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Biomedical subjects

E Berger

Publications and source records attributed to E Berger.

At least 73 records · Page 4Linked to original sources

Enhancing smoking cessation rates in primary care.

BACKGROUND: The Agency for Health Care Policy and Research (AHCPR) guidelines on smoking cessation recommend that primary care physicians provide both brief advice against smoking and follow-up care for all smokers. Surveys show that although physicians understand the importance of smoking cessation, the actual implementation of these guidelines is limited. The main objective of our study was to evaluate the comparative effectiveness of 2 different approaches to smoking cessation counseling: practice-based and community-based. METHODS: Both smoking cessation approaches consisted of 1 recruitment session and 6 computer-assisted counseling sessions. In the practice-based approach, counseling was provided by office nurses and telephone counselors; in the community-based approach, the counseling was given by telephone counselors only. Four practices in 3 mid-Michigan communities participated, including 120 physicians and 487 patients who were smokers. The physicians were trained to provide brief advice for smoking cessation consistent with the AHCPR guidelines; the nurses and telephone counselors were trained in relapse prevention, computer skills, and individual case management. Sixty-two percent of the participants obtained free nicotine replacement therapy. RESULTS: At 6 months, quit rates (7-day smoke-free status) were 35% in the practice-based group and 36% in the community-based group. Participants who completed at least 4 sessions showed higher quit rates than those who did not. CONCLUSIONS: Nurses in primary care practices and counselors can be trained to deliver effective relapse-prevention counseling during office visits and by telephone. Our study showed an increase in the reported rates of smoking cessation by using these counseling methods.

Behavior Therapy↗

CA-125 concentrations in the serum and pregnancy outcome in IVF cycles.

PURPOSE: CA-125 has been proposed as a potential marker for endometrial receptivity in assisted reproduction. This study was designed to evaluate whether the levels of CA-125 in the serum of patients undergoing IVF-embryo transfer (ET) is correlated with the outcome. METHODS: Levels of serum CA-125 were measured on the day before and on the day of human chorionic gonadotropin (hCG) administration, ovum pickup (OPU), and ET in 74 patients undergoing 100 IVF cycles between January 1994 and March 1995. Patients were treated with a midluteal-phase gonadotropin-releasing hormone (GnRH) agonist protocol and follicular-phase human menopausal gonadotropin. RESULTS: One hundred oocyte retrievals resulted in 91 ETs, and 22 clinical pregnancies (22%/OPU and 24.2%/ET). The live-born rate was 21%/OPU and 23.1%/ET. Neither the CA-125 serum levels nor their increase from the day of hCG until the day of ET showed any prognostic significance to the outcome of IVF, and they were not correlated with the endometrium thickness or the number of oocytes retrieved or fertilized. CONCLUSIONS: The CA-125 serum levels in conventional IVF cycles were not correlated with the IVF outcome and yielded no prognostic information in a GnRH agonist down-regulation protocol.

Adult↗

Serum pregnancy-specific beta1-glycoprotein before embryo transfer is related to endometrial thickness and to outcome prognosis in women undergoing in-vitro fertilization treatment.

We have previously observed the repeated presence of low but detectable amounts of the trophoblast marker pregnancy-specific beta1-glycoprotein (SP1) in the serum of some women undergoing in-vitro fertilization (IVF) treatment around the time of oocyte retrieval. The occurrence of these signals seemed to be restricted to a defined group of patients which also showed a lower pregnancy success rate in a preliminary study. To test our hypothesis we have analysed 173 consecutive cycles leading to an embryo transfer. Fifty-four cycles (31%) had a serum SP1 level of at least 0.1 ng/ml between days embryo transfer -5 and embryo transfer (group A). Five pregnancies were obtained in this group (pregnancy rate = 9.3%), while in group B, defined by the absence of detectable SP1 before embryo transfer (119 cycles), 36 ongoing pregnancies were achieved (30.3%). Ten of the 41 pregnancies were achieved in 33 first-time non-pregnant patients undergoing further attempts during the study period. Again the pregnancy rate was higher in the first-time group B women (9/23 versus 1/10 for group A). Patients tended to remain in their groups A or B, the latter being associated with a better immediate as well as subsequent chance for pregnancy. Group A cycles had a significantly lower endometrial thickness two days before oocyte retrieval than group B (P = 0.0011). We postulate that the presence of an unknown, maternal and progesterone- or follicle stimulating hormone-independent factor in some patients could stimulate tonic ectopic SP1 synthesis and at the same time negatively influence endometrial development.

