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Biomedical subjects

P Heath

Publications and source records attributed to P Heath.

At least 19 recordsLinked to original sources
PubMed2006

Development of a real time PCR for the detection of Taylorella equigenitalis directly from genital swabs and discrimination from Taylorella asinigenitalis.

A discriminatory real time PCR for the detection of Taylorella equigenitalis, the causative agent of contagious equine metritis (CEM), and the related species T. asinigenitalis was developed for the direct examination of genital swabs. The 112bp amplicons produced from the two species were discriminated from each other using TaqMan probes labelled with different fluorophores. The TaqMan PCR was shown to be specific for the 16S ribosomal DNA of the two species of taylorella and did not cross-hybridise with the 16S ribosomal DNA of other bacteria tested. Direct amplification from genital swabs was shown to be equally sensitive to that of culture methods. Prevalence in a sample set from The Netherlands was shown to be equivalent to that demonstrated by culture. A companion real time PCR that amplified a fragment of the 16S rDNA gene of equine commensal bacteria was developed to ensure bacterial DNA was extracted from swab material supplied for testing. The use of a rapid and reliable real time PCR for the organism causing CEM should aid the control of this disease.

Animals↗
PubMed2005

The prevention of neonatal group B streptococcal disease: a report by a working group of the Medical Screening Society.

Streptococcus agalactiae, or Lancefield group B streptococcus (GBS), is the most frequent cause of serious bacterial sepsis, including neonatal meningitis, in UK neonates. Early-onset neonatal GBS infection, but not late-onset, can be prevented by screening to identify high-risk pregnancies and administering penicillin during delivery. A vaccine has been developed as an alternative means of prevention but it is awaiting a randomized trial before being available for general use. In this review we examine the published literature to assess the morbidity and mortality attributable to neonatal GBS infection, quantify the screening performance of the two alternative modes of screening (microbiological and risk factor based), review the evidence on the efficacy of the vaccine, and estimate the numbers of deaths and cases of serious disability that each strategy in turn might prevent in the UK, in order to assess the most effective means of prevention for the UK.

Antibiotic Prophylaxis↗
PubMed2005

Sustainable sewage solutions for small agglomerations.

In a significant number of European countries, the need for providing appropriate treatment for the effluents of small rural communities is still especially relevant. In fact, in countries like Portugal, Spain, and many others, significant amounts of investment will be addressed in the next few years to the construction of small Wastewater Treatment Plants (WWTP). The problems faced when constructing and operating WWTP serving small communities may be relevant when energy and labour costs are relatively high, or when the visual impact on the surrounding areas is especially negative. Sustainable treatment solutions require the selection of appropriate technologies using fewer resources. In this paper, information is presented about sustainability indicators of twenty-one small secondary wastewater treatment plants, including conventional (trickling filters and extended aeration plants) and non-conventional treatment systems (constructed wetlands). The data refer to allocated areas per inhabitant, amounts of concrete per inhabitant, power per inhabitant, and construction and installation costs per inhabitant. The data seem to show that for different reasons, constructed wetlands are promising treatment solutions for application to rural areas in particular because of the relatively low power requirements and relatively low construction costs for served populations below 500 inhabitants.

Animals↗
PubMed2003

Conflicting advice.

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Child, Preschool↗
PubMed2003

Severe and unrecognised: pertussis in UK infants.

