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Biomedical subjects

J Beyer

Publications and source records attributed to J Beyer.

At least 73 records · Page 4Linked to original sources
PubMed2001

Chemotherapy in patients with metastatic or relapsed germ-cell tumours.

The optimal treatment in patients with poor prognosis germ-cell tumours (GCT), according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification, and in patients with refractory or relapsed disease after cisplatin-based chemotherapy is controversial. As the majority of patients will suffer systemic relapses, chemotherapy is the mainstay of treatment. However, the question of whether or not to use conventional-dose or high-dose chemotherapy (HDCT) in these patients arises. Prognostic factors have recently been recognised to aid in this decision. However, reliable data on chemotherapy as primary treatment in poor prognosis patients and as the first-salvage attempt in patients with relapsed or refractory GCT are lacking. This report reviews the recent developments in first-line and salvage HDCT strategies and discusses the role of predictive factors for treatment outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Detection of European porcine reproductive and respiratory syndrome virus in porcine alveolar macrophages by two-colour immunofluorescence and in-situ hybridization-immunohistochemistry double labelling.

Two groups of five pigs aged 6 weeks were each infected oronasally with one of two different European isolates of porcine reproductive and respiratory syndrome virus (PRRSV). The animals were killed sequentially at 4, 7, 14 or 21 days post-inoculation for examination. The methods used consisted of histopathology, and mono- and double-labelling techniques based on in-situ hybridization, immunofluorescence and immunohistochemistry. Porcine alveolar macrophages (PAMs) contained large amounts of PRRSV antigen and PRRSV RNA, as shown by double labelling with (1) either PRRSV immunofluorescence or PRRSV-specific in-situ hybridization with digoxigenin-labelled riboprobes, and (2) immunolabelling with Mac 387 antibody for calprotectin. Expression of PRRSV-RNA was not detectable in cytokeratin-positive hypertrophic and proliferating pneumocytes or in cells of alveolar ducts or bronchiolar epithelium. The use of two-colour immunofluorescence with confocal laser scanning microscopy and double labelling with in-situ hybridization-immunohistochemistry showed that PAMs were the only pulmonary target cells. This contradicts earlier reports that epithelial pulmonary cells may also be infected by PRRSV.

Animals↗
PubMed2001

Eligibility for home treatment of deep vein thrombosis: a prospective study in 202 consecutive patients.

PURPOSE: Home treatment of deep vein thrombosis (DVT) has been shown to be safe and effective. However, this conclusion has been drawn from studies with predefined patient selection criteria. Eligibility for home treatment has never been properly assessed. METHODS: In a 9-month period, we prospectively evaluated the possible reasons for hospital treatment in consecutive patients with acute DVT by using a check list that included medical reasons, home care situation, preferences, and hospital service logistics. Treatment consisted of low-molecular-weight heparin and concomitant oral vitamin K antagonists and compression therapy. A 3-month follow-up examination included assessment of recurrent venous thromboembolism (VTE), bleeding events, and mortality. RESULTS: A total of 202 patients were included in the study; 117 patients (58%) were outpatients and 85 patients (42%) were hospitalized before DVT diagnosis. Of the 117 outpatients, 95 (81%) were considered eligible for home treatment. Only two patients (1.7%) were admitted to the hospital for DVT-related morbidity, one (0.85%) because of comorbidity, 11 (9.4%) for home care reasons, and eight (6.83%) because of hospital service logistics. Of the hospitalized patients, 79 (92.94%) remained inpatients, and six (7.05%) could be discharged within 48 hours. The only reason for hospitalization was pre-existing comorbidity. In outpatients, the outcome after 3 months showed a 4% rate of recurrent VTE, no major bleeding, and an 8% mortality rate; 75% of deaths were caused by cancer. No patient died of VTE. In inpatients, a statistically significant higher mortality rate was found (8% vs 19%; P < .02). CONCLUSION: Less than 3% of patients with DVT who were outpatients had to be hospitalized because of DVT morbidity. For the entire DVT population, the main reason for hospital treatment is comorbidity, rather than management issues or DVT morbidity.

