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Biomedical subjects

K Bauer

Publications and source records attributed to K Bauer.

At least 109 records · Page 6Linked to original sources
PubMed1996

Detection of common hepatitis C virus subtypes with a third-generation enzyme immunoassay.

The causal agent of most posttransfusion non-A and non-B hepatitis infections was characterized in 1989 by molecular biological techniques as a positive-stranded, enveloped RNA virus, designated hepatitis C virus (HCV). Only since 1990 has it been possible to screen for an infection with antibody tests or direct amplification assays for the nucleic acid (i.e., reverse-transcription polymerase chain reaction [PCR]). However, these nucleic acid based tests are time consuming and rather expensive. Recently, third-generation enzyme immunoassays (EIAs) for HCV infection were introduced (i.e., Abbott Laboratories, North Chicago, IL; Ortho Diagnostics, Inc., Raritan, NJ; and Roche Diagnostics, Basel, Switzerland). The Roche Diagnostics EIA has been evaluated with our patient population. To this end, 1,090 samples were assayed by both EIA and PCR; 946 of all samples (87%) were negative, and 107 samples (9.8%) were positive by both tests. Thirty of the patients (2.7%) showed antibodies but no detectable virus, whereas 7 of all patients tested (0.6%) were PCR-positive but had not yet developed antibodies to the virus. Of these 7 patients, only one showed normal serum transaminases. Virus strain subtyping and quantification of viral load on the positive samples in parallel have been performed, and the fact that the EIA detects all the virus subtypes found in our hospital can be inferred. No correlation between subtypes, viral load, and immune response could be measured with this antibody test. Our results indicate that, in most circumstances (except in settings where immunocompromised patients are abundant), this EIA can replace the much more expensive PCR tests for the routine screening for HCV infection.

Adolescent↗
PubMed1996

Development and evaluation of a computerized admission diagnoses encoding system.

Hospital information systems designed to support the needs of health care professionals include patient data entered using both freetext and precoded storage schemes. A major disadvantage of freetext storage schemes is that data captured in this format can only be presented as is to the user for review tasks. In the view of many health care scientists, natural language understanding systems capable of identifying, extracting, and encoding information contained in freetext data may provide the necessary tools to overcome this weakness. This paper describes the development and evaluation of a such a system designed to encode freetext admission diagnoses. This system combines both semantic and syntactic linguistic analysis techniques. Evaluation results demonstrate the overall performance of this system to be reasonable, accurately encoding approximately 76% of admission diagnoses. Inefficiencies are primarily due to the inability of this system to generate encodings in roughly 15% of test cases. When encodings are produced, however, accuracy equals that of the current manual coding method. With further modification, this application can partially automate the coding process.

Algorithms↗
PubMed1996

Fluticasone propionate 1 mg daily and beclomethasone dipropionate 2 mg daily: a comparison over 1 yr.

This study was designed primarily to assess the safety and tolerability of fluticasone propionate (FP) 1 mg day-1 by comparison with beclomethasone dipropionate (BDP) 2 mg day-1 over a 12-month study period. Lung function data were also recorded and used to determine whether the potency ratio between the two inhaled corticosteroids observed in previous studies was maintained in the long-term. Two hundred and thirteen patients with an established clinical history of severe chronic asthma and who were currently receiving between 1000 micrograms and 2000 micrograms day-1 of inhaled steroids were randomized to treatment in a ratio of 3:1 for FP:BDP (159 patients FP; 54 patients BDP), both via metered dose inhalers. Both treatments were well tolerated with a similar adverse event profile. No unexpected adverse events were recorded. Most adverse events were related to the patients' asthma, an intercurrent infection or underlying atopy. The incidence of pharmacologically predictable adverse events was equally low in both treatment groups as was the incidence of events suggestive of systemic steroid effect. Mean serum cortisol levels remained within the normal range at all visits for both treatments. At 12 months, however, the mean cortisol levels for the FP group had risen 4% above the baseline value but had dropped 15% below for the BDP group, giving a ratio of FP:BDP of 1.22; P = 0.01; 95% confidence limits (CL) 1.05-1.43. Fluticasone propionate 1 mg day-1 was at least as effective as BDP 2 mg day-1 in improving lung function (PEF, FEV1 and FVC) over this period. Moreover, the difference in FEV1 values at 6 months was significantly greater for the FP group than for the BDP group (P = 0.04; difference = 0.12 1; 95% CL = 0.01, 0.24 1). The difference between treatments in the amount of FEV1 reversibility was also significantly greater for FP at 12 months (difference in treatments = -3%; 95% CL = - 7-0%; P = 0.044). This study supports previous studies and suggests that FP is likely to be of benefit in the long-term treatment of chronic severe asthma.

