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J Beck

Publications and source records attributed to J Beck.

At least 19 recordsLinked to original sources

Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: results of the international randomized phase III trial (MISTRAL).

INTRODUCTION: Sequential high dose (SHiDo) chemotherapy with stem cell support has been shown to prolong the event-free survival in patients with diffuse large B-cell lymphoma. METHODS: To confirm this result in a multicenter trial, we randomized patients with aggressive NHL, to receive either eight cycles of CHOP or SHiDo. The primary endpoint was overall survival. RESULTS: 129 evaluable patients were randomized to receive either CHOP or SHiDo: median age, 48 years; 62% male; stage III+IV: 73%; age adjusted International Prognostic Index 1/2/3: 21%/52%/27%. Toxicity grades 3+4 were more pronounced in the SHiDo-arm with 13% versus 3% of patients with fever; 34% versus 13% with infections; 13% versus 2% with esophagitis/dysphagia/gastric ulcer. The remission rates were similar in SHiDo and CHOP arms with 34%/37% complete remissions and 31%/31% partial remissions, respectively. After a median observation time of 48 months, there was no difference in overall survival at 3 years, with 46% for SHiDo and 53% for CHOP (P = 0.48). CONCLUSION: In this multicenter trial, early intensification with SHiDo did not confer any survival benefit in previously untreated patients with aggressive NHL and was associated with a higher incidence of grades 3/4 toxicity.

Adolescent↗

A clinical trial with chimeric monoclonal antibody WX-G250 and low dose interleukin-2 pulsing scheme for advanced renal cell carcinoma.

PURPOSE: WX-G250 is a chimeric monoclonal antibody that binds to carbonic anhydrase IX(G250/MN), which is present on greater than 95% of RCCs of the clear cell subtype. The suggested working mechanism of WX-G250 is by ADCC. Because the number of activated ADCC effector cells can be increased by a low dose interleukin-2 pulsing schedule, a multicenter study was initiated to investigate whether WX-G250 combined with LD-IL-2 could lead to an improved clinical outcome in patients with progressive RCC. MATERIALS AND METHODS: A total of 35 patients with progressive clear cell RCC received weekly infusions of WX-G250 for 11 weeks combined with a daily LD-IL-2 regimen. Patients were monitored longitudinally for ADCC capacity. Radiological assessment of metastatic lesions was performed at week 16 and regularly until disease progression. RESULTS: A durable clinical benefit was achieved in 8 of 35 patients (23%), including 3 with a partial response and 5 with stabilization at 24 weeks or greater. Mean survival was 22 months. In general treatment was well tolerated with little toxicity. The number of effector cells increased during treatment but lytic capacity per cell did not increase. ADCC and clinical outcome did not appear to correlate. CONCLUSIONS: WX-G250 combined with LD-IL-2 in patients with metastatic RCC is safe and well tolerated. With a substantial clinical benefit and a median survival of 22 months in patients with metastatic RCC who have progressive disease at study entry combination therapy showed increased overall survival compared to WX-G250 monotherapy. Survival was at least similar to that of currently used cytokine regimens but with a favorable toxicity profile.

Adult↗

Periodontal disease and adverse pregnancy outcomes: a systematic review.

