Risk of major gastrointestinal bleeding with aspirin.
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Aged↗
Biomedical subjects
J Paterson
Publications and source records attributed to J Paterson.
Pathologic quiz case 2. Chondrosarcoma of the jugular foramen.
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Aged↗
Dietary intake of schizophrenic patients in Nithsdale, Scotland: case-control study.
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Adult↗
Antiproliferative and apoptotic activities of ketonucleosides and keto-C-glycosides against non-small-cell lung cancer cells with intrinsic drug resistance.
We compared the biological activity of a new group of keto-C-glycosides to that of a narrow spectrum of unsaturated ketonucleosides in a panel of non-small-cell lung cancer (NSCLC) cells with various levels of intrinsic resistance to standard chemotherapy drugs. Unlike cisplatin, etoposide, adriamycin, or taxol, for which a significant difference in the cytotoxic effect was observed between sensitive cell lines (H460, H125, and MGH4) and drug-resistant cell lines (H661, MGH7, and FADU), nucleoside analogs were equally cytotoxic in NSCLC cell lines, with compound 92 being 10-fold more active than compound 43, 44, 81, or 161, while compound 3 was the least active. Apoptotic measurements with flow cytometric analysis of terminal uridine deoxynucleotide nick end-labeled cells revealed that the cytotoxic activity of these nucleosides correlated with their potency to induce apoptosis. Compound 92 triggered death in cells with wild-type p53, mutated p53, or p53 gene deletion. Our findings suggest that keto-C-glycosides may be promising alternative anticancer agents which merit further studies in in vivo cancer models refractory to standard chemotherapy drugs.
Antineoplastic Agents↗
Sedation for intractable distress in the dying--a survey of experts.
Terminal sedation is a phrase that has appeared in the palliative care literature in the last few years. There has not been a clear definition proposed for this term, nor has there been any agreement on the frequency with which the technique is used. A postal survey of 61 selected palliative care experts (59 physicians, two nurses) was carried out to examine their response to a proposed definition for 'terminal sedation', to estimate the frequency of this practice and the reasons for its use, to identify the drugs and dosages used, to determine the outcome, and to explore the decision-making process. Opinions on physician-assisted suicide and voluntary euthanasia were also sought. Eighty-seven per cent of the experts responded from eight countries, although predominantly from Canada and the United Kingdom. Forty per cent agreed unequivocally with the proposed definition, while 4% disagreed completely. Eighty-nine per cent agreed that 'terminal sedation' is sometimes necessary and 77% reported using it in the last 12 months--over half of these for up to four patients. Reasons for using this method included various physical and psychological symptoms. The most common drugs used were midazolam and methotrimeprazine. Decision making usually involved the patient or family, and varied with respect to the ease with which the decision was made. The use of sedation was perceived to be successful in 90 out of 100 patients recalled. Ninety per cent of respondents did not support legalization of euthanasia. In conclusion, sedating agents are used by palliative care experts as tools for the management of symptoms. The term 'terminal sedation' should be abandoned and replaced with the phrase 'sedation for intractable distress in the dying'. Further research into the management of intractable symptoms and suffering is warranted.
Adult↗
Health risk assessment of drinking water contaminants in Canada: the applicability of mixture risk assessment methods.
