Tissue distribution of retinoids in common dolphins (Delphinus delphis).

Exposure to organochlorines induces retinoid deficiency in mammals; hence, retinoids are potential biomarkers of the impact of these pollutants. Appropriate target tissues to monitor retinoids in cetaceans have not been properly identified because of a lack of information on the contribution of each tissue to total body retinoids. Therefore, we have addressed this issue by studying the contribution of the main body tissues to retinoids in 21 common dolphins obtained from incidental catches and in apparent good health and nutritive condition. Although concentrations in the liver were highest, those in blubber were also high and accounted for 43% of the total retinoid load of the compartments examined. As blubber can be obtained using non-invasive biopsy techniques, this tissue is proposed as a reliable indicator of retinoid status in cetaceans. However, blubber topographical variation in structure and composition requires standardization of sampling sites. Retinoid concentrations did not differ significantly between sexes or with body size for any of the tissues, but the lipid content of blubber strongly influenced these concentrations. Biopsies from healthy, free-ranging individuals are preferred to samples from stranded animals. Further research on the influence of factors (age, sex, reproductive condition, diet) that potentially affect retinoid levels is required to implement the use of retinoids as biomarkers of pollutant exposure in cetaceans.

Treatment of pleural malignancies by photo-induction combined to systemic chemotherapy: Proof of concept on rodent lung tumors and feasibility study on porcine chest cavities.

BACKGROUND: Low-dose, Visudyne®-mediated photodynamic therapy (photo-induction) was shown to selectively enhance tumor vessel transport causing increased uptake of systemically administered chemotherapy in various tumor types grown on rodent lungs. The present experiments explore the efficacy of photo-induced vessel modulation combined to intravenous (IV) liposomal cisplatin (Lipoplatin®) on rodent lung tumors and the feasibility/toxicity of this approach in porcine chest cavities. MATERIAL AND METHODS: Three groups of Fischer rats underwent orthotopic sarcoma (n = 14), mesothelioma (n = 14), or adenocarcinoma (n = 12) implantation on the left lung. Half of the animals of each group had photo-induction (0.0625 mg/kg Visudyne®, 10 J/cm(2) ) followed by IV administration of Lipoplatin® (5 mg/kg) and the other half received Lipoplatin® without photo-induction. Then, two groups of minipigs underwent intrapleural thoracoscopic (VATS) photo-induction (0.0625 mg/kg Visudyne®; 30 J/cm(2) hilum; 10 J/cm(2) apex/diaphragm) with in situ light dosimetry in combination with IV Lipoplatin® administration (5 mg/kg). Protocol I (n = 6) received Lipoplatin® immediately after light delivery and Protocol II (n = 9) 90 minutes before light delivery. Three additional animals received Lipoplatin® and VATS pleural biopsies but no photo-induction (controls). Lipoplatin® concentrations were analyzed in blood and tissues before and at regular intervals after photo-induction using inductively coupled plasma mass spectrometry. RESULTS: Photo-induction selectively increased Lipoplatin® uptake in all orthotopic tumors. It significantly increased the ratio of tumor to lung Lipoplatin® concentration in sarcoma (P = 0.0008) and adenocarcinoma (P = 0.01) but not in mesothelioma, compared to IV drug application alone. In minipigs, intrapleural photo-induction combined to systemic Lipoplatin® was well tolerated with no toxicity at 7 days for both treatment protocols. The pleural Lipoplatin® concentrations were not significantly different at 10 and 30 J/cm(2) locations but they were significantly higher in protocol I compared to II (2.37 ± 0.7 vs. 1.37 ± 0.7 ng/mg, P  < 0.001). CONCLUSION: Visudyne®-mediated photo-induction selectively enhances the uptake of IV administered Lipoplatin® in rodent lung tumors. Intrapleural VATS photo-induction with identical treatment conditions combined to IV Lipoplatin chemotherapy is feasible and well tolerated in a porcine model. Lasers Surg. Med. 47:807-816, 2015. © 2015 Wiley Periodicals, Inc.

Oxidative stress in gastric mucosa of asymptomatic humans infected with Helicobacter pylori: effect of bacterial eradication.

