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Biomedical subjects

Peter Berger

Publications and source records attributed to Peter Berger.

36 records · Page 2Linked to original sources
PubMed2003

Body mass index: a risk factor for unstable angina and myocardial infarction in patients with angiographically confirmed coronary artery disease.

BACKGROUND: In patients with coronary artery disease (CAD), acute thrombosis frequently occurs in coronary arteries with only mild or moderate stenoses. Obesity increases the risk of atherosclerosis, but it is not known whether it also increases the risk of coronary thrombosis. We hypothesized that body mass index (BMI) might be an independent predictor of an acute coronary syndrome in patients with established coronary atherosclerosis. METHODS AND RESULTS: Of 504 patients undergoing coronary angiography, those with evidence of >10% coronary artery stenoses were divided into 2 groups, with either stable (n=226) or unstable CAD (unstable angina or myocardial infarction; n=156). After adjusting for other risk factors (age, gender, blood pressure, lipid levels, insulin resistance, leptin, fibrinogen, C-reactive protein (CRP), CAD severity on angiography, smoking status, and a history of myocardial infarction or hypertension), BMI had a significant independent association with an acute coronary syndrome, with an odds ratio of 1.49 (P=0.014). This positive relation between BMI and the risk of acute coronary events was evident for even mildly elevated BMI values. Multivariate analysis also showed that CRP and the number of coronary lesions were independent predictors of risk of an acute coronary event. CONCLUSIONS: In patients with established coronary atherosclerosis, BMI, as well as CRP and number of coronary lesions, are independently associated with acute coronary syndromes. There is evidence of increased risk even at mildly elevated BMI levels.

Angina, Unstable↗
PubMed2003

What is the role for improved long-term antiplatelet therapy after percutaneous coronary intervention?

BACKGROUND: Coronary stent placement has replaced balloon angioplasty as the percutaneous coronary intervention (PCI) method of choice, primarily because of its lower restenosis rate. Compared with aspirin (ASA) monotherapy or ASA plus warfarin, the ticlopidine and ASA combination is superior in reducing thrombotic events after stenting. Clopidogrel plus ASA appears to be at least as effective as ticlopidine and ASA. Intravenous glycoprotein IIb/IIIa inhibitors effectively prevent periprocedural thrombotic complications, but their short duration of action and parenteral dosing don't allow for long-term protection. This review aimed to answer how long after PCI with a stent patients are at risk for recurrent thrombotic events and what the optimal way to prevent them is. RESULTS: Classically, ASA has been prescribed indefinitely, whereas adenosine diphosphate receptor antagonists have been discontinued after 2 to 4 weeks. However, the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial found that long-term dual antiplatelet therapy with clopidogrel and ASA was more effective than ASA alone in preventing major cardiovascular events in patients with acute coronary syndrome, including those treated with PCI. CONCLUSION: Results from additional ongoing studies are needed to clarify the role of long-term dual oral antiplatelet therapy in preventing ischemic events in patients who have undergone PCI.

Angioplasty, Balloon, Coronary↗
PubMed2003

Investigations of a common genetic variant in betaine-homocysteine methyltransferase (BHMT) in coronary artery disease.

Hyperhomocysteinemia, a risk factor for cardiovascular disease, can be caused by genetic mutations in enzymes of homocysteine metabolism. Homocysteine remethylation to methionine is catalyzed by folate-dependent methionine synthase, or by betaine-homocysteine methyltransferase (BHMT), which utilizes betaine as the methyl donor. Since genetic variants in folate-dependent remethylation have been reported to increase risk for cardiovascular disease and other common disorders, we screened BHMT for sequence changes that might alter risk for coronary artery disease (CAD). A variant in exon 6-R239Q-was identified. The frequency of this change was examined in 504 individuals who had undergone coronary angiography and were stratified into controls (those with no or mild disease) and cases (those with significant [>50% reduction in luminal diameter stenosis] 1-, 2-, 3-vessel disease). Although this variant did not affect plasma homocysteine, the QQ genotype was present in higher frequency in those with no or mild disease, compared with those with significant disease (11 vs. 6%), suggesting that it may decrease risk of CAD; a statistically-significant decrease was seen in the older subjects (13 vs. 7%). Multivariate analysis for the entire group revealed an odds ratio of 0.48 (95% CI: 0.21-1.06) for the QQ genotype; this association was similar in the younger (OR=0.36; 95% CI: 0.09-1.41) and older subjects (OR=0.42; 95% CI: 0.15-1.18). Our study suggests that the Q allele of the R239Q mutation may decrease the risk of CAD and that this variant warrants additional investigation of its relationship with the development of CAD as well as other homocysteine-dependent disorders.

