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R Becker

Publications and source records attributed to R Becker.

At least 145 records · Page 8Linked to original sources
PubMed1996

Static electricity as a mechanism of bacterial transfer during endoscopic surgery.

BACKGROUND: During endoscopic surgery it is often difficult to describe the procedure based on the video screen image. To compensate, the surgeon may point to the monitor to define more exactly what is intended by the verbal cues. Experiments were conducted to determine if the electrostatic field of the monitor could serve as a mechanism of bacterial transfer from the video screen to the patient. METHODS: A gloved hand traversed the monitor in a standard fashion at varying distances from the screen. The fingertips were then cultured onto blood agar plates. RESULTS: Bacterial growth occurred on 28 of the 30 cultures taken at 1, 2, and 4 cm from the video screen. No growth occurred on any of the 8 cm cultures, or the 20 controls. The number of bacterial colonies cultured from the glove was inversely related to the distance between the glove and video screen (p < 0.001). CONCLUSIONS: We conclude the electrostatic field generated by the video monitor could serve as a mechanism of bacterial contamination during endoscopic surgery. Also, we conclude that placing the gloved hand in proximity to the video monitor screen during an operative procedure constitutes a break in sterile technique and must be avoided.

Bacteria↗
PubMed1996

Standardized mitotic counts in breast cancer. Evaluation of the method.

Twenty-one pathologists and technicians participated in a study evaluating the variation present in mitotic counts for prognostication of breast cancer. The participants counted the mitotic figures in 20 breast cancer samples from ten high power fields (mitotic activity index, MAI, giving the results in mitotic figures per 10 fields) and also made a correction for field size and area fraction of the neoplastic epithelium to get the standardized mitotic index (volume fraction corrected mitotic index, or M/VV index, giving the result in mitotic figures per square mm of neoplastic epithelium). The difference in variation between the two methods was not big, but the standardized mitotic index (SMI) showed consistently smaller variation among all participants and different subgroups. Experienced pathologists had the highest variation in mitotic counts, and specially trained technicians, the lowest. The efficiency of the mitotic counts in grading (the grading efficiency) was used to evaluate the mitotic counts. In groups without special training for mitotic counts the mean grading efficiency was lower (experienced and training pathologists both on average had the potential to grade 88% of the cases correctly) than in the group specially trained for the purpose (trained technicians had the potential to grade 95% of the cases correctly). Among the specially trained technicians, the grading efficiency was of the same magnitude as the grading efficiency achieved in determining the S-Phase fraction of cells from paraffin embedded breast cancers by flow cytometry in different laboratories. The results suggest that special training is helpful in making mitotic counts more reproducible, and that in trained hands, the mitotic counts give results comparable to more sophisticated methods of determining proliferative activity in breast cancer.

Breast Neoplasms↗
PubMed1996

Ha-rasVal12 but not p53Ser247 leads to a significant neoplastic transformation rate of the putative rat liver stem cells (oval cell).

In order to test the controversially discussed hypothesis that oval cells are part of a liver stem cell compartment and can give rise to cholangiocellular as well as hepatocellular carcinomas in the course of liver carcinogenesis, we transfected an oval cell line established in our laboratory with an oncogenically activated genomic Ha-ras clone (pUC EJ 6.6), carrying a valine at position 12 instead of the wild-type glycine, or a rat p53 cDNA mutated by site-directed mutagenesis at codon 247, which corresponds to codon 249 in the human p53. This codon is of particular interest since it represents a mutation hotspot observed in hepatocellular carcinoma especially in regions with high aflatoxin B1 exposure. Independent Ha-rasVal12 and p53Ser247 recombinant clones were subcutaneously injected into syngeneic newborn rats and the resulting tumours were analysed histopathologically. Each of two p53Ser247 clones gave negligible tumour yields (one tumour out of 13 injected animals), whereas each of two Ha-rasVal12 clones gave marked tumour yields (four tumours out of 13 and seven out of 12 treated animals, respectively). In addition, the p53Ser247-induced tumours appeared only after 11 months and were small, whereas the Ha-rasVal12-induced tumours appeared already after 6-8 weeks and grew rapidly. Histopathological analysis of the tumours revealed only undifferentiated carcinomas. Interestingly, one tumour that arose upon injection of Ha-rasVal12-transfected cells stained positive for albumin, showing at least a partial hepatocytic differentiation.

Animals↗
PubMed1996

Iron and copper nutrition-dependent changes in protein expression in a tomato wild type and the nicotianamine-free mutant chloronerva.

