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C Kastner

Publications and source records attributed to C Kastner.

12 recordsLinked to original sources
PubMed2006

The Charlson comorbidity score: a superior comorbidity assessment tool for the prostate cancer multidisciplinary meeting.

INTRODUCTION: Multidisciplinary team (MDT) meetings use precise prognostic factors to select treatment options for patients with prostate cancer. Comorbidity is judged subjectively. Recent publications favour the Charlson comorbidity score (CS) for the use in the management of prostate cancer. We assess the feasibility of using the CS by our MDT in planning the treatment of patients with prostate cancer. PATIENTS AND METHODS: Patients from the histopathology database aged less than 75 years and with a diagnosis of localized prostate cancer between 1993 and 1995 were included in a notes audit. A second group consisted of patients recommended for curative treatment for localized prostate cancer by the local MDT in 2004. Data on comorbidity, prostatic malignancy and survival up to 10 years was collected. The prognostic accuracy of the CS was assessed for those patients offered radical treatment between 1993 and 1995. RESULTS: Of 1043 patients initially assessed, 37 patients with localized prostate cancer were identified. Using Cox regression, we found the CS to be a statistically significant predictor of survival, following radical treatment for localized prostate cancer (P=0.005). Current practice in 2004 (56 patients) shows a mean (range) Charlson probability of 10-year survival for radical prostatectomy of 0.823 (0.592-0.923) and for radical radiotherapy of 0.653 (0.07-0.936). CONCLUSIONS: Our results support the findings of recent research. We also found the CS easy to calculate and therefore feasible to use in our MDT setting. We propose the introduction of the Charlson score by prostate cancer MDTs to assess age and comorbidity.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Measurement of immunoglobulins in seminal fluid with modified nephelometry--an alternative diagnostic tool for chronic prostatitis.

The objectives of the study were to investigate the feasibility of the modified nephelometry technique to measure immunoglobulin G and A in seminal fluid and to evaluate their use in diagnosis and follow-up of chronic prostatitis.IgG and A in seminal fluid of healthy individuals (HI) and chronic prostatitis patients (CP) were measured with modified nephelometry. The literature values were confirmed. IgG reflects the long-term healing process of chronic prostatitis. IgA was significantly increased in patients with exacerbation of the disease. Nephelometry proves to be a reliable and inexpensive test to obtain IgG and IgA in seminal fluid. IgG and IgA are useful as objective parameters to confirm subjective symptom scores in a chronic prostatitis research setting.

Adult↗
PubMed2003

Improving the effectiveness of the emergency management of renal colic in a district general hospital: a completed audit cycle.

OBJECTIVES: To assess the current practice of emergency management of renal colic in a district hospital, review literature, implement new guidelines, and assess them. METHODS: Data were collected about the use of analgesia, waiting time for intravenous urography (IVU), and admission status of patients presenting to the hospital with symptoms of renal colic over the period of three months. A literature search into the use of analgesia, imaging, and treatment was performed. Members of the involved departments were consulted and new guidelines developed and implemented. This was followed by further data collection over three months. RESULTS: Seven of 14 patients were admitted. Five to wait for their IVU. Their average waiting time was 12.3 (SD 2.2) hours. Mainly intramuscular opioid analgesia was used. Literature recommended the use of diclofenac. Although computed tomography was favoured it was decided to continue to use IVU because of circumstances within the hospital. The literature recommended a cut off between conservative and surgical treatment at a calculus size of >4 mm. Existing policies of the relevant departments were obeyed and a training system for the junior doctors was introduced. Emergency department staff were encouraged to perform 3-film IVUs. After this, of 5 of 19 patients were admitted, only one of those to wait for an IVU. The average waiting time for an IVU was 4.1 (SD 0.96) hours. Rectal diclofenac was noted to be the drug of choice. CONCLUSION: Coordination of efforts, interdepartmental communication, and a practical application of available literature has resulted in a significant improvement of effectiveness without affecting medical standards, workload, or resources. Accident and emergency senior house officers felt highly satisfied at being able to complete management from presentation to diagnosis and treatment. Interdisciplinary communication has to be continued to maintain smooth operation of the guidelines.

Analgesics, Opioid↗
PubMed2000

Familial associations of lipid profiles: a generalized estimating equations approach.

Elevated plasma levels of apolipoproteins A1 (apoA1) and B (apoB) are important protective factors and risk factors, respectively, for atherosclerosis and coronary heart disease. It is well known that both apoA1 and apoB reveal strong familial aggregation. Our goal was to investigate whether exogenous variables influence these associations. We used marginal regression models for the mean and association structure (generalized estimating equations 2; GEE2) to analyse data from 1435 family members within 469 families of different sizes included in the Donolo-Tel Aviv Three-Generation Offspring Study. The usual robust variance matrix was approximated by extensions of jack-knife estimators of variance to GEE2 models. Estimation of standard errors in models with quite complex correlation structures was possible using this approach. All analyses were easily carried out using a menu-driven stand-alone software tool for marginal regression modelling. We demonstrate that a variety of hypotheses can be tested using Wald statistics by modelling regression matrices for the association structure. We show that correlation for apoB between parent-offspring pairs increased with decreasing age difference and that pairs with individuals of the same gender had more similar apoA1 levels than individuals of different gender. Associations between different relative pairs did not all agree with those expected from differences in kinship coefficients. The analysis using GEE2 models revealed structures that would not have been detected by other models and should therefore be used in addition to traditional approaches of analysing family data. GEE2 should be considered a standard method for the investigation of familial aggregation.