BACKGROUND: Inducible nitric oxide synthase (iNOS) and interleukin 8 (IL-8) are positive in approximately 50% of Helicobacter pylori-related diseases but it is not clear whether oxidative stress is also present in H. pylori asymptomatic humans. Our aim was to study the expression of iNOS, superoxide dismutase, catalase and IL-8 production in H. pylori-infected asymptomatic humans, and to investigate the effect of eradication of H. pylori. MATERIALS AND METHODS: Biopsies of corpus and antrum of asymptomatic H. pylori positive and negative humans served for determination of the gastritis score and H. pylori status; iNOS was measured by reverse transcriptase polymerase chain reaction and immunohistochemistry and superoxide dismutase and catalase by immunohistochemistry. IL-8 in biopsies was assessed by enzyme-linked immunosorbent assay. RESULTS: Immunostaining of iNOS, catalase and superoxide dismutase was significantly associated with H. pylori infection and was localized to inflammatory cells. IL-8 concentrations were greater in the H. pylori positive than H. pylori negative group and decreased after bacterial eradication. A decrease in staining for iNOS and catalase was observed after H. pylori eradication. CONCLUSIONS: INOS and antioxidant enzymes are present in gastric biopsies of asymptomatic H. pylori positive humans. Eradication caused a significant decrease in staining for iNOS and catalase. These results indicate that oxidative stress occurs in asymptomatic patients and can be modulated by H. pylori eradication.

Maladie de Whipple: quand y penser [Whipple's disease, when to think about it?].

Whipple's disease is a chronic, systemic, bacterial infection caused by Tropheryma whipplei. Its cardinal symptoms include intermittent and recurrent arthralgia or arthritis together with chronic diarrhoea, abdominal pain and weight loss. It may mimick many chronic inflammatory diseases, and the diagnosis remains a challenge. Salivary and faecal quantitative PCR for T. whipplei should be ensued, if positive, by an upper endoscopy for duodenal biopsies. The treatment consists of a combination of oral doxycycline and hydroxychloroquine for 12 months followed by life-long doxycycline. Whipple's disease, although rare, is an entity that should be considered regularly, as its progression may be fatal if left untreated.

Expression of Glycogen Phosphorylase Isoforms in Cultured Muscle from Patients with McArdle´s Disease Carrying the p.R771PfsX33 PYGM Mutation

Mutations in the PYGM gene encoding skeletal muscle glycogen phosphorylase (GP) cause a metabolic disorder known as McArdle's disease. Previous studies in muscle biopsies and cultured muscle cells from McArdle patients have shown that PYGM mutations abolish GP activity in skeletal muscle, but that the enzyme activity reappears when muscle cells are in culture. The identification of the GP isoenzyme that accounts for this activity remains controversial.

Foreword

Le livre décrit l'utilisation de l'ultrasonographie pour explorer le système musculo-squelettique et les nerfs périphériques et pour guider des interventions (ponctions, infiltrations, biopsies, etc.) sur ces structures.

E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis.

E2F transcription factors are known regulators of the cell cycle, proliferation, apoptosis, and differentiation. Here, we reveal that E2F1 plays an essential role in liver physiopathology through the regulation of glycolysis and lipogenesis. We demonstrate that E2F1 deficiency leads to a decrease in glycolysis and de novo synthesis of fatty acids in hepatocytes. We further demonstrate that E2F1 directly binds to the promoters of key lipogenic genes, including Fasn, but does not bind directly to genes encoding glycolysis pathway components, suggesting an indirect effect. In murine models, E2F1 expression and activity increased in response to feeding and upon insulin stimulation through canonical activation of the CDK4/pRB pathway. Moreover, E2F1 expression was increased in liver biopsies from obese, glucose-intolerant humans compared with biopsies from lean subjects. Finally, E2f1 deletion completely abrogated hepatic steatosis in different murine models of nonalcoholic fatty liver disease (NAFLD). In conclusion, our data demonstrate that E2F1 regulates lipid synthesis and glycolysis and thus contributes to the development of liver pathology.

Ultrasound-guided fine-needle aspiration of thyroid nodules: assessment of the ideal number of punctures

OBJECTIVE: To determine the number of punctures in fine-needle aspiration biopsies required for a safe cytological analysis of thyroid nodules. MATERIALS AND METHODS: Cross-sectional study with focus on diagnosis. The study population included 94 patients. RESULTS: The mean age of the patients participating in the study was 52 years (standard-deviation = 13.7) and 90.4% of them were women. Considering each puncture as an independent event, the first puncture has showed conclusive results in 78.7% of cases, the second, in 81.6%, and the third, in 71.8% of cases. With a view to the increasing chance of a conclusive diagnosis at each new puncture, two punctures have showed conclusive results in 89.5% of cases, and three punctures, in 90.6% of cases with at least one conclusive result. CONCLUSION: Two punctures in fine-needle aspiration biopsies of thyroid nodules have lead to diagnosis in 89.5% of cases in the study sample, suggesting that there is no need for multiple punctures to safely obtain the diagnosis of thyroid nodules.

