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Biomedical subjects

J E Harris

Publications and source records attributed to J E Harris.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparison of epidural butamben to celiac plexus neurolytic block for the treatment of the pain of pancreatic cancer.

OBJECTIVE: To compare pain relief in metastatic pancreatic cancer patients between neurolytic celiac plexus block (NCPB) and epidural 5% butamben suspension (EBS), a material-based delivery system of a local anesthetic that produces a long-lasting differential nerve block. DESIGN: Open-label patient-selected parallel groups. SETTING: Urban tertiary care medical center. PATIENTS: Twenty-four adult patients with metastatic pancreatic cancer experiencing pain uncontrolled by systemic opioids who were referred to a multidisciplinary pain clinic for interventional therapy. INTERVENTIONS: Antecrural NCPB-block with ethanol and epidural 5% butamben suspension injections. MEASURES: Subjective global pain relief assessments on a 0-100% scale were made weekly for 4 weeks and then monthly. Change in opioid use postintervention. RESULTS: Eight patients had a single NCPB and three patients had two NCPB. Four of the former and two of the latter had successful pain relief defined to be a more than 75% reduction in pain when compared with pretreatment maintained for more than 4 weeks or until death (if less than 4 weeks). Thirteen patients received EBS in divided doses. Eleven patients received a cumulative EBS dose of 5 grams, one patient received a cumulative EBS dose of 2.5 grams, and one patient received a cumulative EBS dose of 8.75 grams. Nine of the eleven patients and each of the other two patients had successful pain relief. The overall incidence (85% EBS vs. 55% NCPB), the duration of successful pain relief, and the percent reduction in opioid use did not differ between the two groups. There were no serious complications. CONCLUSION: EBS appears to be a safe and effective alternative to NCPB in the treatment of pancreatic cancer pain.

Adult↗
PubMed2000

High yield criteria for emergency cranial computed tomography in adult patients with no history of head injury.

OBJECTIVES: A recent American study identified clinical factors which effectively predicted those patients who would have significant findings on cranial computed tomography. It was proposed to apply these criteria in a UK setting and to determine whether modifications could be made to improve their efficiency. METHODS: A prospective observational study was conducted over a four month period including all non-trauma adult patients referred from the accident and emergency (A&E) department for urgent cranial computed tomography. Presenting symptoms and signs were analysed for ability to predict clinically significant computed tomography findings, namely: acute infarct, malignancy, acute hydrocephalus, intracranial haemorrhage, or intracranial infection. RESULTS: Sixty two patients were included; 22 (35%) had significant findings on computed tomography. Applying the original criteria (any of: age 60 years or older, focal neurology, headache with nausea or vomiting, altered mental status) to the study population showed that no clinically significant tomograms would have been omitted but only 11% fewer performed. Modifying the criteria by removing "age 60 years or older" and replacing "altered mental status" with a Glasgow coma score <14, still ensured 100% sensitivity and would have resulted in 19% fewer scans being performed. CONCLUSION: Simple clinical criteria can be usefully applied to patients presenting to an A&E department in this country to target patients most likely to have clinically significant findings on urgent cranial computed tomography.

Adult↗
PubMed2000

A phase II study of gemcitabine and 5-fluorouracil in metastatic pancreatic cancer: an Eastern Cooperative Oncology Group Study (E3296).

Gemcitabine has recently been compared favorably to 5-fluorouracil (5-FU) as the standard chemotherapy for advanced pancreas cancer. Based on phase I data that combining gemcitabine with 5-FU is safe and has evidence for clinical activity, a phase II trial was conducted by the Eastern Cooperative Oncology Group (ECOG). Patients with metastatic disease, good performance status and organ function were eligible and enrolled after providing informed consent. Patients were given gemcitabine (1,000 mg/m(2)) followed by 5-FU (600 mg/m(2)) weekly for 3 weeks of every 4. Of 37 patients enrolled over a 3-month period, 36 were eligible. Partial responses were seen in 5 patients (14%). Median survival was 4.4 months with a 1-year survival rate of 8.6%. A randomized trial of the combination of 5-FU and gemcitabine versus gemcitabine alone is currently accruing patients in ECOG.

