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Biomedical subjects

R F Smith

Publications and source records attributed to R F Smith.

At least 37 records · Page 2Linked to original sources

Determining which patients require evaluation for blunt cardiac injury following blunt chest trauma.

The objective of this study was to determine prospectively which risk factors require cardiac monitoring for blunt cardiac injury (BCI) following blunt chest trauma. All patients who sustained blunt chest trauma had an electrocardiogram (ECG) on admission to our urban level I trauma center. Those with ST segment changes, dysrhythmias, hemodynamic instability, history of cardiac disease, age > 55 years, or a need for general anesthesia within 24 hours (group 1) were admitted to the intensive care unit (ICU) for 24 hours where they were subjected to serial ECGs, creatinine phosphokinase (CPK) assays, and echocardiography (ECHO). Those with only mechanism for BCI, i.e., none of the above risk factors (group 2), were admitted to a nonmonitored bed and had a follow-up ECG 24 hours later. A series of 315 patients were admitted with blunt chest trauma during a 17-month period; 144 patients were in group 1 and 171 in group 2. Overall, 22 patients were diagnosed as BCI (+BCI), defined as evolving ST segment changes, dysrhythmias, a CPK-MB index of > 2.5, or hemodynamic instability. Of the 18 +BCI patients in group 1, all were symptomatic (i.e., none was included solely for a cardiac history, age, or need for general anesthesia). Six of these patients required treatment for dysrhythmias, hypotension, or pulmonary edema; one of whom died. Four patients with +BCI were in group 2 and had ECG changes at 24 hours; none of these four had any sequelae from their +BCI. None of the ECHOs demonstrated abnormal wall motion. Patients who sustain blunt chest trauma with a normal ECG, normal blood pressure, and no dysrhythmias on admission require no further intervention for BCI. Patients with ST segment changes, dysrhythmias, or hypotension following blunt chest trauma should be monitored for 24 hours, as this subgroup occasionally requires further treatment for complications of BCI. ECHO adds nothing as a screening test.

Adult↗

Urine test for the assessment of smoking status.

A simple, quick and inexpensive test for smoking status would be useful in a variety of settings. The non-polar barbituric acid derivative 1,3-dibutyl-2-thiobarbituric acid (DBTB) is described as a novel derivatisation reagent for nicotine and its metabolites in the König reaction to assess smoking status. The relative performance of qualitative methods for assessing smoking status using DBTB and the previously employed derivatisation reagent 1,3-diethyl-2-thiobarbituric acid (DETB), as well as quantitatively-based methods for determining 'total nicotine metabolites' (TNMs) using these two reagents, were evaluated against a cotinine-based radioimmunoassay (RIA) as the 'gold standard'. Clinical sensitivity and specificity for all the approaches studied were in excess of 94%. Simple qualitative assessment by eye was superior to quantitatively-based measures of smoking status. Correlation between estimation of nicotine metabolites using DBTB, DETB and RIA were good. The most efficient and convenient method to distinguish between smokers and non-smokers was the simple qualitative method using the more lipophilic reagent DBTB.

Biomarkers↗

Adolescent cocaine and injection stress effects on the estrous cycle.

