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A Koch

Publications and source records attributed to A Koch.

At least 55 records · Page 3Linked to original sources
PubMed2004

No evidence for mutations or altered expression of the Suppressor of Fused gene (SUFU) in primitive neuroectodermal tumours.

The sonic hedgehog (Shh) and the Wnt signalling pathways are involved in the development of medulloblastomas (MBs), the most frequent malignant brain tumours in children. Components of these two developmental and cancer-associated pathways, including (Patched) PTCH, SMOH, adenomatous polyposis coli (APC), beta-catenin and AXIN1 show somatic mutations in sporadic MBs. In this study we analysed SUFU (human Suppressor of Fused), which acts as a negative regulator of both the Shh and Wnt signalling pathways and therefore represents a putative tumour suppressor gene, to find out if it is also involved in the pathogenesis of sporadic MBs. We screened 145 primitive neuroectodermal tumours (PNETs) including 90 classic MBs, 42 of the desmoplastic variant and two medullomyoblastomas as well as 11 MB cell lines for mutations using single-strand conformational polymorphism (SSCP) and sequencing analysis. 18% of the MBs exhibited allelic losses on chromosome 10q. In contrast to a previous report, in which truncating mutations of SUFU have been identified in 9% of MBs, we were not able to identify somatic mutations of SUFU in our large tumour panel. We uncovered single nucleotide polymorphisms (SNPs) in exon 4, 8, 11 and in intron 2 in the SUFU gene. Expression analysis by competitive reverse transcription-polymerase chain reaction (RT-PCR) revealed no difference in SUFU mRNA levels of both MB subtypes and normal foetal or adult cerebellar tissues. Our results indicate that genetic alterations of the SUFU gene, do not contribute significantly to the molecular pathogenesis of MBs.

Adolescent↗
PubMed2004

Effect of smoking on MAP kinase-induced modulation of IL-8 in human alveolar macrophages.

Inflammatory cytokine production by alveolar macrophages (AMs) is regulated by transcriptional activation and may be increased by cigarette smoking. The smoking-induced regulation of interleukin (IL)-8 by extracellular signal-regulated kinase (ERK)-1 and -2, p38 mitogen-activated protein kinase (MAPK) and the transcription factor nuclear factor-kappaB (NF-kappaB) in lipopolysaccharide-stimulated AMs was assessed in nine smokers compared with nine healthy nonsmokers. IL-8 production was dependent on phosphorylation of ERK-1 and -2 and p38 MAPK, as examined by PD 098059 (10 microM), an inhibitor of the upstream activator of MAPK kinase (MKK)-1, and SB 203580 (10 microM), an inhibitor of p38 MAPK. IL-8 release and the inhibitory effect of PD 098059 were increased in AMs from smokers. Moreover, ERK-2 messenger ribonucleic acid expression, as examined by reverse transcriptase polymerase chain reaction and phosphorylation of ERK-2 using Western blots, were increased in AMs from smokers, indicating a smoking-induced modulatory role of ERK-1 and -2. Lipopolysaccharide-induced IL-8 production was dependent on activation of NF-kappaB, as examined by SN 50 (100 microM), an inhibitor of NF-kappaB translocation, and the specific NF-kappaB inhibitor kinase-2 inhibitor, AS 602868 (10 microM), with no differences in AMs from smokers and nonsmokers. SN 50 but not PD 098059 and SB 203580 blocked NF-kappaB deoxyribonucleic acid-binding, and this occurred to the same extent in AMs from smokers and nonsmokers, as examined by electromobility shift assay. It is concluded that cigarette smoking enhances mitogen-activated protein kinase activation more than nuclear factor-kappaB activation to increase lipopolysaccharide-induced interleukin-8 production in alveolar macrophages.

Adult↗
PubMed2003

Aortic root abscess complicated by fistulization and intracerebral hemorrhagic infarction.