Adult↗
PubMed2001

Therapy of isolated calf muscle vein thrombosis with low-molecular-weight heparin.

There are no data from prospective studies concerning the treatment of isolated calf muscle vein thrombosis (soleal and gastrocnemial muscle veins), found in 20-40% of patients with lower extremity thrombosis of the calf. We investigated the outcome in two cohorts of consecutive patients, the first receiving low-molecular-weight heparin for 10 days at therapeutic doses and compression therapy; the second cohort, compression therapy alone. In patients on therapeutic heparin (n = 52), no progression to deep vein thrombosis occurred [0%; 95% confidence interval (CI), 0-6.8%]. Patients without anticoagulation (n = 32) showed a statistically significant higher percentage of progression into the deep calf veins (25%; 95% CI, 11.5-43.4%) as well as recurrent muscle vein thrombosis. No symptomatic pulmonary embolism or bleeding event occurred; one patient died in each group, both related to malignancy. The data suggest a need for short-term anticoagulation in such patients to prevent further thromboembolic complications. Randomized prospective studies are now warranted in a larger study population.

Adolescent↗
PubMed2001

Comparative in vitro activity of ABT-773, a novel antibacterial ketolide.

The in vitro activities of ABT-773, erythromycin, clarithromycin, and azithromycin were compared. ABT-773 was the most active compound against macrolide-susceptible Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Staphylococcus epidermidis, Listeria monocytogenes, and Enterococcus spp. and multidrug-resistant Streptococcus pneumoniae. It also had good activity against gram-negative and atypical respiratory tract pathogens and Helicobacter pylori.

Anti-Bacterial Agents↗
PubMed2001

Glycoprotein D-independent infectivity of pseudorabies virus results in an alteration of in vivo host range and correlates with mutations in glycoproteins B and H.

Infection of cells by herpesviruses is initiated by the interaction of viral envelope glycoproteins with cellular receptors. In the alphaherpesvirus pseudorabies virus (PrV), the causative agent of Aujeszky's disease in pigs, the essential glycoprotein D (gD) mediates secondary attachment of virions to target cells by binding to newly identified cellular receptors (R. J. Geraghty, C. Krummenacher, G. H. Cohen, R. J. Eisenberg, and P. G. Spear, Science 280:1618-1620, 1998). However, in the presence of compensatory mutations, infection can also occur in the absence of gD, as evidenced by the isolation in cell culture of an infectious gD-negative PrV mutant (PrV-gD(-) Pass) (J. Schmidt, B. G. Klupp, A. Karger, and T. C. Mettenleiter, J. Virol. 71:17-24, 1997). PrV-gD(-) Pass is replication competent with an only moderate reduction in specific infectivity but appears to bind to receptors different from those recognized by wild-type PrV (A. Karger, J. Schmidt, and T. C. Mettenleiter, J. Virol. 72:7341-7348, 1998). To analyze whether this alteration in receptor usage in vitro influences infection in vivo, the model host mouse and the natural host pig were intranasally infected with PrV-gD(-) Pass and were compared to animals infected by wild-type PrV. For mice, a comparable progress of disease was observed, and all animals infected with mutant virus died, although they exhibited a slight delay in the onset of symptoms and, correspondingly, a longer time to death. In contrast, whereas wild-type PrV-infected pigs showed clinical signs and histological and histopathological findings typical of PrV infection, no signs of disease were observed after infection with PrV-gD(-) Pass. Moreover, in these animals, virus-infected cells were not detectable by immunohistochemical staining of different organ samples and no virus could be isolated from nasal swabs. Mutations in glycoproteins B and H were found to correlate with, and probably contribute to, gD-independent infectivity. In conclusion, although PrV-gD(-) Pass is virulent in mice, it is apparently unable to infect the natural host, the pig. This altered host range in vivo correlates with a difference of receptor usage in vitro and demonstrates for the first time the importance of gD receptors in alphaherpesvirus infection of an animal host.

