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1.
Int J Colorectal Dis ; 33(7): 871-878, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29536238

ABSTRACT

PURPOSE: Damage control strategy (DCS) is a two-staged procedure for the treatment of perforated diverticular disease complicated by generalized peritonitis. The aim of this retrospective multicenter cohort study was to evaluate the prognostic impact of an ongoing peritonitis at the time of second surgery. METHODS: Consecutive patients who underwent DCS for perforated diverticular disease of the sigmoid colon with generalized peritonitis at four surgical centers were included. Damage control strategy is a two-stage emergency procedure: limited resection of the diseased colonic segment, closure of oral and aboral colon, and application of a negative pressure assisted abdominal closure system at the initial surgery followed by second laparotomy 48 h later. Therein, decision for definite reconstruction (anastomosis or Hartmann's procedure (HP)) is made. An ongoing peritonitis at second surgery was defined as presence of visible fibrinous, purulent, or fecal peritoneal fluid. Microbiologic findings from peritoneal smear at first surgery were collected and analyzed. RESULTS: Between 5/2011 and 7/2017, 74 patients underwent a DCS for perforated diverticular disease complicated by generalized peritonitis (female: 40, male: 34). At second surgery, 55% presented with ongoing peritonitis (OP). Patients with OP had higher rate of organ failure (32 vs. 9%, p = 0.024), higher Mannheim Peritonitis Index (25.2 vs. 18.9; p = 0.001), and increased operation time (105 vs. 84 min., p = 0.008) at first surgery. An anastomosis was constructed in all patients with no OP (nOP) at second surgery as opposed to 71% in the OP group (p < 0.001). Complication rate (44 vs. 24%, p = 0.092), mortality (12 vs. 0%, p = 0.061), overall number of surgeries (3.4 vs. 2.4, p = 0.017), enterostomy rate (76 vs. 36%, p = 0.001), and length of hospital stay (25 vs. 18.8 days, p = 0.03) were all increased in OP group. OP at second surgery occurred significantly more often in patients with Enterococcus infection (81 vs. 44%, p = 0.005) and with fungal infection (100 vs. 49%, p = 0.007). In a multivariate analysis, Enterococcus infection was associated with increased morbidity (67 vs. 21%, p < 0.001), enterostomy rate (81 vs. 48%, p = 0.017), and anastomotic leakage (29 vs. 6%, p = 0.042), whereas fungal peritonitis was associated with an increased mortality (43 vs. 4%, p = 0.014). CONCLUSION: Ongoing peritonitis after DCS is a predictor of a worse outcome in patients with perforated diverticulitis. Enterococcal and fungal infections have a negative impact on occurrence of OP and overall outcome.


Subject(s)
Diverticulitis/surgery , Intestinal Perforation/surgery , Peritonitis/complications , Aged , Anastomosis, Surgical , Colostomy , Diverticulitis/complications , Diverticulitis, Colonic , Female , Forecasting , Humans , Male , Prognosis , Retrospective Studies
2.
World J Surg ; 42(10): 3189-3195, 2018 10.
Article in English | MEDLINE | ID: mdl-29541823

ABSTRACT

PURPOSE: Optimal surgical management of perforated diverticulitis of the sigmoid colon has yet to be clearly defined. The purpose of this study was to evaluate efficacy of a "Damage Control Strategy" (DCS). MATERIALS AND METHODS: Patients with perforated diverticulitis of the sigmoid colon complicated by generalized peritonitis (Hinchey III and IV) surgically treated according to a damage control strategy between May 2011 and February 2017 were enrolled in the present multicenter retrospective cohort study. Data were collected at three surgical centers. DCS comprises a two-stage concept: [1] limited resection of the perforated colon segment with oral and aboral blind closure during the emergency procedure and [2] definitive reconstruction at scheduled second laparotomy (anastomosis ∓ loop ileostomy or a Hartmann's procedure) after 24-48 h. RESULTS: Fifty-eight patients were included into the analysis [W:M 28:30, median age 70.1 years (30-92)]. Eleven patients (19%) initially presented with fecal peritonitis (Hinchey IV) and 47 patients with purulent peritonitis (Hinchey III). An anastomosis could be created during the second procedure in 48 patients (83%), 14 of those received an additional loop ileostomy. In the remaining ten patients (n = 17%), an end colostomy was created at second laparotomy. A fecal diversion was performed in five patients to treat anastomotic complications. Thus, altogether, 29 patients (50%) had stoma at the end of the hospital stay. The postoperative mortality was 9% (n = 5), and median postoperative hospital stay was 18.5 days (3-66). At the end of the follow-up, 44 of 53 surviving patients were stoma free (83%). CONCLUSION: The use of the Damage Control strategy leads to a comparatively low stoma rate in patients suffering from perforated diverticulitis with generalized peritonitis.


