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Biomedical subjects

D Wilson

Publications and source records attributed to D Wilson.

At least 55 records · Page 3Linked to original sources
PubMed2003

A European outbreak of Salmonella enterica serotype Typhimurium definitive phage type 204b in 2000.

OBJECTIVE: To describe the clinical, epidemiologic and microbiological features of a large outbreak of infection with a multiresistant Salmonella enterica serotype Typhimurium definitive type DT204b infection involving at least 392 people in five European countries. METHODS: Icelandic public-health doctors responded to a report on an Internet news site of an outbreak of infection with a multiresistant strain of Typhimurium DT104 in England by contacting the Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC). An international alert was sent out through Enter-net. All strains from England & Wales, The Netherlands, Scotland and Germany, and 17 of the outbreak isolates from Iceland, were phage-typed, screened for antimicrobial resistance, and subjected to molecular typing. Hypothesis-generating interviews were conducted, followed by case-control studies performed in Iceland and England. RESULTS: Isolates from cases in Iceland, England and Wales, The Netherlands, Scotland and Germany were identified as Typhimurium DT204b. The antimicrobial resistance pattern was ACGNeKSSuTTmNxCpL. All strains tested displayed an identical plasmid profile. Strains from five cases in England & Wales and five cases in Iceland possessed identical pulsed-field profiles. Although a common source was suspected, only Iceland implicated imported lettuce as a vehicle, with an analytic epidemiologic study (OR = 40.8; P = 0.005; 95% CI 2.7-3175). CONCLUSION: The identification of international outbreaks, necessary for investigation and control, can be facilitated by standardized phage-typing techniques, the electronic transfer of molecular typing patterns, formal and informal links established through international surveillance networks, and the early reporting of national outbreaks to such networks.

Adolescent↗
PubMed2003

Hypoparathyroidism and 22q11 deletion syndrome.

AIMS: To investigate a population of individuals with 22q11 deletion syndrome for hypocalcaemia. METHODS: A detailed clinical history enquiring into symptoms of hypocalcaemia and blood sampling to assess for hypocalcaemia and hypoparathyroidism, of patients outside the neonatal period known to have the 22q11 microdeletion from fluorescent in situ hybridisation studies was taken. RESULTS: Sixty one individuals were identified, of whom 23 were untraceable and one was unable to give informed consent. Biochemical investigations were performed on 27 subjects. Ten subjects had review of notes only. Four subjects had previously identified hypoparathyroidism. A new case of hypoparathyroidism was identified. Three subjects had borderline hypocalcaemia. DISCUSSION: In this population of patients with 22q11 deletion syndrome, 13% of the total or 30% of those biochemically assessed had evidence of reduced serum calcium concentrations. It is likely that 13-30% of patients with 22q11 deletion syndrome have possible hypoparathyroidism outside the neonatal period. Reported symptoms of hypocalcaemia did not correlate with biochemical evidence of persisting hypocalcaemia. We have shown that previously undiagnosed asymptomatic hypoparathyroidism occurs in patients with 22q11 deletion syndrome and conclude that screening of this population should be considered.

Adolescent↗
PubMed2003

Small "indeterminate" lesions on CT of the liver: a follow-up study of stability.

Distinguishing between small benign malformations in the liver and early metastatic disease remains difficult. We identified a group of 115 patients with known or suspected malignant disease who had "indeterminate" small liver lesions and who underwent 2-16 CT examinations (median 5) over a follow up period of 6-60 months (median 16). The size, shape, edge, homogeneity and attenuation of each of these lesions was assessed. The lesions were classified by their behaviour on follow up CT as either stable (79%) or unstable (21%). The unstable lesions (n=62) included 37 that grew larger and 25 that became smaller or disappeared in patients undergoing anti-tumour therapy. Image features predictive of stable behaviour were small size and sharp edge. Heterogeneity and soft tissue attenuation were significantly associated with unstable behaviour, but these features were seen in only a small minority of cases. Shape had no predictive value. A logistic regression model was constructed based on size and edge to allow an estimate to be made of the likelihood of an individual lesion being unstable. In patients with known or suspected malignant disease, the majority of isolated small liver lesions found on CT are benign. Although size under 5 mm and a sharp margin are favourable features, this appearance does not exclude malignancy.

Colonic Neoplasms↗
PubMed2003

Removal of well-fixed, cementless, acetabular components in revision hip arthroplasty.

