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Biomedical subjects

P Wilson

Publications and source records attributed to P Wilson.

At least 109 records · Page 6Linked to original sources
PubMed1999

Reduction in susceptibility to Brugia malayi of F2 progeny of Aedes togoi treated with ethyl methanesulfonate.

The susceptibility to Brugia malayi infection was tested in F2 female progeny derived from male and female Aedes togoi treated with ethyl methanesulfonate (EMS). Three-day-old males and females were treated with 0.025, 0.050, and 0.075, 0.10, 0.15, or 0.20% EMS by allowing them to feed for 5 days on sugar cubes containing EMS and then mated at random. Percentage of susceptibility and mean number of infective larvae (L3) in F2 females were analyzed over a 2-wk period. Reductions in susceptibility were significant in the F2 populations arising from the 3 highest EMS concentrations. F2 infections were reduced by 80%, indicating that EMS-induced mutations affect loci associated with filarial nematode susceptibility.

Aedes↗
PubMed1999

Sex and attitude: a randomized vignette study of the management of depression by general practitioners.

BACKGROUND: The management and detection of depression varies widely, and the causes of variation are incompletely understood. AIMS: To describe and explain general practitioners' (GPs') current practice in the recognition and management of depression in young adults, their attitudes towards depression, and to investigate associations of GP characteristics and patient sex with management. METHOD: All GP principals in the Greater Glasgow Health Board were randomized to receive questionnaires with vignettes describing increasingly severe symptoms of depression in either male or female patients, and asked to indicate which clinical options they would be likely to take. The Depression Attitude Questionnaire was used to elicit GP attitudes. RESULTS: As the severity of vignette symptoms increased, GPs responded by changing their prescribing and referral patterns. For the most severe vignette, the majority of GPs would prescribe drugs (76.4%) and refer the patient for further help (73.7%). Male and female patients were treated differently: GPs were less likely to ask female patients than male patients to attend a follow-up consultation (odds ratio [OR] = 0.55), and female GPs were less likely to refer female patients (OR = 0.33). GPs with a pessimistic view of depression, measured using the 'inevitable course of depression' attitude scale, were less willing to be actively involved in its treatment, being less likely to discuss a non-physical cause of symptoms (OR = 0.77) or to explore social factors in moderately severe cases (OR = 0.68). CONCLUSIONS: Accepting the limitations of the method, GPs appear to respond appropriately to increasingly severe symptoms of depression, although variation in management exists. Educational programmes should be developed with the aim of enhancing GP attitudes towards depression, and the effects on detection and management of depression should be rigorously evaluated.

Attitude of Health Personnel↗
PubMed1999

Quality-assessed reviews of health care interventions and the database of abstracts of reviews of effectiveness (DARE). NHS CRD Review, Dissemination, and Information Teams.

OBJECTIVES: Database of Abstracts of Reviews of Effectiveness (DARE) (http:@www.york.ac.uk/inst/crd/) at the NHS Centre for Reviews and Dissemination provides a unique international resource of structured summaries of quality-assessed reviews of health care interventions. These reviews have been identified from searches of electronic databases and by hand-searching journals. This paper describes and summarizes the DARE database, including the topic areas covered and the review methods used. METHODS: The first 480 structured abstracts on the DARE database were summarized. Data were extracted from each database field and coded for analysis. RESULTS: Most of the systematic reviews investigated the effectiveness of treatments: 54% investigated the effectiveness of medical therapies, and 10% assessed surgical interventions. Around two-thirds used meta-analytic methods to combine primary studies. The quality of the reviews was variable, with just over half of the reviews (52%, n = 251) having systematically assessed the validity of the included primary studies. Narrative reviews were more likely than meta-analyses to reach negative conclusions (42% vs. 25%, p = .0001). The 21 reviews that reported drug company funding were more likely to reach positive conclusions (81% vs. 66%, p = .15). CONCLUSION: The DARE database is a valuable source of quality-assessed systematic reviews, and is free and easily accessible. It provides a valuable online resource to help in filtering out poorer quality reviews when assessing the effectiveness of health technologies.

Abstracting and Indexing↗
PubMed1999

The prevalence of gender dysphoria in Scotland: a primary care study.

A questionnaire was sent to senior partners in all general practices in Scotland designed to elicit experience of patients with gender dysphoria: a subjective experience of incongruity between genital anatomy and gender identity. Responses were received from 73% of practices. The prevalence of gender dysphoria among patients aged over 15 years was calculated as 8.18 per 100,000, with an approximate sex ratio of 4:1 in favour of male-to-female patients. One-third of gender-dysphoric patients known to practices had registered in the preceding 12 months, suggesting that patients with this condition are increasingly likely to present for medical care.

Family Practice↗
PubMed1999

Phase I clinical and pharmacokinetic study of PK1 [N-(2-hydroxypropyl)methacrylamide copolymer doxorubicin]: first member of a new class of chemotherapeutic agents-drug-polymer conjugates. Cancer Research Campaign Phase I/II Committee.

