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Biomedical subjects

J Wood

Publications and source records attributed to J Wood.

At least 55 records · Page 3Linked to original sources
PubMed2001

Falls risk factors in the hospital setting: a systematic review.

The objective of this systematic review was to summarize the best available evidence on the factors that increase the risk of patients falling during hospitalization. Studies included in the review were those that involved adult patients in hospital, that attempted to identify risk factors for falling, and used a cohort or case-control research design. The search strategy covered all major databases and including MEDLINE, CINAHL, Current Contents, Psyclit, Embase and the Cochrane Library. Results were summarized by a narrative discussion, identifying risk factors that were commonly identified in a range of practice settings. Eighteen papers met the review inclusion criteria and are reported in this paper. Factors associated with an increased risk of falling include impaired mental status, special toileting needs, impaired mobility, and a history of falling. While findings are contradictory, it appears that both medications and advanced age will also influence a patient's risk of falling.

Accidental Falls↗
PubMed2001

Testicular implants and patient satisfaction: a questionnaire-based study of men after orchidectomy for testicular cancer.

OBJECTIVES: To assess the satisfaction of men with their testicular implants after undergoing orchidectomy for testicular cancer, and to determine their reasons for accepting or declining a prosthesis. PATIENTS AND METHODS: In all, 424 men who had undergone radical orchidectomy and were part of the testicular cancer follow-up programme were sent an anonymous questionnaire comprising 10 questions covering two main areas. First, the reasons for accepting or declining an implant and second (if they received an implant) their satisfaction with the size, position, feel, shape and overall comfort; 234 men (55%) responded. RESULTS: About a third (71 men) accepted an implant, a third declined and a third were not offered the choice. Of the men who replied 91% felt that it was extremely important to be offered an implant at the time of surgery. Of the 71 who received an implant, 19 (27%) were dissatisfied and felt that they had an average or poor cosmetic result. The reasons for this dissatisfaction are presented and discussed. CONCLUSIONS: All men undergoing orchidectomy should be offered a testicular implant, irrespective of age. Sample implants in all sizes should be available in the outpatient department. This will give men realistic expectations and allow them to choose a suitable size of implant. The dimensions of the available implants should be improved to create a more elliptical prosthesis, to avoid dissatisfaction with the shape. Adequate fixation to the base of the scrotum is important to avoid the 'high riding' implant.

Adolescent↗
PubMed2001

Ethical decision making.

Members of the health care profession have a responsibility to identify and regulate their practice to protect consumers and assure the delivery of quality service. In this case study in which a patient wakes up during surgery, the nurse's code of ethics, standards of care, and ethical decision-making models provide guidance toward the resolution of this clinical dilemma. Such resolution requires sound nursing knowledge, knowledge of the facts of the situation, knowledge of the law, and application of critical thinking skills to facilitate positive outcomes for all parties involved.

Cooperative Behavior↗
PubMed2001

Inhibition of growth and metastasis of human pancreatic cancer growing in nude mice by PTK 787/ZK222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases.

Since vascular endothelial growth factor (VEGF) plays a major role in tumor angiogenesis, we determined whether blockage of VEGF receptor signaling using a novel tyrosine kinase inhibitor (PTK 787) decreases the growth and metastasis of human pancreatic carcinoma growing orthotopically in nude mice. Human pancreatic L3.6pl cells were injected into the pancreas of nude mice. Seven days later, groups of mice were given daily oral administrations of PTK 787 alone, twice weekly i.p. injections of gemcitabine, or combination therapy. The mice were necropsied when control mice became moribund (day 35). Therapy with PTK 787 alone, gemcitabine alone, or the combination of both agents produced respectively 60%, 70%, and 81% inhibition in the volume of pancreatic cancers. The combination therapy significantly decreased the incidence of lymph node and liver metastasis, leading to a significant increase in survival. Microvessel density (MVD) was significantly decreased in tumors treated with either PTK 787 alone or PTK 787 plus gemcitabine. MVD directly correlated with tumor cell proliferation and inversely correlated with apoptosis of tumor cells and associated endothelial cells. Collectively, our results demonstrate that blockade of VEGF-R signaling may provide an additional approach to the therapy of pancreatic cancer.

