Deterministic rather than stochastic factors explain most of the variation in the expression of skin telangiectasia after radiotherapy.

BACKGROUND: The large patient-to-patient variability in the grade of normal tissue injury after a standard course of radiotherapy is well established clinically. A better understanding of this individual variation may provide valuable insights into the pathogenesis of radiation damage and the prospects of predicting the outcome. PURPOSE: To estimate the relative importance of the stochastic vs. patient-related components of variability in the expression of radiation-induced normal tissue damage. METHODS AND MATERIALS: The study data were selected from the dose fractionation studies of Turesson in Gothenburg. Patients treated with bilateral internal mammary fields, who completed at least 10 years of follow-up, were included. The material included 22 different fractionation schedules (11 on each side). Telangiectasia was graded on an arbitrary 6-point scale using clinical photographs of the irradiated fields. For each field, in each patient, a curve showing the grade of telangiectasia as a function of time was constructed. A measure of radioresponsiveness was obtained from the difference between the area under the curve (AUC) for a specific field in an individual patient minus the mean AUC of fields receiving the same dose fractionation schedule. As a confirmatory procedure, the same analysis was repeated with a weighted area under the curve (WAUC) approach, in which the time spent at or above each of the 5 nonzero grades was calculated for each field in each patient. These times were used as explanatory variables in a linear regression analysis of biological equivalent dose to establish statistically the weight of each grade providing the optimal relationship between dose and effect. Using these regression coefficients, the weighted area under the grade-time curve (WAUC) was estimated. RESULTS: The AUC was significantly correlated with the isoeffective dose in 2-Gy fractions (ID2). An analysis of variance components, using the maximum likelihood method, showed that 90% (with 95% confidence limits 65% and 100%) of the variance in radioresponsiveness in the right-sided field was explained by the radioresponsiveness on the left-sided field. Through the linear regression analysis between the AUC and the ID2, it was estimated that patients with a reaction that is 1 SD from the population mean would require a dose modification of approximately 23 Gy (from the group mean of 56 Gy) to give them a level of reaction similar to the group average. Similarly, the WAUC was significantly correlated with the ID2, and 81% (with 95% confidence limits 49% and 100%) of the variance in radioresponsiveness in the right-sided field was explained by the radioresponsiveness on the left-sided field. Patients with a reaction that is 1 SD from the population mean would require a dose modification of approximately 21 Gy (from the group mean of 56 Gy) to give them a level of reaction similar to the group average. CONCLUSION: For a given fractionation schedule, patient-related factors explain 81-90% of the patient-to-patient variation in telangiectasia level seen after radiotherapy. The remaining 10-19% are explained by stochastic effects. This observation encourages further research into genetic or phenotypic assays of normal tissue radioresponsiveness.     

Intrauterine contraceptive devices: MR imaging

To assess the safety of magnetic resonance (MR) imaging in women who have an intrauterine contraceptive device (IUD) in place, in vitro and in vivo studies were performed at both 0.35 and 1.5 T. Two commonly used IUDs were tested, one all of plastic, the other with a coil of copper wire on it. Specifically, the study assessed possible motion of the IUD in the magnetic field, potential of the IUD to heat up during two spin-echo imaging sequences commonly used in MR imaging of the pelvis (2,000/30 and 60 [repetition time, msec/echo time, msec], and 500/30), and the appearance on MR images of the IUD devices. A retrospective review of MR images of the pelvis in six women who had an IUD in place was also performed. Results show that an IUD does not move under the influence of the magnetic field, does not heat during spin-echo sequences commonly used for pelvic imaging, and does not produce artifacts in vitro or in vivo. Patients with either type of IUD can be safely imaged with MR, and MR images of the pelvis are not degraded by the presence of an IUD.     

Lymphoceles: imaging characteristics and percutaneous management

Twenty-five patients who had lymphoceles underwent sectional imaging and interventional radiologic procedures. Viewed using sonography, lymphoceles were hypoechoic to anechoic, occasionally with internal septa and debris. Low numbers (occasionally negative values) were observed using computed tomography (CT); these numbers strongly suggest the diagnosis of lymphocele. Calcification was observed on CT images of one patient. Diagnostic aspiration revealed tan to yellow fluid containing many lymphocytes; pathognomonic fat globules were observed in four cases. Malignant cells were found in two collections, an unusual occurrence. Therapeutic needle aspiration and short-term catheter drainage were usually unsuccessful (only one of five patients [20%] was cured). Long-term (1-5-week) catheter drainage cured 11 of 14 patients (78.6%). Sclerosing agents may have been beneficial for lymphocele obliteration in three of four patients. For most patients, lymphoceles may be diagnosed and treated successfully using radiologic means.     

Markers of HIV infection in the Concorde trial. Concorde Co-ordinating Committee

The Concorde trial compared immediate (Imm) with deferred (Def) AZT monotherapy in asymptomatic HIV-positive participants. Haematological and immunological markers and weight were measured throughout, and correlated with clinical endpoints. Markers associated with disease progression (CD4 lymphocyte count and percentage, platelets, p24 antigen and beta 2 microglobulin favoured Imm: those associated with toxicity (haemoglobin, neutrophils and white cell count) favoured Def. CD8 and total lymphocyte count did not differ significantly between groups. In multivariate analysis, the combination of baseline CD4, p24 antigen and beta 2m was the best baseline predictor of disease. Including change in CD4 and beta 2m at 12 weeks, or changes over follow- up in these markers significantly improved the fit. Markers were also incorporated into the definition of 'clinical' endpoints. Hazard ratio estimates from end-points that included CD4 < 50 and CD4 < 25 were closest to those for AIDS or death alone, but added very few extra events. Use of other landmark CD4 counts (100 or greater) or relative decreases in counts (25% or more) increased the number of events, but overestimated the effect of immediate AZT. Although AZT had a beneficial effect on the surrogate markers of efficacy evaluated, these changes did not predict clinical outcome, nor could the markers be usefully incorporated into an endpoint definition.      