Adult↗
PubMed2000

Adjuvant active specific immunotherapy for stage II and III colon cancer with an autologous tumor cell vaccine: Eastern Cooperative Oncology Group Study E5283.

PURPOSE: A randomized phase III clinical trial of adjuvant active specific immunotherapy (ASI) with an autologous tumor cell-bacillus Calmette-Guérin (BCG) vaccine was conducted to determine whether surgical resection plus ASI was more beneficial than resection alone in stage II and III colon cancer patients. PATIENTS AND METHODS: Patients (n = 412) with colon cancer (297 with stage II disease, 115 with stage III disease) were randomly allocated to an observation arm or to a treatment arm in which they received three weekly intradermal vaccine injections of 10(7) irradiated autologous tumor cells beginning approximately 4 weeks after surgery. The first two weekly injections also contained 10(7) BCG organisms. Patients were observed for determination of time to recurrence and disease-free and overall survival. RESULTS: This was a negative study in that after a 7.6-year median follow-up period, there were no statistically significant differences in clinical outcomes between the treatment arms. However, there were disease-free survival (P =.078) and overall survival (P =.12) trends in favor of ASI when treatment compliance was evaluated, ie, patients who received the intended treatment had a delayed cutaneous hypersensitivity (DCH) response to the third vaccination (induration >/=5 mm). Also, the magnitude of the DCH response correlated with improved prognosis. The 5-year survival proportion was 84.6% for those with indurations greater than 10 mm, compared with 45.0% for those with indurations less than 5 mm. CONCLUSIONS: When all randomized patients were evaluated, no significant clinical benefit was seen with ASI in surgically resected colon cancer patients with stage II or III colon cancer. However, there was an indication that treatment compliance with effective immunization results in disease-free and overall survival benefits.

Adjuvants, Immunologic↗
PubMed2000

Immunohistochemical analyses of focal adhesion kinase expression in benign and malignant human breast and colon tissues: correlation with preinvasive and invasive phenotypes.

The focal adhesion kinase (FAK) is a protein tyrosine kinase linked to signaling events between cells and the extracellular matrix. Studies at the Western blot level have demonstrated up-regulation of FAK expression in invasive breast and colon cancers. To assess p125FAK expression at the cellular level, we developed monoclonal antibodies that specifically detected FAK in formalin-fixed, paraffin-embedded tissue sections and analyzed the levels of FAK expression in human breast and colon tissues. Monoclonal antibody 4.47 demonstrated FAK-specific focal adhesion staining by immunofluorescence assays on BT-474 breast cancer cells and detected a Mr 125,000 protein by both Western blotting and immunoprecipitation analyses. Using immunohistochemical techniques, the expression of p125FAK was analyzed in 36 normal and 43 preinvasive or invasive human breast and colon tissues from individual patients. FAK was weakly expressed in most benign breast epithelium but was up-regulated at moderate or strong levels in 14 of 18 invasive breast carcinomas. In seven samples of ductal carcinoma-in situ, FAK was overexpressed. Borderline-to-weak expression of FAK was detected in the normal colonic epithelium. In the invasive colon cancers, FAK was overexpressed at moderate or strong levels in 13 of 15 tumors. Furthermore, FAK expression was up-regulated in areas of dysplastic, premalignant colon epithelium. These results provide the first evidence at the cellular level that FAK expression is variably overexpressed in breast and colon cancer and suggest that up-regulation occurs at an early stage of tumorigenesis.

Animals↗
PubMed2000

Immune cell functions in pancreatic cancer.

Pancreatic cancer kills nearly 29,000 people in the United States annually-as many people as are diagnosed with the disease. Chemotherapeutic treatment is ineffective in halting progression of the disease. Yet, specific immunity to pancreatic tumor cells in subjects with pancreatic cancer has been demonstrated repeatedly during the last 24 years. Attempts to expand and enhance tumor-specific immunity with biotherapy, however, have not met with success. The question remains, "Why can't specific immunity regulate pancreatic cancer growth?" The idea that tumor cells have evolved protective mechanisms against immunity was raised years ago and has recently been revisited by a number of research laboratories. In pancreatic cancer, soluble factors produced by and for the protection of the tumor environment have been detected and are often distributed to the victim's circulatory system where they may effect a more generalized immunosuppression. Yet the nature of these soluble factors remains controversial, since some also serve as tumor antigens that are recognized by the same T cells that may become inactivated by them. Unless the problem of tumor-derived immunosuppressive products is addressed directly through basic and translational research studies, successful biotherapeutic treatment for pancreatic cancer may not be forthcoming.