Chronic cocaine exposure during critical periods of development induces short- and long-term effects. During the pubertal period, the hypothalamic-pituitary-gonadal (HPG) axis undergoes many dynamic changes. The present study investigated whether chronic periadolescent cocaine alters reproductive maturity in the rat. Sixty female Long-Evans hooded rats were randomly assigned to one of three conditions (20 mg cocaine/kg/day, saline injected and uninjected), for dosing from postnatal day 21 (P21) through P60. Several indicators of reproductive maturation and functioning were assessed during and following treatment. Cocaine exposure had no effect on the onset of puberty or on the date of first ovulation. The number of proestrus-estrus transitions was significantly lower in cocaine-exposed females compared to uninjected females, but not compared to saline-injected controls. This reduction was observed during exposure to cocaine, as well as after the cessation of injections. During the dosing period, cocaine-exposed rats also exhibited a greater number of cycles that had no clear P-E transition than did UN subjects; this effect disappeared once injections stopped. These alterations suggest immediate, and possibly persisting, alterations in the control of ovulation after chronic cocaine exposure throughout adolescence. Interestingly, during the injection period, the saline-injected females had a significantly greater number of diestrus days compared to uninjected and cocaine-injected animals, as well as a lower proportion of regular 4- and 5-day cycles. These differences disappeared once injections stopped. These results suggest a stress-induced irregularity of the estrous cycle, possibly attenuated by cocaine and recoverable after exposure. The present findings indicate that the HPG axis is susceptible to short-term, and possibly to long-term, alterations induced by cocaine exposure throughout the adolescent period.

Aging↗

What is stress, and how does it affect reproduction?

Stress is revealed by the inability of an animal to cope with its environment, a phenomenon that is often reflected in a failure to achieve genetic potential. Field data from dairy cows show that stressors such as milk fever or lameness increase the calving to conception interval by 13-14 days, and an extra 0.5 inseminations are required per conception. We suggest that a variety of endocrine regulatory points exist whereby stress limits the efficiency of reproduction. Transport produces an immediate constant increase in arginine vasopressin (AVP) and corticotrophin-releasing hormone (CRH) secretion in ewes, but adrenocorticotrophic hormone (ACTH) reaches a maximum in the first hour while cortisol is highest during the second hour. In contrast, after an insulin injection, the hypothalamo-pituitary-adrenal (HPA) response is delayed occurring only after glucose decreases below a threshold. Changes in AVP, CRH and ACTH each follow a similar time course, but eventually the secretion of AVP and CRH decreases while glucose is still at a nadir. Negative feedback effects appear to operate mainly at the pituitary level during transport but at the hypothalamus during hypoglycaemia. We also have endocrine evidence to show that stressors interfere with precise timings of reproductive hormone release within the follicular phase. Transport, or insulin, reduce the frequency and amplitude of gonadotrophin-releasing hormone and LH pulses, suggesting that these stressors exert effects at the hypothalamus or higher centres in the brain. Both stressors also delay the onset of the luteinising hormone (LH) surge. Preliminary results suggest that opioids mediate these effects but progesterone/glucocorticoid receptors are not involved because the antagonist, RU486, is unable to reverse insulin-induced delays in the LH surge. There is also evidence to support effects at pituitary level because exogenous ACTH, or transport, reduce the amount of LH released by challenges with GnRH. The reduction in endogenous GnRH/LH secretion ultimately deprives the ovarian follicle of adequate gonadotrophin support leading to reduced oestradiol production by slower growing follicles. Thus, there is a level of interference by stressors at the ovary. Reproduction is such an important physiological system that animals have to ensure that they can respond to their surroundings; thus, it is advantageous to have several protein mechanisms, i.e. at higher brain, hypothalamus, pituitary and target gland levels. However, when pushed too far, subfertility occurs.

Animals↗

Experience with over 2500 diagnostic peritoneal lavages.

This study was undertaken to confirm the safety and efficacy of diagnostic peritoneal lavage (DPL) for trauma patients. A prospectively maintained database of all DPLs performed in the past 75 months was analyzed. A red blood cell count of 100,000/mm(3) was considered positive for injury in blunt trauma; 10,000/mm(3) was considered positive for peritoneal penetration in penetrating trauma. Information relative to type of injury, DPL result, laparotomy result and complications, was analysed to determine if DPL was more or less suited to any specific indication or type of patient. Over a 75 month period, 2501 DPLs were performed at our urban level I trauma center. The overall sensitivity, specificity and accuracy for the above thresholds were 95, 99 and 98%. The majority (2409, 96%) were performed using percutaneous or "closed" seldinger technique. Ninety-two (4%) were performed using open technique because of pelvic fractures, previous scars and pregnancy. Open DPL was less sensitive than closed DPL in patients who sustained blunt trauma (90 vs 95%) but slightly more sensitive in determining penetration (100 vs 96%). Overall, there were 21 complications (0.8%). There was no difference in complication rate between open and closed DPL. In conclusion, DPL remains a highly accurate, sensitive and specific test with an extremely low complication rate. It can be performed either open or closed with comparable results. We recommend its use in the evaluation of both blunt and penetrating trauma.

