Childhood refractory autoimmune haemolytic anaemia: is there a role for anti-CD20 therapy (rituximab)?
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Adolescent↗
Biomedical subjects
A Hodgson
Publications and source records attributed to A Hodgson.
A novel and selective approach to enantiomerically pure bicyclic-trans-lactams via a titanium enolate of a thiopyridyl ester.
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Crystallography, X-Ray↗
Survival and sequelae of meningococcal meningitis in Ghana.
BACKGROUND: Meningococcal meningitis epidemics are frequent in the Sahel zone of Africa but there is little information on the frequency of long-term sequelae. We analysed excess mortality in the two years following the 1997 epidemic in northern Ghana and carried out a case-control study to assess sequelae in the survivors. METHODS: Two-year survival of 696 meningitis cases recorded at the War Memorial Hospital, Navrongo, was analysed using data from a demographic surveillance system. A structured questionnaire on disability and on psychiatric, neuropsychological and behavioural problems was administered to 505 of the survivors and 505 age- sex- and location-matched controls as well as to their respective relatives. Cases and controls underwent full neurological and neuropsychological examination and were evaluated for hearing impairment by audiometry. RESULTS: Survival rates after the first month following the attack were similar in cases and controls. Hearing impairment was the major sequela, and was reported in 6 per cent of cases and 2 per cent of controls (odds ratio [OR] = 3.10; 95% CI : 1.48-7.09). Audiometry detected severe and profound hearing loss in the worse affected ear (> or =70 db) in 8/496 (1.6%) survivors but in only one control. Survivors of meningitis were more likely to suffer from feelings of tiredness (OR = 1.47; 95% CI : 1.03-2.11) and were more often reported by relatives to have insomnia (OR = 2.31; 95% CI : 1.17-4.82) and daily alcohol consumption. INTERPRETATION: Meningococcal meningitis annually causes approximately 10 000 cases of deafness in sub-Saharan Africa; there is a need for early detection of affected survivors and promotion of simple hearing devices. There is a sizeable burden of depressive disorders secondary to meningitis which should be identified and looked after appropriately.
Activities of Daily Living↗
Dosimetric models for thorium and practical problems in assessing intakes.
An overview is given of the models recommended by the International Commission on Radiological Protection (ICRP) for assessing intakes and doses, and summarises biokinetic data obtained after the deposition of different chemical compounds of thorium in the rat lung. The results emphasise the importance of using material-specific data rather than default reference values for absorption into blood. The limitations of external monitoring of the chest or urine analysis are discussed, and comments made on alternative strategies for radiological protection of the worker.
Administration, Inhalation↗
An open-label study of the role of adjuvant hemostatic support with protein C replacement therapy in purpura fulminans-associated meningococcemia.
Activated protein C (APC) is a natural anticoagulant that plays a pivotal role in coagulation homeostasis. Severe inherited or acquired deficiency results in a clinical syndrome called purpura fulminans. In addition, APC also appears to have potent cytokine-modifying properties and is protective in animal models of sepsis. The dual functional properties of APC are particularly relevant to severe meningococcemia, where acquired PC deficiency is accompanied by multiorgan failure and purpura fulminans. The authors conducted an open-label prospective study assessing the efficacy of PC replacement therapy in patients with severe meningococcal septicemia, purpura fulminans, and multiorgan failure. The morbidity and mortality were compared with predicted morbidity using the Glasgow Meningococcal Septicemia Prognostic Score. Thirty-six patients with a mean age of 12 years (range 3 months to 72 years) were enrolled in the study. The mean +/- SD for plasma PC was 18 +/- 7 IU/mL. PC was significantly lower than antithrombin or protein S and was also significantly lower than PC levels in a cohort of patients who developed meningococcemia without multiorgan failure and purpura fulminans. A total of 3 of 36 (8%) patients died, which compares favorably with predicted mortality of 18 of 36 (50%). Amputations were required in 4 of 33 (12%) survivors and in 2 of 31 (6.5%) patients who received PC within 24 hours of admission into the hospital, in comparison with the predicted amputation rate of 11 of 33 (30%). In conclusion, PC replacement therapy in severe meningococcal septicemia was associated with a reduction in predicted morbidity and mortality. The beneficial effect of PC replacement may reflect both the anticoagulant and anti-inflammatory properties of the PC pathway. (Blood. 2000;96:3719-3724)
Adolescent↗
Energy disposal during desorption of D2 from the surface and subsurface region of Ni(111).
