Alterations in vasomotor control of coronary resistance vessels in remodelled myocardium of swine with a recent myocardial infarction

The mechanism underlying the progressive deterioration of left ventricular (LV) dysfunction after myocardial infarction (MI) towards overt heart failure remains incompletely understood, but may involve impairments in coronary blood flow regulation within remodelled myocardium leading to intermittent myocardial ischemia. Blood flow to the remodelled myocardium is hampered as the coronary vasculature does not grow commensurate with the increase in LV mass and because extravascular compression of the coronary vasculature is increased. In addition to these factors, an increase in coronary vasomotor tone, secondary to neurohumoral activation and endothelial dysfunction, could also contribute to the impaired myocardial oxygen supply. Consequently, we explored, in a series of studies, the alterations in regulation of coronary resistance vessel tone in remodelled myocardium of swine with a 2 to 3-week-old MI. These studies indicate that myocardial oxygen balance is perturbed in remodelled myocardium, thereby forcing the myocardium to increase its oxygen extraction. These perturbations do not appear to be the result of blunted β-adrenergic or endothelial NO-mediated coronary vasodilator influences, and are opposed by an increased vasodilator influence through opening of KATP channels. Unexpectedly, we observed that despite increased circulating levels of noradrenaline, angiotensin II and endothelin-1, α-adrenergic tone remained negligible, while the coronary vasoconstrictor influences of endogenous endothelin and angiotensin II were virtually abolished. We conclude that, early after MI, perturbations in myocardial oxygen balance are observed in remodelled myocardium. However, adaptive alterations in coronary resistance vessel control, consisting of increased vasodilator influences in conjunction with blunted vasoconstrictor influences, act to minimize the impairments of myocardial oxygen balance

A Prospective Comparison of Younger and Older Patients' Preferences for Adjuvant Chemotherapy and Hormonal Therapy in Early Breast Cancer

AbstractBackgroundIt is unknown what minimal benefit in disease-free survival older patients with breast cancer require from adjuvant systemic therapy, and if this differs from that required by younger patients. We prospectively examined patients' preferences for adjuvant chemotherapy (aCT) and adjuvant hormonal therapy (aHT), factors related to minimally-required benefit, and patients' self-reported motivations.Patients and MethodsFifty-two younger (40-64 years) and 29 older (≥ 65 years) women with a first primary, invasive tumor were interviewed post-surgery, prior to receiving aCT/aHT recommendation.ResultsThe proportions of younger versus older participants who would accept, refuse, or were undecided about therapy were 92% versus 62%, 4% versus 24%, and 4% versus 14% for aCT, and 92% versus 59%, 8% versus 17%, and 0% versus 24% for aHT. The proportion of older participants who would refuse rather than accept aCT was larger than that of younger participants (P = .005). No significant difference was found for aHT (P = .12). Younger and older participants' minimally-required benefit, in terms of additional 10-year disease-free survival, to accept aCT (median, 5% vs. 4%; P = .13) or aHT (median, 10% vs. 8%; P = .15) did not differ. Being single/divorced/widowed (odds ratio [OR], 0.16; P = .005), presence of geriatric condition (inability to perform daily activities, incontinence, severe sensory impairment, depression, polypharmacy, difficulties with walking; OR, 0.27; P = .047), and having a preference to make the treatment decision either alone or after considering the clinician's opinion (active role; OR, 0.15; P = .012) were independently related to requiring larger benefits from aCT. The most frequent motivations for/against therapy included the wish to survive/avoid recurrence, clinician's recommendation, side effects, and treatment duration (only aHT).ConclusionWhereas older participants were less willing to accept aCT than younger participants, no significant difference was found for aHT. However, a majority of older participants would still accept both therapies. Adjuvant systemic therapy should be discussed with eligible patients regardless of age

Gut-directed hypnotherapy in children with irritable bowel syndrome or functional abdominal pain (syndrome): A randomized controlled trial on self exercises at home using CD versus individual therapy by qualified therapists

Background: Irritable bowel syndrome (IBS) and functional abdominal pain (syndrome) (FAP(S)) are common pediatric disorders, characterized by chronic or recurrent abdominal pain. Treatment is challenging, especially in children with persisting symptoms. Gut-directed hypnotherapy (HT) performed by a therapist has been shown to be effective in these children, but is still unavailable to many children due to costs, a lack of qualified child-hypnotherapists and because it requires a significant investment of time by child and parent(s). Home-based hypnotherapy by means of exercises on CD has been shown effective as well, and has potential benefits, such as lower costs and less time investment. The aim of this randomized controlled trial (RCT) is to compare cost-effectiveness of individual HT performed by a qualified therapist with HT by means of CD recorded self-exercises at home in children with IBS or FAP(S).Methods/Design: 260 children, aged 8-18 years with IBS or FAP(S) according to Rome III criteria are included in this currently conducted RCT with a follow-up period of one year. Children are randomized to either 6 sessions of individual HT given by a qualified therapist over a 3-month period or HT through self-exercises at home with CD for 3 months.The primary outcome is the proportion of patients in which treatment is successful at the end of treatment and after one year follow-up. Treatment success is defined as at least 50% reduction in both abdominal pain frequency and intensity scores. Secondary outcomes include adequate relief, cost-effectiveness an

