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Right ventricular (RV) ejection fraction (EF) by cardiac magnetic resonance (CMR) correlates to outcome in precapillary pulmonary hypertension (pPH) patients, but is insensitive to early changes. Strain might provide incremental information. In this study, we compare right atrial (RA) and RV strain in pPH patients to healthy controls, and evaluate the prognostic value of strain in pPH. In this cross-sectional study, 45 pPH patients and 20 healthy controls underwent CMR, and feature-tracking derived RA and RV strain were evaluated. pPH patients had impaired RA reservoir and conduit strain, and RV longitudinal strain (LS), compared to healthy controls. In pPH patients with preserved RVEF (≥ 50%, n = 18), RA reservoir (35% ± 9 vs. 41% ± 6, p = 0.02) and conduit strain (16% ± 8 vs. 23% ± 5, p = 0.004), and RV–LS (−25% ± 4 vs. −31% ± 4, p < 0.001) remained impaired, compared to healthy controls. The association of strain with the primary endpoint (combination of all-cause death, lung transplantation, and heart failure hospitalization) was evaluated using a multivariable Cox regression model. RV–LS (HR 1.18, 95%–CI 1.04–1.34, p = 0.01) and RA strain (reservoir: HR 0.87, 95%–CI 0.80–0.94, p = 0.001; conduit: HR 0.85, 95%–CI 0.75–0.97, p = 0.02, booster: HR 0.81, 95%-CI 0.71–0.92, p = 0.001) were independent predictors of outcome, beyond clinical and imaging features. In conclusion, pPH patients have impaired RA strain and RV–LS, even when RVEF is preserved. In addition, RA strain and RV–LS were independent predictors of adverse prognosis. These results emphasize the incremental value of RA and RV strain analyses, to detect alterations in RV function, even before RVEF declines.

ABSTRACTIntroduction: Acanthamoebaspp. is a ubiquitous free-living amoeba that causes human infections affecting predominantly the cornea and central nervous system. The diagnosis and treatment of Acanthamoebaencephalitis is very challenging. Case summary: A 53-year-old male with HIV/AIDS was admitted for altered mental status and fever. On initial examination, he had left hemianopia with left-sided weakness and numbness. MRI revealed an inflammatory and enhancing parenchymal mass associated with leptomeningeal enhancement in the occipitoparietal lobe containing multiple punctate hemorrhages. He was treated with empiric antibiotics for presumptive toxoplasmosis, brain abscess, fungal infection and tuberculosis with an unremarkable lymphoma work up. Initial brain biopsy studies were unremarkable except for non-specific granulomas and adjacent necrotic tissue. The patient passed away 2.5 months after initial presentation with no diagnosis. Post-mortem testing by the Centers for Disease Control and Prevention (CDC) confirmed the diagnosis of granulomatous amoebic encephalitis (GAE) by visualization with immunohistochemistry staining and PCR. Recovery is rare from GAE likely due to delay in diagnosis. Conclusions: This case illustrates the importance of including GAE into the differential diagnosis of brain mass. We advocate early molecular testing of tissue specimen by the CDC to achieve an appropriate diagnosis, and a multidisciplinary approach for the management of this condition.

Cross-sectional study. To describe experienced sitting-related health and stability problems among persons with paraplegia (PP) or tetraplegia (TP) and to investigate associations with personal, lesion and wheelchair characteristics as well as satisfaction with sitting posture. Dutch community. A self-report questionnaire on seating was developed and completed by wheelchair-users living with Spinal Cord Injury (SCI) for ≥10 years (N= 264). Sitting-related problems and satisfaction with sitting posture were compared between participants with PP and TP using Chi-square and t-tests. Logistic regression analyses were performed to investigate associated characteristics. Reported sitting-related problems comprised: sitting to be tiring (regularly to always) (33%), sitting to be painful (28%), pressure ulcers in the last three months (29%), instability while sitting (8%) and instability during reaching (33%). Except for instability during reaching, no differences in occurrence of sitting-problems were found between lesion-group. Persons with TP were more dissatisfied with their sitting posture than persons with PP: 51% vs 36% (p= 0.022) and 51% and 47% respectively thought their sitting posture could be improved (p= 0.670). ‘Experienced lack of support in the wheelchair’ was associated with most sitting-problems. Pain and instability were associated with dissatisfaction with sitting posture. Sitting-related problems and dissatisfaction with sitting posture were frequently reported by persons with long-standing SCI. Sitting problems appeared to associate with lacking support in the wheelchair/seating. A comprehensive feedback from the wheelchair user and a stability check (reach task), as part of the wheelchair/seating-user fitting, may contribute to prevention of sitting-related problems.

Study design:The study design includes expert opinion, feedback, revisions and final consensus.Objectives:The objective of the study was to present the new knowledge obtained since the International Spinal Cord Injury (SCI) Core Data Set (Version 1.0) published in 2006, and describe the adjustments made in Version 2.0, including standardization of data reporting.Setting:International.Methods:Comments received from the SCI community were discussed in a working group (WG); suggestions from the WG were reviewed and revisions were made. All suggested revisions were considered, and a final version was circulated for final approval.Results:The International SCI Core Data Set (Version 2.0) consists of 25 variables. Changes made to this version include the deletion of one variable ‘Total Days Hospitalized’ and addition of two variables ‘Date of Rehabilitation Admission’ and ‘Date of Death.’ The variable ‘Injury Etiology’ was extended with six non-traumatic categories, and corresponding ‘Date of Injury’ for non-traumatic cases, was defined as the date of first physician visit for symptoms related to spinal cord dysfunction. A category reflecting transgender was added. A response category was added to the variable on utilization of ventilatory assistance to document the use of continuous positive airway pressure for sleep apnea. Other clarifications were made to the text. The reporting of the pediatric SCI population was updated as age groups 0–5, 6–12, 13–14, 15–17 and 18–21.Conclusion:Collection of the core data set should be a basic requirement of all studies of SCI to facilitate accurate descriptions of patient populations and comparison of results across published studies from around the world.

Objective:To describe the changes made to the international spinal cord injury (SCI) skin and thermoregulation function basic data set in version 1.1.Setting:International.Methods:An international working group reviewed suggested changes to the international SCI skin and thermoregulation function basic data set version 1.0. These changes were discussed and the agreed changes were made. Subsequently, the recommended adjustments were circulated for review to the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, the American Spinal Injury Association (ASIA) Board, around 40 national and international societies, and to interested individuals who had signed up wishing to have the opportunity to review. In addition, the suggested changes were displayed at the ISCoS and ASIA websites for at least a month for possible comments.Results:The recommendation ‘largest diameter, including undermining’ is changed to: ‘Largest undermining’, and a description of how to measure this is inserted. The ‘smallest opening diameter’ is changed to: ‘Width’ as the maximum dimension perpendicular to the length axis. In the literature, there is a tendency to replace ‘grades’ or ‘stages’ with ‘categories’; therefore, the word ‘category’ is used instead of ‘grade’ or ‘stage’.Conclusions:Impracticable measurements have been adjusted and new terminology adopted. All are to be found on ISCoS website: http://www.iscos.org.uk/international-sci-skin-and-thermoregulation-function-data-sets.

