Search PubMed⌕ Search

Biomedical subjects

J Guy

Publications and source records attributed to J Guy.

At least 37 records · Page 2Linked to original sources
PubMed1997

Nursing students' approaches to studying.

The Approaches to Study Inventory (ASI), developed by Entwistle & Ramsden (1983), was administered to all nursing students at an Australian university (response rate = 67%). The purpose was to find out whether ASI constructs also apply to nursing students and to see whether nursing students change in their study approaches in the course of their nursing education. The ASI was construct validated through factor analysis. While it was possible to reconstruct a majority of the subscales based on individual items, only the meaning and reproducing study orientations were supported. These two orientations also demonstrated satisfactory levels of internal consistency for group comparisons. The authors conclude that the ASI is a useful and robust instrument for use in nursing education with respect to the two main study orientations. Ideally, nursing education should successively pave the way for an increase in meaning orientation scores (deep learning) and a reduction in reproducing orientation scores (surface learning). However, in this study there was no change in study orientations from first to third year. The association between meaning orientation scores and academic performance was weak.

Adolescent↗
PubMed1997

The expression of bacterial nitroreductase in transgenic mice results in specific cell killing by the prodrug CB1954.

The enzyme nitroreductase, isolated from Escherichia coli B, converts CB1954 ((5-aziridin-1-yl)-2,4-dinitro-benzamide) into a cytotoxic DNA interstrand cross-linking agent. The E. coli B gene (nfnB, NTR) encoding nitroreductase (NTR) was cloned into eukaryotic expression vectors. When driven by a CMV promoter, 5-10% of the stably transfected mouse fibroblasts expressed the NTR enzyme. These cells were killed at a concentration of 20 microM CB1954 in comparison to nonexpressing cells which were killed at a much higher concentration (500 microM). We subsequently generated transgenic mice to test the prodrug system in vivo. Nitroreductase was expressed specifically in T cells driven by the control elements of the human CD2 locus. Upon CB1954 treatment, transgenic mice show extensive cell depletion in thymus and spleen (14-16% of normal cell numbers), whereas all other tissues are unaffected by prodrug administration. These results raise the possibility of using the NTR gene in anticancer therapy.

Animals↗
PubMed1997

Comparison of remifentanil and fentanyl in patients undergoing craniotomy for supratentorial space-occupying lesions.

BACKGROUND: Remifentanil hydrochloride is an ultra-short-acting, esterase-metabolized mu-opioid receptor agonist. This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions. METHODS: Sixty-three adults gave written informed consent for this prospective, randomized, double-blind, multiple-center trial. Anesthesia was induced with thiopental, pancuronium, nitrous oxide/oxygen, and fentanyl (n = 32; 2 micrograms.kg.-1. min-1) or remifentanil (n = 31; 1 mu.kg-1.min-1). After tracheal intubation, infusion rates were reduced to 0.03 microgram.kg-1.min-1 (fentanyl) or 0.2 microgram.kg-1.min-1 (remifentanil) and then adjusted to maintain anesthesia and stable hemodynamics. Isoflurane was given only after specified infusion rate increases had occurred. At the time of the first burr hole, intracranial pressure was measured in a subset of patients. At bone flap replacement either saline (fentanyl group) or remifentanil (approximately 0.2 microgram.kg-1.min-1) were infused until dressing completion. Hemodynamics and time to recovery were monitored for 60 min. Analgesic requirements and nausea and vomiting were observed for 24 h. Neurological examinations were performed before operation and on postoperative days 1 and 7. RESULTS: Induction hemodynamics were similar. Systolic blood pressure was greater in the patients receiving fentanyl after tracheal intubation (fentanyl = 127 +/- 18 mmHg; remifentanil = 113 +/- 18 mmHg; P = 0.004). Intracranial pressure (fentanyl = 14 +/- 13 mmHg; remifentanil = 13 +/- 10 mmHg) and cerebral perfusion pressure (fentanyl = 76 +/- 19 mmHg; remifentanil = 78 +/- 14 mmHg) were similar. Isoflurane use was greater in the patients who received fentanyl. Median time to tracheal extubation was similar (fentanyl = 4 min: range = -1 to 40 min; remifentanil = 5 min: range = 1 to 15 min). Seven patients receiving fentanyl and none receiving remifentanil required naloxone. Postoperative systolic blood pressure was greater (fentanyl = 134 +/- 16 mmHg; remifentanil = 147 +/- 15 mmHg; P = 0.001) and analgesics were required earlier in patients receiving remifentanil. Incidences of nausea and vomiting were similar. CONCLUSIONS: Remifentanil appears to be a reasonable alternative to fentanyl during elective supratentorial craniotomy.

