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Biomedical subjects

G Riley

Publications and source records attributed to G Riley.

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

Attenuation of haloperidol-induced catalepsy by a 5-HT2C receptor antagonist.

Atypical neuroleptics produce fewer extrapyramidal side-effects (EPS) than typical neuroleptics. The pharmacological profile of atypical neuroleptics is that they have equivalent or higher antagonist affinity for 5-HT2 than for dopamine D2 receptors. Our aim was to identify which 5-HT2 receptor contributed to the atypical profile. Catalepsy was defined as rats remaining immobile over a horizontal metal bar for at least 30 s, 90 min after dosing. Radioligand binding assays were carried out with homogenates of human recombinant 5-HT2A, 5-HT2B and 5-HT2C receptors expressed in Human Embryo Kidney (HEK293) cells. Haloperidol (1.13 mg kg(-1) i.p.) induced catalepsy in all experiments. The selective 5-HT2C/2B receptor antagonist, SB-228357 (0.32-10 mg kg(-1) p.o.) significantly reversed haloperidol-induced catalepsy whereas the 5-HT2A and 5-HT2B receptor antagonists, MDL-100907 (0.003-0.1 mg kg(-1) p.o.) and SB-215505 (0.1-3.2 mg kg(-1) p.o.) respectively did not reverse haloperidol-induced catalepsy. The data suggest a role for 5-HT2C receptors in the anticataleptic action of SB-228357.

Animals↗
PubMed1999

Sex knowledge and sexual attitudes among medical and nursing students.

OBJECTIVES: The aim of this study was to assess the relationship between background and sociodemographic variables, attitudes toward controversial aspects of human sexuality and sex knowledge among medical and nursing students. METHOD: The study design was a questionnaire-based survey of medical and nursing students in Western Australia. Participants were first- through fifth-year medical students at the University of Western Australia and first- through third-year undergraduate nursing students at Edith Cowan University. Outcome measures were students' attitudes toward controversial aspects of human sexuality expressed on a five-point Likert scale and a modified version of the Kinsey Institute/Roper Organization National Sex Knowledge Test. RESULTS: A significant relationship was found between certain background and sociodemographic variables, sexual attitudes and sex knowledge. The background variable most strongly related to both attitudes and knowledge was frequency of attendance at religious services of any religious denomination during the past month, with those attending three or more times more likely to express negative attitudes and have lower sex knowledge scores. Lower sex knowledge was related to negative attitudes toward gay/lesbian/bisexual behaviour, masturbation, premarital sex and contraception. Other important background and sociodemographic variables related to negative attitudes were: never having experienced sexual intercourse; right-wing political orientation; lower family income; gender and ethnicity. CONCLUSIONS: Negative attitudes toward controversial aspects of human sexuality and lower sex knowledge scores among medical and nursing students can be predicted on the basis of background and sociodemographic variables. Education aimed at increasing sex knowledge and modifying negative attitudes may increase students' ability to function more effectively as sexual history takers and sex counsellors.

Attitude↗
PubMed1999

Analysis of two IL-4 promoter polymorphisms in a cohort of atopic and asthmatic subjects.

The Th2 cytokine interleukin 4 (IL-4) has been identified as having a central role in driving the inflammatory immune responses which are present in atopic airway disease. This study examined the distribution of two putative IL-4 promoter polymorphisms (-285 C-T and -81 A-G) in groups of patients with severe and moderate asthma, non-asthmatic atopy and control subjects. Neither polymorphism was identified in any of the samples tested. The data suggest that either the polymorphisms are present at very low frequencies or are artefacts of the B cell lines from which they were identified.

Adult↗
PubMed1999

Survival and treatment for colorectal cancer Medicare patients in two group/staff health maintenance organizations and the fee-for-service setting.

The current study compares treatment use and long-term survival in colorectal cancer patients between Medicare beneficiaries enrolled in two large prepaid group/staff health maintenance organizations (HMOs) and the fee-for-service (FFS) setting. The study is based on 15,352 colorectal cancer cases diagnosed between 1985 and 1992 and followed through 1995. Survival differences between the HMO and FFS cases were assessed using Cox regression. Treatment differences were evaluated using logistic regression. HMO cases had a lower overall mortality than did FFS cases but not a significantly lower colorectal cancer-specific mortality. Use of surgical resection was similar between HMO and FFS cases. However, rectal cancer cases in the HMOs were more likely to receive postsurgical radiation therapy than FFS cases. Superior overall survival in the HMOs may be the result of increased colorectal cancer screening, greater use of adjuvant therapies, and selection of healthier individuals.

