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Biomedical subjects

M Ward

Publications and source records attributed to M Ward.

At least 37 records · Page 2Linked to original sources
PubMed1999

Clinical and laboratory features of patients of Vietnamese descent with systemic lupus erythematosus.

The prevalence rate and disease manifestations of systemic lupus erythematosus (SLE) have been noted to vary among different ethnic groups. There has been no description in the English literature of SLE in the Vietnamese population. This is the first report, which details the clinical and laboratory features as well as an estimation of the prevalence of SLE in patients with a Vietnamese ancestry living in the United States. We performed a retrospective chart review of clinical and laboratory features of patients of Vietnamese descent with SLE. The case finding was performed by a review of the rheumatology clinic records at two large teaching hospitals in Santa Clara County searching for patients with SLE with a Vietnamese surname. In addition, we recruited patients by contacting all of the rheumatologists practicing in the county. Twenty-three patients of Vietnamese descent were identified with SLE in Santa Clara County. The estimated prevalence of SLE in the patients of Vietnamese descent was 42 cases per 100 000 persons. Eighty-seven per cent of the cases were born in Vietnam. The clinical and laboratory features of SLE were similar to prior published reviews except for a relatively high prevalence of anti-RNP antibody (54%). The patients with anti-RNP antibody exhibited features of overlap syndrome. There was a high rate of exposure to tuberculosis (TB). Fifty-eight per cent of patients had a positive purified protein derivative (PPD) skin test and 27% of patients had a history of clinical TB. Forty-four per cent of patients had evidence of hepatitis B exposure. The prevalence of SLE in the Vietnamese population in Santa Clara County is similar to that of other Asian populations. There was a relatively high prevalence of anti-RNP antibody in our patient group which was associated with overlap features. As expected in an immigrant population from Southeast Asia, there was a high rate of prior exposure to tuberculosis and hepatitis B. Clinicians should diligently screen for these infections and appropriately prophylaxe and treat patients.

Adult↗
PubMed1998

High-level transfer and long-term expression of the human beta-globin gene in a mouse transplant model.

Insertion of a normally functioning human beta-globin gene into the hematopoietic stem cells (HSC) of patients with beta-thalassemia may be an effective approach to the therapy of this disorder. Safe, efficient gene transfer and long-term, high-level expression of the transferred human beta-globin gene in animal models are prerequisites for HSC somatic gene therapy. We have recently shown for the first time that, using a modified beta-globin retroviral vector in a mouse transplant model, long-term, high-level expression of a transferred human beta-globin gene is possible. The human beta-globin gene continues to be detected up to eight months post-transplantation of beta-globin-transduced hematopoietic cells into lethally irradiated mice. The transferred human beta-globin gene is detected in three of five mice surviving long-term (> 4 months) transplanted with bone marrow cells transduced with high-titer virus. The unrearranged 5.1 kb human beta-globin gene-containing provirus is seen by Southern blotting in two of these mice. More importantly, long-term expression of the transferred gene is seen in two mice at levels of 5% and 20% that of endogenous murine beta-globin. We document stem cell transduction by showing continued high-level expression of the human beta-globin gene in secondarily transplanted recipient mice. These results provide evidence of HSC transduction with a human beta-globin gene in animals and demonstrate that retroviral-mediated unrearranged human beta-globin gene transfer leads to a high level of human beta-globin gene expression in the long term for the first time. A gene therapy strategy may be a feasible therapeutic approach to the beta-thalassemias if consistent human beta-globin gene transfer and expression into HSC can be achieved.

Animals↗
PubMed1998

Novel natural product 5,5-trans-lactone inhibitors of human alpha-thrombin: mechanism of action and structural studies.

