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Biomedical subjects

J Beck

Publications and source records attributed to J Beck.

At least 37 records · Page 2Linked to original sources
PubMed2004

Characterization and chromosome localization of a processed pseudogene related to the bovine laminin receptor gene family.

A bovine BAC clone containing a processed laminin receptor pseudogene (LAMR1P) has been isolated and characterized. A 2,901-bp sequence was produced from the clone, of which 1,187 bp represented seven identifiable exon-like domains, but no intervening sequences. The pseudogene sequence reveals several transversions and transitions, as well as insertions and deletions. A premature stop codon motif is present at nucleotide position 115 located in the exon-2-like domain. Physical mapping of the gene was performed by FISH and RH panel mapping and assigned LAMR1P to BTA4q24-->q26 with the closest linkage to BM6458 (19 cR, LOD score of 11.6). The functional laminin receptor putatively plays an important role in the transmission of bovine spongiform encephalopathy (BSE). In this process, the receptor supposedly acts as the binding site for prion proteins to enter mammalian cells. Considering the existence of several human laminin receptor pseudogenes forming a complex family, any knowledge of even pseudogene sequences might be helpful to isolate the functional bovine laminin receptor gene.

Animals↗
PubMed2003

Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.

The inhibition by imatinib of the cytochrome p450 3A4 isoenzyme may reduce the CYP3A4-mediated metabolic clearance of clinically important coadministered drugs. The main purpose of this study was to evaluate the effect of the coadministration of imatinib on the pharmacokinetics of simvastatin, a probe CYP3A4 substrate. In total, 20 patients with chronic myeloid leukaemia received an oral dose of 40 mg of simvastatin on study day 1. On study days 2-7, each patient received 400 mg of imatinib once daily orally and on study day 8, 400 mg imatinib together with 40 mg of simvastatin was given. Blood levels of simvastatin were measured predose and for 24 h postdose on study days 1 and 8. Two additional blood samples were taken for imatinib pharmacokinetic (PK) assessment on day 8 before, and 24 h after, imatinib administration. Imatinib increased the mean maximum concentration (C(max)) value of simvastatin two-fold and the area under concentration-time curve (AUC ((0-inf))) value 3.5-fold (P<0.001) compared with simvastatin alone. There was a statistically significant decrease in total-body clearance of drug from the plasma (CL/F) with a mean reduction of 70% for simvastatin (P<0.001): the mean half-life of simvastatin was prolonged from 1.4-2.7 h when given together with imatinib. No changes in imatinib PK parameters were found when given concomitantly with simvastatin. In conclusion, the coadministration of imatinib at steady state with 40 mg simvastatin increases the exposure (C(max) and AUCs) of simvastatin significantly (P<0.001) by two-three-fold. Caution is therefore required when administering imatinib with CYP3A4 substrates with a narrow therapeutic window. The coadministration of simvastatin with imatinib (400 mg) was well tolerated and no major safety findings were reported in this study.

Administration, Oral↗
PubMed2003

Comparison of exhaled breath condensate from nasal and oral collection.

BACKGROUND: Analysis of exhaled breath condensate may provide new insights into pulmonary inflammatory processes. A new collection method via suction of nasally expired air especially suitable for younger children was presented recently. Here we compare this nasal suction method with the more widely used oral collection method regarding the amount of condensate collected as well as the concentrations of hydrogen peroxide (H2O2), nitrite and nitrate, respectively. MATERIALS AND METHODS: Exhaled breath condensate was collected from 11 healthy adults for the measurements of the amount of condensate and H2O2 concentration and from 17 children for the measurements of nitrite and nitrate. Condensate was collected via nasal suction and oral exhalation from each subject. RESULTS: Overall, no differences between both collection methods were found for all variables assessed except the concentration of H2O2, whereas the latter closely correlated (Spearman r = 0.88, p = 0.0007) between both collection methods. No correlation was found for the amount of condensate collected and the concentration of nitrite and nitrate. The Bland-Altman limits of agreement scattered over a wide range with clinical impact, proving significant differences between both collection methods for all variables measured. CONCLUSIONS: Although nasal and oral collection method proved again suitable for the collection of exhaled breath condensate, the variability of the results obtained precludes the interchangeable usage of the inflammatory markers assessed here.

Adult↗
PubMed2003

[Fabry's disease, glomerulonephritis with crescentic and granulomatous interstitial nephritis. Case of one family].