Adult↗

[Involuntary sterilization of mentally handicapped patients].

Medical discourse on "racial hygiene" and the law on the prevention of hereditary disease in progeny passed in 1933 in Nazi Germany presents us the historical background to the topic. By analyzing six case histories from "hereditary health" court decisions during the years 1942-45, we illuminate how the law of 1933 was applied in Austria. Coming to the present, we put historical events into a more general perspective by reviewing recent debates and presenting a case history from today. There are similarities between the past and present decisions regarding carrying out sterilization of mentally handicapped persons, but the justification given for doing so has changed. The argument of today "protection of the individual" supplants "racial hygiene".

Adult↗

Anti-tumor necrosis factor-alpha improves myocardial recovery after ischemia and reperfusion.

OBJECTIVES: This study sought to assess the importance of locally released or paracrine myocardial tumor necrosis factor-alpha (TNF-alpha) in the evolution of postischemic myocardial dysfunction and to use immunohistochemical studies to localize TNF-alpha within the myocardium. BACKGROUND: TNF-alpha is implicated as a systemic mediator in the development of myocardial ischemia-reperfusion injury by promoting leukocyte myocardial infiltration, and it has been shown to originate from noncardiac peripheral mononuclear cells. We have recently documented in a blood-free environment the release of TNF-alpha from the ischemic-reperfused myocardium. METHODS: Isolated rat hearts undergoing 1 h of global cardioplegia-induced ischemia and 30 min of reperfusion were investigated with use of the modified Langendorff model. Hearts were randomly divided into three subgroups: group A, control group; and groups B and C, isolated hearts receiving cardioplegic solution containing monoclonal hamster antimurine TNF-alpha antibodies (group B) or hamster IgG (group C). RESULTS: Significant amounts of TNF-alpha were detected in group A and group C effluent on 1 min of reperfusion (752 +/- 212 and 958 +/- 409 pmol/ml, respectively). However, in group B, TNF-alpha was below detectable levels. In this group, postischemic left ventricular peak systolic pressures, first derivative of the rise in left ventricular pressure (dP/dtmax), pressure-time integral, coronary flow and O2 consumption improved (analysis of variance [ANOVA] p < 0.0001 for all variables) compared with values in groups A and C; creatine kinase levels decreased (p < 0.005); and myocardial structure was preserved. Immunohistochemical staining localized TNF-alpha to cardiac myocytes and to endothelial cells. CONCLUSIONS: Anti-TNF-alpha neutralizes local TNF-alpha release from cardiac myocytes after ischemia and improves myocardial recovery during reperfusion, indicating that postischemic paracrine TNF-alpha release plays an active role in myocardial dysfunction.

Animals↗

Mechanistic roles of tyrosine 149 and serine 124 in UDP-galactose 4-epimerase from Escherichia coli.

