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Biomedical subjects

F Keller

Publications and source records attributed to F Keller.

At least 127 records · Page 7Linked to original sources
PubMed1995

[Crystal-associated destructive arthropathy of the shoulder].

Crystal-associated destructive arthropathy of the shoulder is most commonly observed in elderly women. Functional impairment and social impact define its importance especially in this group. Clinical features include pain at rest and on use, large cool effusion and instability. Radiographs show attrition of bone and cartilage with a paucity of reparative changes. Synovial fluids are viscous, with low cell counts, and stain positively for the presence of apatite-containing particles and often also for calcium-pyrophosphate crystals.

Aged↗
PubMed1995

Changes in suicide numbers in psychiatric hospitals: an analysis using log-linear time-trend models.

We examined the hypothesis that there is an increase in the number of suicides committed by psychiatric inpatients. Data were recorded in five psychiatric hospitals/departments in Baden-Württemberg (Germany) for the period between 1970 and 1992. Statistical analysis was performed by means of log-linear time-trend models that allowed us to test several hypothesis, to compare their goodness of fit, and to correct for related factors (number of admissions, number of suicides in the general population). Results showed that the model of a general increase could be rejected. The separation of the yearly frequencies into two parts (1970-1979 and 1980-1992) revealed an increase in the inpatient suicide rate during the years 1970-1979 and a slowly decreasing inpatient suicide rate during the years 1980-1992, especially when taking admission numbers into account. Diagnostic subgroups (schizophrenia and depression) did not seem to deviate from these trends. The correction for the suicide numbers in the general population of Baden-Württemberg, which exhibited a remarkable decrease in the 1980s, did not influence these results. We speculate that, after some starting difficulties, the effects of the more humane treatment procedures introduces in the 1970s are beginning to be felt.

Depressive Disorder↗
PubMed1995

[Modification of fecal bile acid excretion by fish oil in healthy probands].

Several studies indicated a protective effect of fish oil on colon carcinogenesis which might be due to alterations in prostaglandin E2 synthesis of the colonic mucosa. Additional effects on fecal bile acid excretion may also play a role since especially secondary bile acids are known to act as promoters in colon cancer development. In the present study possible influences on bile acid excretion were investigated in 12 healthy volunteers whose daily diet was supplemented for 4 weeks with 11 g of fish oil (FO) and corn oil (CO) per day, respectively. Fecal bile acids were analyzed by gas-liquid-chromatography. Fecal excretion of total bile acids was not different during the periods of FO and CO-supplementation (301.9 vs. 320.3 mg/day). However, a non-significant trend to a lower daily excretion of the secondary bile acid lithocholic acid was found after FO compared to CO-ingestion (99.6 vs. 109.4 mg/day; p = 0.22). Since secondary bile acids are known promoters of colon carcinogenesis, these findings may implicate a favorable situation with respect to colon cancer prevention.

Adult↗
PubMed1995

Centrifugal and roller pumps--are there differences in coagulation and fibrinolysis during and after cardiopulmonary bypass?

A number of hemostatic parameters reflecting the activation of coagulation and fibrinolysis were investigated in a prospective study of 24 patients undergoing cardiopulmonary bypass (CPB) during heart surgery. The patients were randomized to a group in which either a roller (group 1) or a centrifugal pump (group 2) was used. Blood samples were taken preoperatively, at the onset of and every 20 min during CPB, after the administration of protamine, and 4, 20, 44, and 68 h postoperatively. The groups did not differ significantly in hematocrit, fibrinogen, factor XIII, and antithrombin III. Significant differences in favor of group 2 during and after CPB were found in prothrombin fragment F1 + 2, plasmin-antiplasmin complex (PAP), thrombin-antithrombin complex (TAT), and D-dimer (F1 + 2 P < 0.01 after 80-min CPB, PAP P < 0.005 after 40-min CPB, TAT and D-dimer P < 0.05 after 100-min CPB, D-dimer and PAP P < 0.05 after protamine administration, TAT and F1 + 2 4 h after CPB). These findings indicate the activation of fibrinolysis preceding thrombin generation during cardiopulmonary bypass. In addition, we conclude that centrifugal blood pumping is beneficial in avoiding excessive activation of both coagulation and fibrinolysis.

Aged↗
PubMed1995

Red-cell and serum folate levels in depressed inpatients who commit violent suicide: a comparison with control groups.

There has been some discussion in the recent literature regarding the possible relationship between peripheral levels of folate and serotonin deficiency in the CNS. At the same time, such a serotonin deficiency has been implicated in the biology of suicidal behavior. Thus, decreased peripheral folate levels may be expected in patients who commit violent suicide. In this study, the red-cell and serum folate levels in nine persons who later committed suicide are compared with those in age- and sex-matched control groups. A one-way analysis of variance showed no significant difference between the groups.

