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Biomedical subjects

F Keller

Publications and source records attributed to F Keller.

At least 109 records · Page 6Linked to original sources
PubMed1997

Transient alkaline hyperphosphatasaemia in an adult: biochemical peculiarities.

We report on a 27-year-old healthy female with transient hyperphosphatasaemia of adulthood (it is the eighth case ever recorded). A maximum alkaline phosphatase activity of 1950 U/l, 11-fold the upper reference limit, was measured. The activity normalized within 11 weeks. Electrophoresis revealed the typical pattern for alkaline phosphatase isoenzymes observed in transient hyperphosphatasaemia of infancy: a fast-migrating liver isoenzyme and a bone isoenzyme. Contrary to the findings in transient hyperphosphatasaemia of infancy the liver isoenzyme did not precipitate with wheat-germ lectin whereas the bone isoenzyme partially bound to lectin. Biochemical features of transient hyperphosphatasaemia in an adult may be different from those in infancy. Recognition of an atypical pattern could help avoid unnecessary extensive investigations.

Adult↗
PubMed1997

Dosage adjustment of antiinfective therapy in patients with renal impairment.

Schematic dosage adjustments for aminoglycosides, vancomycin, and ciprofloxacin were derived from published data on the prolongation of elimination half-lives in patients with renal impairment. Therapeutic drug monitoring was retrospectively evaluated with 84 severely ill patients, 29 of whom needed renal replacement therapy (35%). Mortality (n = 27) and antiinfective failures were high (n = 23). Toxicity was suspected in 5 patients, though it was demonstrated only in 1 case. As compared to the patients with normal renal function, patients with renal impairment exhibited peak levels that tended to be lower, although their trough levels tended to be higher; the aminoglycoside troughs even were significantly elevated in renal replacement patients (1.0 mg/l (0.6-1.4) versus 0.6 mg/l (0.3-0.8)). Seen in relation to toxicity, antiinfective failure was by far the greater problem even with dosage adjustments at high trough levels. Multivariate analysis showed antiinfective failure to be significantly correlated to 10 canonical variables (age, weight, leucocyte count, peak level, trough level, initial creatinine, increase in creatinine, fever, change of dosage, and renal replacement therapy). Among these variables, it were neither drug levels nor renal replacement, but only persistent fever and deteriorating renal function that independently contributed to antiinfective failure. For adjustment of antiinfective therapy, paradoxically we conclude that trough concentrations higher than normal must be allowed for to avoid underdosage in renal replacement patients.

Aminoglycosides↗
PubMed1997

[Quality assurance in inpatient treatment of depression. Aspects of quality monitoring and external quality assurance exemplified by a pilot project of inpatient treatment of depression].

Aspects of a Pilot Study on Depression Treatment According to Quality Monitoring and External Quality Assurance: Experiences and results of a pilot study on quality of the treatment of depressed inpatients in 4 different psychiatric hospitals (2 state mental hospitals, 1 university clinic, 1 psychiatric clinic at a city general hospital) according to so-called process and outcome quality, are reported. Outcome data (self-ratings, observer rating, clinical global impression admission versus discharge, patient satisfaction with treatment, duration of inpatient stay/and patient data are reported while comparing the 4 hospitals. Difficulties and problems of data collection, assessments and comparison of 4 different hospitals are discussed.

Adult↗
PubMed1997

Selective screening for the Factor V Leiden mutation: is it advisable prior to the prescription of oral contraceptives?

The cumulative thrombotic risk of Factor V (FV) Leiden and oral contraceptives (OC) recommends screening for the mutation. Assuming that a family history of thrombosis increases the patient's likelihood of bearing FV Leiden, a selective rather than universal screening would be performed. We studied the utility of a family history of thrombosis for screening of FV Leiden before prescription of OC and, furthermore, the utility of screening even if oral contraception is favoured. 101 patients who had their first and single thromboembolic event while using OC were interviewed. 609 women without any history of thromboembolism recruited by gynecologists completed a standard questionnaire. 101 of these women, age-matched and currently using OC, were selected for a case-control study. Regarding patients with previous thromboembolism, a family history in a first-degree relative had a positive predictive value (PPV) of only 14% for FV Leiden. A PPV of 12% was calculated by investigating the 609 thrombosis-free women. Inherited FV Leiden (odds ratio = 4.9) and acquired risk factors (odds ratio = 10.1) were both found to be the most prominent, but independent additional risks. Nevertheless, FV Leiden carriers, both heterozygotes and homozygotes, did not suffer earlier from thromboembolism than patients without the mutation. In conclusion, family history is an unreliable criterion to detect FV Leiden carriers. Screening for factor V Leiden can be worthwhile even if the advantages of oral contraception are higher assessed than the thrombotic risk. Affected women knowing about their additional risk could contribute to the prevention of thrombosis in risk situations.