Subject(s)
Colon, Sigmoid/surgery , Colostomy/adverse effects , Diverticulitis, Colonic/complications , Peritonitis/etiology , Shock, Septic/complications , Surgical Stomas/statistics & numerical data , Adult , Aged , Aged, 80 and over , Anastomosis, Surgical/adverse effects , Colonic Diseases , Diverticulitis, Colonic/etiology , Female , Humans , Ileostomy , Intestinal Perforation/etiology , Length of Stay , Male , Middle Aged , Retrospective Studies , Shock, Septic/etiology , Treatment Outcome
3.
Neoplasma ; 63(4): 518-22, 2016.
Article in English | MEDLINE | ID: mdl-27268914

ABSTRACT

With regard to complex structure of tissues, laser capture microdissection represents an important step in analytical workflow streaming to proper molecular characterization of different cell types in examined samples. Therefore the simple method for simultaneous processing of higher numbers of microdissected tissues leading not only to rapid and efficient DNA isolation but allowing also the repeated sampling and easy storage may be useful in the practice of histopathological laboratories. We elaborated such a methodology applicable downstream after the microdissection from formalin-fixed paraffin embedded tissues.The tissues for examination are microdissected directly into the circular areas having the diameter 2 mm and marked on the microscopic slide. In this way, one slide is able to accommodate multiple samples. The DNA extraction is performed in low volume of buffer with Proteinase K in a droplet covered by mineral oil just on the slide. Mineral oil in the quality for molecular biology not only avoids evaporation during DNA extraction, but it helps to position the microdisssected tissue, to control the level of cell lysis microscopically and to protect the DNA sample during subsequent manipulations. We provided the evidence that DNA isolated by our methodology remains in the positions on microscopic slide for months without any changes in the lengths of available fragments and that it may be removed from each position repetitively for different kinds of analysis. The new methodological approach presented by us can be practically applied in broad spectrum of laboratories performing routinely genetic analysis on microdissected tissues.


Subject(s)
DNA/isolation & purification , Microdissection/methods , Tissue Extracts/chemistry , Cytogenetic Analysis , Humans , Paraffin Embedding/methods , Tissue Fixation/methods
4.
Neoplasma ; 63(3): 402-10, 2016.
Article in English | MEDLINE | ID: mdl-26925785

ABSTRACT

Tubulocystic renal cell carcinoma (TRCC) represents a rare tumor with incidence lower than 1 % of all renal carcinomas. This study was undertaken to contribute to characterization of molecular signatures associated with TRCC and to compare them with the features of papillary renal cell carcinoma (PRCC) at the level of genome wide methylation analysis.We performed methylated DNA immunoprecipitation (MeDIP) coupled with microarray analysis (Roche NimbleGen). Using the CHARM package, we compared the levels of gene methylation between paired samples of tumors and control renal tissues of each examined individual. We found significant global demethylation in all tumor samples in comparison with adjacent kidney tissues of normal histological appearance but no significant differences in gene methylation between the both compared tumor entities. Therefore we focused on characterization of differentially methylated regions between both tumors and control tissues. We found 42 differentially methylated genes.Hypermethylated genes for protocadherins (PCDHG) and genes coding for products associated with functions of plasma membrane were evaluated as significantly overrepresented among hypermethylated genes detected in both types of renal cell carcinomas.In our pilot study, we provide the first evidence that identical features in the process of carcinogenesis leading to TRCC and/or to PRCC may be found at the gene methylation level.


