Biomedical subjects
Publications and source records attributed to R L Reid.
Menstrual cycle-related exacerbation of common medical conditions such as migraine, epilepsy, asthma, irritable bowel syndrome, and diabetes, is a well-recognized phenomenon. Accurate documentation of symptoms on a menstrual calendar allows identification of women with cyclic alterations in disease activity.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant that has profound deleterious effects on development and reproduction. TCDD may act at one or more levels to alter the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. The objective of this study was to investigate whether TCDD modulates neuroendocrine systems by altering gene expression of arginine vasopressin (AVP), corticotrophin-releasing hormone (CRH), or pro-opiomelanocortin (POMC), which are important neuroregulators of the HPA and HPG axes. Four groups of female cynomolgus monkeys (Macaca fascicularis) were administered daily oral doses of gelatin capsule containing TCDD (0, 1, 5, or 25 ng/kg body weight) mixed with glucose 5 days a week for 1 year. At the end of the dosing period, animals were euthanized and brains were harvested. CRH, AVP, and POMC mRNA levels were semiquantified by in situ hybridization histochemistry on 30-microm coronal sections of the brain. Blood collected on the day of euthanasia was assayed for cortisol and progesterone. CRH mRNA levels in the paraventricular nucleus (PVN) were significantly increased by the 2 higher TCDD doses (5 and 25 ng/kg/day) compared to controls (p < 0.05). There was a trend towards increased AVP mRNA levels in both the supraoptic nucleus (SON) and PVN. No effect of TCDD on POMC was observed. Cortisol levels were significantly increased in TCDD-exposed animals. Progesterone concentrations and menstruation data indicated that TCDD did not interfere with ovulation. We conclude that TCDD stimulated the HPA axis by a central effect involving CRH, but had no effect on the HPG axis at the doses tested.
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BACKGROUND AND OBJECTIVE: This research evaluated the effectiveness of a new nonlaser prototype short-arc lamp to achieve photodynamic ablation of endometrium in a rat. STUDY DESIGN/MATERIALS AND METHODS: Thirty female Sprague-Dawley rats were divided into two groups. 5-Aminolevulinic acid (ALA), the precursor to the photosensitizer protoporphyrin IX, was injected into the left uterine horn and vehicle alone (Hyskon) was injected into the right horn of 23 rats (group 1). An additional seven rats received vehicle only into both uterine horns (group 2). Three hours later, a cylindrical diffusing optical fiber was inserted into the lumen of the uterine horns, and light treatment was delivered from either a laser or a nonlaser light source. Rats in group 1 received either 1 hour (n = 15) or 10 minutes (n = 8) of light treatment into both uterine horns. In rats in group 2, the left horn was exposed to 1 hour of light treatment. Uterine tissues were examined histologically 4 days after light treatment. RESULTS: One hour of light exposure to the uterine horns injected with ALA produced extensive necrosis of the rat uterine wall. No difference in the magnitude of destruction was seen between the groups treated with the laser and nonlaser light sources. Ten minutes of light exposure resulted in endometrial ablation that was comparable in both the laser- and the prototype-treated groups, but the destruction of the deepest layers of the uterine wall was more consistent in the group treated with the nonlaser prototype. One hour of light treatment from either light source did not result in any histological changes in the uterine horns not exposed to ALA. CONCLUSION: The extent of endometrial ablation in the rat uterine horn achieved with the nonlaser prototype was comparable to that achieved with the laser. Thus, the nonlaser prototype may provide a less expensive approach to photodynamic endometrial ablation.
OBJECTIVE: To report our experience developing and implementing an introductory course on research methods for Canadian obstetrics and gynecology residents. METHODS: A program entitled "An Introduction to Research," originating at Queen's University, developed into an annual series of regional courses across Canada, under the auspices of the Association of Professors of Obstetrics and Gynaecology of Canada. Didactic lectures, interactive workshops, and online computer demonstrations introduced participants to the basic elements of clinical research. RESULTS: Since its inception, over 1000 participants have attended the program. Nearly all of the 296 respondents to a course evaluation agreed that the program was well organized, presented material at an appropriate level, and was useful. CONCLUSION: This course ensured that residents in obstetrics and gynecology across Canada were given a basic level of research training, as required by the Royal College of Physicians and Surgeons of Canada.
