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Biomedical subjects

S Appleton

Publications and source records attributed to S Appleton.

At least 19 recordsLinked to original sources
PubMed2006

Long-acting beta2-agonists for poorly reversible chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by partially reversible airflow limitation. Many patients have little reversibility to short acting bronchodilators, but long acting bronchodilators are frequently advocated. OBJECTIVES: To determine the effectiveness of long acting beta-2 adrenoceptor agonists (LABAs) in COPD patients demonstrating poor reversibility to short-acting bronchodilators. SEARCH STRATEGY: The Cochrane Airways Group Specialised Register was searched ('all years' to 2005) along with the reference lists from identified randomised controlled trials (RCTs). SELECTION CRITERIA: All RCTs comparing inhaled LABAs (salmeterol or formoterol) with placebo in the treatment of patients with stable, poorly reversible COPD. Studies were a minimum of four weeks in duration. DATA COLLECTION AND ANALYSIS: Two authors independently performed data extraction and study quality assessment. If we required additional data, we contacted authors and pharmaceutical companies sponsoring the identified RCTs. MAIN RESULTS: Twenty-three published and unpublished studies (6061 participants) were included in the review. There was a significant change in forced expiratory volume in 1 second (FEV1) in favour of salmeterol 50 mcg twice daily (BID) of 51 mls (95% confidence intervals (CI) 32 to 70), end of study morning peak expiratory flow (PEF) 14.89 L/min (95% CI 10.86 to 18.91). Supplemental short-acting bronchodilator usage was reduced by just under one puff per day. There were significant differences in the total, activity and impact domain scores of the St George's respiratory questionnaire in favour of salmeterol 50 mcg BID. Findings from other health status measurements and symptom scores were conflicting. There was no significant difference in exercise tolerance. The number of participants experiencing exacerbations was significantly reduced with salmeterol 50 mcg treatment compared with placebo (numbers needed to treat to benefit 21). AUTHORS' CONCLUSIONS: This review shows that the treatment of patients with COPD with salmeterol 50 mcg produces modest increases in lung function. There were varying effects for other important outcomes such as health related quality of life or reduction in symptoms. However, there was a consistent reduction in exacerbations which may help people with COPD who suffer frequent deterioration of symptoms prompting healthcare utilisation. The strength of evidence for the use of salmeterol 100 mcg, formoterol 12 mcg, 18 mcg, 24 mcg was insufficient to provide clear indications for practice.

Adrenergic beta-Agonists↗
PubMed2006

Ipratropium bromide versus long-acting beta-2 agonists for stable chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a condition associated with high morbidity, mortality and cost to the community. Patients often report symptomatic improvement with long acting beta-2 agonists (LABAs) and anticholinergic bronchodilator medications, both of which are recommended in COPD guidelines. These medications have different mechanisms of action and therefore theoretically could have an additive effect when combined. As these medications are prescribed in COPD as long term therapy, it is important to assemble reliable evidence on their relative and additive effects. OBJECTIVES: To compare the relative efficacy and safety of regular long term use (at least four weeks) of ipratropium bromide and LABA in patients with stable COPD. Comparisons were made between single agents and in combination versus LABAs alone. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of Trials (August 2005) and reference lists of articles. We also contacted drug companies for relevant trial data. SELECTION CRITERIA: All randomised controlled trials comparing treatment for at least four weeks with an anticholinergic agent (ipratropium bromide) alone or in combination with LABA versus LABA alone, delivered via metered dose inhaler or nebuliser, in non-asthmatic adult subjects with stable COPD. DATA COLLECTION AND ANALYSIS: Three review authors independently performed data extraction and study quality assessment. We contacted study authors and pharmaceutical companies for missing data. MAIN RESULTS: Seven studies met the inclusion criteria of the review (2652 participants). Monotherapy comparison (six studies): There was a significantly greater change in favour of salmeterol in morning PEF and FEV1. There were no significant differences in quality of life, exacerbations, or symptoms. Formoterol appeared to confer some benefits over ipratropium treatment in terms of morning peak flow. Combination comparison (three studies): There was a significant improvement in post-bronchodilator lung function, supplemental short-acting beta-agonist use and HRQL in favour of combination therapy compared with salmeterol alone. AUTHORS' CONCLUSIONS: The available data from the trials suggest that there is little difference between regular long term use of IpB alone and salmeterol if the aim is to improve COPD symptoms and exercise tolerance. However, salmeterol was more effective in improving lung function variables. In terms of post-bronchodilator lung function, combination therapy conferred modest benefits and a significant improvement in HRQL, and reduced supplemental short-acting beta-agonist requirement, although this effect was not consistent. Additional studies are needed to assess the relative effects of combining therapies, using validated subjective measurements, and should consider concordance and the convenience of people having to use different inhaler devices.

