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Biomedical subjects

Rainer Koch

Publications and source records attributed to Rainer Koch.

At least 37 records · Page 2Linked to original sources
PubMed2005

Feasibility and limitations of comorbidity measurement in patients undergoing radical prostatectomy.

OBJECTIVE: To compare different comorbidity classifications as predictors of survival after radical prostatectomy (RPE). METHODS: 444 consecutive RPE patients (mean follow-up 6.9 years) were stratified according to age, Charlson score, American Society of Anesthesiologists Physical Status classification (ASA), New York Heart Association classification of cardiac insufficiency, classification of angina pectoris of the Canadian Cardiovascular Society and a combination of both cardiac risk scores. Comorbid and overall mortality were the study endpoints. Mantel-Haenszel hazard ratios, p values and 8-year survival probabilities were used for comparison. A modified Charlson score was created by a restriction to the five individual conditions significantly associated with comorbid mortality. RESULTS: When three strata (low, intermediate, high risk) were used, all stratifications displayed dose-response patterns and reached statistical significance as predictors of survival at least for the high-risk group. Only the ASA classification, however, discriminated three significantly different risk groups. Only the modified (restricted) Charlson score reached statistical significance as predictor of comorbid mortality in the age group of 70 or more years. CONCLUSION: Although all investigated comorbidity classifications had some prognostic relevance in patients selected for RPE, their clinical applicability appears to be limited beyond the 70th year of life. The results of this study might, nevertheless, assist the treatment decision in patients with low-risk tumors eligible for modern watchful waiting strategies who mainly belong to the age group between 60-69 years where comorbidity seems to be of distinct prognostic value.

Aged↗
PubMed2005

Comparison of tumor- and comorbidity-related predictors of mortality after radical prostatectomy.

OBJECTIVES: To identify and compare tumor- and non-tumor-related predictors of survival after radical prostatectomy and to incorporate the latter into the tumor node metastasis classification of prostate cancer. MATERIAL AND METHODS: A total of 402 patients who underwent radical prostatectomy (mean follow-up period 6.9 years) were stratified according to postoperative tumor stage, Gleason score, prostate-specific antigen level, age and five comorbidity classifications. Cox proportional hazard models were used to identify independent prognostic factors predicting overall survival. RESULTS: Comorbidity (American Society of Anesthesiologists Physical Status classification), Gleason score and age, but not tumor stage, were independent predictors of overall survival. Based on tumor stage and the identified independent prognostic factors, an easily applicable prognostic score was developed to predict overall mortality. CONCLUSION: A prognostic classification of radical prostatectomy patients based on Gleason score, comorbidity and age and supplementary to a coarsened variant of the tumor node metastasis classification may be of clinical value.

Aged↗
PubMed2005

Influence of CARD15 mutations on disease activity and response to therapy in 65 pediatric Crohn patients from Saxony, Germany.

OBJECTIVES: Certain genetic variants in the CARD15 gene are accompanied by an enhanced risk to develop Crohn disease with the main activity in the terminal ileum and ensuing stricturing early in life. The objective of this study was to evaluate the relation between CARD15 mutations and overall disease activity and response to therapy in pediatric patients. METHODS: 65 genomic DNA samples from such patients were tested for the presence of three main Crohn associated mutations in CARD15 by direct genomic sequencing. The number of mutations (none, one or two alleles affected) was correlated with body mass index and height, Pediatric Crohn Disease Activity Index, therapy and therapeutical success in terms of body mass index and Pediatric Crohn Disease Activity Index improvement. RESULTS: The authors found a nonsignificant trend of a lower body mass index and higher Pediatric Crohn Disease Activity Index in patients with CARD15 mutations. Physicians uninformed about their CARD15 status prescribed significantly more budesonide and prednisolone intermittently and more alimentary supplementation to these patients. The average improvement in terms of body mass index and Pediatric Crohn Disease Activity Index after 2 years of therapy was roughly similar in all patient groups. CONCLUSIONS: Pediatric Crohn patients with CARD15 mutations have a higher disease activity and need a more intensive therapy. With some exceptions, their medium-term response to therapy is nevertheless satisfying.

