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Biomedical subjects

Richard J Shaw

Publications and source records attributed to Richard J Shaw.

16 recordsLinked to original sources
PubMed2006

Cytokine and antibody subclass responses in the intestinal lymph of sheep during repeated experimental infections with the nematode parasite Trichostrongylus colubriformis.

The expression of interleukin (IL)-4, IL-5, IL-10, IL-13, TNF-alpha and IFN-gamma genes, and parasite-specific IgM, IgG1, IgG2, IgA and total IgE levels, were monitored daily in intestinal lymph of sheep infected repeatedly with the nematode parasite Trichostrongylus colubriformis. Host genotype had a significant influence on IL-13 gene activity, with resistant-line (R) sheep consistently expressing higher levels of mRNA than susceptible-line (S) sheep. Mean gene expression of IL-13, IL-4 and IFN-gamma did not differ significantly between the first and second nematode challenge. Field-primed R and S as well as field-primed R and naïve S sheep had lower mean gene expression of IL-5 and IL-10, respectively, during the second when compared to primary challenge. Genes for IL-13 and IL-5 were transiently and strongly up-regulated after nematode infection, particularly in animals with previous exposure to nematodes. Genes for TNF-alpha and IFN-gamma were also transiently up-regulated, but to a lesser extent and more typically after primary challenge. Naïve sheep of both genotypes produced relatively little antibody response after primary challenge. A second nematode challenge resulted in large increases in the lymphatic levels of all antibody sub-classes which were significant for adult antigen-specific IgA and larval antigen-specific IgG1. In naïve S line sheep, the larval-specific IgA and IgG2 response appeared delayed when compared to the R line animals. Field-primed R and S line sheep had relatively high lymphatic IgG1 levels prior to experimental infection and these did not change significantly afterwards. These results demonstrate that during nematode infections, the intestinal micro-environment of sheep is transiently skewed towards Th2 cytokine dominance, although IFN-gamma gene expression continues. This response is accompanied by increases of nematode-specific IgG1, IgA, IgG2 and IgM, as well as of total IgE in lymph plasma.

Animals↗
PubMed2006

Discovery of quantitative trait loci for resistance to parasitic nematode infection in sheep: I. Analysis of outcross pedigrees.

BACKGROUND: Currently most pastoral farmers rely on anthelmintic drenches to control gastrointestinal parasitic nematodes in sheep. Resistance to anthelmintics is rapidly increasing in nematode populations such that on some farms none of the drench families are now completely effective. It is well established that host resistance to nematode infection is a moderately heritable trait. This study was undertaken to identify regions of the genome, quantitative trait loci (QTL) that contain genes affecting resistance to parasitic nematodes. RESULTS: Rams obtained from crossing nematode parasite resistant and susceptible selection lines were used to derive five large half-sib families comprising between 348 and 101 offspring per sire. Total offspring comprised 940 lambs. Extensive measurements for a range of parasite burden and immune function traits in all offspring allowed each lamb in each pedigree to be ranked for relative resistance to nematode parasites. Initially the 22 most resistant and 22 most susceptible progeny from each pedigree were used in a genome scan that used 203 microsatellite markers spread across all sheep autosomes. This study identified 9 chromosomes with regions showing sufficient linkage to warrant the genotyping of all offspring. After genotyping all offspring with markers covering Chromosomes 1, 3, 4, 5, 8, 12, 13, 22 and 23, the telomeric end of chromosome 8 was identified as having a significant QTL for parasite resistance as measured by the number of Trichostrongylus spp. adults in the abomasum and small intestine at the end of the second parasite challenge. Two further QTL for associated immune function traits of total serum IgE and T. colubiformis specific serum IgG, at the end of the second parasite challenge, were identified on chromosome 23. CONCLUSION: Despite parasite resistance being a moderately heritable trait, this large study was able to identify only a single significant QTL associated with it. The QTL concerned adult parasite burdens at the end of the second parasite challenge when the lambs were approximately 6 months old. Our failure to discover more QTL suggests that most of the genes controlling this trait are of relatively small effect. The large number of suggestive QTL discovered (more than one per family per trait than would be expected by chance) also supports this conclusion.

Animals↗
PubMed2006

Methylation enrichment pyrosequencing: combining the specificity of MSP with validation by pyrosequencing.

It has been suggested that detection of aberrant DNA methylation in clinical specimens such as sputum or saliva may be a valuable tumour biomarker. Any clinically applicable detection technique must combine high sensitivity with high specificity. In this study we describe methylation enrichment pyrosequencing (MEP), which benefits from the high sensitivity and specificity of methylation-specific PCR (MSP) but has a second, confirmatory, pyrosequencing step. The pyrosequencing reaction is rapid, relatively inexpensive and offers significant logistical advantages over previously described validation methods. As proof of principle, we illustrate MEP using assays of p16 and cyclin A1 promoters in a methylated DNA dilution matrix and also in a clinical setting using paired saliva and oral tumour specimens. Our results confirm that mis-priming of MSP, with subsequent false positive results, can occur frequently (perhaps 10%) in assays combining high numbers of PCR cycles and low concentrations of starting DNA. In our clinical example, MEP of saliva-derived DNA was more sensitive than standard non-methylation-specific pyrosequencing as illustrated using p16 and cyclin A1 promoter methylation assays.