Study design:This is a multicenter prospective cohort study.Objectives:The objective of this study was to describe and compare the impact of health problems secondary to spinal cord injury (SCI) on functioning at home and on social activities at 1 and 5 years after discharge from first inpatient rehabilitation.Setting:The study was conducted in a Dutch community.Methods:Participants with SCI who use a wheelchair for everyday mobility (N=110) completed a self-report questionnaire as part of a larger cohort study including four items on extra time needed (body care, bladder and bowel regulation, ‘organization’ and transportation) and impact of 10 health problems on functioning at home and on social activities. The 10 health problems include secondary health conditions (bladder regulation, bowel regulation, decubitus, pain, spasticity, gain in body weight and edema), psychosocial problems (sexuality, having difficulty with being dependent on help from others) and handicap management.Results:Median extra time needed for self-management and transportation was not significantly higher 1 year after discharge (16 (IQR 13.5) h per week) compared with 5 years after discharge (13 (IQR 17) h per week) (P=0.925). Participants reported slightly less impact, comparing the severity sum-score (range 10–50) of the 10 health problems on functioning at home and in social activities, 5 years post discharge (20 and 17, respectively) than 1 year post discharge (21 and 18, respectively; P<0.05). Most frequently mentioned health problems were handicap management, being dependent on help from others, bladder regulation, bowel regulation, pain and sexuality.Conclusions:The impact of health problems after SCI is considerable and hardly diminishes over time. These results emphasize the need for structured long-term care for people with SCI.

Objectives:To study disability-management self-efficacy (DMSE) and its correlates in a large sample of Dutch people with long-standing spinal cord injury (SCI). DMSE is the confidence that people with SCI may have in their ability to manage the consequences of their condition with respect to the various domains in their life. Research questions were: (1) What is the level of DMSE in Dutch people with long-standing SCI?; (2) Is DMSE associated with demographic and lesion characteristics?; and (3) Is DMSE associated with participation and life satisfaction if these associations are adjusted for demographic and lesion characteristics and mood?Methods:Eligible people were identified from all eight rehabilitation centers with a specialty in SCI rehabilitation in the Netherlands (N=261). Data were collected using a self-report questionnaire. DMSE was measured using the University of Washington Self-Efficacy Scale–Short Form (UW-SES-6). Correlation and linear regression analyses were used.Results:Levels of UW-SES-6 scores were largely independent of demographic and lesion characteristics. UW-SES-6 scores were bivariately moderately to strongly associated with mood (0.47), participation (0.39–0.51) and life satisfaction (0.46). In the regression analyses, UW-SES-6 scores still explained a significant amount of variance of participation (standardized β 0.31–0.33) and life satisfaction (standardized β 0.21) when controlling for demographic and lesion characteristics and mood, and explained an additional 3.2–8.1% of the variance of participation and life satisfaction.Conclusion:DMSE is a psychological resource associated with higher levels of participation and life satisfaction after SCI. The UW-SES-6 is a brief and easy to use measure of this psychological resource.

Study design:Cross-sectional.Objectives:To compare differences in self-reported health status, participation and life satisfaction outcomes between adults with a spinal cord injury (SCI) sustained during paediatric (P) versus adulthood (A) years.Setting:Ontario, Canada.Methods:Secondary analysis of data from the Study of Health and Activity in People with SCI. Eighty-seven participants who sustained an SCI prior to age 19 (M±s.e.=25±1.5 years postinjury (YPI)) were matched for lesion level (C2–L5), severity (complete/incomplete), gender, age, education and ethnicity with 87 participants who sustained an SCI at ⩾age 19 years (MYPI=12.8±1.1).Results:Those with a paediatric SCI reported significantly less pain, fewer visits to the physician in the past year, greater functional independence, social participation, occupational participation and minutes per day of moderate-to-vigorous physical activity than those who sustained an SCI in adulthood. No significant differences were found for the measures of depression, perceived health status or life satisfaction (P>0.05). With the exception of moderate-to-vigorous physical activity and visits to the physician in the past year, between-group differences were independent of YPI.Conclusions:Regardless of time since injury, people who sustained a paediatric SCI reported better health and greater participation than those injured in adulthood. Nevertheless, both groups scored well below able-bodied normative values for all measures. The results highlight the importance of a comprehensive life-course approach to SCI rehabilitation, irrespective of age at the time of injury.

Study design:Explorative retrospective files study.Objectives:To document end-of-life decisions (ELDs) in in-hospital deaths after new traumatic spinal cord injury (TSCI).Setting:The Netherlands.Methods:Discharge letters concerning patients with TSCI discharged from Dutch acute hospitals in 2010 were analysed. Data were extracted on survival, personal and lesion characteristics, comorbidities, other injuries, preexisting spinal stenosis, stabilising surgery, length of hospital stay and the presence and types of ELDs. Characteristics of deceased patients and survivors were compared using χ2and T-tests. Characteristics of the deceased patients and ELDs were further explored.Results:A total of 185 patients with new TSCI were identified. Twenty-six patients were excluded as their survival status at discharge was unknown—for example, because of discharge to another hospital without information about their final discharge. Thirty of the remaining 159 patients died during their initial hospital stay (18.9%). Deceased patients were older and had more often high cervical and motor complete injuries than survivors. The circumstances of death were sparsely documented, and in nine cases, it was not possible to determine the absence or the presence of an ELD. ELDs were reported in 19 deaths (63.3%). All were non-treatment decisions, and almost all (89.5%) were decisions of withdrawal of treatment. There were no cases of documented euthanasia or physician-assisted suicide.Conclusion:ELDs were reported in the majority of in-hospital deaths after new TSCI in the Netherlands (63.3%), and all were non-treatment decisions.

The effect of haemodynamic monitoring of pulmonary artery pressure has predominantly been studied in the USA. There is a clear need for randomised trial data from patients treated with contemporary guideline-directed-medical-therapy with long-term follow-up in a different health-care system.

