Facial Squamous Cell Carcinoma and Abdominal Peripheral Nerve Sheath Tumour with Rhabdomyoblastic Differentiation in a Rough-toothed Dolphin (Steno bredanensis).

We report the pathological features of a facial squamous cell carcinoma (SCC) and an abdominal peripheral nerve sheath tumour (PNST) with rhabdomyoblastic differentiation in an aged free-ranging rough-toothed dolphin (Steno bredanensis). The animal was found stranded dead in poor body condition. On external examination, there was a 25 × 7 × 3 cm extensively ulcerated area on the right maxillary region of the rostrum, involving the oral mucocutaneous junction with prominent nodular edges, severe soft tissue loss and extensive maxillary and premaxillary bone lysis. On abdominal dissection, a 5 × 4 × 3.5 cm pale tan to red, raised mass expanded the inner aspect of the right transverse abdominis muscle. Microscopically, the aggressive facial lesion was an acantholytic SCC with extensive osteolysis; there was no evidence of metastasis in the tissues examined. The abdominal mass had cytohistomorphological features compatible with a localized PNST, including whorling, Antoni A and Antoni B areas and Verocay bodies intermixed with rhabdomyoblastic components, as suggested by phosphotungstic acid haematoxylin stain. This neoplasm was locally infiltrative, yet no metastases were observed in the tissues examined. No immunohistochemical investigations could be performed due to lack of tissue availability. Total DNA from the formalin-fixed and paraffin wax-embedded SCC was extracted and tested by polymerase chain reaction for herpesvirus and papillomavirus genetic material. There was no amplification for either of these genera. Other pathological findings observed in this animal were related to the 'live-stranding stress response'. The severity and extent of the facial SCC likely related to anorexia and poor body condition and might have played a role in the stranding and death of this dolphin. These two tumour subtypes add to the relatively uncommon reports of neoplasia in cetaceans. Specifically, these appear to be the first neoplasia records for rough-toothed dolphins, including the first documentation of a PNST with features compatible with rhabdomyoblastic differentiation in a marine mammal.

EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.

OBJECTIVES: Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). METHODS: Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. RESULTS: Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. CONCLUSIONS: Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.

Megacolon tóxico en una paciente con colitis seudomembranosa / Toxic megacolon in a patient with colitis pseudomembranous

La colitis seudomembranosa es una patología relacionada con el uso de antibióticos. En raras ocasiones, evoluciona a megacolon tóxico que podría requerir resolución quirúrgica. Comunicamos el caso de una mujer de 22 años, que recibió amoxicilina/ácido clavulánico unos días antes de la consulta. Presentó diarrea, fiebre y vómitos. Radiografía y tomografía computarizada de abdomen: distensión de colon derecho >6 cm. Toxina para Clostridium: positiva. Comienza con el tratamiento médico y requiere cirugía por megacolon tóxico. El megacolon tóxico es una complicación infrecuente de la colitis seudomembranosa. Es rara en pacientes jóvenes y sin comorbilidades. Se llega al diagnóstico mediante los criterios de Jalan. La tasa de mortalidad se aproxima al 70%. Se debe mantener alto nivel de alerta ante signos de toxicidad sistémica y la dilatación colónica es diagnóstica de la entidad. El uso indiscriminado de antibióticos constituye un serio factor de riesgo.(AU)

Pseudomembranous colitis is a condition associated with the use of antibiotics. On rare occasions, it evolves to toxic megacolon which may require surgical resolution. We report the case of a 22-year-old woman who received amoxicillin/clavulanic acid a few days before the consultation. She referred diarrhea, fever and vomiting. Radiography and computed tomography of abdomen: distension of the right colon >6 cm. Clostridium toxin: positive. Medical treatment is administered and surgery is needed for toxic megacolon. Toxic megacolon is an infrequent complication of pseudomembranous colitis. It is rare in young patients without comorbidities. The diagnosis is reached using the Jalan criteria. The mortality rate approaches 70%. A high level of alertness should be maintained for signs of systemic toxicity and colonic dilation is diagnostic of the entity. Indiscriminate use of antibiotics is a serious risk factor.(AU)

Survival prognostic factors of gastro-enteric-pancreatic neuroendocrine tumors after primary tumor resection in a single tertiary center: Comparison of gastro-enteric and pancreatic locations.

