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Biomedical subjects

R Davenport

Publications and source records attributed to R Davenport.

At least 19 recordsLinked to original sources

West Nile virus encephalitis causing fatal CNS toxicity after hematopoietic stem cell transplantation.

We describe here a patient who died of progressive CNS deterioration following allogeneic stem cell transplant with West Nile virus as the sole pathogen on the cerebrospinal fluid and brain tissue analysis. A 50-year-old male with Philadelphia chromosome-positive acute lymphocytic leukemia (ALL) underwent allogeneic PBSCT from his HLA identical sister. After engraftment, the patient developed fever with progressive and ultimately fatal neurological deterioration. Imaging studies of the brain including CT and MRI scans were remarkable for mild low attenuation lesions of the white matter. CSF analysis was negative for neoplastic cells, bacteria, AFB, CMV, HSV, fungal infections and leukemic relapse. However, serological analysis of both the serum and CSF was positive for West Nile virus-specific IgM antibodies. At autopsy, West Nile virus PCR and cultures were positive in the mid-brain tissue. Electron micrographs showed evidence of viral particles. Given the recent increase in the spread of West Nile virus infections and the increased susceptibility of BMT patients to infectious complications, West Nile virus encephalitis should be considered in patients undergoing transplantation.

Autopsy↗

Congenital lumbar hernias: A case report.

Congenital lumbar hernias are rare and associated with other malformations. There have been 42 cases reported to date. The authors report the first case in the literature of isolated bilateral congenital lumbar hernias.

Hernia↗

A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms.

We describe a map of 1.42 million single nucleotide polymorphisms (SNPs) distributed throughout the human genome, providing an average density on available sequence of one SNP every 1.9 kilobases. These SNPs were primarily discovered by two projects: The SNP Consortium and the analysis of clone overlaps by the International Human Genome Sequencing Consortium. The map integrates all publicly available SNPs with described genes and other genomic features. We estimate that 60,000 SNPs fall within exon (coding and untranslated regions), and 85% of exons are within 5 kb of the nearest SNP. Nucleotide diversity varies greatly across the genome, in a manner broadly consistent with a standard population genetic model of human history. This high-density SNP map provides a public resource for defining haplotype variation across the genome, and should help to identify biomedically important genes for diagnosis and therapy.

Chromosome Mapping↗

Skeletogenesis in sea urchin interordinal hybrid embryos.

Reciprocal interordinal crosses were made between the sea urchins Strongylocentrotus purpuratus and Lytechinus pictus. Previous research indicated that the expression of many L. pictus genes is reduced in the hybrid embryos. The S. purpuratus gene encoding the spicule matrix protein SM50 and the L. pictus gene encoding its orthologue LSM34 were both expressed at normal levels per gene copy in hybrid embryos, and in about 32 skeletogenic primary mesenchyme cells (PMCs) in hybrid and natural gastrulae. In many embryos of all crosses, 16 PMCs initially ingressed, while 32-64 PMCs were present in gastrulae. The skeletal spicules of most hybrid plutei were predominantly like those of S. purpuratus, consistent with the predominance of expression of S. purpuratus genes in hybrid embryos. The spicules of some hybrid plutei showed features characteristic of L. pictus, such as recurrent rods, branched body rod tips, or convergent ventral transverse rods; a few hybrid spicules were predominantly like those of L. pictus. Based on our observations and the literature, we propose the following. Cues from the ectodermal epithelium position the PMCs as they elaborate the initial triradiate spicules. Their orientation and outgrowth appears to be responsible for the convergence of the tips of body rods in most S. purpuratus and hybrid embryos, unlike in most L. pictus embryos. Variations among hybrid and natural embryos in skeletal branching pattern reflect differences in interpretation by PMCs of patterning cues produced by the ectodermal epithelium that probably have similar spatial distributions in the two species.

Animals↗

Single-nucleotide polymorphisms in the public domain: how useful are they?

There is a concerted effort by a number of public and private groups to identify a large set of human single-nucleotide polymorphisms (SNPs). As of March 2001, 2.84 million SNPs have been deposited in the public database, dbSNP, at the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/SNP/). The 2.84 million SNPs can be grouped into 1.65 million non-redundant SNPs. As part of the International SNP Map Working Group, we recently published a high-density SNP map of the human genome consisting of 1.42 million SNPs (ref. 3). In addition, numerous SNPs are maintained in proprietary databases. Our survey of more than 1,200 SNPs indicates that more than 80% of TSC and Washington University candidate SNPs are polymorphic and that approximately 50% of the candidate SNPs from these two sources are common SNPs (with minor allele frequency of > or =20%) in any given population.

