BACKGROUND: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling axis has emerged as a novel target for cancer therapy. Agents that inhibit this pathway are currently under development for lung cancer treatment. In the present study, we have tested whether dual inhibition of PI3K/Akt/mTOR signaling can lead to enahnced antitumor effects. We have also examined the role of autophagy during this process. METHODS: We analyzed the combination effect of the mTOR inhibitor, temsirolimus, and the Akt inhibitor, GSK690693, on the survival of NCI-H460 and A549 non-small cell lung cancer cells. Cell proliferation was determined by MTT assay and apoptosis induction was evaluated by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Autophagy induction was also evaluated by acridine orange staining. Changes of apoptosis or autophagy-related proteins were evaluated by western blot analysis. RESULTS: Combination treatment with temsirolimus and GSK690693 caused synergistically increased cell death in NCI-H460 and A549 cells. This was attributable to increased induction of apoptosis. Caspase 3 activation and poly(ADP-ribose) polymerase cleavage accompanied these findings. Autophagy also increased and inhibition of autophagy resulted in increased cell death, suggesting its cytoprotective role during this process. CONCLUSION: Taken together, our results suggest that the combination of temsirolimus and GSK690693 could be a novel strategy for lung cancer therapy. Inhibition of autophagy could also be a promising method of enhancing the combination effect of these drugs.
Acridine Orange ; Apoptosis ; Autophagy ; Axis, Cervical Vertebra ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung ; Caspase 3 ; Cell Death ; Cell Proliferation ; DNA Nucleotidylexotransferase ; Flow Cytometry ; Lung Neoplasms ; Oxadiazoles ; Phosphatidylinositol 3-Kinases ; Poly(ADP-ribose) Polymerases ; Proteins ; Sirolimus ; TOR Serine-Threonine Kinases

Heparin-induced thrombocytopenia (HIT) is a heparin-dependent antibody-mediated platelet activating syndrome frequently accompanying thrombocytopenia, thromboembolism. We experienced a case of cardiopulmonary bypass using hirudin, a direct thrombin inhibitor, in a patient with HIT. The patient who showed thrombocytopenia and thrombosis after heparin re-exposure was highly suspected of having HIT. Hirudin was used in this case as an anticoagulating agent during cardiopulmonary bypass (CPB) to prevent serious complications of heparin. Hirudin 0.3 mg/kg was mixed with a priming solution of CPB and a 0.2 mg/kg IV bolus followed by a continuous infusion of hirudin 0.15 mg/kg given for anticoagulation. After CPB, forced diuresis and platelet transfusion was performed and the patient was recovered without complication.
Blood Platelets ; Cardiopulmonary Bypass* ; Diuresis ; Heparin ; Hirudins* ; Humans ; Platelet Transfusion ; Thrombin ; Thrombocytopenia* ; Thromboembolism ; Thrombosis

OBJECTIVE: We investigated plantar nerve injuries associated with calcaneal fracture and severity of disability. METHOD: From July, 2001 to June, 2002, twelve patients who had calcaneal fractures with persistent foot pain and paresthesia were included in our study. We examined electromyography for medial and lateral plantar nerve, inferior calcaneal nerve, also evaluated types of calcaneal fracture and severity of pain and disability with nerve injury. RESULTS: The intraarticular types were 13 cases, extraarticular type was 1 case and communited types were 2 cases. In the electromyographic findings, the 9 cases were diagnosed asneuropathy. In a cases with neuropathy, 8 persons complained over moderate degree of pain and all persons complained over moderate degree of walking disability. However one of three persons without neuropathy complained over moderate degree of walking disability. So disability tended to be more severe in cases with neuropathy. CONCLUSION: We think that neuropathy associated with calcaneal fracture is a cause of aggravation of pain and walking disability, and electromyography for nerves of foot will be needed in the calcaneal fracture.
Electromyography ; Foot ; Humans ; Paresthesia ; Walking

OBJECTIVE: To evaluate the correlation of electrodiagnostic severity, severity of symptom, and clinical severity in carpal tunnel syndrome (CTS). METHOD: The sixty eight patients with documented CTS in outpatient clinic from January, 2000 to June, 2001 were included (9 male, 59 female, averaged age 50.0+/-8.8 years). We evaluated the severity of symptom, functional status of ADL with the Levine' questionnaire, and clinical severity with 3 kinds of examination (thenar atrophy, sensory change, and Phalen's test). The electrodiagnostic severity was classified according to Stevens' classification and compared with the severity of symptom, functional status, and clinical severity. RESULTS: The electrodiagnostic severity was classified into three degrees. Five patients (7.4%) were classified into mild degree, 32 patients (47.1%) moderate degree, 31 patients (45.6%) severe degree. The average of severity of symptom scores were 28.4+/-8.5, 31.8+/-7.4, and 31.8+/-9.1 respectively, and there was no significant difference (p>0.05) between the groups. Functional status scales were 14.2+/-6.7, 15.6+/-5.4 and 18.9+/-7.0 respectively and no significant difference (p=0.07) but there was a tendency that the severer was electrodiagnostic severity, the more decreased functional status scale. The clinical severity showed a significant correlation with the electrodiagnostic severity (p<0.05). CONCLUSION: The electrodiagnostic severity has a significant correlation with the clinical severity, but not with the severity of symptom, the functional status in CTS.
Activities of Daily Living ; Ambulatory Care Facilities ; Atrophy ; Carpal Tunnel Syndrome* ; Classification ; Female ; Humans ; Male ; Surveys and Questionnaires ; Weights and Measures