Adrenergic beta-Agonists↗
PubMed2006

Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a condition associated with high morbidity, mortality and cost to the community. Patients often report symptomatic improvement with short-acting beta-2 agonists (SABA) and anticholinergic bronchodilator medications, and both are recommended in COPD guidelines. These medications have different mechanisms of action and therefore could have an additive effect when combined. OBJECTIVES: To compare the relative efficacy and safety of regular long term use (at least four weeks) of ipratropium bromide and short- acting beta-2 agonist therapy in patients with stable COPD. SEARCH STRATEGY: The Cochrane Airways Group Specialised Register of Trials was searched. Bibliographies were checked to identify relevant cross-references. Drug companies were contacted for relevant trial data. The searches are current to August 2005. SELECTION CRITERIA: All randomised controlled trials comparing at least 4 weeks of treatment with an anticholinergic agent (ipratropium bromide) alone or in combination with a beta-2 agonist (short acting) versus the beta-2 agonist alone, delivered via metered dose inhaler or nebuliser, in non-asthmatic adult subjects with stable COPD. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment was performed independently by three reviewers. Authors of studies and relevant manufacturers were contacted if data were missing. MAIN RESULTS: Eleven studies (3912 participants) met the inclusion criteria of the review. Small benefits of ipratropium over a short-acting beta-2 agonist were demonstrated on lung function outcomes. There were small benefits in favour of ipratropium on quality of life (HRQL), as well as a reduction in the requirement for oral steroids. Combination therapy with ipratropium plus a short-acting beta-2 agonist conferred benefits over a short-acting beta-2 agonist alone in terms of post-bronchodilator lung function. There was no significant benefit of combination therapy in subjective improvements in HRQL, but again there was a reduction in the requirement for oral steroids. AUTHORS' CONCLUSIONS: The available data from the trials included in this review suggest that the advantage of regular long term use of ipratropium alone or in combination with a short-acting beta-2 agonist or over a beta-2 agonist alone are small, if the aim is to improve lung function, symptoms and exercise tolerance. Until further data are available, the strategy of providing a short-acting beta-2 agonist on a PRN basis, and then either continuing with the short-acting beta-2 agonist regularly or conducting an "n of 1" trial of regular beta-2 agonist or regular anticholinergic to determine the treatment that gives the best relief of symptoms (and continuing with it), would seem cost effective. This strategy does need formal evaluation. Patient preference is also important, as is the relative importance of avoiding the use of systemic corticosteroids.

Adrenergic beta-Agonists↗
PubMed2004

A randomised controlled trial of a psychoeducational intervention for women at increased risk of breast cancer.

This study aimed to compare the impact of two versions of a psychoeducational written intervention on cancer worry and objective knowledge of breast cancer risk-related topics in women who had been living with an increased risk of familial breast cancer for several years. Participants were randomised to three conditions: scientific and psychosocial information pack (Group 1), scientific information pack only (Group 2) or standard care control (Group 3). They completed postal questionnaires at baseline (n=163) and 4 weeks (n=151). As predicted, there was a significant decrease in cancer worry for Group 1, but not Group 2. Objective knowledge significantly improved for both Group 1 and Group 2 as expected, but not Group 3. However, there was an unpredicted decline in cancer worry for Group 3. This study supports the value of a scientific and psychosocial information pack in providing up-to-date information related to familial risk of breast cancer for long-term attendees of a familial breast cancer clinic. Further research is warranted to determine how the information pack could be incorporated into the existing clinical service, thus providing these women with the type of ongoing psychosocial support that many familial breast cancer clinics are currently lacking.

