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Biomedical subjects

J Southern

Publications and source records attributed to J Southern.

At least 19 recordsLinked to original sources

Evaluation of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b vaccine given concurrently with meningococcal group C conjugate vaccine at 2, 3 and 4 months of age.

BACKGROUND AND OBJECTIVE: In view of the possible introduction of diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib, eg Pediacel) vaccine in the UK, a study of the immunogenicity of Pediacel when given with one of two different meningococcal group C conjugate (MCC) vaccines at 2, 3 and 4 months of age was conducted. METHODS: Randomised controlled study in 241 infants. RESULTS: Post vaccination, the proportion of infants with anti-polyribosylribitol phosphate (PRP) levels > or =0.15 microg/ml was 93.2% (95% confidence interval (CI) 86.6 to 96.7) in the Pediacel group compared with 100% (95% CI 96.4 to 100) in the diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae type b (DTwP-Hib) group. The anti-PRP response was lower in infants receiving either Pediacel or DTwP-Hib when these vaccines were given concomitantly with meningococcal group C conjugate with diphtheria-derived protein CRM(197) as conjugate protein (MCC-CRM) compared with meningococcal group C conjugate with tetanus toxoid as conjugate protein (MCC-TT). For group C meningococcus, the proportion of infants with serum bactericidal antibody (SBA) titre > or =1:8 in the Pediacel group was 99.0% compared with 100% in the DTwP-Hib group. The MCC SBA geometric mean titre (GMT) was lower in those receiving Pediacel with MCC-TT than in those receiving DTwP-Hib with MCC-TT, although all titres were well above the protective threshold. The MCC SBA GMT was similar in those receiving Pediacel and DTwP-Hib and MCC-CRM. Responses to all other vaccine components were equivalent in the two groups. CONCLUSIONS: Pediacel is immunogenic when given at 2, 3 and 4 months of age. Coadministration of MCC vaccine can influence the Hib response, and the MCC response to a tetanus conjugate can be influenced by the nature of the coadministered DTP-Hib vaccine.

Diphtheria-Tetanus-Pertussis Vaccine↗

Immunogenicity of one, two or three doses of a meningococcal C conjugate vaccine conjugated to tetanus toxoid, given as a three-dose primary vaccination course in UK infants at 2, 3 and 4 months of age with acellular pertussis-containing DTP/Hib vaccine.

Reduction of the number of injections necessary to confer protection in the infant schedule would reduce discomfort, improve cost-effectiveness and create space for the addition of new vaccinations in the future. This study assessed the immunogenicity of one, two or three doses of meningococcal C conjugate vaccine conjugated to tetanus toxoid (MCC-TT) [Neis-VacC] given concomitantly with a combined diphtheria/tetanus/acellular pertussis/Haemophilus influenzae type b -TT conjugate (DTaP-Hib-TT) [Infanrix-Hib] vaccine at 2, 3 and 4 months of age. A total of 106 healthy UK infants were enrolled and randomised into two groups, one in which blood was taken after the first and third dose and the other after the second and third dose. The meningococcal serogroup C serum bactericidal antibody (SBA) geometric mean titre (GMT) rose significantly from post-first dose (491, 95% CI 275, 877) to post-second dose (1052, 95% CI 774, 1433) (p=0.03), with no significant change after the third dose (1024, 95% CI 768, 1366). An SBA titre of >or=8 was achieved by 92% after the first dose and 100% after the second and third doses. The Hib IgG geometric mean concentration (GMC) rose significantly after each dose: post-first (0.14 microg/ml 95% CI 0.10, 0.18), post-second (0.54 microg/ml, 95% CI 0.33, 0.90), post-third (2.04 microg/ml, 95% CI 1.52, 2.74). The Hib GMC after the third dose was higher than reported previously when this DTaP/Hib was given either on its own or concomitantly with a MCC-CRM conjugate vaccine according to the UK 2, 3 and 4 month schedule. This suggests some enhancement of the response to a Hib-TT vaccine by concomitant administration of MCC-TT. These results suggest that a reduced number of doses of MCC-TT would be adequate in infancy if given concomitantly with an acellular pertussis-containing vaccine.

