Successful treatment of refractory ascites in a child with transjugular intrahepatic portosystemic shunt

A 16-y-old boy who had undergone bone marrow transplantation for relapsed acute lymphoblastic leukaemia developed liver cirrhosis and refractory ascites, which did not respond to salt restriction, diuretics and abdominal paracentesis. Liver transplantation was not feasible because of poor nutritional status, pre-existing renal dysfunction and uncertainty about the prognosis of his leukaemia. The patient underwent a successful transjugular intrahepatic portosystemic shunt (TIPS), with immediate resolution of ascites, enabling cessation of diuretics and improvement in nutritional status. At 24 mo following TIPS there has been no re-accumulation of ascites. CONCLUSION: TIPS may have a role in the management of refractory ascites secondary to liver cirrhosis in selected children.     

Percutaneous drainage of chest abscesses in children

Seven patients ranging in age from 3 to 18 years underwent percutaneous drainage of eight intrathoracic abscesses. Five of the abscesses were mediastinal or paramediastinal and resulted from esophageal perforation or esophageal anastomotic leakage. The abscesses resolved in each case, with a mean catheter drainage time of 28 days and no need for surgical intervention. Three of the abscesses were intrapulmonary, and each lay adjacent to a pleural surface. All three lung abscesses resolved within 19-24 days, without thoracotomy or wedge resection.     

Inhibition of radiation-induced neoplastic transformation by beta-lapachone.

Beta-lapachone is a potent inhibitor of DNA repair in mammalian cells and activates topoisomerase I. We show that beta-lapachone can prevent the oncogenic transformation of CHEF/18A cells by ionizing radiation. Potentially lethal DNA damage repair (PLDR) occurs while x-irradiated cells are held in medium containing low serum prior to replating. PLDR processes permitted survival recovery but also drastically increased the number of foci per plate (i.e., transformation) of CHEF/18A cells. By blocking PLDR with beta-lapachone, both survival recovery and enhanced transformation were prevented. At equivalent survival levels, exposure of x-irradiated cells to beta-lapachone resulted in an 8-fold decrease in the number of foci per dish as compared to the number of transformants produced after PLDR. Early PLDR-derived increases in transformation may be the result of error-prone genetic rearrangements dependent on topoisomerase I, which are thereby prevented by beta-lapachone. Beta-lapachone exposure decreased the rejoining of DNA strand breaks and produced additional double-strand breaks in x-irradiated cells during PLDR. The activation of topoisomerase I by beta-lapachone may convert repairable single-strand DNA breaks into the more repair-resistant double-strand breaks, thereby preventing PLDR and neoplastic transformation. These results suggest a new direction for the development of anticarcinogenic agents.     

Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus

Bilateral, high-frequency stimulation (HFS) of the subthalamic nucleus (STN) is the surgical therapy of choice for movement disability in advanced Parkinson's disease (PD), but this procedure evokes debilitating psychiatric effects, including depressed mood, of unknown neural origin. Here, we report the unexpected finding that HFS of the STN inhibits midbrain 5-hydroxytryptamine (5-HT) neurons to evoke depression-related behavioral changes. We found that bilateral HFS of the STN consistently inhibited (40-50%) the firing rate of 5-HT neurons in the dorsal raphe nucleus of the rat, but not neighboring non-5-HT neurons. This effect was apparent at clinically relevant stimulation parameters (> or =100 Hz, > or =30 microA), was not elicited by HFS of either neighboring or remote structures to the STN, and was still present in rat models of PD. We also found that bilateral HFS of the STN evoked clear-cut, depressive-like behavior in a widely used experimental paradigm of depression (forced swim test), and this effect was also observed in a PD model. Importantly, the depressive-like behavior elicited by HFS of the STN was reversed by a selective 5-HT-enhancing antidepressant, thereby linking the behavioral change to decreased 5-HT neuronal activity. Overall, these findings link reduced 5-HT function to the psychiatric effects of HFS of the STN observed in PD patients and provide a rational basis for their clinical management. More generally, the powerful interaction between the STN and 5-HT system uncovered here offers insights into the high level of comorbidity of basal ganglia disease and mood disorder.     

Cost-effectiveness of multidisciplinary management of Tinnitus at a specialized Tinnitus centre

Background  

Tinnitus is a common chronic health condition that affects 10% to 20% of the general population. Among severe sufferers it causes disability in various areas. As a result of the tinnitus, quality of life is often impaired. At present there is no cure or uniformly effective treatment, leading to fragmentized and costly tinnitus care. Evidence suggests that a comprehensive multidisciplinary approach in treating tinnitus is effective. The main objective of this study is to examine the effectiveness, costs, and cost-effectiveness of a comprehensive treatment provided by a specialized tinnitus center versus usual care. This paper describes the study protocol.     

Aprotinin or tranexamic acid in cardiac surgery: a propensity analysis

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -     

Posttreatment exposure to camptothecin enhances the lethal effects of x-rays on radioresistant human malignant melanoma cells.

Little is known about the molecular mechanisms responsible for the survival recovery process(es) (known as potentially lethal damage repair), which occurs in mammalian cells following ionizing radiation. Previously, we presented data indicating a role for the DNA unwinding enzyme, topoisomerase I, in DNA repair. We now demonstrate that camptothecin, a specific inhibitor of topoisomerase I, causes dramatic radiosensitization of an extremely resistant human melanoma (U1-Mel) cell line. Camptothecin radiosensitized U1-Mel cells when it was administered either during or immediately following x-irradiation. U1-Mel cells were optimally radiosensitized with 4 microM camptothecin for a period of 4-6 hrs after x-irradiation. Enhanced cell killing by camptothecin was proportional to the initial extent of damage created by x-irradiation; the higher the dose of ionizing radiation, the greater the radiosensitization. The apparent synergy observed with camptothecin and x-rays was irreversible; camptothecin-treated U1-Mel cells were not able to carry out PLDR in a 48 hr period after the drug was removed. We hypothesize that the administration of camptothecin causes lesion modification through a topoisomerase I-mediated mechanism. These data support a role for topoisomerase I in DNA repair and indicate that camptothecin, or more effective derivatives, may have clinical use.