Adult↗
PubMed2004

Assessment of the elution of charcoal, cellulose acetate, and other particles from cigarettes with charcoal and activated charcoal/resin filters.

This experiment was designed to study the release of cellulose acetate fibers, charcoal, and other particles from cigarettes with charcoal and activated charcoal/resin filters. For the first time in such studies, efforts were made to identify the particles that were eluted using other analytical techniques in addition to light microscopy. Other corrective measures were also implemented. During the studies it was found that trimming of larger filters to fit smaller filter housings introduced cellulose acetate-like particles from the fibers of the filter material. Special, custom made-to-fit filters were used instead. Tools such as forceps that were used to retrieve filters from their housings were also found to introduce fragments onto the filters. It is believed that introduction of such debris may have accounted for the very large number of cellulose acetate and charcoal particles that had been reported in the literature. Use of computerized particle-counting microscopes appeared to result in excessive number of particles. This could be because the filter or smoke pads used for such work do not have the flat and level surfaces ideal for computerized particle-counting microscopes. At the high magnifications that the pads were viewed for particles, constant focusing of the microscope would be essential. It was also found that determination of total particles by using extrapolation of particle count by grid population usually gave extremely high particle counts compared to the actual number of particles present. This could be because particle distributions during smoking are not uniform. Lastly, a less complex estimation of the thickness of the particles was adopted. This and the use of a simple mathematical conversion coupled with the Cox equation were utilized to assess the aerodynamic diameters of the particles. Our findings showed that compared to numbers quoted in the literature, only a small amount of charcoal, cellulose acetate shards, and other particles are released. It was also shown that those particles would have a low likelihood of reaching the lung.

Adhesives↗
PubMed2003

A randomised controlled trial of breast cancer genetics services in South East Scotland: psychological impact.

This study compared the psychological impact of two models of breast cancer genetics services in South East Scotland. One hundred and seventy general practices were randomised to refer patients to the existing standard regional service or the novel community-based service. Participants completed postal questionnaires at baseline (n=373), 4 weeks (n=276) and 6 months (n=263) to assess perceived risk of breast cancer, subjective and objective understanding of genetics and screening issues, general psychological distress, cancer worry and health behaviours. For participants in both arms of the trial, there were improvements in subjective and objective understanding up to 4 weeks which were generally sustained up to 6 months. However, improvements in subjective understanding for the women at low risk of breast cancer (i.e. not at significantly increased risk) in the standard service arm did not reach statistical significance. Cancer worry was significantly reduced at 6 months for participants in both arms of the trial. The two models of cancer genetics services tested were generally comparable in terms of the participants' psychological outcomes. Therefore, decisions regarding the implementation of the novel community-based service should be based on the resources required and client satisfaction with the service.

Adolescent↗
PubMed2003

Ionisers for chronic asthma.

BACKGROUND: Previous reports have shown that ion content in the air may have an effect on respiratory function. Results from studies which test the efficacy of air ionisers to reduce asthma symptoms are often inconclusive and their use as a treatment for asthma remains debatable. OBJECTIVES: We conducted a systematic review of the available evidence to determine the effectiveness of positive and negative ion generators in people with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Asthma trials register (January 1966 to March 2003), Cochrane Central Register of Controlled Trials (Cochrane Library issue 2, 2003) as well as The Alternative Medicine Database AMED (1985 to March 2003). SELECTION CRITERIA: Randomised controlled trials (parallel or crossover design studies) comparing ionisers with dummy ionisers (being negative or positive ion emitters), in children or adults with chronic asthma. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed titles and abstracts of studies and assessed trial quality. Study quality was determined using two methods:The Cochrane approach to allocation concealment and the five point Jadad scale. MAIN RESULTS: Six studies were selected for inclusion (106 participants). No results were combined as the studies were all of a crossover design. EFFECTS OF NEGATIVE ION GENERATORS (five studies)No study reported a significant difference in lung function between ionised and control air (morning Peak expiratory flow (PEF) - three studies; forced expiratory flow in one second (FEV1) - one study). There were no significant differences in symptoms or beta-2 agonist usage between ionised and control air in three studies. EFFECTS OF POSITIVE ION GENERATORS (one study)This study demonstrated that although positively ionised air was associated with a larger fall in FEV1 with exercise, this did not reach statistical significance. Baseline FEV1 was not demonstrated to be significantly different between treatment groups. REVIEWER'S CONCLUSIONS: Based on the evidence currently available from randomised controlled trials, a recommendation cannot be given for the use of room air ionisers to reduce symptoms in patients with chronic asthma.