Adolescent↗
PubMed2003

Serum androgen levels in men: impact of health status and age.

OBJECTIVES: To investigate the impact of health status on androgen levels in men and to assess the age-related changes in androgen levels. METHODS: Sera were obtained from 526 men (age 20 to 89 years) participating in a health screening project and 35 men selected according to the SENIEUR protocol, which excludes those with underlying disease. The health screening project participants were divided into two groups: healthy men (n = 133; group 1) and the remainder (n = 393; group 2). The total testosterone and sex hormone-binding globulin levels were quantified, and the amount of free testosterone (cfT) was calculated. RESULTS: The lowest annual declines in androgen level were observed in group 3 (testosterone 0.2%; cfT 0.4%), followed by group 1 (testosterone 0.4%; cfT 0.8%) and group 2 (testosterone 0.8%; cfT 0.9%). Body mass index and levels of cholesterol, triglycerides, and glucose correlated negatively (P <0.01) with testosterone and cfT. Decade-adjusted reference values (mean +/- 2 standard deviations) for testosterone and cfT were defined. The proposed lower testosterone reference value declined gradually from 3.1 ng/mL (20 to 29 years) to 1.7 ng/mL (70 years or older). CONCLUSIONS: In this cross-sectional study, serum androgens declined in aging men, and the extent of this decrease correlated with health status. A fixed, non-age-adjusted reference value does not adequately reflect this and might lead to a false diagnosis of androgen deficiency, particularly in elderly men. The clinical value of age-related reference values, however, needs to be determined in prospective studies.

Adult↗
PubMed2003

Association of increased neopterin production with decreased humoral immunity in the elderly.

Tetanus toxoid (TT) antibodies of 447 adult persons aged 27-69 years were investigated and analyzed in relationship with the time span since the last vaccination against tetanus as well as the serum concentration of neopterin. Neopterin is a pteridine, which is produced by monocytes/macrophages upon stimulation with the type 1 T cell-derived cytokine interferon-gamma. There was an inverse correlation between serum neopterin and TT antibody concentrations (Spearman's rank correlation coefficient: r(s)=-0.259; p<0.0001) which was even stronger when persons with neopterin concentrations and TT antibodies below the third quartile of the study population were excluded (residual group: n=210; r(s)=-0.718; p<0.0001). The study demonstrates that an immunoregulatory shift towards type 1 immunity as indicated by higher neopterin concentrations coincides with lower TT antibody concentrations in the elderly.

Adult↗
PubMed2003

Sexual sadism.

Definitions of sexual sadism in ICD-10 and DSM-IV will be presented as well as the historical routes of the concept. Today studies on differently selected clinical samples reveal a different distribution of sexual sadism versus masochism with masochism prevailing in general especially outpatient psychiatric facilities, and sadism prevailing in forensic settings, thus corroborating the concept of two separated diagnoses sadism versus masochism. In forensic settings the diagnosis of a sadistic character disorder (sadistic personality disorder [SPD] according DSM-III-R) is found to a much higher degree than in other clinical samples (50-fold). Our own follow-up study on a forensic sample implies that sadism as a paraphilia is of relevance for relapse-rates of sex-offenders. Symptoms of SPD can be combined with sexual sadism, or occur independently. This may corroborate arguments in favor of a dimensional concept of sexual sadism. Symptoms of SPD may then be a sign of generalization of sadistic traits at least in some cases. A concept of two factors contributing to sadistic pleasure is suggested, one taking the aspect of bodily gratification by sexual-aggressive stimuli as decisive, and the other taking inner representation of hostile objects into consideration (stressing the antisocial-anger-rage aspect).