The objectives of this article are: (i) to review the current approaches of Health Canada to the risk assessment of drinking water contaminants, and (ii) to examine the applicability of mixture risk assessment methods to drinking water contaminants. Health Canada's current approaches to drinking water risk assessment, like those of many regulatory agencies, focus almost solely on the effects of individual chemicals. As such, no formal method is currently used for developing mixtures guidelines or for modifying guidelines of individual chemicals to account for the possibility of the occurrence of interactions (supraadditive or infraadditive). Recent interest in the risk assessment of mixtures, at least in part, stems from concerns over the potential health risks of mixtures of very commonly occurring compounds in Canadian drinking water supplies, namely the disinfection by-products. Before any mixtures methods can be considered for incorporation into Health Canada's current approaches to the risk assessment of drinking water contaminants, it is essential to consider the limitations and data requirements of the various mixture risk assessment methods (i.e., whole mixture approach, similar mixture approach, components-based approaches, interactions-based assessment). Among the existing mixture risk assessment methods, the components-based and interactions-based approaches could be applicable to drinking water contaminants. Specifically, among the components-based approaches, dose-addition, response-addition, and the toxic equivalency factor approaches are the most applicable ones for drinking water contaminants. Until an interactions-based, mechanistic risk assessment approach (e.g., physiological model-based approach) becomes available for routine use, the components-based approaches remain the default methods for consideration. Progress in the development and validation of an interactions-based risk assessment methodology should facilitate a more realistic assessment of risk due to drinking water contaminants without increasing the levels of uncertainty in risk estimates above those associated with existing single-chemical methods.
Canada↗
Pelvic floor exercises as a treatment for post-micturition dribble.
OBJECTIVE: To determine the effectiveness of pelvic floor exercises and urethral milking as treatments for post-micturition dribble. PATIENTS AND METHODS: A method of measuring small amounts of urine loss during normal activity was developed; pads were worn for short periods (< 4 h) and then stored in two sealed plastic bags which were weighed within 72 h. Forty-nine men (age range 36-83 years) drawn from a hospital out-patient population, who had not undergone surgery on the bladder, urethra or prostate gland, entered the study. They were randomly assigned to one of three treatment groups; pelvic muscle exercise, urethral milking or counselling. Participants in each group followed the treatment specific to their group for 12 weeks. At 5, 9 and 13 weeks, urine loss was assessed using the method described. RESULTS: The groups were comparable for age, height, weight and pelvic muscle contraction strength and compliance of the men who completed the study was excellent. The outcome measure (improvement in pad weight gain) was strongly influenced by initial pad weight gain, or degree of urine loss at the start of the study and this was treated as a covariate in an analysis of variance model. After allowing for the effects of initial pad weight gain, the counselling group showed no improvement, the urethral milking group showed an adjusted mean improvement in urine loss of 2.9 g after 13 weeks, compared with 4.7 g in the exercise group. CONCLUSION: Both pelvic floor exercises and urethral milking are effective treatments for post-micturition dribble compared with counselling alone. Pelvic floor exercises were more effective in reducing urine loss than urethral milking in this study.
Adult↗
Liposomal distribution in malignant glioma: possibilities for therapy.
We investigated the potential of 111In-labelled liposomes to specifically target recurrent high-grade glioma in eight patients, all of whom had clinical and radiological evidence of relapse following prior treatment with surgery and radiotherapy. The phospholipid liposomes were labelled with 74 MBq 111In and injected intravenously. The distribution of radioactive material in the brain was imaged using a dedicated neuro-SPET imager. Images were taken 1 h post-injection and repeated at 24, 48 and 72 h. In addition, whole-body images were performed with a gamma camera and blood taken for radioactivity determination. At 72 h post-injection, excellent tumour demarcation could be seen in seven of eight patients. The images obtained correlated well with the corresponding computed tomography images. Blood radioactivity levels gradually declined over the 72 h. Tumour uptake continued to rise throughout this time and, together with the steady fall in normal brain tissue, the tumour-to-brain contrast gradually increased (maximum 7:5). Whole-body images indicate that the liver is the major organ of uptake with up to 50% of the injected dose. No toxicity could be attributed to the injected liposomes. Although the total percentage uptake was low (1.1%), the tumour-to-brain contrast ratios, together with the SPET images, suggest the potential for tumour-specific targeting.
Brain Neoplasms↗
The role of ErbB-2 tyrosine kinase receptor in cellular intrinsic chemoresistance: mechanisms and implications.
