Search PubMed⌕ Search

Biomedical subjects

D Richard

Publications and source records attributed to D Richard.

At least 109 records · Page 6Linked to original sources
PubMed1994

Overview of the lenograstim pharmacoeconomics programme.

Lenograstim is a recombinant colony-stimulating factor that has been shown to be a useful adjunctive agent in cancer chemotherapy. Clinical trials have demonstrated the efficacy of lenograstim in correcting chemotherapy-induced neutropenia and associated complications in inflammatory breast cancer and non-Hodgkin's lymphoma, and in facilitating dose intensification of chemotherapy in small cell lung cancer. To meet increasing demands for economic data on new drug entities, a lenograstim pharmacoeconomics programme was established. This programme involved prospective economic evaluations of lenograstim that were undertaken as part of phase III randomised clinical trials by a combined German/Italian health-economics team (inflammatory breast cancer), a French team (non-Hodgkin's lymphoma), and a team from the UK (small cell lung cancer).

Adjuvants, Immunologic↗
PubMed1994

Pharmacoeconomic evaluation of lenograstim. Conclusions and future directions.

To evaluate the safety and efficacy of lenograstim, a new recombinant human granulocyte colony-stimulating factor (rHuG-CSF), as an adjunct to cancer chemotherapy, 3 phase III randomised clinical trials were recently conducted in Europe in patients with inflammatory breast cancer, non-Hodgkin's lymphoma, and small cell lung cancer. To explore the economic implications of lenograstim therapy, a multinational pharmacoeconomics programme was undertaken using data collected during these clinical trials. This programme consisted of concurrent prospective economic evaluations undertaken by study teams in France (non-Hodgkin's lymphoma), Germany and Italy (a combined evaluation in inflammatory breast cancer) and the UK (small cell lung cancer). In these studies, attention was focused on the direct costs of medical care-principally the costs of cancer chemotherapy as well as its associated morbidity. In 2 of the pharmacoeconomic evaluations (i.e. the French, German/Italian), lenograstim was found to generate cost savings as a result of reductions in morbidity associated with chemotherapy. However, the cost of lenograstim therapy would be likely to exceed these savings, leading to an overall increase in the costs of cancer treatment. Whether the use of lenograstim is cost-effective will therefore largely depend on its impact on patient survival and quality of life, and current practical use. These issues are the focus of additional clinical studies currently underway. In addition, new research is focusing on the clinical benefits of lenograstim in other areas of oncology and haematology. Further pharmacoeconomic studies in these areas are also warranted.

Adjuvants, Immunologic↗
PubMed1994

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)

Adipose Tissue↗
PubMed1993

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.

Analysis of Variance↗
PubMed1993

Arterial oxygen saturation in preterm neonates without respiratory failure.

To obtain normal data on arterial oxygen saturation as measured by pulse oximetry (SpO2; Nellcor N200), we obtained 12-hour tape recordings of SpO2, photoplethysmographic waveforms, instantaneous pulse rate, and observations of breathing movements on 55 preterm neonates (25 girls) who had been admitted to one of four special care baby units but had no signs of respiratory distress and were breathing room air at 24 hours of age. Their median gestational age at birth was 35 weeks (range, 30 to 36), and their median age at the time of study 1 day (range, 1 to 7). Median baseline SpO2, measured only during regular breathing, was 99.4% (range, 90.7 to 100; 5th percentile, 95.5). Ten recordings (18%) contained a total of 83 episodes of desaturation (defined as a fall in SpO2 to < or = 80% for > or = 4 seconds). The 95th percentile for desaturation frequency was eight per recording. One infant had 55 episodes of desaturation and thus accounted for two thirds of all episodes observed. Only one of the episodes of desaturation in this infant, and none of those in the other nine infants, had been noted clinically, nor had the abnormally low baseline SpO2 (90.7%) in one infant. Baseline SpO2 in these nondistressed preterm neonates was higher than might be expected, given the SpO2 levels currently recommended for preterm infants with respiratory failure. A minority of infants, however, had a low baseline SpO2 or a high frequency of episodes of desaturation, the potential effects of which remain to be determined.

Arteries↗
PubMed1993

Energy balance and lipid metabolism in transgenic mice bearing an antisense GCR gene construct.