The nicotianamine-deficient mutant chloronerva resembles phenotypically an Fe-deficient plant despite the high accumulation of Fe in the leaves, whereas if suffers from Cu deficiency in the shoot. Two-dimensional electrophoretic separation of proteins from root tips and leaves of wild-type Lycopersicon esculentum Mill. cv Bonner Beste and the mutant grown with and without Fe showed a number of consistent differences. In root tips of the Fe-deficient wild type and the Fe-sufficient as well as the Fe-deficient mutant, the expression of glyceraldehyde-3-phosphate dehydrogenase, formate dehydrogenase, and ascorbate peroxidase was increased. In leaves of the Fe-sufficient and -deficient mutant, Cu-containing chloroplastic and cytosolic superoxide dismutase (Cu-Zn) and plastocyanin (Cu) were nearly absent. This low plastocyanin content could be restored by supplying Cu via the xylem, but the superoxide dismutase levels could not be increased by this treatment. The differences in the protein patterns between wild type and mutant indicate that the apparent Fe deficiency of mutant plants led to an increase in enzymes involved in anaerobic metabolism as well as enzymes involved in stress defense. The biosynthesis of plastocyanin was diminished in mutant leaves, but it was differentially induced by increased Cu content.

Amino Acid Sequence↗
PubMed1996

Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?

Despite recent advances in the molecular genetics of Alzheimer's disease (AD), several fundamental questions concerning risk of illness are unresolved, namely, if Mendelian factors account for the incidence of the disease, and if AD is an inevitable consequence of the aging process. This study was designed to address these issues and other aspects of familial aggregation of the disorder. A consecutive sample of 1,694 patients who met criteria for a diagnosis of probable or definite AD were ascertained in 13 centers participating in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) project. Lifetime risk and age at onset of AD among various strata of 12,971 first-degree relatives was estimated using survival analysis procedures. The lifetime risk of AD in first-degree relatives was 39.0% +/- 2.1% by age 96 years. Age-specific risk of AD declined after age 90 and the data set included 61 apparently unaffected persons who survived to age 96 without becoming demented. Female relatives had a higher risk of AD than male relatives at all ages. By age 80, children of conjugal AD couples had a cumulative risk of 54%, 1.5 times greater than the sum of the risks to children having affected mothers or fathers, and nearly 5 times greater than the risk to children having normal parents. Children of affected fathers had a cumulative risk that was 1.4 times the corresponding risk to children of affected mothers. Risk assessment in early-onset and late-onset families, using various strategies for determining the age cut-off, yielded contradictory results. These data suggest the following: (1) the lifetime risk among relatives does not support a simple autosomal dominant inheritance pattern of disease; (2) women are innately more susceptible to AD than men; (3) the proportion of hereditary cases may be higher in men than women; (4) distinction between early- onset and late-onset forms of AD has little meaning in the absence of a biological marker; (5) the risk of AD decreases after age 90; and (6) AD therefore may not be an inevitable concomitant of the aging process, a conclusion that has profound implications for basic and applied AD research. The age- and sex-specific lifetime risks derived from this study are sufficiently robust to be a reliable source of information for counseling relatives of AD patients.

Age Factors↗
PubMed1996

[Examinations with the Cardiff Acuity Test].

Recently, a new preferential looking (PL) test has been presented for measuring visual acuity in infants and young children (Cardiff Acuity Test, CAT). The PL target is a schematic vanishing picture composed of isoluminant lines with different spatial orientations. Fifty-three healthy children (4-34 months, group 1), 28 (4-35 months) children at risk for amblyopia due to strabismus (group 2), 19 healthy subjects, and 157 patients (group 3) were tested with the CAT. In group 2 the CAT was compared with the fixation preference test. In group 3 the CAT was compared with a recognition test (Landolt C test). In group 1 the interocular difference of the CAT data was a maximum of 1 dB (70% 0 dB, 30% 1 dB, 1/3 so-called octave). Thus, an interocular difference of > 1 dB was considered to be suggestive of monocular or asymmetrical visual impairment. The maximum value 6/6 was frequently achieved (RE 44%, LE 36%, > 18 months RE 57%, LE 46%). In group 2 only 20% of the monolateral strabismic children showed an interocular difference > 1 dB in the CAT. In group 3 we found significant correlations between the CAT and Landolt acuity. A ratio of about 1.7/1 between CAT and Landolt acuity remained constant in cataract eyes as compared to healthy eyes. In amblyopic eyes due to strabismus this ratio was 3.7/1. Thus, amblyopia was underestimated with the CAT. Without limiting the examination distance, interocular differences > 1 dB in the CAT occurred in 52% of the strabismic amblyopic patients (potential sensitivity). At a distance of 1 m this rate decreased to 22% (real sensitivity). In conclusion, the CAT definitely lacks sensitivity for strabismic amblyopia. The data suggest that the real sensitivity could be improved by using higher spatial frequencies. The use of familiar shapes instead of gratings such as PL targets affects cooperation favorably in 12- to 36-month-old children.

