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Biomedical subjects

F Keller

Publications and source records attributed to F Keller.

At least 145 records · Page 8Linked to original sources
PubMed1994

[D-penicillamine-induced myasthenia gravis].

D-penicillamine has been used in the treatment of rheumatoid arthritis for years. As a rare complication of this treatment the occurrence of myasthenia gravis has been described, the clinical features of this complication being indistinguishable from that of idiopathic myasthenia gravis. Both D-penicillamine induced and idiopathic myasthenia gravis show elevated titers of acetylcholine receptor antibodies and respond to acetylcholinesterase inhibitor treatment. We report on a patient with rheumatoid arthritis who, under treatment with D-penicillamine, developed severe myasthenia gravis which required temporary acetylcholinesterase inhibitor therapy. 8 months after D-penicillamine was discontinued the acetylcholine receptor antibodies had disappeared and the acetylcholinesterase inhibitors could be withdrawn. Clinical findings and possible pathogenetic aspects of D-penicillamine induced myasthenia gravis are discussed.

Aged↗
PubMed1994

The use of ion-sensitive electrodes and fluorescence imaging in hippocampal slices for studying pathological changes of intracellular Ca2+ regulation.

The physiological regulation of the intracellular Ca2+ homeostasis and its pathological alteration has been studied in rat and gerbil hippocampal slices using ion-sensitive electrodes and the fluorescence imaging technique. The ischemia-induced intracellular Ca2+ rise, accentuated in the synaptic/dendritic layer of the vulnerable CA1 neurons was observed in vivo and could be replicated at an accelerated time course in the "ischemic" hippocampal slice superfused with unoxygenated, glucose-free medium. The intracellular Ca2+ loading, thought to be instrumental for the generation of postischemic nerve cell damage, seems to result from an increased Ca2+ release out of intracellular stores as well as from an enhanced synaptic Ca2+ influx. The latter is attributed to a depolarization-induced opening of the voltage-dependent Ca2+ channels and to an uncontrolled influx through "upregulated" NMDA receptor-operated channels. Such an ischemia-induced upregulation which is reported to occur physiologically by the activation of PKC, is reflected by the selective loss of the depressive control of the synaptic NMDA Ca2+ influx by adenosine. Ischemia also leads to a hypertrophy of astrocytes which may go along with an impairment of their physiological function to take up glutamate adding to the extracellular rise of the excitotoxic amino acids. A pathological activation of microglial cells and their transformation into macrophages, known to release oxygen radicals, may further add to neuronal damage. The observed neuroprotection by adenosine can be primarily ascribed to its limiting effect on a pathological membrane depolarization and its deleterious consequences. The more powerful neuroprotection by propentofylline, thought to act analogue to adenosine, seems to be achieved by additional mechanisms. This pharmacon depresses the ischemia-induced neuronal Ca2+ loading in vivo and in vitro, prevents the activation of astrocytes and interferes with the transformation as well as with the free radical formation of microglia-derived macrophages as demonstrated in complementary studies with fluorescence techniques on cell cultures.

Animals↗
PubMed1994

[Clinical management of hemolytic-uremic syndrome and thrombotic-thrombocytopenic purpura].

BACKGROUND: According to recent research, the hemolytic-uremic syndrome (HUS) and thrombotic-thrombocytopenic purpura (TTP) are variable expressions of the same entity (HUS-TTP) with a common pathomechanism (endothelial cell damage, microthrombi) and common treatment (plasma infusion, plasmapheresis). The condition is still serious with a poor prognosis, and the therapeutic regimen is not yet standardized (cryosupernatant and factor VIII free plasma, steroids, immunoglobulins, anticoagulation, dextrane, prostacyclin, vincristine, splenectomy?). CLINICAL OBSERVATIONS AND REVIEW OF THE LITERATURE: Over an observation period of 15 years we considered the differential diagnosis of HUS-TTP in 34 patients, and treated 11 patients with 12 clinical courses specifically with fresh-frozen plasma (plasmapheresis was additionally performed in 10 of them). The 12 courses were retrospectively evaluated and compared with results achieved in the literature. The mean age of the patients was 43 years (+/- 14), and 9 of the 11 patients were women (2 courses given to one woman). The hemolysis improved in 9 of 12 courses, the cerebral manifestation in 3 of 4 cases, and the thrombocytopenia in 2 of 4 cases. Renal failure responded in only 4 of 9 cases and the response was delayed in these patients. Three patients died: one of brain edema due to TTP-specific cerebral microangiopathy and two due to the underlying disease (lupus erythematosus, mixed connective tissue disease). CONCLUSION: Treatment of HUS-TTP is started with fresh-frozen plasma infusions (1-1.5 liters/day), but plasmapheresis should be added 2 days later (3 x 4 liters/week, whereby 2 liters should be given as fresh-frozen plasma). The administration of fresh-frozen plasma must be continued every day. In resistant cases, specific therapy should not be terminated before 4 weeks.