Adult↗
PubMed2003

Underdiagnosed asthma in South Australia.

BACKGROUND: The prevalence of undiagnosed asthma in the general population and the clinical and demographic characteristics of these patients compared with those with diagnosed asthma are unclear. METHODS: The North West Adelaide Health Survey (NWAHS) is a population household interview survey of adults (age>18 years) in the north western suburbs of Adelaide, South Australia (regional population 0.6 million). Data obtained were weighted to the closest census data to provide population representative estimates. Positive answers to: "Have you ever had asthma?"; "Has it been confirmed by a doctor?"; "Do you still have asthma?" determined current physician diagnosed asthma. A positive bronchodilator response on spirometric testing according to ATS criteria without a physician's diagnosis determined undiagnosed asthma. Other measures included the SF-12 health survey questionnaire, the Selim index of severity of chronic lung disease, skin allergy tests, and demographic data. RESULTS: Of the 3422 individuals interviewed, 2523 (74%) agreed to participate in the clinical assessment. Of these, 292 (11.6%) had asthma, 236 (9.3%) with a doctor's diagnosis of asthma and 56 (2.3%) with undiagnosed asthma defined on spirometric criteria; thus, 19.2% of the total asthma group were undiagnosed. Those undiagnosed were more likely (p<0.05) to be >40 years old, on government benefits, with an income 65 years. Health service use over the previous year was similar for both asthma groups. CONCLUSION: Undiagnosed asthma is common among the Australian population, with a similar clinical spectrum to those with diagnosed asthma.

Adult↗
PubMed2000

Home care by outreach nursing for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction, worsening exercise performance and deterioration in health. It is associated with significant morbidity, mortality and costs to health care systems. Care strategies, such as outreach nursing in the community, may reduce this burden. OBJECTIVES: To evaluate the effectiveness of outreach respiratory health care worker programmes for patients with COPD in terms of improving lung function, exercise tolerance and health related quality of life (HRQL) of patient and carer, and reducing mortality and hospital service utilisation. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group database. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTS were contacted for other published and unpublished studies. SELECTION CRITERIA: Only randomised control trials of patients with COPD were included. The intervention was an outreach nurse visiting patients in their homes, providing support, education, monitoring patient status and providing liaison with physicians. Interventions that used nurse practitioners who provided therapeutic intervention were also included. Studies in which the therapeutic intervention under test was physical training were not included. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment were performed independently by two reviewers. Where further or missing data was required, authors of studies were contacted. MAIN RESULTS: Four studies were found. Three assessed mortality following twelve months of care (n=96, 152 and 301), and one after seven months(n=75). Meta-analysis demonstrated that mortality was not significantly reduced by the intervention, Peto Odds Ratio 0.72; 95 % confidence interval 0.43, 1.21. Post hoc subgroup analysis suggested that mortality was reduced by the outreach nursing programme in patients with less severe disease. Significant improvements in health related quality of life were reported in one study in moderate COPD, but not in a study in patients with severe disease. No changes in lung function or exercise performance were found in the studies where data were available. Hospital admissions were reported in only one study in patients with severe disease and no benefit was observed. REVIEWER'S CONCLUSIONS: Patients with moderate COPD may have mortality and health related quality of life gains from a nursing outreach programme, but there are no data about reductions in hospital utilisation. Patients with severe COPD do not appear to have benefit from such programmes and one large study found no reduction in hospital admissions in such patients.