Adult↗
PubMed1997

Increase of manganese superoxide dismutase, but not of Cu/Zn-SOD, in experimental optic neuritis.

PURPOSE: To evaluate the role of manganese superoxide dismutase (Mn-SOD) and copper/zinc superoxide dismutase (Cu/Zn-SOD) in cellular protection of the optic nerve against the oxidative injury that contributes to demyelination in experimental allergic encephalomyelitis (EAE). METHODS: Immunocytochemistry for Mn-SOD and Cu/Zn-SOD and ultracytochemical localization of hydrogen peroxide (H2O2) were performed on the optic nerves of guinea pigs with EAE and normal guinea pigs. Cell-specific enzyme expression of SOD was quantitated by computerized morphometric analysis. RESULTS: Light microscopy showed a perivascular distribution of Mn-SOD-positive cells in the optic nerves of animals with EAE. Electron microscopy showed that the Mn-SOD immunogold was confined exclusively to mitochondria, whereas Cu/Zn-SOD immunogold was found in the cytoplasmic matrix and nucleus of cells of the optic nerve in both animals with EAE and normal animals. Results of quantitative analysis of the optic nerves of animals with EAE showed an 8-fold increase in Mn-SOD immunogold in astroglial cells and a 13-fold increase in microglial/phagocytic cells in comparison with that of normal animals. Increases in Mn-SOD immunogold were contiguous to H2O2-derived reaction product. No increases in Cu/Zn-SOD immunogold were detected in EAE. CONCLUSIONS: Increases in Mn-SOD activity in astroglial cells and microglial/phagocytic cells may contribute to the relative sparing of these cells from injury in EAE, whereas the low level of Mn-SOD in oligodendroglial cells and axons may increase their vulnerability to the effects of superoxide-induced oxidative injury that results in demyelination.

Animals↗
PubMed1997

Postoperative nausea and vomiting. A retrospective analysis in patients undergoing elective craniotomy.

Nausea and vomiting are important complications after craniotomy, for which there are little published epidemiologic data. We retrospectively examined the incidence of postcraniotomy nausea and vomiting to define risk factors. Medical records from 199 adults undergoing elective craniotomy were identified. Data extracted from surgery and the initial 48 hours postoperatively included gender, age, supratentorial versus infratentorial craniotomy, type of anesthesia (general versus monitored anesthesia care), intraoperative fentanyl dose, duration of anesthesia, antiemetic administration intraoperatively and postoperatively, and incidence of postoperative nausea, emesis, and opioid use. Postoperative nausea was recorded in 99 patients (50%) and emesis in 78 patients (39%). Postoperative opioids were administered to 170 patients (85%). Antiemetics were given intraoperatively to 13 patients (7%) and postoperatively to 121 patients (61%). More women (61%) than men (37%) had nausea (P = 0.001); emesis (women = 46%; men = 31%, P = 0.03); and postoperative antiemetic use (women = 69%; men = 51%, P = 0.013). The incidence of postoperative nausea (P = 0.04) and vomiting (P = 0.06) was greater in patients having infratentorial surgery. Emesis was more frequent in younger patients (P = 0.03). Postoperative nausea and vomiting were independent of anesthetic duration, fentanyl dose, or postoperative opioid use and occurred with similar frequency after general anesthesia or monitored anesthesia care. We conclude that postoperative nausea and vomiting occur frequently after craniotomy. Infratentorial surgery, female gender, and younger age are significant risk factors for this complication.

Adolescent↗
PubMed1996

Localization of NADPH diaphorase/nitric oxide synthase in the optic nerve of the normal guinea pig: a light and electron microscopic study.

