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Biomedical subjects

R Steinert

Publications and source records attributed to R Steinert.

At least 19 recordsLinked to original sources

[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↗

Proteomic prediction of disease outcome in cancer : clinical framework and current status.

Better than gene sequencing or quantitative amplification, proteomics tools allow the study of tumor phenotype. Indeed, most current prognostic tests in cancer (carcinoembryonary antigen [CEA], prostate-specific antigen [PSA], CA 19-1, CA 125, alpha-fetoprotein [AFP], etc.) are based on the detection and quantification of single proteins in body fluids. However, a common characteristic of these tests is their relatively low predictive value, so that they are usually complemented with other procedures such as biopsy and/or endoscopy. Recently, improved analytical and bioinformatics tools have driven the attention on pattern recognition approaches rather then single-marker tests for prognostic forecasting. It is expected that predicting metastasization on the basis of tumoral protein patterns will soon be a reality. However, currently available technologies either limit the number of proteins that can be analyzed simultaneously or they are expensive, difficult, and time-consuming. Moreover, the tools adapted for expression proteomics might not be the same as those for prognostic studies that require investigation of protein function over time. We believe that clinical proteomics research designed within a precise clinical and pathology framework should be strongly supported, since many prognostic factors are determined not by the tumor itself, but by the patient, the treatment and the environment.

Animals↗

Ethical, legal and economic issues raised by the use of human tissue in postgenomic research.

Ethical, legal and economic framework issues concerning human samples, genetic data and bioresources are rapidly evolving. In most cases, international standards have not been defined. National legislations on the use and exploitation of human sample collections differ widely. Legislations relating to intellectual property rights, access to database information for public or private bodies, of national or foreign origin, are similarly diverse. Importation and exportation rules, concerning in particular data protection, biosafety and protection of individual rights, have not always been defined. This article makes a short assessment of the legal, ethical and economic framework in selected EC countries (Germany, France and UK), and compares them with the conditions in the USA. On the basis of the information collected, it is obvious that the use of human cells, tissues and organs in medical research has to be considered as a global, worldwide question. Such use has profound ethical, cultural and economic consequences not only in the country of origin, but also globally. Biotechnology and pharmaceutical companies conducting research with human samples are facing different framework conditions in the area of data protection, policy measures, economic support, exportation, etc., that already influence trade activities and investments of such firms at the international level. Over the 3 last years, a trend towards harmonization can be recognized: the World Health Organization has recognized the problems of postgenomic medical research as a priority. The OECD has created a taskforce on centers for biological resources. Biobanks are a common theme of the French and the German National Ethic Councils. A lack of international harmonization and consistency might not only present a challenge to biotechnology and pharmaceutical companies, but can also endanger the goals the laws and regulations seek to achieve.

Culture Techniques↗

The role of proteomics in the diagnosis and outcome prediction in colorectal cancer.

Colorectal cancer is the second most frequent cancer in Western countries. Exogenous factors play a major role in the aetiology of sporadic colorectal cancer representing about 90% of all cases, hereditary cancers accounting for about 10% of patients. Thus, in the large majority of cases, cell dysfunction in CRC results from multiple rather than single, gene interactions. Numerous cellular events and environmental influences modify gene expression or post-translational protein modifications. Changes like glycosylation of proteins and lipids which are a common feature in colorectal cancer and influence cancer cell behaviour, cannot be directly detected by genetic studies. Better than genomics studies, functional proteomics studies allow the investigation of environmental factors over time, allowing the monitoring of metabolic responses to various stimuli. However, proteomics studies also have several drawbacks: a) current tools only allow narrow-range analyses, b) identification of proteins of interest remains cumbersome, c) protein studies address multiple compounds of high complexity, d) large amount of proteins are necessary to allow analysis, e) protein research require specific tools, e.g. tagged antibodies, that first have to be developed. Some protein tests are already in application for CRC: a classical prognostic test in colorectal cancer is based on the detection and quantification of a single protein (CEA) in body fluids. Recently, a screening assay based on APC protein truncation test has also been proposed. However, studies linking large protein expression patterns with clinical outcome in colorectal cancer are still in their infancy. To be able to predict occurrence of disease, and treatment outcome, more studies on genotype-phenotype correlations are needed both in sporadic and in hereditary colorectal cancer.

Colorectal Neoplasms↗

Discordance between K-ras mutations in bone marrow micrometastases and the primary tumor in colorectal cancer.

