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Biomedical subjects

P Richmond

Publications and source records attributed to P Richmond.

At least 19 recordsLinked to original sources

Management of soft tissue knee injuries in an accident and emergency department: the effect of the introduction of a physiotherapy practitioner.

OBJECTIVE: To assess the effect of the introduction of a physiotherapist with an extended scope of practice in the management of acute soft tissue knee injuries in an accident and emergency (A&E) department. METHODS: The A&E department established an Acute Knee Screening Service (AKSS) in 1998. An experienced physiotherapist was appointed to run the AKSS after additional training. Local guidelines and protocols were developed in conjunction with trauma knee surgeons, radiologists, physiotherapists, and A&E doctors. This study describes 100 consecutive patients managed by the AKSS over a three month period and comparisons are made over a similar period before the introduction of the AKSS. RESULTS: The initial diagnosis of patients with acute knee injuries referred to the service showed meniscal injuries (38%), cruciate ligament injuries (18%), fractures (2%), patellofemoral joint injuries (10%), and others (32%). Ninety five per cent of patients referred to AKSS were seen within one week. Medical time was saved in both A&E and trauma clinic. Fifty nine per cent of patients were treated and discharged from the service without further medical review. Thirty nine per cent (39) were referred to trauma clinic and of these 44% (17) had MRI scans performed as requested by the physiotherapist. Eighty eight per cent (15) of these scans showed significant abnormality: (nine, anterior cruciate ligament tears, one, posterior cruciate ligament tears, and nine meniscal tears). CONCLUSIONS: A physiotherapy practitioner working with an extended role is a valuable addition to an A&E department. The AKSS improves the quality of care of acute knee injuries, saves medical time, and fosters cooperation across services within the NHS.

Adolescent↗

Development and use of a population based injury surveillance system: the all Wales Injury Surveillance System (AWISS).

This report details the development and use of a population based emergency room surveillance system in the UK. Despite some difficulties in accessing high quality data the system has stimulated a considerable number of research and intervention projects. While surveillance systems with high quality data collection and coding parameters remain the gold standard, imperfect systems, particularly if population based, can play a substantial part in stimulating injury prevention initiatives.

Accident Prevention↗

Influence of prior meningococcal C polysaccharide vaccination on the response and generation of memory after meningococcal C conjugate vaccination in young children.

To determine whether the immunological hyporesponsiveness induced by meningococcal AC polysaccharide (MACP) vaccines can be overcome by meningococcal C conjugate (MCC) vaccine in young children, serum bactericidal antibody (SBA) serogroup C-specific IgG and IgG avidity indices were measured in young children who received MACP vaccine, followed 7 months later by MCC vaccine, and their responses were compared with those in age-matched MACP-naive control children, who received a single dose of MCC vaccine. For children <1 year of age at MACP vaccination, the SBA geometric mean titer (GMT) after MCC vaccination was lower (P=.022) and proportions with SBA titers <8 (P=.0083) or <128 (P=.0091) were higher than those in the control children. For older children, there was no difference in the SBA GMTs between the study and control groups (P>.5) or in the proportion with SBA titers <8 (P=1.00) or <128 (P=.98). No increase in avidity occurred after MACP vaccination, whereas avidity increased significantly 1 month after MCC vaccination, with a further increase at 6 months, which indicates that the induction of immunological memory was not impaired.

Age Factors↗

Evaluation of De-O-acetylated meningococcal C polysaccharide-tetanus toxoid conjugate vaccine in infancy: reactogenicity, immunogenicity, immunologic priming, and bactericidal activity against O-acetylated and De-O-acetylated serogroup C strains.

The polysaccharide capsule of serogroup C Neisseria meningitidis (MenC) has been integral to vaccine development. Licensed MenC vaccines contain the O-acetylated (OAc+) form of polysaccharide. Some MenC strains have de-O-acetylated (OAc-) polysaccharide, which may affect antibody specificity and functional activity when used in a vaccine. We evaluated an OAc-MenC conjugate-tetanus toxoid conjugate (MCC-TT) vaccine given concomitantly with whole-cell diphtheria-tetanus-pertussis, Haemophilus influenzae type b, and oral polio immunization in 83 infants at 2, 3, and 4 months of age. Serum bactericidal activities (SBA) against OAc+ and OAc- MenC strains and OAc+ and OAc- polysaccharide-specific immunoglobulin G (IgG) levels were evaluated. MCC-TT vaccine was well tolerated. All infants produced SBA titers of > or = 8 after a single dose at 2 months of age. The SBA geometric mean titer for OAc+ strain C11 increased from 2.7 (95% confidence interval [CI] 2.2 to 3.2) to 320 (95% CI, 237 to 432), 773 (95% CI, 609 to 982), and 1,063 (95% CI, 856 to 1319) after one, two, and three doses of MCC-TT, respectively. OAc- IgG levels were twice as high as OAc+ IgG levels after the primary series of MCC-TT vaccine, and the SBA was significantly higher against the OAc- MenC strain. Antibody responses to booster vaccination with either OAc+ MenC polysaccharide vaccine (MACP) or a fourth dose of MCC-TT at 14 months of age provided evidence of immunologic memory. The acetylation status of the booster vaccine influenced the specificity of the response, with significantly higher OAc- IgG levels and SBA after MCC-TT vaccine compared to MACP vaccine but similar OAc+ antibody levels. MCC-TT vaccine is highly immunogenic and primes for immunologic memory against OAc+ and OAc- MenC strains in infancy.

