Neural mechanisms involved in the corticosteroid feedback effects on the hypothalamo-pituitary-adrenocortical axis.
Explore the source record for details and available documents.
Adrenal Cortex Hormones↗
Biomedical subjects
S Feldman
Publications and source records attributed to S Feldman.
Effects of gender, pregnancy, and anesthesia on the pharmacokinetics of zidovudine in rats.
PURPOSE: The effects of gender, pregnancy and anesthesia on the pharmacokinetics of zidovudine (AZT) were studied in rats. METHODS: Unanesthetized male (MR), female (FR) and pregnant (day 20, PR) rats received 50 mg/kg AZT via a jugular vein cannula. Female (FRA), pregnant (day 20, PRA) and pregnant (day 20, PRR) rats maintained under ketamine: acepromazine:xylazine anesthesia also received 50 mg/kg AZT. Two fetuses were removed at each sampling time from the PRR group. Plasma samples were collected and analyzed by RIA. RESULTS: With the exception of a lower non-renal clearance in female rats, there were no gender differences in the disposition of AZT. No significant differences were noted in total clearance, non-renal clearance or volume of distribution between pregnant and female rats, however, significant differences in renal clearance values were evident. Anesthesia resulted in decreased total, renal and non-renal clearances in female and pregnant rats. The removal of fetuses during the experiments did not alter the total clearance of AZT in pregnant rats, however, renal clearance and volume of distribution were decreased by cesarian section. CONCLUSIONS: The rat appears to be a suitable laboratory animal model for investigating AZT disposition during pregnancy. However, results of pharmacokinetic studies when animals are maintained under anesthesia with ketamine:acepromazine:xylazine must be interpreted with caution.
Anesthesia↗
Progressive outer retinal necrosis secondary to varicella zoster virus in acquired immune deficiency syndrome.
BACKGROUND: A syndrome consisting of rapidly progressive outer retinitis in patients with suppressed immune systems has been described. The etiologic agent appears to be a member of the herpes virus family. METHODS: A 41-year-old man with acquired immune deficiency syndrome (AIDS) developed bilateral outer retinitis and choroiditis, which progressed despite antiviral treatment. A transscleral eye wall biopsy specimen and whole globe were submitted for microbiologic and histologic study. RESULTS: Polymerase chain reaction of a transscleral eye wall biopsy specimen and of the enucleated specimen determined the etiologic agent to be varicella zoster virus (VZV). Histologic studies demonstrated intranuclear inclusions consistent with viral particles in choroidal cells. CONCLUSION: Our study revealed intranuclear inclusions in choroidal cells, a previously undocumented finding in progressive outer retinal necrosis. Polymerase chain reaction was very useful in identifying the causative agent.
AIDS-Related Opportunistic Infections↗
Critical interaction therapy: couples therapy in combat-related posttraumatic stress disorder.
There is a need for family therapy interventions that are specific to the conditions found in families of traumatized people such as combat veterans. In these families, the historically "real" event of the trauma often continues to exert influence on the family system despite collusive arrangements that serve to keep it hidden. In families of combat veterans, a situation develops whereby the veteran becomes triangulated with a dead buddy without the spouse's knowledge. The discrepancy between past and present emerges in what we call the critical interaction between the spouses. This article outlines a method of couples therapy that attempts to demystify this critical interaction, and begins to integrate the discrepant narratives of each spouse. The establishment of a nascent mutuality of perspective within the couple releases energies that can be directed toward support rather than symptom-formation in the family system.
Combat Disorders↗
Bambuterol in the treatment of asthma. A placebo-controlled comparison of once-daily morning vs evening administration.