High-dose atorvastatin therapy in severe heterozygous familial hypercholesterolaemia

Lipid targets can be difficult to attain in familial hypercholesterolaemia. To compare atorvastatin with simvastatin- fenofibrate and simvastatin-cholestyramine therapy, we studied 54 patients with familial hypercholesterolaemia over periods of 2-6 months on each therapeutic regimen. The atorvastatin regimen reduced total cholesterol by 41.2 +/- 11.2%, LDL by 45.6 +/- 15.5%, triglycerides by 33.8 +/- 24.8%, and increased HDL by 2.3 +/- 37.0%. Simvastatin- fenofibrate therapy achieved reductions of 33.9 +/- 8.5% in cholesterol, 42.0 +/- 12.2% in LDL, 34.7 +/- 38.3% for triglycerides, and a 25.4 +/- 55.1% increase in HDL. Simvastatin-cholestyramine gave a reduction of 31.3 +/- 11.8% in cholesterol, 36.0 +/- 14.4% in LDL, 13.7 +/- 36.3% in triglycerides, and a 1.1 +/- 30.3% rise in HDL. The atorvastatin regimen was marginally but not significantly better than simvastatin-fenofibrate in improving the LDL:HDL ratio, LDL:apoB and and apolipoprotein B:A1 ratios. Eleven patients (20.4%) had side- effects: two discontinued atorvastatin due to side-effects; two patients had rashes; six had myalgia and two had diarrhoea. Gastrointestinal side-effects were described in 16 (30.1%) patients on simvastatin-cholestyramine therapy and four cases of myalgia (11.2%) were seen with simvastatin-fenofibrate. In nine patients on atorvastatin (20.4%) a 30% or greater fall in HDL was observed, compared to five patients with resin therapy (9.2%) and two with fibrate therapy (5.5%). There were no significant differences in liver or muscle biochemistry between the regimens, but atorvastatin did raise transaminase and creatine kinase concentrations significantly compared to pre-treatment values (p = 0.001). Atorvastatin significantly improves the lipid profile in most patients compared with other regimens. It has a comparable incidence of side-effects to combination therapy regimens.      

Characterization of the epitope recognized by a monoclonal antibody highly specific for blood group M antigen

The mouse monoclonal antibody M2A1 of IgG1 class, which is highly specific for blood group M antigen, was obtained and characterized by means of hemagglutination, enzyme-linked immunosorbent assay, immunoblotting, and inhibition assays. The use of modified M glycoprotein preparations for inhibition tests and of variant McN and Henshaw red cell membranes for immunoblotting showed that M2A1 recognized an epitope including the NH2-terminal serine and sialic acid residues of glycophorin A, whereas the fifth glycine residue was not involved. The reactivity of the antibody with M antigen was distinctly dependent on ionic strength and pH; the optimum was at pH 8 to 9. The alpha-amino group of terminal serine residue was not necessary for the reaction with M2A1 antibody, and the results obtained suggested that the positive charge of this group contributed to decreasing antigen-antibody reactions at pH below 8. The reaction of the antibody with blood group N antigen was not detectable in any of the assays used.     

Mental health and discrimination among migrants from Africa: An Italian cross-sectional study

This study aimed to assess depression, anxiety, posttraumatic stress disorder (PTSD) and discrimination in African migrants and investigate determinants. A cross-sectional study was conducted in Italy (July 2019–February 2020). Inclusion criteria: being a citizen of an African country or having parents who are citizens of an African country. Questionnaires included tests for depression, anxiety, PTSD, discrimination. Multivariable regressions were performed. Participants were 293. The prevalence of depression, anxiety, and PTSD was: 12.1%, 12.1%, and 24.4%. Only 7.2% declared not to be discriminated. Among significantly associated factors, waiting for/being in possession of temporary permits and discrimination were associated with all mental outcomes. Being (or having parents from) Sub-Saharan Africa increased the likelihood of discrimination. A relevant prevalence of mental illnesses was reported. Particularly, Sub-Saharan Africans potentially offer a unique point of view. Migrants' mental health should be a priority for national and international programs of health monitoring.     

Head-Up Tilt Test in Patients with High Pretest Likelihood of Neurally Mediated Syncope: An Approximation to the "Real Sensitivity" of this Testing

This study was designed to examine the "true sensitivity" of a specific head-up tilt (HUT) testing protocol using clinical findings. The HUT protocol used 45 minutes at 60 degrees for the baseline portion and intermittent boluses of 2, 4, and 6 micrograms of isoproterenol in the second phase. Eighty-eight patients (40 men and 48 women; mean age of 33.8 +/- 16 years) with recurrent syncope and high pretest likelihood of neurally mediated syncope were included. The following were considerated as high pretest likelihood criteria: (1) at least two syncopal episodes; (2) no structural heart disease and normal baseline ECG; (3) age < 65 years; (4) a typical history of neurally mediated syncope, triggering factors plus premonitory signs; and (5) short duration of symptoms and fast recovery without neurological sequelae. Fifty-four patients (61%) had a positive tilt test (34/88 baseline [39%] and 20/50 with isoproterenol [40%]). The shorter time interval between the last syncopal episode and baseline HUT test was the only predictor for a positive response (P < 0.003). Conversely, this time interval was not predictor of positive responses during isoproterenol-tilt testing. In conclusion: (1) we claim a "sensitivity" for this combined protocol of 61%; and (2) our results indicate that patients with syncope of unknown origin must be tilted nearest as possible to the last syncope to increase the positive responses of HUT test.