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Biomedical subjects

A Webb

Publications and source records attributed to A Webb.

At least 19 recordsLinked to original sources
PubMed2006

Novel aspects of endothelium-dependent regulation of vascular tone.

The vascular endothelium plays a crucial role in the regulation of vascular homeostasis and in preventing the initiation and progress of cardiovascular disease by controlling mechanical functions of the underlying vascular smooth muscle. Three vasodilators: nitric oxide (NO), prostacyclin, and endothelium-derived hyperpolarizing factor, produced by the endothelium, underlie this activity. These substances act in a co-ordinated interactive manner to maintain normal endothelial function and operate as support mechanisms when one pathway malfunctions. In this review, we discuss recent advances in our understanding of how gender influences the interaction of these factors resulting in the vascular protective effects seen in pre-menopausal women. We also discuss how endothelial NO synthase (NOS) can act in both a pro- and anti-inflammatory action and therefore is likely to be pivotal in the initiation and time course of an inflammatory response, particularly with respect to inflammatory cardiovascular disorders. Finally, we review recent evidence demonstrating that it is not solely NOS-derived NO that mediates many of the beneficial effects of the endothelium, in particular, nitrite acts as a store of NO released during pathological episodes associated with NOS inactivity (ischemia/hypoxia). Each of these more recent findings has emphasized new pathways involved in endothelial biology, and following further research and understanding of the significance and mechanisms of these systems, it is likely that new and improved treatments for cardiovascular disease will result.

Adult↗
PubMed2006

A phase III trial comparing CHOP to PMitCEBO with or without G-CSF in patients aged 60 plus with aggressive non-Hodgkin's lymphoma.

The management of older patients with aggressive non-Hodgkin's lymphoma presents a challenge to the physician. Age is a poor prognostic indicator, due to reduced ability to tolerate and maintain dose-intensive chemotherapy. Generally, older patients demonstrate a lower response rate, reduced survival and increased toxicity, although the majority of large randomised trials exclude older patients. This randomised trial was conducted in patients 60 years or over to compare CHOP (cyclophosphamide 750 mg m(-2), doxorubicin 50 mg m(-2), vincristine 1.4 mg m(-2), prednisolone 100 mg) with PMitCEBO (mitoxantrone 7 mg m(-2), cyclophosphamide 300 mg m(-2), etoposide 150 mg m(-2), vincristine 1.4 mg m(-2), bleomycin 10 mg m(-2) and prednisolone 50 mg). Due to the myelosuppressive nature of these regimens, patients were also randomised to the addition of G-CSF. The formal results of this trial with long-term follow-up are now reported. Data were analysed to assess efficacy and toxicity. Overall response rate was 84% in the CHOP arm and 83% in the PMitCEBO arm, with overall response rates of 83% for the use of G-CSF and 84% for no G-CSF. At median 44 months follow-up, there was no significant difference in failure-free, progression-free or overall survival between the CHOP and PMitCEBO arms. At 3 years, the actuarial failure-free survival was 44% in CHOP recipients and 42% in PMitCEBO recipients and the 3-year actuarial overall survival was 46% and 45% respectively. There was no significant difference in the failure-free, progression-free or overall survival with the addition of G-CSF.

Age Factors↗
PubMed2005

Spatially complex distribution of dissolved manganese in a fjord as revealed by high-resolution in situ sensing using the autonomous underwater vehicle Autosub.

