Telomerase activity in prognostic histopathologic features of melanoma.

BACKGROUND: Telomerase activity (TA) is believed to play a role in the regulation of senescence and to limit the number of cell divisions. The deregulation of telomerase appears to contribute to oncogenesis and the formation of immortal cell lines. As a result, it is believed that it could be used as a prognostic marker in melanoma. METHODS: TA was assayed by the polymerase chain reaction PCR-ELISA-based telomeric repeat amplification protocol (TRAP assay). One hundred and eight samples were distributed in four histological groups: 30 samples from primary cutaneous melanomas, 24 from peritumoural skin sites, 28 from benign melanocytic lesions, and 26 from normal skin sites as a control. RESULTS: TA was different among the four tested groups (Kruskall-Wallis test p<0.001), and increasing values of TA were observed progressing from normal skin to benign and then to malignant lesions. Among melanoma samples, there was a significant association between TA and ulceration (p=0.025), TA and vascular invasion (p=0.018) and TA and mitotic rate (p=0.029) (Mann-Whitney test). A linear regression analysis showed significant associations between the increase of TA with Breslow thickness (p=0.004) and the presence of satellites (p=0.002). CONCLUSIONS: We observed that TA had increased from control skin to peritumoural skin, and then to benign melanocytic lesions and finally to melanoma, suggesting tumour progression. TA showed higher values in the presence of some important histopathologic parameters related to poor prognosis in cutaneous melanoma such as ulceration, vascular invasion, satellites, high rates of mitosis, and in thicker tumours.     

Colonization with methicillin-resistant Staphylococcus aureus after liver transplantation.

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of infection after orthotopic liver transplantation (OLT). Colonization with MRSA is associated with a higher risk of infection. Previous studies have shown a high prevalence of MRSA colonization among OLT candidates. However, the risk of colonization with MRSA after OLT is still unclear. The objective of this study was to estimate the incidence and the factors associated with colonization with MRSA after OLT. This was a prospective cohort study including patients submitted to OLT between the years 2000 and 2002. Surveillance cultures of nasal swab specimens were performed within the 1st 72 hours of hospital admission and, subsequently, on weeks 2, 6, 13, and 26. Patients whose baseline cultures revealed nasal carriage of MRSA were excluded. A total of 60 patients were included in the study. The median follow-up was 72 days. A total of 9 patients (15%) became colonized. In multiple logistic regression analyses, the use of a urinary catheter for > or =5 days (P = .006), postoperative bleeding at the surgical site (P = .009), and preoperative use of fluoroquinolones (P = .08) were associated with a higher risk of colonization. Patients without any of these risk factors did not become colonized. In conclusion, nasal carriage of MRSA is frequently acquired after OLT. Periodic postoperative screening for MRSA carriage should be an integral component in programs designed to reduce nosocomial MRSA transmission in these patients. Further studies are needed to set up and validate a predictive model that could allow targeting postoperative screening to high-risk OLT recipients.     

Phosphatase activity on the cell wall of Fonsecaea pedrosoi.

The activity of a phosphatase was characterized in intact mycelial forms of Fonsecaea pedrosoi, a pathogenic fungus that causes chromoblastomycosis. At pH 5.5, this fungus hydrolyzed p-nitrophenylphosphate (p-NPP) to p-nitrophenol (p-NP) at a rate of 12.78 +/- 0.53 nmol p-NP per h per mg hyphal dry weight. The values of Vmax and apparent Km for p-NPP hydrolyses were measured as 17.89 +/- 0.92 nmol p-NP per h per mg hyphal dry weight and 1.57 +/- 0.26 mmol/l, respectively. This activity was inhibited at increased pH, a finding compatible with an acid phosphatase. The enzymatic activity was strongly inhibited by classical inhibitors of acid phosphatases such as sodium orthovanadate (Ki = 4.23 micromol/l), sodium molybdate (Ki = 7.53 micromol/l) and sodium fluoride (Ki = 126.78 micromol/l) in a dose-dependent manner. Levamizole (1 mmol/l) and sodium tartrate (10 mmol/l), had no effect on the enzyme activity. Cytochemical localization of the acid phosphatase showed electrondense cerium phosphate deposits on the cell wall, as visualized by transmission electron microscopy. Phosphatase activity in F. pedrosoi seems to be associated with parasitism, as sclerotic cells, which are the fungal forms mainly detected in chromoblastomycosis lesions, showed much higher activities than conidia and mycelia did. A strain of F. pedrosoi recently isolated from a human case of chromoblastomycosis also showed increased enzyme activity, suggesting that the expression of surface phosphatases may be stimulated by interaction with the host.     