Subject(s)
Carcinoma, Papillary/genetics , Carcinoma, Renal Cell/genetics , DNA Methylation , Kidney Neoplasms/genetics , Adult , Aged , Carcinogenesis/genetics , Carcinoma, Papillary/pathology , Carcinoma, Renal Cell/pathology , Female , Genome-Wide Association Study , Humans , Immunoprecipitation , Kidney Neoplasms/pathology , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Pilot Projects
5.
Tech Coloproctol ; 20(8): 577-83, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27448296

ABSTRACT

BACKGROUND: The best surgical strategy for the management of perforated diverticulitis with generalized peritonitis of the sigmoid colon is not clearly defined. The aim of this retrospective cohort study was to evaluate the value of a damage control strategy. METHODS: All patients who underwent emergency laparotomy for perforated diverticular disease of the sigmoid colon with generalized peritonitis between 2010 and 2015 were included. The damage control strategy (study group), included a two- stage procedure: limited resection of the diseased colonic segment, closure of proximal colon and distal stump, and application of an abdominal vacuum at the initial surgery followed by second-look laparotomy 24-48 h later At this point a choice was made between anastomosis and Hartmann's procedure. The control group consisted of patients receiving definitive reconstruction (anastomosis or Hartmann's procedure) at the initial operation. RESULTS: Thirty-seven patients were included in the study. Damage control strategy was applied in 19 patients and the control group consisted of 18 patients. Both groups were comparable in terms of demographics, severity of peritonitis, and comorbidities. The overall postoperative mortality was 11 % (n = 4). There were no statistically significant differences between both groups regarding postoperative morbidity and mortality; however, a significantly higher proportion of patients in the control group had a stoma after the initial hospital stay (83 vs. 47 %, p = 0.038). This difference was still significant after adjustment for sex, age, Mannheim Peritonitis Index, American Society of Anesthesiologists class and presence of septic shock at presentation. At the end of the follow-up period, 15 of 17 survivors in the study group and 13 of 16 survivors in the control group had their intestinal continuity restored (p = 0.66). CONCLUSIONS: Damage control strategy in patients with generalized peritonitis due to perforated diverticulitis leads to a significantly reduced stoma rate after the initial hospital stay without an increased risk of postoperative morbidity.


Subject(s)
Colon, Descending/surgery , Diverticulitis, Colonic/surgery , Intestinal Perforation/surgery , Peritonitis/etiology , Rectum/surgery , Adult , Aged , Aged, 80 and over , Anastomosis, Surgical/adverse effects , Colectomy/adverse effects , Colon, Sigmoid , Colostomy/adverse effects , Diverticulitis, Colonic/complications , Female , Humans , Ileostomy/adverse effects , Intestinal Perforation/etiology , Male , Middle Aged , Negative-Pressure Wound Therapy , Retrospective Studies , Second-Look Surgery
7.
Anaesthesist ; 63(8-9): 691-6, 2014 Sep.
Article in German | MEDLINE | ID: mdl-25056410

ABSTRACT

BACKGROUND: Prehospital emergency medicine is a challenge for trainee emergency physicians. Rare injuries and diseases as well as patients in extreme age groups can unexpectedly face emergency physicians. In the regulations on medical education the German Medical Association requires participation in 50 emergency missions under the supervision of an experienced emergency physician. This needs to be improved because on-the-job training does not generally represent the whole spectrum of emergency medicine and a good and structured training under on call conditions is nearly impossible. AIM: The subject of the model project described was whether practical training for emergency physicians can be achieved by participation in simulation training instead of real emergency situations. MATERIAL AND METHODS: After modification of the Saarland regulations on medical education it was possible to replace up to 25 participations in emergency missions by simulation training. The concept of the course NASimSaar25 requires participants to complete 25 simulator cases in 3 days in small training groups. Emergency situations from all medical disciplines need to be treated. A special focus is on the treatment of life-threatening and rare diseases and injuries. Modern simulators and actors are used. The debriefings are conducted by experienced tutors based on approved principles. Medical contents, learning targets from the field of crew resource management (CRM) and soft skills are discussed in these debriefings. RESULTS: Education in the field of emergency medicine can be improved by simulator-based learning and training. However, practical work under a tutor in real and clinical experience cannot be completely replaced by simulation. Simulator training can only be successful if theoretical knowledge has already been acquired. CONCLUSION: A simulator-based course concept can result in an improvement of emergency medical education. The model project NASimSaar25 was well received by the target audience and mostly very well evaluated in terms of learning and reality. If this project becomes established the demand on simulation-based training will increase. The training should achieve a consistent standard of quality.


