PubMed Health⌕ Search

Biomedical subjects

M E Hill

Publications and source records attributed to M E Hill.

At least 19 recordsLinked to original sources
PubMed2004

Phase II study of irinotecan and 5-fluorouracil/leucovorin in patients with primary refractory or relapsed advanced oesophageal and gastric carcinoma.

BACKGROUND: The purpose of this study was to assess the efficacy and toxicity of irinotecan and 5-fluorouracil (5-FU) in primary refractory or relapsed locally advanced or metastatic oesophagogastric (O-G) carcinoma. PATIENTS AND METHODS: Patients with documented progression on or within 3 months of chemotherapy were recruited between July 2000 and May 2002. Irinotecan (180 mg/m(2)) was given with 5-FU (400 mg/m(2) bolus) and leucovorin (folinic acid) (125 mg/m(2)) followed by 5-FU (1200 mg/m(2) infusion over 48 h) every 2 weeks. Response confirmed by computed tomography was assessed at 12 and 24 weeks. RESULTS: Thirty-eight of 40 registered patients (95%) were assessable. Median follow-up was 9.3 months and median age was 59.0 years. Thirty-three patients (86.8%) had metastatic disease and 37 patients (97.4%) had previously received platinum-based chemotherapy. Overall response rate was 29% (95% confidence interval 15.4% to 45.9%) while an additional 34% had stable disease. Improvement in tumour-related symptoms included dysphagia 78.6%, reflux 60.0%, pain 54.5%, anorexia 64.3% and weight loss 72.7%. Grade 3/4 toxicities were anaemia 13.2%, neutropenia 26.4%, febrile neutropenia 5.2%, stomatitis 2.6%, nausea and vomiting 13.2% and diarrhoea 7.9%. Median failure-free survival was 3.7 months and median overall survival was 6.4 months. CONCLUSION: 5-FU/irinotecan is a valuable regimen for second-line treatment in 5-FU/platinum-resistant O-G carcinoma.

Adenocarcinoma↗
PubMed2003

Voyager 1 exited the solar wind at a distance of approximately 85 Au from the Sun.

The outer limit of the Solar System is often considered to be at the distance from the Sun where the solar wind changes from supersonic to subsonic flow. Theory predicts that a termination shock marks this boundary, with locations ranging from a few to over 100 au (1 Au approximately 1.5 x 10(8) km, the distance from Earth to the Sun). 'Pick-up ions' that originate as interstellar neutral atoms should be accelerated to tens of MeV at the termination shock, generating anomalous cosmic rays. Here we report a large increase in the intensity of energetic particles in the outer heliosphere, as measured by an instrument on the Voyager 1 spacecraft. We argue that the spacecraft exited the supersonic solar wind and passed into the subsonic region (possibly beyond the termination shock) on about 1 August 2002 at a distance of approximately 85 Au (heliolatitude approximately 34 degrees N), then re-entered the supersonic solar wind about 200 days later at approximately 87 au from the Sun. We show that the composition of the ions accelerated at the putative termination shock is that of anomalous cosmic rays and of interstellar pick-up ions.

Journal Article↗
PubMed2003

A randomised study of protracted venous infusion of 5-fluorouracil (5-FU) with or without bolus mitomycin C (MMC) in patients with carcinoma of unknown primary.

No standard regimen has been identified for patients with a carcinoma of unknown primary (CUP). This study compared protracted venous infusion 5-fluorouracil (PVI 5-FU) with or without mitomycin C (MMC) in patients with CUP in a multicentre, prospectively randomised study. 88 patients were randomised to PVI 5-FU (300 mg/m(2)/day for a maximum of 24 weeks) +/-MMC (7 mg/m(2) 6 weekly for four courses). The overall response rate was 11.6% for PVI 5-FU alone compared with 20.0% for PVI 5-FU plus MMC (P=0.29). Median failure-free survival (FFS) was 4.1 months for PVI 5-FU and 3.6 months for PVI 5-FU plus MMC (P=0.78) with an equivalent overall survival (OS) (6.6 versus 4.7 months, P=0.60). Symptomatic benefit was observed in most patients in each arm. PVI 5-FU is a well tolerated outpatient treatment regimen for patients with CUP, although the addition of MMC provides little extra benefit. PVI 5-FU may be a potential reference regimen in randomised trials with newer chemotherapy agents in patients with CUP.

