Effect of dietary intake on steroid feedback on release of luteinizing hormone in ovariectomized cows.

This study tested the hypothesis that the decline in pulsatile release of luteinizing hormone (LH), resulting from steroid negative feedback, is greater in animals fed a low, compared with a high, plane of nutrition. Two-year-old cows were ovariectomized and six days later were fed diets to provide 1.5 x maintenance requirements (n = 6, supplemented) or 0.5 x maintenance requirements (n = 6, restricted) (Round 1). Pulsatile release of LH was measured over a 14-h period on the fifth day of feeding these diets (Day 1); at 6 h, all animals were treated with an intravaginal insert containing 1.38 g progesterone, which remained in place until the end of Day 3. Pulsatile release of LH was again measured for 14 h on Day 3; at 6 h, all animals were injected intramuscularly with oestradiol benzoate (ODB; 1 mg per 500 kg live weight). Three days later, this protocol was repeated, in a cross-over design, with cows that were previously restricted now being supplemented and those cows previously supplemented, now restricted (Round 2). Plasma concentrations of progesterone after intravaginal progesterone treatment were 1.01 ng mL(-1) higher in restricted cows compared with supplemented cows (P < 0.001) and were also higher in Round 1 than in Round 2 and on Day 1 than on Day 3 (P < 0.001). Plasma concentrations of oestradiol following injection with ODB did not differ between supplemented and restricted cows (P > 0.1). Dietary intake did not affect mean concentrations of LH, pulse frequency or amplitude during the 6-h period before steroid treatment or the change in these variables following steroid treatment; however, the slope of the decline in concentrations of LH following progesterone treatment was significantly more negative in cows fed restricted diets compared with those fed supplemented diets. In Round 2, mean concentrations of LH were higher preceding, and decreased more following, progesterone treatment compared with the decrease after ODB treatment. In conclusion, acute dietary restriction resulted in a more rapid decline in the release of LH following treatment with intravaginal progesterone, and was associated with higher concentrations of progesterone in plasma.

Effect of treatment with progesterone and oestradiol benzoate on ovarian follicular turnover in postpartum anoestrous cows and cows which have resumed oestrous cycles.

Two experiments were carried out to determine the effect of a low dose of progesterone (P) with and without the addition of an injection of oestradiol benzoate (ODB) on ovarian follicle dynamics, oestradiol production and LH pulsatility in postpartum anoestrous cows, compared with cows which had resumed oestrous cycles (cycling cows). In the first experiment, anoestrous Jersey cows were treated with (AN+P, n=8) or without (AN-3, n=3) a previously used intravaginal progesterone releasing (CIDR) device for 10 days, commencing 3 or 4 days after emergence of a new dominant follicle (DF1) as determined by transrectal ultrasonography. Contemporary cycling cows (CYC+P, n=8) were similarly treated with used CIDR devices and injected with prostaglandin F(2alpha) (PGF) at the time of device insertion. Follicle turnover was monitored by daily ultrasonography and pulsatile release of LH was measured on the ninth day after device insertion. During the period of CIDR device insertion, a second dominant follicle emerged in 4/8 of the CYC+P group and 7/8 of the AN+P group (P=0.14). Maximum diameter of DF1 was greater in cows in the CYC+P compared with the AN+P group (P=0.02), but did not differ between cows in the AN+P and AN-P groups (P>0.1). Frequency of LH pulses was greater in cows in the CYC+P than AN+P group (P=0.06), and in cows in the AN+P than AN-P group (P=0.02). In the second experiment, anoestrous (n=20) and cycling (n=11) Friesian cows were treated with a new CIDR device for 6 days commencing 3 days after emergence of a new dominant follicle (DF1). Cycling cows were also injected with PGF on the day of device insertion. Half of the cows in each group were injected with 2mg ODB on the day of device insertion. Daily ultrasonography was used to monitor follicular dynamics throughout the experimental period. Follicular turnover was increased by ODB in cycling (5/5 versus 1/6; P<0.05), but not anoestrous cows (5/9 versus 4/11). Persistence of DF1 was reduced by ODB treatment in both cycling and anoestrous cows (P<0.001). Maximum diameter of DF1 was influenced by ODB treatment and reproductive status (P<0.05). In anoestrous cows in which a second dominant follicle did not emerge during the period of device insertion, the interval from emergence of DF1 to emergence of a second dominant follicle was significantly delayed by treatment with ODB (P=0.04). In conclusion, P treatment of anoestrous cows increased pulsatile release of LH, but did not induce the development of persistent follicles. Injection of ODB in association with P treatment reduced the persistence of dominant follicles in both cycling and anoestrous cows, but delayed subsequent follicular development in a proportion of anoestrous cows.

