Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The compound CMB-401 is an immunoconjugate consisting of the monoclonal antibody (MAb) hCTM01 directed against polymorphic epithelial mucin covalently bound to the cytotoxic antibiotic calicheamicin by an amide linker. We evaluated CMB-401 as monotherapy for the treatment of recurrent platinum-sensitive epithelial ovarian carcinoma (EOC). Twenty-one 21 women aged 38 to 80 years with recurrent EOC (recurrence >6 months after initial platinum-containing chemotherapy) were enrolled. Tumor response and serum cancer antigen 125 (CA125) levels were assessed before and after active treatment. After an initial intravenous (i.v.) dose of hCTM01 (without calicheamicin), the calicheamicin-linked CMB-401 (16 mg/m(2 ) i.v.) was administered over 60 min for up to 7 cycles, with 4 weeks between cycles. Nineteen patients were evaluable. Measurable changes observed following administration of CMB-401 did not meet the criteria for partial remission (PR). CMB-401 was not effective as monotherapy for this type of EOC. Adverse events experienced by patients in the study included nausea (95%), asthenia (90%), abdominal pain (62%), headache (57%), anorexia (57%), and diarrhea (57%), mostly at a toxicity grade level of 1 or 2. Based on published efficacy of conjugates that deliver calicheamicin via hybrid (bifunctional) linkers [e.g. gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia], we hypothesize that the amide linker used in CMB-401 may have contributed to its failure to induce PR in patients in this study. Use of hybrid linkers to target hCTM01 or other antibodies to EOC may warrant further investigation.
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PMID:A phase 2 study of the cytotoxic immunoconjugate CMB-401 (hCTM01-calicheamicin) in patients with platinum-sensitive recurrent epithelial ovarian carcinoma. 1266 49

The presence of circulating autoantibodies to gut enterocytes has been very rarely described in adults and is considered a possible cause of refractory sprue. Our aims was to describe the case of an adult patient with serum anti-enterocyte autoantibodies associated with a clinical picture characterized by involvement of both the small intestine and colon. A female, age 50, had suffered from diarrhea with mucus and blood, abdominal pain, thinness, anemia, and leukopenia since the age of 20. She also suffered from HCV infection and had mild chronic hepatitis. Family history was positive for autoimmunity. Symptoms were reported to worsen after eating gluten-containing foods, but anti-transglutaminase and anti-endomysial antibodies were negative. Intestinal histology showed mild, patch villous atrophy with a high intraepithelial lymphocyte count, but a normal number of intraepithelial lymphocytes carrying the gamma/delta+ receptor. HLA was: A11, A31 (19), B52 (5), DR 15 (2), DR 14 (6), DR 51, DR 52, DQ1. Colonoscopy did not show ulcerations or erosions and colon histology showed a moderate inflammatory infiltrate without minor crypt distortion or granuloma. RAST tests were positive for lactalbumin, lactoglobulin, casein, egg, and gliadin. After commencement of an oligoantigenic diet, stool frequency initially decreased, but the presence of mucus in the stools persisted, with episodes of bloody diarrhea. After one year of diet, nutritional parameters were low and anemia associated with a low leukocyte count persisted. Upper and lower gastrointestinal endoscopy and histology of the small intestine and colon were virtually unchanged. Consequently, natural autoantibodies and enterocyte autoantibodies were assayed. The patient was positive for IgG class enterocyte autoantibodies at a titer of 1:34. No other organ-specific or non-organ-specific autoantibodies were positive. Prednisolone treatment was started and the symptoms improved. After one year of this treatment plus elimination diet she was reevaluated. Bowel movement frequency was normal, body weight increased, and the asthenia had completely regressed. IgG anti-enterocyte autoantibodies were absent. Histology of the distal duodenum showed a normal villus/crypt ratio and IEL infiltration was reduced. Colon histology showed a reduction in inflammatory infiltrate in the lamina propria. In conclusion, we report a case of generalized gut disorder in an adult patient, affecting both the small intestine and the colon and characterized by the presence of circulating anti-enterocyte autoantibodies. Systematic testing for enterocyte autoantibodies should be performed not only in patients with refractory sprue, but also in subjects with upper and lower intestinal symptoms who have not been definitively diagnosed.
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PMID:Autoimmune enteropathy and colitis in an adult patient. 1292 54