BACKGROUND: Recent studies suggest that periodontal disease, as a source of subclinical and persistent infection, may induce systemic inflammatory responses that increase the risk of adverse pregnancy outcomes. OBJECTIVES: To examine the existing evidence on the relationship between periodontal disease and adverse pregnancy outcomes. SEARCH STRATEGY: Published studies identified via searches of the MEDLINE, EMBASE, CINAHL, and Current Contents full-text databases. SELECTION CRITERIA: We identified and selected observational studies (i.e. case-control, cross-sectional, and cohort) and nonrandomised controlled studies or randomised controlled trials that examined periodontal disease as a risk factor for adverse pregnancy outcomes. DATA COLLECTION AND ANALYSIS: Odds ratios (OR) or risk ratios (RR) were extracted or calculated from the studies' data. We calculated pooled effect size for two clinical controlled trials but not for the observational studies due to the heterogeneity in definitions for periodontal disease and adverse pregnancy outcomes across studies. MAIN RESULTS: Twenty-five studies (13 case-control, 9 cohort, and 3 controlled trials) were identified. The studies focused on preterm low birthweight, low birthweight, preterm birth, birthweight by gestational age, miscarriage or pregnancy loss, and pre-eclampsia. Of the chosen studies, 18 suggested an association between periodontal disease and increased risk of adverse pregnancy outcome (ORs ranging from 1.10 to 20.0) and 7 found no evidence of an association (ORs ranging from 0.78 to 2.54). Three clinical trial studies suggest that oral prophylaxis and periodontal treatment can lead to a 57% reduction in preterm low birthweight (pooled RR 0.43; 95% CI 0.24-0.78) and a 50% reduction in preterm births (RR 0.5; 95% CI 0.20-1.30). AUTHOR'S CONCLUSIONS: Periodontal disease may be associated with an increased risk of adverse pregnancy outcome. However, more methodologically rigorous studies are needed for confirmation.

Abortion, Spontaneous↗

Vibronic energies and spectra of molecular dimers.

We consider three distinct methods of calculating the vibronic levels and absorption spectra of molecular dimers coupled by dipole-dipole interactions. The first method is direct diagonalization of the vibronic Hamiltonian in a basis of monomer eigenstates. The second method is to use creation and annihilation operators leading in harmonic approximation to the Jaynes-Cummings Hamiltonian. The adiabatic approximation to this problem provides insight into spectral behavior in the weak and strong coupling limits. The third method, which serves as a check on the accuracy of the previous methods, is a numerically exact solution of the time-dependent Schrodinger equation. Using these methods, dimer spectra are calculated for three separate dye molecules and show good agreement with measured spectra.

Journal Article↗

Assessment of changes in cerebral circulation time due to vasospasm in a specific arterial territory: effect of angioplasty.

This study demonstrates that in experienced hands, intracranial angioplasty is a feasible and safe option in a selected group of patients with severe (>50% stenosis) symptomatic vasospasm following subarachnoid hemorrhage. Cerebral circulation time is a surrogate parameter closely linked to cerebral perfusion. The study presented shows that not only stenosis but also changes in circulation time are obtained by angioplasty. Twenty angioplasties of one or two vessel segments were performed over 2 years in 18 consecutive patients with posthemorrhagic vasospasm fulfilling criteria for invasive treatment. In all patients, degree of stenosis and circulation time could be reduced by angioplasty. Clinical results were ranked according to Glasgow Outcome Scale. Imaging after 15/20 angioplasties showed no additional infarction. In 4/20 cases, CT showed demarcation of infarction after angioplasty. In 1/20 cases of posterior circulation angioplasty, CT is not sensitive enough to exclude smaller infarctions. Imaging and clinical outcome reveal a definite benefit.

Adolescent↗

Technique and image quality of intraoperative indocyanine green angiography during aneurysm surgery using surgical microscope integrated near-infrared video technology.

OBJECTIVE: To describe the technical integration of indocyanine green (ICG) near-infrared technology into the optical path of the surgical microscope and to report on the image quality achieved by this method. We hypothesized that ICG angiography permits a simple and quick intraoperative assessment of vessel patency and aneurysm occlusion after clip placement. METHODS: A special arrangement of filters was designed to allow the passage of near-infrared light required for the excitation of ICG fluorescence (700-850 nm) from a modified microscope light source into the surgical field and the passage of ICG fluorescence (780-950 nm) from the surgical field back into the optical path of the surgical microscope (Carl Zeiss, Oberkochen, Germany). Thus, ICG angiography could be completely performed with a surgical microscope. 20 patients with intracranial aneurysms were included in the technical evaluation of the new method. RESULTS: Image quality and spatial resolution were excellent and permitted a real-time assessment of vessel patency and aneurysm occlusion if the structures of interest were visible to the surgeon's eye under the microscope, including perforating arteries with a diameter of less than 1 millimeter. In 1 patient, vessel occlusion by the clip was found and in 1 case residual filling of the aneurysm was diagnosed. Both cases could be treated by clip correction within 2 minutes after primary placement of the clip. In all cases, the intraoperative findings correlated with the postoperative digital subtraction angiography. CONCLUSIONS: ICG angiography using a surgical microscope is valuable for the intraoperative imaging of arterial and venous flow in all visible vessels including small perforating arteries. The simplicity of the method and the speed with which the investigation can be performed indicate that this technique may help to improve the quality and outcome of surgical procedures and reduce the need for intra- or postoperative angiography in selected cases.

