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Biomedical subjects

C Keller

Publications and source records attributed to C Keller.

At least 235 records · Page 13Linked to original sources
PubMed1995

Identification of the valine 408 to methionine mutation in the LDL receptor in a Greek patient with homozygous familial hypercholesterolemia.

We have identified the cytosine to thymine change in the codon for amino acid 408 which causes valine to be replaced by methionine in exon 9 of the LDL receptor gene in a 12-year-old Greek boy living in Germany, with homozygous familial hypercholesterolemia, by using polymerase chain reaction-amplified genomic DNA and subsequent restriction digestion. Homozygosity was confirmed by direct DNA sequencing. The mutation was present in both his parents, and his brother, grandmother, uncle and cousin. Six restriction fragment length polymorphisms of the LDL receptor gene were used to determine the haplotype of the defective allele. The haplotype was different from the one reported earlier in African Afrikaners and from Holland. We conclude that the mutation in the Greek boy probably occurred as an independent mutation. Because the parents are from different areas in Greece, this mutation may be common in Greeks.

Base Sequence↗
PubMed1995

Ten LDL receptor mutants explain one third of familial hypercholesterolemia in a German sample.

Mutational defects in the LDL receptor are responsible for familial hypercholesterolemia (FH); thus far more than 150 mutations have been described. Nevertheless, systematic searches among the Germans have not been conducted. We used single-strand conformational polymorphism and polymerase chain reaction to find mutations in 10 index patients and in 40 other individuals with heterozygous FH. Our screen in the 10 index patients revealed 7 hitherto undescribed mutations. A screen of the 40 additional FH patients disclosed 20 defective of 54 total alleles and allowed specific diagnoses in 88 family members. We also found two families in which the children were markedly affected by FH, but the expected parental expression of the trait was not manifest. This observation suggests a role for additional environmental and genetic influences. Our report represents the first comprehensive effort to identify FH mutations in Germany. We found 10 mutations and these mutations explain 37% of FH cases. Our data may have relevance to expected FH patterns in central Europe.

Adult↗
PubMed1995

Beneficial effects of donor-specific transfusions on long-term renal allograft function.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 163 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor-recipient combinations were at least one-haplotype disparate, and 21 were two-haplotype disparate. Transient sensitization occurred in 2% and permanent sensitization in 7%. Over a 10-year period, the DST+Aza allograft survival rate is similar to the HLA-identical sibling transplants. The CMV sepsis rate was only 2%, and there were no lymphoproliferative neoplasms. The low rate of sensitization (7%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of early rejection (3%) argues for a modification of the immunologic response.

Azathioprine↗
PubMed1995

Where does it hurt? An interdisciplinary approach to improving the quality of pain assessment and management in the neonatal intensive care unit.

Identifying a premature infant's response to noxious stimuli and knowing when it is appropriate to intervene are major issues for the caregiver. After completing a pilot study, the staff of a 42-bed neonatal intensive care unit targeted improved pain assessment and management for further analysis. Using a series of Plan, Do, Check, and Act cycles they designed a stepwise set of interventions that resulted in the improved assessment and management of the neonate in pain.

Academic Medical Centers↗
PubMed1995

Measurement of body fat and fat distribution.

Overweight and obesity are increasing in prevalent and thus an important area for intervention and investigation. Researchers and clinicians have a variety of measurement techniques to assess body fatness and regional fat. These techniques are chosen for their accuracy and precision in light of their cost, convenience, and safety. This article introduces techniques for the measurement of body fatness and regional fat, their advantages and disadvantages and accuracy. Recommended measurement techniques for investigators and clinicians are provided.

Absorptiometry, Photon↗
PubMed1994

Treatment of primary hypercholesterolemia: fluvastatin versus bezafibrate.

The effects of fluvastatin and bezafibrate on lipids, lipoproteins, and apoproteins (apo) were investigated in a multicenter randomized, double-blind, parallel-group study. After 8 weeks of strictly controlled (computer-based assessment) dietary stabilization, patients with primary hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] > or = 160 mg/dL; triglycerides < or = 300 mg/dL) were enrolled into a 6-week placebo phase. Altogether, 131 patients were randomized to receive either fluvastatin at 40 mg once daily (n = 64; mean age 53 years) or bezafibrate at 400 mg once daily (n = 67; mean age 52 years) for 12 weeks. Compliance with the diet was monitored (3-day food records) after 6 and 12 weeks. Fluvastatin led to significant reductions in LDL-C (-23%), total cholesterol (-17%), LDL-C/high-density lipoprotein cholesterol (HDL-C) (-24%) and apo B (-19%). Fluvastatin significantly increased LpA-I (+8%) and apo E (+20%). Bezafibrate produced significant reductions in LDL-C (-17%), total cholesterol (-13%), LDL-C/HDL-C (-24%), triglycerides (-28%), apo B (-15%), and LpA-I (-10%) and significantly increased HDL-C (+12%), apo A-I (+9%), apo A-II (+30%), apo E (+14%), and Lp(a) (+3%). No clinically notable increases in levels of liver enzymes or creatine phosphokinase were observed with either treatment. Both treatments were well tolerated. There was a low incidence of adverse events that tended to be mild and included headache, muscular pain, angina, and dyspepsia. The frequency of adverse events was similar in both treatment groups, and no significant differences in dietary behavior were observed. In conclusion, fluvastatin is a well tolerated 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia. Effects of fluvastatin on LpA-I occur irrespective of changes in HDL-C.

