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Biomedical subjects

P G Smith

Publications and source records attributed to P G Smith.

At least 19 recordsLinked to original sources
PubMed1992

Neuropeptide Y inhibits sympathetic neurotransmission in ipsilaterally innervated but not contralaterally reinnervated superior tarsal smooth muscle of the rat.

The superior tarsal smooth muscle (STM), which elevates the upper eyelid, normally is innervated by sympathetic neurons from the ipsilateral superior cervical ganglion that are not neuropeptide Y-immunoreactive (NPY-ir). Following neonatal ganglionectomy, this target is reinnervated by sympathetic nerves from the contralateral superior cervical ganglion that are strongly NPY-ir. We examined the effects of exogenously administered NPY on STM tone, response to norepinephrine, and sympathetic neurotransmission in ipsilaterally innervated and contralaterally reinnervated STMs. NPY (2-10 micrograms/kg iv) increased blood pressure but did not alter STM tone. Similarly, contractile responses to co-administered norepinephrine were not affected. These findings imply an absence of direct and indirect postjunctional actions of NPY on STM. Contractions elicited by stimulation of the cervical sympathetic nerve (1.5 Hz) were not affected by NPY on the contralaterally reinnervated side; however, ipsilateral contractions were decreased in a dose-dependent fashion, with an inhibition of about 40% at 10 micrograms/kg. We conclude that while the STM is unresponsive to exogenously administered NPY, this peptide exerts selective inhibitory effects on the ipsilateral NPY-ir-negative but not the contralateral NPY-ir-positive innervation. This suggests that the neonatally denervated STM is reinnervated by contralateral fibers that are functionally different from the normal ipsilateral innervation in being devoid of functional prejunctional NPY receptors.

Animals↗
PubMed1992

Immunoprophylactic trial with combined Mycobacterium leprae/BCG vaccine against leprosy: preliminary results.

In an attempt to find a vaccine that gives greater and more consistent protection against leprosy than BCG vaccine, we compared BCG with and without killed Mycobacterium leprae in Venezuela. Close contacts of prevalent leprosy cases were selected as the trial population since they are at greatest risk of leprosy. Since 1983, 29,113 contacts have been randomly allocated vaccination with BCG alone or BCG plus 6 x 10(8) irradiated, autoclaved M leprae purified from the tissues of infected armadillos. We excluded contacts with signs of leprosy at screening and a proportion of those whose skin-test responses to M leprae soluble antigen (MLSA) were 10 mm or more (positive reactions). By July, 1991, 59 postvaccination cases of leprosy had been confirmed in 150,026 person-years of follow-up through annual clinical examinations of the trial population (31 BCG, 28 BCG/M leprae). In the subgroup for which we thought an effect of vaccination was most likely (onset more than a year after vaccination, negative MLSA skin-test response before vaccination), leprosy developed in 11 BCG recipients and 9 BCG/M leprae recipients; there were 18% fewer cases (upper 95% confidence limit [CL] 70%) in the BCG/M leprae than in the BCG alone group. For all cases with onset more than a year after vaccination irrespective of MLSA reaction the relative efficacy was 0% (upper 95% CL 54%; 15 cases in each vaccine group). Retrospective analysis of data on the number of BCG scars found on each contact screened suggested that BCG alone confers substantial protection against leprosy (vaccine efficacy 56%, 95% CL 27-74%) and there was a suggestion that several doses of BCG offered additional protection. There is no evidence in the first 5 years of follow-up of this trial that BCG plus M leprae offers substantially better protection against leprosy than does BCG alone, but the confidence interval on the relative efficacy estimate is wide.

BCG Vaccine↗
PubMed1992

Sensory nerves impair sympathetic reinnervation and recovery of smooth muscle function.

Neuronal populations projecting to a common target may compete for neurotrophic substances. To determine if competition impairs target reinnervation, we examined the effect of capsaicin-induced sensory denervation on sympathetic nerve ingrowth to the sympathectomized rat superior tarsal smooth muscle. In tarsal muscles with intact sympathetic innervation, capsaicin injection on Day 2 reduced numbers of perimuscular CGRP-ir sensory nerves by 68% at 3-4 months; however, it did not alter dopamine-beta-hydroxylase-ir nerve density, response to nerve stimulation, or tarsal muscle adrenoceptor-mediated contraction. Tarsal muscles denervated by ipsilateral superior cervical ganglionectomy on Postnatal Day 4 were partially reinnervated by fibers from the contralateral ganglion, as noted in previous studies. Sensory denervation by capsaicin improved sympathetic reinnervation, as evidenced by a 174% increase in numbers of DBH-ir nerves and a 62% increase in neurally mediated smooth muscle contraction evoked by electrical stimulation of the contralateral pathway relative to reinnervated muscles of vehicle-injected rats; smooth muscle function was also influenced, as indicated by a decrease toward normal in adrenoceptor sensitivity. Tarsal muscles denervated at 30 days were not reinnervated in either vehicle-injected or capsaicin-treated rats, indicating that sensory denervation does not extend the developmental window during which contralateral reinnervation can occur. Both the vehicle-injected and capsaicin-treated preparations with sustained juvenile sympathectomy showed sensory hyperinnervation as adults; thus, a chronic reduction in competition from sympathetics is a sufficiently powerful stimulus to overcome the decreased nerve density induced by neonatal capsaicin treatment. We conclude that sensory nerves limit the extent of sympathetic reinnervation and functional recovery that can occur following neonatal sympathetic denervation.

