Radiotherapy for multiple myeloma with skin involvement.

Multiple myeloma metastatic to the skin is a rare occurrence that usually reflects a high tumour burden. Here, we report the case of a woman with known multiple myeloma who developed cutaneous lesions on the right leg. Limited-field radiation treatment was successfully used to decrease her tumour bulk. Unfortunately, the patient died of complications related to systemic treatment a few months after developing the cutaneous involvement.

Sci-Fri PM: Planning-04: Dose escalation study using anatomy-based aperture IMRT and SPECT perfusion images for lung cancer.

In the case of non-small cell lung cancer, doses typically prescribed (60-66 Gy) are not sufficient to ensure a satisfactory tumor control probability. Dose escalation needs to be realized, but dose to organs at risk (OARs) must be kept under widely accepted clinical thresholds. Also, lung functionality is not homogeneously distributed over all the volume: single-photon emission computed tomography (SPECT) allows spatial characterization of perfusion, open the way to the design of treatments plans that could preferentially avoid highly-functional lung. In this study, three cases of lung cancer were retrospectively used to assess the capacity of an anatomy-based aperture inverse planning system to realize dose escalation while limiting dose to perfused lung. Plans were generated for four-beam non-coplanar configurations, mixing 6 and 23 MV photon beams. All dose calculations were performed using Pinnacle3 superposition/convolution algorithm. An increasing dose was prescribed to a subvolume of the initial planning target volume. Levels of escalation achieved for the three cases studied were 81 Gy, 111 Gy and 66 Gy to the subvolume. Escalation was limited in two cases by the dose to the esophagus and in the other case by the presence of overdosages near beam entry ports. Calculation of dose-volume parameters for OARs shows that they respect clinical thresholds. Plans generated by the system are less complex than plans generated in beamlet-based IMRT, because of the use of few, large segments. The approach used in this study allows important dose escalation, potentially improving treatment outcome.

Effect of estrogen replacement therapy on distribution of myocardial blood flow in female anesthetized rabbits.

Estrogen replacement therapy reduces risk of cardiovascular events by altering coronary vasoregulation and distribution of blood flow. Vessel reactivity and blood flow distribution were assessed in anesthetized female rabbits in the following groups: 1) sham, 2) ovariectomy, 3) ovariectomy + 17beta-estradiol, and 4) ovariectomy + dehydroepiandrosterone. After a 2-wk treatment, cardiac hemodynamics, vascular reserve, and blood flow were evaluated during the following infusions: 1) NaCl, or vehicle (0.5 ml/min), 2) acetylcholine (2 mg/kg), 3) isoproterenol (2 mg. kg(-1). min(-1)), and 4) chromonar (8 mg/kg). In hearts from ovariectomized rabbits, autoregulatory blood flow was preserved despite lower diastolic perfusion pressures (55 +/- 8 vs. 64 +/- 8 mmHg in sham) and rate-pressure product (14.4 +/- 0.8 vs. 19.3 +/- 0.8 beats/min. mmHg x 10(-3)). Estrogen replacement therapy restored coronary pressure and reserve, and all drugs increased vascular conductance. In conclusion, in hearts from ovariectomized rabbits, vascular reserve declined because coronary pressure was lower; however, blood flow was preserved at a higher level than expected for oxygen demand. Estrogen replacement therapy restores myocardial oxygen supply-demand indices and returns coronary pressure-flow data to levels observed in animals with intact ovaries.

Interaction of corticosterone and gonadal steroids on lipid deposition in the female rat.

The present study was designed to evaluate the interaction of corticosterone (CORT) and female gonadal steroids on energy balance and lipid metabolism. To this end, a 2 x 4 factorial experiment was carried out in which two cohorts of rats differing in their ovary status [OV status: intact (INT) and ovariectomy (OVX)] were each divided into four groups defined by their CORT status [CORT status: nonadrenalectomized (non-ADX), ADX without CORT replacement (placebo subcutaneous pellet), ADX with low-dose CORT replacement, and ADX with high-dose CORT replacement]. After 3 wk of treatment and a 12-h fast, rats were killed and their carcasses analyzed for energy (lipid and protein) content. In addition, indexes of endogenous triglyceride (TRIG) production (liver TRIG content), transport into plasma (triglyceridemia), and incorporation into fat stores [lipoprotein lipase (LPL) activity in adipose tissue (AT)] were assessed. OV and CORT status interacted on body weight gain, total energy, and fat gains. The interactions arose from the fact that the twofold increase in these variables brought on by OVX was abolished by ADX and restored by CORT replacement. Although in ADX groups there was a dose-related restoration of total energy and fat gain by CORT replacement in both INT and OVX cohorts, the impact thereupon of OVX observed in the non-ADX group reappeared only in ADX animals receiving the high dose of CORT. Protein gain was increased by OVX solely in non-ADX rats, whereas the high dose of CORT prevented any net protein gain independently of the OV status. Consistent with treatment effects on total body fat gain, OVX resulted in an increase in liver TRIG content, AT weight, AT LPL activity, and plasma insulin. All these effects of OVX were abolished by ADX and restored by the high dose of CORT. Plasma TRIG were unaffected by OV status but were highly responsive to CORT status. All treatment effects were highly correlated with cumulative food intake. This study shows that the presence of CORT is required for OVX to exert its action on global energy balance and the concomitant, closely integrated adaptations of lipid metabolism.

