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W Jones

Publications and source records attributed to W Jones.

At least 19 recordsLinked to original sources

Understanding the influence of polymorphism on phonon spectra: lattice dynamics calculations and terahertz spectroscopy of carbamazepine.

Rigid molecule atomistic lattice dynamics calculations have been performed to predict the phonon spectra of the four polymorphs of carbamazepine, and these calculations predict that there should be differences in the spectra of all four forms. Terahertz spectra have been measured for forms I and III, and there are clearly different features between polymorphs' spectra, that are accentuated at low temperature. While carbamazepine adopts the same hydrogen bonded dimers in all of its known polymorphs, the calculations show that differences in packing arrangements of the dimers lead to changes in the frequency ranges for each type of hydrogen bond vibration, giving a physical explanation to the observed differences between the spectra. Although the agreement between calculated and observed spectra does not allow a definitive characterization of the spectra, it is possible to make tentative assignments of many of the observed features in the terahertz region for the simpler form III; we can only make some tentative assignments of specific modes in the more complex spectrum of form I. While harmonic rigid molecule lattice dynamics shows promise for understanding the differences in spectra between polymorphs of organic molecules, discrepancies between observed and calculated spectra suggest areas of improvement in the computational methods for more accurate modeling of the dynamics in molecular organic crystals.

Carbamazepine↗

Differential chemosensory function and receptor expression of splanchnic and pelvic colonic afferents in mice.

Lumbar splanchnic (LSN) and sacral pelvic (PN) nerves convey different mechanosensory information from the colon to the spinal cord. Here we determined whether these pathways also differ in their chemosensitivity and receptor expression. Using an in vitro mouse colon preparation, individual primary afferents were tested with selective P2X and transient receptor potential vanilloid receptor 1 (TRPV1) receptor ligands. Afferent cell bodies in thoracolumbar and lumbosacral dorsal root ganglia (DRG) were retrogradely labelled from the colon and analysed for P2X3- and TRPV1-like immunoreactivity (LI). Forty per cent of LSN afferents responded to alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-meATP; 1 mm), an effect that was concentration dependent and reversed by the P2X antagonist pyridoxyl5-phosphate 6-azophenyl-2',4'-disulphonic acid (PPADS) (100 microm). Significantly fewer PN afferents (7%) responded to alpha,beta-meATP. Correspondingly, 36% of colonic thoracolumbar DRG neurones exhibited P2X3-LI compared with only 19% of colonic lumbosacral neurones. Capsaicin (3 microm) excited 61% of LSN afferents and 47% of PN afferents; 82% of thoracolumbar and 50% of lumbosacral colonic DRG neurones displayed TRPV1-LI. Mechanically insensitive afferents were recruited by alpha,beta-meATP or capsaicin, and were almost exclusive to the LSN. Capsaicin-responsive LSN afferents displayed marked mechanical desensitization after responding to capsaicin, which did not occur in capsaicin-responsive PN afferents. Therefore, colonic LSN and PN pathways differ in their chemosensitivity to known noxious stimuli and their corresponding receptor expression. As these pathways relay information that may relate to symptoms in functional gastrointestinal disease, these results may have implications for the efficacy of therapies targeting receptor modulation.

Adenosine Triphosphate↗

Improved sensitivity of sputum smear microscopy after processing specimens with C18-carboxypropylbetaine to detect acid-fast bacilli: a study of United States-bound immigrants from Vietnam.

The goal of this study was to evaluate the effect of the specimen-processing method that uses the detergent C18-carboxypropylbetaine (CB-18) on the sensitivity of acid-fast bacillus (AFB) staining. Vietnamese immigrants with abnormal chest radiographs provided up to three sputum specimens, which were examined for acid-fast bacilli by use of direct auramine and Ziehl-Neelsen staining. The remaining sputum was split; half was cultured, and the other half was incubated with CB-18 for 24 h, centrifuged, and examined for AFB by both staining methods. CB-18 processing improved the sensitivity of AFB staining by 20 to 30% (only differences in auramine sensitivity were statistically significant) but reduced specificity by approximately 20% (P < 0.05). These findings have direct utility for overseas migrant tuberculosis screening programs, for which maximizing test sensitivity is a major objective.

Adult↗

Results of tuberculosis screening in applicants for migration in Vietnam and Cambodia.

