PURPOSE: Pulmonary hypertension can occur in patients who have disorders associated with altered platelet serotonin storage, including collagen vascular disease and platelet storage pool disease. We tested the hypothesis that primary pulmonary hypertension (PPH) may be also associated with impaired handling of serotonin by platelets, resulting in increased plasma serotonin levels. PATIENTS AND METHODS: We used radioenzymatic assays to measure serotonin in platelets and plasma and serotonin released during in vitro platelet aggregation in 16 patients with PPH, and in 16 normal controls matched for age and sex. Six patients were restudied after heart-lung transplantation to determine whether serotonin abnormalities persisted after pulmonary arterial pressure returned to normal. RESULTS: Patients had decreased platelet serotonin concentration (1.8 +/- 0.6 x 10(-18) mol/ platelet versus 3.2 +/- 0.2 X 10(-18) mol/platelet in controls; P <0.01) and increased plasma serotonin concentration (30.1 +/- 9.2 x 10(-9) mol/L versus 0.6 +/- 0.1 x 10(-9) mol/L in controls; P <0.001). Serotonin released during in vitro platelet aggregation was higher in patients than in controls. After heart-lung transplantation, platelet serotonin concentrations remained decreased and plasma levels remained increased. CONCLUSIONS: Abnormal handling of serotonin by platelets leading to an increase in plasma serotonin occurs in PPH. The persistent decrease in platelet storage of serotonin after heart-lung transplantation suggests that this platelet abnormality is not secondary to PPH.
BackgroundInterest in monitoring health-related quality of life (HRQoL) in general populations has increased in the past 20 years, reinforced by population ageing and repeated economic crises. This study aims to identify temporal trends in HRQoL in France between 1995 and 2016 and to assess disparities according to demographic and socioeconomic characteristics.MethodsData from repeated population-based cross-sectional surveys conducted in 1995, 2003 and 2016 were used. HRQoL was measured using the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire.ResultsA substantial decrease in score was observed between 1995 and 2016 for both genders in almost all subscales of the SF-36, with the largest decrease being in the mental health dimension for men. However, the age group 18–54 years were the most affected with persistent negative or even worsening trends in HRQoL. The largest decreases were among men aged 45–54 years and women aged 35–44 years in most dimensions, and among the age group 18–24 years in vitality. Conversely, an overall improvement was noted among the age group 65–84 years. People in employment were more affected than the unemployed by the decline in several HRQoL dimensions.ConclusionA general decline in HRQoL was found between 1995 and 2016 in the French population, but with wide disparities in trends between age groups. Young and especially middle-aged, employed people exhibited persistent negative and worsening trends. Consistent with evidence from traditional mental health morbidity and mortality indicators, our findings raise questions about the potential influence of macro-socioeconomic factors, especially the 2008 crisis; these observations deserve special attention from health policy-makers.,An 18 year old man and his mother both presented with persistent, isolated raised serum creatine kinase (hyperCKaemia) without muscle symptoms. Analysis of caveolin-3 protein expression in muscle biopsy of the propositus showed a reduction in the protein. Genetic analysis revealed a new heterozygous mutation in the caveolin-3 (CAV-3) gene: a C→T transition at nucleotide position 83 in exon 1 leading to a substitution of a proline for a leucine at amino acid position 28 (P28L). This is the first pathogenic mutation in the CAV-3 gene associated with isolated familial hyperCKaemia. It expands the genetic heterogeneity in patients with caveolin-3 deficiency and confirms that caveolin-3 deficiency should be considered in the differential diagnosis of isolated hyperCKaemia.,OBJECTIVETo assess the effect of inhaled nitric oxide (NO) on severe postoperative pulmonary hypertension in children after surgical repair of a congenital heart defect. DESIGNA pilot study of NO administration to 7 consecutive children who required adrenergic support and in whom postoperative mean pulmonary artery pressure was more than two thirds of mean systemic pressure and persisted despite alkalotic hyperventilation. SETTINGRoutine care after cardiac surgery for congenital heart disease in a multidisciplinary paediatric intensive care unit. METHODSContinuous inhalation of NO, initially at 15 ppm. Therefore, daily attempts at complete weaning or at reducing NO to the lowest effective dose. RESULTSIn 6 of the 7 children NO inhalation selectively decreased mean (SD) pulmonary artery pressure from 51 (12) to 31 (9) mm Hg (P < 0.05) while mean systemic arterial pressure was unchanged (68 (10) v 71 (7) mm Hg) (NS) and the arteriovenous difference in oxygen content decreased from 6.7 (0.9) to 4.8 (0.8) vol% (P < 0.05). Concomitantly PaO2 increased from 158 (98) to 231 (79) mm Hg) (P < 0.05). The seventh child showed no response to NO up to 80 ppm, could not be weaned from cardiopulmonary bypass, and died in the operating room. In responders, attempts at early weaning from NO inhalation always failed and NO at concentrations of less than 10 ppm was continuously administered for a median of 9.5 days (range 4 to 16 days) until complete weaning was possible from a mean dose of 3.9 (2.9) ppm. Methaemoglobinaemia remained below 2% and nitrogen dioxide concentrations usually ranged from 0.1 to 0.2 ppm. One child later died and five were discharged. A few months after surgery Doppler echocardiography (and catheterisation in one) showed evidence of regression of pulmonary hypertension in all 5. CONCLUSIONSInhalation of NO reduced pulmonary artery pressure in children with severe pulmonary hypertension after cardiac surgery and this effect was maintained over several days at concentrations carrying little risk of toxicity.
