Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer.

Lessons Learned: Colorectal cancers exhibit a high level of cyclooxygenase-2 (COX-2) expression with strong preclinical rationale for improved clinical outcomes with COX-2 inhibition. Celecoxib is a COX-2 inhibitor and we have shown that it can be safely combined with capecitabine and oxaliplatin as part of neoadjuvant treatment with radiation therapy (RT) in rectal cancer.There was a significant improvement in skin toxicity with this combination as compared with historical data.

Assessment of the frequency of allelic imbalance in human tissue using a multiplex polymerase chain reaction system.

Genomic instability can generate chromosome breakage and fusion randomly throughout the genome, frequently resulting in allelic imbalance, a deviation from the normal 1:1 ratio of maternal and paternal alleles. Allelic imbalance reflects the karyotypic complexity of the cancer genome. Therefore, it is reasonable to speculate that tissues with more sites of allelic imbalance have a greater likelihood of having disruption of any of the numerous critical genes that cause a cancerous phenotype and thus may have diagnostic or prognostic significance.

Effects of cigarette smoke on degranulation and NO production by mast cells and epithelial cells.

Exhaled nitric oxide (eNO) is decreased by cigarette smoking. The hypothesis that oxides of nitrogen (NOX) in cigarette smoke solution (CSS) may exert a negative feedback mechanism upon NO release from epithelial (AEC, A549, and NHTBE) and basophilic cells (RBL-2H3) was tested in vitro. CSS inhibited both NO production and degranulation (measured as release of beta-hexosaminidase) in a dose-dependent manner from RBL-2H3 cells.

Primary angiomyolipoma of the pancreas.

Angiomyolipoma (AML) is a rare tumor characterized histologically by a mixture of spindle cells, adipose tissue, epithelioid cells, and blood vessels. AML usually occurs in the kidney but can involve the liver and, rarely, other sites. We describe a 74-year-old woman without tuberous sclerosis who presented with spontaneous hemorrhage into a primary AML of the pancreas and underwent curative surgical resection.

Nicorandil inhibits the release of TNFalpha from a lymphocyte cell line and peripheral blood lymphocytes.

Modulation of cytokine release may be of interest in modulating inflammatory diseases. This study determined whether nicorandil, a potassium channel opener, and nitric oxide (NO) donor could inhibit the release of tumour necrosis factor alpha (TNFalpha) from lymphocytes. Nicorandil significantly and dose-dependently inhibited the TNFalpha release from a human Epstein Barr virus-transformed B lymphocyte cell line (EBV-B) and peripheral blood B and T lymphocytes.

The end-of-study patient survey: methods influencing response rate in the AVID Trial.

Patient surveys are commonly distributed at the end of a multicenter clinical trial. This Antiarrhythmics Versus Implantable Defibrillators (AVID) substudy prospectively explored the relationship between methods used in distributing a survey and the quantity of responses received. AVID was a multicenter, randomized trial comparing survival in arrhythmia patients treated with antiarrhythmic drugs versus implantable defibrillators.

Effects of inhaled tumour necrosis factor alpha in subjects with mild asthma.

Background: Inhaled tumour necrosis factor alpha (TNF alpha) has previously been shown to induce airway neutrophilia and increased airway reactivity in normal subjects. It was hypothesised that a similar challenge would increase airway reactivity in those with mild asthma, but that the inflammatory profile may differ.

Methods: Ten mild asthmatic subjects were recruited on the basis of clinical asthma and either a sensitivity to methacholine within the range defined for asthma or a 20% improvement in forced expiratory volume (FEV(1)) after 200 micro g salbutamol.

Nicorandil inhibits degranulation and TNF-alpha release from RBL-2H3 cells.

Objective: Nicorandil is a potassium channel opener and nitric oxide (NO) donor, and the hypothesis was tested that these modes of action may inhibit cellular degranulation and release of tumour necrosis factor-alpha (TNF-alpha).

Materials And Methods: TNF-alpha and beta-hexosaminidase secretion were measured from rat basophilic leukemia cells (RBL-2H3) activated via the high affinity IgE receptor with dinitrophenyl-albumin (DNP-A) challenge in the presence of nicorandil. Inhibitors of K+ openers and NO were pre-incubated with the RBL-2H3 cells to determine the principal mode of action.

Quality-of-life six months after CABG surgery in patients randomized to ICD versus no ICD therapy: findings from the CABG Patch Trial.

Unlabelled: ICDs can affect a patient's perceived quality-of-life (QOL). This article describes the QOL in patients who participated in The CABG Patch Trial. This trial evaluated the potential benefit of empiric ICD implantation in patients with an increased risk of arrhythmic cardiac death as determined by reduced ejection fraction (<0.

Surgical therapy of pancreatic cancer.

Surgical resection remains the only curative modality for pancreatic cancer. Improvements in surgical technique have greatly reduced the morbidity and mortality from pancreatic resection. These results clearly justify the use of pancreatic resection for localized and resectable pancreatic cancer.

Correlates of response to IL-2 therapy in patients treated for metastatic renal cancer and melanoma.

Purpose: We evaluated the characteristics of patients with metastatic renal cancer or metastatic melanoma prior to and during treatment with bolus intravenous interleukin-2 to define prognostic indicators of subsequent response to therapy.