Adult↗
PubMed1994

The HELP-LDL-apheresis multicentre study, an angiographically assessed trial on the role of LDL-apheresis in the secondary prevention of coronary heart disease. II. Final evaluation of the effect of regular treatment on LDL-cholesterol plasma concentrations and the course of coronary heart disease. The HELP-Study Group. Heparin-induced extra-corporeal LDL-precipitation.

The efficacy of the heparin-induced extracorporeal LDL-precipitation (HELP)-apheresis procedure has been studied in an open prospective multicentre trial. After 2 years of regular weekly HELP-treatment the data from 39 of 51 patients could be evaluated according to the study criteria. Twelve of the initially recruited study patients were omitted from the evaluation either because of premature termination of the treatment or because they did not fulfil the exact guidelines of the study protocol. A mean of 2.831 plasma was regularly treated on average every 7.85 days. The mean pre-/post-apheresis LDL-cholesterol levels decreased from 286/121 mg dl-1 at the first HELP treatment to 203/77 mg dl-1 after 1 year and to 205/77 mg dl-1 after 2 years of regular apheresis; the corresponding values for fibrinogen were 314/144, 246/98 and 250/105 mg dl-1, respectively. In contrast, the mean pre-/post-apheresis HDL-cholesterol levels rose from 41/38 through 51/44 mg dl-1 after 1 year to 52/43 mg dl-1 after 2 years of treatment. The overall result was a normalization of the atherogenic index (LDL-/HDL-cholesterol ratio) from 6.9/3.2 to 4.0/1.9. The angiographies from 33 patients obtained before and after 2 years of regular treatment could be evaluated blindly using the cardiovascular angiography analysis system. The mean degree of stenosis of all segments decreased from 32.5% (SD = 16) to 30.6% (SD = 16.8) over the 2 years. A regression > 8% was observed in 50/187 (26.7%) segments, whereas 29/187 (15.5%) segments showed progression. In 108/187 (57.8%) segments the lesions were stable (< 8% deviation) over 2 years. We conclude that regular treatment with HELP-LDL-apheresis is able to stabilize progressive atherosclerotic disease and to induce almost twice as much regression as progression of atherosclerotic lesions.

Adult↗
PubMed1994

Identification of defective binding of low density lipoprotein by the U937 proliferation assay in German patients with familial defective apolipoprotein B-100.

Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder characterized by decreased binding of low density lipoprotein (LDL) to the LDL receptor due to a substitution of glutamine for arginine in residue 3500 of apolipoprotein B-100. We present the results of the U937 cell proliferation assay for the detection of familial defective apo B100 in 13 German FDB patients. Due to a defect in the pathway of cholesterol synthesis the human myelomonocytic tumour cell line U937 lacks the ability to synthesize cholesterol which makes proliferation of these cells dependent on the presence of exogenous LDL-cholesterol. U937 cells were incubated with LDL from 13 FDB-patients, 10 healthy normocholesterolaemic individuals (NC) and 26 patients with familial hypercholesterolaemia due to a defective LDL-receptor (FH). At LDL-cholesterol concentrations below 1 microgram ml-1 no proliferation occurred. In the presence of LDL from FDB patients at concentrations between 2.5 micrograms ml-1 and 15.0 micrograms ml-1, the proliferation was significantly reduced compared to LDL from FH-patients and normocholesterolaemic controls. At 5 micrograms ml-1 the reduction was 31-80% regardless of age, sex, apo E genotype, Lp(a)- and lipid levels. At concentrations above 25.0 micrograms ml-1 no further differences were observed. The present results indicate that the U937 proliferation assay is a reliable test for the detection of defective LDL-binding due to the 3500 mutation in FDB patients. It may be useful for the detection of defective binding of LDL due to other mutations in the apo B-100 gene.

