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Biomedical subjects

M Baier

Publications and source records attributed to M Baier.

At least 73 records · Page 4Linked to original sources
PubMed1995

Treatment of thyroid carcinoma in dogs by surgical resection alone: 20 cases (1981-1989).

Of 82 dogs with thyroid carcinoma seen between January 1981 and October 1989, 20 had freely movable tumors without evidence of metastasis and were treated with surgical excision alone. Uncensored mean and median survival times for these 20 dogs were both 20.5 months. Kaplan-Meier survival analysis, which censors for nontumor-related deaths and dogs lost to follow-up, indicated that median survival time was greater than 36 months. Seven dogs died of tumor-related causes: 2 died because of metastasis or local recurrence of the tumor, 5 died of treatment-related complications (eg, laryngeal paralysis, hypocalcemia, tracheostomy complications). Eight dogs died of unrelated causes; 1 dog was lost to follow-up at 26 months after surgery; 3 dogs were alive 19, 24, and 26 months after surgery. Cause of death could not be determined in the remaining dog. Long-term survival is possible following surgical removal of mobile thyroid carcinomas in dogs.

Adenocarcinoma↗
PubMed1995

Components of an effective transitional residential program for homeless mentally ill clients.

UNLABELLED: Review of clinical records of 228 former clients of a Transitional Residential PROGRAM for severely, persistently mental ill homeless persons was conducted to examine PROGRAM results for completers and noncompleters. Of the 228 clients, 110 (48.3%) completed the PROGRAM: they became psychiatrically stabilized, found secure housing, and began receiving disability pensions. Completers participated in significantly more activities than noncompleters. Psychiatric diagnosis was unrelated to successful PROGRAM completion. Individuals who left against advice had significantly fewer previous hospitalizations.

Activities of Daily Living↗
PubMed1995

Relationship between ventilatory threshold and onset of ischaemia in ECG during stress testing.

UNLABELLED: The study was carried out to determine the relationship between ventilatory threshold and the onset of ischaemia, as shown on the ECG (horizontal and/or descending ST depression of 0.05 mV, on average). Twenty-seven male patients (aged 58 +/- 7 years) with angiographically documented coronary artery disease (CAD) were assessed by cardiopulmonary exercise testing without medication. Oxygen uptake (VO2), heart rate (HR), rate-pressure-product (RPP) and blood lactate were measured and/or calculated every 30 s during exercise. In addition, 10 patients, comparable with the above group, were examined to find out the acute effects of isosorbide dinitrate (ISDN) at ventilatory threshold in relation to ischaemic threshold. The first cardiopulmonary exercise test was carried out without medication, the second 1 h later with 5 mg ISDN, taken sublingually 30 min before the test. RESULTS: (means, SD): (1) The mean ventilatory threshold preceded the ischaemic threshold in relation to exercise capacity (48 +/- 14 vs 55 +/- 20 watts; P < 0.05), VO2.kg-1 (10.0 +/- 2.2 vs 12.0 +/- 2.9 ml.kg-1.min; P < 0.05), HR (93 +/- 15 vs 100 +/- 16.min-1; P < 0.01), RPP (15095 +/- 4424 vs 17166 +/- 5245; P < 0.01) and blood lactate (1.28 +/- 0.53 vs 1.44 +/- 0.60 mmol.l-1; P < 0.05). (2) This relationship was observed more often in the subgroup of patients with angina during cardiopulmonary exercise testing or with myocardial infarction or with three-vessel disease than in patients without angina or infarction or with one- and two-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Evaluation of a transitional residential programme for homeless chronically mentally ill people.

This paper reports a successful transitional programme in the USA. The research programme evaluation covered 5.5 years and 228 severely and persistently mentally ill homeless clients who lived in a transitional residential centre. Forty-eight per cent of the residents achieved the Programme's goals of obtaining and maintaining permanent housing and a disability pension or a job. Achievement of client goals was positively related to length of stay of 3 months or more, to five or more previous psychiatric hospitalizations, and to participation in two or more ongoing activities whilst in the programme. Psychiatric diagnosis was not directly related to goal attainment in this programme.

Adult↗
PubMed1994

Cardiopulmonary exercise capacity in healthy normals of different age.