Once-daily morning (7 AM) vs evening (10 PM) administration of the terbutaline prodrug bambuterol (20-mg tablet dose) was investigated in a double-blind, cross-over, randomized, and placebo-controlled study involving 29 diurnally active patients with asthma. Terbutaline plasma concentration, spirometry, and drug tolerance were assessed during 39-h inpatient studies. A 7-day washout period separated each treatment. Mean 24-h plasma concentration was comparable for morning and evening bambuterol (13.2 vs 14.0 nmol/L). The Cmax for evening vs morning dosing was 17.2 vs 15.5 nmol/L (p < 0.02). The 24-h mean FEV1 was greater (p < 0.001) for bambuterol (morning: 3.2 L; evening: 3.4 L) vs placebo (2.9 L) as it was for FVC, FEF25-75%, and peak expiratory flow rate (PEFR), with the maximum effect at 4 AM independent of medication time. Evening dosing, however, resulted in greatest 7 AM (awakening) FEV1, FEV25-75, and PEFR (p < 0.03). With reference to corresponding-in-time placebo values, improvement in FEV1 at the end of the 24-h dosing intervals amounted to 0.34 L (13.5%) (p < 0.0004) and 0.35 L (15.9%) (p < 0.0012) with evening and morning bambuterol dosing, respectively. Side effects were greater for bambuterol than placebo, but not significantly so. Once-daily bambuterol therapy proved to be an effective treatment for asthma, whether administered in the evening or morning. Evening dosing seems best for nocturnal asthma since airway patency overnight and on awakening at 7 AM is most improved.
Adolescent↗
Antipyrine pharmacokinetics in the tail-suspended rat model.
As space flight becomes more commonplace, the influence of physiologic changes associated with the microgravity environment become of greater concern. Exposure to weightlessness has been shown to have numerous effects on body composition and organ function in animals and humans. However, studies examining possible alterations in drug metabolism and pharmacokinetics are not readily available. Antipyrine is a marker of hepatic oxidative function and total body water. The purpose of our study was to examine the effects of simulated weightlessness on the pharmacokinetics of antipyrine. Weightlessness was simulated through the use of the tail-suspended rat model. Rats were suspended for a total of 7 days. During the study period, antipyrine pharmacokinetics, after a single 20 mg/kg i.v. or p.o. dose, were evaluated at base line (day-1) and 1, 3 and 7 days after the initiation of suspension. Total body clearance was significantly elevated in the tail suspended rats from both the i.v. and p.o. dosing groups after 3 and 7 days of simulated weightlessness. In addition, clearance was elevated after 1 day of tail-suspension in the p.o. dosing group. Steady-state volume of distribution was not statistically different over the entire study period in either dosing group. Data from the present study suggest that brief periods of tail-suspension may markedly alter the pharmacokinetics of drugs in the rat and that more studies are required in models of weightlessness and actual space flight to understand the complex interaction between microgravity and hepatic metabolic activity.
Administration, Oral↗
Low-risk metastatic gestational trophoblastic tumors.
Explore the source record for details and available documents.
Antineoplastic Agents↗
A four-year retrospective study of 3i threaded implants.
The use of osseointegrated implants can be considered as one of the most productive developments in dentistry during this century. Although initially introduced for use in fully edentulous patients, their present widespread use in nearly all forms of tooth loss, as well as for the rehabilitation of maxillofacial prosthetics and in orthodontics, has significantly expanded the realm of restorative dentistry. The present multicentre retrospective study evaluates the results of 327 patients rehabilitated with 1047, 3i (Implant Innovations Inc.) threaded implants over a four-year period. Eight patients with 22 implants dropped out and were excluded from the study as they could not be evaluated. A total of 319 patients with 1025 implants remained. Nine implants failed in the mandible and 14 in the maxilla. There was a success rate of 98.2 percent in the mandible and 97.3 percent in the maxilla. The mean overall success rate was 97.75 percent, with little variation between the four study centres. These results are similar to previously published studies on titanium threaded implants and indicate that, with careful adherence to accepted principles of surgery and restorative dentistry, the 3i threaded implant system can be used confidently to provide the necessary support for an osseointegrated implant-supported prosthesis.
Adolescent↗
Differential effect of amygdaloid lesions on CRF-41, ACTH and corticosterone responses following neural stimuli.