Adult↗
PubMed1995

In vitro infection of peripheral blood mononuclear cells by hepatitis C virus.

To study the in vitro susceptibility of peripheral blood mononuclear cells (PBMC) to hepatitis C virus (HCV), we incubated cells from healthy donors with HCV-positive sera. Using RT-PCR and in situ hybridization, the genomic viral RNA was detected in PBMC and in their supernatants until 25 days post-incubation. The PBMC of the different donors were not all permissive to HCV, but results were more constantly positive when cells from four donors were pooled. Quantification of the genomic viral RNA by the branched-DNA assay showed a decrease in the HCV RNA concentration during the first week of culture followed by a peak during the second or third week, and also an increase in the total amount of viral RNA in the inoculated cells. Although HCV RNA could be detected in the supernatants by RT-PCR, the concentration was very low. Using a sense-specific RT-PCR method, the HCV negative-strand was also detected in the cells but not in the supernatants. In two experiments PBMC were successfully infected using HCV-positive culture supernatants, therefore suggesting that infectious particles can be produced in this system. Our findings demonstrate that PBMC are permissive for HCV replication in vitro but the replication level is very low. The HCV RNA concentration measured in PBMC of 10 chronically infected patients was not significantly higher than the maximal concentration obtained in PBMC infected in vitro.

Base Sequence↗
PubMed1995

Risk factors and outcome of 107 patients with decompensated liver disease and acute renal failure (including 26 patients with hepatorenal syndrome): the role of hemodialysis.

The prognosis of acute renal failure in patients with preexisting liver decompensation is poor, and hemodialysis is considered futile, especially for hepatorenal syndrome (HRS). Since we observed a more favorable outcome in some patients, we retrospectively evaluated 107 patients with decompensated liver disease and acute renal failure (serum creatinine > 200 mumol/L) treated at the medical department of a university hospital in a 10-year period (1980-1990). HRS in the strict sense (urine-Na < 20 mmol/L while on furosemide) was diagnosed in 26 of 107 patients (24%). Renal function remained compensated in 25 patients, while 82 patients fulfilled the criteria for dialysis treatment (creatinine > 500 mumol/L and/or diuresis < 500 mL/day). In contrast to the current doctrine, 38 of the 82 patients were given hemodialysis (46%). Using the Cox proportional hazard model, the relative risk (presence vs. absence of a risk factor) of dying was increased 8.2-fold (3.9-17.2) in patients with thrombocytopenia < 100/nL, 3.9-fold (1.4-11.3) in those with hepatic encephalopathy and prothrombin time < 30%, 2.8-fold (1.6-4.8) in patients with malignoma, and 2.7-fold (1.5-4.8) in patients not submitted to dialysis despite its indication. In the CART statistics (classification and regression trees), the 33 patients with the poorest outcome were characterized exclusively by thrombocytopenia < 100/nL. HRS in the strict sense was not an independent risk factor. The CART group of 43 patients with favorable prognosis (compensated renal failure or treatment by hemodialysis, absent malignancy) had a 1-year survival rate of 38%. We conclude that thrombocytopenia, encephalopathy, and malignoma, but not HRS per se, are fatal signs that make hemodialysis futile in patients with acute renal failure and decompensated liver disease.

Acute Kidney Injury↗
PubMed1995

Fundamental concepts and immunosuppressive treatment in the various forms of glomerulonephritis.

Immunosuppressive treatment in glomerulonephritis (GN) is still controversial. Most of the secondary forms of glomerulonephritis have the histologic features of one of the primary types of glomerulonephritis. Eight histologic expressions of primary glomerulonephritis can be distinguished and ordered in terms of severity of symptoms and prognosis: endocapillary GN, minimal change GN, mesangioproliferative GN, membranous GN, focal-sclerosing GN, membranoproliferative GN, focal-necrotizing GN, and rapidly progressive GN. Agreement exists only to the extent that immunosuppression is not required in endocapillary glomerulonephritis, although it is recommended in the other extreme of rapidly progressive GN. Primarily, an indication for immunosuppression is given by the severity of symptoms with a urinary protein excretion > 3.5 g per day and/or serum creatinine > 150 mumol per liter. As for anti-GBM, the type of glomerulonephritis is more important than the severity of symptoms in guiding therapy, whereas for IgA nephropathy it is controversial whether the prospective prognosis of even inexorably deteriorating renal function justifies immunosuppression. Renal biopsy is required to identify the type of glomerulonephritis so as to establish the specific immunosuppressive concept with different intensity and duration of treatment. Immunosuppression can reduce urinary protein excretion and improve deterioration of renal function; however, the proportion of patients responding varies with and depends on the different forms of GN.

