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Biomedical subjects

R Clarkson

Publications and source records attributed to R Clarkson.

13 recordsLinked to original sources

Activation of mesolimbic dopamine function by phencyclidine is enhanced by 5-HT(2C/2B) receptor antagonists: neurochemical and behavioural studies.

Administration of the non-competitive NMDA receptor antagonists phencyclidine (PCP) (0.6-5 mg/kg s.c.) and MK-801 (0.1-0.8 mg/kg s.c. ) dose-dependently increased locomotor activity in the rat. Pre-treatment of rats with SB 221284 (0.1-1 mg/kg, i.p.) a 5-HT(2C/2B) receptor antagonist or SB 242084 (1 mg/kg, i.p.) a selective 5-HT(2C) receptor antagonist, doses shown to block mCPP induced hypolocomotion, significantly enhanced the hyperactivity induced by PCP or MK-801. Neither compound altered locomotor activity when administered alone. Furthermore, systemic administration of PCP (5 mg/kg s.c.) increased nucleus accumbens dopamine efflux in the rat to a maximum of approximately 220% of basal, 40-60 min after administration. Pre-treatment with the 5-HT(2C/2B) receptor antagonist SB 221284 (1 mg/kg, i.p.) and the 5-HT(2C) receptor antagonist SB 242084 (1 mg/kg i.p.) failed to affect nucleus accumbens dopamine efflux per se but significantly enhanced the magnitude and duration of the increase induced by PCP. However, the time course of the neurochemical and behavioural effects were qualitatively and quantitatively different, suggesting the potential involvement of other neurotransmitter pathways. Nevertheless, the present results provide behavioural and neurochemical evidence which demonstrate that, in the absence of effects per se, blockade of 5-HT(2C) receptors enhanced the activation of mesolimbic dopamine neuronal function by the non-competitive NMDA receptor antagonists PCP and MK-801.

Aminopyridines↗

Australian women's perceptions of hormone replacement therapy over 10 years.

The knowledge, beliefs and experience of 60 women with HRT was studied when the women were premenopausal, and 10 years later when they were postmenopausal. Thirty-eight women had taken HRT by 1993. In 1993 women no longer considered clinics and self help groups to be the most useful sources of information about the menopause. They were more likely to think that doctors' knowledge of HRT was not adequate and to favour the use of HRT. Their reservations about all postmenopausal women receiving HRT continued. The women's understanding of long-term use of HRT varied. The women continued to maintain a desire not to experience withdrawal bleeding with HRT. More than 60% of women considered that HRT helped hot flushes, non-specific emotional changes and vaginal dryness. Women in 1993 were more likely to consider that HRT would help the menopausal symptoms of osteoporosis, insomnia and loss of muscle tone while fewer considered anxiety and depression would be relieved by HRT. Only one third believed HRT would reduce the incidence of heart disease. Women were more likely to take or have taken HRT if they were working and had achieved a higher work status (professional), considered reading material as the most useful source of information about menopause, had experienced menopause symptoms as distressing, considered menopause made relationships with husband and children more difficult and supported the universal use of HRT for all women.

Attitude↗

[Does laparoscopic appendectomy have advantages? Laparoscopic appendectomy in comparison with conventional appendectomy--an observational study during introduction of laparoscopy].

From October 1990 to October 1992 the first 23 laparoscopically operated patients were recorded. 11 patients retrospectively including a supplementary questioning to missing data, 12 patients prospectively with a follow-up 6-8 weeks later. They were compared with 35 from April 1991 to April 1992 conventionally operated and prospectively observed patients. Laparoscopy was performed on patients with subacute clinical signs. The median age was comparable. Acute appendicitis was histologically confirmed in 18% of the laparoscopically and in 80% of the conventionally operated patients. Operating time was in mean 110 minutes for laparoscopic and 65 minutes for open appendectomy. The postoperative complications for laparoscopy included 4 Douglas abscesses (2 x open and 2 x pararectal revisions), one peritonitis due to a defect Roeder-loop and an haematoma of the abdominal wall. One case of wound infection (3%), one pericoecal abscess which needed an ileoascendostomy and a postoperative fatigue syndrome were recorded for open appendectomy. The postoperative return to normal diet was faster for laparoscopy. Return to normal bowel habits, the need of analgesia and the nominal analogue scales concerning pain, quality of sleep, well-being and appetite showed no obvious differences between the two operation methods. The postoperative stay was on average 6.7 days for laparoscopy and 5.6 days for the open operation. The results show the severe complications which may happen when introducing this new operation method. The laparoscopic appendectomy should only be performed electively in subacute appendicitis or when diagnostic exploration shows an inflamed appendix. Careful rinsing of the operation site and perioperative antibiotic treatment are mandatory. We made good experiences when using a stapler for the removal of the appendix.

