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Biomedical subjects

N C Smith

Publications and source records attributed to N C Smith.

At least 19 recordsLinked to original sources
PubMed1995

A randomized prospective trial comparing single dose prostaglandin E2 vaginal gel with forewater amniotomy for induction of labour.

A prospective randomized parallel-group study was carried out to compare the efficacy of a single dose vaginal prostaglandin E2 gel with forewater amniotomy for induction of labour at term in 260 parturients (110 primigravid and 150 parous women) with low risk pregnancy and favourable cervix. In the prostaglandin E2 (PGE2) managed group, the primigravidae were treated with 2 mg PGE2 gel and parous patients with 1 mg PGE2 gel. Forewater amniotomy was performed 4 h later, or sooner if women requested analgesia. In the amniotomy group, artificial forewater amniotomy was carried out and a repeat cervical assessment done 4 h later, or sooner if women requested analgesia. In both groups, intravenous oxytocin was established if there was evidence of disordered uterine activity, 6 h after the start of initial intervention. An assessment of consumers' views was carried out by using a standardized questionnaire completed 48 h after delivery. There was a significant reduction in the requirement for oxytocin augmentation in women treated with PGE2: primigravidae, odds ratio (OR), 0.27 and 95% confidence interval (CI), 0.12-0.61; multiparae, OR, 0.19 and 95% CI, 0.08-0.45. Fewer primigravidae managed with PGE2 gel required epidural analgesia (OR, 0.16; 95% CI, 0.06-1.00). Fewer parous women managed with PGE2 gel required parenteral opiates (OR, 0.44; 95% CI, 0.23-0.85) and more women required inhalation analgesia or no analgesia (OR, 2.22; 95% CI, 1.76-2.79). The intervention to delivery intervals were shortened in PGE2 groups independent of parity but the differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Eimeria maxima gametocyte antigens: potential use in a subunit maternal vaccine against coccidiosis in chickens.

Affinity-purified gametocyte antigens (APGA) from Eimeria maxima, emulsified in Freund's adjuvant, were injected intramuscularly into breeding hens on two or three occasions. As a result, progeny of the immunized hens were partially immune to infection with E. maxima, Eimeria tenella and Eimeria acervulina (with a reduction in total oocyst output of 45-63% as compared with progeny of untreated hens). Thus, APGA in Freund's adjuvant appears to have great potential as part of a maternally applied vaccine against coccidiosis. The ability of APGA to induce partial cross-species protection is most probably due to the existence of conserved epitopes in the different species as indicated by comparative Western blots of E. maxima and E. tenella. Surprisingly, Freund's adjuvant by itself also induced significant levels of maternal immunity to coccidiosis (with a 12-35% reduction in oocyst output in the progeny). In contrast to the purified antigens or Freund's alone, crude extracts from gametocytes as well as other developmental stages, induced little if any significant maternal immunity despite provoking the production of large amounts of parasite-specific IgG, including antibodies to APGA. This result indicates that a successful maternal vaccine against coccidiosis requires, in addition to good recognition of protective antigens, the exclusion of irrelevant antigens from the vaccine preparation.

Animals↗
PubMed1995

Cytokine and immunoglobulin subclass responses of rats to infection with Eimeria nieschulzi.

SIV rats infected with a high dose (50,000 oocysts) of Eimeria nieschulzi displayed clinical symptoms of coccidiosis such as diarrhoea (days 6 and 7 post-primary infection) and weight loss (days 6-8 post-primary infection) and were completely immune to challenge with a similar dose. The ability of rats to produce tumour necrosis factor (TNF) in vivo was enhanced during the period of oocyst excretion in the primary infection but significant production of TNF did not occur after challenge infection. Thus, TNF does not appear to be an important factor in resistance to infection with E. nieschulzi but may play some role in resistance to primary infection and in the pathology associated with E. nieschulzi infection. Parasite-specific serum IgM levels (measured by enzyme-linked immunosorbent assay) were also increased during primary infection but returned to background levels at the end of the patent period and were not affected by challenge infection. In contrast to TNF and IgM, serum concentrations of E. nieschulzi-specific IgG1, IgG2a, IgG2b, IgG2c and intestinal tissue levels of IgA did not begin to increase until after day 12 post-primary infection, reached peak levels between days 20 and 30 post-primary infection and were slightly increased by challenge infection.

