Search PubMed⌕ Search

Biomedical subjects

D T Williams

Publications and source records attributed to D T Williams.

At least 19 recordsLinked to original sources

Emerging viral diseases of Southeast Asia and the Western Pacific.

Over the past 6 years, a number of zoonotic and vectorborne viral diseases have emerged in Southeast Asia and the Western Pacific. Vectorborne disease agents discussed in this article include Japanese encephalitis, Barmah Forest, Ross River, and Chikungunya viruses. However, most emerging viruses have been zoonotic, with fruit bats, including flying fox species as the probable wildlife hosts, and these will be discussed as well. The first of these disease agents to emerge was Hendra virus, formerly called equine morbillivirus. This was followed by outbreaks caused by a rabies-related virus, Australian bat lyssavirus, and a virus associated with porcine stillbirths and malformations, Menangle virus. Nipah virus caused an outbreak of fatal pneumonia in pigs and encephalitis in humans in the Malay Peninsula. Most recently, Tioman virus has been isolated from flying foxes, but it has not yet been associated with animal or human disease. Of nonzoonotic viruses, the most important regionally have been enterovirus 71 and HIV.

Animals↗

A study on organotin levels in Canadian drinking water distributed through PVC pipes.

A study on organotin compounds in Canadian drinking water was carried out in winter-spring 1996 (28 sites) and autumn 1996 (21 sites). Approximately 29% and 40% of distribution waters supplied through PVC pipes installed recently (typically less than 6 months) contained organotin compounds in the winter-spring and autumn surveys respectively. Monomethyl-, dimethyl-, monobutyl- and dibutyltin levels ranged up to 291 ng Sn/L, 49.1 ng Sn/L, 28.5 ng Sn/L and 52.3 ng Sn/L, respectively. An additional study in summer 1996, of locations where the highest organotin levels were detected in the winter-spring survey, indicated that organotin levels had decreased in most distribution water samples. Samples of PVC pipe/tubing contained organotin compounds consistent with the organotin patterns found in the distribution water samples.

Canada↗

Propranolol treatment of chronically hospitalized aggressive patients.

Violent behavior in psychiatric patients may result in long-term hospitalization. There is no FDA-approved psychopharmacologic treatment for aggression. In this study, 20 chronically aggressive hospitalized patients were administered 1 week of placebo followed by an open trial of increasing doses of propranolol. Patients who had an equivocal or definite clinical response were entered into an open add-on double-blind discontinuation study phase. Aggressive behavior was objectively documented throughout the study. After the open phase of the study, 7 patients had a greater than 50% decrease in aggressive behavior. Four patients entered the double-blind discontinuation phase. The clinical course of 3 of those patients was consistent with the positive response to propranolol. The results of this study are consistent with a therapeutic effect of propranolol in some patients with aggressive behavior. Further studies are indicated.

Adrenergic beta-Antagonists↗

Health risk assessment of drinking water contaminants in Canada: the applicability of mixture risk assessment methods.

The objectives of this article are: (i) to review the current approaches of Health Canada to the risk assessment of drinking water contaminants, and (ii) to examine the applicability of mixture risk assessment methods to drinking water contaminants. Health Canada's current approaches to drinking water risk assessment, like those of many regulatory agencies, focus almost solely on the effects of individual chemicals. As such, no formal method is currently used for developing mixtures guidelines or for modifying guidelines of individual chemicals to account for the possibility of the occurrence of interactions (supraadditive or infraadditive). Recent interest in the risk assessment of mixtures, at least in part, stems from concerns over the potential health risks of mixtures of very commonly occurring compounds in Canadian drinking water supplies, namely the disinfection by-products. Before any mixtures methods can be considered for incorporation into Health Canada's current approaches to the risk assessment of drinking water contaminants, it is essential to consider the limitations and data requirements of the various mixture risk assessment methods (i.e., whole mixture approach, similar mixture approach, components-based approaches, interactions-based assessment). Among the existing mixture risk assessment methods, the components-based and interactions-based approaches could be applicable to drinking water contaminants. Specifically, among the components-based approaches, dose-addition, response-addition, and the toxic equivalency factor approaches are the most applicable ones for drinking water contaminants. Until an interactions-based, mechanistic risk assessment approach (e.g., physiological model-based approach) becomes available for routine use, the components-based approaches remain the default methods for consideration. Progress in the development and validation of an interactions-based risk assessment methodology should facilitate a more realistic assessment of risk due to drinking water contaminants without increasing the levels of uncertainty in risk estimates above those associated with existing single-chemical methods.