The recombination of surface and subsurface D atoms on Ni(111) has been studied using resonance-enhanced multiphoton ionisation (REMPI) to measure the internal state and translational energy distributions of the desorbing product. By detecting D2 formed during temperature-programmed desorption we were able to examine the reaction between subsurface and surface D atoms, and the recombination of two D atoms chemisorbed on the surface. Translational energy distributions for D2 formed by recombination of surface D are very sensitive to coverage. Desorption from a low coverage surface produced a translational energy release of 2.6 kT, but a thermal rotational distribution, reflecting an entrance channel barrier to dissociative chemisorption on the clean Ni(111) surface. Sticking probabilities predicted from detailed balance are consistent with molecular beam adsorption measurements. Desorption from D coverages above 0.5 ML resulted in a sub-thermal energy release, desorption being mediated by a molecular precursor state with D2 dissociation occurring via a non-activated, trapping-dissociation channel. In contrast, the reaction of subsurface D produces translationally hot D2, with a mean energy approaching 8 kTs at 180 K. This is consistent with the energetics for direct recombination of a chemisorbed D atom with a metastable subsurface D atom, which overcomes an activation barrier to resurface of between 0.35 and 0.47 eV depending on D concentration. The energy release decreases at higher temperature, probably as a result of a reduction in the energy of resurfacing D as the subsurface D concentration drops. This low energy component is attributed to accommodation of resurfacing D which is unable to react directly, followed by slow thermal desorption via the high coverage, surface D recombination channel. No internal rotational or vibration excitation was found in D2 formed by reaction of subsurface D.
Journal Article↗
An investigation into diet treatment for adults with previously untreated phenylketonuria and severe intellectual disability.
There is evidence in the literature which suggests that adults with previously untreated phenylketonuria (PKU) benefit from a low phenylalanine diet. A prospective study providing a phenylalanine-restricted diet to five subjects with severe intellectual disability arising from untreated PKU is reported. Physical, social and behavioural measures were used to monitor the effects of the diet Four out of the five subjects derived considerable benefit. It is concluded that the restricted diet is worth trying in most individuals with previously untreated PKU, and that possible benefits are in the areas of concentration, alertness, mood, irritability and adaptive behaviour.
Adult↗
A pilot scheme for the development of evidence-based practice.
This article presents an evaluative account of a pilot scheme that aimed to introduce evidence-based practice in one NHS trust. The scheme was based on collaboration between staff in the quality assurance department and a nurse researcher based in a university. This collaboration enabled three designated staff to develop skills required for evidence-based practice and guide the production of information that could be disseminated to nurses throughout the trust. Evaluation demonstrated that participants had examined eight practice-based topics and devised protocols that could be applied to practice in a range of hospital and community settings throughout the trust. Evaluation also highlighted the importance of ensuring that members of other disciplines are aware of, and feel involved in, new developments even if they are not directly concerned with them.
Community Health Nursing↗
Microheterogeneity of serogroup A (subgroup III) Neisseria meningitidis during an outbreak in northern Ghana.
During a meningitis outbreak in the eastern subdistrict of the Kassena-Nankana District of the Upper East Region of Ghana, we analysed cerebrospinal fluid from suspected meningitis cases for the most common causative organisms. In 50 of 92 samples analysed, serogroup A Neisseria meningitidis were detected. The ages of serogroup A N. meningitidis patients ranged from 4 months to 64 years. The case fatality ratio was 20%. Coma or stupor on presentation worsened the prognosis. All serogroup A N. meningitidis isolates recovered revealed the A: 4: P1.9, 20 phenotype characteristic for the subgroup III clonal grouping. No evidence for resistance to penicillin G, chloramphenicol, cefotaxime, ciprofloxacin, rifampicin or tetracycline was found. All strains were resistant to sulphadiazine. Restriction analysis patterns of opa, iga and ingA genes were characteristic for the majority of N. meningitidis serogroup A subgroup III bacteria isolated in Africa after the 1987 epidemic in Mecca. Differences in pulsed-field gel electrophoresis patterns of NheI and SpeI digested DNA revealed microheterogeneity among the Ghanaian isolates.
Adolescent↗
Body mass index: a comparison between self-reported and measured height and weight.
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Adolescent↗
Assessment of physico-chemical and biokinetic properties of uranium peroxide hydrate UO4.