AIMS: To diagnose pertussis using culture, polymerase chain reaction, and serology, in children admitted to intensive care units (PICUs) and some paediatric wards in London, and in their household contacts to determine the source of infection. METHODS: Infants <5 months old admitted to London PICUs between 1998 and 2000 with respiratory failure, apnoea and/or bradycardia, or acute life threatening episodes (ALTE), and children <15 years admitted to paediatric wards at St Mary's and St George's Hospitals between 1999 and 2000 with lower respiratory tract infection, apnoea, or ALTE were studied. RESULTS: Sixty seven per cent of eligible children (142/212) were recruited; 23% (33/142) had pertussis, 19.8% (25/126) on the PICU and 50% (8/16) on wards. Two died. Only 4% (6/142) were culture positive. Pertussis was clinically suspected on admission in 28% of infants (7/25) on the PICU and 75% (6/8) on the wards. Infants on PICU with pertussis coughed for longer, had apnoeas and whooped more often, and a higher lymphocyte count than infants without pertussis. Pertussis and respiratory syncytial virus (RSV) co-infection was frequent (11/33, 33%). Pertussis was confirmed in 22/33 (67%) of those who were first to become ill in the family. For 14/33 children the source of infection was a parent; for 9/33 the source of pertussis was an older fully vaccinated child in the household. CONCLUSIONS: Severe pertussis is under diagnosed. An RSV diagnosis does not exclude pertussis. Future changes to the UK vaccination programme should aim to reduce pertussis transmission to young infants by their parents and older siblings.

Anti-Bacterial Agents↗
PubMed2002

Delayed transient sciatic nerve palsy after total hip arthroplasty.

Sciatic nerve palsy after total hip arthroplasty is a well-known complication, but delayed sciatic nerve palsy is rare. We report such a case with profound clinical manifestations and well-documented electrophysiologic changes. We found no helpful guidance to managing delayed palsy in the literature. We also are unaware of any previous cases reported in which nearly full recovery has occurred.

Arthroplasty, Replacement, Hip↗
PubMed2002

Should the new pneumococcal vaccine be used in high-risk children?

A new conjugate 7-valent vaccine to prevent pneumococcal infection (Prevenar, Wyeth) has recently received a European licence for use in young healthy children. The vaccine is not currently included in the universal immunisation schedule in the UK or elsewhere in Europe, although it is being used widely in the USA. Its availability for purchase raises the question whether paediatricians should consider using it in high risk children, including those for whom the polysaccharide 23-valent vaccine was previously recommended, until (or unless) it is introduced into general use-indeed the Chief Medical Officer for England and Wales has recently made a recommendation regarding such children aged less than 2 years. We review the evidence concerning use of the vaccine in such children and make suggestions as to how the vaccine may be used while further information is collected.

Anemia, Sickle Cell↗
PubMed1999

Adverse effects and sero-responses to an acellular pertussis/diphtheria/tetanus vaccine when combined with Haemophilus influenzae type b vaccine in an accelerated schedule.

UNLABELLED: Acellular pertussis vaccines provide protection against pertussis with few adverse effects. Differences in the reactogenicity and immunogenicity of available pertussis vaccines may be influenced by the immunisation schedule employed. We assessed responses to an acellular pertussis, diphtheria, tetanus vaccine mixed with Haemophilus influenzae type b (Hib) vaccine, (PRP-T) given at age 2, 3 and 4 months. Parents kept a symptom diary for 3 days after each immunisation. Antibodies to diphtheria, tetanus, pertussis toxin and filamentous haemagglutinin were measured by enzyme immunoassay at 2 and 5 months. Results were compared with historical controls who received a combination whole-cell pertussis, diphtheria, tetanus/PRP-T vaccine in the same schedule. A total of 262 infants were recruited, of whom 251 were fully evaluated after three doses of vaccine. Systemic and most local reactions were less frequent following the acellular combination. Fever > or = 38 degrees C was reported after only 0.6% of doses. Redness or swelling > or = 2.5 cm were unusual after the first two doses (2-5%), but rates rose to 13% after the third dose. Antibody responses to diphtheria and tetanus toxoids were lower, while those to pertussis antigens were higher, more uniform and less attenuated by pre-immunisation antibody than in infants who received the whole-cell combination. All infants achieved protective antibody titres of at least 0.1 IU/ml for diphtheria and 0.01 IU/ml for tetanus. CONCLUSION: The acellular combination vaccine was immunogenic for diphtheria, tetanus and pertussis components and was associated with low rates of fever following immunisation.

Analysis of Variance↗
PubMed1998

Effect of combination with an acellular pertussis, diphtheria, tetanus vaccine on antibody response to Hib vaccine (PRP-T).