Canada↗

A decay-accelerating factor-binding strain of coxsackievirus B3 requires the coxsackievirus-adenovirus receptor protein to mediate lytic infection of rhabdomyosarcoma cells.

The composition of the cellular receptor complex for coxsackievirus B3 (CVB3) has been an area of much contention for the last 30 years. Recently, two individual components of a putative CVB3 cellular receptor complex have been identified as (i) decay-accelerating factor (DAF) and (ii) the coxsackievirus-adenovirus receptor protein (CAR). The present study elucidates the individual roles of DAF and CAR in cell entry of CVB3 Nancy. First, we confirm that the DAF-binding phenotype of CVB3 correlates to the presence of key amino acids located in the viral capsid protein, VP2. Second, using antibody blockade, we show that complete protection of permissive cells from infection by high input multiplicities of CVB3 requires a combination of both anti-DAF and anti-CAR antibodies. Finally, it is shown that expression of the CAR protein on the surface of nonpermissive DAF-expressing RD cells renders them highly susceptible to CVB3-mediated lytic infection. Therefore, although the majority of CVB3 Nancy attaches to the cell via DAF, only virus directly interacting with the CAR protein mediates lytic infection. The role of DAF in CVB3 cell infection may be analogous to that recently described for coxsackievirus A21 (D. R. Shafren, D. J. Dorahy, R. A. Ingham, G. F. Burns, and R. D. Barry, J. Virol. 71:4736-4743, 1997), in that DAF may act as a CVB3 sequestration site, enhancing viral presentation to the functional CAR protein.

Cell Line↗

Speciation of organotin and organolead compounds in drinking water by gas chromatography--atomic emission spectrometry.

Raw and treated water samples and distribution system water samples were collected in forty-five Canadian municipalities for the analysis of organotin and organolead compounds. After extraction from the water samples organotin and organolead compounds were alkylated with pentylmagnesium bromide and butylmagnesium chloride respectively and analysed by gas chromatography-microwave induced plasma atomic emission spectrometry (GC-AED) using wavelengths specific for tin (326.23 nm) and lead 405.78 nm). The GC-AED system was optimised for trace level analysis, especially for organolead compounds. Organotin compounds, mainly methyltin and butyltin at concentrations up to 22 ng Sn/L and 43.6 ng Sn/L respectively, were detected in distributed water samples from six municipalities. No organotin compounds were detected in raw water samples indicating that the organotin compounds were leaching into the water from some component of the distribution system. One raw water sample contained six organolead compounds at concentrations from 0.5 to 10 ng Pb/L and five raw water and three distributed water samples contained trace levels ( < 0.5 ng Pb/L) of organolead compounds. Due to the lack of authentic standards the identity of the organolead compounds could not be confirmed by gas-chromatography mass-spectrometry.

Canada↗

Pilot study on the contamination of drinking water by organotin compounds from PVC materials.

Raw and treated water samples and tap water samples from four to six houses located on distribution lines where PVC pipe/tubing had been recently installed were collected in five Canadian municipalities for the analysis of organotin compounds. After derivatisation with sodium tetraethylborate the ethylated organotin compounds were extracted with hexane and analysed by gas chromatography-microwave induced plasma atomic emission spectrometry using a wavelength (326.234 nm) specific for tin. Organotin compounds, mainly methyltin and dimethyltin at concentrations ranging respectively from 0.5 to 257 ng Sn/L and from 0.5 to 6.5 ng Sn/L, were detected in samples from ten of the twenty-two houses. No organotin compounds were detected in raw water or treated water leaving the treatment plant, indicating that the organotin compounds were leaching into the water from some component of the distribution system.

Borates↗

Outcome after diagnosis of psychogenic nonepileptic seizures.

Information regarding outcome in patients with psychogenic nonepileptic seizures (PNES) is limited. We attempted to contact 72 consecutive patients with PNES confirmed by video-EEG monitoring: 51 of 72 (71%) were reached a mean of 15 months (range 12-27 months) after diagnosis and agreed to answer a structured telephone questionnaire. The questionnaire assessed the number of PNES in the last 6 months, antiepileptic drug (AED) use, occupational status, global self-rating, and extent of psychotherapeutic treatments. PNES had ceased in 18 of 51 (35%), decreased > 80% in 21 of 51 (41%), and decreased < 80% in 12 of 51 (24%). Thirty-three of 51 (65%) were not taking AEDs. Occupational status improved in 20% and did not change in 75%. Overall, 29 of 51 (57%) rated themselves markedly improved and 15 of 51 (29%) rated themselves unchanged or worse. Persisting PNES were associated with longer duration of PNES before diagnosis (p < 0.02) and presence of additional psychiatric disease (p < 0.01). Persisting PNES were not associated with gender, presence of epileptic seizures, or extent of psychotherapeutic treatments after diagnosis. Placebo saline infusion had been administered in some patients to help precipitate PNES. This did not affect the number of psychotherapy visits or outcome. We conclude that PNES cease or significantly decrease in most patients, but occupational status does not improve as often. Earlier diagnosis may improve outcome.