To assess the response rate and the tolerance of irinotecan as first-line therapy, 40 patients with metastatic gastric cancer received irinotecan 350 mg m(-2) every 3 weeks administered as a 30 min infusion. Among the 35 patients evaluable for response, two complete and five partial responses were recorded (response rate: 20.0% (95% CI:8.4-36.9%)). In total, 16 patients achieved stable disease and 12 progressive disease. In all, 66 percent of the patients benefited from tumour growth control. The median time to progression was 3.0 months (95% CI: 2.3-4.4%). The median overall survival was 7.1 months (95% CI: 5.2-9.0%). The probability of being alive at 6 months and 9 months was 61.0 and 32.4%, respectively. The median number of cycles per patient was 3 (range 1-14), and the relative dose intensity was 0.98. The most common grade 3-4 toxicities by patients were diarrhoea 20%, asthenia 10%, nausea 7.5%, vomiting 5.0%, abdominal pain 5%, neutropenia 38.5%, leucopenia 28.2%, anaemia 12.8% and thrombocytopenia 5.1%. Febrile neutropenia occurred in 12.5% of patients. These findings indicate that irinotecan is active and well tolerated in patients with metastatic gastric adenocarcinoma and warrants further evaluation in this clinical setting.
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PMID:Irinotecan is active in chemonaive patients with metastatic gastric cancer: a phase II multicentric trial. 1296 15

The purpose of this analysis was to compare treatment-emergent adverse events (TEAE) related to use of levetiracetam (LEV) reported by young and elderly patients with anxiety and cognitive disorders, and young epilepsy patients. The LEV database includes reports of TEAE from trials of patients with diagnoses of a cognitive disorder (N=719), an anxiety disorder (N=1510), or localization-related epilepsy (N=1023) who participated in clinical trials lasting up to 16 weeks. Patients were grouped as young (<65 years) or elderly (> or = 65 years). The most common TEAE occurring most frequently in the LEV-treated groups were abdominal pain, asthenia, headache, anorexia, weight loss, dizziness, insomnia, somnolence, and tremor. The only significant differences in TEAE were seen between young and elderly groups with anxiety disorders (>3% higher for LEV than for placebo-treated patients) in headache (5.2% elderly, -0.9% young, P=0.041), and tremor (5.2 and -0.5%, respectively, P=0.022) and between young anxiety patients and young epilepsy patients for somnolence (-0.7 and 5.4%, respectively, P=0.036). For the other TEAEs there was no evidence for consistent differences between young and elderly patients and between patients with different CNS disorders. Overall, LEV was well tolerated by all patient groups. The favorable adverse event profile suggests that LEV might be suitable for use by elderly patients.
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PMID:Tolerability of levetiracetam in elderly patients with CNS disorders. 1464 98

Cetuximab is a chimeric monoclonal antibody highly selective for the epidermal growth factor receptor (EGFR), which is over-expressed by 25-80% of colorectal cancer tumours and associated with advanced disease. Cetuximab induces a broad range of cellular responses in tumours expressing EGFR, enhancing sensitivity to radiotherapy and chemotherapeutic agents. In a large, randomised, open-label, multicentre study in adult patients with irinotecan-refractory, metastatic colorectal cancer expressing EGFR, cetuximab 400 mg/m2 initial dose followed by 250 mg/m2 weekly plus irinotecan (various doses) produced a greater rate of partial response and disease control (partial response plus stable disease), and increased time to disease progression, compared with cetuximab monotherapy; survival was similar in both groups. The same dosage of cetuximab combined with irinotecan, fluorouracil and folinic acid (various regimens) produced partial responses in 43-58% of patients, a complete response in 5% of patients (one study only) and stable disease in 32-52% of patients with treatment-naive metastatic colorectal cancer expressing EGFR in three small, open-label trials. The most common grade 3/4 adverse events associated with cetuximab monotherapy were acne-like rash, asthenia, abdominal pain and nausea/vomiting. In patients receiving cetuximab plus irinotecan, these were diarrhoea, asthenia, leucopenia and neutropenia.
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PMID:Cetuximab: in the treatment of metastatic colorectal cancer. 1472 61