PK1 comprises doxorubicin covalently bound to N-(2-hydroxypropyl)methacrylamide copolymer by a peptidyl linker. Following cellular uptake via pinocytosis, the linker is cleaved by lysosomal enzymes, allowing intratumoral drug release. Radically altered plasma and tumor pharmacokinetics, compared to free doxorubicin, and significant activity in animal tumors have been demonstrated preclinically. We aimed to determine the maximum tolerated dose, toxicity profile, and pharmacokinetics of PK1 as an i.v. infusion every 3 weeks to patients with refractory or resistant cancers. Altogether, 100 cycles were administered (range, 20-320 mg/m2 doxorubicin-equivalent) to 36 patients (20 males and 16 females) with a mean age of 58.3 years (age range, 34-72 years). The maximum tolerated dose was 320 mg/m2, and the dose-limiting toxicities were febrile neutropenia and mucositis. No congestive cardiac failure was seen despite individual cumulative doses up to 1680 mg/m2. Other anthracycline-like toxicities were attenuated. Pharmacokinetically, PK1 has a distribution t(1/2) of 1.8 h and an elimination t(1/2) averaging 93 h. 131I-labeled PK1 imaging suggests PK1 is taken up by some tumors. Responses (two partial and two minor responses) were seen in four patients with NSCLC, colorectal cancer, and anthracycline-resistant breast cancer. PK1 demonstrated antitumor activity in refractory cancers, no polymer-related toxicity, and proof of principle that polymer-drug conjugation decreases doxorubicin dose-limiting toxicities. The recommended Phase II dose is 280 mg/m2 every 3 weeks. Studies are planned in colorectal, NSCLC, and breast cancer patients.

Adult↗
PubMed1998

Survival of very young children with medulloblastoma (primitive neuroectodermal tumor of the posterior fossa) treated with craniospinal irradiation.

PURPOSE: Very young children with medulloblastoma are considered to have a worse prognosis than older children. As radiotherapy remains an important part of the treatment, the adverse prognosis could be due to inadequate radiation treatment rather than biological factors. We analyzed the published literature to examine the impact of radiotherapy on survival in this group. METHODS AND MATERIALS: A Medline search was performed and we reviewed studies of treatment of medulloblastoma where radiotherapy was delivered using megavoltage equipment and the minimum follow-up allowed the calculation of 5-year survival rates. RESULTS: Thirty-nine studies were published between 1979 and 1996 with a treatment including craniospinal irradiation and boost to the posterior fossa. Eleven studies comprising 1366 patients analyzed survival by age at diagnosis. Eight of 11 studies showed a worse 5-year survival for the younger patient group which reached statistical significance in two. There is also a suggestion of a higher proportion of children with metastatic disease at presentation in the very young age group. The usual policy in younger children was to give a lower dose of radiotherapy to the craniospinal axis (CSA) and posterior fossa (PF) with reduction of dose in the range of 15 to 25% compared to standard treatment. As dose reduction to the posterior fossa is associated with worse survival and local recurrence is the predominant site of failure, the major determinant of worse survival in very young children with medulloblastoma may be suboptimal radiotherapy. Protocols including postoperative chemotherapy with delayed, omitted, or only local tumor irradiation do not reach survival rates of protocols with standard radiotherapy, also suggesting a continued importance for irradiation. CONCLUSION: Very young children with medulloblastoma have a worse prognosis than older children. Inadequate radiation dose and technique to the primary tumor region may be a major contributing factor. Current chemotherapeutic regimes alone are not sufficient to compensate for reduced radiation doses and volumes.

Age Factors↗
PubMed1998

Cytomegalovirus polymerase chain reaction viraemia in patients receiving ganciclovir maintenance therapy for retinitis.

OBJECTIVES: To determine whether recurrence of polymerase chain reaction (PCR) viraemia during maintenance ganciclovir for cytomegalovirus (CMV) retinitis correlates with (i) CMV disease at a new anatomical site, (ii) progression of the presenting retinitis, or (iii) acquisition of genetic changes in gene UL97 associated with resistance to ganciclovir. DESIGN: A previously described cohort of 45 patients presenting with first episode retinitis was followed clinically using ophthalmoscopy and serial tests for PCR viraemia for a median of 7 months. CMV viral load and genetic markers of ganciclovir resistance were measured in PCR-positive samples. METHODS: PCR amplification of the glycoprotein B region of CMV and quantitative competitive PCR assays were employed. Genetic changes in UL97 were identified by sequencing/point mutation assay. RESULTS: PCR viraemia correlated significantly with new episodes of CMV disease (P=0.011) and a trend was seen for the association with progression of retinitis (P=0.07). Amongst the 14 patients PCR-positive during maintenance ganciclovir, 10 (71%) had genetic markers of resistance. None of these patients became PCR-negative in blood after reinduction ganciclovir therapy compared with three out of four without markers of resistance (P=0.022). CONCLUSIONS: CMV PCR viraemia correlated strongly with the development of new episodes of CMV disease. Most patients with progression of retinitis remained PCR-negative in blood, consistent with therapeutic failure due to poor intraocular penetration of ganciclovir. However, the minority who were PCR-positive in blood may have reinfected their eye, and frequently had markers of ganciclovir resistance. The implications of these findings for the management of patients with CMV disease are discussed.

