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Biomedical subjects

H Pelzer

Publications and source records attributed to H Pelzer.

At least 19 recordsLinked to original sources
PubMed1995

Induction chemotherapy followed by concomitant chemoradiotherapy for advanced head and neck cancer: impact on the natural history of the disease.

PURPOSE: To determine survival rates and the pattern of failure in head and neck cancer patients treated with induction chemotherapy, limited surgery and concomitant chemoradiotherapy. PATIENTS AND METHODS: Three cycles of induction chemotherapy with cisplatin, fluorouracil (5-FU), leucovorin, and interferon alfa-2b (PFL-IFN) were followed by optional surgery, and seven or eight cycles of 5-FU, hydroxyurea, and concurrent radiation for 5 days (FHX) for a total radiation dose of 65 to 75 Gy. Surgical resection was performed with the intent to spare organ function. RESULTS: Seventy-one patients were treated at three institutions. Sixty-five patients (91%) had stage IV disease with N2/3 in 46. Thirty-three patients (51%; 95% confidence interval, 39% to 63%) achieved a clinical complete response (CR) to PFL-IFN. Local therapy consisted of surgery in 37 and/or FHX in 55 patients. With a median follow-up duration of 37 months, there have been 20 recurrences (15 local, four distant, and one both local and distant), and 29 deaths, 15 in patients with disease progression and 14 not directly related to the primary tumor. Four patients have developed second malignancies. At 3 years, 69% (+/- 6%) are progression-free and the overall survival rate is 60% (+/- 6%). Toxicity of PFL-IFN included severe or life-threatening mucositis (54%) and myelosuppression (60%). Five patients died of toxicity. During FHX, 70% of patients had grade 3 or 4 mucositis. CONCLUSION: PFL-IFN is highly active, producing clinical CRs in 51% of patients, and, when followed by FHX, resulting in high local and distant control and overall survival rates. Second malignancies and intercurrent medical disease emerge as major risks to long-term survival. In view of the high toxicity and long treatment duration, further modifications of this approach are required.

Adolescent↗
PubMed1994

Multicentric evaluation of a new PT reagent based on recombinant human tissue factor and synthetic phospholipids.

A new PT reagent based on recombinant human tissue factor and synthetic phospholipids (phosphatidyl choline and phosphatidyl serine) with defined fatty acid side chains was calibrated against BCT/253 and CRM 149R. A small but consistent bias in the International Sensitivity Index (ISI) value was obtained using either the human or rabbit brain reference material. ISI values were around 1.0 or slightly lower depending on the respective instrument. Mixing studies with factor deficient plasmas showed a high factor sensitivity especially for factor VII as compared to commercial rabbit brain or human placenta thromboplastin. In an international field trial the reagent was tested using fully or semi automated Electra coagulometers in 4 different laboratories. Results with normal samples were in excellent agreement among the different laboratories. Mean values were 10.9, 10.9, 11.0, 11.2 s with a range of 9.5 to 12.5 s. Results of males and females were not different. In patients with liver disease very similar PT activities were found as compared to sensitive rabbit brain or human placental thromboplastins. In normals and patients with oral anticoagulation INR values correlated very well against BCT (r = 0.98, regression line y = -0.07 + 0.9 x). The distribution of samples was linear over the whole range. In the comparison against sensitive rabbit brain thromboplastin or human placental thromboplastin similar correlations were found. In a few cases higher INR values were observed for the recombinant reagent especially in patients with intensive treatment. Factor assays in those patients showed at least the strong reduction of one vitamin K-dependent coagulation factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Prothrombin activation fragment 1 + 2 and thrombin antithrombin III complexes in patients with angina pectoris: relation to the presence and severity of coronary atherosclerosis.

