Search PubMed⌕ Search

Biomedical subjects

A Koch

Publications and source records attributed to A Koch.

At least 19 recordsLinked to original sources
PubMed1999

[Statistical models and analysis of observational studies].

Although randomized clinical trials can be regarded as the gold standard in many fields of clinical research, non-randomized (so called observational) studies are indispensable. Methodologic quality of such studies is at least as important as that of randomized trials but has been much less standardized. The analysis and interpretation of the results of observational studies is a very demanding job which needs a high level of knowledge and experience--medical as well as statistical. Basis for these analyses are complex statistical models the grounds and application of which are discussed in the following article.

Humans↗
PubMed1999

[Testing, estimating, "significance"--concepts and terminology of medical biometry].

The justification for the application of medical treatments and diagnostic methods has gained importance during the last decades. Together with scientific argumentations also the concepts of medical statistics have found a wide-spread use and are nowadays indispensible tools for clinical research. In publications of clinical trials, epidemiological investigations and animal experiments p-values, statistical tests and confidence intervals help the reader to evaluate the significance and relevance of the provided results. A prerequisite is a clear understanding of the concepts underlying these methodological terms. This paper presents the basic concepts of medical statistics and demonstrates the conclusions that can be drawn with the aid of these concepts.

Animals↗
PubMed1999

Childhood hepatoblastomas frequently carry a mutated degradation targeting box of the beta-catenin gene.

Hepatoblastomas (HBs) are embryonal tumors affecting young children and representing the most frequent malignant liver tumors in childhood. The molecular pathogenesis of HB is poorly understood. Although most cases are sporadic, the incidence is highly elevated in patients with familial adenomatous polyposis coli. These patients carry germline mutations of the APC tumor suppressor gene. APC controls the degradation of the oncogene product beta-catenin after its NH2-terminal phosphorylation on serine/threonine residues. APC, as well as beta-catenin, has been found to be a central effector of the growth promoting wingless signaling pathway in development. To find out if this pathway is involved in the pathogenesis of sporadic HBs, we examined 52 biopsies and three cell lines from sporadic HBs for mutations in the APC and beta-catenin genes. Using single-strand conformational polymorphism analysis, deletion screening by PCR, and direct sequencing, we found a high frequency of beta-catenin mutations in sporadic HBs (48%). The mutations affected exon 3 encoding the degradation targeting box of beta-catenin leading to accumulation of intracytoplasmic and nuclear beta-catenin protein. The high frequency of activating mutations in the beta-catenin gene indicates an important role in the pathogenesis of HB.

Adolescent↗
PubMed1999

Low density lipoprotein receptor as a candidate receptor for hepatitis C virus.

Hepatitis C virus (HCV) binds to different human cell lines in vitro. However, the efficiency of adsorption is very low due mainly to a relatively small fraction of the virus being able to bind to these cells. Free low density lipoprotein (LDL > 200 microg/ml) is able to block the attachment of HCV to human fibroblasts in vitro completely. COS-7 cells being primarily not able to bind HCV were transfected with a vector containing the entire coding sequence of the human LDL-receptor (LDLR). HCV was now bound to these cells. We propose that HCV and LDL are competitive for the cellular LDLR and that LDL in sera of patients may regulate the binding of HCV to this target.

Adsorption↗
PubMed1999

Catatonia as a psychomotor syndrome: a rating scale and extrapyramidal motor symptoms.