Adult↗
PubMed2003

A rare case of intravascular lymphoma diagnosed on bone marrow trephine.

Intravascular lymphoma (IVL) is an extremely rare form of extra-nodal non-Hodgkins lymphoma characterised by the proliferation of neoplastic lymphocytes within the lumina of small arteries, veins and capillaries. The great majority of reported cases appear to be of B cell lineage. There is a wide variation in clinical presentation, and multiple organs are usually affected. We report a case of a 67-year-old man who presented with constitutional symptoms and neurological deficit and was diagnosed following bone-marrow trephine. His disease responded to polychemotherapy treatment but he died 15 months after diagnosis. This case in unusual in that it is generally felt that bone marrow is relatively spared until late in the disease and is often not clearly demonstrable histologically. In addition, this case supports the limited data that responses can be obtained following polychemotherapy treatment, although the prognosis remains generally poor.

Aged↗
PubMed2003

Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases.

BACKGROUND: The role of palliative resection of the primary tumour in patients who present with metastatic colorectal cancer is unclear. AIMS: This study compared the incidence of major intestinal complications in such patients who received chemotherapy treatment with or without prior palliative resection of the primary tumour. PATIENTS: The incidence of intestinal obstruction, perforation, fistula formation, and gastrointestinal haemorrhage, and the requirement for abdominal radiotherapy in patients with metastatic colorectal cancer treated at a single institution over a 10 year period was determined. RESULTS: Eighty two patients received initial treatment with chemotherapy without resection of the primary tumour (unresected group) and 280 patients had undergone prior resection (resected group). In the unresected group, the incidence of peritonitis, fistula formation, and intestinal haemorrhage was 2.4% (95% confidence interval (CI) 0.3-8.5%), 3.7% (95% CI 0.8-10.3%), and 3.7% (95% CI 0.8-10.3%), respectively, and was not significantly different from the resected group. Intestinal obstruction affected 13.4% (95% CI 6.9-22.7%) of patients in the unresected group and 13.2% (95% CI 9.2-17.2%) of patients in the resected group. More patients in the unresected group required >/=3 blood transfusions (14.6% v 7.5%; p=0.048) and abdominal radiotherapy (18.3% v 9.6%; p=0.03) than the resected group. CONCLUSIONS: The incidence of major intestinal complications in patients with unresected colorectal cancer and synchronous metastases who receive initial treatment with chemotherapy is low. Chemotherapy may be successfully used as initial treatment for such patients with no increased risk of most major intestinal complications compared with patients who have undergone initial resection of the primary tumour.

Adult↗
PubMed2002

Magnitude of the inflammatory response to cardiopulmonary bypass and its relation to adverse clinical outcomes.

