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Biomedical subjects

M R Thomas

Publications and source records attributed to M R Thomas.

At least 55 records · Page 3Linked to original sources
PubMed1998

Inhaled fluticasone propionate delivered by means of two different multidose powder inhalers is effective and safe in a large pediatric population with persistent asthma.

BACKGROUND: Inhaled corticosteroids are increasingly being used to treat mild-to-moderate asthma in children. However, data regarding therapy with this class of compounds, especially in children under age 6 years, is limited. Fluticasone propionate is a third generation inhaled corticosteroid with an optimal therapeutic index. Few large prospective clinical trials have been conducted to evaluate the efficacy and safety of fluticasone propionate powder in children. OBJECTIVE: We sought to determine the efficacy and safety of fluticasone propionate powder administered by means of the Diskus and Diskhaler multidose powder inhalers in pediatric patients with persistent asthma. METHODS: Fluticasone propionate powder (50 microg or 100 microg twice daily) or placebo was administered by means of the Diskus or Diskhaler inhalers to 437 children (4 to 11 years old) with persistent asthma for 12 weeks in a randomized, double-blind, parallel-group, multi-center trial. Patients were stratified according to whether they were receiving prior treatment with inhaled corticosteroids or cromolyn or beta2-agonists alone. RESULTS: Fluticasone propionate powder administered by means of Diskus or Diskhaler significantly improved FEV1 (mean increase from baseline of 0.22 to 0.24 L; p < or = 0.023), clinic morning peak expiratory flow (mean increase from baseline of 48 to 55 L/min; p < or = 0.006), patient-measured morning (p < or = 0.001) and evening (p < or = 0.003) peak expiratory flow, and asthma symptom scores (in all but the 50 microg Diskus group; p < or = 0.036), as well as reduced albuterol use (p < or = 0.002) and nighttime awakenings (p < or = 0.019) at endpoint. Efficacy parameters were not significantly different between the two doses with either device. More placebo-treated patients discontinued the study because of lack of efficacy than patients in any fluticasone propionate group (p < 0.001). Fluticasone propionate did not suppress morning plasma cortisol concentrations and did not affect 24-hour urinary free-cortisol excretion. Adverse events were primarily pharmacologic effects of inhaled corticosteroids, and those related to the study drug occurred with low frequency. Patient satisfaction with both the Diskus and Diskhaler devices was high, with a majority of patients (> 80%) rating them favorably. CONCLUSION: This study demonstrated that fluticasone propionate powder, at the conventional recommended doses of up to 200 microg/day administered by means of Diskus or Diskhaler, was well tolerated and improved lung function in children even as young as 4 and 5 years old regardless of whether they were previously treated with inhaled corticosteroids or cromolyn or beta2-agonists alone.

Administration, Inhalation↗
PubMed1998

In-vitro investigation of the antibacterial activity of agents which may be used for the oral treatment of lung infections in CF patients.

