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Biomedical subjects

B Göke

Publications and source records attributed to B Göke.

At least 37 records · Page 2Linked to original sources
PubMed2004

Dexamethasone enhances the cytotoxic effect of radioiodine therapy in prostate cancer cells expressing the sodium iodide symporter.

Recently, we have reported the induction of prostate-specific radioiodine accumulation in prostate cancer cells (LNCaP) using a prostate-specific antigen (PSA)-promoter-directed expression of the sodium iodide symporter (NIS) gene. This offers the potential to treat prostate cancer with radioiodine. The aim of our current study was to examine the regulation of PSA-promoter-directed NIS expression in NIS-transfected LNCaP cells (NP-1) by dexamethasone (Dex). For this purpose, NIS mRNA and protein expression levels were examined in NP-1 cells by Northern and Western blot analysis, respectively, after incubation with Dex (10(-8)-10(-6) M) in the presence of 10(-9) M mibolerone. NIS functional activity was measured by iodide uptake assay. In addition, we examined regulation of in vitro cytotoxicity of 131-I by Dex in an in vitro clonogenic assay. After incubation with Dex, iodide accumulation in NP-1 cells increased up to 1.5-fold, whereas NIS mRNA and protein expression levels were increased up to 1.7-fold. This effect of Dex was blocked by the androgen receptor antagonist casodex (10(-6) M). The killing effect of 131-I in NP-1 cells was increased from 55% when incubated with mibolerone alone to 95% when treated with Dex (10(-7) M) plus mibolerone. Treatment of NP-1 cells with Dex resulted in an additional antiproliferative effect as measured by clonogenic assay and nonradioactive proliferation assay. In conclusion, in addition to an antiproliferative effect, treatment with Dex increases androgen-dependent NIS mRNA and protein expression as well as iodide accumulation, resulting in an increased cytotoxic effect of 131-I in prostate cancer cells stably expressing NIS under the control of the PSA-promoter.

Antineoplastic Agents, Hormonal↗
PubMed2003

[Aim, design and methods of the "Hypertension and diabetes screening and awareness" -- (HYDRA) study].

Aim of the study is a comprehensive clinical-epidemiological description of the prevalence of arterial hypertension and diabetes among primary care patients along with an assessment of doctor's recognition rates and prescription behaviour. The paper describes methods and design of the study and provides background information on the sampling process, instruments used as well as characteristics of doctors and patients. The study is based on a nationally representative sample of 1,912 primary care doctors and 45,000 patients that attended the doctors' office on the target days. The patients were also characterized by laboratory tests. The first stage of study consisted of a comprehensive description of the doctors' characteristics in terms of psychosocial, qualification- and provider aspects as well as attitudes towards hypertension and diabetes and their management. In the second stage all patients completed a questionnaire to describe their health behaviour and attitudes as well as the treatment history and therapy. In the third stage all patients were characterized by their doctors in terms of their diagnostic status and their past and current interventions.

Adolescent↗
PubMed2003

[Management of diabetes and hypertension: how do primary care physicians judge their performance?].

With regard to the management of hypertension and diabetes, HYDRA reveals that doctors report multiple problems in their everyday practice. Being confronted with an average of 73 patients a day, with almost every second having either diabetes or hypertension, frequently associated with multiple comorbid conditions, the core obstacle is the time factor. Doctors do not have sufficient time to perform diagnostic tests and especially no time for non-drug interventions of any type. Further available treatment guidelines are only used in 1 out of 2 doctors. Further they seem not to affect doctors performance significantly.

Adult↗
PubMed2003

[Hypertension, diabetes mellitus and comorbidity in primary care].

Almost every second patient seeing a primary care doctor suffers from arterial hypertension and about every fifth has diabetes mellitus. These diseases often occur at the same time. They are associated in more than 80% of the cases with other severe concomitant and subsequent diseases (heart attack, stroke, renal failure, neuropathy etc.). The magnitude especially of subsequent and concomitant diseases, the dimension of the personal suffering and the immense diagnostic and therapeutic challenges for the doctors have been massively underestimated so far. The article informs about the prevalence of the above disease, and structure of the problem. Before the background of an extremely high patient load seen by German General Physicians, the mainstay challenge is highlighted how to achieve further improvements of the quality of care on the basis of scientific guidelines alone, without a concomitant change in the system structure.

Adolescent↗
PubMed2003

[Diagnostic evaluation of pancreatic carcinoma prompting treatment decisions].

