Application of the quality index methodology for dosimetric verification of build-up effect beyond air-tissue interface in treatment planning system algorithms.

We have designed a simple benchmark test for the user of a treatment planning system to check the calculation algorithm's ability to model the build up effect beyond an air/tissue interface. The expected result is expressed as an inhomogeneity correction factor CF derived from measurements and from Monte Carlo calculations for a full range of photon beam qualities. The linear regression lines obtained from plotting CF as a function of beam quality index form the basis for a quantitative check of the algorithm performance.     

Heterogeneity of calcium channels in mast cells and basophils and the possible relevance to pathophysiology of lung diseases: a review

Calcium plays a critical role in the formation and secretion of a wide variety of chemical mediators. Calcium slow-channel blockers, e.g. nifedipine and verapamil, have been shown to inhibit the synthesis of SRS (SRS-A, leukotrienes) in human and guinea pig lung tissue, thromboxane A2 formation in rat lung and platelet activating factor in human neutrophils. Verapamil and nifedipine also prevent the release of lysosomal enzymes from rabbit and human polymorphonuclear neutrophils. Calcium-channel blockers produce variable inhibitory effects on allergic and nonallergic histamine secretion. Ca++-entry blockers also inhibit the Ca++ uptake (influx) into mast cells. Many of these inhibitory effects of Ca++ antagonists are antagonized by an increased extracellular Ca++ ion concentration. The magnitude of the inhibitory influences of Ca++-channel blockers on allergic and nonallergic release of chemical mediators appears to depend on the cell source, species, nature and the concentration of the secretory stimuli as well as on the composition and pH of buffers and the concentration of Ca++-entry blockers used. The data summarized in this review suggest the existence of a functional heterogeneity of Ca++ channels in leukocytes, mast cells and basophils. Interference with the Ca++-dependent steps involved in the formation and/or release of chemical mediators appears to be the primary mode of action for Ca++-channel blockers in these cells. The differential effects of Ca++ antagonists on Ca++-dependent activation of phospholipase A2,5-lipoxygenase, and calmodulin (or other intracellular Ca++-binding proteins) in different cell types (mast cells, basophils, leukocytes, lung tissue, etc.) may explain the variation of their effectiveness in inhibiting the synthesis/release of chemical mediators and antagonizing bronchoconstriction in response to diverse stimuli. During the process of hypersensitization and in immediate hypersensitivity diseases, Ca++ homeostasis (uptake, mobilization, distribution, relocation, etc.) may be altered in leukocytes (mast cells, basophils) and lung tissues. The altered Ca++ homeostasis could be responsible for the induction of airway hyperreactivity in asthmatics and for hyperreleasability of chemical mediators from leukocytes, mast cells and other cell types.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cyclosporine enhances salt sensitivity of body water composition as assessed by impedance among psoriatic patients with normal renal function.

OBJECTIVE: Cyclosporine (CsA) therapy may be accompanied by a significant increase in blood pressure, either sodium (Na+) independent or Na+ dependent. The relationship between Na+ intake and body water distribution among patients treated with CsA has not been evaluated. We report the study, by bioelectrical impedance analysis (BIA), of water composition changes after dietary salt manipulations both before and during CsA treatment of psoriatic patients. METHODS: Ten normotensive psoriatic patients, ages 37 +/- 12 years (range, 19 to 54), with normal renal function were included. Each patient was assessed by BIA in 2 phases, before (phase 1) and during (phase 2) CsA therapy (3 mg/kg/day). In both phases, each patient was assessed in basal conditions (basal1 and basal2), on day 7 of a low-sodium diet (LS1 and LS2; 20 mEq/day) and on day 7 of a high-sodium diet (HS1 and HS2; 350 mEq/day). Plasma creatinine (Pcr), urinary volume excretion (Uv), urinary sodium (UNa+), urinary potassium (UK+), urinary osmolality (UOsmo), weight (Wt), resistance (R), reactance (Xc), total body water (TBW), extracellular water (ECW), intracellular water (ICW), Na:K exchangeable (Nae:Ke), phase angle (PA), and body cell mass (BCM) were evaluated. Blood pressure was monitored during 24 hours on the last day of each diet. Paired Student's t-test was used to analyze the different phases. RESULTS: Before CsA treatment, Wt, TBW and Nae:Ke were lower during LS1 than during basal1, whereas TBW was higher during HS1 than during LS1. During CsA, Wt, TBW, ECW, and Nae:Ke were lower during LS2 than during basal2, whereas ICW and PA were higher during LS2 than during basal2. HS2 showed higher TBW, ECW, and Nae:Ke and lower ICW, PA, and BCM than during LS2. Systolic blood pressure was higher during HS2 than during LS2 or HS1. In addition, diastolic blood pressure was higher during HS2 than during HS1. CONCLUSION: Body hydration status was more sensitive to dietary salt fluctuations during CsA treatment than without CsA, and a high-sodium diet seemed to enhance the CsA-induced hypertension side effect. Moreover, patients on low sodium intake under CsA treatment displayed neither any disturbance of body water composition nor any blood pressure change. Our data suggest that a low sodium intake might be very useful in preventing undesirable pressure and volume changes brought about by CsA treatment.     