Subject(s)
Emergency Medicine/education , Patient Simulation , Physicians , Clinical Competence , Computer Simulation , Curriculum , Emergency Medicine/legislation & jurisprudence , Germany , Humans , Inservice Training
8.
Z Gastroenterol ; 51(5): 450-7, 2013 May.
Article in German | MEDLINE | ID: mdl-23681899

ABSTRACT

Patients with ulcerative colitis and Crohn's colitis are at increased risk of colorectal cancer (CRC). This risk is dependent on the duration and extent of disease, inflammatory activity and possible additional risk factors. Thus, the aim is to reduce this risk and to detect dysplastic and malignant lesions at an early stage. The working group for Inflammatory Bowel Diseases (IBD) of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) has developed consensus statements on the following topics: risk of colorectal cancer, screening and surveillance, procedure of surveillance colonoscopy, dysplasia and its management, and chemoprevention. This consensus is intended to increase awareness of the increased risk of CRC in IBD and to support a standardised approach in cancer prevention.


Subject(s)
Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Early Detection of Cancer/standards , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/prevention & control , Population Surveillance/methods , Practice Guidelines as Topic , Austria/epidemiology , Colorectal Neoplasms/epidemiology , Humans , Inflammatory Bowel Diseases/epidemiology , Prevalence
9.
Chem Commun (Camb) ; 57(95): 12804-12807, 2021 Nov 30.
Article in English | MEDLINE | ID: mdl-34783334

ABSTRACT

Silica is widely used in industrial applications and its performance is partially decided by its surface hydroxyl density αOH. Here we report a quick, simple liquid 1H NMR method to determine αOH using a benchtop 1H NMR spectrometer. The results show excellent agreement with the literature with an αOH range from 4.16 to 6.56 OH per nm2.

10.
Haemophilia ; 16(5): 726-30, 2010 Sep 01.
Article in English | MEDLINE | ID: mdl-20236353

ABSTRACT

SUMMARY: Two male first cousins with mild haemophilia A had baseline factor VIII levels of 12-15% and experienced bleeding requiring coagulation factor infusion therapy with trauma and surgical procedures. Both the patients with haemophilia A also had electrocardiographically documented symptomatic paroxysmal atrial fibrillation (PAF) for several years that had become resistant to pharmacological suppression. Radiofrequency ablation was considered in both the cases but deferred considering refusal of consent by the patients to undergo the procedure. Remission of arrhythmias has been reported in patients with iron-overload syndromes. Body iron stores assessed by serum ferritin levels were elevated in both men but neither had the C282Y or H63D genes for haemochromatosis. Calibrated reduction of iron stores by serial phlebotomy, avoiding iron deficiency, was followed by remission of symptomatic PAF in both cases. Iron reduction may be an effective treatment for arrhythmias apart from the classic iron-overload syndromes and deserves further study particularly in patients with bleeding disorders who might be at risk for arrhythmias and other diseases of ageing.


Subject(s)
Atrial Fibrillation/etiology , Atrial Fibrillation/therapy , Hemophilia A/complications , Iron Overload/complications , Iron Overload/therapy , Phlebotomy , Factor VIII/administration & dosage , Ferritins/blood , Hemophilia A/therapy , Humans , Male , Middle Aged , Treatment Outcome
11.
Science ; 194(4272): 1424-7, 1976 Dec 24.
Article in English | MEDLINE | ID: mdl-188128

ABSTRACT

High-field (63.4 kilogauss) Fourier transform nuclear magnetic resonance spectroscopy 13C in natural abundance has been used to study the structural organization and molecular dynamics of constituent lipids of normal human very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). The same method was used to study the abnormal beta-VLDL of two type III hyperlipoproteinemia patients having markedly differing ratios of VLDL cholesterol to triglyceride (0.3 and 0.6, respectively). Resolution obtained at 63.4 kilogauss has made possible the assignment of several additional resonances of cholesterol ring carbon atoms, not resolved in earlier studies at lower fields, in the VLDL spectra. The rotational reorientation of the ring portion of cholesteryl esters in VLDL (normal) and beta-VLDL (abnormal) is not highly anisotropic and is similar to that for cholesteryl esters disolved in excess triolein. The rotations of cholesteryl esters in LDL are more highly anisotropic and significantly more restricted. The results suggest that the structural organization of the lipid components in beta-VLDL resembles that found in normal VLDL but differs significantly from that for normal LDL.