Pulmonary hypertension is generally characterized by increased thickening of the walls of pulmonary arteries, narrowing of the pulmonary-artery lumen, increased pulmonary vascular resistance, and right-sided heart failure. 1 – 3 Clinically, patients have increasing dyspnea, cyanosis, precordial discomfort, anginal pain, and cardiomegaly. 1 – 3 Histologically, pulmonary arteries with such resistance, particularly those less than 100 μm in diameter, show various degrees of intimal thickening and muscular hypertrophy. 1 , 4 , 5 Pulmonary hypertension can be either idiopathic (primary) or due to other disease conditions. A number of humoral factors have been implicated in the pathogenesis of pulmonary hypertension, but there is no evidence that any . . .
An outstanding feature of the study of nursing ethics is that it raises questions concerning moral virtue, conscience, consistency and character. A considerable section of the literature is devoted to ideas of how best to teach ethics to health professionals. It has been shown that when faced with ethical dilemmas nurses tended to rely on intuition and instinct to resolve them, with little systematic analysis to help the process. Nurses who have been in practice for a number of years may experience particular difficulties in resolving ethical dilemmas, for although they may be able easily to identify ethical problems they may feel powerless to behave appropriately through lack of theoretical background and/or confidence in participating in informed debate. An educational programme was designed to meet the needs of mature registered nurses who were undertaking a post-qualification part-time honours degree in nursing studies. A variety of teaching methods were employed in teaching the nurses. These included discussion, student-led seminars, structured debate and role play. A session which dealt with sudden death and organ donation is described in some detail. Because the topic involved communication between professionals and patients and/or relatives and was linked with ethics, role play was used to explore the dynamics in these areas. The participants were invited to act out the situation as they felt it might occur. Role play highlighted the stress and shock attached to such an experience. Before working through the dynamics of a situation the nurses were conscious of being part of decision-making 'in the cold' and 'in isolation'. As a result of the experiential learning they felt more able to reflect analytically and to participate in discussions in an informed and articulate way.,BONE tumours in the dog and cat are usually malignant and, although they display a spectrum of behaviour, many are very aggressive. Middle-aged to older animals are generally affected. Tumours may arise from any of the tissues comprising the bone, including the periosteum, endosteum or medullary cavity. In addition, tumours arising in adjacent soft tissues may invade bone directly, and tumours may metastasise to bone from distant sites. This article discusses the management of tumours of the appendicular skeleton in the dog and cat.
This study sought to determine whether neurohormonal activation occurs in isolated right heart failure. Neurohormonal activation appears to parallel the severity of left heart failure, but little is known about its role in right heart failure. We evaluated neurohormonal activation and endothelin levels in 21 patients with primary pulmonary hypertension at the time of right heart catheterization. Plasma norepinephrine levels correlated significantly with pulmonary artery pressure (r = 0.66, p < 0.01), cardiac index (r = −0.56, p < 0.01) and pulmonary vascular resistance (r = 0.69, p < 0.001). Atrial natriuretic peptide levels were higher in the pulmonary artery than the right atrium and femoral artery and correlated closely with pulmonary artery oxygen saturation (r = −0. 73, p < 0.0001). Plasma renin levels were not elevated. Endothelin levels were increased and correlated with right atrial pressure (r = 0.74, p < 0.0001) and pulmonary artery oxygen saturation (r = −0.070, p < 0.0004). Neurohormonal activation occurs in patients with isolated right ventricular failure and inherently normal left ventricles and appears to be related to the overall severity of cardiopulmonary derangements. The elevation in endothelin levels is consistent with its release in response to pulmonary hypertension.