Adenocarcinoma↗
PubMed2001

Association studies of cytosolic phospholipase A2 polymorphisms and schizophrenia among two independent family-based samples.

An association between the cytosolic phospholipase A2 locus (cPLA2) and schizophrenia has been reported using two polymorphic DNA markers. In an attempt to replicate these results, two independent family-based samples were ascertained from the United States and India (86 and 159 families, respectively). No significant associations were detected in either sample.

Base Sequence↗
PubMed2001

Hepatitis C virus 3'X region interacts with human ribosomal proteins.

To identify proteins that can bind the 3' untranslated region (UTR) of hepatitis C virus (HCV) we screened human cDNA libraries using the Saccharomyces cerevisiae three-hybrid system. Screening with an RNA sequence derived from the 3'-terminal 98 nucleotides (3'X region) of an infectious clone of HCV (H77c) yielded clones of human ribosomal proteins L22, L3, S3, and mL3, a mitochondrial homologue of L3. We performed preliminary characterization of the binding between the 3'X region and these proteins by a three-hybrid mating assay using mutant 3'X sequences. We have further characterized the interaction between 3'X and L22, since this protein is known to be associated with two small Epstein-Barr virus (EBV)-encoded RNA species (EBERs) which are abundantly produced in cells latently infected with EBV. The EBERs, which have similar predicted secondary structure to the HCV 3'X, assemble into ribonucleoprotein particles that include L22 and La protein. To confirm that L22 binds HCV 3'X we performed in vitro binding assays using recombinant L22 (expressed as a glutathione S-transferase [GST] fusion protein) together with a 3'X riboprobe. The 3'X region binds to the GST-L22 fusion protein (but not to GST alone), and this interaction is subject to competition with unlabeled 3'X RNA. To establish the functional role played by L22 in internal ribosome entry site (IRES)-mediated translation of HCV sequences we performed translational analysis in HuH-7 cells using monocistronic and bicistronic reporter constructs. The relative amount of core-chloramphenicol acetyltransferase reporter protein translated under the control of the HCV IRES was stimulated in the presence of L22 and La when these proteins were supplied in trans.

3' Untranslated Regions↗
PubMed2001

Lack of association between parental alcohol or drug addiction and behavioral inhibition in children.

OBJECTIVE: "Behavioral inhibition to the unfamiliar" has been proposed as a precursor to anxiety. A recent study proposed that it may also be a precursor to alcoholism. The authors sought to replicate the latter finding through a secondary analysis of data from a large study of young children (age 2-6 years)-offspring of parents with panic and depressive disorders-who had been assessed for behavioral inhibition through laboratory-based observations. METHOD: The offspring were stratified on the basis of presence or absence of parental lifetime history of DSM-III-R alcohol dependence (N=115 versus N=166, respectively) or drug dependence (N=78 versus N=203). The rates of behavioral inhibition were then compared between groups. RESULTS: Despite adequate power to detect associations, neither parental alcohol dependence nor drug dependence was associated with a higher risk for behavioral inhibition in the offspring. CONCLUSIONS: These results are not consistent with the hypothesis linking behavioral inhibition to addictions.

Alcoholism↗
PubMed2001

Molecular mechanisms of cardiac hypertrophy induced by toxicants.

Cardiac hypertrophy is an end point of chronic cardiac toxicity from a number of toxicants. Doxorubicin, cocaine, acetaldehyde, monocrotaline, and azide are examples of these toxicants, which may induce hypertrophy by increasing oxidants, circulating levels of catecholamines, and hemodynamic load or by inducing hypoxia. We summarize here the major signal transduction pathways and common changes in gene expression found with the classical hypertrophy inducers angiotensin II, endothelin 1, and catecholamines. Activation of G-proteins, calcium signaling, phosphoinositide 3-kinase (PI3K), certain family members of protein kinase Cs (PKCs), and three branches of mitogenactivated protein kinases (MAPKs), i.e. extracellular signal-regulated kinases (ERKs), p38, and c-Jun N-terminal kinases (JNKs), are important for developing a hypertrophic phenotype in cardiomyocytes. Characteristic changes of gene expression in hypertrophy include the elevated transcription of atrial natriuretic factor (ANF), beta-myosin heavy chain (beta MHC), skeletal alpha-actin (SkA), certain variants of integrins and perhaps tubulin genes, and reduced expression of the sarcoplasmic reticulum proteins phospholamban and sarco(endo)plasmic reticulum Ca2+-ATPase 2 alpha (SERCA2 alpha), and of the ryanodine receptors. Although which toxicants induce these molecular changes remains to be tested, increasing lines of evidence support that oxidants play a central role in cardiac hypertrophy. Oxidants activate small G-proteins, calcium signaling, PI3K, PKCs, and MAPKs. Oxidants cause cardiomyocytes to enlarge in vitro. Recent developments in transgenic, genomic, and proteomic technologies will provide needed tools to reveal the mechanism of chronic cardiac toxicity at the cellular and molecular levels.