Acellular pertussis vaccines provide protection against whooping cough with few adverse effects. Their introduction to routine immunisation programmes would be facilitated by their incorporation with other routinely administered vaccines. 262 infants were immunised with an acellular pertussis vaccine containing pertussis toxin and filamentous haemagglutinin, combined with diphtheria and tetanus toxoids. This vaccine was mixed with Haemophilus influenzae type b tetanus toxoid vaccine (PRP-T) so that infants received a single injection at age 2, 3 and 4 months. One month after the third dose the geometric mean titre of Hib IgG antibody was 0.48 microgram ml-1. Eighty-two percent of infants achieved a titre of 0.15 microgram ml-1, with only 27% achieving 1.0 microgram ml-1. This combination vaccine induced low Hib antibody responses when compared to other studies in which PRP-T was mixed with acellular or whole-cell pertussis vaccines. The combined vaccine did, however, appear to prime a subset of 35 infants for response to a fourth dose of PRP-T at 13 months of age, with a rise in GMT from 0.21 microgram ml-1 to 36.6 micrograms ml-1. These data have important implications for the introduction of combination acellular pertussis vaccines.

Antibodies, Viral↗
PubMed1998

Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene.

X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.

Antigens, CD↗
PubMed1997

Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn's disease.

BACKGROUND: Tumour necrosis factor-alpha (TNF alpha) is thought to have a central role in the pathogenesis of Crohn's disease. We tested the hypothesis that CDP571, a genetically engineered human antibody to TNF alpha, is effective in modifying disease activity in patients with moderately active Crohn's disease. METHODS: In this double-blind, placebo-controlled study, 31 patients were randomly assigned to CDP571 (n = 21) or placebo (n = 10). The primary endpoint was change in Crohn's disease activity index 2 weeks after a single infusion of CDP571 (5 mg/kg), or human albumin as placebo. One patient who attended no follow-up assessments was excluded from the analyses (CDP571 group). FINDINGS: The median Crohn's disease activity index fell from 263 (IQR 186.5-323.5) at baseline to 167 (137.5-294.0) at 2 weeks in the CDP571-treated patients (p = 0.0003); the change in the placebo group (253 [240-334] to 247 [183-256]) was not significant. In the treated group, there were also significant differences between baseline and 2 weeks in Harvey-Bradshaw score (p = 0.0005), key symptom score (p = 0.049), alpha 1-glycoprotein concentration (p = 0.012), and erythrocyte sedimentation rate (p = 0.01); concentrations of C-reactive protein fell, but not significantly (p = 0.067). Six patients achieved remission (Crohn's disease activity index < or = 150) and three others had activity indices of 156 or lower. There were no significant changes in the placebo group. INTERPRETATION: A single 5 mg/kg infusion of CDP571 reduced disease activity in Crohn's disease at 2 weeks. These data suggest that antibody neutralisation of TNF alpha is a potentially effective strategy in the management of Crohn's disease. The use of CDP571 in Crohn's disease requires further study.

Adolescent↗
PubMed1997

Treatment of ulcerative colitis with an engineered human anti-TNFalpha antibody CDP571.

BACKGROUND: Tumour Necrosis Factor-alpha (TNFalpha) is a pro-inflammatory cytokine whose expression is increased in the colonic mucosa of patients with active ulcerative colitis. TNFalpha antibodies have been shown to be beneficial in animal models of bowel inflammation and in Crohn's disease but have not previously been studied in ulcerative colitis. METHODS: Patients with mild/moderate ulcerative colitis were treated openly with a single intravenous infusion of 5 mg/kg of an engineered human IgGgamma4 antibody CDP571 and monitored for 8 weeks. RESULTS: Fifteen patients entered the study, eight males and seven females, with a mean age of 44 years. Eleven had left-sided disease, four extensive disease and six patients were steroid-unresponsive. The treatment was well tolerated and plasma half-life of CDP571 was approximately 7 days. There was a significant reduction from 6.7 to 4.6 (P = 0.023) in the mean Powell-Tuck score by 1 week post-infusion and a reduction to 5.5 was seen at 2 weeks (P = 0.218). Significant but modest reductions also occurred in erythrocyte sedimentation rate and serum C reactive protein in the first 2 weeks. Mean Interleukin-6 plasma concentrations fell from 6.9 to 5.4 pg/mL by week 1, and to 6.1 pg/mL by week 2 (NS). Reductions in sigmoidoscopic score and number of liquid stools were noted but failed to reach statistical significance. CONCLUSION: A consistent improvement in disease activity was seen in the initial 2 weeks after infusion and the treatment was well tolerated. These promising results support the testing of CDP571 in a larger controlled trial.

