Mixed medullary and follicular cell carcinoma of the thyroid in a 71-year-old man with history of malignant melanoma.

BACKGROUND: Mixed medullary-follicular carcinoma of the thyroid with a pleomorphic pattern is a rare malignant epithelial tumor characterized by clinical and immunohistochemical features of follicular and parafollicular thyroid cells. Different molecular mechanisms for mixed thyroid tumors have been suggested. CASE REPORT: We describe a 71-year-old man with a history of malignant melanoma with mixed medullary-follicular thyroid carcinoma. Cytology results of a fine needle aspiration biopsy were suspicious of a thyroid carcinoma. The patient underwent a total thyroidectomy for a solitary thyroid nodule in the right lobe. No lymph node metastases were present. Histopathology and immunohistochemistry revealed a mixed medullary and follicular cell carcinoma that showed characteristic patterns and calcitonin and thyroglobulin positivities in many of the tumor cells. The tumor was not associated with multiple endocrine neoplasia type 2. Detection of RET proto-oncogene point mutations in risk exons 10, 11, 13, 14, 15, and 16 was negative. Two polymorphisms, one in exon 11 G691S (GGT-->AGT) and another in exon 15 S904S (TCC-->TCG) were detected. CONCLUSIONS: A mixed differentiated thyroid tumor is a diagnostic challenge with fine needle aspiration. Definitive diagnosis remains the domain of histology because of the necessity of topographic information. The origins of this rare tumor entity are unclear. The possible association with the uncommon polymorphism G691S of the RET proto-oncogene is discussed.     

The morphology of the lymphatics of the coronary arteries in the dog.

On the supposition that pericoronary lymphatics play an important role in the efflux of interstitial fluid from the blood vessel wall, we examined the morphology of pericoronary arterial lymphatics in the dog. After ligation of the principal epicardial drainage lymphatics, after ligation of the left anterior descending coronary artery, after induced pericoronary inflammation and after instillation of India Ink into the pericardial sac using light, dissecting, and electron microscopy. The findings were compared with non-operated (control) dogs. Lymphatic drainage of the coronary arteries is via adventitial lymphatics, which do not penetrate to the media and via periadventitial lymphatics consisting of a subepicardial lymphatic plexus overlying the coronary arteries. The smaller arterioles in the ventricular muscle have many more accompanying lymphatics than do epicardial coronary arteries. In the latter arteries, prelymphatic channels formed by collagen fibers in the media likely transport interstitial fluid to the adventitial and periadventitial lymphatics. Arterial contraction also likely plays a role in propulsion of coronary arterial interstitial fluid towards adventitial lymphatics.     

Analysis of direct oil contrast lymphography of upper limb lymphatics traversing the axilla – A lesson from the past – Contribution to the concept of axillary reverse mapping

Introduction

Axillary reverse mapping (ARM) is a method to preserve upper extremity (UE) lymphatics during axillary surgery in breast cancer patients. This may reduce the incidence of lymphedema. Very precise method to demonstrate lymphatic drainage is direct X-ray lymphography.

Materials and methods

The evaluation of direct lymphography X-ray images of the axilla and proximal part of the upper extremity was performed in 9 subjects. As contrast was used Lipiodoil injected on the dorsal side of hand.

Results

The lymph from UE is drained by 2–4 main afferent collectors, which in 5 of 9 cases entered into one node in the lateral axilla (ARM node). This node was considered to be the sentinel lymph node for the UE. In 4 cases a cranial collector was shown, which led directly to nodes in the upper part of the axilla. This collector had numerous anastomoses with other collectors before entering the axillary nodes. The most important finding is the demonstration of numerous lymphatic anastomoses that take place between all imaged nodes in the axilla including the caudal nodes, which is the most frequent localization of the breast sentinel lymph node.

Conclusion

The relationship of lymphatic drainage of the UE and breast are closely related and share numerous connections. These connections represent the main problem of the ARM concept because they may pose potencional route for metastatic cancer cells in sentinel node positive breast cancer patients. Further studies are necessary to improve understanding of this method.Axillary reverse mapping – breast cancer – lymphedema – sentinel node biopsy.     