Adult↗
PubMed1994

Multicentric evaluation of a new PT reagent based on recombinant human tissue factor and synthetic phospholipids.

A new PT reagent based on recombinant human tissue factor and synthetic phospholipids (phosphatidyl choline and phosphatidyl serine) with defined fatty acid side chains was calibrated against BCT/253 and CRM 149R. A small but consistent bias in the International Sensitivity Index (ISI) value was obtained using either the human or rabbit brain reference material. ISI values were around 1.0 or slightly lower depending on the respective instrument. Mixing studies with factor deficient plasmas showed a high factor sensitivity especially for factor VII as compared to commercial rabbit brain or human placenta thromboplastin. In an international field trial the reagent was tested using fully or semi automated Electra coagulometers in 4 different laboratories. Results with normal samples were in excellent agreement among the different laboratories. Mean values were 10.9, 10.9, 11.0, 11.2 s with a range of 9.5 to 12.5 s. Results of males and females were not different. In patients with liver disease very similar PT activities were found as compared to sensitive rabbit brain or human placental thromboplastins. In normals and patients with oral anticoagulation INR values correlated very well against BCT (r = 0.98, regression line y = -0.07 + 0.9 x). The distribution of samples was linear over the whole range. In the comparison against sensitive rabbit brain thromboplastin or human placental thromboplastin similar correlations were found. In a few cases higher INR values were observed for the recombinant reagent especially in patients with intensive treatment. Factor assays in those patients showed at least the strong reduction of one vitamin K-dependent coagulation factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Vancomycin dosing in haemodialysis patients and Bayesian estimate of individual pharmacokinetic parameters.

A dose reduction of vancomycin to 1000 mg once a week usually is recommended for haemodialysis patients. Our modified dosing schedule consists of a loading dose of 1000 mg and a maintenance dose of 500 mg administered 3 times a week after haemodialysis. Different vancomycin regimens were retrospectively evaluated by therapeutic drug monitoring and bayesian parameter estimates in 39 dialysis patients. The mean (+/- SD) trough level in 7 patients receiving only the conventional dosage regimen was significantly lower than in 17 patients strictly treated by the modified schedule (7 +/- 4 versus 17 +/- 8 mg/L; p = 0.001). The corresponding peaks were low in both groups and no different (23 +/- 10 versus 27 +/- 12 mg/L). The one week average vancomycin clearance was significantly lower in the conventional dosage group compared to the modified dosage group (6 +/- 3 versus 10 +/- 3 ml/min; p = 0.001). High-flux dialysers were not used in the conventional dosage group but for 30 percent of the procedures in the modified dosage group, where the vancomycin one week average elimination half-life was 66 hours (+/- 18) and the volume of distribution 50 litres (+/- 5). As compared to the bayesian programme, NONMEM calculated comparable pharmacokinetic parameters but could be applied only in 5 cases with a sufficient number of concentration measurements. Ototoxicity occurred in 1 patient, whereas vancomycin treatment was judged as ineffective against infection in 5 of the 39 patients. Their troughs were below 15 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1993

Widespread vasculopathy with hemolytic uremic syndrome, perimyocarditis and cystic pancreatitis in a young woman with mixed connective tissue disease. Case report and review of the literature.

