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Biomedical subjects

S G Wilson

Publications and source records attributed to S G Wilson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sex differences in supraspinal morphine analgesia are dependent on genotype.

Several variables have been reported to affect the expression of sex differences in the analgesic potency of morphine. Although the effect of genetic background on morphine analgesia has been well documented, the relevance of genotype to sex differences in morphine analgesia has rarely been considered. The present study investigated morphine dose-response relationships in male and female mice of 11 inbred mouse strains on the tail-withdrawal test after i.c.v. administration. Large differences in morphine analgesic potency were observed between strains, reflecting the important influence of genotype on this trait. We identified three strains (AKR/J, C57BL/6J, and SWR/J) in which males displayed approximately 3.5- to 7.0-fold greater sensitivities to the analgesic effects of morphine than did their female counterparts. In contrast, in the CBA/J strain, females were found to be approximately 5-fold more sensitive to morphine than were the males. In all other strains, morphine potency estimates between the sexes were not statistically different. These data support the importance of genotype, sex, and their interaction in the mediation of morphine analgesia and suggest that equivocal findings regarding opioid sex differences in the literature may be partially accounted for by the use of different subject populations. The fact that female mice of the AKR/J and CBA/J strains exhibit 35-fold different morphine analgesic potency and that males of these strains are equally sensitive should facilitate the mapping and identification of sex-specific genes of relevance to morphine analgesia.

Analgesia↗
PubMed1999

Pharmacogenetic variability in neuronal nicotinic receptor-mediated antinociception.

The ability to predict interindividual differences in drug efficacy or toxicity, based on genetic factors that influence drug disposition or drug action, is fast becoming a realistic goal. The purpose of the present study was to determine whether epibatidine, a prototypical nicotinic analgesic drug, exhibits pharmacogenetic variability in antinociceptive activity. Eight inbred mouse strains (A, AKR, BALB/c, C3H/He, C57BL/6, C57BL/10, DBA/2, and SM) were surveyed for their sensitivity to the antinociceptive effects of epibatidine. All strains exhibited statistically significant antinociception that peaked between 10 and 20 min following the systemic injection of 50 microg/kg epibatidine. However, there was fourfold variability in the magnitude of peak effect between strains, with DBA/2, BALB/c and A strains showing much greater sensitivity than all others. A return to baseline nociceptive threshold at 30 min post-injection was observed for all but the A strain. In contrast, these mice exhibited significant antinociception for at least 3 h following epibatidine administration. Thus, expressing the data as area under the time-latency curve to take into account both the magnitude and duration of effect, epibatidine displayed approximately 20-fold higher antinociceptive potency in the A strain compared with the C3H/He strain. The effects of epibatidine in both the A and C3H/He strains were dose-dependent and sensitive to antagonism by the selective neuronal nicotinic channel blocker mecamylamine. Taken together, these data demonstrate the existence of pharmacogenetic variability in neuronal nicotinic receptor-mediated antinociception between inbred stains of mice and presage the potential for similar variability in analgesic response to nicotinic-based analgesics among humans. Future studies will seek to identify the chromosomal loci underlying this variability.

Analgesics↗
PubMed1998

[Phe1psi(CH2-NH)Gly2]nociceptin-(1-13)-NH2 acts as an agonist of the orphanin FQ/nociceptin receptor in vivo.

The orphanin FQ/nociceptin (OFQ/N) derivative peptide, [Phe1psi(CH2-NH)Gly2] nociceptin-(1-13)-NH2 (Phe(psi)), has been claimed to be both an antagonist and an agonist of the orphan opioid receptor (ORL1) in different in vitro assays. We now report the dose-dependent inhibition of morphine analgesia by Phe(psi) in mice, an effect parallel to that of OFQ/N. Further, the anti-opioid actions of OFQ/N are not blocked by Phe(psi). Thus, Phe(psi) acts as an ORL1 receptor agonist, not an antagonist, in vivo.

Analgesia↗
PubMed1998

The effect of genotype on sensitivity to inflammatory nociception: characterization of resistant (A/J) and sensitive (C57BL/6J) inbred mouse strains.