The erbB family of tyrosine kinase receptors is involved in the regulation of a variety of vital functions including cell proliferation, cell differentiation, and stress response. Alteration in the expression of erbB receptors occurs in numerous tumor types and plays an important role in cancer development, cancer progression, and susceptibility to cell killing by anticancer agents. Of particular interest is the intrinsic drug resistance associated with overexpression of the erbB-2 receptor. In general, tumor cells overexpressing erbB-2 are intrinsically resistant to DNA-damaging agents such as cisplatin. While the molecular mechanisms by which erbB-2 induces drug resistance are not yet established, there is evidence that this may be a consequence of altered cell cycle checkpoint and DNA repair mechanisms and dysregulation of apoptotic pathway(s). The apoptotic signal induced by many anticancer drugs originates at a receptor on the cell membrane and is transduced through a signaling cascade to the nucleus. Drug-induced apoptosis is dependent on the balance between cell cycle checkpoints and DNA repair mechanisms. Blockade of erbB-2 signaling using erbB-2 antagonists, dominant negative mutants, or chemical inhibitors of erbB-2 tyrosine kinase activity induces cell cycle arrest, inhibits DNA repair, and (or) promotes apoptosis. Less understood are downstream signal transduction cascades by which erbB-2 affects these regulatory mechanisms. The diversity of erbB receptors results in an interconnected network of cell signaling pathways that determine tumor cell fate in response to chemotherapy stress. Further investigations on the role of erbB-coupled signaling in the regulation of stress responsive genes are critical to understand the mechanisms by which tumor cells escape cell death, and will contribute to the development of alternative therapeutic targets to overcome intrinsic drug resistance in clinical settings.
Animals↗
Using factor analysis to explore nurses' fear of AIDS in the United States of America.
The purpose of this study was to create a reliable research instrument to test the fear of AIDS (FOA) and to explore the dimension of FOA among nurses. We hypothesized that certain factors, such as physical closeness to AIDS patients or HIV-positive blood and nontolerance of homosexuals, increase fear of AIDS among nurses. A sample of 365 nurses in a mid-Atlantic state of the United States was surveyed with an 82-item Knowledge, Attitudes, and Practice (KAP) questionnaire to examine the fear of AIDS among nurses in the United States. Using correlation, item and factorial analysis, a 23-item FOA Scale II (alpha = 0.826) was created and seven FOA factors were identified. Factor analysis was used to help understand the dimensions of FOA as measured by FOA Scale II. Principal components analysis was used to analyse the correlation matrix because some items were on a five-point scale and some were on a three-point scale. The varimax rotation was used, because if one were to define dimensions then these dimensions should be as independent of each other as possible. The coefficient alpha of 0.826 obtained from using FOA Scale II indicated that FOA could be considered to be a general factor; but the general factor could be exhibited through several avenues. It was determined that FOA could be represented by four or by seven dimensions, and if one uses the eigenvalue of 1 for a cut-off point then one would argue that there were seven factors. If one used the screen test, then one could assume that there were four factors of interest. Our decision for the analysis of this paper was to attempt the interpretation of the seven factors. We used both the factor loadings-the correlation of the item score with the linear combination-and the factor score coefficients (the weights of the items to form the linear combinations) to interpret the factor. The factor analysis thus seems to give insight into the dimensions of FOA as measured by FOA Scale II. Fear of AIDS seems to be exhibited in the following seven ways: (a) support for policies which would protect me from AIDS, (b) fear of contact with blood and bodily fluids of AIDS patient, (c) turning against those who have AIDS, (d) only care for those who deserve to be helped, (e)concern that I would have no help if I had AIDS, (f) concern about the financial burden of AIDS, and (g) loss of self-worth for one who has AIDS.
Acquired Immunodeficiency Syndrome↗
A study of FRAXE in mentally retarded individuals referred for fragile X syndrome (FRAXA) testing in the United Kingdom.