Regional Distribution of Neurofibrillary Tangles and Senile Plaques in the Cerebral Cortex of Elderly Patients: A Quantitative Evaluation of a One-Year Autopsy Population from a Geriatric Hospital

Detailed analyses of the neuropathologic changes in the cerebralcortex of elderly individuals and Alzheimer's disease patientshave demonstrated that certain components of the neocorticaland hippocampal circuits are likely to be selectively vulnerable.Based on the distribution of neurofibrillary tangles (NFTs)and senile plaques, it has been proposed that a global cortico-corticaldisconnection leads to the loss of integrated functions observedin Alzheimer's disease. In order to investigate the distributionof lesions associated with aging as well as with the earliestsymptoms of senile dementia, we performed a quantitative neuropathologicavaluation of a large series of elderly patients representingthe entire autopsy population for the year 1989 from a geriatrichospital. Among the 145 cases quantitatively assessed, therewere 102 nondemented patients, 33 patients presenting clinicallywith globally intact intellectual function but early signs ofimpairment of specific cognitive functions, and 10 cases withsenile dementia of the Alzheimer type. All of the cases hadNFTs in layer II of the entorhinal cortex, regardless of theirclinical diagnosis, and most cases had some NFTs in the CA1field of the hippocampus. Severe pathologic changes within theinferior temporal neocortex were observed only in the dementedcases. The extent of amyloid deposition was not correlated withthe clinical diagnosis and seemed to be present in the neocorticalareas earlier than in the hippocampal formation. Also, severalcases contained NFTs without amyloid deposition, but amyloidnever occurred without NFTs. These results suggests that involvementof certain structures within the hippocampal formation is aconsistent feature of aging. Thus, involvement of the hippocampalformation may be a necessary, but not sufficient, conditionfor the clinical expression of dementia, which is likely tobe more closely related to the progressive degeneration of selectneuronal populations in the neocortex.     

Oral leiomyosarcomas: report of two cases with immunohistochemical profile.

Leiomyosarcoma of the oral cavity is a very rare tumor associated with aggressive clinical behavior and low survival. In this paper, we report 2 cases of leiomyosarcoma, affecting the gingival mucosa of a 54-year-old female and the maxillary bone of a 63-year-old male. Histologically, the tumors were composed of variably oriented fascicles of spindle-shaped cells with cigar-shaped nuclei and eosinophilic cytoplasm. The lesions were treated by surgical resection. Immunoreactivity to anti-vimentin, anti-smooth muscle actin, anti-desmin, anti-laminin, and anti-muscle-specific actin antibodies were found; conversely, the tumor cells were negative for anti-S100 and AE1/AE3 proteins. This report emphasizes the role of immunohistochemical study for correct diagnosis of leiomyosarcoma.     

Laparoscopic Deployment of Biliary Self-Expandable Metal Stent (SEMS) for One-Step Palliation in 23 Patients with Advanced Pancreatico-Biliary Tumors—a Pilot Trial

Background Exploratory laparoscopy is commonly undertaken in patients with highly suspicious biliary and pancreatic lesions to facilitate diagnosis and staging cancer is present. If an unresectable tumor is identified, a second endoscopic procedure may be required do deploy a self-expandable metal stent (SEMS) for palliation. As endoscopic retrograde cholangio pancreatography (ERCP) may be unsuccessful in up to 20% of patients, we evaluated the feasibility and safety of deployment of self-expandable metal stents at the same time as the initial laparoscopy. Patients and Methods A total of 23 eligible patients (8 male and 15 female) with malignant obstruction of the common bile duct underwent deployment of SEMS at laparoscopy. Primary outcome measure was the successful laparoscopic deployment of stent and secondary outcome measure was complications rates. Results Indications for stent deployment were unresectable pancreatic cancer in 18, cholangiocarcinoma in two, neuroendocrine tumor in one and ampullary adenocarcinoma in two patients. The median age was 73 years (range 49–93). Twenty-two of 23 stents were deployed successfully: 17 stents were deployed transcystically and five via a choledochotomy. Median times for laparoscopic exploration and SEMS deployment were 165 min (range 105–230) and 20 min (range 10–50), respectively. Pre- and post-procedures median total bilirubin were 9.4 mg/dl (range 5.4–17.5) and 4.0 (range 2.6–7.1). The median size of the pancreatic mass was 3 cm (range 2–5 cm) and that of the common bile duct (CBD) from 9.2 mm (range 7.2–17.4). The mean duration of laparoscopy was 170 min (range 120–230 min) and that for stent deployment 23 min (range 10–50 min). Complications included bleeding, obstruction, and wound infection. Bleeding occurred on day 7 in two patients and on day 30 in one patient; bleeding occurred at the gastrojejunal anastomosis site and was successfully treated with endoscopic hemostasis. A total of three stent obstructions were identified: one each at 60, 90, and 120 days follow-up. All complications were successfully managed endoscopically. There were a total of seven deaths, six as a result of progressive cancer and one of surgical wound infection and ensuing complications. Conclusion This study demonstrates that laparoscopic deployment of self-expandable metal bile duct stents is feasible and safe. This option appears to be a reasonable option in patients with inoperable malignant obstruction of the distal common bile duct.