Antibodies, Bacterial↗

DT5aP-Hib-IPV and MCC vaccines: preterm infants' response to accelerated immunisation.

AIMS: To describe the immune response of preterm infants to combined diphtheria/tetanus/5 component acellular pertussis-Haemophilus influenzae type b inactivated polio vaccine (DT5aP-Hib-IPV) and meningococcal serogroup C conjugate vaccine (MCC) under accelerated schedule. To compare results with term infants immunised with DT5aP-Hib-IPV and with historical data from preterm infants immunised with a DT3 component aP-Hib vaccine. METHODS: Prospective observational study in preterm infants born at <32 weeks gestation with comparison to contemporary cohort of term infants. DT5aP-Hib-IPV and MCC vaccines were given at 2, 3, and 4 months. RESULTS: Fifty preterm infants (mean gestational age 28.5 weeks) completed the study. After three doses of vaccines Hib polysaccharide IgG geometric mean concentration (GMC) was 1.21 microg/ml with 80% > or =0.15 microg/ml; MCC serum bactericidal assay geometric mean titre (GMT) was 1245 with 100% > or =8. All infants achieved protective titres to diphtheria, tetanus, and the three poliovirus types with > or =80% achieving protective rises in IgG against the five pertussis antigens. CONCLUSION: Preterm infants immunised with DT5aP-Hib-IPV and MCC vaccines show IgG responses to Hib and MCC greater than seen historically in both term and preterm infants with a DT3aP-Hib vaccine, and for pertussis antigens and poliovirus type 1 responses similar to that seen in term infants immunised with DT5aP-Hib-IPV. Responses to poliovirus types 2 and 3 are reduced, but all infants achieved protective titres.

Antibody Formation↗

Responses to a fourth dose of Haemophilus influenzae type B conjugate vaccine in early life.

OBJECTIVE: To describe the immune response of preterm infants, with a reduced response to primary Haemophilus influenzae type B (Hib) immunisation, to a fourth dose of Hib conjugate vaccine given in early life. DESIGN: Prospective observational study. SETTING: Five Wessex Neonatal Units. PATIENTS: Infants born at < 32 weeks and immunised with three doses of combined acellular pertussis-Hib vaccine, with a Hib IgG geometric mean concentration (GMC) < 1.0 microg/ml after these primary immunisations. INTERVENTIONS: An additional fourth dose of Hib conjugate vaccine given before 1 year of age. Blood taken to assess Hib IgG concentration and avidity after immunisation. MAIN OUTCOME MEASURES: Hib IgG GMC and avidity index. RESULTS: Ninety six infants (mean gestational age at birth 29.1 weeks) received a fourth dose of Hib at a mean age of 7.8 months. Hib IgG GMC after the primary immunisations was 0.17 microg/ml (95% confidence interval (CI) 0.14 to 0.20) rising to 4.68 microg/ml (95% CI 3.36 to 6.57) after the fourth dose (p < 0.0001). The IgG response to the fourth dose correlated positively with the response after the primary immunisations (p < 0.001). Hib IgG geometric mean avidity index (GMAI) after the primary immunisations was 30.87 (95% CI 20.40 to 46.73). This increased to 124.73 (95% CI 109.93 to 141.51) after the fourth dose (p < 0.0001). CONCLUSION: Preterm infants with very low IgG responses to Hib after primary immunisations with a combined acellular pertussis-Hib vaccine mount a good response to a fourth dose of Hib. This study suggests that all infants will benefit from a fourth dose of Hib, regardless of the age at which it is given.

Haemophilus Infections↗

Acellular pertussis vaccine given by accelerated schedule: response of preterm infants.

