Vaccination with irradiated autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor augments antitumor immunity in some patients with metastatic non-small-cell lung carcinoma.

PURPOSE: We demonstrated that vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific, and long-lasting antitumor immunity in multiple murine models and patients with metastatic melanoma. To test whether this vaccination strategy enhances antitumor immunity in patients with metastatic non-small-cell lung cancer (NSCLC), we conducted a phase I clinical trial. PATIENTS AND METHODS: Resected metastases were processed to single-cell suspension, infected with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines consisted of 1 x 10(6), 4 x 10(6), or 1 x 10(7) cells, depending on overall yield, and were administered intradermally and subcutaneously at weekly and biweekly intervals. RESULTS: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 513 ng/10(6) cells/24 h. Toxicities were restricted to grade 1 to 2 local skin reactions. Nine patients were withdrawn early because of rapid disease progression. Vaccination elicited dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates in 18 of 25 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransfected tumor cells in 18 of 22 patients. Metastatic lesions resected after vaccination showed T lymphocyte and plasma cell infiltrates with tumor necrosis in three of six patients. Two patients surgically rendered as having no evidence of disease at enrollment remain free of disease at 43 and 42 months. Five patients showed stable disease durations of 33, 19, 12, 10, and 3 months. One mixed response was observed. CONCLUSION: Vaccination with irradiated autologous NSCLC cells engineered to secrete GM-CSF enhances antitumor immunity in some patients with metastatic NSCLC.     

Angiogenesis during tumor progression in the oral cavity is related to reduced apoptosis and high tumor cell proliferation

Angiogenesis, the growth of new blood vessels, is believed to aid tumor progression and metastasis. Tumor progression is also influenced by the extent of proliferation and apoptosis. This study, therefore, analyzed in lesions of the oral cavity, the significance of angiogenesis in relation to apoptosis, expression of apoptosis regulatory p53, bax and bcl-2 proteins as well as tissue proliferation defined by cyclin D1 expression. Results from this study suggest that angiogenesis increases as histological abnormality increases in the oral mucosa. The expression of apoptosis regulatory proteins also appears to be altered in a histologically dependent manner. The correlation seen between CD34 expression, cyclin D1 and TUNEL reactive cells suggests that increased angiogenesis, decreased apoptosis and deregulated proliferation occur simultaneously during tumor progression in the oral mucosa. Presence of a mutant p53, increased bcl-2 expression and altered bax expression are also involved in this complex process.     

Antihyperlipidemic effect of Eugenia jambolana seed kernel on streptozotocin-induced diabetes in rats.

Abnormalities in lipid profile are one of the most common complications in diabetes mellitus, which is found in about 40% of diabetics. In the present study, anti-hyperlipidemic efficacy of Eugenia jambolana seed kernel (EJs-kernel) was evaluated in streptozotocin (STZ)-induced diabetic rats and the efficacy was compared with standard hypoglycemic drug, glibenclamide. The effect of oral administration of ethanolic extract of EJs-kernel (100 mg/kg body weight) was examined on the levels of cholesterol, phospholipids, triglycerides and free fatty acids in the plasma, liver and kidney tissues of STZ (55 mg/kg body weight)-induced diabetic rats. The plasma lipoproteins and tissues fatty acid composition were also monitored. STZ-induced diabetic rats, showed significant increase in the levels of cholesterol, phospholipids, triglycerides and free fatty acids which were considerably restored to near normal in EJs-kernel or glibenclamide treated animals. The plasma lipoproteins (HDL, LDL, VLDL-cholesterol) and fatty acid composition were altered in STZ-induced diabetic rats and these levels were also reverted back to near normalcy by EJs-kernel or glibenclamide treatment. It may be concluded that, EJs-kernel possesses hypolipidemic effect, which may be due to the presence of flavonoids, saponins, glycosides and triterpenoids in the extract. The hypolipidemic effect mediated by EJs-kernel may also be anticipated to have biological significance and provide a scientific rationale for the use of EJs-kernel as an anti-diabetic plant.     