Adolescent↗
PubMed2005

The influence of contractures and variation in measurement stretching velocity on the reliability of the Modified Ashworth Scale in patients with severe brain injury.

OBJECTIVE: To determine the influence of contractures and different stretching velocities on the reliability of the Modified Ashworth Scale (MAS) in patients with severe brain injury and impaired consciousness. DESIGN: Cross-section observational study. SETTING: A rehabilitation centre for adult persons with neurological disorders. SUBJECTS: Fifty patients with impaired consciousness due to severe cerebral damage of various aetiologies. MEASUREMENT PROTOCOL: Three experienced and trained medical professionals rated each patient in a randomized order once daily for two consecutive days. Shoulder, elbow, wrist, knee and ankle spasticity were assessed by the use of the MAS with different stretching velocities. The presence of contractures was assessed by a goniometer. MAIN OUTCOME MEASURES: Retest and inter-rater reliability (k(w) = weighted kappa) of the MAS. RESULTS: The retest reliability of the MAS was good (shoulder joints (k(w) 0.74), elbow joints (k(w) 0.74), wrist joints (k(w) 0.72), knee joints (k(w) 0.72), ankle joints (k(w) 0.77)) and the inter-rater reliability was moderate (shoulder joints (k(w) 0.49), elbow joints (k(w) 0.52), wrist joints (k(w) 0.51), knee joints (k(w) 0.54) ankle joints (k(w) 0.49)). The presence of contractures significantly influenced the reliability of MAS in shoulder and wrist joints. No influence of stretching velocity on the reliability of the MAS was found. CONCLUSION: In patients with impaired consciousness due to severe brain injury the MAS has good retest, but only limited inter-rater, reliability. The presence of contractures may influence reliability of the MAS, but stretching velocity does not.

Brain Injuries↗
PubMed2005

Reliability of the Modified Tardieu Scale and the Modified Ashworth Scale in adult patients with severe brain injury: a comparison study.

OBJECTIVE: To assess and to compare the reliability of the Modified Tardieu Scale with the Modified Ashworth Scale in patients with severe brain injury and impaired consciousness. DESIGN: Cross-sectional observational comparison study. SETTING: An early rehabilitation centre for adults with neurological disorders. SUBJECTS: Thirty patients with impaired consciousness due to severe cerebral damage of various aetiologies. MEASUREMENT PROTOCOL: Four experienced physical therapists rated each patient in a randomized order once daily for two consecutive days. Shoulder, elbow, wrist, hip, knee and ankle spasticity were assessed by the use of Modified Tardieu Scale and Modified Ashworth Scale data collection procedures. MAIN OUTCOME MEASURES: Test-retest and inter-rater reliability (kappa = kappa value) of the Modified Tardieu Scale and the Modified Ashworth Scale. RESULTS: The test-retest reliability of the Modified Ashworth Scale was moderate to good (kappa = 0.47-0.62) and of the Modified Tardieu Scale moderate to very good (kappa = 0.52-0.87). Test-retest reliability was significantly higher within the Modified Tardieu Scale in comparison with the Modified Ashworth Scale (Z > 1.96; p < 0.05) except for shoulder extensor and internal rotator muscles (Z < 1.96; p > 0.05). Although inter-rater reliability of both scales was poor to moderate (Modified Ashworth Scale: kappa = 0.16-0.42; Modified Tardieu Scale: kappa = 0.29-0.53), significantly higher K-values were revealed with the Modified Tardieu Scale for all tested muscle groups (Z > 1.96; p < 0.05) except for wrist extensors (Z < 1.96; p > 0.05). CONCLUSION: In patients with severe brain injury and impaired consciousness the Modified Tardieu Scale provides higher test retest and inter-rater reliability compared with the Modified Ashworth Scale and may therefore be a more valid spasticity scale in adults.

Brain Injuries↗
PubMed2004

No evidence for germline mutations of the LKB1/STK11 gene in familial pancreatic carcinoma.