A 26-year-old female patient was admitted to the hospital because of fever of unknown origin and renal failure. Diagnosis of Fabry's disease, extracapillary proliferative (crescentic) glomerulonephritis and granulomatous interstitial nephritis was made by histological, immunohistochemical and electron microscopical diagnosis in a kidney biopsy and confirmed by further investigations. Years ago the brother of the patient had a kidney biopsy diagnosed as metabolic disease. The re-evaluation of this biopsy confirmed Fabry's disease while in this patient an association with tubulointerstitial nephritis occurred. To our knowledge this is the first family with two members having Fabry's disease combined with further kidney diseases.

Adult↗
PubMed2003

Difference in configuration of ruptured and unruptured intracranial aneurysms determined by biplanar digital subtraction angiography.

There is an ongoing discussion about the risk of bleeding from unruptured intracranial aneurysms. Management guidelines were developed recently and some of the recommendations for decision making are based on the anatomical configuration of the aneurysm. The common assumption is that the presence of multiple lobes or a daughter sac indicates a higher risk of rupture. We have investigated the anatomical configuration of ruptured and unruptured intracranial aneurysms using biplanar digital subtraction angiography (DSA). The objective was to determine, whether there was a difference between ruptured and unruptured aneurysms regarding lobulation, the presence of a daughter sac or the shape as measured by the height/neck ratio. Biplanar DSA images of 124 patients were retrospectively analyzed. A total of 53 unruptured and 94 ruptured aneurysms were found (=147 aneurysms in total). Aneurysms of less than 10 mm diameter accounted for 82% of all aneurysms. Overall, 10% of unruptured aneurysm showed a multilobular appearance on DSA compared with 20% of ruptured aneurysms (Fisher's exact test, p=0.10). In the 5-9 mm aneurysm group, multiple lobes were found significantly more frequent in ruptured aneurysms (26% vs. 4%, Fisher's exact test, p<0.05). A height/neck ratio of less than 1.5 was not found in unruptured aneurysms (0/26) but in 21% (12/57) of ruptured aneurysms (p<0.05). Our data provide scientific support for using morphological features for the decision making process in the management of unruptured intracranial aneurysms. An irregular multilobar appearance was significantly more common in aneurysms of 5-9 mm size that ruptured.

Aneurysm, Ruptured↗
PubMed2003

Safety evaluation in chickens of candidate human vaccines against potential pandemic strains of influenza.

Two candidate formalin-inactivated vaccines, made from high-growth reassortant viruses with the HA and NA genes from avian viruses in a background of genes derived from A/Puerto Rico/8/34 (PR8), were prepared against H5N1 and H9N2 subtypes (designated as H5N1/PR8 and H9N2/PR8, respectively). These viruses bear the genotypes, antigenicity, and attenuation in mouse models that are desirable in candidate vaccines. The pathogenicity of the newly generated avian-human reassortant vaccine viruses was also evaluated in chickens. Neither H5N1/PR8 nor H9N2/PR8 were highly pathogenic for chickens. No clinical signs, gross legions, or histological lesions were observed in chickens that were administered H5N1/PR8 either intranasally (i.n.) or intravenously (i.v.), and virus was not detected in oropharyngeal or cloacal swabs. When H9N2/PR8 was administered i.n., no clinical signs, gross lesions, or histological lesions were observed and no virus was detected in cloacal swabs. However, virus was isolated at low titer from oropharyngeal swabs of all eight chickens. Although no clinical signs were observed when H9N2/PR8 was administered i.v., mild tracheitis was seen in one of two chickens. Moderate amounts of antigen were observed in tracheal respiratory epithelium, and low titers of virus were recovered from oropharyngeal and cloacal swabs of some chickens. In summary, both reassortant vaccine viruses replicated poorly in chickens. These studies suggest that these candidate vaccine viruses carry a low risk of transmission to chickens.

Animals↗
PubMed2002

Safety and efficacy of STI-571 (imatinib mesylate) in patients with bcr/abl-positive chronic myelogenous leukemia (CML) after autologous peripheral blood stem cell transplantation (PBSCT).