INTRODUCTION: Cardiopulmonary bypass (CPB) induces an inflammatory response believed to contribute to postoperative morbidity. We hypothesized that the magnitude of the inflammatory response following CPB would be associated with adverse clinical outcomes. METHODS: Twenty-nine patients had plasma TNF, IL-6, IL-8, elastase, histamine, complement C5a, and complement C3a measured by ELISA before, during, and after cardiac operations employing CPB. Inflammatory mediator levels were analyzed with respect to outcomes. RESULTS: Mediator levels peaked at 4 h post-CPB and either returned to baseline or substantially decreased by 24 h. Patients with peak mediator levels above the median for the group as a whole were classified as 'hyper-responders'; those with levels below the median were classified as 'normal responders'. While IL-8, C3a, and IL-6 levels were independently associated with adverse outcomes, TNF, histamine, and C5a levels were not. Elastase levels trended towards adverse outcomes. IL-8 'hyper-responders' experienced significantly greater postoperative weight gain and had higher IL-8 levels at 24 h (p<0.05), with trends towards renal impairment and protracted supplemental oxygen requirements. C3a 'hyper-responders' strongly trended towards increased bleeding, delayed extubation, greater postoperative weight gain, and decreased levels of independent functioning at discharge (p < or = 0.10). IL-6 'hyper-responders' experienced significantly more postoperative bleeding, delayed extubation, and higher IL-6 levels at 24 h compared to 'normal responders' (p < 0.05). They strongly trended towards greater postoperative weight gain and decreased levels of independent functioning at discharge (p < or = 0.10). CONCLUSIONS: Patients who have an exaggerated inflammatory response to CPB tend to bleed more, require more respiratory support, demonstrate greater capillary leak via weight gain, and display a decline in independent functioning relative to normal responders. Thus, it appears that the magnitude of the inflammatory response to CPB adversely influences clinical outcomes.

Aged↗
PubMed2002

Baseline quality of life predicts survival in patients with advanced colorectal cancer.

The aim of this study was to investigate the influence of baseline quality of life (QoL) on survival in patients with advanced colorectal cancer. From 1992 to 1998, four randomised clinical trials in advanced colorectal cancer were conducted at this institution. The European Organization for Research and Treatment of Cancer-Quality of Life Core 30 (EORTC-QLQ-C30) questionnaire was completed prior to the commencement of chemotherapy. Analyses were performed on median-dichotomised baseline Quality of Life (QoL) and clinical prognostic factors. Baseline QoL questionnaires were completed by 501 patients. One-year survival was 38.3 and 72.5% (P<0.0001) for patients with global QoL scores below and above the median (67), respectively. Other than cognitive functioning, fatigue, appetite, constipation, diarrhoea and financial domains, all QoL scales were significant independent predictors of survival (P<0.035). In the final model, the global QoL score remained highly significant as an independent predictor of survival (P<0.0001). Baseline QoL is a strong independent predictor of survival in patients with advanced colorectal cancer. Measurements should be routinely recorded in clinical trials to stratify cohorts and aid in trial comparison.

Adult↗
PubMed2002

A multicentre phase II trial of primary chemotherapy with cisplatin and protracted venous infusion 5-fluorouracil followed by chemoradiation in patients with carcinoma of the oesophagus.

BACKGROUND: We undertook a multicentre phase II trial to evaluate the safety and efficacy of primary chemotherapy followed by chemoradiation for localised adenocarcinoma or squamous carcinoma of the oesophagus. PATIENTS AND METHODS: Chemotherapy comprised five 3-weekly cycles of cisplatin and protracted continuous infusion 5-fluorouracil, with conformally planned radiotherapy commencing at the start of the fifth cycle. RESULTS: The planned treatment programme was completed by 39 of 72 patients (54%), and a further 13% completed chemotherapy and proceeded to surgical oesophagectomy. Response rates to chemotherapy and to the entire treatment programme were 47% [95% confidence interval (CI) 34% to 60%] and 56% (CI 43% to 68%). The dysphagia score improved in 54% of patients. The median survival duration was 14.6 months with 1- and 2-year survival rates of 58.7% and 44.1%, respectively. Grade III/IV chemotherapy-related toxicity occurred in 38% of patients, and there were no treatment-related deaths. CONCLUSIONS: This is a feasible and active treatment regimen providing palliative benefits for patients with poor-prognosis localised oesophageal cancer.

Adenocarcinoma↗
PubMed2001

High-gradient millimeter-wave accelerator on a planar dielectric substrate.

We report the first high-gradient studies of a millimeter-wave accelerator, employing for the first time a planar dielectric accelerator, powered by means of a 0.5-A, 300-MeV, 11.424-GHz drive electron beam, synchronous at the 8th harmonic, 91.392 GHz. Embedded in a ring-resonator circuit within the electron beam line vacuum, this structure was operated at 20 MeV/m, with a circulating power of 200 kW, for 2 x 10(5) pulses, with no sign of breakdown, dielectric charging, or other deleterious high-gradient phenomena. We also present the first measurement of the quadrupolar content of an accelerating mode.