BACKGROUND: Catatonia was first described by Kahlbaum as a psychomotor disease with motor, behavioral, and affective symptoms. In keeping with this concept, we developed a rating scale for catatonia (Northoff Catatonia Scale [NCS]) with three different categories of symptoms (i.e., motor, behavioral, affective). Furthermore, the question of the relationship among catatonic symptoms, extrapyramidal motor symptoms, and neuroleptics was addressed in the present study. METHOD: 34 acute catatonic patients and 68 age-, sex-, diagnosis-, and medication-matched psychiatric control subjects were investigated on days 0, 1, 3, 7, and 21 with the NCS, with other already validated catatonia rating scales by Rosebush, Bush (BFCRS), and Rogers (MRS), as well as with scales for hypokinetic (SEPS) and dyskinetic (AIMS) extrapyramidal motor features. Validity and reliability of the new scale, factor analysis, correlational analysis, and differences between catatonic patients and psychiatric control subjects were statistically calculated. RESULTS: NCS showed high validity (i.e., significant positive correlations [p <0.0001] with the other scales, significant differences between catatonic and control subjects), high intra-and interrater reliabilities (r = 0.80-0.96), and high affective subscores. Factor analysis revealed four factors best characterized as affective, hypoactive, hyperactive, and behavioral. Catatonic scores in NCS correlated significantly with AIMS on day 0 and SEPS on days 7 and 21. There were no significant differences in catatonic (i.e., NCS, MRS, BFCRS) and extrapyramidal (i.e., AIMS, SEPS) scores between neuroleptically treated and untreated catatonic subjects. CONCLUSIONS: The following conclusions were drawn: (1) the NCS has to be considered as a valid and reliable rating instrument for catatonia; (2) catatonia can be characterized by psychomotor symptoms encompassing motor, affective, and behavioral alterations; and (3) extrapyramidal hyperkinesias like dyskinesias are apparently closely related to catatonic symptoms which, in general, seem to be relatively independent of previous neuroleptic medication.

Acute Disease↗
PubMed1999

[Laparoscopic creation of stomas--an ideal single indication in minimally invasive surgery].

The laparoscopic creation of ileostomas and colostomas can be performed in a quick, safe and technically effective manner. The advantages of the minimally invasive approach are low morbidity and mortality, minimal blood loss and fast recovery in these mostly multimorbid patients as well as shorter time of hospitalization. We report on a total of 20 patients who underwent laparoscopic creation of colostoma in 19 cases and creation of ileostoma in one case in a period of 2 years. There were no intraabdominal complications and no lethal outcome. All patients reached their preoperative level of mobilization at the 2nd postoperative day. The indications for the laparoscopic enterostomy are described.

Aged↗
PubMed1999

[Psychological status and motivation for psychosocial intervention in patients with allergic disorders].

The aim of this study was to compare the psychological stress of patients with different forms of immediate type hypersensitivity and urticaria. Moreover, the patients' motivation for different forms of psychological treatment was assessed and an indication for psychosocial support was defined. 228 consecutive inpatients with insect venom allergies (ins), food intolerance (food), drug hypersensitivities (dru) and urticaria (urt) were evaluated by validated questionnaires regarding psychological strain and motivation for psychosocial treatments. Patients with food intolerance and urticaria showed significantly elevated psychological stress and higher motivation for psychosocial support as compared to those with insect venom allergies and drug intolerance. Patient education was the favourite technique for the patients (food 78%, urt 57%, dru 24%, ins 17%), followed by relaxation treatment. The most important predictors for the motivation were the wish for self-responsibility, a feeling of helplessness and social limitations. If strong indication criteria are applied, psychosocial support is indicated in only small subgroups of each patient group. In spite of that, the management of allergic disease should consider the potential need for psychosocial support.

Age Factors↗
PubMed1999

[Use of coronary angiography after acute myocardial infarction in Germany: a comparison of daily clinical practice with international guidelines. MITRA Study].