We report an unusual case of a 12-year-old male with aortic root abscess complicated by fistulization and intracerebral hemorrhagic infarction. Transesophageal echocardiography provided exact information about the location and dimension. Color-flow mapping demonstrated fistulous communication between the abscess and both the aorta and the left ventricle, causing severe diastolic regurgitation through the paravalvular leak. Pulmonary autograft aortic root replacement was performed with good result.

Abscess↗
PubMed2003

ACE-inhibitors but not endothelin receptor blockers prevent podocyte loss in early diabetic nephropathy.

AIMS/HYPOTHESIS: It was the aim of our study to investigate the influence of a selective ET-A receptor antagonist LU 135252 alone and in combination with the ACE-inhibitor, trandolapril on podocyte number and morphology in streptozotocin diabetic rats. METHODS: Male Sprague-Dawley rats were injected with 65 mg streptozotocin i.v. and subsequently developed diabetes. Animals were left untreated or received daily either trandolapril (0.3 mg/kg body weight), LU 135252 (50 mg/kg body weight) or a combination of both. After 6 months the experiment was terminated. Glomerular geometry and cellularity were assessed by stereological techniques. Protein expression of TGF-beta, ET-1, PDGF-AB, fibronectin, desmin and alpha-smooth muscle cell actin was investigated by immunohistochemistry. RESULTS: The mean number of podocytes per glomerulus was lower (86+/-17 vs. 138+/-25; p<0.05) and mean podocyte volume was higher in untreated diabetic animals than in non-diabetic controls. Only ACE-i alone and in combination, but not ET(A)-RB alone prevented loss of podocytes and podocyte hypertrophy. In diabetic rats, increased numbers of PCNA positive and p27(kip1) positive cells (mainly podocytes) were reduced by all treatments, but only ACE-i decreased numbers of desmin positive podocytes and tubulointerstitial expression of TGF-beta. Albuminuria was increased in untreated diabetes and was prevented only by ACE-i and combination treatment. CONCLUSION/INTERPRETATION: Podocyte hypertrophy and degeneration is an early event in diabetic nephropathy leading to a loss of podocytes. Treatment with an ACE-i, but not with an ET(A)-RB, prevented the development of albuminuria as well as damage and loss of podocytes. The well known anti-proteinuric effect of ACE-i is presumably due at least in part to conservation of podocyte structure. Increased plasma endothelin-1 (ET-1) concentrations and urine excretion of ET-1 have been documented in patients with diabetes and proteinuria [1]. It has been shown that experimental diabetes mellitus increases renal ET-1 gene transcription [2]. To assess the relevance of the ET-system in the pathogenesis of renal structural changes in the model of the STZ-induced diabetic rat we compared the effect of an ET(A)-receptor specific antagonist with the well known beneficial effect of an ACE-i, especially on podocyte cell number and morphology.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Comparison of the electronic structures of imine and hydrazone side-chain functionalities with the aid of 13C and 15N NMR chemical shifts and PM3 calculations. The influence of C=N-substitution on the sensitivity to aromatic substitution.

Benzaldehyde derivatives possessing a C=N double bond in the side-chain of the aromatic ring exhibit a reverse dependence of the (13)C NMR chemical shifts of the C=N carbon on the benzylidenic substituents X. Thus, electron-withdrawing substituents cause shielding (shift is reduced), while electron-donating ones cause deshielding. The origin of this phenomenon, which is in contrast with the idea of the generalized electronic effect, is extensively studied here by comparing the behavior of sets of benzaldehyde derivatives bearing various substitutents Y on the C=N nitrogen (Y-N=CH-C(6)H(4)-X). The effects of substituents X on the C=N unit change when Y is varied. Combination of the influences of the substituents X and Y gives a sensitive balance between the different resonance structures of the compounds. Our graphical treatment, where the rho(I) and rho(R) values observed for substituent X are plotted against the sigma(p)(+) value of substituent Y, is a novel use of Hammett-type substituent parameters. The justification of this method and our conclusions could be verified, for instance, by the fair correlation between the rho(I) or rho(R) values and the atomic charges of the imine carbon of the unsubstitued phenyl derivatives as well as by the correlations of the relevant bond orders and/or bond lengths both with the substituent parameters and with the atomic charges.