Loch Etive is a fjordic system on the west coast of Scotland. The deep waters of the upper basin are periodically isolated, and during these periods oxygen is lost through benthic respiration and concentrations of dissolved manganese increase. In April 2000 the autonomous underwater vehicle (AUV) Autosub was fitted with an in situ dissolved manganese analyzer and was used to study the spatial variability of this element together with oxygen, salinity, and temperature throughout the basin. Six along-loch transects were completed at either constant height above the seafloor or at constant depth below the surface. The ca. 4000 in situ 10-s-average dissolved Mn (Mnd) data points obtained provide a new quasi-synoptic and highly detailed view of the distribution of manganese in this fjordic environment not possible using conventional (water bottle) sampling. There is substantial variability in concentrations (<25 to >600 nM) and distributions of Mnd. Surface waters are characteristically low in Mnd reflecting mixing of riverine and marine end-member waters, both of which are low in Mnd. The deeper waters are enriched in Mnd, and as the water column always contains some oxygen, this must reflect primarily benthic inputs of reduced dissolved Mn. However, this enrichment of Mnd is spatially very variable, presumably as a result of variability in release of Mn coupled with mixing of water in the loch and removal processes. This work demonstrates how AUVs coupled with chemical sensors can reveal substantial small-scale variability of distributions of chemical species in coastal environments that would not be resolved by conventional sampling approaches. Such information is essential if we are to improve our understanding of the nature and significance of the underlying processes leading to this variability.

Environmental Monitoring↗
PubMed2005

A randomised comparison between 6 months of bolus fluorouracil/leucovorin and 12 weeks of protracted venous infusion fluorouracil as adjuvant treatment in colorectal cancer.

BACKGROUND: We performed a multicentre randomised trial to compare the efficacy and toxicity of 12 weeks of protracted venous infusion (PVI) 5-fluorouracil (5-FU) against the standard bolus monthly regimen of 5-FU/leucovorin (LV) given for 6 months as adjuvant treatment in colorectal cancer (CRC). PATIENTS AND METHODS: Patients with curatively resected stage II and III CRC were randomly assigned to 5-FU/LV [5-FU 425 mg/m(2) intravenously (i.v.) and LV 20 mg/m(2) i.v. bolus days 1-5 every 28 days for 6 months] or to PVI 5-FU (300 mg/m(2)/day for 12 weeks). RESULTS: Between 1993 and 2003, 801 eligible patients were randomised to 5-FU/LV (n=404) or PVI 5-FU (n=397). With a median follow-up of 5.3 years, 231 relapses and 220 deaths have been observed. Five-year relapse-free survival (RFS) was 66.7% [95% confidence interval (CI) 61.6% to 71.3%] and 73.3% (95% CI 68.4% to 77.6%) with bolus 5-FU/LV and PVI 5-FU, respectively [hazard ratio (HR) 0.8; 95% CI 0.62-1.04; P=0.10]. Five-year overall survival (OS) was 71.5% (95% CI 66.4% to 75.9%) and 75.7% (95% CI 70.8% to 79.9%) with bolus 5-FU/LV and PVI 5-FU, respectively (HR 0.79; 95% CI 0.61-1.03; P=0.083). There was a significant survival advantage for patients starting adjuvant chemotherapy within 8 weeks (P=0.044). Significantly less diarrhoea, stomatitis, nausea and vomiting, alopecia, lethargy, and neutropenia (all with P <0.0001) were seen with PVI 5-FU. CONCLUSIONS: There was no OS difference between the two arms, although PVI 5-FU was associated with a trend towards better RFS and OS compared with bolus 5-FU/LV, as well as significantly less toxicity. Based on our results, the probability of 12 weeks of PVI 5-FU being inferior to 6 months of bolus 5-FU/LV is extremely low (P <0.005), and therefore shorter duration of adjuvant treatment should be explored further.

Adult↗
PubMed2005

Accessibility and availability of abortion in six European countries.

OBJECTIVES: The accessibility and availability of abortion are a reflection of abortion law and the accessibility and availability of abortion services. Experiences from six European countries with different political, cultural, social and religious backgrounds (the Netherlands, France, Great Britain, Slovenia, Hungary and Turkey) are presented. RESULTS: Abortion laws in Europe range from complete prohibition to complete liberalization of abortion. Some countries demand a waiting period for the procedure, pre-abortion counseling, parental approval for minors, and in the others there are no mandatory requirements. Abortions are generally performed in authorized facilities by gynecologists or general practitioners. Abortion services are easily accessible, in terms of the law, availability of facilities and health insurance coverage of the procedure in the Netherlands, France and Slovenia. Abortion service is less accessible in United Kingdom, Hungary and Turkey, as a result of limited accessibility to abortion services or a relatively high abortion fee. In some Eastern European countries there has been a tendency in the last decade to limit the availability and access to abortion. CONCLUSIONS: In Europe abortion is generally well accessible in terms of abortion laws. There are differences in accessibility to abortion services between the countries, and in some countries, also between different areas of the country.