Using a spatiotemporal model to estimate the impact of suicide prevention in small areas

Health Services and Outcomes Research Methodology - Evaluating the impact of suicide prevention programs is more challenging in smaller counties, where reliable estimates of suicide rates are...     

COVID-19 risk in breast cancer patients receiving CDK4/6 inhibitors: literature data and a monocentric experience

Substantial changes in the management of cancer patients have been required worldwide in response to the COVID-19 pandemic. Beyond the due details on the primitive cancer site and setting at diagnosis, these latter adaptions are most commonly exemplified by a significant reduction in the screening of asymptomatic subjects, delays in elective surgery and radiotherapy for primary tumors, and dose reductions and/or delays in systemic therapy administration. Advanced breast cancer patients with hormonal receptor positive, HER2 negative tumors are usually treated with endocrine therapy combined with CDK 4/6 inhibitors as first- and second-line treatment. During the pandemic, experts’ recommendations have suggested the omission or delay of CDK 4/6 inhibitors delivery, or a careful evaluation of their real need due to the hypothesized increased risk of SARS-Cov-2 infection and disease possibly related to neutropenia. The inherent literature is sparse and inconsistent. We herein present data on the use of CDK 4/6 inhibitors during the pandemic. The evidence reported punctually reflects the experience matured at our Institution, a comprehensive cancer centre, on the topic of interest.     

Effects of growth hormone on leptin metabolism and energy expenditure in hemodialysis patients with protein-calorie malnutrition

The relationships among growth hormone (GH), leptin, and resting energy expenditure (REE) are not understood. It has been reported that in malnourished hemodialysis patients, GH increases muscle protein synthesis, a process that requires energy. The present study evaluated the arterial levels and the forearm exchange of leptin, as well as the REE of the same patients during their participation in the same study, in four sequential 6-wk periods: I, baseline; II, GH treatment; III, washout; and IV, GH + intradialytic parenteral nutrition. During periods II and IV, patients received GH (5 mg three times per week). REE rose by 5% in period II, declined during period III, and rose by 7% during period IV. Basal leptin levels were low (2.0 +/- 0.19 ng/L). Insulin and leptin levels, as well as leptin release from the forearm, were unchanged during periods I through III but rose (+ 36%; P: < 0.05) during period IV. Changes in arterial leptin were directly related to changes in forearm leptin release (P: < 0.002), indicating a role of leptin production by peripheral tissues on leptinemia. Changes in leptin release were directly related to insulin (P: < 0.001) and, less consistently, to insulin-like growth factor-binding protein-1 levels (P: < 0.02). Similarly, variations in leptin levels were directly related to insulin (P: < 0.01). Variations in REE were not related to variations in leptin or insulin levels but to changes in muscle protein synthesis (P: < 0.025). The data show that in malnourished hemodialysis patients, treatment with GH is not invariably associated with an increase in leptin production. An increase in leptin release by peripheral tissues and leptin levels occurs only in the setting of hyperinsulinemia. The increase in REE that is induced by treatment with GH is not dependent on changes in leptin but is largely accounted for by the energy cost of the stimulation of muscle protein synthesis.