Search

Multiple myeloma (MM) is a clonal neoplasm of plasma cells which offers an excellent model to study multistep molecular oncogenesis. In 20-25% of primary tumors and cell lines examined, cyclin D1 is overexpressed due to the translocation t(11;14)(q13;q32). We have characterized cyclin-dependent kinase inhibitor p15 (CDKN2B), p16 (CDKN2A) and p18 (CDKN2C) deletions in cyclin D1-expressing and non-expressing MM cell lines. p18 was found to be frequently deleted (38%); in some cases p18 deletions coexisted with hemizygous p16 deletion. To examine the function of p18 as a putative tumor suppressor in myeloma cells, a zinc-inducible p18 construct was stably transfected into KMS12, a MM cell line with biallelic p18 and monoallelic p16 deletions as well as cyclin D1 over-expression. Ectopic expression of p18 caused 40-45% growth suppression as determined by trypan blue exclusion and MTS assays. p18 induction also resulted in apoptosis, suggesting that inhibition of the cyclin D1/CDK/pRb pathway in these tumor ceils could be a crucial step toward the induction of tumor regression via apoptotic cell death. This cell cycle pathway is thus frequently mutated and provides a potentially novel target for gene therapeutic or pharmacologic approaches to human myeloma. [ABSTRACT FROM AUTHOR]

Background: Delay in the diagnosis of intraabdominal pathology is a major contributor to the morbidity and mortality of intensive care unit (ICU) patients. Laparoscopy is a valuable diagnostic tool that can be used safely and efficiently in the evaluation of intraabdominal processes that may be difficult to diagnose with conventional methods. Our goal was to show that laparoscopy performed at the bedside in the ICU could be used as a routine diagnostic tool in the evaluation of critically ill patients, just as computed tomography (CT), ultrasonography (US), and radiography are. Methods: We present 11 patients who underwent 12 bedside examinations in the ICU of a community teaching hospital. Several different surgeons with varying degrees of laparoscopic experience performed these procedures over a 1-year period. Results: Four patients had previously undergone recent abdominal operations. Nontherapeutic laparotomy was avoided in six patients because of diagnostic laparoscopy. One patient also underwent a therapeutic maneuver at the time of diagnostic laparoscopy. None of the patients required general anesthesia, although local anesthetics and sedation with midazolam or propofol were used. One patient underwent the procedure without endotracheal intubation. There were no complications or mortalities directly related to the procedure. Conclusion: We conclude that bedside laparoscopy in the ICU under local anesthesia is a diagnostic and potentially therapeutic tool that can be used safely in the work-up of potential abdominal pathology in critically ill patients. [ABSTRACT FROM AUTHOR]