Abdominal Injuries↗

Plasma norepinephrine and atrial natriuretic peptide in heart failure: influence of felodipine in the third Vasodilator Heart Failure Trial. V-HeFT III investigators.

BACKGROUND: Reflex activation of the sympathetic nervous system by short-acting dihydropyridine calcium channel antagonists has been reported to harm hypertensive patients. Different neurohormonal profiles and their response to treatment may influence the effectiveness of dihydropyridine vasodilator treatment of heart failure. METHODS: Four hundred fifty men with left ventricular (LV) systolic dysfunction were administered standard heart failure treatment and felodipine extended release (ER) or placebo in the Vasodilator Heart Failure Trial III (V-HeFT III). Plasma norepinephrine (PNE) levels, atrial natriuretic peptide (ANP) levels, exercise capacity, LV ejection fraction (EF), cardiac dimensions and function, and arrhythmia frequency were measured. Hospital-free survival for baseline neurohormonal classes was assessed. RESULTS: Distributions of ANP and PNE levels at baseline in patients with heart failure of ischemic and nonischemic causes were virtually identical. ANP levels at baseline were inversely related to LVEF (r = -0.39; P = .0001), exercise duration (r = -0.19; P = .0001), and peak oxygen consumption (r = -0.27; P = .008) and directly related to LV (r = 0.23; P = .0006) and right ventricular dilatation (r = 0.23; P = .0008). The increase in ANP levels between baseline and 3 months (P = .02) and 1 year (P = .03) was significantly less in the felodipine-ER group than in the placebo group, but PNE levels did not differ between treatment groups. Hospital-free survival was directly related to baseline ANP (P = .0002) and PNE levels (P = .004). All-cause mortality was related to baseline PNE levels (P = .02) but not baseline ANP levels. CONCLUSION: Levels of ANP and PNE hormones are related to LV dysfunction, exercise performance, and hospital-free survival in heart failure and PNE levels are related to all-cause mortality. Treatment with felodipine ER did not adversely affect survival in any neurohormone subclass.

Administration, Oral↗

Neospora caninum-associated abortion in cattle: the time of experimentally-induced parasitaemia during gestation determines foetal survival.

The parasite, Neospora caninum is an important cause of abortion in cattle. It is transmitted vertically or horizontally and infection may result in abortion or the birth of a live, healthy but infected calf at full-term. Only a proportion of infected cattle abort and the pathogenesis of abortion is not understood. Groups of cattle were infected with 10(7) N. caninum tachyzoites intravenously at different times relative to gestation. Intravenous inoculation was chosen to reproduce the putative haematogenous spread of N. caninum following either recrudescence of endogenous infection or de novo infection. In all cattle, infection was accompanied by high gamma-interferon and lymphoproliferative responses, and a biased IgG2 response indicating that N. caninum infection is accompanied by a profound Th1 helper T cell-like response. Infection at 10 weeks gestation resulted in foetopathy and resorption of foetal tissues 3 weeks after infection in 5 out of 6 cows. Infection at 30 weeks gestation resulted in the birth of asymptomatic, congenitally-infected calves at full term in all 6 cows, whereas the 6 cows infected before artificial insemination gave birth to live, uninfected calves. These results suggest that the reason some cows abort is related to the time during gestation when they become infected or an existing infection recrudesces.

Abortion, Veterinary↗

Prognosis of penetrating trauma in elderly patients: a comparison with younger patients.

