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Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 145 records · Page 8Linked to original sources
PubMed2000

Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis.

PURPOSE: Recent randomized trials in women with node-positive breast cancer who received systemic treatment report that locoregional radiation therapy improves survival. Previous trials failed to detect a difference in survival that results from its use. A systematic review of randomized trials that examine the effectiveness of locoregional radiation therapy in patients treated by definitive surgery and adjuvant systemic therapy was conducted. METHODS: Randomized trials published between 1967 and 1999 were identified through MEDLINE database, CancerLit database, and reference lists of relevant articles. Relevant data was abstracted. The results of randomized trials were pooled using meta-analyses to estimate the effect of treatment on any recurrence, locoregional recurrence, and mortality. RESULTS: Eighteen trials that involved a total of 6,367 patients were identified. Most trials included both pre- and postmenopausal women with node-positive breast cancer treated with modified radical mastectomy. The type of systemic therapy received, sites irradiated, techniques used, and doses of radiation delivered varied between trials. Data on toxicity were infrequently reported. Radiation was shown to reduce the risk of any recurrence (odds ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.83), local recurrence (odds ratio, 0.25; 95% CI, 0.19 to 0.34), and mortality (odds ratio, 0.83; 95% CI, 0.74 to 0.94). CONCLUSION: Locoregional radiation after surgery in patients treated with systemic therapy reduced mortality. Several questions remain on how these results should be translated into current-day clinical practice.

Breast Neoplasms↗
PubMed2000

A sensitive solid-phase fluoroimmunoassay for detection of opiates in urine.

An automated flow fluorometer designed for kinetic binding analysis was adapted to develop a solid-phase competitive fluoroimmunoassay for urinalysis of opiates. The solid phase consisted of polymer beads coated with commercial monoclonal antibodies (MAbs) raised against morphine. Fluorescein-conjugated morphine (FL-MOR) was used as the fluorescein-labeled hapten. The dissociation equilibrium constant (K(D)) for the binding of FL-MOR to the anti-MOR MAb was 0.23 nM. The binding of FL-MOR to the anti-MOR MAb reached steady state within minutes and was displaced effectively by morphine and other opiates. Morphine-3-glucuronide (M3G), the major urinary metabolite of heroin and morphine, competed effectively with FL-MOR in a concentration-dependent manner for binding to the antimorphine MAb and was therefore used to construct the calibration curve. The sensitivity of the assay was 0.2 ng/mL for M3G. The assay was effective at concentrations of M3G from 0.2 to 50 ng/mL, with an IC50 of 2 ng/mL. Other opiates and heroin metabolites that showed >50% crossreactivity when present at 1 microg/mL included codeine, morphine-6-glucuronide, and oxycodone. Methadone showed very low crossreactivity (<5%), which is a benefit for testing in patients being treated for opiate addictions. The high sensitivity of the assay and the relatively high cutoff value for positive opiate tests allows very small sample volumes (e.g., in saliva or sweat) to be analyzed. A double-blind comparison using 205 clinical urine samples showed good agreement between this single-step competitive assay and a commercially performed enzyme multiplied immunoassay technique for the detection of opiates and benzoylecgonine (a metabolite of cocaine).

Antibodies, Monoclonal↗
PubMed2000

Melatonin administration can entrain the free-running circadian system of blind subjects.

Although melatonin treatment has been shown to phase shift human circadian rhythms, it still remains ambiguous as to whether exogenous melatonin can entrain a free-running circadian system. We have studied seven blind male subjects with no light perception who exhibited free-running urinary 6-sulphatoxymelatonin (aMT6s) and cortisol rhythms. In a single-blind design, five subjects received placebo or 5 mg melatonin p.o. daily at 2100 h for a full circadian cycle (35-71 days). The remaining two subjects also received melatonin (35-62 days) but not placebo. Urinary aMT6s and cortisol (n=7) and core body temperature (n=1) were used as phase markers to assess the effects of melatonin on the During melatonin treatment, four of the seven free-running subjects exhibited a shortening of their cortisol circadian period (tau). Three of these had taus which were statistically indistinguishable from entrainment. In contrast, the remaining three subjects continued to free-run during the melatonin treatment at a similar tau as prior to and following treatment. The efficacy of melatonin to entrain the free-running cortisol rhythms appeared to be dependent on the circadian phase at which the melatonin treatment commenced. These results show for the first time that daily melatonin administration can entrain free-running circadian rhythms in some blind subjects assessed using reliable physiological markers of the circadian system.

Adult↗
PubMed2000

Late component ERPs are associated with three syndromes in schizophrenia.