Study design:Follow-up measurement in a multicenter prospective cohort study.Objectives:To examine the prevalence of impaired respiratory function (pulmonary function and perceived respiratory function), the incidence of respiratory infection and the associations among these parameters in people with spinal cord injury (SCI) 5 years after initial inpatient rehabilitation. Second, we assessed associations between respiratory function and health-related quality of life (HRQOL).Setting:Eight rehabilitation centers with specialized SCI units in the Netherlands.Methods:Measurements were performed 5 years after discharge of inpatient rehabilitation. Pulmonary function was determined by forced vital capacity (FVC) and perceived respiratory function by self-reported cough strength and dyspnea. HRQOL was measured using the Sickness Impact Profile 68 and the 36-item Short Form Health Survey.Results:One-hundred forty-seven people with SCI participated. Of this sample, 30.9% had impaired FVC, 35.9% poor or moderate cough strength, 18.4% dyspnea at rest and 29.0% dyspnea during activity. In the year before the measurements, 8.9% had had respiratory infection. FVC was associated with cough strength, but not with dyspnea. All respiratory function parameters were associated with social functioning, whereas other HRQOL domains were associated with dyspnea only.Conclusion:Five years after initial inpatient rehabilitation, impaired respiratory function and respiratory infection were common in people with SCI. More severely impaired respiratory function was associated with lower HRQOL.Sponsorship:The Netherlands Organisation for Health Research and Development.

Study design:Prospective observational cohort study.Objectives:To describe time to occur and time until closure of hospital-acquired pressure ulcers (HAPUs) in patients with spinal cord injury (SCI).Setting:Specialised SCI acute care and rehabilitation clinic in Switzerland.Methods:Daily registration of the presence and severity of HAPUs in a consecutive sample of SCI patients during their entire in-patient stay.Results:Out of 185 observed SCI patients, 55 patients (29.7%) developed at least one HAPU. Within the first 30 days after admission, 50% of all HAPUs occurred. Less severe HAPUs occurred earlier than severe HAPUs. The occurrence of HAPUs was significantly associated with reason of admission (P<0.01), and was highest in first rehabilitation (51.4%) and orthopaedic surgery patients (41.4%). The incidences of first HAPU in these groups were 1.04 and 2.31 per patient-year, respectively. Patients in first rehabilitation or readmitted because of pressure ulcer (PU) showed an initial lower risk for HAPUs in the Kaplan–Meier curve compared with patients readmitted for other reasons. Cox regression analysis revealed an association between longer time since SCI and time until occurrence (P=0.01). Closure of the HAPUs during hospitalisation was observed in 37 patients (67.3%) after 38.9 days on average. No significant associations were found between patient characteristics and time until closure.Conclusion:The dynamics of HAPUs varied according to admission reason and time since lesion. However, ongoing awareness to prevent HAPUs is needed in all patients with SCI.

Study design:Consensus decision-making process.Objectives:The objective of this study was to develop an International Spinal Cord Injury (SCI) Activities and Participation (A&P) Basic Data Set.Setting:International working group.Methods:A committee of experts was established to select and define A&P data elements to be included in this data set. A draft data set was developed and posted on the International Spinal Cord Society (ISCoS) and American Spinal Injury Association websites and was also disseminated among appropriate organizations for review. Suggested revisions were considered, and a final version of the A&P Data Set was completed.Results:Consensus was reached to define A&P and to incorporate both performance and satisfaction ratings. Items that were considered core to each A&P domain were selected from two existing questionnaires. Four items measuring activities were selected from the Spinal Cord Independence Measure III to provide basic data on task execution in activities of daily living. Eight items were selected from the Craig Handicap Assessment and Reporting Technique to provide basic data on the frequency of participation. An additional rating of satisfaction on a three-point scale for each item completes the total of 24 A&P variables.Conclusion:Collection of the International SCI A&P Basic Data Set variables in all future research on SCI outcomes is advised to facilitate comparison of results across published studies from around the world. Additional standardised instruments to assess activities of daily living or participation can be administered, depending on the purpose of a particular study.

Study design:Pre-test and post-test designs with 14 participants. Measurements were taken at baseline (T1), immediately after the intervention (T2) and at 3-month follow-up (T3).Objectives:Psyfit is an online self-help program designed to enhance well-being in persons with depressed mood. We examined the feasibility of Psyfit in people with spinal cord injury (SCI).Setting:Community, the Netherlands.Methods:Participants chose two of the six Psyfit modules. The researcher maintained telephone contact with the participants. Feasibility was inferred from the completion rate of the modules and feedback from the participants. Outcome measures were the Mental Health Inventory-5, the Center for Epidemiological Studies Depression scale and the Warwick-Edinburgh Mental Well-Being Scale.Results:Overall, 75% of the first module and 39% of the second module were completed. Seven participants were considered as study completers and were included in the evaluation. They evaluated Psyfit as a useful program and helpful for persons with SCI. Several technical problems were reported that mainly concerned browser compatibility. An increase in mental health and nonsignificant change of well-being were found at the end of the intervention period, but these were not maintained at follow-up.Conclusion:Psyfit seems a potentially feasible program. However, adaptation to the SCI population and further study with a controlled design and utilizing a larger sample size are necessary before it can be recommended as part of SCI rehabilitation.

Study design:Cross-sectional validation study.Objectives:To examine the construct and concurrent validity of the International Spinal Cord Injury (SCI) Quality of Life (QoL) Basic Data Set.Setting:Dutch community.Participants:People 28–65 years of age, who obtained their SCI between 18 and 35 years of age, were at least 10 years post SCI and were wheelchair users in daily life.Measure(s):The International SCI QoL Basic Data Set consists of three single items on satisfaction with life as a whole, physical health and psychological health (0=complete dissatisfaction; 10=complete satisfaction). Reference measures were the Mental Health Inventory-5 and three items of the World Health Organization Quality of Life measure.Results:Data of 261 participants were available. Mean time after SCI was 24.1 years (s.d. 9.1); 90.4% had a traumatic SCI, 81.5% a motor complete SCI and 40% had tetraplegia. Mean age was 47.9 years (s.d. 8.8) and 73.2% were male. Mean scores were 6.9 (s.d. 1.9) for general QoL, 5.8 (s.d. 2.2) for physical health and 7.1 (s.d. 1.9) for psychological health. No floor or ceiling effects were found. Strong inter-correlations (0.48–0.71) were found between the items, and Cronbach’s alpha of the scale was good (0.81). Correlations with the reference measures showed the strongest correlations between the WHOQOL general satisfaction item and general QoL (0.64), the WHOQOL health and daily activities items and physical health (0.69 and 0.60) and the Mental Health Inventory-5 and psychological health (0.70).Conclusions:This first validity study of the International SCI QoL Basic Data Set shows that it appears valid for persons with SCI.

Chronic pulmonary thromboembolic disease is an important cause of severe pulmonary hypertension, and as such is associated with significant morbidity and mortality. The prognosis of this condition reflects the degree of associated right ventricular dysfunction, with predictable mortality related to the severity of the underlying pulmonary hypertension. Left untreated, the prognosis is poor. Pulmonary endarterectomy is the treatment of choice to relieve pulmonary artery obstruction in patients with chronic thromboembolic pulmonary hypertension and has been remarkably successful. Advances in surgical techniques along with the introduction of pulmonary hypertension-specific medication provide therapeutic options for the majority of patients afflicted with the disease. However, a substantial number of patients are not candidates for pulmonary endarterectomy due to either distal pulmonary vascular obstruction or significant comorbidities. Therefore, careful selection of surgical candidates in expert centres is paramount. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options.