OBJECTIVE: To describe the immune response of preterm infants to a diphtheria/tetanus/three component acellular pertussis (DTaP) vaccine, under an accelerated schedule, and the effects of steroids on this response. To compare responses with those of term infants. DESIGN: Prospective observational study. SETTING: Five Wessex neonatal units; Hertfordshire immunisation clinics. PATIENTS: Infants born at < 32 weeks; term controls. INTERVENTIONS: DTaP-Haemophilus influenzae type b vaccine given at 2, 3, and 4 months. Blood taken to assess antibody responses to vaccines. MAIN OUTCOME MEASURES: IgG geometric mean concentrations (GMC) to vaccines. RESULTS: A total of 130 preterm (mean gestational age 29.1 weeks) and 54 term infants were recruited. After the third immunisation, preterm infants had similar GMCs to controls to diphtheria, tetanus, filamentous haemagglutinin (FHA), and pertactin (PRN), but a significantly lower GMC to pertussis toxin (PT). Responses to tetanus and PRN increased with age at the third immunisation, and those to tetanus, FHA, PRN, and PT increased with gestational age at birth. Response to tetanus correlated negatively with the number of doses of antenatal steroids received. There was no association between responses and postnatal steroids. CONCLUSION: When immunised with a combined acellular pertussis- H influenzae type b vaccine under an accelerated schedule, IgG GMC of preterm infants to PT was reduced. GMCs to tetanus, FHA, PRN, and PT increased with gestational age at birth, and GMCs to tetanus and PRN increased with age at the third immunisation. There is, however, no benefit in delaying immunisation. Anti-tetanus IgG decreased with increasing number of doses of antenatal steroids. There was no effect for postnatal steroids.

Age Factors↗

Immune response of premature infants to meningococcal serogroup C and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus influenzae type b conjugate vaccines.

To determine the immune response of premature infants to meningococcal serogroup C capsular polysaccharide (MCC) and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus influenzae type b (DTaP-Hib) conjugate vaccines, 105 infants born at <32 weeks' gestation had Hib IgG geometric mean concentrations (GMCs) and MCC serum bactericidal antibody (SBA) geometric mean titers (GMTs) measured 1 month after the third immunization. Term infants served as control subjects. Premature infants had Hib GMCs of 0.27 microg/mL, with 21% achieving GMCs >1.0 microg/mL, compared with 0.81 microg/mL and 46% in term infants (P<.001 and P=.003, respectively). The MCC SBA GMT was 398, with 99% achieving an SBA > or =8, compared with 380 and 98% in term infants (P=.84 and P=1.0, respectively). Hib IgG was associated with age at third immunization (P<.001). When combined with the DTaP vaccine used in this study, the Hib GMC of premature infants was extremely low. The SBA GMT to MCC was similar to that of term infants.

Antibodies, Viral↗

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↗

Comparison of antibody kinetics following meningococcal serogroup C conjugate vaccine between healthy adults previously vaccinated with meningococcal A/C polysaccharide vaccine and vaccine-naïve controls.

Few data are available on the kinetics of meningococcal serogroup C-specific antibody production following meningococcal serogroup C conjugate (MCC) vaccination, particularly in those who have received prior meningococcal A/C polysaccharide (MACP) vaccination(s). Laboratory staff who had previously received either one dose (n = 35), two doses (n = 18) of MACP vaccine or who were naïve to previous meningococcal vaccination (n = 42) were vaccinated with MCC. Bloods were taken pre-vaccination, on the subsequent 4 days and on days 10 and 28. Serogroup C serum bactericidal antibody (SBA), and anti-serogroup C-specific IgG, IgM and IgA were measured. There were no significant differences between the groups who had received either 2 or 1 prior dose(s) of MACP, therefore, these results were combined. Up to day 4 there was no evidence of a significant increase or decrease in the median levels of SBA, IgG, IgM or IgA in either the naïve or MACP groups, although about 20% of individuals did have 4-fold SBA rises by day 4. By day 10 there were large significant increases in the levels of SBA, IgG, IgM and IgA with respective fold increases from pre-vaccination levels of 4.6, 1.9, 1.2 and 2.1 in the MACP group and 270, 13.4, 4.8 and 33.8 in the naïve group. Further significant increases were seen between day 10 and 28 for SBA, IgG and IgM (naïve group only). By day 28, 4-fold SBA rises had occurred in 63.5% of the MACP group and 97.6% of the naïve group. The SBA GMT on day 28 significantly differed between the naïve and MACP groups with GMTs 2.8-fold higher in the naïve group (P = 0.021). In conclusion, no decline in serogroup C-specific antibody levels was demonstrated immediately post-MCC vaccination whilst these levels had risen significantly by day 10. Putative protective SBA titres (> or =8, 32 or 128) were observed by day 10 following MCC vaccination regardless of MACP history.