Sixty-nine healthy normals from the 3rd to the 6th decade were stressed to exhaustion by means of a cardiopulmonary exercise test on a bicycle ergometer. Peak VO2, VCO2 and ventilation differed significantly between the four decades: peak VO2 (mean +/- SD) was 3,393 +/- 516; 3,061 +/- 444; 2,817 +/- 801 and 2,589 +/- 687 ml/min (p < 0.001). The mean value for respiratory gas exchange ratio (R) at ventilatory threshold (VT) was 0.86 and for ventilatory equivalent O2 (EqO2) 0.24. Mean VO2 at VT was 1,662 +/- 521; 1,462 +/- 308; 1,474 +/- 559 and 1,268 +/- 232 ml/min (p < 0.05). The VO2 of the four age groups at VT was between 47 and 49% of peak VO2 (n.s.), and both parameters correlated significantly (r = 0.67, p < 0.001). The average increase of VO2 in relation to work rate (ml/W/min) was 11.5 +/- 1.2 for the total exercise and was below VT lower (9.4 +/- 1.9) than above VT (12.9 +/- 1.2) (p < 0.001).

Adult↗
PubMed1994

Mast cell growth factor (c-kit ligand) restores growth of multipotent progenitors in myelodysplastic syndrome.

In vitro growth of primitive hematopoietic progenitors is severely impaired in the myelodysplastic syndromes (MDS). To determine if the c-kit ligand mast cell growth factor (MGF) can improve progenitor growth in MDS, we evaluated in vitro responsiveness of bone marrow progenitors from 25 patients to MGF and/or GM-CSF, interleukin-3 (IL-3) and PIXY 321, and examined the relationship between progenitor response and cellular expression of the c-kit receptor. MGF and erythropoietin gave rise to macroscopic colonies and dose-dependently increased CFU-GEMM and BFU-E up to 27-fold in 15 (60%) and 20 (80%) patients, respectively. Among 17 patients with absent growth in lymphocyte-conditioned media, MGF stimulated CFU-GEMM recovery in 59%, compared to 23% with PIXY 321, 12% with IL-3 and 8% with GM-CSF. Cytokine combinations did not augment recovery of erythropoietin-dependent progenitors above that achieved with MGF alone. MGF and/or IL-3 were comparatively weak stimulants of CFU-GM formation, whereas GM-CSF and PIXY in combination with MGF increased colony number 2- to 15-fold in 60 and 70% of patients, respectively, while preserving maturation competence as evidenced by colony composition and increased colony/cluster ratio. The stimulatory effects of MGF were observed in all morphologic categories of MDS except chronic myelomonocytic leukemia. A mononuclear cell population expressing the c-kit receptor was identified by flow cytometry in 57% of cases. Neither SR-1 reactivity nor cytogenetic pattern predicted progenitor response to MGF. These data indicate that MGF improves the colony-forming capacity of hematopoietic progenitors in MDS and is a potent co-stimulant of multipotent and committed progenitor recovery. The heterogeneity in MGF responsiveness implies an intrinsic defect in growth regulation not explained by cellular loss of c-kit display.

Adolescent↗
PubMed1993

The contribution of contact and non-contact residues of antibody in the affinity of binding to antigen. The interaction of mutant D1.3 antibodies with lysozyme.

We have analysed the contribution of residues of the D1.3 Fv fragment to binding of hen egg lysozyme. We altered residues at the contact interface by site-directed mutagenesis, and determined the affinity of the mutant Fv fragments for lysozyme by fluorescence quench titration. We found that a band of residues at the centre of the contact interface were much more important for binding affinity than those at the periphery. We also subjected the seFv fragment to random mutagenesis to simulate somatic mutation and affinity maturation. By display of the mutants on the surface of filamentous phages, and selection of the phages with biotinylated lysozyme, we were able to select mutants with modest improvements in binding affinity to lysozyme. By combining the mutations we obtained a scFv fragment with a fivefold improved affinity (Kd approximately 0.6 nM compared to wild-type Kd = 3.3 nM). However, none of the altered residues leading to improved affinity was located in the contact interface. This indicates that the interactions of a few residues at the centre of the contact interface are responsible for the binding affinity to antigen, but that these interactions can be modulated by alterations of residues outside the binding site. This may represent a typical mechanism for the affinity maturation of antibodies.

Animals↗
PubMed1993

Radiation therapy salvage of Hodgkin's disease following chemotherapy failure.