Cytotoxicity, Immunologic↗
PubMed1999

The continuum-of-addiction: cigarette smoking in relation to price among Americans aged 15-29.

We studied the relationship between current cigarette smoking and price among 34145 respondents, aged 15-29 years, to the 1992-1993 Tobacco Use Supplements to the Current Population Survey. The price elasticity of current smoking varied inversely with age: -0.831 (S.E. 0.402) for ages 15-17; -0.524 (S.E. 0.256) for ages 18-20; -0.370 (S.E. 0.188) for ages 21-23; -0.202 (S.E. 0.175) for ages 24-26; and -0.095 (S.E. 0.157) for ages 27-29. In response to higher prices, older youth were more likely to reduce the number of cigarettes smoked per day than to quit entirely. Among 15-17-year-olds, smoking cigarettes 'some days' was more sensitive to price than smoking 'every day'. Cigarette smoking was inversely related to the prices of premium brands, but not discount brands.

Adolescent↗
PubMed1999

Immunoregulation in pancreatic cancer patients.

Metastatic pancreatic cancer is one of the most aggressive cancer known in man yet specific antitumor immunity has been demonstrated in lymph nodes draining the sites of pancreatic tumors. Despite this immunity, pancreatic cancer patients suffer a quick demise. To further define tumor immunity in patients with metastatic pancreatic cancer, we sought to characterize helper T cell subsets, serum cytokines, cellular cytotoxicity that is both T-cell and non-T cell mediated, as well as known tumor-derived immunosuppressive products that may be present in their peripheral blood. Significantly heightened levels of interleukin 2 (IL-2), a Th1 cytokine, were found in patients before treatment with chemotherapy while serum IL-10, a Th2 cytokine, were at significantly lower levels than observed in normal donors tested between their fifth and seventh decades of life. IL-10 levels increased progressively with age as a serum-bound protein in normal, healthy donors tested between the ages of 24 through 61. An age associated progression of increased IL-10 levels was not observed in pancreatic cancer patients. Few patients had detectable serum levels of soluble fas ligand but approximately half had elevated levels of a tumor marker, detected with the CA-15.3 assay, known as soluble MUCIN 1 (MUC1). Cell mediated cytotoxicity including T-cell mediated killing of pancreatic tumor cell lines was detected in many patients. These data suggest that pancreatic cancer patients have activated type 1 helper T cells that can support development of cell-mediated immunity, and that their sera contain lowered levels of the "anti-inflammatory" type 2 cytokine, IL-10.

Age Factors↗
PubMed1999

Do lipoxygenases modulate normal or aberrant lympho-hematopoiesis?

Whether 5- (and the 12- or 15-) lipoxygenases participate in normal or malignantly transformed hematopoietic cell proliferation and differentiation, or contribute to programmed or necrotic cell death has been difficult to decide. Recent evidence concerning these questions is reviewed and some reasons for these difficulties are considered.

Animals↗
PubMed1999

Induction of type 1 programmed cell death in U937 cells by the antioxidant, butylated hydroxy-toluene or the free radical spin trap, NTBN.

