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Biomedical subjects

G Hommel

Publications and source records attributed to G Hommel.

At least 19 recordsLinked to original sources

Blood coagulation and thrombosis in patients with ovarian malignancy.

Ovarian cancer cells appear to be capable of both thrombin formation and induction of fibrin degradation which may be essential prerequisites for the development of deep vein thrombosis (DVT) as well as the spread of malignancy. To study further this coagulation-cancer interaction in 60 patients with untreated ovarian cancer of FIGO stage I-IV the incidence of DVT was recorded pre-operatively, post-operatively on day 1, 3, 5, 7, 10, before each of six cycles of Cisplatinum/ Epirubicin/Cyclophosphamide chemotherapy, during follow-up and in the post-operative period of second look surgery. In addition, blood coagulation tests results were determined prospectively. Two patients were excluded from these calculations due to previous DVT 5 to 6 weeks before the diagnosis of ovarian cancer but all patients were eligible for surgery and randomized to receive either daily low molecular weight heparin (LMWH) (n = 28) or unfractionated heparin (UFH) (n = 32) for perioperative thrombosis prophylaxis until the 7th post-operative day. According to the FIGO stage, patients were equally distributed in the 2 heparin treatment groups. The predictive value of pre-operative coagulation test results, clinical parameters, and type of heparin used were tested in univariate and multivariate analysis for development of post-operative DVT and overall patients survival. Impedance plethysmography for DVT screening was used. The presence of DVT was then confirmed by phlebography. Only D-dimer and fibrinogen levels were correlated significantly with the FIGO stage while antithrombin, protein C, and plasminogen activator inhibitor activity were not. The incidence of DVT was 6.7% (4/60) up to the 7th and 8.3% (5/60) between the 8th and 29th post-operative day. DVT occurred in 10.6% (5/47) during chemotherapy. Pre-operative coagulation test results, the type of heparin used, and clinical parameters were not significant risk factors for post-operative DVT development in univariate analysis. The D-dimer and fibrinogen levels were significant risk factors for reduced overall survival in univariate analysis but only the FIGO stage was an independent predictor (in multivariate analysis). After a median follow up of 26.5 months (min. 8 months, max. 41 months), 21.4% of LMWH treated and 37.5% of UFH-treated patients died of cancer (p = 0.26). Pre-operative test results were neither predictive for DVT nor the outcome of cancer but patients showed an improved though not statistically significant overall survival after LMWH treatment.

Aged

Prognostic value of E-cadherin expression in 413 gastric carcinomas.

E-cadherin is a Ca(2+)-dependent intercellular adhesion molecule known to exert an invasion-suppressor function. In the present study, E-cadherin expression was immunohistochemically investigated in a retrospective series of 413 RO-resected gastric carcinomas using the monoclonal antibody (MAb) 5H9. Of these cases, 108 tumors revealed a preserved E-cadherin expression similar to that of normal gastric mucosa. In 95 tumors, E-cadherin expression was moderately reduced and in 86 tumors highly reduced. In 124 tumors, no or only a very weak dotted expression could be detected. There was a significant correlation between the degree of E-cadherin expression and the grade of tumor differentiation, as well as with histological type according to the Laurén and the WHO classifications. In contrast, no correlation could be demonstrated between E-cadherin expression and the prognostic parameters depth of invasion, lymph node involvement and vascular invasion. As shown by univariate Cox regression analysis, patients with E-cadherin-positive tumors had significantly better 3-and 5-year survival rates than patients with E-cadherin-negative tumors. This prognostic impact remained present in a multivariate Cox regression analysis, including the prognostic parameters pT category, pN category and vascular invasion.

Adult

Immunohistochemical study on the prognostic value of MIB-1 in gastric carcinoma.

