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Biomedical subjects

E Hall

Publications and source records attributed to E Hall.

At least 19 recordsLinked to original sources
PubMed2005

Randomized phase III trials of adjuvant FAMTX or FEMTX compared with surgery alone in resected gastric cancer. A combined analysis of the EORTC GI Group and the ICCG.

BACKGROUND: In patients who underwent radical resection for gastric cancer, we investigate the relative efficacy of combined 5-fluorouracil+adriamycin or epirubicin and methotrexate with leucovorin rescue (FAMTX or FEMTX) compared with a control arm. PATIENTS AND METHODS: This report is a prospective combined analysis of two randomized clinical trials conducted on patients who underwent radical resection for histologically proven adenocarcinoma of the stomach or esophago-gastric junction. Three hundred and ninety-seven untreated patients, 206 from 23 European Organization for Research and Treatment of Cancer (EORTC) institutions and 191 from 16 International Collaborative Cancer Group (ICCG) institutions, were randomized. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and the treatments were compared for these end-points by means of the log-rank test, retrospectively stratified by trial. RESULTS: In a planned combined analysis of the two trials, no significant differences were found between the treatment and control arms for either DFS (hazards ratio: 0.98, P=0.87) or OS (hazards ratio: 0.98, P=0.86). The 5-year OS was 43% in the treatment arm and 44% in the control arm and the 5-year DFS was 41% and 42%, respectively. CONCLUSION: Neither FAMTX nor FEMTX can be advocated as adjuvant treatment in patients who undergo resection for gastric cancer.

Adenocarcinoma↗
PubMed2005

Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects.

Radical radiotherapy is a standard form of management of localised prostate cancer. Conformal treatment planning spares adjacent normal tissues reducing treatment-related side effects and may permit safe dose escalation. We have tested the effects on tumour control and side effects of escalating radiotherapy dose and investigated the appropriate target volume margin. After an initial 3-6 month period of androgen suppression, 126 men were randomised and treated with radiotherapy using a 2 by 2 factorial trial design. The initial radiotherapy tumour target volume included the prostate and base of seminal vesicles (SV) or complete SV depending on SV involvement risk. Treatments were randomised to deliver a dose of 64 Gy with either a 1.0 or 1.5 cm margin around the tumour volume (1.0 and 1.5 cm margin groups) and also to treat either with or without a 10 Gy boost to the prostate alone with no additional margin (64 and 74 Gy groups). Tumour control was monitored by prostate-specific antigen (PSA) testing and clinical examination with additional tests as appropriate. Acute and late side effects of treatment were measured using the Radiation Treatment and Oncology Groups (RTOG) and LENT SOM systems. The results showed that freedom from PSA failure was higher in the 74 Gy group compared to the 64 Gy group, but this did not reach conventional levels of statistical significance with 5-year actuarial control rates of 71% (95% CI 58-81%) in the 74 Gy group vs 59% (95% CI 45-70%) in the 64 Gy group. There were 23 failures in the 74 Gy group and 33 in the 64 Gy group (Hazard ratio 0.64, 95% CI 0.38-1.10, P=0.10). No difference in disease control was seen between the 1.0 and 1.5 cm margin groups (5-year actuarial control rates 67%, 95% CI 53-77% vs 63%, 95% CI 50-74%) with 28 events in each group (Hazard ratio 0.97, 95% CI 0.50-1.86, P=0.94). Acute side effects were generally mild and 18 weeks after treatment, only four and five of the 126 men had persistent > or =Grade 1 bowel or bladder side effects, respectively. Statistically significant increases in acute bladder side effects were seen after treatment in the men receiving 74 Gy (P=0.006), and increases in both acute bowel side effects during treatment (P=0.05) and acute bladder sequelae (P=0.002) were recorded for men in the 1.5 cm margin group. While statistically significant, these differences were of short duration and of doubtful clinical importance. Late bowel side effects (RTOG> or =2) were seen more commonly in the 74 Gy and 1.5 cm margin groups (P=0.02 and P=0.05, respectively) in the first 2 years after randomisation. Similar results were found using the LENT SOM assessments. No significant differences in late bladder side effects were seen between the randomised groups using the RTOG scoring system. Using the LENT SOM instrument, a higher proportion of men treated in the 74 Gy group had Grade > or =3 urinary frequency at 6 and 12 months. Compared to baseline scores, bladder symptoms improved after 6 months or more follow-up in all groups. Sexual function deteriorated after treatment with the number of men reporting some sexual dysfunction (Grade> or =1) increasing from 38% at baseline to 66% at 6 months and 1 year and 81% by year 5. However, no consistent differences were seen between the randomised groups. In conclusion, dose escalation from 64 to 74 Gy using conformal radiotherapy may improve long-term PSA control, but a treatment margin of 1.5 cm is unnecessary and is associated with increased acute bowel and bladder reactions and more late rectal side effects. Data from this randomised pilot study informed the Data Monitoring Committee of the Medical Research Council RT 01 Trial and the two studies will be combined in subsequent meta-analysis.