Removal of well-fixed, cementless, acetabular components during revision arthroplasty remains a challenging problem. Further damage to host bone may limit options for reconstruction and compromise the long-term result of the revision operation. We report the results of 31 hips with well-fixed, cementless sockets which were removed using a new cup extraction system. In all hips the socket was removed without difficulty and with minimal further bone loss.

Acetabulum↗
PubMed2002

Altered venous function and deep venous thrombosis following proximal femoral fracture.

The effect of surgery for femoral neck fracture on lower limb venous blood flow and its relationship to deep vein thrombosis was investigated in 179 patients. Blood flow was measured using strain gauge plethysmography before surgery, in the 1st week after surgery, and at 6 week review. There was a significant reduction in both venous outflow and venous capacitance, affecting both fractured and non-fractured legs but significantly greater in the fractured leg. Venous function remained significantly impaired in both lower limbs 6 weeks after surgery. There was a significant correlation between the reduction in venous function and the development of deep vein thrombosis.

Aged↗
PubMed2002

Cross-reactivity of Sydney funnel-web spider antivenom: neutralization of the in vitro toxicity of other Australian funnel-web (Atrax and Hadronyche) spider venoms.

Australian funnel-web spiders are recognized as one of the most venomous spiders to humans world-wide. Funnel-web spider antivenom (FWS AV) reverses clinical effects of envenomation from the bite of Atrax robustus and a small number of related Hadronyche species. This study assessed the in vitro efficacy of FWS AV in neutralization of the effects of funnel-web spider venoms, collected from various locations along the eastern seaboard of Australia, in an isolated chick biventer cervicis nerve-muscle preparation. Venoms were separated by SDS-PAGE electrophoresis to compare protein composition and transblotted for Western blotting and incubation with FWS AV.SDS-PAGE of venoms revealed similar low and high molecular weight protein bands. Western blotting with FWS AV showed similar antivenom binding with protein bands in all the venoms tested. Male funnel-web spider venoms (7/7) and female venoms (5/10) produced muscle contracture and fasciculation when applied to the nerve-muscle preparation. Venom effects were reversed by subsequent application of FWS AV or prevented by pretreatment of the preparation with antivenom.FWS AV appears to reverse the in vitro toxicity of a number of funnel-web spider venoms from the eastern seaboard of Australia. FWS AV should be effective in the treatment of envenomation from most, if not all, species of Australian funnel-web spiders.

Antivenins↗
PubMed2002

Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial.

BACKGROUND: Previous studies suggest that sublingual immunotherapy (SLIT) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed. OBJECTIVE: To evaluate the efficacy and safety of SLIT in grass pollen-induced seasonal rhinoconjunctivitis. METHODS: A randomized, placebo-controlled trial in 56 adults over 18 months. Outcome measures included diary scores of seasonal symptoms and medication use, overall assessments, conjunctival and intradermal provocation tests and serum antibody measurements. To investigate possible mechanisms, sublingual biopsies were taken for measurement of local T cells, antigen-presenting cells and IL-12 mRNA expression. RESULTS: There were no significant differences between the immunotherapy (IT) and placebo groups for diary symptom scores (P = 0.48) or rescue medication (P = 0.19). The patients' overall assessment of hayfever severity compared with previous years showed a highly significant improvement in favour of the IT group (P < 0.02). After treatment the late skin response was smaller (P = 0.003) and the ratio of serum allergen-specific IgG4/IgE was higher (P = 0.05) in the IT group. Both of these variables correlated with the clinical response to SLIT. There were no differences between groups in either the sublingual epithelium or lamina propria for numbers of CD3+ cells (epithelium: P = 0.9, lamina propria: P = 0.2), CD1a+ cells (P = 0.3, P = 0.25), CD68+ cells (P = 0.9, P = 1.0) or IL-12 mRNA+ cells (P = 0.6, P = 0.4). Local side-effects were minor and there were no serious treatment-related adverse events. CONCLUSION: Grass pollen sublingual immunotherapy was well tolerated. Although there was no significant change in diary scores, the improvement in overall assessments, which correlated with inhibition of the late skin response and increases in serum IgG4 : IgE ratio, indicates the need for larger, dose-ranging studies.

Administration, Sublingual↗
PubMed2002

Effect of the methodology on circulating peptides determination and consequences on net flux measurements across the gastrointestinal tract of sheep.