PURPOSE: To study bone marrow micrometastases from colorectal cancer patients for the presence of K-ras mutations and to compare their genotype with that of the corresponding primary tumor. PATIENTS AND METHODS: Bilateral iliac crest aspiration was performed in 51 patients undergoing surgery for colorectal cancer, and bone marrow micrometastases were detected by immunohistochemistry. The presence of K-ras mutations was determined by single-strand conformation polymorphism analysis on both primary tumors and paired bone marrow samples and was confirmed by sequencing. RESULTS: In six patients with primary tumor mutations, it was possible to amplify a mutated K-ras gene also from the bone marrow sample. In three of those patients the pattern of K-ras mutations differed between both samples, in two patients the mutation was identical between the bone marrow and its primary tumor, and in one patient the same mutation plus a different one were found. Fifteen of 17 K-ras mutations found in primary tumors were located in codon 12, whereas in bone marrow, five of seven mutations were found in codon 13 (P =.003). CONCLUSION: Our results demonstrate that, at least for K-ras mutations, disseminated epithelial cells are not always clonal with the primary tumor and they question the malignant genotype of bone marrow micrometastases. They also indicate that different tumoral clones may be circulating simultaneously or sequentially in the same patient. Analysis of the type of mutations suggests that cell dissemination might be an early event in colorectal carcinogenesis.

Aged↗

Accuracy of two-dimensional electrophoresis for target discovery in human colorectal cancer.

Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is increasingly used for target discovery in human disease to complement genomic studies. We have assessed the possibilities and limits of 2-D PAGE applied to human colorectal cancer. Up to 10(8) epithelial cells were purified from paired normal and pathological biopsies using Ber-EP4 coated magnetic beads, allowing the elimination of cellular and fluid contaminations. The mean coefficient of variation (CVAR) of repeated 2-D PAGE analysis with silver staining was lying between 20 and 28%. However, only 47% (interrun) to 76% (intrarun) of spots could be matched within a triplicate experiment. Interindividual phenotypic variability was high. Intratumoral phenotypic variability was not found to be significant. When method and tumor variability were added, 90% of CVAR were inferior to 48%. Thus, two-fold up- or down-regulation of protein expression reveals biological significance. Serial paired comparison of 923 proteins in 10 patients showed highly reproducible differences between normal and cancer tissues. Under well defined experimental conditions and after the high variability of the technique has been considered, 2-D PAGE parallel analysis of paired colorectal samples allows patient-specific tumor profiling.

Colorectal Neoplasms↗

Clinical evaluation of the Unfolder.

PURPOSE: To evaluate the clinical acceptability of the Unfolder for implantation of AMO PhacoFlex II (model SI-30NB or SI-40NB) intraocular lenses (IOLs). SETTING: Six investigational sites in five states in the United States: Utah, Texas, Missouri, Minnesota, and Massachusetts. METHODS: One hundred one patients from six investigational sites had implantation of an SI-30NB or SI-40NB IOL. Investigators evaluated the clinical acceptability of the Unfolder by comparing their experience with the injector with that using other implantation systems. Internal incision size (dimensions) was measured three times during surgery using a calibrated instrument. Data on safety and efficacy were collected. RESULTS: The investigators rated the Unfolder as clinically acceptable. Mean internal incision size after phacoemulsification but before IOL implantation was 3.0 mm +/- 0.1 (SD) (range 2.7 to 3.2 mm). Average internal incision size after IOL implantation was 3.1 +/- 0.1 mm. There were no reports of haptic deformation, lens optic damage, or postoperative complications related to the Unfolder. No adverse events were reported. CONCLUSIONS: Investigators found the Unfolder easy to use. It provided controlled lens implantation through incisions 2.7 to 3.2 mm, with post-IOL implantation incisions ranging from 2.9 to 3.3 mm.

Evaluation Studies as Topic↗

Characteristics influencing outcomes of excimer laser photorefractive keratectomy. Summit Photorefractive Keratectomy Phase III Study Group.