We examined safety and efficacy of STI-571 in 24 bcr/abl-positive patients with CML post PBSCT. At start of STI-571 therapy, nine patients presented in blast crisis (BC) or in accelerated phase (AP), and 15 in chronic phase (CP). Patients were evaluated for hematologic, cytogenetic and molecular response, survival and toxicity. In general, STI-571 was well tolerated in this heavily pretreated group of patients with a non-hematologic and hematologic toxicity profile similar to that observed in a previous phase I trial at comparable doses. Five of nine patients with CML in transformation (AP, BC) were evaluable for hematologic response. Two of five patients had transient reductions in WBC and blasts, and three patients achieved a sustained hematologic response (>4 weeks). Cytogenetic analysis in these patients revealed numerical and/or structural responses. In CML chronic phase, STI-571 induced complete hematologic responses in all patients and major cytogenetic responses in 61% of patients with a complete cytogenetic response rate of 46%. This report indicates that STI-571 is a safe and effective drug in heavily pretreated patients. No apparent additional side-effects were noted in this patient cohort. The high rate of complete hematologic and complete cytogenetic responses in CP patients is remarkable, as intensive treatment approaches plus IFN-alpha failed to be efficient in achieving long-term stabilization of CML in this patient cohort.

Adult↗
PubMed2002

A phase I study of oral uracil-ftorafur plus folinic acid in combination with weekly paclitaxel in patients with solid tumors.

INTRODUCTION: Ftorafur is an orally available prodrug of 5-fluorouracil (5-FU). Its combination with uracil in a molar ratio of 1:4 (UFT) increases the 5-FU concentration in tumor cells compared with ftorafur alone. Paclitaxel has a broad spectrum of activity against solid tumors and synergic effects with UFT have been demonstrated in vitro. A phase I study was performed to determine the maximum tolerated dose of the combination of UFT and paclitaxel in patients with advanced solid tumors. STUDY DESIGN: UFT and folinic acid were applied at 300 mg/m2/day and 90 mg/day, respectively, on days 1-28, repeated on day 36. Paclitaxel was applied on days 1, 8, 15 and 22 of each cycle. The starting dose of paclitaxel was 50 mg/m2 and escalation in 10 mg/m2 steps was performed up to 100 mg/m2 weekly. RESULTS: Forty-seven consecutive patients with various solid tumors have been included in six different dose levels. One hundred and thirty cycles have been applied. The treatment was well tolerated overall. Most frequently encountered adverse effects were gastrointestinal and hematological toxicity (diarrhea CTC 3/4 in 6% of patients, anemia in 11%, leukocytopenia in 9%, polyneuropathy in 9%, fatigue in 11%, other in 6%). Partial remissions were observed in 28% of patients. CONCLUSION: Owing to the lack of overlapping toxicities, UFT/folinic acid plus paclitaxel can be combined at doses of proven single agent activity. Side effects are mainly attributable to the gastrointestinal toxicity of UFT and to the neuro- and hematotoxicity of paclitaxel. The recommended doses for phase II studies are 300 mg/m2 of UFT plus 90 mg of folinic acid on days 1-28, and 90 mg/m2 of paclitaxel weekly.

Administration, Oral↗
PubMed2002

A new top-loading venous bag provides vacuum-assisted venous drainage.

A new venous bag has been developed, prototyped, and tested. The new bag has its inlet, outlet purge, and infusion tubes extending upward from the top of the bag, and are threaded through, bonded to, and sealed within a flat rigid top plate. This design allows the bag to be hung from its top plate by its tubes. It also allows the bag to be: 1) dropped into or removed from its holder, as is done with existing hard-shell reservoirs so that its weight pulls it into the holder without the need for eyelets and hooks and 2) placed closer to the floor so that gravity drainage is facilitated. The V-Bag (VB) is easily sealed within an accompanying rigid housing. Once sealed, vacuum applied to the housing is transmitted across the flexible walls of the bag to the venous blood. Thus, vacuum-assisted venous drainage (VAVD) is obtained as it is with a hard-shell reservoir, but without any contact of air with the blood. Bench tests, using a circuit that simulated the venous side of the cardiopulmonary bypass (CPB) circuit, showed that applying suction to the housing increased venous flow, and the fractional increase in flow was not a function of the venous cannula, but of the level of vacuum applied. In the gravity drainage mode, the bubble counts at the outlet of the V-Bag compared to two other bags were lower at any pumping condition. When used in the VAVD mode, bubble counts were two orders of magnitude lower than when using kinetically assisted venous drainage (KAVD) with a centrifugal pump. Results obtained with the VB suggest its clinical usefulness.