DNA↗

Oral health status of second grade school children in upstate New York.

This report summarizes the results of a survey of second grade children conducted in upstate New York. The survey was designed to monitor progress toward achieving Healthy People 2000 objectives and Maternal and Child Health Services Block Grant performance measures. Data on oral health status, use of preventive measures and insurance coverage were collected on 2,474 children from 76 schools. In addition to obtaining population estimates, disparities in oral health between poor and nonpoor children were assessed. The results showed that approximately 52% of second grade children had dental caries, and 35% had untreated disease. Approximately 43% received fluoridated water, and 44% of children living in non-fluoridated areas used fluoride supplements on a regular basis. Only 25% of the children had dental sealants. The percentage of children covered by comprehensive and basic insurance plans was approximately 19% and 41%, respectively. Many of the national oral health objectives were not met primarily because of the higher rate of disease among the poor and their lower use of preventive services. These findings regarding oral health status and use of preventive services are similar to the national data.

Child↗

Protein kinase C-mediated changes in synaptic efficacy at the neuromuscular junction in vitro: the role of postsynaptic acetylcholine receptors.

Activation of a mouse in vitro neuromuscular synapse produces a reduction in synaptic efficacy which is greater for nonactivated than for activated inputs to the myotubes. This has been shown to require thrombin and thrombin receptor activation and to involve a protein kinase C (PKC)-mediated step. We show in the present work that phorbol ester activation of PKC produces physiological loss of synapses in a time- and dose-related manner. We observe, using quantitative imaging methods, a parallel loss of acetylcholine receptors (AChR) from synaptically functional neurite-associated receptor aggregates in nerve-muscle cocultures. Biochemical measurements of total AChR show that PKC activation reduces both AChR stability (increases receptor loss) and receptor insertion into the surface membrane. Taken together, the data suggest that PKC activation decreases the stability of AChR aggregates in the muscle surface membrane. We conclude that PKC plays a crucial role in activity-dependent synapse reduction and does so, at least in part, by altering AChR stability.

Animals↗

Neurological emergencies: acute stroke.

Stroke causes a vast amount of death and disability throughout the world, yet for many healthcare professionals it remains an area of therapeutic nihilism, and thus uninteresting. This negative perception is shared by the general public, who often have a poor understanding of the early symptoms and significance of a stroke. Yet within the past few years there have been many important developments in the approach to caring for stroke patients, for both the acute management and secondary prevention. After the completion of numerous clinical trials, there is now robust evidence to either support or discredit various interventions. Even more exciting is the prospect of yet more data becoming available in the near future, testing a whole array of treatments, as clinical interest in stroke expands exponentially. In this review an evidence based approach to the management of acute stroke within the first few days is presented, including ischaemic and haemorrhagic events, but not subarachnoid haemorrhage. It is explained why stroke is regarded as a medical emergency, and the importance of a rational, methodic approach to the initial assessment, which is the key to accurate diagnosis and subsequent management, is emphasised. The potential early problems associated with stroke are identified and specific interventions for different stroke types are discussed. The review ends with a brief discussion of the implications that the evolving treatments have for the organisation of modern stroke services.

Acute Disease↗

Use of a neonatal blood pressure cuff to monitor blood pressure in the adult finger--comparison with a standard adult arm cuff.

BACKGROUND: There are few suitable methods for monitoring blood pressure continuously (or intermittently) for research in adult stroke patients, who are ill but do not justify invasive intensive care monitoring. METHOD: We tested a neonatal arm blood pressure in adults by placing it on the forefinger ("finger cuff"). We compared the repeatability of the finger cuff with blood pressure measured by a standard adult arm cuff using the oscillometric technique in 168 ambulatory outpatients attending a cerebrovascular disease clinic. RESULTS: The mean difference between sequential mean blood pressure readings with the finger cuff was 0.55 mm Hg (95% confidence interval (CI) -14.36 to 15.47 mm Hg), and for the arm cuff was 3.31 mm Hg (95% CI -23.33 to 16.71 mm Hg). Measurements made with the arm cuff were shown to affect subsequent arm cuff readings made within a few minutes of the first. The mean difference between the finger cuff and arm cuff mean blood pressure readings was 0.03 mm Hg (95% CI -26.07 to 26.14 mm Hg) and agreement was better when the blood pressure was measured with the finger cuff first rather than the arm cuff. However, although there was no difference in the mean blood pressure recordings both systolic and diastolic blood pressure measurements differed systematically between arm and finger cuff. CONCLUSION: The reproducibility of sequential blood pressure measurements made with the finger cuff was better than with the arm cuff. The performance of the finger cuff compared with that of the arm cuff was sufficiently good to encourage use of the finger cuff in research involving automatic intermittent monitoring to observe sequential blood pressures over time in stroke patients. However, measurements of systolic and diastolic pressure were not the same with the two cuffs and further work on calibration of the finger cuff would be useful.