Synthesis and overexpression of a gene encoding Escherichia coli UDP-galactose 4-epimerase and engineered to facilitate cassette mutagenesis are described. General acid-base catalysis at the active site of this epimerase has been studied by kinetic and spectroscopic analysis of the wild-type enzyme and its specifically mutated forms Y149F, S124A, S124V, and S124T. The X-ray crystal structure of Y149F as its abortive complex with UDP-glucose is structurally similar to that of the corresponding wild-type complex, except for the absence of the phenolic oxygen of Tyr 149. The major effects of mutations are expressed in the values of kcat and kcat/Km. The least active mutant is Y149F, for which the value of kcat is 0.010% of that of the wild-type epimerase. The activity of S124A is also very low, with a kcat value that is 0.035% of that of the native enzyme. The values of Km for Y149F and S124A are 12 and 21% of that of the wild-type enzyme, respectively. The value of kcat for S124T is about 30% of that of the wild-type enzyme, and the value of Km is similar to that of the native enzyme. The reactivities of the mutants in UMP-dependent reductive inactivation by glucose are similarly affected, with kobs being decreased by 6560-, 370-, and 3.4-fold for Y149F, S124A, and S124T, respectively. The second-order rate constants for reductive inactivation by NaBH3CN, which does not require general base catalysis, are similar to that for the native enzyme in the cases of S124A, S124T, and S124V. However, Y149F reacts with NaBH3CN 12-20-fold faster than the wild-type enzyme at pH 8.5 and 7.0, respectively. The increased rate for Y149F is attributed to the weakened charge-transfer interaction between Phe 149 and NAD+, which is present with Tyr 149 in the wild-type enzyme. The charge-transfer band is present in the serine mutants, and its intensity at 320 nm is pH-dependent. The pH dependencies of A320 showed that the pKa values for Tyr 149 are 6.08 for the wild-type epimerase, 6.71 for S124A, 6.86 for S124V, and 6.28 for S124T. The low pKa value for Tyr 149 is attributed mainly to the positive electrostatic field created by NAD+ and Lys 153 (4.5 kcal mol-1) and partly to hydrogen bonding with Ser 124 (1 kcal mol-1). The pKa of Tyr 149 is the same as the kinetic pKa for the Bronsted base that facilitates hydride transfer to NAD+. We concluded that Tyr 149 provides the driving force for general acid-base catalysis, with Ser 124 playing an important role in mediating proton transfer.

Bacterial Proteins↗

Family history of cancer and risk of lung cancer in lifetime non-smokers and long-term ex-smokers.

BACKGROUND: Genetic factors appear to play a role in the aetiology of lung cancer. METHODS: To examine the association between family history of cancer (all types) and risk of lung cancer among non-smokers, we conducted a case-control study. Cases (n = 618) were identified through the Missouri Cancer Registry for the period 1986 through 1991, and included 432 lifetime non-smokers and 186 ex-smokers who had stopped at least 15 years prior to diagnosis or had smoked for less than one pack-year. Controls (n = 1402) were selected through drivers licence and Medicare files. RESULTS: The risk of lung cancer increased directly in relation to the number of family members affected with cancer. The odds ratio (OR) associated with five or more first-degree relatives with cancer was 2.7 (95% confidence interval [CI] 1.2-6.1), with a significant linear trend in risk according to the number of relatives affected (P = 0.03). Increased lung cancer risk was associated with two or more affected siblings (OR = 1.4; 95% CI: 1.0-1.9) and with two or more affected offspring (OR = 3.2: 95% CI: 1.3-8.1). Risk was slightly elevated for family history of lung cancer (OR = 1.3; 95% CI: 1.0-1.8). CONCLUSIONS: Our study identified a slight increase in risk of lung cancer in relation to five or more relatives with cancer. Preventive implications of this increased risk are unclear because the attributable fraction is low in comparison to a variety of other factors.

Adult↗

Osteogenic growth peptide increases blood and bone marrow cellularity and enhances engraftment of bone marrow transplants in mice.

The osteogenic growth peptide (OGP) was characterized recently in regenerating bone marrow (BM) and normal serum. In vitro, the OGP regulates stromal-cell proliferation and differentiated functions. In vivo, an increase in serum OGP accompanies the osteogenic phase of postablation BM regeneration. The present results in normal mice show that OGP induces a balanced increase in WBC counts and overall BM cellularity. In mice receiving myeloablative irradiation and syngeneic or semiallogeneic BM transplants, OGP stimulates hematopoietic reconstruction and doubles the survival rate; these effects are dependent on initiating the OGP administration before irradiation. Chimerism measurements in semiallogeneic graft recipients suggest no preferential effect of OGP on residual host cells. The data implicate OGP in the acceleration of hematopoiesis secondary to expansion of the stromal microenvironment and/or enhancement of stroma-derived signals to stem cells. The low-dose effectiveness of OGP is explained by the demonstration of an autocrine positive feedback loop that together with the OGP-binding protein sustains high serum levels of the peptide. A potential OGP-based treatment in combination with chemoradiotherapy is attractive because of the OGP-induced balanced multi-lineage enhancement of hematopoiesis and possible replacement of expensive recombinant cytokines by a readily synthesized peptide.

