Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CT-2584 HMS, 1-(11-dodecylamino-10-hydroxyundecyl)-3, 7-dimethylxanthine-hydrogen methanesulphonate, is a modulator of intracellular phosphatidic acid. We treated 30 patients as part of a Phase I and pharmacokinetic study to determine the maximum-tolerated dose of CT-2584 HMS, toxicity profiles, pharmacokinetic profile and antitumour effects at escalating dose levels. CT-2584 HMS was given as a continuous infusion for 6 hours for 5 consecutive days every 3 weeks. Plasma samples for pharmacokinetic studies were analysed using a validated high-performance liquid chromatographic assay. Mean C(max)and AUC values for each dose group were similar on days 1 and 5 and increases in plasma concentration (C(max)and AUC) appeared proportional to the dose. CT-2584 HMS had a mean elimination half-life of 7.3 hours. Values of V(d)and clearance were independent of dose and duration of treatment. Dose escalation was halted at 585 mg/m(2)because of malaise and lethargy, which was sometimes accompanied by nausea and headache. 26 patients were evaluable for response, one patient with pleural mesothelioma achieved a partial response to treatment confirmed by CT scanning. A dose level of 520 mg/m(2)daily x 5 days would be suitable for Phase II testing. Alternative schedules of CT-2584 HMS to overcome the limiting toxicity of malaise would be worthy of examination.
 ...
PMID:Phase I and pharmacologic study of CT-2584 HMS, a modulator of phosphatidic acid, in adult patients with solid tumours. 1110 52

A 19 year old man presented with a six month history of chest pain, dyspnoea, and lethargy and was found on an echocardiogram to have a dilated left ventricle with a small pericardial effusion. Ramipril and a course of steroids were tried but serial echocardiograms showed a persistently thickened pericardium and slowly developing features of constriction. On computed tomography, a large mediastinal mass encasing the heart, along with para-aortic and paratracheal lymphadenopathy, was found. Right heart catheter studies showed equal pressures in all four chambers. His deteriorating clinical condition led to a pericardiectomy. Histology confirmed primary pericardial mesothelioma. The patient died soon after surgery.
 ...
PMID:Primary pericardial mesothelioma presenting as pericardial constriction: a case report. 1467 67

Primary tumors of serosal surfaces are uncommon in veterinary medicine. Mesothelial neoplasms can be benign or malignant, and are classified as predominantly epitheloid, mixed (biphasic), or fibrous (spindle cell, fibrosarcomatous), with fibrous mesotheliomas reported least in domestic species. A 9-year-old Domestic Shorthair cat presented on emergency with a brief history of weakness and lethargy. On presentation, the cat was semicomatose, hypothermic, and hypotensive with a markedly distended abdomen. Approximately 1 liter of serosanguineous fluid was removed via abdominocentesis. Diagnostic imaging and cytologic evaluation of fine-needle aspirates were suggestive of neoplasia, and the cat was subsequently euthanized. At necropsy, the omentum was contracted cranially into an irregular lobular mass that surrounded the stomach and proximal intestinal tract, and focally infiltrated the spleen. Both visceral and parietal peritoneal surfaces were thickened and contained off-white friable material and occasionally firm fibrous plaques. Microscopically, serosal surfaces were expanded by neoplastic spindle cells, which were often accompanied by moderate to abundant fibrous stroma. Neoplastic cells had varying degrees of immunoreactivity for cytokeratin, vimentin, desmin, and smooth muscle actin, which was consistent with the diagnosis of mesothelioma.
 ...
PMID:Peritoneal fibrosarcomatous mesothelioma in a cat. 2190 98

A 37-year-old female yellow-naped Amazon parrot (Amazona auropalliata) was presented with a history of lethargy, inappetence, and decreased vocalizations. On examination, the coelom was moderately distended and palpated fluctuant, and the heart was muffled on auscultation. Coelomic ultrasound, coelomocentesis, and radiographs were performed and revealed an enlarged cardiac silhouette and marked coelomic effusion. Pericardial effusion was confirmed by echocardiography. A well-circumscribed, hyperechoic soft tissue density was observed at the level of the right atrium on initial echocardiography; however, a cardiac mass was not identified by computed tomography scan or repeat echocardiograms. Ultrasound-guided pericardiocentesis was performed under anesthesia, and cytology results were consistent with hemorrhage; no neoplastic cells were identified. A repeat echocardiogram 4 days after pericardiocentesis revealed recurrence of the pericardial effusion. Due to the grave prognosis, the owners declined endoscopic pericardiectomy, and the patient died the following day. On postmortem examination, the pericardial surface of the heart was covered in a white to yellow, multinodular mass layer. Histologic analysis revealed a multinodular mass extending from the atria, running along the epicardium distally, and often extending into the myocardium. Neoplastic cells present in the heart mass and pericardium did not stain with a Churukian-Schenk stain, and thyroglobulin immunohistochemistry was negative. Cytokeratin and vimentin stains showed positive expression in the neoplastic cells within the mass. These results are consistent with a diagnosis of mesothelioma. This is the first report of mesothelioma in a psittacine bird.
 ...
PMID:Pericardial Mesothelioma in a Yellow-naped Amazon Parrot (Amazona auropalliata). 2586 68

A 10-year-old female striped skunk (Mephitis mephitis) was admitted with severe abdominal distension and lethargy. Cytological examination of the peritoneal fluid revealed activated mesothelial cells. At necropsy, numerous growing together, projecting, 2 to 20 mm in diameter tawny to white masses were scattered throughout the peritoneum including the mesentery, omentum and intestinal serosa. Microscopically, the tumor was composed of prominent papillo-tubular structures, and immunohistochemically, the spindle to polygonal-shaped tumor cells with nuclear polymorphism were strongly reactive for calretinin. Based on those diagnostic features, the neoplasia was diagnosed as malignant mesothelioma. This is the first case report of mesothelioma in the skunk.
...
PMID:Primary diffuse malignant peritoneal mesothelioma in a striped skunk (Mephitis mephitis). 2656 87