Adenocarcinoma↗
PubMed2003

Liver-related biochemical changes in the serum of dogs being treated with phenobarbitone.

The concentrations of phenobarbitone, albumin, bile acids and cholesterol, and the activities of alkaline phosphatase (AP), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT) and glutamate dehydrogenase (GLDH) were measured in the serum of 95 epileptic dogs whose clinical signs were controlled with phenobarbitone. The dogs were divided into groups on the basis of the concentration of phenobarbitone in their serum, the dose administered and the duration of the treatment. The concentration of phenobarbitone in serum was directly related to the activities of ALT, AP, GGT and GLDH and inversely related to the concentration of albumin. There was no significant relationship between the duration of treatment and the serum concentration of phenobarbitone, but there was a significant relationship between the duration of treatment and the activities of ALT, AP and GLDH. Thirty-five of the dogs (37 per cent) had serum activities of AP above the normal range, 19 had abnormally high activities of ALT, and 15 had high activities of GLDH, but these incidences were not related to the serum concentration of phenobarbitone. The dogs receiving higher doses for longer periods had the highest incidence of high activities of AP, ALT and GLDH. The concentration of bile acids in seven of the dogs was above the normal range but there was no relationship between the concentration and either the serum concentration, dose or duration of treatment with phenobarbitone.

Alanine Transaminase↗
PubMed2003

Aromatase inhibitors as adjuvant therapies in patients with breast cancer.

There is increasing evidence that endocrine therapy has an important role in patients with oestrogen receptor positive breast cancer. Several large meta-analyses have reinforced the value of both ovarian ablation and tamoxifen in improving survival. Over the past decade, aromatase inhibitors have become the treatment of choice for second-line therapy of metastatic breast cancer, and the third generation inhibitors have now an established reputation for good patient tolerability. Early studies indicated that aminoglutethimide/hydrocortisone could benefit postmenopausal patients with primary breast cancer, and in 2001, the ATAC study showed that the third generation aromatase inhibitor, anastrozole, seemed superior to tamoxifen in that anastrozole-treated patients had a longer disease-free survival. Other studies will report on the relative merits of the steroidal inhibitor exemestane as well as non-steroidal letrozole. The exact duration and sequencing of treatment, together with the long-term effects on bone are at present, unknown.

Aromatase Inhibitors↗
PubMed2002

Preclinical studies characterizing the anti-migraine and cardiovascular effects of the selective 5-HT1D receptor agonist PNU-142633.