The prognostic significance of tumour cell proliferation was investigated in a series of 418 gastric carcinomas using the monoclonal antibody MIB-1. Owing to strong intratumoural heterogeneity of MIB-1 expression three different proliferation indices (PIs) were determined in all carcinomas: (1) PImax in areas of maximal tumour cell proliferation, (2) PIrand in areas randomly distributed over the whole tumour. (3) PIfront in areas exclusively located at the tumour invasion front. There was a strong intertumoral heterogeneity with PImax ranging from 4.9% to 92.2%, PIrand ranging from 3.4% to 81.4% and PIfront ranging from 4.2% to 87.1%. The mean values were 51.3% +/- 19.7 for PImax, 34.2% +/- 18.3 for PIrand and 37.2% +/- 19.5 for PIfront. Whereas no statistically significant correlation could be found between proliferative activity and the clinicopathological parameters depth of invasion, lymph node involvement or grade of tumour differentiation, there was a positive correlation between a high proliferation index at the tumour invasion front (PIfront) and the presence of blood or lymphatic vessel invasion. No significant correlation could be demonstrated between the different proliferation indices and survival, even when different subgroups of patients were analysed separately. The present results suggest that the immunohistochemical evaluation of the proliferation activity has no predictive value for the prognosis of gastric cancer patients or the identification of subgroups of patients who may be at higher risk.

Adult

Randomized trial of intravenous immunoglobulins versus prednisolone in Graves' ophthalmopathy.

Glucocorticoids are usually given for management of Graves' ophthalmopathy (GO), but they may cause side effects. By comparison, intravenous administration of immunoglobulins resulted in clinical improvement and decreased antibody titres in a large number of autoimmune diseases. Therefore, a randomized trial was done, in which 19 patients with active GO were treated with a 20-week course of oral prednisolone (P, starting dose 100 mg/day), and 21 received 1 g immunoglobulin/kg body weight for 2 consecutive days every 3 weeks. The immunoglobulin course was repeated six times. Before and at the end (20 weeks) of immunomodulating therapy, ophthalmological investigation and quantitative magnetic resonance (MR) imaging were performed. A successful outcome was observed in 12 (63%) P- and in 13 (62%) immunoglobulin-treated patients. Overall, there were no marked differences in degree of improvement between the two groups. Responders to treatment in both groups showed improvements in proptosis (median from 24.5 to 21.5 mm; P < 0.005), visual acuity (from 0.6 to 0.85; P < 0.001), intraocular pressure (from 25 to 20 mmHg; P < 0.0001), lid aperture (from 14 to 12 mm: P < 0.01) and a decrease in eye muscle area (inferior, from 44 to 33 mm2; medial, from 43 to 34 mm2; both P < 0.0005). Among the immunoglobulin-treated patients, there was a marked decrease of thyroid antibody titres. Side effects were more frequent and severe during P than during immunoglobulin therapy. Thus, with respect to the above mentioned objective parameters, P and immunoglobulin appeared to be equally effective in treatment of active GO.

Administration, Oral

Blood coagulation during adjuvant epirubicin/cyclophosphamide chemotherapy in patients with primary operable breast cancer.

PURPOSE: Influences of adjuvant epirubicin/cyclophosphamide (EC) chemotherapy on blood coagulation were investigated in patients with operable breast cancer and the incidence of thromboembolic events was recorded. PATIENTS AND METHODS: In 50 consecutive node-positive breast cancer patients, serial coagulation studies (fibrinogen method of Clauss, antithrombin III, protein C amidolytic methods, D dimer enzyme-linked immunoadsorbent assay [ELISA] techniques, and plasminogen activator inhibitor [PAI] activity u-PA inhibition test) and impedance plethysmography (IPG) for screening of deep vein thrombosis (DVT) were performed preoperatively and postoperatively, before each of six cycles of adjuvant chemotherapy (60 mg/m2 epirubicin and 600 mg/m2 cyclophosphamide) and 3 months thereafter. Seventy-two healthy women served as controls. RESULTS: During chemotherapy, the phlebographically proven DVT incidence was 10% (n = 2 after second cycle; n = 3 after third cycle). Preoperative levels of D-dimer, fibrinogen, and the PAI activity were significantly higher than in healthy women and only mean levels of the D-dimer were significantly higher in patients with DVT compared with patients without DVT. Postoperatively, only D-dimer and fibrinogen levels significantly increased, while in the course of chemotherapy, these levels were significantly decreased. Mean D-dimer levels and PAI increased steadily in patients with DVT. Preoperatively and during chemotherapy, levels of antithrombin III and protein C were within the normal range. Only one patient with DVT had decreased protein C levels throughout chemotherapy. CONCLUSION: Monitoring with sophisticated coagulation tests during adjuvant EC chemotherapy for breast cancer does not identify patients at higher risk for DVT development. Preoperatively, in patients with later DVT, an imbalance of hemostasis is already present; thus, thrombosis might predominantly be initiated by malignancy-induced hypercoagulability and secondarily by the influence of EC chemotherapy. Prospective randomized trials must determine whether prophylactic anticoagulation during EC chemotherapy reduces the incidence of DVT.

