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M Wood

Publications and source records attributed to M Wood.

At least 37 records · Page 2Linked to original sources
PubMed2002

Hyphenated techniques in anticancer drug monitoring. II. Liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry.

High-performance liquid chromatography has become the separation technique of choice for the monitoring of generally thermolabile anticancer agents. With the introduction of electrospray mass spectrometry, the coupling of liquid chromatogaphy and mass spectrometry has opened the way to widely and routinely applied anticancer drug monitoring. Real-time metabolism versus degradation can now be distinguished, since derivatization is no longer obligatory. This is important for the monitoring of the anabolic and catabolic pathways of the same agent, such as 5-fluorouracil. Detection limits almost equal to those obtained with capillary gas chromatography-mass spectrometry are realistic with the latest generation of mass spectrometers, enabling quantitative analysis of various anticancer agents and their metabolites down to the low ng/ml level. Furthermore, sample clean-up and chromatography can be downscaled markedly using the latest column technologies, such as the generally applied 10 cm x 2.8 mm I.D. RP 18 columns. The coupling of capillary electrophoresis to mass spectrometry is today far from a routine application in anticancer drug monitoring. Nevertheless, interesting applications have been reported and are selected for the present review.

Antineoplastic Agents↗
PubMed2002

Hyphenated techniques in anticancer drug monitoring. I. Capillary gas chromatography-mass spectrometry.

Most anticancer agents are relatively unstable substances and are subjected to intensive metabolism in vivo and radiation during sample pretreatment. Hyphenated techniques including a separation technique and, most frequently, mass spectrometry are therefore chosen to obtain insight into the in vivo behavior of anticancer agents. Once established, simpler assays can be derived from those based on hyphenation, which are less expensive. Capillary gas chromatography (cGC)-mass spectrometry (MS) is amongst the most frequently applied hyphenated analytical technologies in anticancer drug monitoring. Here a selection has been made of: (i) cGC-MS applied to the analysis of agents frequently used in clinical oncology (e.g. tamoxifen, oxazaphosphorines); (ii) cGC-MS applied to the development of new agents (Swainsonine and Brefeldin); (iii) cGC-MS applied to the analysis of agents for which comparisons with other frequently applied hyphenation technologies are possible (see Part I of this series). cGC-MS played a key role in the elucidation of the in vivo behavior of the oxazaphosphorine cyclophosphamide, historically the most frequently applied anticancer agent. cGC-MS appeared to be of special interest in the analysis of cyclophosphoramide and congeners in human erythrocytes by coupling of the hyphenated technique with a measurement of sediment technique. This resulted in the quantitative and qualitative analysis of oxaphosphorine-related mustard gas moieties in human erthrocytes for the first time.

Antineoplastic Agents↗
PubMed2002

A randomized trial of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon.

BACKGROUND: Conventional interferon monotherapy fails to achieve virological clearance in most hepatitis C-infected patients. The use of high-dose induction regimens may improve the initial clearance of virus, while the addition of ribavirin appears to improve the rates of sustained response once clearance is achieved. AIM: To compare the efficacy and safety of re-treatment with an induction regimen of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon monotherapy. METHODS: Previous virological non-responders to standard dose interferon (3-5 MU three times weekly for > or = 12 weeks) were randomized to receive, unblind, either 10 MU interferon alpha-2b daily for 10 days, then 5 MU daily for 74 days, then 5 MU three times weekly for 24 weeks (total 36 weeks) (group A), or the above regimen with the addition of ribavirin, 1000-1200 mg/day, at day 11 (group B). All patients were followed up for 24 weeks after completion of therapy. RESULTS: End of treatment virological response was noted in one of 10 (10%) patients in group A and in eight of 15 (54%) patients in group B (P=0.04). The sole end treatment responder in group A and three in group B relapsed on follow-up. The apparent improvement in response in group B compared to group A nearly reached statistical significance (group B 5/15 vs. group A 0/10; P=0.06). CONCLUSIONS: In this small pilot study, a 36-week high-dose induction interferon monotherapy protocol did not yield sustained responses in previous non-responders to standard dose interferon. However, the same regimen with ribavirin yielded a 33% sustained response rate, nearly reaching statistical significance. The therapy was well tolerated, despite the higher doses of interferon used and the addition of ribavirin. High-dose interferon with ribavirin appears to be a therapeutic option for non-responders to conventional interferon monotherapy.