The present study describes the preclinical pharmacology of a highly selective 5-HT1D receptor agonist PNU-142633. PNU-142633 binds with a Ki of 6 nm at the human 5-HT1D receptor and a Ki of> 18 000 nm at the human 5-HT1B receptor. The intrinsic activity of PNU-142633 at the human 5-HT1D receptor was determined to be 70% that of 5-HT in a cytosensor cell-based assay compared with 84% for that of sumatriptan. PNU-142633 was equally effective as sumatriptan and a half-log more potent than sumatriptan in preventing plasma protein extravasation induced by electrical stimulation of the trigeminal ganglion. Like sumatriptan, PNU-142633 reduced the increase in cat nucleus trigeminal caudalis blood flow elicited by electrical stimulation of the trigeminal ganglion compared with the vehicle control. The direct vasoconstrictor potential of PNU-142633 was evaluated in vascular beds. Sumatriptan increased vascular resistance in carotid, meningeal and coronary arteries while PNU-142633 failed to alter resistance in these vascular beds. These data are discussed in relation to the clinical findings of PNU-142633 in a phase II acute migraine study.

Analgesics↗
PubMed2001

A randomized multicenter trial of crotalinae polyvalent immune Fab (ovine) antivenom for the treatment for crotaline snakebite in the United States.

BACKGROUND: Current therapy for crotaline snakebite includes antivenin (Crotalidae) polyvalent, an antivenom with numerous adverse effects. We compared the efficacy and safety of 2 dosing regimens with a new antivenom, Crotalinae polyvalent immune Fab (Fab AV). METHODS: A single dose of Fab AV alone (as-needed [PRN] group) was compared with an initial dose plus repeated treatments during 18 hours (scheduled group) in a multicenter randomized trial. The study included patients with minimal or moderate envenomation by a crotaline snake within the preceding 6 hours, aged 10 years or older, in whom worsening of the envenomation syndrome was observed before Fab AV treatment. After treatment with Fab AV to achieve initial control, patients were randomized to the scheduled or PRN treatment group. Scheduled group patients received additional doses of Fab AV every 6 hours for 3 doses. The PRN group received no planned additional doses of antivenom. RESULTS: The mean severity score of the 31 patients decreased from 4.35 to 2.39 points (P<.001); there was no difference between scheduled and PRN groups. No patient in the scheduled group received unplanned Fab AV doses, but 8 of 16 patients in the PRN group received unplanned doses (P =.002). Acute reactions occurred in 6 patients (19%), and serum sickness occurred in 6 (23%) of 26 patients who returned for follow-up. CONCLUSIONS: In the first randomized trial of antivenom in the United States, Fab AV effectively terminated venom effects. Since the unplanned use of Fab AV in the PRN group was common, the treatment regimen may require more than 1 initial dose.

Adolescent↗
PubMed2001

Differences in the expression of human class I MHC alleles and their associated peptides in the presence of proteasome inhibitors.

We have studied the contributions of proteasome inhibitor-sensitive and -insensitive proteases to the generation of class I MHC-associated peptides. The cell surface expression of 13 different human class I MHC alleles was inhibited by as much as 90% or as little as 40% when cells were incubated with saturating concentrations of three different proteasome inhibitors. Inhibitor-resistant class I MHC expression was not due to TAP-independent expression or preexisting internal stores of peptides. Furthermore, it did not correlate with the amount or specificity of residual proteasome activity as determined in in vitro proteolysis assays and was not augmented by simultaneous incubation with multiple inhibitors. Mass spectrometry was used to directly characterize the peptides expressed in the presence and absence of proteasome inhibitors. The number of peptide species detected correlated with the levels of class I detected by flow cytometry. Thus, for many alleles, a significant proportion of associated peptide species continue to be generated in the presence of saturating levels of proteasome inhibitors. Comparison of the peptide-binding motifs of inhibitor-sensitive and -resistant class I alleles further suggested that inhibitor-resistant proteolytic activities display a wide diversity of cleavage specificities, including a trypsin-like activity. Sequence analysis demonstrated that inhibitor-resistant peptides contain diverse carboxyl termini and are derived from protein substrates dispersed throughout the cell. The possible contributions of inhibitor-resistant proteasome activities and nonproteasomal proteases residing in the cytosol to the peptide profiles associated with many class I MHC alleles are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Double-blind randomized phase II study of hyperbaric oxygen in patients with radiation-induced brachial plexopathy.