Antibodies, Bacterial↗

On assessment of success and the IMPACT of FAIR.

Early in 2001, the authors were awarded an Accompanying Measure by the Agri-Food Directorate of DG Research to assess the IMPACT of a selected subset of projects recently completed within the FAIR RTD program. We have three aims: To specifically evaluate the impact of 25 projects supported under the EU FAIR Programme. To develop and validate a methodology for assessing the impact of collaborative projects in the food area. To identify any generic messages which could relate to the forthcoming European Research Area (ERA). A series of Workshops are being held with FAIR participants and stakeholders around the Community to facilitate the development of the methodology. At the time of writing meetings have been held in the UK, Ireland and Denmark. Diet and Health will a key driver for innovation in food during the 21st century and will play a major role in both EU and national research. Participation in the HEALFO Food and Health Conference allowed us to meet and discuss IMPACT with an important group of both past and future contributors to EU research. This paper outlines the workshop methodology and outlines some interim findings together with emerging hypotheses.

Community Health Planning↗

Reduced antibody response to revaccination with meningococcal serogroup A polysaccharide vaccine in adults.

Widespread use of meningococcal A and C polysaccharide (MACP) vaccines has raised concerns about induction of hyporesponsiveness to these polysaccharides. Immunological hyporesponsiveness to C polysaccharide has been clearly documented in infants, children and adults but only limited data from Gambian children are available for A polysaccharide. We investigated whether a second dose of MACP, given 6 months after an initial dose affected the immunological response as measured by the serum bactericidal assay (SBA) and enzyme-linked immunosorbent assay (ELISA), to serogroup A meningococci in young adults (university students, n=36). Serogroup A SBA responses 1 month following the second dose of MACP (geometric mean titre (GMT) 103.6, 95% CI 45.6-235.1) were approximately one third of the levels observed 1 month post first dose (GMT 281.9, 95% CI 134.9-581.4). The serogroup A-specific IgG levels post second dose (GMC 21.2, 95% CI 15.3-29.4) were also significantly lower at an average of three-quarters the level post first dose (GMC 28.7, 95% CI 20.8-39.7). This confirms that revaccination with MACP vaccine, 6 months following the initial dose, results in a reduced immunological response to A polysaccharide in adults. Repeated vaccination with MACP vaccine may be ineffective and development and use of meningococcal serogroup A conjugate vaccines should be encouraged.

Adolescent↗

Ability of 3 different meningococcal C conjugate vaccines to induce immunologic memory after a single dose in UK toddlers.

To test for immunologic memory after a single dose of meningococcal C conjugate (MCC) vaccine in toddlers, 226 children 12-18 months old were randomized to receive 1 of 3 MCC vaccines, with a C polysaccharide booster 6 months later. The protein conjugate was diphtheria mutant toxoid in 2 vaccines (MCC-CRM(197)) and was tetanus toxoid in the third (MCC-TT). One month after the MCC vaccines, 91%-100% of children had serum bactericidal antibody (SBA) titers > or =8, and 89%-100% had a > or =4-fold increase. Geometric mean titer (GMT) increased from <4 to 215 (95% confidence interval [CI], 166-279). MCC-TT induced higher SBA GMTs (P<.001) and higher proportions with SBA > or =8 (P=.02) than did the MCC-CRM(197) vaccines. By 6 months, GMTs had decreased to 55.1 (95% CI, 40-76), but IgG antibody avidity increased (P<.001). Induction of immunologic memory was confirmed by a GMT of 1977 (range, 1535-2547) after the polysaccharide booster and a further increase in avidity. This evidence justified the use of a single dose in a catch-up immunization program for children 1-18 years old.

Antibodies, Bacterial↗

Meningococcal C polysaccharide vaccine induces immunologic hyporesponsiveness in adults that is overcome by meningococcal C conjugate vaccine.