Adolescent↗

Immunogenetic heterogeneity in rheumatoid disease as illustrated by different MHC associations (DQ, Dw and C4) in articular and extra-articular subsets.

Genetic variants at DRB1 (Dw subtypes), DQB, and C4 loci were compared in rheumatoid disease subjects with or without the extra-articular feature of Felty's syndrome or major vasculitis. DR4 positive subjects with rheumatoid arthritis alone showed no preferential associations with DQB or Dw variants or with C4 null alleles. Felty's subjects showed associations with the DQB encoded DQw7 allele and with the C4B null allele but no preferential associations with any Dw subtype of DR4. By contrast DR4 +ve rheumatoid-vasculitic subjects showed associations with the Dw14 as well as with DQw7 and the C4A null allele. These different MHC associations in different clinical disease subsets show that rheumatoid disease is immunogenetically heterogeneous and suggest that MHC genes outside the DRB1 locus may also influence susceptibility or modify expression of the rheumatoid disease process.

Alleles↗

DQw7 and the C4B null allele in rheumatoid arthritis and Felty's syndrome.

DQ beta and C4 null alleles have been defined in patients with rheumatoid arthritis, Felty's syndrome, and in control subjects. Comparison of DR4 positive subjects shows that rheumatoid disease without extra-articular features has no preferential associations with either DQ beta or C4 null variants. In Felty's syndrome there are significant associations with both the class II major histocompatibility complex (MHC) DQw7 allele (86% of DR4 positive patients with Felty's syndrome and 53% of DR4 positive controls) and the class III MHC C4B null allele (50% of patients with Felty's syndrome and 20% of DR4 positive controls). DQw7 and the C4B null allele are in linkage disequilibrium and the B44-Bf *S-C4A*3-C4B*Q0-DR4-DQw7 haplotype accounts for five of 24 DR4 positive haplotypes assigned in subjects with Felty's syndrome. The results were not accounted for by articular disease severity and suggest that articular and extra-articular forms of rheumatoid disease may be immunogenetically heterogeneous.

Alleles↗

Studies of a C2 DNA polymorphism in RA, Felty's and normal subjects.

A restriction fragment length polymorphism at the C2 locus was studied in rheumatoid arthritis (RA), Felty's and control subjects. No association was found between any C2 variant and either RA itself or within the rheumatoid population with Felty's syndrome. The C2 DNA polymorphism can be used to subdivide Bf*S- as well as Bf*F-bearing haplotypes. The 2.65-kb C2 DNA allele showed allelic association with HLA-B44 and C4B*Q0 and may help to further characterize the haplotype B44-Bf*S-C4A*3-C4B*Q0-DR4, which has previously been described in Felty's syndrome.

Alleles↗

Acute chromium poisoning in a 2 year old child.

Sodium dichromate ingestion in children is uncommon and potentially lethal. The most appropriate management is uncertain because of the lack of sound data contained in the few reports of successfully treated patients. Immediate treatment should include urgent induction of emesis, administration of ascorbic acid as an antidote, followed by supportive treatment.

Antidotes↗

Molecule--receptor specificity.

The specificity of binding between small molecules and macromolecular receptors may be studied by comparing theoretically calculated conformational potential energy surfaces of a series of chemically similar molecules which have a range of receptor binding energies and biological activities. In this way essential requirements for binding may be highlighted, including the necessity of the small molecule adopting, or passing through, conformations which are not at energy minima and not found either in the solid state or in aqueous solution. In particular the conformational demands of the adrenergic beta-receptor and histamine H1 receptor are considered.

Animals↗