Synthesis and initial in vitro evaluations of novel antioxidant aroylhydrazone iron chelators with increased stability against plasma hydrolysis

Oxidative stress is known to contribute to a number of cardiovascular pathologies. Free intracellular iron ions participate in the Fenton reaction and therefore substantially contribute to the formation of highly toxic hydroxyl radicals and cellular injury. Earlier work on the intracellular iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH) has demonstrated its considerable promise as an agent to protect the heart against oxidative injury both in vitro and in vivo. However, the major limitation of SIH is represented by its labile hydrazone bond that makes it prone to plasma hydrolysis. Hence, in order to improve the hydrazone bond stability, nine compounds were prepared by a substitution of salicylaldehyde by the respective methyl- and ethylketone with various electron donors or acceptors in the phenyl ring. All the synthesized aroylhydrazones displayed significant iron-chelating activities and eight chelators showed significantly higher stability in rabbit plasma than SIH. Furthermore, some of these chelators were observed to possess higher cytoprotective activities against oxidative injury and/or lower toxicity as compared to SIH. The results of the present study therefore indicate the possible applicability of several of these novel agents in the prevention and/or treatment of cardiovascular disorders with a known (or presumed) role of oxidative stress. In particular, the methylketone HAPI and nitro group-containing NHAPI merit further in vivo investigations.     

New model system for testing effects of flavonoids on doxorubicin-related formation of hydroxyl radicals

Doxorubicin belongs to anthracycline cytotoxic drugs and it is widely used as a major therapeutic agent in the treatment of various types of tumors. However,its therapeutic use is limited by the development of myelosuppression and cardiotoxicity after a specific cumulative dose is reached. The aim of this study was to investigate the effect of flavonoids, either natural or synthetic on doxorubicin-mediated formation of oxidative stress implicated in doxorubicin toxicity. Doxorubicin caused a concentration-dependent increase in the formation of hydroxyl radicals in minipig liver microsomes used as an in-vitro model system. When bacterial membranes heterologously expressing human NADPH cytochrome-P450 oxidoreductase were incubated with doxorubicin, formation of the superoxide radical under aerobic conditions and the doxorubicin–semiquinone radical under anaerobic conditions was detected. Forty different flavonoids were tested for their potency to prevent NADPH-induced or Fe2+-induced peroxidation of lipids in the microsomal system. According to the results, seven flavonoids were selected for evaluation of their potency to inhibit doxorubicin-dependent formation of hydroxyl radicals assessed by electron spin resonance. Myricetin, fisetin, and kaempferol were found to produce a significant protective effect against hydroxyl radicals in the minipig liver microsomal system. In conclusion, this study shows the use of a novel cost-effective in-vitro model system for preselection of antioxidants for testing of their protective effects against toxicity of anthracyclines and potentially other oxidative stress-inducing chemicals.     

Distribution of Anopheles albimanus, Anopheles vestitipennis, and Anopheles crucians associated with land use in northern Belize

Anthropogenic land use changes often alter natural patterns of disease transmission. The goal of this study was to determine whether phosphorus input from sugarcane, Saccharum officinarum L., cultivation in northern Belize could pose a significant environmental impact on malaria transmission by changing vegetation structure and composition of wetlands and associated larval habitats. Our primary focus was on the increased dominance of cattail, Typha domingensis Pers., a favored habitat for Anopheles vestitipennis Dyar & Knab. A land cover classification based on satellite imagery was used to select 20 marshes impacted by agricultural runoff and 20 marshes surrounded by forest (nonimpacted). A 100-m transect was established into each of the 40 marshes. Water, vegetation, and larval sampling were conducted at the 0-, 10-, 25-, 50-, and 100-m locations along the transect. Analyses of larval density data indicated that Anopheles albimanus Wiedemann was negatively correlated with percentage of cover of Typha (R2 = 0.39, P < 0.001) but positively correlated with sparse Eleocharis cellulosa Torr. (rush) cover (R2 = 0.19, P < 0.05) and presence of cyanobacterial mats (CBM) (R2 = 0.33, P < 0.0001). An. vestitipennis was found to be positively correlated with percentage of cover of Typha (R2 = 0.19, P < 0.001). Canonical correspondence analysis identified CBM and light as the variables associated with the presence of An. albimanuts larvae, Typha cover with An. vestitipennis larvae, and Eleocharis and absence of light with Anopheles crucians (Wiedemann). A positive correlation also existed between marshes adjacent to agricultural activities and presence of An. vestitipennis (R2 = 0.37, P < 0.05). These results indicate that marshes in proximity to agricultural fields are conducive for Typha growth, thereby providing habitat for the more efficient malaria vector