Subject(s)
Hyperlipidemias/blood , Cholesterol , Humans , Lipoproteins, LDL , Lipoproteins, VLDL/blood , Magnetic Resonance Spectroscopy , Molecular Conformation , Triglycerides
13.
Curr Oncol ; 25(3): e193-e199, 2018 06.
Article in English | MEDLINE | ID: mdl-29962845

ABSTRACT

Malnutrition is a frequent manifestation in patients with head-and-neck cancer undergoing radiation therapy and a major contributor to morbidity and mortality. Thus, body composition is an important component of an overall evaluation of nutrition in cancer patients. Malnutrition is characterized by weight loss, loss of muscle mass, changes in cell membrane integrity, and alterations in fluid balance. Bioelectrical impedance analysis is a method to analyze body composition and includes parameters such as intracellular water content, extracellular water content, and cell membrane integrity in the form of a phase angle (Φ). Bioelectrical impedance analysis has consistently been shown to have prognostic value with respect to mortality and morbidity in patients undergoing chemotherapy. The goal of the present study was to evaluate the relationship between Φ, time, intracellular water content, and weight for head-and-neck cancer patients undergoing radiotherapy. The results demonstrate that Φ decreases with time and increases with intracellular water content and weight.


Subject(s)
Electric Impedance/therapeutic use , Head and Neck Neoplasms/radiotherapy , Malnutrition/etiology , Adult , Aged , Body Weight , Humans , Male , Malnutrition/pathology , Middle Aged , Nutrition Assessment , Prognosis
14.
Clin Microbiol Infect ; 24(3): 267-272, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28669844

ABSTRACT

OBJECTIVES: We report on a large prospective, multicentre clinical investigation on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori. METHODS: Therapy-naive patients (n = 2004) who had undergone routine diagnostic gastroscopy were prospectively included from all geographic regions of Austria. Gastric biopsy samples were collected separately from antrum and corpus. Samples were analysed by histopathology and real-time PCR for genotypic resistance to clarithromycin and quinolones. Clinical and demographic information was analysed in relation to resistance patterns. RESULTS: H. pylori infection was detected in 514 (26%) of 2004 patients by histopathology and confirmed in 465 (90%) of 514 patients by real-time PCR. PCR results were discordant for antrum and corpus in 27 (5%) of 514 patients, indicating inhomogeneous infections. Clarithromycin resistance rates were 17% (77/448) and 19% (84/455), and quinolone resistance rates were 12% (37/310) and 10% (32/334) in antrum and corpus samples, respectively. Combination of test results per patient yielded resistance rates of 21% (98/465) and 13% (50/383) for clarithromycin and quinolones, respectively. Overall, infection with both sensitive and resistant H. pylori was detected in 65 (14%) of 465 patients. CONCLUSIONS: Anatomically inhomogeneous infection with different, multiple H. pylori strains is common. Prospective clinical study design, collection of samples from multiple sites and microbiologic methods that allow the detection of coinfections are mandatory for collection of reliable data on antimicrobial resistance patterns in representative patient populations. (ClinicalTrials.gov identifier: NCT02925091).


Subject(s)
Drug Resistance, Bacterial , Helicobacter Infections/microbiology , Helicobacter pylori/drug effects , Helicobacter pylori/genetics , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Austria , Biopsy , Clarithromycin/pharmacology , Female , Gastric Mucosa/microbiology , Gastric Mucosa/pathology , Genes, Bacterial , Genetic Variation , Helicobacter pylori/isolation & purification , Histocytochemistry , Humans , Male , Middle Aged , Prospective Studies , Quinolones/pharmacology , Real-Time Polymerase Chain Reaction , Young Adult
15.
Oncogene ; 10(12): 2421-5, 1995 Jun 15.
Article in English | MEDLINE | ID: mdl-7784093