The folate-sensitive fragile site FRAXE is located in proximal Xq28 of the human X chromosome and lies approximately 600 kb distal to the fragile X syndrome (FRAXA) fragile site at Xq27.3. The cytogenetic expression of FRAXE is thought to be associated with mental handicap, but this is usually mild compared to that of the more common fragile X syndrome that is associated with the expression of the FRAXA fragile site. The exact incidence of FRAXE mental retardation is uncertain. We describe here the results of a U.K. survey designed to assess the frequency of FRAXE in a population of individuals referred for fragile X syndrome testing and found to be negative for expansion events at the FRAXA locus. No FRAXE expansion events were found in 362 cytogenetically negative males studied, and one expansion event was identified in a sample of 534 males for whom cytogenetic analyses were either unrecorded or not performed. Further FRAXE expansion events were detected in two related females known to be cytogenetically positive for a fragile site in Xq27.3-28. To gain insight into the FRAXE phenotype, the clinical details of the identified FRAXE male plus three other FRAXE individuals identified through previous referrals for fragile X syndrome testing are presented. For the population studied, we conclude that FRAXE mental retardation is a relatively rare but significant form of mental retardation for which genetic diagnosis would be appropriate.
Base Sequence↗
Stenting for inferior caval obstruction.
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Aged↗
Elevated DNA repair capacity is associated with intrinsic resistance of lung cancer to chemotherapy.
Non-small cell lung cancer (N-SCLC) is generally unresponsive to chemotherapy even without previous drug treatment, as opposed to small cell lung cancer (SCLC), which is initially responsive to chemotherapy. The mechanisms of this intrinsic resistance are unknown. This study was designed to investigate the role of DNA repair in intrinsic resistance of N-SCLC to cisplatin. A panel of primary N-SCLC cell cultures and established cell lines were examined and compared to SCLC cell lines established previously from untreated patients. The overall DNA repair capacity was estimated by the ability of cells to reactivate the pRSV-CAT plasmid damaged by cisplatin ("host cell reactivation" assay). Cytotoxicity was determined for cisplatin in vitro. N-SCLC cells were found to be significantly more resistant to cisplatin than SCLC cell lines isolated from untreated patients (P < 0.01). The capacity of N-SCLC cells to reactivate pRSV-CAT plasmid damaged with cisplatin and transfected into cells was higher in N-SCLC cells than in SCLC cells originating from patients who were untreated previously (P < 0.05). Correlation was also observed between chloramphenicol acetyltransferase activity and intrinsic resistance to cisplatin. However, no significant difference was observed between primary N-SCLC cultures and established cell lines. This study indicates that elevated DNA repair capacity is associated with drug resistance in lung cancer and suggests that modulation of DNA repair mechanism(s), such as the incorporation of specific DNA repair inhibitor(s) in therapeutic regimens, may help to improve therapeutic strategies of N-SCLC.
Aged↗
The effects of fescue toxicosis on beef cattle productivity.
Consumption of tall fescue forage infested with the endophytic fungus Acremonium coenophialum can result in a condition termed "fescue toxicosis," which is characterized by decreased weight gains, milk production, conception, and serum prolactin and an inability to dissipate body heat by beef cattle. These decreases in productivity have been estimated to cost beef producers more than $600 million annually. The unthrifty appearance of cattle consuming endophyte-infected tall fescue (E+) is most evident during periods of environmental heat or cold stress, suggesting an interaction with environmental conditions. Without temperature stress, cows consumed similar amounts of E+ and endophyte-free tall fescue (E-). But, when temperatures exceeded 32 degrees C, cows that grazed E+ consumed less forage than cows that grazed E-. After removal of E+ from the diet of steers, compensatory growth was observed, indicating no long-term negative effects of E+. A decrease in serum prolactin but apparently little change in other hormones has been measured after consumption of E+. Under periods of heat stress, animals had reduced ability to dissipate body heat, and blood flow to peripheral (rib skin), core-body (duodenum colon), and brain (cerebellum) tissues was decreased. Due to the depressive effects of E+ on prolactin and heat dissipation, dopamine antagonist therapy has been used in an attempt to rectify these changes. Dopamine antagonists have increased serum prolactin but there is limited evidence to suggest an improvement in heat dissipation. Experiments to elucidate the effects of E+ on alpha-1 and -2 adrenergic receptors may also offer insights into developing strategies to overcome the negative effects of E+ consumption. Preliminary results suggest that injections of an alpha-1 adrenergic antagonist (prazosin) in rats fed E+ under 32 degrees C conditions increased DM intake and reduced rectal temperature.
