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Biomedical subjects

G Gross

Publications and source records attributed to G Gross.

At least 19 recordsLinked to original sources
PubMed1999

Inhaled salmeterol and fluticasone: a study comparing monotherapy and combination therapy in asthma.

BACKGROUND: The current stepwise approach to pharmacotherapy in the treatment of asthma includes the initiation of an inhaled corticosteroid with the addition of a long-acting inhaled bronchodilator if low dose inhaled corticosteroid fails to control asthma symptoms. OBJECTIVE: To determine whether initiation of salmeterol and fluticasone propionate treatment together improves asthma control greater than initiation of monotherapy with the individual agents alone with no additional safety risk in patients with asthma who had not previously been treated with inhaled corticosteroids. METHODS: A total of 136 male and female patients at least 12 years of age with asthma [forced expiratory volume in 1 second (FEV) between 50% and 80% of predicted] were randomized to twice daily salmeterol 42 microg, fluticasone propionate 88 microg, fluticasone propionate 220 microg, salmeterol 42 microg plus fluticasone propionate 88 microg, salmeterol 42 microg plus fluticasone propionate 220 microg, or placebo for 4 weeks. RESULTS: Patients treated with salmeterol combined with fluticasone propionate had improvements over baseline in FEV at endpoint that were at least twice as great (0.6 to 0.7 L) as improvements in patients treated with salmeterol (0.3 L) or fluticasone propionate alone (0.3 L) (P < .05). Patient-rated data (peak expiratory flow, asthma symptom scores, percent of days with no asthma symptoms) confirmed greater (P < .05) mean change from baseline improvements after combined treatment compared with fluticasone propionate alone. No clinically significant differences were noted between treatment groups in any safety measurement. CONCLUSION: Initiation of maintenance therapy with salmeterol and fluticasone propionate in patients with asthma treated with short-acting beta2-agonists alone provides greater improvements in pulmonary function and symptom control than initiation of maintenance therapy with fluticasone propionate alone.

Adolescent↗
PubMed1999

Diskus and diskhaler: efficacy and safety of fluticasone propionate via two dry powder inhalers in subjects with mild-to-moderate persistent asthma.

BACKGROUND: Fluticasone propionate is a topically active glucocorticoid with potent antiinflammatory activity in the treatment of asthma. OBJECTIVE: This study evaluated the safety and efficacy of fluticasone propionate administered via the Diskus and Diskhaler powder delivery devices in subjects with mild-to-moderate asthma. METHODS: Fluticasone propionate (500 microg twice daily) or placebo was administered via the Diskus and Diskhaler to 213 adolescent and adult asthma subjects in a randomized, double-blind, double-dummy, parallel-group study for 12 weeks. Subjects were stratified according to baseline therapy of inhaled corticosteroids or beta2-agonists alone. Subjects were dropped from the study if they met predefined criteria for lack of efficacy. RESULTS: Fluticasone propionate improved pulmonary function both in subjects previously treated with inhaled corticosteroids or beta2-agonists alone. At endpoint, fluticasone propionate significantly improved forced expiratory volume in 1 second (P < .001), morning and evening peak expiratory flow (P < .001), and asthma symptom scores (P < or = .016), and significantly reduced nighttime awakenings (P = .016; Diskhaler group only) and rescue albuterol use (P < .001). Overall, efficacy measurements for the Diskus and Diskhaler were similar. More placebo-treated subjects (34%) withdrew from the study due to lack of efficacy than subjects in the Diskus (5%) or Diskhaler (5%) groups. The incidence and severity of adverse events were similar across groups. Measurement of plasma fluticasone propionate and cortisol concentrations showed no apparent influence of device on systemic exposure. CONCLUSION: Fluticasone propionate powder, administered via the Diskus or Diskhaler inhalation devices, was well tolerated and effective in the treatment of mild-to-moderate persistent asthma.

Administration, Inhalation↗
PubMed1999

A new pyrrolyl-quinoxalinedione series of non-NMDA glutamate receptor antagonists: pharmacological characterization and comparison with NBQX and valproate in the kindling model of epilepsy.

