America's new refugees--seeking affordable surgery offshore.
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Bankruptcy↗
Biomedical subjects
Mark Smith
Publications and source records attributed to Mark Smith.
Quality grand rounds: the case for patient safety.
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Aged, 80 and over↗
Numb chin syndrome--a reflection of systemic malignancy.
BACKGROUND: Numb chin is an uncommon underappreciated though well documented neurological manifestation of metastatic malignancy. CASE PRESENTATION: A 50-year-old patient presented with right numb chin for few days. No dental cause was found. He later developed generalized vague symptoms. In few weeks his liver and renal functions deteriorated. Blood picture showed leucoerythroblastic picture. CT scan and bone marrow biopsy done at this stage revealed underlying high grade lymphoblastic lymphoma. He went into multiorgan failure, requiring ventilatory support and death within a short period. CONCLUSION: Numb Chin is a syndrome which initially presents with unilateral numbness or orofacial pain in the distribution of the inferior alveolar nerve and its branches with an underlying systemic malignancy. We emphasise that physicians and dentists should consider metastatic cancer in any patient who presents with chin or jaw numbness where no other obvious cause for their complaint is found.
Journal Article↗
Evaluation of the utility and reliability of COSHH Essentials.
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Hazardous Substances↗
Organophosphate levels in apple composites and individual apples from a treated Canadian orchard.
Azinphos-methyl, phosalone, and phosmet were applied individually to separate rows of trees within a commercial apple orchard in Quebec, Canada, during the 2003 agricultural season. Apples were collected for residue analysis immediately prior to the harvesting of the remaining apples for market distribution and were prepared for analysis as both individual apples and as composites of eight individuals. Analysis of the three applied compounds, as well as five organophosphate insecticides that were not applied, was performed using gas chromatography-mass spectrometry. Azinphos-methyl, phosalone, and phosmet, which were applied, were detected in all samples analyzed at concentrations ranging from 0.004 ng/g to 2260 ng/g. Methidathion was not observed in any sample. Chlorpyrifos, diazinon, dimethoate, and malathion concentrations ranged from below method detection limits to 0.71 ng/g, and the detection frequency for these compounds ranged from 20% to 100%. Residues measured in this study were all below the Canadian maximum residue limit for apples. Variability factors ranged from 2 to 19 for all compounds observed in this study. Composite samples may not accurately reflect the extremes of exposure from consumption of single servings of apples.
Canada↗
Genomic anatomy of the Tyrp1 (brown) deletion complex.
Chromosome deletions in the mouse have proven invaluable in the dissection of gene function. The brown deletion complex comprises >28 independent genome rearrangements, which have been used to identify several functional loci on chromosome 4 required for normal embryonic and postnatal development. We have constructed a 172-bacterial artificial chromosome contig that spans this 22-megabase (Mb) interval and have produced a contiguous, finished, and manually annotated sequence from these clones. The deletion complex is strikingly gene-poor, containing only 52 protein-coding genes (of which only 39 are supported by human homologues) and has several further notable genomic features, including several segments of >1 Mb, apparently devoid of a coding sequence. We have used sequence polymorphisms to finely map the deletion breakpoints and identify strong candidate genes for the known phenotypes that map to this region, including three lethal loci (l4Rn1, l4Rn2, and l4Rn3) and the fitness mutant brown-associated fitness (baf). We have also characterized misexpression of the basonuclin homologue, Bnc2, associated with the inversion-mediated coat color mutant white-based brown (B(w)). This study provides a molecular insight into the basis of several characterized mouse mutants, which will allow further dissection of this region by targeted or chemical mutagenesis.
Animals↗
Optimal in-vitro expansion of chondroprogenitor cells in monolayer culture.
A continuous production of large quantities of chondroprogenitor cells for the manufacture of engineered cartilage tissue products is required. Expansion of the cell population in vitro has become an essential step in the process of tissue engineering of articular cartilage and the optimization of the culture conditions is a fundamental problem that needs to be addressed. The analysis of both seeding density and passage length was considered crucial in the optimization of expansion processes, and their correct selection should be taken as a requisite to establish culture conditions for monolayer systems. The determination of the optimal seeding density and the corresponding passage length for cell expansion in a serial passaging operation was found to be a compromise between growth kinetics and process time. This optimal determination was carried out using a mathematical approach that led to values of 10(4) cell/cm(2) for seeding density and 73 h for passage length. Additional considerations concerning the running cost of the process were introduced. Although the optimal passage length gave the desired expansion factor in a minimum process time, the selection of an alternative value of 120 h was shown to reduce the cost of the expansion process in more than 60%. The optimization approach presented will contribute to the development of feasible large scale expansion operations of chondroprogenitor cells required by the cartilage tissue engineering industry.