Diagnostic and Statistical Manual of Mental Disord↗
PubMed2003

Preparation and characterization of new WHO reference reagents for human chorionic gonadotropin and metabolites.

BACKGROUND: The currently used standards for human chorionic gonadotropin (hCG) and its alpha and beta subunits (hCGalpha and hCGbeta) contain substantial amounts of contaminating variants of hCG and other impurities. Furthermore, some partially degraded forms of hCG and its subunits have become of potential clinical importance, e.g., "nicked" forms of hCG (hCGn) and hCGbeta (hCGbetan), which contain cuts in the peptide backbone between amino acids 44-45 or 47-48 in hCGbeta, and a fragment of hCGbeta (hCGbetacf) consisting of amino acids 6-40 and 55-92 bound together by disulfide bridges. The IFCC appointed a working group with the aim of preparing new standards for hCG and related substances to improve standardization of their immunoassays. METHODS: Large amounts of hCG and its subunits as well as of hCGn, hCGbetan, and hCGbetacf were prepared by previously developed purification methods in combination with hydrophobic interaction chromatography and reversed-phase HPLC. Each preparation was characterized on the basis of amino acid and sequence analyses, carbohydrate composition, and electrophoretic patterns. Immunoassays for relevant contaminating proteins were also performed. RESULTS: The major preparations were homogeneous and free of contaminating proteins. Concentrations of the final preparations were determined by amino acid analysis. CONCLUSIONS: Calibrated in substance concentrations (mol/L) based on amino acid analyses, these preparations will facilitate improved standardization of immunoassays for hCG and its metabolites. The six preparations have now been established by the WHO as new 1st Reference Reagents for immunoassays with the following codes: hCG 99/688, hCGbeta 99/650, hCGalpha 99/720, hCGn 99/642, hCGbetan 99/692, and hCGbetacf 99/708. In contrast to the 3rd International Standard (75/537), the clinically most important Reference Reagent for hCG (99/688) contains no hCGn and negligible amounts of free subunits.

Blotting, Western↗
PubMed2002

Neuroendocrine differentiation of human prostatic primary epithelial cells in vitro.

BACKGROUND: Dispersed prostatic neuroendocrine cells are involved in growth regulation of the prostate and are considered to play a role in the pathogenesis of prostate carcinoma and benign prostatic hyperplasia (BPH). They are meant either to be derived from the neural crest during embryogenesis or by direct differentiation of the cells from locally present precursor cells. METHODS: An in vitro model was developed for human prostatic epithelial and neuroendocrine cell differentiation. Minced explants from radical prostatectomies were seeded on collagen I-coated plates. RESULTS: The majority of outgrowing cells were basal cells, positive for cytokeratin markers K 5/14 and CD 44, as determined by confocal laser scanning microscopy. A small fraction of interdispersed single cells expressing c-kit, which is found on pluripotent precursors, was identified by immunofluorescence. From these basal cells, in vitro differentiation of cells with neuroendocrine morphology could be achieved within 3 days. These were at rest, i.e., non-bromodeoxyuridine incorporating cells and characteristically coexpressed K 5/14, K 18, and the neuroendocrine marker chromogranin A. Luminal cells staining for K 8 or 18 were not observed. CONCLUSION: Neuroendocrine differentiation of adult prostatic cells was achieved in vitro, favoring the hypothesis that neuroendocrine cells are derived from peripheral precursor cells. The acceleration of this differentiation pathway may be the reason for the increased presence of neuroendocrine cells in areas of epithelial hyperplasia in BPH.

