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Biomedical subjects

T Forster

Publications and source records attributed to T Forster.

At least 19 recordsLinked to original sources

Retroperitoneoscopic pyeloplasty for ureteropelvic junction obstruction (UPJO): solving the technical difficulties.

OBJECTIVES: To evaluate our current practice in retroperitoneoscopic pyeloplasty in patients with ureteropelvic junction obstruction (UPJO). Special interest was paid to technical difficulties associated with the retroperitoneoscopic approach. METHODS: Our retroperitoneoscopic approach for pyeloplasty is explained step for step including the most technically challenging part: the ureteropelvic anastomosis. RESULTS: Within 49 months a total of 47 retroperitoneoscopic pyeloplasties we performed at our institution. Before pyeloplasty an endopyelotomy had failed in five patients (11%). We did not necessarily perform a ventral transposition of the anastomosis in cases with a crossing vessel. Two (4%) conversions to open surgery were required because of scarring after previous endopyelotomy and massive obesity resulting in a limited working space. There were no intraoperative complications. A recurrence of UPJO was observed in 2% (n = 1). CONCLUSION: Functional results after retroperitoneoscopic pyeloplasty are excellent and comparable to those of open surgery. However, special knowledge of retroperitoneoscopy is necessary to provide the patient with a safe and effective minimally invasive alternative to open pyeloplasty.

Adolescent↗

[Photoselective vaporization of the prostate: experience with prostate adenomas >80 cm3].

BACKGROUND: We report about our experiences with photoselective vaporization of the prostate (PVP) in patients with symptomatic benign prostatic hyperplasia (BPH) and total prostate volume larger than 80 cm(3). PATIENTS AND METHODS: The study included 201 patients with BPH: 51 (25.4%) patients had a prostate volume larger than 80 cm(3) and 150 (74.6%) patients had a volume smaller than 80 cm(3) in the preoperative transrectal ultrasound. RESULTS: The mean operation time for patients with large prostates was 79 min. Neither TUR syndrome nor severe bleeding was observed. In patients with large adenomas peak urinary flow increased by 135, 136, and 132% after 6, 12, and 24 months, respectively. The overall complication rate was comparable in both groups. CONCLUSION: PVP is characterized by excellent perioperative safety and significant improvement of voiding parameters. PVP is feasible in patients with large prostates.

Aged↗

Cardiotoxicity of anthracycline in young breast cancer female patients: the possibility of detection of early cardiotoxicity by TDI.

Tissue Doppler imaging (TDI) was investigated for its applicability for detecting cardiac function and early cardiotoxicity in breast cancer patients treated with anthracyclines. A total of 40 women (age range 18 to 65 years) were enrolled, who had not received anthracyclines previously and had normal systolic and diastolic cardiac function. All healthy patients in the control group were of the same age. Each patient underwent not only standard echocardiographic measurements (ventricular dimensions and wall thickness, ejection fraction, E-wave deceleration time (DT), E/A ratio), but also specific imagings (E-septum separation, pulmonary venous flow), and in addition the myocardial velocity of many segments of mitral anulus obtained with pulsed wave tissue Doppler imaging were performed during the one year of observation period. Based on the results we found that systolic left ventricular function did not change significantly - neither in the study nor in the control group. Diastolic left ventricular function was impaired in 39 patients (97.5%), and 30 (75%) of these showed clear changes by means of both the traditional E/A ratio and TDI. Diastolic dysfunction in 9 patients (22.5%), however, could be detected only with TDI. The analysis of myocardial velocity in different segments showed that diastolic dysfunction does not develop in a homogeneous way but in a different way in segments. Diastolic function was intact in the control group during the study. The detectable myocardial damage occurred in the study group of young female patients without risk factors as a result of one year anthracycline therapy was so severe that the possible outcome might be serious congestive heart failure or death. Our results confirmed our assumptions that TDI is a more precise and useful examination method than traditional ones (E/A ratio or deceleration time) to demonstrate isolated diastolic dysfunction as a result of chemotherapy. Relevant extra information might be given by TDI compared to parameters describing diastolic functions depending on several changing values. TDI may become a regularly and more widely used noninvasive method to detect subclinical cardiotoxicity emerging after chemotherapy.

Adult↗

[Contribution of the Public Health Service to cost of illness studies].

