Expression of actin isoforms and intermediate filament proteins in childhood orbital rhabdomyosarcomas

The diagnosis of orbital rhabdomyosarcoma (RMS) in childhood gives rise to several clinical and anatomo-pathological problems. Antibodies recognizing structural proteins and cytoskeletal components have been shown to increase the diagnostic accuracy of different neoplastic lesions. In this study we examined anatomo-clinically and, where possible, by means of immunohistochemistry and electron microscopy, a series of 14 cases of orbital RMS in childhood. In the 12 cases studied by immunohistochemistry, desmin was always present, although showing variable patterns, and alpha-sarcomeric actin was found in 10 cases. alpha-Smooth muscle actin was always absent. The other markers tested (myoglobin, polyclonal actin, vimentin and enolase) proved unreliable for several reasons. We conclude that antibodies against desmin and alpha-sarcomeric actin are useful for the diagnostic definition of RMS. In addition, immunohistochemical analysis supplies data regarding the degree of tumor differentiation and may be applied to monitor radio- and chemotherapy.     

Burkitt's lymphomas express VH genes with a moderate number of antigen-selected somatic mutations.

The normal counterpart of the neoplastic B cells occurring in Burkitt's lymphomas (BL) is an issue of controversial debate. To clarify this matter, a semi-nested primer polymerase chain reaction was performed to amplify the VDJ rearrangements of the immunoglobulin heavy chain (VH) gene of DNA extracts from 10 (8 sporadic and 2 endemic) BL cases. The resulting amplificates were sequenced for comparison with known germ line VH segments. The control cases comprised six cases of B cell chronic lymphocytic leukemia and six cases of mantle cell lymphoma known to display naive nonmutated, ie, pre-germinal center VH configurations; and eight cases of follicular center lymphoma known to display mutated VH genes with signs of a still-ongoing mutation reaction, characteristic for germinal center cells and lymphomas that derive therefrom. The results of this approach revealed that both sporadic and endemic BL express mutated VH genes with a mutation frequency considerably lower (4.9% and 5.4%, respectively) than that observed in follicular center lymphoma (11.8%). In addition, after subcloning the amplificates, sequence analysis revealed no signs of ongoing mutations. These results led us to conclude that the derivation of neoplastic B cells in BL is definitely not from naive, nonmutated pre-germinal center B cells. Instead, our findings support the view that BL cells stem either from early centroblasts that are arrested after an initial hypermutation reaction, or from germinal center B cells that have differentiated in terms of surface immunoglobulin profile and mutation pattern but not in terms of morphology and proliferation toward SIgM+ IgD- memory B cells because of the deregulated c-myc gene expression.     

Burkitt's lymphoma: new insights into molecular pathogenesis

The World Health Organisation classification reports three subcategories of Burkitt's lymphoma (BL)--endemic, non-endemic, and immunodeficiency associated--proposed to reflect the major clinical and genetic subtypes of this disease. These different types of BL have been reviewed and studied by immunohistochemistry and molecular methods. The results point out the heterogeneity of BL and suggest that AIDS related BL may have a different pathogenesis from that of classic BL.     

Let it snow! Let it snow! Let it snow! Estimating cocaine production using a novel dataset based on reported seizures of laboratories in Colombia

BackgroundData on the cocaine market appear inconsistent, as they tend to show declining prices vis-a-vis steady or increasing demand and a declining supply. This paper proposes an explanation for this trend by providing evidence of an under-estimation of the supply of cocaine.MethodsWe propose a conservative estimate of cocaine production in Colombia for 2008, using data based on all reported seizures from 328 laboratories made by the counteracting organisations operating within the Colombian territory.ResultsOur conservative estimate of 935 tons from the seized laboratories is at least twice the estimate declared in official statistics of 295–450 tons. We are careful to keep all variables to their minimum boundary values. Our methodology could prove to be a useful tool, especially if used in parallel with the standard tools. Moreover, its characteristics (affordability, ease of use and potential for worldwide adoption) make it a powerful instrument to counteract cocaine production.     

Simplified Histologic Mucosal Healing Scheme (SHMHS) for inflammatory bowel disease: a nationwide multicenter study of performance and applicability

Techniques in Coloproctology - Assessment of mucosal healing is important for the management of patients with inflammatory bowel disease (IBD), but endoscopy can miss microscopic disease areas that...     