Distal 5q deletion syndrome: phenotypic correlations.

We describe the phenotypes of two male sibs with partial monosomy of chromosome 5 [46,XY,der(5)inv ins(1;5)(p32;q35.4q34)]; maternally derived from a balanced insertion of 1 and 5 [inv ins (1;5)(p.32;q35.4q34)]. One sib had microcephaly, cleft lip and palate, facial anomalies, atrial (ASD) and ventricular (VSD) septal defects, camptodactyly 4th and 5th fingers, and developmental delay. The other sib showed microcephaly, facial anomalies, ASD, hypotonia, primary optic nerve hypoplasia, and developmental delay. Only seven other patients with 5q deletions distal to 5q33 have been reported and none showed the putative breakpoints identified in our two patients. All nine showed developmental delay or malformations of the CNS and facial anomalies; six of nine had defects of cardiac septation. Our two patients and one other were shown to have only one copy of the cardiac specific hCSX gene that defines in part the etiology of their ASD and VSD. The other components of their phenotypes cannot be related at present to genes identified in the deleted segments.

Interstitial duplication of the short arm of chromosome 1 in a newborn with congenital heart disease and multiple malformations.

Interstitial duplications of chromosomes 1p are rare, with only 14 cases previously reported in the literature, and those have not revealed a unique syndrome. The phenotypes include multiple congenital abnormalities and both intra- and extra-uterine growth retardation. In general, the patients do poorly and do not survive beyond the age of several months. We report a newborn male with karyotype 46, XY, inv dup(1)(qter--> p34.3::p34.3-->p32.3::34.3-->pter) with multiple congenital abnormalities including congenital heart disease and co-existing portal and pulmonary hypertension. The chromosome 1 origin of the extra material was confirmed with fluorescent in situ hybridization (FISH). Review of the GDB [Human Genome Database, 1990] reveals that the duplicated region includes the locus EDN2 that encodes endothelin-1, a potent vasoconstrictor, making genetic overdosage of this protein a likely etiology of the pulmonary hypertension. The diffuse abnormalities show effects in multiple cell lines and suggest that this region of chromosome 1p could be involved in determining cell migration and/or differentiation during organogenesis.

Molecular and cytogenetic analysis of familial Xp deletions.

Five families in which an Xp deletion is segregating and two families in which an X chromosome rearrangement including a deletion of the short arm is segregating were ascertained for study. Normal fertility was seen in all families. Members from 5 of the 7 families manifested short stature (height <5th centile), while normal height was present in two families. Studies of both the FMR-1 and the androgen receptor loci using PCR based X-inactivation analysis demonstrated that in all families analyzed, there is preferential inactivation of one X chromosome. Molecular cytogenetic analysis showed that members of 3 of the 7 families share a common breakpoint in an approximate 2-3 Mb region at Xp22.12, suggesting a possible hotspot for chromatin breakage. Previous genotype-phenotype correlations and deletion mapping have indicated that a gene for stature resides within the pseudoautosomal region in Xp22.33. Our findings indicate that the loss of this region is not always associated with short stature, suggesting that other factors may be involved.

Cancer genetics for the clinician: recommendations on screening for BRCA1 and BRCA2 mutations.

Mutations in the BRCA1 and BRCA2 genes confer a greatly increased risk of breast cancer, ovarian cancer, and other malignant diseases. This paper offers recommendations about who should be screened for BRCA mutations, and insights into the ramifications of BRCA testing.

Effect of ventilation and filtration on submicrometer particles in an indoor environment.