Journal Article↗
PubMed2001

Elevated intestinal fatty acid binding protein and gastrointestinal complications following cardiopulmonary bypass: a preliminary analysis.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with poorly understood alterations in gastrointestinal (GI) perfusion. Intestinal fatty acid binding protein (IFABP), a cytosolic protein uniquely located in mature small-intestinal enterocytes, has been shown to be a sensitive biochemical marker of early intestinal ischemia when assayed in urine. We hypothesized that if significant small-intestinal ischemia occurs with CPB, then urine IFABP levels should be concomitantly elevated. METHODS: Twenty-nine patients (15 low risk and 14 high risk) undergoing cardiac surgery with CPB were studied prospectively. Serial urine IFABP levels were measured and results were correlated with clinical outcomes. RESULTS: None of the low-risk patients had IFABP elevations or experienced GI complications. Five of the high-risk patients had IFABP elevations, and three of the five developed GI complications. Within the high-risk cohort, the only significant difference between patients with or without IFABP elevations was the GI complication rate (P = 0.03). Overall, patients with IFABP elevations had a significantly higher mean ASA class and significant increases in mean CPB and aortic cross-clamp times, mean time to oral intake, median ICU and postoperative lengths of stay, and GI complications. CONCLUSIONS: In low-risk bypass patients, small-bowel mucosal perfusion appeared to be maintained, while in the high-risk population, 21% of the patients sustained clinically significant mucosal compromise. In this pilot study, urine IFABP was 100% sensitive and 92% specific with respect to GI complications. Since elevated urine IFABP concentrations appeared to correlate with clinical GI complications, urine IFABP may be a useful marker to identify the patient at risk for postbypass GI complications.

Aged↗
PubMed2001

Solitary pancreatic metastasis from a primary colonic tumor detected by PET scan: report of a case.

PURPOSE: A case of a solitary pancreatic metastasis from a primary colonic carcinoma is reported. METHODS: The history and use of carcinoembryonic antigen, computed tomography, and positron emission tomography in this case and the follow-up of colorectal cancer are reviewed. RESULTS: Recurrent disease was suspected by an increasing carcinoembryonic antigen level. However, conventional imaging with computed tomography on more than one occasion failed to identify any recurrence. The pancreatic metastasis was accurately localized by positron emission tomography scanning and confirmed on subsequent laparotomy. A histologically complete resection was performed and the patient remained in remission with a normal carcinoembryonic antigen 12 months postoperatively. CONCLUSION: This case reports an unusual site of solitary metastasis in colorectal cancer and supports the further investigation of positron emission tomography in follow-up of colorectal cancer.

Adenocarcinoma↗
PubMed2001

Toward a definition of HIV expertise: a survey of experienced HIV physicians.

Medical care for human immunodeficiency virus (HIV)-infected persons has grown increasingly complex, yet few studies have examined experienced HIV physicians' views about current HIV medical care. The objective of this study was to examine the relationship between physicians' HIV experience, self-perceived expertise, and confidence with providing 18 aspects of HIV medical care and between confidence in aspects of care and medical specialty. At geographically diverse, HIV continuing medical education programs conducted in the fall of 1999, 359 currently practicing HIV physicians completed a written survey measuring participants' demographic characteristics, experience, HIV expertise, and level of confidence providing essential aspects of HIV care. Participants currently managed a median of 50 HIV-infected patients with a career total of 300. Significant correlations were found between experience and expertise items and experience and 15 of 18 confidence items. Confidence levels varied from 11% to 85% highly confident across 18 aspects of HIV care. Physicians' confidence with providing aspects of HIV care varied by the three predominant specialty groups (infectious diseases, internal medicine, and family practice/general medicine). Physicians who have informally specialized in HIV care reported a range of self-perceived expertise and confidence, indicating the complexity of HIV medical care today. Our results suggest that even the most experienced HIV physicians in the United States continue to benefit from more experience and that each medical specialty examined in this study brings its own set of skills needed to provide optimal HIV care. This study constitutes a first step toward defining and formalizing HIV medical care.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Oculopharyngeal muscular dystrophy: phenotypic and genotypic studies in a UK population.