Plasma levels of the prothrombin activation fragment 1 + 2 (F 1 + 2) and of thrombin antithrombin III complexes (TAT) were determined in 225 patients with angina pectoris undergoing coronary angiography. Oral anticoagulant therapy was associated with a marked reduction in mean F1 + 2 (0.63 vs 1.62 nmol/l, p < 0.0001) and TAT levels (1.65 vs 2.23 micrograms/l, p < 0.0001). Omitting patients on oral anticoagulants, TAT values showed a positive association with patients' age (r = 0.18; p = 0.01) and were slightly higher in patients with a history of myocardial infarction than in those without (2.47 vs 2.11 micrograms/l; p = 0.06). Both F1 + 2 and TAT levels were increased in patients with angiographically verified coronary atherosclerosis as compared to patients with angina and angiographically normal coronaries (F1 + 2: 1.76 vs 1.36 nmol/l, TAT: 2.35 vs 2.00 micrograms/l; p-values after adjusting for age, sex and past history of myocardial infarction 0.06 and 0.11 respectively). However, no graded relationship between F1 + 2 or TAT values and severity of atherosclerosis was observed. This study provides suggestive evidence that a procoagulant state exists in patients with angina pectoris and coronary atherosclerosis. Its relevance in predicting coronary ischaemic events needs to be studied prospectively.

Adult↗
PubMed1993

Expression of the double-stranded RNA-dependent protein kinase (p68) in squamous cell carcinoma of the head and neck region.

OBJECTIVE: p68 is an interferon-inducible protein kinase that is believed to be an important factor in the regulation of both viral and cellular protein synthesis. We have previously shown that p68 expression correlates with differentiation in a variety of tumors, including squamous cell carcinoma of the head and neck region. The current study aims to identify the prognostic significance of p68 expression in squamous cell carcinoma of the head and neck. DESIGN: Archival material from a cohort of 75 patients with primary squamous carcinomas of the head and neck was immunostained for p68 with the monoclonal antibody TJ4C4. Overall scores for p68 expression were tabulated based on staining intensity and percentage of immunoreactive tumor cells. Clinical information including tumor grade, stage, site, treatment, disease-free, and total survival was tabulated and compared by p68 expression group. SETTING: Veterans Administration Lakeside Medical Center and outpatient clinics (Northwestern University and Veterans Administration Lakeside Medical Center, Chicago, Ill). PATIENTS: Seventy-five consecutive patients with primary squamous cell carcinoma of the head and neck (excluding the esophagus), with tissue blocks available for study, a known primary site, no history of prior carcinoma, and demographic and follow-up information available. MAIN OUTCOME MEASURED: Disease-free and overall survival rates. RESULTS: While there was a wide range of outcomes within each group, as a group, high levels of p68 expression correlated with a lower incidence of recurrent or residual disease and longer disease-free and total survival times compared with groups with lower levels of p68 expression. These differences could not be explained on differences in patient age, tumor grade, and TNM stage. CONCLUSIONS: High-level p68 expression is associated with prolonged disease-free and overall survival in a series of patients with squamous cell carcinoma of the head and neck region. Additional study is needed to monitor changes in p68 expression with treatment or tumor progression.

Aged↗
PubMed1993

Correlation of the expression of double-stranded RNA-dependent protein kinase (p68) with differentiation in head and neck squamous cell carcinoma.

p68 is an inducible protein kinase which is believed to be an important factor in the regulation of both viral and cellular protein synthesis. We have produced a monoclonal antibody (TJ4C4) which specifically detects p68, and which can be used to detect this antigen in formalin-fixed, paraffin-embedded tissues. Because p68 plays an important role in cellular protein synthesis, we hypothesized that it may correlate with normal and neoplastic cellular differentiation. One hundred and seventy-seven head and neck squamous cell carcinoma specimens, representing 82 patients, were studied. The relative amount, frequency, and distribution of p68 expression were determined by microscopic evaluation of ABC immunoperoxidase-stained specimens. A spectrum of immunoreactivity was detected in 156 of 177 tumors, as well as within the normal squamous epithelium. Normal, actively proliferating cells, such as the basal layer of squamous epithelium, expressed comparatively little p68. Increased p68 expression was noted to parallel the morphologic features of cellular differentiation. In neoplastic tissue, p68 expression also increased with the degree of cellular differentiation. These data demonstrate that the expression of p68 parallels the degree of cellular differentiation in squamous cell carcinoma of the head and neck region, as well as within normal squamous mucosa. Therefore, p68 may provide an objective biologic measure of cellular differentiation which does not depend on morphologic features.