. This study characterized mortality in a group of Mexican children (n = 18, mean [±SD] age 9.9 ± 3 years) with primary pulmonary hypertension and investigated the factors associated with their survival. . Primary pulmonary hypertension is a progressive, fatal disease of unknown cause. Establishing the diagnosis earlier in life may influence prognosis. . A dynamic cohort of children with primary pulmonary hypertension were enrolled between December 1977 and May 1991 and followed up through September 1992. Measurements included hemodynamic and pulmonary function variables in addition to demographic data, medical history and response to vasodilator treatment. We also compared the survival estimates of these children with those of our adult patients with primary pulmonary hypertension (n = 42, mean age 27.9 ± 8.5 years). . Baseline mean (±SD) pulmonary artery pressure was similar in children and adults (66 ± 15 vs. 65 ± 18 mm Hg, p = NS), but a higher cardiac index resulted in a lower mean pulmonary vasclar resistance index in children (18 ± 7 vs. 26 ± 12 U/m , p < 0.01). The proportion of patients who had a positive hemodynamic response to vasodilator treatment was higher in children than in adults (41% vs. 25%). Estimated median survival in children was 4.12 years (95% confidence interval [Cl], 0.75 to 8.66) and 3.12 years in adults (95% CI 0.5 to 13.25, chi-square log-rank 0.81, p = NS). Elevated right atrial pressure (rate ratio 10.2) and decreased stroke volume index (rate ratio 32.9) were the only significant predictors of mortality (Cox proportional hazards model). . Children with primary pulmonary hypertension have a poor survival expectancy, which does not appear to differ from that in adults with primary pulmonary hypertension. Mortality in childhood primary pulmonary hypertension is also associated with variables that assess right ventricular dysfunction.
The purpose of this study was to determine the prevalence and progression of pulmonary hypertension over a 5-year follow-up period in 28 patients with systemic lupus erythematosus (SLE) who were originally enrolled in an echocardiographic study of pulmonary hypertension in 1985 and 1986. Twenty healthy volunteers without cardiac or pulmonary disease participated as normal controls. Each patient and control underwent a complete Doppler echocardiographic study. Doppler echocardiographic recordings of tricuspid insufficiency, with saline contrast enhancement when necessary, were used to calculate pulmonary artery systolic pressure according to the modified Bernoulli equation. Doppler echocardiographic measurement of cardiac output was performed at rest for each subject, and pulmonary resistance was calculated by dividing the pulmonary artery systolic pressure by the cardiac output. These results were compared to results of the original studies to detect serial changes in pulmonary pressure and pulmonary resistance; results were also compared to the group of normal controls. The prevalence of pulmonary hypertension increased from 14% at the first study to 43% at follow-up. A significant increase in mean systolic pulmonary artery pressure was detected in the SLE patients during the follow-up period: 23.4 vs 27.5 mm Hg (p < 0.005). In addition, a significantly higher pulmonary artery pressure was detected in the SLE patients compared with the normal controls (p < 0.005). An increase in pulmonary resistance during the follow-up period was detected for the SLE group as a whole (p < 0.001) and for the subgroup of patients with pulmonary hypertension at the second study (p < 0.001), implying that the mechanism for pulmonary hypertension was an increase in pulmonary vascular resistance. In conclusion, pulmonary hypertension is common in SLE, is gradually progressive over time, and is related to an increase in pulmonary resistance.
Primary pulmonary hypertension (PPH) is a rare disease of unknown etiology characterized by a constant progression toward right ventricular failure and death. Vasoconstriction is 1 of the pathophysiologic factors responsible for the increase of pulmonary vascular resistance (PVR) and pulmonary artery pressure (PAP) in patients with PPH. Thus vasodilator treatment is considered 1 of the logical approaches to medical therapy of such a condition. Acute drug challenge with a short-acting, titratable vasodilator during heart catheterization is recommended to select patients who are most likely to respond to longterm treatment. Accurate methodologic guidelines need to be followed to minimize the spontaneous variability of PAP and pulmonary arteriolar resistance. Pathophysiologic interpretation of pharmacologic trials requires analysis of the 2 components of the right ventricular hydraulic toad, i.e., resistance and compliance of the pulmonary vascular bed. Reduction of the calculated PVR may be considered as a demonstration of pulmonary vasodilation only if PVR is assessed using the critical opening pressure or if it is associated with a simultaneous reduction of PAP. Only those patients in whom a reduction of PVR of greater than or equal to 20% is associated with a decrease in PAP of greater than or equal to 20% should be considered as ''responders'' to the acute tests. In clinical studies only 20-30% of the patients are short-term responders. The most intensively studied short-acting drug for shortterm challenge is prostacyclin, but other agents such as acetylcholine, adenosine, and nitric oxide have been utilized. Prostacyclin has been shown to predict pulmonary vasodilator response