Antagonists at the ionotropic non-NMDA [AMPA (amino-methyl proprionic acid)/kainate] type of glutamate receptors have been suggested to possess several advantages compared to NMDA (N-methyl-D-aspartate) receptor antagonists, particularly in terms of risk/benefit ratio, but the non-NMDA receptor antagonists available so far have not fulfilled this promise. From a large series of pyrrolyl-quinoxalinedione derivatives, we selected six new competitive non-NMDA receptor antagonists. The basis of selection was high potency and selectivity for AMPA and/or kainate receptors, high in vivo potency after systemic administration, and an acceptable ratio between neuroprotective or anticonvulsant effects and adverse effects. Pharmacological characteristics of these novel compounds are described in this study with special emphasis on their effects in the kindling model of temporal lobe epilepsy, the most common type of epilepsy in humans. In most experiments, NBQX and the major antiepileptic drug valproate were used for comparison with the novel compounds. The novel non-NMDA receptor antagonists markedly differed in their AMPA and kainate receptor affinities from NBQX. Thus, while NBQX essentially did not bind to kainate receptors at relevant concentrations, several of the novel compounds exhibited affinity to rat brain kainate receptors or recombinant kainate receptor subtypes in addition to AMPA receptors. One compound, LU 97175, bound to native high affinity kainate receptors and rat GluR5-GluR7 subunits, i.e. low affinity kainate binding sites, with much higher affinities than to AMPA receptors. All compounds potently blocked AMPA-induced cell death in vitro and, except LU 97175, AMPA-induced convulsions in vivo. In the kindling model, compounds with a high affinity for GluR7 (LU 97175) or compounds (LU 115455, LU 136541) which potently bind to AMPA receptors and low affinity kainate receptor subunits were potent anticonvulsants in the kindling model, whereas the AMPA receptor-selective LU 112313 was the least selective compound in this model, indicating that non-NMDA antagonists acting at both AMPA and kainate receptors are more effective in this model than AMPA receptor-selective drugs. Three of the novel compounds, i.e. LU 97175, LU 115455 and LU 136541, exerted potent anticonvulsant effects without inducing motor impairment in the rotarod test. This combination of actions is thought to be a prerequisite for selective anticonvulsant drug action.

Amygdala↗
PubMed1999

Hydrofluoroalkane-134a beclomethasone dipropionate, 400 microg, is as effective as chlorofluorocarbon beclomethasone dipropionate, 800 microg, for the treatment of moderate asthma.

OBJECTIVE: The improved lung deposition of hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extrafine aerosol compared with chlorofluorocarbon beclomethasone dipropionate (CFC-BDP) suggests that lower doses of HFA-BDP may be required to provide equivalent asthma control. The present study was undertaken to test this hypothesis. DESIGN: A 10- to 12-day run-in period confirmed that patients met established criteria of at least moderate asthma and the asthma was inadequately controlled by current therapy (inhaled beta-agonist and CFC-BDP [< or = 400 microg/d]). A short course of oral prednisone, 30 mg/d for 7 to 12 days, was followed to establish the patients were steroid responsive and to provide an "in-study" baseline of "optimal" asthma control. PATIENTS: A total of 347 patients were then randomized to HFA-BDP 400 microg/d, CFC-BDP 800 microg/d, or HFA-placebo for 12 weeks. RESULTS: Morning peak expiratory flow (AM PEF) measurements showed that HFA-BDP 400 microg/d achieved equivalent control of asthma to CFC-BDP 800 microg/d at all time intervals after oral steroid treatment. All other efficacy variables supported the AM PEF results and both active treatments were more effective than placebo. The safety profile of HFA-BDP compared favorably with that of CFC-BDP with no unexpected adverse events reported. CONCLUSIONS: These findings demonstrate that HFA-BDP provides equivalent control of moderate or moderately severe asthma as CFC-BDP in the population studied, but at half the total daily dose.

Adult↗
PubMed1999

Inhibition of monoamine oxidase type A, but not type B, is an effective means of inducing anticonvulsant activity in the kindling model of epilepsy.