Adult↗

[Recommendations for the management of patients with aneurysmal subarachnoid hemorrhage].

After SAH, primary and secondary complications are frequent and often require neurosurgical interventions to avoid secondary brain damage. The authors of the present paper have summarized the available data about the treatment modalities often used for patients with SAH. The present recommendations have been developed as a neurosurgical and neuroanestesiological consensus. Evidence from prospective, randomized, double blind, placebo-controlled studies support grade A recommendations (standard) for the prophylaxis and treatment of cerebral vasospasm with oral Nimodipine in good grade patients. For intravenous Nimodipine or for oral nimodipine treatment in poor grade patients, available data only support grade C recommendations (options). Despite the lack of data supporting standards (grade A) or guidelines (grade B), avoidance and rigorous treatment of hypotension and hypovolemia remains the mainstay in the prophylaxis and treatment of a delayed ischemic neurological deficit (DIND). Prophylactic hypervolemia or prophylactic hypertension and hypervolemia was shown to be ineffective in reducing symptomatic vasospasm and improving outcome (grade B). Therapeutic hypertensive hypervolemic hemodilution is recommended as a treatment of symptomatic vasospasm but no prospective studies are available (grade C recommendation). Suggested target values for moderate triple-H-therapy are CPP 80- 120 mmHg (MAP 90-130), CVP > 7 mmHg and Hk 0.25-0.40. Balloon angioplasty should be considered for treatment of DIND cause by focal, proximal cerebral vasospasm. There is no evidence supporting the routine use of antifibrinolyticals, steroids or anticonvulsive prophylaxis. Clinical data indicate that current prophylaxis and treatment of cerebral vasospasm is still insufficient and aggressive triple-H-therapy is associated with an increased incidence of complications.

Angioplasty, Balloon↗

[Paraneoplastic lupus anticoagulans syndrome].

The antiphospholipid antibody syndrome (Lupus anticoagulans syndrome) is a rare form of coagulopathy due to the presence of autoantibodies against phospholipids or phospholipid-binding protein cofactors that can lead to vascular thrombosis. We report the case of a 57-year-old female patient presenting with decompensated duodenal stenosis due to a pancreatic tumor. Perioperative testing of coagulation markers revealed with 26 % a strongly decreased Quick-Test and with 81.4 s a prolonged partial thromboplastin time that persisted despite intravenous application of 80 mg vitamin K (Konakion) and 10 units of fresh frozen plasma. Subsequent screening for common causes of thrombophilia revealed antiphospholipid antibodies. Consequently, low molecular weight heparin (Dalteparin-Natrium) was administered perioperatively while a gastroenterostomy with entero-enterostomy was performed with uneventful postoperative course. With this presentation and an analysis of the contemporary literature we would like to discuss different aspects of Lupus anticoagulans syndrome.

Anticoagulants↗

Comparison of a corn silage hybrid with high cell-wall content and digestibility with a hybrid of lower cell-wall content on performance of Holstein cows.

