Safety of new DAAs for chronic HCV infection in a real life experience: role of a surveillance network based on clinician and hospital pharmacist.

BACKGROUND: Direct Antiviral Agents (DAAs) for HCV therapy represents a step ahead in the cure of chronic hepatitis C. Notwithstanding the promising results in several clinical trials, few data are available on adverse effects in real life settings. METHODS: We have evaluated 170 patients with persistent infection and on those eligible to treatment we have followed up them through a network managed by clinician and hospital pharmacist. RESULTS: According to our data we have found that 41% (32 out of 78) of enrolled patients experienced adverse reactions, of these 40% were in those under 65 years while 60% was in patients older than 65 years, SVR was achieved in 88% of the patients (including drop-out). We had 4 drop-out treatment due to major adverse reaction (heart and lung related). CONCLUSION: Even if new antiviral drugs seem to be promising, according to SVR, they require careful follow-up, possibly managed by clinician and hospital pharmacist, to avoid unrecognized side effects which may affect adherence and the real impact of these drugs on chronically infected subjects.

A case of advanced second-degree atrioventricular block in a ferret secondary to lymphoma.

A female ferret was referred as an emergency for severe respiratory distress symptoms. At presentation, the patient was listlessness, dyspnoeic, and hyper-responsive. The clinical examination evidenced dyspnea with cyanosis, altered cardiac rhythm, and hepatomegaly. Electrocardiography showed an advanced second-degree atrioventricular (AV) block. The liver aspirate was diagnostic for lymphoma. The patient did not respond to supportive therapy and rapidly died. Post-mortem exams confirmed the presence of lymphoma with hepatic involvement. Moreover, a pericardial lymphocytic infiltration and a widespread myocardial nodular localization of lymphoma were evidenced as well. This condition was probably the cause of the cardiac arrhythmia. To the best of our knowledge, ours is the first report of cardiac lymphoma causing heart block in ferrets.

Electroporation Enhances Bleomycin Efficacy in Cats with Periocular Carcinoma and Advanced Squamous Cell Carcinoma of the Head.

BACKGROUND: Advanced carcinoma of the head represents a substantial health problem in cats for local control and overall survival. OBJECTIVES: Evaluate the capability of electrochemotherapy (ECT) to improve bleomycin efficacy in cats with periocular carcinoma and advanced carcinoma of the head. ANIMALS: Twenty-one cats with periocular carcinoma (17 squamous cell carcinoma [SCC] and 4 anaplastic carcinoma) and 26 cats with advanced SCC of the head. METHODS: Nonrandomized prospective controlled study. Periocular carcinoma cohorts: 12 cats were treated with bleomycin (15 mg/m(2) i.v.) coupled with ECT under anesthesia; 9 cats were treated with bleomycin alone. Advanced head SCC cohorts: 14 cats were treated with bleomycin (15 mg/m(2) i.v.) coupled with ECT administered under sedation; 12 control cats were treated with bleomycin alone. ECT treatments (2-8) were performed every other week until complete remission (CR) or tumor progression occurred. RESULTS: Toxicities were minimal and mostly treated symptomatically. Overall response rate in the ECT treated animals was 89% (21 Complete Response [CR] and 2 Partial Response [PR]) whereas controls had response rate of 33% (4 CR and 3 PR). Median time to progression in ECT group was 30.5 months, whereas in controls it was 3.9 months (P < .0001). Median time to progression for ECT cohorts was 24.2 months for periocular cohort and 20.6 in advanced head SCC cohort, respectively. CONCLUSIONS: Electrochemotherapy is well tolerated for advanced SCC of the head in cats; its use may be considered among loco-regional strategies for cancer therapy in sensitive body regions such as periocular region.

Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter, randomized, phase-II study.