Journal Article↗
PubMed2003

[Importance of rectal extirpation for the therapy concept of low rectal cancers].

INTRODUCTION: The main objective of surgery of rectal carcinomas is to avoid a permanent colostomy by sphincter-sparing surgical procedures. A variety of different abdominoperineal resection rates is described in the literature. MATERIAL/METHOD: The study was performed in 2000 within the framework of a multicentric study including 282 hospitals. The purpose of the study was to document the quality of diagnosis and therapy for colorectal carcinomas.A total of 9477 patients were included in this study: 3402 suffering from a rectal carcinoma and 6075 suffering from a colon carcinoma. RESULTS: A total of 866 abdominoperineal resections was performed. This corresponds to an abdominoperineal resection rate of 27.4%. In 30.4% of all men and in 23.0% of all women an abdominoperineal resection was performed. Of all tumor patients who underwent abdominoperineal resection, 8.3% had a pT4 carcinoma and 57.5% a pT3 carcinoma. Adapted to the localization of the tumor in the rectum, i.e., the distance of the aboral tumor margin to the anal verge, the following abdominoperineal resection rates were found: <4 cm from the anal verge 84.6%, 4-7.9 cm 43.9%, 8-11.9 cm 5.8%, and 12-16 cm 0.5%.Intraoperative complications occurred in 11.8%, specific postoperative complications in 33.1%, and general postoperative complications in 27.4% of the patients. The postoperative lethality was 2.8%. The mean postoperative hospital stay was 21.7 days. Logistic regression identified the body mass index, gender, the distance of the carcinoma from the anal verge, and the T category as independent factors influencing the abdominoperineal resection rate. DISCUSSION: Despite an overall decrease in use, abdominoperineal resection will continue to play an important role for the surgical treatment of low rectal cancers in routine clinical practice in Germany. It will remain an individual decision for each patient whether the tumor and the patient allow sphincter preservation or whether abdominoperineal resection seems to be necessary. According to the results of the present study,a general definition of an abdominoperineal resection rate in an unselected group of patients should be viewed critically.

Adult↗
PubMed2003

The effect of storage on allergen and microbial agent levels in frozen house dust.

BACKGROUND: House dust samples collected for exposure studies are often stored for variable time periods until analysis. However, there is currently no information on the effects of dust storage on the content of biocontaminants. Therefore, associations were analysed between the levels of mite allergens (Der p 1, Der f 1), cat allergen (Fel d 1) and microbial components (endotoxin, beta(1-->3)-glucan) on the one hand and the storage duration of dust samples at -20 degrees C on the other hand. METHODS: Within the framework of a study on the influences of INdoor factors and Genetics on Asthma (INGA), dust samples were collected from living room floors between June 1995 and August 1998 and extracted according to a standardized protocol. The concentrations of Der p 1, Der f 1, Fel d 1 and beta(1-->3)-glucan were determined with specific enzyme immunoassays. Endotoxin content was quantified using a chromogenic kinetic Limulus amoebocyte lysate (LAL) test. All concentrations were expressed per gram of dust RESULTS: Dust samples (n = 1236) were obtained from 655 homes in Hamburg, Hettstedt, Zerbst and Bitterfeld. Storage duration (range 8-298 days) was grouped into four categories ( 120 d). After adjustment for city of residence and season of dust sampling, means ratios comparing categories 2-4 to the first category were not statistically significant for Der p 1, Der f 1, endotoxin and beta(1-->3 glucan). However, Fel d 1 concentrations significantly declined with increased storage times of dust samples. CONCLUSIONS: Storage of house dust at -20 degrees C for up to 10 months has no effect on mite allergen, endotoxin and beta(1-->3)-glucan levels. A potential loss of Fel d 1 during storage of frozen dust samples needs further investigations by repeated measurements of allergen in identical dust samples.

Air Pollution, Indoor↗
PubMed2003

Polydactylous Bowen's disease.