Animals↗

Avian exposure and risk of lung cancer in women in Missouri: population based case-control study.

OBJECTIVE: To investigate the association, previously reported in three European studies, between ownership of pet birds and the risk of lung cancer. DESIGN: A population based case-control study with a structured questionnaire administered by telephone. SETTING: Missouri, a midwestern state in the United States with a population of about 5 million. SUBJECTS: All newly diagnosed cases of primary lung cancer in women aged 30-84 years in Missouri from 1 January 1993 to 31 January 1994 reported to the state cancer registry were invited to participate (n = 652); and 629 population based controls. MAIN OUTCOME MEASURES: Odds ratios were computed in relation to whether or not the study subject ever kept pet birds, the type of bird kept, and several measures of intensity or duration of exposure. Odds ratios were adjusted for smoking. RESULTS: The odds ratio (95% confidence interval) for the development of lung cancer associated with keeping pet birds was 0.84 (0.65 to 1.09). The results were similar for the type of pet bird kept, the number of birds kept, the location of the bird in the house, and the duration of ownership. CONCLUSION: The keeping of pet birds carries no excess risk for the development of lung cancer.

Adult↗

A method of quantitative autoradiography for the spatial localization of proteoglycan synthesis rates in cartilage.

Incorporation of [35S]-sulfate into cartilage tissue indicates the synthesis of aggrecan, the large aggregating proteoglycan (PG) that endows cartilage with resistance to compression. Scintillation counting of tissue digests provides a quantitative measure of incorporated sulfate but does not provide information on the spatial location of synthesis within the tissue. Such spatially specific information is necessary to determine which cell populations respond to diffusible factors and to correlate local mechanical events (e.g., deformation, interstitial fluid stress) to cellular biosynthetic responses. The aim of this study was to develop and characterize a liquid emulsion autoradiography technique, including an automated grain counting procedure, to derive spatial profiles of aggrecan synthesis rates in cartilage. We chose mature 10-14-month-old bovine humeral head articular cartilage as a model system and applied a liquid emulsion autoradiography technique to [35S]-sulfate-labeled, resin-embedded, and semithin-sectioned tissue explants. High-magnification light microscopy color images were captured on a computer. Automated image analysis for grain number determination included a color thresholding procedure to discriminate grains from the lightly stained structural image and computation of the average area of a single grain from each image. Determination of grain number, whether originating from single grains or grain clusters, was performed by dividing the total grain area in the image by the average area of a single grain in the same image. This procedure largely eliminated the effects of variations of microscope light intensity, camera performance, image focus, section stain intensity, and thresholding on the resulting grain numbers. By altering the specific activity of the medium radiolabel and the emulsion exposure times, we demonstrated a linear dose dependence, without saturation, of grain number on radioactive content in the underlying section. By cutting specimens in half and performing liquid scintillation counting on one half and autoradiography on the other half, we found that each disintegration occurring in the section during exposure resulted in 0.67 +/- 0.21 grains (mean +/- SD; n = 58). Therefore, counted grain numbers can be directly converted to incorporated sulfate, largely reflecting the synthesis of the PG aggrecan. As an example of calculated intratissue profiles of aggrecan synthesis rates, we found for the mature bovine tissue in serum-free medium that aggrecan synthesis increases monotonically from the articular surface to the radial zone by as much as tenfold.

Animals↗

[Rudolf Ekstein's contributions to psychotherapy and child psychiatry].