BACKGROUND: Luminal breast cancer is a highly endocrine responsive disease. However, the therapeutic benefit of chemotherapy (CT) in this population is not fully characterized. This study investigates the value of CT and hormone therapy (HT) in luminal breast cancer patients in the neoadjuvant setting. PATIENTS AND METHODS: Patients with operable breast cancer and immunophenotypically defined luminal disease (ER+/PR+/HER2-/cytokeratin 8/18+) were recruited. Patients were randomized to CT (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) 4 cycles followed by docetaxel 100 mg/m(2 )4 cycles [EC-T]) or HT (exemestane 25 mg daily 24 weeks [combined with goserelin in premenopausal patients]). The primary end point was the clinical response measured by magnetic resonance imaging. RESULTS: Ninety-five patients were randomized (47 CT, 48 HT). The clinical response rate was 66% for CT and 48% for HT (P = 0.075). We performed an unplanned analysis based on Ki67 levels (cut-off of 10%). Similar clinical response was seen between arms in patients with low Ki67 (CT: 63%, HT: 58%; P = 0.74); patients with high Ki67 had a better response with CT (67 versus 42%; P = 0.075). Grade 3/4 toxicity was more frequent with CT. CONCLUSIONS: Luminal immunophenotype is not enough to identify patients who do not benefit from neoadjuvant CT. Luminal patients with low proliferation index could potentially avoid CT.

Cytotoxic effects induced by combination of heliantriol B2 and dequalinium against human leukemic cell lines.

Natural occurring compounds are considered an important source of antitumoral agents. In the present study, the cytotoxic potential of three pentacyclic triterpenes isolated from Chuquiraga erinacea (Asteraceae), against the human leukemic cell lines NB4 and K562 was assessed. Heliantriol B2 (HB2) showed the highest cytotoxic activity after 24 h treatment showing IC(50) values of 1.98 ± 0.12 µm and 3.52 ± 0.14 µm for NB4 and K562 cells, respectively. This activity was higher than that of the reference compound dequalinium (DQA). Apoptosis and necrosis induced by HB2 in both NB4 and K562 cell lines were analysed by Annexin V/PI labeling. Mitochondrial alterations including reactive oxygen species (ROS) production and mitochondrial transmembrane potential (ΔΨm) were also tested. The results demonstrated that HB2 induced cell death by apoptosis and necrosis and showed enhanced cytotoxic effects in combination with DQA. Besides, HB2 induced ROS overproduction in NB4 cells and a slight decrease of ΔΨm. Consequently, our findings prompt further studies on the HB2 mechanism of action and its selectivity to tumor cells in order to assess the potential of HB2 as an agent for cancer treatment.

Pilot study on recurrent aphthous stomatitis (RAS): a randomized placebo-controlled trial for the comparative therapeutic effects of systemic prednisone and systemic montelukast in subjects unresponsive to topical therapy.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is characterized by recurrent painful oral ulcers whose etiology remains largely unknown. Numerous therapeutic protocols have been tried so far, but effectiveness remains an issue. OBJECTIVE: To test a new drug for patients with recurrent oral aphthae nonresponsive to local corticosteroid therapy, we compared the therapeutic effectiveness and adverse effects of systemic prednisone and systemic montelukast in a placebo-controlled trial. STUDY DESIGN: Sixty patients suffering from minor RAS for > or =6 months were studied and randomly assigned to 3 groups of 20 each in a double-blind study. Patients of group A took 25 mg prednisone orally daily for 15 days, 12.5 mg daily for 15 days, 6.25 mg daily for 15 days, then 6.25 mg on alternate days for 15 days. Patients of group B took 10 mg montelukast orally every evening and then on alternate days for the second month. Patients of group C took 100 mg cellulose (placebo) by mouth daily for the first month and on alternate days for the second month. Outcomes assessed were days til pain cessation, days to ulcer healing, and number of aphthae occurring during the follow-up period. RESULTS: Both prednisone and montelukast were effective in reducing the number of lesions and improving pain relief and ulcer healing when compared with placebo. Prednisone was more effective than montelukast in pain cessation (P < .0001) and in accelerating ulcer healing (P < .0001). However, adverse drug reactions recorded during the entire trial were more common in the prednisone group compared with montelukast (10%) and placebo (10%). CONCLUSIONS: These data suggest that the effectiveness of systemic montelukast is similar to that of systemic prednisone in patients with RAS. The lack of serious side effects makes montelukast a candidate drug to use in cases of RAS where pharmacologic therapy for long periods is needed.