Animals↗
Characterization of a novel polymorphic form of celecoxib.
A new solid form (Form IV) of celecoxib was prepared in the presence of Polysorbate 80 and HPMC. A celecoxib suspension containing the Form IV had significantly higher bioavailability (>4 times) in dogs than the marketed capsules and the suspension containing bulk drug powders (Form III). The new form was characterized using differential scanning calorimetry, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), infrared spectroscopy, and Raman spectroscopy. The solids separated from the suspension containing the new form showed a melt onset at 145-148 degrees C, which was about 12-15 degrees less than known melting points of Form I, II ,and III of celecoxib. The PXRD pattern of the separated solids was not consistent with any of the known celecoxib crystal forms or the known excipients in the suspension. The formation of the new solid form (Form IV) was dependent upon the concentration and ratio of HPMC and Polysorbate 80. A faster dissolution rate (>2 times) of Form IV was observed compared to the thermodynamically stable form of celecoxib (Form III). There were no measurable changes in the solid state of Form IV either in dried solids or in the suspension for at least 6 months at 40 degrees C and 16 months at 25 degrees C.
Animals↗
Expansion of chondroprogenitor cells on macroporous microcarriers as an alternative to conventional monolayer systems.
Routine tissue culture methodologies can hardly cope with the scale of cell production required for the manufacture of engineered cartilage tissue products. In vitro cell expansion has become an essential step in the process of tissue engineering of articular cartilage and the optimization of expansion protocols is a fundamental issue that needs to be addressed. The expansion suitability of chondroprogenitor cells isolated from the superficial zone of articular cartilages was evaluated in both conventional monolayer and macroporous microcarrier in spinner flask cultures. Although monolayer systems promoted rapid in vitro expansion of undifferentiated cells, they present limited scalability. Alternatively, the use of CultiSpher-G microcarriers resulted in cell densities of 5.5 x 10(5) cell/ml, representing a 17-fold expansion in batch cultures. In addition, chondroprogenitor cells were capable of undergoing bead-to-bead migration, which allowed subcultivation to be performed without a harvesting step, thus improving the scalability of the expansion process. By employing macroporous microcarrier cultures it will be possible to obtain large number of chondroprogenitor cells for tissue engineering applications. Not only its satisfactory expansion potential, but more importantly the cost and operational advantages over traditional monolayer culture make this system a feasible alternative method for the extensive expansion of chondroprogenitor cells.
Animals↗
Wireless handheld computers and voluntary utilization of computerized prescribing systems in the emergency department.
Illegible or invalid hand-written prescriptions can result in avoidable medical errors. Computer-based prescribing can mitigate the problem. An observational study was performed to examine the effect of wireless handheld computers (handhelds) on voluntary utilization of computerized prescribing within an Emergency Department. Handhelds with prescription-writing software were provided to physicians and the numbers of hand-written and computer-generated prescriptions were compared before and after the introduction of the handhelds. The resulting increase in computer-based prescribing was statistically significant and was observed largely among physicians who already used desktop computers for prescribing. The study concluded that handhelds increased voluntary utilization of computerized prescribing, but that the physicians most likely to use handhelds were those who already used desktop-based prescribing.
Attitude to Computers↗
Evaluation of engineered meniscal cartilage constructs based on different scaffold geometries using magnetic resonance imaging and spectroscopy.
Magnetic resonance imaging (MRI) and spectroscopy (MRS) were used to evaluate the properties different scaffold geometries for the production of bioartificial meniscal cartilage constructs. Engineered were generated in perfusion bioreactors from mature sheep meniscal fibrochondrocytes,scaffolds cut from a knitted polyethylene therephtalate (PET) fabric, with a distribution of fibers, 50 microm pores and a density of 45 mg/cm(3) (NF scaffolds), and from two versions of this fabric, which included larger pore sizes (1500 x 500 microm(2)) and densities of (sIV scaffolds) and 83 mg/cm(3) (sV scaffolds). MRI methods were used to determine the permeability the constructs to a low molecular weight MR contrast agent and to measure the macroscopic of medium through and around the constructs. These parameters were correlated with measurements of cell growth and cellular energetics. Cell-free sIV scaffolds were 2- and 5-more porous to flow than the empty sV and NF scaffolds, respectively. These scaffolds, after days of cell growth, were also more permeable to an MR contrast agent. sIV scaffolds yielded(n = 9) with higher cellularities (41 +/- 1%) compared with NF (32 +/- 1%, p < 0.0001) and sV (30 +/- 1%, p < 0.0001) and, when normalized to cell numbers, demonstrated proportionally levels of nucleoside triphosphates (NTP), indicating increased cell viability. Scaffold geometry a marked effect on the properties of engineered meniscal cartilage. MRI and MRS are powerful techniques that can be used to optimize the design of engineered meniscal cartilage and that could be used subsequently to evaluate clinical outcome postimplantation.
