Search PubMed⌕ Search

Biomedical subjects

S Armstrong

Publications and source records attributed to S Armstrong.

At least 145 records · Page 8Linked to original sources
PubMed1976

Effects of intracranial injections of 6-OHDA on food and water intakes, body temperature and body weight regulation in the rat.

6-Hydroxydopamine was injected either intraventricularly (320 mug in 10 mul) or intrahypothalamically (64 mug in 2 mul) into rats kept under either free feeding or body weight reduced conditions. Intraventricular injections caused a temporary aphagia and hypodipsia in free feeding rats but daily measurements failed to reveal any long term effects; body weight reduced rats did not display the temporary aphagia but were initially hyperphagic. Injections into the more rostral hypothalamic areas of free feeding rats also showed only minimal short term effects; however, some of the body weight in both body weight reduced group died within several days of injection. Injections made at more posterior loci again showed very little effect in both body weight reduced and free feeding groups; some temporary disruption of feeding occurred from lesions in the proximity of the zone incerta of some free feeding animals.

Animals↗
PubMed1976

Noradrenergic feeding system in monkey hypothalamus is altered by localized perfusion of glucose, insulin, 2-DG and eating.

Hypothalamic sites in the monkey were labelled by micro-injections of 3H-NE and successive push-pull perfusions were carried out at a rate of 25 mul/min. When the monkey was fed, 3H-NE within the perifornical region increased. When 2-deoxy-D-glucose (2-DG) was added to the perfusate, 3H-NE release was also enhanced, whereas insulin perfused at the same rate caused a delated increase in catecholamine levels as reflected by increased radioactivity. Glucose supressed the release of 3H-NE, suggesting overall that the noradrenergic feeding system in the hypothalamus of the monkey is modulated by the regional level of glucose as well as the local concentration of insulin.

Animals↗
PubMed1975

Arteriomegaly.

Arteriomegaly describes tortuous, ectatic, irregular vessels with prolonged blood flow. Seven cases of this entity are outlined with representative case reports. The increased incidence of aneurysms, thrombosis and embolization is noted in this and other series. The possibility that tortuous vessels may be confused with aneurysms on examination is also discussed. Due to the prolongation of blood flow, adequate arteriographic evaluation may be quite difficult.

Aged↗
PubMed1975

Comparison of the effects of intracranial injections of 6-OHDA and guanethidine on consummatory behavior and monoamine depletion.

6-Hydroxydopamine (6-OHDA) has been used extensively to study the effects of catecholamine depletion on feeding and drinking behavior. The results from these experiments are variable and do not clarify the involvement of catecholamines in these behaviors. Guanethidine, which has been used in studies of the peripheral autonomic nervous system, provides an alternative method of catecholamine depletion. In the experiments reviewed here the effects of injections of 6-OHDA and guanethidine into the rat brain on consummatory behavior and temperature regulation have been compared and related to changes in monoamine levels as shown by fluorescence histochemistry. Injections of 6-OHDA into anterior hypothalamic areas have lethal effects on food deprived animals. This effect may be explained in terms of loss of ability to regulate temperature. Animals whose catecholamines were depleted by guanethidine injections into anterior lateral hypothalamus showed a consistent reduction in food and water intake and an elevation of body temperature. Reconciliation of these findings appears difficult. However, a comparative study of the intracranial diffusion patterns of guanethidine and 6-OHDA has revealed marked differences in the extent of diffusion as seen with the fluorescence histochemical method when injected acutely or chronically into the lateral hypothalamus, the substantia nigra or the amygdala of the rat brain. Cannulation damage extended up to 1 mm in diameter. Generalized damage was far greater for 6-OHDA (2 mm) than for guanethidine (0.3 mm). At the doses used guanethidine, but not 6-OHDA caused specific damage to catecholamine-containing neurons up to a distance of at least 3 mm from the cannula tip. Guanethidine was less selective for dopaminergic compared to noradrenergic neurons. These differences between the effects of the two drugs are explained in terms of their unique pharmacological properties and their estimated decay in CNS tissue. An attempt has been made to account for the differences in behavioral data and in particular the variability of the 6-OHDA data in terms of the differences in the type of damage produced by the two drugs and the extent of their diffusion. It is also argued that the different patterns of damage would not easily be distinguished by biochemical analysis, and further, that changes in injection volume and concentration may lead to different damage patterns.