High-throughput screening of methanolic extracts from the leaves of the plant Lantana camara identified potent inhibitors of human alpha-thrombin, which were shown to be 5,5-trans-fused cyclic lactone euphane triterpenes [O'Neill et al. (1998) J. Nat. Prod. (submitted for publication)]. Proflavin displacement studies showed the inhibitors to bind at the active site of alpha-thrombin and alpha-chymotrypsin. Kinetic analysis of alpha-thrombin showed tight-binding reversible competitive inhibition by both compounds, named GR133487 and GR133686, with respective kon values at pH 8.4 of 1.7 x 10(6) s-1 M-1 and 4.6 x 10(6) s-1 M-1. Electrospray ionization mass spectrometry of thrombin/inhibitor complexes showed the tight-bound species to be covalently attached, suggesting acyl-enzyme formation by reaction of the active-site Ser195 with the trans-lactone carbonyl. X-ray crystal structures of alpha-thrombin/GR133686 (3.0 A resolution) and alpha-thrombin/GR133487 (2.2 A resolution) complexes showed continuous electron density between Ser195 and the ring-opened lactone carbonyl, demonstrating acyl-enzyme formation. Turnover of inhibitor by alpha-thrombin was negligible and mass spectrometry of isolated complexes showed that reversal of inhibition occurs by reformation of the trans-lactone from the acyl-enzyme. The catalytic triad appears undisrupted and the inhibitor carbonyl occupies the oxyanion hole, suggesting the observed lack of turnover is due to exclusion of water for deacylation. The acyl-enzyme inhibitor hydroxyl is properly positioned for nucleophilic attack on the ester carbonyl and therefore relactonization; furthermore, the higher resolution structure of alpha-thrombin/GR133487 shows this hydroxyl to be effectively superimposable with the recently proposed deacylating water for peptide substrate hydrolysis [Wilmouth, R. C., et al. (1997) Nat. Struct.Biol. 4, 456-462], suggesting the alpha-thrombin/GR133487 complex may be a good model for this reaction.

Acylation↗
PubMed1998

An antiviral protein from Bougainvillea spectabilis roots; purification and characterisation.

An antiviral protein active against mechanical transmission of tomato spotted wilt virus was identified in the root tissues of Bougainvillea spectabilis Willd. Bougainvillea Antiviral Protein I (BAP I) was purified to apparent homogeneity from the roots of Bougainvillea by ammonium sulphate precipitation, CM- and DEAE-Sepharose chromatography and reverse phase HPLC. BAP I is a highly basic protein (pI value > 8.6) with an Mr of 28,000. The N-terminal sequence of BAP I showed homology with other plant antiviral proteins. Preliminary tests suggest that purified BAP I is capable of interfering with in vitro protein synthesis.

Amino Acid Sequence↗
PubMed1998

Feasibility of multidrug resistance (MDR-1) gene transfer in patients undergoing high-dose therapy and peripheral blood stem cell transplantation for lymphoma.

We have performed a pilot study of MDR-1 gene transfer in patients receiving CD34-selected peripheral blood stem cell (PBSC) transplant for lymphoma. To ensure minimum engraftment thresholds and facilitate CD34 purification, mobilisation of > 2 x 10(6) CD34 cells/kg was a condition for recruitment. Of 11 patients counselled for study entry, only five achieved this target in a single apheresis. In three consenting patients, purified CD34 cells were exposed to A12M1 MDR-1 retroviral supernatant for 6 h, cryopreserved then thawed and readministered following ablative chemotherapy. No delay in engraftment was observed, although one patient received additional back-up cells. Gene transfer was demonstrated by polymerase chain reaction (PCR) for vector-derived MDR-1 cDNA sequence in all cases. Analysis of peripheral blood and bone marrow cells after transplant has, however, shown no evidence of in vivo gene transfer with a follow-up of 12, 15 and 18 months. The effect of MDR-1 substrate drugs has not yet been tested as all patients remain in clinical and radiological remission of their lymphoma. These results confirm the difficulty of achieving in vivo gene transfer in human haemopoietic cells and indicate major logistical constraints in PBSC mobilisation in patients with relapsed and resistant disease in whom initial studies are appropriate.

Adolescent↗
PubMed1998

Hepatic Doppler perfusion index: measurement in nine healthy volunteers.

Nine healthy volunteers were studied to validate the reproducibility of the Doppler perfusion index--the ratio of hepatic arterial to total liver blood flow--and to evaluate the method of its derivation and the influence of the variable parameters necessary for its calculation. Wide intraobserver variability was observed, and Doppler perfusion index values were consistently outside the previously reported normal range.

Adult↗
PubMed1998

Phase I trial of retroviral-mediated transfer of the human MDR1 gene as marrow chemoprotection in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation.

