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Biomedical subjects

L Jones

Publications and source records attributed to L Jones.

At least 127 records · Page 7Linked to original sources
PubMed1999

Adjuvant therapy for pancreatic cancer.

Pancreatic cancer is a major cause of cancer death; and despite advances in the standards of surgery and supportive care, the median and long-term survival rates have not shown similar dramatic improvements. Techniques such as radical surgery alone cannot guarantee a cure. Previous work with conventional chemotherapy and radiotherapy in patients with advanced pancreatic cancer has indicated a role for adjuvant therapy for patients with resectable tumors. The main modalities that have been assessed are based on the Gastrointestinal Tumour Study Group (GITSG) results using 5-fluorouracil chemotherapy, external beam radiation therapy (EBRT), or both. Alternative approaches such as neoadjuvant therapy have been used, which may increase the number of patients suitable for resection; and regional therapy techniques have been used to increase the therapeutic potential by concentrating agents to the tumor bed. The results of single or combination therapy do show some improvement in survival but have been limited in most cases to retrospective nonrandomized series of patients. Therefore the results must be assessed as such. There are several large randomized trials that will deliver definitive answers in the near future as to whether conventional adjuvant therapy is effective. New approaches using novel agents for advanced disease are currently being assessed, and they may eventually identify the most appropriate and effective agents to use for pancreatic cancer in the adjuvant setting.

Antimetabolites, Antineoplastic↗
PubMed1999

Splenic rupture in a patient with acute myeloid leukemia undergoing peripheral blood stem cell transplantation.

Splenic rupture is a rare but well-recognized complication of hematological malignancies. Here, we present the case of a 22-year-old woman with the diagnosis of acute myeloid leukemia who was undergoing peripheral blood stem cell transplantation. On day + 10 she developed a hypovolemic shock due to rupture of her spleen and went to emergency laparotomy. This is the first report of splenic rupture during peripheral blood stem cell transplantation.

Adult↗
PubMed1999

Angiogenesis and the atherosclerotic carotid plaque: an association between symptomatology and plaque morphology.

PURPOSE: Symptomatic carotid disease resulting from generation of thromboemboli has been associated with plaque instability and intraplaque hemorrhage. These features of the lesion could be influenced by the fragility and position of neovessels within the plaque. The purpose of this study was to determine whether any association exists between neovessel density, position, morphology, and thromboembolic sequelae. METHODS: Carotid endarterectomy samples were collected from 15 asymptomatic patients with greater than 80% stenoses and from 13 highly symptomatic patients who had suffered ipsilateral carotid stenotic events within 1 month of surgery. Both groups were matched for gender, age, risk factors, degree of carotid artery stenosis, and plaque size. Samples were stained with hematoxylin/eosin and van Geison. Immunohistochemistry was performed by using an endothelial specific antibody to CD31. Plaques were assessed for histologic characteristics, and neovessels were counted and characterized by size, site, and shape. RESULTS: There were significantly more neovessels in plaques (P <.00001) and fibrous caps (P <.0001) in symptomatic compared with asymptomatic plaques. Neovessels in symptomatic plaques were larger (P <.004) and more irregular. There was a significant increase in plaque necrosis and rupture in symptomatic plaques. Plaque hemorrhage and rupture were associated with more neovessels within the plaque (P <.017, P <.001) and within the fibrous cap (P <.046, P <.004). Patients with preoperative and intraoperative embolization had significantly more plaque and fibrous cap neovessels (P <.025, P <.001). CONCLUSION: Symptomatic carotid disease is associated with increased neovascularization within the atherosclerotic plaque and fibrous cap. These vessels are larger and more irregular and may contribute to plaque instability and the onset of thromboembolic sequelae.

Arteriosclerosis↗
PubMed1999

Use of reverse geometry rigid gas permeable contact lenses in the management of the postradial keratotomy patient: review and case report.

Radial keratotomy (RK) is a well-known procedure for reducing myopia. However, the complications associated with the procedure and the development of newer technologies, such as photorefractive keratectomy and laser-assisted in situ keratomileusis, has resulted in the technique of RK falling out of favor. A number of patients who received RK during the 1980s are now experiencing a shift in their prescription and are presenting to primary care practitioners for contact lens fitting. These patients pose a significant challenge to the contact lens practitioner, and novel methods frequently are required to fit corneas that exhibit such abnormal topography. This article reviews the potential problems associated with fitting patients who have received RK and describes a case in which a novel lens design was used to achieve a successful lens fit.

