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Biomedical subjects

B Jäger

Publications and source records attributed to B Jäger.

At least 19 recordsLinked to original sources

Efficacy of eprosartan in combination with HCTZ in patients with essential hypertension.

This randomised, double-blind study was designed to investigate the efficacy of a once-daily (OD) combination of the AT(1) receptor blocker, eprosartan 600 mg, and the thiazide diuretic, hydrochlorothiazide (HCTZ) 12.5 mg, in patients with mild to moderate hypertension (sitting diastolic blood pressure (sitDBP) > or =98 mm Hg and < or =114 mm Hg) not adequately controlled with eprosartan 600 mg OD. A total of 494 patients entered the open-label monotherapy run-in phase, which consisted of eprosartan 600 mg OD for 3 weeks. Patients who responded to monotherapy were not eligible to enter the randomised phase of the study and were withdrawn. The remaining 309 patients were then randomised to either eprosartan 600 mg plus HCTZ 12.5 mg OD or to continue on eprosartan 600 mg OD. In the eprosartan plus HCTZ combination group, both sitDBP and sitting systolic blood pressure (sitSBP) were significantly reduced compared with the eprosartan monotherapy group. In addition, the response rate was higher in the combination group compared with the monotherapy group. There were no significant effects on reduction of sitDBP due to gender, prior use of antihypertensives or baseline severity of hypertension. The tolerability profile for the combination group was similar to that for the monotherapy group. Headache was the most frequent adverse event in both treatment groups. The majority of adverse events were mild to moderate in intensity. In this study of patients who were unresponsive to eprosartan monotherapy for 3 weeks, a combination product of eprosartan 600 mg and HCTZ 12.5 mg was shown to be an effective and well tolerated treatment.

Acrylates↗

Local hyperthermia, radiation, and chemotherapy in recurrent breast cancer is feasible and effective except for inflammatory disease.

PURPOSE: To investigate the feasibility and effectiveness of radiochemothermotherapy (triple-modality therapy) in patients with inoperable recurrent breast cancer. PATIENTS AND METHODS: Patients with inoperable recurrent lesions, World Health Organization (WHO) performance status of 2 or greater, life expectancy of more than 3 months, adequate bone marrow, hepatic and renal function were eligible for this Phase I/II study. Conventionally fractionated or hyperfractionated radiotherapy (RT) was performed. Once-weekly local hyperthermia (HT) combined with chemotherapy (CT; epirubicin 20 mg/m(2), ifosfamide 1.5 g/m(2)) was applied within 30 min after RT. RESULTS: Twenty-five patients, all heavily pretreated (18/25 preirradiated), received a mean total dose of 49 Gy. The median number of HT/CT sessions was 4. Skin toxicity was low, whereas bone marrow toxicity was significant (leucopenia Grade 3/4 in 14/1 patients). The overall response rate was 80% with a complete response (CR) rate of 44%. Response rates in patients with noninflammatory disease (n = 14; CR 10 patients, partial response [PR] 3 patients) were far better than in patients with inflammatory disease (n = 11; CR 1 patient, PR 6 patients). CONCLUSIONS: In patients with recurrent breast cancer, triple-modality therapy is feasible with acceptable toxicity. High remission rates can be achieved in noninflammatory disease, however, local control is limited to a few months. Whether the addition of chemotherapy has a clear-cut advantage to radiothermotherapy alone remains an open question.

Adult↗

Eprosartan versus enalapril in elderly patients with hypertension: a double-blind, randomized trial.