We hypothesized that substituting a corn hybrid with high cell-wall content and high neutral detergent fiber (NDF) digestibility (HCW) for a hybrid with lower cell-wall content and lower NDF digestibility (LCW) would improve feed intake and milk production in lactating Holstein cows. There was a 3.6 percentage unit difference in NDF content and a 4.1 percentage unit difference in 30-h in vitro NDF digestion between the 2 corn hybrids. In trial 1, 40 cows (12 primiparous) ranging in milk production from 24.1 to 44.0 kg/d, following a 2-wk preliminary period, were used in a crossover design with 2-wk periods. Diets consisted of 45% corn silage (HCW or LCW), 10% alfalfa hay, and 45% concentrates. The DMI (25.4 vs. 24.2 kg/d) and 4% FCM yield (34.3 vs. 31.7 kg/d) were higher for cows fed the HCW diet compared with the LCW diet. When HCW was substituted for LCW on a DM basis, there was no relationship between pretrial milk yield (preliminary period) and subsequent response to HCW silage. In trial 2, 40 cows (8 primiparous) ranging in milk production from 20.6 to 49.0 kg/d, following a 2-wk preliminary period, were used in a crossover design with 2-wk periods. Diets consisted of the same LCW diet as trial 1 and a diet containing HCW at a concentration (40% of DM) that resulted in equal NDF content (30.8%) between the 2 diets (HCWN). The DMI (26.8 kg/d) was unaffected by diet, although there was a trend for greater DMI (% of BW) for cows fed the HCWN diet compared with LCW silage (4.24 vs. 4.12). Milk fat (3.91 vs. 3.79%) and 4% FCM yield (34.9 vs. 33.4 kg/d) were greater for cows fed HCWN vs. LCW diet. When HCW was substituted for LCW silage on an NDF basis, cows with greater milk production during the preliminary period had a greater milk response to HCW than lower-producing cows. Results of these trials supported our hypothesis that HCW corn silage results in greater DMI and milk yield than LCW silage, whether substitution occurs on a DM or NDF basis.

Animal Nutritional Physiological Phenomena↗

A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients.

Chimeric monoclonal antibody G250 (WX-G250) binds to a cell surface antigen found on >90% of renal cell carcinoma (RCC). A multicentre phase II study was performed to evaluate the safety and efficacy of WX-G250 in metastatic RCC (mRCC) patients. In all, 36 patients with mRCC were included. WX-G250 was given weekly by intravenous infusion for 12 weeks. Patients with stable disease (SD) or response were eligible to receive additional treatment for 8 weeks. None of the 36 enrolled patients experienced any drug-related grade III or IV toxicity. Only three patients had grade II toxicity possibly related to the study medication. In all, 10 patients had SD and received extended treatment. One complete response and a significant regression was observed during the follow-up of the treatment. Five patients with progressive disease at study entry were stable for more than 6 months after study entry. The median survival after treatment start was 15 months. The weekly schedule of WX-G250 was well tolerated. With a median survival of 15 months after the start of this treatment and two late clinical responses, WX-G250 seems to be able to modulate mRCC. To improve the activity of WX-G250-specific antibody-dependent cellular cytotoxicity and the clinical response rate, currently combinations of WX-G250 with cytokines are in phase II trials.

Adult↗

Prospective documentation and analysis of the pre- and early clinical management in severe head injury in southern Bavaria at a population based level.

Treatment of patients suffering from severe head injury is so far restricted to general procedures, whereas specific pharmacological agents of neuroprotection including hypothermia have not been found to improve the outcome in clinical trials. Albeit effective, symptomatic measures of the preclinical rescue of patients (i.e. stabilization or reestablishment of the circulatory and respiratory system) or of the early clinical care (e.g. prompt diagnosis and treatment of an intracranial space occupying mass, maintenance of a competent circulatory and respiratory system, and others) by and large constitute the current treatment based on considerable organizational and logistical efforts. These and other components of the head injury treatment are certainly worthwhile of a systematic analysis as to their efficacy or remaining deficiencies, respectively. Deficits could be associated with delays of providing preclinical rescue procedures (e.g. until intubation of the patient or administration of fluid). Delays could also be associated in the hospital with the diagnostic establishment of intracranial lesions requiring prompt neurosurgical intervention. By support of the Federal Ministry of Education and Research and under the auspices of the Forschungsverbund Neurotraumatology, University of Munich, a prospective system analysis was carried out on major aspects of the pre- and early clinical management at a population based level in patients with traumatic brain injury. Documentation of pertinent data was made from August 1998 to July 1999 covering a catchment area of Southern Bavaria (5.6 mio inhabitants). Altogether 528 cases identified to suffer from severe head injury (GCS < or = 8 or deteriorating to that level within 48 hrs) were enrolled following admission to the hospital and establishment of the diagnosis. Further, patients dying on the scene or during transport to the hospital were also documented, particularly as to the frequency of severe head injury as underlying cause of mortality. The analysis included also cases with additional peripheral trauma (polytrauma). The efficacy of the logistics and organization of the management was studied by documentation of prognosis-relevant time intervals, as for example until arrival of the rescue squad at the scene of an accident, until intubation and administration of fluid, or upon hospital admission until establishment of the CT-diagnosis and commencement of surgery or transfer to the intensive care unit, respectively. The severity of cases studied in the present analysis is evident from a mortality of far above 40% of cases admitted to the hospital, which was increased by about 20% when including prehospital mortality. The outcome data notwithstanding, the emerging results demonstrate a high efficacy of the pre- and early clinical management, as indicated by a prompt arrival of the rescue squad at the scene, a competent prehospital and early clinical management and care, indicative of a low rate of avoidable complications. It is tentatively concluded on the basis of these findings that the patient prognosis is increasingly determined by the manifestations of primary brain damage vs. the development of secondary complications.