Cardiopulmonary Bypass↗
PubMed2002

Utilization of Bt corn residues by grazing beef steers and Bt corn silage and grain by growing beef cattle and lactating dairy cows.

Three experiments were conducted to evaluate the impact of the Bacillus thuringiensis (Bt)-11 transformation event in two parental corn hybrids differing in date of maturity on beef and dairy cattle performance. Sixteen lactating Holstein dairy cows in replicated 4 x 4 Latin squares were assigned to four diets in a 2 x 2 factorial arrangement: Bt vs non-Bt trait and early- vs late-maturing corn hybrids. The diets contained 40% of the test corn silage plus 28% corn grain from the same corn hybrid (DM basis). There was no effect of the Bt trait on efficiency of milk production, ruminal pH, acetate:propionate ratio, or in situ digestion kinetics of NDF. The early-maturing corn hybrids resulted in greater total VFA concentrations in the rumen and efficiency of 4% fat-corrected milk production than the later-maturing hybrids (P < 0.05). Sixty-seven steer calves were used in a 70-d corn residue grazing trial for the late-maturing corn hybrids only. Daily BW gain of steers was similar for those grazing Bt and non-Bt corn residues, and the steers exhibited no grazing preference between Bt and non-Bt corn residue. One hundred twenty-eight steer calves were assigned to four silage-based growing diets in a 2 x 2 factorial arrangement: Bt vs non-Bt trait and early- vs late-maturing corn hybrids. The diets contained 90% corn silage and 10% supplement (DM basis). The DMI was higher for steers fed Bt compared with non-Bt hybrids (P < 0.02). An interaction (P < 0.03) was observed for feed efficiency between hybrid genotype and incorporation of the Bt trait. Feed efficiency was greater (P < 0.05) for steers fed the later-maturing non-Bt hybrid compared with the later-maturing Bt hybrid; however, feed efficiency was similar between steers fed early-maturing Bt and non-Bt corn silages. Steers fed the early-maturing hybrid gained 11% faster and were 7% more efficient compared with those fed the late-maturing hybrid. These latter results agree with the dairy experiment in which the early-maturing hybrid resulted in 5% greater efficiency of milk production than the later-maturing corn hybrid. In all experiments, incorporation of the Bt trait into corn had no consistent effect on cattle performance. In addition, background genetics of the corn hybrids appeared to have a more consistent impact on performance than did presence of the Bt trait.

Animal Feed↗
PubMed2001

Sporadic--but not variant--Creutzfeldt-Jakob disease is associated with polymorphisms upstream of PRNP exon 1.

Human prion diseases have inherited, sporadic, and acquired etiologies. The appearance of the novel acquired prion disease, variant Creutzfeldt-Jakob disease (vCJD), and the demonstration that it is caused by the same prion strain as that causing bovine spongiform encephalopathy, has led to fears of a major human epidemic. The etiology of classical (sporadic) CJD, which has a worldwide incidence, remains obscure. A common human prion-protein-gene (PRNP) polymorphism (encoding either methionine or valine at codon 129) is a strong susceptibility factor for sporadic and acquired prion disease. However, a quantitative-trait-locus study of prion incubation periods in mice has demonstrated an important factor that is close to Prnp but is independent of its coding sequence or that of the nearby prion-like doppel gene (Prnd). We have analyzed the PRNP locus for such tightly linked susceptibility factors. Fifty-six polymorphic sites have been identified within 25 kb of the PRNP open reading frame, including sites within the PRNP promoter and the PRNP 3' untranslated region. These have been characterized in 61 Centre d'Etude du Polymorphisme Humain (CEPH) families, demonstrating extensive linkage disequilibrium around PRNP and the existence of 11 major European PRNP haplotypes. Haplotype frequencies estimated in healthy U.K. control individuals were very similar to those deduced in the CEPH families. A common haplotype was overrepresented in patients with sporadic CJD (sCJD). Through use of a log-linear modeling approach to simultaneously model Hardy-Weinberg and linkage disequilibria, a significant independent association was found between sCJD and a polymorphism upstream of PRNP exon 1 (P=.005), in addition to the strong susceptibility conferred by codon 129 (P=2x10(-8)). However, although our sample size was necessarily small, no association was found between these polymorphisms and vCJD or iatrogenic CJD, in keeping with their having distinct disease mechanisms. In addition, there was no evidence of a PRNP founder effect in the first reported geographical cluster of vCJD.