Previous studies have revealed various abnormalities in late-component ERP amplitude and latency in schizophrenia, considered as a diagnostic category. The aim of this study was to investigate the within-sample associations between late-component ERPs and three primary syndromes of schizophrenia Reality Distortion, Psychomotor Poverty and Disorganisation. Subjects included 40 schizophrenics and 40 age and sex matched nonpsychiatric controls. Auditory ERPs (N100, N200, P200, P300) were elicited using an auditory oddball paradigm. Between-group analyses of target data showed reduced N100, N200 and P300 amplitude, increased P200 amplitude and delayed N200 latency in schizophrenics compared to controls. For non-target data, schizophrenics showed similarly reduced N100 amplitude and delayed N200 latency. Within-group analyses of target data showed that the three syndromes (determined by principal component analysis of PANSS ratings) were differentiated by ERP latency, but not amplitude (Disorganisation delayed left hemisphere P200 and P300 latency; Reality Distortion earlier global, midline and left hemisphere N200 latency; Psychomotor Poverty delayed posterior N100 latency). Notably, only Disorganisation showed a divergent pattern of associations with non-target ERP data: reduced P200 amplitude and delayed N100 latency.

Adolescent↗
PubMed2000

Phase II study of dolastatin-10 in patients with hormone-refractory metastatic prostate adenocarcinoma.

Dolastatin-10 is a natural, cytotoxic peptide with microtubule-inhibitory and apoptotic effects. It has demonstrated in vitro and in vivo efficacy in the DU-145 human prostate cancer model. A Phase II clinical trial was designed in patients with hormone-refractory prostate cancer. Dolastatin-10 was administered at a dose of 400 microg/m2 i.v. every 3 weeks. Dose escalation to 450 microg/m2 was permitted. Toxicity evaluation was conducted every 2 weeks, and assessment of response was done at the end of every two cycles. Sixteen patients were enrolled between October 1998 to December 1999. The median age was 71 years (range, 59-79 years). Median prostate-specific antigen value was 108 ng/ml (range, 15.3-1672 ng/ml). Of the 15 eligible patients, 7 were Caucasian and 8 were African-American. Eight patients had bone-only metastases, and seven had measurable disease with or without bone metastases. A total of 56 cycles have been administered. Only 2 patients required dose adjustment because of toxicity, and in 5 patients, dose escalation was feasible to 450 microg/m2. The major toxicities observed were grade 3 and 4 neutropenia in 8 patients and grade 3 neuropathy in 1 patient. All 15 patients are evaluable for response. Three patients demonstrated stable disease; 2 of these had bone disease, and 1 had nodal metastasis. All others had disease progression. Dolastatin-10 is very well tolerated in this elderly, pretreated population but lacks significant clinical activity as a single agent.

Adenocarcinoma↗
PubMed2000

New evidence for antioxidant properties of vitamin C.

This study was designed to examine the effect of 500 to 5,000 mg of ascorbic acid on DNA adducts, natural killer (NK) cell activity, programmed cell death, and cell cycle analysis of human peripheral blood leukocytes. According to our hypothesis, if ascorbic acid is a pro-oxidant, doses between 500 and 5,000 mg should enhance DNA adduct formation, decrease immune function, change the cell cycle progression, and increase the rate of apoptosis. Twenty healthy volunteers were divided into four groups and given either placebo or daily doses of 500, 1,000 or 5,000 mg of ascorbic acid for a period of 2 weeks. On days 0, 1, 7, 15, and 21, blood was drawn from them, and the leukocytes were separated and examined for intracellular levels of ascorbic acid, the level of 8-hydroxyguanosine, NK cell activity, cell cycle progression, and apoptosis. Depending on the subjects, between a 0% and a 40% increase in cellular absorption of ascorbic acid was observed when daily doses of 500 mg were used. At doses greater than 500 mg, this cellular absorption was not increased further, and all doses produced equivalent increases in ascorbic acid on days 1 to 15. This increase in cellular concentration of ascorbic acid resulted in no statistically meaningful changes in the level of 8-hydroxyguanosine, increased NK cytotoxic activity, a reduced percentage of cells undergoing apoptosis, and switched cell cycle phases from S and G2/M to G0/G1. After a period of 1 week, with no placebo or vitamin washout, ascorbic acid levels along with functional assays returned to the baseline and became equivalent to placebos. In comparison with baseline values, no change (not more than daily assays variation) was seen in ascorbate concentrations or other assays during oral placebo treatment. We concluded that ascorbic acid is an antioxidant and that doses up to 5,000 mg neither induce mutagenic lesions nor have negative effects on NK cell activity, apoptosis, or cell cycle.

Administration, Oral↗
PubMed1999

Expression of cyclic nucleotide-gated cation channels in airway epithelial cells.