This paper reflects on the different approach-es of top-down and bottom-up analysis when calculating sickness costs. Following an analysis of the standard procedures to be followed in tuberculosis contact tracing performed by public health bureaux in Hamburg, a top-down estimate is presented de-spite some accounting limitations. The val-ue of epidemiologic data on infectious dis-eases held by the Public Health Service for bottom-up-modelling is shown by a cost-of-illness study on hepatitis A in Germany.However, broader efforts may be required by local service providers to justify their existence from an economic perspective. This could also contribute to improving cooperation between public health authorities and schools of public health in this rapidly developing scientific field.

Accounting↗

Legionella pneumophila associated with the protozoan Hartmannella vermiformis in a model multi-species biofilm has reduced susceptibility to disinfectants.

Legionella pneumophila will infect biofilm-associated protozoa, and in this way might be protected from disinfectants in potable water systems. A base biofilm containing Pseudomonas aeruginosa, Klebsiella pneumoniae, and Flavobacterium spp. was grown on steel coupons in potable water prior to the addition of L. pneumophila and the protozoan H. vermiformis. After 7 d, coupons were removed and treated with 0.5 mgl(-1) free residual chlorine (FRC) or 0.5 mgl(-1) monochloramine (MCA) for 15, 60, or 180 min or 24 h. In a second experiment, only L. pneumophila and the base biofilm organisms were present but with an identical treatment protocol. Treatment of L. pneumophila for 180 min in a system without H. vermiformis resulted in log reductions of 2.07 and 2.11 for FRC and MCA, respectively. When H. vermiformis was present, however, the treatment resulted in log reductions of 0.67 and 0.81 for FRC and MCA, respectively. A similar pattern was observed for 15 and 60 min contact times. These results indicate that L. pneumophila was less susceptible to MCA or FRC when associated with biofilm-associated H. vermiformis in a model potable water biofilm.

Animals↗

Coronary flow reserve, insulin resistance and blood pressure response to standing in patients with normoglycaemia: is there a relationship?

AIMS: To establish the relationships between coronary flow reserve, cardiovascular autonomic function, and insulin resistance characterized by the homeostasis model assessment insulin resistance score in patients with normal carbohydrate metabolism according to the World Health Organization (WHO) and American Diabetes Association (ADA) criteria, and with morphologically normal epicardial coronary arteries. METHODS: Twenty-five patients [12 women and 13 men, mean (sd) age: 53 +/- 11 years] with normal coronary angiography were enrolled into the study. Coronary flow reserve was measured during stress transoesophageal echocardiography. Autonomic dysfunction was assessed by means of five standard cardiovascular reflex tests. The fasting serum glucose and insulin levels were determined and the homeostasis assessment model insulin resistance score was calculated. RESULTS: In patients with normal carbohydrate metabolism, negative correlations were observed between the coronary flow reserve and both the serum insulin level (r = -0.445, P = 0.026) and the homeostasis assessment model insulin resistance score (r = -0.449, P = 0.024). The systolic blood pressure response to standing also correlated with the coronary flow reserve (r = -0.519, P = 0.011). The heart rate response to deep breathing, the Valsalva ratio, the 30/15 ratio and the sustained handgrip test results were not correlated with the coronary flow reserve. CONCLUSIONS: Our data suggest the possible role of insulin resistance and early sympathetic nerve dysfunction in the development of decreased coronary flow reserve in patients without diabetes mellitus or impaired glucose tolerance.

Adult↗

Genetic association analysis of the IGFBP7, ADAMTS3, and IL8 genes as the potential osteoarthritis susceptibility that maps to chromosome 4q.