OBJECTIVE: To describe a program for residents in obstetrics and gynecology to design, research, and present an innovative teaching activity to secondary-school students in reproductive health. METHODS: An interactive 3-hour assembly was held for 285 grade-9 and -10 students. Six residents chose topics that encompassed key areas in adolescent health (menstruation, contraception, risk-taking behaviors, sexuality, and sexually transmitted diseases [STDs]). Each gave an interactive presentation designed to address issues identified through anonymous questions submitted by the students in advance. Touch-pad technology was used throughout the presentations to ascertain the students' knowledge about, and attitudes toward, a range of reproductive health issues. Each resident participant completed a follow-up questionnaire. RESULTS: Touch-pads provided a unique format, allowing teens to respond candidly to sensitive topics anonymously while providing important feedback to resident educators to help them focus their presentations and address areas of greatest need. Resident participants reported that by preparing these presentations, they honed their knowledge about contraception, STDs, and teen sexuality; identified important community resources for teens; and were sensitized to issues unique to teen sexual-health counseling. CONCLUSION: This project provided an opportunity for residents to improve their knowledge of teenage sexuality and to develop skills as teachers, while forging a valuable link between the community and the university.
Ovarian steroids increase hypothalamic-pituitary-adrenal (HPA) axis activity and sensitize the hypothalamic-pituitary-ovarian (HPO) axis to stress-induced inhibition. The present study investigated the effect of ovarian steroids on CRH and arginine vasopressin (AVP) messenger RNA (mRNA) levels in the rhesus monkey hypothalamus, as both neuropeptides have been shown to stimulate the HPA axis and inhibit the HPO axis in this species. This was accomplished by measuring CRH and AVP mRNA in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) by in situ hybridization histochemistry. Menstrual cycles were simulated in ovariectomized (OVX) rhesus monkeys by sequential addition and removal of SILASTIC brand (Dow Corning Corp.) tubing containing either 17beta-estradiol (E2) or progesterone (P4). On the morning of day 11 of the simulated follicular phase (E2 alone) or day 21 of the luteal phase (E2 + P4), animals were anesthetized, and the brains were perfused with paraformaldehyde via the carotid artery. Coronal sections (30 microm) were cut, and mRNA for CRH and AVP in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) were semiquantified by in situ hybridization. CRH mRNA in the PVN of E2-replaced OVX animals (n = 7) was 2-fold greater than that in untreated OVX controls (n = 4), whereas CRH mRNA after E2 + P4 (n = 4) was no different from that in controls (optical density + SEM, 0.38 +/- 0.06, 0.13 +/- 0.08, and 0.14 +/- 0.09 for OVX + E2, OVX + E2 + P4, and OVX, respectively; P = 0.02). CRH in the SON was undetectable. In contrast to CRH, AVP mRNA in the PVN and the SON was similar in the three treatment groups. We conclude that E2 and E2 + P4 replacement to OVX monkeys exert different effects on CRH and AVP gene expression, as estrogen stimulation of CRH mRNA in the PVN was abrogated by progesterone, whereas no effect of ovarian steroids on AVP mRNA in either the PVN or SON was observed. We postulate that ovarian steroid regulation of CRH synthesis and release may in part explain the central nervous system mechanisms by which ovarian steroids affect the HPA and HPO axes during basal and stress conditions.
Exacerbation of certain medical conditions at specific phases of the menstrual cycle is a well-recognized phenomenon. We review the effects of the menstrual cycle on medical conditions, including menstrual migraine, epilepsy, asthma, rheumatoid arthritis, irritable bowel syndrome, and diabetes. We discuss the role of medical suppression of ovulation using gonadotropin-releasing hormone agonists in the evaluation and treatment of these disorders. Peer-reviewed publications from English-language literature were located via MEDLINE or from bibliographies of relevant articles. We reviewed all review articles, case reports and series, and therapeutic trials. Emphasis was placed on diagnosis and therapy of menstrual cycle-related exacerbations of disease processes. Abrupt changes in the concentrations of circulating ovarian steroids at ovulation and premenstrually may account for menstrual cycle-related changes in these chronic conditions. Accurate documentation of symptoms on a menstrual calendar allows identification of women with cyclic alterations in disease activity. Medical suppression of ovulation using gonadotropin-releasing hormone agonists can be useful for both diagnosis and treatment of any severe, recurrent menstrual cycle-related disease exacerbations.