Aging↗
PubMed1992

Developmental regulation of parasympathetic nerve density by sympathetic innervation in the tarsal smooth muscle of the rat.

The developmental influence of sympathetic innervation on parasympathetic nerve density was investigated in the tarsal smooth muscle of the rat. Specificity of acetylcholinesterase staining as a marker for parasympathetic innervation was first determined by acute selective denervations. Excision of the ipsilateral superior cervical ganglion caused a 39% reduction in the density of acetylcholinesterase-positive nerves seven days later, indicating that sympathetic nerves contribute to cholinesterase-positive tarsal muscle innervation. Excision of the pterygopalatine ganglion concurrent with superior cervical ganglionectomy caused a virtually complete disappearance of acetylcholinesterase-positive innervation within seven days, indicating that non-sympathetic cholinesterase-positive fibers derive from the pterygopalatine ganglion and are presumed to be parasympathetic. Analysis of the control population indicated that parasympathetic nerve density did not vary significantly between males and females, between the superior and inferior muscles, or in rats studied at four and 12 months of age. The influence of sympathetic innervation on parasympathetic nerve density during postnatal development was examined by conducting surgical sympathectomies on postnatal day 5 and quantifying acetylcholinesterase-positive nerve density at four months of age. Neonatal sympathectomy caused a 46% reduction in cholinesterase-positive nerve density beyond that which occurred in acutely sympathectomized adult controls. It is concluded that sympathetic innervation is required for developing parasympathetic nerves to attain their normal density within the rat tarsal muscle. This finding is consistent with the idea that sympathetic nerves can exert positive effects on parasympathetic nerve outgrowth during development.

Acetylcholinesterase↗
PubMed1992

Expression of alpha, mu and pi class glutathione S-transferases in oval and ductal cells in liver of rats placed on a choline-deficient, ethionine-supplemented diet.

Expression of the alpha, mu and pi class glutathione S-transferases (GSTs) in hepatocytes, oval cells and ductal cells derived from the livers of rats placed on a choline-deficient, ethionine-supplemented (CDE) diet for 5 weeks was investigated. An overall decrease in the expression of alpha and mu class GSTs and an over-expression of pi class GST was observed in the liver after CDE treatment as indicated by Northern blotting analysis. Massive disruption of the liver with oval cell infiltration in the sinusoids throughout the lobule occurred after 5 weeks CDE treatment. 'Duct-like' structures consisting of oval-like cells (ductal cells) with rounder nuclei and more cytoplasm than oval cells within the sinusoids were also apparent. Immunocytochemical analysis revealed that the altered expression of GST in the whole liver is attributed to a differential expression of alpha, mu and pi class GSTs in the different cell types in the liver, including hepatocytes, oval cells around the portal region and among the sinusoids, and oval-like cells (ductal cells) in the 'duct-like' structures. In vitro studies using purified oval-ductal cells and hepatocyte populations confirmed the differential expression of GSTs in the varying cell populations in situ. The expression of the alpha and mu class GSTs in hepatocytes does not appear to be altered by the CDE diet. Heterogeneity in distribution of pi class GST was observed in the hepatocyte population, some hepatocytes were stained strongly while no staining was observed in others. Oval and ductal cells represent two distinct populations displaying different expression of GSTs. Pi class GST was detected in the majority of oval and ductal cells. Alpha class GST was detected in < 5% of the oval cell population and was found in > 50% of the ductal cell population. In contrast, mu class GST was absent in ductal cells and was present in 24% of oval cells around the portal region. This supports the view that ductal cells are not of bile ductal origin since mu GST is present in normal bile duct epithelial cells. Furthermore the change in expression of GSTs in the liver after CDE treatment is attributed to the large increase in oval and ductal cell populations.

Animals↗
PubMed1992

Measurement of interrupter resistance in rabbits exposed to methacholine aerosols.

We studied the effect of increasing airway resistance on equilibration of airway and alveolar pressure during passive expiratory airflow interruption. In 10 anesthetized and paralyzed rabbits, airway and alveolar pressures were compared before and after airway resistance was increased with methacholine. In all studies, airway pressure rose to equilibrate with alveolar pressure immediately after the interruption (delta Pinit) regardless of increases in airway resistance. The pressures then remained equal during the interruption while gradually increasing to plateau (delta Pdiff). Before methacholine exposure, delta Pdiff was small (0.6 +/- 0.3 cmH2O). Steady-state resistance calculated from the sum of delta Pinit and delta Pdiff was similar to airway resistance calculated from delta Pinit alone. After methacholine, increased airway resistance was accompanied by increased delta Pdiff (2.0 +/- 0.5 cmH2O), causing disproportionate increase in steady-state resistance. delta Pdiff increases were equal in the airway and alveoli, implying resistive changes distal to the sampled alveoli. Thus increasing airway resistance did not delay pressure equilibration across airways. However, increases in airway resistance were accompanied by tissue resistive changes that were greater than the increases in airway resistance.