Abortion, Induced↗
PubMed2004

The Voice Symptom Scale (VoiSS) and the Vocal Handicap Index (VHI): a comparison of structure and content.

Self report measures of voice function are in frequent use, but have had inadequate psychometric evaluation. We aimed to perform a substantial factor analysis of two measures of voice impairment, the Voice Symptom Scale (VoiSS) and the Voice Handicap Index (VHI). Both the 30-item questionnaires were completed by 319 dysphonic voice clinic attenders (99M, 220F). Principal components analysis confirmed that both instruments reflected general voice abnormality. The VoiSS comprised three factors - impairment (15 items), emotional (8 items) and related physical symptoms (7 items) - each with a good internal consistency. Analysis of the VHI suggested that it contains only two subscales. When a three-factor solution was imposed on the data, analysis failed to support the currently advised three 10-item subscale interpretations. Instead, we found a physical (voice impairment) domain (8 items), a psychosocial domain (14 items) and a factor with 8 items related to difficulty in being heard. The VHI requires further statistical refinement to identify its subscale structure. The VoiSS was developed from 800 subjects and is psychometrically the most robust and extensively validated self report voice measure available.

Adult↗
PubMed2004

The reliability and sensitivity to change of acoustic measures of voice quality.

This study aimed to evaluate the reliability and sensitivity to change of three commonly used acoustic parameters as measured by the Multi-Dimensional Voice Programme (MDVP); jitter, shimmer and noise-to-harmonic ratio. A total of 231 subjects' voices were recorded and analysed. The sample comprised 145 dysphonic patients who received intervention (surgery or voice therapy), 36 dysphonic patients who received no intervention, and 50 non-dysphonic (normal) subjects. All voices were recorded and analysed on two occasions (before and after treatment, or test-retest assessment) using a standard procedure. These data were analysed using standard psychometric procedures for assessing reliability and responsiveness. The acoustic analysis measures demonstrated poor to moderate reliability and effect size with respect to their sensitivity to change. Caution should be exercised in the injudicious use of computer-based acoustic analysis systems as an isolated measure of voice outcome in any clinical trial of interventions aimed at improving voice quality.

Adolescent↗
PubMed2003

Is surgery necessary after complete clinical remission following neoadjuvant chemotherapy for early breast cancer?

PURPOSE: This retrospective analysis aimed to identify whether breast cancer patients receiving radiotherapy alone following a complete clinical remission (cCR) to neoadjuvant chemotherapy had a worse outcome than those treated with surgery. PATIENTS AND METHODS: One hundred thirty-six patients who had achieved a cCR to neoadjuvant chemotherapy for early breast cancer were identified from a prospectively maintained database of 453 patients. Of these, 67 patients had undergone surgery as their primary locoregional therapy, and 69 patients had radiotherapy alone. Outcome was assessed in relation to local recurrence-free survival, disease-free survival, and overall survival. RESULTS: Median follow-up was 63 months in the surgery group and 87 months in the no surgery group. Prognostic characteristics were well balanced between the two groups. For surgery and no surgery, respectively, there were no significant differences in disease-free survival or overall survival (5-year, 74% v 76%; 10-year, 60% v 70%, P =.9) between the two groups. There was a nonsignificant trend toward increased locoregional-only recurrence for the no surgery group (21% v 10% at 5 years; P =.09), but no long-term failures of local control. Patients in the no surgery group who also achieved an ultrasound complete remission had a 5-year local recurrence rate of only 8%. CONCLUSION: In patients achieving a cCR to neoadjuvant chemotherapy, radiotherapy alone achieve survival rates as good as with surgery, but with higher local recurrence rates. Ultrasound may identify a low recurrence rate subgroup for assessing no surgery in a prospective trial.

Adult↗
PubMed2003

Cytokines in the seronegative spondyloarthropathies and their modification by TNF blockade: a brief report and literature review.