Adolescent↗
PubMed1996

Dipeptide uptake by adenohypophysial folliculostellate cells.

Dipeptide uptake was studied in primary cultures from rat anterior pituitaries by use of radiolabeled carnosine and the fluorescent dipeptide derivative beta-Ala-Lys-N epsilon-AMCA (AMCA is 7-amino-4-methylcoumarin-3-acetic acid). Fluorescence microscopic studies revealed that the reporter peptide specifically accumulated in the S-100 positive folliculostellate cells that do not produce any known hormone. The dipeptide derivative was taken up in unmetabolized form by an energy-dependent saturable process with apparent kinetic constants as follows: Michaelis constant, 19 microM; maximum velocity, 5.5 nmol.mg protein-1.h-1. This high-affinity transporter was strongly affected by inhibitors of sodium/proton exchangers and thus appeared to be driven by a proton gradient. Competition studies revealed that the peptide transporter exhibits broad substrate specificity with a preference for hydrophobic dipeptides. In contrast to free amino acids and the pseudotetrapeptide amastatin, tripeptides were also accepted. Compounds without an alpha- and beta-amino group, such as captopril, thiorphan, and benzylpenicillin, did not affect uptake of the reporter peptide, although they were substrates of the well-characterized intestinal and renal dipeptide transporters.

Amino Acids↗
PubMed1996

mtDNA sequence diversity in Africa.

mtDNA sequences were determined from 241 individuals from nine ethnic groups in Africa. When they were compared with published data from other groups, it was found that the !Kung, Mbuti, and Biaka show on the order of 10 times more sequence differences between the three groups, as well as between those and the other groups (the Fulbe, Hausa, Tuareg, Songhai, Kanuri, Yoruba, Mandenka, Somali, Tukana, and Kikuyu), than these other groups do between one other. Furthermore, the pairwise sequence distributions, patterns of coalescence events, and numbers of variable positions relative to the mean sequence difference indicate that the former three groups have been of constant size over time, whereas the latter have expanded in size. We suggest that this reflects subsistence patterns in that the populations that have expanded in size are food producers whereas those that have not are hunters and gatherers.

Agriculture↗
PubMed1996

Successful emergency splenectomy during pregnancy in a patient with life-threatening idiopathic thrombocytopenia. Case report.

Thrombocytopenia can be a pathophysiological feature of pregnancy. In the case reported, the thrombocyte count was reduced to 1% of normal (1 x 10(9) thrombocytes/l) at 28 weeks of gestation. In chronological order, the patient showed epistaxis, macrohematuria and gingival, conjunctival, intracerebral and pulmonary bleeding. The latter was life-threatening. An emergency splenectomy was undertaken, without complications. The operation was followed by a massive increase in the thrombocyte count, reaching 200 x 10(9)/l four days later. Unfortunately, a premature rupture of the membranes, with signs of amnion infection, occurred on the seventh day. A Cesarean section was undertaken (30 weeks of gestation), without complications. Both mother and baby are in good health 10 months later. The newborn had a normal thrombocyte count at delivery and thereafter. The life-threatening hemorrhage of the mother, the delivery of an unaffected baby and the relatively quick remission after splenectomy suggest an upregulated destruction of thrombocytes by the maternal spleen. The increased level of Macrophage-Colony Stimulating Factor (M-CSF), a normal feature of pregnancy, has the potential to augment thrombocyte destruction by activating macrophages. The production of anti-thrombocyte antibodies, especially if localized in the spleen, could result in increased thrombocyte sequestration by macrophages with severe effects focused on the mother.