Widespread use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of hyporesponsiveness to C polysaccharide. Whether meningococcal C conjugate (MCC) vaccine overcomes any immunologic refractoriness following MACP vaccination in adults was investigated. University students vaccinated 6 months previously with MACP vaccine were randomized to receive MACP or MCC vaccine, and antibody responses were compared with those of previously unvaccinated students receiving MACP or MCC vaccine. In students primed with MACP vaccine, MCC vaccine induced significantly higher IgG and serum bactericidal antibody levels than did a second dose of MACP vaccine. Responses to a second dose of MACP vaccine were significantly lower than to the first dose. Previous receipt of MACP vaccine reduced serum bactericidal antibody but not IgG responses to MCC vaccine compared with those in previously unvaccinated students. This confirms that MACP vaccine induces immunologic hyporesponsiveness to C polysaccharide in adults, but this can be overcome with MCC vaccine. Repeated vaccination with MACP vaccine may be ineffective, and MCC vaccines should provide better long-term protection.

Adolescent↗

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Journal Article↗

Meningococcal serogroup C-specific IgG antibody responses and serum bactericidal titres in children following vaccination with a meningococcal A/C polysaccharide vaccine.

In the UK, a co-ordinated series of phase II studies is being undertaken with meningococcal serogroup C conjugate (MCC) vaccines. The use of meningococcal A/C polysaccharide (MACP) vaccines in control arms in young children has been avoided because of the well recognised short comings of these vaccines. Following a cluster of serogroup C disease centred on a day nursery, intervention by MACP vaccination was performed as an outbreak control measure. Using this cohort, serogroup C-specific IgG ELISA and serum bactericidal assays (SBA) were performed using both de-O-acetylated (Oac(-)) and acetylated (Oac(+)) serogroup C antigen, the measurement of primarily high avidity antibody and using baby rabbit or human complement in the SBA. The effect of subject age (either less than or greater than 2 years of age) was assessed for the different assays and significant differences (P<0.05) were found using both antigen sources in the high avidity ELISA and in the rabbit complement SBA but not in the standard ELISA. When assessing results from different studies it is important that methodologies utilised allow such comparisons since the choice of reagents can have a profound influence. The importance of standardised assays is paramount at a time where immunogenicity trials are replacing efficacy trials for the introduction of MCC vaccines.

Animals↗

Safety and immunogenicity of a new Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in healthy adults.

UNLABELLED: We evaluated the safety and immunogenicity of a single dose of a new serogroup C O-deacetylated meningococcal polysaccharide-tetanus toxoid conjugate vaccine in 30 healthy adult volunteers. The vaccine was well tolerated with no serious adverse events and minimal local reactions and systemic symptoms. All subjects developed a fourfold or greater increase in serum bactericidal antibody (SBA) to serogroup C meningococcus. SBA geometric mean titre increased from 11 to 3649 (p<0.001). Serogroup C-specific IgG levels increased postvaccination from 0.65 to 17.02 microg/ml (p<0.001). Bactericidal titres pre- and postimmunisation showed significant correlation with serogroup C-specific IgG (r(2)=0.693). Antibody levels fell by 6 months postvaccination, however, meningococcal C IgG avidity increased indicating the successful induction of a T-cell-dependent antibody response. CONCLUSION: meningococcal C-tetanus toxoid conjugate vaccine is immunogenic and well tolerated in healthy adults.

Adult↗

Immunogenicity and reactogenicity in UK infants of a novel meningococcal vesicle vaccine containing multiple class 1 (PorA) outer membrane proteins.

The development of effective vaccines against serogroup B meningococci is of great public health importance. We assessed a novel genetically engineered vaccine containing six meningococcal class 1 (PorA) outer membrane proteins representing 80% of prevalent strains in the UK. 103 infants were given the meningococcal vaccine at ages 2, 3 and 4 months with routine infant immunisations, with a fourth dose at 12-18 months. The vaccine was well tolerated. Three doses evoked good immune responses to two of six meningococcal strains expressing PorA proteins contained in the vaccine. Following a fourth dose, larger bactericidal responses to all six strains were observed, suggesting that the initial course had primed memory lymphocytes and revaccination stimulated a booster response. This hexavalent PorA meningococcal vaccine was safe and evoked encouraging immune responses in infants. Vaccines of this type warrant further development and evaluation.

Antibodies, Bacterial↗

Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1.