Energy balance and lipid metabolism were investigated in transgenic mice bearing an antisense glucocorticoid receptor (GCR) gene construct that impairs the normal expression of the GCR gene. Food intake was recorded during the 15 days preceding decapitation of adult normal and transgenic mice, and feces were collected to derive the digestible energy intake. Body composition measurements consisted of the determination of energy, protein, and fat content of the carcass. Carcass energy was determined by bomb calorimetry, whereas carcass protein was measured by the Kjeldahl procedure. Energy expenditure was estimated from the continuous oxygen consumption (VO2) monitoring over a 24-h period. Lipoprotein lipase (LPL) activity was quantified in epididymal white adipose tissue (WAT), heart, and vastus lateralis muscle (VLM) by measuring the in vitro hydrolysis of labeled triolein in the presence of tissue homogenates. Norepinephrine (NE) content of both interscapular brown adipose tissue (BAT) and heart were determined by high-performance liquid chromatography (HPLC). Energy intake and expenditure were significantly lower in transgenic mice than in controls. Concurrently, both fat content and total energy of the carcasses were significantly higher in the transgenic animals. In comparison with normal mice, heart and VLM LPL activity was significantly reduced in transgenic mutants. There was no difference between groups in LPL activity in WAT. Finally, heart and BAT NE contents were lower in transgenic animals than in control mice. These results suggest that a defective GCR system may affect energy balance through increasing energetic efficiency, and they emphasize the modulatory effects of hypothalamic-pituitary-adrenal axis changes on muscle LPL activity.

Adipose Tissue, Brown↗
PubMed1993

The organization of the suprachiasmatic circadian pacemaker of the rat and its regulation by neurotransmitters and modulators.

The long-term goal of our research is to understand how cells of the suprachiasmatic nucleus (SCN) are organized to form a 24-hr biological clock, and what roles specific neurotransmitters and modulators play in timekeeping and resetting processes. We have been addressing these questions by assessing the pattern of spontaneous neuronal activity, using extracellular and whole-cell patch recording techniques in long-lived SCN brain slices from rats. We have observed that a robust pacemaker persists in the ventrolateral region of microdissected SCN, and have begun to define the electrophysiological properties of neurons in this region. Furthermore, we are investigating changing sensitivities of the SCN to resetting by exogenous neurotransmitters, such as glutamate, serotonin, and neuropeptide Y, across the circadian cycle. Our findings emphasize the complexity of organization and control of mammalian circadian timing.

Animals↗
PubMed1993

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.

Adipose Tissue↗
PubMed1992

The 5-hydroxytryptamine agonist fenfluramine increases Fos-like immunoreactivity in the brain.

This study was designed to assess the effects of the 5-hydroxytryptamine (5-HT) indirect agonist fenfluramine on the brain distribution of Fos- and corticotropin-releasing factor-like immunoreactivity (F-LI and CRF-LI). A single intraperitoneal injection of either DL-fenfluramine (25 mg/kg) or saline was given to resting Sprague-Dawley rats housed on a 12-12 h light-dark cycle and fed libitum. Sixty min following injections, rats were killed and brains removed and sliced (40 microns thick) in a coronal plane from the anterior olfactory bulb to the brainstem. Brain slices were then stored at -40 degrees C pending the tissue localization of F-LI and CRF-LI. F-LI and CRF-LI were determined by means of a double immunostaining procedure using the peroxidase-avidin:biotin complex (ABC) method. Fenfluramine injection led to a marked increase in F-LI in the caudate-putamen (CPu), the parvocellular division of the hypothalamic paraventricular nucleus (PVN), and the central amygdaloid nucleus (CeA). In the PVN, most of the F-LI was co-localized with CRF-LI. There was no attempt to identify which types of neurons displayed F-LI in CPu and CeA. While F-LI was readily observable in all rats treated with fenfluramine, it was not discernible in the control animals. This study provides evidence for an involvement of the immediate-early genes c-fos in the central action of fenfluramine.

Amygdala↗
PubMed1992

Effects of fasting and food restriction on sympathetic activity in brown adipose tissue in mice.