Adult↗
PubMed1995

Rapid stimulation of type I 5'-deiodinase in rat pituitaries by 3,3',5-triiodo-L-thyronine.

The negative feedback control of thyrotropin production by the anterior pituitary involves local 5'-deiodination of L-thyroxine (L-T4) to the active thyroid hormone 3,3',5-triiodo-L-thyronine (T3) by two 5'-deiodinase isozymes which are distinctly regulated by thyroid hormone. T3 rapidly increased steady-state mRNA levels and activity of type I iodothyronine-5'-deiodinase (5'DI) in rat anterior pituitary and in reaggregate cultures of anterior pituitaries. Type II 5'-deiodinase activity determined in parallel with 3,3',5-triiodo-L-thyronine (rT3) as substrate was markedly lower than that of 5'DI. 5'DI mRNA levels and activity were higher in anterior pituitaries of female compared to male rats. Neither gender differences nor T3 stimulation of 5'DI activity were found in the posterior part. These data demonstrate a T3 dependent expression of 5'DI in euthyroid anterior pituitary and suggest that this isozyme serves a major function within the complex network of thyroid hormone homeostasis.

Animals↗
PubMed1995

Prophylaxis and therapy with factor VII concentrate (human) immuno, vapor heated in patients with congenital factor VII deficiency: a summary of case reports.

Hereditary factor VII deficiency is a rare autosomal recessive condition, usually associated with normal or reduced levels of a functionally defective molecule. The available means of treating this condition in North America presents serious health risks to the patient. Transfusion with fresh frozen plasma carries a risk of volume overload and a significant risk for viral transmission. Sustained prothrombin complex therapy is associated with a high risk for thrombogenic complications. This communication describes the use of Factor VII Concentrate (Human) Immuno, Vapor Heated--an intermediate purity factor VII concentrate from Immuno A.G.--for the treatment of 13 patients with factor VII deficiency. Treatment regimens described include those for long-term prophylaxis (three children), acute hemorrhages (two children, one adult), peripartum prophylaxis (one patient), and surgical coverage (two children, four adults). Prophylaxis and therapy were successful in all cases, the medication was well-tolerated, and there were no complications. In the three cases of long-term prophylaxis in children, doses of 10-50 IU/kg were given one to three times a week; one patient has undergone long-term prophylaxis for approximately 8 years, one patient for 1 year, and one patient for 1 1/2 years. Three cases in which Factor VII Concentrate was principally used for treatment of acute episodes of bleeding are described. One infant received Factor VII Concentrate on about 50 occasions for treatment of mucosal bleeding; a correction to 40-100% resulted in cessation of bleeding within 15 min in all cases. For treatment of an episode of intracranial bleeding, an 8-year-old boy received a dose of 37 IU/kg Factor VII Concentrate every 6 hr for peak factor VII levels of approximately 100% and troughs as low as 4% over the 11-day treatment period. A 37-year-old adult male with intracranial bleeding received alternating doses of 16 IU/kg and 8 IU/kg every 6 hr for 10 days with peak factor VII levels in the upper thirties (%). The peak favor VII level during surgical coverage with Factor VII Concentrate (neurosurgery, open reduction of ankle bones, dental surgery, pituitary adenoma surgery, closed liver biopsy) was approximately 100% in all cases, with trough levels ranging from 8 to 65% over treatment periods of 24 hr to 16 days using treatment intervals of 6-12 hr.

Adult↗
PubMed1995

Randomized controlled trial of Ringer solution versus serum for partial exchange transfusion in neonatal polycythaemia.

