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Biomedical subjects

E Keller

Publications and source records attributed to E Keller.

At least 19 recordsLinked to original sources
PubMed1992

[Non-enzymatic marking of gene probes using digoxigenin for the diagnosis of sickle cell mutation and beta thalassemia].

A method is described in which allele-specific oligonucleotides (ASO) are labeled non-enzymatically with digoxigenin (DIG). The ASOs were synthesized in a DNA synthesizer. A primary C6-alkylamine was incorporated at the 5'end of the ASO. The derivative was coupled to digoxigenin-3-0-methylcarbonyl-epsilon-aminocaproic acid-N-hydroxy-succinimide ester. The DIG-ASO probes were isolated from the crude preparation and hybridized with amplified genomic DNA. The annealed probes were detected with an ELISA test. The DIG-ASO probes were successfully used for the identification of sickle cell disease genotypes and the most common beta-thalassemia mutations.

Adult↗
PubMed1992

Rebound of plasma vancomycin levels after haemodialysis with highly permeable membranes.

Vancomycin is usually given only once a week to haemodialysis (HD) patients. If highly permeable dialysis membranes are used, however, high clearance values have been reported, so the aim of the study was to determine whether high clearance of vancomycin resulted in sufficient drug elimination to induce subtherapeutic plasma levels after one week. In 18 chronic HD patients, treated with polysulfone dialyzers (1.2 m2), the pharmacokinetics of vancomycin were studied after administration of 1 g. Concentrations were determined by fluorescence polarisation immunoassay. At a blood flow of 219 ml.min-1, HD clearance of vancomycin was 62.3 ml.min-1. Immediately after dialysis plasma concentrations were 38% lower than predialysis levels. However, marked rebound in the vancomycin level was observed 5 h later, resulting in plasma levels only 16% lower than prior to dialysis. 3 HD treatments in 1 week removed about one third of the initial dose. After one week 15 of 18 patients still had a therapeutic plasma level (greater than 4 micrograms.ml-1). In conclusion, polysulfone membranes show high clearance of vancomycin. However, transfer of drug from blood to dialysate appears to be faster than from tissues to blood. Because of a marked rebound in plasma level after treatment, therapeutic drug concentrations will still be present in most patients after one week.

Female↗
PubMed1992

Effect of nifedipine and captopril on glomerular hyperfiltration in normotensive man.

Glomerular hyperfiltration and hypertension induced by extensive loss of renal parenchyma are suspected to accelerate progression of renal failure. Amino acid infusion or protein ingestion also modify renal hemodynamics and increase glomerular filtration rate (GFR). This phenomenon was used to study the influence of two commonly used antihypertensive agents, captopril and nifedipine, on renal hemodynamics at rest and during glomerular hyperfiltration. Thirteen healthy volunteers were studied on three separate days (days A, B, and C) in random sequence: inulin and p-amino hippurate (PAH) clearance were measured first under glucose infusion and afterwards under stimulation by amino acid infusion (0.35 mmol/kg/min; 4 mg/kg/min). Day A served as a control, where no medication was given. On day B, 10 mg nifedipine, and on day C, 25 mg captopril, were administered orally before study. Without premedication (= day A, control) GFR increased from 108.0 +/- 6.9 mL/min (SEM) to 131.7 +/- 7.0 mL/min (P less than 0.05). On day B (nifedipine), GFR before stimulation by amino acids was already elevated to 121.8 +/- 4.2 mL/min (P less than 0.05 compared with day A) and increased to 132.6 +/- 6.3 mL/min with infusion of amino acids, thus to the same range as on day A without medication. On day C, after captopril, GFR did not increase with infusion of amino acids (from 112.5 +/- 7.2 to 117.3 +/- 6.3 mL/min). Our results indicate the calcium channel antagonist nifedipine and the angiotensin-converting enzyme (ACE) inhibitor captopril differ in their effect on intrarenal hemodynamic parameters. Nifedipine induces hyperfiltration at rest and allows maximal hyperfiltration to develop under amino acid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[The preoperative marking of nonpalpable breast lesions: the technic and results].

