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Biomedical subjects

J E Hall

Publications and source records attributed to J E Hall.

At least 73 records · Page 4Linked to original sources
PubMed2001

Sedative, analgesic and cognitive effects of clonidine infusions in humans.

This placebo-controlled, randomized study evaluated, on separate days, the dose-response relationship for 1 h infusions of clonidine 1, 2 and 4 microg kg(-1) h(-1), in eight healthy volunteers aged 22-30 yr. Response end-points included sedation (bispectral index, visual analogue scale and observer assessment of sedation), analgesia to a cold pressor test, memory (recall of word lists), cognitive function (digit symbol substitution test (DSST)), respiratory function (respiratory rate, end-tidal carbon dioxide, oxygen saturation) and haemodynamic stability (heart rate and mean arterial pressure). Clonidine infusions resulted in significant and progressive sedation, but all subjects were easily awoken to perform tests and evaluations. Statistically significant analgesia, memory impairment and reduced performance on the DSST occurred during 4 microg kg(-1) h(-1) infusions (resulting in a plasma concentration of 2 ng ml(-1). There were no statistically significant changes in cardiorespiratory variables throughout the study.

Adrenergic alpha-Agonists↗
PubMed2001

Gastric residual volume in children: a study comparing efficiency of erythromycin and metoclopramide as prokinetic agents.

Metoclopramide may be used to stimulate gastric emptying when anaesthetizing children for emergency operations. Unfortunately, metoclopramide is associated with extrapyramidal side effects. Erythromycin, a motilin receptor agonist, is a prokinetic agent but its use has been little investigated in children. This randomized double-blind study compared the effects of premedication with oral metoclopramide 0.15 mg kg(-1) or erythromycin 1 mg kg(-1) on gastric emptying in 80 children undergoing tonsillectomy. Pre-operative fluids, premedication and anaesthetic technique were standardized and gastric volume was measured with an orogastric tube. Post-operative nausea and vomiting was recorded. Metoclopramide and erythromycin produced similar gastric volumes (0.29 and 0.24 ml kg(-1)) and there was no difference in post-operative vomiting. In the erythromycin group there were more patients with negative aspirates (45.9%) than in the metoclopramide group (35.1%), but the difference was not statistically significant. These results indicate that erythromycin may be as effective as metoclopramide as a prokinetic agent.

Administration, Oral↗
PubMed2001

Aetiology, previous menstrual function and patterns of neuro-endocrine disturbance as prognostic indicators in hypothalamic amenorrhoea.

BACKGROUND: Hypothalamic amenorrhoea (HA) is a syndrome associated with infertility and osteopenia in reproductive-age women. METHODS: To understand better the natural history of this disorder, 28 women participated in a retrospective, questionnaire-based analysis to elucidate factors associated with spontaneous recovery. RESULTS: 54% of subjects developed HA related to an eating disorder, 21% related to stress +/- weight loss, and 25% without obvious contributing factors (idiopathic). HA associated with a clear precipitant had a better prognosis than idiopathic HA (71 versus 29% recovery; P < 0.05). Reversal of the inciting factor appeared necessary but not sufficient for recovery (83% recovery if factor reversed). Normal menarche occurred in 61% of subjects, oligomenorrhoea in 32%, and primary amenorrhoea in 7%. Oligomenorrhoea and normal menarche showed a trend toward better prognosis than primary amenorrhoea (NS). Compared with controls, 46% of HA patients had decreased frequency of LH pulses, 7% decreased amplitude, 18% decreases in both frequency and amplitude, 18% absent pulses, and 11% normal-appearing pulses. Pulse pattern at baseline did not predict recovery. CONCLUSIONS: The aetiology of HA at the time of presentation predicts subsequent recovery of menstrual function. In stress, weight loss, or eating disorder-related HA, rates of recovery exceeded 80% when precipitating factors were reversed. Idiopathic HA may represent a different disorder as recovery rates were <30%.

Adolescent↗
PubMed2001

Cardiovascular and renal responses to a high-fat diet in Osborne-Mendel rats.