Amygdala↗
PubMedDate not supplied

Phase I/II trial of human recombinant granulocyte-colony-stimulating factor (filgrastim) and escalating doses of cyclophosphamide, mitoxantrone, and 5-FU in the treatment of advanced breast cancer.

PURPOSE: We performed a phase I/II dose-escalation trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (CNF) in combination with human recombinant granulocyte-colony-stimulating factor (G-CSF, filgrastim) in patients with advanced breast cancer. The objectives of this trial were (1) to gain experience with filgrastim given to patients with advanced breast cancer and receiving standard-dose CNF, and (2) to determine the maximum tolerated dose of CNF that could be given with filgrastim support by incremental dose escalation of two components of the CNF regimen, cyclophosphamide and mitoxantrone. METHODS: Four patients who had received prior therapy for advanced disease received standard-dose CNF with filgrastim support. Sequentially enrolled patients who had received no prior chemotherapy for advanced disease were treated with standard-dose CNF without filgrastim (5 patients), standard-dose CNF with filgrastim (15 patients), or were entered into sequential cohorts of 3-6 patients to be treated with increasing doses of CNF with filgrastim support (29 patients). RESULTS: The maximum tolerated doses that could be given with filgrastim support were 1500 mg/ml cyclophosphamide, 20 mg/m2 mitoxantrone, and 500 mg/m2 5-FU. Overall, 7 complete (14%) and 13 partial responses (26%) were observed. Despite the use of filgrastim, repeated cycles of CNF at doses of 2000 mg/m2 cyclophosphamide, 25 mg/m2 mitoxantrone, and 500 mg/m2 5-FU could not be given because of neutropenia and thrombopenia. Among 18 patients with bidimensionally measurable disease there were 3 complete (17%) and 5 partial (28%) responses. The median progression-free survival of all patients was 236 days (34 weeks). CONCLUSION: The use of filgrastim allows CNF to be given at approximately twice the dose intensity of "standard"-dose CNF. Because nonhematopoietic toxicity was not dose-limiting, further dose escalation of this regimen might be possible with more effective hematopoietic support. The response rate and survival of patients treated in this study were within the range expected with standard-dose chemotherapy.

Adult↗
PubMedDate not supplied

Effects of norepinephrine applied to the lateral hypothalamus on schedule induced polydipsia.

Intrahypothalamic injections of 3 doses of norepinephrine were administered to rats under conditions of 80 percent body weight reduction (prepolydipsia), 80 percent body weight reduction (schedule induced polydipsia), and normal body weight (postpolydipsia). The only significant reduction in water intake occurred with the highest dose of norepinephrine, under the prepolydipsic condition. The fact that norepinephrine failed to block schedule induced polydipsia indicates that this behavior is regulated by a different biochemical system than that of deprivation induced drinking.

Animals↗
PubMedDate not supplied

Intracranial injection of drugs: comparison of diffusion of 6-OHDA and guanethidine.

Marked differences in extent of diffusion have been shown with the fluorescence histochemical method between guanethidine and 6-OHDA(64 mug in 2 mul) when injected acutely or chronically into the lateral hypothalamus, the substantia nigra or the amygdala of the rat brain. Cannulation damage up to 1 mm in diameter and attributed to the implantation of cannulae and placebo injection was observed. A further area of generalized damage occurred following the injection of drugs and was far greater for 6-OHDA (2 mm) than for guanethidien (0.3 mm). Guanethidine, but not 6-OHDA, caused specific damage to catecholamine-containing nerurons up to a distance of at least 3 mm and more from the cannula tip. These striking differences between the effects of intracranial injection of 6-OHDA and guanethidine are discussed in terms of the uptake and degradation of the two drugs and the anatomical features of the injection site; they are not explicable in terms of experimental conditions such as concentration, volume of injection, molecular weight or lipid solubility. The different patterns of damage would not easily be distinguished by biochemical analyses and the catecholamine specificity of 6-OHDA in studies of the central nervous system must be seriously questioned. Vascularization of chronically implanted cannula tracks and the presence of anatomical diffusion barriers are also discussed in relation to the diffusion of drugs injected intracranially.

