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F Keller

Publications and source records attributed to F Keller.

At least 19 recordsLinked to original sources
PubMed2007

[Reliability and validity of the Revised Beck Depression Inventory (BDI-II). Results from German samples].

BACKGROUND: The Beck Depression Inventory (BDI) underwent revision in 1996 (BDI-II) with the goal of addressing DSM-IV depression criteria. The present study assessed psychometric properties of the German version of the BDI-II. PATIENTS AND METHODS: The BDI-II was translated into German and evaluated in a series of studies with clinical and nonclinical samples. RESULTS: The content validity of the BDI-II has improved by following DSM-IV symptom criteria. Internal consistency was satisfactorily high (alpha>or=0.84), and retest reliability exceeded r>or=0.75 in nonclinical samples. Associations with construct-related scales (depression, dysfunctional cognitive constructs) were high, while those with nonsymptomatic personality assessment (NEO-FFI) were lower. The BDI-II differentiated well between different grades of depression and was sensitive to change. CONCLUSION: The German BDI-II demonstrates good reliability and validity in clinical and nonclinical samples. It may now replace the older version of the BDI for assessing self-rated severity of depression and course of depressed symptoms under treatment.

Adolescent↗
PubMed2006

Sex-dependence of the relative number of elastic fibres in human heart valves.

The aim of the current study was to find out whether there are sex-dependent differences in the relative number of elastic fibres in human heart valves. Twenty-six aortic valves, 26 mitral valves, 33 pulmonary valves and 28 tricuspid valves of both sexes were obtained at autopsy from newborn to 89-year-old patients who died of noncardiac diseases. The quantitatively morphometric investigations were carried out on conventionally stained (Resorcinfuchsin) histological sections. The results were qualitatively examined with immuno-histochemically marked (anti-elastin antibodies) histological sections. Earlier examinations by Leutert [1976. Z. Gesamte Inn. Med. 31, 97-104] showed that the atrioventricular valves have the following layers: endothelium, atrial fibroelastic tissue (S1), fibrous tissue, ventricular fibroelastic tissue (S2) and endothelium. In our study, the ventricular side of the semilunar valves corresponds to side S1, whereas the vessel side corresponds to side S2. Three regions of interest were examined on each side of the valves: base, mid and tip. The number of elastic fibres per measuring area for all four human heart valves was significantly higher (p < 0,001) in fibroelastic tissue of side S1 than in fibroelastic tissue of side S2. Neither on side S1 nor on side S2 were there significant gender-related differences in the relative number of elastic fibres per measuring area. The results suggest a characteristic distribution of the elastic fibre system which is not sex-dependent but closely related to the function of the heart valves.

Adolescent↗
PubMed2006

Antiproliferative and overadditive effects of everolimus and mycophenolate mofetil in pancreas and lung cancer cells in vitro.

BACKGROUND: Everolimus inhibits the growth of several tumor cell lines in vitro as well as tumor growth in a rat model. Mycophenolate mofetil (MMF) inhibits growth of a Walker sarcoma in a rat model in vivo. Herein we tested the in vitro antiproliferative capacity of everolimus and MMF on a pancreatic tumor cell line Panc-1 and on a small cell lung cancer cell line ScLc. MATERIALS AND METHODS: Cells were cultured under standardized conditions. Everolimus was added in increasing doses from 0.005 to 500 microg/mL; MMF was used from 0.05 to 5000 microg/mL. For co-incubation experiments, we combined everolimus (0.005 microg/mL and 0.05 microg/mL) with five concentrations of MMF; and MMF (0.5 microg/mL and 5 microg/mL) with five concentrations of everolimus. The antiproliferative capacity was assessed by a BrdU incorporation assay. RESULTS: Everolimus and MMF inhibited BrdU incorporation into Panc-1 and ScLc in a dose-dependent fashion. A 50% inhibition was seen in Panc-1 only at 50 microg/mL everolimus, but in ScLc at 5 microg/mL everolimus. MMF was clearly more potent in Panc-1: 50% inhibition was observed at 5 microg/L. In ScLc, 40% inhibition of BrdU incorporation was seen only at 50 microg/L MMF. In co-incubation, an effective combination for both Panc-1 and ScLc was 5 microg/mL MMF with 0.005 microg/mL everolimus resulting in 50% inhibition of BrdU incorporation (P < .001). CONCLUSIONS: Everolimus and MMF showed dose-dependent antiproliferative effects in tumor cell lines in vitro both alone and in combination. The combined use of everolimus and MMF showed supra-additive effects at concentrations used for therapeutic immunosuppression in patients.

Animals↗
PubMed2006

Resolution of sirolimus-induced pneumonitis after conversion to everolimus.