A 15-year-old girl had severe Raynaud's phenomenon and arthralgias. A high ANA-IF titer was found and undifferentiated connective tissue disease was diagnosed. After 7 years of moderately flaring disease the patient deteriorated and presented with congestive heart failure, pleuropericardial effusion, hemolytic uremic syndrome, proteinuria and moderate hypertension. Autoantibodies against DNA, Sm-protein, and very high titers against U1RNP were detected. Therapy with high steroid doses, a cyclophosphamide pulse and 4 weeks of plasmaphresis with plasma exchange improved the heart, but not the renal condition. Symptomatic pancreatitis became the dominant problem of a progressively consuming process that resulted in the death of the patient. Post-mortem examination revealed widespread vasculopathy with intima proliferation and only minimal fibrosis involving the kidneys, heart and other main organs, including the pancreas. Taken together, the clinical picture was of an overlap between scleroderma and systemic lupus erythemathosus; the serologic and histopathologic findings suggest a diagnosis of a severe form of mixed connective tissue disease (MCTD).

Adolescent↗
PubMed1993

Nonlinear kinetics and the 1-exp function in nephropharmacology.

The basic law in nephropharmacology states that pharmacokinetic parameters depend linearly on renal function. Few exceptions to linear dependence have been reported, e.g. substances with saturable tubular reabsorption or secretion. A further example is cyclosporin, which was found to be eliminated according to log-concave nonlinear kinetics in 3 patients with hepatotoxicity after kidney transplantation. The nonlinear cyclosporin kinetics were computer-fitted to the integrated forms of the 1-exp function and the Michaelis-Menten equation by nonlinear regression analysis. The same maximal velocity (Vmax = 23 ng ml-1 h-1) and Michaelis constant (Km = 686 ng ml-1) were calculated for cyclosporin when applying either the 1-exp function or the Michaelis-Menten equation. The nonlinear elimination of cyclosporin, however, was described even more closely by the 1-exp function than by the Michaelis-Menten equation.

Humans↗
PubMed1993

The effect of cyclosporine on the progression of human immunodeficiency virus type 1 infection transmitted by transplantation--data on four cases and review of the literature.

Two women and two men were infected with the human immunodeficiency virus type 1 (HIV-1) transmitted by renal transplantation from i.v. drug-addicted donors in 1984. The four recipients were treated with cyclosporine and methylprednisolone (one patient only for three months because of early graft failure). Two patients died 66 and 74 months after transplantation, one of endocarditis and one of cerebral hemorrhage. Despite several infections including urinary tract infection (n = 8), peritonitis (n = 1), shunt infection (n = 1), bronchitis (n = 1), salmonellosis (n = 1), herpes stomatitis (n = 2), herpes zoster (n = 1), and cytomegalovirus (n = 1), and despite treatment of several rejection episodes (n = 8), none of them had or has infections typical of the acquired immunodeficiency syndrome (AIDS). However, two patients developed cervical lymphadenopathy and one autoimmune thrombocytopenia 15-20 months after HIV-1 infection. Their T helper cell counts (355/microliters to 75/microliters) and helper/suppressor T cell ratios (1.0-0.2) are distinctly lowered. One patient has membranous glomerulopathy with virus-like particles within and on the outside of the basement membrane and tubuloreticular inclusions in glomerular endothelial cells. We evaluated the case reports of 53 patients with HIV-infection caused by an infected transplant or by blood transfusions during or shortly after transplantation. The cumulative incidence of AIDS was significantly lower in 40 transplant patients with an immunosuppressive regimen including cyclosporine than in 13 transplant patients receiving immunosuppressive treatment without cyclosporine (5-year cumulative risk of AIDS: 31% versus 90%, P = 0.001).

Acquired Immunodeficiency Syndrome↗
PubMed1993

Nonparametric meta-analysis of published data on kidney-function dependence of pharmacokinetic parameters for the aminoglycoside netilmicin.