The important role of genetic factors in the mediation of sensitivity to pain and pain inhibition is being increasingly appreciated. In an attempt to systematically study the genotypic influences on inflammatory nociception, we conducted a survey of the nociceptive responsivity of three common outbred mouse strains and 11 inbred mouse strains on the formalin test. The formalin test is known to display a biphasic temporal pattern of behavioral and electrophysiological activity, defined by an acute/early phase and a tonic/late phase. Nociceptive sensitivity (licking/biting of the affected area) to a subcutaneous injection of 5% formalin (25 microl volume) into the plantar surface of the right hindpaw displayed moderate heritability in both phases (0.38 and 0.46, respectively). One strain, A/J, was identified as extremely resistant to formalin nociception, displaying total licking in the acute and tonic phases that was 60% and 87% lower, respectively, than the grand mean of all strains. A subsequent series of experiments were performed to characterize the difference between A/J and C57BL/6J mice. The findings establish this inbred strain comparison as a useful genetic model of nociceptive sensitivity.

Animals↗
PubMed1997

Nociceptive and morphine antinociceptive sensitivity of 129 and C57BL/6 inbred mouse strains: implications for transgenic knock-out studies.

Gene-targeting studies of pain, using transgenic 'knock-out' mice possessing null mutations of pain-relevant genes, are becoming increasingly common. This approach is a potentially powerful tool for the molecular dissection of complex traits such as pain modulation, but is subject to several theoretical drawbacks. One problem arises from the fact that the genetic background of knock-out mice is virtually always a mixture of alleles from two different strains; commonly 129 and C57BL/6. A more general caveat to knock-out findings derives from the demonstration that null mutations interact with genetic background to produce phenotypic changes. The present study investigated basal' nociceptive sensitivity (on the 49 degrees C tail-immersion/withdrawal test) and sensitivity to morphine antinociception in 129 and C57BL/6 mice (129/J, 129/Sv-+(p)+(Tyr-c)+(Mgf-SIJ), and C57BL/6J substrains). C57BL/6 mice displayed almost two-fold greater initial sensitivity to thermal stimulation than 129 mice, and three-fold reduced sensitivity to morphine inhibition of that noxious stimulus. These findings suggest that gene targeting studies of pain are particularly subject to the aforementioned concerns, and that C57BL/6 mice represent a suboptimal background strain for such efforts.

Journal Article↗
PubMed1996

Adrenalitis and the adrenocortical response of resistant and susceptible mice to acute murine cytomegalovirus infection.

Murine cytomegalovirus (MCMV) induces adrenalitis in BALB/c mice but does not compromise adrenal function, assessed by levels of circulating adrenocorticotropic hormone (ACTH) and by the response to challenge with synthetic ACTH. Levels of corticosterone increased 2 days after infection in mice of this strain, consistent with previously established interactions between mediators of acute inflammation and activation of the hypothalmus-pituitary-adrenal axis. Moreover, an adrenocortical response was critical to survival of BALB/c (but not C57BL/6) mice 3 days after infection, as pharmacologically or surgically adrenalectomized BALB/c mice died when given doses of virus up to fivefold lower, than they could normally tolerate. However, death could not be prevented by the administration of soluble cytokine receptors to inhibit the action of interleukin 1 (IL-1) or tumour necrosis factor alpha (TNF alpha). The corticosteroid response did not mediate.MCMV-induced thymic atrophy. As the above traits were all less evident in C57BL/6 mice, a common genetic basis is discussed.

Acute Disease↗
PubMed1996

A comparison of papillary retention versus full-thickness flaps with internal mattress sutures in anterior periodontal surgery.

Esthetic considerations pose therapeutic dilemmas in the selection of surgical techniques in anterior periodontal surgery. Two surgical techniques designed to maximize postoperative esthetics in the anterior regions are described. Changes in interdental papillary height are reported and compared at 1 year postoperative. This study discusses the surgical techniques, their advantages and disadvantages, and their indications. Since there is less risk of recession and more potential for gain in papillary height, the papillary retention procedure, when possible, may be the procedure of choice in anterior regions.

Esthetics, Dental↗
PubMed1995

On the nature of streaks in signal detection.