Oxidative stress can initiate programmed cell death and contributes to the patho-physiology of a number of diseases. Low micromolar to millimolar concentrations of various antioxidants or free radical scavengers promote cell growth and reduce cellular suicide induced by several functionally distinct agents, including some known to produce oxidative stress. Severe anoxia or inhibitors of oxidative phosphorylation also initiate programmed cell death. These results seem paradoxical. In order to compare the response of U937 monoblastoid cells to higher concentrations of an antioxidant or a free radical-spin trap, cells were cultured with 20-80 microM concentrations of butylated hydroxy-toluene or with 5 to 60 mM concentrations of the free radical spin trap, N-tertiary butyl phenyl-nitrone. At these concentrations, both agents inhibited cellular proliferation and induced oligosomic DNA, detected by its 'laddering' after electrophoresis on agarose, confirmed by TUNEL (BHT) or flow cytometric (NTBN) evidence of hypodiploid DNA and ultrastructural evidence of a type 1 programmed cell death. The ability of hydroxy-toluenes to oxidize DNA and promote carcinogenesis and whether free radical spin traps could augment or interfere with the response of malignantly transformed cells to chemotherapy or ionizing radiation provide the raison d'etre of these studies.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1999

Free radicals and reactive oxygen species in programmed cell death.

Oxidative stress, originating from reactive oxygen species and free radicals provides a constant challenge to eukaryotic cell survival. While implicated in a number of degenerative diseases, some associated with aging and with aging itself, the manner and extent to which oxidative stress contributes to the initiation or implementation of programmed-cell death is problematic. If oxidative stress is an important modulator of programmed-cell death, any ability intentionally to augment or inhibit it might ameliorate diseases in which the process is abnormally underactive or overactive.

Animals↗
PubMed1999

Free radical spin traps as adjuncts for the prevention and treatment of disease.

Free radical spin traps exhibit properties consistent with a role in the prevention or amelioration of diseases mediated by the formation of free radical species in excess of optimum constitutive requirements. At first view, it may be surprising that they have not found a place in clinical medicine. Some studies of diseases in which free radicals and oxidative stress are aberrantly over- or underabundant and which might be ameliorated by inhibiting or augmenting their formation have been reported. A number of pathophysiologic categories in which such agents have been or might be employed are briefly summarized.

Animals↗
PubMed1999

Conventional dose melphalan is inactive in metastatic melanoma: results of an Eastern Cooperative Oncology Group Study (E1687).

Despite reports that i.v. melphalan is active in the settings of conditioning regimens utilizing high-dose chemotherapy for autologous bone marrow transplantation and in isolated limb perfusion for the treatment of malignant melanoma, its activity at conventional doses has never been defined in this disease. We conducted a phase II study of conventional-dose i.v. melphalan (30 mg/m2) in 17 patients with metastatic melanoma. All patients were previously untreated with chemotherapy with performance status 0, 1 or 2. Forty-seven cycles were given with a median of two cycles. One patient was not evaluable due to early death. There were no responses in the 16 patients, resulting in a 0% response rate (95% confidence interval = 0-17%). We conclude that conventional-dose melphalan by i.v. administration has no appreciable activity in patients with metastatic malignant melanoma.

Adrenal Gland Neoplasms↗
PubMed1999

Evaluation of mitoguazone in patients with refractory chronic lymphocytic leukemia: a phase II study (P-H482) of the Eastern Cooperative Oncology Group.

Mitoguazone is a unique antitumor agent that interferes with polyamine synthesis that has been reported to have activity against AIDS-related malignant lymphoma. We, therefore, tested this agent for activity against chronic lymphocytic leukemia (CLL) in this phase II study. Mitoguazone, 500 mg/M2 was given intravenously weekly to 13 patients with relapsed or refractory, previously treated Rai stages 2-4 CLL. There were no complete or partial responses as judged by standard criteria. Toxicity was acceptable. Mitoguazone in the dose and schedule employed in this study has no significant activity as a single agent in patients with relapsed or refractory CLL.

Aged↗
PubMed1999

The role of physical activity in the management of obesity.

Sedentary lifestyle is associated with obesity and obesity-related chronic diseases. Increased physical activity can produce clinically significant changes in body composition and a reduction in risk of obesity-related chronic diseases in obese people. Because a great proportion of a primary care physician's patient population will be obese, it is essential that physicians know the scientific facts about the role of physical activity in the treatment of obesity and how to effectively prescribe it. This article summarizes significant research conclusions about the relationship between physical activity, obesity, and health. It also provides practical strategies for helping obese patients integrate physical activity into their lives.

Body Composition↗