Biology, prognosis and response to therapy of breast carcinomas according to HER2 score.

BACKGROUND: The standardization of the HER2 score and recent changes in therapeutic modalities points to the need for a reevaluation of the role of HER2 in recently diagnosed breast carcinoma. PATIENTS AND METHODS: A multicenter, retrospective study of 1794 primary breast carcinomas diagnosed in Italy in 2000/2001 and scored in HER2 four categories according to immunohistochemistry was conducted. RESULTS: Ductal histotype, vascular invasion, grade, MIB1 positivity, estrogen and progesterone receptor expression differed significantly in HER2 3+ tumors compared with the other categories. HER2 2+ tumors almost showed values intermediate between those of the negative and the 3+ subgroups. The characteristics of HER2 1+ tumors were found to be in between those of HER2 0 and 2+ tumors. With a median follow-up of 54 months, HER2 3+ status was associated with higher relapse rates in node-positive and node-negative subgroups, while HER2 2+ only in node positive. Analysis of relapses according to type of therapy provided evidence of responsiveness of HER2-positive tumors to chemotherapy, especially taxanes. CONCLUSIONS: The present prognostic significance of HER2 is correlated to receptor expression level and points to the need to consider HER2 2+ and HER2 3+ tumors as distinct diseases with different outcomes and specific features.

Estudio microbiológico de bacteriemias y fungemias en pacientes en hemodiálisis crónica / [Microbiologic study of bacteremia and fungemia in chronic hemodialysis patients]

Microbiologic study of bacteremia and fungemia in chronic hemodialysis patients. Bloodstream infections are the second cause of death in patients in chronic hemodialysis (CHD), and the knowledge of the epidemiology is useful to establish proper empiric therapies. The aim of this study was to evaluate the frequency and distribution of microorganisms, in bacteremia and fungemia in 530 patients in CHD. Two hundred and forty eight blood culture series from 114 patients with suspected bacteremia were processed; 44

(n=78) were clinically significative and belonged to 58 patients. Sixty eight percent of these isolates were gram-positive cocci (n:53), and 22

gram-negative rods (n:17). Staphylococcus aureus was the most prevalent pathogen showing 23

of methicillin-resistance. Candida spp. was the fourth pathogen most common in frequency.

Glomus tumor of the lower lip. A case report.

A glomus tumor is a benign neoplasm originating from the modified smooth muscle cells of the vascular glomus. This neoplasm was firstly considered by Masson in 1924, and generally it has a solitary lesions but in some cases multiple lesions were described. Differential diagnosis is usually made with Kaposi sarcoma and hemangiopericytoma. The histopathologic examination is essential together with the immunohistochemical study. The clinical case of a 65-year-old man with a glomus tumor of the lower lip is described.

Cyclooxygenase-2 expression in oral squamous cell carcinoma.

Cyclooxygenase (COX), the key enzyme in prostaglandin cascade, is expressed in two isoforms: the constitutive COX-1 and the inducible COX-2. Hyper-expression of COX-2 has been implicated in the pathogenesis of colon-rectal cancer in humans but it appears to play a significant role as a tumour progression factor also in other forms of human cancer, including oral cancer. The aim of this study was to analyze the expression of COX-2, at the protein level, in 45 cases of oral squamous cell carcinoma. Standard immunohistochemical streptavidin-biotin peroxidase analysis was carried out with highly specific antibody against human COX-2 and cell specific markers, in 45 oral squamous cell carcinomas. Our study revealed a moderate to high COX-2 expression in 35 out of the 45 oral squamous cell carcinoma specimens (77.8%). COX-2 expression appeared particularly abundant in the superficial ulcerated layers of relatively well differentiated carcinomas. However, we were unable to assess any statistically significant association between COX-2 hyper-expression and tumor site, tumor grading, tumor size, presence of lymph node metastases, tumor stage and age at onset, respectively. Interestingly, COX-2 expression was detected not only in areas of epithelial dysplasia adjacent to the primary layers (86% of the cases) but also in normal-appearing epithelium at the boundaries of squamous cell carcinoma (77%), indicating a possible involvement in tumour progression by the apparently normal tissue surrounding the lesion. Moreover, intense COX-2 staining was observed in endothelial cells of intra-tumour vessels and extra-tumour vessels adjacent to the tumour nests, in a high proportion of cases (82%). COX-2 positivity was associated with CD34 and VEGF positivity, indicating that these vessels were probably neo-formed ones. From this study as well as from other works, it appears that indeed COX-2 is over-expressed in this important human malignancy. However, further studies are necessary to understand the exact magnitude of this over-expression and, mostly, the possible role of COX-2 in the pathogenesis and progression of oral cancer.