BACKGROUND: It has previously been shown that elderly patients have a worse prognosis than their younger counterparts after sustaining blunt trauma. This is due in part to a higher incidence of comorbid conditions as well as less physiologic reserve in an elderly population sustaining largely blunt trauma. We compared the outcome after penetrating trauma in elderly patients to matched "younger" patients to determine whether they had a similarly poor prognosis. METHODS: Elderly patients (> or = 65 years) were identified from our trauma registry. Sex, mechanism of injury, and Abbreviated Injury Score/Injury Severity Score were determined from the registry. Patients presenting with traumatic arrest were excluded. The registry was then searched for patients aged 15 to 40 years with the same sex, mechanism of injury, and Abbreviated Injury Score in each region. A chart review was then performed to determine additional details of their hospital stay. The two groups were then compared using Student's t test and Fisher's exact chi2 test, as appropriate. RESULTS: Eighty-five elderly patients (OLD group) were admitted with penetrating trauma between 1983 and 1998. They were compared with 85 matched young patients (YOUNG group). Each group included 66 male and 19 female patients. In each group, gunshot wounds occurred in 45.9%, stab wounds in 52.9%, and shotgun wounds in 1.2% of patients. The average Injury Severity Score in each group was 5.5 +/- 5.6 (range, 1-29) and the regional Abbreviated Injury Scores were likewise equal in both groups. The OLD patients had an average hospital stay of 6.9 +/- 9.1 days compared with 4.3 +/- 5.7 days in the YOUNG patients (p < 0.05). Twenty-seven OLD patients spent 7.3 +/- 9.2 days in the intensive care unit compared with 19 YOUNG patients who stayed 3.4 +/- 3.2 days (p < .05). A total of 91 comorbidities were identified in 58 OLD patients compared with 18 in 15 YOUNG patients (p < .0001). Eighty-six invasive procedures were performed in the OLD group compared with 96 in the YOUNG group (p = not significant). Nineteen OLD patients (22.3%) and 15 YOUNG patients (17.6%) suffered one or more complications, including death (p = not significant). A total of 91% of surviving OLD patients were discharged to home compared with 100% of surviving YOUNG patients (p < .01). CONCLUSION: Elderly patients who sustain penetrating trauma have more comorbidities than their younger counterparts. This may account for their longer hospital stay and lesser ability to be discharged home. These patients do not have an increased complication rate and should continue to be managed aggressively.

Adolescent↗

Nutrient intakes during pregnancy: the influence of smoking status and age.

STUDY OBJECTIVE: To examine the relation of antioxidant and other nutrient intakes in pregnancy to smoking and sociodemographic variables. DESIGN: Cohort study. SETTING: St Mary's Maternity Hospital, Portsmouth. PARTICIPANTS: Pregnant nulliparous women, with no existing complications of pregnancy, were recruited from antenatal booking clinics. A total of 774 women completed seven day food diaries, and supplied detailed data on their use of nutrient supplements. MAIN RESULTS: Smokers had lower intakes of most micronutrients. After adjustment for the confounding effects of maternal age, height, and education, only vitamin C and carotenoid intakes remained significantly depressed. Age was strongly and significantly associated with the intake of most nutrients, including antioxidants, and this association was independent of other maternal factors. Antioxidant intake was therefore lowest in young women who smoked: for example smokers under 24 years had a mean vitamin C intake of 57 mg (SD 35) compared with 106 mg (SD 52) for non-smokers aged 28 and over (difference 49 mg, 95% CI 39, 59). The corresponding intakes of carotenoid equivalents were 1335 micrograms (SD 982) and 2093 micrograms (SD 1283) (difference 758 micrograms, 95% CI 496, 1020). CONCLUSIONS: The study has identified, for the first time, young pregnant women as a group at particular risk of low micronutrient intake. The health implications of poor nutrition now need to be evaluated, particularly for those women who smoke.