The anticonvulsant activity of inhibitors of monoamine oxidase (MAO) was reported early after the development of irreversible MAO inhibitors such as tranylcypromine, but was never clinically used because of the adverse effects of these compounds. The more recently developed reversible MAO inhibitors with selectivity for either the MAO-A or MAO-B isoenzyme forms have not been studied extensively in animal models of epilepsy, so it is not known which type of MAO inhibitor is particularly effective in this respect. We compared the following drugs in the kindling model of epilepsy: 1) L-deprenyl (selegiline), i.e., an irreversible inhibitor of MAO-B, which, however, also inhibits MAO-A at higher doses, 2) the novel reversible MAO-B inhibitor LU 53439 (3,4-dimethyl-7-(2-isopropyl-1,3, 4-thiadiazol-5-yl)-methoxy-coumarin), which is much more selective for MAO-B than L-deprenyl, 3) the novel reversible and highly selective MAO-A inhibitor LU 43839 (esuprone; 7-hydroxy-3, 4-dimethylcoumarin ethanesulfonate), and 4) the irreversible nonselective MAO inhibitor tranylcypromine. Esuprone proved to be an effective anticonvulsant in the kindling model with a similar potency as L-deprenyl. In contrast to esuprone and L-deprenyl, the selective MAO-B inhibitor LU 53439 was not effective in the kindling model; this substantiates the previous notion that the anticonvulsant activity of L-deprenyl is not related to MAO-B inhibition, but to other effects of this drug, such as inhibition of MAO-A. Drugs inhibiting both MAO-A and MAO-B to a similar extent (tranylcypromine) or combinations of selective MAO-A and MAO-B inhibitors (esuprone plus LU 53439) had no advantage over MAO-A inhibition alone, but were less well tolerated. The data thus suggest that selective MAO-A inhibitors such as esuprone may be an interesting new approach for the treatment of epilepsy.

Animals↗
PubMed1998

Bmp-2 downstream targets in mesenchymal development identified by subtractive cloning from recombinant mesenchymal progenitors (C3H10T1/2).

ABmp-dependent in vitro model was used to identify cDNAs during the manifestation of mesenchymal lineages. This model involves the recombinant expression of Bmps (Bmp-2, Bmp-4-7) in murine mesenchymal C3H10T1/2 progenitors, which leads to the differentiation into three lineages: the osteogenic, the chondrogenic and the adipogenic lineage, albeit in varying efficiencies. By subtractive cloning, 21 Bmp-2-regulated cDNAs from C3H10T1/2 mesenchymal progenitors were identified; 20 were related to known sequences and 1 was not. During mouse embryonic development, many of these cDNAs are expressed in chondrogenic, osteogenic, and in adipogenic tissues. Novel findings include a G0/G1 switch gene (G0S2), which was demonstrated to be predominantly expressed in adipose tissue during late murine embryonic development. Furthermore, the membrane-standing glycoprotein autotaxin (ATX) is expressed, at precartilage condensations, joint regions, and during tooth development. An as yet undescribed cDNA, 29A, which encodes a putative secreted factor, is expressed in developing osteo-/chondrogenic tissues of vertebrae, ribs, tooth, and the limb bud. C3H10T1/2-progenitors, therefore, may serve as a legitimate model for the investigation of the Bmp-mediated events during mesenchymal differentiation.

Amino Acid Sequence↗
PubMed1998

Perceptions of bed rest by anorexic patients.

OBJECTIVE: Few studies have investigated perceptions of operant conditioning programs by anorexic patients. This study examined patients' perceptions of the Bed Rest (BR) component which is employed in some operant conditioning programs. METHODS: A sample of 48 anorexic inpatients was administered a survey to elicit their attitudes towards BR. RESULTS: Results from the survey suggested that most patients perceived BR in a negative way. The main complaint, however, was not punishment or humiliation, as predicted, but isolation and boredom. A number of patients concluded that they wanted more individualization and distraction and less restriction while on BR. DISCUSSION: The findings justify the use of BR within a humane framework in the inpatient treatment of anorexia nervosa, but suggest that patients' perceptions of BR warrant systematic scrutiny.

Adolescent↗
PubMed1998

[Epidemiology of sexually transmitted diseases in the catchment area of the Rostock University Dermatology Clinic after 1945].

The decline of STD in the region of Rostock, Germany, since 1945 is explained by a decreasing incidence of gonorrhoea and trichomoniasis. On the other hand chlamydial and candidal infections have increased. The rate of chlamydia infections was about 45% in our venerological patients, as common as gonorrhea used to be. Genital candidal infections were to be found in 23%. Mycoplasmas were identified in 15%, usually combined with other pathogens except in some cases of vaginitis.