Adult↗
PubMed2002

Does prospective monitoring improve cataract surgery outcomes in Africa?

AIMS: To determine if prospective monitoring influences cataract surgical outcomes in east Africa. METHODS: A prospective observational study of all routine extracapsular cataract extractions with posterior chamber lens implants carried out at Kikuyu Eye Unit, Kenya, between 1 January 1999 and 31 December 1999. RESULTS: Out of 1845 eligible eyes 1800 were included in the study. Two months' follow up was available in 67.2% of patients. The proportion achieving a good outcome increased steadily from 77.1% in the first quarter to 89.4% in the fourth quarter (chi(2) for trend, p<0.001). There was no change in the incidence of operative complications; however, the proportion of patients achieving a good visual outcome following vitreous loss increased from 47.2% in the first 6 months to 71.0% in the last 6 months (chi(2) p<0.05). Of the eyes with poor outcome (best corrected acuity <6/60 at 2 months) half were due to pre-existing eye diseases. The proportion of patients with known ocular comorbidity decreased from 10.2% in the first quarter to 5.9% in the fourth quarter (chi(2) for trend, p<0.05). Poor outcome was associated with age over 80 years, known diabetes, preoperative bilateral blindness, any ocular comorbidity, and intraoperative vitreous loss. CONCLUSIONS: This study demonstrates improvement in visual outcome results after cataract surgery over a 1 year period. Monitoring of outcomes appears to be associated with a change in surgeons' attitudes, leading to greater emphasis on appropriate case selection, better management of surgical complications, and improved visual outcomes.

Aged↗
PubMed2002

The clinical diagnosis of influenza.

Effective management of influenza depends on early recognition of influenza in the community and on rapid diagnosis. Early recognition is achieved by integrated clinical and laboratory based surveillance programmes in representative populations. The recent introduction of 'near patient tests' for influenza provide increased opportunities for surveillance but diagnosis remains largely clinically based. The combination of cough and fever in conditons of known local influenza virus circulation provide a useful indicator of diagnosis to guide management.

Humans↗
PubMed2002

Nursing-related determinants of 30-day mortality for hospitalized patients.

The purpose of this study was to further our understanding of the effects of nursing-related hospital variables on 30-day mortality rates for hospitalized patients. A retrospective design was used to test the proposed 30-Day Mortality Model. The sample consisted of 75 acute-care hospitals in the province of Ontario, Canada. To develop hospital mortality rates, 46,941 patients discharged from these hospitals who had a most responsible diagnosis of acute myocardial infarction, stroke, pneumonia, or septicemia were included. To develop hospital-level nursing predictor variables, 3,998 responses to the Ontario Registered Nurse Survey of Hospital Characteristics were also included. The findings support a relationship between lower 30-day mortality and 3 predictors: a richer registered nurse skill mix, more years of experience on the clinical unit, and reported larger number of shifts missed. These findings can be used to predict the effects of hospital changes in nursing skill mix and years of RN experience on patient mortality.

Diagnosis-Related Groups↗
PubMed2001

Pharmacological characterisation of human 5-HT2 receptor subtypes.