Animals↗
PubMed1994

Nippostrongylus brasiliensis: ability of plasma to prime free radical generation by leukocytes in response to adult worms not due to gamma-interferon or tumour necrosis factor.

Plasma-borne factors prime leukocytes from both infected and uninfected rats for radical generation in response to N. brasiliensis. The concentration of these factors is increased following infection and reaches maximal levels on day 8 post-infection (p.i.) as demonstrated by the striking ability of plasma from infected rats to prime leukocytes from uninfected rats to produce free radicals in response to adult worms. The cytokines, gamma-interferon and tumour necrosis factor (TNF) can be detected in plasma during infection with a variety of organisms and several lines of immunological and pathophysiological evidence, including radical generation, weight loss, anaemia and diarrhoea, implicate generation of these proteins in response to infection with N. brasiliensis. We therefore investigated whether gamma-interferon and TNF were detectable in the plasma of rats infected with N. brasiliensis and whether the presence of these cytokines correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis. However, gamma-interferon was not detected in the plasma of rats at any time after infection with N. brasiliensis and neutralizing monoclonal antibody to rat gamma-interferon had no effect on the ability of plasma to prime free radical generation. TNF was detected in the plasma of heavily-infected rats but only at very low levels (< 1 ng/ml), though copius in vivo synthesis of TNF could be induced by treatment of the infected rats with lipopolysaccharide (LPS). However, neither parasite-induced nor parasite plus LPS-induced plasma TNF correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Maternal transfer of antibodies induced by infection with Eimeria maxima partially protects chickens against challenge with Eimeria tenella.

Infection of breeding hens with Eimeria maxima induces production of Eimeria-specific IgG antibodies which are transferred to hatchlings via the egg yolk and confer a high degree of maternal immunity against homologous challenge and partial immunity to infection with another important species, Eimeria tenella. As an example, in an experiment using hatchlings from eggs collected between days 28 and 39 after infection of the hens with 20,000 sporulated E. maxima oocysts, control chicks (challenged with 100 sporulated oocysts) excreted 6.8 +/- 1.2 million (mean +/- S.E., n = 10) or 5.8 +/- 1.2 million (n = 8) oocysts of E. maxima or E. tenella, respectively, compared to 0.9 +/- 0.4 million (n = 5) E. maxima oocysts or 2.2 +/- 0.4 million (n = 9) E. tenella oocysts excreted by hatchlings of infected hens. This represents an 87% reduction in oocyst excretion with regard to E. maxima and a 62% reduction in oocyst excretion with regard to E. tenella in the progeny of the infected hens. In another experiment, eggs were collected from days 28 to 37 and again from days 114 to 123 after infection of the hens with E. maxima and hatchling oocyst excretion rates were 82% and 62%, respectively, reduced for E. maxima and 43% and 41%, respectively, reduced for E. tenella in the progeny of hens infected with E. maxima compared to the progeny of uninfected hens. ELISA and Western blot analyses of maternally-derived IgG revealed a high degree of cross-reactivity to antigens of E. maxima and E. tenella.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Eimeria maxima: ELISA and western blot analyses of protective sera.

Infection of chickens with Eimeria maxima induces the production of parasite-specific antisera which can be used passively to protect naive chickens against infection. Globulin fractions of these antisera can also be used passively to protect chickens. Similarly, intramuscular injection of soybean lectin affinity purified gametocyte antigens of E. maxima in Freund's Complete Adjuvant induces production of antibodies which are maternally transferred and thereby protect hatchlings against E. maxima. ELISA analyses of serum pools having varying protective capacities revealed good correlations between passive protection and levels of anti-unsporulated oocyst, anti-sporulated oocyst, anti-merozoite and anti-gametocyte antibodies. Western blotting demonstrated that the sera mainly recognized a number of high molecular weight antigens in all developmental stages and that the intensity of the reactions reflected the degree of protection induced by the sera. Sera from birds immunized with gametocyte antigens also recognized high molecular weight antigens from all the developmental stages, with banding patterns remarkably similar to those observed for sera from infected birds. Taken together, these results indicate that antibodies can protect against infection with E. maxima and these antibodies may recognize and act against asexual and/or sexual stages of the parasite.

