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Biomedical subjects

N C Smith

Publications and source records attributed to N C Smith.

At least 73 records · Page 4Linked to original sources
PubMed1993

Glomerular morphometry in reflux nephropathy: functional and radiological correlations.

Using computerized digitometry, we investigated the relationships between renal size, glomerular filtration rate (GFR), proteinuria, incidence of segmental and global glomerulosclerosis, glomerular size, hilar arteriolar wall thickness and hyaline deposition in renal biopsies obtained from 24 children and adolescents with reflux nephropathy, of whom only 4 were hypertensive. Age-matched controls comprised minimal-change nephrotic syndrome (6) and recurrent haematuria with normal biopsy (13). The mean sectional area of patients' glomeruli was double that of controls. Glomerular size correlated with the amount of proteinuria (measured as protein/creatinine ratios in early morning urine) and inversely with renal size and GFR. Segmental sclerosis, invariably of hilar origin, was observed in 8 patients and the percentage of glomeruli affected correlated strongly with glomerular size and proteinuria. Global sclerosis was found equally in patients and controls, and showed no similar correlations. Compared with controls, patients' hilar arterioles showed increased wall thickness, more intramural hyaline deposits and decreased luminal diameter when related to glomerular size. The proteinuria and glomerular changes are consistent with hyperfiltration, while the previously undescribed hilar vascular changes, which both precede and accompany sclerosis, resemble abnormalities reported experimentally following renal ablation.

Adolescent↗
PubMed1993

Use of IgG- and IgM-specific ELISAs for the assessment of exposure status of chickens to Eimeria species.

Simple and reliable methods for the determination of the exposure status of chickens to Eimeria species are required. For this purpose an enzyme-linked immunosorbent assay (ELISA) detecting specific IgG and IgM antibodies in serum samples was evaluated. Sera from chickens hyperimmunized by intramuscular injection of a saline extract of Eimeria tenella sporozoites were used to determine optimal reaction conditions in the ELISA which were found to be at a serum dilution of 1:100 and an antigen concentration of 0.2 microgram per reaction well. Saline extracts of sporulated oocysts and purified sporozoites of E. tenella were also potent antigens but most studies were carried out with sporozoite antigen. In a trial with 80 chickens, concentrations of serum IgM directed against sporozoite antigen increased significantly 9 days after primary infection with 10,000 oocysts of E. tenella per animal. IgM levels subsequently decreased rapidly reaching a plateau level only slightly higher than uninfected controls by about 15 days post-infection. In chickens challenged with 10,000 oocysts 21 days after primary infection significant increases of IgM levels were observed 2, 6 and 12 days later. In contrast IgG levels increased only slightly after primary infection but significant increases occurred after challenge infection so that by Day 12 after challenge sporozoite-specific IgG levels were much higher than in control chickens. Thus, it may be possible to discriminate between chickens actually infected with Eimeria (as indicated by high levels of antiparasite IgM), chickens which have been repeatedly exposed to Eimeria (as indicated by high levels of antiparasite IgG) and unexposed birds. The applicability of this ELISA, using sporozoite antigen of E. tenella to practical situations was substantially confirmed, since sampling of over 1000 sera from commercially reared broilers and laying hens indicated that broilers, maintained on medicated food, had low levels of IgM and IgG whereas 84-97% of the laying hens, receiving drug-free feed, had relatively high IgG concentrations. These results reflect low and rare exposure to Eimeria infections in broilers and repeated exposure of the hens.

Analysis of Variance↗
PubMed1993

Restrictive dermopathy: a disorder of skin differentiation with abnormal integrin expression.

Clinical features and histological findings in two sibs who died from restrictive dermopathy in the neonatal period are described. Fibroblasts cultured from a skin biopsy from the second sib and fibroblasts from normal neonatal skin were studied using monoclonal antibodies to visualise integrin subunits by immunocytochemistry. Restrictive dermopathy fibroblasts displayed increased expression of the alpha-1 and alpha-2 subunits of integrin, those responsible for collagen binding. The increase was not matrix dependent. Integrins may play an important role in tissue differentiation, and our findings support the hypothesis that restrictive dermopathy is a disorder of skin differentiation.

Abnormalities, Multiple↗
PubMed1992

Cytokines, free radicals and resistance to Eimeria.