Patients And Methods: A consecutive series of 509 patients with progressive metastatic cancer were treated with intravenous interleukin-2 from September 1985 to July 1993. Pretreatment demographic characteristics, treatment history, results of laboratory tests, and metastatic sites of disease were evaluated.

Goal-directed therapy with dopexamine, dobutamine, and volume expansion: effects of systemic oxygen transport on hepatic ultrastructure in porcine sepsis.

Objectives: Can the hepatic structural deterioration that occurs during peritonitis be attenuated by increasing cardiac output and oxygen consumption (VO2)? Do the agents used to achieve these increases have any characteristic affects on these hepatic structural changes?

Design: Randomized, prospective, observational animal study.

Setting: Research laboratory of a university medical school.

Subjects: Twenty-five Middle White adolescent pigs, weighing 25 to 30 kg, divided into five groups.

Thyroid dysfunction in 281 patients with metastatic melanoma or renal carcinoma treated with interleukin-2 alone.

The purpose of this prospective study was to determine the incidence of thyroid dysfunction in cancer patients receiving immunotherapy with interleukin-2 (IL-2) alone, and to assess the relationship of hypothyroidism to clinical response. A cohort of 281 consecutive patients with metastatic melanoma or renal carcinoma were treated with IL-2 alone from July 1, 1989 until June 30, 1993. The majority (n = 216) received high-dose IL-2 and the remainder (n = 65) received low-dose therapy.

Hypersensitivity reactions to chemotherapy agents in patients receiving chemoimmunotherapy with high-dose interleukin 2.

Background: Treatment with the immune system modulator interleukin 2 (IL-2) can result in a number of immunologic abnormalities ranging from suppression of delayed-type hypersensitivity responses and neutrophil activity to autoimmune thyroiditis and hypersensitivity reactions against iodine-containing radiographic contrast media. There are a number of published reports of chemoimmunotherapy using IL-2 in combination with various chemotherapeutic agents to treat patients with certain cancers, but none have described hypersensitivity responses to the chemotherapeutic agents given.

Purpose: In the early stages of an ongoing clinical trial of the efficacy of combination chemoimmunotherapy for the treatment of patients with metastatic melanoma, we discovered that a number of the patients experienced unexpected hypersensitivity reactions after receiving chemotherapy.

A quantum mechanical study of the active site of aspartic proteinases.

We have performed ab initio self-consistent field (SCF) and configuration interaction (CI) calculations on the active site of the aspartic proteinases pepsin and endothiapepsin. The active site, which carries a formal negative charge to effect hydrolysis, was modeled as a formic acid/formate anion moiety and a water molecule, and the nearest hydrogen bonding residues (Gly34, Ser35, Gly217, and Thr218, with respect to the residue numbering in endothiapepsin) were modeled as formamide and methanol molecules. Four possible binding modes for the active-site water molecule were considered.

Nicotinylalanine increases cerebral kynurenic acid content and has anticonvulsant activity.

1. Nicotinylalanine is an analogue of kynurenine which has been reported to inhibit the enzymes kynurenine hydroxylase and kynureninase. 2.

Prevention of acute gastric erosions in the rat by novel semi-synthetic amphipathic analogues of pepstatin.

Pepstatin is a potent aspartyl proteinase inhibitor which is virtually insoluble in physiological media. Five semi-synthetic amphipathic analogues of pepstatin, prepared by N terminal substitution of native pepstatin with hydrophilic oligopeptides, have been assessed for their ability to protect the mucosa in two animal models of acute gastric erosions. Concentrations of approximately 90 pmol/mg were achieved in the rat gastric mucosa after oral administration of a 20 mmol solution.

Effect of nitroglycerin ointment placement on the severity of headache and flushing in patients with cardiac disease.

Fifty-six patients with cardiac disease participated in a study to determine the effect of site placement on patient reports of headache and flushing after topical nitroglycerin ointment placement. Nitroglycerin was placed on the upper arm, chest, and pelvis in random order. Approximately 30 minutes after application, patients were asked to evaluate their headache and flushing using a visual analogue scale.

O-phosphohomoserine, a naturally occurring analogue of phosphonate amino acid antagonists, is an N-methyl-D-aspartate (NMDA) antagonist in rat hippocampus.

O-Phosphohomoserine, an analogue of the excitatory amino acid antagonist 2-amino-phosphonovalerate, has been synthesized and tested for activity as an excitatory amino acid antagonist. The tests were carried out on 500 micron thick slices of rat hippocampus superfused in vitro at 30 degrees C. Antidromic and orthodromic potentials were studied in the CA1 region, recording from the pyramidal cell layer.

A rational approach to the specific chemotherapy of pancreatitis.

Oedematous pancreatitis is pancreatic acinar cell damage with leakage into the peritoneal cavity and circulation of the inactive zymogens of digestive enzymes and active amylase and lipase. Pancreatic oedema and intra-abdominal fat necrosis occur. Necrotising pancreatitis is pancreatic acinar cell damage accompanied by the specific conversion of trypsinogens to trypsins, at a rate, and on a scale, sufficient to overwhelm local defences.