Adult↗

Effect of adrenocorticotrophic hormone (ACTH1-24) on ovine pituitary gland responsiveness to exogenous pulsatile GnRH and oestradiol-induced LH release in vivo.

The present experiment was designed to determine if and how exogenous ACTH replicates the effects of stressors to delay the preovulatory LH surge in sheep. Twenty-four hours after oestrous synchronisation with prostaglandin in the breeding season, groups of 8-9 intact ewes were injected with 50 microg oestradiol benzoate (0 h) followed 8 h later by 3 injections of saline or GnRH (500 ng each, i.v.) at 2 h intervals (controls). Two further groups received an additional 'late' injection of ACTH (0.8 mg i.m.) 7.5 h after oestradiol, i.e., 0.5 h before the first saline or GnRH challenge. To examine if the duration of prior exposure to ACTH was important, another group of ewes was given ACTH 'early', i.e. 2.5 h before the first GnRH injection. The first GnRH injection produced a maximum LH response of 1.9+/-0.4 ng/ml which was significantly (p < 0.01) enhanced after the second and third GnRH challenge (7.1+/-1.5 ng/ml and 7.0+/-1.7 ng/ml, respectively; 'self-priming'). Late ACTH did not affect the LH response after the first GnRH challenge (1.9+/-0.4 vs. 1.8+/-0.3 ng/ml; p > 0.05) but decreased maximum LH concentrations after the second GnRH to 35% (7.1+/-1.5 vs. 4.6+/-1.1 ng/ml; p = 0.07) and to 40% after the third GnRH (7.0+/-1.7 vs. 4.0+/-0.8 ng/ml; p = 0.05). When ACTH was given early, 4.5 h before the second GnRH, there was no effect on this LH response suggesting that the effect decreases with time after ACTH administration. Concerning the oestradiol-induced LH surge, exogenous GnRH alone delayed the onset time (20.5+/-2.0 vs. 27.8+/-2.1 h; p > 0.05) and reduced the duration of the surge (8.5+/-0.9 vs. 6.7+/-0.6 h; p > 0.05). The onset of the LH surge was observed within 40 h after oestradiol on 29 out of 34 occasions in the saline +/- GnRH treated ewes compared to 11 out of 34 occasions (p < 0.05) when ACTH was also given, either late or early. In those ewes that did not have an LH surge by the end of sampling, plasma progesterone concentrations during the following oestrous cycle increased 2 days later suggesting a delay, not a complete blockade of the LH surge. In conclusion, we have revealed for the first time that ACTH reduces the GnRH self-priming effect in vivo and delays the LH surge, at least partially by direct effects at the pituitary gland.

Adrenocorticotropic Hormone↗

Anthropomorphic carotid bifurcation phantom for MRI applications.

Anthropomorphic carotid bifurcation flow phantoms that incorporate different stenotic geometries within the internal carotid artery have been developed. This technique produces high-fidelity, life-size vascular flow models that are compatible with magnetic resonance techniques. The models, in conjunction with a computer-controlled flow pump, address the need for a complex vascular geometry that can be used to verify magnetic resonance angiography (MRA) techniques that quantify stenosis severity and blood flow. Stenotic geometries, with up to 80% diameter reduction, have been fabricated in two different phantom materials. Plastic phantoms provide a durable, rigid geometry where the absolute dimensions of the model are well known. Agar gel phantoms provide tissue-like signal (T1, T2) up to the lumen boundary and are also compatible with ultrasound techniques. In this paper the technique to produce vascular flow phantoms is outlined and the compatibility of these phantoms with MRA techniques is demonstrated. J. Magn. Reson. Imaging 1999;10:533-544.

Carotid Arteries↗

The utility of head computed tomography after minimal head injury.