BACKGROUND: Sirolimus-induced pneumonitis usually requires the complete cessation of sirolimus. Herein we have reported five cases of recovery from sirolimus pneumonitis after conversion from sirolimus to everolimus. PATIENTS: All five cases were comparable with regard to their clinical conditions. The ages were between 46 and 64 years. They had received kidney transplants 3 to 18 years earlier. In four cases, the reason for sirolimus therapy was toxicity due to calcineurin inhibitors on a transplant biopsy; three of the patients also displayed malignant tumors: renal cell carcinoma, spinocellular carcinoma, or melanoma. Their serum creatinine levels were elevated between 150 and 350 micromol/L. In all five cases, bronchoscopy disclosed lymphocytic pneumonitis and bronchiolitis obliterans. The immunosuppressive co-medications were prednisolone in three, azathioprine in one, and mycophenolate mofetil in four cases. The previous sirolimus dose was 1 to 4 mg/day, with sirolimus trough levels between 5 and 12 ng/mL. The patients were switched to everolimus at doses between 1 x 0.25 and 2 x 0.75 mg/day to achieve trough concentrations between 3 and 8 ng/mL. Pulmonary symptoms and radiological findings resolved completely within 1 to 4 weeks. CONCLUSION: Everolimus is more hydrophilic by virtue of differing from sirolimus by one hydroxyl group. Sirolimus-induced pneumonitis improved after conversion to everolimus.

Aged↗
PubMed2006

High-dose intravenous immunoglobulin pulse therapy in patients with progressive immunoglobulin A nephropathy: a long-term follow-up.

In progressive immunoglobulin A nephropathy (IgAN), intravenous immunoglobulin (IVIg) treatment has been used to delay disease progression, but the long-term efficacy is largely unknown. We report the clinical outcomes after IVIg therapy in six male patients with progressive IgAN [median glomerular filtration rate (GFR) 31 ml/min per 1.73 m(2)] followed for a median observation period of 8 years. In this single-arm, non-randomized study, IVIg was given monthly at a dose of 2 g/kg body weight for 6 months. The course of renal function was assessed by linear regression analysis of GFR and proteinuria, and was compared to eight patients with IgAN (median GFR 29 ml/min per 1.73 m(2)) without IVIg as a contemporaneous control group. IgAN disease progression was delayed after IVIg therapy on average for 3 years. The mean loss of renal function decreased from -1.05 ml/min per month to -0.15 ml/min per month (P = 0.024) and proteinuria decreased from 2.4 g/l to 1.0 g/l (P = 0.015). The primary end-point (GFR < 10 ml/min or relapse) occurred 5.2 years (median; range 0.4-8.8) after the first IVIg pulse, and after 1.3 years (median; range 0.8-2.4) in the control group (P = 0.043). In Kaplan-Meier analysis, the median renal survival time with IVIg was prolonged by 3.5 years (IVIg 4.7 years versus control 1.2 years; P = 0.006). IVIg pulse therapy may be considered as a treatment option to reduce the loss of renal function and improve proteinuria in patients with progressive IgAN.

Adult↗
PubMed2005

Dominantly inherited beta thalassaemia intermedia caused by a new single nucleotide deletion in exon 2 of the beta globin gene: Hb morgantown (beta91 CTG>CG).

Family members in multiple generations of an Irish-American family were investigated for moderate to severe microcytic anaemia, inherited in an autosomal dominant fashion. A novel frameshift mutation of the beta globin gene was discovered. This study highlights the importance of considering dominantly inherited beta thalassemia in the investigation of anaemia, even in patients with ethnic backgrounds not usually associated with beta thalassaemia.

Adult↗
PubMed2004

[Psychiatric-psychotherapeutic inpatient treatment for depression. Process and outcome quality based on a model project in Baden-Wurttemberg].

During 1998-2000 a quality assurance program for diagnosis and treatment of depression was conducted in 24 hospitals for psychiatry and psychotherapy in Baden-Wurttemberg (southern Germany). Process and outcome quality of 3,000 depressive patients was documented at admission and discharge. The article focuses on therapeutic measures, duration, outcome, patient satisfaction, and their interactions. The results show that the patients' satisfaction with the care received is very high and the pre-post effect sizes of inpatient treatment for depression are high.

Adjustment Disorders↗
PubMed2004

Enhanced APOE2 transmission rates in families with autistic probands.

