The product of the imprinted H19 gene is an oncofetal RNA.

AIMS/BACKGROUND: The H19 gene is an imprinted, maternally expressed gene in humans. It is tightly linked and coregulated with the imprinted, paternally expressed gene of insulin-like growth factor 2. The H19 gene product is not translated into protein and functions as an RNA molecule. Although its role has been investigated for more than a decade, its biological function is still not understood fully. H19 is abundantly expressed in many tissues from early stages of embryogenesis through fetal life, and is down regulated postnatally. It is also expressed in certain childhood and adult tumours. This study was designed to screen the expression of H19 in human cancer and its relation to the expression of H19 in the fetus. METHODS: Using in situ hybridisation with a [35S] labelled probe, H19 mRNA was detected in paraffin wax sections of fetal tissues from the first and second trimesters of pregnancy and of a large array of human adult and childhood tumours arising from these tissues. RESULTS: The H19 gene is expressed in tumours arising from tissues which express this gene in fetal life. Its expression in the fetus and in cancer is closely linked with tissue differentiation. CONCLUSIONS: Based on these and previous data, H19 is neither a tumour suppressor gene nor an oncogene. Its product is an oncofetal RNA. The potential use of this RNA as a tumour marker should be evaluated.     

Pain relief by continuous intraperitoneal nebulization of ropivacaine during gynecologic laparoscopic surgery--a randomized study and review of the literature

STUDY OBJECTIVE: To evaluate the efficacy of intraperitoneal nebulization of ropivacaine on pain relief during and after gynecologic laparoscopic procedures including a review of the literature. DESIGN: Double-blinded, randomized, controlled, clinical trial (Canadian Task Force classification I). SETTING: University hospital ambulatory gynecoendoscopic department. PATIENTS: Forty patients (20 patients in each arm) undergoing elective gynecologic same-day outpatient laparoscopic surgery including unilateral/bilateral salpingo-oophorectomy or unilateral/bilateral ovarian cystectomy. INTERVENTIONS: The study group received 10 mL of 1% ropivacaine and the control group received 10 mL of sterile water by intraperitoneal nebulization. During surgery, vital signs were recorded and summarized. Postoperatively patients were followed up for 24 hours including visual analog scale scores and analgesic use. MEASUREMENTS AND MAIN RESULTS: No significant differences existed between the groups during surgery and at the recovery department in terms of arterial blood pressure (p = .42) or heart rate (p = .60). Regarding postoperative analgesia, no difference existed between the groups in terms of morphine consumption (p = .52) or other analgesics (p = .53). No significant difference existed between the groups in postoperative visual analog scale scores including visceral, abdominal wall, and shoulder pain during rest and during cough at the different time frames (30, 60, and 120 minutes and 6 and 24 hours after surgery). CONCLUSION: Our study is the first to examine the effects of intraperitoneal nebulization of ropivacaine throughout laparoscopic gynecologic procedures on patients undergoing general anesthesia. Nebulization of 100 mg of ropivacaine under our specific regimen of anesthesia does not improve patients' outcome in terms of intraoperative and postoperative pain along with consumption of analgesics. Further research with other regimens is required.     

Multiple myeloma involving the thyroid cartilage: case report

Multiple myeloma involving the thyroid cartilage is exceedingly rare. We describe a patient with progressive airway obstruction due to diffuse involvement of the thyroid cartilage with multiple myeloma. CT revealed a conglomerate of calcifications of the thyroid cartilage. Additional classic lytic lesions of multiple myeloma were subsequently found in the bones, without associated calcifications. Calcified matrix in multiple myeloma involving the thyroid cartilage should now be included as an additional manifestation of extraosseous multiple myeloma.     