Adult

The relationship of p53 expression to the prognosis of 418 patients with gastric carcinoma.

BACKGROUND: Mutations of the p53 gene belong to the most common genetic alterations in human cancer that have been implicated in tumorigenesis and tumor progression. Although p53 expression appears to be correlated with prognosis in patients with breast cancer and some other types of cancer, its prognostic role in gastric cancer is still uncertain. In the present study, therefore, the prognostic impact of p53 expression was evaluated in 418 patients with curatively resected gastric carcinomas without residual tumor (RO-resection). METHODS: Tumor sections of 418 RO-resected gastric carcinomas were stained with the monoclonal antibody DO-1 after microwave processing. p53 expression was statistically compared with clinico-pathologic features and postoperative survival. RESULTS: p53 expression was detected in 57.5% of all tumors, with strong inter- and intratumor heterogeneity. No immunoreactivity was observed in the normal mucosa adjacent to the tumor. Statistically, no significant correlation between p53 overexpression and depth of invasion, lymph node involvement, or grade of tumor differentiation was detected. The correlations with blood vessel invasion (P = 0.049) and lymphatic vessel invasion (P = 0.047) were of marginal significance. Survival analysis revealed no significant impact of p53 expression on survival, the 5-year survival rates were 40.6% +/- 7.8% for patients with p53 positive tumors and 49.2% +/- 8.9% for patients with p53 negative tumors (P = 0.43). Furthermore, no correlation with survival was found when four different levels of p53 expression were analyzed (P = 0.51). p53 expression had no influence on survival, in either the lymph node positive or negative groups. CONCLUSIONS: The data suggest that the immunohistochemical detection of p53 expression is at present not a predictor of outcome of patients with gastric cancer or to identify subgroups of patients who may be at higher risk.

Adult

A rapid algorithm and a computer program for multiple test procedures using logical structures of hypotheses.

It is demonstrated how improvements of general multiple test procedures can be obtained using information about the logical structures among the hypotheses. Based on a procedure of Bergmann and Hommel (B. Bergmann and G. Hommel, Improvements of general multiple test procedures for redundant systems of hypotheses, in Multiple Hypothesenprüfung--Multiple Hypotheses Testing, Eds. P. Bauer, G. Hommel and E. Sonnemann, pp. 100-115 (Springer-Verlag, Berlin, 1988)), a computer program was written by Bernhard (G. Bernhard, Computerunterstützte Durchführung von multiplen Testprozeduren--Algorithmen und Powervergleich, Doctoral thesis (Mainz, 1992)) using this information. It is applicable for a general class of systems of hypotheses which can be expressed in a linear way. By means of a simulation study it is shown that the proposed procedure is often substantially more powerful than other usual multiple test procedures.

Algorithms

Azathioprine combined with prednisolone or monotherapy with prednisolone in active Crohn's disease.

BACKGROUND: The role of azathioprine (AZA) in the treatment of active Crohn's disease (CD) is still controversial. This study examined whether AZA combined with standard prednisolone therapy improved the therapeutic outcome compared with monotherapy with prednisolone. METHODS: Forty-two patients with a Crohn's Disease Activity Index (CDAI) of > 150 were randomized into two groups. Both received 60 mg of prednisolone daily in a tapering regimen to a maintenance dose of 10 mg. In addition, group 1 received 2.5 mg AZA/kg body wt and group 2 received a placebo over the whole study period of 4 months. RESULTS: At the end of the trial, 16 of 21 patients (76%) in group 1 were in remission (CDAI < 150), compared with 8 of 21 (38%) in group 2 (P = 0.03). The CDAI in group 1 dropped from 290 +/- 97 (SD) to 72 +/- 84 and from 285 +/- 110 to 155 +/- 105 in group 2. The differences between activity indices in groups 1 and 2 became statistically significant after 8 weeks. The average prednisolone dose per day was 20.9 mg in group 1 and 26.7 mg in group 2 (P = 0.02). No major side effects were observed in this study. CONCLUSION: The combination of prednisolone and AZA was superior to the treatment with prednisolone alone in active CD. Patients receiving AZA showed remission more frequently, more quickly, and with lower doses of prednisolone.

Adolescent

Tumor-cell dissociation at the invasion front: a new prognostic parameter in gastric cancer patients.