ABSTRACT

Expression of the cyclin D1 gene is induced when quiescent fibroblasts are stimulated to reenter the cell cycle by addition of growth factors. Moderate ectopic expression of cyclin D1 in early G1 facilitates progression through G1. When transiently overexpressed at the G1/S boundary, cyclin D1 prevents S phase entry, suggesting a dual role for this protein in cellular growth control. It was shown that the retinoblastoma protein (pRB) can activate cyclin D1 gene expression; furthermore, there is evidence that expression of the cyclin D1 gene is down-regulated by the SV40 large T and adenovirus E1A genes, both of which were shown to target pRB. We now report that in diploid human fibroblasts functional inactivation of pRB by adenovirus E1A is not sufficient for efficient repression of cyclin D1 gene expression, since the E1B gene product, in addition to E1A, is required for repression of the cyclin D1 gene. Since E1B was shown to target p53, we investigated the role of p53 for expression of the cyclin D1 gene. In a cell line with temperature-sensitive p53, cyclin D1 is moderately expressed at the restrictive temperature. Induction of p53 function by temperature shift leads to an increase of cyclin D1 mRNA and protein, parallel to the activation of p21WAF-1/CIP1 gene expression in this system. When the capability of adenovirus gene products to affect expression of either gene was analysed, we found that infection of Ad5 drastically reduced cyclin D1 and p21WAF-1/CIP1 gene expression in cells where p53 function is limiting. Under these conditions E1A and E1B cooperate to reduce the cyclin D1 level, while p21WAF-1/CIP1 expression was found insensitive to E1A expression. In cells containing elevated p53 function, modulation of gene expression by E1B was severely compromised; under these conditions, expression of E1A reduced expression of cyclin D1 without affecting p21WAF-1/CIP1. The data suggest that E1A and E1B cooperate to inhibit expression of cyclin D1 and identify the cyclin D1 gene as a new downstream target for p53.


Subject(s)
Adenovirus E1A Proteins/physiology , Adenoviruses, Human/genetics , Cyclins/metabolism , Fibroblasts/metabolism , Genes, p53/physiology , Oncogene Proteins/metabolism , Oncogenes/physiology , Retinoblastoma Protein/metabolism , Adenovirus E1A Proteins/metabolism , Adenovirus E1B Proteins/metabolism , Adenovirus E1B Proteins/physiology , Cyclin D1 , Cyclin-Dependent Kinase Inhibitor p21 , Cyclins/genetics , Gene Expression Regulation, Viral , Humans , Oncogene Proteins/genetics , Temperature
16.
Oncogene ; 15(21): 2561-76, 1997 Nov 20.
Article in English | MEDLINE | ID: mdl-9399644

ABSTRACT

Activation of Myc triggers a rapid induction of cyclin E/cdk2 kinase activity and degradation of p27. Overt degradation of p27 is preceded by a specific dissociation of p27 from cyclin E/cdk2, but not from cyclin D/cdk4 complexes. We now show that cyclin E/cdk2 phosphorylates p27 at a carboxy-terminal threonine residue (T187) in vitro; mutation of this residue to valine stabilises cyclin E/cdk2 complexes. This reaction is not significantly inhibited by high concentrations of p27, suggesting that cdk2 bound to p27 is catalytically active. In vivo, p27 bound to cyclins E and A, but not to D-type cyclins is phosphorylated. Myc-induced release of p27 from cdk2 requires cdk2 kinase activity and is delayed in a T187V mutant of p27. After induction of Myc, p27 phosphorylated at threonine 187 transiently accumulates in a non cdk2 bound form. Our data suggest a mechanism in which p27 is released from cyclin E/cdk2 upon phosphorylation; in Myc-transformed cells, release is efficient as phosphorylated p27 is transiently bound in a non-cdk2 containing complex and subsequently degraded.


Subject(s)
CDC2-CDC28 Kinases , Cell Cycle Proteins , Cyclin E/metabolism , Cyclin-Dependent Kinases/metabolism , Genes, myc/physiology , Microtubule-Associated Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Tumor Suppressor Proteins , Animals , Cells, Cultured , Cyclin-Dependent Kinase 2 , Cyclin-Dependent Kinase Inhibitor p27 , Mice , Phosphorylation , Rabbits
17.
Circulation ; 103(25): 3092-8, 2001 Jun 26.
Article in English | MEDLINE | ID: mdl-11425774