Amblyopia↗
PubMed1996

[New aspects of defibrillator therapy].

The implantable cardioverter defibrillator is currently a therapy of first choice in patients with malignant therapy refractory ventricular arrhythmias. The occurrence of malignant ventricular tachycardia cannot be suppressed by the defibrillator but is treated using antitachycardia pacing, cardioversion or defibrillation. During recent years, electrodes, defibrillation shockforms and device size were continuously optimized. The development of transvenous lead systems resulted in significant reduction of perioperative mortality and morbidity. With the availability of biphasic shockforms and single-lead unipolar devices marked reduction of defibrillation thresholds were achieved and transvenous lead systems without subcutaneous could be implanted. Improvements in device technology lead to smaller devices which can be implanted subpectorally even using local anaesthesia. But there is still enormous potential to develop an ideal antiarrhythmic device. One of the most significant problems of the defibrillator therapy represents the delivery of inappropriate shocks due to supraventricular tachyarrhythmias and sinustachycardia. To solve this problem different approaches are currently developed. Extension in memory allows to store several data logs and intracardiac electrograms for individual adapted adjustment of the therapy. Intracardiac electrogram width measurement for discrimination between ventricular and supraventricular arrhythmias is currently evaluated. Dual-chamber arrhythmia discrimination algorithms of an integrated dual-chamber pacemaker and defibrillator are clinically studied. Hemodynamic sensors for determining the severity of the arrhythmia are currently under experimental evaluation. The combination of latissimus dorsi dynamic cardiomyoplasty and ICD therapy may improve survival in patients with severely depressed left ventricular function and malignant ventricular arrhythmias. Several randomized prospective trials are currently in progress potentially expanding the use of the ICD in patients at risk for sudden cardiac death. The high costs of defibrillator therapy is still a limitation for its use, but higher production figures and advancing technology could reduce the system prize.

Anti-Arrhythmia Agents↗
PubMed1995

4,5-Dihydro-3-(methanesulfonamidophenyl)-1-phenyl-1H-2,4-benzodiazepines: a novel class III antiarrhythmic agents.

A series of 4,5-dihydro-3-[2-(methanesulfonamidophenyl)ethyl]-1-phenyl- 1H-2,4-benzodiazepines has been identified as potential antiarrhythmic agents that interact at the delayed rectifier myocardial potassium channels (IKr) and prolong the ventricular effective refractory period (ERP) in rabbit isolated Langendorff heart preparations. Structure-activity relationship (SAR) studies based upon prolongation of ERP indicate that placement of the sulfonamido group is important for potent activity in this model. Furthermore, methanesulfonamido has enhanced activity over its ethyl or trifluoromethyl analogs. Slightly greater activity was observed in compounds that had a heteroatom in the ethyl bridge that connects the methanesulfonamidophenyl to the benzodiazepine. Further incremental improvements in activity were noted when the 1-phenyl ring was substituted with a variety of substituents. Chirality of the compounds of interest in this series does not appear to influence activity in this model. Several of these compounds were chosen for advanced evaluation, and all possess high selectivity for blockade of potassium current in hearts relative to other ion channels. In addition, these compounds prolong cardiac refractoriness in dogs following oral dosing. Thus, these agents may represent potential new class III agents, but with the potential liability of myocardial IKr blockers.

Animals↗
PubMed1995

Sulfonylureas and sulfonylcarbamates as new non-tetrazole angiotensin II receptor antagonists. Discovery of a highly potent orally active (imidazolylbiphenylyl)sulfonylurea (HR 720).