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disorder of late onset that commonly presents with ptosis and dysphagia. The genetic basis of the condition has been identified recently as a stable trinucleotide repeat expansion in exon 1 of the poly(A) binding protein 2 gene (PABP2), in which (GCG)(6) is the normal repeat length. The prevalence of OPMD is greatest in patients of French-Canadian origin. It is not clear if expansion repeat length is a reliable test in other populations. In this study, we analysed the phenotypic and genotypic characteristics of 31 patients with OPMD in the UK. Ptosis was the first reported symptom in two-thirds of the patients, and half of the subjects studied had evidence of ophthalmoplegia. All but one family had a pathological expansion in the PABP2 gene, ranging from (GCG)(8) to (GCG)(13). In contrast to the French-Canadian population, (GCG)(10) was almost as common as (GCG)(9), evidence against a strong founder effect in the UK population. There was a weak association between repeat length and age of disease onset. Patients with longer repeat lengths, such as (GCG)(13), developed severe limb weakness early in the disease. We were unable to detect the (GCG)(7) polymorphism in over 200 normal controls, suggesting that the frequency of this expansion is lower than that found in the French-Canadian population. One family was negative for the expansion. Affected members presented with the classical features of OPMD, namely ptosis, dysphagia and cytoplasmic inclusions on muscle biopsy, although with some atypical features, such as early age of onset, high serum levels of creatine kinase and a profound ophthalmoplegia. This family is an example of a GCG expansion-negative oculopharyngeal syndrome requiring further genetic investigation. We conclude that PABP2 analysis is a reliable non-invasive diagnostic test for OPMD in the UK population.

Adolescent↗
PubMed2001

Knowledgeable, consistent, competent care: meeting the challenges of delivering quality cancer care in remote northern communities.

The Northwestern Ontario Regional Cancer Centre (NWORCC) has created outreach services that provide chemotherapy and supportive care to clients in thirteen small, remote communities. Located 100-600 km from the NWORCC, these satellite oncology services are staffed by local physicians, specially prepared nurses and support staff. The present paper reports selected findings from an evaluation of the service, based on two rounds of site visits, interviews and surveys of providers and clients. Although the consensus was that quality care was being delivered, local hospitals and other organizations had to address a variety of challenges. Those discussed in the paper include: maintaining provider competency, strengthening supportive care networks, and adjusting staffing and other resources to meet increased demands for care.

Cancer Care Facilities↗
PubMed2000

ECF in gastric cancer.

Explore the source record for details and available documents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Are 18fluorodeoxyglucose positron emission tomography and magnetic resonance imaging useful in the prediction of relapse in lymphoma residual masses?

