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Biomedical subjects

D Wood

Publications and source records attributed to D Wood.

At least 19 recordsLinked to original sources
PubMed1992

Paralytic poliomyelitis in England and Wales, 1985-91.

OBJECTIVES: To ascertain all cases of paralytic poliomyelitis in England and Wales during 1985-91 and to determine the source of infection in each case. DESIGN: Descriptive study of cases reported between 1985 and 1991. SETTING: All health districts in England and Wales. SUBJECTS: Patients normally resident in England and Wales whose clinical features were consistent with paralytic poliomyelitis or with laboratory evidence of recent poliovirus infection and compatible symptoms. MAIN OUTCOME MEASURES: Clinical, epidemiological, and laboratory features in identified cases. RESULTS: Of 54 suspected cases of poliomyelitis, 33 were excluded, leaving 21 cases, of which 13 were vaccine associated (nine recipient and four contact) cases, five were imported cases, and three were cases whose source of infection was unknown. No cases due to indigenous wild polioviruses were identified; two were imported cases due to wild viruses. One patient died during the acute phase of the illness, and two children with previously unrecognised severe congenital immune deficiency died between one and two months after the onset of paralysis after the first or second dose of oral polio vaccine. The estimated risk of vaccine associated paralysis is 1.46 per million for the first dose, 0.49 for the second, zero for the third and fourth doses, and 0.33 for the fifth. CONCLUSIONS: Indigenous wild poliovirus seems to have been eradicated, although wild virus may be imported; improved surveillance of suspected cases including immediate notification and characterisation of the virus to ensure that eradication is maintained is essential.

Adolescent↗
PubMed1992

A phase I pharmacokinetic study of recombinant human tumor necrosis factor administered by a 5-day continuous infusion.

Nineteen patients with advanced cancer were entered into a phase I clinical trial of Tumor Necrosis Factor (TNF) which was designed to determine the pharmacokinetic profile, safety, and maximal tolerated dose (MTD) of the recombinant human cytokine in vivo. TNF was administered by continuous infusion for 24 hours followed by pharmacokinetics and a 120-hour infusion repeated every 3 weeks. The initial dose was 40 micrograms/m2 and was ultimately escalated to 200 micrograms/m2. A total of forty 5-day cycles were administered to 18 of these patients; and all were evaluable for toxicity. Toxicities in this trial included fever, chills, rigors, hypotension, headaches, seizures, lethargy, weight loss, and malaise. At all dose levels, but more significantly at the highest doses, hematological toxicities were observed and grade 3 neurotoxicity (headache and confusion), and hypotension were noted. Two patients expired during the study, and this was felt to be related to septic episodes. Because of these severe toxicities, 160 micrograms/m2 was defined as the MTD. At 160 micrograms/m2 peak serum levels occurred within 5-20 minutes of initiation and were not detectable 1 hour later. No anti-tumor responses were observed. No measurable plasma levels of TNF were observed with the administration of doses of 80 micrograms/m2. This dose level could be further studied in phase II studies alone and in combination with other agents, utilizing a continuous infusion schedule.

Adenocarcinoma↗
PubMed1992

Immunogenicity and antigenicity of chimeric picornaviruses which express hepatitis A virus (HAV) peptide sequences: evidence for a neutralization domain near the amino terminus of VP1 of HAV.

We evaluated the antigenic characteristics of chimeric picornaviruses created by inserting peptide sequences from hepatitis A virus (HAV) capsid proteins into the B-C loop of VP1 of Sabin strain type 1 poliovirus (PV-1). Fifteen viable chimeras were generated. Each retained the ability to be neutralized by polyclonal PV-1 antisera. Two chimeras (H15 and H2) stimulated production of low levels of HAV neutralizing antibodies in immunized rabbits or mice, although in both cases only a small fraction of immunized animals produced this response. The H15 chimera, which contains residues 13-24 of HAV VP1, elicited HAV neutralizing antibodies in three of nine rabbits and at least one of seven immunized mice. These results indicate that a neutralization domain exists in this region of VP1. However, human sera with high titers of antibodies to HAV failed to neutralize or immunoprecipitate this chimera, suggesting the absence of a significant antibody response to this neutralization domain following natural infection. Sera from rabbits immunized with H15 that did not develop HAV neutralizing antibodies contained antibodies reactive with the HAV peptide segment expressed by the H15 virus, indicating substantial differences in the specificities of antibodies elicited by this peptide segment among individual immunized rabbits. The H15 peptide insert was an effective antigen, as indicated by a high level of sensitivity of the H15 chimera to neutralization by a related anti-peptide antibody which was itself devoid of HAV neutralizing activity. One of 16 rabbits immunized with the H2 chimera (residues 101-108 of HAV VP1) developed HAV neutralizing antibodies, confirming both the presence and the highly conformational nature of a neutralization antigenic site involving these residues of HAV.