The adrenal localization of a primary non-Hodgkin lymphoma (NHL) is rare. We report a case of a 66-yr-old woman who had severe asthenia, diffuse skin hitching and abdominal pain. The physical examination revealed poor general conditions, irritability, pallor, dehydration and diffuse skin scratching lesions. The abdomen was painful at left hypochondrium and the Giordano's maneuvre was positive on both sides. A peripheral blood smear showed the presence of big rare lymphocytes with dyshomogeneous chromatin and granulated and hyperbasophil cytoplasm. She underwent abdominal ultrasonography which showed the presence of a hypoechogenic ovoidal mass (major diameter 8.4 cm) within the splenorenal left region. The presence of the suprarenal mass was confirmed by computed tomography (CT) scan which showed an enlarged left adrenal gland (8.1 x 6.2 cm) of solid structure. The right adrenal gland was also enlarged and of round shape (4.5 cm). CT scan-guided fine needle aspiration biopsy was then carried out on the left adrenal mass. It revealed the presence of NHL type B with large cells and modest T-lymphocyte reactive component. The patient was treated with three cycles of cyclophosphamide, adriamycin, vincristine and prednisolone. At the end of the third cycle, there was a transient clinical improvement and the hitching disappeared, but the patient worsened rapidly and she died few weeks later.
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PMID:Bilateral adrenal non-Hodgkin lymphoma type B. 1500 52

Rosuvastatin (Crestor), an HMG-CoA reductase inhibitor (statin), has a favorable pharmacologic profile, including its selective uptake by hepatic cells, hydrophilic nature, and lack of metabolism by cytochrome p450 (CYP) 3A4 isoenzyme. This last property means that the potential for CYP3A4-mediated drug interactions and, as a consequence, adverse events is low in those requiring concomitant therapy with a statin and agents metabolized by CYP3A4. In a broad spectrum of adult patients with dyslipidemias, oral rosuvastatin 5-40 mg once daily effectively and rapidly improved lipid profiles in several large, randomized, mainly double-blind, multicenter trials of up to 52 weeks' duration. After 12 weeks' treatment, rosuvastatin was significantly (all p < 0.05) more effective at milligram equivalent dosages than atorvastatin, pravastatin, and simvastatin in improving the overall lipid profiles of patients with hypercholesterolemia (intent-to-treat analyses). Moreover, overall a significantly (all p < 0.001) higher proportion of patients achieved National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein-cholesterol (LDL-C) goals with rosuvastatin 10 mg/day than with therapeutic starting dosages of these other statins after 12 weeks' treatment in pooled analyses. Rosuvastatin treatment for up to 52 weeks was generally well tolerated in patients with dyslipidemias in clinical trials. The most commonly reported treatment-related adverse events were myalgia, constipation, asthenia, abdominal pain, and nausea; these were mostly transient and mild. The incidence of proteinuria or microscopic hematuria with rosuvastatin 10 or 20 mg/day was <1% versus <1.5% with rosuvastatin 40 mg/day; these events were mostly transient and not associated with acute or progressive deterioration in renal function at recommended dosages. Importantly, very few patients experienced elevations in serum creatine phosphokinase (CPK) levels of over [corrected] 10-fold the upper limit of normal (0.2-0.4% of patients) or treatment-related myopathy (<or=0.1%) [i.e. muscle aches or weakness plus the same elevated serum CPK levels] at dosages of 5-40 mg/day. In conclusion, rosuvastatin treatment effectively and rapidly improves the lipid profile in patients with a broad spectrum of dyslipidemias. In those with hypercholesterolemia (including high-risk patients), rosuvastatin was more efficacious than and generally as well tolerated as atorvastatin, simvastatin, and pravastatin, with significantly more rosuvastatin recipients achieving their NCEP ATP III target LDL-C levels. Thus, rosuvastatin has emerged as a valuable choice for first-line treatment in the management of low- to high-risk patients requiring lipid-lowering drug therapy.
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PMID:Rosuvastatin: a review of its use in the management of dyslipidemia. 1504 23