Glomerulonephritis↗
PubMed1995

Porphyria cutanea tarda and hepatitis C viral infection. A clinical and virologic study.

BACKGROUND AND DESIGN: The role of hepatitis C virus (HCV) infection in porphyria cutanea tarda (PCT) is probable since the global HCV antibody prevalence among patients with PCT is about 70%. The purpose of this study was to evaluate the virologic characteristics in 12 patients with sporadic PCT and in one patient with familial PCT. Anti-HCV antibodies were detected by enzyme-linked immunosorbent assay and confirmed by recombinant immunoblot assay. Hepatitis B virus and antihuman immunodeficiency virus markers were also determined. The polymerase chain reaction was performed to detect the following: (1) both positive and negative HCV RNA strands, (2) HCV RNA titer, and (3) HCV RNA genotype. RESULTS: Seven of the 12 patients with sporadic PCT were HCV positive, and the patient with familial PCT was HCV negative. The age at onset of PCT was significantly lower in HCV-positive patients than in HCV-negative patients. The HCV RNA was detected in all patients who had HCV antibodies, and the replicative intermediate of HCV was detected in three of them. The positive RNA titer ranged from 1:10 to 1:10(6). Four patients were infected by HCV genotype I, two by genotype II, and one patient was coinfected by type I and type II. Three of the seven HCV-positive patients also had HBV antibodies, but HBV DNA was never detected. All patients were negative for the human immunodeficiency virus. CONCLUSIONS: The HCV infection rate was high (58%) in this series, and all HCV-infected patients had HCV RNA, reflecting an active replication of the virus. The young age at onset of PCT suggests that HCV is a major triggering factor of PCT. Nevertheless, the clinical changes of PCT were not related to the virologic findings, suggesting an indirect role of HCV.

Adult↗
PubMed1995

Saturable first-pass kinetics, plasma protein binding, and the furosemide intricacies.

An equation for saturable nonlinear first-pass kinetics is presented to discuss some contra-intuitive findings encountered with furosemide bioavailability. The diverging effects on steady-state bioavailability (Fss) are simulated for changes in maximal metabolic capacity (Vm), volume of distribution (Vd), Michaelis constant (Km), steady-state plasma concentration (Css), repetitively administered drug dose (Dss), dosage interval (Tau), liver plasma flow (Ql), absorption rate constant (Ka), and free plasma fraction (fp), where (Cssf = fp Css = const.) and (Kmf = fp Km = const.). [Formula: see text] The present concept is in line with observations indicating that furosemide bioavailability decreases from 60 to 45% in nephrotic syndrome patients whose plasma protein binding is reduced and hepatic clearance increased. These observations and our equation-based simulations show that furosemide must have a first-pass effect. Hepatic extraction of furosemide is not facilitated by albumin, and saturable first-pass kinetics can not be used to explain an albumin paradox.

Animals↗
PubMed1995

Circulating type VI collagen and undulin, in patients with kidney diseases, after kidney transplantation and on hemodialysis.

Chronic kidney diseases are characterized by alterations in connective tissue turnover resulting in fibrosis. We measured circulating peptides related to type VI collagen and undulin in serum and urine of 125 patients with various kidney diseases, on chronic hemodialysis and after kidney transplantation. Using a double-armed ELISA technique (median, 95% CI), normal serum concentrations for type VI collagen were 50 ng/ml [46-63] with no type VI collagen detectable in urine. Normal values for undulin were 215 ng/ml [207-241] in serum and 240 micrograms/d [223-284] in urine. The serum concentrations of undulin were most significantly (477 ng/mg [358-737]) increased in 18 hemodialysis patients. A significant increase (330 ng/ml [306-368]) was also observed in patients with various kidney diseases not requiring dialysis. No differences were found between the various forms of glomerulonephritis, interstitial nephritis and other kidney diagnoses. Although very low in normals (1.16 ml/min [1.05-1.27]) renal undulin clearance was even significantly lower in patients with kidney diseases (0.5 ml/min [0.4-0.6]). Serum concentrations for undulin were in the normal range in the direct postoperative phase after kidney transplantation (207 ng/ml [167-306]), whereas in kidney transplant out-patient levels were elevated to 425 ng/ml [357-563]. There was a slight but significant correlation between serum undulin and creatinine values and between renal undulin clearance and creatinine clearance. Values of serum type VI collagen increased in analogy to those of undulin. We conclude, that type VI collagen and undulin are novel serum parameters of renal extracellular matrix turnover that merit further exploration in patients with chronic kidney diseases.