Craniocerebral Trauma↗

Survival in nephroblastoma treated according to the trial and study SIOP-9/GPOH with respect to relapse and morbidity.

BACKGROUND: Recent Wilms' tumor (WT) trials and studies have tried to determine the minimal therapy needed for cure. The goal was survival without morbidity. PATIENTS AND METHODS: From January 1989 to March 1994 the German Society of Pediatric Oncology and Hematology registered 440 patients (median age 2.9 years; 231 male, 209 female) with WTs (preoperative chemotherapy 362) for therapy according to the International Society of Pediatric Oncology Trial and Study 9. Therapy for relapse depended on site of relapse and therapy already received. Follow-up included inquiries for morbidity. Prognostic factors for relapse and death were evaluated. RESULTS: Five-year survival of WTs was 89.5%; 98.2% (385 of 392) of survivors had a follow-up of 5 years (range 0.8-12.6; median 8). In non-anaplastic WTs, young age (<2 years) was of significance (P = 0.026) for a better survival. Non-anaplastic WTs (407 patients) had a 5-year survival of 92.3%, versus 48.5% in anaplastic WTs (33 patients), and a 5-year relapse-free survival of 87.6% versus 42.4%. Survival after relapse was significantly worse for anaplastic than for non-anaplastic WTs (residual 3-year survival 11.8% versus 54.3%; P <0.0001). In preoperatively treated WTs, anaplasia was a strong prognostic factor for death [relative risk (RR) 4.7], followed by poor response to preoperative therapy (RR 3.6), stage IV (RR 3.2) and abdominal stage III (RR 2.2). Low abdominal stages (<III) dominated (280 versus 82). In the 334 unilateral stage I-IV WTs (median age 3.2 years), diffuse anaplasia (21 patients) had a 5-year relapse-free survival of 38.1%, versus 58.4% in blastemal WTs (25 patients); survival was 42.9% in diffuse anaplasia versus 84% in blastemal WTs. None of 46 patients (median age 1.9 years; 91.3% stages I or II) with differentiated WTs (nine epithelial, 37 stromal) relapsed despite their non-response; two died (one therapy related, one due to bilaterization). In the 25 non-anaplastic bilateral WTs, differentiated cases (one epithelial, eight stromal, 33.3% abdominal stage III) were more frequent (P = 0.048) than in unilateral WTs (one stromal, abdominal stage III relapsed). In all, 52.9% of the 5-year survivors had received adriamycin (250-400 mg/m(2)), 25.7% radiation, 6.4% ifosfamide (24-30 g/m(2)) and 6.7% carboplatin plus etoposide. Abnormal parameters according to the National Cancer Institute score were seen in 18.9% during follow-up, but only 6.4% were treated for morbidity at the end of follow-up. Three WTs developed renal failure due to Drash syndrome, but none due to tumor therapy. After adriamycin 1.9% of WTs (9% of those receiving 400 mg/m(2)) required therapy for cardiac toxicity. CONCLUSIONS: Initial therapy should be more individualized, taking the above risk groups (age in non-anaplastic WTs, poor response, anaplasia, etc.) into account, as morbidity even after relapse therapy with ifosfamide, carboplatin and etoposide was not high. Milder therapy in low stages of differentiated and of well responding WTs should be tested.