BACKGROUND: Radiation-induced brachial plexopathy (RIBP) is an untreatable complication of curative radiotherapy for early breast cancer, characterized by chronic neuropathic pain and limb paralysis. Hyperbaric oxygen (HBO2) therapy is known to promote healing of tissue rendered ischaemic by radiotherapy, but is untested in RIBP. METHODS: Thirty four eligible research volunteers suffering from RIBP were randomized to HBO2 or control group. The HBO2 group breathed 100% oxygen for 100 min in a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks. The control group accompanied the HBO2 group and breathed a gas mixture equivalent to breathing 100% oxygen at surface pressure. All volunteers and investigators, except the operators of the hyperbaric chamber and the trial statistician, were blind to treatment assignments. The warm sensory threshold, which measures the function of small sensory fibres, was selected as the primary endpoint. FINDINGS: Pre-treatment neurophysiological tests were grossly abnormal in the affected hand compared to the unaffected hand in both HBO2 and control groups, as expected, but no statistically significant differences were noted in either group at any time up to 12 months post-treatment. However, normalization of the warm sensory threshold in two of the HBO2 group was reliably recorded. Two cases with marked chronic arm lymphoedema reported major and persistent improvements in arm volume for at least 12 months after treatment with HBO2. IINTERPRETATION: There is no reliable evidence to support the hypothesis that HBO2 therapy slows or reverses RIBP in a substantial proportion of affected individuals, although improvements in warm sensory threshold offer some suggestion of therapeutic effect. Improvement in long-standing arm lymphoedema was not anticipated, and justifies further investigation.

Action Potentials↗
PubMed2001

Making space for the 'intellectual' in geographies of disability.

There is a growing body of work on geographies of deinstitutionalisation and its consequences, but the weight of this scholarship has focussed on people with mental health problems and physically disabled people. With only few exceptions, the 'post asylum geographies' of intellectually disabled people remain neglected by geographers. We advocate a redressing of this imbalance. First, we assess reasons for the relative absence of 'intellectual' considerations in geographies of disability. We then consider ways in which the full spectrum of those with mental differences might be included in geographical research. We conclude that Wolpert's call 25 years ago to 'open closed spaces' is just as applicable to our efforts to conceptually link health, place, and disability, as it is to the material welfare of vulnerable groups in society.

Deinstitutionalization↗
PubMed2001

HOPE for patients with Type 2 diabetes: an application of the findings of the MICRO-HOPE substudy in a British hospital diabetes clinic.

AIMS: The MICRO-HOPE substudy demonstrated that when ramipril treatment was added to people with Type 2 diabetes and additional cardiovascular risk factors cardiovascular events were reduced by 25% in 4.5 years. We wished to determine the proportion of people with Type 2 diabetes and additional cardiovascular risk factors registered with a hospital diabetes service. METHODS: Non-proteinuric people (n = 1370) with Type 2 diabetes identified on our diabetes register were subject to analysis. Anticipated reductions in cardiovascular events due to ramipril treatment were based on reductions observed in the MICRO-HOPE substudy. RESULTS: Non-proteinuric people (n = 1075 (78%)) with Type 2 diabetes had at least one additional cardiovascular risk factor. Twenty-nine percent were already taking an angiotensin-converting enzyme inhibitor. The remaining 764 patients were similar to ramipril-treated participants in the MICRO-HOPE substudy. Treatment with ramipril for 4.5 years would be anticipated to reduce cardiovascular deaths by 26, revascularization procedures by 19 and admissions for myocardial infarction and stroke by 18 and 26, respectively. CONCLUSIONS: Of non-proteinuric people with Type 2 diabetes, 78% have additional cardiovascular risk factors. Only a small proportion currently receive treatment with an angiotensin-converting enzyme inhibitor. The incidence of cardiovascular events could be reduced if more patients were treated with ramipril and other cardiovascular risk factors were addressed.

