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Biomedical subjects

P Bramlage

Publications and source records attributed to P Bramlage.

33 records · Page 2Linked to original sources
PubMed2003

[IRMA-pRAcs: irbesartan in the treatment of microalbuminuria and proteinuria in patients with type 2 diabetes and hypertension-prospective observational study involving 38,016 patients in the general practice setting].

BACKGROUND AND AIMS: In daily practice, nephropathy is diagnosed in a high percentage of type 2 diabetics, including those in whom blood pressure is well controlled. The aim of the present study was to reduce albuminuria in these patients by changing over antihypertensive treatment to the AT, blocker irbesartan. 9,838 general practitioners recruited a total of 38,016 type 2 diabetics aged at least 18 years to an open observational study: In the majority of cases, current antihyprertensive treatment was discontinued and patients given 300 mg (a small percentage received 150 mg or 75 mg) irbesartan, either as monotherapy or in combination with 12.5 mg hydrochlorothiazide (HCT). The primary target outcome for efficacy was the 6-months normalization rate in patients with microalbuminuria or proteinuria; secondary target parameters included the change in protein excretion (grades: negative, 20 mg, 50 mg, 100 mg), normalisation of the systolic or diastolic blood pressure, and responder and blood pressure normalization rates. The target criterion for tolerability was the number of patients with adverse events (AE). RESULTS: 46% of the patients were controlled with 300 mg irbesartan alone, and 40% with irbesartan in combination with HCT. Albumin excretion normalized in 60.5% of the patients, improved by at least one grade in 81.9%, remained unchanged in 17.5%, and increased in 0.7% of the cases. The beneficial response was found to be independent ofthe type of prior antihypertensive treatment (including ACE-inhibitors) and was also seen in normotensive patients. Only 0.4 % of the patients reported AEs. CONCLUSION: In type 2 diabetics, treatment with 300 mg irbesartan administered alone or in combination with 12.5 mg HCT produced a pronounced nephroprotective effect.

Adolescent↗
PubMed2003

[Aim, design and methods of the "Hypertension and diabetes screening and awareness" -- (HYDRA) study].

Aim of the study is a comprehensive clinical-epidemiological description of the prevalence of arterial hypertension and diabetes among primary care patients along with an assessment of doctor's recognition rates and prescription behaviour. The paper describes methods and design of the study and provides background information on the sampling process, instruments used as well as characteristics of doctors and patients. The study is based on a nationally representative sample of 1,912 primary care doctors and 45,000 patients that attended the doctors' office on the target days. The patients were also characterized by laboratory tests. The first stage of study consisted of a comprehensive description of the doctors' characteristics in terms of psychosocial, qualification- and provider aspects as well as attitudes towards hypertension and diabetes and their management. In the second stage all patients completed a questionnaire to describe their health behaviour and attitudes as well as the treatment history and therapy. In the third stage all patients were characterized by their doctors in terms of their diagnostic status and their past and current interventions.

Adolescent↗
PubMed2003

[Management of diabetes and hypertension: how do primary care physicians judge their performance?].

With regard to the management of hypertension and diabetes, HYDRA reveals that doctors report multiple problems in their everyday practice. Being confronted with an average of 73 patients a day, with almost every second having either diabetes or hypertension, frequently associated with multiple comorbid conditions, the core obstacle is the time factor. Doctors do not have sufficient time to perform diagnostic tests and especially no time for non-drug interventions of any type. Further available treatment guidelines are only used in 1 out of 2 doctors. Further they seem not to affect doctors performance significantly.

Adult↗
PubMed2003

[Hypertension, diabetes mellitus and comorbidity in primary care].

Almost every second patient seeing a primary care doctor suffers from arterial hypertension and about every fifth has diabetes mellitus. These diseases often occur at the same time. They are associated in more than 80% of the cases with other severe concomitant and subsequent diseases (heart attack, stroke, renal failure, neuropathy etc.). The magnitude especially of subsequent and concomitant diseases, the dimension of the personal suffering and the immense diagnostic and therapeutic challenges for the doctors have been massively underestimated so far. The article informs about the prevalence of the above disease, and structure of the problem. Before the background of an extremely high patient load seen by German General Physicians, the mainstay challenge is highlighted how to achieve further improvements of the quality of care on the basis of scientific guidelines alone, without a concomitant change in the system structure.