Journal Article↗
PubMed1999

Dietary questions as determinants of mortality: the OXCHECK experience.

OBJECTIVE: To determine whether responses to simple dietary questions are associated with specific causes of death. DESIGN: Self-reported frequency intakes of various classes of foods and data on confounding factors were collected at the baseline survey. Death notifications up to 31 December 1997 were ascertained from the Office for National Statistics. Relative risk (RR) of death and 95% confidence intervals (CI) associated with baseline dietary factors were calculated by Cox regression. SETTING: Prospective follow-up study based on five UK general practices. SUBJECTS: Data were used from 11,090 men and women aged 35-64 years (81% of the eligible patient population) who responded to a postal questionnaire in 1989. RESULTS: After 9 years of follow-up, 598 deaths were recorded, 514 of these among the 10,522 subjects with no previous history of angina. All-cause mortality was positively associated with age, smoking and low social class, as expected. Among the dietary variables, all-cause mortality was significantly reduced in participants who reported relatively high consumption of vegetables, puddings, cakes, biscuits and sweets, fresh or frozen red meat (but not processed meat), among those who reported using polyunsaturated spreads and among moderate alcohol drinkers. These associations were broadly similar for deaths from ischaemic heart disease (IHD), cancer and all other causes combined, and were not greatly attenuated by adjusting for potential confounding factors including social class. CONCLUSIONS: Responses to simple questions about nutrition were associated with mortality. These findings must be interpreted with caution since residual confounding by dietary and lifestyle factors may underlie the associations.

Adult↗
PubMed1999

Vascular surgical society of great britain and ireland: angiogenesis and the atherosclerotic carotid plaque: association between symptomatology and plaque morphology

BACKGROUND: Symptomatic carotid disease due to thromboembolism has been associated with acute plaque instability and intraplaque haemorrhage. These features may be influenced by the fragility and position of plaque neovessels. The purpose of this study was, therefore, to determine whether any association existed between neovessel density, position, morphology and thromboembolic sequelae. METHODS: Carotid endarterectomy (CEA) samples were collected from 15 asymptomatic patients with greater than 80 per cent stenosis and from 13 patients with greater than 80 per cent stenosis and symptoms within 30 days of CEA. Groups were matched for sex, age, risk factors and plaque size. Samples were stained with haematoxylin and eosin, and Van Gieson stains. An endothelial-specific antibody to CD31 was used for immunohistochemistry. Plaques were assessed for histological characteristics while neovessels were counted and characterized by size, site and shape. RESULTS: There were more neovessels in plaques (P < 0.00001) and fibrous caps (P < 0.0001) from symptomatic than asymptomatic patients. Symptomatic plaque neovessels were larger in size (P < 0.004) and more irregular in shape. There was a significant increase in plaque necrosis and rupture in symptomatic plaques. Plaque haemorrhage and rupture were associated with more neovessels within the plaque (P < 0.02, P < 0. 001) and fibrous cap (P < 0.05, P < 0.004). Patients with preoperative or intraoperative embolization had more plaque and fibrous cap neovessels (P < 0.03, P < 0.001). CONCLUSION: Symptomatic carotid disease is associated with increased neovascularization within the atherosclerotic plaque and fibrous cap; these vessels appear larger in size, more irregular in shape and may contribute to plaque instability and onset of thromboembolic events.

Journal Article↗
PubMed1999

Production and inhibition of the gelatinolytic matrix metalloproteinases in a human model of vein graft stenosis.