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OBJECTIVE: To report the occurrence of menopausal-like hot flashes in women of reproductive age (18-45 years). DESIGN: Observational, prospective cohort study with a retrospective survey component. SETTING: Tertiary care premenstrual syndrome (PMS) clinic and university campus. PATIENT(S): Patients with confirmed PMS (n = 157) were compared with those with chronic menstrual cycle-related symptoms (n = 27). Women without menstrual cycle-related symptoms were solicited as controls (n = 58). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The frequency of episodes of chills and sweats and the magnitude of menstrual cycle-related symptoms were recorded over one cycle using the Prospective Record of the Impact and Severity of Menstrual Symptomatology (PRISM) Calendar. Characteristics of the episodes of chills and sweats were ascertained by a retrospective questionnaire. RESULT(S): In each group, the frequency of episodes of chills and sweats closely patterned the mean daily PRISM Calendar scores. At least one episode of chills and sweats was reported by 83.4% of the PMS group and 81.5% of the chronic group compared with 43.1% of the control group. The mean (+/-SD) number of episodes per cycle was 5.6 +/- 4.9 for the PMS group and 9.5 +/- 9.1 for the chronic group compared with 1.2 +/- 2.0 for the control group (the difference between all means was statistically significant). CONCLUSION(S): Episodes of chills and sweats similar to menopausal hot flashes were commonly reported by women with cyclic and chronic menstrual cycle-related symptoms.
BACKGROUND: The veracity of adult allegations of remote childhood sexual abuse have been the focus of intense debate fueled by the controversy over both repressed and false memory syndromes. Likewise, increased awareness of physician misconduct in recent years has mandated numerous policy statements and task force guidelines to protect patients. CASE: A 23-year-old woman alleged that she had suffered incestuous rape at age 12 years, resulting in pregnancy. She named a physician who she claimed had performed an illegal pregnancy termination. Subsequent evaluations revealed that she had uterovaginal agenesis. CONCLUSION: Neither sexual abuse nor physician misconduct should be tolerated, and all such allegations deserve thorough and expeditious investigations. However, we must remain cognizant that any such allegation may be false and have devastating consequences for the unjustly accused.
OBJECTIVE: To compare the efficacy of heparin-saturated oxidized regenerated cellulose absorbable adhesion barrier, Interceed (TC7; Johnson and Johnson Medical Inc., New Brunswick, NJ) to oxidized regenerated cellulose alone for the prevention of postoperative adhesions. DESIGN: Clinical trial. By random assignment, one ovary was wrapped in oxidized regenerated cellulose, and the contralateral ovary was wrapped in oxidized regenerated cellulose saturated with a heparin solution (1,000 U/mL). PATIENT(S): Forty women with defects on both ovaries due to adhesiolysis and/or ovarian cystectomy. MAIN OUTCOME MEASURE: Adhesion formation and raw ovarian surface area were assessed at second-look laparoscopy 10 days to 16 weeks later. RESULT(S): At the second-look laparascopy-adhesions were present on 52.5% (21/40) of the ovaries treated with oxidized regenerated cellulose plus heparin and in 65% (26/40) of the contralateral ovaries treated with oxidized regenerated cellulose alone. For ovaries treated with oxidized regenerated cellulose plus heparin, the raw surface area was reduced from 9.41 +/- 1.27 cm2 (mean +/- SE) at laparotomy to 1.33 +/- 0.52 cm2 at second-look laparoscopy. The corresponding figures for ovaries treated with oxidized regenerated cellulose alone were from 10.24 +/- 1.08 to 1.92 +/- 0.54 cm2, respectively. The mean difference between the reductions in raw surface area (85.9% for oxidized regenerated cellulose plus heparin; 81.3% for oxidized regenerated cellulose alone) was not significantly different from zero (difference = - 0.24 cm2; 95% confidence interval = -2.56 to 3.04). CONCLUSION(S): Adding heparin did not enhance significantly the adhesion-reducing capacity of oxidized regenerated cellulose adhesion barrier when applied to ovarian surfaces after cystectomy and/or ovariolysis at laparotomy. This conclusion is subject to the possibility of a type II error.