ABSTRACT

BACKGROUND: The purpose of our study was to define the incidence and mechanisms of atypical right atrial flutter. METHODS AND RESULTS: A total of 28 (8%) of 372 consecutive patients with atrial flutter (AFL) had 36 episodes of sustained atypical right AFL. Among 24 (67%) of 36 episodes of lower loop reentry (LLR), 13 (54%) of 24 episodes had early breakthrough at the lower lateral tricuspid annulus, whereas 11 (46%) of 24 episodes had early breakthrough at the high lateral tricuspid annulus, and 9 (38%) of 24 episodes showed multiple annular breaks. Bidirectional isthmus block resulted in elimination of LLR. A pattern of posterior breakthrough from the eustachian ridge to the septum was observed in 4 (14%) of 28 patients. Upper loop reentry was observed in 8 (22%) of 36 episodes and was defined as showing a clockwise orientation with early annular break and wave-front collision over the isthmus. Two patients had atypical right AFL around low voltage areas ("scars") in the posterolateral right atrium. CONCLUSIONS: Atypical right AFL is most commonly associated with an isthmus-dependent mechanism (ie, LLR or subeustachian isthmus breaks). Non-isthmus-dependent circuits include upper loop reentry or scar-related circuits.


Subject(s)
Atrial Flutter/physiopathology , Heart Atria/physiopathology , Aged , Cohort Studies , Electrocardiography , Heart Conduction System/physiopathology , Humans , Middle Aged , Tachycardia/physiopathology
18.
J Am Coll Cardiol ; 35(5): 1276-87, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10758970

ABSTRACT

OBJECTIVES: This study was directed at developing spatial 62-lead electrocardiogram (ECG) criteria for classification of counterclockwise (CCW) and clockwise (CW) typical atrial flutter (Fl) in patients with and without structural heart disease. BACKGROUND: Electrocardiographic classification of CCW and CW typical atrial Fl is frequently hampered by inaccurate and inconclusive scalar waveform analysis of the 12-lead ECG. METHODS: Electrocardiogram signals from 62 torso sites and multisite endocardial recordings were obtained during CCW typical atrial Fl (12 patients), CW typical Fl (3 patients), both forms of typical Fl (4 patients) and CCW typical and atypical atrial Fl (1 patient). All the Fl wave episodes were divided into two or three successive time periods showing stable potential distributions from which integral maps were computed. RESULTS: The initial, intermediate and terminal CCW Fl wave map patterns coincided with: 1) caudocranial activation of the right atrial septum and proximal-to-distal coronary sinus activation, 2) craniocaudal activation of the right atrial free wall, and 3) activation of the lateral part of the subeustachian isthmus, respectively. The initial, intermediate and terminal CW Fl wave map patterns corresponded with : 1) craniocaudal right atrial septal activation, 2) activation of the subeustachian isthmus and proximal-to-distal coronary sinus activation, and 3) caudocranial right atrial free wall activation, respectively. A reference set of typical CCW and CW mean integral maps of the three successive Fl wave periods was computed after establishing a high degree of quantitative interpatient integral map pattern correspondence irrespective of the presence or absence of organic heart disease. CONCLUSIONS: The 62-lead ECG of CCW and CW typical atrial Fl in man is characterized by a stereotypical spatial voltage distribution that can be directly related to the underlying activation sequence and is highly specific to the direction of Fl wave rotation. The mean CCW and CW Fl wave integral maps present a unique reference set for improved clinical detection and classification of typical atrial Fl.


Subject(s)
Atrial Flutter/classification , Atrial Flutter/diagnosis , Body Surface Potential Mapping/methods , Electrocardiography/methods , Endocardium , Heart Conduction System , Aged , Algorithms , Atrial Flutter/drug therapy , Atrial Flutter/etiology , Atrial Flutter/physiopathology , Body Surface Potential Mapping/instrumentation , Discriminant Analysis , Electrocardiography/instrumentation , Endocardium/physiopathology , Female , Heart Conduction System/physiopathology , Heart Diseases/complications , Humans , Male , Middle Aged , Reproducibility of Results , Risk Factors , Rotation , Sensitivity and Specificity , Time Factors
19.
Clin Cancer Res ; 5(5): 1025-33, 1999 May.
Article in English | MEDLINE | ID: mdl-10353735