Community-Institutional Relations↗
PubMed2000

Long-acting beta2-agonists for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation which is only partially reversible. Long acting beta2-agonists, effective in the management of asthma,are also recommended for COPD management so it is important to establish whether these drugs are effective in reducing COPD symptoms in view of the potential side effect and cost burden. OBJECTIVES: To determine the effectiveness of long acting beta2-adrenoceptor agonists in improving lung function and quality of life and reducing dyspnoea in patients with COPD. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group register. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTs were contacted for other published and unpublished studies. In addition, unpublished studies were also obtained from the pharmaceutical companies that manufacture long acting beta2- adrenoceptor agonists. SELECTION CRITERIA: All randomised controlled trials over four weeks in duration comparing treatment with long-acting beta2-adrenoceptor agonists (salmeterol and formoterol) with placebo in patients with stable non-reversible COPD. Outcome measures included forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR), symptom scores, six minute walk distance, quality of life scores, Borg scores for dyspnoea and rescue bronchodilator use. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment was performed independently by two reviewers. Where further or missing data were required, authors of studies were contacted. MAIN RESULTS: Thirty three abstracts were identified as potentially relevant. Of these, four randomised controlled trials (RCTs) were included in this review. Two were parallel group studies of 16 week duration and two were cross-over studies with four week treatment arms. All four RCTs assessed the efficacy of salmeterol in COPD. In a 16 week study of salmeterol 50 mcg and 100 mcg twice daily treatment, a significant increase in FEV1 was seen in both treatment groups. The weighted mean difference (WMD) for the increase in FEV1 for the 50 mcg group was 0.10 litre (95% CI: 0.05;0. 15) and in the 100 mcg group the WMD was 0.12 litre (95% CI: 0.06; 0. 17 ). In the two cross-over studies of four weeks treatment, salmeterol 50 mcg twice daily treatment did not show significant increases in FEV1 (WMD = 0.04 litre, 95% CI: -0.06; 0.15). Similarly, morning and night time PEFR was not significantly improved with salmeterol treatment. In a 16 week study, disease-specific quality of life, measured using the St. George's Respiratory Questionnaire (SGRQ), showed a significant improvement after 50 mcg twice daily, but not after 100 mcg twice daily. This improvement exceeded the threshold for a clinically significant change with this questionnaire. General health status, as measured by the Medical Outcomes Short Form 36, did not improve in any of the eight components with either salmeterol dose. No significant difference was demonstrated in the mean change from baseline in the six minute walk distance (WMD = 1.9 metres, 95% CI: -15.4;19.3). Breathlessness was reduced in one study in patients receiving salmeterol 50 mcg twice daily group. Significantly more patients in this group had Borg scores for breathlessness less than three (a score of three indicating moderate dyspnoea) compared to the placebo treated group (Peto Odds Ratio = 0.60, 95% CI: 0.40; 0.88). Neither dose of salmeterol influenced the incidence of COPD exacerbations, (50 mcg: Peto Odds Ratio = 0.74, 95% CI: 0.47, 1.15) and (100 mcg: Peto Odds Ratio = 0.98, 95% CI: 0.64, 1.52). REVIEWER'S CONCLUSIONS: Treatment of patients with COPD with long acting beta2-agonists produces only small increases in FEV1. In one study, a dose of salmeterol 50 mcg twice daily produced a reduction in breathlessness and a clinically significant improvement in quality of life. (ABSTRACT TRUNCATED)

Adrenergic beta-Agonists↗
PubMed1997

Induction of caspase-3 protease activity and apoptosis by butyrate and trichostatin A (inhibitors of histone deacetylase): dependence on protein synthesis and synergy with a mitochondrial/cytochrome c-dependent pathway.

