Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz

The present study investigated the effects of dietary oltipraz on cigarette smoke-related lipophilic DNA adduct formation. Female Sprague- Dawley rats were exposed daily to sidestream cigarette smoke in a whole- body exposure chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained on control diet while another group received the same diet supplemented with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz, starting 1 week prior to initiation of smoke exposure until the end of the experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated 32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5 predominated in both the lung and the heart while adduct nos 3 and 2 predominated in the trachea and bladder, respectively. Quantitative analysis revealed that the total adduct level was the highest in lungs (270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48 adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides) and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz treatment reduced the adduct levels in lungs and bladder by >60%, while the reduction in lungs in the low-dose group was approximately 35%. In trachea, the effect of low and high dietary oltipraz on smoke DNA adduction was equivocal, while smoke-related DNA adducts in the heart were minimally inhibited by high-dose oltipraz. In a repeat experiment that employed a 3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to inhibit the formation of DNA adducts in rat lungs and trachea by 80 and 65%, respectively. These data clearly demonstrate a high efficacy of oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts in the target tissues.      

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.     

Long-term results of infrainguinal arterial reconstruction with spliced veins are equal to results with non-spliced veins.

OBJECTIVES: to determine the long term patency of spliced and non-spliced infrainguinal vein grafts. METHODS: a prospective registry of all patients undergoing infrainguinal arterial reconstruction with autogenous vein material was retrospectively interrogated. RESULTS: between October 1988 and August 2000, 515 infrainguinal arterial reconstructions were performed on 472 patients. A total of 429 bypasses were performed with uninterrupted greater saphenous vein, 86 reconstructions using spliced vein segments. There was no significant difference in primary (63% vs 57%) and primary assisted patency (81% vs 81%) of limb salvage (88% vs 91%) at 5 years. Limb salvage was not different (88% and 91% respectively). CONCLUSION the splicing of vein grafts does not compromise patency of limb salvage.     

Position statement: Continuous subcutaneous insulin infusion in very young children with type 1 diabetes

Insulin pump therapy has become increasingly popular for the treatment of type 1 diabetes in pediatric patients. Although significant experience has accrued with the use of this modality in older children and adolescents, much less data are available regarding continuous subcutaneous insulin infusion in the very young. Policies of individual physician practices and insurance companies vary widely, and there is currently no consensus regarding the appropriateness of insulin pump therapy in the under 6 age group. However, we have witnessed in recent years a significant increase in the number of clinical trials investigating the use of continuous subcutaneous insulin infusion in young patients, and reports of > 100 preschool-aged diabetic children treated with insulin pumps are available in the literature. Although these studies have been of relatively short duration (< or = 12 months), the results are remarkably consistent. Although there is no evidence that insulin pump therapy results in a sustained improvement in glycemic control in this age group, risks associated with these devices in the hands of reliable adults who are managing diabetes in very young children are low. Parental satisfaction related to the increased flexibility that continuous subcutaneous insulin infusion affords anecdotally seems to be high, although formal examination of parental stress and health-related quality of life in this setting has been minimal. Important questions remain regarding selection of appropriate candidates for insulin pump therapy, whether benefits of continuous subcutaneous insulin infusion outweigh the costs, and what eventual outcomes will be in children treated with pumps from a very young age. Long-term follow-up of medical, psychological, and neurocognitive parameters in these young patients will be paramount. Our goal with this review is to summarize efficacy and safety of continuous subcutaneous insulin infusion in children < or = 6 years of age, present potential pros and cons of using insulin pumps in this population, and propose clinical management guidelines that could be useful for both practitioners and third-party payers alike.     

An update on the treatment of precocious puberty in McCune-Albright syndrome and testotoxicosis

McCune-Albright syndrome and testotoxicosis are rare forms of peripheral precocious puberty. Our understanding of the pathophysiology and mechanism of these diseases has significantly increased following identification of their underlying molecular etiology. However, their treatment remains challenging. We provide a review of the various treatment modalities used in both conditions with an update on recent trials using novel and promising pharmacological agents.     

Immunoprofile of the adenomatoid odontogenic tumor

This study was focused on the immunohistochemical profile of the adenomatoid odontogenic tumor. A Pub/Medline search revealed a number of immunohistochemical studies including cytokeratin profiles, extracellular matrix proteins, Integrins, ameloblast‐associated proteins resorption regulators (RANK, RANKL), p53, PCNA, MDM2 protein, cyclin D1, Ki‐67, Bcl‐2 metallothionein, metalloproteinases, D56 hepatocyte growth factor, c‐met, DNA methyltransferase, podoplanin, TGF‐βI, Smad‐2/3, Smad‐I‐5/‐8, Smad 4, beta‐ catenin, calretinin, and clonality. Careful interpretation of the findings indicates that the adenomatoid odontogenic tumor may be more of a hamartomatous than neoplastic nature.