Adolescent↗
PubMed1996

Different binding and degradation of proinsulin, insulin and insulin-like growth factor-1 (IGF-1) in cultured renal proximal tubular cells. Implications for the prolonged serum half-life of proinsulin.

Recent studies have reported that elevated proinsulin levels are indicative of an increased cardiovascular risk. Renal proximal tubular cells represent a major site for the metabolism of insulin-like hormones after glomerular filtration into the tubular lumen. To determine the binding and degradation of proinsulin in comparison with insulin and insulin-like growth factor-1 (IGF-1), we have used a rabbit proximal tubular cell line (PT-1). As confirmed by electron microscopy. PT-1 cells exhibit bipolar differentiation, demonstrating apical microvilli and invaginations of the basolateral membrane. To allow selective incubation of both compartments, cells were grown on filter membranes. Performing equilibrium binding assays with 125I-labelled hormones, severalfold higher binding was found at the apical than at the basolateral cell membrane, with the capacity range IGF-1 > insulin > proinsulin. Half-maximal displacement of 125I-labelled insulin and IGF-1 was observed at 0.6 and 2 nM, respectively, while crossover binding to the alternate receptor occurred with a 10- to 100-fold lower affinity. Half-maximal displacement of 125I-proinsulin binding was obtained at approx. 8 nM proinsulin and insulin, whereas IGF-1 was 10-fold less potent. The relative degradation of specifically bound tracer was lowest for proinsulin (apical 10%, basolateral: 13%). IGF-1 was degraded by 20% at the apical cell membrane, and up to 78% at the basolateral membrane. In contrast, almost the total amount of insulin bound was degraded at both membrane sites (apical 99%, basolateral: 83%). These results suggest separate insulin and IGF-1 receptors while proinsulin binds with high affinity to a third insulin-like receptor on the apical membrane of PT-1 cells.

Animals↗
PubMed1996

Changes in coagulation and fibrinolytic parameters caused by extracorporeal circulation.

During cardiopulmonary bypass (CPB) mechanical stress and the contact of blood with artificial surfaces lead to the activation of pro- and anticoagulant systems and the complement cascade, and to changes in cellular components. This phenomenon causes the "postperfusion-syndrome", with leukocytosis, increased capillary permeability, accumulation of interstitial fluid, and organ dysfunction. In this study, we focused on the influence of the extracorporeal circulation, sternotomy, and heparin administration on the activation of coagulation and fibrinolysis. In 15 patients we investigated coagulation parameters before, during and post CPB, i.e., fibrinogen, antithrombin (AT) III, thrombin-antithrombin complex (TAT), prothrombin fragments F1 + 2 (F1 + 2), factor (F) XIIa, tissue factor (TF), and parameters of the fibrinolytic system, i.e., plasmin-antiplasmin-complex (PAP), D-dimer, tissue-plasminogen-activator (tPA), urokinase-type plasminogen activator (uPA), and plasminogen-activator inhibitor type 1 (PAI 1). The results demonstrate distinct alterations in the above mentioned parameters. Despite administration of a high dose of heparin (activated clotting time [ACT] > 450s) combined with a low dose of aprotinin, activation of the coagulation and fibrinolytic pathways was observed. We found this activation was mainly caused by CPB and not by sternotomy. The activation of coagulation was due to foreign surface contact (F XII => F XIIa) as well as to an effect of tissue factor release in the late phase of CPB. The enhanced fibrinolytic activity during CPB was, at least in part, caused by tPA and was followed by PAI 1 release.

Anticoagulants↗
PubMed1996

Osmotic nephrosis due to high-dose immunoglobulin therapy containing sucrose (but not with glycine) in a patient with immunoglobulin A nephritis.