Apolipoproteins A↗
PubMed2000

Fibrin specificity and procoagulant effect related to the kallikrein-contact phase system and to plasmin generation with double-bolus reteplase and front-loaded alteplase thrombolysis in acute myocardial infarction.

This study was undertaken to compare the effects of reteplase and alteplase regimens on hemostasis and fibrinolysis in acute myocardial infarction (AMI). Thrombolytic treatment in patients with AMI is hampered by paradoxical procoagulant effects that favor early reocclusion. In vivo data comparing this effect and the fibrin specificity of double-bolus reteplase and front-loaded alteplase regimens are not available. In a prospective, randomized study, 50 patients with AMI were either treated with double bolus (10 + 10 U) reteplase or with front-loaded alteplase (up to 100 mg) within 6 hours of symptom onset. Thirty apparently healthy persons served as controls. Molecular markers of coagulation and fibrinolysis were serially examined for up to 5 days. Paradoxical thrombin activation at 3 hours after initiation of therapy was comparable between reteplase and alteplase. Reteplase (65 +/- 5 U/L) and alteplase (72 +/- 8 U/L) caused significantly elevated kallikrein activity at 3 hours after adminstration (p <0.01 vs controls 30 +/- 1 U/L). Fibrin specificity was less for reteplase (p <0.05) with a decrease in fibrinogen at 3 hours to 122 +/- 27 mg/dl versus 224 +/- 28 mg/dl for alteplase (p <0.01 and p <0.05 vs controls). D-Dimer levels at 3 hours were higher (p <0.05) after reteplase (5,459 +/- 611 ng/ml) versus alteplase (3,445 +/- 679 ng/ml) (both p <0.01 vs controls 243 +/- 17 ng/ml). Plasmin generation (plasmin-antiplasmin complexes) was significantly (p <0.01) increased at 3 hours with both regimens to 27,079 +/- 3,964 microg/L (reteplase) and 19,522 +/- 2,381 microg/L (alteplase). The data from 3 hours after start of thrombolytic therapy proved less marked fibrin specificity of the reteplase regimen (in vivo) compared with front-loaded alteplase. Both regimens have a moderate procoagulant effect without differences in activation of the kallikrein system.

Adult↗
PubMed1999

Significant evidence for linkage of a simulated trait to D1G024--a conclusion reached using multiallelic transmission/disequilibrium tests.

We applied three versions of the transmission/disequilibrium test (TDT) for detecting linkage in nuclear families using the a priori information of possibly present association. For our analyses we employed all marker data for a simulated trait. Results for replicate 11 showed significant linkage to D1G024 using the multiallelic Tmhet statistic and the extended TDT. The TDT for the most frequent parental allele which had been applied successfully in previous studies failed to detect linkage. This result may have happened because the data did not arise from a realistic simulation of the evolution of a real population, where mutations might be expected to occur against a specific haplotype. Simulation studies are required to elucidate the applicability of the TDT for the most frequent parental allele in realistic situations. Furthermore, guidelines have to be developed for how to pool categories in large, sparse contingency tables to obtain larger cell frequencies and lower degrees of freedom.

Alleles↗
PubMed1998

Thrombolytic therapy in acute myocardial infarction: comparison of procoagulant effects of streptokinase and alteplase regimens with focus on the kallikrein system and plasmin.

BACKGROUND: Thrombolytic therapy in patients with acute myocardial infarction (AMI) is hampered by procoagulant effects. In vitro studies have indicated that plasmin stimulation activates the kallikrein-contact-phase system, resulting in thrombin activation. This prospective comparative study was designed to examine the procoagulant effects of streptokinase or alteplase in AMI. METHODS AND RESULTS: Sixty-one patients with AMI received 1.5 million U of streptokinase or front-loaded alteplase (up to 100 mg) and systemic heparin. Twenty-four patients with AMI and no thrombolytic therapy and 30 control subjects were examined for comparison. Molecular markers of thrombin, plasmin activation, and coagulation activities were determined before therapy and serially for up to 10 days. Moderate thrombin (initial thrombin-antithrombin [TAT] complex 18+/-5 versus 4+/-0.3 microg/L, P<0.05) and kallikrein (up to 45+/-4 versus 30+/-1 U/L at 3 hours, P<0.01) activation occurs in patients with AMI. D-Dimers are increased (P<0.01), and plasmin is stimulated (P<0.01). Streptokinase and alteplase increase TAT to 50+/-17 and 51+/-18 microg/L at 3 hours and to 50+/-17 and 33+/-14 microg/L at 6 hours, respectively (P<0.01). Kallikrein activity is elevated (P<0. 01) to 76+/-5 and 71+/-7 U/L at 3 hours and 64+/-6 and 47+/-5 U/L by streptokinase and alteplase, respectively, at 6 hours. Reductions in fibrinogen and increases in D-dimers and plasmin-antiplasmin complexes are more marked (P<0.05 and 0.01) after streptokinase versus alteplase. Correlations were found among TAT, kallikrein activity, and plasmin activation (P<0.01). CONCLUSIONS: The data indicate a more marked procoagulant action of the streptokinase regimen compared with front-loaded alteplase, thus supporting the hypothesis of a plasmin-mediated kallikrein activation with consecutive procoagulant action in vivo.