Computed tomography-guided percutaneous biopsy of pancreatic masses using pneumodissection

Objective To describe the technique of computed tomography-guided percutaneous biopsy of pancreatic tumors with pneumodissection. Materials and Methods In the period from June 2011 to May 2012, seven computed tomography-guided percutaneous biopsies of pancreatic tumors utilizing pneumodissection were performed in the authors' institution. All the procedures were performed with an automatic biopsy gun and coaxial system with Tru-core needles. The biopsy specimens were histologically assessed. Results In all the cases the pancreatic mass could not be directly approached by computed tomography without passing through major organs and structures. The injection of air allowed the displacement of adjacent structures and creation of a safe coaxial needle pathway toward the lesion. Biopsy was successfully performed in all the cases, yielding appropriate specimens for pathological analysis. Conclusion Pneumodissection is a safe, inexpensive and technically easy approach to perform percutaneous biopsy in selected cases where direct access to the pancreatic tumor is not feasible.

Positive predictive values of Breast Imaging Reporting and Data System (BI-RADS®) categories 3, 4 and 5 in breast lesions submitted to percutaneous biopsy

Objective To evaluate the BI-RADS as a predictive factor of suspicion for malignancy in breast lesions by correlating radiological with histological results and calculating the positive predictive value for categories 3, 4 and 5 in a breast cancer reference center in the city of São Paulo. Materials and Methods Retrospective, analytical and cross-sectional study including 725 patients with mammographic and/or sonographic findings classified as BI-RADS categories 3, 4 and 5 who were referred to the authors' institution to undergo percutaneous biopsy. The tests results were reviewed and the positive predictive value was calculated by means of a specific mathematical equation. Results Positive predictive values found for categories 3, 4 and 5 were respectively the following: 0.74%, 33.08% and 92.95%, for cases submitted to ultrasound-guided biopsy, and 0.00%, 14.90% and 100% for cases submitted to stereotactic biopsy. Conclusion The present study demonstrated high suspicion for malignancy in lesions classified as category 5 and low risk for category 3. As regards category 4, the need for systematic biopsies was observed.

Screening of breast lesions: a comparative study between mammography, B-mode ultrasonography, sonoelastography and histological results

Objective To compare the capacity of mammography, sonoelastography, B-mode ultrasonography and histological analysis to differentiate benign from malignant breast lesions. Materials and Methods A total of 12 histopathologically confirmed breast lesions were documented. The lesions were assessed by means of mammography, B-mode ultrasonography and sonoelastography, and histopathological analysis was utilized as a gold standard. Sensitivity and specificity were calculated. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic performance of the mentioned techniques. Results Sensitivity and specificity in the differentiation between benign and malignant lesions were respectively 100% and 50% for mammography, 100% and 71% for B-mode ultrasonography, and 67% and 83% for sonoelastography. The area under the ROC curve was calculated for the three imaging modalities and corresponded to 0.792 for mammography, 0.847 for B-mode ultrasonography, and 0.806 for sonoelastography. Conclusion Sonoelastography demonstrated higher specificity and lower sensitivity as compared with mammography and B-mode ultrasonography. On the other hand, B-mode ultrasonography had the largest area under the ROC curve. Sonoelastography has demonstrated to be a promising technique to detect and evaluate breast lesions, and could potentially reduce the number of unnecessary biopsies.

Poorly differentiated clusters (PDC) in colorectal cancer: what is and ought to be known.