The effect of filtration and ventilation on reduction of submicrometer particle concentration indoors was investigated in an office building. The air-handling system consisting of dry media filters and an air-conditioning unit, reduced particle concentration levels by 34%. The characteristics of indoor airborne particles were dominated by, and followed the pattern of, outdoor air, with vehicle combustion aerosols as the main pollutant. The ratio indoor/outdoor particle concentration varied between 14 and 26% for different sub-zones. The presence of significant source of particles indoors was not observed. A simple mathematical model predicting evolution of particles indoors is presented. The model, based on a particle number balance equation, was validated with experimental data and showed very good agreement between predicted and measured parameters.

Relation between indoor and outdoor exposure to fine particles near a busy arterial road.

Various studies on indoor and outdoor particulate matter in the urban environment in the vicinity of busy arterial roads in the centre of the subtropical city of Brisbane have indicated that the revised United States Environmental Protection Agency National Ambient Air Quality Standards (US EPA NAAQS) for Particulate matter PM2.5 could be exceeded not only outdoors but also indoors. The aim of this work was to investigate outdoor exposure to submicrometer particles and their relationship with indoor exposure in a hypothetical office building located in the vicinity of a busy arterial road. The outdoor exposure values and trends were measured in terms of particle number in the submicrometer size range and were then recalculated to represent mass concentration trends. The results of this study indicate that exposure to PM0.7 particles in ambient air close to a busy road often exceeds the levels of the annual and 24-hour US EPA NAAQS PM2.5 standards. It is likely that exposure to PM2.5 is even higher, and may significantly exceed these standards.

Insemination at the second of two induced oestrous periods in anoestrous dairy cows increases conception rates to first service.

AIM: To determine whether mating previously anoestrous cows on their second, rather than first, oestrus post pm-turn could increase conception rates to that service. METHODS: Cows diagnosed as anovulatory anoestrus were allocated to two groups, starting treatment on Day -17 (OES2) or on Day -7 (OESI) where the date of the planned start of mating = Day 0. All cows were treated with intravaginal progesterone (CIDR device) for 6 days and an injection of 1 mg oestradiol benzoate 24 h after removal of the device. Cows in the OES2 group were also injected with prostaglandin F2alpha on Day 0. RESULTS: During the first 7 days of mating, 61.8% (207/335) and 88.2% (328/372) of cows in the OES2 and OESl groups, respectively, were inseminated on detection of oestrus (p <0.001). Oestrus without ovulation occurred in 1.5% of cows in the OES2 group and 6.2% of cows in the OESl group during this period (p <0.01). Of those cows inseminated in the first week of mating, conception rates were 54.0% in the OES2 group and 45.5% in the OESl group (p = 0.05). There was no significant difference in median interval from start of mating to conception between the two groups (24 and 22 days for OES2 and OESl, respectively, p >0.05). CONCLUSION: Mating previously anoestrous cows on their second, rather than first oestrus post partum increased conception rates to that service. However, median intervals from start of mating to conception were not altered.

Combined assessment of myocardial perfusion and left ventricular function with exercise technetium-99m sestamibi gated single-photon emission computed tomography can differentiate between ischemic and nonischemic dilated cardiomyopathy.

The purpose of this study was to determine whether exercise technetium-99m sestamibi gated single-photon emission computed tomography (SPECT) accurately distinguishes between patients with ischemic cardiomyopathy and patients with nonischemic left ventricular systolic dysfunction. Noninvasive tests have previously failed to accurately separate patients with ischemic cardiomyopathy from those with nonischemic cardiomyopathy. Technetium-99m gated SPECT imaging offers advantages that have the potential to overcome the limitations of previous studies. Thirty-seven adults with a left ventricular ejection fraction < or = 35%, including 24 patients with nonischemic cardiomyopathy and 13 patients with ischemic cardiomyopathy, were prospectively evaluated using symptom-limited metabolic exercise treadmill testing with technetium-99m sestamibi gated SPECT imaging. Interpretation of myocardial perfusion and regional wall motion was performed, using a 17-segment model. Summed stress, rest, and reversibility perfusion defect scores were determined, and the variance of segmental wall motion scores was computed. Summed stress, rest, and reversibility perfusion defect scores were significantly lower in nonischemic cardiomyopathy patients, compared with those with ischemic cardiomyopathy (summed stress defect score: 6.9 +/- 3.8 vs 32.9 +/- 7.7, respectively, p <0.001). Variability in segmental wall motion was also significantly lower in patients with nonischemic cardiomyopathy compared with those with ischemic cardiomyopathy (variance: 0.3 +/- 0.3 vs 1.2 +/- 0.8, respectively, p <0.001). Thus, assessment of myocardial perfusion and regional ventricular function with exercise technetium-99m sestamibi gated SPECT imaging can reliably distinguish between patients with ischemic cardiomyopathy and patients with nonischemic dilated cardiomyopathy.