189 non-palpable breast lesions in 182 patients were localized using conventional mammographic apparatus, a wire grid compression plate and a cannula with a hooked mandrin. The technique of the examination for defining the lesion in three planes and fixation of the lesion with the wire is described. In 173 instances (91.5%), the lesion was found at the first biopsy and subsequent biopsies were necessary on only 24 occasions. One lesion (0.5%) was missed completely. 47 carcinomas were found (24.9%) and the incidence of malignancy increased from 14.3% to 33.3% during the series. The mean ratio defining the size of the biopsy and the size of the lesion was 3.3 and indicates good preservation of breast tissue. Radiographs of the specimen taken with compression showed 186 lesions (98.4%). The method, which is comfortable for the patient, provides satisfactory detection and localization of the lesions; results are similar to those of stereotactic methods but this method is quicker and much less expensive.

Adult↗
PubMed1992

Identification of molecular defects causing congenital adrenal hyperplasia by cloning and differential hybridization of polymerase chain reaction-amplified 21-hydroxylase (CYP21) genes.

Congenital adrenal hyperplasia (CAH), one of the most common autosomal recessive disorders, is caused primarily by defects in the gene encoding steroid 21-hydroxylase, CYP21B. The molecular diagnosis of CAH, important for prenatal diagnosis, carrier detection, and a better understanding of the various clinical CAH forms, is complicated by the close proximity of a highly similar pseudogene, CYP21A, containing (and probably donating, by gene conversion-like events) most of the defects underlying CAH. In this study, we describe an efficient strategy to identify molecular defects causing CAH: polymerase chain reaction-amplified CYP21 loci are cloned and hybridized to a set of oligonucleotides, allowing rapid and allele-specific identification of all known CYP21B mutations relevant to 21-hydroxylase function. Possible new mutations can be identified by subsequent nucleic acid sequencing provided they reside within the cloned CYP21B fragment (from the TATA box to the 8th of the 10 CYP21B gene exons). Using this method, the CYP21B gene mutations of a heterozygous carrier and 25 CAH patients have been identified by oligonucleotide hybridization. All disease haplotypes seem to have been generated by recombinational events involving the CYP21A pseudogene. In 5 individuals, these data were subsequently verified by nucleic acid sequencing. The procedure can be used for diagnostic applications and may facilitate identification of new CYP21B defects.

Adrenal Hyperplasia, Congenital↗
PubMed1992

Stimulation of nitrogen and whole-body protein metabolism in growth hormone-deficient children by recombinant human growth hormone: relationship to growth.

The effect of a mammalian-cell-derived recombinant human growth hormone (rhGH) on nitrogen and whole-body protein metabolism was assessed in 12 children with complete growth hormone (GH) deficiency. All the patients received single oral doses of 15N-glycine (95 atom % 15N), 20 mg/kg body weight, prior to and following 7 days of treatment with rhGH, 1.7 IU/m2 body surface area (BSA) per day, administered subcutaneously. Prior to rhGH, mean urinary 15N-nitrogen excretion was 42.8 +/- 8% of the administered dose, which fell significantly to 22.8 +/- 7% during rhGH administration (p < 0.0001). Stimulation of protein metabolism by rhGH resulted in a protein net gain rate of 1.1 +/- 0.4 g/kg/day, which was significantly higher than the 0.6 +/- 0.5 g/kg/day rate seen prior to rhGH (p < 0.001). In patients subsequently placed on daily subcutaneous injections of rhGH 1.7 IU/m2 BSA, mean height velocity standard deviation score (HV SDS) for chronological age significantly increased from -3.8 +/- 2.6 to +8.5 +/- 3.1 and +3.3 +/- 2.2, during the 1st and 2nd years of treatment, respectively. However, there was no correlation between the long-term response to rhGH treatment and the short-term changes in nitrogen or protein metabolism in GH-deficient children.

Adolescent↗
PubMed1992

Recombinant human growth hormone and oxandrolone in treatment of short stature in girls with Turner syndrome.