Aerosols↗
PubMed1992

Neurotologic considerations in the treatment of advanced clival tumors.

Head and neck manifestations of advanced clival tumors result from subtle, yet progressive mass effect or direct involvement of multiple cranial nerves. Misinterpretation of clinical or radiographic findings in these patients may result in inappropriate treatment planning, increased patient morbidity, and probable tumor recurrence. Our combined experience in managing 21 patients with advanced clival tumors has shown that preoperative loss of vision, diplopia, or facial hypesthesia suggests superior parasellar disease. Facial twitching or neurotologic symptoms result from posterior central tumor growth, while inferior extension of disease leads to basal cranial nerve deficits with associated speech, voice, and swallowing dysfunctions. The purpose of this article is to correlate the complex anatomy of the clivus, brainstem, and cranial base and the various neurotologic findings associated with neoplasms in this region. Lateral skull base surgical procedures, based on preoperative clinicoradiographic assessment, will be detailed with particular emphasis on preservation of critical neurovascular structures.

Adolescent↗
PubMed1991

Sprouting of aberrant neuropeptide Y-immunoreactive sympathetic nerves into neonatally denervated smooth muscle.

Sympathetic nerves normally project ipsilaterally to lateral cranial targets. Following unilateral superior cervical ganglionectomy in neonatal rats, however, neurons from the contralateral superior cervical ganglion sprout into the denervated region. In the present study we examined neuropeptide Y immunoreactivity (NPY-ir) of neurons comprising ipsilateral (control) and denervation-induced contralateral pathways to the superior tarsal smooth muscle of the eyelid. Fluoro-Gold injection of the control muscle retrogradely labelled 133 +/- 18 neurons in the ipsilateral superior cervical ganglion; of these, 21 +/- 3% displayed detectable NPY-ir. Fluoro-Gold injections of the reinnervated muscle labelled 20 +/- 4 neurons in the contralateral superior cervical ganglion, of which 85 +/- 3% contained detectable NPY-ir. Examination of the control tarsal muscle revealed DBH-ir noradrenergic nerves throughout the muscle and vasculature, while NPY-ir nerves were present primarily around blood vessels. In the reinnervated preparation, NPY-ir fibers innervated both blood vessels and tarsal muscle in a pattern similar to that of DBH-ir innervation. Acute excision of the remaining superior cervical ganglion eliminated all DBH-ir fibers bilaterally; NPY-ir was reduced markedly in the reinnervated preparations, though some fibers remained. We conclude that, following neonatal denervation, the tarsal muscle is reinnervated by a subpopulation of sympathetic neurons that differs in neuropeptide phenotype from that of the normal ipsilateral innervation.

Animals↗
PubMed1991

BCG vaccination in the first year of life protects children of Indian subcontinent ethnic origin against tuberculosis in England.

STUDY OBJECTIVE: The aim was to assess the protection conferred by BCG given during the first year of life against tuberculosis among children of Asian ethnic origin born in England. DESIGN: This was a matched case-control study. SETTING: Cases were selected from notifications of tuberculosis and controls were selected from child health or school health records in 14 English health districts. PARTICIPANTS: 111 cases of childhood tuberculosis with Asian names were selected. For each case there were five controls with Asian names, matched for age, sex and district of birth. MEASUREMENTS AND MAIN RESULTS: Child health or school health records were searched to determine the proportions of cases and controls who had been vaccinated with BCG. Overall, BCG vaccination given in the first year of life was estimated to confer 49% protection against tuberculosis with 95% confidence interval 14-62%. CONCLUSIONS: BCG vaccination in infancy was found to be associated with a lower protective efficacy than has been found for the secondary school age BCG programme (80%) but nevertheless the protection is substantial and, in the United Kingdom, BCG vaccination of infants considered to be at relatively higher risk of tuberculosis is likely to reduce the incidence of childhood tuberculosis.

Asia, Western↗
PubMed1991

Cancer of the testis, socioeconomic status, and occupation.

The risk of testicular cancer in relation to lifetime histories of socioeconomic status, occupation, and occupational exposures was examined in a case-control study in England. Interviews were conducted with 259 cases, 238 control patients treated at radiotherapy and oncology centres, and 251 controls who were hospital inpatients in other departments. Risk of testicular cancer was raised in men of high socioeconomic status measured both by occupation and in other ways, and was similar in relation to status measured at birth and at various later stages of life. The occupations with highest risk of the tumour were paper and printing workers, professionals, and administrators. Exposures to various specific occupational agents that have been suggested in publications as potential risk factors were examined, but none showed an association with risk. The relative risk for occupational exposure to ionising radiation was 1.62 (95% confidence interval 0.83-3.17).

Adolescent↗