This study examined the cardiovascular, renal, and hormonal responses of dietary-induced obesity in Osborne-Mendel (OM) rats. Male OM rats were fed either a low (LF; n = 10)- or high-fat (HF; n = 11) diet for 17 wk. During week 15 of the study, arterial pressure was measured directly, 24 h/day, from chronically indwelling catheters. Body and kidney weights were 46 +/- 5 and 33 +/- 5% greater, respectively, in rats fed HF vs. LF diet. Left and right ventricular weights were also greater in rats fed HF diet (21 +/- 7 and 36 +/- 6%, respectively). Direct measurement of arterial pressure revealed only a slight increase in mean arterial pressure (88 +/- 1 in rats fed HF diet vs. 85 +/- 1 mmHg in rats fed LF diet), whereas there was no difference in resting heart rate between the two groups. Consumption of HF diet was also associated with a 3.5-fold increase in plasma insulin, a 16 +/- 4% higher blood glucose, and a 40 +/- 6% reduction in plasma renin activity compared with LF-fed rats. Thus feeding OM rats HF diet led to obesity, cardiac and renal hypertrophy, and hyperinsulinemia but only a slight increase in mean arterial pressure.

Animals↗
PubMed2001

Inhibition of NO synthesis enhances chronic cardiovascular and renal actions of leptin.

Acute studies suggest that leptin has pressor and depressor actions, including stimulation of sympathetic activity as well as increased release of NO from the vascular endothelium. The goal of this study was to examine the role of NO in modulating the chronic blood pressure, heart rate, and renal responses to hyperleptinemia, comparable to that found in obesity-induced hypertension. Male Sprague-Dawley rats were implanted with arterial and venous catheters, and mean arterial pressure and heart rate were monitored continuously 24 h/d. After a 4-day control period, the rats were infused with isotonic saline vehicle (n=6) or N(G)-nitro-L-arginine methyl ester (L-NAME, 10 microgram/kg per minute; n=9) to inhibit NO synthesis for 7 days. After 7 days of vehicle or L-NAME administration, leptin was infused intravenously for 7 days at a rate of 0.5 microgram/kg per minute, followed by a leptin infusion at 1.0 microgram/kg per minute for 7 days, along with vehicle or L-NAME. A 21-day infusion of L-NAME alone (n=6) served as a control for the L-NAME+leptin rats. Although the low dose of leptin alone did not significantly elevate arterial pressure, it raised the heart rate by 18+/-3 bpm. The higher leptin infusion rate raised arterial pressure from 96+/-3 to 104+/-3 mm Hg but did not increase the heart rate further. L-NAME+leptin increased arterial pressure by 40+/-6 mm Hg and heart rate by 79+/-19 bpm compared with pretreatment levels. In control L-NAME rats, mean arterial pressure increased by 31+/-4 mm Hg, whereas the heart rate was not altered significantly compared with pretreatment levels. Neither chronic leptin infusion alone nor L-NAME alone altered the glomerular filtration rate or renal plasma flow significantly, but L-NAME+leptin reduced glomerular filtration rate by 27+/-11% and renal plasma flow by 47+/-9%. These results indicate that impaired NO synthesis mildly enhances the chronic renal hemodynamic and hypertensive effects of leptin but markedly amplifies the tachycardia caused by hyperleptinemia.

Animals↗
PubMed2001

Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism.

Mutations in the GnRH receptor (GNRHR) have been described as a cause of reproductive failure in a subset of patients with idiopathic hypogonadotropic hypogonadism (IHH). Given the apparent rarity of these mutations, we set out to determine the frequency and distribution of GNRHR mutations in a heterogeneous population of patients with IHH who were well characterized with respect to diagnosis, phenotype, and mode of inheritance and to define their distribution within the receptor protein. One hundred and eight probands with IHH were screened for mutations in the coding sequence of GNRHR. Forty-eight of the 108 patients had a normal sense of smell, whereas the remaining 60 had anosmia or hyposmia (Kallmann syndrome). Exon segments in the GNRHR were screened for mutations using temperature gradient gel electrophoresis, and all mutations were confirmed by direct sequencing. Five unrelated probands (3 men and 2 women), all normosmic, were documented to have changes in the coding sequence of the GNRHR. Two of these probands were from a subgroup of 5 kindreds consistent with a recessive mode of inheritance, establishing a GNRHR mutation frequency of 2 of 5 (40%) in patients with normosmic, autosomal recessive IHH. The remaining 3 probands with GNRHR mutations were from a subgroup of 18 patients without evidence of familial involvement, indicating a prevalence of 3 of 18 (16.7%) in patients with sporadic IHH and a normal sense of smell. Among the five individuals bearing GNRHR mutations, a broad spectrum of phenotypes was noted, including testicular sizes in the male that varied from prepubertal to the normal adult male range. Three probands had compound heterozygous mutations, and two had homozygous mutations. Of the eight DNA sequence changes identified, four were novel: Thr(32)Ile, Cys(200)Tyr, Leu(266)Arg, and Cys(279)TYR: COS-7 cells transiently transfected with complementary DNAs encoding the human GNRHR containing each of these four novel mutations failed to respond to GnRH agonist stimulation. We conclude that 1) the spectrum of phenotypes in patients with GNRHR mutations is much broader than originally anticipated; 2) the frequency of GNRHR mutations may be more common than previously appreciated in familial cases of normosmic IHH and infrequent in sporadic cases; and 3) functional mutations of the GNRHR are distributed widely throughout the protein.