We have previously described linkage/association between reelin gene polymorphisms and autistic disorder. APOE also participates in the Reelin signaling pathway, by competitively antagonizing Reelin binding to APOE receptor 2 and to very-low-density lipoprotein receptors. The APOE2 protein variant displays the lowest receptor binding affinity compared with APOE3 and APOE4. In this study, we assess linkage/association between primary autism and APOE alleles in 223 complete trios, from 119 simplex Italian families and 44 simplex and 29 multiplex Caucasian-American families. Statistically significant disequilibrium favors the transmission of epsilon2 alleles to autistic offspring, over epsilon3 and epsilon4 (allele-wise transmission/disequilibrium test [TDT], chi2 = 6.16, 2 degrees of freedom [d.f.], P<0.05; genotype-wise TDT, chi2 = 10.68, 3 d.f., P<0.05). A novel epsilon3r allele was also discovered in an autistic child and his mother. Autistic patients do not differ significantly from unaffected siblings (allele-wise TDT comparing autistic patients versus unaffected sibs, chi2 = 1.83, 2 d.f., P<0.40, not significant). The major limitation of this study consists of our small sample size of trios including one unaffected sibling, currently not possessing the statistical power necessary to conclusively discriminate a specific association of epsilon2 with autism, from a distorted segregation pattern characterized by enhanced epsilon2 transmission rates both to affected and unaffected offspring. Our findings are thus compatible with either (a) pathogenetic contributions by epsilon2 alleles to autism spectrum vulnerability, requiring additional environmental and/or genetic factors to yield an autistic syndrome, and/or (b) a protective effect of epsilon2 alleles against the enhanced risk of miscarriage and infertility previously described among parents of autistic children.

Apolipoprotein E2↗
PubMed2004

Retrospective comparison of 5 different methods for long-term LDL-apheresis in 20 patients between 1986 and 2001.

PURPOSE: To compare long-term efficacy and biocompatibility of the 5 most commonly applied LDL-apheresis techniques using a specifically modified calculation method of the area under the curve (AUC) for laboratory parameters. DESIGN: Retrospective long-term analysis of 20 patients with homozygous or severe heterozygous familial hypercholesterolemia. PROCEDURES: The following 5 extra-corporeal LDL-apheresis methods were compared: IMAL (Immuno Adsorption of Lipoproteins), DSA (Dextran Sulphate Adsorption), HELP (Heparin Induced Extra-corporeal LDL Precipitation), DALI (Direct Adsorption of Lipoproteins), MDF (Membrane Differential Filtration). MAIN OUTCOME MEASURES: AUC derived plasma concentrations (C(AUC)) of lipoproteins between two apheresis procedures and their long-term course. Comparison of biocompatibility and efficacy concerning the LDL-C target of < 2.6 mmol/L of 5 apheresis techniques. Progression of atherosclerosis in patients with severe hypercholesterolemia. MAIN FINDINGS: The means of AUC derived average plasma concentrations (C(AUC)) of all treatment intervals were for LDL-C and the LDL/HDL ratio as follows: IMAL (5.59 mmol/L; ratio 4.1), DSA (3.03 mmol/L; ratio 2.0), HELP (4.06 mmol/L; ratio 2.2), DALI (3.83 mmol/L; ratio 3.3), MDF (3.26 mmol/L; ratio 3.2). Coronary heart disease and cardiac events (myocardial infarction, PTCA/ stent implantation, CABG) progressed in only 2 patients whereas atherosclerosis manifestations (sclerosis abdominal aorta, carotid artery stenosis, peripheral vascular disease) worsened in 13 patients. Mean ergometric capacity improved from 112 to 118 Watt. CONCLUSIONS: All 5 apheresis methods (IMAL, DSA, HELP, DALI, MDF) proved to be safe and suitable for long-term treatment in patients with severe hypercholesterolemia. The introduction of the C(AUC) revealed that the target of LDL-C < 2.6 mmol/L was not achieved with regard to the time averaged concentration (C(AUC)).

Adult↗
PubMed2003

[Minimal Change Glomerulonephritis].

We report two cases of minimal change glomerulonephritis (synonyms: idiopathic nephrotic syndrom, minimal change disease). A 47-year old female patient was admitted to our unit with a relapsing nephrotic syndrome since childhood. Another patient, a 22-year old female, presented with moderately swollen legs that developed over several months and a complaint of frequent upper respiratory tract infections during the last year. In both cases we suspected a minimal change glomerulonephritis which can only be proven by renal biopsy. Therapeutic options comprise steroids, cyclosporin, tacrolimus or even cyclophosphamide, depending on the clinical presentation of the disease in the individual case.

Adult↗
PubMed2002

Serotonin transporter gene promoter variants do not explain the hyperserotoninemia in autistic children.