Comprehensive studies on the radiotoxicological risk of an intermediate compound UO4, which is not specified in ICRP Recommendations, were motivated by its increased use in the nuclear fuel cycle and the lack of information such as physico-chemical and biokinetic properties. The aim of this work was to give an experimental basis for assessing the appropriate limits on intake for workers exposed to UO4 and to provide guidance for the interpretation of personal monitoring data. Particle size measurement of the UO4 dust indicated a geometric diameter D of 0.5 microm, which corresponds to an activity median aerodynamic diameter (AMAD) of 1.1 microm. In vitro experiments conducted in culture medium showed that UO4 is a soluble compound with 66.2% dissolved in 1.9 d and 33.8% in 78 d. Results of dissolution obtained with macrophages showed a significant decrease of 50% at 1 d in terms of solubility. Biokinetic data in the rat obtained from two in vivo studies involving intratracheal instillation in rats indicated half-times in the lung of 0.5 d (96.6%) and 27 d (3.4%) for an initial lung deposit (ILD) of 195 microg, and 1.2 d (90.3%) and 38 d (9.7%) for an ILD of 7.6 microg. Absorption parameters to blood as defined in the ICRP Publication 66 human respiratory tract model were calculated with the specific software GIGAFIT and led to the rapid fraction fr (0.800 to 0.873), the rapid rate sr (0.525 to 0.928 d(-1)), and the slow rate ss (1.57 x 10(-2) to 2.42 x 10(-3) d(-1)). Effective dose coefficients by inhalation for this UO4 compound using the in vivo experimental results were calculated to be between 0.52 and 0.70 x 10(-6) Sv Bq(-1). Comparison of these values with effective dose coefficients defined in ICRP Publication 68 for workers showed that UO4 could be considered as a fast soluble compound of Type F.
Animals↗
Fluoride supplement dosage.
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Drug Labeling↗
Priorities for values of adolescents in multicultural schools.
The Rokeach Instrumental Values Survey was used to identify the priorities for instrumental values (desired ways to behave) of 172 adolescents in multicultural schools in Miami, Florida. The data are reported by grade, sex, and ethnicity.
Adolescent↗
Optimising the removal of inhaled plutonium and americium from the rat by administration of ZnDTPA in drinking water.
1. The efficacy of ZnDTPA administered in drinking water has been investigated for removing 238Pu and 241Am from the rat after their simultaneous inhalation as nitrates. 2. The continual administration of ZnDTPA 95 mumol kg-1 d-1 over a 21 d interval commencing 1 h after exposure reduced the 238Pu content of the lungs and total body to 2% and 8% of those in untreated animals; the corresponding values for 241Am were 3% and 5%. 3. The continual intakes of 950 mumol kg-1 d-1, intermittent intakes of 3600 mumol kg-1 d-1 and the repeated injection of 30 mumol kg-1 body weight were considered no more effective. 4. All orally administered concentrations of ZnDTPA, commencing 7 d after exposure, reduced the total body contents of 238Pu and 241Am to 17% and 20% of controls by 28 d. 5. Histopathological examination of the kidneys, liver and gastrointestinal tract showed no apparent effects of these treatment protocols. 6. It is concluded that the oral administration of ZnDTPA could be an effective treatment for the removal of inhaled transportable forms of Pu and Am after human exposure.
Administration, Inhalation↗
Molecular analysis and characterization of a broad-host-range plasmid, pEP2.
Plasmid pEP2 was found to encode a protein, RepA, which is essential and rate limiting for its replication in Escherichia coli and Corynebacterium pseudotuberculosis. Mutations which altered the rate of synthesis of this protein in E. coli affected the copy number and segregational stability of pEP2 in the two hosts. RepA contains 483 amino acid residues and has the calculated molecular weight of 53,925. It shows 45% amino acid residue identity with open reading frame ORF2 of pSR1, a plasmid isolated from Corynebacterium glutamicum (J. A. C. Archer and A. J. Sinskey, J. Gen. Microbiol. 139:1753-1759, 1993). Plasmid pEP2 was shown to accumulate single-stranded DNA corresponding to the RepA coding strand during its replication in E. coli and C. pseudotuberculosis, suggesting that it may replicate by a rolling circle mechanism. However, RepA has no significant sequence homology with the replication initiator proteins of plasmids known to use this mode of replication.
Amino Acid Sequence↗
Removal of inhaled plutonium and americium from the rat by administration of ZnDTPA in drinking water.