Rudolf Eksteins scientific career is closely linked to his personal history, with his Jewish heritage, his political involvement and his social work with young people, which guided him towards psychoanalytic educational theory. Following his forced emigration to the USA in 1938 he became a world-famous child therapist, psychoanalyst, scientist and professor of medical psychology at the Department of Psychiatry, UCLA. The most significant areas of Eksteins extensive scientific output are described in an attempt to do justice to his contributions to psychotherapy and child psychiatry. Eksteins introduction of a special technique for treating psychotic children with psychoanalytic psychotherapy was of major importance. His underlying concept of schizophrenic psychosis and borderline personality disorders in children is outlined. Further, we have tried to show in what way his contributions to psychoanalytic theory and techniques were influenced by his profound knowledge of philosophy and linguistics. Finally Eksteins dedications to the teaching and learning of psychotherapy is stressed, from which a whole generation of Austrian psychiatrists, psychologists and pedagogues have profited enormously, as a result of his long-standing teaching commitments as guest professor at Vienna University.

Austria↗

Randomized controlled trial of ACE-inhibitors and beta-blockers with and without vasodilating activity in chronic glomerulonephritis.

A prospective double-blind, randomized study was conducted to compare the effects of the beta 1 antagonist, beta 2 agonist celiprolol (200 mg daily) on renal hemodynamics and protein excretion with those of the beta 1 antagonist atenolol (50 mg daily), the ACE-inhibitor ramipril (2.5 mg daily), and placebo in 11 patients with proteinuria > 400 mg/24 h due to chronic glomerulonephritis. All 4 substances were given in a double-blind, randomized manner according to a latin-square design over a period of 4 weeks with a wash-out period of 2 weeks in between. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and PAH clearance. Proteinuria was assessed by urine sampling at the end of each treatment period. Mean arterial pressure (MAP) was reduced significantly (p < 0.01) by all 3 drugs compared to placebo (108 +/- 9 mmHg placebo, 98 +/- 12 mmHg atenolol, 101 +/- 11 mmHg celiprolol, and 98 +/- 8 mmHg ramipril). Celiprolol induced a significant increase in ERPF compared to placebo (322 +/- 109 ml/min under placebo versus 391 +/- 110 ml/min under celiprolol, p < 0.05). GFR was slightly but insignificantly increased under atenolol and celiprolol. Filtration fraction (FF) remained unchanged in case of atenolol and celiprolol treatment and was slightly but not significantly reduced by ramipril. Proteinuria was significantly (p < 0.05) reduced compared to placebo by all 3 drugs (1.8 +/- 1.3 g/24 h under placebo, 1.2 +/- 1.2 g/24 h under atenolol, 1.2 +/- 1.1 g/24 h under celiprolol, and 1.4 +/- 1.4 g/24 h under ramipril). These data demonstrate that new beta-blocking agents show favorable effects on proteinuria and renal blood flow in patients with chronic glomerulonephritis and arterial hypertension. This may be attributed to their vasodilating properties.

Adrenergic beta-1 Receptor Antagonists↗

What's happening with consumer participation?

Consumer empowerment, both individually and within the service, is a growing trend in mental health. This trend is such that consumers are having more input into the service being provided. Shared control is a wave of the future, thereby increasing consumer empowerment not only within the service but within our own lives. The road is long and there are many bumps along the way for both the consumer and the health worker, yet the results of consumers leading quality lifestyles gives other consumers hope that they too can be capable of being active participants rather than relying on others to take care of them.

Consumer Advocacy↗

Design and synthesis of potent retinoid X receptor selective ligands that induce apoptosis in leukemia cells.

Structural modifications of the retinoid X receptor (RXR) selective compound 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2- naphthyl)ethenyl]benzoic acid (LGD1069), which is currently in phase I/IIA clinical trials for cancer and dermatological indications, have resulted in the identification of increasingly potent retinoids with > 1000-fold selectivity for the RXRs. This paper describes the design and preparation of a series of RXR selective retinoids as well as the biological data obtained from cotransfection and competitive binding assays which were used to evaluate their potency and selectivity. The most potent and selective of the analogs is 6-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2- yl)cyclopropyl]nicotinic acid (12d; LG100268). This compound has proven useful for investigating RXR dependent biological pathways including the induction of programmed cell death (PCD) and transglutaminase (TGase) activity. Our studies indicate that the induction of PCD and TGase in human leukemic myeloid cells is dependent upon activation of RXR-mediated pathways.

Apoptosis↗