OBJECTIVES: Two third of patients with acute myocardial infarction are admitted to hospitals without cardiac catheterization facilities. Whether a postinfarction patient will undergo cardiac catheterization or not is more often decided by general physicians than by cardiologists. The purpose of this presentation is to investigate the determinants for decision making to use cardiac catheterization in patients after myocardial infarction. METHODS: MITRA is a prospective, multicenter registry, which enrolls all consecutive patients with acute Q wave infarction admitted to 54 hospitals in Southwestern Germany. During the pilot phase 949 consecutive survivors of acute myocardial infarction were included, and inhospital outcome as well as therapeutic strategies were registered. RESULTS: Only half of the patients underwent cardiac catheterization regardless of whether a catheterization facility was available or not. In 63% of the patients under 65 years of age coronary angiography was performed; however, every fourth patient with age above 70 years was transferred to an invasive therapeutic strategy. The percentage of male patients was twice a high in the invasive group, whereas patients with prior infarction, clinical signs of congestive heart failure, patients with moderately or severely impaired left ventricular function, and finally patients with a prehospital delay of more than 4 hours were more frequent in the conservative group. The following three parameters were calculated to be independent determinants of an invasive strategy: pathological stress ECG (OR: 2.8; CI: 1.80-4.60), patients < 70 years without stress ECG (OR: 2.18; CI: 1.5-3.18), and male gender (OR: 1.45: CI: 1.10-2.00). Independent factors of a conservative strategy were primary PTCA (OR: 0.2; CI: 0.09-0.46), prehospital delay > 4 hours (OR: 0.71; CI: 0.51-0.97), and the combination of age > 70 years and the absence of a stress ECG (OR: 0.78; CI: 0.55-1.11). CONCLUSIONS: In Germany, patients with acute myocardial infarction are less likely to undergo cardiac catheterization compared to patients in other Western countries (e.g. , the United States). Despite recommended guidelines, invasive strategies are more frequent in low risk groups (younger patients, male gender) than in postinfarction patients at high risk (severely impaired left ventricular function, clinical signs of congestive heart failure, the elderly).

Adult↗
PubMed1999

Circumscribed intestinal protein loss with deficiency in CD4+ lymphocytes after the Fontan procedure.

UNLABELLED: Protein-losing enteropathy is an important complication after right heart bypass operations (Fontan procedure). Laboratory examinations usually reveal hypoalbuminaemia, hypoproteinaemia, elevated alpha(1)-antitrypsin clearance, and lymphocytopenia. A case of protein-losing enteropathy after Fontan procedure is reported with a circumscribed protein loss in the region of the terminal ileum despite good haemodynamics. The patient developed only mild hypoalbuminaemia and no diarrhoea but severe cellular and humoral immune abnormalities, namely a markedly decreased proportion of CD4+ lymphocytes but normal proportion of CD8+ lymphocytes (CD4+ 14%, CD8+ 23%) and decreased serum levels of immunoglobulin G. Intestinal biopsies revealed normal mucosa. This report is unique as it is the first to describe a ratio of CD4+ to CD8+ lymphocytes <1 due to an almost selective loss of CD4+ lymphocytes and a circumscribed intestinal protein loss in a patient who developed protein-losing enteropathy after Fontan operation. CONCLUSION: There is a severe decrease of CD4+ lymphocytes of unknown origin in a patient with circumscribed intestinal protein loss after Fontan operation. Passive leakage of lymph fluid due to abnormal systemic venous pressure is not a sufficient explanation of the almost selective loss of CD4+ lymphocytes. Primary or secondary activation of the immune system may influence structural integrity and permeability of the intestinal wall and may play a triggering role in protein-losing enteropathy after the Fontan procedure.

CD4 Lymphocyte Count↗
PubMed1999

The role of randomization in clinical studies: myths and beliefs.

On the basis of a survey of the methodological literature, we analyze widespread views on randomization and the advantage of randomized over nonrandomized studies. These views follow from theoretical considerations and at least three types of empirical investigations into the results of published studies. Randomization is often credited with advantages that it does not possess or confer. Several popular theoretical arguments in favor of randomization are shown to be either incorrect or imprecise. The published empirical comparisons of randomized with nonrandomized studies have methodological weaknesses and do not give any convincing information about the value of carefully designed and conducted nonrandomized studies. Six arguments, most of which are pragmatic rather than epistemological, are given to support our belief that randomization should not be avoided without compelling need. We conclude that although there are good arguments in favor of randomization, these are not the ones usually found in the literature. The very negative view on nonrandomized studies sometimes encountered in biostatistics and medicine may be comprehensible from a historical, pragmatic, or educational viewpoint, but it is not well founded on epistemological grounds.

Causality↗
PubMed1999

Expression of major histocompatibility class II antigens on polymorphonuclear neutrophils in patients with Wegener's granulomatosis.