Animals↗
Dorsoventral patterning in hemichordates: insights into early chordate evolution.
We have compared the dorsoventral development of hemichordates and chordates to deduce the organization of their common ancestor, and hence to identify the evolutionary modifications of the chordate body axis after the lineages split. In the hemichordate embryo, genes encoding bone morphogenetic proteins (Bmp) 2/4 and 5/8, as well as several genes for modulators of Bmp activity, are expressed in a thin stripe of ectoderm on one midline, historically called "dorsal." On the opposite midline, the genes encoding Chordin and Anti-dorsalizing morphogenetic protein (Admp) are expressed. Thus, we find a Bmp-Chordin developmental axis preceding and underlying the anatomical dorsoventral axis of hemichordates, adding to the evidence from Drosophila and chordates that this axis may be at least as ancient as the first bilateral animals. Numerous genes encoding transcription factors and signaling ligands are expressed in the three germ layers of hemichordate embryos in distinct dorsoventral domains, such as pox neuro, pituitary homeobox, distalless, and tbx2/3 on the Bmp side and netrin, mnx, mox, and single-minded on the Chordin-Admp side. When we expose the embryo to excess Bmp protein, or when we deplete endogenous Bmp by small interfering RNA injections, these expression domains expand or contract, reflecting their activation or repression by Bmp, and the embryos develop as dorsalized or ventralized limit forms. Dorsoventral patterning is independent of anterior/posterior patterning, as in Drosophila but not chordates. Unlike both chordates and Drosophila, neural gene expression in hemichordates is not repressed by high Bmp levels, consistent with their development of a diffuse rather than centralized nervous system. We suggest that the common ancestor of hemichordates and chordates did not use its Bmp-Chordin axis to segregate epidermal and neural ectoderm but to pattern many other dorsoventral aspects of the germ layers, including neural cell fates within a diffuse nervous system. Accordingly, centralization was added in the chordate line by neural-epidermal segregation, mediated by the pre-existing Bmp-Chordin axis. Finally, since hemichordates develop the mouth on the non-Bmp side, like arthropods but opposite to chordates, the mouth and Bmp-Chordin axis may have rearranged in the chordate line, one relative to the other.
Animals↗
Towards the creation of an international toxicology information centre.
A pilot toxicology database system has been created which is accessible on-line via the world-wide web or in-house via an intranet. It is intended to be suitable as a source of toxicological information and to support structure-activity relationship studies, and it can be searched on chemical structural and substructural as well as toxicological and physico-chemical data. Successful completion of the pilot has led to an ongoing project to develop and expand the system.
Databases as Topic↗
A comparison of health service use in two jurisdictions with and without compulsory community treatment.
BACKGROUND: This study examines whether community treatment orders (CTOs) reduce psychiatric admission rates or bed-days for patients from Western Australia compared to control patients from a jurisdiction without this legislation (Nova Scotia). METHOD: A population-based record linkage analysis of an inception cohort using a two-stage design of matching and multivariate analyses to control for sociodemographics, clinical features and psychiatric history. All discharges from in-patient psychiatric services in Western Australia and Nova Scotia were included covering a population of 2.6 million people. Patients on CTOs in the first year of implementation in Western Australia were compared with controls from Nova Scotia matched on date of discharge from in-patient care, demographics, diagnosis and past in-patient psychiatric history. We analysed time to admission using Cox regression analyses and number of bed-days using logistic regression. RESULTS: We matched 196 CTO cases with an equal number of controls. On survival analyses, CTO cases had a significantly greater readmission rate. Co-morbid personality disorder and previous psychiatric history were also associated with readmission. However, on logistic regression, patients on CTOs spent less time in hospital in the following year, with reduced in-patient stays of over 100 days. CONCLUSIONS: Although compulsory community treatment does not reduce hospital admission rates, increased surveillance of patients on CTOs may lead to earlier intervention such as admission, so reducing length of hospital stay. However, we do not know if it is the intensity of treatment, or its compulsory nature, that effects outcome.
Adult↗
Identification and bisection of temporal durations and tone frequencies: common models for temporal and nontemporal stimuli.