Canalicular adenoma of the parotid gland: a case report.

Canalicular adenoma is an uncommon benign neoplasm that occurs almost exclusively in the upper lip and, very rarely, in other sites. We describe a case arising in the left parotid gland as a firm, painful mass, in order to underline morphological and immunohistochemical findings, particularly in relation to differential diagnosis with low-grade carcinomas of the salivary glands.

[Congenital hepatic fibrosis in pregnancy]. / Su un caso di fibrosi epatica congenita in gravidanza.

The purpose of this study was to analyse the course of pregnancy of a 20-year-old woman suffering from congenital hepatic fibrosis (CHF), a genetic disease with recessive autosomic transmission, attributed to the group of hepato-nephro-pancreatic fibropolycystic familial diseases. This was the only time such a case had ever been encountered in a pregnancy in the history of Turin University's Obstetrics and Gynaecological Clinic. The case of a 20-year-old woman is considered. She was admitted to our observation at the Obstetrics and Gynaecological Department of Faculty "B" of the University of Turin, suffering from CHF, a primigravid in the eighth week of gestation. Haematochemical tests carried out on the patient showed a platelet deficiency without evident changes in liver and renal function. Objective examination revealed a slight hepatosplenomegaly confirmed by abdominal echotomography. The haematochemical examinations subsequently carried out confirmed thrombocytopenia due to hepatosplenic hyperhaemocataresis. In agreement with the will of the patient and her family, and after having heard the opinion of our hospital's anaesthetists and internists, a conservative approach was decided on and close monitoring of maternal and foetal conditions was planned, with hospitalisations scheduled for every fortnight. Together with the internists and anaesthetists, it was decided to allow the pregnancy to proceed as far as foetal maturity but not to term, to avoid problems relating to the excessive increase in uterine volume which would have led to pressure on the portal tree and so favoured haemorrhaging due to rupture of the oesophageal varices. Caesarean delivery was planned for the 37th week of gestation. The birth went according to plan and the foetus was a live, vital male with Apgar index of 9/9. The placenta presented normal characteristics and a weight of 590 g. No haemorrhagic complications were observed either in the course of surgery or in the postoperative phase, notwithstanding the preoperative finding of a platelet count of 64,000 platelets/ mm3. Although in our case neither the pregnancy nor the delivery constituted a serious danger for the life of the mother, possible obstetric complications are among the most serious encountered in obstetric pathology and can lead both to maternal death and to the intrauterine death of the foetus. For these reasons we believe it essential to provide correct, clear and adequate information about the risks involved for patients suffering from congenital hepatic fibrosis, especially if they are associated with renal polycystic disease, and who are admitted to our wards with the desire to programme a pregnancy.

[Traumatic neuroma of the great auricular nerve. A clinical case]. / Neuroma traumatico del nervo grande auricolare. Caso clinico.