AIM: To compare the efficacy and safety of eprosartan and enalapril to lower systolic blood pressure in elderly patients with essential hypertension. METHODS: 334 patients >65 years with sitting systolic blood pressure (sitSBP) > or = 160 mmHg and diastolic blood pressure (sitDBP) 90-114 mmHg were randomized to 12 weeks of double-blind treatment with eprosartan, 600-800 mg once daily (o.d.) or enalapril (5-20 mg o.d.), with flexible dose titration to lower systolic blood pressure below 140 mmHg. The primary outcome measure was change in sitSBP at endpoint. RESULTS: Least-squares mean changes from baseline in sitSBP were -18.0 and -17.4 mmHg in the eprosartan and enalapril groups, respectively (difference eprosartan-enalapril -0.6, 95% confidence interval, CI, -4.1 to 3.0, p = 0.76). The corresponding figures for sitDBP were -9.4 and -9.6 mmHg (difference eprosartan-enalapril 0.2, 95% CI -1.7 to 2.0, p = 0.84). Normalization and response rates were also similar in the two groups. Adverse events were recorded in 61 (35.7%) patients on eprosartan (one with dry cough) and 83 (50.9%) patients on enalapril (10 with dry cough). CONCLUSIONS: Eprosartan and enalapril were equally effective in reducing sitSBP and sitDBP in elderly patients with predominantly systolic hypertension. Eprosartan was better tolerated and, in particular, lacked the propensity of enalapril to cause dry cough.

Acrylates↗

Relevance of N-acetyltransferase 1 and 2 (NAT1, NAT2) genetic polymorphisms in non-small cell lung cancer susceptibility.

The highly polymorphic N-acetyltransferases (NAT1 and NAT2) are involved in both activation and inactivation reactions of numerous carcinogens, such as tobacco derived aromatic amines. The potential effect of the NAT genotypes in individual susceptibility to lung cancer was examined in a hospital based case-control study consisting of 392 Caucasian lung cancer patients [152 adenocarcinomas, 173 squamous cell carcinomas (SCC) and 67 other primary lung tumours] and 351 controls. In addition to the wild-type allele NAT1*4, seven variant NAT1 alleles (NAT1*3, *10, *11, *14, *15, *17 and *22) were analysed. A new method based on the LightCycler (Roche Diagnostics Inc.) technology was applied for the detection of the polymorphic NAT1 sites at nt 1088 and nt 1095. The NAT2 polymorphic sites at nt 481, 590, 803 and 857 were detected by polymerase chain reaction-restriction fragment length polymorphism or LightCycler. Multivariate logistic regression analyses were performed taking into account levels of smoking, age, gender and occupational exposure. An increased risk for adenocarcinoma among the NAT1 putative fast acetylators [odds ratio (OR) 1.92 (1.16-3.16)] was found but could not be detected for SCC or the total case group. NAT2 genotypes alone appeared not to modify individual lung cancer risk, however, individuals with combined NAT1 fast and NAT2 slow genotype had significantly elevated adenocarcinoma risk [OR 2.22 (1.03-4.81)] compared to persons with other genotype combinations. These data clearly show the importance of separating different histological lung tumour subtypes in studies on genetic susceptibility factors and implicate the NAT1*10 allele as a risk factor for adenocarcinoma.

Aged↗

[The effects of psychodynamic inpatient treatments on personality data of patients with anorexia nervosa and bulimia nervosa - results of the German multicenter study (TR-EAT)].

OBJECTIVES: How are the effects of a psychodynamic inpatient treatment on personality data of patients with anorexia nervosa and bulimia nervosa? In how many patients can a successful change in the personality area be observed? METHODS: 732 patients were assessed at the beginning and the end of an inpatient treatment as well as 2 1/2 years after this treatment. Data were collected by means of the personality inventories "Freiburger Persoenlichkeitsinventar (FPI-R)" and "Narzissmusinventar". A definition of success was constructed using the clinical significance concept. It is related to the scales life satisfaction, inhibition (FPI-R), powerless self and negative body self (Narzissmusinventar). RESULTS: The results in both questionnaires show the clinically well known psychopathology characteristics of eating disorder patients. During the inpatient treatment and also afterwards, there are improvements in the personality data, but not to the extent of the values obtained from a healthy control group. In the outcome measure, one third of the patients experienced remarkable improvements. The success in the personality area is positively correlated to the success in the eating disorder symptoms. This success could not be predicted by initial data or by therapy data. CONCLUSIONS: There are marked impairments of the patients in the personality data. Changes in this domain take time and are rather small.

