Origin of subepicardial cells in rat embryos

Background: The role of the villi and vesicles of the epicardium primordium in the formation of the epicardium has been extensively studied over the last decades. With regard to the cellular contents of the villi and vesicles of the epicardium primordium, in quail the presence of mesenchymal cells in the villi recently has been described. In the present study, we have determined whether the villi and vesicles of the epicardium primordium in rat embryos contain mesenchymal cells that originate from the transverse septum and if so, whether these cells will become part of the subepicardium. Methods: Mesenchymal cells in the transverse septum of rat embryos were labelled by a method consisting of in vitro whole embryo culture and labelling of the ectoderm and its daughter cells, using wheat germ agglutinin-gold (WGA-Au) as a marker. Results: In concordance with our observations in the standard noncultured rat embryos, labelled cells were present in the transverse septum, extending from the umbilical ring, i.e., the transition of amniotic epithelium to ectoderm, up to the villi, in the villi and vesicles, and subepicardially. Conclusions: These observations suggest that the epicardium primordium contains mesenchymal cells derived from the transverse septum. These cells reach the subepicardium, using the villi and vesicles of the epicardium primordium as their vehicle. © 1995 Wiley-Liss, Inc.     

An unusual case of renovascular hypertension-renal artery stenosis of a pelvic kidney with aberrant blood supply.

Case Mr. G.L. aged 32 was referred to the Department of Renal Medicineat Derby City Hospital with unexplained hypertension. At 13years of age he had suffered a cerebrovascular accident causinga left hemiparesis. At the time there were no risk factors identifiedto account for his stroke including normal intracerebral arteries.During his     

Selection criteria for liver donation: a review

An overview of the criteria that are currently being used for the selection of liver donors is presented. The validity of the different criteria is discussed. The potential benefits of introducing other modalities is dealt with.All authors are part of the Liver Transplant Group of the University Hospital Groningen     

DTI-based assessment of ischemia-reperfusion in mouse skeletal muscle.

Diffusion tensor imaging (DTI) is frequently applied to characterize the microscopic geometrical properties of tissue. To establish whether and how diffusion MRI responds to transient ischemia of skeletal muscle, we studied the effects of ischemia and reperfusion using DTI and T2-weighted MRI before and during ischemia and up to 24 hr after reperfusion. Ischemia was induced by 50 min of hindlimb occlusion with or without dorsal flexor stimulation. During ischemia the apparent diffusion coefficient (ADC) tended to decrease (up to 15%), whereas the fractional anisotropy (FA) and T2 showed a varied response depending on the protocol and muscle type. During reperfusion the ADC and T2 initially increased and subsequently renormalized for the occlusion protocol. For the occlusion plus stimulation (OS) protocol, the FA was decreased by 13% and the ADC and T2 were increased by 20% and 57%, respectively, after 24 hr in the stimulated muscle complex. In the latter tissue the three DTI eigenvalues gradually increased upon reperfusion. The smallest eigenvalue (lambda3) showed the largest relative increase. Changes in DTI indices in the reperfusion phases followed a similar time course as the changes in T2. The changes in MR indices after 24 hr correlated with the tissue damage quantified with histology. The highest correlation was observed for lambda3 (R2 = 0.81). This study shows that DTI can be used to assess ischemia-induced damage to skeletal muscle.     

Dosimetric pre-treatment verification of IMRT using an EPID; clinical experience.