Transcatheter embolisation is widely used to close pulmonary arteriovenous malformations (PAVMs) in patients with hereditary haemorrhagic telangiectasia (HHT). Data on the direct cardiovascular haemodynamic changes induced by this treatment are scarce. We investigated the direct haemodynamic effects of transcatheter embolisation of PAVMs, using non-invasive finger pressure measurements. During the procedure, blood pressure, heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and delta pressure/delta time (dP/dt) were continuously monitored using a Finometer®. Potential changes in these haemodynamic parameters were calculated from the pressure registrations using Modelflow® methodology. Absolute and relative changes were calculated and compared using the paired sample t-test. The present study includes 29 HHT patients (mean age 39 ± 15 years, 11 men) who underwent transcatheter embolotherapy of PAVMs. The total number of embolisations was 72 (mean per patient 2.5). Directly after PAVM closure, SV and CO decreased significantly by −11.9 % (p= 0.01) and −9.5 % (p= 0.01) respectively, without a significant change in HR (1.8 %). Mean arterial blood pressure increased by 4.1 % (p= 0.02), while the TPR and dP/dt did not increase significantly (5.8 % and 0.2 %, respectively). Significant haemodynamic changes occur directly after transcatheter embolisation of PAVMs, amongst which a decrease in stroke volume and cardiac output are most important.

Inflammation is associated with preterm premature rupture of membranes (PPROM) and adverse neonatal outcomes. Subchorionic thrombi, with or without inflammation, may also be a significant pathological finding in PPROM. Patterns of inflammation and thrombosis may give insight into mechanisms of adverse neonatal outcomes associated with PPROM. To characterize histologic findings of placentas from pregnancies complicated by PPROM at altitude, 44 placentas were evaluated for gross and histological indicators of inflammation and thrombosis. Student's t-test (or Mann–Whitney U-test), ?2analysis (or Fisher's exact test), mean square contingency and logistic regression were used when appropriate. The prevalence of histologic acute chorioamnionitis (HCA) was 59%. Fetal-derived inflammation (funisitis and chorionic plate vasculitis) was seen at lower frequency (30% and 45%, respectively) and not always in association with HCA. There was a trend for Hispanic women to have higher odds of funisitis (OR = 5.9; P= 0.05). Subchorionic thrombi were seen in 34% of all placentas. The odds of subchorionic thrombi without HCA was 6.3 times greater that the odds of subchorionic thrombi with HCA (P= 0.02). There was no difference in gestational age or rupture-to-delivery interval, with the presence or absence of inflammatory or thrombotic lesions. These findings suggest that PPROM is caused by or can result in fetal inflammation, placental malperfusion, or both, independent of gestational age or rupture-to-delivery interval; maternal ethnicity and altitude may contribute to these findings. Future studies focused on this constellation of PPROM placental findings, genetic polymorphisms and neonatal outcomes are needed.

Abstract: Background: Data on long-term complications in adult patients with congenital heart disease (ACHD) and a prosthetic valve are scarce. Moreover, the influence of prosthetic valves on quality of life (QoL) and functional outcome in ACHD patients with prosthetic valves has not been studied. Objectives: The primary objective of the PROSTAVA study is to investigate the relation between prosthetic valve characteristics (type, size and location) and functional outcome as well as QoL in ACHD patients. The secondary objectives are to investigate the prevalence and predictors of prosthesis-related complications including prosthesis-patient mismatch. Methods: The PROSTAVA study, a multicentre cross-sectional observational study, will include approximately 550 ACHD patients with prosthetic valves. Primary outcome measures are maximum oxygen uptake during cardiopulmonary exercise testing and QoL. Secondary outcomes are the prevalence and incidence of valve-related complications including prosthesis-patient mismatch. Other evaluations are medical history, physical examination, echocardiography, MRI, rhythm monitoring and laboratory evaluation (including NT-proBNP). Implications: Identification of the relation between prosthetic valve characteristics in ACHD patients on one hand and functional outcome, QoL, the prevalence and predictors of prosthesis-related complications on the other hand may influence the choice of valve prosthesis, the indication for more extensive surgery and the indication for re-operation.

Abstract: Background: Percutaneous left atrial appendage (LAA) closure can be an alternative to coumadin treatment in patients with atrial fibrillation (AF) at high risk for thromboembolic events and/or bleeding complications. We report the initial experience with this new technique. Methods: Patients were eligible if they had AF with a high stroke risk (CHADS2 score >1), and/or contraindication for coumadin therapy. The procedure was performed under general anaesthesia, using biplane fluoroscopy and (3D) transoesophageal echocardiography (TEE) guidance. Patients were discharged on coumadin until a TEE was repeated at 45 days after closure to evaluate LAA occlusion. If LAA occlusion was achieved, oral anticoagulation was discontinued and aspirin started. Results: Percutaneous LAA closure was performed in 10 patients (50% male, age 61.6 ± 9.6 years). The median CHADS2 score was 3 (range 2–4), median CHA2DS2-VASc score 3.5 (range 2–6) and HAS-BLED score 1.5 (range 1–4). Nine patients had a history of stroke and 2 patients had a history of major bleeding while on coumadin. Concomitant pulmonary vein isolation was performed in 9 patients. The device was successfully placed in all patients within a median of 56 min (38–137 min). Asymptomatic catheter thrombus occurred in one patient. At 45-day follow-up, no thromboembolic events occurred, TEE showed minimal residual flow in the LAA in three patients. In one patient the LAA device was dislocated, requiring successful percutaneous retrieval. Conclusion: Device closure of the LAA may provide an alternative strategy to chronic coumadin therapy in patients with AF and high risk of stroke and/or bleeding complications using coumadin.

