Rapid Progression of Native Renal Artery Fibromuscular Dysplasia Following Kidney Donation

Fibromuscular dysplasia is the second commonest anatomical abnormality apart from multiple renal arteries in the potential live donors. Pretransplant evaluation of the donors may include an angiography to evaluate the renal arteries, and failure to recognize renal arterial stenosis, particularly fibromuscular dysplasia, by noninvasive methods may eventually lead to hypertension and ischemic renal failure. We report a case of fibromuscular dysplasia that was undetected by computed tomographic angiography prior to donation. One year after kidney donation, it rapidly progressed to severe symptomatic stenosis with hypertension and acute renal failure. Following renal artery angioplasty, her blood pressure normalized over a period of 2 weeks without any need for antihypertensive medications and the serum creatinine returned to her baseline. The acceptability of renal donors with fibromuscular dysplasia depends on the age, race and the availability of the other suitable donors. Mild fibromuscular dysplasia in a normotensive potential renal donor cannot be considered a benign condition. Such donors need regular follow-up postdonation for timely detection and treatment.     

Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy

The purpose of this work is to evaluate the predictive strength of the relative seriality, parallel and LKB normal tissue complication probability (NTCP) models regarding the incidence of radiation pneumonitis, in a large group of patients following breast cancer radiotherapy, and furthermore, to illustrate statistical methods for examining whether certain published radiobiological parameters are compatible with a clinical treatment methodology and patient group characteristics. The study is based on 150 consecutive patients who received radiation therapy for breast cancer. For each patient, the 3D dose distribution delivered to lung and the clinical treatment outcome were available. Clinical symptoms and radiological findings, along with a patient questionnaire, were used to assess the manifestation of radiation-induced complications. Using this material, different methods of estimating the likelihood of radiation effects were evaluated. This was attempted by analysing patient data based on their full dose distributions and associating the calculated complication rates with the clinical follow-up records. Additionally, the need for an update of the criteria that are being used in the current clinical practice was also examined. The patient material was selected without any conscious bias regarding the radiotherapy treatment technique used. The treatment data of each patient were applied to the relative seriality, LKB and parallel NTCP models, using published parameter sets. Of the 150 patients, 15 experienced radiation-induced pneumonitis (grade 2) according to the radiation pneumonitis scoring criteria used. Of the NTCP models examined, the relative seriality model was able to predict the incidence of radiation pneumonitis with acceptable accuracy, although radiation pneumonitis was developed by only a few patients. In the case of modern breast radiotherapy, radiobiological modelling appears to be very sensitive to model and parameter selection giving clinically acceptable results in certain cases selectively (relative seriality model with Seppenwoolde et al and Gagliardi et al parameter sets). The use of published parameters should be considered as safe only after their examination using local clinical data. The variation of inter-patient radiosensitivity seems to play a significant role in the prediction of such low incidence rate complications. Scoring grades were combined to give stronger evidence of radiation pneumonitis since their differences could not be strictly associated with dose. This obviously reveals a weakness of the scoring related to this endpoint, and implies that the probability of radiation pneumonitis induction may be too low to be statistically analysed with high accuracy, at least with the latest advances of dose delivery in breast radiotherapy.     

In vitro effect of alpha-interferon on mononuclear cells of normal and autoimmune patients

The effect of lymphoblastoid interferon (IFN-alpha) on cell-mediated and humoral immunity was studied in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The base-line natural killer (NK) and antibody dependent cytotoxic cell (ADCC) activity was higher than normal in individuals with RA. The NK and ADCC activities were tested after IFN-alpha pretreatment and the augmentation of NK and ADCC activity was less in these patients than in normals. Lymphoblastoid IFN inhibited antigen induced T-cell proliferation in SLE to a lesser extent than in normal individuals. Finally, the addition of lymphoblastoid IFN was also less effective at suppressing in vitro polyclonal antibody formation by mononuclear cells from patients with SLE than from normals, with enhancement observed in some patients at the lower IFN-alpha concentrations tested.     

Loss of lymphocyte chalone activity in mice with autoimmune disease.

Lymphocyte chalone from the spleens of old BALB/c, young BALB/c and young NZB mice caused significant suppression of the proliferative response of BALB/c and NZB spleen cells to T and B mitogens, whereas lymphocyte chalone from old NZB spleen did not suppress. Lymphocyte chalone from young and old NZB mice was tested using different ages of NZB/NZW responding spleen cells; at all ages concanavalin A- and lipopolysaccharide-induced proliferation was suppressed less by the chalone from old NZB mice than from that of young NZB mice. The responding NZB/NZW cells were suppressed equivalently at all ages studied. The basis for the loss of lymphocyte chalone activity in old NZB mice remains unknown; however, it appears likely that this event has a role in the disturbance of the negative feedback control system which contributes to NZB autoimmune disease.     