A clinical case of neuroma resulting from an amputation which occurred following parotid surgery is reported. The present paper discusses the importance of differential diagnosis relating to this pathology and the surgical techniques that may contribute to setting a limit on its onset. Traumatic neuroma is a possible complication of parotid surgery together with motor deficiencies and Frey's syndrome and the less frequent salivary fistulas. It may also occur following oncological or plastic-reconstructive surgery. During parotidectomy operations, section of the great auricular nerve may be required to facilitate access to the parotid region. This manoeuvre may, however, also be associated with the onset of a neuroma during a time period varying from 2 to 10 years, according to the various authors who have examined the subject. The laterocervical tumefaction associated with neuroma poses a number of diagnostic problems as it has to be differentiated from a likely relapse or possibly from more complex inflammatory or metastatic lymphnodal pathology. A correct clinical and diagnostic multidisciplinary approach is fundamental if the pathology is to be classified in the right way and contributes to alleviating a state of mental unease in the patient that is associated with the sudden appearance of the tumefaction. Sectioning the nervous trunk by means of thermocautery and its subsequent sinking below the main trunk of the sternocleidomastoid muscle, are simple surgical manoeuvres that are useful for preventing the onset of traumatic neuroma.

[A new method of neovagina in Rokitansky's syndrome. A review of the literature and description of a series]. / Proposta di nuova metodica di neovagina nella sindrome di Rokitansky. Revisione della letteratura ed illustrazione della casistica.

BACKGROUND: The absence or hypoplasia of the vagina is a frequent finding in Rokitansky-Mayer-Küster-Hauser syndrome. METHODS: A group of 13 patients with Rokitansky-Mayer-Küster-Hauser syndrome were treated between 1982 and December 2001 at the Plastic Surgery Department of C.T.O. (Turin) and the 2nd Obstetrics-Gynecology Clinic of Turin University. Surgery was the proposed therapy in all patients, using a modified version of the McIndoe technique. RESULTS: In this series, the cytological tests of neovaginal tissue carried out one year after surgery showed a syndrome of slight atrophy in 8 cases, but this was not sufficient to impede the sexual activity of these patients. Two patients were lost in the follow-up; 3 patients declared that they were reasonably satisfied with their sex life, whereas the remaining 8 reported a normal sex life. CONCLUSIONS: The treatment of choice for complete vaginal agenesia is a neovagina using the skin graft method. This technique produces excellent anatomical results, especially in young patients, even without regular dilatation or frequent sexual relationships. The only drawback of this method is that the vagina tends to retract in some patients, a problem that has been largely solved by the most recently proposed surgical variants.

Negative immunomagnetic purging of peripheral blood stem cell harvests from breast carcinoma patients reduces tumor cell contamination while not affecting hematopoietic recovery.

BACKGROUND: Because tumor contamination of hematopoietic stem cell grafts may influence the outcome in breast carcinoma (BC) patients undergoing high dose chemotherapy (HDC), several ex vivo procedures for the purging of autologous harvests have been investigated. The authors studied the presence of epithelial tumor cells and the growth of hematopoietic progenitors in peripheral blood stem cell (PBSC) collections from patients with metastatic breast carcinoma before and after a purging procedure performed by a negative immunomagnetic BC cell separation. METHODS: Eighteen patients entered the study. Tumor contamination was assessed by conventional immunocytochemistry (ICC) and by a liquid culture assay developed in the study laboratory. Committed and more primitive hematopoietic progenitors were quantitated before and after the negative selection. Ten patients received HDC with purged PBSC support. RESULTS: Before purging, 4 of 18 PBSC collections were found to be contaminated by liquid culture; among these samples, only 1 was positive by ICC. Three of the four positive collections, including the ICC positive sample, became negative after immunomagnetic selection whereas BC cells still were present after the procedure in one harvest. A high recovery of both primitive and mature hematopoietic progenitors was found after the purging procedure. Patients receiving purged PBSC after myeloablation had a prompt and complete hematopoietic reconstitution, and no graft failure was observed at a median follow-up of 1 year. CONCLUSIONS: The preliminary results of the current study suggest that negative selection of BC cells is able to purge PBSC effectively while having no apparent affect on hematopoietic progenitor recovery in vitro and in vivo.

Polyphenolic compounds from Plantago lagopus L.

In the present study we report the isolation of a phenylpropanoid glucoside, plantamajoside, together with rosmarinic acid, chlorogenic acid and luteolin-7-O-monoglucoside. This is the first report of these compounds from Plantago lagopus.