The distribution and elimination of various drugs depend on kidney function. This dependence is published either as a linear regression equation or as the discrete extreme values for normal kidney function and anuria. A meta-analysis of the published pharmacokinetic data is required to build up a knowledge-based computer system for dosage adjustment in renal failure. A sample comparison of 4 statistical methods for meta-analysis was performed by applying them to 13 publications about the aminoglycoside netilmicin. Parametric meta-analytical methods I and II are based on regression equations alone (Z-transformation, maximum likelihood) and yield unreliable data, especially with regard to extreme values for anuria. The parametric meta-analytical method III is based on means of extreme values (standard 2-stage approach) and does not permit a decision as to whether linear interpolation of a parameter (e.g. volume of distribution) can be used for all degrees of renal insufficiency. In contrast, the nonparametric median (meta-analytical method IV) is based on the extreme values calculated from regression equations and empirical extreme values combined into 1 group of data on normal kidney function and another on anuria. For netilmicin, the meta-analytical median with the 95% confidence interval (95% CI) yields a significant increase in the dominant elimination half-life from 2h (95% CI 1.9h, 2.6h) in patients with normal kidney function to 45h (95% CI 41h, 301h) in those with anuria (p = 0.001). For a normal bodyweight of 65kg, the volume of distribution also increases significantly from 13L (95% CI 9L, 15L) to 20L (95% CI 14L, 21L) in patients with anuria (p = 0.04). Thus, drug dosage adjustment according to therapeutic peak and trough concentrations requires knowledge of the distribution and elimination parameters, since they can both be independently altered in renal failure. We conclude that the most robust meta-analysis of these alterations is achieved with the nonparametric median of extreme values.

Creatinine↗
PubMed1993

[Lidocaine elimination and MEGX formation after oral lidocaine administration--a practicable test for assessment of quantitative liver function].

Oral load with 200 mg Lidocain was performed in 370 patients with chronic liver disease. The 120- and 240-minute Lidocain plasma concentrations as well as the 30- and 60-minute MEGX plasma concentrations, main metabolite of Lidocain, were measured by means of gas chromatography and with the commercial TDX test from the firm Abbott. No side effects caused by the load were observed and all of the patients resorbed Lidocain. Peak concentrations were found both for Lidocain and for MEGX in the 60-minute tests. Patients with liver cirrhosis of different aetiology showed significantly higher Lidocain plasma concentrations and lower MEGX values than patients with chronic non-cirrhotic liver disease. The differentiation of these two groups of patients was most successful via the determination of the 240-minute Lidocain plasma concentration. Oral load with 200 mg Lidocain has turned out to be a practicable and meaningful test for the estimation of the Cytochrom P450-dependent liver function.

Administration, Oral↗
PubMed1993

Hopelessness and the tendency to commit suicide in the course of depressive disorders.

In patients with major affective disorders, research has indicated that the extent of hopelessness is a promising variable for predicting suicide. In this prospective follow-up study, the predictive power of Beck's hopelessness scale (HS) was investigated in 61 depressive inpatients. The examination included the HS, the Beck Depression Inventory (BDI), and personal interviews at admission, at discharge, and 1 year after discharge. There were eight suicide attempts and two suicides during the follow-up period. The sensitivity of the HS was high, i.e., a score of 8 or more correctly identified 90% of the eventual suicidal actions, but the percentage of false-positives was also high. The HS score at discharge differentiated between the groups with and without suicidal behavior during follow-up, as did the BDI. Several limitations of these findings are discussed.

Depressive Disorder↗
PubMed1993

Propeptide levels of procollagen type IV (NC1) and III (PIIINP) in patients undergoing haemodialysis.

In active liver disease and different forms of renal diseases the serum levels of the propeptides of procollagen types IV (NC1) and III (PIIINP) are elevated. The propeptide levels were measured by specific radioimmunoassays in 22 patients undergoing haemodialysis. NC1 concentrations in 6 chronic haemodialysis patients were within normal range (8.2 +/- 2.0 ng/ml). As compared to normal values (8.0 +/- 3 ng/ml), PIIINP concentrations were 10-fold higher in 5 intensive care patients with multi-organ failure and acute renal failure (72.9 +/- 17.9 ng/ml) and 3-fold higher in 11 chronic dialysis patients (24.3 +/- 8.7 ng/ml). Haemodialysis itself had no effect on the elimination of PIIINP. PIIINP might be a valuable marker of acute and chronic increase of collagen turnover in patients undergoing haemodialysis.

Acute Kidney Injury↗