BACKGROUND: Wegener's granulomatosis is a systemic inflammatory disease of unknown etiology. Many studies suggest that autoimmune reactions are involved, and there is good evidence for the participation of immunocompetent cells. In that context, we examined the activation of polymorphonuclear neutrophils (PMNs) of patients with Wegener's granulomatosis. METHODS: In a prospective study, the expression on the surface of PMNs of CD64 and of the major histocompatibility class II (MHC II) antigen was measured by cytofluorometry in whole blood. The expression of those antigens was correlated to disease activity. RESULTS: Up to 15% of the peripheral PMNs of patients with active disease expressed MHC II. Follow-up studies showed that expression correlated closely with disease activity and that it decreased rapidly under immunosuppressive therapy. Expression of CD64 was seen in approximately 50% of the patients, regardless of disease activity. CONCLUSION: MHC II expression on PMNs might serve as a novel diagnostic marker for active disease and appears to be suitable for monitoring immunotherapy. Moreover, our data provide evidence that PMNs, which are normally MHC II negative, acquire MHC II antigens in the course of disease and may be an unrecognized function within the afferent limb of the immune response.

Anti-Inflammatory Agents↗
PubMed1999

Lack of association between mannose-binding lectin, acute otitis media and early Epstein-Barr virus infection among children in Greenland.

Low serum levels of mannose-binding lectin (MBL) have been associated with recurrent infections in early childhood. Otitis media (OM) is frequent in Greenlandic children and the first episode of acute OM (AOM) occurs early, as is the case also with Epstein-Barr virus (EBV) infection. We have therefore investigated the association between MBL genotypes, episodes of AOM, and early EBV infection in 82 community-based, unselected children in Greenland. Nasopharyngeal aspirations for EBV and MBL genotype examination, nasopharyngeal bacterial cultures, and history of AOM episodes were obtained. MBL genotypes were established in 73 specimens: 68% of these were homozygous for normal wildtype (AA), and 32% were homozygous or heterozygous for variant alleles that are associated with absence or low MBL serum level. The allele frequencies were: A = 0.88, B = 0.08 (codon 54) and D = 0.04 (codon 52). EBV was found in 41 specimens, more often with increasing age, and significantly related to ethnicity. Presence of variant MBL alleles or EBV infection was not associated with AOM, recurrent AOM (rAOM) or age at first AOM episode and EBV positive children with homozygosity for the normal MBL genotype did not have significantly more episodes of AOM, rAOM or earlier age at the first AOM episode. MBL genotypes and EBV infection alone or in interplay are not associated with the high prevalence of OM in Greenlandic children. The study suggests that low MBL level does not by itself predispose to AOM in community-based, unselected children.

Acute Disease↗
PubMed1999

Measuring in situ central airway resistance in patients with laryngotracheal stenosis.

OBJECTIVES: To evaluate a newly developed bronchoscopic technique for the assessment of intratracheal pressures. STUDY DESIGN: In situ measurement of central airway resistance in 20 consecutive spontaneously breathing subjects. Thirteen patients had benign glottic or subglottic stenosis. Seven patients without central airway disease served as normal control subjects. METHODS: A pressure catheter was introduced into the trachea via the working channel. The pressure swing was measured upstream and downstream of the stenosis. Central airflow was monitored simultaneously using a commercial pneumotachograph attached to a mouthpiece. Data acquisition frequency was 500 Hz. Prestenotic and poststenotic inspiratory and expiratory resistances could be calculated and displayed from the raw data off-line. RESULTS: Inspiratory and expiratory resistances measured in mid-trachea or below the stenosis (subglottic) were 0.36 +/- 0.13 and 0.35 +/- 0.13 kPa.s/L for the control subjects (C), 1.11 +/- 0.47 and 0.65 +/- 0.26 kPa.s/L for patients who did not need to be operated on (NOOP), 7.11 +/- 7.19 and 3.35 +/- 2.25 kPa.s/L respectively for those who required surgical correction (OP). Supraglottic inspiratory and expiratory resistances for C were 0.22 +/- 0.09 and 0.25 +/- 0.06 kPa.s/L, for NOOP 0.15 +/- 0.10 and 0.14 +/- 0.11 kPa.s/L, and for OP 0.26 +/- 0.13 and 0.24 +/- 0.07 kPa.s/L respectively. The cut-off point for surgical correction was estimated to be > 2.5 kPa.s/L of inspiratory resistance. Concurrent expiratory values showed a considerable overlap between OP and NOOP. No correlation could be established between local resistance values and dyspnea score. CONCLUSIONS: In situ subglottic flow-pressure tracing in spontaneously breathing patients who present with benign obstruction of the upper airways is well tolerated and may help to identify patients who need surgical correction.