Adult↗
PubMed1994

Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

BACKGROUND: The purpose of this study was to compare combination antithrombotic therapy with aspirin plus anticoagulation versus aspirin alone, when added to conventional antianginal therapy in patients with unstable rest angina or non-Q-wave myocardial infarction who were nonprior aspirin users. METHODS AND RESULTS: Two hundred fourteen patients were randomized; 109 were randomized to receive aspirin alone (162.5 mg daily) and 105 to receive a combination of aspirin plus anticoagulation, ie, aspirin 162.5 mg daily plus heparin (activated partial thromboplastin time, two times control) followed by aspirin 162.5 mg daily plus warfarin (international normalized ratio, 2 to 3). Trial therapy was begun by 9.5 +/- 8.8 hours of qualifying pain and was continued for 12 weeks. Primary end points were recurrent angina with ECG changes, myocardial infarction, and/or death. Analysis by intention to treat of primary events at 12 weeks was performed. At 14 days, there was a significant reduction in total ischemic events in the combination group versus aspirin alone (10.5% versus 27%, P = .004). An efficacy analysis of primary events at 12 weeks also revealed a large reduction in total ischemic events in the combination group versus aspirin alone (13% versus 25%, P = .06). Bleeding complications were slightly more common with combination therapy. CONCLUSIONS: In nonprior aspirin users, combination antithrombotic therapy with aspirin plus anticoagulation significantly reduces recurrent ischemic events in the early phase of unstable angina.

Angina, Unstable↗
PubMed1994

A novel test model for routine microbiological control of automated washer/disinfectors for flexible endoscopes.

Concerns exist about effective methods for endoscope cleaning, disinfection and sterilization. The aim of this study was to establish a model for controlling the function of automatic washer/disinfectors for flexible endoscopes under routine conditions. The team developed a dummy endoscope channel system representing two complete gastroscopes and a colonoscope, with channels joined together and fitted with adaptors to allow the models to fit into different washer/disinfectors. The models were artificially contaminated with various combinations of four test organisms and coagulating blood and run through test cycles in different washer/disinfectors. A total of 24 test runs were performed. The reduction of a given microbial burden by at least five log steps is an established measure of efficacy of a decontamination procedure. When the two challenge tests (45 channels) and the six positive controls are excluded, only 13/309 channels (4.2%) failed the proof of efficacy. In contrast, the failure rate in the challenge test was 65.3%. The difference of the final bioburden is statistically significant. The data suggest this test model could be regarded as a first step in rational and reliable biological control of flexible endoscope reprocessing.

Central Supply, Hospital↗
PubMed1994

[An unusual form of silicosis caused by exposure to a priming putty (Asplit ET)].

A case report on a 59-year-old male patient is given who had been exposed for 30 years to silica flour when mixing the primer Asplit ET. To some extent the diagnostic findings were uncommon for silicosis and rather suggested the diagnosis of a usual interstitial pneumonitis. Only transbronchial lung biopsy and histologic examination inclusive energy-dispersing x-ray microanalysis was able to prove a complicated form of silicosis.

Biopsy↗
PubMed1994

[Therapy of hyperlipidemia].

The identification of patients with monogenetic lipid disorders and a very high risk of premature coronary heart disease is the prerequisit for an intensive cholesterol lowering therapy with the goal to normalize serum cholesterol and prevent early coronary death which seems possible with the new potent drugs.

Adult↗
PubMed1993

Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant.

OBJECTIVE: To study the efficacy and toxicity of ganciclovir prophylaxis given at engraftment to cytomegalovirus (CMV)-seropositive, allogeneic bone marrow transplant recipients. DESIGN: A double-blind, placebo-controlled study. SETTING: The Fred Hutchinson Cancer Research Center, a referral marrow transplant center. PATIENTS: This study was conducted from November 1990 to August 1991. Ninety-three CMV-seropositive patients were entered into the study before marrow transplant, with 64 patients randomized to receive the study drug after marrow engraftment. Thirty-one patients received placebo, and 33 received ganciclovir. The dose was 5 mg/kg body weight administered intravenously twice daily for 5 days, followed by once daily until day 100 after transplant. MEASUREMENTS: Outcome variables measured were CMV infection, monitored by weekly cultures, and neutropenia, defined as an absolute neutrophil count of 0.750 x 10(-9)/L for 2 consecutive days. Cytomegalovirus disease and mortality were secondary end points. RESULTS: Fourteen (45%) placebo recipients developed CMV infection in the first 100 days after marrow transplant compared with one (3%) ganciclovir recipient (P < 0.001). Nine (29%) placebo recipients developed CMV disease compared with no cases in the ganciclovir group during the first 100 days (P < 0.001). Neutropenia occurred in 10 ganciclovir recipients (30%) compared with no cases in the placebo group during the period of observation (P = 0.001). In a separate analysis, patients on ganciclovir who became neutropenic were at greater risk (relative risk, 4.3; P = 0.02) for bacterial infection. Mortality between the two study groups did not differ statistically at 100 and 180 days. CONCLUSION: Ganciclovir given prophylactically after engraftment is effective in suppressing CMV infection and disease. Neutropenia is an important side effect of ganciclovir use and is associated with an increased risk for bacterial infection.

Adolescent↗