The aim of this study is to determine the presence and subcellular distribution of NADPH diaphorase (NADPH-d)/nitric oxide synthase (NOS) in the optic nerve of the normal guinea pig. Optic nerve specimens were stained by NADPH-d histochemistry, and double labeled by combining NADPH-d histochemistry with immunostaining for (a) anti-glial fibrillary acidic protein (GFAP) antibody for recognition of astrocytes, (b) griffonia simplicifilia B4-isolectin (GSA-IB4) horse radish peroxidase (HRP)-conjugate for identification of microglia, or (c) oligodendrocyte-associated antibodies to carbonic anhydrase isoenzyme II (CA-II) or to galactocerebroside (GalC) for visualization of oligodendrocytes. In addition, constitutive NOS (cNOS) and inducible NOS (iNOS) immunostaining were used for colocalization with NADPH-d histochemistry. Light microscopy revealed NADPH-d reaction product in the blood vessels and neuroglia of the unmyelinated optic nerve head and myelinated retrobulbar optic nerve. Double labeling with GFAP immunoperoxidase combined with NADPH-d histochemistry revealed both activities in astrocytes. Microglia were labeled with GSA-IB4 isolectin HRP-conjugate, but they did not have NADPH-d activity. Oligodendroglia were immunolabeled with anti CA-II or anti GalC antibodies, but they did not have NADPH-d activity. Both iNOS and cNOS immunoperoxidase labeled astrocytes, but not microglia or oligodendroglia. Under transmission electron microscopy, NADPH-d reaction product appeared as electron-dense particles. These particles were seen in the cytoplasm of endothelial cells, perivascular smooth muscle cells and fibrous astrocytes. Axons and myelin were devoid of NADPH-d activity. This study demonstrates the existence and cellular distribution of NADPH-d/NOS activity in endothelial cells, perivascular smooth muscle cells and fibrous astrocytes of the optic nerve of the normal guinea pig. The presence of these non-neuronal sources of NOS in the optic nerve provides the foundation for future comparative studies of the functional role of reactive oxygen induced toxicity in disorders affecting the optic nerve.

Animals↗
PubMed1996

The occurrence of serum autoantibodies against enolase in cancer-associated retinopathy.

Cancer-associated retinopathy (CAR) is an uncommon paraneoplastic disease in which degeneration of the retina occurs as a remote effect of cancer in a distant part of the body. Immunoreactivity of sera from CAR patients and controls have been analyzed. Immunostaining of human retinal proteins showed that a soluble protein of Mr approximately 46 kDa (p46) is labeled by antibodies from several CAR patients with various types of cancer (lung, breast, bladder, prostate, salivary gland, and gastrointestinal tract cancer and chronic lymphocytic leukemia). These sera did not show reactivity with the 23-kDa protein previously associated with CAR. To identify and further characterize p46, the retinal protein was purified to homogeneity by anion-exchange chromatography and preparative gel electrophoresis. Protein sequence analysis of the peptides from p46 revealed a high homology with human enolase, an important glycolytic enzyme. Although enolase has been previously identified as a product of several types of tumors, and enolase activity has been detected in the sera of some cancer patients, the existence of autoantibodies directed to enolase has not been described. This is the first report of the presence of serum antibodies to retinal enolase in the patients with cancer and the CAR syndrome. When antibodies of specific isotypes (IgG, IgM, and IgA) were measured, IgG1 isotype was dominant. The significance of these antibodies for the disease process is under investigation.

Aged↗
PubMed1996

Herpetic stromal disease: response to acyclovir/steroid therapy.

The efficacy of combined acyclovir and steroid therapy in the treatment of herpetic stromal disease was evaluated by clinical evaluation of disease, the rebound of disease following termination of therapy, and the recovery of virus and viral DNA from corneas in a rabbit model. Therapy with acyclovir alone produced a significant reduction in corneal thickness in 10% of eyes. Addition of steroid to acyclovir therapy decreased the severity of stromal disease as measured by corneal thickness and increased the frequency of response to treatment to 63% of eyes. All eyes receiving acyclovir alone experienced rebound of disease following termination of therapy. Combined therapy increased the severity of rebound of corneal disease. Virus was recovered from cell cultures established after recovery from rebound in 50% of untreated and treated eyes. Viral DNA was detected by PCR in five of the nine corneal cultures which did not produce infectious virus.

Acyclovir↗
PubMed1996

A "humanized" green fluorescent protein cDNA adapted for high-level expression in mammalian cells.