Amino Acid Sequence↗
PubMed2001

Specific factors predict the response to pulsatile gonadotropin-releasing hormone therapy in polycystic ovarian syndrome.

Ovulation induction is particularly challenging in patients with polycystic ovarian syndrome (PCOS) and may be complicated by multifollicular development. Pulsatile GnRH stimulates monofollicular development in women with anovulatory infertility; however, ovulation rates are considerably lower in the subgroup of patients with PCOS. The aim of this retrospective study was to determine specific hormonal, metabolic, and ovarian morphological characteristics that predict an ovulatory response to pulsatile GnRH therapy in patients with PCOS. Subjects with PCOS were defined by chronic amenorrhea or oligomenorrhea and clinical and/or biochemical hyperandrogenism in the absence of an adrenal or pituitary disorder. At baseline, gonadotropin dynamics were assessed by 10-min blood sampling, insulin resistance by fasting insulin levels, ovarian morphology by transvaginal ultrasound, and androgen production by total testosterone levels. Intravenous pulsatile GnRH was then administered. During GnRH stimulation, daily blood samples were analyzed for gonadotropins, estradiol (E(2)), progesterone, inhibin B, and androgen levels, and serial ultrasounds were performed. Forty-one women with PCOS underwent a total of 144 ovulation induction cycles with pulsatile GnRH. Fifty-six percent of patients ovulated with 40% of ovulatory patients achieving pregnancy. Among the baseline characteristics, ovulatory cycles were associated with lower body mass index (P < 0.05), lower fasting insulin (P = 0.02), lower 17-hydroxyprogesterone and testosterone responses to hCG (P < 0.03) and higher FSH (P < 0.05). In the first week of pulsatile GnRH treatment, E(2) and the size of the largest follicle were higher (P < 0.03), whereas androstenedione was lower (P < 0.01) in ovulatory compared with anovulatory patients. Estradiol levels of 230 pg/mL (844 pmol/L) or more and androstenedione levels of 2.5 ng/mL (8.7 nmol/L) or less on day 4 and follicle diameter of 11 mm or more by day 7 of pulsatile GnRH treatment had positive predictive values for ovulation of 86.4%, 88.4%, and 99.6%, respectively. Ovulatory patients who conceived had lower free testosterone levels at baseline (P < 0.04). In conclusion, pulsatile GnRH is an effective and safe method of ovulation induction in a subset of patients with PCOS. Patient characteristics associated with successful ovulation in response to pulsatile GnRH include lower body mass index and fasting insulin levels, lower androgen response to hCG, and higher baseline FSH. In ovulatory patients, high free testosterone is negatively associated with pregnancy. A trial of pulsatile GnRH therapy may be useful in all PCOS patients, as E(2) and androstenedione levels on day 4 or follicle diameter on day 7 of therapy are highly predictive of the ovulatory response in this group of patients.

Adult↗
PubMed2001

Differential regulation of inhibin A and inhibin B by luteinizing hormone, follicle-stimulating hormone, and stage of follicle development.