Familial pancreatic cancer (FPC) (approximately 3% of all cases) has not been linked to defects in any specific gene. Germline inactivation of the gene LKB1/STK11 have been shown to cause Peutz-Jeghers syndrome (PJS) associated with a approximately 100-fold higher risk for the development of pancreatic cancer. We have analysed 39 index patients from European FPC families for mutations of LKB1/STK11 by sequencing of their DNA. No germline mutation was found within the complete coding region. Therefore, our results indicate that LKB1/STK11 is not altered in the germline of patients with hereditary pancreatic cancer.

AMP-Activated Protein Kinase Kinases↗
PubMed2004

1H-1,3-diazepines, 5H-1,3-diazepines, 1,3-diazepinones, and 2,4-diazabicyclo[3.2.0]heptenes.

Tetrazolo[1,5-a]pyridines/2-azidopyridines 1 undergo photochemical nitrogen elimination and ring expansion to 1,3-diazacyclohepta-1,2,4,6-tetraenes 3, which react with alcohols to afford 2-alkoxy-1H-1,3-diazepines 4 (5), with secondary amines to 2-dialkylamino-5H-1,3-diazepines 16, sometimes via isolable 2-dialkylamino-1H-1,3-diazepines 15, and with water to 1,3-diazepin-2-ones 19. The latter are also obtained by elimination of isobutene or propene from 2-tert-butoxy- or 2-isopropoxy-1H-1,3-diazepines 4 or 5. 1,3-Diazepin-2-one 22B and 1,3-diazepin-4-one 24 were obtained from hydrolysis of the corresponding 4-chlorodiazepines. Diazepinones 19 undergo photochemical ring closure to diazabicycloheptenones 25 in high yields. The 2-alkoxy-1H-1,3-diazepines 4 and 5 interconvert by rapid proton exchange between positions N1 and N3. The free energies of activation for the proton exchange were measured by the Forsén-Hoffman method as DeltaG([double dagger])298= 16.2 +/- 0.6 kcal mol(-1) as an average for 4a-c in CD2Cl2, acetone-d6, and methanol-d4, and 14.1 +/- 0.6 kcal mol(-1) for in 4c acetone/D2O. The structures of 2-methoxy-5,6-bis(trifluoromethyl)-1H-1,3-diazepine 4k, 1,2-dihydro-4-diethylamino-5H-1,3-diazepin-2-one 22bB, and diazabicycloheptanone were 26 determined by X-ray crystallography. The former represents the first reported X-ray crystal structure of any monocyclic N-unsubstituted 1H-azepine.

Journal Article↗
PubMed2004

[Acute psychiatric day hospital treatment: is the effectiveness of this treatment approach still questionable?].

OBJECTIVE: Currently, there is still a severe lack of methodologically sound empirical studies on acute psychiatric day hospital treatment in German-speaking countries that analyse the effectiveness of this increasingly important mode of service provision. METHODS: Within a randomised controlled study design implemented at the Department of Psychiatry and Psychotherapy, Dresden University of Technology, 99 general psychiatric patients received conventional inpatient treatment and 92 patients received acute day hospital treatment. At up to four time-points during the index-treatment episode patients were assessed at different levels of outcome: Psychopathology was rated by researchers using the Brief Psychiatric Rating Scale (24-Item-Version), and patients evaluated their satisfaction with treatment (Patientenbogen zur Behandlungszufriedenheit); at admission and discharge patients also assessed their subjective quality of life (Manchester Assessment of Quality of Life). Mean scale scores of these instruments are used for the intention-to-treat-analysis. Discharge status on these scales as well as mean ratings on these scales within the index-treatment episode serve as measures of effectiveness. For statistically identifying differences between the two settings five linear (co-)variance-analytical models were calculated for each target variable. Four models were adjusted to baseline-rating or to the individual period spent in treatment. RESULTS: Initially, both groups did not differ in their relevant socio-demographic and illness-related features. Day hospital treatment (87,7 days) lasted significantly longer than inpatient treatment (67,8 days). Only results from an unadjusted statistical model as well as from a model adjusted to the individual period of index-hospitalisation demonstrated superior effectiveness of day hospital treatment on the discharge status of psychopathological symptomatology. However, in all statistical models there were no systematic differences of treatment-effectiveness related to satisfaction with treatment and subjective quality of life. CONCLUSION: For the first time in German-speaking countries, this study provides evidence for the effectiveness of acute day hospital treatment as compared to conventional inpatient treatment. If detailed eligibility criteria for patients are used as defined here, approximately 30 % of the general psychiatric patients in need of acute hospital-based treatment may be cared for in this special mode of day hospital service provision.