Using the whole-cell patch-clamp technique, the selectivity and pharmacology of 8-Br-cGMP-stimulated currents in the human alveolar cell line A549 was compared to 8-Br-cGMP-stimulated currents in HK293 cells transfected with halphaCNC1. Whole cell currents stimulated by 8-Br-cGMP in HK293 cells transfected with halphaCNC1 or A549 cells are carried by inward sodium and outward potassium with nearly the same selectivity. The whole-cell inward currents that are stimulated by 8-Br-cGMP in HK293 cells transfected with halphaCNC1 are inhibited by l-cis-diltiazem with an IC(50) of 154 microm, by 2',4'-dichlorobenzamil with an IC(50) of 50 microm and by amiloride with an IC(50) of 133 microm. The whole-cell inward currents in A549 cells that are stimulated by 8-Br-cGMP, are inhibited by l-cis-diltiazem with an IC(50) of 87 microm, by 2'4'-dichlorobenzamil with an IC(50) of 38 microm and by amiloride with an IC(50) of 32 microm suggesting that these airway cells contain cyclic nucleotide-gated cation channels. RT-PCR data suggest that mRNA of both alphaCNC1 and betaCNC subunits are present in A549 cells and the presence of the betaCNC subunit, may as previously reported, increase the affinity of these channel blockers compared to the halphaCNC1 subunit alone. The mRNA of two other isoforms of this channel, CNC2 and CNC3, are also expressed in the A549 cell line. This study documents the IC(50) of externally applied channel blockers that can be used for in vitro or in vivo experiments to document sodium absorption via cyclic nucleotide-gated cation channels in airway cells.

Cations↗
PubMed1999

Sleep apnoea.

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Humans↗
PubMed1999

The consultant orthodontic service--1996 survey.

OBJECTIVE: To evaluate the working patterns and facilities of the consultant orthodontist service. DESIGN: A cross-sectional survey. SETTING: Consultant orthodontist departments in the UK. SUBJECTS AND METHODS: All consultant orthodontists in the UK were sent a questionnaire that gathered information on the individual consultant, the facilities available, the new patients referred and patients under current treatment. RESULTS: The consultant orthodontist service provided treatment to a high number of patients who were in definite need of orthodontic treatment. A marked reduction in the use of removable appliances suggests improving standards of care and provision of more complex treatment. The caseload was high and a fair proportion of patients were returned to their referring dentists with treatment plans. The consultant service has not completely evolved into a service that provides treatment at a super-specialist level alone. CONCLUSIONS: There has been little change in the consultant orthodontist service over the past ten years. Arguably, this is because of the wishes of the purchasers and the shortage of trained orthodontic manpower as a direct result of poor manpower planning and lack of funds for post-graduate training.

Cross-Sectional Studies↗
PubMed1999

Environmental engineering: energy value of replacing waste disposal with resource recovery

Although in the past, environmental engineering has been primarily concerned with waste disposal, the focus of the field is now shifting toward viewing wastes as potential resources. Because reclamation usually consumes less energy than producing new materials, increasing reclamation not only reduces pollution but saves energy. Technological innovations contributing to this shift are summarized here, and are variously classified as emerging technologies or research topics, as either new departures or incremental improvements, and as opportunistic innovations, or examples of a unifying strategy. Both liquid and solid waste examples are given, such as a recent discovery of effects in disinfecting microfiltered reclaimed wastewater with ultraviolet light. In addition to its value in reducing pollution and conserving energy, this reorientation of environmental engineering could contribute to a more general shift toward greater cooperation among organizations dealing with the environment.

Journal Article↗
PubMed1999

Evidence-based practice. Guiding lights.

Traditional methods of implementing clinical guidelines and changing professional practice endure despite evidence that they are ineffective. The increasing demand for guideline implementation will have to be met within existing resources. Work in one health authority, which marries the methods of changing practice shown to be effective with the limited resources available, is already showing dividends.

Education, Medical, Continuing↗
PubMed1999

No silent areas

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Journal Article↗
PubMed1999

Assessment of an automated solid phase competitive fluoroimmunoassay for benzoylecgonine in untreated urine.

A new solid phase fluoroimmunoassay using a fully automated flow fluorometer adapted for urinalysis of drug metabolites is described. Fluorescein-conjugated benzoylecgonine (FL-BE) and monoclonal antibodies (mAb) against benzoylecgonine (BE) were the reagents used for demonstration. The solid phase consisted of anti-BE mAbs immobilized on the surface of polymethyl methacrylate (PMMA) beads. Free BE in solution competed with FL-BE and reduced bead-bound fluorescence in a concentration-dependent manner. The binding of FL-BE to the anti-BE mAb reached steady-state within minutes. FL-BE was not bound by uncoated beads nor beads coated with non-specific proteins or IgG. The signal-to-noise ratio was 33, and the sensitivity of the assay was 2 ng ml(-1) for BE. The effective concentration of BE was 1 to 100 ng ml(-1), with an IC50 value of 12 ng ml(-1). The mAb showed equal affinities for BE, cocaine, and cocaethylene, but a five order-of-magnitude lower affinity for ecgonine and ecgonine methylester. In a double-blind comparison using clinical urine samples, the data from this single-step competitive assay had excellent agreement with results obtained using a fiber-optic biosensor (FOB), and the EMIT assay performed commercially. The assay provided kinetic data rapidly and can be used to detect small analytes for which antibodies and fluorescein conjugates are available. The affinity of the mAb for FL-BE, calculated from kinetic analysis of the time course of the on and off reaction, was 2.25 x 10(-9) M.