UNLABELLED: We tested whether crystalliod solutions could be used instead of colloid solutions for partial exchange transfusions (PET) in polycythaemic neonates because crystalloid solutions are cheap, carry no risk of anaphylactic reactions and can be sterilized. We randomly assigned 20 term neonates with venous haematocrit (Hct) > 0.65 l/l to PET with either a serum preparation (BISEKO) or Ringer solution. Plasma volume (PV) was measured with Evans blue dilution. Blood volume (BV) and red cell mass were calculated from PV and venous Hct. Before PET both serum and Ringer groups had the same Hct (0.69 (0.66-0.76) vs 0.69 (0.66-0.71) l/l; median (range)) and BV (108 (81-116) versus 96 (68-121) ml/kg. During PET an equivalent amount of blood was withdrawn stepwise (19 (14-26) versus 17 (13-25) ml/kg and replaced by either serum or Ringer solution. More of the Ringer solution (median 77%) than of the serum (median 36%) given left the intravascular space within 4 h after PET (P = 0.016); but there was no significant difference in Hct after Ringer-PET compared to serum-PET (median 0.58 vs 0.56 l/l). No infant required repeat PET. Ringer-PET reduced BV from high to normal values (from median 96 to 83 ml/kg; P = 0.005), whereas after serum-PET BV remained high (from median 108 to 98 ml/kg; not significant). CONCLUSION: PET with Ringer solution resulted in a haemodilution comparable to PET with serum and a correction of hypervolaemia.

Blood Component Transfusion↗
PubMed1995

Effect of solution and suspension type aerosol of formoterol on tremor response and airways in patients with asthma.

BACKGROUND: Aerosol delivery and deposition to the oropharynx and the lungs have been found to be different for solution-type and suspension-type metered-dose aerosols used for treatment of asthma. We investigated possible differences in clinical effects between solution and suspension metered-dose formoterol aerosols. METHODS: A total of 24 patients with asthma (forced expiratory volume in 1 second, < or = 70% predicted) inhaled single doses (12 micrograms or 24 micrograms) of formoterol solution and suspension so that we could investigate the immediate tremor, airway, and cardiovascular responses in a randomized, double-blind, crossover trial. Fenoterol suspension aerosol (400 micrograms) was used for comparison (single-blind, poststudy, nonrandomized administration). Fenoterol (400 micrograms) as a rescue medication was inhaled after 120 minutes on each of the 5 study days. RESULTS: The order of mean (+/- SEM) maximum tremor acceleration was as follows: 12 micrograms formoterol solution (67.92 +/- 4.54 cm x sec-2) < 24 micrograms solution (73.46 +/- 4.51 cm x sec-2) < 12 micrograms suspension (80.87 +/- 5.08 cm x sec-2) < fenoterol (84.13 +/- 4.21 cm x sec-2) < 24 micrograms formoterol suspension 88.54 +/- 6.26 cm x sec-2). Maximum increase in specific airway conductance ranged from 0.48 +/ 0.03 to 0.55 +/- 0.04 sec-1 x kPa-1 for all drugs (p > 0.05). No change in cardiovascular parameters occurred (p > 0.05). CONCLUSION: No difference in the bronchial response to either formulation of formoterol was found. Tremor response to suspension aerosol (24 micrograms > 12 micrograms) was higher than that to solution aerosol (24 micrograms > 12 micrograms), indicating possible differences in systemic absorption because of a different deposition pattern. Rescue medication demonstrated systemic effects on tremor that were additive to those of formoterol.

Adult↗
PubMed1995

A chromogenic assay for activated protein C resistance.

Resistance to activated protein C (APC) diagnosed on the basis of prolongation of clotting time in an activated partial thromboplastin time (aPTT) assay is now considered a major cause of inherited thrombophilia. The majority of patients with APC resistance carry a factor V molecule with a point mutation at one APC cleavage site (Arg506Gln) which prevents the optimal inactivation of activated factor V by APC. To overcome the limitations of aPTT-based assays in the diagnosis of APC resistance, we have developed a chromogenic assay which is based on the capacity of APC to limit the generation of factor Xa by inactivating factor VIIIa in plasma. The ratio of the factor Xa amidolytic activity in a sample without APC to its factor Xa activity with the addition of APC reflects the response of the plasma coagulation system to APC. The normal range in 44 healthy individuals was 1.62-2.06. APC response ratios as measured by the chromogenic assay correlated with ratios measured by the aPTT assay and were below the normal range in 23/24 individuals with Arg506Gln mutant factor V from three different families with familial thrombosis and from 11 unrelated asymptomatic individuals. In reconstitution experiments, purified factor V corrected the decreased APC response in plasma samples from patients with the Arg506Gln mutation as well as with factor V deficiency, and increased the APC response in normal plasma, whereas the addition of activated factor V had no enhancing effect.