BACKGROUND AND PURPOSE: In our clinic a QA program for IMRT verification, fully based on dosimetric measurements with electronic portal imaging devices (EPID), has been running for over 3 years. The program includes a pre-treatment dosimetric check of all IMRT fields. During a complete treatment simulation at the linac, a portal dose image (PDI) is acquired with the EPID for each patient field and compared with a predicted PDI. In this paper, the results of this pre-treatment procedure are analysed, and intercepted errors are reported. An automated image analysis procedure is proposed to limit the number of fields that need human intervention in PDI comparison. MATERIALS AND METHODS: Most of our analyses are performed using the gamma index with 3% local dose difference and 3mm distance to agreement as reference values. Scalar parameters are derived from the gamma values to summarize the agreement between measured and predicted 2D PDIs. Areas with all pixels having gamma values larger than one are evaluated, making decisions based on clinically relevant criteria more straightforward. RESULTS: In 270 patients, the pre-treatment checks revealed four clinically relevant errors. Calculation of statistics for a group of 75 patients showed that the patient-averaged mean gamma value inside the field was 0.43 +/- 0.13 (1SD) and only 6.1 +/- 6.8% of pixels had a gamma value larger than one. With the proposed automated image analysis scheme, visual inspection of images can be avoided in 2/3 of the cases. CONCLUSION: EPIDs may be used for high accuracy and high resolution routine verification of IMRT fields to intercept clinically relevant dosimetric errors prior to the start of treatment. For the majority of fields, PDI comparison can fully rely on an automated procedure, avoiding excessive workload.     

Rehabilitation outcomes of long-term survivors treated for head and neck cancer

Background. Little is known about the rehabilitation outcomes of long-term survivors following treatment for head and neck cancer. There are, for example, no studies on physical and psychosocial rehabilitation outcomes of T1 glottic larynx carcinoma, despite the fact that these form the majority of head and neck cancer sites. Thus, this investigation afforded a unique opportunity for examining similarities and differences among T1 glottic larynx patients, laryngectomy patients, and those who had surgery for cancer of the oral cavity and/or oropharynx along a variety of physical and psychosocial dimensions. Methods. To describe the impact of these three types of head and neck cancer and their treatment on the physical and psychosocial functioning of long-term survivors, a selfreport questionnaire was completed by 110 patients treated between 2 and 6 years previously in a major cancer center. Results. Data indicate that a higher percentage of patients treated with laryngectomy or commando procedures still experience severe psychosocial distress between 2 and 6 years after their last treatment than do patients treated with radiotherapy for a T1 carcinoma of the glottic larynx. Psychosocial and physical complaints are still reported by many laryngectomy patients, apparently the result of problems in effective communication with others. Many commando procedure patients experience problems with respect to food intake, and with disfigurement and its consequences. T1 Iarynx patients mainly experience a considerable number of physical complaints. The greater the time that had elapsed since treatment, the fewer the psychosocial problems associated with head and neck tumors. Open discussion of the illness in the family, social support, and perceptions of adequate information from the specialist are the most important predictors of positive rehabilitation outcomes. Conclusions. This study indicates that T1 Iarynx patients report many physical complaints even though several years had elapsed since treatment. Also, Iaryngectomy patients may need psychosocial guidance for a longer posttreatment period and that health care personnel must involve the partner as much as possible in all communications. Commando procedure patients in particular feel hindered by their disfigurement and its consequences. Future research with respect to validation of the specific head and neck modules is needed.     

5-Hydroxytryptamine-induced contractions of the human isolated saphenous vein: involvement of 5-HT2 and 5-HT1D-like receptors,and a comparison with grafted veins