Two methodologies for the measurement of peptide amino acids (PAA) in blood were compared to evaluate their effects on the measurement of the net flux of peptides across the gastrointestinal tract of sheep. These methods consisted of a chemical deproteinization of blood samples with sulfosalicylic acid (1.6 M, 0.1 ml for 1 ml of sample) or perchloric acid (1 M, 1 ml for 1 ml of sample) followed by ultrafiltration through a 3,000-Da cut-off filter (SSA + UF3 kD) or gel filtration through a Sephadex G-15 column (1,500-Da cut-off filter; PCA + G-15), respectively, prior to PAA analysis. Peptide concentrations as determined by amino acid concentrations before and after hydrolysis of samples were slightly greater with the SSA + UF3 kD (991 microM) than with the PCA + G-15 (605 microM) methodology. However, both methodologies gave similar net portal-drained viscera flux data in sheep fed on alfalfa pellets with histidine as the only significant uptake of peptide amino acid.

Amino Acids↗
PubMed2001

Neuromagnetic spectral distribution of implicit processing of words.

Neuromagnetic spectral distributions when silently viewing words and non-words were investigated using a 151-channel whole head MEG system. The data were analyzed with synthetic aperture magnetometry (SAM). The dominant changes of spectral power were identified in the parietal and occipital cortices in 15-30 Hz, 30-60 Hz and 60-125 Hz bands following both word and non-word stimulations. The changes in Broca's and Wernicke's areas were consistently observed in 60-125 Hz bands, mainly following word stimulation. The results indicated that the occipital and parietal cortices were most probably involved in visuospatial processing of words and non-words. The language areas, particularly Broca's and Wernickes's areas, might be involved in implicit word processing such as verbal searching and/or internal speech.

Adult↗
PubMed2001

NFkappaB activation is required for the neuroprotective effects of pigment epithelium-derived factor (PEDF) on cerebellar granule neurons.

Pigment epithelium-derived factor (PEDF) protects immature cerebellar granule cells (1-3 days in vitro) against induced apoptosis and mature cells (5+ days in vitro) against glutamate toxicity, but its precise mechanism is still unknown. Because the transcription factor NFkappaB blocks cell death, including neuronal apoptosis, we have investigated the ability of PEDF to exert its effects via NFkappaB activation. PEDF induced an increased phosphorylation of IkappaBalpha, decreased levels of IkappaB proteins, and translocation of p65 (RelA) to the nucleus followed by a time-dependent increase of NFkappaB-DNA binding activity in both immature and mature neurons. The protective effects of PEDF against both induced apoptosis and glutamate toxicity were blocked by the addition of either the IkappaB kinase inhibitor BAY 11-7082, which inhibits the phosphorylation of IkappaB, or N-acetyl-Leu-Leu-norleucinal, which blocks proteosome degradation of IkappaB, demonstrating that NFkappaB is required for the neuroprotective effects of PEDF. Reverse transcription-polymerase chain reaction analysis revealed that up-regulation of the anti-apoptotic genes for Bcl-2, Bcl-x, and manganese superoxide dismutase was observed in PEDF-treated immature but not mature neurons. Up-regulation of nerve growth factor, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor mRNA was long-lasting in mature neurons. These results suggest that PEDF promotes neuronal survival through activation of NFkappaB, which in turn induces expression of anti-apoptotic and/or neurotrophic factor genes.

Animals↗
PubMed2001

Discovery and structure of a potent and highly specific blocker of insect calcium channels.

We have isolated a novel family of insect-selective neurotoxins that appear to be the most potent blockers of insect voltage-gated calcium channels reported to date. These toxins display exceptional phylogenetic specificity, with at least a 10,000-fold preference for insect versus vertebrate calcium channels. The structure of one of the toxins reveals a highly structured, disulfide-rich core and a structurally disordered C-terminal extension that is essential for channel blocking activity. Weak structural/functional homology with omega-agatoxin-IVA/B, the prototypic inhibitor of vertebrate P-type calcium channels, suggests that these two toxin families might share a similar mechanism of action despite their vastly different phylogenetic specificities.

Amino Acid Sequence↗
PubMed2001

Congenital glioblastoma multiforme: a report of three cases and a review of the literature.