An experience with "research by committee".

The Nursing Research Committee of a community hospital describes the difficulties and unexpected pitfalls encountered during an attempt to conduct "research by committee." The steps of the process, from initial development of a research question through research design and implementation and termination of the project, are related. A retrospective analysis of the difficulties encountered serves as a basis for recommendations to others who might consider research by committee. Although a valid means for conducting research, the experiences of this committee indicate how forces, in their control and beyond their control, might influence completion of a project.

A new approach to assessment and documentation of conscious sedation during endoscopic examinations.

Assessment and documentation of patient responses to treatment and/or invasive procedures are important facets of nursing care. The purpose of this article is to describe a tool for assessing and quantifying a patient's response to sedation and tolerance of a specific diagnostic and/or therapeutic procedure. Use of the conscious sedation scale will allow the nurse to objectively measure the patient's outcome. This tool will also facilitate better patient care and documentation and substantiate nursing intervention.

Predictors of referral to cardiac rehabilitation and cardiac exercise self-efficacy.

Cardiac rehabilitation (CR) has known benefits after myocardial infarction (MI) or coronary artery bypass surgery (CABG). Yet, only a small percentage of patients are referred for outpatient CR after hospital discharge. This study investigates patient characteristics related to referral to CR and cardiac exercise self-efficacy, a salient predictor of health behavior change and maintenance. Two hundred nineteen patients enrolled in the study. Of the 185 patients who were CR candidates, 74 were referred to CR. Logistic regression analysis was used to identify variables related to CR referral. Results indicate that patient characteristics of having had fewer MIs or CABGs, having attended CR in the past, and being less physically active during leisure time are related to an increased likelihood of being referred to CR. Multiple regression analysis indicates that leisure physical activity is a predictor of cardiac exercise self-efficacy. Implications for nurses who recruit patients for CR are discussed.

Urinary cyclic GMP, endothelin, and prostaglandin E2 in normal pregnancy and preeclampsia.

Cyclic GMP, endothelin and prostaglandin E2 (PGE2) all have systemic vasoactive properties (with cyclic GMP acting as a second messenger of nitric oxide). Intrarenally they act as natriuretics and urinary levels reflect intrarenal production. Cyclic GMP and PGE2 also act as important inhibitors of platelet activation and thrombosis. The purpose of this study was to determine if urinary levels of cyclic GMP, endothelin, and PGE2 differ in preeclamptic as compared to normal pregnancies. Parameters were compared in 13 normotensive, nonpreeclamptic pregnancies, and 32 preeclamptic pregnancies. Preeclamptic women had significantly lower levels of urinary cyclic GMP (0.67 +/- 0.12 vs. 2.1 +/- 0.5 nmol/g creatinine), endothelin (0.88 +/- 0.09 vs. 3.75 +/- 1.4 ng/g creatinine), and PGE2 (26 +/- 4 vs. 9 ng/g creatinine) as compared to normals (p < 0.05). Intrarenal production of cyclic GMP, endothelin, and PGE2 are all disturbed in preeclampsia and may have implications in the sodium retention, hypertension, and intrarenal thrombosis and vasospasm of preeclamptic pregnancy.

Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration.

Irregular firing patterns are observed in most central neurons in vivo, but their origin is controversial. Here, we show that two types of inhibitory neurons in the cerebellar cortex fire spontaneously and regularly in the absence of synaptic input but generate an irregular firing pattern in the presence of tonic synaptic inhibition. Paired recordings between synaptically connected neurons revealed that single action potentials in inhibitory interneurons cause highly variable delays in action potential firing in their postsynaptic cells. Activity in single and multiple inhibitory interneurons also significantly reduces postsynaptic membrane time constant and input resistance. These findings suggest that the time window for synaptic integration is a dynamic variable modulated by the level of tonic inhibition, and that rate coding and temporal coding strategies may be used in parallel in the same cell type.

