The contribution of reactive oxygen species and p38 mitogen-activated protein kinase to myofilament oxidation and progression of heart failure in rabbits

Background and purpose:

The formation of reactive oxygen species (ROS) is increased in heart failure (HF). However, the causal and mechanistic relationship of ROS formation with contractile dysfunction is not clear in detail. Therefore, ROS formation, myofibrillar protein oxidation and p38 MAP kinase activation were related to contractile function in failing rabbit hearts.

Experimental approach and key results:

Three weeks of rapid left ventricular (LV) pacing reduced LV shortening fraction (SF, echocardiography) from 32 ± 1% to 13 ± 1%. ROS formation, as assessed by dihydroethidine staining, increased by 36 ± 8% and was associated with increased tropomyosin oxidation, as reflected by dimer formation (dimer to monomer ratio increased 2.28 ± 0.66-fold in HF vs. sham, P < 0.05). Apoptosis (TdT-mediated dUTP nick end labelling staining) increased more than 12-fold after 3 weeks of pacing when a significant increase in the phosphorylation of p38 MAP kinase and HSP27 was detected (Western blotting). Vitamins C and E abolished the increases in ROS formation and tropomyosin oxidation along with an improvement of LVSF (19 ± 1%, P < 0.05 vs. untreated HF) and prevention of apoptosis, but without modifying p38 MAP kinase activation. Inhibition of p38 MAP kinase by SB281832 counteracted ROS formation, tropomyosin oxidation and contractile failure, without affecting apoptosis.

Conclusions and implications:

Thus, p38 MAP kinase activation appears to be upstream rather than downstream of ROS, which impacts on LV function through myofibrillar oxidation. p38 MAP kinase inhibition is a potential target to prevent or treat HF.     

Decisive role of SPECT/CT in localization of unusual periscapular sentinel nodes in patients with posterior trunk melanoma: three illustrative cases and a review of the literature

Sentinel node mapping is widely applied in patients with melanoma. Although this type of skin cancer usually drains to the standard regional nodal basins, some patients have drainage to an unpredicted site. Nodes lying along a lymphatic channel, between the primary melanoma site and a common basin, are often called interval, in-transit, ectopic, intercalated, or aberrant nodes. They must be considered sentinel lymph nodes because they receive direct lymphatic drainage from a primary tumor site. Most investigators agree that interval sentinel nodes should be harvested; however, the management of melanoma patients with an involved interval sentinel node without established metastasis in the regional basin downstream is controversial. New and innovating technologies have improved nuclear medicine images, including single-photon emission computed tomography/computed tomography (SPECT/CT), a multimodal technique that fuses the radioactivity distribution detected by SPECT with the anatomic information harvested by CT. SPECT/CT does not replace the conventional planar images; it should be considered as a complementary modality for the search of sentinel lymph nodes. We report three illustrative cases that underline the decisive role of SPECT/CT with two-dimensional and three-dimensional reconstruction images to localize the uncommon periscapular sentinel nodes in patients with melanoma of the posterior trunk. The use of this image fusion technique on these patients leads to improved preoperative visualization of the sentinel nodes, may help identify additional periscapular interval sentinel nodes, and enables precise localization of the nodes with their surrounding anatomic structures. The cases are discussed together with a review of the literature.     

New boundaries for lymphatic mapping-report of the Fifth International Sentinel Node Conference

The Fifth Biennial International Sentinel Node Society meeting was held in Rome from 1 to 4 November 2006. Compared with previous meetings, there was a shift in focus from aspects of the clinical technique of the procedure to aspects of basic science that indicate the biology of the disease. The authors report on conference presentations relating to melanoma, including discussion of results from the Multicentre Selective Lymphadenectomy Trial 1 in intermediate thickness primary melanoma.     

The posterior lymphatic network of the breast rediscovered

Although the posterior lymphatic network of the breast has been described at the end of the 18th century, this anatomical entity had been almost forgotten. The observation of an increased visualization of extra-axillary sentinel nodes after image guided intralesional radiocolloid injection in non-palpable breast tumors has focused our attention again on the lymphatics on the posterior surface of the breast.     