The induction of apoptosis of tumor cells by the colonic fermentation product butyrate is thought to be an important mechanism in protection against colorectal cancer. Because a major action of butyrate is to inhibit histone deacetylase (leading to chromatin relaxation and altered gene expression), butyrate may induce apoptosis by derepression of specific cell death genes. Here we show that butyrate and trichostatin A (a more selective inhibitor of histone deacetylase) induce the same program of apoptosis in Jurkat lymphoid and LIM 1215 colorectal cancer cell lines that is strictly dependent on new protein synthesis (within 10 h) and that leads to the conversion of the proenzyme form of caspase-3 to the catalytically active effector protease (within 16 h) and apoptotic death (within 24 h). Cells primed with a low concentration of butyrate that itself did not induce activation of caspase-3 or apoptosis were, nevertheless, rendered highly susceptible to induction of apoptosis by staurosporine (an agent that has recently been shown to act by causing mitochondrial release of cytochrome c). Synergy between butyrate and staurosporine was due to the presence of a factor in the cytosol of butyrate-primed cells which enhanced over 7-fold the activation of caspase-3 induced by the addition of cytochrome c and dATP to isolated cytosol. We propose that changes at the level of chromatin structure, induced by a physiological substance butyrate, lead to the expression of a protein that facilitates the pathway by which mitochondria activate caspase-3 and trigger apoptotic death of lymphoid and colorectal cancer cells.

Apoptosis↗
PubMed1995

Genetic and biochemical normalization in female carriers of Duchenne muscular dystrophy: evidence for failure of dystrophin production in dystrophin-competent myonuclei.

We studied 19 symptomatic female carriers of the Duchenne muscular dystrophy (DMD) gene. Most of these dystrophinopathy patients had had an erroneous or ambiguous diagnosis prior to dystrophin immunofluorescence testing. We assessed clinical severity by a standardized protocol, measured X-chromosome inactivation patterns in blood and muscle DNA, and quantitated the dystrophin protein content of muscle. We found that patients could be separated into two groups: those showing equal numbers of normal and mutant dystrophin genes in peripheral blood DNA ("random" X-inactivation), and those showing preferential use of the mutant dystrophin gene ("skewed" X-inactivation). In the random X-inactivation carriers, the clinical phenotype ranged from asymptomatic to mild disability, the dystrophin content of muscle was > 60% of normal, and there were only minor histopathologic changes. In the skewed X-inactivation patients, clinical manifestations ranged from mild to severe, but the patients with mild disease were young (5 to 10 years old). The low levels of dystrophin (< 30% on average) and the severe symptoms of the older patients suggested a poor prognosis for those with skewed X-inactivation, and they all showed morphologic changes of dystrophy. The random inactivation patients showed evidence of biochemical "normalization," with higher dystrophin content in muscle than predicted by the number of normal dystrophin genes. Seventy-nine percent of skewed X-inactivation patients (11/14) showed genetic "normalization," with proportionally more dystrophin-positive nuclei in muscle than in blood. In 65% of the skewed X-inactivation patients, dystrophin was not produced by dystrophin-positive nuclei; an average of 20% of myofiber nuclei were genetically dystrophin-positive but did not produce stable dystrophin. Biochemical normalization seems to be the main mechanism for rescue of fibers from dystrophin deficiency in the random X-inactivation patients. In the skewed X-inactivation patients, genetic normalization is active, but production failure of dystrophin by dystrophin-normal nuclei may counteract any effect of biochemical normalization. In the skewed X-inactivation patients, the remodeling of the muscle through cycles of degeneration and regeneration led to threefold increase in the number of dystrophin-competent nuclei in muscle myofibers (3.3 +/- 4.6), while dystrophin content was on the average 1.5-fold less then expected (-1.54 +/- 3.38). Our results permit more accurate prognistic assessment of isolated female dystrophinopathy patients and provide important data with which to estimate the potential effect of gene delivery (gene therapy) in DMD.

Adult↗
PubMed1987

Hemodynamic effects of hydralazine in infants with idiopathic dilated cardiomyopathy and congestive heart failure.