Adolescent↗

Removal of soluble biologic response modifiers (complement and chemokines) by a bedside white cell-reduction filter.

BACKGROUND: Biologic response modifiers infused with stored platelet concentrates (PCs) are believed to contribute to symptoms seen during transfusion reactions. Although prestorage white cell reduction is known to decrease the production of some biologic response modifiers during storage, the possibility that poststorage (bedside) white cell reduction could reduce the amount of biologic response modifiers already present in stored PCs during bedside filtration has not been well studied. STUDY DESIGN AND METHODS: Individual PCs were pooled on storage Days 2 and 5 and passed through a third-generation white cell-reduction filter. The results from a series of in vitro PC assays were studied, before and immediately after filtration, as were levels of C3a and interleukin 8 (n = 5). Levels of other biologic response modifiers-C5a, interleukin 1 beta, interleukin 6, tumor necrosis factor alpha, and RANTES-were also studied. Removal of interleukin 8 and RANTES was studied further by using serial filtration of units of PC. RESULTS: For the in vitro platelet assays studied, pH was unchanged after filtration from prefiltration values in units of PCs pooled on storage Day 2 or 5. A 4 log10 reduction in white cells was reliably seen after filtration in Day 2 and 5 pooled PCs. Postfiltration platelet loss was 14.8 percent for Day 2 pooled PCs and 9.6 percent for Day 5 pooled PCs. For pools of both Day 2 and Day 5 platelets, postfiltration levels of CD62 (P-selectin, CD62P) were unchanged from prefiltration levels, as were results for morphology scores. Levels of C3a decreased after filtration in both the Day 2 pooled PCs (448 ng/mL before filtration vs. 20 ng/mL after filtration) and the Day 5 pooled PCs (1976 ng/mL before filtration vs. 124 ng/mL after filtration). Levels of interleukin 8 were similarly reduced after filtration in the Day 2 pooled platelets (188 pg/mL before filtration vs. 27 pg/mL after filtration) and the Day 5 pooled platelets (2234 pg/mL before filtration vs. 799 pg/mL after filtration). Levels of interleukin 8 in other components evaluated after filtration declined similarly. However, levels of the proinflammatory cytokines interleukin 1 beta and interleukin 6 did not decline after filtration. Serial filtration studies showed that, although levels of interleukin 8 and RANTES were initially lowered by filtration, they returned to prefiltration values with increases in the volume of filtration. CONCLUSION: The third-generation bedside filter used in this study reliably reduced the level of white cell contamination to 4 log10 white cells per PC. It also lowered the levels of interleukin 8, RANTES, and C3a. The filter did not, however, remove (scavenge) the proinflammatory cytokines interleukin 1 beta and 6. The mechanism of chemokine and C3a removal by the filter is unknown, but it may be related to ionic interactions between these biologic response modifiers and the filter medium.

Blood Transfusion↗

Quality of life for patients with obsessive-compulsive disorder.

OBJECTIVE: The health-related quality of life of patients with obsessive-compulsive disorder was compared to published norms for the general U.S. population and for patients with either depressive disorders or diabetes. METHOD: Sixty medication-free outpatients with moderate to severe obsessive-compulsive disorder were evaluated by using the Structured Clinical Interview for DSM-III-R and the Yale-Brown Obsessive Compulsive Scale. Health-related quality of life was measured with the self-rated Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: The instrumental role performance and social functioning of the patients with obsessive-compulsive disorder were worse than those of the general population and of diabetes patients. The more severe the obsessive-compulsive disorder, the lower were the patients' social functioning scores, even after depression ratings were controlled for; scores on instrumental role performance did not correlate with severity of obsessive-compulsive disorder. The ratings of the obsessive-compulsive disorder patients on physical health domains resembled those of the general population and exceeded those of the diabetes patients. The general health and physical health ratings of the obsessive-compulsive disorder patients exceeded those of the depressed patients. In mental health domains, after adjustment for differences in gender distribution, quality of life ratings were similar for the patients with obsessive-compulsive disorder and those with depressive disorders. CONCLUSIONS: Moderate to severe obsessive-compulsive disorder is associated with impaired social functioning and impaired instrumental role performance, but only impairment in social functioning is linearly related to severity of obsessive-compulsive disorder.