Acute renal failure has been described as a complication of immunoglobulin therapy. It is not clear whether the immunoglobulin per se or the sucrose that is used as a stabilizer is the cause. We describe a patient with immunoglobulin A nephropathy who was treated with sucrose-containing immunoglobulin. He developed acute renal failure with osmotic nephrosis found on kidney biopsy. When using a glycine-containing immunoglobulin no acute renal impairment was observed in this patient.

Acute Kidney Injury↗
PubMed1996

[Depression and electrodermal response measures in a habituation experiment. Results from over 400 depressed inpatients].

Depressed inpatients of the Weissenau Depression Treatment Unit take part in an over ten years unchanged psychophysiological habituation experiment with auditive stimuli to study their electrodermal reactivity. An overview on EDA-results of about 400 inpatients (ICD-9: 296.1/300.4/309.1, without delusional depression and without bipolar affective psychosis) is given. Women compared to men and also endogenous (ICD-9: 296.1) compared to psychogenic depression (ICD-9: 300.4/309.1) show significantly more non- and hypo-response.

Adult↗
PubMed1996

The German Glomerulonephritis Therapy Study: 10 years of controlled randomized trials for the treatment of idiopathic glomerulonephritis.

The German Collaborative Glomerulonephritis Therapy Study, which celebrated its 10th anniversary in 1996, has collected data on more than 1,000 patients with biopsy-proven glomerulonephritis. 929 patients could be evaluated and 500 were treated according to at least one of various protocols developed for a randomized controlled trial. Current results show that prednisolone is effective in minimal-change nephropathy, and in combination with other immunosuppressants it can reduce proteinuria in individual cases of focal and segmental glomerulosclerosis, membranous glomerulonephritis and nephrotic IgA nephropathy. The majority of tested treatment protocols did not prove to be superior to symptomatic therapy for long-term outcome.

Adolescent↗
PubMed1996

The 1-exp function as an alternative model of non-linear saturable kinetics.

Non-linear saturation kinetics can be described through a potency function, a trigonometric function, a logarithmic function, a hyperbolic function, or an exponential function. Saturable enzyme reaction kinetics can be alternatively formulated as a 1-exp function without the limitations of a steady-state assumption (d[C]/dt = 0, where C is the enzyme-substrate complex). The time-dependent substrate conversion (-d[S]/dt = V(max) [1-exp(-Ka [S])]) depends on the maximum velocity (V(max)), the association constant (Ka) and substrate concentration [S]. In contrast to the classical Michaelis-Menten equation, the 1-exp function has an explicit solution for the substrate concentration [S] in an integrated form. [S] = (1/Ka) ln[1-exp(Ka [S]o)) exp(- Ka V(max) t)] A deceleration term must be introduced to describe enzyme reaction kinetics realistically. The 1-exp function with deceleration term can also be expanded to describe the three inhibition types of enzyme reaction kinetics.

Binding, Competitive↗
PubMed1996

[Suicidal ideation in depressed patients with concomitant anxiety symptoms].

Initial findings of panic disorder as an independent risk factor for suicidal ideation and behavior could not be replicated in studies with psychiatric patients. Instead, it was concluded that panic and anxiety disorders are risk factors when they co-occur with a primary mood disorder. In the present study, the effect of diagnostic comorbidity on rates of suicidality is analyzed on depressive inpatients treated at special depression wards. In a prospective follow-up study, suicidality and anxiety were assessed by means of a modified German version of the Diagnostic Interview Schedule (DIS). Patients with the symptom of panic attacks showed significantly elevated lifetime prevalence rates of suicidality in comparison with patients who did not report this additional symptom. For the follow-up period, however, there were no significant differences between these two groups. According to these results, the group of depressives with additional panic attacks is not more at risk for suicidal behavior, after being treated in an adequate manner.

Adult↗
PubMed1996

Statistical analysis of heterogeneous pharmacokinetic data from the literature.