Amygdala↗
PubMedDate not supplied

Effects of chronic intracranial injection of low and high concentrations of guanethidine in the rat.

Low (64 mug in 2 mul) or high 320-1280 mug in 2 mul) doses of guanethidine sulphate were injected daily for up to 19 days into the lateral hypothalamus, substantia nigra, locus coeruleus, dorsal raphe nucleus, or amygdala region of the rat brain. Effects on monoamine-containing neurons were determined using fluorescence histochemistry. The noradrenergic terminals of the hypothalamus were depleted over a diameter of 7 mm by both low and high doses of guanethidine whereas, even with high doses, the dopaminergic terminals of the median eminence, amygdala and acudate nucleus were only partially depleted. Fluorescence levels of dopaminergic cell bodies of the sub stantis nigra and 5HT-containing cell bodies of the dorsal raphe nucleus were unaltered by low doses of guanethidine. Low doses of guanethidine did not affect the fluorescence of the noradrenergic cell bodies of the locus coeruleus, however high doses caused a substantial reduction in fluorescence levels. Normal levels of fluorescence were observed in all catecholamine-containing neurons within 14 days from cessation of injections. Thus, the xon retraction and eventual degeneration of peripheral sympathetic adrenergic neurons, which occurs as a result of chronic intraperitoneal injections of guanethidine does not occur with the catecholamine-containing neurons in the central nervous system. The rapid recovery of centrat catecholamine-containing neurons is remarkable in view of the extensive areas of brain damage produced by chronic injection of such high concentrations of drug. Fluorescence in peripheral adrenergic nerves was unaffected by chronic injection of guanethidine into the lateral hypothalamus but adhesions of some internal organs were observed. Blood vessels in the vicinity of the cannula were heavily reinnervated by fluorescent fibres probably arising from intracranial catecholamine-containing neurons. Some of the advantages of intracranial injection of guanethidine compared to 6-hydroxydopamine for behavioral experiments are discussed.

Amygdala↗
PubMedDate not supplied

Cafeteria behavior in the rat after hypothalamic cholinergic and adrenergic stimulation.

Norepinephrine, carbachol, or placebo was micro-injected into the perifornical region of the rat hypothalamus, via stereotaxically implanted cannulas. Ingestive behavior was observed in the hour after injection in a cafeteria situation in which water, milk, mash, powdered food, and lab chow were all freely available. After adrenergic stimulation, animals ingested significant amounts of mash only; after cholinergic stimulation, animals ingested significant amounts of water and milk, but water was significantly preferred to milk. These findings are seen as providing further support for the behavioral specificity of direct chemical stimulation of the brain, and as casting serious doubts on the interpretation of milk-ingestion as eating behavior.

Animals↗
PubMedDate not supplied

Factors affecting nonadherence with antibiotics.

Nonadherence with antibiotic therapy has profound implications both for patient health and the health care system that bears the financial costs incurred. Significant levels of nonadherence with antibiotic prescriptions have been demonstrated. Of the many proposed variables involved, those that are potentially modifiable relate to aspects of the doctor-patient interaction and drug regimen. Despite the potential for intervention with these variables, there have been very few methodologically sound studies examining their effect on adherence with either medications generally or antibiotics specifically. Only two studies were located that had tested the effectiveness of reduced complexity of antibiotic dosage schedules. The results suggest that the less complex the schedule, the greater is the adherence. Both practitioners and patients must be encouraged to use and accept simpler dosage schedules, preferably once-daily schedules wherever possible. The paucity of well-controlled studies to date highlights the need for further research evaluating intervention strategies that utilize variations in dosage schedule and elements of the doctor-patient interaction to improve adherence with antibiotic medications.

Anti-Bacterial Agents↗