Aged↗
PubMed1998

The selective 5-HT1B receptor inverse agonist 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2, 4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro- spiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289) potently blocks terminal 5-HT autoreceptor function both in vitro and in vivo.

5-HT1 receptors are members of the G-protein-coupled receptor superfamily and are negatively linked to adenylyl cyclase activity. The human 5-HT1B and 5-HT1D receptors (previously known as 5-HT1Dbeta and 5-HT1Dalpha, respectively), although encoded by two distinct genes, are structurally very similar. Pharmacologically, these two receptors have been differentiated using nonselective chemical tools such as ketanserin and ritanserin, but the absence of truly selective agents has meant that the precise function of the 5-HT1B and 5-HT1D receptors has not been defined. In this paper we describe how, using computational chemistry models as a guide, the nonselective 5-HT1B/5-HT1D receptor antagonist 4 was structurally modified to produce the selective 5-HT1B receptor inverse agonist 5, 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2, 4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6, 7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289). This compound is a potent antagonist of terminal 5-HT autoreceptor function both in vitro and in vivo.

Animals↗
PubMed1998

Functional characterisation of the human cloned 5-HT7 receptor (long form); antagonist profile of SB-258719.

1. The functional profile of the long form of the human cloned 5-HT7 receptor (designated h5-HT7(a)) was investigated using a number of 5-HT receptor agonists and antagonists and compared with its binding profile. Receptor function was measured using adenylyl cyclase activity in washed membranes from HEK293 cells stably expressing the recombinant h5-HT7(a) receptor. 2. The receptor binding profile, determined by competition with [3H]-5-CT, was consistent with that previously reported for the h5-HT7(a) receptor. The selective 5-HT7 receptor antagonist SB-258719 ((R)-3,N-Dimethyl-N-[1-methyl-3-(4-methylpiperidin-1-yl)propyl]ben zene sulfonamide) displayed high affinity (pKi 7.5) for the receptor. 3. In the adenylyl cyclase functional assay, 5-CT and 8-OH-DPAT were both full agonists compared to 5-HT and the rank order of potency for agonists (5-CT > 5-HT > 8-OH-DPAT) was the same in functional and binding studies. 4. Risperidone, methiothepin, mesulergine, clozapine, olanzapine, ketanserin and SB-258719 antagonised surmountably 5-CT-stimulated adenylyl cyclase activity. Schild analysis of the antagonism by SB-258719 gave a pA2 of 7.2+/-0.2 and slope not significantly different from 1, consistent with competitive antagonism. 5. The same antagonists also inhibited basal adenylyl cyclase activity with a rank order of potency in agreement with those for antagonist potency and binding affinity. Both SB-258719 and mesulergine displayed apparent partial inverse agonist profiles compared to the other antagonists tested. These inhibitory effects of antagonists appear to be 5-HT7 receptor-mediated and to reflect inverse agonism. 6. It is concluded that in this expression system, the h5-HT7(a) receptor shows the expected binding and functional profile and displays constitutive activity, revealing inverse agonist activity for a range of antagonists.

Adenylyl Cyclases↗
PubMed1998

Guidelines for documentation of treatment efficacy for young children who stutter.

The pressing need to document treatment efficacy for young children who stutter is discussed. Guidelines for such documentation are suggested and illustrated. Measures for verifying treatment effects in four realms are delineated: (a) conditions of documentation, (b) dependent variables to be measured, (c) establishment of treatment integrity, and (d) verification of the relationship between treatment and outcome. Illustrations of the application of the suggested guidelines are presented for 2 children.

Child, Preschool↗
PubMed1997

Increased dopamine activity associated with stuttering.