Abstract: Introduction: Pulmonary endarterectomy (PEA) is the most effective treatment for chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study is to evaluate long-term survival and freedom from clinical worsening after PEA. Methods: All patients who underwent PEA in our hospital between May 2000 and August 2009 were included. Follow-up parameters were all-cause mortality and time to clinical worsening, defined as a combination of death, need for pulmonary hypertension-specific medication or 15% decrease in six-minute walk distance without improvement in functional class. The Cox proportional hazard regression was used to identify predictors. Results: Seventy-four consecutive patients (mean age 55.9 ± 13.8 years, 51% female) underwent PEA. Prior to surgery, 55 patients were in NYHA functional class III or higher. The mean pulmonary artery pressure was 41.3 ± 11.9 mmHg with a mean pulmonary vascular resistance of 521 ± 264 dyn·s·cm−5 (range 279–1331 dyn·s·cm−5). Five patients (6.8%) died in-hospital. Out of hospital, 5 out of 69 patients (7.2%) died during a median follow-up of 3.7 ± 2.2 years [range 0.1–8.5 years]). The one- and five-year survival rates were 93% and 89%, respectively. During follow-up, clinical worsening occurred in 13 out of 69 patients (18.8%). The one- and five-year rates of freedom from clinical worsening were 94% and 72%, respectively. The baseline NT-pro BNP level tended to be a predictor for occurrence of clinical worsening. Conclusion: Pulmonary endarterectomy is associated with good long-term survival in patients with CTEPH. However, clinical worsening occurred in a substantial number of patients at long-term follow-up.

Abstract: Aims: We evaluate the incidence of epicardial lead failure and try to identify risk factors in patients with congenital heart disease.Methods: All patients with a congenital heart defect and an epicardial pacing system, implanted within a timeframe of 25 years, were included in this study. Patients’ medical records and lead data were reviewed. Lead failure was defined as the primary endpoint. Results: In total 198 active epicardial leads (atrial 40, ventricular 158) were implanted in 93 patients (median age at implantation 4.4 years (range 0–58.6)). During a total follow-up of 1235 lead-years, 29 lead failures (14.6%, 4 atrial, 25 ventricular) were documented in 22 patients (23.7%). Lead failure occurred at a median time period of 4.8 years (range 1.2–24.1) after implantation. Five-year freedom of lead failure was 88%. The only independent predictor for lead failure was the age at implantation (HR 0.44; 95%CI 0.20–0.97, p = 0.04), other characteristics failed to predict lead failure. Sudden cardiac death occurred in four patients (4.3%), in one a lead failure was documented. Conclusion: A high incidence of epicardial lead failures is found in patients with congenital heart disease. Unfortunately, it is difficult to predict this potentially life-threatening complication.

Abstract: Background. Percutaneous mitral valve (MV) repair using the edge-to-edge clip technique might be an alternative for patients with significant mitral regurgitation (MR) and an unacceptably high risk for operative repair or replacement. We report the short-term safety and efficacy of this new technique in a high-risk population. Methods. All consecutive high-risk patients who underwent percutaneous MV repair with the Mitraclip® between January and August 2009 were included. All complications related to the procedure were reported. Transthoracic echocardiography for MR grading and right ventricular systolic pressure (RVSP) measurement were performed before, and at three and 30 days after the procedure. Differences in NYHA functional class and quality of life (QoL) index were reported. Results. Nine patients were enrolled (78% male, age 75.9±9.0 years, logistic EuroSCORE 33.8±9.0%). One patient developed inguinal bleeding. In one patient partial clip detachment occurred, a second clip was placed successfully. The MR grade before repair was ≥3 in 100%, one month after repair a reduction in MR grade to ≤2 was present in 78% (p=0.001). RVSP decreased from 43.9±12.1 to 31.6±11.7 mmHg (p=0.009), NYHA functional class improved from median 3 (range 3 to 4) to 2 (range 1 to 4) (p=0.04), and QoL index improved from 62.9±16.3 to 49.9±30.7 (p=0.12). Conclusion. In high-risk patients, transcatheter MV repair seems to be safe and a reduction in MR can be achieved in most patients, resulting in a short-term improvement of functional capacity and QoL. (Neth Heart J 2010;18:437-43.)

Abstract: Background. Inoperable chronic thromboembolic pulmonary hypertension (CTEPH) is associated with a poor survival. Objectives. To evaluate the long-term response to a dual endothelin receptor antagonist in patients with inoperable CTEPH. Methods. All consecutive 18 patients (mean age 63±14 years) treated with bosentan for symptomatic inoperable CTEPH were included. Efficacy was evaluated by the log value of serum levels of N-terminal-pro brain natriuretic peptide (log NTpro BNP), New York Heart Association functional class (NYHA), and the six-minute walk test (6-MWT). All follow-up data (median 31 months) were compared with baseline and divided into: short-term (<12 months), mid-term (between 12 and 24 months), and long-term follow-up (>24 months). Results. At baseline, 15 patients were in NYHA class III and three in NYHA class IV, mean log NT-pro BNP level was 7.2±1.4 log pg/ml, and mean 6-MWT distance was 404±125 m. During short-term follow-up (n=18), the NYHA class improved (p=0.001), 6-MWT distance increased by 33 m (p=0.03), and log NT-pro BNP decreased to 6.9±1.4 log pg/ml (p=0.007). During mid-term follow-up (n=17), the NYHA class improved (p<0.001), the mean 6-MWT distance increased by 41 m (p=0.01), and log NT-pro BNP was 6.9±1.4 log pg/ml (p=0.31). During late followup (n=14) the NYHA class was still improved (p=0.03), the 6-MWT distance decreased by 9 m (p=0.73), and log NT-pro BNP was 7.1±1.5 log pg/ml (p=0.91). The overall four year survival rate was 88%. Conclusion: Bosentan seems to be effective during long-term treatment in patients with inoperable CTEPH. (Neth Heart J 2009;17:329–33).

Abstract: Background: Percutaneous patent foramen ovale (PFO) closure seems to reduce the risk of recurrent thromboembolism. We report the safety and efficacy of percutaneous PFO closure in our centre. Methods: All patients, >16 years of age, who underwent a percutaneous PFO closure in our centre were included. Reoccurrence of stroke, transient ischaemic attack (TIA) and peripheral thromboembolism were assessed. Periprocedural and midterm complications are reported. Results: Eighty-three consecutive patients (mean age 49±13 years) were included. Indications for PFO closure were cryptogenic stroke (59.0%), TIA (33.7%), peripheral embolism (2.4%) and other (4.8%). For PFO closure, a Cardioseal/Starflex device was used in 63 patients and an Amplatzer PFO occluder device in 20 patients. Stroke recurred in 1.2%, TIA in 3.6%, peripheral embolism in 0% during a mean follow-up of 1.9±1.2 years. Major periprocedural complications occurred in 1.2%. The mid-term complication rate was 2.4% and only consisted of minor complications. During follow-up, a residual right-to-left shunt was present in 5.7% of the patients. No significant difference in outcome, complications or residual shunting could be documented between the two device types. Conclusion: In our centre, the percutaneous closure of a PFO seems to be a safe and effective procedure to prevent recurrence of paradoxical thrombo-embolic events. (Neth Heart J 2008;16:332-6.)