The effect of amygdaloid (AMG) lesions on changes in median eminence (ME) CRF-41 and serum ACTH and corticosterone (CS) levels following neural stimuli were investigated in rats. In intact animals photic or acoustic stimuli caused CRF-41 depletion from the ME and a rise in serum ACTH and CS levels. In rats with medial or central AMG nuclei lesions, these responses were blocked. Basal AMG lesions were not effective. Also, all groups of animals responded normally to ether stress. These results indicate a differential effect of AMG nuclei on the hypothalamo-pituitary-adrenocortical (HPA) axis and demonstrate that the facilitatory effect of the AMG nuclei on the HPA axis responses involves the release of ME CRF-41, which stimulates ACTH and consequently CS secretion.
Acoustic Stimulation↗
Measles immunization of 2-year-olds in a rural southern state.
OBJECTIVE: To assess the measles vaccine coverage of 2-year-old children living in Mississippi during the national measles epidemic of 1989 and 1990. DESIGN: Survey of 2-year-olds randomly selected from the 1987 birth cohort. The status of measles-mumps-rubella (MMR) vaccination was determined by medical record reviews and family contacts. SETTING: A predominantly rural state in the southeastern United States with a large black minority population (35%) and a low per capital income ($9827 to $12,899). Approximately 80% of MMR immunizations are given by public health service nurses working in nine health districts. SUBJECTS: A total of 2450 preschool-aged children representing 6% of the 1987 birth cohort (n = 41,279). Three hundred forty-one children were considered ineligible, leaving 2109 in the final sample. MAIN OUTCOME MEASURES: Confirmed vaccination by the age of 2 years. Rates of immunization were calculated for the entire state, its health districts, and subgroups based on population density, per capita income, type of clinic visited, and race. RESULTS: The statewide immunization rate was 87% (95% confidence interval, 86% to 88%). Among the nine health districts, rates varied from 79% to 97% (median, 88%). They were similar for white and black children in each health district and within the state as a whole. The level of vaccine coverage was significantly higher in districts with lower population densities (89% vs 85%, P = .02) and in those with higher per capita incomes (89% vs 86%, P = .03). There were four minor outbreaks of measles during 1989 and 1990; half of the cases occurred in unimmunized children too young to receive the MMR vaccine. CONCLUSION: A high rate of measles immunization is attainable among 2-year-olds living in a rural state with a large black minority population and limited economic resources.
Child, Preschool↗
Small animal model of weightlessness for pharmacokinetic evaluation.
As the United States seeks a greater presence in space, physiologic changes associated with space flight become of greater concern. Exposure to a weightless environment has been shown to have numerous effects on body composition and organ function. Alterations include decreases in muscle and liver mass, changes in bone structure and integrity, and fluid shifts markedly affecting cardiovascular functioning. Furthermore, metabolic activity of the liver has been found to be altered in rats after extended periods of weightlessness. As the length of space travel increases, the probability for the need to administer pharmacologic agents to crew members during space flight for prophylaxis or treatment becomes greater. Thus, because of the observed physiologic and metabolic changes associated with weightlessness, it is reasonable to assume that the pharmacokinetics and pharmacodynamics of xenobiotics administered during space flight may be different that those found in 1g environment. To address these possible changes, the development of a model of weightlessness to investigate possible alterations in drug pharmacokinetics and pharmacodynamics before space flight is of importance. The tail-suspended rat is a well-described model of weightlessness. During the time of the suspension, the pharmacokinetics of marker compounds can be used to evaluate changes in hepatic and renal physiology. Rats suspended for different periods allow for the investigation of the length of weightlessness exposure and drug pharmacology. Results from the use of the suspended rat model provide valuable information regarding possible pharmacokinetic and pharmacodynamic changes associated with weightlessness, and therefore, provide space biomedical researchers with a method of investigating drug administration during space flight missions.
Animals↗
Two-year follow-up of 263 patients with post/perimenopausal vaginal bleeding and negative initial biopsy.