ABSTRACT

Human gliomas, especially of low-grade type, have been shown to express high-affinity somatostatin receptor type 2 (J-C. Reubi et al., Am. J. Pathol, 134: 337-344, 1989). We enrolled seven low-grade and four anaplastic glioma patients in a pilot study using the diffusible peptidic vector 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) for receptor targeting. The radiopharmakon was locoregionally injected into a stereotactically inserted Port-a-cath. DOTATOC competes specifically with somatostatin binding to somatostatin receptor type 2 in the low nanomolar range as shown by a displacement curve of 125I-[Tyr3]-octreotide in tumor tissue sections. Diagnostic (111)In-labeled DOTATOC-scintigraphy following local injection displayed homogeneous to nodular intratumoral vector distribution. The cumulative activity of regionally injected peptide-bound 90Y amounted to 370-3300 MBq, which is equivalent to an effective dose range between 60 +/- 15 and 550 +/- 110 Gy. Activity was injected in one to four fractions according to tumor volumes; 1110 MBq of 90Y-labeled DOTATOC was the maximum activity per single injection. We obtained six disease stabilizations and shrinking of a cystic low-grade astrocytoma component. The only toxicity observed was secondary perifocal edema. The activity:dose ratio (MBq:Gy) represents a measure for the stability of peptide retention in receptor-positive tissue and might predict the clinical course. We conclude that SR-positive human gliomas, especially of low-grade type, can be successfully targeted by intratumoral injection of the metabolically stable small regulatory peptide DOTATOC.


Subject(s)
Brain Neoplasms/radiotherapy , Glioma/radiotherapy , Neoplasm Proteins/antagonists & inhibitors , Octreotide/analogs & derivatives , Radioisotopes/therapeutic use , Radiopharmaceuticals/therapeutic use , Receptors, Somatostatin/antagonists & inhibitors , Ytterbium/therapeutic use , Adult , Astrocytoma/metabolism , Astrocytoma/pathology , Astrocytoma/radiotherapy , Binding, Competitive , Brain Edema/chemically induced , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Diffusion , Disease Progression , Female , Glioblastoma/metabolism , Glioblastoma/pathology , Glioblastoma/radiotherapy , Glioma/metabolism , Glioma/pathology , Humans , Injections, Intralesional , Male , Middle Aged , Octreotide/administration & dosage , Octreotide/adverse effects , Octreotide/pharmacokinetics , Octreotide/therapeutic use , Oligodendroglioma/metabolism , Oligodendroglioma/pathology , Oligodendroglioma/radiotherapy , Pilot Projects , Radioisotopes/administration & dosage , Radioisotopes/adverse effects , Radioisotopes/pharmacokinetics , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/adverse effects , Radiopharmaceuticals/pharmacokinetics , Radiotherapy Dosage , Stereotaxic Techniques , Tissue Distribution , Ytterbium/administration & dosage , Ytterbium/adverse effects , Ytterbium/pharmacokinetics
20.
Surg Endosc ; 19(10): 1315-9, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16206012

ABSTRACT

BACKGROUND: From 1996, the entire number of fundoplications performed in Austria increased dramatically, favoring the laparoscopic technique. Despite good results, some patients experience failure of antireflux surgery and therefore require redo surgery if medical therapy fails to control symptoms. The aim of the study was to describe the refundoplication policy in Austria with evaluation of the postoperative results. METHODS: A questionnaire was sent to all Austrian surgical departments at the beginning of 2003 with questions about redo fundoplications (number, techniques, intraoperative complications, history, migration of patients, preoperative workup, mortality, and postoperative long-term complaints). It also included questions about primary fundoplications (number, technique, postoperative symptoms). RESULTS: Out of 4,504 primary fundoplications performed in Austria since 1990, 3,952 have been carried out laparoscopically. In a median of 31 months after the primary operation, 225 refundoplications have been performed, laparoscopically in the majority of patients. The Nissen and the partial posterior fundoplication were the preferred techniques. The conversion rate in these was 10.8%, mainly because of adhesions and lacerations of the spleen, the stomach, and the esophagus. The mortality rate after primary fundoplications was 0.04%, whereas the rate after refundoplications was 0.4%, all resulting from an open approach. CONCLUSION: Laparoscopic refundoplications are widely accepted as a treatment option after failed primary antireflux surgery in Austria. However, the conversion rate is 6 times higher and the mortality rate is 10 times higher than for primary antireflux surgery. Therefore, redo fundoplications should be performed only in departments with large experience.


Subject(s)
Fundoplication , Gastroesophageal Reflux/surgery , Austria , Fundoplication/statistics & numerical data , Humans , Reoperation/statistics & numerical data , Surveys and Questionnaires
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