PURPOSE: To identify preoperative and intraoperative characteristics associated with outcomes of photorefractive keratectomy (PRK). METHODS: In the phase III multicenter clinical trials of the Summit Technology excimer laser for corrections of 1.5 to 6.0 diopters (D) of myopia, three principal outcomes of PRK on 612 patients were examined: (1) uncorrected visual acuity of 20/40 or better, (2) predictability of refractive outcome within 1.0 D of attempted correction, and (3) stability of refractive result between 12 and 24 months. Multiple logistic regression was used to test for independent associations of multiple preoperative and intraoperative characteristics with each of these outcomes. RESULTS: Older age was independently associated with lesser likelihood of achieving 20/40 or better uncorrected visual acuity (odds ratio = 1.08 per incremental year of age, 95% confidence interval [CI] = 1.04-1.12) and with decreased predictability, specifically with overcorrection (odds ratio = 1.09, 95% CI = 1.06-1.12), but age was not associated with stability of refraction. Greater attempted correction was associated independently with a decreased likelihood of 20/40 or better uncorrected visual acuity (odds ratio = 2.78 for corrections of 3.5-5.5 D, 95% CI = 1.18-6.75; odds ratio = 4.19 for corrections of > or = 5.5 D, 95% CI = 1.66-10.58), with decreased predictability (odds ratio = 1.72 for corrections of 3.5-5.5 D, 95% CI = 1.05-2.85; odds ratio = 2.95 for corrections of > or = 5.5 D, 95% CI = 1.65-5.26), and with a reduced likelihood of stability of refraction (odds ratio = 3.46 for corrections of > or = 5.0 D, 95% CI = 1.32-9.11). No intraoperative characteristics were associated with any of the outcomes assessed. CONCLUSIONS: Using this specific excimer laser system with an optical zone of 4.5 or 5.0 mm, patient age and attempted correction are important preoperative characteristics associated with postoperative uncorrected visual acuity and predictability of PRK. Stability of refraction is strongly associated with attempted correction. Such information may help guide patient selection, determine timing of fellow eye treatment, and suggest changes in the laser treatment algorithm for individual patients. Although these findings may be representative of PRK in general, similar analyses should be performed before modifying patient treatments using either a 6.0-mm treatment zone or other laser systems.

Adult↗

A multicenter trial of photorefractive keratectomy for residual myopia after previous ocular surgery. Summit Therapeutic Refractive Study Group.

PURPOSE: The Summit Therapeutic Refractive Clinical Trial is a nine-center prospective, nonrandomized, self-controlled trial to assess the efficacy, stability, and safety of using a standardized technique of excimer laser photorefractive keratectomy (PRK) to correct residual myopia in eyes with previous refractive surgery or cataract surgery. PATIENTS AND METHODS: Eligible eyes with a mean residual myopia of -3.7 +/- 1.8 diopters (D) (range, -0.63 to -11.00 D) underwent PRK with a 193-nm excimer laser for myopic corrections between -1.50 and -7.50 D. Standardized settings were used for the ablation zone, ablation rate, repetition rate, and fluence. One hundred seven of the first 114 treated eyes were examined 1 year after PRK, with 98% of eyes having had refractive keratotomy and 2% having had cataract surgery. RESULTS: One year postoperatively, the mean manifest spherical equivalent refraction was -0.6 +/- 1.4 D (range, -6.50 to 2.50 D); 63% of eyes were within +/-1.00 D of the attempted correction; and uncorrected visual acuity was 20/40 or better in 74% of eyes. Twenty-nine percent of eyes lost two or more Snellen lines of best-corrected visual acuity, and central corneal haze was moderate or severe in 8% of eyes. CONCLUSIONS: Excimer laser PRK is effective in reducing residual myopia after previous refractive and cataract surgery. However, it is less accurate than PRK in eyes that did not undergo surgery and is more likely to cause a loss of best-corrected visual acuity 1 year after treatment.

Adult↗

[Genetic disposition to chronic polypoid sinusitis and alpha 1-proteinase inhibitor deficiency types].

Chronic polypoid sinusitis is often accompanied with bronchitis, asthma and various allergies. All of these disorders have immunologic defects in common. The present study was devised to measure the genetically determined parameter of alpha-1-protease inhibitor by isoelectric focusing. Genetic polymorphism of alpha-1-antitrypsin is the source for biochemically less active types of the protease inhibitor. In this investigation the alpha-1-protease inhibitor type of 86 patients from Niedersaxony and 95 patients from Schleswig-Holstein was determined. All patients required sinus surgery as treatment for chronic polypoid sinusitis. The alpha-1-protease inhibitor deficiency types PI-MS and PI-MZ were found five times more frequently in patients from Niedersachsony and three times more often in patients from Schleswig-Holstein than in a control (normal) group of 127 subjects (p < 0.01). These findings were comparable to data in other publications. Results clearly showed a connection between alpha-1-protease inhibitor deficiency types and chronic polypoid sinusitis. These findings indicate that a genetic predisposition to chronic polypoid sinusitis is somehow correlated with the gene locus for alpha-1-protease inhibitor.

Adolescent↗

[Orbital pseudotumor].

