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Biomedical subjects

D Rose

Publications and source records attributed to D Rose.

At least 73 records · Page 4Linked to original sources
PubMed1996

A mathematical model for analysis of pharmacologically induced changes in the kinetics of cardiac muscle.

A mathematical model of the isometric contraction of cardiac muscle is developed and utilized to characterize the inotropic and lusitropic effects of cardioactive compounds in isolated guinea pig left atria. In contrast to metrics that are based on minima and maxima of an isometric twitch and its derivative function, the entire time course of the twitch is used to quantify the kinetics of the contraction-relaxation cycle. The model relates observed tension to a time-dependent activation function that describes generation of internal force and a coupling function that determines mechanical response to the activation function. The model is structured so that it is suitable for nonlinear curve fitting to observed data. Results obtained using the model for fitting experimental data from tissues treated with different classes of cardioactive compounds agree with more qualitative results presented by other authors. Experiments using the model to fit data over an extended (90 min) time course revealed differences in the kinetic profiles of milrinone and forskolin. Computer simulations that demonstrate the effect of each model parameter on twitch kinetics are presented, and the relationships between the model and other theoretical and empirical models of cardiac muscle are discussed. The mathematical model is useful to enable a more quantitative understanding of the kinetics of cardiac muscle contraction and relaxation and identify compounds that may be selective for inotropic or lusitropic effects.

Animals↗
PubMed1996

[Iodine-125-brachytherapy of malignant choroid melanoma. II: Long-term functional outcome].

BACKGROUND: Following I-125 brachytherapy of choroidal melanoma, a good primary postoperative visual acuity results. The aim of this study is to evaluate postoperative, longterm visual acuity answering the following questions: 1) When do radiogenic complications begin to develop; 2) How long does the postoperative visual acuity remain stable; 3) Is there a difference if the treated tumor is < or = or > 3 mm off the disc and foveola respectively. PATIENTS AND METHODS: Between 12/1984-12/1989, 19 patients were treated with I-125 brachytherapy for choroidal melanoma. Height of tumor was x 5.8 mm, maximum base diameter x 11.6 mm. In 10 eyes (group A), the posterior tumor border was < or = 3 mm off the disc and foveola respectively, in 9 (group B) > 3 mm. The plaque was in situ x 7.5 days, apical radiation dose x 70 Gy, and scleral contact dose x 355 Gy. Follow-up ranged at x 6.3 years. RESULTS: Between preoperative visual acuity in group A and group B there was a statistically significant difference (p < 0.05), which remained stable 1 1/2 years postoperatively. Subsequent deterioration of visual acuity occurred later in group B than in group A, but was present after 4 1/2 years in all patients and ranged at < or = 20/400. This decrease was due to subsequent radiogenic oculopathy. CONCLUSIONS: Radiogenic complications following I-125 brachytherapy begin within the first 6 months. In group B visual acuity deteriorated later, but after 4 1/2 years, it decreased due to radiogenic oculopathy to 20/400 in all patients. Prospective longterm studies are needed to evaluate whether I-125 should be indicated for larger melanomas and Ruthenium-106 for smaller melanomas to obtain better longterm visual results.

Adult↗
PubMed1996

Perceptual learning of stereoacuity.

It has often been noted that with repeated exposure to random-dot stereograms the time required to perceived depth decreases. Further, with extensive practice, stereoacuity thresholds have been shown to decrease. For both types of learning some researchers have reported specificity of the improvements to retinal location, and have thus suggested that the learning may be localised at early levels of visual processing, such as in primary visual cortex. However, these studies have not adequately ruled out the possibility that the specificity shown may be due to the operation of selective-spatial-attention mechanisms. In the present study this possibility was examined by training observers to judge the relative depth of a pair of stereograms presented equally often in two spatial locations, but stimuli were only presented with one direction of disparity (ie crossed or uncrossed) in any one location. Results indicated that, as expected, observers' judgements improved with practice. However, this improvement transferred completely to stimuli presented with the other direction of disparity in each location. Thus, it is argued that previous findings of retinal-location-specific improvements in stereoacuity may well be due to selective-spatial-attention mechanisms, rather than to learning localised at an early level of visual processing.

Adult↗
PubMed1996

The quality of hospital discharge: a survey of discharge arrangements for the over-65s.