Can external signs of trauma guide management?: Lessons learned from suicide bombing attacks in Israel

BACKGROUND: Following a suicide bombing attack, scores of victims suffering from a combination of blast injury, penetrating injury, and burns are brought to local hospitals. OBJECTIVE: To identify external signs of trauma that would assist medical crews in recognizing blast lung injury (BLI) and effectively triaging salvageable and nonsalvageable victims. DESIGN: Retrospective analysis of all 15 suicide bombing attacks that occurred in Israel from April 1994 to August 1997. SETTING: National survey. PATIENTS: One hundred fifty-three victims died and 798 were injured as a result of 15 attacks. Medical records were reviewed for external signs of trauma, such as burns and penetrating injuries, and the presence of BLI.Main Outcome Measure The odds ratio for BLI and death. RESULTS: Three settings were targeted: buses, semiconfined spaces, and open spaces. Sixty survivors (7.5%) suffered from BLI, which was more common in buses (37 of 260) than semiconfined spaces (14 of 279) and open spaces (9 of 259) (P<.001). Victims with BLI were more likely to suffer from penetrating injury to the head or torso, burns covering more than 10% of the body surface area, and skull fractures (odds ratios, 4, 11.6, and 55.8, respectively; P<.001). Victims who died at the scene were more likely to suffer from burns, open fractures, and amputations in comparison with survivors (odds ratios, 6.5, 18.6, and 50.1, respectively; P<.001). CONCLUSIONS: Following a suicide bombing attack, external signs of trauma should be used to triage victims to the appropriate level of care both at the scene and in the hospital. Triage of salvageable and nonsalvageable victims should take into account the presence of amputations, burns, and open fractures.     

Regulation of ROMK and channel-inducing factor (CHIF) in acute renal failure due to ischemic reperfusion injury

BACKGROUND: Acute renal failure caused by ischemia followed by reperfusion is often associated with severe hyperkalemia. The present study was undertaken to characterize the effects of renal ischemia and reperfusion on plasma potassium (K) and on the gene expression of channel-inducing factor (CHIF), a putative K channel regulator, and of ROMK, the distal nephron secretory K channel. METHODS: The following groups of rats were studied: (1) sham operated (sham); (2) after one hour of ischemia by bilateral renal artery clamping (I), and after one hour of ischemia; (3) one hour of reperfusion (I-R 1 h); (4) 24 hours of reperfusion (I-R 24 h); (5) 48 hours of reperfusion (I-R 48 h); and (6) 72 hours reperfusion (I-R 72 h). The expression of CHIF and ROMK was examined by Northern blot hybridization in renal cortex, medulla, and papilla and in the colon. The abundance of ROMK protein was determined in the renal cortex and medulla by immunoblotting. RESULTS: Maximal plasma creatinine and potassium levels after ischemia and reperfusion were 470 +/- 16 micromol/L, P < 0.0001 versus sham, and 9.65 +/- 0.33 mmol/L, P < 0.0001 versus sham, respectively. The expression of CHIF was significantly down-regulated in the medulla and papilla, with a maximal decrease of 80% at 48 to 72 hours. In contrast, a most significant increase in CHIF mRNA expression (250% of baseline) was noted in the colon after 24 to 48 hours of reperfusion. ROMK expression was reduced in the cortex and was completely abolished in the medulla at 48 to 72 hours of reperfusion. Ischemia and reperfusion injury significantly decreased ROMK protein abundance to 10% of control in the medullary fractions. CONCLUSIONS: These results suggest that down-regulation of renal CHIF and ROMK may contribute at least partly to the hyperkalemia of acute renal failure after ischemia and reperfusion, while CHIF up-regulation in the colon may act as a compensatory mechanism of maintaining K balance via increased K secretion.     

New therapeutic approaches in sepsis: A critical review

This paper reviews several recent, randomized, double-blind, placebo-controlled trials of monoclonal antibodies against endotoxin, interleukin-1 receptor antagonist (IL-1 ra), and monoclonal antibody against tumor necrosis factor (TNF) in sepsis.     