Catchment Area, Health↗
PubMed1998

Moderate zinc and vitamin A deficiency in breast milk of mothers from East-Jakarta.

OBJECTIVE: To gain information about the micronutrient status of urban, middle-income, breast-feeding mothers in relation to zinc and selected fat-soluble vitamins in plasma and breast milk and to assess possible interaction between the measured micronutrients. DESIGN: Cross-sectional study. SUBJECTS: 91 mothers and their infants living in middle-income areas of Jakarta, Indonesia. RESULTS: None of the measured anthropometric data of the mothers (e.g. BMI: 22.0+/-3.1 kg/m2) and their infants (birth weight: 3.2+/-0.5 kg) gave any indication of undernutrition. The mean concentrations in blood were 124+/-18 g/l for hemoglobin, 385+/-111 microg/l for retinol, 34+/-23 microg/l for alpha-carotene, 104+/-72 microg/l for beta-carotene, 7.7+/-3.3 mg/l for alpha-tocopherol, 0.57+/-0.23 mg/l for gamma-tocopherol, 855+/-242 microg/l for zinc, and the median concentration of lycopene was 29 microg/l. The median breast milk concentrations were 420 microg/l for retinol, 7.8 microg/l for beta-carotene, and 2.7 mg/l for zinc. With increased duration of lactation, vitamin A and zinc concentrations significantly decreased in breast milk whereas plasma zinc concentration increased. Plasma alpha- and beta-carotene were positively correlated (P < 0.0001) with each other and with plasma lycopene. Breast milk beta-carotene was positively correlated with breast milk retinol and with plasma beta-carotene (P < 0.0001). There was no correlation between zinc and vitamin A in either breast milk or plasma. Forty per cent of the mothers were anemic, 29.1% had a low plasma zinc concentration, and 23.7% had a moderately low plasma vitamin A concentration. Breast milk from 70% of the women had a low concentration of vitamin A and that from 66% had a low concentration of zinc. CONCLUSIONS: Multi-micronutrient intervention should be considered to provide a sufficient supply of zinc and vitamin A for growth of exclusively breast-fed infants.

Adult↗
PubMed1998

Prevalence of antibodies against virus-like particles of Epidermodysplasia verruciformis-associated HPV8 in patients at risk of skin cancer.

There is increasing evidence for widespread occurrences of infection with Epidermodysplasia verruciformis-related human papillomaviruses, both in the general population and in immunosuppressed patients. In order to test for the prevalence of antibodies directed against the native L1 epitopes exposed on the surface of the virions, we have established an IgG-specific enzyme-linked immunosorbent assay with L1 virus-like particles of the Epidermodysplasia verruciformis-specific human papillomavirus 8 as antigen to screen 567 representative serum samples from the general population and immunosuppressed/dermatologic patients. Among healthy European donors (n = 210), 7.6% were found to be seropositive. In a group of renal transplant recipients (n = 185) the antibody prevalence was elevated to 21.1%, irrespective of the presence or absence of skin cancer. High positivity rates could be detected among (i) immunocompetent patients with nonmelanoma skin tumors (45.6%, n = 79) and (ii) Psoralene/UVA treated psoriasis patients (42.9%, n = 42). In contrast, anti-human papillomavirus 8-virus-like particle antibodies were found in only 6.8% of Hodgkin lymphoma patients (n = 44).

Antibodies, Viral↗
PubMed1998

Recombinant interferon beta gel as an adjuvant in the treatment of recurrent genital warts: results of a placebo-controlled double-blind study in 120 patients.