Summary The receptors mediating the contractile effect of 5-hydroxytryptamine (5-HT) on the human isolated saphenous vein, obtained from 42 patients undergoing coronary bypass surgery, have been further characterized using a number of 5-HT-related drugs. The rank order of agonist potency was 5-carboxamidotryptamine (5-CT) 5-HT > methysergide sumatriptan -methyl-5-HT 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1-Hindolesuccinate (RU 24969) 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) > 2-methyl-5-HT > 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT). Flesinoxan was inactive as an agonist. Ketanserin (1 mol/l) hardly affected sumatriptan-induced contractions but it caused a rightward shift of the upper part of the concentration-response curve of 5-HT and 5-CT. The same concentration of ketanserin caused a parallel rightward shift of the concentration-response curves of -methyl-5-HT and DOI with pK_B values of 7. 1 and 7.1, respectively. The responses to sumatriptan were antagonized by methiothepin (0.1 mol/l), metergoline (0.1 and 1 mol/l), rauwolscine (1 mol/l) and cyanopindolol (1 mol/l); the calculated pK_B values were 7.3, 6.9, 7.3, 6.7 and 6.5, respectively. Contractions to 5-HT were antagonized by methysergide (1 mol/l), methiothepin (0.1 mol/l; pKB = 7.1), ICS 205-930 (1 mol/l; pK_B = 5.9) and flesinoxan (30 mol/l; pK_B = 5.3). Remarkably, the contractions elicited by 2-methyl-5-HT were not attenuated by ICS 205-930, but were antagonized by methiothepin (0.1 mol/l) and, more markedly, by ketanserin (1 mol/l).There was a high correlation between the functional pD₂ values of 5-HT₁-like receptor agonists (5-CT, 5-HT, methysergide, sumatriptan, RU 24969 and 8-OH-DPAT) and their reported binding affinities for the 5-HT_1D receptor in human or calf brain membranes. Such a correlation for the antagonism of sumatriptan-induced responses was less marked than for the agonists, but of the 5-HT₁-like receptor subtypes it was the highest for the 5-HT_1D receptor identified in human or calf brain membranes.In 3 patients, undergoing heart transplantation, saphenous vein which had previously functioned as a graft for 6–11 years, was dissected out from the heart. Though the contractions to potassium were significantly smaller in the grafted veins, the pD₂ and E_max values (calculated as percentage of potassium-induced contractions) for 5-HT and sumatriptan were similar to those found in the veins obtained directly from the lower leg.It is concluded that contractions in the human isolated saphenous vein induced by 5-HT are mediated by 5-HT₂ receptors as well as by a 5-HT₁-like receptor resembling the 5-HT_1D subtype found in brain membranes. It is also to be noted that 2-methyl-5-HT, considered selective for the 5-HT₃ receptor, contracts the saphenous vein mainly via 5-HT₂ receptors.This study was supported by the Netherlands Heart Foundation, grant 89.252 Send offprint requests to W. A. Bax at the above address     

Cost-Effectiveness of Pediatric Influenza Vaccination in The Netherlands

ObjectiveThis study evaluates the cost-effectiveness of extending the Dutch influenza vaccination program for elderly and medical high-risk groups to include pediatric influenza vaccination, taking indirect protection into account.MethodsAn age-structured dynamic transmission model was used that was calibrated to influenza-associated GP visits over 4 seasons (2010-2011 to 2013-2014). The clinical and economic impact of different pediatric vaccination strategies were compared over 20 years, varying the targeted age range, the vaccine type for children or elderly and high-risk groups. Outcome measures include averted symptomatic infections and deaths, societal costs and quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Costs and QALYs were discounted at 4% and 1.5% annually.ResultsAt an assumed coverage of 50%, adding pediatric vaccination for 2- to 17-year-olds with quadrivalent live-attenuated vaccine to the current vaccination program for elderly and medical high-groups with quadrivalent inactivated vaccine was estimated to avert, on average, 401 820 symptomatic cases and 72 deaths per year. Approximately half of averted symptomatic cases and 99% of averted deaths were prevented in other age groups than 2- to 17-year-olds due to herd immunity. The cumulative discounted 20-year economic impact was 35 068 QALYs gained and €1687 million saved, that is, the intervention was cost-saving. This vaccination strategy had the highest probability of being the most cost-effective strategy considered, dominating pediatric strategies targeting 2- to 6-year-olds or 2- to 12-year-olds or strategies with trivalent inactivated vaccine.ConclusionModeling indicates that introducing pediatric influenza vaccination in The Netherlands is cost-saving, reducing the influenza-related disease burden substantially.     

Health-related quality of life deviations from population norms in patients with lumbar radiculopathy: associations with pain,pain cognitions,and endogenous nociceptive modulation

Quality of Life Research - The primary goal of this study was to compare the health-related quality of life (HRQoL) of people with lumbar radiculopathy to age- and sex-adjusted population norms....