The synthesis and pharmacological activity of new potent nonpeptide non-tetrazole angiotensin II (AII) receptor antagonists are described. These compounds are 4-thioimidazole derivatives linked on N1 to a biphenylsulfonyl fragment by a methylene spacer. Different acidic sulfonamides such as sulfonylureas 12, sulfonylcarbamates 15, sulfonylamides 16, and sulfonylsulfonamides 17 have been investigated as replacements to the known potent tetrazole moiety at the 2'-biphenyl position. Their activity were evaluated by AII receptor binding assay as well as by in vivo (i.v. and po) assays such as inhibition of the AII-induced pressor response in pithed rats. Most of the synthesized sulfonyl derivatives showed nanomolar affinity for the AT1 receptor subtype. The N-propylsulfonylurea 12d and the ethyl sulfonylcarbamate 15b as representative members of this series exhibited high oral activity in the pithed rat model with ID50 values of 0.38 and 0.4 mg/kg, respectively. Structure-activity relationships on the imidazole ring linked to the methylbiphenyl N-propylsulfonylurea fragment demonstrated similar features to those found in the corresponding tetrazole series. For both class of compounds, the linear butyl chain in position 2 and a carboxylic acid in position 5 were important for high in vitro and in vivo activity. In most cases, replacement of the carboxylic acid was detrimental to in vivo activity while maintaining the in vitro binding affinity. Introduction of a methylthio group in position 4 was found to enhance oral activity compared to compounds with chloro or other alkylthio, (polyfluoroalkyl)thio, and arylthio groups. 2-Butyl-4-(methylthio)-1-[[2'- [[[(propylamino)carbonyl]amino[sulfonyl](1,1'-biphenyl)-4- yl]methyl]-1-H-imidazole-5-carboxylic acid (12d) as the most promising example of the series was synthesized as its dipotassium salt (50, HR 720). This compound 50 inhibited the specific binding of [125I]-AII to rat liver membranes with an IC50 value of 0.48 nM. In vivo, 50 dose-dependently inhibited the AII-induced pressor response in normotensive pithed rats (ID50 = 0.11 mg/kg i.v. and 0.7 mg/kg po). In addition, this compound produced a marked and long-lasting decrease in blood pressure in high renin animal models and proved to be superior to the corresponding tetrazole 45 as well as to DuP 753 or its active metabolite EXP 3174. Compound 50 has been selected for in-depth investigations and is currently undergoing phase II clinical trials.

Administration, Oral↗
PubMed1995

[Acute torsion of hydrosalpinx. 2 cases after laparoscopic sterilization].

We report on two laparoscopically sterilised patients who presented with increasing lower abdominal pain and sonographically proven adnexal masses. The first patient, who had been sterilised two years ago, underwent primary laparotomy. The mass was found to correspond to the cystically altered distal part of the right sterilised tube being torquated twice. Standard salpingectomy was performed. On the second patient, sterilised ten years before presentation at our clinic, we performed laparoscopy because of the suspected diagnosis of a pyosalpinx. In this case we found a torsion of the ampullary part of the left tube, which was subsequently removed by laparoscopy.

Adult↗
PubMed1995

[Fetal macrosomy and hydramnios. Intrauterine symptoms of a combination of Sturge-Weber-Krabbe- and Klippel-Trenaunay syndrome].

The authors report on a case where the Klippel-Trenaunay symptom complex was combined with a Sturge-Weber-Krabbe syndrome, which, however, was only noticeable during pregnancy by fetal macrosomy and hydramnios. The child was delivered on term by Caesarean section and presented no paediatric problems; however, during the first few years of its life mental retardation became clearly evident.

Adult↗
PubMed1995

Malignantly transformed non-parenchymal liver epithelial cells and transformed oval cells suppress the homotypical gap junctional intercellular communication of co-cultured rat liver parenchymal cells.

Isolated rat liver parenchymal cells (PC) were co-cultured with a non-parenchymal rat liver epithelial cell line (NEC) or with an oval cell line. The homotypical gap junctional intercellular communication (GJIC) between the liver PC was measured after microinjection of Lucifer Yellow by dye transfer. The rat liver PC were dye coupled between 87% and 100% for at least 1 week in both co-cultures, in contrast to PC In monoculture between which no dye coupling was left after 1 week. When liver PC were co-cultured with a transformed and tumorigenic NEC or with a transformed and tumorigenic oval cell line the homotypical GJIC between the liver PC was drastically decreased with culture time, and the PC were then compressed and displaced by the expansive growth of the transformed cell lines. The disturbance of the GJIC between normal cells by adjacent tumorigenic cells might be a new mechanism to explain the expansive growth of tumors.

Animals↗
PubMed1994

The microsomal epoxide hydrolase has a single membrane signal anchor sequence which is dispensable for the catalytic activity of this protein.