Aged↗
PubMed1993

Laboratory methods for detecting disseminated intravascular coagulation (DIC): new aspects.

The objective was to diagnose a hypercoagulative state or "pre-DIC" with new laboratory tests. APACHE II score was used as a measure of primary illness. Ventilator time was used as a reflexion of secondary complications. Twenty-three ICU patients were divided into two groups depending on time on the ventilator: Group 1 > 7 days and Group II < or = 7 days. If, after admittance patients deteriorated or complications occurred, new quantitative coagulation tests were done: soluble fibrin, prothrombin fragment 1 + 2, thrombin-antithrombin complex, D-dimer and elastase. We found a positive correlation between SF levels, the APACHE II score and the ventilator time. Diagnostic efficacy for SF was 87%, sensitivity 91%, specificity 83%, the predictive value of a positive result was 87% and the predictive value of a negative result 91%. The levels of the other new tests were also generally higher in the clinically worse group, although not significantly. Prothrombin complex, APTT, platelet count and AT III were pathologic to the same extent in both groups. The patients who developed most secondary complications, resulting in longer ventilator treatment (Group I), were also hypercoagulative. Soluble fibrin, in particular, seems to be valuable in the diagnosis of "pre-DIC" and possibly of predictive value for organ system complications.

Adult↗
PubMed1992

Multicentric evaluation of a new assay for prothrombin fragment F1+2 determination.

A multicenter study of a recently developed ELISA for the determination of prothrombin fragment F1+2 was performed in order to evaluate analytical and clinical aspects. Mean intra-assay and inter-assay reproducibility were found to be 11.0 and 12.6%, respectively. The measuring range covered by the calibration curve reaches from 0.04 to 10.0 nM/l F1+2. Testing 133 healthy subjects a reference range of 0.37 to 1.11 nM/l F1+2 (2.5-97.5 percentile) with a median of 0.66 nM/l F1+2 was calculated. Minor difficulties with blood sampling (venous occlusion for 2 min) did not affect F1+2 plasma concentrations. Significantly increased F1+2 levels were measured in patients with leukemia (p < 0.0001), severe liver disease (p < 0.005) and after myocardial infarction (p < 0.01). Elevated F1+2 concentration before the beginning of heparin therapy (1.25 nM/l) decreased to 0.77 nM/l (p < 0.0001) after 1 day of therapy. For patients in the stable phase of oral anticoagulant therapy decreasing F1+2 concentrations were measured with increasing INR. F1+2 levels were already significantly reduced in patients with INR < 2.0 (0.56 nM/l; p = 0.0005). Thus F1+2 determination may be helpful in identifying activation processes as well as in monitoring anticoagulant therapy.

Administration, Oral↗
PubMed1992

Elevated levels of thrombin-heparin cofactor II complex in plasma from patients with disseminated intravascular coagulation.

An ELISA assay for quantitation of the thrombin-heparin cofactor II complex (T-HC II) in plasma was developed. Plasma was incubated with immobilized, specific antibodies to human thrombin. The second, biotinylated antibody was directed against human HC II. The assay was insensitive to thrombin-antithrombin complex (TAT) and to uncomplexed HC II. In plasma samples from 31 normal individuals (aged 21-68, mean 43.3 years), the T-HC II ranged 0.3-6.1 ng/ml; median 1.5, mean 2.0, and SD 1.6 ng/ml. In plasma samples from 13 patients with disseminated intravascular coagulation (DIC), T-HC II ranged 0.4-30.0 (median 13.5) ng/ml. In plasma samples from 6 patients in which the clinical suspicion of DIC was not verified, T-HC II complex ranged 1.4-14.3 (median 3.6) ng/ml. In plasma samples with elevated T-HC II levels, TAT was usually elevated, and on the average more than was T-HC II. These results indicate that HC II contributes significantly to the inactivation of in vivo generated thrombin.