Adult↗
PubMed1999

The anterior and posterior 'stomach' regions of larval Aedes aegypti midgut: regional specialization of ion transport and stimulation by 5-hydroxytryptamine.

The 'stomach' region of the larval mosquito midgut is divided into histologically distinct anterior and posterior regions. Anterior stomach perfused symmetrically with saline in vitro had an initial transepithelial potential (TEP) of -66 mV (lumen negative) that decayed within 10-15 min to a steady-state TEP near -10 mV that was maintained for at least 1 h. Lumen-positive TEPs were never observed in the anterior stomach. The initial TEP of the perfused posterior stomach was opposite in polarity, but similar in magnitude, to that of the anterior stomach, measuring +75 mV (lumen positive). This initial TEP of the posterior stomach decayed rapidly at first, then more slowly, eventually reversing the electrical polarity of the epithelium as lumen-negative TEPs were recorded in all preparations within 70 min. Nanomolar concentrations of the biogenic amine 5-hydroxytryptamine (5-HT, serotonin) stimulated both regions, causing a negative deflection of the TEP of the anterior stomach and a positive deflection of the TEP of the posterior stomach. Phorbol 12,13-diacetate also caused a negative deflection of the TEP of the anterior stomach, but had no effect on the TEP of the posterior stomach. These data demonstrate that 5-HT stimulates region-specific ion-transport mechanisms in the stomach of Aedes aegypti and suggest that 5-HT coordinates the actions of the Malpighian tubules and midgut in the maintenance of an appropriate hemolymph composition in vivo.

Aedes↗
PubMed1999

[Minimally invasive concepts in esophageal surgery--thoracoscopic anastomosis. An animal experiment study].

Based on animal trials the presented study describes two versions of thoracoscopic oesophageal anastomosis within the scope of abdomino-thoracoscopic oesophagectomy. This experimental approach is considered to provide a solution for the oncological problem to salvage the tumor bearing oesophagus. We describe the procedure of intrathoracic stapler anastomosis under thoracoscopic vision. By using a laparoscopic purse string suture clamp we were enabled to prepare the proximal oesophageal stump for anastomosis. A circular stapling instrument turned out to be very suitable for the thoracoscopic use. The final evaluation of the importance of minimally invasive surgery for the resection of oesophageal carcinomas should not be given until multicenter studies are performed.

Anastomosis, Surgical↗
PubMed1998

Expression of the ATM gene is significantly reduced in sporadic breast carcinomas.

The gene mutated in ataxia telangiectasia (A-T) patients (ATM) is located on chromosome 11q22-23, a region frequently altered in mammary tumors. Patients homozygous for ATM mutations are prone to develop a variety of different neoplasms. Female heterozygotes have been reported to carry a 5- to 8-fold increased risk of breast cancer. However, germline mutations in the ATM gene are rare in women with sporadic breast carcinomas. Most of the alterations described in A-T patients result in a functionally inactive ATM protein. Moreover, it has been suggested that mutations of the ATM gene in A-T patients influence the amount of ATM mRNA and that this may affect the severity of the disease. In the present study, we have analyzed ATM transcripts in a series of 39 breast carcinomas, 14 benign breast lesions and 12 normal breast tissue samples. ATM mRNA levels were determined by semiquantitative competitive RT-PCR. Competitor RNA molecules for the ATM gene and the housekeeping gene beta-2-microglobulin (B2M) were generated by PCR mutagenesis. Low concentrations of ATM transcripts were detected in breast carcinomas, intermediate levels in benign lesions and highest levels in normal breast tissue specimens (F-test, p = 0.0013). Our results indicate that reduced expression of the ATM gene may contribute to the development and/or malignant progression of breast carcinomas.

Ataxia Telangiectasia Mutated Proteins↗