PURPOSE: This study evaluates the efficacy of comprehensive salvage radiation therapy, with or without chemotherapy, in selected patients with Hodgkin's disease who have failed primary combination chemotherapy. METHODS AND MATERIALS: Between 1972 and 1991, 28 patients with advanced Hodgkin's disease failing intensive combination chemotherapy in previously unirradiated nodal and/or pulmonary sites were treated with salvage radiotherapy with curative intent. Treatment consisted of comprehensive extended field radiotherapy to all known areas of disease. Total radiation doses ranged from 17.0 to 50.0 Gy, with only five patients (18%) receiving < 30.0 Gy to any field. Twelve patients also received chemotherapy as part of their salvage regimen. RESULTS: Twenty-six patients (93%) achieved a complete response and 14 (50%) remain in continuous complete remission at 14 to 133 months. In addition, three patients (11%) who failed salvage radiotherapy are now without evidence of disease following additional therapy. With a median follow-up of 47 months (range 14+ to 198+), actuarial median relapse-free survival and overall survival are 46 and 97 months, respectively. Actuarial 5-year relapse-free survival and overall survival are 40% and 63%, respectively. Patients with an initial complete response to chemotherapy had a significantly longer actuarial relapse-free survival than those with an initial partial response (p = 0.02). Salvage therapy was generally well-tolerated and resulted in no treatment-related deaths. CONCLUSION: Comprehensive salvage radiotherapy is of significant benefit in selected patients and should be considered an option for patients with advanced Hodgkin's disease following chemotherapy failure.

Adolescent↗
PubMed1993

Human anti-self antibodies with high specificity from phage display libraries.

Recently we demonstrated that human antibody fragments with binding activities against foreign antigens can be isolated from repertoires of rearranged V-genes derived from the mRNA of peripheral blood lymphocytes (PBLs) from unimmunized humans. The heavy and light chain V-genes were shuffled at random and cloned for display as single-chain Fv (scFv) fragments on the surface of filamentous phage, and the fragments selected by binding of the phage to antigen. Here we show that from the same phage library we can make scFv fragments encoded by both unmutated and mutated V-genes, with high specificities of binding to human self-antigens. Several of the affinity purified scFv fragments were shown to be a mixture of monomers and dimers in solution by FPLC gel filtration and the binding kinetics of the dimers were determined using surface plasmon resonance (k(on) = 10(5)-10(6) M-1s-1, k(off) = 10(-2)s-1 and Ka = 10(7) M-1). The kinetics of association are typical of known Ab-protein interactions, but the kinetics of dissociation are relatively fast. For therapeutic application, the binding affinities of such antibodies could be improved in vitro by mutation and selection for slower dissociation kinetics.

Amino Acid Sequence↗
PubMed1993

Phase I clinical and pharmacokinetic evaluation of high-dose mitoxantrone in combination with cytarabine in patients with acute leukemia.

PURPOSE: To determine the maximally tolerated dose of mitoxantrone in combination with cytarabine in patients with acute leukemia and advanced phases of chronic myelogenous leukemia (CML), and to assess the pharmacokinetics of high-dose mitoxantrone in this patient population. PATIENTS AND METHODS: In a phase I study, 68 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and accelerated- and blastic-phase CML received induction therapy consisting of cytarabine 3 g/m2 by infusion over 3 hours daily for 5 days, with escalating doses of mitoxantrone 40 to 80 mg/m2 over 1 to 2 days by intravenous infusion over 15 minutes. Mitoxantrone pharmacokinetics were evaluated by high-performance liquid chromatography (HPLC) in 15 patients given a single dose of mitoxantrone ranging from 40 to 80 mg/m2 in combination with cytarabine. RESULTS: Severe, but reversible hyperbilirubinemia (> three times normal) was considered the dose-limiting toxicity, and was observed in 25% of all patients and in 35% of those who received 70 to 80 mg/m2 of mitoxantrone. Other extramedullary toxicity, including cardiac dysfunction, was mild. Myelosuppression was universal and the median time to complete remission (CR) was 28 days (range, 19 to 77). The CR rate for previously untreated and relapsed patients with AML was 85% (17 of 20) and 38% (seven of 18), respectively. Eighty-three percent (15 of 18) of patients with ALL achieved a CR, including all patients with previously untreated disease. Eight of 12 patients with advanced-phase CML achieved a CR. No significant changes in mean mitoxantrone plasma elimination rates (ie, terminal plasma half-life and total-body clearance rate) occurred as the mitoxantrone dose doubled, indicating linear pharmacokinetics. CONCLUSIONS: The recommended phase II dose of mitoxantrone is 80 mg/m2 administered over 15 minutes as a single intravenous infusion in combination with cytarabine 3 g/m2/d for 5 days. At this dose, high concentrations of mitoxantrone are achievable in vivo to levels that have been shown to be extremely cytotoxic in vitro.