Rheumatoid arthritis (RA) is a disease well characterised by proinflammatory cytokine secretion (particularly tumour necrosis factor, interferon gamma, interleukin (IL) 1, and IL6). Less has been reported about the cytokine profiling in the spondyloarthropathies (SpA). Several trials suggest that, similar to RA, proinflammatory cytokines are globally expressed in the SpA. However, other studies report a down regulation of these cytokines in the SpA, with a relative anti-inflammatory polarisation (featuring increases in IL4, IL5, and IL10). This review summarises current published reports and the variation in cytokine data in the SpA. Additionally, results of cytokine profiles in patients with ankylosing spondylitis before and after treatment with etanercept are reported.

Antirheumatic Agents↗
PubMed2002

A phase I dose-finding study of a combination of pegylated liposomal doxorubicin (Doxil), carboplatin and paclitaxel in ovarian cancer.

Standard chemotherapy for advanced epithelial ovarian cancer is a combination of platinum-paclitaxel. One strategy to improve the outcome for patients is to add other agents to standard therapy. Doxil is active in relapsed disease and has a response rate of 25% in platinum-resistant relapsed disease. A dose finding study of doxil-carboplatin-paclitaxel was therefore undertaken in women receiving first-line therapy. Thirty-one women with epithelial ovarian cancer or mixed Mullerian tumours of the ovary were enrolled. The doses of carboplatin, paclitaxel and doxil were as follows: carboplatin AUC 5 and 6; paclitaxel, 135 and 175 mg m(-2); doxil 20, 30, 40 and 50 mg m(-2). Schedules examined included treatment cycles of 21 and 28 days, and an alternating schedule of carboplatin-paclitaxel (q 21) with doxil being administered every other course (q 42). The dose-limiting toxicities were found to be neutropenia, stomatitis and palmar plantar syndrome and the maximum tolerated dose was defined as; carboplatin AUC 5, paclitaxel 175 mg m(-2) and doxil 30 mg m(-2) q 21. Reducing the paclitaxel dose to 135 mg m(-2) did not allow the doxil dose to be increased. Delivering doxil on alternate cycles at doses of 40 and 50 mg m(-2) also resulted in dose-limiting toxicities. The recommended doses for phase II/III trials are carboplatin AUC 6, paclitaxel 175 mg m(-2), doxil 30 mg m(-2) q 28 or carboplatin AUC 5, paclitaxel 175 mg m(-2), doxil 20 mg m(-2) q 21. Grade 3/4 haematologic toxicity was common at the recommended phase II doses but was short lived and not clinically important and non-haematologic toxicities were generally mild and consisted of nausea, paraesthesiae, stomatitis and palmar plantar syndrome.

Adult↗
PubMed2002

An open-label trial of combination therapy with interferon beta-1a and oral methotrexate in MS.

An open-label study was performed to evaluate the safety and efficacy of combination therapy with weekly oral methotrexate (20 mg) and interferon beta-1a (IFN beta-1a) in 15 patients with MS who had experienced exacerbations while receiving IFN beta monotherapy. Nausea was the only major side effect. A 44% reduction in the number of gadolinium-enhanced lesions seen on MRI scan was observed during combination therapy (p = 0.02). There was a trend toward fewer exacerbations. This combination therapy appears to be safe and well tolerated, and should be studied in a controlled trial.

Adolescent↗
PubMed2002

Gastro-omental free flaps in oral and oropharyngeal reconstruction:surgical anatomy, complications, outcomes.

Free gastro-omental flaps can be used to reconstruct defects in the oral cavity after ablative cancer surgery. The omentum can provide as much bulk as required. The generous gastro-omental pedicle allows mobility. The gastric mucosal lining has the advantage that it produces mucus, does not carry hair follicles and is not prone to troublesome desquamation. This paper reviews the surgical anatomy of free gastro-omental flaps and presents a series of eight cases in which these flaps were used for oral and oropharyngeal reconstruction.

Abdominal Abscess↗
PubMed2002

Outreach health adviser in a community clinic screening programme improves management of genital chlamydia infection.

