Intrathecal Isoniazid for Refractory Tuberculous Meningitis with Cerebral Infarction.

A 30-year-old Vietnamese woman, about 19 weeks pregnant, was admitted for acute cerebral infarction with stenosis of the left middle cerebral artery (LMCA), tuberculous meningitis, and miliary tuberculosis. Treatment with heparin, quadruple anti-tuberculosis therapy, and dexamethasone afforded prompt symptomatic improvement. However, she delivered a stillbirth, after which there was recurrence of acute cerebral infarction with LMCA occlusion, sinus thrombosis, and cranial base inflammation. A thrice-weekly 100 mg dose of intrathecal isoniazid (INH) improved the signs of meningeal inflammation. The patient was discharged ambulatory after 7 months. In refractory tuberculous meningitis, multimodal therapy with intrathecal INH and steroids should be considered.

[Palliative care during chemotherapy for advanced colon cancers].

BACKGROUND: The median survival time following chemotherapy for unresectable metastatic colorectal cancer (mCRC) is approximately 2 years. Although palliative care during the chemotherapy period is very important, it has not been reported in detail. PATIENTS AND METHODS: Information on the palliative care of 110 patients with Stage IV mCRC, who were treated from September 2007 to March 2011, was retrospectively examined. RESULTS: Following an explanation of their recurrence or metastases of mCRC, all the patients received mental care from nurses or psychiatrists. They also needed care to prevent the side effects of chemotherapy. Some patients experienced pain associated with tumor growth. Thus, they required NSAIDs or opioids to reduce the cancer-related pain. After they could not be taken chemotherapy, 87.5% of these patients consulted medical social workers to discuss where they would live. CONCLUSIONS: The patients required palliative care depending on the duration of chemotherapy for mCRC. Thus, we believe that palliative care is an important part of treatment for advanced cancer.

Pharmacological characterization and feeding-suppressive property of FMS586 [3-(5,6,7,8-tetrahydro-9-isopropyl-carbazol-3-yl)-1-methyl-1-(2-pyridin-4-yl-ethyl)-urea hydrochloride], a novel, selective, and orally active antagonist for neuropeptide Y Y5 receptor.

We evaluated the pharmacological profiles of FMS586 [3-(5,6,7,8-tetrahydro-9-isopropyl-carbazol-3-yl)-1-methyl-1-(2-pyridin-4-yl-ethyl)-urea hydrochloride], a novel tetrahydrocarbazole derivative as a neuropeptide Y (NPY) Y5 receptor antagonist. This compound showed a highly selective in vitro affinity for Y5 (IC(50) = 4.3 +/- 0.4 nM) relative to other NPY receptor subtypes like Y1 or Y2. Its binding to Y5 was found to be fully antagonistic from cyclic AMP accumulation assays in human embryonic kidney 293 cells. Pharmacokinetic analysis revealed sufficient oral availability and brain permeability of this compound accompanied with clear dose relation. We attempted to assess the selectivity of FMS586 and, thereby, to infer the physiological role of Y5 in the following feeding experiments in normal rats. An intracerebroventricular injection of NPY and Y5-selective agonist peptide induced acute and robust feeding responses in satiated rats, and prior administration of FMS586 at the doses from 25 to 100 mg/kg clearly inhibited these responses by approximately 55 and 90%, respectively. This compound also showed dose-dependent but transient suppression in natural feeding models of both overnight fasting-induced hyperphagia and spontaneous daily intake. FMS586 did not modulate food intake induced by the topical injection of norepinephrine, galanin, or gamma-aminobutyric acid receptor agonist muscimol to the paraventricular nucleus. In addition, we confirmed the Y5-specific activity profile of FMS586 by immunohistochemical analysis. Taken together, we propose not only that our compound potentially expresses specific blockade of central Y5 signals but also that Y5 receptor would certainly contribute to physiological regulation of food intake in normal rats, as suggested from its origin.