Position emission tomography using 6-FDOPA as a marker of presynaptic dopaminergic activity was used to investigate the role of the dopamine system in stuttering. Three patients with moderate to severe developmental stuttering were compared with six normal controls. Stuttering subjects showed significantly higher 6-FDOPA uptake than normal controls in medial prefrontal cortex, deep orbital cortex, insular cortex, extended amygdala, auditory cortex and caudate tail. Elevated 6-FDOPA uptake in ventral limbic cortical and subcortical regions is compatible with the hypothesis that stuttering is associated with an overactive presynaptic dopamine system in brain regions that modulate verbalization.

Adult↗
PubMed1997

Analysis of Neisseria gonorrhoeae in Ontario, Canada, with decreased susceptibility to quinolones by pulsed-field gel electrophoresis, auxotyping, serotyping and plasmid content.

The incidence of Neisseria gonorrhoeae with reduced susceptibility to quinolones increased from 0.18% (63 of 3285) in 1992 to 0.56% (15 of 2663) in 1993 and 0.62% (46 of 2846) in 1994. In all, 65 of the 67 isolates of Neisseria gonorrhoeae with decreased susceptibility to quinolones were characterised by pulsed-field gel electrophoresis (PFGE), auxotyping, serotyping and plasmid content. The strains were distributed among 14 auxotype/serovar (A/S) classes. Thirty isolates (46.2%) which were penicillin-susceptible with ciprofloxacin MIC90 of 0.12 mg/L and norfloxacin MIC90 of 1.0 mg/L belonged to a single A/S class, OUHL/IA-2. All but two of the 30 isolates had identical PFGE restriction profiles with NheI restriction endonuclease. Fifteen isolates (23.1%) with MICs in the intermediate (or resistant) categories for penicillin and with ciprofloxacin and norfloxacin MIC90 of 0.25 and 4.0 mg/L and (0.5 and 4.0 mg/L) respectively, belonged to A/S class P/IB-1. The 15 isolates showed nine different patterns with NheI and eight patterns with SpeI restriction endonucleases. Two of three beta-lactamase-producing (PPNG) isolates belonged to A/S class P/IB-5 and had a dissimilar PFGE restriction profile with NheI endonuclease; the other isolate belonged to A/S class P/IB-8. The remaining 17 isolates were distributed among 11 A/S classes. Three isolates within the common A/S class NR/IB-1 were subdivided into two types by PFGE as were three isolates belonging to A/S class NR/IB-2. Overall the 65 isolates of N. gonorrhoeae were distributed into 30 NheI and 26 SpeI macrorestriction profiles. All but one isolate harboured the 2.6-MDa cryptic plasmid and 18 isolates carried the 24.5-MDa transferable plasmid. The three PPNG isolates carried the 4.5-MDa Asian beta-lactamase-producing plasmid and a 25.2-MDa conjugative plasmid was found in the two TRNG isolates.

4-Quinolones↗
PubMed1997

In vivo characterization of sustained-release formulations of human growth hormone.

Long-acting formulations of recombinant human growth hormone (rhGH) were prepared by stabilizing and encapsulating the protein into three different injectable, biodegradable microsphere formulations composed of polymers of lactic and glycolic acid. The formulations were compared in juvenile rhesus monkeys by measuring the serum levels of rhGH and two proteins induced by hGH, insulin-like growth factor-I and IGF binding protein-3 (IGFBP-3) after single s.c. administration. All three formulations, which differed principally in the composition of the polymer, provided sustained elevated levels of all three proteins for several weeks, and the rate of release of rhGH differed among the formulations consistent with the molecular weight of the polymer used. All three formulations induced a higher level of insulin-like growth factor-I and insulin-like growth factor binding protein than was induced by daily injections of the same amount of rhGH in solution. After three monthly injections of one of the formulations, both the rhGH and IGF-I levels remained elevated for nearly 90 days. Immunogenicity of the rhGH released from this formulation, as assessed by the incidence of seroconversion to hGH and the titer of anti-hGH antibody in both the rhesus monkeys and transgenic mice expressing rhGH, was no greater than that of the unencapsulated protein. In addition, the microsphere injection sites appeared normal by macroscopic evaluation between 1 to 2 mo after microsphere administration and by microscopic evaluation between 2 to 3 mo. These results show that serum levels of a therapeutic protein can be sustained for an extended period when encapsulated into different formulations of injectable, biodegradable microspheres.

Animals↗