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↗
Biomedical subjects
A Hodgson
Publications and source records attributed to A Hodgson.
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↗
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↗
Factors affecting the in vitro dissolution of cobalt oxide.
In a recent interspecies comparison of the lung clearance of cobalt oxide (57Co3O4), differences of up to 4-fold were found in the translocation rates of 57Co to blood between seven different animal species, including man. This study investigated some factors that could influence the dissolution of this material in vitro. The effect of bicarbonate and citrate concentrations (over physiological ranges) and medium pH on in vitro dissolution of 57Co from 57Co3O4 particles was measured in a simple noncellular system. pH levels of 4.5, 6.1, and 7.2 were used to correspond to those in the alveolar macrophage lysosome, its cytoplasm, and the extracellular lung fluid. Measurements of the fractional dissolution rate were made weekly for 3 months. pH had the greatest effect on dissolution rates, with particles suspended in the lowest pH medium (4.5) dissolving at a significantly faster rate than at higher pH values. Increasing citrate concentrations resulted in slightly higher dissolution rates, but there was no effect of bicarbonate concentration. There was no evidence of synergism between the factors studied.
Antacids↗
Effect of bronchopulmonary lavage on lung retention and clearance of particulate material in hamsters.
Hamsters were exposed to an aerosol of fused aluminosilicate particles (FAP) labeled with 57Co. Three groups of animals were given bronchopulmonary lavage, beginning at either 1 week, 1 month, or 6 months after exposure. Each treated group was lavaged eight times over a period of 25 days. Each lavage involved 10 saline washes of the lungs. For each group, about 60-70% of the body content of 57Co at the start of lavage treatment was removed; nearly half of this was recovered in the first two lavages. A positive correlation was demonstrated between the macrophage content and 57Co activity of the washings. The subsequent fractional clearance rate of 57Co from lavaged animals was not significantly different from that in a group of untreated control animals.
Aerosols↗
Involvement of cellular division cycle in the susceptibility of Escherichia coli to cold- and osmotic-shock.
Susceptibility of Escherichia coli to cold-shock, osmotic-shock and cold-osmotic-shock has been evaluated throughout the cellular division cycle for a variety of generation time. Two periods of sensitisation were detected. The first of these was towards cold-shock which occurred 60 min prior to cell division and might correspond to initiation of DNA replication. The second period of sensitisation was towards both cold-, osmotic- and cold-osmotic-shock and occurred immediately prior to and during cell division. Patterns and extents of sensitisation towards each of these three stresses during the second period were suggestive of a common sensitising event associated with constriction of the cell and separation.
Cell Cycle↗
The efficacy of DFO-HOPO, DTPA-DX and DTPA for enhancing the excretion of plutonium and ameriicum from the rat.
A hydroxypridinone derivative of desferrioxamine (Na-DFO-HOPO), a dihydroxamic derivative of diethylenetriaminepenta-acetic acid (ZnNa-DTPA-DX), and DTPA (CaNa3- and ZnNa3-DTPA) were tested at dosages of 30 mumol kg-1 for their ability to remove 238Pu or 241Am from rats after their intravenous injection as citrate or inhalation as nitrate. The most effective treatment regimen for injected Pu was the repeated administration of DFO-HOPO; by 7 days the body content was reduced to 8% of that in untreated animals. Repeated dosages of 3 mumol kg-1 DFO-HOPO were as effective as those of 30 mumol kg-1 DTPA. After inhalation of Pu nitrate, repeated treatment with DTPA, DTPA-DX or DFO-HOPO reduced the body content by 7 days to, respectively, 10, 15 and 31% of those in untreated animals. After inhalation of Am, DTPA-DX and DTPA were equally effective, the body contents being reduced to 7% of control values with repeated treatment. Injection of DFO-HOPO was ineffective for enhancing the elimination of inhaled or injected Am. The results confirm the strategy of examining the use of siderophore analogues for the decorporation of Pu or Am. However, at present DTPA should remain the agent of choice, particularly after inhalation.
Administration, Inhalation↗