Animals↗
PubMed2001

Factors influencing blood flow in the equine digit and their effect on uptake of 99m technetium methylene diphosphonate into bone.

It was hypothesised that exercise may promote perfusion of the distal part of the limbs and enhance uptake of radiopharmaceutical into bone, but bandaging and lameness would have no effect. Two hundred and two horses undergoing routine nuclear scintigraphic examination for assessment of lameness or poor performance between November 1998 and November 1999 were assigned randomly to one of 4 groups: no bandages and no exercise (NB/NE); bandages and no exercise (B/NE); no bandages and exercise (NB/E); bandages and exercise (B/E). In the bandage groups, the distal forelimbs were bandaged for at least 16 h prior to injection of radiopharmaceutical. In the exercise groups, horses were lunged for 15 min at trot and canter prior to injection. Quantitative values for perfusion of the front feet and uptake of the radiopharmaceutical into the bones of the distal limb were obtained from scintigraphic measurements during the vascular and bone phases of radiopharmaceutical distribution. Perfusion of the front feet was classified as good in 60% of limbs, reduced in 21% and poor in 19%. There was a strong positive relationship between exercise and both perfusion of the front feet and uptake of the radiopharmaceutical into bone. Bandaging had no effect. There was a relationship between environmental temperature and both perfusion and uptake of the radiopharmaceutical into bone. Estimation of foot surface temperature using thermography was helpful in predicting perfusion of the distal limbs. There was no relationship between lameness and uptake of the radiopharmaceutical into bone. It is therefore recommended that, whenever possible, horses are exercised for 15 min prior to injection of radiopharmaceutical if nuclear scintigraphy of the distal parts of the limb is to be performed.

Analysis of Variance↗
PubMed2001

Vascular endothelial growth factor (VEGF) receptor-2 antagonists inhibit VEGF- and basic fibroblast growth factor-induced angiogenesis in vivo and in vitro.

Exponential tumor growth is angiogenesis-dependent. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are potent angiogenic inducers that act synergistically in vivo and in vitro. We assessed the effect of specific inhibitors of VEGF receptor (VEGFR)-2 tyrosine kinase activity in in vivo and in vitro models of VEGF- and bFGF-induced angiogenesis. In an implant mouse model of angiogenesis, VEGFR-2 inhibitors completely blocked angiogenesis induced by VEGF, and, surprisingly, also inhibited the effect of bFGF to various extents. In vitro, VEGF- and bFGF-induced bovine microvascular and aortic endothelial (BME and BAE) cell collagen gel invasion could be blocked by the VEGFR-2 inhibitors by 100 and approximately 90%, respectively. Similar results were obtained with VEGFR-1-IgG and VEGFR-3-IgG fusion proteins and with VEGFR-2 blocking antibodies. Both BME and BAE cells produce VEGF and VEGF-C, which is not modulated by bFGF. Thus, the unexpected inhibition of bFGF-induced angiogenesis by VEGFR-2 antagonists reveals a requirement for endogenous VEGF and VEGF-C in this process. These findings broaden the spectrum of mediators of angiogenesis that can be inhibited by VEGFR-2 antagonists and highlight the importance of these compounds as agents for inhibiting tumor growth sustained by both VEGF and bFGF.

Angiogenesis Inhibitors↗
PubMed2001

Eight-year hemodynamic follow-up after aortic valve replacement with the Toronto SPV stentless aortic valve.