Treatment of both Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) frequently results in a residual mass visible radiologically. Such patients may receive radiotherapy unnecessarily because the residual mass may represent benign fibrotic tissue rather than residual active lymphoma. Radiotherapy has been shown to have significant short and more worrying long-term toxicity. Refining the criteria for its use would be a major advance. A number of clinical investigations have been evaluated to more accurately determine the nature of such lesions, including erythrocyte sedimentation rate (ESR), magnetic resonance imaging (MRI) and high-dose gallium-67 scanning (HDGS) but none has proven utility. 18[F]-fluorodeoxyglucose positron emission tomography (FDG-PET) is an imaging technique that has been shown to be useful in distinguishing fibrosis from residual active disease in solid tumours. The aim of this study was to compare FDG PET and MRI in the assessment of residual masses following treatment for lymphoma. Patients with NHL/HD who had a residual mass following chemotherapy were eligible for this study. Patients had a combination of MRI and/or PET. All scans were completed within 5 months of the end of treatment. Patients were followed-up for relapse. 56 patients had an MRI scan, 24 had a PET scan and 22 patients had both investigations. Overall sensitivity and specificity, respectively, were for MRI 45% and 74%, PET 50% and 69%, and PET/MRI concurring 50% and 67%. There was a trend for improved relapse-free survival (RFS) with a negative result of both MRI and PET, but this was not statistically significant. The predictive value for both tests failed to reach statistical significance. Subgroup analysis suggests that PET may be better at predicting relapse in patients with NHL, especially those with masses above the diaphragm. There is no convincing evidence that either MRI or PET or the combination can reliably predict relapse within residual masses after treatment for lymphoma. A negative PET scan however appears to be more informative than a positive result and may well aid clinical decision making. There are a number of factors that may produce false-positive results, including post-treatment inflammatory changes, the sensitivity of the test in the setting of minimal residual disease and the heterogeneity of the histological subtypes studied. A negative PET (or MRI) result in lymphoma residual masses following therapy may negate the necessity for further therapy such as chemotherapy or radiotherapy and their concomitant toxicities.

Adolescent↗
PubMed2000

Combining platinum, paclitaxel and anthracycline in patients with advanced gynaecological malignancy.

Two meta-analyses have suggested that the addition of an anthracycline to platinum-based chemotherapy may improve survival in advanced ovarian cancer, and two randomised trials have demonstrated superiority of paclitaxel over cyclophosphamide in platinum combinations. A combination of platinum, anthracycline and paclitaxel would, therefore, be a reasonable experimental arm of any future randomised trial in patients with epithelial ovarian carcinoma (EOC). Patients who required chemotherapy for EOC but were ineligible for standard trials or had other gynaecological tumours that required similar platinum-based chemotherapy were considered for this pilot. The platinum/anthracycline/paclitaxel regimen (G-CAT) was given 3-weekly and consisted of doxorubicin 50 mg/m(2) or epirubicin 60 mg/m(2) intravenously (i.v.) bolus, paclitaxel 175 mg/m(2) (i.v.) over 3 h and either cisplatin 75 mg/m(2) (i.v.) or carboplatin AUC 6, with granulocyte colony-stimulating factor (G-CSF) at the neutrophil nadir. Different combinations were used in order to determine the least toxic regimen. Toxicity and response were assessed according to CTC and WHO criteria, respectively. 26 patients entered the study, 13 with EOC and 13 with other gynaecological cancers (peritoneal, fallopian tube, mixed Mullerian). Median age was 49 years (range: 27-67). 8 patients received carboplatin/doxorubicin/paclitaxel, 8 cisplatin/doxorubicin/paclitaxel and 10 carboplatin/epirubicin/paclitaxel. A total of 135 cycles of chemotherapy were delivered, with a median of 6 cycles per patient (range: 2-6). 54 (40%) cycles required G-CSF support and 17 (65%) patients required at least one dose reduction. All patients experienced grade 4 neutropenia and 13 (50%) patients developed grade 3-4 thrombocytopenia (12 of whom had received carboplatin). There were 4 (15%) patients with grade 3/4 infections but no septic deaths. Non-haematological toxicities were manageable, lethargy occurred in 75% of cisplatin-treated patients. Grade 1/2 cardiotoxicity, as assessed pre- and post-treatment by left ventricular ejection fraction, was observed in 6/13 (46%) patients who had received doxorubicin and 2/7 (29%) epirubicin-treated patients. No clinically detectable cardiac toxicity was encountered. The response rate in 25 evaluable patients was 76% (12 CR, 7 PR). Dose intensity was highest in the carboplatin/epirubicin/paclitaxel combination. G-CAT shows high activity and can be administered safely, but only very fit patients are suitable for this regimen as it is associated with considerable toxicity. Carboplatin/epirubicin/paclitaxel was the best tolerated regimen overall.

Adult↗