AIM: This study aimed to evaluated prognostic factors of patients with GEP-NETs after primary tumor resection comparing pancreatic and gastro-enteric locations. METHODS: Patients undergone surgery for primary GEP-NETs between 01/2000 and 03/2012 were considered. All specimens were reclassified according to the WHO 2010 scheme. RESULTS: A total of 83 patients were considered: 37 pancreatic NETs (pNET) and 46 gastroenteric NETs (GE-NET). The two groups were similar in terms of age, sex and tumors size. A higher rate of patients with pNETs had Ki67 score ≥3 (64.8% vs. 39%, p = 0.027) while the rates of Mitotic Index ≥2x10HPF (62% pNET vs. 50% GE-NET, p = 0.374) and diagnosis of neuroendocrine carcinoma NEC (16.2% pNET vs. 17.3% GE-NET, p = 0.100) were similar. The rates of distant metastases (GE-NETs 30.4% vs. p-NETs 29.7%, p = 0.944) and liver metastases (19.5% GE-NET vs. 27% pNET, p = 0.421) were comparable. Radical resection was achieved in a similar proportion in both groups [33 patients (89.1%) pNET vs. 36 (78.2%) GE-NET, p = 0.393]. After a median follow-up of 47.1 months overall 3, 5 and 10-years survival rates of whole patients were 88.1%, 81.2% and 76.7%. There was not difference on 5-years overall survival between pNET (81.4%) and GE-NET (81%, p = 0.901). At multivariate analysis age ≥70 [OR 4.177 (CI 95% 1.26-13.8), p = 0.019] and NEC [OR 5.932 (CI 95% 1.81-19.40), p < 0.001] were negative prognostic factors of survival. CONCLUSION: Overall survival of GEP-NET after resection of primary tumors seems to be correlated to patient's age and WHO 2010 staging system but not to primary tumor site.

Successful mobilization of PBSCs predicts favorable outcomes in multiple myeloma patients treated with novel agents and autologous transplantation.

Incorporation of novel agents into auto-SCT for patients with multiple myeloma has led to improvement in their outcomes. However, the effects of new drugs, either single or combined, on PBSC mobilization have not been fully evaluated, particularly in phase 3 clinical studies. We analyzed the impact of two novel agent-based induction treatments in patients enrolled in the GIMEMA MMY-3006 study comparing bortezomib, thalidomide and dexamethasone (VTD) versus thalidomide and dexamethasone (TD) in preparation for double auto-SCT. Results showed that a short-term induction therapy with VTD did not adversely affect CD34(+) cell yields as compared with TD (9.75 vs 10.76 × 10(6) CD34(+) cells/kg, P=0.220). For poor mobilizers (<4 × 10(6) CD34(+) cells/kg), 5-year rates of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were significantly shorter than for successful mobilizers (TTP:17 vs 48%, P<0.0001; PFS: 16 vs 46%, P<0.0001; OS: 50 vs 80%, P<0.0001). These differences were retained across patients randomized to the TD arm; conversely, no differences in outcomes were seen in patients treated with VTD, irrespective of the number of harvested CD34(+) cells. The number of collected PBSCs predicted better outcomes after auto-SCT and VTD overcame the negative impact of a poor stem cell mobilization.

Osteoblastoma of cervical spine causing an unusual neck pain.

Osteoblastoma is a rare benign tumor of bone that accounts for approximately 1% of primary skeletal neoplasms, with around 90% of cases diagnosed in the second and third decades of life. Cervical spine is an usual localization of osteoblastoma. The main clinical manifestation in case of cervical spine location is a progressive and resistant pain, possibly accompanied by stiffness, scoliosis or other ailments, including severe neurological deficits. Owing to a non-specific clinical presentation of osteoblastoma, the delay in diagnosis is common. Osteoblastomas may have an aggressive behavior, tend to enlarge and damage the bone and adjacent structures. The treatment of choice is, therefore, a wide and complete surgical excision of the lesion in order to achieve full recovery and prevent recurrence or, in some cases, malignant transformation. In the case of persistent neck pain, not readily relieved by aspirin and possibly accompanied by stiffness, scoliosis or neurological deficits, especially in young subjects, osteoblastoma of cervical spine may be one of the diagnostic options to be considered, in order to avoid delay in diagnosis. We report the case of a 41-year-old male affected by cervical spine osteoblastoma causing a lasting neck pain.

Probiotics in the gastrointestinal diseases of the elderly.