Inhibin B and inhibin A exhibit unique patterns of secretion across the follicular phase of the menstrual cycle. To test the hypothesis that the distinct patterns of inhibin B and inhibin A secretion result from differential regulation by LH and FSH, a series of controlled experiments was designed to dissect the specific effects of LH and FSH at distinct stages of follicle development. After GnRH agonist desensitization, women with small antral follicles were treated with recombinant human LH (rhLH), rhFSH, or rhFSH and estradiol (E(2)). rhLH or rhFSH was also administered when follicles reached the preovulatory stage in gonadotropin-stimulated or spontaneous cycles. At the small antral stage of development, rhFSH, but not rhLH, administration increased inhibin B (17.4 +/- 4.6 to 321.0 +/- 97.0 pg/mL; P < 0.05), inhibin A (0.6 +/- 0.1 to 2.6 +/- 0.6 IU/mL; P < 0.05), and E(2) [15.8 +/- 3.6 to 95.3 +/- 26.9 pg/mL (58.0 +/- 13.2 to 349.8 +/- 98.7 pmol/L); P < 0.05]. The inhibin B increase preceded inhibin A by 48 h. Addition of E(2) to FSH resulted in a greater increase in inhibin B (23.2 +/- 6.4 to 865.2 +/- 294.5 pg/mL; P < 0.05) than FSH alone (P < 0.05). At the preovulatory stage, rhLH administration increased inhibin A (15.9 +/- 10.3 to 21.5 +/- 13.7 IU/mL; P < 0.05) and E(2) [669.4 +/- 285.5 to 943.6 +/- 388.1 pg/mL (2457.4 +/- 1048.1 to 3464.0 +/- 1424.7 pmol/L); P < 0.05], but not inhibin B, as did rhFSH administration in spontaneous cycles [E(2): 226.4 +/- 102.7 to 264.7 +/- 121.0 pg/mL (831.1 +/- 377.0 to 971.7 +/- 444.2 pmol/L); P < 0.05; inhibin A: 2.6 +/- 1.3 to 3.7 +/- 1.9 IU/mL; P < 0.05; and inhibin B: 76.3 +/- 32.2 to 77.6 +/- 32.8 pg/mL; P = NS]. These findings suggest that increases in both FSH and E(2) in the early follicular phase result in increased inhibin B secretion at early stages of follicle development, whereas the selective LH rise in the late follicular phase favors inhibin A secretion from more mature follicles. Thus, both differential secretion of LH and FSH and the stage of follicle development determine the patterns of inhibin A and inhibin B secretion in the normal menstrual cycle.

Adult↗
PubMed2000

Comparison of single- and dual-rod techniques for posterior spinal instrumentation in the treatment of adolescent idiopathic scoliosis.

STUDY DESIGN: Two groups of patients undergoing posterior spinal instrumentation and arthrodesis for treatment of adolescent idiopathic scoliosis were reviewed retrospectively. OBJECTIVE: To compare intraoperative concerns (operative time and blood loss), complications, and outcome in patients undergoing single or double posterior rod instrumentation for treatment of adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: The current treatment of idiopathic scoliosis includes posterior spinal instrumentation and arthrodesis. The standard configuration is a rectangular construct of dual rods connected by cross-links. Use of a single rod with multiple fixation points has been proposed as an alternative method to decrease operative time and blood loss, and to avoid late deep infections. METHODS: In this study, 21 patients underwent posterior instrumentation using a standard dual-rod construct, and 25 patients underwent posterior instrumentation using a solitary rod with multiple fixation points. Patients were assessed after a minimum 2-year follow-up period. RESULTS: No significant differences were found in blood loss, operative time, or overall frequency of long-term complications. Although not statistically significant, the trend was toward implant prominence in the double-rod group and implant failure in the single-rod group. Implant failure occurred only in instrumentations extending into the lumbar spine. There was no statistical difference in curve progression. CONCLUSIONS: Single-rod instrumentation and dual-rod constructs offered similar curve correction, blood loss, and operative time. However, single-rod instrumentation may be more prone to implant failure when extended into the lumbar spine.

Adolescent↗
PubMed2000

Simultaneous determination of lamivudine and zidovudine concentrations in human seminal plasma using high-performance liquid chromatography and tandem mass spectrometry.

A HPLC-MS-MS method was developed and validated to measure lamivudine and zidovudine simultaneously in small volumes of human seminal plasma. Sample preparation was simple and rapid, requiring 25 microl of sample, the use of isotopically labeled lamivudine and zidovudine as internal standards and ultrafiltration through a molecular mass cut-off membrane. Lamivudine and its internal standard were separated from zidovudine and its internal standard with isocratic HPLC. Detection was carried out using tandem mass spectrometry. This validated method was used to analyze seminal samples obtained from six HIV-positive patients prescribed lamivudine and zidovudine.

Anti-HIV Agents↗
PubMed2000

Annexins V and XII insert into bilayers at mildly acidic pH and form ion channels.

The functional hallmark of annexins is the ability to bind to the surface of phospholipid membranes in a reversible, Ca(2+)-dependent manner. We now report that human annexin V and hydra annexin XII reversibly bound to phospholipid vesicles in the absence of Ca(2+) at low pH; half-maximal vesicle association occurred at pH 5.3 and 5. 8, respectively. The following biochemical data support the hypothesis that these annexins insert into bilayers at mildly acidic pH. First, a photoactivatable reagent (3-trifluoromethyl)-3-(m-[(125)I]iodophenyl)diazirine) which selectively labels proteins exposed to the hydrophobic domain of bilayers reacted with these annexins at pH 5.0 and below but not at neutral pH. Second, in a Triton X-114 partitioning assay, annexins V and XII act as integral membrane proteins at low pH and as hydrophilic proteins at neutral pH; in the presence of phospholipids half-maximal partitioning into detergent occurred at pH approximately 5.0. Finally, annexin V or XII formed single channels in phospholipid bilayers at low pH but not at neutral pH. A model is discussed in which the concentrations of H(+) and Ca(2+) regulate the reversible conversion of three forms of annexins-soluble, peripheral membrane, and transmembrane.