Base Sequence↗
PubMed2005

Oral rehabilitation after treatment for head and neck malignancy.

BACKGROUND: Advances in the management of oral malignancy have resulted in significant improvements in survival and functional outcome. Ablation of oral tissues and radiotherapy render many patients unable to wear conventional prostheses, and these patients are, thus, candidates for oral rehabilitation with osseointegrated implants. We aim to present outcomes and complications of such treatment over a 14-year period in a single unit. METHODS: Data were collected for 81 consecutive patients, most of whom had received microvascular free flap reconstruction after surgical ablation of oral squamous cell carcinoma. Three hundred eighty-six implants were placed after a delay of 12 months after surgery. Sixty-five percent of implants were placed in the anterior mandible. Radiotherapy was used in 47% of the patients, and hyperbaric oxygen treatment was routinely used in irradiated subjects during the latter half of the series. Retrospective analysis of implants and prostheses was made by use of case notes, radiographs, and a computerized database. RESULTS: Data are presented for 364 of the 386 implants in 77 of the 81 patients after a median follow-up of 4 years. Two hundred sixty-five (73%) of the implants were in function supporting prostheses, 56 (15%) had been lost, and 43 (12%) were present but not loaded (ie, "sleepers"). Implant loss seemed patient specific and was also correlated with host bone type. Thirteen percent of patients in whom implants were placed in the mandible lost at least one implant, and the equivalent values for the maxilla was 40%. Thirty-six percent of patients in whom implants were placed in bone graft or flap lost at least one implant. The effects of implant manufacture, dimensions, radiotherapy, and hyperbaric oxygen did not reach statistical significance in this series. Cases of a second primary malignancy were noteworthy; however, the impact of recurrence was minimized by the delay between resection and rehabilitation. Of the 42 fixed and 29 removable prostheses fitted, 12 (17%) failed. CONCLUSIONS: Implants placed in mandible were reliable, but failure rates in vascularized bone graft and maxilla were higher. Radiotherapy did not seem to prejudice implant survival, and hyperbaric oxygen had no demonstrable benefit in this series. Despite some persistent soft tissue problems and implant loss, most patients reached a successful prosthetic and functional outcome.

Adolescent↗
PubMed2004

Comparison of miniplates and reconstruction plates in mandibular reconstruction.

BACKGROUND: The aim of this study is to compare complication rates of miniplates versus reconstruction plates in the fixation of vascularized grafts into segmental mandibular defects. METHODS: Retrospective analysis of 143 consecutive successful microvascular composite flaps performed between 1993 and 2001 was performed. Data were gathered from a computerized database, case notes and pathology reports. Complications were classified as dehiscence, infection, plate or bone removal. RESULTS: In the series, 49% of patients received miniplates, and 51% received plates. No significant differences in complication rates were found between those grafts fixed with miniplates (27%) and those with reconstruction plates (30%). Plate choice was primarily determined by consultant preference. No significant differences were found in patient, defect, treatment, or follow-up characteristics between the plate groups. Twenty-nine percent of patients had at least one late complication at the reconstructed site, and this was higher (39%) in those who had postoperative radiotherapy. CONCLUSIONS: No evidence was found in this study that the increased rigidity offered by reconstruction plates influences the rate of plate or bone removal, infection, or plate exposure. Thus, the decision to use reconstruction or miniplates is not dependent on the rate of plate complications.

Adult↗
PubMed2004

The influence of the pattern of mandibular invasion on recurrence and survival in oral squamous cell carcinoma.

BACKGROUND: Controversy exists over the predictive value of the presence and pattern of tumor invasion of the mandible in oral squamous cell carcinoma (SCC). Many authors have questioned increasing the classification of small tumors to T4 on the basis of mandibular invasion alone. There are little data on the influence of the pattern of invasion on prognosis. METHODS: We prospectively reviewed 100 consecutive mandibular resections for previously untreated oral SCC. Clinical and pathologic data collected included details of soft and hard tissue histologic findings. Outcomes included recurrence (local, regional, and distant metastases), disease-specific survival, and death from other causes. The median follow-up for survivors was 65 months. RESULTS: Of 100 cases, 65 involved segmental and 35 involved marginal resections. Sixty-two percent of mandibles were invaded by tumor. Local recurrence occurred in 21% and was strongly correlated with tumor size, nodal involvement, and pattern of soft tissue invasion. The 5-year disease-specific survival was 68%, and the crude survival was 50%. Mandibular invasion predicted for recurrence and disease-specific survival, even after correcting for the effects of other variables. The pattern of mandibular invasion (erosive/infiltrative) was also predicted for recurrence and disease-specific survival. CONCLUSIONS: Even in the presence of mandibular invasion, soft tissue factors are the most important determinants of prognosis. Upstaging tumors on the basis of mandibular invasion is justified. An infiltrative pattern of bone invasion is a marker of aggressive tumor biology and should be included in the pTNM classification.

