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Biomedical subjects

S A Williams

Publications and source records attributed to S A Williams.

At least 37 records · Page 2Linked to original sources
PubMed2000

Application of a polymerase chain reaction-ELISA to detect Wuchereria bancrofti in pools of wild-caught Anopheles punctulatus in a filariasis control area in Papua New Guinea.

Chemotherapy-based eradication programs are aimed at stopping transmission of Wuchereria bancrofti by its obligatory mosquito vector. This study compares one year post-treatment W. bancrofti infection rates of Anopheles punctulatus, the main vector of lymphatic filariasis in Papua New Guinea, using traditional dissection techniques and a polymerase chain reaction (PCR)-based ELISA of a parasite-specific Ssp I repeat. A total of 633 mosquitoes in 35 batches were dissected. Six batches contained W. bancrofti-infected mosquitoes, giving a minimum infection rate of 0.9%. This value was not different than the actual infection rate, which was 9 (1.4%) of 633 mosquitoes (P = 0.48). The DNA was extracted from 47 pools containing a mean of 13.2 mosquitoes per pool. A total of 621 mosquitoes were processed for the PCR-ELISA, including 486 caught by human bait and 135 by light trap, which included both dead and live mosquitoes. Of 23 pools of alcohol-preserved human-bait mosquitoes, seven were positive by the PCR-ELISA, giving an infection rate identical to that obtained by dissection of individual mosquitoes (1.4%). The minimum infection rates for pools of light-trap mosquitoes found dead and alive were 2.7% (2 of 74) and 4.9% (3 of 61), respectively. These values did not differ from each other (P = 0.84), but the overall infection rate of light-trap mosquitoes was greater than that of mosquitoes captured by human bait (3.7% versus 1.4%; P = 0.09). These data indicate that the PCR-ELISA of a W. bancrofti Ssp I repeat using pools of mosquitoes is comparable to traditional dissection techniques for monitoring transmission intensity following introduction of mass chemotherapy. This approach may also be useful for rapid and cost-effective assessment of transmission in endemic areas where the frequency of overt lymphatic pathology is low.

Animals↗
PubMed1999

Cumulative effect of anatomical risk factors for schizophrenia: an MRI study.

BACKGROUND: Although schizophrenic and control subjects differ on a variety of neuroanatomical measures, the specificity and sensitivity of any one measure for differentiating between groups are low. This study investigated the cumulative effect of deviant brain structure on diagnosis. METHODS: Hemisphere and third ventricle volume and the normalized (Talairach) location of three association cortex sulcal landmarks were measured on high-resolution MRI scans in 37 male patients with schizophrenia and 33 male control subjects matched on age, handedness, and parental socioeconomic status. RESULTS: While there were few group differences on individual anatomical measures, the 10 variables reliably discriminated between the two groups when used in concert in a discriminant function analysis (F[10.59] = 3.6, p < .0009) with 77% of the subjects correctly classified. Five of the measures (left posterior cingulate, left inferior frontal sulcus, right sylvian fissure, and left and right halves of the third ventricle) correlated significantly with the discriminant function (p < .005). CONCLUSIONS: This is the first study to demonstrate that schizophrenics can be distinguished from matched controls on the basis of brain anatomy alone. The risk of schizophrenia may depend on the total amount of neural deviance, rather than on anomalies in a single structure or circuit.

Adolescent↗
PubMed1999

Specificity from the synapsis of DNA elements by the Sfi I endonuclease.

The synapsis of DNA sites is a prerequisite for the reactions of many proteins that act at specific DNA sequences. The requirement for synapsis was investigated by analysing the reactions of Sfi I, a tetrameric restriction enzyme that cleaves DNA only after interacting with two recognition sites. In the presence of Mg2+, oligonucleotide duplexes with the cognate recognition sequence were cleaved rapidly, with cooperative kinetics, while non-cognate duplexes were not cleaved. In the absence of Mg2+, the primary complex formed by Sfi I with cognate DNA contained two duplexes synapsed by the tetramer: a secondary complex containing one duplex was seen only at elevated Sfi I concentrations. In contrast, the principal complex with non-cognate DNA contained one duplex bound to Sfi I. Pairs of non-cognate duplexes, or one cognate and one non-cognate duplex, generally failed to form synaptic complexes. On adding Mg2+to complexes with cognate DNA, cleavage occurred much more rapidly in the synaptic complex than in the secondary complex. DNA synapsis thus acts to enhance the specificity of Sfi I for its recognition sequence, by demanding two cognate sites for a catalytically active complex and by excluding non-cognate sites from the synaptic complex.