The hemodynamic performance of stentless aortic bioprostheses has been well described during the first few months after surgery. The purpose of the present study was to describe the hemodynamic performance of the Toronto SPV valve (St. Jude Medical, Inc, St. Paul, MN) in a multicenter trial through 8 years. The long-term study of the Toronto SPV valve includes 447 consecutive patients from 6 investigative centers. Echocardiographic follow-up was performed at specified intervals, with quantitative analysis performed at a centralized core laboratory. Mean transvalvular gradient decreased significantly between discharge and 6 months, between 6 months and 1 year, and between 1 year and 2 years after surgery, without further significant change. The effective orifice area increased significantly early after surgery and continued to increase through 6-year follow-up. The left ventricular (LV) stroke volume increased progressively from discharge through 6-year follow-up. The LV mass index decreased significantly from discharge through 3 years after surgery and stabilized through 5 years. There was a gradual increase in LV outflow tract diameter between 1 year and 6 years after surgery. The prevalence of any aortic regurgitation (AR) (including trivial) and > or = mild AR increased significantly between discharge and 6-year to 8-year follow-up. However, the prevalence of > or = moderate AR remained very low at 6 years (2.6%) and 8 years (4.5%) after surgery. In conclusion, the Toronto SPV stentless tissue aortic valve is associated with excellent hemodynamics early after surgery and through 8 years after surgery. LV mass decreases early, and returns to within the range of normal by 1 year after surgery. There is evidence of continued LV mass regression involving the LV outflow tract, potentially contributing to a small but significant late improvement in hemodynamics. The prevalence of significant AR remains low through 8 years.

Adult↗
PubMed2001

Clustering of autoimmune thyroid diseases in children and adolescents: a study of 66 families.

Autoimmune thyroid diseases (AITD) are known to be clustered in families, but to what extent this occurs in childhood and adolescence is not well defined. In order to establish the prevalence of AITD in the siblings of affected children and adolescents, we examined 73 siblings from 66 families selected on the basis of a pediatric index patient. Sixty-six families, including a total of 146 offspring, were selected on the basis of diagnosis of chronic lymphocytic thyroiditis (CLT) (n = 55) or Graves' disease (GD) (n = 11). Among the 73 siblings examined, 20 new cases of CLT (27%) were detected. L-Thyroxine therapy was required in 4/20. History of AITD was recorded in 24/66 mothers (36%), and in two fathers. Overall in these families, considering both the index patients and the new patients, 86/141 (61%) children and adolescents were affected with AITD, with a female/male ratio of 3.3:1. Our study confirms that AITD clusters in families with a high prevalence in the siblings of affected children and adolescents. These children should be followed in order to avoid undiagnosed hypothyroidism. Prospective studies are warranted to identify predictive factors for overt thyroid disease.

Adolescent↗
PubMed2000

Stromal-derived factor 1-induced megakaryocyte migration and platelet production is dependent on matrix metalloproteinases.

Despite the discovery of thrombopoietin (TPO) and its contribution to megakaryocytopoiesis, the exact mechanisms and sites of platelet production are unknown. It has been shown that mature megakaryocytes (MKs) functionally express the stromal-derived factor 1 (SDF-1) receptor, CXCR4. SDF-1-induced migration of mature MKs through endothelial cell layers results in increased platelet production. Because the migration of polyploid MKs from the bone marrow microenvironment requires remodeling of the perivascular extracellular matrix, it was hypothesized that mature polyploid MKs may express matrix metalloproteinases (MMPs), facilitating their exit into the bone marrow extravascular space. In this report, it is demonstrated that SDF-1 induces the expression and release of gelatinase B (MMP-9) by purified mature polyploid human MKs and an adeno-CXCR4-infected megakaryocytic cell line. Neutralizing antibody to MMP-9, but not MMP-2, blocked SDF-1-induced migration of MKs through reconstituted basement membrane, suggesting that expression of MMP-9 is critical for MK migration. Incubation of mature MKs with a synthetic MMP inhibitor, 5-phenyl-1,10-phenanthrolene, resulted in the inhibition of platelet formation, suggesting that the expression of MMPs is not only critical for megakaryocyte migration but also for subsequent platelet release. Confirming these results, adeno-SDF-1 injection into normal mice resulted in increased platelet counts, a process that could be blocked by a synthetic MMP inhibitor. These results suggest mobilization of MKs involves sequential expression and activation of chemokine receptors such as CXCR4, MMP-9, followed by transendothelial migration. MMP inhibitors may have potential use in the treatment of thrombotic and myeloproliferative disorders. (Blood. 2000;96:4152-4159)

Adult↗
PubMed2000

Antiangiogenic gene therapy for cancer via systemic administration of adenoviral vectors expressing secretable endostatin.