Adolescent↗
PubMed2003

[Microalbuminuria is an early marker for increased morbidity and mortality].

Recent studies have shown the beneficial effects of a blockade of the renin-angiotensin system (RAS) not only for blood pressure reduction but also end organ protection. One of the markers that is closely correlated with the increased cardiovascular risk is microalbuminuria. A common mediator for the development of both, microalbuminuria and end organ damage seems to be Angiotensin II, the blockade of which apparently reduces microalbuminuria as well as end organ damage. Therefore we had a closer look into pathophysiology of microalbuminuria and the relevance for end organ damage and discuss current medical strategies to alleviate these diseases.

Albuminuria↗
PubMed2003

[Diabetes, hypertension and microalbuminuria in primary care].

Microalbuminuria has been widely appreciated in recent years to be a valuable risk marker for an increased cardiovascular disease morbidity and mortality. Thus guidelines for the treatment of type-2-diabetes in Germany and the US recommend an annual screening as soon as the diagnosis of diabetes is established and a quarterly control when microalbuminuria is present. While nationally representative epidemiologic data from the US have been available, data from Germany, especially from the primary care sector are missing. This is especially important in light of the gatekeeper function of the primary care physician. The "Hypertension and Diabetes Risk Screening Study" (HYDRA) has been identifying 37.8% of patients with hypertension and diabetes to have a positive dipstick test for microalbuminuria on the study day while only 12.5% of these are diagnosed by the doctor as having nephropathy. These patients additionally show a high burden of associated comorbidities and thus call for early detection and intervention especially because effective therapy is available. Although screening for microalbuminuria is recommended in the guidelines the value of a routine screening for microalbuminuria in primary care is under recognized.

Adult↗
PubMed2003

[Nephropathy: an overview for daily practice].

The examination of renal function in the daily practice may give important information on the risk status of a given patient. For example, the diagnosis of microalbuminuria carries high predictive value for a future cardiovascular risk of patients with hypertension, diabetes, congestive heart failure, as well as myocardial infarction. The findings of the Hypertension and Diabetes Screening and Awareness Study (HYDRA) indicate that screening for microalbuminuria is performed not often enough in patients with diabetes or hypertension, respectively, and a positive screening finding often does not trigger necessary consequences as for additional diagnosis or therapy.

Adult↗
PubMed2001

Homocysteine inhibits TNF-alpha-induced endothelial adhesion molecule expression and monocyte adhesion via nuclear factor-kappaB dependent pathway.

Cellular adhesion molecules play a pivotal role in the pathogenesis of atherosclerosis by mediating the adherence of blood leukocytes. Since hyperhomocysteinemia appears to be an independent risk factor for the development of atherosclerosis, in this study we investigated the effect of homocysteine on basal and TNF-alpha-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell-adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin) on human umbilical-vein endothelial cells. Incubation of endothelial cells with homocysteine resulted in dose-dependent reduction in TNF-alpha-induced (5 ng/ml) expression of VCAM-1, E-selectin, and ICAM-1 (the latter less pronounced). This effect was found to be specific since other thiol compounds-cysteine and glutathione-did not mimic homocysteine activity. Homocysteine attenuated TNF-alpha-stimulated U-937 adhesion to the endothelial monolayer and reduced TNF-alpha-induced activation of the transcription factor NF-kappaB, indicating that NF-kappaB inhibition may play a role in inhibiting expression of adhesion molecules in endothelial cells.

Cell Adhesion↗
PubMed2001

Soluble substances released from postischemic reperfused rat hearts reduce calcium transient and contractility by blocking the L-type calcium channel.