Malignant nail tumours are rare. We report on a 52-year-old patient with chronic verrucous lesions of the nail bed of fingers and toes. Nail biopsy revealed polydactylous Bowen's disease. This is the first case reported with hand and foot lesions.

Bowen's Disease↗
PubMed2003

Normal values of B type natriuretic peptide in infants, children, and adolescents.

OBJECTIVE: To determine normal values of plasma B type natriuretic peptide from infancy to adolescence using a commercially available rapid assay. SETTING: Tertiary referral centre. DESIGN: The study was cross sectional. Plasma BNP concentration was measured in 195 healthy infants, children, and adolescents from birth to 17.6 years using the triage BNP assay (a fluorescence immunoassay). RESULTS: During the first week of life, the mean (SD) plasma concentration of BNP in newborn infants decreased significantly from 231.6 (197.5) to 48.4 (49.1) pg/ml (p = 0.001). In all subjects older than two weeks plasma BNP concentration was less than 32.7 pg/ml. There was no significant difference in mean plasma BNP measured in boys and girls younger than 10 years (8.3 (6.9) v 8.5 (7.5) pg/ml). In contrast, plasma concentration of BNP in girls aged 10 years or older was significantly higher than in boys of the same age group (12.1 (9.6) v 5.1 (3.5) pg/ml, p < 0.001). Plasma BNP concentrations were higher in pubertal than in prepubertal girls (14.4 (9.7) v 7.1 (6.6) pg/ml, p < 0.001) and were correlated with the Tanner stage (r = 0.41, p = 0.001). CONCLUSIONS: Plasma BNP concentrations in newborn infants are relatively high, vary greatly, and decrease rapidly during the first week of life. In children older than 2 weeks, the mean plasma concentration of BNP is lower than in adults. There is a sex related difference in the second decade of life, with higher BNP concentrations in girls. BNP concentrations in girls are related to pubertal stage.

Adolescent↗
PubMed2003

Noninvasive myocardial contractility monitoring with seismocardiography during simulated dives.

OBJECTIVE: To determine if bradycardia during hyperbaric exposure is accompanied by a negative influence on myocardial contractility. METHODS: Accelerometer-based registration of myocardial compression waves with Seismocardiography (SCG) for noninvasive contractility monitoring. Comparative pulmonary artery (PA) catheter study (9 ICU-patients, mean = 67ys) with ejection-fraction (EF) equivalent versus sum of g-values of contraction phase in SCG, and Preload (leg-positioning). Test with monitoring of changes in Contractility Index (ContrI) derived from the SCG-power spectrum (contraction phases, area under curve). Hyperbaric chamber study (0.6MPa dive-simulation) in 14 healthy divers. Quantitative SCG-(ContrI, power spectra) and ECG-recording. RESULTS: Correlation between changes in EF (PA catheter) and in the g-values (SCG) was r(SP) = 0.87 (p < 0.0001). ContrI increased in the leg-positioning test parallel to preload increase, heart rate remained stable. During hyperbaric exposure (0.6MPa) heart rate decrease was highly significant (68 to 58 min(-1); p < 0.001), ContrI and power spectra remained nearly unchanged, SCG registration was noise free. CONCLUSIONS: Hyperoxic bradycardia during simulated dives is not accompanied by impaired contractility measured with SCG, which is concordant to findings with invasive methods in current literature. SCG is suitable for noninvasive and stress free contractility monitoring and patient surveillance in a hyperbaric chamber.

Adult↗
PubMed2002

["Colon-/rectal carcinoma" prospective studies as comprehensive surgical quality assurance].