OBJECTIVE: To assess the effectiveness of an outreach health adviser on treatment, partner notification and outcome for clients diagnosed with genital chlamydia (CT) infection at a community young people's clinic. METHODS: From August 1999 to March 2000, a genitourinary medicine (GUM) based health adviser helped to develop testing and undertook outreach management of clients aged under 26 years diagnosed with CT infection. In addition to facilitating referral to GUM, she gave antibiotic treatment based on a GUM derived patient group direction to those not wishing to travel to the GUM clinic. She also advised them on contact tracing and the need for a compliance check (CC). RESULTS: Chlamydia positive tests with ligase chain reaction (LCR), on first void urine, were obtained for 62 (12.9%) of 481 female clients, one (5%) of 20 male clients, and nine (53%) of 17 male contacts of female positive cases. All 72 testing positive received their result and were treated. Two urine samples positive for CT showed positive LCR tests for gonorrhoea. Proportions of named contacts seen (67%) and reattendances for compliance checks (60%) were similar to those for women seen in GUM services. CONCLUSIONS: Health adviser input with the ability to treat can be effective in reducing the growth of identified but untreated genital chlamydia infection consequent upon community based screening. Such a strategy appears comparable with, and can add to, GUM based treatment of infection. It helps to address the need for alternative management strategies in the light of the national sexual health strategy.

Adolescent↗
PubMed2002

Use of the Tesio catheter for hemodialysis in patients with end-stage renal failure: a 2-year prospective study.

BACKGROUND: The Tesio catheter system has been proposed to be a reliable source of vascular access for the dialysis patient with low rates of infection and other complications. Whether such catheters provide reliable short- and long-term access remains undetermined. METHODS: This study prospectively examined all Tesio lines inserted over a 2-year period in patients with end-stage failure with careful recording of all catheter complications and reasons for catheter loss. RESULTS: 100 catheters were inserted in 82 patients giving a total experience of 13,749 catheter days; 74 catheters were inserted into the jugular veins, the remainder into the femoral veins; 82 insertions were covered with antibiotics. At the end of the study, 29 catheters remained in situ. Of the remaining 71 catheters, 27 catheters were removed because of fashioning of definitive access. Nine catheters were lost due to infection and 10 were lost due to non-function; 19 patients died with a functioning catheter. Episodes ofnon-function were the major complications, although catheter patency was restored in 90% of cases utilizing urokinase and warfarin. Overall 80% of femoral and 16% of jugular catheters required anticoagulation. CONCLUSIONS: Tesio catheters inserted into the jugular or femoral veins can provide excellent access whilst awaiting definitive dialysis access. They are well-tolerated with a low complication rate compared to standard temporary central venous catheters. Non-function remains a significant problem, especially in femoral catheters, which should be anticoagulated following insertion. Because of our results we suggest that these catheters be used as part of the co-ordinated approach to the management of vascular access in end-stage renal failure patients without definitive access.

Adolescent↗
PubMed2002

What do women want? Counselling in contraception.

As Snowden (1) said nearly 20 years ago, 'The methods of fertility regulation from which most couples choose represent a choice among unpleasant alternatives. The choice is not so much a positive discrimination but a negative one, in that the methods not chosen are even more disliked than the method that is chosen. The contraceptive methods most people use are therefore the least unpleasant of the unpleasant set of alternatives. However, it is most important that this realistic summary is set against the other reality that consumers greatly prefer the available range of methods to no methods at all.' The choice of methods has now expanded but the decision process has not. Women want what everyone wants. They want their agenda to be addressed in a sensitive, considerate, complete and timely manner. They want to be given all relevant information in a way that they can understand by a person they like and who they can trust to advise them fully, correctly, confidentially and safely. They are quite happy to answer questions as long as they believe that they are necessary. They want the clinician to treat them with respect and to take into account their cultural and personal needs. The clinician must be able to advise them not only on contraceptive issues but also on all areas of sexual health. In short, just like all of us, women want to be treated as equals and trusted with information to enable them to make decisions about their life. Services can always improve and listening to our clients can help us aim for the sky. Let me share with you what they have to say.

Adolescent↗