An early diagnosis or even sufficient screening tools may allow improved and/or more successful treatment strategies for pancreatic carcinomas. Presently,we have no useful screening tools available. The 5 year survival rates of those suffering from pancreatic cancer is around 3%, with only 15% of patients at diagnosis available for curative resection protocols. Thus, better diagnostic procedures for populations at risk are urgently required. Today,endosonography complements new CT and MRI tests. High resolution CT and contrast enhanced MRI procedures are rapidly evolving and may offer more precise diagnostic opportunities. PET tests help discriminating benign from neoplastic tumors, and new molecular markers may offer the opportunity to screen patients at risk with the hope for an early diagnosis. Nevertheless, the technical progress made in tomographic procedures is developing so rapidly that comparative studies are often outdated at publication. Therefore,we have reason to hope for improved diagnostic skills, but presently have only limited data for the new techniques currently available.

Biomarkers, Tumor↗
PubMed2003

[Therapy of hyperlipoproteinemia in the elderly].

Atherosclerosis associated diseases are the major cause of mortality in men and women over 65 years. Although the epidemiological relationship between hypercholesterolemia and cardiovascular disease is less prominent in elderly than in younger patients, the results of numerous intervention trials show that risk reduction can also be achieved in elderly and old patients. The numbers needed to treat to prevent one cardiovascular event is usually lower in this age group because of the high absolute rate of events. Therefore, in secondary prevention settings these patients should be treated similar to younger patients, i.e. a LDL-cholesterol below 100 mg/dl should be achieved. In hyper- or dyslipoproteinemic patients without evidence of clinical or subclinical atherosclerosis cholesterol lowering drugs should be used restrictively.

Aged↗
PubMed2003

[MRI in Crohn's disease after transduodenal contrast administration using negative oral MRI contrast media].

PURPOSE: To compare the efficacy and quality of conventional and MR enteroclysis with different filling methods regarding the assessment of extension and extraluminal manifestations in Crohn's disease. MATERIAL AND METHODS: 190 patients with known Crohn's disease were studied following small bowel enteroclysis, after oral administration or direct transduodenal filling in the MRI-department.T1- and T2-weighted breathhold MRI-scans w/o spectral fat suppression w/o i.v. Gd-DTPA were applied using negative oral superparamagnetic contrast media. RESULTS: Typical findings were marked bowel wall thickening with laminated wall contrast enhancement. In 135 patients 98,2% of affected bowel segments, 97,5% of stenoses and all 16 fistulas were detected, when conventional enteroclysis was employed as standard of reference. Additional important extraluminal findings such as ileoileal (n = 18), ileosigmoidal adhesions (n = 12), extraluminal abscesses (n = 35) and pseudotumors (n = 8) were visualized in 73/135 patients. Concerning the distension of jejunum and ileum, oral filling was rated significantly inferior to transduodenal filling in all small bowel segments,whereas filling in the MRI-unit was rated superior to fluoroscopic, mostly due to a mean transport time of 20 min to the MRI-unit. CONCLUSION: No clinically important findings of enteroclysis were missed when using MRI. Therefore, in patients with Crohn's disease, conventional enteroclysis can be replaced by MRI. For optimal bowel distension oral contrast administration is inferior to transduodenal filling, if a larger time delay between filling and the MRI-scan can be avoided.

Administration, Oral↗
PubMed2003

[Inflammatory bowel diseases (IBD) -- critical discussion of etiology, pathogenesis, diagnostics, and therapy].

AIMS: Crohn's disease and ulcerative colitis are the most frequent inflammatory bowel diseases (IBD) with a prevalence of approximately one out of 500. Cytokine research opened new and potent treatment options and thus stimulated clinical and basic research.However, the IBD still remain a challenge for patients and physicians,demanding close cooperation between gastroenterologists,radiologists and surgeons. The basic understanding of IBD,which is necessary for efficient diagnostic and therapeutic concepts is reviewed. METHODS: Based upon recent publications and our clinical experience we discuss aspects of etiology,pathogenesis,diagnostics,and therapy of Crohn's disease and ulcerative colitis. RESULTS: A genetically influenced, exaggerated and sustained immune response against the own gut flora seems to be one of the most important factors in the pathogenesis of IBD. Not less important are environmental influences. For instance, cigarette smoking had been judged to have some negative influence on the natural course of Crohn's disease.Now,however, recent studies show that smoking is even a significant independent risk factor in the pathogenesis of IBD. Since IBD and especially Crohn's disease can effect the whole body, detailed analysis of inflammatory organ involvement is necessary before therapy. For instance, the MRI enteroclysis technique adds a necessary diagnostic tool for the exploration of those parts of the small bowel that cannot been reached by routine endoscopy like the upper ileum and the lower jejunum. In terms of therapy, a change of paradigms can be observed: patients will no longer be treated only when symptoms arise, but will early be integrated into a therapeutic concept, which is determined by site and extent of the disease and adapted to the abilities and needs of the patient.Furthermore,immunosuppressive agents like azathioprine and 6-mercaptopurine will establish as central concept in the medical treatment of IBD. DISCUSSION: IBD-therapy should rather be adapted to the patient's individual inflammatory pattern than be oriented to schematic treatment rules. New endoscopic and radiologic techniques provide the necessary diagnostic tools.