The objective of the present study was to determine if the concentration of protoporphyrin IX (PpIX) in the rat endometrium could be increased by administering 5-aminolevulinic acid (ALA) in multiple doses or by continuous infusion. The effect of pH, temperature and time in solution on the stability of ALA were also investigated. Estrogen-filled silastic capsules were implanted subcutaneously into ovary intact female rats (200-225 g) (n = 66). On the third day of hormonal priming, ALA (10 mg or 25 mg) dissolved in saline and adjusted to a pH of 5-5.5 was administered intrauterine either as a single bolus or as two injections 3 hours apart (n = 10). A fifth group of rats was infused with 25 mg ALA over a 12 hour period using an osmotic minipump (n = 6). In a second experiment, ALA (25 mg) was injected immediately after being dissolved in saline (pH 2) (n = 16) or after incubation at 37 degrees C for 12 hour (pH 2) (n = 7). PpIX was then extracted from the endometrium and myometrium using a 1:1 methanol/perchloric acid solution and quantified spectrofluorometrically. A dose-response relationship was observed between 10 and 25 mg of ALA and endometrial PpIX concentrations. However, no differences in endometrial PpIX concentrations were detected between rats administered ALA either as a single bolus or as two doses. Continuous infusion of 25 mg of ALA resulted in statistically lower endometrial PpIX concentrations compared to 25 mg ALA injected either as a single bolus or as two injections. Neither pH, temperature, nor time in solution affected ALA-induced PpIX accumulation. We conclude that the simplest way of achieving the highest PpIX concentration in the rat endometrium in vivo is to administer a bolus injection of 25 mg of ALA.
Insulin-induced hypoglycemia inhibits luteinizing hormone (LH) secretion and has been used as a model to study stress-induced inhibition of reproductive function. Endogenous opioid peptides have been implicated in mediating the inhibitory effect of hypoglycemia on LH secretion in sheep and rat. The objective of the present study was to determine if corticotropin-releasing hormone (CRH) and endogenous opiates are involved in the LH response to hypoglycemia in the nonhuman primate. Blood samples were collected at 15-min intervals for 6 h from ovariectomized rhesus monkeys (n = 6). Hypoglycemia was induced by injecting insulin 1 h after initiating blood collection. Animals were pretreated 15 min prior to insulin with either saline (n = 6), naloxone, a nonselective opiate receptor antagonist (n = 4), or alprazolam (n = 6), a potent benzodiazepine which has been shown to inhibit CRH. The LH, glucose, adrenocorticotropin (ACTH), and cortisol responses to insulin were determined. Insulin-induced hypoglycemia significantly inhibited LH secretion and increased ACTH and cortisol concentrations. Alprazolam prevented hypoglycemia-induced inhibition of LH independent of an effect on glucose concentrations. The mean (+/- SEM) LH pulse interval in response to hypoglycemia was decreased in the alprazolam pretreated group compared to the saline pretreated group (77.4 +/- 6.0 vs. 130.0 +/- 18.4 min), while LH pulse amplitude and mean LH levels were significantly increased (56.2 +/- 7.1 vs. 28.3 +/- 5.5 ng/ml, and 105.6 +/- 14.4 vs. 60.9 +/- 12.1 ng/ml respectively). In contrast, naloxone did not prevent hypoglycemia-induced LH inhibition. The mean LH pulse interval, LH pulse amplitude, and LH concentration in the naloxone pretreated monkeys were 152.1 +/- 33.4 min, 37.1 +/- 8.9 ng/ml, and 63.7 +/- 9.1 ng/ml respectively. Alprazolam pretreatment also markedly attenuated the ACTH response to hypoglycemia whereas the cortisol response was only moderately affected. We conclude that insulin-induced hypoglycemia in the monkey inhibits LH secretion through a mechanism involving CRH but not endogenous opiates.
Corticotropin-releasing Factor (CRF) is an important inhibitory neuromodulator of GnRH/LH secretion, and mediates in part the inhibitory effects of stress on the hypothalamic-pituitary-gonadal axis. The purpose of the present study was to further investigate CRF's role in regulating LH secretion in primates. This was accomplished by examining LH secretion in ovariectomized rhesus monkeys (n = 7) following cortisol synthesis inhibition with metyrapone. Infusion of metyrapone (5 mg/kg per h) for 4 h decreased cortisol levels to less than 20% of controls while increasing ACTH approximately 10-fold. LH concentrations were not affected by this acute activation of the hypothalamic-corticotroph axis. In a second experiment, metyrapone was infused for 10 h before collecting serial blood samples every 15 min for 6 h. Although this protocol produced a sustained increase in ACTH, no apparent effect on pulsatile LH secretion compared with saline controls was observed. Mean LH (+/- SEM) levels calculated for consecutive 2-h increments were 87.6 +/- 9.2 (0-2 h) 82.1 +/- 5.5 (2-4 h), and 80.7 +/- 4.8 (4-6 h) ng/ml in saline pretreated animals compared with 83.6 +/- 4.9, 79.8 +/- 5.8, and 72.5 +/- 6.2 ng/ml, respectively, in metyrapone pretreated monkeys. The same regimen of metyrapone infusion increased CRF messenger RNA levels in the paraventricular nucleus by approximately 33% (P < 0.0002). In a final experiment designed to examine the potential synergy between CRF and cortisol, the LH response to insulin-induced hypoglycemia was contrasted in saline and metyrapone pretreated monkeys. LH concentrations were reduced to approximately 40% of basal levels following insulin in both metyrapone and saline pretreated monkeys. Therefore, even though inhibition of cortisol synthesis leads to an increase in CRF messenger RNA in the paraventricular nucleus and a robust increase in ACTH secretion in rhesus monkeys, presumably due in part to increased neuroendocrine CRF secretion, LH secretion was not inhibited during either the acute or more chronic phase of corticotroph activation. Absence of LH inhibition was not due to low cortisol concentrations resulting from metyrapone because metyrapone did not prevent hypoglycemia-induced suppression of LH secretion. We conclude that increased neuroendocrine CRF secretion following metyrapone does not inhibit LH secretion under these conditions. Several explanations for this result are discussed.