3' Untranslated Regions↗
PubMed2001

Electrical activity of the diaphragm during pressure support ventilation in acute respiratory failure.

We compared crural diaphragm electrical activity (EAdi) with transdiaphragmatic pressure (Pdi) during varying levels of pressure support ventilation (PS) in 13 intubated patients. With changing PS, we found no evidence for changes in neuromechanical coupling of the diaphragm. From lowest to highest PS (2 cm H(2)O +/- 4 to 20 cm H(2)O +/- 7), tidal volume increased from 430 ml +/- 180 to 527 ml +/- 180 (p < 0.001). The inspiratory volume calculated during the period when EAdi increased to its peak did not change from 276 +/- 147 to 277 +/- 162 ml, p = 0.976. Respiratory rate decreased from 23.9 (+/- 7) to 21.3 (+/- 7) breaths/min (p = 0.015). EAdi and Pdi decreased proportionally by adding PS (r = 0.84 and r = 0.90, for mean and peak values, respectively). Mean and peak EAdi decreased (p < 0.001) by 33 +/- 21% (mean +/- SD) and 37 +/- 23% with the addition of 10 cm H(2)O of PS, similar to the decrease in the mean and peak Pdi (p < 0.001) observed (34 +/- 36 and 35 +/- 23%). We also found that ventilator assist continued during the diaphragm deactivation period, a phenomenon that was further exaggerated at higher PS levels. We conclude that EAdi is a valid measurement of neural drive to the diaphragm in acute respiratory failure.

Acute Disease↗
PubMed2001

Autopsy-confirmed familial early-onset Alzheimer disease caused by the l153V presenilin 1 mutation.

BACKGROUND: Three affected individuals are described from a small English kindred with early-onset autosomal dominant familial Alzheimer disease (FAD) caused by a leucine-to-valine change at codon 153 (L153V) of the presenilin 1 (PSEN1) gene. METHODS: Clinical information on the pedigree was collected directly from family members and from hospital records. Samples of DNA were screened by means of direct sequencing of all coding exons of PSEN1. One patient underwent neuropathological examination. RESULTS: Mean age at onset of symptoms was 35.3 years (95% confidence interval [CI], 34.6-36.0 years); at death, 44.0 years (95% CI, 39.1-48.9 years). Mean duration of illness was 8.3 years (95% CI, 4.7-11.9 years). Myoclonus was a late feature in 1 patient; seizures were not reported in any subjects. Spastic paraparesis and extrapyramidal signs were absent. The neuropsychometric profile of 1 patient showed relatively preserved naming skills in the setting of global cognitive deficits. Results of neuropathological examination demonstrated the signature lesions of Alzheimer disease and the presence of occasional cortical Lewy bodies. CONCLUSIONS: The PSEN1 L153V mutation lies in the main mutation cluster of PSEN1 in the second transmembrane domain. It causes early-onset FAD with clinical features similar to those of other reported FAD pedigrees.

Adult↗
PubMed2001

Correlates of knowledge of one's blood pressure and cholesterol levels among older members of a managed care plan.

We examined factors predicting knowledge of one's blood pressure, total cholesterol, and high-density lipoprotein levels (HDL) among older persons who reported a recent blood pressure or cholesterol test. Data come from a self-administered, health risk assessment that was mailed to health plan members, age 55 and older, in a Santa Barbara, California medical group. Despite their universal access to health care and high levels of reported compliance with preventive health care screening practices, 41%, 49%, and 77% of respondents reported that they did not know their blood pressure, cholesterol, or HDL levels, respectively. After controlling for potential confounders, age and low income were inversely associated with the respondents' ability to report each level. In addition, current smoking and obesity were inversely associated with self-reported knowledge of both cholesterol measures. Persons taking medication for hypertension or hypercholesterolemia were much more likely than those not taking medication to be able to report their blood pressure and cholesterol levels. Except for persons currently undergoing treatment for related conditions, these results suggest that a substantial proportion of the older persons at high risk for cardiovascular disease do not know their levels of these important biological risk factors. This lack of knowledge has important implications for public health education, and may hinder risk-reduction efforts among the elderly.

Aged↗