Adult↗
PubMed1997

The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects.

Recent studies have suggested that theophylline, a nonspecific phospho-diesterase inhibitor, has useful anti-inflammatory actions in asthma. Phosphodiesterase 4 (PDE4) represents the predominant PDE isoenzyme present in inflammatory cells. PDE4 inhibitors might, therefore, have beneficial effects in asthma. Side-effects, specifically nausea, have limited the use of existing agents. CDP840 is an orally active, potent and selective PDE4 inhibitor. We have examined the effect of CDP840 on the allergen-induced asthmatic response, its possible modes of action, and its tolerability at therapeutic doses. A total of 54 patients were recruited to three double-blind, placebo-controlled studies. The first study examined the effect of CDP840 (15 mg b.i.d. for 9.5 days) on the allergen-induced asthmatic response in patients with known dual response to allergen. A second study examined the effect of CDP840 (15 mg b.i.d. for 9.5 days) on airway responsiveness to histamine. A third study examined whether single dose CDP840 (15 and 30 mg) had significant bronchodilatory effects. In all studies, CDP840 was well-tolerated, with no patients reporting nausea. CDP840 did not lead to changes in baseline forced expiratory volume in one second (FEV1) as compared to placebo. The late asthmatic response (LAR) to allergen, expressed as area under the curve at 3-8 h (AUC3-8h), was inhibited by 30% (p=0.016), an effect which persisted to the end of the observation period. The early asthmatic response (EAR) was unaffected, and there was no bronchodilatory effect at the doses used. Treatment with CDP840 did not affect bronchial hyperresponsiveness to histamine. In conclusion, CDP840 significantly attenuated the late asthmatic response to allergen challenge in the absence of any bronchodilatory or histamine antagonist effect. This suggests that CDP840 may exert its effects via an anti-inflammatory mechanism.

Adolescent↗
PubMed1996

Anti-ganglioside antibodies in patients with rheumatoid arthritis complicated by peripheral neuropathy.

Gangliosides are a diverse class of glycolipids found in the plasma membrane of mammalian cells and are particularly abundant in cells of the nervous system. Serum antibodies to gangliosides have been detected in various neurological disorders with some evidence that they play a pathogenic role. In this study, we have investigated whether anti-ganglioside antibodies were elevated in a group of patients with rheumatoid arthritis (RA) who developed peripheral neuropathy (PN). An ELISA technique was used to test sera from 28 patients with RA and PN. 38 RA patients without PN and 20 normal controls for the presence of IgG and IgM anti-GM1 and sulphatide antibodies. The patients with RA and PN had higher pain scores (P < 0.005), more extra-articular features (P < 0.05), higher erosive scores (P < 0.0001), lower haemoglobin (P < 0.005), higher ESR (P < 0.001) and were more often on disease-modifying drugs (P < 0.05). Twelve RA patients with PN (43%), but only two RA controls (5%), had positive titres against one or more gangliosides (P < 0.001). The neurologic disability score (NDS) correlated with RA duration (P < 0.05), and with levels of IgM anti-GM1 (P < 0.001) and IgM anti-sulphatide (P < 0.05) antibodies. We conclude that PN is more common in patients with severe rheumatoid disease, and a significant proportion have elevated levels of anti-ganglioside antibodies.

Aged↗