Acremonium↗
Differentiation and tumor response to retinobenzoic acid RE-80 in a malignant conversion model.
The synthetic retinobenzoic acid RE-80 was evaluated for its potential as an inductor of tumor cell differentiation and as a chemopreventive agent. A minimally toxic dose of RE-80 in vitro produced morphologic changes typical differentiation in epidermal tumor cell colonies. Indirect immunofluorescence indicated induction of a differentiation-associated keratin of internal stratified epithelia, K13, and inhibition of the differentiation-associated epidermal keratin K1. Cultured cells were skin-grafted to athymic nu/nu mice to evaluate RE-80 effects on early stage malignant progression in vivo. When tumors had grown to 3 to 4 mm in diameter, mice were treated by intraperitoneal injection with RE-80 (67 micrograms, 170 mmol, i.p., two times per week) or vehicle (100 microliters 20% ethanol). Papillomas (benign) and moderately differentiated squamous cell carcinomas were reduced in volume about 4-fold by RE-80 treatment. Larger, poorly differentiated squamous cell carcinomas were unaffected. RE-80 resulted in a lower proportion of proliferative cells (detectable by bromodeoxyuridine incorporation) and a higher proportion of moderately to well differentiated tumors after 40 days of treatment compared with control tumors, which were mainly poorly differentiated squamous cell carcinomas. K13 induction in vitro was correlated with response to retinoid in vivo. Induction of differentiation may be mechanism of the response to RE-80 in vivo since carcinoma cells expressing K13 did not incorporate bromodeoxyuridine and were on a terminal pathway.
Animals↗
New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome.
The neural cell-adhesion molecule L1 is involved in intercellular recognition and neuronal migration in the CNS. Recently, we have shown that mutations in the gene encoding L1 are responsible for three related disorders; X-linked hydrocephalus, MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome, and spastic paraplegia type I (SPG1). These three disorders represent a clinical spectrum that varies not only between families but sometimes also within families. To date, 14 independent L1 mutations have been reported and shown to be disease causing. Here we report nine novel L1 mutations in X-linked hydrocephalus and MASA-syndrome families, including the first examples of mutations affecting the fibronectin type III domains of the molecule. They are discussed in relation both to phenotypes and to the insights that they provide into L1 function.
Abnormalities, Multiple↗
X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene.
X-linked hydrocephalus, spastic paraplegia type I and MASA syndrome are related disorders with loci in subchromosomal region Xq28. We have previously shown that X-linked hydrocephalus is caused by mutations in the gene for neural cell adhesion molecule L1 (L1CAM), an axonal glycoprotein involved in neuronal migration and differentiation. Here we report mutations of the L1 gene in MASA syndrome and SPG1, in addition to HSAS families. Two of the HSAS mutations would abolish cell surface expression of L1 and represent the first functional null mutations in this disorder. Our results indicate that these three syndromes from part of a clinical spectrum resulting from a heterogeneous group of mutations in the L1 gene.
Aphasia↗
A new look at national medical workforce strategy.
The efforts of governments in medical workforce policy have been unimpressive, and this has had serious consequences. Political compromise, theoretical error and administrative laxity have all contributed. It is demonstrated that market evidence, viewed through the prism of orthodox price theory, allows useful prescriptions to be made. These can be implemented through vigorous continuing maintenance and adjustment work on the Commonwealth Medical Benefits Schedule, together with periodic adjustments to rates of undergraduate and specialist medical education and training.
Australia↗