Adolescent↗
PubMed1991

Determination of human prothrombin activation fragment 1 + 2 in plasma with an antibody against a synthetic peptide.

The present investigation describes a novel approach to prepare a specific antibody against prothrombin activation fragment 1 + 2 (F 1 + 2). The antibody discriminates between native prothrombin and F 1 + 2 in plasma. A synthetic peptide from the negatively charged region of F 1 + 2, which becomes the carboxy-terminal sequence after cleavage of prothrombin by factor Xa, was used for immunization of rabbits. Obtained antiserum was immunopurified and an enzyme-linked immunosorbent assay (ELISA) was constructed for determination of F 1 + 2. The test system follows the sandwich principle and uses two different antibodies directed against F 1 + 2 and prothrombin, respectively. The ELISA was calibrated with purified F 1 + 2 added to F 1 + 2-poor plasma. The lower limit of sensitivity of the assay was 0.02 nmol/l. Coefficients of variation of 6.9 to 10.4% (intraassay) and 6.7 to 11% (interassay) were found for F 1 + 2 concentrations between 0.08 and 4.9 nmol/l. A reference range from 0.32 to 1.2 nmol/l was calculated from 95 healthy donors (mean value +/- SD: 0.67 +/- 0.19 nmol/l). In patients with deep vein thrombosis (n = 7) confirmed by phlebography and in patients with pulmonary embolism (n = 8) confirmed by lung scan, F 1 + 2 levels were found up to 1.5 to 9.5 nmol/l. In plasma samples of patients under oral anticoagulant therapy in the stable state F 1 + 2 concentrations were found to be in the range of 0.08 to 0.5 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

D-Dimers, thrombin antithrombin III complexes and prothrombin fragments 1+2: diagnostic value in clinically suspected deep vein thrombosis.

This study was performed to determine the accuracy of D-Dimer fibrin derivatives, thrombin-antithrombin III (TAT) complexes and prothrombin fragments 1 + 2 (F 1 + 2) determinations for the diagnosis of deep vein thrombosis (DVT). One hundred and sixteen consecutive patients referred to the angiology unit of our hospital for a clinically suspected DVT were investigated. They were submitted to mercury strain gauge plethysmography and to ultrasonic duplex scanning examination; in cases of inconclusive results or of proximal DVT (n = 35), an ascending phlebography was performed. After these investigations were completed, the diagnosis of DVT was confirmed in 34 and excluded in 82. One half of the patients were already under anticoagulant therapy at the time of investigation. The 3 biological markers were assayed using commercially available ELISA techniques and the D-Dimer was also assayed with a fast latex method. The normal distribution of these markers was established in 40 healthy blood donors. The most accurate assay for the diagnosis of DVT was the D-Dimer ELISA which had both a high sensitivity (94%) and a high negative predictive value (95%). The D-Dimer latex, TAT complexes and F 1 + 2 were far less sensitive and provided negative predictive values which ranged between 78 and 85%. In spite of positive and significant correlations between the levels of the 3 markers, their association did not improve their overall accuracy for detecting DVT. Therefore, with the exception of the D-Dimer ELISA, these markers were of little value for the diagnosis of DVT in this specific population.