The clinical histories, histologic features, and immunohistochemical staining patterns for glial fibrillary acidic protein, vimentin, p53, and epidermal growth factor receptor (EGFR) of three cases of congenital glioblastoma multiforme are given and previous case reports are reviewed. Of the three cases reported in this series, two have had long-term survivals of greater than 2 1/2 and 5 1/2 years after surgery and surgery followed by chemotherapy, respectively. Both of these cases also demonstrated p53 protein accumulation, a finding in pediatric glioblastoma multiforme associated with poor prognosis. The third case occurred in an infant who died at birth and demonstrated a well-circumscribed tumor that did not invade adjacent brain parenchyma. Considering these three cases, the biological behavior in congenital glioblastoma multiforme may not be unfavorable as portrayed in the literature or as seen in its adult counterpart.

Adolescent↗
PubMed2001

Community thrombolysis in the Coromandel region. Audit of the "Cardiac Events in the Coromandel-Assessment Strategy and Triage" (CE-COAST) pilot program.

AIM: To audit the experience of a pilot program for community thrombolysis undertaken within the Coromandel region. METHODS: Community thrombolysis for patients suffering acute myocardial infarction (MI) was undertaken in areas within the Coromandel peninsula greater than half an hour by road from Thames Hospital. Thrombolytic therapy (Retelapse) was given following a discussion and review of a digitally transmitted ECG with the cardiology registrar. Treatment times and patients demographics were prospectively recorded. Subsequent clinical events were by chart review. Comparison of treatment times were made with an historical cohort for the same population which had received in-hospital thrombolysis between 1993 and 1998. RESULTS: Between July 1998 and December 1999, nineteen patients received thrombolysis in the community. There were no arrhythmic events during transportation and no deaths or reinfarctions during hospital stay. Median time from pain onset to thrombolysis was 135 (mean 175.5 +/- 144.9 SD) minutes which equated to a reduction in median time delay of 135 minutes compared to that experienced by the historical cohort (median 270, mean 316.7 +/- 145.8 SD minutes), p=0.0003. CONCLUSION: Community thrombolysis is logistically feasible within the New Zealand setting and results in major time reductions in the treatment of patients with acute MI.

Aged↗
PubMed2001

Gender differences in virologic response to treatment in an HIV-positive population: a cohort study.

OBJECTIVE: To establish whether a gender difference in virologic response to highly active antiretroviral treatment (HAART) exists. METHODS: A cohort of HIV-positive individuals was examined. OUTCOMES: Achievement of viral load <500 copies/ml and "failure" (failure to suppress viral load <500 copies/ml after 24 weeks or two consecutive measurements above this level after having suppressed below it). Hazard ratios (HRs) comparing the rate in women to that in men were derived using the Cox model. RESULTS: Of 366 male subjects, 79% were white and 82% were homosexual. Sixty-three percent of the 91 female subjects were African and 87% were heterosexual. The median follow-up after HAART was 94 weeks. The baseline CD4 count was higher in men (228 x 106 per liter) than in women (171 x 106 per liter) (p =.01), but the viral load was similar (p =.88). The median time to <500 copies/ml was 16 weeks. Women achieved a viral load of <500 copies/ml at a faster rate than men, with an adjusted HR of 1.46 (95% confidence interval [CI]: 0.99-2.16; p =.06). Some 261 patients failed treatment (58% of men and 53% of women) with an HR of 0.78 (95% CI: 0.51-1.21; p =.27). CONCLUSIONS: Women may achieve virologic suppression at a faster rate than men and have a more durable response. Further research should examine these responses in conjunction with clinical outcomes, because gender differences in virologic response may ultimately be of little relevance if clinical outcomes are similar.

Adult↗
PubMed2001

Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre.

OBJECTIVE: To describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic. SUBJECTS: A total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC). RESULTS: The median CD4 count at starting HAART was 171 x 10(6) cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years; P = 0.0008], as were previously treatment-naive patients (RH, 0.65; P = 0.0050), those in a clinical trial (RH, 0.64; P = 0.027) and those who started nelfinavir (RH, 0.57; P = 0.035). Patients who started with four or more drugs (RH, 2.21, P < 0.0001), who included ritonavir in the initial regimen (RH, 1.41; P = 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51; P < 0.0001) were more likely to modify HAART. CONCLUSIONS: There was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance.

Antiretroviral Therapy, Highly Active↗