The activity of the sympathetic nervous system in mice that were either fed ad libitum, food restricted or fasted was estimated by measuring the accumulation of dopamine following the inhibition of dopamine beta-hydroxylase activity. Mice in each group were injected with the dopamine beta-hydroxylase inhibitor 1-cyclohexyl-2-mercaptoimidazole and were exposed to either 30 degrees C (warm) or 4 degrees C (cold). Mice were killed 1 h after the injection. Both heart and brown adipose tissue were then quickly removed and homogenized in ice-cold perchloric acid. Dopamine and noradrenaline were determined using high performance liquid chromatography. Regardless of whether mice were warm or cold exposed, both content and concentration of brown adipose tissue and dopamine were predictably higher in 1-cyclohexyl-2-mercaptoimidazole-injected mice than in non-injected animals. In mice fed ad libitum, post-injection content and concentration of dopamine in both brown adipose tissue and heart were higher in cold-exposed mice than in warm-exposed animals. In food-restricted and fasted mice, post-injection concentrations of dopamine in brown adipose tissue were higher in cold-exposed mice than in warm-exposed animals. In food-restricted and fasted mice there was no difference between warm- and cold-exposed animals with respect to post-injection contents and concentrations of dopamine in heart tissue. In fasted mice there was no difference between warm- and cold-exposed animals in post-injection content of dopamine in brown adipose tissue. This study provides further evidence that fasting, in contrast to food restriction, may blunt the tissue sympathetic nervous system response in brown adipose tissue of cold-exposed mice.

Adipose Tissue, Brown↗
PubMed1992

Adrenalectomy attenuates the effect of chemical castration on energy balance in rats.

The individual and combined influences of castration and adrenalectomy on energy balance in rats were investigated in a 2 x 2 factorial design. Castration was chemically achieved by treating rats with Buserelin, a gonadotropin-releasing hormone (GnRH) agonist. During the treatment, the rats were weighed every 2 or 3 d, and the total amount of food consumed was determined. At the end of the 14-d treatment period, rats were killed and their carcasses were analyzed for protein, fat and energy content. In the sham-operated groups, body weight gain was greater in Buserelin-treated rats than in saline-infused animals. However, in the adrenalectomized rats, there was no difference in body weight gain between the Buserelin- and saline-infused animals. In sham-operated groups, body protein and body fat gains were significantly larger in Buserelinthan in saline-infused animals. In saline-infused groups, protein gain was greater in adrenalectomized than in sham-operated animals. On the other hand, in the Buserelin-infused rats, there was no difference in the protein gain between the adrenalectomized and sham-operated rats. The adrenalectomized groups of rats ate less and deposited less fat and energy than their respective sham-operated counterparts. In the sham-operated groups, both the intake and the gain of energy were larger in the Buserelin-treated than in saline-infused rats. The present study indicates that adrenalectomy can significantly attenuate the influence of castration on energy gain, providing evidence that adrenals and ovaries can interact in the regulation of energy balance.

Adipose Tissue↗
PubMed1992

Tissue specificity of SNS response to exercise in mice exposed to low temperatures.

The present study was carried out to investigate the tissue specificity of the sympathetic nervous system (SNS) response to acute exercise in adult mice exposed to four ambient temperatures. SNS activity estimates in heart, pancreas, and brown adipose tissue (BAT) were obtained from the measurement of the dopamine (DA) tissue contents 1 h after the inhibition of the DA-beta-hydroxylase with 1-cyclohexyl-2-mercaptoimidazole (CHMI). DA was measured by electrochemical detection after the separation of the monoamine using high-performance liquid chromatography. In both heart and pancreas, temperature and activity influenced DA tissue contents after the CHMI injection. In these tissues, and regardless of whether mice were resting or exercising, the DA contents gradually increased while the ambient temperature was dropped from a thermoneutral temperature of 32 to 5 degrees C. In BAT, however, there was a significant interaction between temperature and activity on the tissue DA content; in contrast to what was observed in resting animals, DA did not uniformly augment in exercising mice when the temperature was decreased from 32 to 5 degrees C. In summary, the present results show that exercise can attenuate the stimulating effect of cold on SNS activity in BAT. This effect is seemingly specific to BAT because, in mice exposed to low ambient temperatures, SNS activity in both heart and pancreas is not lower in exercising than in resting animals.