Adult↗

Isolation and characterization of a novel type of neurotoxic peptide from the venom of the South African scorpion Parabuthus transvaalicus (Buthidae).

The venom of the South African scorpion Parabuthus transvaalicus was characterized using a combination of mass spectrometry and RP-HPLC separation and bioassays. The crude venom was initially separated into 10 fractions. A novel, moderately toxic but very high abundance peptide (birtoxin) of 58 amino-acid residues was isolated, identified and characterized. Each purification step was followed by bioassays and mass spectroscopy. First a C4 RP-HPLC column was used, then a C18 RP Microbore column purification resulted in > 95% purity in the case of birtoxin from a starting material of 230 microg of crude venom. About 12-14% of the D214 absorbance of the total venom as observed after the first chromatography step was composed of birtoxin. This peptide was lethal to mice at low microgram quantities and it induced serious symptoms including tremors, which lasted up to 24 h post injection, at submicrogram amounts. At least seven other fractions that showed different activities including one fraction with specificity against blowfly larvae were identified. Identification of potent components is an important step in designing and obtaining effective anti-venom. Antibodies raised against the critical toxic components have the potential to block the toxic effects and reduce the pain associated with the scorpion envenomation. The discovery of birtoxin, a bioactive long chain neurotoxin peptide with only three disulfide bridges, offers new insight into understanding the role of conserved disulfide bridges with respect to scorpion toxin structure and function.

Amino Acid Sequence↗

A & E nursing and the Internet.

The Internet is a relatively new addition to the world of information technology which can be incorporated for use in Accident & Emergency (A & E) nursing, It can provide an information resource and a communications tool for helping A & E nurses in their work. This paper explains the Internet for novices. It discusses the requirements for accessing it and how it can be used by A & E nurses. The aim of the paper is to inform, stimulate and encourage A & E nurses who know little about the Internet to adopt it into their nursing practice.

Computer Communication Networks↗

Slime production, adherence and hydrophobicity in coagulase-negative staphylococci causing peritonitis in peritoneal dialysis.

Attachment of coagulase-negative staphylococci to plastic surfaces by means of hydrophobic interaction and slime production may be important in producing catheter associated infections. In continuous ambulatory peritoneal dialysis (CAPD), the relationship between these properties and disease is unclear and the effect of dialysate fluid is not considered. For a collection of coagulase-negative staphylococci from CAPD patients, slime production and adherence were measured by colorimetric methods and hydrophobicity was determined by autoaggregation in ammonium sulphate solution. Comparison of 73 nasal isolates with 69 isolates from peritonitis showed no significant differences with respect to three properties, with the exception of a greater adherence of peritoneal isolates in dialysate because of a greater proportion of staphylococcal species other than Staphylococcus epidermidis. Fewer strains showed adherence in dialysate (12/142 8.5%) than in broth (94/142 66%) but the proportion of strains producing slime was similar. The milieu of the bacteria rather than the organisms themselves may be of greater importance in the establishment of infection.

Bacterial Adhesion↗

Pathology of fatal perioperative myocardial infarction: implications regarding pathophysiology and prevention.

The aim of this study was to determine the pathology of fatal postoperative myocardial infarction (MI) and compare it with that of non-operative myocardial infarction. Histopathological analyses of coronary arteries and myocardium were performed on autopsy heart specimens (n = 67), and clinical attributes were studied. Findings of perioperative MI (n = 42) were compared to those of non-perioperative MI (n = 25). Significant atherosclerotic obstruction (> 50% cross-sectional narrowing) was observed in the majority of patients (93%). Left main (> 50% cross-sectional narrowing) and/or three-vessel coronary artery disease were especially common (44%) in this group. Evidence of unstable plaques with disruption was noted in 55% of perioperative MI patients (n = 23); plaque hemorrhage was found in 45% (n = 19). Predicting the site of infarction based on severity of underlying stenosis would have been unsuccessful in more than half the patients in both perioperative and nonoperative MI groups. Clinical profiles of the patients in the two groups were similar in terms of prior cardiac history, gender and age. Fatal perioperative MI occurs predominantly in patients with multivessel coronary disease, especially left main and three-vessel disease. The severity of preexisting underlying stenosis did not predict the resulting infarct territory. Evidence of acute plaque disruption in the infarct-related artery is common. Perioperative MIs have similar coronary artery pathology to non-operative MIs with regard to coronary plaque hemorrhage, rupture, and thrombus formation and probably occur by a similar mechanism.