PURPOSE: Normal bone marrow cells have little or no expression of the MDR p-glycoprotein product and, therefore, are particularly susceptible to killing by MDR-sensitive drugs, such as vinca alkaloids, anthracyclines, podophyllins, and paclitaxel and its congeners. Here we report the results of a phase I clinical trial that tested the safety and efficacy of transfer of the human multiple drug resistance (MDR1, MDR) gene into hematopoietic stem cells and progenitors in bone marrow as a means of providing resistance of these cells to the toxic effects of cancer chemotherapy. PATIENTS AND METHODS: Up to one third of the harvested cells of patients who were undergoing autologous bone marrow transplantation as part of a high-dose chemotherapy treatment for advanced cancer were transduced with an MDR cDNA-containing retrovirus; these transduced cells were reinfused together with unmanipulated cells after chemotherapy. RESULTS: High-level MDR transduction of erythroid burst-forming unit (BFU-E) and colony-forming unit-granulocyte macrophage (CFU-GM) derived from transduced CD34+ cells was shown posttransduction and prereinfusion. However, only two of the five patients showed evidence of MDR transduction of their marrow at a low level at 10 weeks and 3 weeks, respectively, posttransplantation. The cytokine-stimulated transduced cells may be out-competed in repopulation by unmanipulated normal cells that are reinfused concomitantly. The MDR retroviral supernatant that was used was shown to be free of replication-competent retrovirus (RCR) before use, and all tests of patients' samples posttransplantation were negative for RCR. In addition, no adverse events with respect to marrow engraftment or other problems related to marrow transplantation were encountered. CONCLUSION: These results indicate the feasibility and safety of bone marrow gene therapy with a potentially therapeutic gene, the MDR gene.

Adult↗
PubMed1997

Long-term transfer and expression of the human beta-globin gene in a mouse transplant model.

Somatic gene therapy of hemoglobinopathies depends initially on the demonstration of safe, efficient gene transfer and long-term, high-level expression of the transferred human beta-globin gene in animal models. We have used a beta-globin gene/beta-locus control region retroviral vector containing several modifications to optimize gene transfer and expression in a mouse transplant model. In this report we show that transplantation of beta-globin-transduced hematopoietic cells into lethally irradiated mice leads to the continued presence of the gene up to 8 months posttransplantation. The transferred human beta-globin gene is detected in 3 of 5 mice surviving long term (>4 months) transplanted with bone marrow cells transduced with high-titer virus. Southern blotting confirms the presence of the unrearranged 5.1-kb human beta-globin gene-containing provirus in 2 of these mice. In addition, long-term expression of the transferred gene is seen in 2 mice at levels of 5% and 20% that of endogenous murine beta-globin at 6 and 8 months posttransplantation. We further document stem cell transduction by the successful transfer and high-level expression of the human beta-globin gene from mice transduced 9 months earlier into irradiated secondary recipient mice. These results demonstrate high-level, long-term somatic human beta-globin gene transfer into the hematopoietic stem cells of an animal for the first time, and suggest the potential feasibility of a retroviral gene therapy approach to sickle cell disease and the beta thalassemias.

Animals↗
PubMed1997

Community-led services for mental health care: a study.

This paper reports findings from a study into the effects of relocating untrained personnel from the hospital into the community, over a nine-month period. The study measured the dependent variables of hospital admissions, length of stay, resultant cost savings and community caseloads. Non-significant decreases occurred in bed occupancy as well as increases in bed occupancy, more demanding community psychiatric nurse (CPN) caseloads and an increasing use of the community services by females. Future studies will need to distinguish the most appropriate models of service delivery in a community setting. The findings, verified nationally, have major ramifications for mental health nurses if they are to provide effective care to the seriously mentally ill patient.

Community Health Nursing↗
PubMed1997

Neuroprotective effects of the antioxidant LY231617 and NO synthase inhibitors in global cerebral ischaemia.