Involvement of the medial preoptic area in the anorectic action of estrogens.

The implication of the medial preoptic area (MPOA) as a site for estrogen in the regulation of energy balance was investigated. Food intake, O2 consumption (VO2), and CO2 production were measured in ovariectomized rats injected with estradiol (E2) in the medial preoptic nucleus (MPN). Moreover, knowing the potential for corticotropin-releasing factor (CRF) in the anorectic effects of estrogens, we identified estrogen receptors (ER) colocalized in CRF-containing cells of the MPOA and how MPN injections of CRF compared with estrogen injections with respect to VO2 and the VO2-to-CO2 production ratio (respiratory quotient RQ). These energy balance measurements after the injections of four different doses of E2 or CRF were carried out in meal-fed rats chronically implanted with a guide cannula targeted to the MPN. The identification of cells colocalizing ER and CRF was determined using a double-immunostaining procedure revealing ER and CRF immunoreactivities with two different couplers. The injection of E2 into the MPN induced a dose-dependent reduction in food intake, whereas it did not affect VO2 or RQ. Conversely, the injection of CRF into the MPN had no effect on food intake but increased VO2 and decreased RQ. The colocalization of ER and CRF immunoreactivities was found in the MPOA and adjacent regions of the bed nucleus of the stria terminalis. In conclusion, the results of this study provide evidence that the MPOA may represent a potential site for the anorectic effects of E2. Furthermore, the presence of ER and CRF in neurons of the MPOA and adjacent areas suggests a direct interaction between estrogens and the CRF system in the MPOA that is consistent with a role for CRF in the anorectic effects of estrogens. Finally, the results of this study indicate that the effects of a CRF injection into the MPOA differ from those of estrogens, suggesting that if CRF neurons are involved in the anorectic effect of estrogens they likely exert their action outside the MPOA.

The food-hoarding threshold is not raised by acute intraventricular NPY in male rats.

We studied the influence of acute intracerebroventricular (i.c.v.) NPY on the relation existing in the rat between food-hoarding behavior and the body weight of the animals. Six male rats were trained to feed every day from 1000 to 1200 h. Then, their threshold for the onset of food hoarding was measured from the intercept of the regression line relating the food hoarded during meal time (Y axis) to the body weight (X axis). Thirty minutes before the hoarding session, the rats were injected i.c.v. with either 4 micrograms of NPY or saline control. The mean threshold for food hoarding was not modified after NPY. Mean food intake during the hoarding sessions was also unchanged. These results suggest that intracerebral NPY at 4 micrograms did not acutely alter the set-point for body weight regulation.

Involvement of type I corticosteroid receptor in the effects of ovariectomy on energy balance.

The effects of the glucocorticoid receptor antagonist, RU-38486 (RU-486), and the mineralocorticoid receptor (MR) antagonist, RU-28318, on energy balance were investigated in a 2 [surgery: ovariectomy (OVX) and sham operation] x 3 (corticosteroid antagonist: placebo, RU-28318, RU-486) experimental design. Rats were treated for 28 days. Food intake and body weight were monitored throughout the treatment period. At the end of the treatment, rats were killed and their carcasses were analyzed for energy and nitrogen contents. Energy content was determined by adiabatic bomb calorimetry, whereas nitrogen was determined in 250-to 300-mg samples of dehydrated carcasses, with the use of the Kjeldahl procedure. The energy as protein was subtracted from total carcass energy to determine energy as fat. The gains in energy, fat, and protein were calculated by subtracting the values obtained at the end of the treatment period from initial values estimated from the body weights measured at the beginning of the experiment. A significant interaction effect of surgery and corticosteroid antagonist was observed on body energy gain, energetic efficiency, and fat gain. Whereas body energy gain, energetic efficiency, and fat gain were larger in OVX rats than in sham-operated animals treated with either placebo or RU-486, they were comparable in OVX and sham-operated rats treated with RU-28318. Surgery, but not corticosteroid antagonist, had a significant effect on digestible energy intake, energy expenditure, and protein gain. All these variables were higher in OVX rats than in sham-operated animals. Surgery also affected corticosterone levels and adrenal weight. Both of these variables were lower in OVX rats than in sham-operated animals. By demonstrating the ability of RU-28318 to attenuate the effects of OVX on energy balance, the present study provides evidence that MR occupation by corticosteroids facilitates the OVX-induced changes in energy balance.

Lesions of hypothalamic paraventricular nuclei do not prevent the effect of estradiol on energy and fat balance.