The microsomal epoxide hydrolase (mEH) catalyses the hydrolysis of reactive epoxides which are formed by the action of cytochromes P-450 from xenobiotics. In addition it has been suggested that mEH might mediate the transport of bile acids. For the mEH it has been shown that it is co-translationally inserted into the endoplasmic reticulum. Here we demonstrate that the N-terminal 20 amino acid residues of this protein serve as its single membrane anchor signal sequence and that the function of this sequence can also be supplied by a cytochrome P-450 (CYP2B1) anchor signal sequence. The evidence supporting this conclusion is as follows: (i) the rat mEH and a CYP2B1-mEH fusion protein, in which the CYP2B1 membrane anchor signal sequence replaced the N-terminal 20 amino acid residues of mEH, was co-translationally inserted into dog pancreas microsomes in a cell-free translation system, whereas a truncated epoxide hydrolase with a deletion of the 20 N-terminal amino acid residues was not co-translationally inserted. (ii) The mEH and the CYP2B1-mEH fusion protein, but not the truncated epoxide hydrolase, were anchored in microsomes in a cell-free translation system and in membrane fractions derived from fibroblasts which expressed these proteins heterologously. These fibroblasts were also used to evaluate the significance of the mEH membrane anchor for the catalytic activity of mEH. The mEH, the truncated mEH and the CYP-EH fusion protein were found to be enzymically active. This result shows that the membrane anchor signal sequence of mEH is dispensable for the catalytic activity of this protein. However, truncated mEH was only expressed at low levels, which might indicate that this protein is unstable.

Amino Acid Sequence↗
PubMed1994

Health of family members caring for elderly persons with dementia. A longitudinal study.

OBJECTIVE: To estimate the change in depression and physical symptoms during a 1-year period in a group of caregivers for elderly persons with dementia and in a group of comparison participants. DESIGN: Cohort study with a comparison group. SETTING: Outpatient geriatric assessment unit and ophthalmology service in an acute care hospital. PARTICIPANTS: 218 close family members of a consecutive sample of patients with dementia and patients having cataract surgery were interviewed to obtain a baseline assessment. Of these, 86 caregivers (family members of patients with dementia) and 95 comparison participants (family members of patients with cataracts) were interviewed again approximately 1 year later. MAIN OUTCOME MEASURES: Center for Epidemiologic Studies depression scale and Aday and Andersen's 24-item physical symptom checklist. RESULTS: For the Center for Epidemiologic Studies depression score, the difference between caregivers and comparison participants with respect to change during the 1-year study period was 2.1 (95% CI, 1.0 to 5.2); for physical symptoms, the difference was 0.4 (CI, -0.3 to 1.1). A higher level of behavioral disturbance in the patients with dementia at time 1 and institutionalization of the patient between time 1 and time 2 were predictive of worsening caregiver depression and physical symptoms during the study period. The magnitude and direction of changes in caregiver health varied considerably. CONCLUSIONS: Overall mean changes in depression and physical symptoms during 1 year were small. The observed variability in the individual response to the caregiving situation suggests that future research should focus on the identification of salient prognostic factors.

Aged↗
PubMed1994

Myeloperoxidase deficiency: an epidemiological study and flow-cytometric detection of other granular enzymes in myeloperoxidase-deficient subjects.

MPO deficiency, as first studied in the 1960s, has been recorded with increasing frequency, following the introduction of the automated cytochemical count into clinical routine. However, with regard to the diseases correlated to MPO deficiency, no exact data on the frequency of co-existence have been recorded. Moreover, the question remains whether or not a further deficiency of other granular enzymes co-exists, especially with regard to acquired MPO deficiency. In order to answer these questions, an epidemiological study of more than 70,000 unselected patients was performed; the resulting prevalence of MPO deficiency was 0.15%. Within this patient group the intercellular content of elastase-like protease (ELP) and lactoferrin was measured semiquantitatively in a flow cytometer by means of indirect immunofluorescence staining. The frequency of coinciding diseases did not differ from the frequency of diseases in the hospital patients in general. The flow-cytometric studies revealed a normal content of ELP and lactoferrin in one group and a reduced content in another, suggesting the inherited form in the former and acquired MPO deficiencies in the latter group and thus indicating that differing mechanisms characterize the two forms of MPO deficiency. Nevertheless, we do not suggest distinguishing between acquired and inherited deficiencies solely with this technique. Instead, molecular-biologic and/or genetic methods should be referred to.

Adolescent↗