Catalysis↗
PubMed1999

Medical emergencies in general dental practice in Great Britain. Part 3: Perceptions of training and competence of GDPs in their management.

OBJECTIVES: To ascertain the training received in management of medical emergencies recalled by general dental practitioners (GDPs), as undergraduates and since graduation, to examine how well prepared they felt to manage such events and how their readiness might be improved. DESIGN: Postal questionnaire survey of a random sample of GDPs in Great Britain. SUBJECTS: 1500 GDPs, 1000 in England & Wales and 500 in Scotland. RESULTS: There was a 74% response. Among respondents, 75% had received training as undergraduates in the management of medical emergencies, 95% had subsequently received training. The proportion considering themselves 'well' or 'fairly well' prepared to manage emergencies rose from 30% at graduation to 80% currently. The 20% who felt themselves 'not very well' or 'not at all' prepared were less likely to possess the drugs and equipment to manage an emergency. Nevertheless, a need for further training was expressed by 96%: only 3% felt no need. CONCLUSIONS: Virtually all GDPs (99.2%), had received training in the management of medical emergencies at some time, principally since graduation. The 20% who feel inadequately prepared are less likely to possess the necessary drugs and equipment. There is a perceived need for further training among the majority of respondents.

Attitude of Health Personnel↗
PubMed1999

Medical emergencies in general dental practice in Great Britain. Part 2: Drugs and equipment possessed by GDPs and used in the management of emergencies.

OBJECTIVE: To ascertain the emergency drugs and equipment possessed by general dental practitioners (GDPs), the treatment provided and drugs used in management of the medical emergency events they reported. DESIGN: Postal questionnaire survey of a random sample of GDPs in Great Britain. SUBJECTS: 1500 GDPs, 1000 in England & Wales and 500 in Scotland. RESULTS: There was a 74% response. An aspirator, an airway, oxygen, adrenaline and an injectable steroid were possessed by about 90% of respondents; glucose, glyceryl trinitrate and a salbutamol inhaler by about 80%. Glucose was used in management of nearly one in ten of the events reported, an inhaler, glyceryl trinitrate and oxygen were the next most commonly used. Cardiopulmonary resuscitation (CPR) was carried out in management of 1.1-1.4% of events not associated with general anaesthesia (GA) and in 4.7-16% of events associated with GA, an average of once in 250 years of practice. CONCLUSIONS: Most respondents possessed drugs and equipment necessary to manage a medical emergency. Half the drugs recommended by the 'Poswillo report' to be available in every dental practice were not used in more than 8000 years of practice.

Adrenergic Agonists↗
PubMed1999

Medical emergencies in general dental practice in Great Britain. Part 1: Their prevalence over a 10-year period.

OBJECTIVE: To assess the prevalence, nature and outcome of medical emergencies experienced by general dental practitioners (GDPs) over a 10-year period. DESIGN: Postal questionnaire survey of a random sample of GDPs in Great Britain. SUBJECTS: 1500 GDPs, 1000 in England & Wales and 500 in Scotland. RESULTS: There was a 74% response. Emergency events were reported by 70.2%: the number reported by a single individual ranged from none to 33. The most commonly experienced events, including those associated with general anaesthesia, were (as a percentage of the total) for England & Wales and Scotland, respectively: fits and seizures (31.0%, 36.3%); swallowed foreign bodies (15.7%, 18.1%); attacks of asthma (13.8%, 11.1%); chest pain associated with angina pectoris (10.1%, 11.0%) and diabetic events (10.6%, 9.0%): none of these resulted in any serious sequelae. More events were reported in Scotland. Overall, there were 20 deaths resulting from medical emergencies reported in the survey, 4 affecting passers-by and none associated with general anaesthesia. 8849 years of practice experience were represented (by 94% of respondents), from which an estimate of the frequency of events was made. CONCLUSIONS: An emergency event was reported, on average, for every 4.5 practice years in England & Wales and 3.6 years in Scotland and death associated with general dental practice, on average, once in 758 and 464 years, respectively.

Cause of Death↗
PubMed1999

Development of a quantitative, competitive polymerase chain reaction--enzyme-linked immunosorbent assay for the detection of Wuchereria bancrofti DNA.