Adolescent↗
PubMed1993

Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia.

PURPOSE: To determine the toxicities and maximum-tolerated dose of cyclosporine (CsA) administered with daunorubicin as a modulator of multidrug resistance (MDR) in acute leukemia, and to evaluate response to treatment and its relationship to mdr1 gene expression. PATIENTS AND METHODS: Patients with poor-risk acute myeloid leukemia (AML) received sequential treatment with cytarabine (3 g/m2/d intravenously [i.v.]) days 1 to 5, and daunorubicin (45 mg/m2/d) plus CsA as a 72-hour continuous infusion (CI) days 6 through 8 in a phase I/II trial. A loading dose of CsA administered over 1 to 2 hours preceded the CI. CsA dose escalations ranged from 1.4 to 6 mg/kg (load) and 1.5 to 20 mg/kg/d (CI). Whole-blood concentrations of CsA were monitored by immunoassay; plasma concentration of daunorubicin and daunorubicinol were determined by high-pressure liquid chromatography (HPLC). Specimens were analyzed for P-glycoprotein expression, and results confirmed by a quantitative RNA polymerase chain reaction (PCR) assay for the mdr1 gene transcript. RESULTS: Forty-two patients are assessable for toxicity and response. P-glycoprotein was detected in 70% of cases. Dose-dependent CsA toxicities included nausea and vomiting (22%), hypomagnesemia (61%), burning dysesthesias (21%), and prolongation of myelosuppression. Transient hyperbilirubinemia developed in 62% of treatment courses and was CsA-dose-dependent. Reversible azotemia occurred in three patients receiving concurrent treatment with potentially nephrotoxic antibiotics. Steady-state blood concentrations of CsA > or = 1,500 ng/mL were achieved in all patients receiving CI doses > or = 16 mg/kg/d. Mean plasma daunorubicin, but not daunorubicinol, levels were significantly elevated in patients who developed hyperbilirubinemia (P = .017). Twenty-six (62%) patients achieved a complete remission (CR) or restored chronic phase and three patients achieved a partial remission (PR) for an overall response rate of 69% (95% confidence interval, 54% to 84%). The response rate was higher in patients who developed hyperbilirubinemia (P = .001), whereas MDR phenotype did not influence response to treatment. Among five patients with MDR-positive leukemia, cellular mdr1 mRNA decreased (n = 1) or was absent from relapsed specimens (n = 4), while mdr1 RNA remained undetectable at relapse in two patients who were MDR-negative before treatment. CONCLUSION: High doses of CsA, which achieve blood concentrations capable of reversing P-glycoprotein-mediated anthracycline resistance in vitro, can be incorporated into induction regimens with acceptable nonhematologic toxicity. Transient hyperbilirubinemia occurs commonly with CsA administration and may alter daunorubicin pharmacokinetics. Recommended doses of CsA for phase II and III trials are a load of 6 mg/kg and CI of 16 mg/kg/d.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Use of therapeutic milieu in a community setting.

1. Many of the same components that contribute to the success of milieu therapy in inpatient facilities also promote treatment success for clients living in the community. 2. Treatment goals at the Rosati Center, a transitional residential program for chronically mentally ill homeless persons in St. Louis, generally include supporting residents as they secure their own permanent housing; helping residents apply for entitlements so that they can support themselves upon discharge; connecting residents with outpatient psychiatric treatment; and assisting residents to structure their time and activities as a means to improving coping skills. 3. Program evaluations of the transitional living program at the Rosati Center revealed that implementation of therapeutic milieu concepts (in combination with case management concepts) can be successful. The facility served 228 persons during a 5 1/2-year period. Nearly half of those persons were discharged having fully met the objectives of the transitional program.

Adult↗
PubMed1992

An analysis of the concept of homesickness.

