity leave-were included in the analysis. Higher satisfaction was reported by active surgeons in subspecialties, certified surgeons, comparatively younger and older surgeons, surgeons working in hospitals outside the capital, and surgeons with a physician as a partner. When entering subjectively assessed variables into the model, the quality of departmental organization and operative volume (P<.001), as well as the status of activity (P<.001), had the strongest effect.

Conclusions: Women surgeons' professional satisfaction highly depends on departmental organization and status of activity. Inadequate leadership, low operative volume, and being on maternity leave have a negative effect on job satisfaction. Private factors seem to be of little influence. Optimal departmental organization would help women to reconcile their professional and their private lives.
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November 2004

Increased prevalence of sublinical brain perfusion abnormalities in patients with autoimmune thyroiditis: evidence of Hashimoto's encephalitis?

Clin Endocrinol (Oxf) 2003 Nov;59(5):637-43

Department of Nuclear Medicine, University of Vienna, Austria.

Objectives: Hashimoto's encephalitis is a term which describes encephalopathy associated with autoimmune thyroiditis, but it is not based on evidence, whether Hashimoto's encephalitis is a distinct clinical entity by itself. In previously reported cases of Hashimoto's encephalitis, abnormal brain perfusion studies have been reported. The aim of this study was to evaluate the prevalence of brain perfusion abnormalities in euthyroid patients with autoimmune thyroiditis.

Methods: 99mTc Ethyl cystein dimer (ECD) single photon emission computed tomography (SPECT) studies were performed in a study group of 41 euthyroid patients with autoimmune thyroiditis and a matched control group of 35 healthy individuals. All study participants had a normal neurological investigation and a detailed neurological history taking. Individuals with known or suspected morphological brain abnormalities were excluded from the study. Zung's Self-Rating Anxiety Scale (SAS) and Zung's Self-Rating Depression Scale (SDS) were used to detect depression and mood disorders. Automatic quantification of perfusion was performed with both a voxel-based analysis as well as a volume-of-interest (VOI) based analysis of 46 predefined cortical and subcortical regions. The findings from both groups were compared to a reference template.

Results: In the voxel-based analysis, there was a significant difference between patients and controls in the mean volume of perfusion defects deviating 2SD below the normal values (21.8 ml vs. 10.4 ml; P = 0.02). Hyperperfused areas, however, did not differ significantly between study patients and controls. A significant correlation of the perfusion defects with time since diagnosis of autoimmune thyroiditis was seen (r = 0.42). In the VOI-based analysis, abnormal regions were more frequent in the study group when compared to controls (P < 0.01) However, no topographic pattern was apparent. Regarding neurological findings, no significant difference was found between study patients and controls. However, both the SAS and SDS scores differed significantly between the two groups, but there was neither a correlation between the two scores and perfusion abnormalities nor an association with depression in our study group.

Conclusions: These findings of impaired brain perfusion in patients with autoimmune thyroiditis further strengthen the hypothesis of a possible cerebral involvement in autoimmune thyroiditis in individual cases. The presence of cerebral hypoperfusion suggests a cerebral vasculitis as the most likely pathogenetic model.
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November 2003

Perioperative GLY-GLN infusion diminishes the surgery-induced period of immunosuppression: accelerated restoration of the lipopolysaccharide-stimulated tumor necrosis factor-alpha response.

Ann Surg 2003 Jan;237(1):110-5

Surgical Research Laboratories, University of Vienna, Austria.

Objective: To investigate whether the administration of different glutamine-containing dipeptides, glycyl-l-glutamine (GLY-GLN) and l-alanyl-l-glutamine, has a differing impact on perioperative immunomodulation.

Summary Background Data: Surgery leads to transitory immunosuppression, which is associated with decreased plasma glutamine (GLN) levels and increased susceptibility to infection and sepsis. A useful tool to detect immunocompetence is the ex vivo lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNF-alpha) secretion in whole blood.

Methods: Forty-five patients undergoing major abdominal surgery were randomized prospectively to receive 0.5 g/kg/24 h GLN dipeptides administered as GLY-GLN or as ALA-GLN or isonitrogenous Vamin (a GLN-free amino acid solution; control group) as a continuous infusion over 72 hours, starting 24 hours before surgery. Blood samples were collected before infusion, at the end of surgery, and 48 hours postoperatively to determine the TNF-alpha release into whole blood stimulated with LPS. Groups were compared by analysis of variance.

Results: The groups were comparable in age, gender distribution, and length of operative time. At the end of surgery a significant reduction in ex vivo LPS-stimulated TNF-alpha production was observed in all groups. In patients who received GLY-GLN, the induced TNF-alpha production was restored after 48 hours.

Conclusions: In this study perioperative infusion of GLY-GLN reduced immunosuppression. The effect of GLN-containing dipeptides seems to be different when administered in glycine or alanine form.
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January 2003