Acute Disease↗
PubMed2004

Which conditions contributing to the Charlson score predict survival after radical prostatectomy?

PURPOSE: The Charlson score is likely to be the most frequently used comorbidity measure in prostate cancer. However, to our knowledge the individual prognostic significance of contributing conditions has not been previously studied in a radical prostatectomy sample. MATERIALS AND METHODS: A total of 444 consecutive patients were entered into this study. The 19 conditions contributing to the Charlson score were obtained from the preoperative cardiopulmonary risk assessment and the hospital discharge document. Mantel-Haenszel hazard ratios were estimated for comorbid (noncancer) and overall survival. Thereafter, the Charlson score was refined by excluding conditions with low predictive value. RESULTS: Mean followup was 5.9 years. Only 3 single conditions (congestive heart failure, peripheral vascular disease and severe renal disease) were significantly associated with excess overall mortality. Concerning comorbid mortality, in addition to these 3 diseases, chronic pulmonary disease was associated with increased risk. Refinement of the Charlson score improved the circumscription of patients at risk for premature death after radical prostatectomy. CONCLUSIONS: This study suggests that restricting the Charlson score to some clinically meaningful diseases may increase its usefulness in candidates for radical prostatectomy. The conventional Charlson score did not add clinically meaningful information supplementary to congestive heart failure, which is the most important single contributing condition.

Aged↗
PubMed2004

A sensitive model for prediction of relapse in adult acute myeloid leukaemia with t(8;21) using white blood cell count, CD56 and MDR1 gene expression at diagnosis.

Acute myeloid leukaemia (AML) carrying t(8;21) has an overall favourable prognosis. However, relapse occurs and the impact of multidrug resistance gene (MDR1) expression on recurring disease in this group of patients is not known. We determined quantifiable MDR1 expression in the bone marrow of 28 AML patients with t(8;21) by a validated real-time polymerase chain reaction assay. Using MDR1 expression, white blood cell count and CD56 expression at diagnosis we observed complete concordance of predicted and observed relapses. A calculated logit out of these three variables was a strong independent prognostic factor for overall (P = 0.007) and disease-free survival (P = 0.002).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Ketene-acetylene [2 + 2] cycloadditions: cyclobutenone and/or oxete formation?

The [2 + 2] cycloaddition of monosubstituted acetylenes to ketene has been studied by ab initio(G2(MP2,SVP) and DFT (B3LYP/6-31Gd)) methods. The activation barrier decreases with increasing electron-donating ability of the acetylene substituent, and it can be roughly correlated with the energy of the acetylene HOMO. The addition to the C[double bond, length as m-dash]C bond of ketene (giving cyclobutenones) is preferred for the less electron-rich acetylenes, but for the most electron rich ones (X = NH(2) and NMe(2)) the addition to the C[double bond, length as m-dash]O bond (giving oxetes) becomes competitive, with activation barriers as low as ca. 45 (30) kJ mol(-1) for the two computational methods used. The cyclobutenones and oxetes can undergo ring opening to vinylketenes and acylallenes, respectively. Furthermore, the latter two compounds can interconvert by a 1,3-shift of the substituent X. The acylallenes become thermodynamically more stable than the vinylketenes for [small pi]-(lone pair) donating substituents X, and the 1,3-shift barrier also decreases, to ca. 130 kJ mol(-1) for X = NMe(2). In contrast, the 1,3-shifts of CH(3) and H have very high barriers.

Journal Article↗
PubMed2003

Neuro-Oncology Working Group 01 trial of nimustine plus teniposide versus nimustine plus cytarabine chemotherapy in addition to involved-field radiotherapy in the first-line treatment of malignant glioma.