Animals↗
PubMed2001

Reversed portal vein pulsatility on Doppler ultrasound secondary to an iatrogenic mediastinal haematoma.

The Doppler ultrasound pattern of reversed pulsatile flow (RPF) of the portal vein (PV) is strongly associated with high atrial pressure. Tricuspid regurgitation is considered to be the main cause of RPF in patients with chronic heart disease, but the precise pathomechanism of this PV flow pattern has not yet been resolved. We describe for the first time a RPF of the PV in a young patient with a mediastinal haematoma after inadvertent puncture of the subclavian artery. In this patient, transcutaneous echocardiography demonstrated normal valves without any tricuspid regurgitation as well as normal diameters of the cardiac cavities. The RPF of the PV in this patient resolved spontaneously within 7 days. An increased hepatic outflow resistance with transmission of hepatic artery pulsations across arterioportal communications seems the most likely pathomechanism to explain our finding.

Adult↗
PubMed2001

ICE--an efficient drug combination for stem cell mobilization and high-dose treatment of malignant lymphoma.

Between 1989 and 1999 we studied the ICE regimen in sequential trials in 290 patients with malignant lymphoma and germ-cell tumours. For patients with relapsed or refractory lymphoma we could demonstrate a comparable efficacy of ICE to other high-dose chemotherapy (HDCT) regimens but with a toxicity profile in favour of ICE. From a retrospective comparative analysis of ICE as HDCT regimen in patients with malignant lymphoma and germ-cell tumours we conclude that the characteristic toxicity profile of ICE varies depending on prior drug exposure of individual patients. Further dose intensification of ICE may be achieved with acceptable toxicity by adding further drugs (e.g. anthracyclines) or by treatment with sequential cycles of ICE (Tandem-HDCT). More convenient drug formulations (e.g. etoposide phosphate) might further improve the therapeutic index of ICE.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

A double-blind trial of perindopril and nitrendipine in incipient diabetic nephropathy.

UNLABELLED: We conducted a randomised, double-blind multicentre trial to compare the efficacy of the inhibitor of the angiotensin-converting enzyme (ACE) perindopril (P) with nitrendipine (N) in incipient diabetic nephropathy. METHODS: Forty-six patients with insulin-treated diabetes mellitus and mild-to-moderate hypertension and stable microalbuminuria were examined. P 4 or 8 mg once daily was compared to N 20 or 40 mg once daily; an optional open combination treatment with indapamide 2.5 mg once daily was given when needed. Main outcome measures were urinary albumin excretion rate, creatinine clearance and isotopic clearance measurements after 12 months. RESULTS: Baseline characteristics (blood pressure, HbA1, renal function) were highly comparable between groups. No serious adverse events occurred during the study period. Blood pressure was controlled (<140/90 mmHg) in all patients except for one in each group who dropped out. At the end of the study, albumin excretion rate was stabilized in both groups (P: 72% of baseline, N: 108%, NS). There were no significant differences found in radiometric clearance measurements. Creatinine clearance rose in patients treated with P by 10.0 ml/min on average, while it decreased by 9.8 m/min under N treatment (group effect: p<0.05). CONCLUSIONS: In this head-to-head comparison, P and N were effective in stabilising most parameters of renal function in incipient diabetic nephropathy.

Adolescent↗
PubMed2000

The relative risk of second nongerminal malignancies in patients with extragonadal germ cell tumors.