Subcutaneous fat necrosis of the newborn is a rare, benign disease usually found in full-term infants. It occurs usually in a few weeks after birth, as one or multiple indurated nodules or plaques on the fat pads-rich fraction of the body and disappeared after few weeks to months. Complications such as hypercalcemia, pain, lipid abnormalities (dyslipidemia), renal failure, and subcutaneous atrophy may occur. We report a case of subcutaneous fat necrosis associated with hypoglycemia and meconium aspiration syndrome in the term infant and review the associated literatures.
Atrophy ; Fat Necrosis ; Humans ; Hypercalcemia ; Hypoglycemia* ; Infant ; Infant, Newborn* ; Meconium Aspiration Syndrome* ; Necrosis* ; Parturition ; Renal Insufficiency ; Subcutaneous Fat*

BACKGROUND: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. METHODS: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. RESULTS: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-G1 phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. CONCLUSION: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.
Apoptosis ; Apoptosis Regulatory Proteins ; Autophagy ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung ; Caspase 3 ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Death ; DNA ; Epidermal Growth Factor ; Flow Cytometry ; Lung ; Lung Neoplasms ; Lysosomes ; Monensin ; Phosphotransferases ; Poly(ADP-ribose) Polymerases ; Proteins ; Quinazolines ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2 ; Sirolimus ; Stress, Physiological ; TOR Serine-Threonine Kinases ; Erlotinib Hydrochloride

The thoracic splanchnic nerve block has been used in managing abdominal pain, especially for pains arising from abdominal cancers. A 27-year-old male patient who had a constant abdominal pain was referred to our clinic for pain management but had no organic disease. The numeric rating scale (NRS) for pain scored 7/10. We applied a diagnostic thoracic splanchnic nerve block under the diagnosis of functional abdominal pain syndrome. Since the block reduced the pain, we applied a radiofrequency thermocoagulation at the T11 and T12 vertebral level. Thereafter, his symptoms improved markedly with pain decreasing to an NRS score of 2-3/10. Hereby, we report a successful management of functional abdominal pain via radiofrequency thermocoagulation of the thoracic splanchnic nerves.
Abdominal Pain ; Adult ; Electrocoagulation ; Humans ; Male ; Pain Management ; Splanchnic Nerves

OBJECTIVE: To find a new method and usefulness of study on sensory nerve conduction of lateral sural cutaneous nerve (LSCN). METHOD: The 60 extremities of 30 adults without peripheral neuropathy were placed in a prone position. Next, each subject was administered with an antidromic stimulation at a point 3 cm lateral from the center of the popliteal fossa. With the aid of active electrodes, the sensory nerve action potentials (SNAPs) were recorded at points 10 cm inferior and 1 cm lateral to the stimulation site. The method of sensory nerve conduction study suggested by Campagnolo et al. was performed simultaneously, to compare of the frequency of SNAPs and the amplitudes. RESULTS: For the sensory nerve conduction study of the LSCN suggested in this report, SNAPs were obtained in 49 extremities, with a revelation rate of 81.7%. The mean amplitude was 11.91+/-3.68micronV. In the results of the tests suggested by Campagnolo et al., the SNAPs were obtained in 29 extremities, with a revelation rate of 48.3%. The mean amplitude was 8.37+/-5.21micronV. Significance testing of the electrodiagnostic method recommended in this study revealed that many SNAPs were observed for the LSCN, with statistically significant action potential amplitudes. CONCLUSION: This study presents the new method and reference values of sensory nerve conduction for LSCN, which is thought to be useful in electrodiagnostic studies to diagnose entrapment neuropathy.
Action Potentials ; Adult ; Electrodes ; Electromyography ; Extremities ; Humans ; Nerve Compression Syndromes ; Neural Conduction ; Organic Chemicals ; Peripheral Nervous System Diseases ; Peroneal Nerve ; Prone Position ; Reference Values ; Sural Nerve

Celiomesenteric trunk is a rare anomaly, and its co-occurrence with an aneurysm is even more unusual. We present a case of celiomesenteric trunk with a concurrent hepatic arterial aneurysm, both of which were found incidentally on screening abdominal ultrasonography.
Abdomen ; Aneurysm ; Hepatic Artery ; Mass Screening

Low-grade endometrial stromal sarcoma (ESS) is an uncommon gynecologic malignancy of mesodermal origin. Pulmonary metastasis of low-grade ESS can occur years and decades after the treatment of the primary disease. Low-grade ESS is frequently mistaken as benign uterine neoplasm like uterine leiomyoma, which can potentially lead to a misdiagnosis. We present a case of a 42-year-old woman with low-grade ESS, that initially presented as an incidental lung mass with multiple pulmonary nodules, seven years after an uterine myomectomy. A 6.9x5.8 cm-sized intrapelvic mass suspected of uterine origin was discovered while searching for potential extrathoracic primary origin. A pelviscopy and simultaneous thoracoscopic lung biopsy were conducted for pathologic diagnosis. Finally, the diagnosis was confirmed as low-grade ESS with lung metastasis based on the histopathologic examination with immunohistochemical stain, which was showed positive for CD10 and hormone receptor markers (estrogen and progesterone receptors) in both pelvic and lung specimens.
Adult ; Biopsy ; Diagnosis ; Diagnostic Errors ; Female ; Humans ; Leiomyoma ; Lung* ; Mesoderm ; Multiple Pulmonary Nodules* ; Neoplasm Metastasis ; Progesterone ; Sarcoma, Endometrial Stromal* ; Uterine Myomectomy ; Uterine Neoplasms