Endothelin and atrial natriuretic peptide levels following radiocontrast exposure in humans.

Radiocontrast exposure is associated with vasoconstriction of the renal vascular bed and, in certain circumstances, with acute renal failure. This may be influenced by the volume of contrast infused or underlying disease, such as diabetes or renal failure. Changes in circulating vascular regulators, such as endothelin and atrial natriuretic peptide (ANP), may play a role in the development and/or prevention of acute renal failure. Nineteen patients undergoing arteriographic procedures were divided into two groups: large-volume contrast (> or = 150 mL; n = 7) and small-volume contrast (< 150 mL; n = 12). Circulating endothelin levels increased significantly (from 12.3 +/- 1.1 pmol/L to 19.4 +/- 2.2 pmol/L; P < 0.05) following large-volume contrast exposure (group 1) but not following small-volume contrast exposure (group 2) (13.9 +/- 1.7 pmol/L to 12.2 +/- 0.09 pmol/L). ANP levels increased significantly in both groups: 43 +/- 15 pg/mL to 75 +/- 21 pg/mL in group 1 and 33 +/- 16 to 106 +/- 39 pg/mL in group 2. Data from an additional eight patients with underlying diabetes mellitus and/or renal insufficiency also were obtained and were considered separately. Endothelin levels were higher at baseline and increased significantly after contrast (25.7 +/- 5 pmol/L to 55.4 +/- 18 pmol/L) despite the relatively small average volume of contrast infused (112 +/- 15 mL). ANP levels were also highest in these patients (211 +/- 43 pg/mL precontrast and 323 +/- 65 pg/mL postcontrast). No group had a significant change in serum creatinine following contrast exposure. In conclusion, large-volume radiocontrast exposure is associated with an increase in both circulating endothelin and ANP levels. Patients with underlying diabetes or renal insufficiency may have higher baseline levels and a greater tendency to increase endothelin after contrast exposure. While an increase in endothelin may contribute to renal vasoconstriction following radiocontrast exposure, simultaneous increases in ANP may serve to offset this response and protect against changes in renal function.

Currents evoked in Bergmann glial cells by parallel fibre stimulation in rat cerebellar slices.

1. Whole-cell recordings were obtained from Bergmann glial cells in rat cerebellar slices. 2. The cells had low input resistances (70 +/- 38 M omega; n = 13) and a mean resting potential of -82 +/- 6 mV (n = 12) with a potassium-based internal solution. Electrical and dye coupling between Bergmann glia were confirmed. 3. Stimulation of parallel fibres induced a complex, mostly inward current which could be decomposed pharmacologically. 4. The ionotropic glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM), but not DL-2-amino-5-phosphonopentanoic acid (DL-APV; 100 microM) consistently blocked an early inward current component that may reflect synaptic activation of AMPA/kainate receptors in Bergmann glia. 5. Addition of cadmium ions (100 microM) to inhibit transmitter release blocked most of the CNQX-APV-insensitive current. This component probably reflects electrogenic uptake of the synaptically released glutamate. 6. Tetrodotoxin (TTX; 1 microM) blocked the remaining inward current: a slow component, possibly produced by the potassium ion efflux during action potential propagation in parallel fibres. An initial triphasic component of the response was also TTX sensitive and reflected passage of the parallel fibre action potential volley. 7. The putative glutamate uptake current was further characterized; it was blocked by the competitive uptake blockers D-aspartate (0.5 mM) and L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC; 0.5 mM), and by replacement of sodium with lithium. Monitoring the triphasic TTX-sensitive component showed that this inhibition did not result from changes of action potential excitation and propagation. 8. Intracellular nitrate ions increased the putative uptake current, consistent with the effect of this anion on glutamate transporters. 9. The putative uptake current was reduced by depolarization, consistent with the voltage dependence of glutamate uptake. 10. It is concluded that a large fraction of the current induced by parallel fibre stimulation reflects the uptake of synaptically released glutamate. The uptake current activated rapidly, with a 20-80% rise time of 2.3 +/- 0.7 ms (n = 10), and decayed with a principal time constant of 25 +/- 6 ms (n = 10).

Increased salt retention and hypertension from non-steroidal agents in the elderly.

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.