BACKGROUND: Pilot studies of adjuvant therapy with topically applied interferons (IFN) have shown promising results in reducing the recurrence of condylomata acuminata (CA). OBJECTIVE: The aim of this multicenter placebo-controlled, double-blind study was to confirm the efficacy and safety of topically applied IFN in a large sample of patients. METHODS: After removal of CA by CO2 laser surgery, electrocautery or cryosurgery, 120 patients applied either recombinant IFN-beta (0.15 or 1.0 x 10(6) IU/g) or placebo gel to the affected areas 5 times daily for 4 weeks. The patients were followed for a total of 24 weeks or until recurrence of CA was observed, respectively. RESULTS: In the 105 patients evaluated for efficacy after 24 weeks, recurrence rates were 75% (27/36 patients) in the placebo group, 62% (21/34) in the 1.0 x 10(6) IU/g group (n.s.) and 54% (19/35) in the 0.15 x 10(6) IU/g group (p = 0.034). Only few mild adverse events were noted, which were almost limited to the application site. CONCLUSION: Topical application of gel containing 0.15 x 10(6) IU/g recombinant IFN-beta is safe and appears to reduce the recurrence of CA after surgical treatment.

Administration, Cutaneous↗
PubMed1998

[Dispersion modelling or organic particles from animal stalls and other comparable installations].

Different numerical models have been used to study air flow and dispersion in the surrounding of stables. The results show a strong dependency on the configuration of the direct neighborhood (other buildings, trees) and on the meteorological conditions (windspeed, thermal stratification). The findings demonstrate the inability of simple models like the Gaussian model in complex situations.

Air Pollutants, Occupational↗
PubMed1997

The onset of schizophrenia.

This survey deals with findings and results of systematic clinical-psychiatric and -psychological studies of the true onset of schizophrenia and its significance. Many symptoms precede the psychotic onset of schizophrenia. These have been described by Huber as 'basic symptoms', who developed the concept of basic stages and basic symptoms gradually since the 1950's. The basic symptoms are experiential and not behavioral in kind and only recognizable by the self-reports of the patients. They are rateable using a structural scale (Bonn Schedule for the Assessment of Basic Symptoms: BSABS) described below. They form the two precursor syndromes: (1) prodromes lead on average within 3.3 years to a psychotic episode; and (2) outpost syndromes that are completely remitting on average within 5 months and precede the first psychotic episode on average 10 years. Basic symptoms can be further divided into level 1 (non-specific) and level 2 (characteristic) basic symptoms. Basic symptoms, positive and negative symptoms have to be differentiated; they also develop in this chronological sequence: first non-specific, then characteristic basic symptoms, followed on average many years later by positive symptoms, and, finally by negative symptoms. Structured ratings of the basic symptoms and their recognition in the precursor syndromes enables physicians to detect early symptoms of a schizophrenic illness that, if treated at this stage, can lead to a better long-term outcome.

Behavioral Symptoms↗
PubMed1997

cDNA and deduced polypeptide sequence of a mouse selenoprotein P.

An 11-day embryonic Swiss Webster/NIH mouse cDNA library was screened with a partial murine selenoprotein P cDNA probe and a murine selenoprotein-P-type cDNA clone of 2075 bp length was obtained. The clone contained a 5'-leader sequence of 132 bp length, the selenoprotein P coding frame, and 803 base pairs in the 3' untranslated region. Alignment and RNA folding studies revealed the presence of two well conserved selenocysteine inserting motifs in the 3' flanking region. The deduced polypeptide sequence comprises 380 residues including ten selenocysteines. Identical amino acid residues in homologous positions are 86%, 71%, and 64% when compared to the previously reported selenoprotein P sequences of rat, man, and cattle, respectively. The comparatively low similarity between the selenoprotein P sequences reported so far leaves open the question whether they belong to the same molecular clade.

Amino Acid Sequence↗
PubMed1997

[Are self-perceivable neuropsychological deficits in patients with neuroses or personality disorder diagnoses indicative of later schizophrenia?].

For the first time, the present study assessed the achievable predictive value of early self-experienced neuropsychological deficits for the fater development of schizophrenia. Ninety-six patients with DSM-III-R diagnoses mainly of the formerly neurotic or personality disordered field, of whom 81% had shown such basic disorders at the time of the index examination and therefore were classified as persons at high risk of developing schizophrenia, were re-examined for schizophrenia. After an average follow-up period of about 8 years, more than half of the re-examined sample had developed a schizophrenic disorder according to DSM-III-R. The outcome of schizophrenia versus no schizophrenia was predicted correctly in 77% of cases by the presence or absence of self-experienced disturbances of perception, thought, speech or action.

Adolescent↗