Antineoplastic Combined Chemotherapy Protocols↗

Tissue at risk concept for endovascular treatment of severe vasospasm after aneurysmal subarachnoid haemorrhage.

OBJECTIVE: To report a case of severe vasospasm after subarachnoid haemorrhage (SAH) where "tissue at risk" was identified by magnetic resonance imaging (MRI), and to demonstrate the haemodynamic consequences with either resolution of the perfusion-diffusion mismatch by balloon angioplasty or evolution of an infarct. METHODS: A 45 year old women with SAH underwent surgical treatment of a ruptured middle cerebral artery (MCA) aneurysm. On day 3 she became obtunded and developed a right hemiparesis. Diffusion weighted (DWI) and perfusion weighted (PWI) imaging were done before and after transluminal balloon angioplasty (TBA) of multifocal proximal vasospasm. RESULTS: The initial MRI revealed no DWI lesion but PWI showed a severe perfusion deficit of 6.7 to 16.4 seconds in the complete left MCA territory. Digital subtraction angiography confirmed severe segmental narrowing of left C1 and M1. The spastic segments were successfully dilated by TBA. Follow up MRI showed that the PWI-DWI mismatch resolved in the anterior and middle MCA territory with no tissue infarction, whereas in the terminal dorsal MCA territory a severe mismatch remained and cerebral infarction evolved. CONCLUSIONS: PWI/DWI can identify tissue at risk for infarction in severe vasospasm following SAH. This may allow selection of patients for angioplasty and the monitoring of treatment effects.

Angioplasty, Balloon↗

Molecular characterization of porcine hyaluronidase genes 1, 2, and 3 clustered on SSC13q21.

Hyaluronidase genes (HYAL) encode hyaluronidase enzymes required for hyaluronan degradation. Both in humans and in mouse, clustered hyaluronidase genes have been identified. Here, the porcine hyaluronidase cluster consisting of genes HYAL1, HYAL2 and HYAL3 was characterized. The porcine cDNA sequences and proteins share homologies to human orthologs of 85 and 81% for HYAL1, 87 and 89% for HYAL2 and 86 and 83% for HYAL3, respectively. The porcine hyaluronidase proteins approximately share a 40% homology with each other. Furthermore, genes FUS1 and FUS2 were found within this cluster, which was assigned to SSC13q21. A total of seven SNPs were detected in the genes (four in HYAL1, two in HYAL2 and one in HYAL3). Three of the four SNPs in HYAL1 led to amino acid exchanges (C622G --> Asp24 to Glu; C633T --> Pro28 to Leu, and G1298T --> Ala250 to Ser). The amino acid replacements induce putative changes in the extended strand at Asp24, in the extended strand and the random coil at Pro28, and finally in the random coil and the alpha helix at Ala250. Frequency estimations for four SNPs located in genes HYAL1 and HYAL3 using animals (n = 295) of nine European and six Chinese pig breeds indicated several significant deviations. For example, there were no significant differences in allele frequencies between pigs representing breeds Hampshire and Jiangquhai at SNP C633T (HYAL1), but between Hampshire respectively Jiangquhai animals and Rongchang pigs. Analysis of the same breeds at SNP C588T (HYAL3) indicates significant differences between Hampshire and Jiangquhai respectively Rongchang, but not between Jiangquhai and Rongchang. The breed Göttingen Minipig displayed significant differences concerning two SNPs with respect to the other European pig breeds tested. For all three hyaluronidase genes, N-glycosylation sites are typical. For HYAL2 the lysosomal character was proven. The catalytic site responsible for HAase activity is conserved in the three enzymes. Expression of hyaluronidases was determined by RT-PCR and quantitative PCR. Broad gene expression was observed in different tissues for the three genes, respectively.

Amino Acid Sequence↗