Changes of the gut microflora in elderly appear to involve a reduction in numbers of healthy bacteria (lactobacilli and bifidobacteria) and an increase in numbers of potentially pathogenic species. These changes are generally described as gastrointestinal disorders and infections. This review analyses benefits of probiotics in old people, with particular interesting for the latest researches relevant to elderly people, e.g. trials examining enteric infections, antibiotic-associated diarrhea and Clostridium difficile associated diarrhea, functional bowel problems (constipation and irritable bowel syndrome), inflammatory bowel diseases, stimulation of the immune system and prevention of cancer. A growing number of researches indicates that some probiotic strains may help to maintain the health in old people, suggesting both health and cost-saving benefits in offering fermented dairy products. These benefits include: establishment of balanced intestinal microflora; improving colonization resistance and or prevention of diarrhea; reduction of fecal enzymes; reduction of serum cholesterol; reduction of potential mutagenes; reduction of lactose intolerance; synthesis of vitamins; predigestion of proteins.

Intensification of GVHD prophylaxis with low-dose ATG-F before allogeneic PBSC transplantation from HLA-identical siblings in adult patients with hematological malignancies: results from a retrospective analysis.

Several studies have shown that chronic GVHD (cGVHD) is more frequent in patients receiving transplants from PBSC than in those receiving BM. In the setting of PBSC-unrelated transplants, the addition of anti-T-cell globulin (ATG) has shown a significant decrease in incidence/severity of cGVHD, without an increase in relapses or infections. However, no prospective data are yet available in the sibling setting. We retrospectively analyzed the effects of intensification of standard GVHD prophylaxis (CsA+MTX) by the addition of low-dose ATG in 245 patients receiving a transplant from HLA-identical sibling. From 1996 to 2001, patients received PBSC as the preferred source (group 2), and then ATG was added before transplant (group 3) because of a high cGVHD rate. Patients receiving BM in the same time period were analyzed as a control group (group 1). The incidence of grade III-IV acute GVHD and cGVHD was not significantly different in the three groups, but extensive cGVHD was highest in group 2 (38%) compared with group 3 (21%) or group 1 (28%; P=0.03). OS, TRM and time to relapse/progression were similar in the three groups. Our analysis shows that adding ATG to PBSC sibling allogeneic transplants can lower cGVHD, without an increase of relapse. Further prospective studies are needed to confirm these findings.

Role of the energy sensor adenosine monophosphate-activated protein kinase in the regulation of immature gonadotropin-releasing hormone neuron migration.

BACKGROUND: The 5'-AMP-activated protein kinase (AMPK) plays a fundamental role in regulating energy homeostasis as well as feeding and metabolism, through central and peripheral actions. AMPK is activated by conditions causing ATP depletion and by different metabolic molecules, such as adiponectin and AMPK agonist, such as 5-aminoimidazole- 4-carboxamide-1-ß-D-ribofuranoside (AICAR). AMPK activation has also been shown to affect the migration of different cell types and to participate in the central control of reproductive function, although information concerning AMPK and the development of the hypothalamic reproductive compartment is lacking. AIM: To explore whether AMPK activation by globular adiponectin (gAdipo) and AICAR may affect the migratory ability of GnRH neurons. MATERIALS AND METHODS: We used GN11 immature GnRH neurons (in vitro model system), RT-PCR and Western blot analysis, and Boyden's chamber assay. RESULTS: gAdipo did not affect FBS-stimulated migration of GN11 cells and activated AMPK through the mandatory phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and Akt, which also interact one to each other. AICAR treatment inhibited FBS-stimulated GN11 cell migration, through a long-lasting activation of AMPK. A downstream activation of ERK1/2 by AICAR was also observed and inhibition of ERK1/2 amplified AICAR-induced inhibition of migration. CONCLUSIONS: The direct, but not the indirect, activation of AMPK appears to negatively affect FBSinduced GN11 cell migration, suggesting that the final balance between pro-migratory and anti-migratory actions may also depend upon the specific sequence of intracellular signals activated by one agent.

The role of radiation therapy in the management of non-functioning pituitary adenomas.