The orbital pseudotumour is an inflammatory infiltration, which ranges from a lymphoid, through a granulomatous to a sclerosing type, depending on its stage of maturity. Its simulataneous appearance with autoimmune-reaction-induced diseases might indicate an immune-allergic aetiology. After clinical diagnostic procedures including imaging techniques (of which magnetic resonance is particularly important) as much of the tissue as possible should be removed by orbitotomy. Therapy with cortisone and/or radiation is indispensable, but seems to be effective only in the early stages. The case histories of three patients over periods of 1.5-12 years are analysed and compared with the currently available results in the literature.

Female↗

[Percutaneous transtracheal ventilation using Nu-Trake cricothyreotomy instruments and tracheoscopic follow-up examination].

Practicability and efficiency of the cricothyreotomy set Nu-Trake was investigated in corpses (n = 10) in the institute of Pathology and clinically in laryngectomy patients (n = 5) including endoscopical controls. The practicability proved to be good, the time needed to perform the coniotomy did not last longer than 2 minutes. But complications in the investigation on the corpses could not be avoided. These were missing the lumen of the trachea, perforation of the pars membranacea tracheae and fracture of the cricoid. The clinical investigation demonstrated a sufficient oxygenation and ventilation in all patients during the whole investigation period (30 min). This can be explained by the diameter of 7.2 mm of the used tube. Endoscopic controls showed a sufficient distance of the tip of the tubes from the pars membranacea tracheae and almost no bleeding within the trachea. Similar as with other coniotomy-technics the cricothyreotomy with the Nu-Trake set bears the risk of typical complications which have to be overcome by training of this important measure of emergency.

Aged↗

[Failed intubation with case reports].

Failed intubation in three patients is reported. All three patients suffered sudden, extreme impaired of mask-ventilation. Twice a coniotomy with subsequent tracheostomy proved to be life saving and without permanent injury. In the other patient tracheostomy had been attempted without success, and subsequent, successful, coniotomy could not prevent cerebral ischemia. Coniotomy is the only correct emergency operation for failed intubation with impaired mask ventilation. It must be followed by a standard tracheostomy with closure of the coniotomy wound to prevent permanent laryngeal damage.

Adult↗

[Sudden deafness today--a review].

Sudden deafness is not a disease in itself. Unilateral impairment of inner ear function of acute onset is a symptom of unknown origin. Recent results of basic science and clinical research favour an alteration of physiological properties and/or a variety of different diseases as a cause of this inner ear dysfunction. It is important to recognise these factors by audiometric and clinical investigations in order to differentiate the resulting inner ear dysfunction from sudden deafness. Our task is to find the cause in almost every case of hearing impairment so that the term "sudden deafness--of unknown cause" can be abandoned. So far we prefer a conservative treatment. Indicators of unfavourable prognosis should be assessed carefully since they demand special treatment, for instance tympanotomy.

Cochlea↗

[Cochlear potentials and reduced blood supply].

In cats the mean arterial blood pressure (MABP) was reduced to 40 or 30 mm Hg by controlled hemorrhage. In 3 animals the cochlea action potentials (CAP) are not changed between 30 and 380 Min by 40 mm Hg MABP. In 4 animals we saw a latent or permanent decrease of CAP between 4 and 115 Min by 30 mm Hg MABP. A singular experiment shows, that a CAP-decrease is caused by injection of an acetylcholin blockade substance. We did not find a correlation to the length of time of the ischemia and a CAP decrease. We found an exact correlation to the hypovolemic sympathetic palsy and a CAP decrease. In reduced blood perfusion the cochlea of cats is more resistant than the brain.

Animals↗

Superior limbic keratoconjunctivitis in contact lens wearers.

Forty patients with daily wear, cosmetic contact lenses (CL) presented with symptoms of ocular irritation and a keratoconjunctivitis clinically resembling superior limbic keratoconjunctivitis (SLK). Typically the patients were either successful hard CL wearers who changed to soft lenses and used a chemical aseptisizing solution or preserved saline solution, or successful soft CL wearers using salt tablets who switched to a preservative-containing system. In all cases, exposure to thimerosal-preserved solutions was documented. Upon discontinuation of lens wear, all signs and symptoms slowly resolved without permanent sequelae. Positive skin and ocular sensitivity reactions to thimerosal were present in one-third (5/15) of patients tested. Light and transmission electron microscopic examination of conjunctival specimens disclosed intercellular epithelial edema, pseudoepitheliomatous hyperplasia, acute and chronic inflammation, and decreased numbers of goblet cells. Exposure to thimerosal is implicated in the etiology of contact lens-superior limbic keratoconjunctivitis (CL-SLK).

Adolescent↗