Bromodeoxyuridine↗
PubMed2002

Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction.

BACKGROUND: Among patients with suspected acute coronary syndromes, cardiac troponin T levels have prognostic value. However, there is concern that renal dysfunction may impair the prognostic value, because cardiac troponin T may be cleared by the kidney. METHODS: We analyzed the outcomes in 7033 patients enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries IV trial who had complete base-line data on troponin T levels and creatinine clearance rates. The troponin T level was considered abnormal if it was 0.1 ng per milliliter or higher, and creatinine clearance was assessed in quartiles. The primary end point was a composite of death or myocardial infarction within 30 days. RESULTS: Death or myocardial infarction occurred in 581 patients. Among patients with a creatinine clearance above the 25th percentile value of 58.4 ml per minute, an abnormally elevated troponin T level was predictive of an increased risk of myocardial infarction or death (7 percent vs. 5 percent; adjusted odds ratio, 1.7; 95 percent confidence interval, 1.3 to 2.2; P<0.001). Among patients with a creatinine clearance in the lowest quartile, an elevated troponin T level was similarly predictive of increased risk (20 percent vs. 9 percent; adjusted odds ratio, 2.5; 95 percent confidence interval, 1.8 to 3.3; P<0.001). When the creatinine clearance rate was considered as a continuous variable and age, sex, ST-segment depression, heart failure, previous revascularization, diabetes mellitus, and other confounders had been accounted for, elevation of the troponin T level was independently predictive of risk across the entire spectrum of renal function. CONCLUSIONS: Cardiac troponin T levels predict short-term prognosis in patients with acute coronary syndromes regardless of their level of creatinine clearance.

Abciximab↗
PubMed2002

[Vaccine protection in the elderly: are Austrian seniors adequately protected by vaccinations?].

OBJECTIVE: The aim of the study was to evaluate, if elderly persons are sufficiently protected against infectious diseases by vaccination. PROBANDS AND METHODS: 300 elderly (> 60 years) and 300 young (< 35 years) persons from five Austrian cities were recruited according to the criteria of a field study. Antibody concentrations against tetanus, diphtheria, tickborne encephalitis and influenza were assessed by ELISA or by haemagglutination inhibition test. Disease and vaccination histories were recorded. RESULTS: The results of the study demonstrate that protection against infectious diseases was frequently insufficient in the elderly. This was partly due to the fact that old persons were not vaccinated according to recommended strategies. However, low antibody concentration and a short duration of protective humoral immunity were also observed in many elderly persons in spite of regular vaccination. This was not only the case in frail, but also in healthy elderlies. CONCLUSION: The data demonstrate that vaccination has a relatively weak and short-lasting effect in old age. The results of the study should stimulate discussions about strategies how vaccinations can be made more effective in old age. Improved campaigns, shortened vaccination intervals as well as the design of novel vaccines tailored to fulfill the specific demands of the aging immune system are imaginable.

Aged↗
PubMed2002

C-reactive protein levels are influenced by common IL-1 gene variations.

Elevated markers of systemic inflammation are associated with the development of acute coronary syndromes, but there is no current explanation for increased inflammation in overtly healthy individuals. The influence of genetic control of the inflammatory response on the observed variability is unknown. We studied the frequency of four polymorphisms in interleukin (IL) 1 genes, known to modulate inflammation, in 454 individuals undergoing coronary angiography and analysed their influence on plasma C-reactive protein (CRP) and fibrinogen levels. Females and smokers had higher levels of CRP than males (Pi = 0.001) and non-smokers (Pi = 0.001). Patients with genotype 2.2 for the IL-1B(+3954) polymorphism had twice the median CRP levels of patients who were genotype 1.1 (4.33 vs 2.01 mg/l; P = 0.001). Patients with genotype 1.2 or 2.2 at the IL-1A(+4845) polymorphism also had higher median CRP (2.92 vs 2.05 mg/l, Pi = 0.023). In multivariate analyses, CRP levels remained significantly associated with IL-1 polymorphisms after adjustment for smoking, gender and age. Fibrinogen levels had similar associations with the IL-1 genotypes. These data indicate that IL-1 gene polymorphisms known to affect the inflammatory response are highly related to plasma levels of CRP and fibrinogen in patients referred for coronary angiography.