Adolescent↗
PubMed1995

Unifying concept of pharmacokinetics derived from drug distribution and elimination in renal failure.

We are in the process of establishing a pharmacokinetic database for drug dosage adjustment to impaired renal function. To meet these demands, the system needs a unifying pharmacokinetic concept. Drug clearance is the common parameter that allows for intersecting the different pharmacokinetic approaches. In addition, two parameters are essentially needed for the concept, either the area-derived volume and the dominant elimination half-life or the moment-derived volume and the mean residence time. For drugs where the area-derived volume decreases with renal impairment, it can be shown that compartment-derived parameters are explicitly convertible into moment-derived parameters and vice versa.

Dosage Forms↗
PubMed1995

Parameters of haemostasis during acute venous thrombosis.

Underlying disorders of the coagulation system such as inhibitor deficiencies or decreased fibrinolysis are common in patients suffering from venous thrombosis. They may lead to the necessity of a lifelong prophylaxis. Prompt diagnosis is obviously to the patients benefit. We investigated 22 patients suffering from venous thromboses for the inhibitors antithrombin III (ATIII), protein C, and protein S during the first 8 to 12 days after admission to hospital and in addition after withdrawal from anticoagulant treatment after several months. At the day of admission ATIII and protein C levels were comparable to those several months later, but after 2 days they shifted downward or upward, respectively. Protein S did not shift during the period of hospitalisation, but was initially slightly lower than several months later. For inhibitors the day of admission to hospital is most suitable to take the samples. About 50% of the patients still had elevated activation markers (prothrombin fragments F1+2, thrombin-antithrombin complex TAT, and D-dimers) after several months.

Acute Disease↗
PubMed1994

Impact of de novo membranous glomerulonephritis on the clinical course after kidney transplantation.

Besides rejection-induced transplant glomerulopathy de novo membranous glomerulonephritis (MGN) is the most frequent cause of nephrotic syndrome after renal transplantation. We evaluated 1029 renal transplantations (271 without and 758 with cyclosporine treatment), performed on 848 patients between 1970 and 1992, which resulted in 872 functioning grafts. De novo MGN was seen in 30 biopsy specimens from 21 patients (about 2%), of whom 10 had received immunosuppressive treatment without and 11 with cyclosporine. Taking into account the longer periods of observation of patients without compared with those with cyclosporine treatment (88 +/- 60 vs. 41 +/- 31 mo., respectively, P = 0.001), the two treatment groups did not differ significantly in prevalence of de novo MGN (4.0% vs. 1.5%). De novo MGN was diagnosed by biopsy 62.7 +/- 44.4 mo. after transplantation; its incidence increased significantly with time (from 0% to 5.3% over 8 years; 95% confidential interval: 1.7-8%). Proteinuria (mean, 3.2 +/- 2.9 g/L) was first observed 47.5 +/- 51.3 mo. after transplantation. Thirteen of the 21 patients (62%) were nephrotic (proteinuria, over 1.5 g/L). Steroid pulses were given to 12 patients with de novo MGN and high proteinuria, which did not decline after treatment. Signs of chronic viral infection (hepatitis B antigen, hepatitis C antibody, or human immunodeficiency virus antibody) were found in 8 of the 21 patients (38%). Signs of vascular or interstitial rejection were seen in 17 and 12 of the 21 patients with de novo MGN, respectively, and cyclosporine arteriolopathy was diagnosed in four. Graft loss occurred in 14 of the 21 patients and was due to rejection in 13 and to de novo MGN in only one, who developed additional transplant vein thrombosis. Patients with de novo MGN did not differ significantly from the other 851 patients in graft survival (71.4 +/- 9.9% vs. 60.8 +/- 2.2% after 5 yr). De novo MGN is a late, often asymptomatic, complication of initially well tolerated grafts and is neither prevented by cyclosporine treatment nor reversed by further steroid medication. It is often associated with vascular changes caused by rejection or cyclosporine toxicity.

Adult↗
PubMed1994

Methods for studying antiviral functions of macrophages and mononuclear phagocytes.

Methods to check the antiviral activities of mononuclear phagocytes or macrophages are described. Two types of antiviral activities are defined. The intrinsic antiviral activity is determined as the outcome of virus replication in the macrophage per se whereas the extrinsic antiviral activity refers to the ability to reduce virus production in other surrounding cells that are normally permissive. The interpretation of the data are discussed.

Animals↗