Anticoagulants↗
PubMed1995

Correlation of placental isoferritin with birth weight and time point of first contractions.

In a prospective study, the correlation between serum levels of placental isoferritin (PLF) and outcome of pregnancy was determined in 56 pregnant women. Women with contractions before the 36th week of pregnancy showed significantly lower PLF values compared with women with later contractions (p < 0.01). Furthermore, a strong correlation of PLF levels with birth weight was observed. In 11 (79%) cases with a birth weight < 2,500 g (group A), PLF values were < 10 U/ml whereas only 14% (6 of 42) of women with babies with a birth weight > 2,500 g (group B) revealed PLF levels < 10 U/ml. Because it has been shown previously that PLF has immunosuppressive properties, the secretion of PLF by the placenta could be responsible for the inhibition of the immunoreactivity of the maternal lymphocytes against the embryo. The strong correlation of low PLF values with preterm contractions and/or low birth weight recommends the determination of this protein as a marker for monitoring women with high risk pregnancies.

Adolescent↗
PubMed1995

Thyroid hormones rapidly and stringently regulate the messenger RNA levels of the thyrotropin-releasing hormone (TRH) receptor and the TRH-degrading ectoenzyme.

The responsiveness of adenohypophyseal target cells for the hypothalamic neuropeptide TRH is known to change depending on the hormonal and physiological conditions of the organism. We describe here the effects of thyroid hormones on the transcript levels of the TRH receptor, the TRH-degrading ectoenzyme, and TSH in rat pituitary, as revealed by Northern blot analysis. After a single injection of T3 (30 micrograms/100 g BW), the transcript levels of the TRH receptor decreased transiently, reaching 35% of control values 4 h after injection, and returned to basal levels within 24 h. In contrast, the messenger RNA (mRNA) levels of the TRH-degrading ectoenzyme increased more dramatically in response to the same hormonal stimulus. Maximal levels (> 10 times above the control value) were present from 6-24 h after the injection, returning to basal values within 96 h. For both transcripts, the observed effects changed in a dose-dependent manner, but the mRNA levels of the TRH-degrading ectoenzyme were more tightly regulated. Under the experimental conditions used, the mRNA levels of PRL and GH were not affected by the application of T3, and those of alpha-subunit exhibited only minor reductions. The TSH beta transcripts however, decreased rapidly in length and slowly in concentration, finally reaching almost undetectable levels 48 h after the injection. Subsequently, newly synthesized TSH beta mRNA, the same size as the transcripts from euthyroid rats, could be detected 96 h after treatment with T3. Upon treatment of the animals with the mild goitrogenic agent n-propylthiouracil (200 mg/liter drinking water), a fast reduction in the transcript levels of the TRH-degrading ectoenzyme became evident. Within 1 day, mRNA levels decreased to less than 50% of control values. At this stage, no effects were observed on the transcript levels of either the TRH receptor or TSH beta. After 4 days of n-propylthiouracil treatment, the mRNA levels of the enzyme decreased further to 15% of control values, whereas the transcript concentrations of the TRH receptor and TSH beta rose by factors of 2 and 3.3, respectively. The extremely stringent regulation of the TRH-degrading ectoenzyme, a mirror image of that of the TRH receptor, strongly suggests that this enzyme represents an important regulatory element, controlling the stimulation of TRH target cells and, thus, adenohypophyseal hormone secretion.