Surgical removal of non-functioning pituitary adenoma (NFPA) is the first-choice therapeutic option, but radical removal of the tumor cannot be accomplished in all patients. The best strategy to prevent regrowth of NFPA is still a matter of debate. Adjuvant radiotherapy is very effective in reducing recurrence rate after incomplete removal of NFPA, but concerns still exist about long-term toxicity of radiation. Different modalities have been developed to irradiate the pituitary region. One major distinction is between radiation techniques that deliver the total dose in multiple sessions using 3 fixed radiation beams and radiosurgical equipment that delivers the total dose to the target volume in a single treatment session. Progression-free survival of patients with NFPA treated by adjuvant radiotherapy is well above 90% at 5 yr in most studies and diminishes only slightly at 10 yr. Very few studies have a more prolonged follow-up. In comparison, the 5- and 10-yr estimated recurrence rate without adjuvant radiotherapy ranged from 15% to 51% and from 44% to 78%, respectively. Complications of radiation include rare but severe side-effects, such as secondary brain neoplasm, optic neuropathy, cerebrovascular accidents, and more frequent but less severe complications, such as pituitary deficiency. Optimal management of patients with residual or recurring NFPA after surgical debulking can be achieved through the judicious use of different treatment options, necessitating close cooperation between neurosurgeons, endocrinologists, and radiation oncologists.

The addition of plerixafor is safe and allows adequate PBSC collection in multiple myeloma and lymphoma patients poor mobilizers after chemotherapy and G-CSF.

We report 13 multiple myeloma (MM) or lymphoma patients who were failing PBSC mobilization after disease-specific chemotherapy and granulocyte-CSF (G-CSF), and received plerixafor to successfully collect PBSCs. Patients were considered poor mobilizers when the concentration of PB CD34(+) cells was always lower than 10 cells/µL, during the recovery phase after chemotherapy and/or were predicted to have inadequate PBSC collection to proceed to autologous transplantation. Plerixafor (0.24 mg/kg) was administered subcutaneously for up to three consecutive days, while continuing G-CSF, 10-11 h before the planned leukapheresis. Plerixafor administration was safe and no significant adverse events were recorded. We observed a 4.7 median fold-increase in the number of circulating CD34(+) cells after plerixafor as compared with baseline CD34(+) cell concentration (from a median of 6.2 (range 1-12) to 21.5 (range 9-88) cells/µL). All patients collected >2 × 10(6) CD34(+) cells/kg in 1-3 leukaphereses. In all, 5/13 patients have already undergone autograft with plerixafor-mobilized PBSCs, showing a rapid and durable hematological recovery. Our results suggest that the pre-emptive addition of plerixafor to G-CSF after chemotherapy is safe and may allow the rescue of lymphoma and MM patients, who need autologous transplantation but are failing PBSC mobilization.

Somatostatin and dopamine receptor interaction in prostate and lung cancer cell lines.

Somatostatin analogues inhibit in vitro cell proliferation via specific membrane receptors (SSTRs). Recent studies on transfected cell lines have shown a ligand-induced formation of receptor dimers. The aim of this study is 1) to evaluate the role of specific ligands in modulating receptor interactions in the androgen-dependent prostate cancer cell line, LNCaP, and in the non-small cell lung cancer line, Calu-6, by co-immunoprecipitation and immunoblot; and 2) to correlate the antiproliferative effect of these compounds with their ability in modulating receptor interactions. In LNCaP, we have demonstrated the constitutive presence of sstr1/sstr2, sstr2/sstr5, sstr5/dopamine (DA) type 2 receptor (D2R), and sstr2/D2R dimers. BIM-23704 (sstr1- and sstr2-preferential compound) increased the co-immunoprecipitation of sstr1/sstr2 and significantly inhibited proliferation (-30.98%). BIM-23244 (sstr2-sstr5 selective agonist) significantly increased the co-immunoprecipitation of sstr2/sstr5, and induced a -41.36% inhibition of proliferation. BIM-23A760, a new somatostatin/DA chimeric agonist with a high affinity for sstr2 and D2R and a moderate affinity for sstr5, significantly increased the sstr5/D2R and sstr2/D2R complexes and was the most powerful in inhibiting proliferation (-42.30%). The chimeric compound was also the most efficient in modulating receptor interaction in Calu-6, increasing the co-immunoprecipitation of D2R/sstr5 and inhibiting cell proliferation (-30.54%). However, behind BIM-23A760, BIM-53097 (D2R-preferential compound) also significantly inhibited Calu-6 proliferation (-17.71%), suggesting a key role for D2R in receptor cross talk and in controlling cell growth. Indeed, activation of monomeric receptors did not affect receptor co-immunoprecipitation, whereas cell proliferation was significantly inhibited when the receptors were synergistically activated. In conclusion, our data show a dynamic ligand-induced somatostatin and DA receptor interaction, which may be crucial for the antiproliferative effects of the new analogues.

Plasma and follicular fluid fatty acid profiles in dairy cows.