Adult↗

Heparin-induced extracorporal low-density-lipoprotein precipitation (H.E.L.P.) to improve the recovery of hearing in patients with sudden idiopathic hearing loss.

The pathogenesis of sudden hearing loss (SHL) is still not well understood. Possible causes include increased blood viscosity, microthrombosis or altered blood flow. Hypercholesterolemia, hyperfibrinogenemia and increased platelet aggregation are frequently observed in patients with SHL. The aim of this study was to investigate whether drastic lowering of plasma cholesterol and fibrinogen by selective extracorporal apheresis could have a beneficial effect on hearing recovery in these patients. Seven patients with SHL were treated with an extracorporal procedure removing fibrinogen and cholesterol from plasma. Six of the seven patients showed an immediate improvement in auditory thresholds following a single treatment of heparin-induced low-density lipoprotein precipitation. These findings indicate for the first time that acute and drastic removal of plasma fibrinogen and low-density lipoproteins may be an effective clinical method for the treatment of patients with SHL.

Adult↗

[Illness-related stress in psoriasis vulgaris. Validation of the "Psoriasis Daily Stress Inventory"].

BACKGROUND AND OBJECTIVE: Illness specific stress plays an important part in the daily life of psoriatic patients. Until now for the measurement of relevant aspects of daily stress only the "Psoriasis Life Stress Inventory" (PLSI) of Gupta & Gupta exists; with the "Psoriasis-Alltagsstress-Inventar" (PAI), a German version of the PLSI is presented and its psychometric properties are discussed. PATIENTS/METHODS: 385 in-patients completed the PAI. The internal validity was examined by factor analysis. Moreover, the correlations between the PAI total score and sociodemographic parameters (ANOVA) and extent of skin involvement (multiple regression) were determined. RESULTS: The PLSI score proves to be sufficiently independent of age, sex, age at onset, and general extent of skin involvement. However, affections of the hands, the lower abdomen and the genitals show a strong influence on the total score. We found marked interrelations with the stigmatization feeling ("Questionnaire on Experience with Skin Complaints" QES, Schmid-Ott et al. 1998). CONCLUSIONS: The results suggest that the PAI is a useful and psychologically relevant questionnaire for psoriatic patients.

Adult↗

[Drug and psychological therapies in chronic subjective tinnitus. Meta-analysis of therapeutic effectiveness].

A metaanalysis on pharmacological and psychological treatment reports was conducted in order to evaluate the overall effectiveness of these treatment conditions in chronic tinnitus. A totality of 109 treatment studies published between 1976 and 3/1995 and meeting minimal inclusion criteria was located, but only 24 studies reporting sufficient information could be analyzed. The methodological quality of the studies was evaluated by a coding scheme, and the resulting index of effectiveness has been weighted by this standard as well as by sample size. Effect sizes of pharmacological studies were ES = 1.27 and by this higher than the ones for psychological studies with ES = 0.88. This finding is attenuated by high (unspecific) placebo effects of ES = 0.65 in pharmacological studies compared to ES = 0.10 in psychological studies. In general, patients from psychological studies further improve after treatment in cases where catamnestic measurements have been conducted.

Anesthetics, Local↗

Which organic acids does hemofiltrate contain in the presence of acute renal failure?