Prompted by conflicting literature, this study compared the pharmacology of human 5-hydroxytryptamine2 (5-HT2) receptors expressed in SH-SY5Y cells using a fluorometric imaging plate reader (FLIPR) based Ca2+ assay. 5-Hydroxytryptamine (5-HT) increased intracellular calcium concentration ([Ca2+]i) at 5-HT2A, 5-HT2B and 5-HT2C receptors (pEC(50)=7.73+/-0.03, 8.86+/-0.04 and 7.99+/-0.04, respectively) and these responses were inhibited by mesulergine (pKB=7.42+/-0.06, 8.77+/-0.10 and 9.52+/-0.11). A range of selective agonists and antagonists displayed the expected pharmacology at each receptor subtype. Sodium butyrate pretreatment increased receptor expression in SH-SY5Y/5-HT2B (15-fold) and SH-SY5Y/5-HT2C cells (7-fold) and increased agonist potencies and relative efficacies. In contrast, sodium butyrate pretreatment of SH-SY5Y/5-HT(2A) cells did not affect receptor expression. The present study provides a direct comparison of agonist and antagonist pharmacology at 5-HT(2) receptor subtypes in a homogenous system and confirms that agonist potency and efficacy varies with the level of receptor expression.

Butyrates↗
PubMed2001

Reducing sediment inputs to Scottish streams: a review of the efficacy of soil conservation practices in upland forestry.

The historical process by which a soil conservation strategy has evolved within the UK forestry industry is briefly reviewed. Particular attention is given to the development of practical and effective guidelines to prevent both soil damage and sediment entering water courses. It is concluded that the 'Forest and Water Guidelines', together with other forest industry manuals, largely provide adequate protection for aquatic habitats from pre-afforestation cultivation and from harvesting activities. The problem of soil erosion owing to ploughing of open furrows has largely been obviated by improved drainage network design coupled with the use of vegetated buffer strips and sediment catchpits. Alternative site preparation techniques, such as 'moling' or 'dolloping' of afforestation sites, are now preferred. However, the effects on slope hydrology and the improved soil conservation associated with these methods require quantifying. Additional understanding of effective buffer strip function, for example, on a variety of slope angles, soil types and vegetation associations would be beneficial. The design of forest roads and the associated network of drains, culverts and sediment catchpits is addressed in forestry guidelines. Future potential in this area may involve the use of Geographical Information Systems in the effective design of road networks which minimise adverse effects on slope hydrology. Similarly computer simulation of flow routing might aid in the design of road drain networks. At the more local scale there remains scope for further research aimed at minimising soil disturbance by machinery. Consideration should also be given to the long-term sustainability of the soil structure through second and subsequent crop rotations.

Conservation of Natural Resources↗
PubMed2001

Cytochrome P2 polymorphisms and susceptibility to scleroderma following exposure to organic solvents.

OBJECTIVE: To determine whether there are specific cytochrome P450 (CYP2) alleles that increase susceptibility to scleroderma in individuals who have been exposed to organic solvents. METHODS: CYP alleles at 2 loci, 2E1 and 2C19, were compared in 7 patients who had developed scleroderma after exposure to solvents versus 71 patients with scleroderma without solvent exposure ("sporadic" disease) and 106 population controls. RESULTS: The 2E1*3 allele was found in 2 of the 7 patients who had been exposed to organic solvents, with a greater frequency than occurred in either the disease controls or the population controls (odds ratio [95% confidence interval] 9.1 [1.5-59.1] and 10.2 [1.8-62.2], respectively). All 7 patients with solvent exposure carried the 2C19EM genotype, compared with 89% of patients with sporadic scleroderma. CONCLUSION: Our results suggest that alleles at CYP loci may be involved in increasing susceptibility to scleroderma among subjects who have been exposed to organic solvents.

Case-Control Studies↗
PubMed2001

Expression, specificity and immunotherapy potential of prostate-associated genes in murine cell lines.

The TRAMP-C1 (C1) and TRAMP-C2 (C2) cell lines were derived from a prostate tumor that arose in a mouse from the transgenic adenocarcinoma mouse prostate (TRAMP) model. However, their similarity to primary prostate tumors and therefore their usefulness in immunotherapy studies has not been clearly defined. We showed using RT-PCR that these cell lines exhibited a variety of prostate-specific genes expressed by human prostate tumors that may be used as tumor-associated antigens for immunotherapy. Interestingly, several of these genes are also expressed in cell lines that are not prostatic in origin. The prostate cell lines were also shown to grow in an androgen-independent manner, to be capable of expressing MHC class I and to be susceptible to specific lysis by cytotoxic T lymphocytes. Therefore, these cell lines will provide us with the ability to evaluate immune responses to and tolerance of prostate-specific protein peptides in an animal model.