Two experiments examined identification and bisection of tones varying in temporal duration (Experiment 1) or frequency (Experiment 2). Absolute identification of both durations and frequencies was influenced by prior stimuli and by stimulus distribution. Stimulus distribution influenced bisection for both stimulus types consistently, with more positively skewed distributions producing lower bisection points. The effect of distribution was greater when the ratio of the largest to smallest stimulus magnitude was greater. A simple mathematical model, temporal range frequency theory, was applied. It is concluded that (a) similar principles describe identification of temporal durations and other stimulus dimensions and (b) temporal bisection point shifts can be understood in terms of psychophysical principles independently developed in nontemporal domains, such as A. Parducci's (1965) range frequency theory.
Attention↗
Selective nerve root injections can predict surgical outcome for lumbar and cervical radiculopathy: comparison to magnetic resonance imaging.
OBJECTIVE: Diagnostic selective nerve root injection (SNI) results were analyzed in 101 patients who underwent lumbar or cervical decompression for radiculopathy and compared to surgical outcome 1 year postoperatively. A comparison of surgical outcomes was also examined between magnetic resonance imaging (MRI) and SNI results. RESULTS: Of the 101 patients, 91 (90%) had positive and 10 had negative SNI results at the level operated. Ninety-one percent of the patients with a positive SNI had good surgical outcomes, whereas 60% of the patients with a negative SNI had good outcomes. Of the patients with a positive MRI result, 87% had good surgical outcomes, whereas a similar percentage of the patients with a negative MRI (85%) had good surgical outcomes. When findings between SNI and MRI differed (n = 20), surgery at a level consistent with the SNI was more strongly associated with a good surgical outcome. Of the patients with a poor surgical outcome, surgery was most often performed at a level inconsistent with the SNI finding. CONCLUSIONS: Our study found that a diagnostic SNI can safely and accurately discern the presence or absence of cervical or lumbar radiculopathy. The diagnostic SNI can persuade surgeons from operating on an initially suspicious, but incorrect, level of radiculopathy. In cases where MRI findings are equivocal, multilevel, and/or do not agree with the patient's symptoms, the result of a negative diagnostic SNI (ie, lack of presence of radiculopathy) becomes superior in predicting the absence of an offending lesion.
Anesthetics, Local↗
Mortality in individuals who have had psychiatric treatment: population-based study in Nova Scotia.
BACKGROUND: Most studies of mortality in psychiatric patients have investigated in-patients rather than those attending out-patient clinics or primary care, where most receive treatment. AIMS: To evaluate the mortality risk in mental illness for patients in contact with psychiatric services or primary care (n=221 048) across Nova Scotia (population 936 025). METHOD: A population-based record-linkage analysis was made of the period 1995-2000, using an inception cohort to calculate mortality rate ratios. RESULTS: The mortality rate was 1.74, with increased ratios for all major causes of death. Male mortality was almost double that of females after controlling for demographic factors, treatment setting and place of residence. Patients of lower income, in specialist psychiatric settings, and with dementia or psychoses were also at greater risk. However, in absolute numbers, 72% of deaths occurred in patients who had only seen their general practitioner. CONCLUSIONS: Mortality risk is increased in all psychiatric patients, not just those who have received in-patient treatment.
Age Factors↗
[Cancer screening].
The purpose of cancer screening is to widen the difference between morbidity and mortality of the target cancer. Since 1983 cancer screening has been supported by the Japanese government. Initially it covered gastric and cervical cancer with lung, breast and endometrial cancers supported from 1987 and colorectal cancer in 1992. Since 1998 support for cancer screening has been transferred to local government. It is generally accepted that the uptake of screening services is too low. Estimates for Japan suggest that at best 30% of the eligible population accept the services. In other parts of the world screening is more widely accepted, for example, 67% for breast cancer and 79% for cervical screening in the USA. Barriers within Japan for increasing screening are complex and include, legal, ethical, financial, technical infrastructure, data related matters and the level of understanding and education of the general public. In 2000 the MHLW conducted an evaluation of cancer screening in terms of usefulness and effectiveness. It concluded that fair or better evidence for reduction in mortality existed for cervical cancer (cytology), breast cancer (mammography with clinical examination for women aged > or = 50 years), colorectal cancer (faecal occult blood test), gastric cancer, lung cancer and liver cancer. As a step towards improving screening services and their uptake by the general public a new Research Centre for Cancer Prevention and Screening was established at the National Cancer Centre in October 2003. This and other initiatives will build on the progress of the past 20 years but it is generally agreed that there is still have a long way to go.
Adult↗