We evaluated the acute hemodynamic responses to hydralazine during cardiac catheterization in 13 infants with idiopathic dilated cardiomyopathy. Ages ranged from 2 to 13 months (6.7 +/- 4.0 months, mean +/- SD). Each infant had congestive heart failure and angiographic evidence of markedly depressed left ventricular ejection fraction (0.24 +/- 0.11; normal = 0.58-0.78) with left ventricular dilation (left ventricular end-diastolic volume = 349 +/- 125% of normal). Hydralazine (0.5 to 1.0 mg/kg administered intravenously) acutely decreased systemic arteriolar resistance from 21.1 +/- 3.3 to 12.0 +/- 2.7 U/m2 (p less than 0.001). This 41 +/- 14% decrease in systemic resistance was accompanied by a 45 +/- 16% increase in cardiac index (3.24 +/- 0.53 to 4.71 +/- 0.99 L/min/m2; p less than 0.001). Mean arterial blood pressure declined from 70 +/- 8 to 60 +/- 11 mm Hg (p less than 0.001). Hydralazine also increased heart rate (122 +/- 19 to 138 +/- 18 bpm; p less than 0.001), but this increase did not account entirely for the change in cardiac index as evidenced by a rise in stroke volume index (26.9 +/- 4.9 to 34.5 +/- 7.5 ml/beat/m2; p less than 0.001). Pulmonary arteriolar resistance and pulmonary capillary wedge pressure fell slightly in response to hydralazine. Subsequently, oral hydralazine was included in the treatment regimen of 10 infants followed for 3 to 38 months (mean = 15 months). Of these, eight demonstrated sustained clinical improvement. We conclude that hydralazine may be a beneficial adjunct to the management of congestive heart failure in young infants with a dilated cardiomyopathy.

Angiography↗
PubMed1985

Improved right ventricular function after intra-atrial repair of transposition of the great arteries.

Current interest in the arterial switch operation for simple transposition of the great arteries (TGA) has led us to evaluate our latest patients who have undergone intra-atrial repair. Right ventricular function and overall results were compared in 32 patients who had undergone the Senning procedure between 1978 and 1983 and 26 patients who had undergone Mustard repair between 1971 and 1978). Deep hypothermia and circulatory arrest were used in all Senning operations and in 18 of 26 Mustard procedures. Cardiac catheterization was performed an average of 1 year after surgery in all patients. Postoperative right ventricular ejection fraction (EF) was below normal (less than 0.49) in 16 of 32 patients who underwent the Senning procedure and averaged 0.48 +/- 0.09. In the patients in this group with abnormal right ventricular EFs after repair there was a fall in the value after surgery (0.51 to 0.40, p less than .001), while in those with normal right ventricular EFs after repair there was no change (0.57 to 0.55, NS). All 32 patients who underwent the Senning procedure were compared with 26 patients who underwent the Mustard operation (13 treated between 1971 and 1974 and 13 treated between 1975 and 1978). An older age at surgery (12 +/- 7 vs 6 +/- 8 months, p less than .006) and a lower preoperative right ventricular EF (0.46 +/- 0.09 vs 0.54 +/- 0.08, p less than .007) characterized the Mustard vs the Senning group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMedDate not supplied

Psychosocial effects of living with an increased risk of breast cancer: an exploratory study using telephone focus groups.

Research to date has mainly focused on the short-term psychological impact of genetic risk counselling for breast cancer. This study aimed to explore the long-term consequences for women of being informed about an increased risk of breast cancer in terms of: the effect on their everyday lives, their coping strategies and their unmet needs in terms of the current service. The participants were 25 women with a family history of breast cancer who had received genetic risk counselling and had consequently been receiving clinical surveillance for at least 2 years. They took part in one of seven telephone focus groups and subsequently completed a feedback questionnaire. Transcripts of the focus groups were qualitatively analysed by three independent researchers with inter-rater agreement between pairs of raters ranging from Kappa = 0.61-0.79. Six key issues emerged from the data, which provide an important insight into the long-term consequences of living with an increased risk of breast cancer concerning: (1) psychological adaptation, (2) behavioural adaptation, (3) family issues, (4) clinical surveillance, (5) provision of information, and (6) peer support. These findings, together with the quantitative results of the feedback questionnaire, have clinical implications that require further investigation in larger scale quantitative research.

Adaptation, Psychological↗