Aged↗
PubMed2001

A self-administered instrument for assessing therapeutic approaches of drug-user treatment counselors.

In this article we describe the development and psychometric properties of a self-administered instrument for assessing drug-user treatment counselors' therapeutic approaches such as psychodynamic or interpersonal, cognitive-behavioral, family systems or dynamics, 12-step, and case management. We generated an initial pool of items corresponding to these five approaches and modified them based on expert ratings. We developed three sets of items. The first concerned the beliefs underlying each therapeutic approach. The second and third concerned the practices of each applicable approach within individual and group counseling, respectively. With the exception of case management, an approach that originated within social work and which is only applicable to individual counseling, the other four approaches are applicable, at least theoretically, to both individual and group counseling. Additionally, we included items that describe techniques used exclusively with groups (i.e., group techniques). Finally, we included some items that are not associated with any of the traditional approaches but which reflect the practical approach that drug-user treatment programs often take to both individual and group counseling (i.e., practical counseling). The initial instrument consisted of 17 subscales with a total of 76 items. This instrument was administered to 226 counselors from 45 drug-user treatment programs in Los Angeles County. Based on this data, we further refined these scales using confirmatory factor analysis to ensure both construct validity and discriminant validity. The final instrument consisted of 14 subscales with a total of 48 items.

Adult↗
PubMed2001

Overexpression of CYP27 in hepatic and extrahepatic cells: role in the regulation of cholesterol homeostasis.

In the liver, sterol 27-hydroxylase (CYP27) participates in the classic and alternative pathways of bile acid biosynthesis from cholesterol (Chol). In extrahepatic tissues, CYP27 converts intracellular Chol to 27-hydroxycholesterol (27OH-Chol), which may regulate the activity of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA-R). This study attempts to better define the role of CYP27 in the maintenance of Chol homeostasis in hepatic and extrahepatic cells by overexpressing CYP27 in Hep G2 cells and Chinese hamster ovary (CHO) cells through infection with a replication-defective recombinant adenovirus encoding for CMV-CYP27. After infection, CYP27 mRNA and protein levels increased dramatically. CYP27 specific activity also increased two- to fourfold in infected cells (P < or = 0.02), with a marked increase in conversion of [(14)C]Chol to [(14)C]27OH-Chol (approximately 150%; P < or = 0.01). Accumulation of 27OH-Chol in CHO cells was associated with a 50% decrease in HMG-CoA-R specific activity (P < or = 0.02). In infected Hep G2 cells, the significant increase in bile acid synthesis (46%; P < or = 0.006), which prevented the accumulation of intracellular 27OH-Chol, resulted in increased HMG-CoA-R activity (183%; P < or = 0.02). Overexpression of CYP27 in Hep G2 cells also increased acyl CoA-cholesterol acyltransferase (71%, P < or = 0.02) and decreased cholesteryl ester hydrolase (55%, P < or = 0.02). In conclusion, CYP27 generates different physiological responses depending on cell type and presence or absence of bile acid biosynthetic pathways.

Adenoviridae↗
PubMed2001

Estimated risks of radiation-induced fatal cancer from pediatric CT.