Model prediction of subendocardial perfusion of the coronary circulation in the presence of an epicardial coronary artery stenosis

The subendocardium is most vulnerable to ischemia, which is ameliorated by relaxation during diastole and increased coronary pressure. Recent clinical techniques permit the measuring of subendocardial perfusion and it is therefore important to gain insight into how measurements depend on perfusion conditions of the heart. Using data from microsphere experiments a layered model of the myocardial wall was developed. Myocardial perfusion distribution during hyperemia was predicted for different degrees of coronary stenosis and at different levels of Diastolic Time Fraction (DTF). At the reference DTF, perfusion was rather evenly distributed over the layers and the effect of the stenosis was homogenous. However, at shorter or longer DTF, the subendocardium was the first or last to suffer from shortage of perfusion. It is therefore concluded that the possible occurrence of subendocardial ischemia at exercise is underestimated when heart rate is increased and DTF is lower

Primary retroperitoneal mucinous cystadenoma with sarcoma-like mural nodule: A case report and review of the literature

Primary retroperitoneal cystadenomas are extremely rare. This is the first report in literature to describe a primary retroperitoneal cystadenoma with a sarcoma-like mural nodule. A 45-year-old woman complained of a left-sided abdominal mass. A computed tomography scan revealed a cystic mass with a mural nodule, which seemed to originate from the tail of the pancreas. At laparotomy the cyst was not adhered to the pancreas but localized retroperitoneally. Histologic examination showed a mucinous cystadenoma with only foci of borderline malignancy with a mural “sarcoma-like” nodule. In view of the surgical and histopathological findings, the mucinous cystadenoma was regarded as primary retroperitoneal. This case demonstrates that in the era of radiological preoperative refinement, pathological diagnosis remains of utmost importance, especially for rare cases

A population-based nested case control study on recurrent pneumonias in children with severe generalized cerebral palsy: ethical considerations of the design and representativeness of the study sample

BACKGROUND: In children with severe generalized cerebral palsy, pneumonias are a major health issue. Malnutrition, dysphagia, gastro-oesophageal reflux, impaired respiratory function and constipation are hypothesized risk factors. Still, no data are available on the relative contribution of these possible risk factors in the described population. This paper describes the initiation of a study in 194 children with severe generalized cerebral palsy, on the prevalence and on the impact of these hypothesized risk factors of recurrent pneumonias. METHODS/DESIGN: A nested case-control design with 18 months follow-up was chosen. Dysphagia, respiratory function and constipation will be assessed at baseline, malnutrition and gastro-oesophageal reflux at the end of the follow-up. The study population consists of a representative population sample of children with severe generalized cerebral palsy. Inclusion was done through care-centres in a predefined geographical area and not through hospitals. All measurements will be done on-site which sets high demands on all measurements. If these demands were not met in "gold standard" methods, other methods were chosen. Although the inclusion period was prolonged, the desired sample size of 300 children was not met. With a consent rate of 33%, nearly 10% of all eligible children in The Netherlands are included (n = 194). The study population is subtly different from the non-participants with regard to severity of dysphagia and prevalence rates of pneumonias and gastro-oesophageal reflux. DISCUSSION: Ethical issues complicated the study design. Assessment of malnutrition and gastro-oesophageal reflux at baseline was considered unethical, since these conditions can be easily treated. Therefore, we postponed these diagnostics until the end of the follow-up. In order to include a representative sample, all eligible children in a predefined geographical area had to be contacted. To increase the consent rate, on-site measurements are of first choice, but timely inclusion is jeopardized. The initiation of this first study among children with severe neurological impairment led to specific, unexpected problems. Despite small differences between participants and non-participating children, our sample is as representative as can be expected from any population-based study and will provide important, new information to bring us further towards effective interventions to prevent pneumonias in this population