It is not generally possible to measure most organic acids in the serum of critically ill patients, due to rapid metabolism and methodological problems. Only the regular measurement of lactic acid and the arterial ketone body ratio (acetoacetate/beta-hydroxybutyrate, AKBR) have been introduced in clinical practice, but these parameters can represent only a part of the disturbed metabolism. In pediatric patients, a chromatographical urine analysis has been established for detection of inborn errors of metabolism, which allows the determination of more than 50 organic acids simultaneously (gas chromatographic (GC) analysis in combination with mass spectrometry (MS)]. In continuous treatment of acute renal failure, hemofiltrate is always available, but it contains only low protein concentrations and after the filtration process, metabolism is rapidly stopped. The sieving coefficient of lactic acid is nearly one in hemofiltration. The aim of our study was to compare results of the regular and CG/MS methods in blood and hemofiltrate for lactic acid, and to find other organic acids of possible clinical importance. We investigated serum (lactic acid) and hemofiltrate of 40 critically ill patitens, similar to the urine analysis method for infants. All patients suffered from acute renal failure and were treated by continuous veno-venous hemofiltration (CVVH). The conditions of treatment were standardized (spontaneous ultrafiltration in the first hour), and the material (blood/hemofiltrate) was taken one hour after the beginning of extracorporeal circulation. Statistical methods included correlation analysis, nonparametric ANOVA with Wilcoxon scores (ranks of data), and stepwise discriminant analysis. Regular and GC/MS methods in hemofiltrate showed a good correlation for lactic acid. The best correlation with lactic acid was found for 4-hydroxy-phenyllactic acid (n=20, r=0.866), 2-hydroxy-valeric acid (n=22, r=0.7491) and 2-hydroxybutyric acid (n=32, r=0.5148). Age, sex, diagnosis, and APACHE II score play a subordinate role, but the presence of glyceric and citric acid possibly have prognostic importance [nonparimetric ANOVA with Wilcoxon scores (ranks of data)], as does the combination of 3-hydroxypropionic acid, glyceric acid, and threonic-acid-4-lacton (stepwise discriminant analysis). It can be concluded that in acute renal failure, the measurement of lactic acid and AKBR can reflect only a small part of disturbed metabolism. Hemofiltrate can be a useful medium in describing metabolic processes in critically ill patients with acute renal failure. Some inherited metabolic diseases in infants (phenylketonuria, maple syrup disease) and ketoacidosis show similar metabolic modifications.

APACHE↗

Validation of a customized LIMS.

The advantages of customized Laboratory Information Management's Systems (LIMS) are their focus on the special aspects of their users' needs. Differences in the research and development or production chain in the individual organizations lead to an increase of interest in customized systems. Usually, also for customized systems, the core software is commercially available. The individual application modules as the Customized part of the LIMS are the most critical elements within the validation process. The topic of this paper is to give an example of the validation of a customized analytical LIMS. Validation of complex computerized systems guarantees the intended use and is therefore an unavoidable requirement of authorities. The audit of the supplier of the individual programmed modules, the user requirement specifications and the acceptance testing and results, respectively, on the software are of special interest within a customized LIMS. The hardware suitability and the principal processing routines are also a very important part of the whole validation process, but they will not be discussed in detail in this paper.

Clinical Laboratory Information Systems↗

Comparison of PCR-based DNA fingerprinting techniques for the identification of Listeria species and their use for atypical Listeria isolates.

Four PCR-based DNA fingerprinting techniques were compared for their ability to identify at the species level a heterogeneous collection of isolates belonging to the six valid Listeria species. 16S rDNA-RFLP analysis identified all species and 16S rDNA-SSCP analysis identified almost all species. Also, isolates with unusual biochemical characteristics and/or unusual antigenic composition could be identified correctly. rRNA-intracistronic length polymorphism analysis suffered from high intraspecific variability, a limited number of fragments per profile, and small length differences between the spacers of different species. tRNA-intergenic length polymorphism analysis resulted in identification of all isolates but one, when fluorescent DNA capillary electrophoresis was used such that fragment length differences of 1 bp could be resolved. The four techniques yielded comparable results relevant to the taxonomy of Listeria. They all indicate a high degree of genetic relatedness between L. innocua and L. welshimeri, homogeneity of L. grayi, distinct but clear relatedness of L. grayi to the other Listeria species, a clear distinction between the two subspecies of L. ivanovii, and a clear distinction between Listeria isolates and isolates from closely related taxa or from species which are phenotypically difficult to distinguish from Listeria. New sequence determination of the 16S rRNA gene was necessary to obtain sequences in accordance with the findings of 16S rDNA-RFLP analysis.

DNA Fingerprinting↗

Stress-induced endocrine and immunological changes in psoriasis patients and healthy controls. A preliminary study.