Animals↗
PubMed1994

Maternal transmission of immunity to Eimeria maxima: western blot analysis of protective antibodies induced by infection.

Infection of breeding hens with Eimeria maxima induces production of parasite-specific antibodies which are transferred, via the egg yolk, to hatchling chicks. These antibodies (immunoglobulin G) are highly protective, mediating up to a 97% reduction in oocyst excretion in challenged hatchlings. However, the degree of maternally derived immunity transferred by the hens to their offspring declines with increasing time after infection of the hens. This decline in immunity is directly related to declining immunoglobulin G titers. However, sera from highly protected hatchlings recognize only a very few E. maxima proteins on Western blots (immunoblots). In particular, a 230-kDa protein band is outstanding for its association with maternally derived immunity to E. maxima in hatchlings. This band was excised from a sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) preparative gel of crude merozoite protein extract. The SDS-PAGE cutout was emulsified in Freund's adjuvant and injected, intramuscularly, into six breeding hens on two occasions, 2 weeks apart. Eggs were collected from these hens 28 to 39 days after the second injection, and the hatchlings from these eggs were challenged with 150 sporulated oocysts of E. maxima. Subsequent oocyst excretion in these hatchlings was, on average, 54% lower than oocyst excretion by control chicks but only 37% lower (significant at P < 0.05) than that by chicks from hens sham immunized with Freund's adjuvant. The latter result is apparently due to the ability of the adjuvant to induce production of antibodies which recognize Eimeria spp. and thereby transfer some degree of protection to hatchlings. These experiments indicate that protective, maternally derived immunoglobulin G antibodies may be useful for the identification of putative anticoccidial vaccine candidates.

Animals↗
PubMed1994

Maternal transmission of immunity to Eimeria maxima: enzyme-linked immunosorbent assay analysis of protective antibodies induced by infection.

Vaccination of broiler chickens against Eimeria infection is problematic because of the need to ensure that birds are protected from the time of hatching. We have therefore investigated the feasibility of protecting hatchling broilers via maternal transfer of protective antibodies from hens to their offspring. Oral infection of broiler breeder hens with 20,000 sporulated Eimeria maxima oocysts caused production of antibodies which were passed into the egg yolk and subsequently to hatchlings. The level of specific antibodies in the yolks to unsporulated oocysts, sporulated oocysts, merozoites, and gametocytes was assessed by enzyme-linked immunosorbent assays. The levels in yolks of antibodies to all developmental stages peaked 3 to 4 weeks after infection of the hens. Groups of 10 hatchlings were challenged at 3 days of age by oral infection with 100 sporulated E. maxima oocysts. In the first experiment, the mean 4-day (days 6 to 9 post-infection) total number of oocysts excreted in the feces of chicks from eggs collected 3 weeks after infection of the hens was (0.6 +/- 0.4) x 10(6) (mean +/- standard error) compared with (9.9 +/- 1.4) x 10(6) for the progeny of uninfected hens, which represents a greater than 90% reduction. However, oocyst excretion by chicks from eggs collected 7 or 8 weeks after infection of the hens was only 47 or 68% lower than control values, reflecting declining levels of protective antibodies. In a second experiment, in which the hens were somewhat older and pretreated by intramuscular injection of saline in the emulsifying agent, Arlacel A, the period for which protective antibodies were transferred to hatchlings was prolonged. Thus, oocyst excretion by challenged hatchlings from eggs collected for an 8-week period after infection of the hens was more than 90% lower than oocyst excretion by control chicks, and even hatchlings of eggs collected 19 weeks after infection of the hens showed a 60% reduction in oocyst output. In both experiments, the levels of immunoglobulin G (IgG) antibodies to all developmental stages in yolks or hatchling sera were very strongly correlated with maternally derived immunity to E. maxima. In contrast, parasite-specific IgM or IgA was not detectable, either in egg yolk or egg white. These results demonstrate the ability of IgG antibodies to protect against E. maxima in poultry, thus raising the possibility of using protective maternally derived IgG antibodies to identify potentially protective parasite antigens and indicating the feasibility of using maternal immunization as a means for parasite control.

Animals↗
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

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↗