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Biomedical subjects

C J Spencer

Publications and source records attributed to C J Spencer.

14 recordsLinked to original sources
PubMed2002

Fetal learning: a prospective randomized controlled study.

OBJECTIVES: To examine whether prenatal exposure to a music stimulus alters fetal behavior and whether this continues into the newborn period. SUBJECTS AND METHODS: A prospective randomized control trial was conducted using an exposure learning model in 20 normal term pregnancies. Music was played to ten fetuses via a headphone on the maternal abdomen. Ten controls had the headphone without sound. All fetal studies took place within 72 h prior to elective delivery. All 20 newborns were exposed to the same music on days 3-5. Computerized assessment of fetal heart rate and activity was documented and neonatal behavioral states were recorded. Nonparametric statistical analysis was used. RESULTS: For the first hour of study, exposed fetuses had higher mean heart rates (FHR) and spent more time exhibiting high FHR variation compared to unexposed fetuses, but neither of these differences was statistically significant. However, by the fourth hour the exposed fetuses not only demonstrated these two features but also exhibited more state transitions (P = 0.01) and higher FHR variation (P = 0.04) compared to unexposed fetuses. These effects were carried over into the neonatal period with prenatally exposed newborns manifesting more state transitions (P = 0.01) and spending a higher proportion of time in awake states (P = 0.05) when exposed to the same music stimulus. CONCLUSION: Prenatal music exposure alters the fetal behavioral state and is carried forward to the newborn period. This suggests that a simple form of fetal programming or learning has occurred.

Embryonic and Fetal Development↗
PubMed2001

Compact long-term recorder for the transabdominal foetal and maternal electrocardiogram.

Foetal heart rate (FHR) monitoring is a proven means of assessing foetal health during the antenatal period. Currently, the only widely available instrumentation for producing these data is based on Doppler ultrasound, a technology that is unsuitable for long-term use. For nearly a century, it has been known that the foetal electrocardiogram (FECG) can be detected using electrodes placed on the maternal abdomen. Although these signals suggest an alternative means of FHR derivation, their use has been limited owing to problems of poor signal-to-noise ratio. However, the eminent suitability of the transabdominal FECG for long-term FHR monitoring has suggested that perseverance with the technique would be worthwhile. The paper describes the design, construction and use of a compact, long-term recorder of three channels of 24 h antenatal transabdominal data. Preliminary use of the recorder in around 400 short recording sessions demonstrates that FHR records of equivalent quality to those from Doppler ultrasound-based instruments can be extracted from such data. The success of FHR derivation is, on average, around 65% of the recording period from around 20 weeks gestation (although this figure is reduced from around 28-32 weeks, and the success rates exhibit a wide range when individual subjects are considered). These results demonstrate that the technique offers, not only a means of acquiring long-term FHR data that are problematic to obtain by other means, but also a more patient-friendly alternative to the Doppler ultrasound technique.

Electrocardiography, Ambulatory↗
PubMed1999

Milameline (CI-979/RU35926): a muscarinic receptor agonist with cognition-activating properties: biochemical and in vivo characterization.

Milameline (E-1,2,5,6-tetrahydro-1-methyl-3-pyridinecarboxaldehyde, O-methyloxime monohydrochloride, CI-979, PD129409, RU35926) was characterized in vitro and evaluated for effects on central and peripheral cholinergic activity in rats and rhesus monkeys. In muscarinic binding studies, milameline displayed nanomolar affinity with an agonist ligand and micromolar affinity with antagonist ligands, with approximately equal affinities determined at the five subtypes of human muscarinic receptors (hM(1)-hM(5)) with whole cells or membranes from stably transfected Chinese hamster ovary (CHO) cells. On binding, milameline stimulated phosphatidylinositol hydrolysis in hM(1) and hM(3) CHO cells and inhibited forskolin-activated cAMP accumulation in hM(2) and hM(4) CHO cells. Additionally, it decreased K(+)-stimulated release of [(3)H]acetylcholine from rat cortical slices. Responses were not caused by the inhibition of acetylcholinesterase, and there was no significant binding to approximately 30 other neurotransmitter binding sites. In rats, milameline decreased spontaneous and scopolamine-induced swimming activity, improved water-maze performance of animals impaired by basal forebrain lesions, increased cortical blood flow, decreased core body temperature, and increased gastrointestinal motility. Electroencephalogram activity in both rats and monkeys was characterized by a predominance of low-voltage desynchronized activity consistent with an increase in arousal. Milameline also reversed a scopolamine-induced impairment of attention on a continuous-performance task in monkeys. Thus, milameline possesses a pharmacological profile consistent with that of a partial muscarinic agonist, with central cholinergic actions being produced in rats and monkeys at doses slightly lower than those stimulating peripheral cholinergic receptors.