OBJECTIVES: To determine by genetic association analysis whether the 4q functional candidate genes IGFBP7, ADAMTS3, and IL8 might encode for susceptibility to osteoarthritis (OA). METHODS: Expression of IGFBP7, ADAMTS3, and IL8 in adult OA articular cartilage chondrocytes was demonstrated by reverse transcription-polymerase chain reaction. The genes were screened for common polymorphic DNA variants by direct sequencing of exons, intron-exon boundaries, and the 5' and 3' untranslated regions. The variants were genotyped in the female probands from the 146 families which each contained two or more sisters who had undergone total hip replacement (THR) and in 375 female controls matched for age. Variants showing evidence for association were subsequently genotyped in 244 female-THR patients with OA. Allele frequencies between the probands (or patients) and the controls were compared by chi(2) analysis. RESULTS: Fourteen common variants were identified in the three genes. An ADAMTS3 single nucleotide polymorphism was associated in the probands (p = 0.015) and an ADAMTS3 insertion/deletion approached significance (p = 0.059). However, neither variant was associated in the additional 244 patients with hip OA, with p values of 0.12 and 0.19, respectively. CONCLUSIONS: The analysis implies that the chromosome 4q female hip OA susceptibility is not coded for by polymorphism within the functional candidates IGFBP7, ADAMTS3, or IL8.

ADAM Proteins↗

Steroid signalling in human ovarian surface epithelial cells: the response to interleukin-1alpha determined by microarray analysis.

The human ovarian surface epithelium (HOSE) is a common site of gynaecological disease including endometriosis and ovarian cancer, probably due to serial injury-repair events associated with successive ovulations. To comprehend the importance of steroid signalling in the regulation of the HOSE, we used a custom microarray to catalogue the expression of over 250 genes involved in the synthesis and reception of steroid hormones, sterols and retinoids. The array included a subset of non-steroidogenic genes commonly involved in pro-/anti-inflammatory signalling. HOSE cells donated by five patients undergoing surgery for non-malignant gynaecological conditions were cultured for 48 h in the presence and absence of 500 pg/ml interleukin-1alpha (IL-1alpha). Total RNA was reverse-transcribed into biotin-labelled cDNA, which was hybridised to the array and visualised by gold-particle resonance light scattering and charge-coupled device (CCD) camera detection. Results for selected genes were verified by quantitative reverse-transcription PCR. In five out of five cases, untreated HOSE cells expressed genes encoding enzymes required for de novo biosynthesis of cholesterol from acetate and subsequent formation of C21-pregnane and C19-androstane steroids. Consistent with the inability of HOSE cells to synthesise glucocorticoids, oestrogens or 5alpha-reduced androgens de novo, CYP21, CYP19 and 5alpha-reductase were not detected. The only steroidogenic gene significantly up-regulated by IL-1alpha was 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1). Other cytokine-induced genes were IL-6, IL-8, nuclear factor kappaB (NFkappaB) inhibitor alpha, metallothionein-IIA and lysyl oxidase: inflammation-associated genes that respond to glucocorticoids. The only steroidogenic gene significantly suppressed by IL-1alpha was 3betaHSD1. Other genes suppressed by IL-1alpha were aldehyde dehydrogenase (ALDH) 1, ALDH 10, gonadotrophin hormone-releasing hormone receptor, peroxisome proliferation-activated receptor-binding protein (PPAR-bp) and nuclear receptor subfamily 2 group F member 2. These results define a steroidogenic phenotype of cultured HOSE cells and provide a limited expression profile for genes with associated signalling functions. IL-1alpha co-ordinately induces 11betaHSD1 and a panel of glucocorticoid-regulated, inflammation-associated genes in HOSE cells, providing further evidence that cortisol generated by 11betaHSD1 could participate in the local resolution of inflammation associated with ovulation.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

Experiments using microarray technology: limitations and standard operating procedures.

Microarrays are a powerful method for the global analysis of gene or protein content and expression, opening up new horizons in molecular and physiological systems. This review focuses on the critical aspects of acquiring meaningful data for analysis following fluorescence-based target hybridisation to arrays. Although microarray technology is adaptable to the analysis of a range of biomolecules (DNA, RNA, protein, carbohydrates and lipids), the scheme presented here is applicable primarily to customised DNA arrays fabricated using long oligomer or cDNA probes. Rather than provide a comprehensive review of microarray technology and analysis techniques, both of which are large and complex areas, the aim of this paper is to provide a restricted overview, highlighting salient features to provide initial guidance in terms of pitfalls in planning and executing array projects. We outline standard operating procedures, which help streamline the analysis of microarray data resulting from a diversity of array formats and biological systems. We hope that this overview will provide practical initial guidance for those embarking on microarray studies.

Animals↗

Outcome after extended follow-up in a prospective study of operable breast cancer: key factors and a prognostic index.