Objective. Ischemic lesion volume is assumed to be an important predictor of poststroke neurological deficits and functional outcome. This critical review examines the methodological quality of MRI studies and the predictive value of hemispheric infarct volume for neurological deficits (at body function level) and functional outcome (at activities level).Methods. Using Medline, PiCarta, and Embase to identify studies, 13 of the 747 identified studies met the authors’ inclusion criteria. Subsequently, studies were tested for adherence to the key methodological criteria for internal, statistical, and external validity. Each criterion was weighted binary, and studies with 6 points or more were judged to be valid for assessing the predictive value of MRI for outcome.Results. The 13 included studies had several methodological weaknesses with respect to internal validity, and none of them took lesion location into account. Only a few used outcome measures according to the International Classification of Functioning, Disability and Health and followed patients beyond 6 months. Correlation coefficients between MRI lesion volume and outcomes were higher for outcomes defined at body function level (National Institutes of Health Stroke Scale; median 0.67; range: 0.57-0.91) than for those defined at the level of activities (Barthel Index; median -0.49; range: -0.33 to -0.74).Conclusions. Methodological shortcomings of most studies confound the prognostic value of MRI in predicting stroke outcome, and few studies have focused on functional outcome. Future studies should investigate the added value of MRI volume over clinical neurological variables in predicting functional outcome beyond 6 months poststroke.

Abstract: A reliable sol gel route to synthesize NiO doped SiO2 films with different NiO content is here described. The films showed detectable and reversible changes in both optical and electrical properties when exposed to some reducing/oxidizing gaseous species at temperatures in the 250°C–350°C range. A functional characterization protocol has been designed and some of the sensing properties of the materials have been investigated for detecting NO2, CH4, CO and H2. An optical transmittance increase up to 2% has been detected for 1% CO in dry air atmospheres, while relative resistance response (R R = R gas/R air) values up to 4.97 for 850 ppm H2/air mixtures have been registered for conductometric gas sensing. Films at all NiO molar concentrations in the 10% NiO - 40% range showed an optical response to the target gas, while only 30% and 40% NiO films provided a detectable gas induced resistance change.

Gastro-esophageal reflux and related pulmonary bile acid aspiration were prospectively investigated as possible contributors to postlung transplant bronchiolitis obliterans syndrome (BOS). We also studied the impact of aspiration on pulmonary surfactant collectin proteins SP-A and SP-D and on surfactant phospholipids—all important components of innate immunity in the lung. Proximal and distal esophageal 24-h pH testing and broncho-alveolar lavage fluid (BALF) bile acid assays were performed prospectively at 3-month posttransplant in 50 patients. BALF was also assayed for SP-A, SP-D and phospholipids expressed as ratio to total lipids: phosphatidylcholine; dipalmitoylphosphatidylcholine; phosphatidylglycerol (PG); phosphatidylinositol; sphingomyelin (SM) and lysophosphatidylcholine. Actuarial freedom from BOS was assessed.

Gastro-esophageal reflux and related pulmonary bile acid aspiration were prospectively investigated as possible contributors to postlung transplant bronchiolitis obliterans syndrome (BOS). We also studied the impact of aspiration on pulmonary surfactant collectin proteins SP-A and SP-D and on surfactant phospholipids—all important components of innate immunity in the lung. Proximal and distal esophageal 24-h pH testing and broncho-alveolar lavage fluid (BALF) bile acid assays were performed prospectively at 3-month posttransplant in 50 patients. BALF was also assayed for SP-A, SP-D and phospholipids expressed as ratio to total lipids: phosphatidylcholine; dipalmitoylphosphatidylcholine; phosphatidylglycerol (PG); phosphatidylinositol; sphingomyelin (SM) and lysophosphatidylcholine. Actuarial freedom from BOS was assessed.

To determine if embolization of pulmonary arteriovenous malformations (PAVMs) decreases the occurrence of migraine.

Objective. To examine the relationship between the volume of the middle cerebral artery stroke lesion and functional status in the subacute phase of stroke.Methods. Infarctvolumes of 94 patients with a 1st middle cerebral artery stroke assessed on conventional MRI scans obtained in the 2nd week poststroke were related to a clinical measure of stroke severity (National Institutes of Health Stroke Scale [NIHSS]) and to functional status: motor impairment (Motricity Index [MI]) and limitation in activities (Barthel Index [BI] and modified Rankin Scale). Separate correlations were computed for patients with large (>30 ml) and small (30 ml) lesions, and to investigate the influence of lesion location on the relationship between volume and functional status, correlations were computed for patients with left and right hemisphere lesions and for patients with cortical and subcortical lesions.Results. Lesion volume correlated strongly with NIHSS scores(R = 0.61) and moderately with the patient’s functional status (MI [R between -0.42 and - 0.49], BI [R = -0.43], and Modified Rankin Scale [R = 0.45]). Right hemisphere lesions and cortical lesions had a stronger correlation with functional status. In patients with small lesion volumes (0-30 ml), no relationship between lesion volumes and functional status was seen at all.Conclusions. Lesion volume is moderately to strongly related to the functional status in the 2nd week poststroke.

Land use, soil management, and cropping systems affect stock, distribution, and residence time of soil organic carbon (SOC). Therefore, SOC stock and its depth distribution and association with primary and secondary particles were assessed in long-term experiments at the North Appalachian Experimental Watersheds near Coshocton, Ohio, through δ13C techniques. These measurements were made for five land use and soil management treatments: (1) secondary forest, (2) meadow converted from no-till (NT) corn since 1988, (3) continuous NT corn since 1970, (4) continuous NT corn-soybean in rotation with ryegrass since 1984, and (5) conventional plow till (PT) corn since 1984. Soil samples to 70-cm depth were obtained in 2002 in all treatments. Significant differences in soil properties were observed among land use treatments for 0 to 5-cm depth. The SOC concentration (g C kg−1of soil) in the 0 to 5-cm layer was 44.0 in forest, 24.0 in meadow, 26.1 in NT corn, 19.5 in NT corn-soybean, and 11.1 in PT corn. The fraction of total C in corn residue converted to SOC was 11.9% for NT corn, 10.6% for NT corn-soybean, and 8.3% for PT corn. The proportion of SOC derived from corn residue was 96% for NT corn in the 0 to 5-cm layer, and it decreased gradually with depth and was 50% in PT corn. The mean SOC sequestration rate on conversion from PT to NT was 280 kg C ha−1y−1. The SOC concentration decreased with reduction in aggregate size, and macro-aggregates contained 15 to 35% more SOC concentration than microaggregates. In comparison with forest, the magnitude of SOC depletion in the 0 to 30-cm layer was 15.5 Mg C/ha (24.0%) in meadow, 12.7 Mg C/ha (19.8%) in NT corn, 17.3 Mg C/ha (26.8%) in NT corn-soybean, and 23.3 Mg C/ha (35.1%) in PT corn. The SOC had a long turnover time when located deeper in the subsoil. Additional research is needed to understand association of SOC with particle and aggregate size fractions and temporal changes and depth-distribution with regard to land use and soil management.