Adult↗
PubMed2003

Identification and characterisation of an aspartyl protease inhibitor homologue as a major allergen of Trichostrongylus colubriformis.

Allergens were identified from the gastrointestinal nematode of sheep, Trichostrongylus colubriformis, by probing Western blots of infective larvae (third stage) somatic antigen with IgE purified from the serum of sheep grazed on worm contaminated pasture. A 31 kDa allergen was frequently recognised by sera from immune sheep, particularly those deriving from a line that has been genetically selected over 23 years for parasite resistance. Using a proteomic approach, the 31 kDa allergen was identified as an aspartyl protease inhibitor homologue. The entire coding sequence of T. colubriformis aspartyl protease inhibitor (Tco-api-1) was obtained and the mature protein expressed in Escherichia coli. Anti-Tco-API-1 antibodies revealed that a commonly observed 21 kDa T. colubriformis allergen species is a truncated form of Tco-API-1. Specific IgE responses to T. colubriformis aspartyl protease inhibitor were significantly correlated with the degree of resistance to nematode infection as measured by faecal egg count in sheep. Surprisingly, IgE responses to Tco-API-1 were not correlated with breech soiling (dag score), which is thought to be caused, in part, by allergic hypersensitivity to worms. Therefore, a specific IgE response to this allergen may be a suitable marker for identifying lambs at an early age that will develop strong immunity to gastrointestinal nematodes.

Allergens↗
PubMed2003

A typology of non-adherence in pediatric renal transplant recipients.

We reviewed 112 pediatric renal transplant recipients to document the rate of medication non-adherence (NA) and to examine the relationships between NA, comorbid psychiatric illness, and the outcome variables of acute and chronic rejection and graft loss. A total of 32.5% of subjects had clinically significant NA with treatment based on review of serum immunosuppressant levels. NA was found to be significantly related to acute and chronic rejection, and graft loss (p < 0.001). NA was also related to the presence of comorbid psychiatric illness (p < 0.001). Logistic regression indicated that NA was a significant predictor for acute and chronic rejection, while psychiatric illness predicted graft loss. Adolescents had significantly higher rates of NA as well as shorter intervals between transplant date and onset of NA when compared with child patients (p < 0.001). Physician ratings of the primary reasons for NA suggested that lack of parental supervision and parent-child conflict were the major factors related to NA.

Adolescent↗
PubMed2002

Pseudologia Fantastica associated with Pervasive Developmental Disorder.

This case study describes the association of Pseudologia Fantastica (PF) and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) in a 14-year-old girl. PF is seen in a number of diagnostic entities, but has not previously been reported in PDD spectrum disorders. Treatment implications are discussed along with a formulation of the psychological and cognitive functions of PF in a person with a PDD diagnosis.

Adolescent↗
PubMedDate not supplied

A comparison of clinical ratings with vocal acoustic measures of flat affect and alogia.

In this report we compare clinical ratings of flat affect and alogia with objective measures of the patient's speech prosody and productivity. Thirty schizophrenic patients were evaluated with the Scale for the Assessment of Negative Symptoms (SANS) and the St. Hans Rating Scale for extra pyramidal side effects. Their speech was recorded and analyzed acoustically for measures of prosody and productivity. Correlations between pairs of SANS items and acoustic measures (e.g. Vocal Inflection and Fundamental Frequency Variance) were weak. The SANS item and global ratings were strongly related. Ratings of bradykinesia overlapped with the SANS ratings but not with the acoustic measures. The SANS ratings appear to be derived from global impressions, with diffuse confounding of flat affect with alogia, and with bradykinesia. Acoustic analysis has the potential to provide objective measures that may help develop operational definitions of these constructs and enhance clinical assessment.

Adult↗
PubMedDate not supplied

Practice patterns in pediatric consultation-liaison psychiatry: a national survey.

The purpose of this survey was to describe the current status of pediatric consultation-liaison (C-L) services in the United States. A total of 144 pediatric C-L programs were surveyed, with a response rate of 33%. Financial and staffing constraints were cited as common problems; 61% of programs reported an increase in consultation requests over the past 5 years, however, 30% of services reported a decrease in funding. Collection rates for professional billings average 30%; 57% of services reported an increase in clinical service demands at the expense of teaching and liaison activities. Discussion includes recommendations based on the results of the survey.

Child↗
PubMedDate not supplied

Acute stress disorder among parents of infants in the neonatal intensive care nursery.

The authors examined the prevalence of acute stress disorder (ASD) in parents of infants hospitalized in the neonatal intensive care unit (NICU). Forty parents were assessed after the birth of their infants. Parents completed self-report measures of ASD, parental stress, family environment, and coping style: 28% of parents developed symptoms of ASD. ASD was associated with female gender, alteration in parental role, family cohesiveness, and emotional restraint. Family environment and parental coping style are significantly associated with the development of trauma symptoms. Results from this study suggest potential interventions to help minimize psychological distress in parents.

Adaptation, Psychological↗