A quantitative, competitive polymerase chain reaction (QC-PCR) assay for the sensitive detection of Wuchereria bancrofti DNA was developed. A competitor sequence was constructed by an exchange of nucleotides in the Wuchereria-specific Ssp I repeat. The PCR products were hybridized to specific DNA probes and their amounts, determined by an enzyme-linked immunosorbent assay (ELISA). In laboratory-prepared samples the QC-PCR-ELISA assay was capable of detecting the amount of DNA equivalent to 0.1 microfilaria (mf) added to 200 microl of blood lysate. The assay was also tested on 78 blood samples collected in endemic areas in Egypt. All 28 samples that were positive both for mf and for circulating antigen were also QC-PCR-ELISA-positive. In addition, one mf-negative but antigen-positive sample was also positive as determined by QC-PCR-ELISA. A positive correlation of mf density with the QC-PCR-ELISA was observed. Samples containing 10 or fewer mf/ml had a mean relative amount of Ssp I PCR product of 19.7 units, whereas samples with 11-100 mf/ml had a mean of 36.3 units and those with more than 100 mf/ml had a mean of 84.6 units. Because of the high standard deviation within each group, estimates of worm burdens in infected individuals using the QC-PCR-ELISA are not recommended. However, we present data indicating that the W. bancrofti QC-PCR-ELISA is a powerful new tool for evaluation of parasitic loads for community-based diagnosis of bancroftian filariasis.

Animals↗
PubMed1999

Diagnosis of Wuchereria bancrofti infection by the polymerase chain reaction employing patients' sputum.

A preliminary evaluation of the diagnostic potential of a polymerase chain reaction (PCR) assay using diurnally collected sputum from bancroftian filariasis patients is described. A new set of PCR primers amplifying a 254-bp-long sequence termed AccI, derived from a long dispersed repeated sequence and SspI primers previously employed for PCR-based diagnosis were employed in this study with similar results. Of the 34 sputum samples from patients, 32 (94%) were PCR positive. Of the 18 patients with low to high microfilaremia (21-1560 microfilariae/ml), 16 (88.8%) were PCR positive. Of the remaining 16 patients, 6 with very low microfilaremia (2-6 microfilariae/ml) and 10 without microfilaremia, all (100%) were PCR positive. Two PCR-positive cases among the 13 endemic normal individuals tested (15.4%) may represent cases of occult filariasis. PCR amplification was also demonstrated with one PCR-positive sputum aliquot when mixed with 14 sputum aliquots from uninfected (PCR-negative) individuals. The potential diagnostic merits of the sputum-PCR assay are discussed.

Animals↗
PubMed1999

Deep within the filarial genome: progress of the filarial genome project.

Four years ago, a WHO/United Nations Development Programme/World Bank-sponsored genome project to study the filarial lymphatic nematode parasite Brugia malayi was initiated. The project took as its aims gene discovery for drug target and vaccine candidate identification, genome mapping, dissemination of genomic data to the world community and training of endemic country partners in genomic research. In this article, the principal investigators in the laboratories behind the project describe the background to the project, the data now emerging and goals for the future. Open access to filarial genome data is emphasized.

Animals↗
PubMed1999

Helminth genome analysis: the current status of the filarial and schistosome genome projects. Filarial Genome Project. Schistosome Genome Project.

Genome projects for the parasitic helminths Brugia malayi (a representative filarial nematode) and Schistosoma were initiated in 1995 by the World Health Organization with the ultimate objectives of identifying new vaccine candidates and drug targets and of developing low resolution genome maps. Because no genetic maps are available, and very few genes have been characterized from either parasite group, the first goal of both Initiatives has been to catalogue new genes for future placement on chromosome and physical maps. These genes have been identified by the expressed sequence tag (EST) approach, utilising cDNA libraries constructed from diverse life cycle stages. To date, the Initiatives have deposited over 16,000 Brugia ESTs and nearly 8000 Schistosoma ESTs in Genbank's dbEST database, corresponding to 6000 and over 3600 genes respectively (33% of Brugia's estimated gene compliment, 18-24% of that of Schistosoma). Large fragment, genomic libraries have been constructed in BAC and YAC vectors for studies of genomic organization and for physical and chromosome mapping, and public, hypertext genomic databases have been established to facilitate data access. We present a summary of progress within the helminth genome initiatives and give several examples of important gene discoveries and future applications of these data.