Acid Phosphatase↗
PubMed2001

Gabapentin is not a GABAB receptor agonist.

Recent experiments have demonstrated that formation of functional type B gamma-aminobutyric acid (GABA(B)) receptors requires co-expression of two receptor subunits, GABA(B1) and GABA(B2). Despite the identification of these subunits and a number of associated splice variants, there has been little convincing evidence of pharmacological diversity between GABA(B) receptors comprising different subunit combinations. However, Ng et al. [Mol. Pharmacol., 59 (2000) 144] have recently suggested a novel and important pharmacological difference between GABA(B) receptor heterodimers expressing the GABA(B1a) and GABA(B1b) receptor subunits. This study suggested that the antiepileptic GABA analogue gabapentin (Neurontin) is an agonist at GABA(B) receptors expressing the GABA(B1a) but not the GABA(B1b) receptor subunit. The importance of this finding with respect to identifying novel GABA(B) receptor subunit specific agonists prompted us to repeat these experiments in our own [35S]-GTPgammaS binding and second messenger assay systems. Here we report that gabapentin was completely inactive at recombinant GABA(B) heterodimers expressing either GABA(B1a) or GABA(B1b) receptor subunits in combination with GABA(B2) receptor subunits. In addition, in both CA1 and CA3 pyramidal neurones from rodent hippocampal slices we were unable to demonstrate any agonist-like effects of gabapentin at either pre- or post-synaptic GABA(B) receptors. In contrast, gabapentin activated a GABA(A) receptor mediated chloride conductance. Our data suggest that gabapentin is not a GABA(B)-receptor agonist let alone a GABA(B) receptor subunit selective agonist.

Acetates↗
PubMed2001

O6-Benzylguanine potentiates BCNU but not busulfan toxicity in hematopoietic stem cells.

OBJECTIVE: Busulfan (BU) is often used in conditioning regimens prior to bone marrow transplantation, but its mechanism of action remains to be resolved. We have examined the possibility that BU may exert part of its toxic effects via DNA alkylation at the O6 position of guanine as this might provide an approach to improving the conditioning regimen. METHODS: Survival of LAMA-84 and RJKO cells was assessed by colony-forming assay and cell counting, respectively. O6-alkylguanine-DNA alkyltransferase (ATase) activity was assayed by transfer of radioactivity from [3H]-methylated DNA. Colony-forming potential of normal human bone marrow cells (BMC) was measured in the presence of appropriate growth factors as the formation of both granulocyte-macrophage colony-forming units (CFU-GM) or burst-forming unit erythroids (BFU-E) within the same assay. Murine hematopoietic precursors were grown under a bone marrow stromal cell line to allow measurement of the frequency of cobblestone area-forming cells (CAFC) that correspond to CFU-GM, spleen colony-forming units (CFU-S), and the primitive stem cells with long-term repopulating ability. RESULTS: Inactivation of ATase by O6-benzylguanine (O6-BeG) sensitized a human erythromegakaryocytic cell line (LAMA-84) and normal human bone marrow progenitors to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) but not to BU toxicity. BCNU, but not BU, inactivated ATase in LAMA-84 cells. Overexpression of human ATase in cDNA transfected Chinese hamster cells attenuated the toxicity of BCNU but not BU. Finally, the in vivo treatment of mice showed that the depletion of primitive stem cells by BU as measured in the CAFC assay was not affected by addition of O6-BeG. O6-BeG did, however, dramatically potentiate BCNU toxicity in all CAFC subsets, leading to depletion of more than 99% stem cells. CONCLUSION: These data suggest that BU does not elicit toxicity via alkylation at the O6 position of guanine in DNA in a way that can be influenced by ATase modulation.