Adrenal Cortex Hormones↗
PubMed2003

[Primary hyperparathyroidism, adrenal tumors and neuroendocrine tumors of the pancreas--clinical diagnosis and imaging requirements].

INTRODUCTION: Diseases of the parathyroids, the adrenals and of neuroendocrine tumors of the pancreas are primarily diagnosed by clinical and endocrinological evaluation. The requirements concerning various imaging techniques and their relative importance in localization strategies of the different tumors are complex. MATERIALS AND METHODS: Current literature search, using PubMed. RESULTS: Evaluation of primary hyperparathyroidism requires bone densitometry by DXA and search for nephrolithiasis by ultrasound or native CT examination. While ultrasound of the thyroid and parathyroids seems useful before any parathyroid surgery, more extensive preoperative localization strategies (sestamibi scintigraphy, MRI) should be restricted to minimal invasive parathyroid surgery or reoperations. For adrenal tumors CT and MRI are of similar diagnostic value. Imaging of pheochromocytomas should be completed by MIBG scintigraphy. Each adrenal incidentaloma requires an endocrinological work-up. A fine-needle aspiration or core needle biopsy of an adrenal tumor is rarely indicated. Before adrenal biopsy a pheochromocytoma has to be excluded. Successful localization strategies for neuroendocrine tumors of the pancreas include somatostatin receptor scintigraphy, endoscopic ultrasound and MRI. DISCUSSION: Specific localization strategies have been established for the aforementioned tumors. The continuous progress of different imaging techniques requires a regular reevaluation of these localization strategies.

Adenoma↗
PubMed2003

Retinoic acid-induced stimulation of sodium iodide symporter expression and cytotoxicity of radioiodine in prostate cancer cells.

We reported recently the induction of androgen-dependent iodide uptake activity in the human prostatic adenocarcinoma cell line LNCaP using a prostate-specific antigen (PSA) promoter-directed expression of the sodium iodide symporter (NIS) gene. This offers the potential to treat prostate cancer with radioiodine. In the current study, we examined the regulation of PSA promoter-directed NIS expression and therapeutic effectiveness of (131)I in LNCaP cells by all-trans-retinoic acid (atRA). For this purpose, NIS mRNA and protein expression levels in the NIS-transfected LNCaP cell line NP-1 were examined by Northern and Western blot analysis following incubation with atRA (10 (-9) to 10(-6) M) in the presence of 10(-9) M mibolerone (mib). In addition, NIS functional activity was measured by iodide uptake assay, and in vitro cytotoxicity of (131)I was examined by in vitro clonogenic assay. Following incubation with atRA, NIS mRNA levels in NP-1 cells were stimulated 3-fold in a concentration-dependent manner, whereas NIS protein levels increased 2.3-fold and iodide accumulation was stimulated 1.45-fold. This stimulatory effect of atRA, which has been shown to be retinoic acid receptor mediated, was completely blocked by the pure androgen receptor antagonist casodex (10(-6) M), indicating that it is androgen receptor dependent. The selective killing effect of (131)I in NP-1 cells was 50% in NP-1 cells incubated with 10(-9) M mib. This was increased to 90% in NP-1 cells treated with atRA (10(-7) M) plus 10(-9) M mib. In conclusion, treatment with atRA increases NIS expression levels and selective killing effect of (131)I in prostate cancer cells stably expressing NIS under the control of the PSA promoter. Therefore atRA may be used to enhance the therapeutic response to radioiodine in prostate cancer cells following PSA promoter-directed NIS gene delivery.

Adenocarcinoma↗
PubMed2002

[Screening for prevention of colorectal carcinoma. Who, when, how?].

Long-term survival of patients with colon carcinoma is largely determined by the timing of the diagnosis. For the identification of early colorectal carcinoma, it is of particular importance to detect and remove local precursor lesions (polyps) by means of effective screening, before they undergo malignant degeneration. The gold standard for such screening continues to be colonoscopy, followed by sigmoidoscopy, which latter, however, leaves large segments of the proximal uninspected. Additional--though less sensitive and more complicated--current screening techniques are the test for occult blood in the stools and the barium Doppler contrast examination, and, possibly in the near future, virtual colonoscopy and genetic testing for tumor DNA in the stools. Detailed screening recommendations are to be found in the guidelines issued by the German Society for Digestive and Metabolic Diseases. A prerequisite for effective prevention of colorectal carcinoma is the provision of information to, and motivation of, both the population and the individual patient, to participate in screening measures.