Human performance in the domain of signal detection is analyzed with respect to the formation of streaks. Streakiness was found to be a general property of auditory and visual discrimination in the sense that correct and incorrect responses have a positive sequential dependency. Success tends to follow success and failure tends to follow failure. Level of streakiness was discovered to be a function of the attentional demand required by the discrimination. Discriminations that make the least demand on attentional resources produce the highest level of streakiness. Monte-Carlo simulations of the observed data sequences suggest that streaky performance is a residue of wave-like variations in perceptual and attentional resources.

Attention↗
PubMed1994

Glucose turnover in pregnant women with acute malaria.

1. Hypoglycaemia is a serious complication of falciparum malaria, especially in pregnant patients. To investigate malaria-associated changes in glucose metabolism in pregnancy, steady-state [6,6-2H2] glucose turnover and clearance were measured in 10 women (eight with uncomplicated falciparum malaria and two with vivax malaria at 16-30 weeks gestation) before treatment, after intravenous quinine infusion (patients with falciparum malaria) and in convalescence. 2. Admission basal plasma glucose concentrations were higher than those in convalescence [median (range); 4.8 (3.6-7.0) versus 4.0 (3.6-4.6) mmol/l, P = 0.02], and there was a significant fall during initial quinine treatment in patients with falciparum malaria [5.0 (4.3-7.6) to 3.6 (3.2-5.4) mmol/l, P < 0.01]. Basal plasma insulin levels were comparable at presentation and follow-up (P = 0.35) and rose an average of only 2m-units/l during quinine infusion (P < 0.05). Pretreatment glucose turnover rates [3.37 (2.57-4.16) mg min-1 kg-1] were comparable with those found in a previously reported study of non-pregnant severely ill patients [3.22 (2.12-4.82) mg min-1 kg-1, n = 11] and correlated significantly with the admission parasitaemia (P < 0.025). In the eight patients with falciparum malaria, there was a significant fall in turnover during intravenous quinine infusion [3.42 (2.58-4.16) to 2.66 [1.94-3.94) mg min-1 kg-1] whereas clearance did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

An autogenous gingival graft technique.

This paper discusses a technique for root coverage using autogenous free gingival grafts. Twenty-two patients who had gingival recession on facial tooth surfaces were studied. The patients underwent surgical treatment, and pretreatment and posttreatment average probing depths for the distal, facial, and mesial tooth surfaces were compared. There was a general decrease in recession for all surfaces. Recession levels tended to remain stable for the duration of the study. There was a slight increase in recession on midfacial surfaces at 4 years that was not statistically significant.

Adult↗
PubMed1991

Physical characteristics of the hand and early clinical skills. Their relationship in a group of dental hygiene students.

Twelve hand measurements were made on 45 first-year dental hygiene students within one week of their entering a dental hygiene program. Multiple regression was performed, using three clinical examinations (use of periodontal probe, use of 3-A explorer, and use of Gracey curets) as dependent variables, to assess whether or not hand measurements predicted early clinical skill development. None of the hand measurements were predictive for the explorer examination. Wrist width accounted for 13% of the variance on the probing examination and 24% of the variance on the curet examination. Finger span added 16% variance to the equation. A total of 40% variance was explained by these measures on the curet examination. Results suggest that wrist width and finger span may be important predictors of early dental hygiene clinical skill development.

Aptitude Tests↗
PubMed1990

Human lactation: forearm trabecular bone loss, increased bone turnover, and renal conservation of calcium and inorganic phosphate with recovery of bone mass following weaning.

The calcium (Ca) metabolism of established human lactation was studied in 40 adult women (mean age 32.4 years) who had been breast-feeding for 6 months (Lac) and in 40 age-matched controls (Con) using fasting urine and blood biochemistry and forearm single-photon bone mineral densitometry (BMD). Serial studies were performed up to 6 months after weaning in Lac women and repeated once in Con women. During lactation the significant findings were (1) a selective reduction (7.1%, P less than 0.03) in BMD at the ultradistal site containing 60% trabecular bone, but not at two more proximal, chiefly cortical bone sites; (2) increased bone turnover affecting bone resorption [fasting hydroxyproline excretion, Lac 2.22 +/- 0.12 mumol/liter GF (mean +/- SEM), Con 1.19 +/- 0.04, P less than 0.001] and affecting bone formation (plasma alkaline phosphatase, Lac 81.9 +/- 2.5 IU/liter, Con 53.5 +/- 2.7, P less than 0.001, and serum osteocalcin, Lac 14.0 +/- 0.7 microgram/liter, Con 7.3 +/- 0.4, P less than 0.001); and (3) renal conservation in the fasting state of both Ca and inorganic phosphate (Pi) with a resultant moderate increase in plasma Pi but not in plasma Ca (total or ionized). There were no differences between the groups in serum parathyroid hormone (PTH, intact and midmolecule assays), 25-hydroxy- and 1,25-dihydroxyvitamin D, nephrogenous cyclic AMP production, or plasma creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Serum free 1,25-dihydroxyvitamin D and the free 1,25-dihydroxyvitamin D index during a longitudinal study of human pregnancy and lactation.