Patients with post- or perimenopausal bleeding (PMB) whose initial endometrial biopsy or dilation and curettage (D&C) reveals benign or insufficient tissue may eventually be diagnosed with endometrial cancer or complex endometrial hyperplasia. We studied 286 consecutive patients with PMB who had either an endometrial biopsy or D&C at Brigham and Women's Hospital during November 1990 to April 1991 and reviewed their subsequent specimens after a minimum of 23 months of follow-up. Of the initial 286 patients with PMB, 6 (2%) had endometrial cancer on their index biopsy, 17 (6%) had complex hyperplasia, and 201 (70%) had other benign findings. Sixty-two (22%) had "tissue insufficient for diagnosis." Excluding the 23 with cancer/complex hyperplasia, there were 263 patients in the cohort, 86 of whom (33%) had further endometrial sampling during the follow-up period. Of these, four (2%) were subsequently found to have a uterine malignancy (2 of the benigns, 2 of the insufficients) and five (2%) were subsequently found to have complex hyperplasia. Of the four patients subsequently found to have cancer, two had stage I adenocarcinoma, one had stage IV adenocarcinoma, and one had stage I high-grade stromal sarcoma.
Aged↗
Early postoperative feeding.
PURPOSE: Our intent was to show that immediate postoperative feeding of a regular diet after elective colorectal surgery was safe, tolerable, and feasible. METHODS: This was a nonrandomized, prospective study of 38 consecutive patients who underwent elective colorectal surgery over a three-month period. Our study parameters included operative length of time, intraoperative blood loss, need for transfusions, day to flatus or defecation, ability to tolerate a diet, placement of nasogastric tubes postoperatively, and length of hospital stay. These patients were compared with patients treated by different surgeons during the same time period but fed only after return of bowel sounds or flatus. RESULTS: Thirty-one of 36 patients eventually included in this study were able to tolerate our early feeding regimen. There were a total of seven other complications that were minor and unrelated to the early feeding. Patients who tolerated early feeding had shorter postoperative length of stays, 5.7 vs. 10.6 days. Patients who tolerated early feeding had shorter length of stays than patients treated in a more conventional manner, 5.7 vs. 8.0 days. Those who did not tolerate early feeding had longer procedures and greater intraoperative blood loss. CONCLUSIONS: Early postoperative feeding is safe and is tolerated by the majority of patients. Early feeding, if tolerated, decreases length of hospital stay and may decrease health care costs. Longer operative time and increased blood loss intraoperatively may indicate a more difficult procedure and identify those patients who will not tolerate early feeding.
Adult↗
Response of immunocompromised children with solid tumors to a conjugate vaccine for Haemophilus influenzae type b.
Serum antibody response to a conjugated Haemophilus influenzae type b polyribosylribitol phosphate-diphtheria toxoid vaccine was assessed in nonvaccinated children aged 1 1/2 to 5 years receiving chemotherapy for solid tumors. Responses occurred in 21 (42%) of 50 children after first vaccination, and in 10 (45%) of 22 revaccinated children.
Antibodies, Viral↗
Depolarizing neuromuscular block--a presynaptic mechanism?
It has been known since 1951 that drugs such as decamethonium and suxamethonium produced an acetylcholine like (agonist) effect on the postsynaptic membrane of the neuromuscular junction causing depolarization. Inspite of evidence of action of these drugs on the motor nerve terminals, it has been widely assumed that the neuromuscular block they produced is the result of depolarization followed by desensitization of the postsynaptic membrane. Evidence questioning the view that these drugs produce their clinical effects as a consequence of depolarization of the postsynaptic membrane or desensitization is presented together with the results of recent experiments which are more readily explained by proposing a presynaptic action of these drugs, initially stimulating then depressing acetylcholine release.
Animals↗
Metabolic cage isolation reduces antipyrine clearance in rats.