Parathyroid hormone-related protein is expressed by transformed and fetal human astrocytes and inhibits cell proliferation

Parathyroid hormone-related protein (PTHrP) and the PTH/PTHrP receptor are expressed in most normal tissues, including brain, where PTHrP is though to act locally in an autocrine or paracrine fashion. Previous in situ localization studies in adult rodents have documented CNS PTHrP expression in neurons but not in glial cells. However, a recent report describing immunoreactive PTHrP in human astrocytomas suggests that PTHrP expression may be a marker of dedifferentiation and/or malignant transformation in glial cells. To begin to test this hypothesis, constitutive and regulated PTHrP expression were examined in cultured fetal and transformed (U-373 MG) human astrocytes. PTHrP was expressed in untreated fetal astrocytes and U-373 MG cells, as determined by Northern analysis, immunocytochemical staining, and detection of PTHrP(1-84) protein in conditioned media. Epidermal growth factor and tumor necrosis factor, important growth factors in astrocyte development and malignant transformation, stimulated PTHrP expression in both cell types. Treatment of U-373 MG cells or fetal astrocytes with PTHrP(1-34) consistently inhibited cellular proliferation, as measured by [(3)H]-thymidine incorporation. These findings suggest that PTHrP, a peptide whose expression is induced by mitogens in both immature and transformed human astrocytes, may feedback inhibit cellular proliferation, an effect that may be of importance during malignant transformation as well as CNS development. Furthermore, when combined with previous evidence of PTHrP expression by PTH/PTHrP receptor-positive neurons, our demonstration of regulated PTHrP expression by receptor-positive astrocytes identifies PTHrP as a potential peptide mediator of cross-talk between glial cells and neurons.     

Radical aortic replacement employing simultaneous modified Bentall and elephant trunk procedure in Takayasu's arteritis

A case of Takayasu's arteritis resulting in extensive fusiform aneurysmal dilatation of the entire aorta extending from the aortic root to the abdominal bifurcation associated with aortic regurgitation is described. She underwent successful radical replacement of the aortic root, ascending, transverse arch and proximal part of the descending aorta employing simultaneous modified Bentall and Elephant trunk techniques. During aortic arch replacement the brain was protected by selective antegrade innominate perfusion under moderate hypothermia. A pattern to the best of our knowledge, has not been reported earlier.     

Misoprostol vs. oxytocin for induction of labor at term.

Efficacy of misoprostol was studied for induction of labor at term. Seventy patients were randomized to Group A (n = 36, oral misoprostol 50 microg four hourly to maximum of 5 doses) and B (n = 34, continuous oxytocin infusion). Induction-delivery interval was shorter with misoprostol (7.7 +/- 2.8 h against 14.3 +/- 4.8 h with oxytocin) but the rates of vaginal delivery, cesarean, neonatal outcome variables were similar. Hence, misoprostol is an effective agent for induction of labor at term.     

Pre-operative assessment of K-nail length in fracture shaft of femur.

Introduction: Internal fixation of diaphyseal fracture of shaft of femur in an adult by Kuntscher nail is the most common operative method of treatment in Nepal where operative facilities for the same exist. Since the complete range of K-nail sizes and length are not available in most operation theatres in Nepal, most orthopaedic surgeons assess the size and length of the K-nail pre-operatively by various methods and keep one size above and below the assessed length for the planned surgery. Materials and Methods: The following measurements were taken in five hundred people involved in the study: Measurement No. 1: Tip of the greater trochanter to lateral knee joint line minus 2cms. Measurement No. 2: Tip of the olecranon process to the tip of little finger, and Measurement No. 3: Tip of the greater trochanter to the upper pole of patella. An average of all three lengths were analysed to see if there were any differences in their mean lengths. Results: Analysis showed that there were significant differences between the mean lengths measured by the three different methods. The average length of measurement no: 2 was 3 cm longer than the average length of measurement no: 1, which is the reference pre-operative length of K.nail. Conclusion: However, in practice since measurement no:2 is more convenient to perform and can also be used when the patient has sustained bilateral fractures of femur, an accurate pre-operative K-nail length assessment can be done by subtracting 3 cm from measurement no:2, i.e. the tip of the olecranon process to the tip of the little finger.     

Water pollution and health.

Water is the important constituent of life support system. No one can live and even dream to live without water. Most of our water bodies have become polluted due to industrial growth; urbanization and man-made problems mainly the result of population growth. Poor sanitation and contaminated drinking water arising from human activity and natural phenomena create serious problems in human health. The chief sources of water pollution are sewage and other waste, industrial effluents, agricultural discharges and industrial wastes from chemical industries, fossils fuel plants and nuclear power plants. They create a larger problem of water pollution rendering water no longer fit for drinking, agriculture and, as well as for aquatic life. More than 2.6 billion people--40% of the world's population--lack basic sanitation facilities and over one billion people still use unsafe drinking water sources. As a result thousands of children die everyday from diarrhoea and other water, sanitation and hygiene-related diseases and many suffer and are weakened by illness.