Adipose Tissue, Brown↗
PubMed1992

Synaptic activation of rat supraoptic neurons by osmotic stimulation of the organum vasculosum lamina terminalis.

Intracellular recordings were obtained from neurons of the supraoptic nucleus in superfused explants of rat hypothalamus in vitro. Transient hyperosmotic stimulation of the organum vasculosum lamina terminalis (OVLT) area caused long-lasting increases in the frequency of excitatory post-synaptic potentials and an associated rise in the rate of action potential discharge. Such responses could be evoked by small (less than + 2%) increases in osmolality, but not by isotonic solutions. These results suggest that the OVLT plays a functional role in the osmoregulation of neurohypophyseal hormone release.

Action Potentials↗
PubMed1991

Acute ethanol treatment induces a bimodal response of phospholipid acylation rates in rat red blood cells.

A single intraperitoneal injection of ethanol (4 g/kg) in rats elicited a bimodal response of acylation rates in phosphatidylcholine and phosphatidylethanolamine of intact red blood cells. Within an initial period, ethanol inhibited acylation rates. The inhibition then reversed, leading to increased values which persisted as long as ethanol was present in plasma. Acylation rates were not correlated to ethanol concentrations in plasma. We suggest that red cells first desensitize to, then overcompensate for the inhibitory effect of ethanol on acylation reactions. These adaptive changes may be one of the events mediating membrane tolerance to ethanol.

Acylation↗
PubMed1991

Effects of exercise on energy balance in meal-fed mice.

The effects of exercise on energy balance have been investigated in mice accustomed to eating their daily food ration in three meals. A meal period lasts 1 hour, and during that period mice were allowed to eat unrestrictedly a pelleted stock diet. Two series of experiments were conducted. In one series of experiments indirect calorimetric measurements were carried out in untrained mice that were assigned to 3 experimental groups; a first group of mice was allowed to rest; a second group of mice was exercised immediately before one of the 3 meals; a third group of mice was exercised immediately after one of the 3 meals. The exercise bout consisted of 1 hour of forced exercise on a rodent treadmill at a speed of 20 meters per minute. O2 consumption (VO2) and CO2 production were monitored throughout a full day except at the time the exercising animals were on the treadmill. In a second series of experiments long-term energy balance measurements were carried out. Mice were then assigned to experimental conditions similar to those previously described for 31 days during which period food intake and body weight were continuously monitored. At the end of 31 days of experiment, mice were killed, and their carcasses were individually analysed for their contents of energy, fat and protein. Carcass and food gross energy contents were assessed by bomb calorimetry. At the end of the long-term energy balance trial, the percentage of fat, the energy gain, the energy density and the weight of the dry carcass were significantly lower in exercised groups of mice than in the resting group of animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The involvement of the sympathetic nervous system in meal-induced thermogenesis in mice.

The acute effect of food intake on the activity of the sympathetic nervous system (SNS) in both heart and brown adipose tissue (BAT) was investigated in mice. Upon delivery to the laboratory mice were housed singly and divided into two groups. Half the mice were accustomed to eat their daily food ration in two meals whereas the other half were given continuous access to food. SNS activity in both heart and BAT was estimated by measuring the accumulation of dopamine (DA) after having blocked the transformation of dopamine into noradrenaline (NA) with 1-cyclohexyl-2-mercapto-imidazole (CHMI). CHMI inhibits the enzyme dopamine beta-hydroxylase. On the day SNS activity was assessed, continuously fed (CF) or meal-fed (MF) mice were injected with either saline or CHMI one hour before being killed. In order to assess the anticipatory effects of being fed, a group of mice already accustomed to the meal-feeding schedule were not allowed to eat after the injections. Additional CF and MF mice were killed without being injected in order to determine the basal levels of both DA and NA. The results show that the accumulation of DA in both heart and BAT was higher in MF than CF mice regardless of whether MF mice were or were not fed after the injection of CHMI. It therefore appears that the intake of food may increase SNS activity in various tissues in mice, and that such a response may be largely of cephalic origin.

Adipose Tissue↗