PubMed Health⌕ Search

Biomedical subjects

C Ilardi

Publications and source records attributed to C Ilardi.

11 recordsLinked to original sources

Phase II study of pemetrexed disodium (Alimta) administered with oral folic acid in patients with advanced gastric cancer.

BACKGROUND: The aim of this study was to assess the activity of pemetrexed in patients with advanced gastric cancer. PATIENTS AND METHODS: Thirty-eight eligible patients (median age 60 years) received pemetrexed 500 mg/m(2) every 3 weeks. Since toxicity was considerable in the first six patients, the protocol was amended to supplement subsequent patients with oral folic acid (5 mg/day on days -2 to +2 of every cycle). RESULTS: Among 36 stage IV patients evaluable for efficacy (six non-supplemented\30 supplemented), there were two complete and six partial responses. The response rate was 21% (95% confidence interval 8% to 32%) according to intention-to-treat analysis. All responding patients were in the supplemented group. The median duration of response was 4.6 months and the median survival was 7.8 months. Five of six non-supplemented patients (83%) developed grade 3/4 neutropenia; two (33%) unsupplemented patients discontinued; two (33%) patients died due to toxicity. In the supplemented group, 12 of 32 patients (37%) had grade 3/4 neutropenia. None of the supplemented patients discontinued treatment due to hematological toxicity. Severe non-hematological toxicities were infrequent. CONCLUSIONS: The activity of pemetrexed is promising in light of the tumor burden in these patients (all patients were stage IV and 39% had three or more organs involved). Toxicities were remarkably decreased with folic acid supplementation. Combination studies are warranted.

Adenocarcinoma↗

Studies on enzymatic activity and conformational stability of muscle acylphosphatase mutated at conserved lysine residues.

An oligonucleotide-directed mutagenesis study was carried out on the five acylphosphatase conserved lysine residues to assess their possible participation in enzyme active site formation and their contribution to the enzyme conformational stability. The study was designed to eliminate the ambiguity arising from the presence of a sulfate ion, an enzyme competitive inhibitor, bound to lysine 32 and 68 in the crystal structure of the erythrocyte isoenzyme. Furthermore, previous kinetic studies suggested the presence of residues with pKa=7.9 and 11, tentatively identified as two lysines. The kinetic parameters for the mutants under investigation are not significantly different from those of the wild-type enzyme, demonstrating that none of the lysine residues are involved in catalysis or in substrate binding. In addition, thermal and urea denaturation experiments performed by circular dichroism indicate that the mutated lysine residues do not play a significant role in the enzyme structural stabilization, as the destabilizing energy averages 1.40 kJ/mol. Such results are in agreement with those obtained with other proteins indicating that lysine residues make little contribution to the stability of the native structure.

Acid Anhydride Hydrolases↗

Neutrophil chemotaxis and neutrophil elastase in the aortic wall in patients with abdominal aortic aneurysms.

To test the hypothesis that elastin-derived peptides (EDP) from human aortic tissue may be chemotactic for inflammatory cells, we studied the chemotaxis of neutrophils and monocytes to EDP derived from abdominal aortic aneurysm (AAA), aortic occlusive disease (AOD), and control aortas. In addition, we determined if neutrophils deliver neutrophil elastase to the aorta in vivo by staining for neutrophil elastase (NE) throughout the course of abdominal aortic aneurysms with the monoclonal antibody to human NE. EDP from AAA, AOD, and control tissue demonstrated significant chemotactic activity for both neutrophils and monocytes. All neutrophils had a greater attraction to EDP from AAA tissue compared to AOD and control aorta. Neutrophils from AAA patients were more attracted to EDP of AAA tissue than were neutrophils of AOD or control patients attracted to their respective aortic EDP. Neutrophil elastase stained positive in the adventitia and thrombus throughout the course of the aneurysm, but was not found in the intima, media, or plaque of the aorta.