The effect of triple therapy with ciprofloxacin, trimethoprim and either sulphadiazine or sulphamethoxazole on the MICs and development of resistance of three strains of Pseudomonas aeruginosa, two strains of Staphylococcus aureus and one of Burkholderia cepacia was compared with that of single or dual therapy with these agents using an agar dilution method. Ciprofloxacin MICs were 0.2-0.8 mg/L for the P. aeruginosa and S. aureus strains. For trimethoprim the MIC ranges were 64-128 and 0.25-1 mg/L for P. aeruginosa and S. aureus, respectively. For the sulphonamides the ranges were 64-2500 and 20-39 mg/L for P. aeruginosa and S. aureus, respectively. All combinations of agents were effective at lower concentrations than the single agents. The combination of ciprofloxacin, sulphonamide and trimethoprim showed enhanced activity against all test organisms. The highest ciprofloxacin concentration was one-tenth of the normally attainable serum concentration of 2.5 mg/L. Thus peak plasma concentrations of > or =8 x MIC for ciprofloxacin against P. aeruginosa and S. aureus are theoretically achievable in the presence of clinically acceptable concentrations of trimethoprim and a sulphonamide, making the development of resistance less likely. The development of resistance, as shown by the proportional increase in MICs, was repressed by the triple regimen as compared with the development of resistance to agents used singly or in pairs. Killing curve determinations also demonstrated the advantage of the triple-agent therapy against all organisms tested: the combination of ciprofloxacin 0.5 mg/L, trimethoprim 1 mg/L and sulphadiazine 20 mg/L had an initial bactericidal effect against log-phase inocula of 10(6) cfu/mL of two clinical strains of P. aeruginosa and one clinical strain of S. aureus. The pseudomonas strains were reduced by 2-4 log cycles. Both recovered over 24 h but did not exceed the initial inoculum. The S. aureus was reduced to 10(2) cfu/mL in 4 h and did not recover over 24 h. A repeat dose of the triple therapy against the more resistant of the P. aeruginosa strains after 12 h also had a bactericidal effect. These data suggest the possibility of an effective exclusively oral therapy for the treatment of lung infections in cystic fibrosis patients.

Administration, Oral↗
PubMed1998

Randomised trial of elective stenting after successful percutaneous transluminal coronary angioplasty of occluded coronary arteries.

BACKGROUND: The value of angioplasty in occluded coronary arteries is limited by a restenosis/reocclusion rate of 50-70%. In patients with subtotal occlusion, stent implantation has been shown to reduce clinical and angiographic restenosis. Retrospective observational studies have suggested that stenting could reduce restenosis in total occlusions. The value of sustained coronary patency on global and regional left ventricular function in this clinical setting has not been defined clearly. OBJECTIVES: To assess the medium term effect of elective intracoronary stent deployment after successful percutaneous transluminal coronary angioplasty (PTCA) of an occluded coronary artery. METHODS: Sixty patients with a total coronary occlusion successfully treated by PTCA were randomised to receive an intracoronary stent or no stent. Patients underwent clinical and angiographic follow up at six months. RESULTS: Thirty patients received a stent (group A) and 30 were treated by angioplasty alone (group B), all with initial success. One patient in group B required repeat angioplasty with stenting at 24 hours and one patient died after 10 days. Angiographic follow up was available for 57 patients. This showed a significantly reduced reocclusion rate in group A compared with group B (7% v 29%, p < 0.01) and a tendency to a reduced restenosis rate (22% v 40%, p = 0.105) in patients with no reocclusion. Left ventricular function, both global and regional, improved in group A. Only the regional left ventricular function in the area supplied by the target coronary artery improved in group B. Recurrence of symptoms and clinical events such as repeat angioplasty, coronary artery bypass grafting, death or myocardial infarction tended to be reduced in group A (4 (13%) v 9 (30%)). CONCLUSIONS: Intracoronary stent insertion is effective in reducing the rate of reocclusion and shows a trend towards reduced restenosis after opening of a total coronary occlusion by balloon angioplasty. Sustained patency of the target coronary artery is associated with improvement in global and regional left ventricular function.

Adult↗
PubMed1998

The impact of a history of childhood abuse on hospital outcome of affective episodes.

OBJECTIVE: Despite increased awareness of the prevalence of a history of childhood abuse among adults with psychiatric disorders, the implications for treatment and outcome are generally unknown. This study examined the impact of childhood sexual abuse (in some cases combined with physical abuse) on the hospital treatment of severe mood disorders. METHODS: A chart review was conducted of 110 cases of consecutively admitted adult inpatients with affective disorders. The abused and nonabused groups were compared in terms of demographic variables, severity of illness, treatment history, duration of hospitalization, and outcome of the hospital treatment episode. RESULTS: A history of childhood abuse was associated with younger age, comorbid personality disorders, and shorter duration of hospitalization. Other measures, such as level of functioning at discharge and recidivism, were not related to abuse status. CONCLUSIONS: The results suggest that childhood abuse may be associated with earlier onset of affective episodes and personality disorders but is not strongly associated with other clinical and outcome measures in the acute treatment setting.