OBJECTIVES: human vein graft stenoses are caused by intimal hyperplasia, a process which is characterised by extensive degradation and accumulation of extracellular matrix. This study investigated the role of the matrix metalloproteinases (MMPs) - the principal physiological mediators of extracellular matrix degradation - in the development of intimal hyperplasia in cultured human long saphenous vein. DESIGN: experimental study. MATERIALS AND METHODS: paired venous segments with the endothelium intact or denuded were cultured in standard conditions for 14 days. At the termination of culture, MMPs were extracted from one half of the tissue, whilst the remainder of the vein was prepared for histological examination. RESULTS: stereologic analysis revealed that the endothelium intact veins developed a significantly thicker neointima when compared to the denuded venous segments (20 micron v. 0 micron, p=0.006). Quantification of MMPs by substrate gel enzymography demonstrated that the development of a neointima was associated with increased production of the gelatinolytic MMP-9 (p=0. 03) in intact veins. Immunocytochemistry showed that the MMP-9 localised to the internal elastic lumina, which suggested a role in facilitating smooth-muscle-cell migration into the intima. The role of MMPs-2 and -9 in intimal hyperplasia was further investigated by culturing intact venous segments with a therapeutic concentration of doxycycline--a potent MMP inhibitor. These experiments demonstrated that a therapeutic dose of doxycycline significantly reduced neointimal thickness (control 21 micron, doxycycline 10 mg/l-5.5 micron), in conjunction with a significant reduction in the production of MMP-9. CONCLUSIONS: these data suggest that elevated levels of MMPs may play a significant role in the development of human intimal hyperplasia and that inhibition of these enzymes may offer a potential therapeutic strategy for the prevention of hyperplastic lesions.

Anti-Bacterial Agents↗
PubMed1999

Accounting for treatment delays when treating highly proliferative tumours.

This study was undertaken to investigate the possibility of increasing the dose per fraction or increasing the number of fractions to account for treatment delays occurring during radiotherapy treatments for highly proliferative tumours. The linear quadratic model with time was used to determine the difference in biological effective dose (BED) for the original schedule and the schedule including a treatment delay. Tables of extra fractions and extra dose per fraction required to account for a number of possible delays have been determined. It has been shown that for tumours with very short potential doubling times it is best to deliver the extra dose as an increase in dose per fraction rather than an increase in the number of fractions, while for tumours with moderately short potential doubling times (above 7 days) the reverse is true. The equivalent uninterrupted schedules, which would have delivered the same effects to the tumour, have also been determined.

Cell Division↗
PubMed1999

Family history taking and genetic counselling in primary care.

OBJECTIVES: We aimed to evaluate the feasibility and acceptability of taking routine family histories and subsequent counselling. METHODS: The study was set in primary care in the UK. The subjects were patients between the ages of 20 and 34 years registered at one general practice. Patients were invited by letter to attend a clinic in their GP surgery, run by a GP and health visitor. A family history was constructed and counselling undertaken for any identified problems. A telephone survey of a sample of nonattenders was also performed. The outcome measures were attendance rate, patient views, patient anxiety as measured by the short form of the Spielberger State-Trait Anxiety Inventory and referrals to secondary care. RESULTS: In total, 16.1% patients attended the clinic; 40.3 % had a family history of at least one disease with a possible genetic component. Anxiety levels fell immediately after the consultation and rose to pre-clinic levels at 12 weeks. The clinic generated three referrals to secondary care and a further seven patients who were counselled by the investigators following advice from a consultant geneticist. CONCLUSIONS: It is possible to take detailed family histories and provide genetic counselling advice in primary care with minimal training of clinical primary care staff. The service is acceptable to patients, does not induce anxiety and has little effect on numbers of patients referred.

Adult↗
PubMed1999

Hormone replacement therapy: patterns of use studied through British general practice computerized records.

OBJECTIVE: We aimed to describe the longitudinal pattern of hormone replacement therapy (HRT) consumption in a cohort of long-term users (defined as use for >1 year). METHOD: We carried out longitudinal analysis of prescription data derived from GPs' computer records. Subjects were recruited through 15 general practices in the former Oxford, South West and North West Thames Regions that contributed to the VAMP/OPCS general practice research database. All women in the practices aged 45-64 years in September 1991 were identified. Of these, the analysis concerned the 1224 long-term users and 1154 non-user controls who remained in the practices from September 1991 to March 1995; 868 (71%) of the users and 698 (61%) of the controls also provided questionnaire data. RESULTS: The prevalence of HRT use was 15% in 1992, a rise of 16% from 1991. The prevalence of long-term use was 10%; 22% of the cohort identified as taking HRT between April and September 1991 had left the practices or were not taking HRT 1 year later. But for the group defined as long-term users in 1992, the rate of discontinuation was less than 5% per year over the following 2 1/2 years. Users of opposed therapy were 50% more likely to discontinue than users of unopposed therapy. Almost all women who had or had not undergone hysterectomy were taking unopposed or opposed therapy, respectively. Over 80% of prescriptions were for oral therapy. A third of users of either opposed or unopposed therapy changed the formulation during the 4 years of observation, and two-thirds of those who used both forms changed at least once in addition. Two changes were required to accommodate 94% of users. CONCLUSIONS: Once women have taken HRT for a year, their continuation rate is over 95% per annum. Although the majority of women stayed with one formulation, a substantial minority changed formulation quite frequently, three formulations being required to accommodate 94% of long-term users over 4 years. Any trial of HRT use will need to recruit long-term users and allow for change in formulation of HRT in its protocol.