INTRODUCTION: Currently, only a small percentage of the diagnostic and therapeutic data on colonic carcinomas has been confirmed by data obtained in randomized controlled studies. For this reason, the results of prospective multicentre observational studies are extremely important. METHOD: Within a multicentre observational study involving 75 surgical departments carried out between 01.01. and 31.12.1999, 3,756 patients with a colorectal carcinoma (2,293 carcinoma of the colon; 1,463 carcinomas or the rectum) were investigated prospectively using a standardised questionnaire. RESULTS: The OP rate was 98.4%, the resection rate 92.5% (colon 94.1%, rectum 89.9%). The rate of rectal extirpations was relatively high at 30.3%. General postoperative morbidity was 27.4% (colon 27.0%, rectum 27.9%); the specific postoperative morbidity was 24.6% (colon 21.8%, rectum 29.1%). The anastomotic insufficiency rate was 5.2% (colon 3.7%, rectum 9.5%). The 30-day mortality rate was 4.7%, and the postoperative mortality rate 5.7%. CONCLUSIONS: Surgical quality control in the form of prospective multicentre observational studies make possible the analysis of the therapeutic situation of a surgical disease under quality assurance aspects. At the same time, the comprehensive data material available will serve the specific planning of prospective randomized studies. With the aid of the present study, a basis for a thorough and complete evaluation of colorectal carcinoma has been created.

Adolescent↗
PubMed2002

[Significance of prospective multicenter observational studies for gaining knowledge in surgery].

The meta-analysis of randomised controlled studies (RCS) achieves the highest degree of reliability. Although the status of prospective multicenter clinical trials (PMS) is the subject of controversial discussion, recent publications suggest that these two forms of analysis reveal comparable results. On the other hand, particularly in the operative part of medicine, the problem of recruitment and performing of controlled studies for the more rapid evaluation of new surgical procedures becomes more evident. We followed these two aspects by using a separate analysis of data and biostatistical models. In the evaluation of single aspects, under no circumstances can non-controlled clinical trials replace randomised clinical studies in surgery. Only the use of a variety of forms of analysis in clinical research will lead to the desired scientific findings.

Data Interpretation, Statistical↗
PubMed2002

[Open vs. laparoscopic appendectomy].

This article discusses the question of whether open or laparoscopic appendectomy is preferable in today's clinical routine. The article is based on data from randomized studies, evaluation of meta-analyses, and data from nonrandomized, multicentric studies evaluating the treatment of appendicitis in routine clinical practice. According to the data analysis, open appendectomy (OA) offers advantages with regard to a significantly shorter operative time and lower hospital costs. Laparoscopic appendectomy (LA) is characterized by a significantly decreased rate of failed septic wound healing and faster recovery. Both procedures can be performed with the same degree of safety and comparable outcome for acute appendicitis. Laparoscopic appendectomy offers significant advantages for establishing a precise diagnosis in young fertile women and overweight patients suffering from lower abdominal pain. The currently available data do not provide precise guidelines for the treatment of perforating appendicitis. However, we found significant evidence indicating an increased rate of postoperative intra-abdominal abscess after laparoscopic appendectomy. Thus, a laparoscopic approach cannot be regarded as a standard technique in advanced appendicitis.

Abdominal Abscess↗
PubMed2002

Predictors of high endotoxin concentrations in the settled dust of German homes.

Endotoxin concentrations in settled house dust were measured within the collaborative study named INGA (Indoor Exposure and Genetics in Asthma) together with other asthma-related indoor factors in 405 randomly selected homes in two German cities. Endotoxin was assayed using the quantitative kinetic chromogenic Limulus Amebocyte Lysate (LAL) method. The mean concentration of 2,274 ng endotoxin/g dust in living rooms is about two orders of magnitude below mean occupational exposure (e.g. agriculture). Endotoxin concentrations are higher in old buildings (means ratio = (MR) 1.52, 95% C.I.: 1.14; 2.04), and in the lower storey of the dwelling (MR = 1.30, 95% C.I.: 1.04; 1.62). Furthermore, higher endotoxin concentrations are associated with longer occupancy in the apartment (MR = 1.63, 95% C.I.: 1.21; 2.18), high utilisation of the apartment during the sampling period (MR = 2.52, 95% C.I.: 1.42; 4.47), infrequent vacuum cleaning of the carpets (MR = 1.67; 95% C.I.: 1.10; 2.54), an indifferent attitude to ventilation (MR = 1.37; 95% C.I.: 1.03; 1.82), keeping cats (MR = 1.91; 95% C.I.: 1.43; 2.55) and dogs (1.57; 95% C.I.: 1.08; 2.30), as well as the occurrence of mice (MR = 1.39; 95% C.I.: 1.00; 1.93). The season and indoor climate (operative temperature and relative humidity) did not effect endotoxin concentration. These results indicate that high endotoxin concentration in settled dust is an indicator of poor hygienic conditions in homes.