Rats are commonly isolated individually in cages during pharmacokinetic studies. However, isolation-induced changes in drug disposition are not commonly examined. Antipyrine is a marker of hepatic oxidative function and total body water. The purpose of the study was to investigate the effect of individual housing on antipyrine pharmacokinetics. Rats were individually housed in either standard polycarbonate boxes (n = 8) or metabolic cages (n = 10). On day 1 and day 9 rats were administered a single intravenous bolus injection of antipyrine 20 mg kg-1. Blood samples (100 microL) were obtained before and at 20, 40, 60, 90, 120, 180, 240, 300 and 360 min following the administration of the dose. Rats remained in their respective cages between evaluations. Serum antipyrine concentrations were determined by capillary electrophoresis. Pharmacokinetic parameters were estimated by model-independent methods. Antipyrine clearance was reduced by 38.4% in rats isolated in metabolic cages for eight days (P = 0.013) while the volume of distribution remained unchanged in both rat groups. These data suggest that the isolation of rats in metabolic cage systems may markedly alter the pharmacokinetics of xenobiotics, thus possibly masking experimental outcome.
Analysis of Variance↗
Effect of the brain constituent anandamide, a cannabinoid receptor agonist, on the hypothalamo-pituitary-adrenal axis in the rat.
Anandamide (arachidonylethanolamide), an endogenous ligand of the cannabinoid receptor, was recently isolated from porcine brain. We report here for the first time on the effect of this ligand on the hypothalamo-pituitary adrenal (HPA) axis in comparison to that of the plant cannabinoid delta 9-tetrahydrocannabinol (THC). Intracerebroventricular injection of anandamide or THC (50 or 150 micrograms/rat) increased significantly the serum levels of ACTH and corticosterone in a dose-dependent manner and caused a pronounced depletion of CRF-41 in the median eminence. These data suggest that anandamide parallels THC in activating the HPA axis via mediation of a central mechanism which involves the secretion of CRF-41.
Adrenal Glands↗
Characterization of the 2-deoxyglucose effect on the adrenocortical axis.
In the present study we examined the mechanisms involved in the activation of the hypothalamo-pituitary-adrenal (HPA) axis after administration of the glucose analog 2-deoxyglucose (2-DG), which inhibits intracellular glucose use. Adult male rats were injected with either 2-DG (400 mg/kg body wt ip) or vehicle and were killed 60 min later. 2-DG increased serum ACTH and corticosterone (CS) by 3- and 7-fold, respectively, as compared to vehicle-treated rats. Bilateral lesions of the lateral hypothalamic area completely inhibited the 2-DG-induced HPA axis activation. Administration of 2-DG caused a significant depletion in the CRF-41 content of the median eminence (ME). Pretreatment with dexamethasone (80 micrograms/kg body wt ip) inhibited the 2-DG-induced depletion of ME CRF-41 and the increase in serum ACTH and CS. To investigate the role of type I and type II corticosteroid receptors in mediating the feedback effect of endogenous glucocorticoids on the responses to 2-DG, specific type I (RU-28318) or type II (RU-38486) receptor antagonists were injected intracerebroventricularly (icv) (1 microgram/kg body wt). In rats pretreated with these antagonists, the recovery of serum ACTH and CS to basal levels after 2-DG was markedly inhibited. Injection of the serotonin (5-HT) neurotoxin, 5,7-dihydroxy-tryptamine, either into the raphe nuclei or icv, which caused a 50 and 70% depletion of the hypothalamic 5-HT content, respectively, did not affect the HPA axis responses to 2-DG. In contrast, icv injection of ketanserin, a 5-HT2 receptor antagonist, completely inhibited the 2-DG-induced activation of the HPA axis. The results suggest that: 1) the lateral hypothalamic area is involved in the mediation of the HPA axis responses to 2-DG; 2) CRF-41 released from the ME plays a dynamic role in mediating the 2-DG-induced adrenocortical response; 3) the effect of 2-DG is sensitive to inhibition by dexamethasone, and the feedback effect exerted by endogenous glucocorticoids is mediated by both type I and type II corticosteroid receptors; and 4) 5-HT is involved in the activation of the HPA axis after 2-DG via its interactions with 5-HT2 receptors.
5,7-Dihydroxytryptamine↗