Hoyeraal-Hreidarsson (HH) syndrome is a multisystem disorder affecting boys characterized by aplastic anaemia (AA), immunodeficiency, microcephaly, cerebellar-hypoplasia and growth retardation. Its pathogenesis is unknown. X-linked dyskeratosis congenita (DC) is an inherited bone-marrow-failure syndrome characterized by skin pigmentation, nail dystrophy and leucoplakia which usually develop towards the end of the first decade of life. AA occurs in >90% of cases of DC. We speculated that mutations in the gene responsible for X-linked DC (DKC1) may account for the HH syndrome, due to the phenotypic similarities between the disease in respect of AA and gender bias. We therefore analysed the DKC1 gene in two HH families. In one family a nucleotide change at position 361(A --> G) in exon 5 was found in both affected brothers; in the other family a nucleotide change at position 146(C --> T) in exon 3 was found in the affected boys. The finding of these two novel missense DKC1 mutations demonstrates that HH is a severe variant of DC. They also show that mutations in DKC1 can give rise to a very wide clinical spectrum of manifestations. Boys with unexplained AA or immunodeficiency should be tested for mutations in DKC1 even though they may lack diagnostic features of DC.

Amino Acid Substitution↗

Meningococcal serogroup C conjugate vaccine is immunogenic in infancy and primes for memory.

The safety, immunogenicity, and immunologic priming of 2 dosages (2 microgram or 10 microgram) of a meningococcal C oligosaccharide-CRM197 conjugate vaccine was evaluated in 114 infants vaccinated at ages 2, 3, and 4 months. Antibody persistence and response to boosting with 10 microgram of meningococcal C polysaccharide were assessed. The meningococcal conjugate vaccine produced fewer local reactions than concurrent routine immunizations. Total serogroup C-specific immunoglobulin geometric mean concentration (GMC) increased from 0.3 microgram/mL before vaccination to 13.1 microgram/mL at age 5 months. Serum bactericidal antibody (SBA) geometric mean titers (GMTs) rose from <1:4 to 1:1057 at 5 months and fell by 14 months to 1:19. Following boosting, anti-C-specific immunoglobulin GMC rose to 15.9 microgram/mL and SBA GMT to 1:495. Antibody responses in the 10-microgram dose cohort were significantly higher at 5 months (P<.01) than in the 2-microgram dose cohort but were lower after polysaccharide boosting (P=.02). This meningococcal conjugate vaccine was well tolerated and immunogenic and induced immunologic memory in infants.

Bacterial Capsules↗

The induction of immunologic memory after vaccination with Haemophilus influenzae type b conjugate and acellular pertussis-containing diphtheria, tetanus, and pertussis vaccine combination.

The significance of reduced antibody responses to the Haemophilus influenzae type b (Hib) component of acellular pertussis-containing combination vaccines (DTaP-Hib) is unclear. A DTaP-Hib vaccine evaluated in infants vaccinated at ages 2, 3, and 4 months showed reduced anti-Hib polysaccharide IgG (geometric mean concentration [GMC], 1.23 microgram/mL; 57%, >1.0 microgram/mL). Polyribitolribosyl phosphate (PRP) and Hib conjugate (PRP-T) vaccine given as a booster during the second year of life was evaluated for the presence of immunological memory. After boosting, most children achieved anti-PRP IgG >1.0 microgram/mL, although the GMC was higher with PRP-T (88.5 microgram/mL) than with PRP vaccine (7.86 microgram/mL, P<.001). The GMC of the PRP group was higher than anticipated for naive PRP recipients of the same age. PRP-specific IgG avidity was significantly higher after boosting than after priming, providing further evidence for the generation of memory. Despite reduced immunogenicity, DTaP-Hib combination vaccines appear to prime for immunologic memory.

Antibodies, Bacterial↗

Rheumatic fever in the Kimberley region of Western Australia.

The objective of this study was to assess the incidence and clinical presentation of acute rheumatic fever in children and young adults in the north west of Western Australia--a region known as the Kimberley. In this five year retrospective study, residents aged less than 30 years, suspected of having had acute rheumatic fever from 1988 to 1992, were identified and their hospital and clinic records were reviewed. There were 96 cases of acute rheumatic fever that met the revised Jones criteria during the five year period. There were 59 initial attacks and 37 recurrences that occurred in 81 people, of whom 80 were of Aboriginal descent. The overall incidence of acute rheumatic fever in the Kimberley region for those aged under 30 years is 136 cases per 100,000 per year and in the Aboriginal population is 241 per 100,000 per year. The group most at risk are Aboriginal school children aged 5-14 years who accounted for 50 cases and have an annual incidence of 375 cases per 100,000 per year. The clinical presenting features were carditis in 50 per cent, polyarthritis in 59 per cent, chorea in 22 per cent, and subcutaneous nodules in 1 per cent. The hospitalization rate was 80 per cent for new cases and 73 per cent for recurrences with average stays of 14.6 and 1.5 days respectively. Rheumatic heart disease (RMD) developed in 31 of the cases; two required surgery and there was one death attributable to RHD in this group. Rheumatic fever continues to be a significant health problem in the Aboriginal population in this region and the recurrence rate, despite secondary prophylaxis, is also unacceptably high.

Acute Disease↗