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Biomedical subjects

Peter G Smith

Publications and source records attributed to Peter G Smith.

40 records · Page 3Linked to original sources

Increased ocular blood vessel numbers and sizes following chronic sympathectomy in rat.

Disease states characterized by ocular vascular pathology are often associated with impaired sympathetic function. This study examined the effect of sympathetic denervation on ocular vasculature of the adult rat. Uveal perfusion and choroidal and retinal blood vessel sizes and numbers were assessed in rats with intact innervation and after short- (2 days) or long-term (6 weeks) sympathetic denervation induced by ipsilateral superior cervical ganglion excision. In rats with intact innervation and after short-term sympathectomy, blood flow in both eyes was comparable. However, after long-term sympathectomy, blood flow was four-fold greater in the denervated than in the innervated eye, but was unaltered in lacrimal gland, cerebral cortex, and masseter muscle. Choroid surface area was not affected by long-term sympathectomy, but choroidal thickness was increased and choroidal cross-sectional area occupied by vascular lumina was greater. Arteriolar number per unit cross-sectional area of choroid was not altered although arteriolar diameters were enlarged. Choroidal venules were larger and more abundant. Choroidal capillary numbers were unchanged, but retinal capillaries of the outer plexiform layer were increased. To determine if these changes result from loss of sympathetic activity, sympathetic preganglionic innervation was excised chronically. This produced significant increases in choroidal thickness and vascular luminal area, and in numbers of arterioles, small venules, and capillaries in the outer plexiform layer. These findings show that sympathetic innervation is critical in regulating choroidal and retinal vascularity, and that chronic loss of sympathetic activity may contribute to abnormal vascular proliferation in diseases such as age-related macular degeneration and diabetic retinopathy.

Animals↗

Role of adrenergic receptors in vascular remodelling of the rat choroid.

1. Choroidal blood vessels, located between the sclera and retina, constitute the principle source of blood flow to ocular structures. The choroid is innervated by vasoconstrictor sympathetic and vasodilator parasympathetic nerves. 2. We have shown previously that sympathetic denervation for 6 weeks leads to significant increases in choroidal thickness, percentage of choroid occupied by vascular lumina, and numbers of choroidal venules, large arterioles and outer retinal capillaries. Sympathetic deafferentation produces similar increases, indicating that loss of sympathetic nerve activity is responsible for increased vascularity after sympathectomy. Thus, sympathetic neurotransmission normally may be important in suppressing vascular proliferation in the adult rodent eye. 3. The aim of the present study was to determine whether sympathetic nerves act by way of adrenergic receptors to maintain normal choroidal vascular integrity. 4. The alpha-adrenoceptor antagonist, phentolamine (1 mg kg(-1) day(-1)), the beta-receptor antagonist, propranolol (1 mg kg(-1) day(-1)), or saline vehicle was infused for 3 weeks using subcutaneously implanted osmotic minipumps. 5. In phentolamine treated rats, no significant changes were noted relative to saline infused controls. However, propranolol treatment resulted in increases in choroidal thickness, vascular luminal area, and numbers of large choroidal venules and both small and large arterioles, approximating the remodelling seen after chronic sympathectomy. 6. We conclude that sympathetic nerves play a role in maintaining normal choroidal vascular architecture through actions mediated primarily by beta-adrenoceptors.

Adrenergic Antagonists↗

The incubation period of kuru.

BACKGROUND: Kuru is a transmissible spongiform encephalopathy that was identified in Papua New Guinea in the late 1950s. Several thousand cases of the disease occurred during a period of several decades. Epidemiologic investigations implicated ritual endocannibalistic funeral feasts as the likely route through which the infectious agent was spread. METHODS: We estimated the incubation period distribution of kuru using a back-calculation model and explored the relation among sex, age at infection, and incubation period. Key assumptions in the model were that the number of new kuru infections in a year was proportional to the number of kuru cases dying that year, and that the epidemic arose from a single case of sporadic Creutzfeldt-Jakob Disease occurring around 1900. RESULTS: The mean incubation period of kuru was estimated at between 10.3 and 13.2 years. Point estimates of the 90th percentile ranged from 21.1 to 27.0 years. The incubation period in females was estimated to be shorter than that in males. The shortest incubation periods were estimated in adult women, who may have been exposed to the largest doses of infectious material. CONCLUSIONS: Our findings suggest that the relatively young age of cases of variant Creutzfeldt-Jakob disease probably reflects increased levels of exposure in young people, rather than age-dependency in the incubation period.

Adolescent↗

MMR vaccination and pervasive developmental disorders: a case-control study.

BACKGROUND: Concern that measles-mumps-rubella (MMR) vaccination might cause autism has led to a fall in vaccine coverage. We investigated whether MMR vaccination is associated with an increased risk of autism or other pervasive developmental disorders. METHODS: We did a matched case-control study using the UK General Practice Research Database. Cases were people born in 1973 or later who had first recorded diagnosis of pervasive developmental disorder while registered with a contributing general practice between 1987 and 2001. Controls were matched on age, sex, and general practice. FINDINGS: 1294 cases and 4469 controls were included. 1010 cases (78.1%) had MMR vaccination recorded before diagnosis, compared with 3671 controls (82.1%) before the age at which their matched case was diagnosed. After adjustment for age at joining the database, the odds ratio for association between MMR and pervasive developmental disorder was 0.86 (95% CI 0.68-1.09). Findings were similar when restricted to children with a diagnosis of autism, to those vaccinated with MMR before the third birthday, or to the period before media coverage of the hypothesis linking MMR with autism. INTERPRETATION: Our findings suggest that MMR vaccination is not associated with an increased risk of pervasive developmental disorders.

Asperger Syndrome↗