Tax1 is essential for human T-cell lymphotropic virus type I (HTLV-I) virus replication and transformation. We have identified and characterized a Tax1 binding protein, TRX, by cDNA screening of a Jurkat T-cell cDNA library. TRX mRNA is ubiquitously expressed in human tissues tested and cell lines analyzed.
OBJECTIVE: Our purpose was to evaluate and compare the conversion of 5-aminolevulinic acid into the endogenous photosensitizer protoporphyrin IX in experimentally induced endometriosis and in other normal tissues in a rat model. STUDY DESIGN: Fluorescence of experimental endometriotic lesions, uterus, peritoneum, bowel mesentery, bladder, eye, skin, and skeletal muscle was assessed 3 hours after either intravenous, oral, or intrauterine administration of 5-aminolevulinic acid with use of spectrophotofluorometry. In another experiment the fluorescence of surgically induced endometriosis and adjacent normal peritoneum was evaluated every 15 minutes after 5-aminolevulinic acid administration to assess the time course of protoporphyrin IX production. RESULTS: In the rat endometriosis model intralesional and systemic 5-aminolevulinic acid produced fluorescence within implants showing viable endometrial cells. Treatment with 5-aminolevulinic acid produced low-intensity fluorescence in peritoneum, bowel mesentery, and eye. Relatively intense fluorescence was seen in skin, bladder, and uterus. No fluorescence was observed in skeletal muscle. The intensity of fluorescence varied with the dosage and route of administration of 5-aminolevulinic acid. Fluorescence intensity of protoporphyrin IX was significantly greater in implants than in adjacent normal peritoneum between 2 and 4 hours after treatment. CONCLUSIONS: Protoporphyrin IX fluorescence in experimentally induced endometriosis lesions after intravenous and oral delivery of 5-aminolevulinic acid was significantly greater than the fluorescence detected in adjacent normal peritoneum.
To investigate whether danazol is more effective than placebo for the treatment of premenstrual syndrome (PMS), we conducted a randomized, double-blind, crossover study comparing three successive cycles of danazol (200 mg bid) to three cycles of placebo. Thirty-one women meeting rigorous criteria for a diagnosis of severe PMS over two pretreatment cycles were enrolled; 28 of these subjects completed at least one cycle of treatment with symptom recordings, which were entered into the analysis. A significant period effect confounded the planned within-subject analysis and therefore, the main treatment comparisons were confined to the first period only. Symptom scores on the Premenstrual Tension Self-Rating Scale (PMTS), Beck Depression Inventory (BDI), and a Visual Analogue Scale (VAS) were compared for the premenstrual week in the last cycle of treatment. For the 16 patients on danazol, scores on the PMTS decreased by an average of 14.0 (10.7) (standard deviation) points from a baseline of 25.4 (5.6) points. For the 12 patients on placebo, PMTS scores decreased by an average of 3.6 (9.5) points from a baseline of 23.5 (5.8) points (14.0 vs. 3.6; p = .0133, unpaired t-test). Seven (43.8%) of the subjects on danazol achieved a clinically relevant reduction of symptoms into the asymptomatic range (PMTS scores < or = 5) as compared to one (8.3%) of the subjects on placebo. Thus, danazol (200 mg bid) provided greater relief from severe PMS during the premenstrual week than did placebo.