Acute Disease↗
PubMed1998

Identifying influential families using regression diagnostics for generalized estimating equations.

The Generalized Estimating Equations (GEE) is an approach to analyze correlated data. It is applied here to data from an epidemiological study of oesophageal cancer in a high incidence area in China to investigate familial aggregation. Regression diagnostics for mean structures and association structures are used to identify families that influence estimates of these structures. It is shown that most of the families influencing the mean structure have a low age of disease onset in common. Most families identified by regression diagnostics for the association structure influence the parent correlation. It is concluded that regression diagnostic techniques can be used to identify clusters influencing mean and association structures of the models.

China↗
PubMed1994

Relationship between multiple biologic effects of rapamycin and the inhibition of pp70S6 protein kinase activity. Analysis in mutant clones of a T cell lymphoma.

Rapamycin (RAP) inhibits several biologic responses in the YAC-1 T cell lymphoma, including the serum-driven proliferation and cyclin A mRNA expression, the induction of Ly-6E Ag expression by IFN, and the induction of IFN-gamma production by IL-1. RAP also suppresses the enzymatic activity of the 70 kDa S6 protein kinase (pp70s6k). To define the mechanistic relationship between these multiple effects of RAP, we have generated stable somatic mutants with altered sensitivities to this drug. A first series of mutants, represented by the R19, 4R16, and 10R13 clones, showed markedly reduced sensitivity to the inhibitory effect of RAP on all biologic responses tested and on pp70s6k activity. Two other mutant types, R103 and R125, were both highly sensitive to RAP-mediated suppression of proliferation, of IL-1-induced IFN-gamma production, and of pp70s6k activity but differed in their Ly-6E response. This response was not affected by RAP in the R125 clone and was enhanced in the R103 clone. Therefore, the inhibitory effects of RAP on proliferation and IL-1-mediated IFN-gamma induction both appear associated with the inhibition of pp70s6k activity, whereas the modulation of Ly-6E induction is independent from the latter. Moreover, the cellular binding of [3H]dihydro-FK-506 was found to be blocked by RAP in all mutant types to the same extent as in wild-type YAC-1 cells, suggesting that the altered sensitivity to the effects of RAP in these mutants is not due to an inability of the drug to enter the cells or to interact with FKBP. Further biochemical characterization of the mutant cells described here is expected to help clarify the mechanisms of RAP action.

Animals↗
PubMed1994

Quantitative and temporal analysis of the cellular interaction of FK-506 and rapamycin in T-lymphocytes.

The structurally related immunosuppressive macrolides FK-506 and rapamycin (RAP) exert distinct biological effects: inhibition of interleukin-2 production and inhibition of interleukin-2-induced proliferation, respectively, through binding to intracellular receptors, termed FKBPs. Although the interaction of these drugs with purified FKBPs in vitro has been well characterized, little is known about their interaction with FKBPs in living cells. Here, we used [3H]-dihydro-FK-506 as a probe to examine the binding of these macrolides in both normal mouse splenic T-cells and the human Jurkat T-cell lymphoma. These cells were found to accumulate the radioligand, predominantly in the cytosol, to a saturable level corresponding to an estimated concentration of 6 to 7 microM. Half-maximal suppression of T-cell activation was shown to require radioligand occupancy of only 3 to 5% of the pool of available intracellular binding sites (FKBPs). Moreover, the binding and immunosuppressive effect of the radioligand could not be removed by extensive washing and remained stable for at least 6 hr upon incubation of the cells at 37 degrees C. However, a molar excess of either FK-506 or RAP was found to rapidly displace [3H]-dihydro-FK-506 from its cellular binding sites. Consistently, FK-506 and RAP were able to antagonize mutually their immunosuppressive activities even when added several hr after each other to T-cell cultures. We took advantage of the reciprocal antagonism of FK-506 and RAP to define their apparent affinities for the functionally relevant cellular receptors by Schild analysis. This indicated that the drugs compete for a single cellular receptor with similar KdS and, therefore, may mediate their immunosuppressive action upon interaction with similar or highly related FKBPs.

Animals↗