Adult↗
PubMed1997

Removal of thrombus from aortocoronary bypass grafts and coronary arteries using the 6Fr Hydrolyser.

This study evaluates the feasibility and safety of a 6Fr hydrodynamic thrombectomy catheter, the Hydrolyser, in native coronary arteries and aortocoronary bypass grafts. With use of a conventional contrast injector, saline solution is injected into the narrow lumen of the catheter which makes a 180 degrees bend at the tip. The resultant high-velocity jet (150 km/hour) is directed over a sidehole near the tip into a wide exhaust lumen. As a consequence of the Venturi effect, thrombus is sucked into that sidehole, fragmented, and removed through the wide exhaust lumen into a collection bag. Thirty-one thrombotic lesions were treated in 31 patients. The culprit vessel was a venous graft in 21 patients (15 with Thrombolysis in Myocardial Infarction Trial [TIMI] grade 0 or 1 flow) and a coronary artery in 11 patients (9 with grade 0 or 1 flow). Twenty-six patients had angina New York Heart Association functional class III or IV heart failure and 5 an acute myocardial infarction. In 26 patients, Hydrolyser therapy was the primary treatment, whereas in 5 patients coronary angioplasty preceded Hydrolyser therapy. In 1 patient the Hydrolyser could not reach the lesion. Thrombus was removed in 29 of the 31 patients. Successful reperfusion (TIMI grade 2 or 3 flow) by Hydrolyser therapy alone was achieved in 14 of the 24 patients with TIMI grade 0 or 1 flow before the procedure. Adjunctive therapy (coronary angioplasty, stent, or thrombolysis) was performed in 28 of the 31 patients. At the end of the total procedure 24 patients had TIMI grade 3 flow. Distal embolization during thrombectomy occurred in 2 patients, which led to a non-Q-wave infarction in 1. No patient died or needed emergency coronary bypass due to the Hydrolyser procedure. Thus, thrombectomy using the 6Fr Hydrolyser is feasible and was performed safely in 31 patients.

Adult↗
PubMed1997

Transradial artery coronary angiography and intervention in patients with severe peripheral vascular disease.

BACKGROUND: Traditionally, cardiac catheterization in patients with severe aorto-iliac disease has been performed using a brachial arteriotomy. This approach is associated with significant vascular and neuronal complications and requires considerable training to achieve an adequate level of expertise. Improvement and miniaturization of catheter equipment now allows the radial artery to be used for coronary investigation and intervention. The lack of important structures close to the radial artery, a good collateral ulnar artery circulation and its superficial position suggests that these procedures should have a low complication rate. The purpose of this study was to assess the efficacy and safety of percutaneous transradial diagnostic and interventional coronary catheterization in patients with severe peripheral vascular disease. PATIENTS AND METHODS: We undertook a non-randomized prospective analysis of 75 patients who had transradial artery diagnostic and interventional coronary catheterization in whom femoral angiography was impossible or relatively contraindicated (22 patients with severe claudication and absent femoral pulses, 24 patients with previous aorto-iliac surgery or intervention, 20 patients with a failed femoral approach, 9 patients with an aortic aneurysm). Three patients had an absent ulnar artery and were excluded. RESULTS: Radial artery cannulation was successful in 73/75 (97%) cases. Seventy-one (95%) patients had a successful diagnostic study. There was a high incidence of 3 vessel disease (73%), and the majority of patients (64%) were referred for coronary bypass surgery. Twelve patients underwent successful follow-on intervention including the insertion of 9 intracoronary stents. Adequate haemostasis was achieved within 20 min after diagnostic angiography and 60 min after interventional procedures. One patient had a forearm haematoma with paraesthesia of the hand which settled with conservative treatment. At 4-6 weeks, all patients had normal hand sensation and function (100%) with a palpable pulse present in 59/62 (96%). All patients undergoing diagnostic angiography were discharged on the same day, and patients undergoing intervention were discharged the following day. CONCLUSIONS: Transradial coronary investigation and intervention can be performed with a high degree of success and a low complication rate with early mobilization and discharge in patients with severe peripheral vascular disease. We suggest that the percutaneous transradial technique should be considered as an alternative to the Sones' technique in these patients.