BACKGROUND: Clinical observations suggest that psychological stress can induce exacerbation of psoriasis. It is hypothesized that these stress effects on the course and outcome of psoriasis are caused by neuroendocrine modulation of immune functions. Therefore we investigated the cardiovascular, endocrine and immunological response to a laboratory stressor in psoriasis patients and healthy controls. METHODS: Untreated (n = 7) and PUVA-treated (n = 4) psoriatics and healthy controls (n = 7) were exposed to a brief laboratory stressor (public speaking and mental arithmetic). Heart rate and blood pressure, catecholamine, cortisol, and DHEA plasma concentration, as well as distribution of T and NK lymphocytes were analyzed before, immediately after and 1 h after stress exposure. RESULTS: Heart rate and blood pressure increased in all three groups during stress exposure with the most pronounced changes in PUVA-treated patients. Psoriasis patients displayed higher adrenaline values but diminished cortisol and DHEA plasma concentrations compared to controls. NK cell numbers (CD16+, CD56+), but not T lymphocyte subsets, increased immediately after stress exposure in untreated patients and controls. This effect was significantly diminished in PUVA-treated patients. CONCLUSIONS: The data of this pilot study indicate an enhanced stress-induced autonomic response and diminished pituitary-adrenal activity in psoriasis patients. PUVA treatment seems to interfere with the cardiovascular and NK cell response to acute psychological stress. Future studies will analyze the stress-induced neuroimmunological mechanisms in psoriatics in more detail.

Adult↗

Safety and tolerability of moxonidine in the treatment of hypertension.

Classical centrally acting antihypertensive agents lower blood pressure by reducing excessive sympathetic tone; however, their clinical use is limited by an adverse effect profile resulting from alpha2-adrenoceptor agonism. Moxonidine is a new centrally acting agent showing selective agonism of imidazoline I1 receptors, but very little alpha2-adrenoceptor agonism. The safety and tolerability of moxonidine was reviewed over an 8-year period (1989 to 1997), including 74 clinical trials and an estimated 370000 patient-years of exposure. Dry mouth and somnolence were the most frequently reported adverse events, followed by headache and dizziness. In phase II to IV controlled studies in patients with hypertension (n = 1460), the incidence of dry mouth was 8 to 9%, somnolence 5 to 8% and headache 6%, as recorded by spontaneous reporting; the percentage of patients discontinuing treatment because of adverse events did not exceed 4%. Subgroup analyses revealed no differences in adverse events related to age or gender. Moxonidine did not exacerbate concomitant conditions such as diabetes mellitus or chronic obstructive pulmonary disease, or interact pharmacokinetically with concurrent medications such as hydrochlorothiazide, digoxin and glibenclamide (glyburide). Coadministration of moxonidine with lorazepam resulted in small additional impairments in tasks requiring attention. A similar distribution of adverse events was observed in uncontrolled studies (n = 1058). The incidence and severity of dry mouth and somnolence were found to decrease with increasing exposure to moxonidine over a period of up to 2 years. Serious adverse events were rare in all trials and could not be attributed to administration of moxonidine. Post-marketing surveillance of the adverse effect profile of moxonidine detected 2 additional adverse effects: nausea and allergic skin reactions. The safety profile of moxonidine, combined with proven antihypertensive efficacy, suggests that it may have an important role to play in the management of mild-to-moderate hypertension.

Antihypertensive Agents↗

[Illness experience and treatment seeking behavior of psoriasis patients].

We analyzed how psoriasis patients sought professional help and correlated it to their illness attitudes and feeling of stigmatization. Semi-structured interviews of 400 patients were reanalyzed to identify homogeneous groups concerning initial reactions at first manifestations of the disease. Four groups ("isolated", "stigmatized", "socially supported" and "non-stigmatized" patients) were found and cross-tabulated with five resulting groups of a second cluster-analysis concerning the "style" of the seeking behaviour of professional and paraprofessional help and medical measures against the psoriasis ("multi-users", "arranged mini-users", "waiting-room patients", "optimists" and "self-therapists"). We were able to describe typical courses of illness behaviour depending on the initial reaction. The results are discussed with regard to the desirable identification of problematic patients within professional care units.