91 girls with Turner syndrome (TS) with a mean chronological age (CA) and bone age (BA) of 10.3 +/- 2.3 and 8.9 +/- 1.9 years, respectively, were randomly assigned to subcutaneous treatment with recombinant human growth hormone (rhGH) alone (n = 47), 2.6 IU/m2 body surface area daily or combination treatment (n = 44) with the same dose of rhGH and oxandrolone 0.1 mg/kg body weight orally, for the first 12 months of this study. During the 1st year of therapy, there was a striking increase in height velocity (HV) in both groups, from 4.0 +/- 0.8 to 6.3 +/- 1.3 cm/year [HV standard (standards of untreated Turner patients) deviation score (SDS) for CA from 0.0 +/- 0.7 to 2.9 +/- 1.3] in the rhGH group and from 4.2 +/- 1.2 to 8.5 +2- 1.7 cm/year (HV SDS-CA from +0.3 +/- 1.0 to 5.6 +/- 1.6) in the combination group. The difference between the groups was statistically significant (p < 0.01). During the 2nd year of treatment, the rhGH dose was increased to 3.4 IU/m2 daily for the rhGH-alone group, whereas in the combination treatment group the oxandrolone dose was reduced to 0.05 mg/kg daily. HV was maintained at significantly higher levels than those prior to treatment, at 5.3 +/- 1.1 cm/year (HV SDS-CA: +2.1 +/- 1.3) and 6.2 +/- 1.5 cm/year (HV SDS-CA: +3.6 +/- 1.4) in the rhGH-alone and the combination group, respectively (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Prenatal diagnosis of 21-hydroxylase deficiency by RFLP analysis of the 21-hydroxylase, complement C4, and HLA class II genes.

In 19 pregnancies at risk for 21-hydroxylase deficiency (21OHD) in 18 families with at least one affected child, prenatal diagnosis was performed by RFLP analysis using the enzymes Taq I and EcoRI and the DNA probes specific for the 21OH genes, the closely linked complement C4 genes and the highly polymorphic HLA class II genes DRB, DQB, and DPB. For fetal DNA analysis either chorionic villi or cultivated amniotic cells were used. In all 19 cases, a clear prenatal diagnosis was possible either with the 21OH probe alone or in most cases, by combining the results of the different closely linked loci.

Adrenal Hyperplasia, Congenital↗
PubMed1991

Plasma level monitoring of mitotane (o,p'-DDD) and its metabolite (o,p'-DDE) during long-term treatment of Cushing's disease with low doses.

Mitotane (o,p'-DDD) can be used for the treatment of various adrenocortical diseases such as Cushing's syndrome, but the usual doses of 6-8 g per day are often associated with severe adverse effects. This paper reports the results of much lower doses of o,p'-DDD (0.5-2 g per day) in two patients with Cushing's disease over periods of 8 and 5 years, respectively, under concomitant monitoring of the plasma levels of the parent drug and its major metabolite, o,p'-DDE. It became apparent that o,p'-DDD and o,p'-DDE have a strong tendency to accumulate in the body due to their high lipophilicity. As a consequence, changes in dose regimens had long lag times before they were reflected in plasma levels and once an increase or decrease had started one had to be careful not to cause overshoot. Steady state plasma levels of o,p'-DDD between 5-10 micrograms/ml appeared sufficient to induce and to maintain remission of the disease, which was accompanied with normal cortisol levels in plasma and urine. DDD-levels below 5 micrograms/ml for several weeks may lead to relapses, whereas DDD-levels over 10 micrograms/ml gave rise to side effects. On the other hand, o,p'-DDE seemed inactive at levels up to 4 micrograms/ml in plasma.

Adolescent↗
PubMed1991

A model for the role of HLA-DQ molecules in the pathogenesis of juvenile chronic arthritis.

Restriction fragment length polymorphism (RFLP) typing of MHC-class II loci DRB, DQA1, DQB1, DQA2 and DPB1 was performed in 94 patients with seronegative juvenile chronic arthritis (JCA) and 184 random controls. Analysis of allele frequencies and MHC-class II 4-loci haplotypes indicate: (1) Susceptibility to JCA is more strongly associated with the HLA-DQ subregion than with the HLA-DR subregion, especially in early onset pauciarticular JCA (EOPA-JCA). (2) Haplotype and sequence analysis show two independent MHC-class II associations for susceptibility to EOPA-JCA, one located in DQA1, the other in DPB1. (3) Two RFLP defined patterns of the DQA1 locus, DQA1.5 (DQA1*0501) and DQA1.8 (DQA1*0401, *0601) are strongly associated with the disease. (4) Analysis of amino-acid (AA) sequences coded in exon 2 of DQA1 reveals an AA sequence of six AAs common to all three associated DQA1 alleles. This suggests a model that includes a functional role for HLA-DQ molecules in the pathogenesis of JCA.

Alleles↗
PubMed1991

[A case of external ophthalmomyiasis].

A 9 year old patient with a right ophthalmomyiasis is presented. The infestation happened in Greece during vacation. The symptoms consisted of conjunctivitis and rinitis. The larvaes were removed from the conjunctiva and specified as larvaes I from Oestrus ovis. The infestation possibilities, different clinical evolutions and therapy are discussed.

Animals↗