Acetylcholine↗
PubMed1998

Design and synthesis of m1-selective muscarinic agonists: (R)-(-)-(Z)-1-Azabicyclo[2.2.1]heptan-3-one, O-(3-(3'-methoxyphenyl)-2-propynyl)oxime maleate (CI-1017), a functionally m1-selective muscarinic agonist.

The synthesis and SAR of a series of (Z)-(+/-)-1-azabicyclo[2.2. 1]heptan-3-one, O-(3-aryl-2-propynyl)oximes are described. The biochemistry and pharmacology of 24Z (PD 142505) and its enantiomers are highlighted. 24Z is functionally an m1-selective muscarinic agonist. Efficacy and m1 selectivity reside in the R enantiomer, (R)-24Z (CI-1017).

3T3 Cells↗
PubMed1996

A prospective randomized comparison of the metabolic and stress hormonal responses of laparoscopic and open cholecystectomy.

BACKGROUND: In a relatively short period of time, therapeutic laparoscopy has become an everyday part of the general surgeon's life. Although laparoscopy provides distinct clinical advantages, it is not yet clear that it lessens the stress response typical of elective surgical procedures, and as such, the morbidity of surgery. The hypothesis that laparoscopic cholecystectomy produces less of a metabolic and stress hormonal response than open cholecystectomy was tested in a prospective randomized trial. STUDY DESIGN: Twenty otherwise healthy women between 18 and 45 years of age with a history of uncomplicated symptomatic cholelithiasis undergoing either laparoscopic (n = 10) or open cholecystectomy (n = 10) were studied. The hormonal response of the adrenocortical (serum adrenocorticotropic hormone, cortisol, and urinary free cortisol), adrenomedullary (plasma and urinary epinephrine and norepinephrine), thyroid (thyroid-stimulating hormone, thyroxine, and triiodothyronine), pituitary (antidiuretic hormone and growth hormone), and glucose (serum glucose, glucagon, and insulin) homeostatic axes were measured serially over a 24-hour period. RESULTS: No difference was seen between the laparoscopic and open groups in operative time (mean plus or minus standard error of the mean, 70 +/- 6 minutes compared with 77 +/- 6.3 minutes) or hospital stay 1.3 +/- 0.2 compared with 1.1 +/- 0.1 days). Assessment of postoperative pain using an analog pain score was less in the laparoscopic group (4.9 +/- 1.3 compared with 12.3 +/- 2.5, p = 0.01). The response of the adrenocortical, adrenomedullary, thyroid, and glucose axes were similar or identical in both groups. Antidiuretic hormone levels were greater in the laparoscopic group at one hour intraoperatively (281 +/- 79 pg/mL compared with 54 +/- 18 pg/mL, p < 0.01), and at extubation (122 +/- 18 pg/mL compared with 36 +/- 7 pg/mL, p < 0.01). Serum glucose levels were greater immediately following laparoscopic cholecystectomy. Glucose and insulin levels were greater at four, 12, and 24 hours after open cholecystectomy. CONCLUSIONS: Elective laparoscopic and open cholecystectomy for uncomplicated cholelithiasis result in similar degrees of perioperative hormonal stimulation. The different hormonal responses in the immediate and later postoperative periods after laparoscopic and open cholecystectomy suggest differential stressful stimuli between the two procedures.

Adolescent↗
PubMed1995

Mutations of aspartate 103 in the Hm2 receptor and alterations in receptor binding properties of muscarinic agonists.

Aspartate 103 (D103) in the third transmembrane domain of the Hm2 receptor was mutated to glutamate (D103E), asparagine (D103N), or alanine (D103A). As measured by [3H]-NMS, no significant binding was observed in D103A, while a 2-fold decrease in ligand affinity was seen in D103E and a 32-fold decrease in affinity was found in the D103N mutant. Examination of reference agonists showed greater loss of affinity in D103N than in D103E with the rank order of change being: L-607,207>carbachol>arecoline>pilocarpine>oxotremorine>McN-A-343. Of the novel 1-azabicyclo[2.2.1]-heptan-3-one oxime agonists examined, arylacetylene oximes showed little alteration in binding in either the D103E or D103N mutants, while the geometric isomers of several bicyclic aryl-ene-yne oximes showed significant changes in affinity, especially in the D103N mutant. Thus, overall size of the agonist and/or spatial orientation of the molecule within the binding pocket contribute to changes measured in binding.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1993

Characterization of muscarinic agonists in recombinant cell lines.

Using recombinant CHO cells that express Hm1-Hm5 receptors, reference muscarinic agonists have been characterized with respect to their activity in receptor binding and second messenger assays. In whole cell [3H]-N-methyl scopolamine binding, no agonist was found to be truly subtype selective, although some showed marked differences between several of the subtypes (e.g. m1 vs. m2). As a functional index of receptor activation, phosphatidyl-inositol (PI) turnover was measured for m1, m3, and m5 receptors while inhibition of forskolin-stimulated cAMP accumulation was measured for m2 and m4 receptors. Both full and partial agonists were delineated in PI turnover, but all agonists showed similar responses on cAMP. Alkylation studies with propylbenzylcholine mustard showed that both efficacy and potency were markedly affected in the functional assays by the number of free receptors. Thus, receptor reserve appears to play a major role in the determination of subtype selectivity for agonists using functional measures. Even with these limitations, however, the use of transformed cell lines is playing a pivotal role in the discovery of selective agonists.