Alkylation↗
PubMed2001

Impact of risk information in a patient education leaflet.

Informed consent requires the communication of information about possible adverse effects of treatment. Health professionals have expressed concern that increased provision of risk information may make patients unduly anxious and change their decisions about treatment. This study compared two patient leaflets about laparoscopy, one containing detailed information about potential side effects. Forty one consenting participants attending an outpatient gynaecology clinic and scheduled for an elective laparoscopic procedure were studied. They were randomly assigned to receive one of two leaflets after their consultation. Knowledge about laparoscopy, satisfaction with information provided, and anxiety were tested 2 days later, between the original consultation and their operation. Results showed that the leaflet containing detailed risk information was associated with greater knowledge about laparoscopy, higher satisfaction with information provision and no increase in anxiety. Provision of detailed information about possible adverse consequences of treatment can improve patients' understanding and satisfaction without inducing increased anxiety.

Adult↗
PubMed2001

Development and application of a sensitive and rapid immunoassay for the quantitation of N7-methyldeoxyguanosine in DNA samples.

N7-Methyldeoxyguanosine (N7-MedG) in DNA is a biomarker of exposure to environmental and endogenous methylating agents and may be of use in epidemiological studies. To quantitate N7-MedG in human samples, a sensitive assay system that uses only small quantities of DNA (<10 microg) is required. To this end, polyclonal antibodies against the imidazole ring-opened form of N7-MedG have been used to develop a highly sensitive immunoslot blot (ISB) assay. The limit of detection of the assay is 0.10 micromol of N7-MedG/mol of deoxyguanosine (dG) using 1 microg of DNA per analysis. The method was optimized using in vitro-methylated calf thymus DNA and then applied to a study of DNA methylation in liver and brain tissues of mice following a single iv dose of the antitumor agent Temozolomide. The amount of N7-MedG in both tissues was strictly proportional to dose over a range of 10-200 mg of Temozolomide/kg of body weight. The ISB assay was then validated using pyloric DNA of rats treated with N-methyl-N'-nitro-N-nitrosoguanidine and DNA samples from human bladder tumors, for both of which N7-MedG levels had already been quantitated by an HPLC/(32)P-postlabeling method previously described. The results showed a high degree of correlation (r = 0.98) between the two assays. The ISB assay was then applied to a range of human samples. A series of peripheral blood mononuclear cell DNA samples from cancer patients following treatment with Temozolomide had levels of N7-MedG ranging from 0.22 to 320 micromol/mol of dG. DNA samples from colon carcinoma and normal colorectal mucosa from individuals not known to be exposed to methylating agents contained levels of 0.11-1.34 micromol of N7-MedG/mol of dG. The ISB assay offers the potential for the rapid and high-throughput analysis of DNA obtained from routine biopsies and blood samples, thus enabling the determination of the extent of human exposure to environmental and endogenous sources of methylating agents in large-scale biomonitoring studies.

Animals↗
PubMed2001

Sperm retrieval, fertilization, and pregnancy outcome in repeated testicular sperm aspiration.

PURPOSE: To report the outcome of sperm retrieval and results after ICSI in up to six repeated testicular sperm aspiration procedures. METHODS: Twenty-two men with obstructive and thirty-four men with nonobstructive azoospermia underwent 50 and 91 needle aspirations, respectively. Sufficiency of spermatozoa for ICSI and cryopreservation, fertilization rate, and pregnancy outcome was analyzed retrospectively. RESULTS: No major differences were found in sperm recovery or pregnancy outcome in the repeated cycles. Testicular aspirate containing motile spermatozoa with maintained fertilizing capacity was obtained in up to six repeated procedures in the nonobstructive group. No postoperative complications were reported for any of the participants. CONCLUSIONS: Testicular sperm aspiration is a simple and effective method of sperm retrieval, which can be performed from the same testis up to several times with good recovery of motile spermatozoa for ICSI and maintaining high fertilization and pregnancy rates, in men with both obstructive and nonobstructive azoospermia.

Adult↗