Antithrombin III↗
PubMed1991

Determination of thrombin-hirudin complex in plasma with an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) was developed for the determination of the thrombin-hirudin complex (TH) in plasma. The test is based on the sandwich principle and uses appropriate antibodies which selectively bind the corresponding moieties of the complex. The assay was calibrated by adding performed TH to normal human citrated plasma. The detection limit of the assay was 1.2 ng/ml. Mean coefficients of variation of 6.0% (intra-assay) and 6.4% (inter-assay) were found. The presence of TH was demonstrated in normal human plasma that was spiked with hirudin and subsequently activated in vitro by calcium-thromboplastin to generate thrombin. This complex was also found in plasma samples from pigs which had been treated with hirudin during experimentally induced septicaemia.

Animals↗
PubMed1991

Prothrombin fragment 1 + 2, thrombin-antithrombin III complexes and D-dimers in acute deep vein thrombosis: effects of heparin treatment.

Plasma levels of prothrombin fragment 1 + 2 (F 1 + 2), of thrombin-antithrombin III complexes (TAT) and of D-dimers were evaluated at several time intervals in 15 patients affected by acute proximal deep vein thrombosis, complicated or not by pulmonary embolism, and treated by conventional heparin therapy for 9 d. The mean levels of the three markers remained significantly increased throughout the period of observation, except for F 1 + 2 on day 9, when compared to normal values established in a population of normal healthy blood donors. However, whereas heparin significantly decreased the plasma levels of F 1 + 2 and of TAT complexes in less than 3 d. D-dimer levels were not significantly altered. Significant correlations were observed between the plasma levels of the three markers but they were not correlated to the actual intensity of heparin treatment evaluated as the activated partial thromboplastin time prolongation. These results indicate that heparin improves the hypercoagulable state associated with a deep vein thrombosis within the first days of treatment as indicated by TAT and F 1 + 2. They also account for the performances of D-dimer assay for the diagnosis of deep vein thrombosis in patients already receiving heparin, a common situation in routine hospital practice.

Acute Disease↗
PubMed1991

Influence of cytostatic treatment on the coagulation system and fibrinolysis in patients with non-Hodgkin's lymphomas and acute leukemias.

Cytostatic therapy is known to aggravate tumor-induced coagulopathy. Therefore, we have studied the effect of different chemotherapeutic regimens on the activation of coagulation and fibrinolysis in patients with non-Hodgkin's lymphomas or acute leukemias. In non-Hodgkin's lymphoma patients treated with an aggressive protocol (COL-BLAM) and in leukemia patients (TAD-9) fibrinopeptide A, prothrombin fragment (F1 + 2) and thrombin antithrombin III complexes (TAT) increased (Tables 4 and 6), while D-dimer did not deviate significantly. The ratio D-dimer/TAT consequently showed a significant decrease, indicating increased formation of thrombin after release of procoagulant factors, which is not paralleled by an activation of fibrinolysis. Both these groups were also characterized by an increase in uric acid and in C-reactive protein and plasminogen-activator inhibitor, two acute-phase reactants. In contrast, patients with non-Hodgkin's lymphomas treated with a less aggressive protocol (COP) showed no significant changes in hemostatic variables, uric acid, or acute-phase reactants. The release of procoagulant factors relates to the cytostatic sensitivity of the tumor and to a high tumor-cell destruction. Our results further emphasize the need for large-scale studies on antithrombotic prophylaxis in patients undergoing cytostatic treatment.

Acute Disease↗
PubMed1990

Intraoperative radiation of canine carotid artery, internal jugular vein, and vagus nerve. Therapeutic applications in the management of advanced head and neck cancers.