Angioplasty, Balloon, Coronary↗
PubMed1997

Selection bias in an inpatient outcomes monitoring project.

Managed care organizations increasingly tout clinical outcomes assessment as the mechanism by which we will ensure quality and compare providers. The authors report on their experience with a multisite inpatient outcomes monitoring project by comparing patients who accepted (N = 51), refused (N = 36), or were not asked (N = 110) to participate in the project. The patients who were asked to participate had significantly longer inpatient stays compared with the unasked group (11.2 vs 6.9 days). Patients who agreed to participate in the project were more likely to have a bipolar (43.1% vs 19.2%) or any affective disorder (94.1% vs 79.5%), and less likely to have a schizophrenic disorder (2.0% vs 11.6%) than the refused and unasked groups. The project participants also had higher 90-day readmit rates (27.5% vs 9.6%), more readmissions (0.51 vs 0.16), and more education (14.59 vs 13.51 years) than nonparticipating patients. In this preliminary study, patient-related variables were found to influence who the staff asked and who consented to participate in this clinical outcomes monitoring project. The authors distinguish clinical outcomes monitoring from treatment effectiveness research and discuss the need to develop methodologies that deal with nonrepresentative patient sampling and intersite variability in recruitment practices.

Adolescent↗
PubMed1997

Impact of shorter lengths of stay on status at discharge in bipolar mania.

UNLABELLED: This study assesses the impact of shortening the inpatient length of stay on status at discharge in patients with mania. METHODS: The authors performed a chart review on 131 patients with discharge diagnoses of bipolar disorder, current episode manic type, admitted to the private attending service at Colorado Psychiatric Hospital between 1985 and 1995. In 1990, a new program (the alternatives program) that provides a continuum of acute care services and shorter inpatient lengths of stay was instituted. Retrospectively assessed GAF, CGI, treatment outcome rating scores, and length of stay (LOS) were compared for the prealternatives (1985-1989), early alternatives (1990-1992), and recent alternatives (1993-1995) program treatment eras. A progressive decrease in inpatient LOS, duration of the acute care episodes, and total service utilization was seen across eras. Despite the more recent shortening in LOS, no significant differences were seen in GAF and treatment outcome rating scores at discharge. GAF and treatment outcome rating scores on hospital days 3 and 7, however, suggested that patients were improving more rapidly in the more recent eras. Inpatient LOS and duration of the acute care episodes have significantly decreased over the last 10 years, but patients appear no more ill at discharge. The authors postulate that changes in psychopharmacologic practice and the inpatient treatment model may have facilitated the more rapid clinical improvement seen in the more recent eras. The authors caution that we need prospective studies that include postdischarge follow-up to assess further the impact of shorter inpatient stays on the posthospital course of manic patients.

Analysis of Variance↗
PubMed1997

Dissociative symptoms in psychotic mood disorders: an example of symptom nonspecificity.

Dissociative symptoms have been the subject of psychiatric inquiry since the beginning of this century (Putnam 1992; Sanders 1986; van der Kolk and van der Hart 1989). Although recent investigations have focused on the four specific dissociative disorders (American Psychiatric Association 1994) and their relationship to early traumatic experiences (Chu and Dill 1990; Putnam 1985; Terr 1991), dissociative symptoms have been reported in virtually every major psychiatric disorder (Bremner et al. 1992; Goff et al. 1992; Steinberg 1992), and, in less severe forms, even in nonpatient populations (Briere 1988; Putnam 1992; Ross and Joshi 1992). These observations raise questions about the clinical significance of dissociative symptoms that occur when other mental disorders are also present (Coons 1984; Fahy 1988).