Tumor-cell dissociation (TCD) is a well-known feature at the invasion front of malignant tumors, but little attention has so far been paid to its biological significance. Therefore, the aim of the present study was to score the degree of TCD at the invasion front (TCD 0-3) in a retrospective series of 445 gastric cancer patients and to compare its prognostic significance with the parameters T-stage, tumor size, grade of tumor differentiation, lymph-node involvement and vascular invasion. We could show that highly significant differences (p less than 0.0001, log-rank test) existed between the 5-year survival rates of patients with different degrees of TCD (TCD 0: 92.3%; TCD 1: 62.1%; TCD 2: 41.2%. TCD 3:38.5%) and that these differences were independent of T-stage 2, tumor size and grade of tumor differentiation. Univariate Cox regression analysis showed that in intestinal-type carcinomas, T-stage (Chi-square: 45.2) followed by blood vessel and lymphatic vessel invasion (Chi-square: 43.6 and 40.0) had the highest prognostic value, whereas TCD (Chi-square: 31.5) revealed a prognostic value quite similar to that of lymph-node involvement (Chi-square: 35.1). This prognostic relevance was still present in multivariate Cox regression analysis, showing that the determination of TCD provided an increase in prognostic information which significantly (P = 0.026) exceeded the information obtained by the combination of T-stage and lymph-node involvement. Our data suggest that TCD is a new prognostic parameter, especially in those gastric carcinomas in which lymph-node involvement or vascular invasion are not present.

Adult

[New histomorphologic prognostic parameters in stomach cancer. A uni- and multivariate analysis of 445 patients].

In a retrospective series of 445 gastric cancer patients, the prognostic significance of classical histological parameters such as T-category, tumor size, lymphnode involvement and tumor grading was compared with the prognostic value of vascular invasion and the degree of tumor cell dissociation (TCD) at the invasion front. As shown in a Cox regression analysis, T-category had the highest prognostic value. Nevertheless, vascular invasion and TCD proved to be independent new parameters in a multivariate analysis, exceeding the prognostic information obtained by the combination of T-category and lymph-node involvement. In contrast, tumor grading provided no significant information. The determination of TCD at the invasion front as well as a careful search for vascular invasion may therefore provide additional useful information for identifying those patients who are at high risk and who may be candidates for adjuvant therapy in future clinical trials.

Adult

Incidence and prognostic significance of vascular invasion in 529 gastric-cancer patients.

The prognostic significance of blood-vessel invasion (BVI) and lymphatic-vessel invasion (LVI) was evaluated in a retrospective series of 529 gastric-cancer patients who underwent potentially curative surgery. Evidence for BVI was found in 127 patients (24.0%), while LVI was demonstrated in 245 patients (46.3%). The incidence of both BVI and LVI run parallel to increasing tumor size and tumor stage as well as to decreasing grade of tumor differentiation. The incidence of BVI and LVI was higher in lymph-node-positive patients than in lymph-node-negative patients. The 5-year-survival rate was significantly lower (p less than 0.0001) in patients with BVI or LVI (14.9% and 22.2% respectively) than in patients without BVI or LVI (54.7% and 64.1% respectively). Both BVI and LVI were shown to be prognostic factors independent of tumor stage, grade of differentiation or lymph-node involvement. In a multivariate Cox regression analysis, the gain of prognostic information provided by the evidence of BVI and LVI was shown to exceed the information obtained by the combination of tumor stage, grade of differentiation and lymph-node involvement. A careful search for vascular invasion in gastric cancer may therefore provide additional useful information for identifying patients who are at high risk and who may be candidates for adjuvant therapy in future clinical trials.

Adult

Thyrotropin-releasing hormone has stimulatory effects on ventilation in humans.