A growing number of antiangiogenesis strategies have been investigated for the treatment of cancer and other angiogenesis-dependent diseases. One of the most promising strategies is to systemically administer one or more antiangiogenic proteins frequently enough to achieve a sufficient long-term steady state level of the protein(s) to achieve the maximum beneficial effect. However, the utility of this strategy is limited because of many technical difficulties, including obtaining both the quantity and quality of the protein(s) necessary for optimal therapeutic benefit. To overcome these difficulties, we hypothesized that a single administration of a replication-defective adenoviral vector expressing a secretable antiangiogenic protein could achieve an optimal long-term systemic concentration. We constructed a recombinant adenoviral vector, Av3mEndo, which encodes a secretable form of murine endostatin. We demonstrated secretion of endostatin from several cell lines transduced with Av3mEndo. Partially purified endostatin secreted from Av3mEndo-transduced mammalian cells was shown to potently inhibit endothelial cell migration in vitro. A single intravenous administration of Av3mEndo in mice was shown to result in (1) prolonged and elevated levels of circulating endostatin, (2) partial inhibition of VEGF-induced angiogenesis in a VEGF implant angiogenesis model, and (3) prolonged survival and in 25% of mice the complete prevention of tumor growth in a prophylactic human colon/liver metastasis xenograft murine model. These results support our contention that adenoviral vector-mediated expression of an antiangiogenic protein(s) represents an attractive therapeutic approach to cancer and other angiogenesis-dependent diseases.

Adenoviridae↗
PubMed2000

Effects of PTK787/ZK 222584, a specific inhibitor of vascular endothelial growth factor receptor tyrosine kinases, on primary tumor, metastasis, vessel density, and blood flow in a murine renal cell carcinoma model.

Antiangiogenic therapy is a promising new strategy to inhibit tumor growth and formation of metastases. Vascular endothelial growth factor (VEGF) and its receptors, VEGF-receptor 1 (VEGF-R1; FLT-1) and VEGF-R2 (KDR), have been shown to play a major role in tumor angiogenesis. PTK787/ZK 222584, a specific inhibitor of both VEGF-receptor tyrosine kinases, was investigated for its antitumoral and antiangiogenic activity in a murine renal cell carcinoma model. After intrarenal application of the renal carcinoma cells, mice develop a primary tumor and metastases to the lung and to the abdominal lymph nodes. Daily oral therapy with PTK787/ZK 222584 at a dose of 50 mg/kg resulted in a significant decrease of 61 and 67% in primary tumors after 14 and 21 days, respectively. The occurrence of lung metastases was significantly inhibited at both time points (98% reduction and 78% reduction, respectively). After 14 days, no lymph node metastases developed in the PTK787/ZK 222584-treated group, whereas after 21 days of treatment, the lymph node metastases were reduced by 87%. Vessel density in tumor tissues, detected by immunohistochemistry with an anti-CD31 antibody, was significantly decreased by PTK787/ZK 222584. Using color Doppler imaging ultrasound, significant changes in blood flow in the tumor feeding renal artery were found under treatment with PTK787/ZK 222584. Blood flow changes correlated with changes in vessel density but not with tumor volume. The compound was well tolerated in all in vivo experiments and had no significant effects on body weight or general well-being of the animals. This was in contrast to the animals treated with the antiangiogenic agent TNP-470. s.c. therapy with 30 mg/kg TNP-470 every other day had to be discontinued after 13 days because of animal weight loss (>20%) and ataxia. These results demonstrate that PTK787/ZK 222584 is a potent inhibitor of tumor growth, metastases formation, and tumor vascularization in murine renal cell carcinoma. Furthermore, we have been able to demonstrate that color Doppler imaging ultrasound can be used to measure blood flow to a tumor and that flow correlates with vessel density. Thus, this may be a valuable noninvasive method for monitoring the effects of antiangiogenic agents such as PTK787/ZK 222584 on tumor vasculature.

Angiogenesis Inhibitors↗