Adaptation, Psychological↗

PCR-based fingerprinting of Mycobacterium bovis isolates.

We investigated a number of PCR-based strategies for sub-typing isolates of Mycobacterium bovis. A panel of 15 PCR primers, designed from random sequences, insertion sequences and repetitive elements, were analyzed for their ability to allow differentiation between eight M. bovis isolates. PCR products were analyzed using agarose gel electrophoresis and polyacrylamide gel electrophoresis. Random primer based PCR, conducted with a variety of primers did not differentiate between isolates of M. bovis. Successful differentiation between isolates was achieved by the amplification of fragments located between DNA repetitive elements and insertion sequences of the M. bovis genome. PCR primers designed from the major polymorphic tandem repeat (MPTR) region and from insertion sequences IS6110 and IS986 allowed differentiation between isolates of M. bovis. This study is presented as a first step towards the development of PCR-based methods to differentiate between isolates.

Animals↗

[Insertion possibility of 16S-23S space amplification and random amplified polymorphic DNA analysis for typing of methicillin-resistant Staphylococcus aureus strains in the context of nosocomial infections].

Within the scope of the present study n = 183 MRSA isolates from the extended area of Düsseldorf and n = 93 international MRSA strains from seven different countries were typed by pulsed-field gel electrophoresis and two PCR methods (RAPD and 16S-23S-spacer amplification). The isolates could be subdivided into 30 different types by PFGE, into 21 by means of RAPD and 18 by 16S-23S-spacer amplification. PFGE had the highest discriminatory potential, however, a combined use of the three typing methods allows a more detailed differentiation even of those isolates with identical PFGE pattern. Both amplification procedures were rapid, easy in handling with reproductable results. For a temporary epidemiological analysis within 24 hours, both amplification methods could be combined. In case the investigated isolates were still suspected of showing a "clonal identity", they should be analysed by additional PFGE (lasting about four days). Although the international isolates were chosen by random selection, several MRSA strains with identical pattern could be found in different countries of the world. Some RAPD-, spacer- and PFGE pattern were constant over many years. This reflects a high genetic stability of single strains.

Cross Infection↗

Differential expression of fructosyllysine-specific receptors on monocytes and macrophages and possible pathophysiological significance.

A differing individual expression of fructosyllysine-specific receptors has been found on the monocytes of 90 insulin-dependent diabetic patients and 101 healthy control subjects. The degree of receptor expression is neither age- nor sex-dependent; however, in the diabetic group it correlates significantly with the severity and age of onset of diabetic microangiopathy. To interpret the results of the human study, spontaneously diabetic and non-diabetic BB/OK rats were used to estimate tissue content of glucose-modified proteins and capillary basement membrane thickness in relation to the receptor expression on macrophages. In non-diabetic and diabetic rats no correlation was found between receptor expression and tissue content (i.e. artery, nerve) of fructosyllsine and fluorescent advanced glycation end products. However, animals which express the fructosyllysine receptor showed a greater increase in muscle capillary basement membrane thickness. There are indications that fructosyllysine receptor expression is positively associated with indices of diabetic complications such as microangiopathy and/or capillary basement membrane thickening.

Adult↗

Psychotherapy and bulimia nervosa: evaluation and long-term follow-up of two conflict-orientated treatment conditions.

Analytic in-patient therapy (n = 32) and systemic out-patient therapy (n = 39) were applied to patients with bulimia nervosa, and the effects were evaluated 14, 26 and 38 months after the start of the treatments. Our assumptions about the general efficacy of both conflict-orientated techniques were confirmed: both therapies satisfactorily reduced the symptomatic behaviour, as well as secondary factors related to bulimia nervosa, in the long term. However, we could not identify differential effects of the two treatment regimes, which we had expected with regard to the very different therapeutic approaches. The similarities of outcome of both therapies predominate, with slightly better results in the case of the analytic in-patient treatment. The results are discussed with regard to the assumption that specific healing factors are involved in conflict-orientated treatments in addition to the "common factors' of psychotherapy.

Adolescent↗