Aminopeptidases↗
PubMed1995

Starvation-induced changes in the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA and the hypothalamic release of proTRH-derived peptides: role of the adrenal gland.

The purpose of this study was to investigate the mechanisms involved in the reduced thyroid function in starved, young female rats. Food deprivation for 3 days reduced the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA, the amount of proTRH-derived peptides (TRH and proTRH160-169) in the paraventricular nucleus, the release of proTRH-derived peptides into hypophysial portal blood and the pituitary levels of TSH beta mRNA. Plasma TSH was either not affected or slightly reduced by starvation, but food deprivation induced marked increases in plasma corticosterone and decreases in plasma thyroid hormones. Refeeding after starvation normalized these parameters. Since the molar ratio of TRH and proTRH160-169 in hypophysial portal blood was not affected by food deprivation, it seems unlikely that proTRH processing is altered by starvation. The median eminence content of pGlu-His-Pro-Gly (TRH-Gly, a presumed immediate precursor of TRH), proTRH160-169 or TRH were not affected by food deprivation. Since median eminence TRH-Gly levels were very low compared with other proTRH-derived peptides it is unlikely that alpha-amidation is a rate-limiting step in hypothalamic TRH synthesis. Possible negative effects of the increased corticosterone levels during starvation on proTRH and TSH synthesis were studied in adrenalectomized rats which were treated with corticosterone in their drinking water (0.2 mg/ml). In this way, the starvation-induced increase in plasma corticosterone could be prevented. Although plasma levels of thyroid hormones remained reduced, food deprivation no longer had negative effects on hypothalamic proTRH mRNA, pituitary TSH beta mRNA and plasma TSH in starved adrenalectomized rats. Thus, high levels of corticosteroids seem to exert negative effects on the synthesis and release of proTRH and TSH. This conclusion is corroborated by the observation that TRH release into hypophysial portal blood became reduced after administration of the synthetic glucocorticosteroid dexamethasone. On the basis of these results, it is suggested that the reduced thyroid function during starvation is due to a reduced synthesis and release of TRH and TSH. Furthermore, the reduced TRH and TSH synthesis during food deprivation are probably caused by the starvation-induced enhanced adrenal secretion of corticosterone.

Adrenal Glands↗
PubMed1995

[Clinical significance of autologous transplantation with hematopoietic stem cells in leukemia and solid tumors].

Autologous Transplantation of hematopoietic tissue with frozen hematopoietic stem cells is increasingly used for leukemias and lymphomas, but also for some solid tumors. In the past, autotransplants have been performed with bone marrow as the source of hematopoietic stem cells. Circulating, blood derived hematopoietic stem cells, however, allow safe engraftment of all cell lines after supralethal chemo-radiotherapy. This survey describes the role of autologous stem cell transplantation in disorders that are currently in the center of clinical and scientific interest. This estimation is based on the proportion of protocols dealing with, and centering on, autologous stem cell transplantation in the context of treatment for leukemias and solid tumors ("Oncodisc", "PDQ").

Combined Modality Therapy↗
PubMed1994

Transport of beta-alanine and biosynthesis of carnosine by skeletal muscle cells in primary culture.

Uptake of beta-alanine and synthesis of carnosine (beta-alanyl-histidine) could be demonstrated in primary cell cultures derived from embryonic chick pectoral muscle. Concomitant with the morphological changes, cessation of cell division and the induction of creatine kinase, a rapid increase in the rate of beta-alanine uptake and also in the rate of carnosine synthesis could be observed. The uptake of beta-alanine is sodium and chloride dependent and obeys Michaelis-Menten kinetics with Km values of about 40 microM that are essentially identical for myoblasts and myotubes. In contrast, Vmax increases considerably during differentiation. The beta-alanine transport system is highly specific for beta-amino acids and exhibits a substantial anion dependency (Cl- > J- > CSN- > SO(4)2-). Stoichiometric studies suggest that the transport of one beta-alanine molecule involves two sodium ions and one chloride ion. This ratio is not altered by the process of cell differentiation.

Animals↗