Adult↗
PubMed1996

Endogenous opioid control of somatodendritic oxytocin release from the hypothalamic supraoptic and paraventricular nuclei in vitro.

Oxytocin release was measured in a perifusion system from microdissected supraoptic (SO) and paraventricular (PV) nuclei of ovariectomised female rats. An initial period of electrical stimulation (S1) applied through a pair of platinum electrodes evoked an increase in peptide release, however, subsequent periods of stimulation (S2, S3, S4) were increasingly less effective, suggesting depletion of releasable stores. However, addition of the opioid antagonist, naloxone (5 x 10(-5) M), during periods S2 and S3 potentiated this stimulated oxytocin release, indicating the presence of an endogenous opioid inhibition. Tissue from ovariectomised animals pre-treated with progesterone for 3 days showed increased basal secretion but no naloxone-induced potentiation of electrically-stimulated release. However, increasing the naloxone concentration (5 x 10(-5) M) again revealed a potentiation, indicating that progesterone had caused a shift in the effective dose of the antagonist. These data demonstrate that, like their axon terminals in the neurohypophysis, the dendrites of magnocellular oxytocin neurones are under control of endogenous opioids, and that progesterone causes an increase in this opioid tone. This may function to regulate intranuclear oxytocin secretion in the pregnant and periparturient animal.

Animals↗
PubMed1996

A cost-benefit analysis of the post-operative use of antibiotic ear drops following grommet insertion.

A prospective randomized controlled study was carried out to investigate the effect of prophylactic antibiotic ear drops used for five days after bilateral grommet insertion. The average improvement in the hearing threshold was significantly better in ears in which there was an effusion (16 dB) compared with no effusion (9 dB). The drops had no significant effect upon grommet function at three months measured by blockage rates, extrusion rates or improvement in pure tone audiometry whether or not there was an effusion. The drops were not therefore cost-effective.

Adolescent↗
PubMed1996

Shortening length of stay without increasing recidivism on a university-affiliated inpatient unit.

The impact of reducing length of stay on readmission rates was examined for privately insured patients treated on a traditional inpatient unit or in an alternatives program with a shorter stay and a continuum of acute care. Billing data were analyzed for length of stay and readmission rates for all admissions between 1985 and 1992 (N = 1,363). The traditional unit was reorganized in 1990 into the alternatives program. Although the program decreased mean length of stay from 20.2 days to 6.2 full-day equivalents, overall readmission rates did not increase (17.2 percent, compared with 18.6 percent for the traditional unit). Rates increased for a subgroup of patients with psychotic disorders (from 13.7 to 35.2 percent).

Adolescent↗
PubMed1995

The time of appearance and disappearance of fetal DNA from the maternal circulation.

A single copy Y-chromosome DNA sequence was amplified using the polymerase chain reaction (PCR) from the peripheral blood of 30 women who had achieved a pregnancy through an in vitro fertilization (IVF) programme. The time of conception was known precisely and was confirmed by serial ultrasound scans. Conceptions were dated as the number of weeks after fertilization plus 2, to give a time equivalent to the obstetric menstrual dating of the pregnancy (LMP). Y-chromosome-specific DNA was detected in all pregnancies with a male fetus (18/30). The earliest detection was at 4 weeks and 5 days, and the latest at 7 weeks and 1 day. Y-chromosome-specific sequences were no longer detected in any of the male pregnancies 8 weeks after delivery. No Y-chromosome sequences were detected in any of the pregnancies where only female babies were delivered. This demonstrates that fetal DNA appears in the maternal circulation early in the first trimester, that it can be identified in all pregnancies tested by 7 weeks, that it continues to be present throughout pregnancy, and that it has been cleared from the maternal circulation 2 months after parturition. Early non-invasive prenatal diagnosis for aneuploidies and inherited disorders will be possible in all pregnancies if fetal cells can be isolated free from maternal contamination (or identified accurately in the presence of maternal cells) without problems of contamination from previous pregnancies.

DNA↗