Pulmonary extraction and accumulation of lipid formulations of amphotericin B

OBJECTIVE: To compare single-dose first pass uptake and accumulation of conventional amphotericin B (cAmB), liposomal amphotericin B (L-AmB), and amphotericin B lipid complex (ABLC) by the intact feline lungs. DESIGN: Prospective, controlled animal study. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: A total of 31 spontaneously breathing, anesthetized cats. INTERVENTIONS: The pulmonary uptake of cAmB, L-AmB, and ABLC during a single passage through the pulmonary circulation, and the pulmonary retention of these drugs were studied after a bolus [cAmB, L-AmB, and ABLC, 1 mg/kg (n = 9 each) and ABLC, 5 mg/kg (n = 4)] administration into the right ventricle. The amount of drug taken up by the lung during the first pass was measured from double indicator-dilution outflow curves. Animals were killed 30 mins (cAmB, n = 4; L-AmB, n = 4), 1 hr (cAmB, n = 5; L-AmB, n = 5; ABLC, n = 5), or 6 hrs (ABLC, 1 mg/kg, n = 4; 5 mg/kg, n = 4) after drug administration. MEASUREMENTS AND MAIN RESULTS: The first-pass uptake of cAmB, L-AmB, and ABLC (mean +/- sD) by the lung was 73%+/-5%, 69%+/-8%, and 82%+/-6% of the injected dose (1 mg/kg), respectively (p > .05). ABLC (1 mg/kg) exhibited prolonged retention in the lung; 23% and 15% of the injected dose of ABLC remained in the lung 1 hr and 6 hrs after its administration, respectively. In contrast, cAmB and L-AmB exhibited rapid back diffusion of the drug out of the lung. After 30 mins, only 4% of the administered cAmB and L-AmB remained in the lung and after 1 hr only 1% to 2% was retained. Increasing the dose of ABLC from 1 mg/kg to 5 mg/kg did not alter pulmonary extraction of the drug; however, compared with the lower dose (1 mg/kg), higher concentrations of the drug were found in the lung 6 hrs after its administration. CONCLUSIONS: The results demonstrate a substantial extraction and accumulation of ABLC by the lung. This affinity for the lungs may have clinical implications for treating fungal infections that primarily involve the lung. Further studies are required to confirm the potential clinical relevance of these data.     

The natural history of bladder carcinoma in situ after initial response to bacillus Calmette-Gúerin immunotherapy

ObjectivesTo explore patterns of recurrence, muscle invasion, and disease specific mortality in patients with bladder carcinoma in situ (CIS) who responded to an induction course with intravesical bacillus Calmette-Gúerin (BCG) immunotherapy.MethodsBetween June 1985 and December 2003, 104 patients (mean age 67 years) were diagnosed with either pure (38 patients) or concomitant (66 patients) CIS. Patients who responded to one (92 patients) or two (12 patients) induction courses of intravesical BCG instillation were included in the study. Response was determined and monitored by routine periodic bladder biopsies. Outcome of patients and the effect of various prognostic parameters were assessed after a median follow-up of 75 months.ResultsThe 5- and 10-year recurrence-free survival rates were 63% and 54%, respectively. The 5- and 10-year muscle-invasive-free survival rates were 79% and 77%, and the 5- and 10-year disease-specific survival rates were 90.5 and 85.8%, respectively. Median time to recurrence, muscle invasion, and disease-specific mortality was 18, 19, and 40 months, respectively. Pure and concomitant CIS were associated with a similar outcome. The recurrence of nonmuscle-invasive tumor did not increase the risk for muscle invasion or mortality.ConclusionsPure and concomitant bladder CIS share similar biologic behavior. Muscle-invasive disease is expected in about 25% of the BCG responders followed for long time periods and disease-specific mortality in 15%. Tumor recurrence, whether nonmuscle-invasive or muscle-invasive, follows a similar time table suggesting that these are not sequential but parallel and independent processes.