Aorta, Abdominal↗

Effects of the cholecystokinin receptor antagonist L-364,718 on experimental pancreatitis in mice.

The effects of the cholecystokinin receptor antagonist L-364,718 was studied in a model of mild pancreatitis induced in mice by repeated injections of the secretagogue caerulein and in a lethal form of pancreatitis induced by feeding mice an ethionine-supplemented choline-deficient diet. L-364,718 prevented the caerulein-induced rise in serum amylase and pancreatic weight in a dose-dependent manner, the most effective dose being 0.1 mg/kg body wt. L-364,718 also prevented the caerulein-induced pancreatic inflammation as seen by light microscopy. L-364,718 offered no protective effects as determined by changes in serum amylase, pancreatic weight, histology, or mortality in the ethionine-supplemented choline-deficient diet model.

Amylases↗

Percutaneous sonographic needle aspiration biopsy of endoscopically negative gastric carcinoma.

We report here the use of ultrasound-guided percutaneous fine needle aspiration gastric biopsies in three patients with endoscopically negative biopsies. Two men, ages 60 and 64, and one woman, age 64, with signs and symptoms of weight loss, abdominal pain, and early satiety, had barium contrast studies suggestive of thickened gastric walls of the antrum and cardia, yet multiple endoscopic biopsies were negative for malignancy. Using real time sector B-scan ultrasonography, percutaneous fine needle aspiration biopsy retrieved signet cell carcinomatous cytologic material in all three patients. No complications were noted. In patients with clinical and radiographic findings compatible with an infiltrative process but negative endoscopic biopsies, in whom sonography can identify a thickened stomach wall, we suggest that percutaneous fine needle aspiration biopsy be attempted.

Adenocarcinoma, Mucinous↗

Paraneoplastic syndrome in squamous cell carcinoma of urinary bladder.

Hypercalcemia with metastatic tumor is a common clinical entity, but without metastasis, hypercalcemia as a manifestation of squamous cell carcinoma of the bladder is rare. We present a case demonstrating immunoreactive parathyroid hormone-like activity in a nonmetastasizing tumor. Hypercalcemia subsided after ablative surgery.

Aged↗

Superior mesenteric artery balloon occlusion. A nonoperative model of small bowel ischemia in dogs.

The purpose of this study was to develop a nonoperative animal model of small bowel ischemia that could be used for subsequent studies of intestinal ischemia. Ten mongrel dogs underwent balloon occlusion of their superior mesenteric artery after percutaneous insertion of a balloon tipped catheter through the femoral artery. Small bowel biopsies taken at various time intervals demonstrated mucosal congestion, hemorrhage, and sloughing consistent with classic small bowel ischemia. These changes consistently began 3 hours after occlusion with transmural necrosis and perforation occurring by 18 hours after occlusion. Fluoroscopy demonstrated little or no flow in the mesenteric circulation during balloon occlusion. This model provides a standard nonoperative approach for the induction of intestinal ischemia in dogs and could be a valuable tool in the study of intestinal ischemia.

Animals↗

Quantitation of human synovial mast cells in rheumatoid arthritis and other rheumatic diseases.

We examined sections of synovial membranes from 14 patients with rheumatoid arthritis (RA), 7 with other rheumatic diseases, and 10 with no apparent joint disease. Patients with RA and other rheumatic diseases had significantly more synovial mast cells/vessel than patients with no joint disease (0.49 and 0.20, respectively, versus 0.03). They also had significantly more total mast cells/10 fields than patients with no joint disease (9.9 and 5.0, respectively, versus 0.4). Within the rheumatoid group, patients with active disease had more total mast cells/10 fields than patients clinically considered to have end-stage disease (P less than 0.05). Synovial basophils were not identified in any patient. Synovial vascularity was similar for all groups (2.3 vessels/field). The role of the synovial mast cell in RA and other rheumatic diseases remains to be determined.

Arthritis, Rheumatoid↗