Pre-dialysis patients' perceived autonomy, self-esteem and labor participation: associations with illness perceptions and treatment perceptions. A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Compared to healthy people, patients with chronic kidney disease (CKD) participate less in paid jobs and social activities. The aim of the study was to examine a) the perceived autonomy, self-esteem and labor participation of patients in the pre-dialysis phase, b) pre-dialysis patients' illness perceptions and treatment perceptions, and c) the association of these perceptions with autonomy, self-esteem and labor participation.</p> <p>Methods</p> <p>Patients (N = 109) completed questionnaires at home. Data were analysed using bivariate and multivariate analyses.</p> <p>Results</p> <p>The results showed that the average autonomy levels were not very high, but the average level of self-esteem was rather high, and that drop out of the labor market already occurs during the pre-dialysis phase. Positive illness and treatment beliefs were associated with higher autonomy and self-esteem levels, but not with employment. Multiple regression analyses revealed that illness and treatment perceptions explained a substantial amount of variance in autonomy (17%) and self-esteem (26%). The perception of less treatment disruption was an important predictor.</p> <p>Conclusions</p> <p>Patient education on possibilities to combine CKD and its treatment with activities, including paid work, might stimulate positive (realistic) beliefs and prevent or challenge negative beliefs. Interventions focusing on these aspects may assist patients to adjust to CKD, and ultimately prevent unnecessary drop out of the labor market.</p

Chronic Kidney Disease as a Risk Factor for Heart Failure With Preserved Ejection Fraction

Heart failure (HF) and chronic kidney disease (CKD) co-exist, and it is estimated that about 50% of HF patients suffer from CKD. Although studies have been performed on the association betwee

Lung diffusing capacity for nitric oxide and carbon monoxide in relation to morphological changes as assessed by computed tomography in patients with cystic fibrosis

Background Due to large-scale destruction, changes in membrane diffusion (Dm) may occur in cystic fibrosis (CF), in correspondence to alterations observed by computed tomography (CT). Dm can be easily quantified via the diffusing capacity for nitric oxide (DLNO), as opposed to the conventional diffusing capacity for carbon monoxide (DLCO). We thus studied the relationship between DLNO as well as DLCO and a CF-specific CT score in patients with stable CF. Methods Simultaneous single-breath determinations of DLNO and DLCO were performed in 21 CF patients (mean ± SD age 35 ± 9 y, FEV1 66 ± 28%pred). Patients also underwent spirometry and bodyplethysmography. CT scans were evaluated via the Brody score and rank correlations (rS) with z-scores of functional measures were computed. Results CT scores correlated best with DLNO (rS = -0.83; p < 0.001). Scores were also related to the volume-specific NO transfer coefficient (KNO; rS = -0.63; p < 0.01) and to DLCO (rS = -0.79; p < 0.001) but not KCO. Z-scores for DLNO were significantly lower than for DLCO (p < 0.001). Correlations with spirometric (e.g., FEV1, IVC) or bodyplethysmographic (e.g., SRaw, RV/TLC) indices were weaker than for DLNO or DLCO but most of them were also significant (p < 0.05 each). Conclusion In this cross sectional study in patients with CF, DLNO and DLCO reflected CT-morphological alterations of the lung better than other measures. Thus the combined diffusing capacity for NO and CO may play a future role for the non-invasive, functional assessment of structural alterations of the lung in CF

How about your peers? Cystic fibrosis questionnaire data from healthy children and adolescents

Contains fulltext : 97967.pdf (publisher's version ) (Open Access)BACKGROUND: The Cystic Fibrosis Questionnaire (CFQ) is widely used in research as an instrument to measure quality of life in patients with cystic fibrosis (CF). In routine patient care however, measuring quality of life is still not implemented in guidelines. One of the reasons might be the lack of consensus on how to interpret CFQ scores of an individual patient, because appropriate reference data are lacking. The question which scores reflect normal functioning and which scores reflect clinically relevant problems is still unanswered. Moreover, there is no knowledge about how healthy children and adolescents report on their quality of life (on the CFQ). With regard to quality of life the effect of normal development should be taken into account, especially in childhood and adolescence. Therefore, it is important to gain more knowledge about how healthy children and adolescents report on their quality of life and if there are any difference in a healthy populations based on age or gender. Without these data we cannot adequately interpret the CFQ as a tool in clinical care to provide patient-tailored care. Therefore this study collected data of the CFQ in healthy children and adolescents with the aim to refer health status of CF youngsters to that of healthy peers. METHODS: The CFQ was completed by 478 healthy Dutch children and adolescents (aged 6-20) in a cross-sectional study. RESULTS: The majority of healthy children (over 65%) did not reach maximum scores on most domains of the CFQ. Median CFQ-scores of healthy children and adolescents ranged from 67 to 100 (on a scale of 0-100) on the different CFQ-domains. Significant differences in quality of life exist among healthy children and adolescents, and these depend on age and gender. CONCLUSIONS: Reference data of quality of life scores from a healthy population are essential for adequate interpretation of quality of life in young patients with CF. Clinicians should be aware that the perception of health-related quality of life is not as disease-specific as one might think and also relies on factors such as age, normal maturation and gender