OBJECTIVE: In light of the rapidly increasing frequency of pediatric CT examinations, the purpose of our study was to assess the lifetime cancer mortality risks attributable to radiation from pediatric CT. MATERIALS AND METHODS: Organ doses as a function of age-at-diagnosis were estimated for common CT examinations, and estimated attributable lifetime cancer mortality risks (per unit dose) for different organ sites were applied. Standard models that assume a linear extrapolation of risks from intermediate to low doses were applied. On the basis of current standard practice, the same exposures (milliampere-seconds) were assumed, independent of age. RESULTS: The larger doses and increased lifetime radiation risks in children produce a sharp increase, relative to adults, in estimated risk from CT. Estimated lifetime cancer mortality risks attributable to the radiation exposure from a CT in a 1-year-old are 0.18% (abdominal) and 0.07% (head)-an order of magnitude higher than for adults-although those figures still represent a small increase in cancer mortality over the natrual background rate. In the United States, of approximately 600,000 abdominal and head CT examinations annually performed in children under the age of 15 years, a rough estimate is that 500 of these individuals might ultimately die from cancer attributable to the CT radiation. CONCLUSION: The best available risk estimates suggest that pediatric CT will result in significantly increased lifetime radiation risk over adult CT, both because of the increased dose per milliampere-second, and the increased lifetime risk per unit dose. Lower milliampere-second settings can be used for children without significant loss of information. Although the risk-benefit balance is still strongly tilted toward benefit, because the frequency of pediatric CT examinations is rapidly increasing, estimates that quantitative lifetime radiation risks for children undergoing CT are not negligible may stimulate more active reduction of CT exposure settings in pediatric patients.

Adolescent↗
PubMed2000

[Coronary angiography in a county hospital].

BACKGROUND: At a county hospital in northern Norway, coronary angiographies have been performed for more than 25 years. We wanted to compare our complication rates with results from larger hospitals. MATERIAL AND METHODS: Data concerning indication for angiography, findings and complications were collected retrospectively from the files of 837 patients who underwent coronary angiography at our hospital during the last ten years. The number of procedures per year has varied from 30 to 125. RESULTS: 50% of the patients had three-vessel and/or left main coronary artery stenosis. Less than 10% of the patients had no significant coronary stenosis or valvular disease at angiography. The total complication rate was 4.8%. Nine patients (1.1%) had myocardial infarction or stroke with sequelae; three patients died (0.4%). INTERPRETATION: Our complication rates are higher than those from other larger hospitals in Norway and internationally, but they have decreased over time. The high percentage of serious coronary pathology among our patients may have contributed significantly to the complication rate. In addition, the annual number of exams may have been too low to give sufficient operator training. The results require a continuing evaluation of our practice.

Aged↗
PubMed2000

[Coronary angiography in a county hospital].

BACKGROUND: At a county hospital in northern Norway, coronary angiographies have been performed for more than 25 years. We wanted to compare our complication rates with results from larger hospitals. MATERIAL AND METHODS: Data concerning indication for angiography, findings and complications were collected retrospectively from the files of 837 patients who underwent coronary angiography at our hospital during the last ten years. The number of procedures per year has varied from 30 to 125. RESULTS: 50% of the patients had three-vessel and/or left main coronary artery stenosis. Less than 10% of the patients had no significant coronary stenosis or valvular disease at angiography. The total complication rate was 4.8%. Nine patients (1.1%) had myocardial infarction or stroke with sequelae; three patients died (0.4%). INTERPRETATION: Our complication rates are higher than those from other larger hospitals in Norway and internationally, but they have decreased over time. The high percentage of serious coronary pathology among our patients may have contributed significantly to the complication rate. In addition, the annual number of exams may have been too low to give sufficient operator training. The results require a continuing evaluation of our practice.

Aged↗
PubMed2000

Outpatient frozen sections by telepathology in a Veterans Administration medical center.

A relatively simple telepathology system is described for evaluating the margins of excision of cutaneous basal and squamous carcinomas. The system uses a microscope with a built-in television camera, but no eyepieces. The image is projected onto an adjacent monitor and transmitted by T1 line at 768 Kbs to a remote, large screen monitor. The microscope is operated by the surgeon under the telephone direction of the pathologist at the remote site. In a series of 66 cases involving more than 400 individual tissue blocks, we have had only 2 cases with false-negative interpretations and 2 in which the block was not fully displayed on the frozen section. In 15 cases, 1 or more surgical margins were positive, and the surgeon proceeded to excise additional tissue. Our success is attributed to dedicated involvement by the surgeon, very high-quality frozen sections, and the experience of the pathologist.

Ambulatory Surgical Procedures↗