Anticonvulsants↗

Utility and reliability of placebo infusion in the evaluation of patients with seizures.

Placebo infusions are occasionally used to elicit psychogenic seizures. How frequently placebo infusions elicit patients' typical events, atypical and potentially confusing events, or even epileptic seizures is not known. We report the results of placebo infusions during video EEG in 68 patients who also had events recorded without placebo. A single investigator administered a saline placebo that was represented to the patient as an activating substance. We compared the events recorded without placebo with events recorded with placebo. Twenty patients had only epileptic seizures without placebo; with placebo, two of 20 (10%) had their typical epileptic seizures and three of 20 (15%) had atypical nonepileptic events. Forty patients had only psychogenic seizures without placebo; with placebo, 33 of 40 (82%) had their typical psychogenic seizures and three of 40 (8%) had atypical events. Eight patients had both psychogenic and epileptic seizures without placebo; with placebo, four of eight had their typical psychogenic seizures. Thus, placebo infusion elicits typical psychogenic events in most patients with psychogenic seizures, but atypical events or epileptic seizures may occur in a minority and lead to incorrect diagnosis.

Adult↗

Neuropsychiatric aspects of adult-onset Tay-Sachs disease: two case reports with several new findings.

Deficiency of hexosaminidase A causes the GM2 gangliosidosis known as Tay-Sachs disease. It is now known that this condition has several late-onset variants that cause numerous neuropsychiatric disturbances. Early recognition is important because treatment with phenothiazines and heterocyclic antidepressants may worsen the course. The authors report two cases with several new findings, including prominent psychiatric symptoms without psychosis early in the course of the illness.

Adult↗

Decrease in erythrocyte glycophorin sialic acid content is associated with increased erythrocyte aggregation in human diabetes.

1. Sialic acid moieties of erythrocyte membrane glycoproteins are the principal determinants of the negative charge on the cell surface. The resultant electrostatic repulsion between the cells reduces erythrocyte aggregation and hence the low shear rate viscosity and yield stress of blood. 2. Using g.c.-m.s., a decrease in sialic acid content has been observed in the major erythrocyte membrane glycoprotein, glycophorin A, obtained from nine diabetic patients compared with that from seven normal control subjects [median (range): 3.30 (0.01-11.90) versus 18.60 (3.20-32.60) micrograms/100 micrograms of protein, P less than 0.02]. 3. Erythrocyte aggregation, measured by viscometry as the ratio of suspension viscosity to supernatant viscosity (LS/S) in fibrinogen solution, was increased in ten diabetic patients compared with ten normal control subjects (mean +/- SEM, 37.6 +/- 1.3 versus 33.8 +/- 0.6, P less than 0.02). 4. In the patients in whom both viscometry and carbohydrate analysis were performed, the decrease in erythrocyte glycophorin sialylation and the increase in erythrocyte aggregation in fibrinogen solution were related statistically (LS/S correlated negatively with glycophorin sialic acid content, r = 0.73, P less than 0.05). 5. Decreased glycophorin sialylation provides an explanation at the molecular level for increased erythrocyte aggregation and it may be important in the pathogenesis of vascular disease in diabetes.

Adult↗

Determination of organic contaminants in residential indoor air using an adsorption-thermal desorption technique.

This field study evaluated the ability of a multi-sorbent sampling tube/thermal desorption technique to identify and to provide quantitative data on volatile organic contaminants in indoor air. Air samples, from 12 Canadian homes, were collected on multilayer sorbent cartridges and analyzed using Adsorption/Thermal Desorption coupled with Gas Chromatography/Mass Spectrometry. The study included the identification and quantitation of 23 target compounds. Analysis of sorbent tubes fortified with these target compounds indicated that recoveries were greater than 70 percent and the precision was usually better than 15 percent. These organic compounds were found to be stable on the sorbent tubes for at least seven days. With some exceptions, the target compounds were usually detected at 1 to 10 micrograms/m3 in indoor air samples; other organics identified qualitatively were saturated hydrocarbons, unsaturated hydrocarbons, cyclic hydrocarbons, substituted aromatics, oxygenates, some halogenates and cyclic species such as camphenes/pinenes and carenes.

Adsorption↗