We constructed gfph, a synthetic version of the jellyfish Aequorea victoria green fluorescent protein (gfp) cDNA that is adapted for high-level expression in mammalian cells, especially those of human origin. A total of 92 base substitutions were made in 88 codons in order to change the codon usage within the gfp10 coding sequence so that it was more appropriate for expression in mammalian cells. We also describe a series of versatile recombinant adeno-associated virus and adenovirus vectors for delivery and expression of genes into mammalian cells and, using these vectors, demonstrate the efficient transduction and expression of the gfph gene in the human cell line 293 and also in vivo, within neurosensory cells of guinea pig eye. Cells infected with recombinant adeno-associated virus-GFPH can be readily sorted by fluorescence-activated cell sorting, suggesting that the newly designed gfph gene could be widely used as a reporter in many gene delivery technologies, including human gene therapy.

Amino Acid Sequence↗
PubMed1996

Endothelial barrier function and Na+/K(+)-ATPase pump density in herpetic stromal disease.

PURPOSE: Corneal edema is a significant component of the various forms of herpes simplex virus type 1 (HSV-1)-induced stromal disease. Maintenance of corneal thickness, a reflection of corneal hydration, depends on a physical barrier formed by endothelial cell-cell junctions and by the activity of Na+/K(+)-ATPase pumps that regulate ion flux and thus influence water movement through this cell layer. These functions were measured in corneas with increased corneal thickness caused by HSV-1-induced stromal disease to determine their contribution to the pathogenesis of the edema. METHODS: Stromal disease with corneal edema was induced in rabbits by intrastromal injection of the RE strain of HSV-1. At various times after infection, during the development of and recovery from stromal disease, endothelial barrier function and Na+/K(+)-ATPase pump sites were measured in excised rabbit corneas. RESULTS: The endothelial permeability coefficient, Ktrans, for 14C-dextran, 3H-inulin, and 14C-mannitol, were not altered significantly during periods of maximal corneal edema and stromal disease. Endothelial Na+/K(+)-ATPase pump density, as measured by ouabain binding, showed a statistically significant (P < 0.05) decrease in HSV-1-infected corneas during peak edema compared to mock antigen-injected or uninjected control corneas. Pump density returned to baseline values by 24 days after infection, concurrent with the resolution of corneal edema. CONCLUSIONS: These results indicate that corneal endothelial barrier function was not altered in this form of HSV-1-induced stromal edema; however, pump density was reduced significantly.

Animals↗
PubMed1996

Long-term safety of the aminobisphosphonate alendronate in adult dogs. I. General safety and biomechanical properties of bone.

Alendronate (4-amino-1-hydroxybutylidene bisphosphonate, ALN) is an aminobisphosphonate that is being developed for the treatment of diseases characterized by increased bone resorption. The purpose of this study was to assess the long-term safety of ALN with special emphasis on bone strength and bone morphology. Thirty-two (16 males and 16 females) 83- to 86-week-old beagle dogs were treated p.o. for up to 3 years with ALN at 0.00, 0.25, 0.5 or 1.0 mg/kg/day. The following parameters of toxicity were assessed: physical signs, body weight, ophthalmology, radiographic evaluation of bone, electrocardiography, hematology, clinical chemistry, urinalysis, necropsy including organ weight assessment, histopathology and biomechanical testing of bone. There were no apparent compound-related alterations in any of the above mentioned parameters except the expected changes (related to the pharmacological activity of ALN) in serum phosphorus and Ca concentrations and in the histology of bones with active endochondral bone formation (rib). There were mild transient reductions in the serum phosphorus and Ca concentrations at the 1.0 mg/kg/day dose level during the early part of the study. There was a dose-dependent delay in bone remodeling in the ribs of all dogs treated with ALN. There was no similar change in the tibia. Most importantly, there were no spontaneous fractures and there were no changes in the structural properties of femoral or vertebral bone. The total ALN content of bone in an average dog (10 kg) after 3 years of treatment with approximately five items of the intended dose for the treatment of osteoporosis was approximately 8 mg, which is only 0.001% of total bone mass (700 g). Introduction.

Administration, Oral↗
PubMed1995

Delivery of DNA into mammalian cells by receptor-mediated endocytosis and gene therapy.