In 1990, 215 patients with operable breast cancer were entered into a prospective study of the prognostic significance of five biochemical markers and 15 other factors (pathological/chronological/patient). After a median follow-up of 6.6 years, there were 77 recurrences and 77 deaths (59 breast cancer-related). By univariate analysis, patient outcome related significantly to 13 factors. By multivariate analysis, the most important of nine independent factors were: number of nodes involved, steroid receptors (for oestrogen or progestogen), age, clinical or pathological tumour size and grade. Receptors and grade exerted their influence only in the first 3 years. Progestogen receptors (immunohistochemical) and oestrogen receptors (biochemical) were of similar prognostic significance. The two receptors were correlated (r=+0.50, P=0.001) and displaced each other from the analytical model but some evidence for the additivity of their prognostic values was seen when their levels were discordant.

Biomarkers, Tumor↗

[HER-2 and TOP 2A gene amplifications in urinary bladder carcinoma].

The HER-2/neu gene is frequently amplified in bladder cancer. Topoisomerase 2 Alpha (TOP2A) which is located nearby the HER-2/neu gene is an important molecular target for several anti cancer drugs. The frequency of TOP2A amplification in urinary bladder cancer is unknown. It was the aim of this study to determine the frequency of HER-2 and TOP2A amplification in urinary bladder cancer and to evaluate the association of these amplifications with tumor phenotype. For this purpose a tissue microarray containing 768 pTa, 425 pT1 and 571 pT2-4 carcinomas was analyzed by fluorescence in situ hybridization (FISH). Amplifications of both genes were significantly associated with advanced tumor stage and high grade. HER-2 amplification was found in 1.6% of pTa, 7.2% of pT1 and 13.8% of pT2-4 carcinomas (p < 0.0001). HER-2 amplification was present in only 1.1% of grade 1 and 0.8% of grade 2 tumors but in 14.2% of grade 3 tumors (p < 0.0001). TOP2A amplification was present in 0.7% pTa, 1.8% pT1 and 3.4% pT2-4 carcinomas (p < 0.0001). TOP2A was found in none of the grade 1, in 0.2% of grade 2 and 3.8% of grade 3 tumors (p < 0.0001). 1% of all analyzed tumors had simultaneously high level amplification of TOP2A and HER-2. Amplification of both genes were significantly associated with tumor specific survival if all tumors were analyzed together. Given the high frequency of HER-2 amplification in urinary bladder cancer, some of these tumors may respond favorable to Herceptin therapy. The TOP2A amplification status may influence response to anthracyclin treatment.

Antigens, Neoplasm↗

Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade.

The number of genes suggested to play a role in cancer biology is rapidly increasing. To be able to test a large number of molecular parameters in sufficiently large series of primary tumours, a tissue microarray (TMA) approach has been developed where samples from up to 1000 tumours can be simultaneously analysed on one glass slide. Because of the small size of the individual arrayed tissue samples (diameter 0.6 mm), the question arises of whether these specimens are representative of their donor tumours. To investigate how representative are the results obtained on TMAs, a set of 2317 bladder tumours that had been previously analysed for histological grade and Ki67 labelling index (LI) was used to construct four replica TMAs from different areas of each tumour. Clinical follow-up information was available from 1092 patients. The histological grade and the Ki67 LI were determined for every arrayed tumour sample (4x2317 analyses each). Despite discrepancies in individual cases, the grade and Ki67 information obtained on minute arrayed samples were highly similar to the data obtained on large sections (p<0.0001). Most importantly, every individual association between grade or Ki67 LI and tumour stage or prognosis (recurrence, progression, tumour-specific survival) that was observed in large section analysis could be fully reproduced on all four replica TMAs. These results show that intra-tumour heterogeneity does not significantly affect the ability to detect clinico-pathological correlations on TMAs, probably because of the large number of tumours that can be included in TMA studies. TMAs are a powerful tool for rapid identification of the biological or clinical significance of molecular alterations in bladder cancer and other tumour types.

Adenocarcinoma↗

Clinical value of left atrial appendage flow velocity for predicting of cardioversion success in patients with non-valvular atrial fibrillation.