OBJECTIVE: To determine if patients who present with a history of loss of consciousness who are neurologically intact (minimal head injury) should be managed with head computed tomography (CT), observation, or both. METHODS: We prospectively studied patients who presented to our urban Level I trauma center with a history of loss of consciousness after blunt trauma and a Glasgow Coma Scale score of 15. All patients underwent CT of the head and were subsequently admitted for 24 hours of observation. RESULTS: A total of 1,170 patients with minimal head injury were studied during a 35-month period. All patients had Glasgow Coma Scale scores of 15 on arrival and had a history of either loss of consciousness or amnesia to the event. Two hundred forty-seven patients (21.1%) were intoxicated with drugs or alcohol on admission; 39 patients (3.3%) had abnormalities detected by CT, including 18 intracranial bleeds; 21 patients (1.8%) had changes in therapy as a direct result of their CT results, including 4 operative procedures. No patient with negative CT results deteriorated during the subsequent observation period. CONCLUSION: CT is a useful test in patients with minimal head injury because it may lead to a change in therapy in a small but significant number of patients. Subsequent hospital observation adds nothing to the CT results and is not necessary in patients with isolated minimal head injury.

Accidents↗

Leptin binding activity changes with age: the link between leptin and puberty.

The timing of the physical transition from child to adult is determined by a biological clock that switches off the pituitary gonadal axis during infancy until puberty. Body composition (and in particular, fat mass), through leptin, are critical signals to this clock. However, no direct relationship between leptin and puberty has been demonstrated. Leptin is bound in the circulation by a high-affinity binding protein, which has been identified as a soluble leptin receptor. We found circulating levels of leptin binding activity (LBA) to be low at birth, to be high in the prepubertal years, to fall through puberty, and then to remain stable during adult life. LBA correlated with pubertal status in both boys and girls. We postulate that the fall in LBA, associated with increasing age and puberty, reflects a reduction in expression of truncated leptin receptors, and leptin is then available to the full-length receptor, which transmits the biological signal for leptin. The high levels of LBA occur during the years when the pituitary gonadal axis is quiescent. Thus, the change in LBA could explain how leptin regulates puberty.

Adolescent↗

Effect of transport on pulsatile and surge secretion of LH in ewes in the breeding season.

The aim of this study was to elucidate the mechanism(s) involved in stress-induced subfertility by examining the effect of 4 h transport on surge and pulsatile LH secretion in intact ewes and ovariectomized ewes treated with steroids to induce an artificial follicular phase (model ewes). Transport caused a greater delay in the onset of the LH surge in nine intact ewes than it did in ten ovariectomized ewes (intact: 41.0 +/- 0.9 h versus 48.3 +/- 0.8 h, P < 0.02; ovariectomized model: 40.8 +/- 0.6 h versus 42.6 +/- 0.5 h, P < 0.02). Disruption of the hypothalamus-pituitary endocrine balance in intact ewes may have reduced gonadotrophin stimulation of follicular oestradiol production which had an additional effect on the LH surge mechanism. In the ovariectomized model ewes, this effect was masked by the exogenous supply of oestradiol. However, in these model ewes, there was a greater suppression of maximum LH surge concentrations (intact controls: 29 +/- 4 ng ml-1 versus intact transported 22 +/- 5 ng ml-1, P < 0.02; ovariectomized model controls: 35 +/- 7 ng ml-1 versus model transported 15 +/- 2 ng ml-1, P < 0.02). Subsequent exposure to progesterone for 12 days resulted in the resumption of a normal LH profile in the next follicular phase, indicating that acute stress leads to a temporary endocrine lesion. In four intact ewes transported in the mid-follicular phase, there was a suppression of LH pulse amplitude (0.9 +/- 0.3 versus 0.3 +/- 0.02 ng ml-1, P < 0.05) but a statistically significant effect on pulse frequency was not observed (2.0 +/- 0.4 versus 1.7 +/- 0.6 pulses per 2 h). In conclusion, activation of the hypothalamus-pituitary-adrenal axis by transport in the follicular phase of intact ewes interrupts surge secretion of LH, possibly by interference with LH pulsatility and, hence, follicular oestradiol production. This disruption of gonadotrophin secretion will have a major impact on fertility.