A three-phase study comprising semi-structured interviews with patients and/or their carers, follow-up postal questionnaires, and a postal survey of the views of professionals involved in the discharge of participating patients was conducted to assess the quality of arrangements for patients over 65 years of age, discharged from hospitals in Chester and Ellesmere Port in the United Kingdom. A large majority of patients (80%) felt they had been adequately consulted about arrangements for their discharge, but less than 2% of health and social care professionals considered all discharges satisfactory. This apparent disparity between patient and professional views may be explained by low levels of expectation among patients in this aspect of their care and their reluctance to express views which they fear may compromise future care. Continuing difficulties with interprofessional communication and liaison suggest that further attention to discharge management is required if improvements are to be effected.

Aged↗
PubMed1996

Environmental tobacco smoke exposure and health effects in children: results from the 1991 National Health Interview Survey.

OBJECTIVE: To determine the effect of environmental tobacco smoke exposure on the health of children in the United States. DESIGN AND SETTING: Cross-sectional study of children who participated in the 1991 National Health Interview Survey. PARTICIPANTS: 17448 children residing in the United States. MAIN OUTCOME MEASURES: Rates of respiratory illnesses and all illnesses, and the morbidity due to these illnesses, in children exposed to environmental tobacco smoke in the home daily compared with those in children not exposed in the home. Our analyses controlled for age, socioeconomic status, race, family size, sex, season, and region of the country. RESULTS: Children who were exposed to environmental tobacco smoke had a higher incidence of acute respiratory illnesses (relative risk (RR) = 1.10, 95% confidence interval (CI) 0.95 to 1.26) and all chronic respiratory diseases (RR = 1.28, 95% CI 0.99 to 1.65) than children who were not exposed, although both CIs included unity, and chance cannot be ruled out as being responsible for these findings. Children who were exposed to environmental tobacco smoke had, on average, 1.87 more days of restricted activity (95% CI 0.20 to 3.54), 1.06 more days of bed confinement (95% CI 0.20 to 1.92), and 1.45 more days of school absence (95% CI 0.40 to 2.50) per year than children who were not exposed. CONCLUSIONS: Environmental tobacco smoke exposure in the home, which is completely preventable, is an important predictor of increased morbidity in children.

Adolescent↗
PubMed1996

Radiographic features of staphylococcal pneumonia in adults and children.

BACKGROUND: Clinical and laboratory features do not accurately correlate with the cause of community acquired pneumonia. A study was performed to examine whether the radiographic features of staphylococcal pneumonia are sufficiently distinct to aid early diagnosis. METHODS: The chest radiographs of 34 patients (including eight children) with proven staphylococcal pneumonia were reviewed by two experienced observers using methods described previously. Features on presentation and follow up were noted. RESULTS: The most striking features were the presence of multilobar consolidation on presentation, cavitation, pneumatocoeles and spontaneous pneumothorax, together with a tendency to radiographic deterioration after admission in both adults and children. Some of these features are much less common with other causes of community acquired pneumonia. However, most of the cases did not have these classic features. CONCLUSIONS: The presence of certain radiographic features, including multilobar shadowing, cavitation, pneumatocoeles, and spontaneous pneumothorax, are seen with staphylococcal pneumonia in adults and children, but their absence does not exclude the diagnosis.

Adult↗
PubMed1996

Novel mouse embryonic renal marker gene products differentially expressed during kidney development.

Investigators approaching the problem of renal organogenesis have been hampered by a paucity of suitable molecular markers that specify distinct developmental phenotypes. To identify such markers, differential display-polymerase chain reaction (DD-PCR) was used to survey the temporal pattern of gene expression in mouse kidney at 11.5, 13.5, 15.5, and 17.5 days after conception and in the adult kidney. Twenty-two differentially expressed amplification products were identified, isolated, and sequenced. Seventeen clones showed no significant similarity with previously reported nucleotide sequences: two were similar to two housekeeping gene products, and three were similar to human or rat expressed sequence tags. To confirm the differential expression patterns observed by DD-PCR, semiquantitative reverse transcription-PCR was performed using sequence-specific oligonucleotide primers. Nineteen of 22 clones were differentially expressed during kidney development [mouse embryonic renal marker (MERM) sequences 1-19]. The value of MERMs as developmental markers was further assessed in mouse metanephric organ culture, where the pattern of MERM transcript expression mimicked that observed in vivo. Therefore, the DD-PCR method permitted development of a panel of marker sequences that can be used to characterize renal developmental processes and that may allow the identification of novel, functionally relevant gene products.

Animals↗
PubMed1996

[Exploratory study of amitriptyline resistance in depressed patients: results of WHO French collaborating center on depressions resistant to treatments].