OBJECTIVES: This study was designed to investigate the effects of cardiodepressant substances released from postischemic myocardial tissue on myocardial calcium-regulating pathways. BACKGROUND: We have recently reported that new cardiodepressant substances are released from isolated hearts during reperfusion after myocardial ischemia. METHODS: After 10 min of global ischemia, isolated rat hearts were reperfused, and the coronary effluent was collected for 30 s. We tested the effects of the postischemic coronary effluent on cell contraction, Ca2+ transients and Ca2+ currents of isolated rat cardiomyocytes by applying fluorescence microscopy and the whole-cell, voltage-clamp technique. Changes in intracellular phosphorylation mechanisms were studied by measuring tissue concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), as well as activities of cAMP-dependent protein kinase (cAMP-dPK) and protein kinase C (PKC). RESULTS: The postischemic coronary effluent, diluted with experimental buffer, caused a concentration-dependent reduction of cell shortening and Ca2+ transient in the field-stimulated isolated cardiomyocytes of rats, as well as a reduction in peak L-type Ca2+ current in voltage-clamped cardiomyocytes. The current reduction resulted from reduced maximal conductance--not from changes in voltage- and time-dependent gating of the L-type Ca2+ channel. The postischemic coronary effluent modified neither the tissue concentrations of cAMP or cGMP nor the activities of cAMP-dPK and PKC. However, the effluent completely eliminated the activation of glycogen phosphorylase after beta-adrenergic stimulation. CONCLUSIONS: Negative inotropic substances released from isolated postischemic hearts reduce Ca2+ transient and cell contraction through cAMP-independent and cGMP-independent blockage of L-type Ca2+ channels.

Animals↗
PubMed2000

Adrenomedullin and myocardial contractility in the rat.

The effects of adrenomedullin in the regulation of myocardial contractility were investigated in the rat. In papillary muscles (n=6), adrenomedullin (0.1 to 10 nM) failed to show contractile effects. NO (nitric oxide) synthase inhibition with N(G)-nitro-L-arginine (L-NOARG) did not unmask any inotropic effect of adrenomedullin. The positive inotropic effect of isoprenaline (0. 01 nM to 10 microM) was identical after adrenomedullin, after L-NOARG, and after L-NOARG plus adrenomedullin (n=6 each). In field-stimulated rat ventricular myocytes, adrenomedullin (1, 10, and 100 nM; n=4 each) had impact neither on cell shortening nor on Ca(2+) transients. In isolated constant-flow perfused hearts (7.3+/-0.3 ml/min), adrenomedullin (1 nM, n=9; 10 nM, n=7) induced significant coronary vasodilation (-28%, -50%). In conclusion, adrenomedullin is a potent coronary vasodilator, but has no significant effects on myocardial contractility in the rat.

Adrenomedullin↗
PubMed2000

Beta1-adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?

A substantial body of evidence suggests involvement of the human beta1-adrenoceptor (beta1-AR) gene in the pathophysiology of dilated cardiomyopathy (DCM), a severe heart disease of significant public health impact. Beta1-AR-mediated signal transduction is dramatically altered due to downregulation, resulting in an impairment of myocardial response. The important role of genetic factors in idiopathic dilated cardiomyopathy (IDCM) recently recognized, we analyzed this prime candidate gene for genetic variation in carefully selected patients and controls. In this preliminary study, 18 single nucleotide polymorphisms were observed, 17 of which were located in the N-terminal and C-terminal region of the coding exon, resulting in 7 amino acid exchanges: Ser-49-Gly, Ala-59-Ser, Gly-389-Arg, Arg-399-Cys, His-402-Arg, Thr-404-Ala, and Pro-418-Ala. These mutations resulted in 11 different beta1-AR genotypes. Importantly, the genotypes carrying the Ser-49-Gly mutation in the N-terminus of the molecule in a heterozygous or homozygous form were observed significantly more frequently in the group of IDCM patients. The present results may provide a clue on the molecular mechanisms involved in IDCM, and add moreover interesting information on nature, distribution, and evolutionary aspects of sequence variation in human adrenergic receptor genes.

Adult↗
PubMed1999

Microvascular endothelial cells remodel cultured adult cardiomyocytes and increase their survival.