Prediction of AVM obliteration after stereotactic radiotherapy using radiobiological modelling

This study was carried out in order to derive the radiobiological parameters of the dose-response relation for the obliteration of arteriovenous malformation (AVM) following single fraction stereotactic radiotherapy. Furthermore, the accuracy by which the linear Poisson model predicts the probability of obliteration and how the haemorrhage history, location and volume of the AVM influence its radiosensitivity are investigated. The study patient material consists of 85 patients who received radiation for AVM therapy. Radiation-induced AVM obliterations were assessed on the basis of post-irradiation angiographies and other radiological findings. For each patient the dose delivered to the clinical target volume and the clinical treatment outcome were available. These data were used in a maximum likelihood analysis to calculate the best estimates of the parameters of the linear Poisson model. The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was studied. AVM radiosensitivity was assumed to be the same for all the patients. The radiobiological model used was proved suitable for predicting the treatment outcome pattern of the studied patient material. The radiobiological parameters of the model were calculated for different AVM locations, bleeding histories and AVM sizes. The range of parameter variability had considerable effect on the dose-response curve of AVM. The correlation between the dosimetric data and their corresponding clinical effect could be accurately modelled using the linear Poisson model. The derived response parameters can be introduced into the clinical routine with the calculated accuracy assuming the same methodology in target definition and delineation. The known volume dependence of AVM radiosensitivity was confirmed. Moreover, a trend relating AVM location with its radiosensitivity was observed.     

The facilitative effect of facial expression on the self-generation of emotion.

Twenty-seven female undergraduates completed three tasks: (1) feel four emotions (happiness, sadness, anger, peacefulness); (2) express these emotions, without trying to feel them; and (3) feel and express clearly these four emotions. During each trial subjects pressed a button to indicate when they had reached the required state, and the latency from emotion cue to button press was measured. Heart rate, skin conductance and EMG from four facial sites (brow, cheek, jaw and mouth) were recorded for 15 s before and after the button press and during a baseline period prior to each trial. Self-reports were obtained after each trial. Facial EMG and patterns of autonomic arousal differentiated among the four emotions within each task. Shorter self-generation latency in the Feel-and-Show versus the Feel condition indicated the facilitative effect of facial expression on the self-generation of emotion. Furthermore, the presence of autonomic changes and self-reported affect in the Show condition supports the sufficiency version of the facial feedback hypothesis. The self-generation method employed as an emotion elicitor was shown to reliably induce emotional reactions and is proposed as a useful technique for the elicitation of various emotional states in the laboratory.     

Heme oxygenase inhibitors transiently increase serum ferritin concentrations without altering other acute-phase reactants in man.

Sn protoporphyrin (SnPP) and Sn mesoporphyrin (SnMP), potent inhibitors of heme oxygenase (HO), significantly suppress bilirubin production, lower serum and biliary bilirubin levels and increase biliary heme output in animals and man. In this study, 20 healthy volunteers, 7 patients with primary biliary cirrhosis and 4 patients with idiopathic hemochromatosis were treated with SnPP and 4 healthy volunteers with SnMP. In all cases, serum ferritin levels increased substantially but transiently after administration of these HO inhibitors. Values returned to baseline within a few days. Infusion of hematin in 4 healthy volunteers did not significantly affect ferritin levels. No increases occurred in 7 other acute-phase reactants. The observation that these HO inhibitors transiently increase serum ferritin levels implies a link between ferritin, iron metabolism and HO activity which may be usefully explored in disorders of iron metabolism.     

The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis

Sprouting angiogenesis is critical to blood vessel formation, but the cellular and molecular controls of this process are poorly understood. We used time-lapse imaging of green fluorescent protein (GFP)-expressing vessels derived from stem cells to analyze dynamic aspects of vascular sprout formation and to determine how the vascular endothelial growth factor (VEGF) receptor flt-1 affects sprouting. Surprisingly, loss of flt-1 led to decreased sprout formation and migration, which resulted in reduced vascular branching. This phenotype was also seen in vivo, as flt-1(-/-) embryos had defective sprouting from the dorsal aorta. We previously showed that loss of flt-1 increases the rate of endothelial cell division. However, the timing of division versus morphogenetic effects suggested that these phenotypes were not causally linked, and in fact mitoses were prevalent in the sprout field of both wild-type and flt-1(-/-) mutant vessels. Rather, rescue of the branching defect by a soluble flt-1 (sflt-1) transgene supports a model whereby flt-1 normally positively regulates sprout formation by production of sflt-1, a soluble form of the receptor that antagonizes VEGF signaling. Thus precise levels of bioactive VEGF-A and perhaps spatial localization of the VEGF signal are likely modulated by flt-1 to ensure proper sprout formation during blood vessel formation.