BACKGROUND: Apart from a recognized association between extragonadal mediastinal germ cell tumors (GCT) and the occurrence of hematologic malignancies, the risk of developing second nongerminal solid tumors after the diagnosis or treatment of extragonadal GCT is unknown. METHODS: Six hundred thirty-five consecutive patients with extragonadal GCT treated at 11 centers in the U.S. and Europe during the era of cisplatin-based chemotherapy (1975-1996) were included into a large database. These patients were evaluated for the occurrence of second malignancies. RESULTS: No treatment-related leukemia was observed in 611 patients treated with chemotherapy. In 7 patients, second solid tumors were observed, resulting in a frequency of 1.86% (95% confidence interval [95% CI], 1.79-1.93%) after a median follow-up of 55 months (95% CI, 50-60 months) (annual incidence, 0.30% [95% CI, 0.14-0.59]). Four solid tumors (57%) developed in patients with primary mediastinal and 3 tumors (43%) developed in patients with retroperitoneal GCT. Three patients (43%) had a nonseminomatous and 4 patients (57%) had a seminomatous histology. Six patients had been treated with chemotherapy and one patient with radiotherapy. Six of 7 solid tumors (86%) had developed within 5 years and 7 of 7 solid tumors within 10 years of diagnosis. The median time period to the occurrence of neoplasia was 47 months (range, 9-145 months). Four cutaneous tumors were observed (melanoma, two patients; basal cell carcinoma, one patient; and squamous cell carcinoma, one patient); the other three tumors were angiosarcoma, nonsmall cell lung carcinoma, and colorectal carcinoma. The overall risk for developing a second tumor was not increased compared with an age-matched general population with a standard incidence ratio (SIR) of 1.49 (95% CI, 0.60-3.06). An elevated risk for skin tumors was observed in all extragonadal GCT patients (SIR, 4.00 [95% CI, 1. 09-10.24]), as well as in the subgroup of patients treated with chemotherapy (SIR, 5.33 [95% CI, 1.45-13.65]). CONCLUSIONS: This analysis excludes an increased biologic risk of developing second solid malignancies in patients with extragonadal GCT except for the previously reported association between primary mediastinal nonseminoma and hematologic disorders. The overall risk of developing second malignancies in extragonadal GCT patients appears to be comparable to that in patients with primary testicular carcinoma. The incremental occurrence of skin malignancies in patients treated with chemotherapy should be investigated further.

Adolescent↗
PubMed2000

[Comparison of hypoglycemia perception and hormonal counterregulation in controlled hypoglycemia. A contribution to diagnosis of hypoglycemia unawareness syndrome in type 1 diabetic patients].

BACKGROUND AND OBJECTIVE: Diabetics with abnormal hypoglycaemia awareness cannot recognize hypoglycaemic symptoms early and adequately enough to respond, thus endangering in everyday life not only themselves but also others. Thus it is important to diagnose such symptoms early and assess the extent to which the diabetic is at risk of severe hypoglycaemia. This study was designed to contribute to the evaluation of hypoglycaemia awareness in type 1 (IDDM) diabetics. PATIENTS AND METHODS: In 57 diabetics (IDDM) awareness of typical hypoglycaemic warning symptoms and of hormonal counterregulation were tested during controlled induced hypoglycaemia. A questionnaire was used to measure at fixed time intervals, along a four-point scale, the severity of 6 autonomic and 6 cerebral warning symptoms, and compare them with synchronously obtained plasma levels of glucagon and epinephrine. RESULTS: The cohort was divided into three groups according to the rise of epinephrine levels induced by the hypoglycaemia. Group A (n = 22) showed a significant rise in epinephrine level at the onset of hypoglycaemia; group B (n = 22): significantly increased epinephrine only after 30 min of hypoglycaemia; group C (n = 15): no epinephrine rise at any time during hypoglycaemia. None of the patients had a significant rise in glucagon levels. There were significant differences between the three groups regarding HbA1c levels and the duration of diabetes. Low levels of HbA1c and duration of diabetes were commonly associated with a loss of hormonal counterregulation. In only 40% of patients was it possible to draw any conclusion about epinephrine-induced hypoglycaemia from symptoms revealed in the past history. CONCLUSIONS: The past history of hypoglycaemic symptoms is an unreliable and inadequate guide for objectively assessing the actual risk of hypoglycaemia in type 1 diabetics. The results of this study indicate that when severe hypoglycaemic attacks (requiring outside help etc.) are suspected, standardized diagnostic tests of hypoglycaemia awareness should be performed in specialized centres, particularly if an official medical report ist required.

Adult↗
PubMed2000

[Predictive genetic investigations. Individualization of diagnosis and treatment in families with multiple endocrine neoplasia type II].