The correction of genetically based disorders by the introduction of a therapeutic genetic construct into the appropriate cell type ("gene therapy"), has become a distinct possibility in recent years. In order for gene therapy to be a practical alternative to more conventional pharmaceutical approaches to treatment, it must be administrable in vivo. This demands that a system be developed that can specifically target the DNA to the desired cell type once introduced into the patient. Among the procedures that are currently being pursued, the delivery of DNA to cells by receptor mediated endocytosis (RME), comes closest to fulfilling this crucial requirement. The natural physiological process of RME can be exploited to deliver genetic material to cells. An antibody or ligand to a cell surface receptor that is known to undergo endocytosis, is complexed with DNA through a covalently linked polycationic adjunct (e.g., polylysine, protamines). Such complexes retain their binding specificity to the cell surface and are taken up into the cell where they enter the endosomal compartment via normal endocytotic processes. In addition, steps must be taken to avoid degradation of the DNA within the endosome-lysosome. Cells can be treated with the lysosomatropic agent chloroquine during the transfection procedure. Alternatively, the components of viruses that enter cells by endocysis and possess an endosomal "break out" capacity can be used. Replication defective adenovirus coupled to the ligand-DNA complex gives transfection efficiencies of virtually 100% on tissue culture cells in vitro. Synthetic peptides that mimic the membrane fusing region of influenza virus hemagglutinin, have also been successfully used as part of the ligand-DNA complex to bring about endosomal escape. Preliminary studies have demonstrated the potential of this method to specifically target DNA to the cell type of choice in vivo. Delivery of genes by receptor-mediated endocytosis offers the greatest hope that gene therapy can be an inexpensive, easily applicable, widespread technology.

Animals↗
PubMed1995

Reducing surgical length of stay: quantifying the impact.

Length-of-stay (LOS) reduction is a strategy encouraged at all levels of health care to manage within a resource limited environment. However, few organizations have attempted to quantitatively understand the impact of reducing LOS. This study examines the relationship between reducing LOS and cost through a retrospective, medical records analysis of three surgical procedures (appendectomy, cholecystectomy and caesarean section) at an Ontario community hospital Department of Surgery. Hypotheses are presented and a methodology is described. The results are discussed with a focus on the factors that hospitals, administrators and physicians might consider in a LOS reduction program.

Adolescent↗
PubMed1995

Clinical efficacy and safety of low-dose flutamide alone and combined with an oral contraceptive for the treatment of idiopathic hirsutism.

BACKGROUND AND OBJECTIVE: High doses of flutamide, which is the only antiandrogen that specifically blocks the androgen receptor, have recently been used with good clinical results in women with hirsutism. Since regression of hair growth requires long-term therapy, clinical and economic considerations are important. The use of the lowest efficacious dosage could reduce costs. This study was undertaken to compare safety and efficacy of a low dose of flutamide (125 mg twice daily) alone and in combination with a triphasic oral contraceptive (OC) in women with idiopathic hirsutism. PATIENTS: Flutamide was administered orally in a low dose of 125 mg twice daily for 12 months alone in women with no risk of pregnancy or during the use of an oral contraceptive. MEASUREMENTS: Women were seen every 3 months and were evaluated for hirsutism score, hormone and lipid measurements. DESIGN: The study, which was conducted as a prospective open trial, was proposed to patients with idiopathic hirsutism, that is, with serum androgen levels in normal range and LH/FSH ratio less than 2. RESULTS: A statistically significant decrease in hirsutism score as compared to baseline was observed after only 3 months with either treatment, flutamide alone (16.9 +/- 1.6 vs 14.2 +/- 1.7, P < 0.0001) or the combination of flutamide with OC (15.6 +/- 0.8 vs 11.9 +/- 0.8, P < 0.001). Three months after cessation of treatment a statistically significant decrease from baseline was observed in the two groups. Nevertheless, at 6 months post-treatment this decrease was still significant only in the group who took flutamide in combination with an oral contraceptive. Flutamide alone does not appear to modify the levels of lipoproteins. The association of flutamide with a triphasic formulation significantly increased the HDL-C levels. CONCLUSIONS: This study shows beneficial effects of a low dose of flutamide in women with idiopathic hirsutism. The addition of an oral contraceptive is judicious to prevent pregnancy and reduce recurrence of hirsutism after cessation of flutamide. Peripheral androgenic blockage does not modify lipid profiles and it might reduce the negative effect of oral contraceptive on HDL-C levels. The addition of electrolysis delays the recurrence of hirsutism after cessation of flutamide.

Adult↗
PubMed1995

Ventilatory management in critical neurologic illness.

Evolution and refinement of airway and ventilatory management has taken place in neurologic critical care. Applications for ventilatory management have been extended to virtually all acute life-threatening illnesses found in neurologic critical care units today. This article focuses on the airway and ventilatory management of patients with acute raised intracranial pressure, cervical spine injuries, and neuromuscular ventilatory failure.

Adolescent↗