Animals↗
PubMed1990

Loss of muscarinic M1 receptors with aging in the cerebral cortex of Fisher 344 rats.

Age-related changes in central cholinergic muscarinic receptors were measured in young (3-6 month), middle-aged (15-17 month), and aged (22-26 month) male Fisher 344 rats by receptor binding techniques. Using [3H]-quinuclidinyl benzilate as the ligand, a significant decrease (14-19%) in the number of muscarinic cortical receptors was measured in aged rats compared to both young and middle-aged rats. With the selective M1 antagonist, [3H]-pirenzepine, a 17% decrease in receptor density was observed in the cortex of aged animals compared to young rats. For both ligands no differences were observed in the striatum or hippocampus between any age group and there was no change in affinity (Kd) in any of the three brain regions for the three age groups. Additionally, there was no difference in choline acetyltransferase activity measured in cortex, hippocampus, or striatum of young and aged rats. Thus, there is a loss of M1 muscarinic receptors in the cerebral cortex of aged male Fisher 344 rats.

Aging↗
PubMed1980

Induction of tyrosine aminotransferase and amino acid transport in rat hepatoma cells by insulin and the insulin-like growth factor, multiplication-stimulating activity. Mediation by insulin and multiplication-stimulating activity receptors.

Insulin stimulates a 2-fold increase in the amount of tyrosine aminotransferase and a 5-10-fold increase in the rate of amino acid transport in dexamethasone-treated rat hepatoma cells. In order to determine whether these effects are mediated by insulin receptors or receptors for insulin-like growth factors, we have examined the binding of 125I-labeled insulin and 125I-labeled multiplication-stimulating activity, a prototype insulin-like growth factor, and compared the biological effects of these polypeptides. Insulin and multiplication-stimulating activity cause an identical increase in transaminase activity and transport velocity; half-maximal biological effects were observed at 35 ng/mg (5.5 nM) insulin and 140 ng/ml multiplication-stimulating activity. The hepatoma cells display typical insulin receptors of appropriate specificity; half-maximal displacement of tracer insulin binding occurred at 33 ng/ml unlabeled insulin, but only at 2500 ng/ml unlabeled multiplication-stimulating activity. Specific multiplication-stimulating activity receptors also were demonstrated with which insulin did not interact even at 10 micrograms/ml. Half-maximal displacement of tracer multiplication-stimulating activity occurred at 200 ng/ml unlabeled multiplication-stimulating activity. We conclude that insulin cannot act via the multiplication-stimulating activity receptor and presumably acts via typical insulin receptors. The effects of multiplication-stimulating activity on enzyme induction and amino acid transport are probably mediated primarily via the multiplication-stimulating activity receptor.

Amino Acids↗
PubMed1978

Prospective randomized multicentre trial of proximal gastric vagotomy or truncal vagotomy and antrectomy for chronic duodenal ulcer: interim results.

In three centres, 222 patients (Birmingham 70, London 87 and Rotterdam 65 patients) with chronic duodenal ulcer were treated by proximal gastrict vagotomy (PGV) (116 patients) or truncal vagotomy and antrectomy (TVA) (106 patients) in a prospective randomized trial. After 1 year 5 recurrent duodenal ulcers (4.3 per cent) have been recorded in the PGV group, compared with 1 (1 per cent) in the TVA group. The reoperation rate was high in both groups-6 after PGV, usually for recurrent ulcer, and 7 after TVA, mostly for gastric retention. PGV showed a marked superiority in the number of patients with a good clinical result Visick I or II) at 1 year after operation, i.e. 82 per cent compared with 56 per cent for TVA.

Chronic Disease↗
PubMed1977

The effects of modelling on the contingent praise of mental retardation counsellors.

A multiple-baseline design was used to evaluate the effects of a simple modelling procedure on the contingent praise of five counsellors while they conducted hygiene-training sessions in toothbrushing and hand-and-face washing with severely retarded children. After varying numbers of baseline sessions, each counsellor watched a model who conducted a series of toothbrushing sessions, in which he conspicuously praised correct toothbrushing responses and approximations to correct responses. No modelling occurred during hand-and-face washing sessions. As a result of several exposures to the model's performance, levels of response-contingent praise provided by four of the five counsellors during toothbrushing sessions increased sharply over baseline. The levels of counsellor praise showed parallel increases during hand-and-face washing sessions. A two-week followup showed that the levels of praise obtained through modelling were maintained in the model's absence.

Activities of Daily Living↗