BACKGROUND: The counting of poorly differentiated clusters of 5 or more cancer cells lacking a gland-like structure in a tumor mass has recently been identified among the histological features predictive of poor prognosis in colorectal cancer. MAIN BODY: Poorly differentiated clusters can easily be recognized in the histological sections of colorectal cancer routinely stained with haematoxylin and eosin. Despite some limitations related to specimen fragmentation, counting can also be assessed in endoscopic biopsies. Based on the number of poorly differentiated clusters that appear under a microscopic field of a ×20 objective lens (i.e., a microscopic field with a major axis of 1 mm), colorectal cancer can be graded into malignancies as follows: tumors with <5 clusters as grade 1, tumors with 5 to 9 clusters as grade 2, and tumors with ≥10 clusters as grade 3. High poorly differentiated cluster counts are significantly associated with peri-neural and lympho-vascular invasion, the presence of nodal metastases or micrometastases, as well as shorter overall and progression free survival to colorectal cancer. CONCLUSION: The morphological aspects and clinical relevance of poorly differentiated clusters counting in colorectal cancer are discussed in this review.

Maladie des griffes du chat et autres bartonelloses [Cat scratch disease and other human infections caused by Bartonella species].

The different Bartonella species can cause various human infections such as cat scratch disease, chronic bacteremia (homeless patient with nonspecific symptom), endocarditis, bacillary angiomatosis, peliosis, and Carrion's disease. Diagnostic approaches include serology, culture and molecular approaches. PCR is especially useful on lymph nodes biopsies from patients with cat-scratch disease and on valvular samples taken from culture-negative endocarditis. Serology exhibits a very high sensitivity in the latter situation. The treatment should be chosen according to the clinical presentation.

Muscle Characteristics and Substrate Energetics in Lifelong Endurance Athletes.

PURPOSE: The goal of this study was to explore the effect of lifelong aerobic exercise (i.e., chronic training) on skeletal muscle substrate stores (intramyocellular triglyceride [IMTG] and glycogen), skeletal muscle phenotypes, and oxidative capacity (ox), in older endurance-trained master athletes (OA) compared with noncompetitive recreational younger (YA) athletes matched by frequency and mode of training. METHODS: Thirteen OA (64.8 ± 4.9 yr) exercising 5 times per week or more were compared with 14 YA (27.8 ± 4.9 yr) males and females. IMTG, glycogen, fiber types, succinate dehydrogenase, and capillarization were measured by immunohistochemistry in vastus lateralis biopsies. Fat-ox and carbohydrate (CHO)-ox were measured by indirect calorimetry before and after an insulin clamp and during a cycle ergometer graded maximal test. RESULTS: V˙O2peak was lower in OA than YA. The OA had greater IMTG in all fiber types and lower glycogen stores than YA. This was reflected in greater proportion of type I and less type II fibers in OA. Type I fibers were similar in size, whereas type II fibers were smaller in OA compared with YA. Both groups had similar succinate dehydrogenase content. Numbers of capillaries per fiber were reduced in OA but with a higher number of capillaries per area. Metabolic flexibility and insulin sensitivity were similar in both groups. Exercise metabolic efficiency was higher in OA. At moderate exercise intensities, carbohydrate-ox was lower in OA but with similar Fat-ox. CONCLUSIONS: Lifelong exercise is associated with higher IMTG content in all muscle fibers and higher metabolic efficiency during exercise that are not explained by differences in muscle fibers types and other muscle characteristics when comparing older with younger athletes matched by exercise mode and frequency.

The role of transrectal ultrasound in the diagnosis of prostate cancer: new contributions

Objective: The present study was aimed at evaluating the contribution of transrectal prostate ultrasound in the screening for prostate neoplasias and in the guidance of prostate biopsies. Materials and Methods: Prospective study developed over a one-year period. All the patients with indication for prostate biopsy were evaluated. Regardless of PSA values, the patients underwent ultrasound in order to identify suspicious nodules (confirmed by two observers). Sextant biopsy was subsequently performed. In cases of finding suspicious nodules, an additional puncture directed to such nodules was done. Results: In a total of 155 cases the prevalence of malignancy was of 53%. Suspicious nodules were detected in 34 patients, and 25 where malignant (positive predictive value of 74%). The specificity and sensitivity for suspicious nodules were 88% and 31% respectively. Comparatively with the randomly obtained sextant specimens, the rate of findings of neoplasia was higher in the specimens obtained with puncture directed to the nodule (p = 0.032). No statistically significant difference was observed in the Gleason score for both types of specimens (p = 0.172). Conclusion: The high positive predictive value and the high rate of findings of neoplasia in specimens of suspicious nodules should be taken into consideration in the future. The authors suggest a biopsy technique similar to the one described in the present study (sextant biopsy plus puncture directed to the suspicious nodule).