Aged↗
PubMed1999

RNA-DNA interactions and DNA methylation in post-transcriptional gene silencing.

Post-transcriptional gene silencing (PTGS) is a homology-dependent process that reduces cytoplasmic RNA levels. In several experimental systems, there is also an association of PTGS with methylation of DNA. To investigate this association, we used plants carrying a transgene encoding the green fluorescent protein (GFP). Gene silencing was induced using potato virus X RNA vectors carrying parts of the coding sequence or the promoter of the GFP transgene. In each instance, homology-based, RNA-directed methylation was associated with silencing. When the GFP-transcribed region was targeted, PTGS affected both transgene and viral RNA levels. When methylation was targeted to a promoter region, transgene RNA levels were reduced; however, viral RNA levels were unaffected. For comparison, we induced PTGS of the gene encoding the endogenous ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco) small subunit (rbcS) by inoculation with potato virus X-rbcS. In this example, no methylation of the rbcS DNA was associated with the reduction in rbcS transcript levels, and viral RNA levels were unaffected. Finally, we investigated DNA methylation by using GFP-transformed plants in which PTGS was induced by localized introduction of a T-DNA carrying GFP sequences. In these plants, there was methylation of a GFP transgene associated with systemic spread of a gene-silencing signal from the infiltrated part of the plant. This transgene methylation was not affected when systemic PTGS was blocked by suppressors of silencing encoded by potato virus Y and cucumber mosaic virus. Combined, these data support an epigenetic model of PTGS in which transgene methylation is associated with an RNA-DNA interaction that ensures that PTGS is maintained.

DNA Methylation↗
PubMed1999

Respiratory syncytial virus G and/or SH protein alters Th1 cytokines, natural killer cells, and neutrophils responding to pulmonary infection in BALB/c mice.

BALB/c mice sensitized to vaccinia virus expressed G protein of respiratory syncytial virus (RSV) develop a Th2-type cytokine response and pulmonary eosinophilia when challenged with live RSV. In this study, BALB/c mice were immunized or challenged with an RSV mutant lacking the G and SH proteins or with DNA vaccines coding for RSV G or F protein. F or G protein DNA vaccines were capable of sensitizing for pulmonary eosinophilia. The absence of the G and/or SH protein in the infecting virus resulted in a consistent increase both in pulmonary natural killer cells and in gamma interferon and tumor necrosis factor expression, as well as, with primary infection, a variable increase in neutrophils and CD11b(+) cells. The development of pulmonary eosinophilia in formalin-inactivated RSV-vaccinated mice required the presence of the G and/or SH protein in the challenge virus. These data show that G and/or SH protein has a marked impact on the inflammatory and innate immune response to RSV infection.

Animals↗
PubMed1999

Standard Kausch-Whipple pancreatoduodenectomy.

Despite the increasing number of clinical trials in pancreatic cancer there are no widely accepted definitions of different types of resection for pancreatic cancer. An agreed definition of the standard Kausch-Whipple pancreatoduodenectomy was derived by a group of international experts at a meeting in Castelfranco Veneto, Italy, in May 1998. The lymph node groups to be removed en bloc with the pancreatoduodenectomy and described using the Japanese Pancreas Society classification were as follows: 13a and 13b; 17a and 17b; 12b1, 12b2 and 12c; and 14a and 14b. Limited segmental major venous resection and adjacent organ resection, if required, may be included as part of a standard pancreatoduodenectomy. The pylorus-preserving procedure also may be included as part of standard resection, but not for tumours of the anterior-superior part of the head of the pancreas. Wider adoption of the definition of standard Kausch-Whipple resection will enable a more objective comparative analysis of the radicality of resection between institutions and permit a more coherant analysis on the type of surgery undertaken in multicentre adjuvant studies.