Alkanesulfonic Acids↗
PubMed2000

pH and calcium regulate the water permeability of aquaporin 0.

Aquaporins increase the water permeability in many cell types across many species. We investigated the effects of external pH and Ca(2+) on water permeability of Xenopus oocytes injected with aquaporin cRNA by measuring the rate of swelling in hypotonic solutions. Lowering pH to 6.5 increased the water permeability of aquaporin (AQP0) 3.4 +/- 0.4-fold. Diethylpyrocarbonate pretreatment increased water permeability 4.2 +/- 0.5-fold and abolished pH sensitivity, suggesting that the pH regulation is mediated by an external histidine. Lowering Ca(2+) increased water permeability 4.1 +/- 0. 4-fold. The effects of Ca(2+) and pH each required the presence of histidine 40, indicating a critical role of this amino acid in facilitating the modulation of water permeability. Clamping intracellular Ca(2+) at high or low values abolished sensitivity to external Ca(2+), suggesting that Ca(2+) acts at an internal site. Three different calmodulin inhibitors each increased AQP0 water permeability, suggesting that Ca(2+) may act through calmodulin. None of the above altered the water permeability induced by AQP1 or AQP4. Because the greatest change in AQP0 water permeability is in the normal pH range found in the lens (7.2-6.5), this paper provides evidence for regulation of an aquaporin by pH under physiological conditions.

Amino Acid Sequence↗
PubMed2000

Pathophysiology of obesity hypertension.

Excess weight gain is a major cause of essential hypertension, and abnormal kidney function appears to be a cause as well as a consequence of obesity hypertension. Excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role in mediating increased blood pressure associated with weight gain. Activation of the renin-angiotensin and sympathetic nervous systems and physical compression of the kidneys appear to contribute to obesity-induced increases in sodium reabsorption and hypertension.

Fatty Acids↗
PubMed2000

Fentanyl supplementation of sevoflurane induction of anaesthesia.

Sevoflurane induction of anasthesia has been examined extensively, but little is known about the usefulness of other drugs as adjuncts to hasten and smooth the process. Sixty patients, undergoing surgery of a type suitable for a spontaneous respiration, laryngeal mask airway anasthetic technique, were randomly allocated to receive 1.0 microgram.kg-1 intravenous fentanyl or the equivalent volume of normal saline, 30 s prior to triple-breath induction with sevoflurane. The study was double-blind. There were no differences between the groups for the times to loss of eyelash reflex, jaw relaxation, insertion of the laryngeal mask airway or regular settled breathing. However, there was a difference in the incidence of adverse airway events (breath-holding, coughing and laryngospasm) between the two groups (16.5% in the fentanyl group and 40% in the placebo group); this did not reach statistical significance. Both groups were haemodynamically stable throughout induction, although the fentanyl group had a statistically significant decrease in systolic blood pressure at 4 min compared with the placebo group, which was not considered clinically relevant. We conclude that fentanyl has no significant influence over the speed and quality of sevoflurane induction.

Adjuvants, Anesthesia↗
PubMed2000

The effect of humidification and smoking habit on the incidence of adverse airway events during deepening of anaesthesia with desflurane.

The effect of two levels of humidification on the incidence of adverse airway events was studied in 58 adult female patients during deepening of anaesthesia using up to 12% desflurane. Humidification was provided by a breathing system filter with either low moisture-conserving performance (17.2 mg x l(-1) at 0.5 1 tidal volume, Group L) or high moisture-conserving performance (33.5 mg x l(-1) at 0.5 1 tidal volume, Group H). Forty-eight per cent of patients smoked and there were more smokers in Group L than in Group H. Adverse airway events consisted of coughing and laryngospasm. For coughing, the dominant explanator was smoking. When both humidity and age were included in the analysis, there was a significant smoking-humidity interaction (p < 0.05), such that high humidity decreased the incidence of coughing in nonsmokers but not in smokers. The incidence of laryngospasm was significantly lower in Group H than in Group L (p < 0.05). We conclude that when patients inspire high concentrations of desflurane during induction of anaesthesia, increasing humidification to the levels achieved in this study decreases the incidence of coughing among nonsmokers and of laryngospasm in both smokers and nonsmokers.

Adult↗