PURPOSE: The role of chemotherapy in the primary treatment of malignant glioma remains controversial. The results from the German-Austrian Glioma trial (GAG, 1983 to 1988) demonstrated a survival benefit for chemotherapy using carmustine (BCNU) plus teniposide (VM26) over BCNU alone in addition to radiotherapy in patients with a Karnofsky performance score (KPS) more than 60. The Neuro-Oncology Working Group (NOA) of the German Cancer Society therefore compared the efficacy of nimustine (ACNU) plus VM26 and ACNU plus cytarabine (Ara-C) chemotherapy in addition to standard radiotherapy in patients with newly diagnosed malignant glioma. PATIENTS AND METHODS: From 1994 to 2000, 375 patients were randomly assigned to receive radiotherapy and cycles of ACNU 90 mg/m2 intravenously (IV) on day 1 and VM26 60 mg/m2 IV on days 1 to 3 (n = 183), or ACNU 90 mg/m2 IV on day 1 and Ara-C 120 mg/m2 IV on days 1 to 3 (n = 179), in 6-week intervals. Thirteen patients were not eligible after central neuropathology review. The remaining 362 patients had glioblastoma (n = 301) or anaplastic glioma (n = 61). RESULTS: Median survival and 2-year survival rates were 17.3 months and 25% for ACNU plus VM26, and 15.7 months and 29% for ACNU plus Ara-C in glioblastoma, and 60 months and 88% for ACNU plus VM26 and 62.5 months and 72% for ACNU plus Ara-C in anaplastic glioma. Multivariate analysis revealed no survival advantage for either arm or for subpopulations defined by histology, age, or KPS. Hematologic toxicity was more prominent in the ACNU plus Ara-C arm. CONCLUSION: The median survival times and 2-year survival rates for patients with anaplastic glioma and glioblastoma achieved in the NOA-01 trial compare favorably with historical trials and with the Radiation Therapy Oncology Group database. The toxicity profile favors ACNU plus VM26 for further evaluation.

Adolescent↗
PubMed2003

[Follicle centre lymphoma: treatment results for stage I and II].

PURPOSE: Radiotherapy is a curative treatment modality in the early stages of follicle centre lymphoma. Survival rates, patterns of failure and prognostic factors were evaluated in a retrospective analysis. PATIENTS AND METHODS: 116 patients with follicle centre lymphoma stage I and II were treated between 1970 and 1999 in Dresden. Therapy modalities were radiotherapy alone (103 patients) or combined radiotherapy/chemotherapy (13 patients). Radiotherapy was applied as involved-field-(IFI)- (104 patients), extended-field- (nine patients) or total-nodal- (three patients) irradiation. Patients received doses between 25 Gy and 50 Gy (median 35 Gy). RESULTS: The 5- and 10-year actuarial overall survival rates were 76% and 51%. Relapse free survival was 62% and 48% respectively. The median follow-up was 4,0 years. Relapses after complete remission were registered in 44 cases. Six patients have had in-field-recurrences. The majority of out-field-recurrences were nodal relapses (50%). 11% of relapses occurred outside of lymph nodes or were disseminated failures (18%). Significant favorable prognostic factors identified by multivariate and univariate analysis were low age (age < 50 years vs. age > 50 years), low stage and performance of bipedal lymphangiography as primary staging procedure. CONCLUSIONS: Radiotherapy is an effective and tolerable treatment modality for follicle centre lymphoma in the early stages I and II. We registered a high proportion of nodal recurrences, which may be minimized by prophylactic extended radiotherapy.

Age Factors↗
PubMed2003

Time course of the effect of a bolus dose of intrathecal baclofen on severe cerebral spasticity.