Combined Modality Therapy↗
PubMed1999

[Gender differences and diabetic status in the relationship of blood apolipoprotein C-III, free fatty acids and triglycerides in subjects at risk for glucose intolerance].

Insulin resistance and hyperinsulinemia can induce overproduction of triglyceride (TG) rich VLDL in the liver by increasing the availability of free fatty acids (FFA). Conversely, apolipoprotein C-III (apoC-III) is an inhibitor of the catabolism of TG-rich lipoproteins. To explore the relationship among FFA, apo C-III and TG in hyperinsulinemic subjects, we studied 103 individuals (63 women and 40 men) with a body mass index (BMI) 25 Kg/m2: 59 subjects with normal glucose tolerance (NGT), and 44 with newly diagnosed type 2 diabetes. After adjustment for age, BMI, fasting insulin and TG, FFA were significantly higher in women than in men and in subjects with diabetes compared with NGT. Subjects with diabetes had higher apo C-III levels compared to NGT, adjusted for age, sex and BMI, and that was largely accounted for by differences in insulin and TG levels. In addition, regression analysis in subjects with diabetes showed that TG were strongly associated with apo C-III in both men and women (r = 0.90 and 0.79, respectively; p < 0.001), while the association tended to be smaller between TG and FFA (r = 0.48, p < 0.05 in men and r = 0.45, p = 0.06 in women). Conversely, in individuals with NGT fasting TG was strongly associated with apo C-III in men (r = 0.83, p < 0.01) but not with FFA, while in women TG was associated with FFA (r = 0.39, p < 0.05) but not with apo C-III. In summary, elevated apo C-III was a predominant factor associated with elevated TG levels in NGT men and all subjects with type 2 diabetes, while FFA were more closely related with TG levels in NGT women.

Adult↗
PubMed1999

Strand displacement amplification and homogeneous real-time detection incorporated in a second-generation DNA probe system, BDProbeTecET.

BACKGROUND: Amplified DNA probes provide powerful tools for the detection of infectious diseases, cancer, and genetic diseases. Commercially available amplification systems suffer from low throughput and require decontamination schemes, significant hands-on time, and specially trained laboratory staff. Our objective was to develop a DNA probe system to overcome these limitations. METHODS: We developed a DNA probe system, the BDProbeTecTMET, based on simultaneous strand displacement amplification and real-time fluorescence detection. The system uses sealed microwells to minimize the release of amplicons to the environment. To avoid the need for specially trained labor, the system uses a simple workflow with predispensed reagent devices; a programmable, expandable-spacing pipettor; and the 96-microwell format. Amplification and detection time was 1 h, with potential throughput up to 564 patient results per shift. We tested 122 total patient specimens obtained from a family practice clinic with the BD ProbeTecET and the Abbott LCx(R) amplified system for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. RESULTS: Based on reportable results, the BDProbeTecET results for both organisms were 100% sensitive and 100% specific relative to the LCx. CONCLUSIONS: The BDProbeTecET is an easy-to-use, high-throughput, closed amplification system for the detection of nucleic acid from C. trachomatis and N. gonorrhoeae and other organisms.

Chlamydia trachomatis↗
PubMed1999

The future of surgery for pancreatic cancer.

Carcinoma of the pancreas has a grim prognosis even following surgical resection. Only a relatively small proportion of patients have a resectable tumour at presentation. At the present time it is uncertain whether the use of radical forms of surgery, or adjuvant therapy improve survival. It is however unlikely that either of these approaches will greatly increase the number of long term survivors. Earlier diagnosis particularly in individuals who are at greater risk of developing carcinoma of the pancreas is one way in which results might be improved. Unfortunately current imaging techniques are inadequate for the diagnosis of early disease. New molecular diagnostics techniques that can identify example mutations in oncogenes such as K-ras or deletions of tumour suppressor genes such as P53 or P16 are being developed. These tumour specific abnormalities are also a target for gene therapy. Surgery alone cannot cure any patient with pancreatic cancer but may in the future in conjunction with these new approaches.

Genetic Therapy↗