Autism is a biologically-heterogeneous disease. Distinct subgroups of autistic patients may be marked by intermediate phenotypes, such as elevated serotonin (5-HT) blood levels, potentially associated with different underlying disease mechanisms. This could lead to inconsistent genetic association results, such as those of prior studies on serotonin transporter (5-HTT) gene promoter variants and autistic disorder. Contributions of 5-HTT gene promoter alleles to 5-HT blood levels were thus investigated in 134 autistic patients and 291 first-degree relatives. Mean 5-HT blood levels are 11% higher in autistic patients carrying the L/L genotype, compared to patients with the S/S or S/L genotype; this trend is not observed in first-degree relatives. The probability of inheriting L or S alleles is significantly enhanced in patients with 5-HT blood levels above or below the mean, respectively (P < 0.05), but quantitative TDT analyses yield a non-significant trend (P = 0.10), as this polymorphism explains only 2.5% of the variance in 5-HT blood levels of autistic patients. In conclusion, 5-HTT gene promoter variants seemingly exert a small effect on 5-HT blood levels in autistic children, which largely does not account for hyperserotoninemia. Nonetheless, the inconsistent outcome of prior association studies could partly stem from a selection bias of hyper- or hypo-serotoninemic probands.

Autistic Disorder↗
PubMed2002

Pharmacokinetics and pharmacodynamics of methylprednisolone after one bolus dose compared with two dose fractions.

OBJECTIVE: Although the elimination half-life of most glucocorticoids is short, they are usually administered once daily, or even on alternate days. Our hypothesis was that this practice might compromise the immunosuppressive effect of those drugs during the second part of the administration interval. METHODS: Eight healthy male volunteers were randomly assigned to receive intravenous methylprednisolone either 32 mg in the morning, or 16 mg in the morning and 16 mg in the evening in a cross-over design. Methylprednisolone concentrations were determined in plasma by high-pressure liquid chromatography. The total number of CD3+ lymphocytes, and CD4+ and CD8+ T-cell subpopulations was measured in blood. The suppression of these cells was used as a surrogate parameter for the immunosuppressive response, and expressed as reduction of the area under the effect time curve (AUETC). Possible adverse effects on blood pressure, glucose, insulin, and endogenous cortisol levels were monitored. RESULTS: There were no significant differences in methylprednisolone half-life (2.2 +/- 0.4 h), clearance (575 +/- 113 mL/min), volume of distribution (106 +/- 22 l), concentration producing the half-maximum effect on CD4+ T-cells (1.5 +/- 0.7 ng/mL), and Hill-coefficient (1.2 +/- 0.1), after single or divided dose. However, the total 24 h effect area (AUETC) of lymphocytes, and mainly CD4+ T-cells was significantly more suppressed (P = 0.008) with the divided dosage regimen than after the single dose (8422 +/- 2163 vs. 11,545 +/- 3020 h cells/microL). The surrogate markers for adverse events were not different, except for cortisol. CONCLUSION: Within a 24-h interval, two dose fractions of methylprednisolone produce a stronger and more sustained immunosuppressive response than one single bolus dose.

Adult↗
PubMed2002

PK-PD curve-fitting problems with the Hill equation? Try one of the 1-exp functions derived from Hodgkin, Douglas or Gompertz.

UNLABELLED: Non-linear phenomena are observed with enzyme kinetics, protein binding, pharmacokinetics or pharmacodynamics. The Hill equation, the Michaelis-Menten equation extended by a power coefficient, is traditionally used for sigmoid curve fitting. Sigmoid saturation phenomena can also be described by exponential functions (1-exp), extended by a power coefficient such as those derived by Hodgkin, Douglas or Gompertz. Comparing the 4 equations, the sigmoid 1-exp function in the form of Hodgkin and Huxley comes closest to the principle of simplicity and succinctness with regard to definition, slope and flexibility of the inflection point. To compare the applicability, a standardized sample of 250 curves was generated by each I of the 4 equations and mutually fitted with the remaining 3. The Hill equation gives the closest fit with the data generated by the other functions. The Douglas variant exhibits the highest rate of convergence. The Gompertz function provides the basic feature of a baseline effect. CONCLUSION: The sigmoid functions investigated (Hill, Hodgkin, Douglas, Gompertz) have differing characteristics and can be used interchangeably for solving specific problems in non-linear modeling.

Mathematics↗
PubMed2001

Barrel pattern formation requires serotonin uptake by thalamocortical afferents, and not vesicular monoamine release.

Thalamocortical neurons innervating the barrel cortex in neonatal rodents transiently store serotonin (5-HT) in synaptic vesicles by expressing the plasma membrane serotonin transporter (5-HTT) and the vesicular monoamine transporter (VMAT2). 5-HTT knock-out (ko) mice reveal a nearly complete absence of 5-HT in the cerebral cortex by immunohistochemistry, and of barrels, both at P7 and adulthood. Quantitative electron microscopy reveals that 5-HTT ko affects neither the density of synapses nor the length of synaptic contacts in layer IV. VMAT2 ko mice, completely lacking activity-dependent vesicular release of monoamines including 5-HT, also show a complete lack of 5-HT in the cortex but display largely normal barrel fields, despite sometimes markedly reduced postnatal growth. Transient 5-HTT expression is thus required for barrel pattern formation, whereas activity-dependent vesicular 5-HT release is not.

Aging↗