Antibody Affinity↗
PubMed1999

Immunogenicity and protective efficacy of a gE, gG and US2 gene-deleted bovine herpesvirus-1 (BHV-1) vaccine.

The efficacy and safety of a gene-deleted bovine herpesvirus-1 (BHV-1) vaccine was determined in a bovine herpesvirus challenge trial in calves. Three different doses of the vaccine were administered intramuscularly at 10(5), 10(6) and 10(7) PFU/ml and compared to a commercial vaccine and non vaccinated control calves. Challenge was performed by intranasal aerosolization with the Cooper strain of BHV-1 (3 x 10(4) PFU/ml). The non-vaccinated calves shed significantly (P < 0.05) more virus than all other groups on days 4, 8 and 10 post challenge. By day 14 post challenge, antibody titers for BHV-1 of calves vaccinated with 10(7) PFU/ml were significantly (P < 0.05) higher than the commercial or non-vaccinated calves. Clinical scores of non-vaccinated calves were significantly (P < 0.05) higher than all other groups on days 4-14 post challenge. With both radioimmunoprecipitation and competitive enzyme-linked immunosorbent assays (C-ELISA), calves in the gene-deleted vaccine groups mounted comparable specific responses against gB, gC and gD post vaccination as calves in the commercial vaccine group, but in a dose dependent manner. These data suggest that the gene-deleted BHV-1 vaccine tested may be used as an effective vaccine in controlling BHV-1 infections.

Administration, Intranasal↗
PubMed1999

Occult vitamin D deficiency in postmenopausal US women with acute hip fracture.

CONTEXT: Low vitamin D levels may contribute to hip fractures in women, although limited data are available on vitamin D levels in US women admitted with acute hip fractures. OBJECTIVE: To determine whether postmenopausal women with hip fractures have low vitamin D and high parathyroid hormone levels compared with nonosteoporotic and osteoporotic women admitted for elective joint replacement. DESIGN: Comparative case series conducted between January 1995 and June 1998. SETTING AND PATIENTS: Ninety-eight postmenopausal community-dwelling women with no secondary causes of bone loss admitted for hip replacement, of whom 30 women had acute hip fractures and 68 women were admitted for elective joint replacement. Of the women admitted for elective joint replacement, 17 had osteoporosis and 51 did not. Women with comorbid conditions or who were taking medications that affect bone density and turnover were excluded. MAIN OUTCOME MEASURES: Primary measures were levels of vitamin D and parathyroid hormone; secondary measures were body composition and markers of bone turnover. RESULTS: Women with hip fractures had lower levels of 25-hydroxyvitamin D than women without osteoporosis admitted for elective joint replacement (P = .02) and than women with osteoporosis admitted for elective joint replacement (P = .01) (medians, 32.4, 49.9, and 55.0 nmol/L, respectively; comparisons adjusted for age and estrogen intake). Parathyroid hormone levels were higher in women with fractures than women in the nonosteoporotic control group (P<.001) or than elective osteoporotic women (P = .001) (medians, 5.58, 3.26, and 3.79 pmol/L, respectively; comparisons adjusted for age and estrogen intake). Fifteen patients (50.0%) with hip fractures had deficient vitamin D levels (< or =30.0 nmol/L) and 11 (36.7%) had a parathyroid hormone level greater than 6.84 pmol/L. Levels of N-telopeptide, a marker of bone resorption, were greater in the women with hip fractures than in the elective nonosteoporotic controls (P = .004). CONCLUSIONS: Postmenopausal community-living women who presented with hip fracture showed occult vitamin D deficiency. Repletion of vitamin D and suppression of parathyroid hormone at the time of fracture may reduce future fracture risk and facilitate hip fracture repair. Because vitamin D deficiency is preventable, heightened awareness is necessary to ensure adequate vitamin D nutrition, particularly in northern latitudes.

Aged↗
PubMed1999

The neurochip: a new multielectrode device for stimulating and recording from cultured neurons.

The neurochip is a silicon micromachined device upon which cultured mammalian neurons can be continuously and individually monitored and stimulated. The neurochip is based upon a 4 x 4 array of metal electrodes, each of which has a caged well structure designed to hold a single mature cell body while permitting normal outgrowth of neural processes. We demonstrate that this device is capable of maintaining cell survival, and that the electrodes can both record and stimulate electrical activity in individual cells with no crosstalk between channels.

Algorithms↗