The comparison of effects of processed Aconiti tuber, U50488H and MK-801 on the antinociceptive tolerance to morphine

In the previous studies, we demonstrated that an oriental herbal medicine, processed Aconiti tuber (PAT), at subanalgesic doses could inhibit or reverse the antinociceptive tolerance to morphine. In the present study, we compared the effect of PAT, trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidin)cyclohexyl)-benzeneacetamide methane sulfonate hydrate (U50488H), a selective kappa opioid receptor (KOR) agonist, and (-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine-maleate (MK-801), a N-methyl-D-aspartate (NMDA) receptor antagonist, on the antinociceptive tolerance to morphine in the same experimental condition. Mice received subcutaneous morphine (10 mg/kg), and oral PAT at a subanalgesic dose (0.3 g/kg for mechanical or 1.0 g/kg for thermal test), or intraperitoneal U50488H at a subanalgesic dose (3 mg/kg), or MK-801 at a subanalgesic dose (0.1 mg/kg) once daily for 14 days. The mechanical nociceptive threshold was measured before, and at 60 min by tail pressure testing, and thermal nociceptive latency was measured before, and at 30 min by hot plate testing, after daily morphine injections. PAT and U50488H could not only inhibit the development of morphine tolerance but also reverse the already-developed morphine tolerance, while MK-801 could only inhibit the development of morphine tolerance but not reverse the already-developed morphine tolerance, in both mechanical and thermal nociceptive tests. These data suggested that PAT, an indirect-acting KOR agonist, share the common pharmacological property of KOR agonists on morphine tolerance, and that PAT may be superior to some NMDA receptor antagonists which do not reverse already-developed morphine tolerance.     

Two Lambert-Eaton Myasthenic Syndrome Patients with Ameliorated Activities of Daily Living Due to Cholinesterase Inhibitors

We herein report two P/Q-type voltage-gated calcium channel (VGCC) antibody-positive Lambert-Eaton myasthenic syndrome (LEMS) patients who responded dramatically to cholinesterase inhibitors. Patient 1, a 76-year-old man, had small-cell lung cancer and developed LEMS during chemotherapy. When symptomatic treatment was started with pyridostigmine, gait disturbance was ameliorated, and his modified Rankin scale decreased from 4 points to 3 points. Patient 2, a 68-year-old man, had cancer-free LEMS. Distigmine bromide was very effective and ameliorated not only his gait disturbance but also autonomic symptoms, and his modified Rankin scale decreased from 2 points to 1 point. Cholinesterase inhibitors alone may be effective in a small portion of LEMS patients.     

Recurrent Squamous Cell Carcinoma of the Breast with Undifferentiated Features: Report of a Case

Squamous cell carcinoma of the breast is a rare type of cancer, the origin of which is still uncertain. We report a case of squamous cell carcinoma of the breast with a recurrent tumor that showed undifferentiated features. The patient was a 55-year-old woman who originally presented with a left breast mass in the upper outer quadrant. Echography showed a 46 × 29 × 23-mm mass with cavity formation, and aspiration cytology confirmed a diagnosis of squamous cell carcinoma. A modified radical mastectomy with level III lymph node dissection was performed. Pathologically, the tumor was composed of squamous cell carcinoma and noninvasive ductal carcinoma. A recurrent tumor showing undifferentiated features was detected in the left forechest 3 months after the operation, and tumorectomy with partial resection of the major and minor pectoralis muscles was performed. Despite intensive therapy including chemotherapy (CEF: cyclophosphamide, epirubicin, 5-fluorouracil) and irradiation (50 Gy), the patient died from pulmonary and skin metastases 20 months after her initial operation. The squamous cell carcinoma of the breast in this patient grew rapidly and her prognosis was poor. Immunohistochemical findings indicated the possibility that the squamous cell carcinoma developed from noninvasive ductal carcinoma of the comedo type, and that the undifferentiated cells from the site of recurrence developed from dedifferentiation of the squamous cell carcinoma. Received: August 10, 2001 / Accepted: March 5, 2002     

Application of laparoscopic distal pancreatectomy for normal anatomy after hiatal hernia repair: A case report

We describe a case of pancreatic tumor associated with a giant type IV hiatal hernia that had prolapsed into the posterior mediastinum. Hiatal hernia repair should be performed first because it enables laparoscopic distal pancreatectomy to be performed in the normal anatomical position.     

TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome-positive leukemia cells

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) have been implicated in antitumor immunity and therapy. In the present study, we investigated the sensitivity of Philadelphia chromosome (Ph1)-positive leukemia cell lines to TRAIL- or FasL-induced cell death to explore the possible contribution of these molecules to immunotherapy against Ph1-positive leukemias. TRAIL, but not FasL, effectively induced apoptotic cell death in most of 5 chronic myelogenous leukemia-derived and 7 acute leukemia-derived Ph1-positive cell lines. The sensitivity to TRAIL was correlated with cell-surface expression of death-inducing receptors DR4 and/or DR5. The TRAIL-induced cell death was caspase-dependent and enhanced by nuclear factor kappa B inhibitors. Moreover, primary leukemia cells from Ph1-positive acute lymphoblastic leukemia patients were also sensitive to TRAIL, but not to FasL, depending on DR4/DR5 expression. Fas-associated death domain protein (FADD) and caspase-8, components of death-inducing signaling complex (DISC), as well as FLIP (FLICE [Fas-associating protein with death domain-like interleukin-1-converting enzyme]/caspase-8 inhibitory protein), a negative regulator of caspase-8, were expressed ubiquitously in Ph1-positive leukemia cell lines irrespective of their differential sensitivities to TRAIL and FasL. Notably, TRAIL could induce cell death in the Ph1-positive leukemia cell lines that were refractory to a BCR-ABL-specific tyrosine kinase inhibitor imatinib mesylate (STI571; Novartis Pharma, Basel, Switzerland). These results suggested the potential utility of recombinant TRAIL as a novel therapeutic agent and the possible contribution of endogenously expressed TRAIL to immunotherapy against Ph1-positive leukemias.     

Mumbai disease in far western Nepal: HIV infection and syphilis among male migrant-returnees and non-migrants

OBJECTIVE: To measure the seroprevalence of human immunodeficiency virus (HIV) infection and syphilis, and to assess the behavioural risk factors for these infections among migrant-returnees and non-migrants in far western Nepal. METHODS: In April 2001, we recruited 97 male migrant-returnees and 40 non-migrants from five rural villages in Doti district where migration to Mumbai is common. For data collection, we conducted a serological examination for HIV and syphilis, and a perception and behaviour survey on HIV and other sexually transmitted infections. RESULTS: We found that 11 of 137 men (8%) were positive for HIV infection and 30 men (22%) for syphilis. The respondents, especially the migrant-returnees from Mumbai, were engaging in risky behaviours such as pre- or extramarital sex, and sex with multiple partners, including sex workers. CONCLUSIONS: This study revealed high HIV and syphilis prevalence among the male migrant-returnees and non-migrants in far western Nepal where migration to Mumbai is common. The prevalent behaviours, particularly among the migrant-returnees, imply urgent needs of the behavioural modification programme in this area to prevent the spread of HIV infection to general population.