SETTING: Pre-migration medical screening programmes in Ho Chi Minh City, Vietnam and Phnom Penh, Cambodia. OBJECTIVE: To compare the rates of newly diagnosed bacteriologically confirmed tuberculosis (TB) in a cohort of migration applicants in Vietnam and Cambodia with current estimates of the TB burden in these countries. DESIGN: Interviews and medical screening of 5108 Vietnamese and 910 Cambodian migration applicants who applied for an Australian visa. RESULTS: On initial testing, the rate of bacteriologically confirmed TB among the Vietnamese cohort was 157 per 100,000 population compared to 989/100,000 among the Cambodian cohort. When cases detected during follow-up testing were included, the rate in the Vietnamese cohort was 489/100,000 compared to 1209/100,000 in the Cambodian cohort. CONCLUSIONS: Although it has been suggested that the rate of newly diagnosed bacteriologically confirmed TB among migration applicants would underestimate the prevalence of TB in the Vietnamese and Cambodian populations, the rates found were substantially higher than current point estimates of the prevalence of TB, particularly for Vietnam. Our findings suggest that current published estimates of the tuberculosis burden in Vietnam and Cambodia may be conservative.

Adolescent↗

Treatment outcome of multidrug-resistant tuberculosis among Vietnamese immigrants.

OBJECTIVE: To review the outcome for MDR-TB treatment among potential migrants from Vietnam. SETTING: All cases of documented MDR-TB treated by the International Organization of Migration (IOM) in Vietnam from 1989 to 2000 were reviewed. METHODS: MDR-TB was defined as isoniazid- and rifampicin-resistant Mycobacterium tuberculosis. All cases of TB treated by the IOM and recorded in the computerised database were reviewed to identify MDR-TB cases. Demographics, chest radiograph results, drug resistance, drug use and dosage, duration of treatment, and outcome were analysed. RESULTS: Forty-four cases of MDR-TB were identified. Treatment consisted of ambulatory directly observed treatment with an 8-drug protocol: isoniazid, rifampicin, pyrazinamide, ethambutol, capreomycin, ethionamide, ofloxacin and cycloserine. This initial protocol was modified due to drug availability or drug intolerance. Patients were treated with a median of 8 drugs (range 6-12). Mean duration of treatment for MDR-TB was 23.0 (SD+/-11.4) months. Thirty-eight (86%) patients were cured and emigrated, one failed treatment (2%), three were lost to follow-up (7%) and two died (4%). CONCLUSION: Treatment for MDR-TB provided by the IOM was effective in preparing a low-income population for migration.

Capreomycin↗

Bleomycin, vincristine, cisplatin/bleomycin, etoposide, cisplatin chemotherapy: an alternating, dose intense regimen producing promising results in untreated patients with intermediate or poor prognosis malignant germ-cell tumours.

Patients with poor and intermediate prognosis metastatic germ-cell tumours (MGCTs) are at a significant risk of relapse after standard platinum-based chemotherapy. Novel treatment regimens are required to improve survival. Dose intense, alternating combinations of drugs with known activity in germ-cell tumours represents one approach. In all, 43 patients with IGCCCG intermediate/poor prognosis MGCT were treated with a dose intense regimen alternating bleomycin, vincristine, cisplatin (BOP) with bleomycin, etoposide, cisplatin (BEP) to a maximum of three cycles. Data were collected on the maintenance of dose intensity, toxicity, response, progression-free (PFS) and overall survival (OS). The complete response rate was 58%; a further 7% of patients being rendered disease free by resection of viable residual tumour. With a median follow-up of more than 4 years in surviving patients, 3-year OS and PFS rates of 81% (95% CI: 66-91%) and 72% (95% CI: 56-83%) are seen, respectively. Bleomycin, vincristine, cisplatin (BOP)/bleomycin, etoposide, cisplatin (BEP) was well tolerated, with 86% of patients completing all planned courses. Toxicity was predominantly haematological with common toxicity criteria grade III neutropenia in 90% of patients. Cisplatin neuropathy and bleomycin-induced pulmonary toxicity represented the most significant nonhaematological toxicity. Bleomycin, vincristine, cisplatin (BOP)/bleomycin, etoposide, cisplatin (BEP) represents a practicable, well-tolerated, dose intense chemotherapy regimen with significant activity in intermediate and poor prognosis MGCT.

Adolescent↗

European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG).

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.

Europe↗

Community based program to improve firearm storage practices in rural Alaska.