Abstract SiO2 sol-gel films doped with cobalt oxide nanocrystals have been fabricated. The nanocrystals precipitate in the glass film at 500_°C, while the film is still porous. The nanocomposite films showed a reversible change in the optical transmittance when exposed to CO in the 250 < ? < 850 nm range. The effects of the residual porosity and testing temperature have been studied. The gas sensing properties of the cobalt oxide nanocrystals doped films are compared with those of nickel oxide nanocrystals doped silica film, previously reported.

Members of the TGF-β family have been shown to play an important role in numerous tissues during development. In the present study we have investigated the spatial and temporal expression of TGF-β3, in human umbilical cord development. Total TGF-β3 protein content, assessed by immunoblotting, increased with advancing gestation as did immunostaining and mRNA in Wharton’s jelly fibroblasts. Immunohistochemical analysis revealed that TGF-β3 was present in all cell types. Temporal changes in TGF-β3 expression were observed in the vascular smooth muscle cells, such that with advancing gestation TGF-β3 protein expression and became mostly restricted to the extracellular compartment of the vascular media. This was associated with a decrease in TGF-β3 mRNA expression in umbilical vascular smooth muscle cells. Of clinical significance, umbilical cords from pregnancies complicated by pre-eclampsia, showed a significant reduction in total TGF-β3 protein expression when compared to those of age-matched patients. Both TGF-β3 mRNA and protein expression were downregulated in the endothelium and smooth muscle layers of the umbilical arteries, as well as in the Wharton jelly fibroblasts. Our data demonstrate that during umbilical cord development TGF-β3 expression is spatially and temporally regulated and that TGF-β3 expression is altered in umbilical cords of pregnancies complicated by pre-eclampsia. We speculate that the downregulation of TGF-β3 expression found in pre-eclamptic umbilical cord may contribute to the abnormal structure and mechanical properties seen in these pathological umbilical cords. Copyright 2002 Elsevier Science Ltd

The aim of the study was to assess which children with congenital and acquired upper limb deficiencies were fitted with prostheses, what types of prostheses were prescribed as first, second and third prostheses, at what age prostheses were first prescribed and how long the children wore their prostheses.The design was a retrospective chart review at De Hoogstraat Rehabilitation Centre, Utrecht (The Netherlands). Medical files of all patients with congenital or acquired upper limb deficiencies who visited the outpatient clinic between 1972 and 1996 were reviewed, collecting data on patient characteristics, prosthesis prescription and use of prostheses.The group included 224 children, of whom 206 (92%) had congenital deficiencies. Of all children with unilateral congenital deficiencies, 54% had been fitted with prostheses, against 3% of all children with bilateral congenital deficiencies and 67% of all children with acquired deficiencies. In the congenital group, it was children with transverse defects of one-third or two-thirds of the forearm who had most frequently had prostheses fitted (85% of the children). Most of the children with unilateral congenital deficiencies had received passive prostheses as their first prostheses (80 of the 90 prescribed prostheses); children with acquired defects usually had active prostheses (8 of the 12 prescribed prostheses). Body-powered prostheses were most commonly prescribed as the second type of prosthesis.In the group of 119 children who had been seen before the age of 4 years and had been followed for at least three years, 63 had been fitted with one or more prostheses at a mean age of 2.6 (SD 2.5) years. Of the 46 children with congenital defects, 30 had been fitted with prostheses, and at the age of 12, two-thirds of them still used their prostheses (63%, 19/30).“De Hoogstraat” rehabilitation centre uses a restrained prosthesis prescription policy, depending on the type of deficiency and the expected functional benefits. Data on prosthesis use are encouraging, although a follow-up study is required to determine the functional outcome for prosthesis users and non-users.

Recent loss-of-function studies in mice show that the transcription factor GATA6 is important for visceral endoderm differentiation. It is also expressed in early bronchial epithelium and the observation that this tissue does not receive any contribution from Gata6 double mutant embryonic stem (ES) cells in chimeric mice suggests that GATA6 may play a crucial role in lung development. The aim of this study was to determine the role of GATA6 in fetal pulmonary development. We show that Gata6 mRNA is expressed predominantly in the developing pulmonary endoderm and epithelium, but at E15.5 also in the pulmonary mesenchyme. Blocking or depleting GATA6 function results in diminished branching morphogenesis both in vitro and in vivo. TTF1 expression is unaltered in chimeric lungs whereas SPC and CC10 expression are attenuated in abnormally branched areas of chimeric lungs. Chimeras generated in a ROSA26 background show that endodermal cells in these abnormally branched areas are derived from Gata6 mutant ES cells, implicating that the defect is intrinsic to the endoderm. Taken together, these data demonstrate that GATA6 is not essential for endoderm specification, but is required for normal branching morphogenesis and late epithelial cell differentiation.

Abstract: Our purpose was to describe the range of MRI findings in infectious and neoplastic involvement of the spine and spinal cord in symptomatic patients with the acquired immunodeficiency syndrome (AIDS). MRI studies in 55 patients with AIDS and neurological signs and symptoms thought to be related to the spine or spinal cord were reviewed. We categorized the findings according to the spinal compartment involved. There were 29 patients with extradural, 11 with intradural-extramedullary and 9 with intramedullary disease. In 6 patients more than one compartment was involved simultaneously, and patients presented with multiple lesions in the same compartment. The most common causes of extradural disease were bone lesions (28); an epidural mass was seen in 14 and spondylodiscitis in 4 patients. Cytomegalovirus polyradiculitis was the most common cause of intradural-extramedullary disease (in 10 cases); herpes radiculitis was seen in two, and tuberculous infection in another two. In three cases leptomeningeal contrast enhancement was due to lymphoma. Human immunodeficiency virus (HIV) myelitis was seen in two patients, presumed vacuolar myelopathy in two, toxoplasma myelitis in four, intramedullary lymphoma in one, and herpes myelitis in one. Familiarity with the various potential pathological entities that can affect the spine and spinal cord in the AIDS population and their imaging characteristics is crucial for initiation of further diagnostic tests and appropriate medical or surgical treatment.