Adult↗

Phototoxicology. 1. Light-enhanced toxicity of TNT and some related compounds to Daphnia magna and Lytechinus variagatus embryos.

Many environmental pollutants interact with solar near-ultraviolet (nuv) light in a manner which greatly increases their toxic effects. The phenomenon of light-mediated toxicity (phototoxicity) is only now becoming generally recognized to any significant degree. Manufacture of, and loading munitions with, the explosive 2,4,6-trinitrotoluene (TNT) in past decades caused contamination of soils and sediments at levels exceeding 1000 ppm and of waters at levels near saturation (100 ppm). Manufacture of TNT produces numerous nitrated by-products, and most of these compounds, including TNT, can be metabolized by many species, including bacteria, fungi, plants, and mammals. This study investigated the phototoxicity of TNT, and 2,3-, 2,4-, 2,6-, and 3,4-dinitrotoluene (DNT) and -diaminotoluene (DAT), and the major metabolites 2-amino-4,6-dinitrotoluene (2A) and 4-amino-2,6-dinitrotoluene (4A), to Daphnia magna (acute toxicity) and Lytechinus variagatus (sea urchin) embryos (subacute, developmental toxicity). Most of the compounds were weakly toxic or nontoxic in the dark. All were phototoxic to sea urchins. In D. magna, 2,3- and 3,4-DNT/DAT and 4A were not toxic but were phototoxic, and 2A was toxic and phototoxic; the other isomers were not toxic or phototoxic to this species.

Animals↗

Phototoxicology. 2. Near-ultraviolet light enhancement of Microtox assays of trinitrotoluene and aminodinitrotoluenes.

Coexposure of 2,4,6-trinitrotoluene (TNT), 2-amino-4,6-dinitrotoluene (2A), or 4-amino-2,6-dinitrotoluene (4A) to near-ultraviolet (nuv) light (lambda max-354 nm) significantly enhanced their toxicity toward Photobacterium phosphoreum (Microtox bioassay) during 30 min but not 15 min. Based on the slopes of the dose-response lines, the nuv coexposure and dark toxic mechanisms of action for TNT, 2A, and 4A appeared to be similar. nuv coexposure of binary mixtures significantly enhanced (supraadditivity) the toxicity of these compounds to P. phosphoreum. Under normal laboratory lighting, the toxicity of TNT + 2A and 2A + 4A mixtures were supraadditive but the toxicity of TNT + 4A mixtures could be explained by simple addition. Supporting these conclusions, the response curves of alpha-terthienyl, a compound known not to require nuv for toxicity, were similar in the dark and with nuv coexposure. In contrast, angelicin and psoralen, compounds known to require nuv coexposure to damage DNA, gave response curves having different slopes in the dark and with nuv coexposure. The nuv coexposure Microtox assay was able to detect and quantify phototoxicity in psoralen, angelicin, alpha-terthienyl, anthracene, TNT, and aminodinitrotoluenes.

Aniline Compounds↗

Phototoxicology. 3. Comparative toxicity of trinitrotoluene and aminodinitrotoluenes to Daphnia magna, Dugesia dorotocephala, and sheep erythrocytes.

2,4,6-Trinitrotoluene (TNT) and compounds associated with its production are toxic and phototoxic to a wide range of biota. The planarian Dugesia dorotocephala, but not Daphnia magna, metabolized TNT (1 mg/liter) to 4-amino-2,6-dinitrotoluene (4A; 0.4 mg/liter) and 2-amino-4,6-dinitrotoluene (2A; 0.2 mg/liter). Coexposure to near-ultraviolet (nuv) light enhanced the toxicity of 2A more than that of TNT and 4A. The toxicities of TNT, 4A, and 2A to Du. dorotocephala were all decreased by glutathione (GSH) conjugation. This suggests that all had mechanisms of toxic action involving formation of quinone-GSH conjugates. Dark and light mechanisms for TNT and 2A depended on GSH conjugation, but the specific mechanisms may be different for each compound. The dark and light mechanisms of toxic action for 4A appeared to be fundamentally different in that the dark toxic mechanism of action was less dependent on GSH conjugation. Hemolysis studies using sheep erythrocytes showed that the light-enhanced toxic mechanism of action for TNT, 2A, and/or 4A did not involve cellular membrane damage in response to nuv-induced anions.

Abnormalities, Drug-Induced↗