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Biomedical subjects

G Gross

Publications and source records attributed to G Gross.

At least 73 records · Page 4Linked to original sources

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↗

A controlled trial of chlorofluorocarbon-free triamcinolone acetonide inhalation aerosol in the treatment of adult patients with persistent asthma. Azmacort HFA Study Group.

STUDY OBJECTIVE: To compare the dose response, efficacy, and safety of inhaled triamcinolone acetonide (TAA) with a hydrofluoroalkane (HFA) propellant (75 microg/puff), TAA with a chlorofluorocarbon propellant (dichlorodifluoromethane [P-12]; 75 microg/puff), and placebo in adult patients with persistent asthma. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 514 adult patients with persistent asthma. INTERVENTIONS AND MEASUREMENTS: Patients received 8 weeks of treatment with 150, 300, or 600 microg/d of TAA HFA, the same doses of TAA P-12, or placebo following a 5- to 21-day baseline period. Efficacy was assessed by spirometry, and by daily recordings of albuterol use, peak expiratory flow (PEF), asthma symptom ratings, and nighttime awakenings throughout the study. RESULTS: Linear trend analysis showed that both formulations of TAA at all doses produced statistically significant improvements compared with placebo in spirometry, asthma symptom scores, albuterol use, and PEF. Significant improvement was seen as early as 24 h for morning PEF and as early as 1 week for FEV(1) (TAA HFA, 600 microg/d; TAA P-12, 300 and 600 microg/d) and albuterol use (all doses of both formulations). The P-12 and HFA formulations had comparable efficacy. A dose response showing greater improvement with higher doses was evident for the majority of parameters for both formulations. The incidences of adverse events were similar across all treatment groups with no dose-related trends. CONCLUSION: HFA and P-12 formulations of TAA inhalation aerosol were therapeutically equivalent and showed comparable safety and dose-related efficacy in the treatment of patients with persistent asthma.

Administration, Inhalation↗

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↗

Effects of LU-111995 in three models of disrupted prepulse inhibition in rats.

LU-111995 is a novel antipsychotic drug in clinical development. It has a clozapine-like receptor profile and affinities for dopamine D(4) and 5-hydroxytryptamine(2A) receptors. The effects of LU-111995 were examined in three models of disrupted prepulse inhibition (PPI) in rats. The first model tested the hypothesis that LU-111995 would normalize the deficit in PPI exhibited by rats treated with the dopamine agonist apomorphine. LU-111995 significantly reduced the effect of apomorphine on PPI but also slightly increased PPI by itself. Thus, the increases in PPI were not specific to the animals treated with apomorphine but reflected an effect of LU-111995 on PPI. LU-111995 also attenuated the apomorphine-induced increase in startle reactivity. The second model tested the hypothesis that LU-111995 would normalize the deficit in PPI exhibited by rats treated with the psychotomimetic phencyclidine (PCP). LU-111995 significantly blocked the PCP-induced increase in startle reactivity but did not alter the PPI-disruptive effects of PCP. The third model tested the hypothesis that LU-111995 would normalize the deficit in PPI exhibited by isolation-reared rats tested as adults. Isolation rearing of rats produced deficits in PPI. LU-111995 reversed the isolation rearing-induced deficit in PPI without having any significant effect on PPI in socially reared rats. In summary, LU-111995 exhibits potential antipsychotic-like activity in two models of disrupted PPI. It remains to be elucidated whether its effects on PPI can be attributed to a blockade of single dopamine and 5-hydroxytryptamine receptor subtypes, especially D(4) and 5-hydroxytryptamine(2A), or a combination of both.

Acoustic Stimulation↗

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↗

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↗

[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↗

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↗

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↗

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↗

Demography, symptomatology, and course of disease in ambulatory zoster patients. A physician-based survey in Germany.

This survey summarises the observations of physicians who prospectively recorded clinically relevant data on their patients with an episode of herpes zoster. These included demography of patients, signs and symptoms during the prodromal phase, relevant history, description of disease at the first visit, therapeutic measures and description of disease, and occurrence of postherpetic neuralgia (pain 4-5 weeks after crusting) at the second visit. A total of 2,063 patients were reported to the data management centre. The age distribution resembles that reported in the literature including the notable increase in zoster frequency with advancing age. Almost 20% of the patients, however, were 30 years old or less, and this contrasts markedly with the published literature. Age modifies the frequency of the dermatome afflicted: more cranial and less thoracic manifestations were observed with increasing age. Almost all patients reported symptoms which may be attributed to a prodromal phase, especially pain in the affected dermatome (82%). The incidence of postherpetic neuralgia was 28%. A complicated disease course such as visceral, ocular, or otological involvement, or progression to additional dermatomes was seen in almost 10% of the patients.

Adolescent↗

[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↗

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↗

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↗