OBJECTIVE: To develop and evaluate a pilot program to reduce unauthorized access to firearms by youth by distributing gun safes and trigger locks to households. DESIGN: Pilot intervention with pre/post-evaluation design. SETTING: Two Alaska Native villages in the Bristol Bay Health Corporation region of southwest Alaska. SUBJECTS: Forty randomly selected households with two or more guns in the home. INTERVENTION: Initially, a focus group of community members who owned guns was convened to receive input regarding the acceptability of the distribution procedure for the gun storage devices. One gun safe and one trigger lock were distributed to each of the selected households during December 2000. Village public safety officers assisted with the distribution of the safes and provided gun storage education to participants. MAIN OUTCOME MEASURES: Baseline data were collected regarding household gun storage conditions at the time of device distribution. Three months after distribution, unannounced onsite home visits were conducted to identify if residents were using the gun safes and/or trigger locks. RESULTS: All selected households had at least two guns and 28 (70%) of the 40 households owned more than two guns. At baseline, 85% of homes were found to have unlocked guns in the home and were most often found in the breezeway, bedroom, storage room, or throughout the residence. During the follow up visits, 32 (86%) of the 37 gun safes were found locked with guns inside. In contrast, only 11 (30%) of the 37 trigger locks were found to be in use. CONCLUSIONS: This community based program demonstrated that Alaska Native gun owners accepted and used gun safes when they were installed in their homes, leading to substantial improvements in gun storage practices. Trigger locks were much less likely to be used.

Adolescent↗

Predictors of tuberculin reactivity among prospective Vietnamese migrants: the effect of smoking.

We investigated the prevalence and predictors of positive tuberculin skin test (TST) results among prospective Vietnamese migrants. We interviewed and medically screened 1395 Vietnamese people aged over 15 years who had applied to migrate to Australia. Approximately 44% of applicants had an induration of 10 mm or more, and 18.6% had an induration of 15 mm or more. A positive tuberculin skin test at 5 mm, 10 mm and 15 mm of induration cut-points was significantly associated with age (OR 1.01-1.02 per year) and duration of smoking (OR 1.03-1.12 per year). Smoking appears to be an important factor associated with increased susceptibility to mycobacterial infection. It is not yet clear whether the increased tuberculin reactivity associated with smoking reflects an increased risk of tuberculosis among these migrants.

Adolescent↗

In vitro identification of metabolic pathways and cytochrome P450 enzymes involved in the metabolism of etoperidone.

1. In vitro studies have been carried out to investigate the metabolic pathways and identify the hepatic cytochrome P450 (CYP) enzymes involved in etoperidone (Et) metabolism. 2. Ten in vitro metabolites were profiled, quantified and tentatively identified after incubation with human hepatic S9 fractions. Et was metabolized via three metabolic pathways: (A) alkyl hydroxylation to form OH-ethyl-Et (M1); (B) phenyl hydroxylation to form OH-phenyl-Et (M2); and (C) N-dealkylation to form 1-m-chlorophenylpiperazine (mCPP, M8) and triazole propyl aldehyde (M6). Six additional metabolites were formed by further metabolism of M1, M2, M6 and M8. 3. Kinetic studies revealed that all metabolic pathways were monophasic, and the pathway leading to the formation of OH-ethyl-Et was the most efficient at eliminating the drug. On incubation with microsomes expressing individual recombinant CYPs, formation rates of M1-3 and M8 were 10-100-fold greater for CYP3A4 than that for other CYP forms. The formation of these metabolites was markedly inhibited by the CYP3A4-specific inhibitor ketoconazole, whereas other CYP-specific inhibitors did not show significant effects. In addition, the production of M1-3 and M8 was strongly correlated with CYP3A4-mediated testosterone 6beta-hydroxylase activities in 13 different human liver microsome samples. 4. Dealkylation of the major metabolite M1 to form mCPP (M8) was also investigated using microsomes containing recombinant CYP enzymes. The rate of conversion of M1 to mCPP by CYP3A4 was 503.0 +/- 3.1 pmole nmole(-1) min(-1). Metabolism of M1 to M8 by other CYP enzymes was insignificant. In addition, this metabolism in human liver microsomes was extensively inhibited by the CYP3A4 inhibitor ketoconazole, but not by other CYP-specific inhibitors. In addition, conversion of M1 to M8 was highly correlated with CYP3A4-mediated testosterone 6beta-hydroxylase activity. 5. The results strongly suggest that CYP3A4 is the predominant enzyme-metabolizing Et in humans.

Chromatography, Liquid↗

Bis[1-hydroxypyridine-2(1H)-thionato-S,O]copper(II).

The crystal structure of the widely used title fungicidal material, [Cu(C(5)H(4)NOS)(2)], has been determined at 150 (2) K from a microcrystalline fragment using synchrotron radiation. The molecule adopts a trans-square-planar configuration, with the Cu atom sited at a crystallographic centre of inversion.

Crystallography, X-Ray↗

Respiratory symptoms among crab processing workers in Alaska: epidemiological and environmental assessment.