Thyrotropin-releasing hormone (TRH) stimulates pituitary thyrotropin synthesis and release and also regulates autonomic nervous system functions by acting as a neuromodulator and neurotransmitter. In experimental animals a stimulation of ventilation by thyrotropin-releasing hormone was shown when applied at central nervous system sites that affect respiratory motor output. It was the goal of our study to investigate the respiratory properties of thyrotropin-releasing hormone on basal and stimulated (i.e. CO2-rebreathing) conditions following systemic thyrotropin-releasing hormone application in healthy humans. Thyrotropin-releasing hormone (200 micrograms, 400 micrograms intravenous) initiated a rapid short lasting rise of minute volume, ventilatory air-flow and alveolar oxygen tension under steady state breathing (P less than 0.001). Breathing frequency was less affected, heart rate rose concomitantly (P less than 0.001). While breathing with increasing concentrations of carbon dioxide, minute volume was higher under thyrotropin-releasing hormone than under placebo alone. Further effects (e.g. nausea, dizziness, palpitations) mostly appeared later than respiratory changes and thus may not be responsible for their initiation. Our findings prove systemic thyrotropin-releasing hormone to be a strong respiratory stimulant in man. Response in respiratory output was also accompanied by central nervous system-effects (e.g. dizziness, restlessness, augmented vigilance). The mode of thyrotropin-releasing hormone effects on respiration after peripheral administration is still speculative. An augmented sympathetic output or a direct receptor mediated action at central nervous system sites may be responsible, while a peripheral effect cannot be excluded.

Adolescent

Comparison of glycemic response and insulin requirements after mixed meals of equal carbohydrate content in healthy, type-1, and type-2 diabetic man.

The postprandial insulin requirements after three mixed meals of equal carbohydrate and energy content were assessed in 10 type-1 and 12 type-2 diabetics by a glucose-controlled insulin infusion system. These were compared with the glycemic response to the same meals of 10 healthy individuals (glycemic index). In type-1 diabetics, we found the highest insulin requirements after consumption of a continental breakfast (low fibre, low protein, high fat). Ten percent less insulin was infused after milk (low fat, high protein) and 30% less after an English breakfast (high fibre, high protein). Type-2 diabetics showed no significant differences in insulin requirements between the three test meals. The glycemic response in healthy individuals had no relation to these insulin requirements. Continental and English breakfast had a similar glycemic effect, whereas milk produced only 30% of the blood glucose response observed after the continental breakfast. These results indicate that neither the carbohydrate content (exchange lists) nor the glycemic index enable prediction of postprandial insulin requirements in insulin-deficient diabetes. For this purpose, we propose the insulin-need index, elaborated by testing whole meals in closed-loop experiments with type-1 diabetics.

Adult

Is the bile duct diameter a reliable parameter to diagnose extrahepatic cholestasis? Relationship between bile duct diameter and bile duct pressure.

The common bile duct (CBD) pressure was determined in 57 patients before endoscopic retrograde cholangiography (ERC) and related to the diameter of the CBD and the common hepatic duct (CHD). We found that despite a weak overall positive correlation in the individual patient, CBD or CHD diameters do not correlate with CBD pressure. In patients without extrahepatic cholestasis and normal CBD pressure, both CBD and CHD diameters were measured in a wide range between 5 and 32 mm. Extrahepatic cholestasis due to distal CBD obstruction is reflected by a high CBD pressure, but cannot be identified reliably by measuring the CBD diameter which is found within the range of patients not obstructed. In cholecystectomized patients, CBD and CHD are significantly (p less than 0.005) wider than in non-cholecystectomized patients (8.8 +/- 1.0 vs. 13.3 +/- 1.2 and 9.2 +/- 0.9 vs. 14.2 +/- 1.2 mm, respectively). The CBD pressure, however, is nearly identical in both groups. It is concluded that the assessment of CBD and CHD diameter is not a reliable parameter for the diagnosis of extrahepatic cholestasis which--in certain cases--could be proved by endoscopic retrograde manometry.

Cholangiography

Comparative column chromatographic estimations of phenylalanine in plasma, whole blood, native and paper-dried capillary blood of healthy children and adults, and patients with hyperphenylalaninaemia.

The concentration of phenylalanine in plasma, whole venous and capillary blood, and paper-dried blood of 75 probands (25 healthy adults, 27 healthy children, and 23 patients with hyperphenylalaninaemia) were measured by use of a sensitive short column chromatography method. The comparison of the values in each group of probands by several statistic methods showed an excellent correlation of the phenylalanine concentration in paper-dried whole blood to those measured in venous plasma. Evaluation of the analytical method revealed a high sensitivity and accuracy by use of a sample volume of 50 microliter. We would therefore suggest that the estimation of phenylalanine for the diagnosis and therapy control in hyperphenylalanine is as accurate in paper-dried blood as in venous plasma and would simplify sampling for the patients as well as enhance the diagnosis and therapy control in hyperphenylalaninaemia.

Adult