Antiviral Agents↗
PubMed1998

Mechanical properties of nickel-titanium endodontic instruments and the effect of sodium hypochlorite treatment.

The purpose of this study was to assess the mechanical properties--torsional moment, maximum angular deflection, maximum bending moment, and permanent angular deflection--of four brands of nickel-titanium (NiTi) endodontic file, and compare them with a conventional stainless-steel instrument, both in the presence and absence of sodium hypochlorite (NaOCl). NiTi instruments from four manufacturers were randomly selected and subjected to NaOCl treatment for 12 or 48 h, or not at all. The mechanical properties under test were then measured automatically by a digital torque memocouple. Torsional moment and maximum angular deflection indicate the resistance to torsional fracture of an instrument, maximum bending moment the stiffness of the instrument, and permanent angular deflection the strength of the base alloy. All instruments evaluated complied with or exceeded ADA/ANSI Specification No. 28, with the sole exception of the Maillefer ISO size 40 for torsional moment. JS Dental and McSpadden NiTi files were the most resistant to torsional fracture, but all NiTi files were inferior when compared with stainless-steel files from a previous study. However, NiTi files were superior in flexibility, and Maillefer and Brasseler instruments were the best of the instruments tested. NiTi files also had negligible permanent deformation angles. Furthermore, for all properties tested, NaOCl had no statistically significant effect.

Corrosion↗
PubMed1998

Cutting efficiency of nickel-titanium endodontic instruments and the effect of sodium hypochlorite treatment.

The purpose of this study was to assess the cutting efficiency of nickel-titanium (NiTi) files in the presence and absence of sodium hypochlorite (NaOCl) treatment, and compare them to a conventional stainless-steel K-type file. NiTi files from four manufacturers were randomly selected and exposed to NaOCl for 12 or 48 h, or not at all. Their cutting efficiencies were then assessed, using a new methodology: "mass of Plexiglass cut per energy used over 50 linear cutting motions." In the absence of NaOCl, Brasseler (318 micrograms/J) and Maillefer (280 micrograms/J) NiTi files were most efficient, followed by JS Dental (71.4 micrograms/J) and McSpadden (40 micrograms/J). These differences were significant (p < 0.0001), except for those between the latter two brands. Moreover, NaOCl treatment did not alter the cutting efficiency of any brand of instruments significantly. When compared with conventional stainless steel files, all NiTi files tested were less efficient.

Dental Instruments↗
PubMed1998

Demonstration of hepatic steatosis by computerized tomography in patients receiving 5-fluorouracil-based therapy for advanced colorectal cancer.

The frequency and severity of fatty infiltration of the liver in patients receiving 5-fluorouracil (5-FU) and folinic acid has not been documented systematically. Its development can result in difficulty assessing disease progression, and treatment may be altered inappropriately. Twenty-seven patients with colon cancer and liver metastases receiving 5-FU and folinic acid were studied with computerized tomography (CT) before treatment and after six or 12 cycles of chemotherapy. Forty-seven per cent of patients developed hepatic steatosis during treatment. There was no correlation between development of hepatic steatosis and the dose of chemotherapy or the liver function tests. Hepatic steatosis occurs commonly in patients receiving 5-FU and folinic acid and can be severe. Its development can make hepatic metastases difficult to assess and if its benign nature is not appreciated treatment may be inappropriately altered.

Adult↗
PubMed1998

Epidemic cutaneous sporotrichosis: report of 16 cases in Queensland due to mouldy hay.

We report an epidemic of sporotrichosis in a south-east Queensland rural community. Sporotrichosis is a fungal infection due to the organism Sporothrix schenckii, typically presenting with cutaneous lesions. Sixteen cases of cutaneous sporotrichosis were seen over a 9 month period in the Darling Downs region of Queensland. All patients had had contact with a batch of mouldy hay presumed to be contaminated by Sporothrix schenckii. Nine of 16 patients were male; the youngest patient was aged 11 and the oldest was 67 years of age. Lymphocutaneous sporotrichosis was seen in 50% of patients; the rest demonstrated the fixed cutaneous form. No cases of disseminated cutaneous or systemic sporotrichosis were seen. One case demonstrated lymphangitis related to sporotrichosis. No apparent difference in the duration to diagnosis was demonstrated to exist between lymphocutaneous or fixed cutaneous types.

Adolescent↗
PubMed1998

Amino acid insertions and deletions contribute to diversify the human Ig repertoire.

The sequence analysis of Ig variable region genes transcribed within different B-cell subpopulations from human tonsil led us to identify a rare DNA sequence modification event consisting of bp insertions and/or deletions (I/D). Although these events were previously reported, they had never been formally associated with the somatic hypermutation process. I/D events share with more conventional somatic hypermutation events their localization within hypervariable regions and, most particularly, within DNA motifs known to be mutational hot spots. Repetitive DNA tracts or DNA elements capable of forming DNA loop intermediates seem to be the preferred substrate for I/D to occur. These characteristics suggest a model for somatic hypermutation reminiscent of the "polymerase slippage" model involved in replication and repair mutations in prokaryotes, yeast, and mammals.

Amino Acid Substitution↗