A multicountry, multicentre double-blind study in a group of depressives, coordinated by the Mental Health Division of the World Health Association (WHO) has been done. The goal of the study is to determine whether the therapeutic effects of amitriptyline can be enhanced and potentiated by combining it with an antioxydant (gingko biloba). An exploratory study has preceded the main study which had the objective to estimate the proportion of non-response patient to amitriptyline. We report the results concerning the French center. 23 inpatients meet the ICD-10 criteria for depression (F32 and F33) and were treated during 6 weeks by amitriptyline with the initial daily dose of 50 mg until the maximum dose of 200 mg. The proportion of non-responsive patient to amitriptyline was 34.78 (95% confidence interval : 15.32 to 54.24%), all clinically deteriorated.

Adult↗
PubMed1995

Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention.

We studied the pharmacokinetic and pharmacodynamic properties of integrelin, a novel platelet glycoprotein IIb/IIIa receptor inhibitor, in patients undergoing elective percutaneous coronary intervention. Patients were randomized to placebo (n = 19) or to 1 of 4 integrelin dosing regimens (total n = 54) that were studied sequentially. All patients received aspirin and heparin. Patients were followed until discharge for the occurrence of adverse clinical events: death, myocardial infarction, coronary artery bypass surgery, repeat intervention, or recurrent ischemia. Bleeding was the primary safety end point. Frequent blood sampling was performed for adenosine diphosphate-induced platelet aggregations. Simplate bleeding times were performed. Adverse clinical events occurred less often in the integrelin-treated patients, although the overall numbers were too small to make a definitive statement as to clinical efficacy. There was no significant increase in serious bleeding among integrelin-treated patients. The 2 highest integrelin boluses (180 and 135 micrograms/kg) immediately (15 minutes after the bolus) provided > 80% inhibition of adenosine diphosphate-induced platelet aggregation in > 75% of treated patients. A constant integrelin infusion of 0.75 micrograms/kg/min maintained this marked antiplatelet effect, whereas an infusion of 0.50 micrograms/kg/min allowed gradual recovery of platelet function. Elective coronary intervention was performed safely and with no significant increase in serious bleeding events using integrelin with aspirin and heparin as an antithrombotic regimen. Integrelin provided rapid, intense, and persistent ex vivo platelet inhibition during coronary intervention. This new antiplatelet agent may be beneficial in reducing platelet-mediated ischemic complications of percutaneous coronary intervention.

Aged↗
PubMed1995

Design and synthesis of conformationally constrained analogues of 4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one (Ro 20-1724) as potent inhibitors of cAMP-specific phosphodiesterase.

The synthesis and biological evaluation of cAMP-specific phosphodiesterase (PDE IV) inhibitors is described. The PDE IV inhibitor 4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one (Ro 20-1724, 2) was used as a template from which to design a set of rigid oxazolidinones, imidazolidinones, and pyrrolizidinones that mimic Ro 20-1724 but differ in the orientation of the carbonyl group. The endo isomer of each of these heterocycles was more potent than the exo isomer in an enzyme inhibition assay and a cellular assay, which measured TNF alpha secretion from activated human peripheral blood monocytes (HPBM). Imidazolidinone 4a inhibited human PDE IV with a Ki of 27 nM and TNF alpha secretion from HPBM with an IC50 of 290 nM. By comparison, Ro 20-1724 is significantly less active in these assays with activities of 1930 and 1800nM, respectively.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Phosphodiesterase type IV inhibition. Structure-activity relationships of 1,3-disubstituted pyrrolidines.

The synthesis of 1,3-disubstituted pyrrolidines 2 and their activities as type IV phosphodiesterase (PDE) inhibitors are described. Various groups were appended to the nitrogen of the pyrrolidine nucleus to enable structure-activity relationships to be assessed. Groups which render the pyrrolidine nitrogen of 2 nonbasic yielded potent PDE-IV inhibitors. Analogs of amides, carbamates, and ureas of 2 were synthesized to determine the effects that substitution on these functional groups had on PDE-IV inhibitor potency. The structural requirements for PDE-IV inhibitor potency differed among the three classes. A representative amide, carbamate, and urea (2c,d,h) were shown to be > 50-fold selective for inhibiting PDE-IV versus representative PDEs from families I-III and V. Furthermore, these same three inhibitors demonstrated potent functional activity (IC50 < 1 microM) by inhibiting tumor necrosis factor-alpha (TNF-alpha) release from lipopolysaccharide (LPS)-activated purified human peripheral blood monocytes and mouse peritoneal macrophages. These compounds were also tested orally in LPS-injected mice and demonstrated dose-dependent inhibition of serum TNF-alpha levels.