BACKGROUND: Crab processing workers may develop respiratory symptoms and specific IgE responses, but the risk factors have not been fully described. METHODS: In 1998, 107 workers at a crab processing facility completed a survey both at the beginning and end of the processing season. The surveys included standardized symptom questionnaires, spirometry, and serological testing, as well as measurement of workplace airborne crab allergens and microscopic analysis of aerosolized materials. RESULTS: Over the crab processing season, asthma-like symptoms developed in 26% of study participants and bronchitic symptoms in 19%. Only 9% of those with new asthma-like symptoms were IgE-sensitized to crab at the end of the season. Among the crab processing jobs, butchering and degilling workers had the highest incidence of respiratory symptoms. CONCLUSIONS: Both personal and process-related factors appear to affect the development of respiratory symptoms in crab processing workers. In this study, crab specific IgE was not detected in most of the workers with new symptoms. Published 2001 Wiley-Liss, Inc.

Adolescent↗

Comparative pulmonary toxicity of 6 abrasive blasting agents.

Inhalation of silica dust is associated with pulmonary fibrosis. Therefore, substitute abrasive materials have been suggested for use in abrasive blasting operations. To date, toxicological evaluation of most substitute abrasives has been incomplete. Therefore, the objective of this study was to compare the pulmonary toxicity of a set of substitute abrasives (garnet, staurolite, coal slag, specular hematite, and treated sand) to that of blasting sand. Rats were exposed to blasting sand or an abrasive substitute by intratracheal instillation and pulmonary responses to exposure were monitored 4 weeks postexposure. Pulmonary damage was monitored as lactate dehydrogenase (LDH) in the acellular lavage fluid. Pulmonary inflammation was evaluated from the yield of polymorphonuclear leukocytes (PMN) obtained by bronchoalveolar lavage. The activity of alveolar macrophages was determined by measuring zymosan-stimulated chemiluminescence. Blasting sand caused lung damage and showed histologic evidence for inflammation and fibrosis. Garnet, staurolite, and treated sand exhibited toxicity and inflammation that were similar to blasting sand, while coal slag caused greater pulmonary damage and inflammation than blasting sand. In contrast, specular hematite did not significantly elevate LDH or PMN levels and did not stimulate macrophage activity 4 weeks postexposure.

Animals↗

Time course of pulmonary response of rats to inhalation of crystalline silica: histological results and biochemical indices of damage, lipidosis, and fibrosis.

Previous studies have determined that alpha-quartz (crystalline silica) can cause pulmonary inflammation, damage, and fibrosis. However, the temporal relationship between silica inhalation and pulmonary inflammation, damage, and fibrosis has not been fully examined. To address this gap in our knowledge of silica-induced pulmonary fibrosis, a chronic inhalation study using rats was designed. Specifically, rats were exposed to a silica aerosol (15 mg/m3 silica, 6 h/d, 5 d/wk, 116 d), and measurements of pulmonary inflammation, damage, and fibrosis were monitored throughout the study. We report (1) data demonstrating that the silica aerosol generation and exposure system produced a consistent silica aerosol of respirable size particles; (2) the time course of silica deposition in the lung; (3) calculations that demonstrate that the rats were not in pulmonary overload; (4) histopathological data demonstrating time-dependent enhancement of silica-induced alveolitis, epithelial hypertrophy and hyperplasia, alveolar lipoproteinosis, and pulmonary fibrosis in the absence of overload; and (5) biochemical data documenting the development of lipidosis, lung damage, and fibrosis.

Administration, Inhalation↗

Activation of mitogen-activated protein kinase p38 and extracellular signal-regulated kinase is involved in glass fiber-induced tumor necrosis factor-alpha production in macrophages.

In a previous study, we demonstrated that the length of glass fibers was a critical determinant of fiber potency in induction of tumor necrosis factor (TNF)-alpha and that activation of NF-kappaB was an important factor in this response. In the present study, we analyzed the role of mitogen-activated protein (MAP) kinases in the induction of TNF-alpha by glass fibers. Glass fibers induced phosphorylation of MAP kinases, p38, and ERK in primary rat alveolar macrophages, and this phosphorylation was associated with TNF-alpha gene expression. Long fibers were more potent than short fibers in activation of MAP kinases. Results from mechanistic analysis support that MAP kinases activate transcription factor c-Jun. The activated c-Jun acts on the TNF-alpha gene promoter through two binding sites, the cyclic AMP response element and the activator protein 1-binding site. These results suggest that in addition to the NF-kappaB pathway for TNF-alpha production, glass fibers are able to activate c-Jun through MAP kinase pathways that lead to induction of TNF-alpha expression.

Animals↗