The chronic effects of estradiol (E2) on energy balance have been investigated in ovariectomized rats with hypothalamic paraventricular nuclei (PVH) lesions. Body weight and food intake were monitored throughout the E2 treatment, which lasted 26 days. At the end of this treatment, rats were decapitated, and their carcasses were processed to determine the body contents in energy, fat, and protein. Plasma adrenocorticotropic hormone (ACTH) and corticosterone were determined by radioimmunoassay and protein-binding assay at the end of the study. Regardless of whether they were sham- or PVH-lesioned, E2-treated rats ate, expended, and gained significantly less energy than untreated animals. In addition, E2-treated rats deposited less fat and protein than the rats not receiving E2. In contrast to the E2 treatment, PVH lesions accelerated the gains in energy and fat regardless of whether the rats were treated with E2 or with a placebo. There were no interaction effects of PVH lesions and the E2 treatment on energy or fat gains. Plasma levels of corticosterone and ACTH were higher in E2-treated rats than in animals receiving the placebo treatment. The present results provide evidence that the hypothalamic PVH is not an essential neuroanatomical structure in the effects of E2 on energy and fat balances.

Tissue- and gender-specific modulation of lipoprotein lipase in intact and gonadectomised rats treated with dl-fenfluramine.

This study evaluated the respective and interactive effects of chronic dl-fenfluramine treatment, an anorectic serotoninergic agonist, and gonadectomy on lipoprotein lipase activity in adipose tissue and skeletal muscle. Male and female Sprague-Dawley rats were gonadectomised. These as well as intact animals were treated with dl-fenfluramine or a placebo for 28 days. Gonadectomy brought about an increase in final body weight of females (16-18%, P < 0.0001), but a decrease in that of male animals (9-13%, P < 0.001). These changes were proportional to those of food intake. The increase in body weight of gonadectomised female rats was paralleled by that of retroperitoneal adipose tissue and vastus lateralis muscle weights, whereas in male rats, gonadectomy diminished muscle weight only. Lipoprotein lipase activity was doubled (P < 0.0001) by gonadectomy in adipose tissue of female rats, but remained unaltered by the surgery in male animals. Enzyme activity in muscle was unaffected by gonadectomy in both genders. Treatment with dl-fenfluramine reduced weight gain in males and females, whether they had been gonadectomised or not. A concomitant reduction was observed in adipose tissue mass and lipoprotein lipase activity, which was reduced to 50-65% of the activity measured in placebo-treated animals (P < 0.01). The drug remained without effect on muscle weight and lipoprotein lipase activity in either gender. Thus removal of gonadal steroids had divergent effects on LPL activity with regard to gender and tissue. In addition, dl-fenfluramine treatment was followed by decreased enzyme activity in adipose tissue, but not in muscle, this pattern being independent of the nature or presence of gonadal steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the 5-hydroxytryptamine agonist D,L-fenfluramine on energy balance in rats: influence of gender.

The effect of the 5-hydroxytryptamine agonist D,L-fenfluramine on energy balance was investigated in male and female rats in order to detect a possible gender difference. Male and female rats, either gonadally intact or castrated, received a daily injection of the 5-hydroxytryptamine (5HT) agonist fenfluramine during 28 days. Body weight and food intake were monitored throughout the treatment period. At the end of the treatment, rats were decapitated and their carcasses were processed in order to determine the carcass contents of energy, fat and protein. Regardless of the gender of the rats, fenfluramine significantly delayed the gains in body weight, body energy and body fat in either castrated or gonadally intact rats. In female rats, castration accelerated body weight gain in rats injected with saline as well as in those treated with fenfluramine. Additionally, castrated female rats deposited more energy, fat and protein than gonadally intact rats. In contrast, castrated male rats, independently of whether they received saline or fenfluramine, gained less body weight and deposited less energy, fat and protein than non-castrated male rats. In conclusion, the results of this study show that D,L-fenfluramine is as effective in altering energy balance in male as it is in female rats.

Treatment with alpha-helical-CRF(9-41) prevents the anorectic effect of 17-beta-estradiol.

The role of corticotropin-releasing factor (CRF) in the anorexia induced by 17-beta-estradiol (E2) has been assessed in castrated female rats that were trained to eat their daily food ration in three separate meals. Each rat was implanted with a permanent guide cannula that was aimed at the right lateral ventricle of the brain. Seven days after the brain surgery each rat was also subcutaneously implanted with an osmotic minipump containing Buserelin, a potent GnRH agonist that induces reversible castration in rats. Eight rats were used in the study, and each of them underwent four experimental treatments that consisted of a) a subcutaneous (SC) injection of oil combined with an intracerebroventricular (ICV) infusion of saline, b) a SC injection of E2 combined with an ICV infusion of saline c) a SC injection of oil combined with an ICV infusion of alpha-helical CRF(9-41), and d) a SC injection of E2 combined with an ICV injection of alpha-helical CRF(9-41). Subcutaneous injections of E2 or oil were carried out the day before the ICV infusions of alpha-helical CRF(9-41) or saline. Intracerebroventricular infusions were performed 30 min before the meal for which the interaction effect of E2 and alpha-helical CRF(9-41) on food intake was determined. E2 and alpha-helical CRF(9-41) interacted on food intake; E2 brought about a 33% reduction in food intake in rats when infused with saline, whereas it was without effect when infused with alpha-helical-CRF(9-41)-treated rats. The present results provide evidence that CRF is involved in the anorectic effect of E2.