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with the fatal evolution. Recent studies in knowledge of the pathogenic mechanisms underlying ALS showed that the excitotoxicity has an important role in the neurodegeneration. The riluzole, an antagonist of glutamate, is the first drug approved by FDA for the treatment of patients with ALS. The efficacy of riluzole (dose recommended 50 mg twice a day) in prolonging the survival of patients with ALS has been demostrated in two principal controlled clinical trials. The most frequent adverse events related to riluzole treatment were: nausea, vomiting, anorexia, diarrhea, asthenia, somnolence, vertigo, circumoral paresthesia, abdominal pain and dizziness. Some events tend to be related to the dose: vertigo, diarrhea, nausea, circumoral paresthesia and anorexia appear more frequently with 200 mg/die that with lower dose. Generally with tree months from the beginning of the treatment with riluzole, an increase serum transaminase levels has been noted; mostly transient and regressing after two-sex months of treatment. A monitoring of serum transaminase levels is suggested during the first year of treatment with riluzole The clinical studies shows that the adverse events produced by riluzole are mostly reversible and dose-dependent, this demostrates a satifying profile of tolerability of the drug. Anyway, a deeper knowledge of its tolerability may lead us to a better use of riluzole, avoiding in this way the interruption of treatment.
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PMID:[Tolerability of riluzole: a review of the literature]. 1514 78

From post-mortem case records, the small bowel is the most frequent site of metastatic melanoma in the gastrointestinal (GI) tract, with gallbladder involvement occurring in 15% of cases. However, few cases have been documented in living patients and, when found, are associated with a poor prognosis. We report a case of a Caucasian man with metastatic gallbladder and small bowel melanoma from an unknown primary. He presented with diffuse abdominal pain, vomiting and progressive asthenia; subsequently, intestinal obstruction occurred. He had no past history of malignant melanoma and the primary lesion was not found. The multiple lesions, together with the absence of mucosal involvement in both the gallbladder and small bowel, led us to believe that the lesions were metastatic deposits from a probably regressed primary melanoma. It should be emphasized that surgical resection for melanoma metastatic to the GI tract is recommended for palliative reasons and can be performed safely. The clinical presentation, diagnosis, treatment and prognosis of previously reported cases of melanoma metastatic to the gallbladder and small bowel are reviewed. The differences between primary and secondary GI tract melanomas are also discussed.
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PMID:Melanoma metastatic to the gallbladder and small bowel: report of a case and review of the literature. 1545 2

The case of a patient, 37 years old, born and resident of Lima, suffering rheumatoid arthritis who underwent treatment with prednisone, methotrexate, and chloroquine is reported. This therapy was substituted for gold salts one month before her admission. After the third dose she presented symptoms of abdominal pain and diarrhea, itching, and jaundice, associated with asthenia and a feverish sensation. Liver biochemistry demonstrated elevated transaminase, bilirubin, alkaline phosphatase, eosinophilia, inversion of the rate albumin/globulin, higher titer of immunoglobulin G, as well as an elevation of amylase and lipase. The anatomopathological study showed cholestasis, hepatocyte ballooning, spotty necrosis, predominantly in zone 3 of the acinus. These findings where found consistent with a toxic reaction.
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PMID:[Hepatotoxicity and pancreatitis associated with gold salts: case report]. 1561 5


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