Recent studies have shown that the novel antioxidant LY231617 protects against ischaemia-induced neuronal damage in rat models of global cerebral ischaemia. In the present studies we have examined the effects of LY231617 in the gerbil model of global cerebral ischaemia. We also examined the effects of four nitric oxide synthase inhibitors (3-bromo-7-nitroindazole, N(G)-nitro-L-arginine methyl ester, aminoguanidine and S-methylisothiourea sulphate) in this model. LY231617 (50 mg/kg p.o. or 30 mg/kg i.p.) was administered either 30 min prior to occlusion or immediately post-occlusion followed by three further doses at 4, 24 and 48 h after the initial dose. 3-Bromo-7-nitroindazole was administered at 40 mg/kg i.p. immediately after occlusion followed by 20 mg/kg i.p. at 3, 6, 24 and 48 h, N(G)-nitro-L-arginine methyl ester was administered at 10 mg/kg i.p. immediately after occlusion followed by 5 mg/kg i.p. at 3, 6, 24 and 48 h. Aminoguanidine was administered at 80 mg/kg i.p. immediately after occlusion followed by 40 mg/kg i.p. at 3, 6, 24 and 48 h and S-methylisothiourea sulphate was administered at 10 mg/kg i.p. immediately, 3, 6, 24 and 48 h after occlusion. We also examined the effects of aminoguanidine administered at 80 mg/kg i.p. immediately after occlusion followed by 40 mg/kg i.p. at 3, 6, 24, 48, 72 and 96 h and S-methylisothiourea sulphate administered at 10 mg/kg i.p. immediately, 3, 6, 24, 48, 72 and 96 h after occlusion. Control animals were either sham operated or subjected to 5 min bilateral carotid occlusion. Extensive neuronal death was observed in the CA1 layer of the hippocampus in 5-min bilateral carotid artery occluded animals 5 days after surgery. LY231617 provided significant neuroprotection against the ischaemia-induced brain damage when administration was initiated before or after occlusion (P < 0.05). The neuronal NO synthase inhibitors, 3-bromo-7-nitroindazole and a general NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester also provided significant neuroprotection (P < 0.05). In contrast aminoguanidine and S-methylisothiourea sulphate (two inducible NO synthase inhibitors) failed to protect against the ischaemia-induced brain damage. These results indicate that free radicals and nitric oxide are involved in ischaemia-induced brain damage following global cerebral ischaemia. Antioxidants such as LY231617 or neuronal NO synthase inhibitors can prevent the ischaemia-induced neurodegeneration and may be useful as anti-ischaemic agents.

Animals↗
PubMed1997

Assessing patient dependency and staff skill mix.

An assessment tool was developed to measure patient dependency and staff skill mix in a child psychiatry inpatient unit. The authors discuss the results of a three-month pilot implementation. The implications for practice include adjustments in staff duty rotas, allocation of skill mix and the systematic assessment of patient dependency before inpatient admission.

Activities of Daily Living↗
PubMed1997

Student nurses' perceptions of health promotion: a study.

This article reports the findings of a comparative descriptive study of Project 2000 student nurses and student nurses following the apprenticeship model of training (conventional). The research compared their perception of health promotion with the perception of their roles as health promoters. The study used a mixture of quantitative and qualitative methodology including a questionnaire, Likert Scale assessment of statements, and interviews. The results showed that there was no significant difference between the two groups except in two areas. The conventional students agreed more strongly than the Project 2000 students that their roles as health promoters were very important. The Project 2000 students were able to name eight different health promotion models/approaches and applied some of them in practice, while the conventional students had no knowledge of health promotion models/approaches. The researcher recommends that a wider understanding of health promotion should be encouraged and that nurse lecturers and clinical staff should work more closely to develop a consistent approach to health promotion.

Attitude of Health Personnel↗
PubMed1997

Prevalence of segmental wire breakage using Cotrel-Dubousset instrumentation in the management of idiopathic scoliosis.

STUDY DESIGN: This is a retrospective radiographic and medical record analysis of 77 patients. OBJECTIVES: To determine whether there is an increased prevalence of segmental sublaminar wire breakage associated with the knurled (diamond) pattern machined onto the Cotrel-Dubousset rod as opposed to a smooth rod. SUMMARY OF BACKGROUND DATA: Segmental fixation of vertebral segments with sublaminar wires is a common surgical technique, and the use of sublaminar wires with a knurled Cotrel-Dubousset rod theoretically could cause premature wire breakage. METHODS: Sixty-six patients with idiopathic scoliosis had the Cotrel-Dubousset (knurled rod) system and comprised the study group, and the Texas Scottish Rite Hospital system (smooth rod) was placed in 14 patients, who served as a control group. Serial radiographs after 3, 6, 12, and 24 months were reviewed. All patients had augmentation of their scoliosis constructs with 16-gauge sublaminar wires in the lumbar spine. Minimum follow-up period was 24 months. RESULTS: No wire breakage was noted in any patient. CONCLUSIONS: There is no increased likelihood that the knurled rod pattern will cause wire breakage, provided a solid fusion is obtained.

Adolescent↗
PubMed1997

Symptomatic spinal calcinosis in systemic sclerosis (scleroderma).

Two patients with diffuse cutaneous systemic sclerosis and spinal calcification, involving the lumbar spine in one and the cervical spine in the other, are described. Computed tomography-guided aspiration of the calcific masses was performed, and material aspirated from one patient was shown to be apatite, Ca5(PO4)3OH. One patient showed improvement following lumbar laminotomy, hemilaminectomy, and diskectomy.

Calcinosis↗