Adult↗
PubMed2002

[Glinides and glitazones in diabetes treatment. Are they really effective?].

Good glucose control is a prerequisite for the prevention of long-term complications in type 2 diabetics. In recent years, two new groups of substances have been approved for the oral treatment of type 2 diabetes: glinides and glitazones. The former are short-acting agents that promote insulin secretion and offer an alternative to the sulfonylureas, in particular in patients with irregular eating habits and high postprandial glucose peaks. The glitazones improve one of the disorders underlying type 2 diabetes, insulin resistance. They are used in particular in patients who are inadequately controlled with a sulfonylurea or metformin and who show insulin resistance. Both groups of substances are a useful addition to the antidiabetic drug armamentarium. Endpoint studies involving these substances have, however, not yet been performed.

Carbamates↗
PubMed2002

[Pathogenesis and epidemiology of sigmoid diverticulosis].

From an epidemiological point of view, left-sided diverticulosis represents a civilizational disease of Western countries. It occurs rarely during childhood and frequently in later years. A diet high in fat and meat, low in vegetables, and with insufficient fiber content apparently encourages its genesis. Physical activity seems to counteract diverticulosis while alcohol consumption, smoking, and caffeine ingestion have no effect. The extent of diverticulosis is not commensurate with the extent of complaints. Only a few patients with diverticula develop diverticulitis. Pathogenetically, several factors play a role in the development of diverticulosis. Elevated intraluminal pressure as well as acquired structural changes of the intestinal wall seem to be decisive factors, which intensify with increasing age. These changes are caused by ultrastructural alterations of the muscle and connective tissue related to collagen and elastin metabolism, which presumably can be genetically determined. Intestinal disturbances of innervation and motility also contribute to the formation of diverticula. The term "hypersegmentation" is an attempt to combine these factors into a single pathogenetic model.

Cross-Sectional Studies↗
PubMed2002

Endoproteolysis by isolated membrane peptidases reveal metabolic stability of glucagon-like peptide-1 analogs, exendins-3 and -4.

These in vitro studies aimed to characterize the pattern and the kinetics of endoproteolysis of the insulinotropic hormone glucagon-like peptide-1 (GLP-1) and related peptides by native ectopeptidases. Peptides were incubated with isolated rat or pig kidney brush-border microvilli membranes, which are a rich source of the ectopeptidases that are responsible for the post-secretory metabolism of peptide hormones. The proteolytic products were separated by reversed-phase HPLC column chromatography and characterised by molecular mass and primary structure. The relative importance of specific peptidases was established by measuring the effects of specific peptidase inhibitors on the kinetics of proteolysis. Dipeptidyl-peptidase-IV was found to be rate-limiting in the endoproteolysis of GLP-1. GLP-1 homologs, exendins-3 and -4, exhibited exceptional stability in the presence of isolated kidney microvilli membranes. Our finding that exendin-4 is several orders of magnitude more stable than GLP-1 and Ser-8-GLP-1 is especially noteworthy given this peptide's widely reported insulinotropic potency.

Animals↗
PubMed2002

Metabolic efficacy and safety of once-daily pioglitazone monotherapy in patients with type 2 diabetes: a double-blind, placebo-controlled study.

Pioglitazone is a novel oral anti-diabetic agent belonging to the thiazolidinedione class. Pioglitazone has been shown to be effective and well tolerated in the treatment of patients with type 2 diabetes, as it reduces insulin resistance and improves glycaemic control and abnormal lipid profiles. This double-blind, randomised, placebo-controlled study was conducted for further evaluation of the efficacy and tolerability of once-daily administration of pioglitazone monotherapy alongside dietary measures in patients with type 2 diabetes. Following a 10-week washout period, 251 patients received one of three treatment regimens for 26 weeks: placebo + diet (n = 84), pioglitazone 15 mg once-daily + diet (n = 89), or pioglitazone 30 mg once-daily + diet (n = 78). Pioglitazone, both 15 and 30 mg/day, in addition to dietary control, was associated with significant reductions (vs. placebo) in mean levels of both glycosylated haemoglobin (HbA 1C ) and fasting blood glucose (FBG). HbA 1C was reduced by 0.92 % and 1.05 %, respectively, and FBG was reduced by 34.3 and 36.0 mg/dl, respectively, compared with the control group. Pioglitazone at 15 and 30 mg/day significantly reduced postprandial blood glucose levels at all visits (- 163 and - 165 mg/dl/hour, respectively) compared with an increase of 47.7 mg/dl/hour on placebo. The profile and frequency of adverse events were similar in all treatment groups. These results indicate that pioglitazone monotherapy together with dietary control is both effective and safe in patients with type 2 diabetes.

Adult↗