Analysis of Variance↗

Effect of transport on pituitary responsiveness to exogenous pulsatile GnRH and oestradiol-induced LH release in intact ewes.

This study examined the effect of transport on GnRH self-priming in vivo as well as the consequential effects on the oestradiol-induced LH surge. The follicular phases of ewes (eight per group) were synchronized with progestin sponges, and 50 micrograms oestradiol benzoate was injected 24 h (time zero) after sponge removal to improve precision in the timing of the LH surge. Beginning 8 h after oestradiol, saline or GnRH (500 ng, i.v.) was given at 2 h intervals with or without 8 h transport beginning 0.5 h before the first GnRH injection (late transport) and effects were compared with those observed during early transport, that is, starting 2.5 h before the first GnRH injection. In all ewes, GnRH alone induced a maximum LH response of 1.9 +/- 0.4 ng ml-1 after the first challenge. The response was enhanced (P < 0.01) after the second and third GnRH injections (7.4 +/- 1.4 ng ml-1 and 7.6 +/- 1.7 ng ml-1, respectively). This self-priming effect after the second GnRH was reduced by late transport (7.4 +/- 1.4 versus 4.2 +/- 0.8 ng ml-1; P < 0.05) but not early transport, that is, transport initiated closer to the time of GnRH administration had greater suppressive effects on LH secretion. Throughout transport, spontaneous LH pulse frequency was lower in treated than it was in control ewes (2.38 +/- 0.53 versus 4.50 +/- 0.53 pulses per 8 h; P < 0.01), with marked effects in the first 4 h of transport (1.0 +/- 0.19 versus 2.63 +/- 0.38 pulses per 4 h; P < 0.02). Spontaneous pulse amplitude also tended to decrease during transport (0.13 +/- 0.02 versus 0.20 +/- 0.03 ng ml-1; P = 0.07). When LH turnover was stimulated by exogenous GnRH, the onset of the LH surge was delayed (controls: 20.5 +/- 2.0 h versus GnRH alone: 25.3 +/- 1.5 h; P < 0.05) and the duration was reduced (8.5 +/- 0.9 versus 6.5 +/- 0.4 h; P < 0.05). Transport tended to delay the LH surge in saline-treated ewes (20.5 +/- 2.0 versus 22.9 +/- 1.9 h; P = 0.08), with a further delay imposed by late transport plus GnRH (27.5 +/- 1.6 h; P < 0.05) but not by early transport plus GnRH (27.8 +/- 2.5 versus 26.4 +/- 2.4 h; P > 0.05), that is, effects mediated by increasing LH turnover were only manifest if transport occurred near the LH surge, when there was insufficient time to replenish stores of releasable LH. In all transported ewes, plasma cortisol increased from 4.5 +/- 1.0 ng ml-1 to 29.2 +/- 5.5 ng ml-1 (P < 0.001) within 15 min of the start of transport and was significantly lower (P < 0.01) by 6.5 h. Plasma progesterone also increased from 0.30 +/- 0.04 to 0.38 +/- 0.04 ng ml-1 (P < 0.05). In conclusion, transport affected the oestradiol-induced LH surge by causing a 50% reduction in the self-priming effect of exogenous GnRH, but hypothalamic effects were also revealed by a two-fold decrease in spontaneous LH pulse frequency in saline-treated ewes.

Analysis of Variance↗

Effect of transport on pulsatile LH release in ovariectomized ewes with or without prior steroid exposure at different times of year.