BACKGROUND AND OBJECTIVE: When multiple endocrine neoplasia type 2 (MEN2) is suspected, genetic tests are at the centre of screening procedures. It was the aim of this study to compare the diagnostic value of molecular biological investigations with that of conventional biochemical tests. PATIENTS AND METHODS: The study cohort consisted of all 144 patients cared for in our department since 1990 with the suspected diagnosis of MEN2 (evidence of a medullary thyroid carcinoma [MTC]), coexistence of two MEN2 tumours or a family history of MEN2. 14 of the 144 patients (from 12 families) were already known to have an hereditary MTC, while the remaining 130 had been referred for further diagnostic investigations. RESULTS: An hereditary MTC was diagnosed in 22 of the 130 patients, a sporadic MTC in 32, while no definitive classification was possible in 20 MTC patients without a positive family history and on whom no mutation analysis had been performed. MEN2 was excluded in 56 family members. All 22 patients with newly diagnosed MTC had abnormally high calcitonin levels. A germ-line mutation in the RET proto-oncogene was found in 8 of the 9 families who had undergone molecular biological tests. The investigate results led to a thyroidectomy in 19 of the 22 patients with hereditary MTC; in all of them the surgical specimen showed C-cell hyperplasia and/o MTC. CONCLUSION: These results emphasize the importance of genetic tests in family screening. Preoperative measurement of calcitonin remains essential in MEN2 families in whom a germ-line mutation is not known. The choice of the appropriate diagnostic test must be individualized to the particular patients so that optimal results are obtained.

Adolescent↗
PubMed2000

Hematologic disorders associated with primary mediastinal nonseminomatous germ cell tumors.

BACKGROUND: The association between primary germ cell tumors of the mediastinum (the space between the lung pleura that contains the heart and other chest viscera) and hematologic malignancies has been described by retrospective analysis of patients treated at individual clinical centers. To better characterize the risk of hematologic disorders in patients with extragonadal germ cell tumors and to describe the clinical and biologic features of the disorders, we studied an unselected population in a large, international, multicenter database. METHODS: Six hundred thirty-five patients treated at 11 centers in the United States and Europe from 1975 through 1996 were evaluated retrospectively. RESULTS: A hematologic disorder was observed in 17 patients with germ cell tumors. All cases developed among the 287 patients with primary mediastinal nonseminomatous germ cell tumors, giving an incidence rate in this group of 2.0% (95% confidence interval [CI] = 1.1%-3.1%) per year over a median follow-up time of 3 years. The risk of developing hematologic disorders was statistically significantly increased in patients with primary mediastinal nonseminomatous germ cell tumors in comparison with the age-matched general population (standardized incidence ratio = 250; 95% CI = 140-405). The median time to onset of hematologic neoplasia was 6 months (range, 0-47 months), and the median survival after diagnosis of the hematologic disorder was 5 months (range, 0-16 months) (two-sided P<.0001, comparing survival from the time of diagnosis of the germ cell tumor of patients with and without hematologic disorders). CONCLUSION: In our study, approximately one in 17 patients with primary mediastinal nonseminomatous germ cell tumors was affected by a hematologic disorder, whereas no cases were seen among 334 patients with other extragonadal germ cell tumors. The hematologic disorder had a statistically significant impact on prognosis, with none of the 17 reported patients surviving for more than 2 years.

Adolescent↗
PubMed2000

[Interdisciplinary consensus on diagnosis and therapy of testicular tumors. Results of an update conference based on evidence-based medicine. German Testicular Cancer study Group (GTCSG)].