Animals↗
PubMed1999

Patterns of Onchocerca volvulus recombinant antigen recognition in a bovine model of onchocerciasis.

The antibody responses of 8 cattle experimentally infected with Onchocerca ochengi to 18 recombinant O. volvulus antigens were measured by ELISA. In addition to establishing antigenic cross-reactivity between the species, the dynamics of antigen-specific responses were examined to assess how the recognition of the antigens compared to the known stage-specificity of expression. Six cattle responded to all of the antigens and 2 animals responded to all but 1. The dynamics of the recognition of 4 antigens (B20, MOv-2, MOv-14 and OvNHR2 02E1) were characterized by rapid seroconversion following infection. Antibody levels to 2 antigens (Ov7 and OvALT-1) increased gradually over the course of infection. Antibody levels to 4 antigens (OvTPX-2, OvL3Chitinase, Ov103 and Ov9m) reached maximum levels coincident with the onset of patency. The levels to 3 antigens (OvProalf C50, OvAldolase, Ov39) varied little over the course of infection. Responses to antigens with functional similarities (OvSOD1, OvSOD2 and OvSOD3 or OvGST1 and OvGST2) showed comparable temporal profiles. This study demonstrates the high degree of immunological cross-reactivity between the antigens of O. volvulus and O. ochengi. The immunogenicity of antigens varied over the course of infection in an antigen-specific manner, which not always reflected developmentally regulated expression of the corresponding gene, possibly owing to cross-reactive epitopes on distinct parasite products.

Animals↗
PubMed1999

Patient's perceptions of an anesthesia preoperative computerized patient interview.

Our desire to elicit a more complete medical history from our patients led to the implementation of a preoperative computerized interview. We previously demonstrated the effectiveness of the interview by computing its mean completion time for the overall patient population (n = 120), and further examined the effects of age, gender, and educational level. In this study, we investigated patient perception of the interview itself. Before and after taking the computer interview, we asked the patients to complete a paper and pencil questionnaire comprised of sixteen questions, expressing their feelings toward the computer interview. Responses elicited prior to taking the computer interview were compared with those obtained afterward. The Stuart-Maxwell test was used to determine statistically significant differences in answers before and after the interview. Initial questionnaire responses reflected a positive attitude toward computer usage which became even stronger after the interview. The only negative responses elicited were really more "doctor positive" than "computer negative." We conclude that patients looked favorably upon participating in a computerized medical interview provided that physician-patient contact is maintained.

Adult↗
PubMed1999

Diagnostic delays in head and neck cancers.

Head and neck cancers are a significant and worsening health problem in the UK. In the absence of screening, minimising diagnostic delay after the onset of symptoms improves prognosis. Delay, from the patient's initial experience of symptoms to the ultimate diagnosis, consists of two elements--the delay prior to presenting to a clinician plus that due to the health professional consulted. This study aimed to establish the period of delay between recognition of the initial tumour symptoms and the formal diagnosis among a sample of patients recently diagnosed with head and neck cancer. Using a semistructured questionnaire, 133 men and 55 women were interviewed by a research nurse, and the results were related to the clinical findings. Tumour size at diagnosis was classified according to T1 (22%), T2 (29%), T3 (27%) and T4 (22%). Of the 186 patients with complete hospital records, 48 (26%) were diagnosed with cancer of the lip and oral cavity (CLOC). From the onset of symptoms to the patients' initial decision to seek professional advice, the median period was 4 weeks among those with CLOC and 3 weeks for those with other head and neck cancers (OHNC). The distribution was highly skewed with delays beyond 6 months occurring among 9% of the OHNC group, compared with 3% of CLOC. From the onset of symptoms to a consultant appointment, the median delay was 8 weeks for OHNC, but 12 weeks for CLOC, with delays beyond 6 months of 13% in each group, respectively. First symptoms included 'change in voice' (26%), 'pain' (27%), 'lump' or 'growth' (12%) as well as dysphagia, 'infection', 'sore throat', 'ulcers' or 'abscess'. No significant association was found between the nature of the first symptoms and the urgency with which patients interpreted their symptoms, nor was this related to diagnostic delay, sex, age or social class. It is concluded that there is substantial variation in time to clinical presentation, particularly for OHNC, although professional delay for the majority of these cases was minimal. For patients with CLOC there was less variation in patient delay, but clinician delay was relatively longer.