This study has examined the efficacy of ZnDTPA administered in drinking water for removing 238Pu and 241Am from the rat after their simultaneous inhalation as nitrates; the dosage used was 95 mumol kg-1d-1. The continuous administration of ZnDTPA over a 14 d interval, commencing 1 h after exposure, reduced the lung and total body contents of 238Pu to, respectively, 11% and 18% of those in untreated rats; the corresponding values for 241Am were 11% and 14%. After the continuous administration of 95 mumol kg-1 from 4 d to 28 d post exposure, the lung and total body contents of 238Pu were, respectively, 5% and 16% of those in controls; the corresponding values for 241Am were 7% and 19%. Further reductions in the actinide contents of body tissues were found when treatment was extended to 52 d or 76 d. These regimens were as effective as twice weekly injections of 30 mumol kg-1 ZnDTPA commencing at 4 d. After the continuous administration of 95 mumol kg-1 d-1 for 72 d, some pathological changes to the gastrointestinal tract were observed but these were considered to be reparable. It was concluded that further work is required to evaluate the toxicity of the ligand and to establish the optimal treatment regimen.
Administration, Inhalation↗
The biokinetics of plutonium-239 and americium-241 in the rat after subcutaneous deposition of contaminated particles from the former nuclear weapons site at Maralinga: implications for human exposure.
As an input to dose assessments, measurements have been made of the clearance of Pu and Am after subcutaneous implantation in rats for six particulate materials and one dust from the Maralinga test sites. The tissue distribution of Pu and Am were measured in groups of six animals at one month and 6 months after implantation. In addition, in vitro solubility tests were carried out on eight different particulate materials. Histological examination of the subcutaneous implantation site was undertaken after one year for selected materials. Autoradiographs of tissue sections showed that particles were surrounded by fibrotic tissue with macrophage and polymorphonuclear cell infiltration, the normal tissue response to foreign materials. The clearance data have been used to make estimates of the likely range in potential radiation doses in humans. To calculate the dose from dissolved 239Pu and 241Am, four different situations have been considered. For the dust, the results suggest that dissolution essentially ceases after the removal of Pu and Am from the surfaces of dust particles. From the values obtained, the acute release of a fraction of 10(-2) of both nuclides from a dust contaminated wound was assumed. For a number of particles the results suggested continued dissolution and the clearance of 10(-3) per year of both nuclides, continuing for a number of years, has therefore been considered. For the least soluble particles, there was no clear evidence of continued clearance and the acute release of 10(-4) has therefore been taken as a lower estimate for dose calculations.(ABSTRACT TRUNCATED AT 250 WORDS)
Americium↗
The efficacies of 3,4,3-LIHOPO and DTPA for enhancing the excretion of plutonium and americium from the rat: comparison with other siderophore analogues.
With DTPA as a comparison, the siderophore analogue code named 3,4,3-LIHOPO has been tested for its ability to remove 238Pu and 241Am from rats after their inhalation or intravenous injection as nitrate. The most effective treatment regimen for inhaled Pu was the repeated administration of 30 mumol kg-1 3,4,3-LIHOPO. By 7 days after exposure, the Pu contents of the lungs and total body were reduced respectively to 2 and 4% of those in untreated animals. These values were six and three times less than when DTPA was administered using the same protocol. For inhaled Am, 3,4,3-LIHOPO and DTPA were considered equally effective, the lung and total body contents being reduced respectively to 13 and 10% of those in controls. Some animals showed slight degenerative changes in the liver and proximal tubules of the kidneys after the repeated administration of 30 mumol kg-1 of 3,4,3-LIHOPO; however these changes were less marked than after DTPA treatment. After the intravenous injection of Pu, the most effective regimen was the single administration of 3 mumol kg-1 3,4,3-LIHOPO. The body content at 7 days was reduced to 7% controls compared with 19% after the repeated administration of 30 mumol kg-1 DTPA. At a dosage of 30 mumol kg-1, 3,4,3-LIHOPO was less effective owing to the higher retention of Pu in the liver. With repeated dosages of 30 mumol kg-1 3,4,3-LIHOPO was more effective than DTPA for the decorporation of Am; the body contents were 16 and 31% of those in controls respectively. Importantly, the body content was still reduced to 28% of control after a single administration of 3 mumol kg-1. The ligand 3,4,3-LIHOPO, which is also superior to other siderophore analogues, could represent a most significant development in the decorporation of Pu and Am.
Administration, Inhalation↗