Amino Acid Sequence↗
PubMed1992

Prenatal prediction of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a common cause of inherited morbidity and mortality in childhood. The wide range of phenotypes in SMA, uncertainty regarding its mode of inheritance, and the suggestion of linkage heterogeneity have complicated the genetic counselling of parents of affected children. The locus responsible for autosomal recessive SMA has been mapped to 5q11.2-q13.3. The most likely order of loci is cen-D5S6-(SMA,D5S125)-(JK53CA1/2,D5S112)-D5S3 9-qter, with highly polymorphic loci being identified at JK53CA1/2 and D5S39. We describe linkage studies with another highly polymorphic locus, D5S127, that is closely linked to D5S39. This genetic map can be used as the basis for genetic counselling in families with autosomal recessive SMA. Appropriate allowance can be made for sporadic cases owing to non-inherited causes and for linkage heterogeneity or misdiagnoses.

Base Sequence↗
PubMed1991

Can infant death from child abuse be prevented?

OBJECTIVE: To assess the effectiveness of a child abuse surveillance and intervention program in protecting infants at risk. DESIGN AND SETTING: A retrospective review of all children discussed by the Suspected Child Abuse and Neglect Team of the Mater Misericordiae Children's Hospital, South Brisbane, over the five year period January 1986 to December 1990. PATIENTS: A total of 2126 children were discussed by the team; 375 were infants (less than 12 months of age) at the time of the initial discussion. Nine infants died suddenly and these nine deaths were examined in detail. RESULTS: All deaths were considered initially to be due to sudden infant death syndrome (SIDS), but autopsy findings in six suggested death was not accidental and in the other three significant doubt was raised by the history. Identifying risk factors for non-accidental injury were clearly present in all cases; however, there were major problems with notification to the appropriate authorities. Even in cases where appropriate identification and notification occurred planned interventions by multiple agencies failed to prevent death of these infants. CONCLUSIONS: There is a growing awareness of child abuse as a significant cause of morbidity and mortality in developed countries, but intervention is fraught with multiple difficulties and prevention programs are few. Recommendations are offered for improvement in recognition and notification of incipient child abuse as well as appropriate interventions to prevent infant deaths. Inappropriate death recording procedures may result in some sudden deaths being recorded as SIDS when in fact they are caused by child abuse.

Cause of Death↗
PubMed1991

Barriers to medical care for homeless families compared with housed poor families.

To evaluate health access and health services utilization of homeless families we selected a systematic sample of 194 homeless families from 10 shelters in Los Angeles and 196 housed poor families from the same geographic regions of Los Angeles selected from welfare offices. Both samples relied primarily on Medicaid for their health insurance (61% and 96%). However, more homeless families than housed poor families were currently uninsured (26% vs 2%), had lost health insurance over the past year (50% vs 21%), and had spent a greater percentage of the past year uncovered by health insurance (22% vs 6%). Homeless families were much less likely to report a regular provider for preventive care (81% vs 94%) or for sick care (72% vs 95%). Moreover, of those reporting a regular provider, homeless families were more likely than housed poor families to use emergency departments or clinics rather than private offices for both preventive care (35% vs 15%) and sick care (37% vs 26%). Barriers to health care more frequently prevented homeless families from obtaining care (38% vs 28%). These findings suggest that homeless families have greater problems of access to health care than other poor families, related to lack of insurance, lack of a regular primary care provider, and other barriers. Programs to address these barriers for homeless families are presented.

Adult↗
PubMed1991

The GTPase stimulatory activities of the neurofibromatosis type 1 and the yeast IRA2 proteins are inhibited by arachidonic acid.