The cytokine, gamma-interferon (IFN-gamma), which is produced by CD4(+) T cells, plays a crucial role in host resistance to Eimeria infections. Karen Ovington and Nick Smith propose that free oxygen radical generation by leukocytes in response to infection with Eimeria is the result of activation by IFN-gamma. The functional role of free oxygen radicals is unclear but these highly reactive radicals are produced by the leukocytes that infiltrate the intestine in large numbers during infection, and the parasites,enterocytes and cells of the immune system may all be vulnerable to oxidative damage. Gamma-interferon also appears to induce the enterocytes inhabited by Eimeria to turn against the parasite. The authors draw from literature documenting similar effects on other protozoa, especially Leishmania and Plasmodium, and speculate that reactive nitrogen intermediates produced by enterocytes have a functional role in resistance to Eimeria.

Journal Article↗
PubMed1992

Fasciola hepatica: free radical generation by peritoneal leukocytes in challenged rodents.

Free radical generation by peritoneal leukocytes from hosts able to develop resistance to reinfection with Fasciola hepatica (rats) was compared with that of hosts unable to develop resistance (mice). Free radical generation by rat leukocytes was 3.5 times higher per cell and 30 times higher per animal than radical production by mouse leukocytes. The capacity of peritoneal leukocytes to produce free radicals in response to adult fluke crude antigen was increased by the presence of host plasma and was quantitatively greater in challenged rats than in naive or primary infected rats. This was not the case for mice, in which cells from primary infected animals were equally as responsive as cells from challenged mice. Further experiments revealed that challenge infection in rats apparently caused the in vivo activation of peritoneal leukocytes and increased levels of unidentified factors in plasma and that both of these responses were involved in the initiation of free radical generation in response to F. hepatica. Dramatic increases in the number of eosinophils present in the peritoneal cavities of primary infected and challenged rats (but not mice) were observed but the role of eosinophils in the production of free radicals in response to F. hepatica remains to be determined.

Animals↗
PubMed1992

Breech delivery and epidural analgesia.

OBJECTIVE: To examine the effect of epidural analgesia on the progress and outcome of spontaneous labour in women with a singleton breech presentation at term (greater than or equal to 37 weeks). DESIGN: A retrospective study. SETTING: Data Bank, Aberdeen Maternity Hospital. SUBJECTS: 643 women (273 primiparae and 370 multiparae) with a singleton breech presentation and spontaneous onset of labour at term. OUTCOME MEASURES: Duration of labour; augmentation of labour with oxytocin infusion; caesarean section rates. RESULTS: Epidural analgesia was associated with a significantly increased need for augmentation of labour with oxytocin infusion (P less than 0.001) and longer duration of labour (P less than 0.001), irrespective of parity. Comparing women who had epidural analgesia with those who did not, there was no significant difference in caesarean section rates in the first stage of labour in primiparae (odds ratio 1.79; 95% CI 0.88-3.63) or multiparae (odds ratio 0.97; 95% CI 0.48-1.96). Epidural analgesia was associated with a significantly increased likelihood of caesarean section in the second stage of labour, both in primiparae (odds ratio 5.43; 95% CI 2.46-11.95) and multiparae (odds ratio 5.37; 95% CI 2.07-13.87). The increased likelihood of caesarean section in the second stage in primiparae with epidurals was independent of the extent of cervical dilatation (less than 3 cm or greater than or equal to 3 cm) on admission. However, in multiparae with epidurals, the difference in second stage caesarean section rate was significant only when initial cervical dilatation was less than 3 cm (odds ratio 3.65; 95% CI 1.14-11.65). CONCLUSION: Epidural analgesia was associated with longer duration of labour, increased need for augmentation of labour with oxytocin infusion and a significantly higher caesarean section rate in the second stage of labour.

Adult↗
PubMed1992

Role of prostaglandin in the management of prelabour rupture of the membranes at term.

OBJECTIVE: To compare conservative versus prostaglandin management of prelabour rupture of the membranes (PROM) in healthy primigravid women at term. DESIGN: A prospective randomized study. SETTING: Labour Ward, Aberdeen Maternity Hospital. SUBJECTS: 230 primigravidae at terms with PROM, 115 allocated to be treated conservatively and 115 to be managed with prostaglandin treatment. INTERVENTIONS: In the conservatively managed group the women were observed for up to 24 h after hospital admission with PROM. The actively managed group had PGE2 gel (2 mg) instilled into the posterior fornix and if contractions had not commenced, a further dose of PGE2 gel (1 mg) was instilled 6 h later. In both groups, if labour had not established 24 h after admission, intravenous oxytocin was given in escalating doses. MAIN OUTCOME MEASURES: PROM to delivery interval, oxytocin augmentation, mode of delivery, maternal and neonatal infective morbidity. RESULTS: There was a significant reduction in the PROM to delivery interval in the women managed actively with PGE2 gel and fewer women in the PGE2 group required oxytocin augmentation (31% vs 51%). The two managements groups were comparable for intrapartum analgesia, antibiotic treatment, babies requiring admission to the special care nursery unit and delivery by caesarean section. CONCLUSION: The early use of prostaglandin is associated with a significant reduction in PROM to delivery interval without a significant increase in infective morbidity or caesarean section rate. However, the advantages of the conservative approach should not be overlooked. More work is still needed in the management of those women where uterine activity fails to establish within 24 h after PROM.