Aged↗

Myocardial adaptation during and after sustained, demand-induced ischemia. Observations in closed-chest, domestic swine.

BACKGROUND: We tested the hypotheses that prolonged, demand-induced myocardial ischemia plateaus and that on relief of stress, myocardial function remains depressed, with proportionate reductions in blood flow and oxygen consumption indicative of hibernation. METHODS AND RESULTS: Closed-chest swine (n = 20) were prepared with an 80% coronary stenosis. Hemodynamics, myocardial blood flow, oxygen, and lactate metabolism were measured in group 1 (n = 9) (1) at baseline, (2) at 10 and 30 minutes of atrial pacing plus intravenous norepinephrine infusion, and (3) in 5 of 9 (group 1a) at approximately 50 minutes after stress. Group 1a had ischemia assessed with 99mTc-labeled BMS 181321. In group 2 (n = 11), myocardial function was determined with radionuclide ventriculography (n = 8), and myocardial necrosis was looked for with trichlorotetrazolium chloride staining (n = 7), histology (n = 10), and myocardial creatine kinase concentration (n = 4). Baseline stenotic-zone endocardial blood flow was reduced versus the normal zone (0.94 +/- 0.33 versus 1.38 +/- 0.27 mL.min-1.g-1, mean +/- SD; P < .05), whereas epicardial flows were comparable (1.15 +/- 0.36 versus 1.16 +/- 0.26 mL.min-1.g-1). Stenotic-zone endocardial flow was unchanged versus baseline at 10 and 30 minutes of stress, whereas epicardial flow increased (1.62 +/- 0.53 mL.min-1.g-1 at 10 minutes and 1.44 +/- 0.51 mL.min-1.g-1 at 30 minutes, both P < .05). Myocardial oxygen consumption increased versus baseline (10.8 +/- 2.9 mL.min-1.100 g-1) at 10 and 30 minutes of stress (14.9 +/- 5.2 and 13.9 +/- 4.5 mL.min-1.100 g-1, both P < .05). After stress, stenotic-zone blood flow and oxygen consumption were reduced approximately 30% (P < .01) versus baseline. In group 2, stenotic-zone contraction with stress declined versus baseline and remained depressed throughout recovery. Histological and biochemical evidence of myocardial necrosis was absent in group 2. CONCLUSIONS: Myocardial ischemia induced by a sustained increase in oxygen demand may not progress to necrosis but may instead plateau. After relief of stress, myocardial function remains depressed, with a proportionate reduction in blood flow and oxygen consumption consistent with myocardial hibernation.

Animals↗

Cyst fluid analysis in the differential diagnosis of pancreatic cysts: a new approach to the preoperative assessment of pancreatic cystic lesions.

Pancreatic cysts include pseudocysts, serous tumors, and mucinous tumors, some of which are malignant. The clinical and radiologic features of these lesions may not permit a preoperative diagnosis. Analysis of percutaneous cyst fluid aspirates for cytologic findings, tumor markers, enzymes, and viscosity has been proposed as an aid to differential diagnosis. The combination of cytologic findings, carcinoembryonic antigen level, and viscosity will usually differentiate mucinous from nonmucinous cysts, whereas cytologic findings and levels of tumor markers CA 15-3 and CA 72-4 are useful to predict malignancy. Pseudocysts can be identified by a combination of cytologic features; levels of tumor markers, including NB/70K; and levels of enzymes, including amylase isoenzymes and leukocyte esterase. Serous tumors are a diagnosis of exclusion, although in 50% of cases the cytologic findings will indicate a serous tumor. When compared with conventional methods of differentiating pancreatic cysts, cyst fluid analysis is a promising new approach to the evaluation of these diagnostically difficult lesions.

Amylases↗