Risk factors associated with mental illness in Oyo State,Nigeria: A Community based study

Background  

The main objective of this study was to determine the prevalence and factors associated with mental illness in Oyo State at community level using the general health questionnaire as a screening tool.     

Prepubic sentinel node location in penile carcinoma

An unusual sentinel node location in a patient with penile carcinoma is described. The preoperative lymphoscintigram showed a prepubic sentinel node. The node could be harvested during surgery. This case illustrates one of the advantages of lymphatic mapping in penile carcinoma: preoperative lymphoscintigraphy can identify lymph nodes outside the usual nodal basins.     

Non-visualization of sentinel lymph nodes in penile carcinoma

Purpose The purpose of this study was to analyse the incidence and cause of non-visualization of sentinel lymph nodes on preoperative lymphoscintigrams for penile cancer and its implications for further management.Methods Preoperative lymphoscintigraphy was performed after injection of ^99mTc-labelled nanocolloid in 123 clinically node-negative penile carcinoma patients. Anterior dynamic lymphoscintigraphy was performed during 20 min immediately after tracer injection. Subsequently, 5-min anterior and lateral static images were obtained 30 min and 2 h post injection.Results Lymphatic drainage to both groins was seen in 98 patients (79%), unilateral drainage in 23 patients (19%) and no drainage at all in two patients (2%). Thus, in 27 (11%) of 246 groins, no sentinel node was visualized. The amount of administered tracer dose was associated with non-visualization (p=0.01). Unilateral drainage was initially interpreted as a normal physiological phenomenon. After the occurrence of a tumour-positive node in a non-visualized groin, we explore non-visualized groins by blue dye mapping and intraoperative palpation. Sentinel nodes were retrieved in four out of eight such groins, of which one contained metastasis.Conclusion In penile carcinoma patients, preoperative lymphoscintigraphy visualizes a sentinel node in 89% of groins. Visualization depends on the administered tracer dose. It is worthwhile to explore non-visualized groins. Sentinel nodes can be intraoperatively identified in more than half of these cases.     

Isolated Limb Perfusion Prolongs the Limb Recurrence-Free Interval After Several Episodes of Excisional Surgery for Locoregional Recurrent Melanoma

Background The influence of isolated limb perfusion (ILP) on the limb recurrence-free interval (LRFI) and the number of lesions per recurrence was studied for patients with frequently recurring regional in-transit metastases previously managed by excisional surgery.Methods All 43 patients who had their first ILP for a third or further limb recurrence were selected from our computer database of 451 patients who underwent therapeutic ILP for recurrent extremity melanoma in our centers. Eighteen patients had resectable and 25 had locally unresectable lesions at the time of ILP. The patients had a total of 269 intervals between treatment of their primary melanoma and last recurrence or last follow-up. Median follow-up was 35 months (interquartile range, 14–64 months).Results The median LRFI decreases over time from primary melanoma to the third or further recurrence for which ILP was performed (P < 0.001). The median LRFI is 4.7 times longer (95% confidence interval [CI], 2.8–7.9; P < 0.001) after ILP in comparison with the last interval before ILP. Patients with resectable lesions have a median LRFI that is 5.9 times longer (95% CI, 2.7–13; P < 0.001). In all patients, the number of lesions increases by 22% per recurrence number (95% CI, 10%–35%; P = 0.02). At the same recurrence number, patients before ILP have a 2.6-fold higher (95% CI, 1.6–4.5) mean number of lesions than do patients after ILP (P < 0.001).Conclusions ILP lengthens the LRFI and decreases the number of lesions per recurrence significantly in patients with repeatedly recurrent limb melanoma. Therefore, ILP could be a valuable adjunct to excisional surgery for in-transit metastases in these patients whose LRFIs tend to shorten over time.