BACKGROUND: Echocardiographic parameters for predicting cardioversion outcome in patients with non-valvular atrial fibrillation are not accurately defined. OBJECTIVE: To evaluate the role of left atrial appendage flow velocity detected by transoesophageal echocardiography for prediction of cardioversion outcome in patients with non-valvular atrial fibrillation enrolled in a prospective. multicentre, international study. METHODS: Four hundred and eight patients (257 males, mean age: 66 +/- 10 years) with non-valvular atrial fibrillation lasting more than 48 h but less than 1 year underwent transthoracic echocardiography and transoesophageal echocardiography before either electrical (n=324) or pharmacological (n=84) cardioversion. RESULTS: Cardioversion was successful in restoring sinus rhythm in 328 (80%) and unsuccessful in 80 patients (20%). Mean left atrial appendage peak emptying flow velocity was significantly higher in patients with successful than in those with unsuccessful cardioversion (32.4 +/- 17.7 vs 23.5 +/- 13.6 cm x s(-1); P<0.0001). At multivariate logistic regression analysis, three parameters proved to be independent predictors of cardioversion success: the atrial fibrillation duration <2 weeks (P=0.011, OR=4.9, CI 95%=1.9-12.7), the mean left atrial appendage flow velocity >31 cm x s(-1) (P=0.0013, OR=2.8, CI 95%=1.5-5.4) and the left atrial diameter <47 mm (P=0.093, OR=2.0, CI 95%=1.2-3.4). These independent predictors of cardioversion success outperformed other univariate predictors such as left ventricular end-diastolic diameter <58 mm, ejection fraction >56% and the absence of left atrial spontaneous echo contrast. CONCLUSION: In patients with non-valvular atrial fibrillation, measurement of the left atrial appendage flow velocity profile by transoesophageal echocardiography before cardioversion provides valuable information for prediction of cardioversion outcome.

Atrial Appendage↗

Improved detection of Mycobacterium spp. using the Bactec MGIT 960 system.

Until 1987, the notification rate for mycobacterial infection was on the decline; however, it now appears to be increasing once more. The reason for this may be multifactoral and include improved reporting of diagnosed cases, increased infection of an ageing population, homelessness, immunosuppression (e.g. due to human immunodeficiency virus infection), and immigration of people from countries where tuberculosis is endemic. This rising incidence and the increasing importance of resistant organisms mean that rapid identification by the clinical microbiology laboratory is required, and this is where an automated detection system can be an advantage. Over a two-year period, 2743 clinical specimen were examined for Mycobacterium spp. using the Bactec MGIT 960, and 286 were positive. Time to detection ranged from three to 14 days (mean: 9.3 days), and M. tuberculosis was recovered from 214 (75.5%). Contamination rate was higher (8.6%) than with manual methods, however. On balance, the Bactec MGIT 960 system proved a valuable tool in the routine microbiology laboratory.

Bacteriological Techniques↗

[The clinical value of coronary flow reserve in ischemic heart disease as measured by dipyridamole stress transesophageal echocardiography].

The relationship between coronary flow reserve and the result of coronarography was examined. 152 patients were investigated by stress transoesophageal echocardiography and coronary angiography. The value of coronary flow reserve was significantly lower in cases of significant coronary stenosis than in those patients who had a normal coronarography (in patients with left anterior descending coronary artery stenosis: 1.77 +/- 0.47 vs in cases with normal coronary angiogram: 3.19 +/- 1.15). There was no difference in the value of CFR in those cases where not only LAD stenosis but CX or RC stenosis was also found. The value of coronary flow reserve was significantly higher in RC or CX patients than that of LAD patients. In patients with positive stress and negative coronarography (X syndrome) the coronary flow reserve was 1.23 +/- 0.2, which value was significantly lower as compared to patients with significant coronary stenosis.

Adult↗

[Impending paradoxical embolism].

The case history of a 49-year-old female patient is reported, who was operated on because of varicose vein in the left lower extremity. A few days after the operation serious signs of cerebrovascular insult appeared. The clinical picture and the result of an urgent transoesophageal echocardiography are described; a serpentine thrombus was found to be trapped in the patent foramen ovale. During continuous intravenous heparin treatment, the patient gradually recovered, but a residual neurological deficit could be detected on discharge from the hospital. Six days after the admission, repeated transoesophageal echocardiographic examination showed no signs of intracardiac thrombus. The clinical feature of the illness, the predisposing factors, the diagnostic and therapeutic possibilities are discussed.

Diagnosis, Differential↗