We investigated the paracrine effect of cardiac microvascular endothelial cells (MVEC) on cultured adult rat cardiomyocytes (ARC). ARC were exposed for 8 days to serum-free medium (CM) conditioned by MVEC. Controls were grown in FCS or FCS-free medium. Protein synthesis of CM-stimulated ARC increased twofold versus 5% FCS-stimulated cells until day 8. Seventy-nine percent of CM-treated myocytes survived, whereas only twenty-four percent of FCS-free ARC retained viability. The phenotype of myocytes exposed to CM was different from control. Analysis by confocal laser microscopy of CM-stimulated myocytes showed actin staining throughout the whole cell body up to the peripheral extensions, with concomitant appearance of myomesin in a cross-striated pattern. The reexpression of fetal alpha-smooth muscle actin determined immunohistochemically and by Western blot increased from day 6 in CM-treated cells, whereas ARC grown in up to 20% serum were negative. These effects could not be mimicked by any of the other cardioactive substances tested here, indicating a novel trophic factor in CM.

Actins↗
PubMedDate not supplied

Pattern of prescriptions issued by nursing home-based physicians versus office-based physicians for frail elderly patients in German nursing homes.

PURPOSE: The purpose of this study was to describe the physician prescription pattern for frail elderly patients in German nursing homes and to identify differences, if any, between that of physicians based in the nursing homes (A) and those with office-based practices (B). METHODS: Retrospective, longitudinal study of medication prescriptions on the basis of the database of a health insurance (Betriebskrankenkasse) in Berlin, Germany. We assessed the medication prescriptions for all 996 unselected insured individuals aged > or = 60 years who were insured throughout 1999 and lived in nursing homes. We analyzed selected patient characteristics and prescription data. Drugs were classified according to the WHO ATC code and were assigned a mean daily defined dose (DDD). RESULTS: 816 individuals were women and 180 were men. A total of 78% of women and 43% of men were aged 80 years or older. Two hundred sixty three patients were seen by nursing home-based physicians (A) and 733 by office-based physicians (B). The median of prescriptions per patient and year was 31 (A) and 37 (B) (p between groups < 0.001). Patients in Group A also received a lower number of DDDs in comparison to Group B (1109 vs 1250; p < 0.01). Costs were substantially higher in group B, and in both groups higher in the 60-69 years old in comparison to the more senior patients. The prescription pattern suggested a considerable frequency of inappropriate drug use in both groups in the following classes: psychopharmacological agents (neuroleptics, antidepressants, hypnotics), pain medication, digitalis glycosides, laxants and loop diuretics. On an average, office-based physicians (B) prescribed relatively more medications in all major classes with the exception of non-opiate analgesics, laxants and anxiolytics. CONCLUSIONS: These data are indicative of a considerable use of inappropriate medication for frail geriatric patients. Differences between the prescribing pattern among nursing home-based and office-based physicians were not substantial, however, the latter group prescribed relatively more drugs.

Aged↗
PubMedDate not supplied

Computer-aided measurement of cell shortening and calcium transients in adult cardiac myocytes.

The contractile cycle of the cardiac myocyte is essentially controlled by the concentration of intracellular calcium ([Ca2+]i). Measurement of [Ca2+]i using Ca2+-dependent fluorescence and simultaneous monitoring of cell dynamics enable characterization of a variety of substances interacting with ion channels and contractile proteins. In this report we describe a novel method featuring up to 480 frames/s for monitoring rapid changes in cellular calcium and cell length, in which every individual cycle allows effective evaluation of major cell parameters. Computers aid in determination of time to peak (in ms), time to 50% decrease (ms), diastolic Ca2+ (relative fluorescence units, rfu), systolic Ca2+ (rfu), Ca2+ transients (rfu), DeltaCa2+/Delta(t) rise (rfu/s), and DeltaCa2+/Delta(t) fall (rfu/s). Contractile parameters are as follows: maximum cell length (microm), minimum cell length (microm), absolute cell shortening (microm), peak DeltaL/Delta(t) shortening (microm/s), and peak DeltaL/Delta(t) relaxation (microm/s). In summary, we succeeded in demonstrating that this system is a unique and valuable tool that allows simultaneous and accurate assessment of contractile parameters and of calcium movements of isolated adult cardiac myocytes.

Animals↗