Adult↗
PubMed1999

A double-blind, placebo-controlled study of the safety, tolerability and pharmacokinetics of CP-101,606 in patients with a mild or moderate traumatic brain injury.

CP-101,606 is a postsynaptic antagonist of the glutamate-mediated NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor. When administered intravenously (i.v.) at the time of injury, CP-101,606 is neuroprotective in animal models of traumatic brain injury (TBI) and ischemia. Minimal adverse effects have been observed in normal human volunteers given i.v. doses of up to 3 mg/kg/hr for 72 hours. The objective of the present clinical trial was to assess the safety, pharmacokinetics, and tolerability of CP-101,606 infused for various times in patients who had suffered either an acute moderate or mild TBI (Glasgow Coma Score 9-14) or hemorrhagic stroke. Patients began receiving treatment within 12 hours of brain injury. A total of 53 subjects (45 with TBI and 8 with stroke) were randomized in a double-blind fashion to receive CP-101,606 or placebo (4 drug: 1 placebo). Drug/placebo was administered by i.v. infusion (0.75 mg/kg/hr) for 2 hours and then stopped (n = 25) or continued for 22 hours (n = 4) or 70 hours (n = 24) at a rate of 0.37 mg/kg/hr. Mean plasma drug concentrations were well above the predicted therapeutic concentration of 200 ng/ml within two hours of initiating treatment and were sustained as long as drug was infused. All the patients tolerated their drug/placebo treatment, and there were no clinically significant cardiovascular or hematological abnormalities in either group. A Neurobehavioral Rating Scale, used to detect personality changes and behavioral disturbances, indicated that all subjects showed an improvement from their postinjury, predosing baseline but did not significantly differ from each other with respect to type of head injury and/or treatment with drug or placebo. Modified Kurtzke Scoring also showed a similar pattern of improvement irrespective of type of head injury or drug/placebo treatment. This study suggests that CP-101,606, infused for up to 72 hours has no psychotropic effects and is well-tolerated in patients who have sustained a mild or moderate TBI or hemorrhagic stroke.

Adolescent↗
PubMed1999

An open-label study of CP-101,606 in subjects with a severe traumatic head injury or spontaneous intracerebral hemorrhage.

CP-101,606 is a postsynaptic antagonist of N-methyl-D-aspartate (NMDA) receptors bearing the NR2B subunit. When administered intravenously (i.v.), it decreases the effects of traumatic brain injury (TBI) and focal ischemia in animal models. Therapeutic plasma concentrations (200 ng/ml) in animals, have been well tolerated in healthy human volunteers. The purpose of the present dose escalation study was to assess the safety, tolerability, and pharmacokinetics of CP-101,606 in subjects who had suffered either an acute severe TBI (Glasgow Coma Scale 3-8) or spontaneous intracerebral hemorrhage. Thirty patients, 20 with a TBI and 10 with a stroke, were enrolled in the trial and began receiving an i.v. infusion of CP-101,606 for 2 hours, 24 hours, or 72 hours within 12 hours of brain injury. For the first two hours, the drug was given a rate of 0.75 mg/kg/hr and then stopped (n = 17) or continued for 22 (n = 2) or 70 hours (n = 11) at 0.37 mg/kg/hr. Plasma and cerebrospinal fluid (CSF) were collected at serial times during and after treatment. There were no consistent changes in blood pressure or pulse nor any clinically significant hematological or electrocardiogram (ECG) abnormalities attributable to CP-101,606. No adverse events or behavioral changes were considered to be related to the drug. Plasma concentrations of CP-101,606 over 200 ng/ml were rapidly achieved in the blood and CSF within two hours and were sustained there as long as the drug was infused. CSF concentrations were slightly higher than that in plasma by the end of infusion suggesting good penetration of CP-101,606 into the CSF. Outcome in the severe TBI patients, as measured by the Glasgow Outcome Score at six months, suggested that a two-hour infusion yielded a range of scores similar to contemporary patients with a severe TBI treated at our hospital while the outcomes of the patients treated with either a 24- or 72-hour infusion were better on average. Thus, these results indicate that CP-101,606 infused for up to 72 hours is well tolerated, penetrates the CSF and brain, and may improve outcome in the brain-injured patient.

Adolescent↗