Animals↗
PubMed1995

Functional separation of global and local stereopsis investigated by cross-adaptation.

Reports that brain lesions may differentially affect global and local stereopsis suggest that anatomically separate mechanisms underlie these two functions. We demonstrate here that adaptation to global stereograms induces an after-effect on local stereopsis as well as on global stereopsis, showing that the two mechanisms cannot be entirely separate. We suggest that global stereopsis depends upon an interaction between primary visual area V1 and higher brain areas such as inferotemporal cortex.

Adolescent↗
PubMed1995

Central effects of 5-HT on respiratory and hypoglossal activities in the adult cat.

The activities of the diaphragmatic, internal intercostal and hypoglossal-innervated muscles were studied in adult decerebrate cats in response to 5-HT and related agents (8-OH-DPAT and DOI). The drugs were placed on the floor of the IVth ventricle. The mean respiratory frequency (Fi) increased (124-193% of the control value) within 3 min of the 5-HT application, and decreased thereafter (30-90%). The mean Ti and Te changed similarly, but opposite to Fi. With some delay, the hypoglossal-innervated muscles were tonically activated or exhibited increased activities. Methysergide pretreatment completely blocked the effect of 5-HT on all the respiratory parameters and the hypoglossal-innervated muscles activities. The responses to 8-OH-DPAT and DOI indicate that 5-HT modulates the respiratory frequency via activation of both 5-HT1A and 5-HT2 receptors. Nevertheless, the effect of 5-HT on both the expiratory and hypoglossal-innervated muscles seems to depend on 5-HT2 receptors activation only.

Animals↗
PubMed1995

Randomized trial of the canalith repositioning procedure.

Thirty-six subjects with confirmed, unilateral benign paroxysmal positioning vertigo of at least 2 months' duration were randomly assigned to one of two treatment groups. After complete informational counseling and explanation of the posttreatment instructions, subjects were randomly assigned to receive either Epley's canalith repositioning procedure or a placebo maneuver. All subjects completed a daily diary for 1 month to document any dizzy spells and their adherence to the posttreatment instructions. Follow-up Dix-Hallpike testing was performed after 1 month by an audiologist who was blinded to the patient's treatment group status. Analysis of Dix-Hallpike results confirmed that those who received the canalith repositioning procedure had significantly more negative responses (88.9%) than did those in the placebo group (26.7%).

Adult↗
PubMed1995

Duration illusions in a train of visual stimuli.

The first stimulus in a sequential train of identical flashes of light appears to last longer than those in the middle of the train. Four flashes (each 600 or 667 ms) were presented and the first was shortened until it appeared to have the same duration as that of the next. The duration of the first stimulus was found to be overestimated by about 50%. The illusion was unaffected by stimulus contrast, size, or interflash interval (between 100 and 600 ms). For some subjects, the last stimulus in the train also appeared to be about 50% longer than the penultimate flash. The results are discussed in terms of theories of how attention, arousal, and stimulus processing can affect duration perception. The mechanisms activated are peculiar to the visual system, since no similar illusion of duration was consistently experienced with a train of auditory tones.

Humans↗
PubMed1995

Resistance of HIV type 1 to proteinase inhibitor Ro 31-8959.

During replication of human immunodeficiency virus type 1 (HIV-1), proteolytic cleavage of Gag and Gag-Pol precursor proteins into different functional protein subunits is catalyzed by the viral proteinase, and this enzyme is the target of the antiviral proteinase inhibitor, Ro 31-8959. We investigated in vitro which HIV mutants with reduced sensitivity to Ro 31-8959 emerged during proteinase inhibition treatment; from three different HIV-1 strains, comparable progeny virus resistant to proteinase inhibitor were found, whereas the same experimental protocol detected no resistant HIV-2 mutants. Molecular analysis of the mutations underlying resistance revealed a multistep mechanism in which an amino acid exchange was common to all resistant isolates, and in all experiments preceded further exchanges at position 90 (leucine to methionine) and/or at position 54 (isoleucine to valine). For wild-type strains the 90% inhibitory concentrations of Ro 31-8959 were close to 20 nM, whereas HIV-1 mutants with all 3 amino acid exchanges had more than 50-fold increased 90% inhibitory concentrations (above 1000 nM). The primary event (Gly-48 to valine) occurs at the hinge of the flaps of the proteinase, thus hampering entry of the inhibitor to the active center and suggesting steric hindrance. Detailed knowledge of this stereotypic process could open inhibitor design, thus preventing conceivable escape of resistant virus on proteinase inhibitor action.

Amino Acid Sequence↗