The initial aim of the present study was to test whether the stress of transport suppresses LH pulsatile secretion in ewes. In a pilot experiment in the late breeding season, transport resulted in an unexpected response in three out of five transported, ovariectomized ewes pretreated with oestradiol and progesterone. Before transport, seasonal suppression of LH pulses had occurred earlier than anticipated, but LH pulsatility suddenly restarted for the period of transport. This finding was reminiscent of unexplained results obtained in ovariectomized ewes infused centrally with high doses of corticotrophin-releasing hormone after pretreatment with low doses of oestradiol with or without progesterone. Hence, an additional aim of the present study was to examine whether these latter results with corticotrophin-releasing hormone could be reproduced by increasing endogenous corticotrophin-releasing hormone secretion by transport. Subsequent experiments used groups of at least eight ovariectomized ewes at different times of the year with or without prior exposure to steroids to assess whether these unexpected observations were associated with season or the prevailing endocrine milieu. In the mid-breeding season, transport for 4 h in the absence of steroid pretreatment for 8 months reduced LH pulse frequency from 7.5 +/- 0.3 to 6.3 +/- 0.4 pulses per 4 h (P < 0.05) and LH pulse amplitude from 2.6 +/- 0.5 to 1.8 +/- 0.3 ng ml-1 (P < 0.05). Similarly, in the mid-breeding season, 34 h after the cessation of pretreatment with oestradiol and progesterone, transport suppressed LH pulse frequency from 6.1 +/- 0.4 to 5.5 +/- 0.3 pulses per 4 h (P < 0.05) with a tendency of effect on amplitude (6.2 +/- 2.7 to 2.61 +/- 0.6 ng ml-1; P = 0.07; note the large variance in the pretransport data). During mid-anoestrus, evidence of a suppressive effect of transport was only observed on LH pulse amplitude (4.7 +/- 0.6 versus 3.0 +/- 0.5 pulses per 4 h; P < 0.05) in ovariectomized ewes that had not been exposed to ovarian steroids for 4 months. Repetition of the pilot experiment with 12 ewes during the transition into anoestrus resulted in one ewe with LH pulses seasonally suppressed but increased by transport; 11 ewes had a distinct pulsatile LH pattern which was decreased by transport in six ewes. In anoestrus, there was no effect of transport on LH pulse frequency or amplitude in intact ewes, or those ovariectomized 2-3 weeks previously, with or without prior oestradiol and progesterone treatment. However, basal concentrations of cortisol were greater in anoestrus than in the breeding season, and the increment in cortisol during transport was similar in anoestrus and the breeding season but greater during the transition into anoestrus (P < 0.05). Progesterone concentrations increased from 0.31 +/- 0.02 ng ml-1 before transport to 0.48 +/- 0.05 ng ml-1 during the second hour of transport (P < 0.05). In conclusion, transport reduced LH pulse frequency and amplitude in ovariectomized ewes that had not been exposed to exogenous steroids for at least 4 months. In most animals, the previously observed increase in LH pulsatility induced by exogenous CRH was not reproduced by increasing endogenous CRH secretion by transport. However, in four ewes, transport did increase LH pulsatility, but only during the transition into anoestrus in ewes with seasonally suppressed LH profiles after withdrawal of steroid pretreatment.

Animals↗

Serum leptin levels during the menstrual cycle of healthy fertile women.

Leptin is a protein, produced by adipose tissue, which has cytokine and hormonal properties. Serum leptin levels can be considered as a measure of body fat mass, and are involved in regulation of body weight. Previous studies suggest that leptin may have an additional role in reproduction, and there is also evidence for involvement in the hypothalamic-pituitary-gonadal axis. In this study, we investigate the possible changes in serum leptin concentration throughout the menstrual cycle. Samples were collected from apparently healthy, fertile women at different stages in their menstrual cycle, timed precisely according to the luteinising hormone (LH) surge. Mean serum leptin levels were significantly higher in the luteal phase (median 11.4 ng/mL) than in the follicular phase (median 10.0 ng/mL) (P < 0.001). In addition, mean serum leptin levels correlated with body mass index (r = 0.54, P < 0.05), but showed no correlation with luteal-phase progesterone levels. Results showed that levels of serum leptin vary during the menstrual cycle, and add to the mounting evidence that leptin has a role in reproduction. These fluctuations should be taken into account whenever studies are performed using female subjects.

Adult↗