BACKGROUND: An "Interdisciplinary Consensus Statement on the Diagnosis and Therapy of Testicular Tumors" was prepared in 1996 by the "Interdisciplinary Testicular Tumor Working Group" (IAH) with input from representatives from diagnostic and therapeutic disciplines of various working groups of the German Cancer Society (Strahlenther Onkol 1997;173:397-406). In 1998 the IAH met again together with the "Testicular Tumor Working Party" of the Urooncology Working Group (AUO) and formed the "German Testicular Cancer Study Group" (GTCSG). Defined and accepted interdisciplinary standards from the initial meeting were revised based on current scientific developments and clinical results. This cooperating effort increased the quality of the initial recommendations and helped to put the recommendations for diagnosing and treating testicular tumor on a broader scientific basis. METHODS: According to the principles of "evidence-based medicine" (EBM), the Consensus from 1996 was modified, based on the current level of evidence from the published literature. The methodological process and evaluation criteria used were that of the "Cochrane Collaboration". RESULTS: An "Interdisciplinary Update Consensus Statement" summarizes and defines the diagnostic and therapeutic standards according to the current scientific practices in testicular cancer. For 21 separate areas scientifically based decision criteria are suggested. For treatment areas where more than one option exist without a consensus being reached for a preferred strategy, such as in seminoma in clinical Stage I or in non-seminoma Stages CS I or CS IIA/B, all acceptable alternative strategies with their respective advantages and disadvantages are presented. This "Interdisciplinary Update Consensus" was presented at the 24th National Congress of the German Cancer Society on March 21st and subsequently evaluated and approved by the various German scientific medical societies.

Evidence-Based Medicine↗
PubMed2000

Successful autologous bone marrow rescue in patients who failed peripheral blood stem cell mobilization.

We assessed autologous bone marrow (BM) harvest and hematologic recovery after high-dose chemotherapy (HDCT) in patients who failed to achieve peripheral blood stem cell (PBSC) mobilization. One hundred and ninety-three patients with germ cell tumor, malignant lymphoma, sarcoma or medulloblastoma were scheduled for HDCT. In 123 patients, PBSC were mobilized by disease-specific chemotherapy plus granulocyte colony-stimulating factor (G-CSF). In 110/ 123 patients (89%) with circulating CD34+ cell counts 2 > or = 10/microl, sufficient hematopoietic autografts were collected (group A). In 13/123 patients (11%) with peripheral CD34 + cell counts < 10/microl, PBSC harvesting was not performed (group B). These latter patients were classified as "poor mobilizers" and underwent second-line BM harvest at a median of 46 (range 10-99) days after mobilization failure. Seventy patients with first-line BM harvest (group C) acted as historical controls. Ten patients from group B proceeded to HDCT and nine were evaluable for hematopoietic reconstitution. Recovery to neutrophils >0.5 x 10(9)/l was comparable with group C patients: 16 (range 9-34) days vs 13 (range 8-98) days. However, platelet (PLT) reconstitution >20 x 10(9)/l was significantly slower, with a median of 35 (range 13-50) days as compared with 19 (range 9-148) days (P = 0.0106) for control patients. Supportive care requirements, febrile days and length of hospital stay were not significantly different between the two groups of patients. We conclude that patients who fail to mobilize PBSC should be evaluated for second-line BM harvest. This approach may preserve the therapeutic option of HDCT for these patients.

Adolescent↗
PubMed2000

Reconstruction and visualization of irregularly sampled three- and four-dimensional ultrasound data for cerebrovascular applications.

Although recent studies have demonstrated the potential value of compounded data for improvement in signal-to-noise ratio and speckle contrast for three-dimensional (3-D) ultrasonography, clinical applications are lacking. We investigated the potential of six degrees-of-freedom (6-DOF) scanhead position and orientation measurement (POM) devices for registration of in vivo multiplanar, irregularly sampled ultrasound (US) images to a regular 3-D volume space. The results demonstrate that accurate spatial and temporal registration of four-dimensional (4-D) US data can be achieved using a 6-DOF scanhead tracking system. For reconstruction of arbitrary, irregularly sampled US data, we introduce a technique based upon a weighted, ellipsoid Gaussian convolution kernel. Volume renderings of 3-D and 4-D compounded in vivo US data are presented. The results, although restricted to the field of cerebrovascular disease, will be of value to other applications of 3-D sonography, particularly those in which compounding of data through irregular sampling may provide superior information on tissue or vessel structure.

Blood Flow Velocity↗