During early pregnancy, placentation occurs in a relatively hypoxic environment which is essential for appropriate embryonic development. Intervillous blood flow increases at around 10–12 weeks of gestation and results in exposure of the trophoblast to increased oxygen tension (Po2). Prior to this time, low oxygen appears to prevent trophoblast differentiation towards an invasive phenotype. In other mammalian systems, oxygen tension effects are mediated by hypoxia inducible factor-1 (HIF-1). We found that the ontogeny of HIF-1α subunit expression during the first trimester of gestation parallels that of transforming growth factor-β3(TGFβ3), an inhibitor of early trophoblast differentiation. Expression of both molecules is high in early pregnancy and falls at around 10 weeks of gestation when placental Po2levels are believed to increase. Antisense-induced inhibition of HIF-1α inhibited the expression of TGFβ3, and stimulated extravillous trophoblast (EVT) outgrowth and invasion. Of clinical significance we found that TGFβ3expression was increased in pre-eclamptic placentae when compared to age-matched controls. Significantly, inhibition of TGFβ3by antisense oligonucleotides or antibodies restored the invasive capability to the trophoblast cells in pre-eclamptic explants. We speculate that if oxygen tension fails to increase, or trophoblasts do not detect this increase, HIF-1α and TGFβ3expression remain high, resulting in shallow trophoblast invasion and predisposing the pregnancy to pre-eclampsia.

Abstract.: The aim of the present study was to investigate the roles of Ca2+ and protein tyrosine kinase (PTK) in the insulin action on cell volume in fetal rat (20-day gestational age) type II pneumocytes. Insulin (100 nm) increased cell volume in the presence of extracellular Ca2+ (1 mm), while cell shrinkage was induced by insulin in the absence of extracellular Ca2+ (<1 nm). This insulin action in a Ca2+-containing solution was completely blocked by co-application of bumetanide (50 μm, an inhibitor of Na+/K+/2Cl− cotransporter) and amiloride (10 μm, an inhibitor of epithelial Na+ channel), but not by the individual application of either bumetanide or amiloride. On the other hand, the insulin action on cell volume in a Ca2+-free solution was completely blocked by quinine (1 mm, a blocker of Ca2+-activated K+ channel), but not by bumetanide and/or amiloride. These observations suggest that insulin activates an amiloride-sensitive Na+ channel and a bumetanide-sensitive Na+/K+/2Cl− cotransporter in the presence of 1 mm extracellular Ca2+, that the stimulatory action of insulin on an amiloride-sensitive Na+ channel and a bumetanide-sensitive Na+/K+/2Cl− cotransporter requires Ca2+, and that in a Ca2+-free solution insulin activates a quinine-sensitive K+ channel but not in the presence of 1 mm Ca2+. The insulin action on cell volume in a Ca2+-free solution was almost completely blocked by treatment with BAPTA (10 μm) or thapsigargin (1 μM, an inhibitor of Ca2+-ATPase which depletes the intracellular Ca2+ pool). Further, lavendustin A (10 μm, an inhibitor of receptor type PTK) blocked the insulin action in a Ca2+-free solution. These observations suggest that the stimulatory action of insulin on a quinine-sensitive K+ channel is mediated through PTK activity in a cytosolic Ca2+-dependent manner. Lavendustin A, further, completely blocked the activity of the Na+/K+/2Cl− cotransporter in a Ca2+-free solution, but only partially blocked the activity of the Na+/K+/2Cl− cotransporter in the presence of 1 mm Ca2+. This observation suggests that the activity of the Na+/K+/2Cl− cotransporter is maintained through two different pathways; one is a PTK-dependent, Ca2+-independent pathway and the other is a PTK-independent, Ca2+-dependent pathway. Further, we observed that removal of extracellular Ca2+ caused cell shrinkage by diminishing the activity of the amiloride-sensitive Na+ channel and the bumetanide-sensitive Na+/K+/2Cl− cotransporter, and that removal of extracellular Ca2+ abolished the activity of the quinine-sensitive K+ channel. We conclude that the cell shrinkage induced by removal of extracellular Ca2+ results from diverse effects on the cotransporter and Na+ and K+ channels.

Epithelial-mesenchymal interactions are required for the development of all solid organs but few molecular mechanisms that underlie these interactions have been identified. Pod1 is a basic-helix-loop-helix (bHLH) transcription factor that is highly expressed in the mesenchyme of developing organs that include the lung, kidney, gut and heart and in glomerular visceral epithelial cells (podocytes). To determine the function of Pod1 in vivo, we have generated a lacZ-expressing null Pod1 allele. Null mutant mice are born but die in the perinatal period with severely hypoplastic lungs and kidneys that lack alveoli and mature glomeruli. Although Pod1 is exclusively expressed in the mesenchyme and podocytes, major defects are observed in the adjacent epithelia and include abnormalities in epithelial differentiation and branching morphogenesis. Pod1 therefore appears to be essential for regulating properties of the mesenchyme that are critically important for lung and kidney morphogenesis. Defects specific to later specialized cell types where Pod1 is expressed, such as the podocytes, were also observed, suggesting that this transcription factor may play multiple roles in kidney morphogenesis.

BACKGROUND: Dyspepsia is prevalent in about 30% of the general population in Europe, but only 25% of people with complaints consult their general practitioner. AIMS: To study the relation between the severity of dyspeptic complaints and the health status of patients presenting to the general practitioner; and the relation with patient characteristics, Helicobacter pylori infection, and psychological distress. METHODS: A cross sectional, general practice based survey of 360 unselected primary care dyspeptic patients from 92 general practices in The Netherlands was conducted. Symptom severity was measured using a validated symptom score, H pylori using a whole blood test, and psychological distress using the GHQ-12 test. Functional health status was assessed using the COOP/Wonca charts. RESULTS: Symptoms lasting more than three months and presence of relevant psychological distress were both associated with higher levels of dyspepsia. H pylori infection, frequency of symptoms, and age had no influence on dyspepsia severity. Severity of dyspepsia and psychological distress, but not H pylori infection or duration of symptoms, affected health status univariately. Dyspepsia correlated with general health, daily activities, and social activities. In logistic modelling, health status was far better predicted by psychological distress than by dyspepsia severity. CONCLUSION: The relation between dyspeptic symptom severity and health status is limited. H pylori infection relates neither to functional health status, nor to intensity of dyspepsia. Psychological distress is a major determinant of impaired health of dyspeptic patients in general practice and may be the clue to improvement of health status in many dyspeptic patients.

Abstract: In 1992 a project was started in which home care technology was made available to patients with cancer or serious infections. Primary care providers were trained and supported to administer parenteral drugs and fluids in the home setting. Between 1992 and 1995 we applied the Rotterdam Symptom Checklist (RSCL) and the Sickness Impact Profile (SIP) as questionnaires for quality of life (QoL) assessment in a group of 112 hospitalized patients who were prepared to receive further treatment at home. Scores on the RSCL revealed a high level of symptomatology in both the physical and the psychological dimension. Factor analysis showed a five-factor rather than a two-factor structure. The SIP showed considerable restrictions in daily living, particularly in the physical dimension. Whereas the RSCL and the SIP correlated well in the psychological and physical dimensions in advanced cancer patients, this correlation disappeared in the group of end-stage cancer patients. The data indicate that the health-related QoL of end-stage cancer patients cannot be reliably be assessed with a symptom-based instrument alone; it needs to be supplemented by other instruments, such as the SIP.