This report analyzes the concept of homesickness, using the pattern for concept analysis presented by Chinn and Jacobs. Concept analysis is a process used to better understand a concept that has been first identified through clinical practice. This concept analysis clarifies and defines the concept of homesickness, and distinguishes homesickness from other concepts, including separation anxiety, school phobia, translocation syndrome, and relocation effects. By carefully defining what homesickness is and what it is not, criteria have emerged so that other instances of similar characteristics can be appropriately labeled. In addition, arising from the literature review and criteria are research questions and nursing interventions.

Adaptation, Psychological↗
PubMed1992

CEDIA--homogeneous immunoassays for the 1990s and beyond.

New homogeneous enzyme immunoassays have been developed for cortisol, digoxin, digitoxin, theophylline, phenytoin, and phenobarbital using the cloned enzyme donor immunoassay technology. As applied to Boehringer Mannheim/Hitachi analysis systems these methods provide rapid, accurate and precise quantification of analytes, with minimal interferences from endogenous serum constituents and low cross-reactivities to structurally-related hormonal precursors, drug metabolites and natural compounds. Additional significant features of the new assays are linear standard curves and two-point calibration. The six CEDIA assays join the two currently available CEDIA assays for determination of the thyroid parameters T4 and T Uptake. Additional new therapeutic drug and anemia monitoring assays are under development, demonstrating the versatility of the cloned enzyme donor immunoassay technology. These tests, in concert with Boehringer Mannheim/Hitachi analyzers, provide a high throughput, random access immunoassay system. The menu of available assays should continue to increase during the 1990s, providing efficient automation while allowing consolidation of testing on a limited number of instrument systems.

Digitoxin↗
PubMed1991

Development of vivo of genetic variability of simian immunodeficiency virus.

Rapid development of genetic variability may contribute to the pathogenicity of lentiviruses as it may allow escape from immune surveillance and/or from suppression of virus replication. Although apathogenic in African green monkeys, simian immunodeficiency virus isolated from African green monkeys is shown to display extensive genetic variability and defectiveness in the V1- and V2-like variable domains of the external envelope protein comparable to that known for human immunodeficiency virus. However, in contrast to the situation in human immunodeficiency virus-infected individuals, a predominant major virus variant was detected neither in a monkey naturally infected for more than 10 years nor in two monkeys infected with a molecular virus clone for 15-20 months. Extensive variability evolves from a single genotype with a maximal rate of 7.7 mutations per 1000 nucleotides per year. A remarkable selection for nonsynonymous mutations that accounts for 92% of all changes indicates continuous selection of variants.

Amino Acid Sequence↗
PubMed1991

Fidelity of reverse transcriptase of the simian immunodeficiency virus from African green monkey.

The in vitro fidelity of highly purified recombinant reverse transcriptase from simian immunodeficiency virus of African green monkeys (SIVagm) was determined. By using the phi X174am16 reversion assay an overall error rate of 1/19,000 was determined. This is 2.4-fold higher than the overall accuracy of purified recombinant HIV-1 reverse transcriptase, measured in parallel. The evaluation of error frequencies from nucleotide pool bias studies suggest an even higher accuracy for the SIVagm-derived reverse transcriptase. T:dGMP mismatches were formed most frequently with an error rate of 1/155,000, followed by G:dGMP (1/230,000), A:dGMP (1/315,000), G:dAMP (1/340,000), T:dCMP (1/540,000), T:dTMP (1/790,000), and A:dCMP (1/1,050,000) mispairs. Thus, according to pool bias effects and depending on the mismatch under consideration SIVagm reverse transcriptase appears to be 2 to 20-fold more accurate than the homologous enzyme from the human immunodeficiency virus type 1. This higher accuracy is not due to a co-purifying exonuclaease activity. Like the enzyme from HIV-1, the simian monkey-derived enzyme was found to be devoid of a proofreading 3' to 5' exonuclease.

Animals↗
PubMed1991

Target weight procedure: preventing water intoxication.

1. Prevention of water intoxication depends on early intervention for polydipsic patients who seem to be retaining fluid. The Target Weight Procedure is designed to detect early signs of fluid retention by means of weight gain and low sodium levels. 2. The use of this protocol, in addition to successfully decreasing the number of acute water intoxication episodes, has also led to increased awareness of the meaning of patient behavior, an increased sense of control of patients with water intoxication over their behavior, and an increased feeling of competence among the staff. 3. The success of the protocol seems to be based on its purpose of identifying patients at risk and those with an impending episode, as well as secondary advantages, for example, giving the patients the option to alter their behavior to be removed from the protocol.

Drinking↗