To obtain the reliable pharmacokinetic quantities necessary for the adjustment of individual drug dosages, the pharmacokinetic data in the literature must be analysed by various appropriate statistical methods. Generally, pharmacokinetic quantities have been calculated from small sample sizes and published in different ways (the coefficient of variation of an estimated pharmacokinetic quantity is often higher than 40 percent). In the present study data were therefore structured and clustered according to the important influence variables. The important influence variables were obtained by known multivariate statistical methods. To obtain optimal estimators (uniformly minimum variance unbiased estimators) for the quantities inside the clusters, goodness of fit tests must be performed. Skewed distributions and samples with heterogeneous variances must be subjected to transformation procedures to obtain normally distributed values with homogeneous variances. The population-derived estimate of the a priori knowledge of pharmacokinetic quantities can be obtained by a statistical algorithm proposed in this paper. Information on the quantities half-life, total body clearance and volume of distribution of vancomycin were extracted from over 200 publications. These data were analysed with the proposed statistical algorithm, yielding population-based estimates for half-life, clearance and volume of vancomycin, taking into consideration the detected influence variables--renal function and the age of the patient. Important dependencies between different variables are discussed.

Age Factors↗
PubMed1996

[Clinical course as a risk factor for chronification of depressive disorders. Results of a 6-year follow-up].

A 6-year follow-up study of unipolar depressive inpatients shows a high percentage of 26% of patients with a chronic course. The chronic patients have significant longer phases of depression in the history of their illness or in the index episode and a longer hospitalisation in the index episode. Patients with chronic course have although more often a first episode before the age of 25 years, were less suicidal by admission to hospital and show less improvement from admission to discharge. The study shows, that although not all aspects of the clinical course are related with chronicity, the duration of depressive phases is a good predictor for a chronic course.

Adolescent↗
PubMed1996

Structured data entry for reliable acquisition of pharmacokinetic data.

A pharmacokinetic database was constructed that is as free of errors as possible. Pharmacokinetic parameters were derived from the literature using a text-processing system and a database system. A random data sample from each system was compared with the original literature. The estimated error frequencies using statistical methods differed significantly between the two systems. The estimated error frequency in the text-processing system was 7.2%, that in the database system 2.7%. Compared with the original values in the literature, the estimated probability of error for identical pharmacokinetic parameters recorded in both systems is 2.4% and is not significantly different from the error frequency in the database. Parallel data entry with a text-processing system and a database system is, therefore, not significantly better than structured data entry for reducing the error frequency.

Data Collection↗
PubMed1995

Inhibition of PC12 cell attachment and neurite outgrowth by detergent solubilized CNS myelin proteins.

Adhesion and neurite outgrowth of PC12 cells, as well as the spreading of 3T3 fibroblasts, were inhibited in a dose dependent manner by detergent solubilized mouse central nervous system myelin proteins as a tissue culture substrate. These inhibitory effects could be neutralized by the monoclonal antibody IN-1 directed against the neurite growth inhibiting proteins NI-35 and NI-250. Separation of the detergent soluble proteins of bovine spinal cord by an anion exchange column showed that the peaks of inhibitory activity for the two cell lines overlapped, such that the PC12 cells were inhibited by a larger number of fractions comprising those inhibitory for 3T3 cells. Neurite outgrowth of PC12 cells was not influenced by the myelin associated glycoprotein, MAG.

Animals↗
PubMed1995

Pharmacokinetics of methylprednisolone and rejection episodes in kidney transplant patients.

Rejection crises after kidney transplantation could be associated with individual variability of pharmacokinetic parameters of steroids. We therefore investigated the individual pharmacokinetics of methylprednisolone on day 2 (60 mg intravenously) and day 4 (60 mg per os) in 40 patients after kidney transplantation. Methylprednisolone was determined in serum by HPLC. Within 6 months, all rejection episodes were recorded and confirmed by kidney transplant biopsy. Values are given as nonparametric medians with the 95% confidence interval (0.95 CI). The 7 patients with a rejection within the first 10 days had a methylprednisolone clearance of 437 ml/min (162-756) that was significantly higher than the 220 ml/min (121-604) in the 22 patients without a rejection episode (P = 0.04). In the complete group of 18 patients having a transplant rejection episode within 6 months, the methylprednisolone elimination half-life after oral dosage was 2.5 hr (1.6-3.9) and significantly shorter than 2.9 hr (1.7-4.0) in 22 patients without rejections (P = 0.03). No differences were seen for body weight, number of mismatches, cold ischemia time, immunosuppressive regimens, and other pharmacokinetic parameters of methylprednisolone (e.g. bioavailability, distribution volume, trough levels). We conclude that pharmacokinetic variability may contribute to the lack of immunosuppressive efficacy in patients with a short halflife of steroids. Therefore, a twice daily dose fraction might be useful for low-dose steroid regimens in kidney transplantation.

Adolescent↗