The changes in three different indices of 1,25-dihydroxyvitamin D (1,25(OH)2D) biological activity were studied longitudinally in 35 women during late pregnancy and lactation and in 26 control women. Measurements were made of maternal serum total 1,25(OH)2D and free 1,25(OH)2D concentration (by centrifugal ultrafiltration) and the free 1,25(OH)2D index (the molar ratio of total 1,25(OH)2D and vitamin D binding protein (DBP]. During late pregnancy total 1,25(OH)2D concentrations were significantly elevated when compared to controls, as were free 1,25(OH)2D and DBP concentrations and the free 1,25(OH)2D index. Serum total 1,25(OH)2D, free 1,25(OH)2D and DBP concentrations all fell dramatically during the first 2 weeks of lactation with total 1,25(OH)2D and free 1,25(OH)2D concentrations falling to levels below those of controls. During the course of lactation both total 1,25(OH)2D and free 1,25(OH)2D levels rose significantly although they were not different from controls at 18 weeks of lactation. In contrast, the free 1,25(OH)2D index fell during the first 2 weeks of lactation, but remained at this level, significantly lower than controls. Neither urinary calcium excretion nor dietary calcium intake correlated with total or free 1,25(OH)2D, DBP, or the free 1,25(OH)2D index. The disagreement in the results of free 1,25(OH)2D concentration and free 1,25(OH)2D index demonstrates that these two approaches to measuring biologically active 1,25(OH)2D are not equivalent. In attempting to account for the increased calcium requirements of human reproduction we conclude that in pregnancy any of the 1,25(OH)2D measurements may be appropriate. In lactation, however, either 1,25(OH)2D is not a major factor or 1,25(OH)2D biological activity is inadequately represented by any of the currently available methods.

Adult↗
PubMed1989

Hypothalamic disease in association with dysgenesis of the corpus callosum.

We describe two cases of dysgenesis of the corpus callosum demonstrated by magnetic resonance. The first patient presented with chronic hyponatraemia. Investigation demonstrated re-setting of the osmoreceptor and thirst centres. The calculated threshold for arginine vasopressin (AVP) release was reduced at 252 mosmol/kg while severe thirst was perceived at a plasma osmolality of 260 mosmol/kg. Insulin-induced hypoglycaemia produced an exaggerated AVP response. The second patient presented with hypothermia. The calculated threshold of AVP release was 296 mosmol/kg with increased sensitivity of AVP response to hypertonic saline. The plasma AVP response to insulin-induced hypoglycaemia was absent. Both cases had normal anterior pituitary function and psychological assessment showed a similar prefrontal defect. Specific tests of callosal function were normal. These cases illustrate the importance of undertaking complete neuroradiological assessment of cases of unexplained hypothalamic disease regardless of the age of presentation to avoid overlooking this rare congenital association.

Adolescent↗
PubMed1988

A multivariable approach toward predicting dental motor skill performance.

The purpose of the present study was to examine the potential of a multivariable approach in predicting dental motor skill performance. Variables measuring cognitive knowledge, motor abilities, educational background, and family demographics were examined. Data were obtained from 33 first-year dental students. Scaling and root planing tests were administered to each student at the beginning and end of a 14-week preclinical periodontal course. Correlations were low and no variable significantly predicted pre- or posttest scaling and root planing performance. Results are discussed in terms of the problems associated with predicting motor performance.

Aptitude Tests↗