Three proteins, GTPase activating protein (GAP), neurofibromatosis 1 (NF1) and the yeast inhibitory regulator of the RAS-cAMP pathway (IRA2), have the ability to stimulate the GTPase activity of Ras proteins from higher animals or yeast. Previous studies indicate that certain lipids are able to inhibit this activity associated with the mammalian GAP protein. Inhibition of GAP would be expected to biologically activate Ras protein. In these studies arachidonic acid is shown also to inhibit the activity of the catalytic fragments of the other two proteins, mammalian NF1 and the yeast IRA2 proteins. In addition, phosphatidic acid (containing arachidonic and stearic acid) was inhibitory for the catalytic fragment of NF1 protein, but did not inhibit the catalytic fragments of GAP or IRA2 proteins. These observations emphasize the biochemical similarity of these proteins and provide support for the suggestion that lipids might play an important role in their biological control, and therefore also in the control of Ras activity and cellular proliferation.

Arachidonic Acid↗
PubMed1991

Glass ceramic approach to controlling the properties of a glass-ionomer bone cement.

Glass-ionomer dental cements have potential as bone cements in joint replacement surgery. However, commercially available glasses used in dental cements suffer from the loss of fluorine during the melting procedure and from phase separation of the glass upon quenching, giving rise to inter- and intra-batch variation. A model glass was examined in which minimal loss of fluorine is observed. This results in a glass whose composition is reproducible between batches. This glass will crystallize both above and below the glass transition temperature following heat treatments. Cements can be produced whose properties vary with the degree of crystallinity of the glass-ceramic. A commercial glass was also examined and was found to crystallize to an apatite phase.

Bone Cements↗
PubMed1991

Antigenic structure of chimeras of type 1 and type 3 polioviruses involving antigenic sites 2, 3 and 4.

Chimeric polioviruses have been made in which regions of the type 1 Sabin strain corresponding to antigenic sites 2, 3 and 4 have been replaced by the corresponding regions of the type 3 Sabin strain. Manipulation of one site or a component of it generally did not affect the reactions of the others, suggesting that they form independent structural features. The extent to which the inserted site expressed the antigenic properties of type 3 could be assessed by reaction with polyclonal or monoclonal antibodies, or by immunogenicity. Site 2 could be expressed on infectious virus and site 3 on heated non-infectious virus (C antigen), but not on the native virion. The results are consistent with the view that sites consisting of a continuous sequence of amino acids may be presented on chimeras, whereas more complex sites, such as site 4 or site 3 of the native virion, are transferred less readily from type 3 to type 1.

Amino Acid Sequence↗
PubMed1991

Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose.

1. Healthy humans ingested the dipeptide carnosine (L-beta-alanyl-L-histidine). Their plasma levels and urinary outputs of carnosine and beta-alanine were monitored over the following 5 h. 2. Large amounts of intact carnosine (up to 14% of the ingested dose) were recovered in the urine over the 5 h after ingestion. However, carnosine was undetectable in the plasma unless precautions were taken to inhibit blood carnosinase activity ex vivo during and after blood collection. 3. The amount of carnosine recovered in urine varied substantially between subjects. It correlated negatively with carnosinase enzymic activity in the plasma. Highest carnosinase activities were observed in those subjects who regularly underwent physical training. 4. Urinary recovery of the disaccharide lactulose also varied considerably between subjects, but was substantially lower than that of carnosine. There was no significant correlation between the recoveries of carnosine and lactulose. 5. When lactulose was ingested with a hypertonic solution, the urinary recovery of lactulose was generally increased. When carnosine was ingested with a hypertonic solution, the urinary recovery of carnosine was reduced: hence the paracellular route probably is not dominant for absorption of intact carnosine. 6. Intact carnosine must have crossed the intestine to an extent much greater than hitherto recognized. Rapid post-absorptive hydrolysis is a severe obstacle to quantification of intact peptide absorption.

Adult↗
PubMed1991

The relationship between neuropsychological measures and self-care skills in patients with cerebrovascular lesions.

The present investigation examined the relationship between performance on the Michigan Neuropsychological Battery (MNB) and selected self-care skills in a group of patients with unilateral cerebrovascular lesions. Among MNB measures, left-sided somatosensory and motor functions were the best predictors of self-care skills, showing that in these stroke patients lower level cerebral functions mediated by the right hemisphere are more strongly related to the self-care skills examined than higher cerebral functions. Also, evidence that patients with cerebrovascular lesions in the left hemisphere performed better than patients with right hemisphere lesions in several self-care categories is further indication that right hemisphere processes have a special role to play in the mediation of these self-care activities. The research and clinical implications of these findings are noted.

Activities of Daily Living↗