Composition of follicular fluid to which the preovulatory follicle is exposed may be one of the major factors determining subsequent fertility, as fatty acids are a precursor of hormones involved in dominance, ovulation and atresia mechanisms. The objective of this paper is to observe fatty acid profiles in various lipid classes according to estrogenic activity of follicles. For each of the 18 cows, we analysed plasma and follicular fluid fatty acid profiles of phospholipids, non-esterified fatty acid (NEFA), cholesteryl esters and triglycerides fractions. Follicles were classified as active (ratio oestrogen to progesterone E2/P4 > 1) and inactive (E2/P4 < 1). For seven cows, we get both types of follicles, six had only one active follicle and five cows had only one inactive follicle. The NEFA profile for palmitic acid, stearic acid, oleic acid, linoleic acid, C20:3n6, arachidonic acid and docosapentaenoic acid (DPA; p < 0.001) is different between inactive and active follicles and plasma. Compared with active follicular fluid and plasma, follicular fluid of inactive follicles showed lower stearic acid, higher oleic acid, arachidonic acid and DPA (p < 0.05) in phospholipids. No significant differences were observed in the cholesteryl ester fraction, which is composted mainly of linoleic acid. Triglyceride concentrations were too low to get reliable results. This study suggests that follicles have a specific fatty acid metabolism depending on oestrogen activity.

Positive effect of silymarin on cell growth and differentiation in bovine and murine mammary cells.

Silymarin, a naturally acknowledged hepatoprotector used in humans to treat liver diseases has been tested in murine (HC11) and bovine (BME-UV) mammary epithelial cell lines to evaluate a possible direct effect on cell growth and differentiation in mammary gland. Silymarin enhanced cell proliferation (p < 0.05) from 10 to 1000 ng/ml in association with growth factors, (up to 20%) or alone (up to 15%) versus controls. Furthermore, silymarin (100 ng/ml) was able to increase (p < 0.05) beta-casein gene expression alone or in association with prolactin (5 microg/ml). These effects may be related with protein kinase B (AKT) activation induced by silymarin treatment (p < 0.05) and/or by a dose-related inhibitory effect (p < 0.05) on caspase-3 activity related to a protective role in cell apoptosis. These data suggest that silymarin should be considered a candidate to support mammary gland activity during a lactogenetic state.

Autopsy reports in extreme longevity.

This study aimed at establishing the prevalence, the type, the severity of various diseases, as well as the main causes of death in the elderly and ultralongevous subjects. The autopsy findings of 140 centenarians (21 males and 119 females) of the age range of 100-109 years were compared to those of 96 elderly subjects (14 males and 82 females) of the age range of 75-95 years. In all cases the clinical diagnosis, the clinical record, the macro- and microscopic findings and the autopsy protocols were evaluated. A lower prevalence (16.3% vs. 39.0%), as well as a slower and less aggressive evolution of neoplastic pathologies (frequency of metastases: 26.0% vs. 55.0%) in the centenarians, as compared to the general aging population, have been found. The chronic-degenerative pathologies, especially the cerebro-degenerative ones were observed more frequently and were of major gravity in the centenarians, compared to the elderly population. The cerebrovascular damage and the consequent cognitive deficit do not influence the survival of the longevous subjects. Intercurrent events or external accidents may interrupt the weak equilibrium of these "frail" subjects.

Access to tuberculosis diagnosis in Itaboraí City, Rio de Janeiro, Brazil: the patient's point of view.

SETTING: Itaboraí Municipality in Rio de Janeiro, Brazil. OBJECTIVE: To evaluate access to tuberculosis (TB) diagnosis for users of the Family Health Program (FHP) and Reference Ambulatory Units (RAUs). DESIGN: A cross-sectional study was conducted in Itaboraí City, Rio de Janeiro, Brazil. Between July and October 2007, a sample of 100 TB patients registered consecutively with the TB Control Program was interviewed using the primary care assessment tool. The two highest scores, describing 'almost always' and 'always', or 'good' and 'very good', were used as a cut-off point to define high quality access to diagnosis. RESULTS: FHP patients were older and had less education than RAU interviewees. Sex and overcrowding did not differ in the two groups. Patient groups did not differ with regard to the number of times care was sought at a unit, transport problems, cost of attending units and availability of consultation within 24 h. Adequate access to diagnosis was identified by 62% of the FHP patients and 53% of the RAU patients (P = 0.01). CONCLUSION: In Itaboraí, Rio de Janeiro, TB patients believe that the FHP units provide greater access to TB diagnosis than RAUs. These findings will be used by the Department of Health to improve access to diagnosis in Itaboraí.