Continuous intrathecal administration of baclofen with implanted programmable pump systems is recommended in the treatment of severe spasticity of cerebral origin. Prior to pump implantation, a baclofen bolus test (BBT) is used to assess the effectiveness of intrathecal baclofen using clinical scales such as the Modified Ashworth Scale (MAS). In the literature, the time and period of maximum effect of a bolus dose of intrathecally administered baclofen in patients with cerebral spasticity is variously reported. The aim of the study was, therefore, to reveal the time course of the effect of a BBT on severe cerebral spasticity by the use of a recently described spasticity measurement method. Spasticity in knee joints of 13 patients with severe cerebral spasticity was repeatedly assessed using the MAS and also continuously recorded by the measurement of force under circular fibreglass casts. Force was recorded as nettorque by multiplying the force by the distance between sensor and joint axis, thus allowing inter-individual comparison. Half-hour time integrals (TI) of net-torque were determined 9 hours before and 22 hours after intrathecal baclofen administration. Post-BBT half-hour time integrals (TI(+0), TI(+0.5), to TI(+22)) were compared with the mean of 17 pre-BBT half-hour time integrals. Significantly lower post-BBT half-hour time integrals compared with were found between TI(+2) and TI(+8) (Dunnett adjusted p < 0.05). The median lowest TI after BBT of the 13 patients was TI(+4). The lowest mean MAS scores were found 4 hours after BBT. The findings suggest that the greatest effect of BBT on cerebral spasticity occurs between 2 and 8.5 hours, with a maximal effect at 4 hours after intrathecal baclofen injection. Clinical scales used to determine the effect of BBT should thus be carried out during this period-ideally at 4 hours after baclofen injection.

Adult↗
PubMed2003

Preoperative cardiopulmonary risk assessment as predictor of early noncancer and overall mortality after radical prostatectomy.

OBJECTIVES: To evaluate the capability of the preoperative cardiopulmonary risk assessment to predict early noncancer and overall mortality after radical prostatectomy for clinically localized prostate cancer. METHODS: In 444 consecutive radical prostatectomy patients, the American Society of Anesthesiologists Physical Status classification and the presence of cardiac insufficiency (New York Heart Association classification), angina pectoris (Canadian Cardiovascular Society classification), diabetes, hypertension, history of thromboembolism, and chronic obstructive or restrictive pulmonary disease were assessed. Kaplan-Meier time-event curves and Mantel-Haenszel hazard ratios were estimated for noncancer (other deaths were censored) and overall mortality. Cox proportional hazard models were used to analyze possible combined effects of risk factors. RESULTS: During an average follow-up of 4.7 years, 36 patients died: 15 of noncancer causes, 14 of prostate cancer, 6 of other cancers, and 1 in a car accident. The comorbidity scores for American Society of Anesthesiologists Physical Status classification, New York Heart Association classification, and Canadian Cardiovascular Society classification and combinations between the latter two scores were significantly associated with early noncancer mortality in a dose-response pattern. Furthermore, patients with chronic obstructive pulmonary disease were at increased risk. The association with overall mortality was less strong. CONCLUSIONS: The preoperative cardiopulmonary risk assessment may be used as a predictor of early noncancer and overall mortality after radical prostatectomy and should be evaluated further as a source of prognostic information in surgical oncology.

Aged↗
PubMed2003

Comparison of the American Society of Anesthesiologists Physical Status classification with the Charlson score as predictors of survival after radical prostatectomy.

OBJECTIVES: To compare the American Society of Anesthesiologists Physical Status (ASA) classification with the Charlson score in the radical prostatectomy setting. The ASA classification is a widely accepted way to evaluate perioperative risk. At present, the Charlson score is probably the most frequently used comorbidity measure to predict long-term survival after radical prostatectomy. METHODS: A total of 444 consecutive patients were enrolled in this study. The ASA classification was obtained from the anesthesia chart, and the Charlson score was assigned based on conditions noted during the preoperative cardiopulmonary risk assessment or mentioned on the discharge document. Kaplan-Meier time-event curves and Mantel-Haenszel hazard ratios were estimated for comorbid (noncancer) and overall survival. RESULTS: After a mean follow-up of 5.9 years, both classifications were able to predict comorbid and overall survival in dose-response patterns. The ASA classification was superior in terms of a clearer discrimination of the survival curves (lower P values, higher hazard ratios). Both classifications identified a high-risk group (ASA 3 and Charlson score 2 or more), but only the ASA classification sufficiently defined a low-risk group (ASA 1). CONCLUSIONS: In experienced hands, the ASA classification is a promising tool to improve the classification of prognostic comorbidity in the radical prostatectomy setting and may be used as an alternative to the Charlson score.

Adenocarcinoma↗