Adult↗
PubMed2002

Impact of radical prostatectomy and TURP on the hypothalamic-pituitary-gonadal hormone axis.

OBJECTIVES: To assess the impact of prostate cancer (PCa) and benign prostatic hyperplasia (BPH) on the hypothalamic-pituitary hormone axis, we determined the endocrine changes after radical prostatectomy (RP) and transurethral resection of the prostate (TURP) for BPH and in a group of men with BPH followed up conservatively. METHODS: Patients with PCa before RP (n = 49), those who underwent TURP for BPH (n = 51), and men with lower urinary tract symptoms for whom a wait-and-see strategy was chosen (n = 46) were included. Serum levels of total testosterone, luteinizing hormone, and follicle-stimulating hormone were determined at baseline and 6 and 12 months later in all patients. RESULTS: No significant endocrine changes were observed in the wait-and-see and TURP groups 6 and 12 months after baseline. In contrast, luteinizing hormone increased from 5.2 to 8.9 mIU/mL (P = 0.0004) and follicle-stimulating hormone from 5.7 to 9.3 mIU/mL (P = 0.0003) 12 months after RP. The rise of total testosterone from 3.9 to 4.4 ng/mL failed to reach statistical significance (P = 0.18). Patients with Gleason score 2 to 6 PCa had higher testosterone values (4.2 ng/mL) at baseline than did those with Gleason score 7 to 10 PCa (2.2 ng/mL, P < 0.05). Although 12 months after RP no changes in testosterone were observed in the low Gleason score group, the testosterone levels more than doubled in those with high-grade tumors. The increases in luteinizing hormone and follicle-stimulating hormone at 12 months, however, were comparable in both groups. CONCLUSIONS: Our findings suggest a significant impact of PCa on the hypothalamic-pituitary axis that is more profound in high-grade cancer. Such an effect was not demonstrable for the transition zone in BPH.

Aged↗
PubMed2002

Human lipocalin-1, a physiological scavenger of lipophilic compounds, is produced by corticotrophs of the pituitary gland.

Lipocalin-1 (Lcn-1), a member of the lipocalin superfamily that binds a broad array of different chemical classes of lipophilic ligands, is believed to act as a physiological scavenger of potentially harmful lipophilic molecules. Thus far, it was thought to be produced exclusively by a number of exocrine glands and tissues, including lachrymal and lingual glands, prostate, secretory glands of the tracheobronchial tract, and sweat glands. Using Northern blotting analysis, we were able to demonstrate Lcn-1 expression by the human pituitary gland. Moreover, double immunolabeling with antibodies against Lcn-1 and pituitary gland hormones and detection with fluorophore-conjugated secondary antibodies revealed that Lcn-1 is specifically produced by corticotrophs, clearly indicating that its distribution is not restricted to exocrine tissues.

Acute-Phase Proteins↗
PubMed2002

Trans-differentiation of prostatic stromal cells leads to decreased glycoprotein hormone alpha production.