Ealuation of thrombolytic treatment of acute myocardial infarct using myocardial scintigraphy with Tc-99-MIBI. Immediate results and follow-up after one year

The aim of the study was to investigate Single Photon Emission Computed Tomography (SPECT) with technetium-99m esakis-2-methoxy isobutyl isonitrile (Tc-99m-MIBI) as a means of evaluating the results of intravenous thrombolytic treatment in patients with acute myocardial infarction. In addition, the evolution of myocardial perfusion pattern was studied. The study group included 15 patients (12 males and 3 females, mean age 57 +/- 8 years) with acute myocardial infarction admitted to the coronary care unit within 4 hours of the onset of symptoms. All patients were injected with 740 MBq of Tc-99m-MIBI before starting the thrombolytic therapy (rt-PA 100 mg i.v. in 3 hours); SPECT was performed 3 to 6 hours later. The tomographic study was repeated 5 days later. Ten patients were re-examined using Tc-99m-MIBI SPECT one year after the acute event. Taking into account the clinical, electrocardiographic and enzymatic data and the findings of two-dimensional echocardiography performed both on the fifth day and after one month, patients were divided into two groups: group A (8 patients) with probably effective reperfusion, group B (7 patients) probably unaffected by therapy. The infarct related vessel was patent in all group A patients and in 2 of the 7 patients of group B. The percent decrease in the perfusion defect size between the first and second scintigraphic studies showed a significant difference between the two groups: group A 61.2 +/- 6.8, group B 4.7 +/- 2.4% (p less than 0.002). A significant difference was also found when the results of the admission scintigraphy were compared with those of the control 1 year after: group A 80.8 +/- 8.7%, group B 20.8 +/- 13.8% (p less than 0.02). The percent decrease in the perfusion defect size between the 5-day and 1-year images was also significantly different in the two groups: group A 52.9 +/- 20.9%; group B 17.8 +/- 12% (p less than 0.02). The late perfusion improvement involved mainly the sub-epicardial layers. In conclusion, Single Photon Emission Computed Tomography with Tc-99m-MIBI clearly identified patients with effective reperfusion after thrombolytic treatment and distinguished them from subjects unaffected by therapy. Both, successfully and unsuccessfully treated patients showed a late perfusion improvement which was more evident in the successfully treated patients.     

Hydrogen peroxide formation in platelets of patients with non-insulin-dependent diabetes mellitus

A group of 29 patients with non-insulin-dependent diabetes mellitus (NIDDM) was compared with a group of 19 patients who had good glycemic control for platelet activity and hydrogen peroxide formation. NIDDM patients showed platelet hyperactivity in response to low ADP concentrations. In addition, stimulated platelets from untreated NIDDM patients produced more hydrogen peroxide than platelets of treated and normal subjects. Hydrogen peroxide accumulation was not related to modification of the enzymatic systems involved in its synthesis and break-down. The specific activities of NAD(P)H cytochrome C reductase, catalase, glutathione peroxidase and glutathione reductase were not different between patients and healthy subjects. It is likely that the platelet intracellular elevation of reactive oxygen free-radicals could play an important role in the vascular complications and thrombotic risk that is often present in NIDDM patients.     

Long-term efficacy and safety of propafenone and sotalol for the maintenance of sinus rhythm after conversion of recurrent symptomatic atrial fibrillation

This study was performed to evaluate, using a randomized double-blind, placebo-controlled protocol, the long-term efficacy and safety of propafenone and sotalol in maintaining sinus rhythm after conversion of recurrent symptomatic atrial fibrillation (AF). The maintenance of sinus rhythm in patients with recurrent AF has several potential benefits, the most important being a reduced risk of thromboembolic events. Three hundred patients with recurrent AF (> or = 4 episodes in the last year) and AF at enrollment lasting < 48 hours were randomized to receive either propafenone (mean daily dose 13 +/- 1.5 mg/kg; 102 patients), sotalol (mean daily dose 3 +/- 0.4 mg/kg; 106 patients), or placebo (92 patients). After 1-year follow-up, Kaplan-Meier estimates of the proportion of patients remaining in sinus rhythm were comparable between propafenone (63%) and sotalol (73%) and superior to placebo (35%; p = 0.001 vs both drugs). Symptomatic recurrences occurred later with propafenone and sotalol than with placebo. Nine patients (9%) in the propafenone group, 11 (10%) in the sotalol group, and 3 (3%) in the placebo group discontinued therapy due to adverse effects. Malignant nonfatal arrhythmias due to proarrhythmic effects were documented with sotalol only, and occurred < 72 hours from the beginning of therapy in 4 patients (4%). During recurrences, the ventricular rate was significantly reduced in patients taking propafenone and sotalol (p = 0.001 for both drugs vs placebo). The likelihood of remaining in sinus rhythm during follow-up was higher in younger patients with smaller left atrial size and without concomitant heart disease. In patients with recurrent symptomatic AF, propafenone and sotalol are not significantly different from each other and are superior to placebo in maintaining sinus rhythm at 1 year. Recurrences occur later and tend to be less symptomatic with propafenone and sotalol compared with placebo.