As a step in the application of intraoperative radiotherapy (IORT) for treating advanced head and neck cancers, preliminary information was obtained on the radiation tolerance of the canine common carotid artery, internal jugular vein, and vagus nerve to a single, high-dose electron beam. Both sides of the neck of eight mongrel dogs were operated on to expose an 8-cm segment of common carotid artery, internal jugular vein, and vagus nerve. One side of the neck was irradiated, using escalating doses of 2500, 3500, 4500, and 5500 cGy. The contralateral side of the neck served as the unirradiated control. At 3 and 6 months after IORT, one dog at each dose level was killed. None of the dogs developed carotid bleeding at any time after IORT. Light microscopic investigations using hematoxylin-eosin staining on the common carotid artery and internal jugular vein showed no consistent changes that suggested radiation damage; however, the Masson trichrome stain and hydroxyproline concentration of irradiated common carotid artery indicated an increase in the collagen content of the tunica media. Marked changes in the irradiated vagus nerve were seen, indicating severe demyelination and loss of nerve fibers, which appeared to be radiation-dose dependent. Four patients with advanced recurrent head and neck cancer were treated with surgical resection and IORT without any acute or subacute complications. The role of IORT as a supplement to surgery, external beam irradiation, and chemotherapy in selected patients with advanced head and neck cancer needs further exploration.

Animals↗
PubMed1990

Beta-adrenoceptor-binding studies of the cardioselective beta blockers bisoprolol, H-I 42 BS, and HX-CH 44 BS to heart membranes and intact ventricular myocytes of adult rats: two beta 1-binding sites for bisoprolol.

beta-Adrenoceptor binding of cardioselective drugs to intact ventricular myocytes was performed using [3H]CGP-12177, a hydrophilic non-beta 1/beta 2-selective antagonist radioligand. The beta-adrenoceptor density on the intact cardiomyocytes was about 2 x 10(5) molecules/cell. The beta 1-selective antagonists H-I 42 BS and HX-CH 44 BS competed for [3H]CGP-12177 binding sites on the ventricular myocytes in an essentially monophasic manner with Ki = 72.6 nM and Ki = 76.7 nM, respectively. This is in contrast to the results of binding data from heart membranes, where these beta 1-antagonists bind in a biphasic manner with about 30% of an additional low affinity site, presumably corresponding to the beta 2-adrenoceptor. The beta 1-selective antagonist bisoprolol revealed two binding sites at the heart membranes and at the myocytes as well with Ki(1) = 34.2 and 20.0 nM and Ki(2) = 3,014 and 918 nM, respectively. Our results suggest that viable adult rat ventricular myocytes may contain two beta 1-adrenoceptor binding sites exhibiting different affinities for bisoprolol, whereas beta 2-adrenergic receptors are completely absent.

Adrenergic beta-Antagonists↗
PubMed1989

Biocompatibility and safety of cytapheresis.

Cytaphereses are safe and can be used routinely like whole blood donations on the premise that standard techniques based on appropriate guidelines and regulations are performed. Before the introduction of a new cell or plasma separator, a thorough clinical investigation is always recommended in order to demonstrate biocompatibility and safety features. In this context cell loss and damage as well as activation of coagulation and complement should be tested primarily. The examination should consist of a direct comparison with an approved system. In addition, it is necessary to repeat periodically on multicenter studies adverse donor reactions such as those already described so that it is possible to recognize even rare side effects. Of special importance are long-term studies of donors undergoing frequent cytaphereses for many years in order to detect relevant immunological changes. On the other hand, harm caused by the plasticizer or cancer due to cancerogenicity of the plastics are only speculative at the moment.

Biocompatible Materials↗
PubMed1989

New trends in the field of coagulation diagnosis--new possibilities to improve monitoring of antithrombotic therapy.

Two specific and sensitive enzyme immunoassays have been developed for the measurement of TAT and PTF, respectively. The TAT-ELISA uses two different antibodies binding selectively to the corresponding antigen moieties of TAT; anti-PTF antibodies were obtained from rabbits using a synthetic peptide from the COOH-terminus of PTF. Concentration in plasma samples of healthy individuals was found to be 1.45 +/- 0.4 micrograms/l for TAT, and 0.65 +/- 0.2 nMol/l for PTF. Patients with coagulation disorders showed markedly increased concentrations of both TAT and PTF. It can be assumed that these parameters might be suitable indicators for monitoring of both anticoagulant and thrombolytic therapy.

Amino Acid Sequence↗