Age-related development of benign prostatic hyperplasia is an important health issue in developed countries. The histopathogenetic hallmark of this disease is the increase in relative and absolute numbers of smooth muscle cells (SMC). Glycoprotein hormone alpha-subunit (GPHalpha) is expressed in the human prostate, and, because of its structural similarities to other cystine knot growth factors, it has been considered to have growth regulatory functions of its own. Primary cell cultures allowing for selective cultivation of prostatic epithelial cells, fibroblasts, and SMC were established. Directed trans-differentiation and cellular homogeneity was pursued by confocal scanning laser microscopy with cell type-specific markers. GPHalpha production by these cells was assessed by immunofluorimetric assays. Its predominant source was young fibroblasts, whereas replicative senescent fibroblasts, SMC, and control fibroblasts from foreskin did not produce significant amounts. Functionally, GPHalpha reduced growth of stromal cells at concentrations of 10 and 100 nmol/liter as shown by cell viability assays. It is concluded that histogenetic reorganization over the adult lifetime, guided by endocrine factors like steroid hormones together with senescence of fibroblasts, leads to a decreased production of growth inhibitors, such as GPHalpha, favoring proliferation and the development of benign prostatic hyperplasia.

Cell Differentiation↗
PubMed2002

Toxic epidermal necrolysis after celecoxib therapy.

Toxic epidermal necrolysis (TEN) is a rare disease that is defined by extensive detachment of full-thickness epidermis. It most often is related to an adverse drug reaction. The drugs implicated in most cases of TEN have been sulfonamides, anticonvulsants, allopurinol, and some of the conventional nonsteroidal antiinflammatory agents. We describe a patient who developed a generalized desquamating rash after therapy with celecoxib.

Aged↗
PubMed2000

Nonorganic insomnia in panic Disorder: comparative sleep laboratory studies with normal controls and placebo-controlled trials with alprazolam.

Objective and subjective sleep and awakening quality was investigated in 11 drug-free patients (4 females, 7 males) aged 30-55 (mean: 44+/-9) years with nonorganic insomnia (F 51.0) related to panic disorder (F 41.0) as compared with 11 age- and sex-matched normal controls aged 30-58 (mean: 44+/-9) years, utilising polysomnography (PSG) and psychometry. PSG demonstrated decreased sleep efficiency (primary target variable), total sleep time (TST) and S2 as well as increased middle and late insomnia, S1, S3+S4, snoring and PLM in patients. There were no intergroup differences in REM variables. Subjective sleep quality deteriorated, as did drive and fine motor activity in the morning, while concentration increased. Blood pressure in the evening and morning and pulse rate in the evening were elevated. These differences as compared with normals were distinct from those observed in other sleep disorders. In a subsequent acute, placebo-controlled cross-over design study, patients received alprazolam 0.5 mg (Xanor((R));) and placebo. As compared with placebo, alprazolam induced an increase in sleep efficiency (primary target variable), TST and S2, a decrease in wakefulness during the total sleep period, S3+S4 and the oxygen desaturation and PLM indices, and improved subjective sleep quality, somatic complaints, drive, affectivity and drowsiness in the morning. There were no changes in REM variables. Thus, alprazolam induced changes that were opposite to the differences observed between patients and controls before treatment, thereby normalizing sleep and awakening quality. As observed in insomnia related to GAD and subsequent benzodiazepine therapy, the present study also points to a key-lock principle in the treatment of insomnia caused by anxiety disorders and neurophysiologically visualizes processes at the receptor level (e.g. benzodiazepine agonists versus inverse agonists). Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗
PubMedDate not supplied

A Darwinian-evolutionary concept of age-related diseases.

Humans and animals are structurally designed as a compromise to guarantee optimal survival until the time of reproduction based on natural selection that is effective until that age. Modern conditions of life including improvement of hygiene, preventive and curative medicine as well as socio-economic and political developments have led to an increase of the mean life expectancy that allows ever larger proportions of the population to reach an age that is far beyond that of the reproductive phase. The concept of a Darwinian-evolutionary basis for the development of age-related diseases in principle postulates that genetic traits that are beneficial in younger years to allow for successful reproduction may become deleterious in the elderly, i.e. when selective pressure does not seem to be effective anymore. Examples for this mechanism of pleiotropic antagonism taken from the work of the Institute for Biomedical Aging Research in Innsbruck, Austria, include atherosclerosis, benign and malignant prostate hypertrophy, Alzheimer's disease and the reciprocal relationship between cellular senescence and cancer.

Adult↗