Administration, Intravaginal↗
PubMed1992

Detection of the fetus at risk.

Successful reproduction has ensured the survival of the human race despite disease and famine. However, a good standard of living, combined with a well-balanced diet, is closely related to low maternal, perinatal and infant mortality rates. In the third world, anaemia, rheumatic heart disease, tuberculosis and other infections are still common and the poorly nourished are more susceptible to them. In the Western world food is plentiful but often the individual's diet is poorly balanced. Invariably the fetus takes all the nutrients required from the mother and, if a deficiency occurs, this is reflected in the maternal reserves only. The weight of the baby at birth has a wide biological variation and correlates in the extremes with maternal weight but there are many other factors responsible for fetal growth. In early pregnancy the developing embryo may be susceptible to specific dietary deficiencies and structural malformations may result. A clear link has recently been established between folic acid supplementation and the prevention of recurrence of neural tube defects. Excessive doses of vitamin A should be avoided.

Body Weight↗
PubMed1991

A role for protein kinase C in the production of free oxygen radicals in response to Nippostrongylus brasiliensis.

The involvement of protein kinase C in the initiation of free oxygen radical generation by rat leukocytes in response to the nematode Nippostrongylus brasiliensis was investigated. Inhibitors of protein kinase C, trifluoperazine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), inhibited free radical generation in response to N. brasiliensis in vitro. Neither inhibitor affected free radical generation by the cell-free xanthine/xanthine oxidase system, indicating that the agents did not scavenge free radicals; they also failed to affect leukocyte viability. Furthermore, activators of protein kinase C, the calcium ionophore A23187 and the diacylglycerol 1-oleoyl-2-acetyl-rac-glycerol (OAG), enhanced free radical generation by leukocytes in response to N. brasiliensis in vitro. Thus, protein kinase C apparently plays an important role in the initiation of free radical generation in response to N. brasiliensis; since free radicals may play a critical role in worm expulsion, this implies that protein kinase C may also be important in the rejection of N. brasiliensis from the small intestine of the rat.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Free radical generation and the course of primary infection with Nippostrongylus brasiliensis in congenitally athymic (nude) rats.

The course of primary infections with Nippostrongylus brasiliensis was followed in nude (CBH/R nu/nu) and heterozygote (CBH/R nu/+) rats. In both nude and heterozygote rats peak egg production by N. brasiliensis occurred on days 7 and 8 post-infection. However, whereas in heterozygote rats egg production declined rapidly thereafter and ceased completely by day 14 post-infection, in nude rats high numbers of N. brasiliensis eggs were still seen on day 27 post-infection, when the experiment was terminated. In comparison with the nude rats, heterozygote rats had a 5-fold greater loss of weight by day 9 post-infection and a 4-fold higher incidence of diarrhoea. Furthermore, infected heterozygote rats became anaemic whereas uninfected rats and infected nude rats showed no evidence of anaemia. Free radical generation was measured in infected (9 days) and uninfected rats. Leucocytes from infected heterozygote rats were able to generate copious quantities of free radicals in response to N. brasiliensis whereas leucocytes from infected nude rats produced only slightly more free radicals than uninfected rats. Thus, worm rejection, weight loss, diarrhoea, anaemia and free radical generation in response to N. brasiliensis infection are all T-cell dependent events.

Analysis of Variance↗
PubMed1990

Oxygen derived free radicals and the course of Eimeria vermiformis infection in inbred strains of mice.

Free radical generation by peritoneal leukocytes from BALB/c and C57BL/6 mice was monitored for 18 days following infection with Eimeria vermiformis. Free radical generation occurred earlier and was quantitatively much greater in resistant BALB/c mice than in susceptible C57BL/6 mice, resistance being indicated by a much lower oocyst production and a shorter patent period of E. vermiformis. Plasma greatly enhanced free radical generation in response to a soluble antigen prepared from sporulated oocysts indicating the presence of plasma-borne factor(s) which enhance free radical generation in response to E. vermiformis.

Animals↗