Ki-ras and the characteristics of mouse lung tumors

Codon 12 mutations are frequent in the Ki-ras oncogene in human lung adenocarcinomas, but the effects of these alterations have not been well characterized in lung epithelial cells. Murine primary lung tumors derived from peripheral epithelial cells also may present Ki-ras mutations and are useful models for study of early phases of tumor development. One hypothesis is that Ki-ras mutation and/or a Ki-ras p21 increase could enhance Ki-ras p21-GTP and cell-cycle stimulation through raf-1 and extracellularly regulated protein kinases (Erks). We examined lung tumors 1-7 mm in largest dimension initiated in male Swiss mice by N-nitrosodimethylamine for pathologic type, Ki-ras mutations and levels of total Ki-ras p21, Ki-ras p21 bound to GTP, raf-1, Erk1 and Erk2 and their phosphorylated (activated) forms, and proliferating cell nuclear antigen. Total Ki-ras p21 and activated ras-GTP were not significantly greater in tumors than in normal lung or in tumors with versus those without Ki-ras mutations. Carcinomas with Ki-ras mutations were significantly smaller than those without mutations. Carcinomas were significantly larger than adenomas only for tumors without mutations. High levels of Erk2 and correlation of Erk2 amount with ras-GTP were specific characteristics of tumors with Ki-ras mutations. Size of all tumors correlated with ras-GTP but not with proliferating cell nuclear antigen. Raf-1 was expressed mainly in alveolar macrophages in normal lung but was focally upregulated in papillary areas of some tumors. The results indicate that Ki-ras influences the characteristics of lung tumors, but a linear ras-raf-Erk-cell-cycle control sequence does not adequately characterize tumorigenic events in this model. Mol. Carcinog. 28:156-167, 2000.     

Antiinflammatory activity of ‘Soymida febrifuga’ (Mansa rohini) in rats and mice

The tree bark of Mansa rohini extract (MRE) showed a dose dependent inhibition of rat paw oedema. MRE also significantly reduced the volume of peritoneal ascites and gamma glutarnyl transpeptidase. The antiinflammatory activity of MRE was comparable to nonsteroidal antiinflammatory agents such as naproxen, ibuprofen and piroxicam. MRE was devoid of ulcerogenic properties and hence it is a potential antiinflammatory agent.     

Toxic epidermal necrolysis associated with denileukin diftitox (DAB389IL-2) administration in a patient with follicular large cell lymphoma

Denileukin diftitox (DAB₃₈₉IL-2 or Ontak®) is a synthetic fusion protein with demonstrated efficacy in a number of lymphoproliferative disorders, including non-Hodgkin's lymphoma. We report the case of a 45-year-old man with progressive follicular large cell lymphoma following an autologous stem cell transplant treated with denileukin diftitox who developed a fatal skin rash associated with extensive erythema, edema and large bullae involving his entire body. The clinical features and pathology were compatible with toxic epidermal necrolysis. This is the first reported case of toxic epidermal necrolysis in the literature associated with denileukin diftitox.     

Local Anaesthesia for Fiberoptic Intubation : A Comparison of Three Techniques

Background

The successful conduct of fiberoptic aided intubation is dependent upon effective local anaesthesia. The aim of the study was to compare three different methods of anaesthetizing the airway.

Methods

60 adult patients (American Society of Anaesthesiologists status I-III and Mallampati class III & IV), scheduled for elective surgery, received sedation followed by spraying of the nares and posterior pharyngeal wall with 4% lignocaine. Thereafter the patients received 4 ml of 4% lignocaine either by transtracheal injection (n=20, group A), via intubating fiberscope (Pentax F1-10P2) using ‘spray as you go’ technique (n=20, group B) or by nebulizer (Devilbiss 5610W) 20 min before intubation, (n=20, group C). Patients were asked to score the procedure using visual analog scale (VAS) and severity scores. Episodes of coughing, choking, stridor, extra / total local anaesthetic used and intubation times were recorded. Patients were monitored continuously for vital parameters.

Results

Group B patients showed better VAS scores with shorter intubation times and had a lower incidence of coughing and choking. The endoscopists’ VAS scores also showed a preference for group B.

Conclusion

In conclusion the ‘spray as you go’ technique was safe, provided effective local anaesthesia and was preferred by both patients and endoscopists.Key Words: Awake intubation, Difficult airway, Fiberoptic intubation     

Efficacy and Toxicity Profile of Methotrexate Chloroquine Combination in Treatment of Active Rheumatoid Arthritis

Background

The present study was conducted to study the efficacy and toxicity profile of methotrexate chloroquine combination in treatment of active rheumatoid arthritis.

Methods

24 patients of rheumatoid arthritis confirming to revised American Rheumatism Association (ARA) criteria were studied prospectively for twenty months. Clinical evaluation was made every 3 months. Clinical disease variables measured at each visit were number of joints with swelling, number of joints with tenderness and pain, duration of morning stiffness and physician and patient assessment of disease activity. Blood counts, liver function tests and other adverse effects due to drugs were monitored every 2 months.

Results

10 patients demonstrated more than 50% improvement. 4 patients withdrew from study, 2 because of excessive nausea and vomiting and 2 because of noncompliance. Other side effects noted were hyperpigmentation, photosensitivity, skin rashes, raised transaminases and stomatitis.

Conclusion

Methotrexate chloroquine combination has good efficacy and toxicity profile. Gastrointestinal side effects are most common and usually responsible for the discontinuation of the drugs.Key Words: Rheumatoid arthritis, Methotrexate, Chloroquine, Efficacy, Toxicity     

The biology of bone grafting

Many approaches are used to repair skeletal defects in reconstructive orthopaedic surgery, and bone grafting is involved in virtually every procedure. The type of bone graft used depends on the clinical scenario and the anticipated final outcome. Autogenous cancellous bone graft, with its osteogenic, osteoinductive, and osteoconductive properties, remains the standard for grafting. However, the high incidence of morbidity during autogenous graft harvest may make the acquisition of grafts from other sources desirable. The clinical applications for each type of bone graft are dictated by the structure and biochemical properties of the graft. An elegant cellular and molecular cascade follows bone transplantation. Bone graft incorporation within the host, whether autogenous or allogeneic, depends on many factors: type of graft (autogenous versus allogeneic, vascular versus nonvascular), site of transplant, quality of transplanted bone and host bone, host bed preparation, preservation techniques, systemic and local disease, and mechanical properties of the graft.