Adult↗
PubMed2002

Atopic sensitization among children in an arctic environment.

BACKGROUND: Asthma has been reported to be rare among Inuits, but so far total and specific IgE levels have never been determined in arctic populations. OBJECTIVE: To determine the prevalence of atopy in children living in an arctic environment, and to examine whether atopy and total IgE levels were associated with parental place of birth, as a measure of ethnicity, and travel history. MATERIAL AND METHODS: All schoolchildren in Sisimiut, a community on the West coast of Greenland, were screened for atopy. Blood samples were analysed for total IgE and for specific IgE against inhalant and food allergens. Information on place of birth of children and their parents was obtained from national registries. Information on travel history was obtained from self-administered questionnaires. RESULTS: A total of 1031 schoolchildren aged 5 to 18 years had a blood sample drawn (85% of available children for the study). Of these, 151 (14.6%) children were sensitized to at least one inhalant allergen and 42 (4.1%) to at least one food allergen. Sensitization to grass was most common, whereas sensitization to mugwort, birch, animal-dander and house-dust mite was infrequent. Children whose parents were both born abroad had a higher risk of sensitization to inhalant allergens compared with children born of Greenlandic parents (OR = 8.6, 95% CI 2.8-27.1). Furthermore, children who had been abroad had a higher risk of sensitization towards pollen (OR = 1.6, 95% CI 1.0-2.5) and animal-dander (OR = 2.1, 95% CI 1.0-4.6) after adjustment for confounders. Both atopic and non-atopic children demonstrated high levels of total IgE (medians of 251 and 58 kU/L). CONCLUSIONS: Compared with European findings Greenlandic children have high levels of total IgE but a low prevalence of allergic sensitization towards inhalant allergens. This may be due to a low genetic susceptibility to atopy and less allergen exposure, as well as to living conditions in an arctic environment.

Adolescent↗
PubMed2002

Routine use of transrectal ultrasound in rectal carcinoma: results of a prospective multicenter study.

BACKGROUND AND STUDY AIMS: Preoperative transrectal ultrasound (TRUS) can establish the depth of penetration of a tumor, and thus provide important information for decisions about further management. In the literature, this method is reported to have a high level of sensitivity and specificity. Our investigation aimed at establishing the quality of the diagnostic procedure and treatment of colorectal carcinoma. PATIENTS AND METHODS: This investigation, which covered a 1-year period, and involved 75 hospitals, was conducted in the form of a prospective multicenter study and included a total of 3756 patients. For rectal carcinomas, all endosonographically determined uT categories were compared with histologically established T categories (pT). RESULTS: At 49 hospitals a total of 499 TRUS examinations in 1463 rectal carcinomas (34.1 %) were performed. A comparison of uT with pT category was possible for 422 TRUS examinations. Agreement between the preoperative endosonographic diagnosis with the histological diagnosis was found in 63.3 % (n = 267) of cases (95 % confidence interval 58.5 % - 67.9 %). The diagnostic accuracy was 50.8 % for pT1 carcinomas, 58.3 % for pT2 lesions, 73.5 % for pT3 tumors, and 44.4 % for pT4 carcinomas. Overstaging was observed in 23.9 %, overall, and understaging in 12.8 %. Understaging was significantly less common than overstaging (P < 0.05, s.). CONCLUSION: The accuracy of transrectal ultrasound used as a routine clinical examination in rectal carcinoma patients was clearly lower than that reported in the literature. We conclude that TRUS may aid decisions relevant to treatment only when used by well-trained investigators with a large case load of rectal carcinoma patients. Centralization of transrectal ultrasonography service is mandatory if a high level of quality is to be achieved with this method.

Carcinoma↗