Expression of keratinocyte growth factor in goat ovaries and its effects on preantral follicles within cultured ovarian cortex

The aims of this study were to evaluate the expression of keratinocyte growth factor (KGF) in goat ovaries and to study its effects on preantral follicle survival and development. The ovaries were used for immunohistochemistry or for in vitro culture for 1 or 7 days with KGF (0, 1, 10, 50, 100, 150, or 200 ng/mL). Noncultured (fresh control) and cultured ovarian slices were processed for histological analysis and transmission electron microscopy (TEM). The results showed that after 7 days of in vitro culture, all treatments had a significant reduction in the percentage of normal follicles compared with the fresh control. After 7 days of culture, the highest KGF concentrations (150 and 200 ng/mL) induced a significant reduction in the percentage of normal follicles compared with the tissues cultured in the absence (α-MEM(+) alone) or presence of 1, 10, and 50 ng/mL KGF. Transmission electron microscopy confirmed follicular integrity after 7 days of culture in 1 ng/mL KGF. In addition, compared with the fresh control, the percentage of growing follicles was significantly increased in all treatments after 1 or 7 days of culture. Immunohistochemical analyses showed the expression of KGF in oocytes and granulosa cells in all follicle developmental stages as well as in thecal and stromal cells. In conclusion, this study demonstrated that, at the lowest concentration (1 ng/mL), KGF maintained the ultrastructure of goat preantral follicles cultured in vitro for up to 7 days. Furthermore, the KGF protein was widely distributed in goat ovaries, especially in ovarian follicles.     

Botulinum neurotoxin serotypes A and C do not affect motor units survival in humans: an electrophysiological study by motor units counting.

OBJECTIVES: Botulinum neurotoxin serotype A (BoNT/A) is a valid therapy for dystonia but repeated BoNT/A injections may induce a clinical immuno-resistance that could be overcome by using other BoNT serotypes. In vitro experiments and our preliminary investigations in vivo, indicate that botulinum neurotoxin serotype C (BoNT/C) could be an effective alternative to BoNT/A. Moreover, in cultured neurons 'in vitro' BoNT/C has been reported to be more toxic than BoNT/A. METHODS: To verify this possibility, we compare the effect of BoNT/C and BoNT/A on the motor units count in humans by using the electrophysiological motor unit number estimation (MUNE) technique ('multiple point nerve stimulation'). Preliminarily, BoNT/C and BoNT/A dosage was calibrated in a mouse hemidiaphragm neuromuscular junction preparation. Subsequently, 8 volunteers were treated with 3IU of BoNT/C in the extensor digitorum brevis muscle of one foot and 3IU of BoNT/A in the contralateral one. Other 4 subjects were similarly injected at higher doses (10IU of BoNT/C or BoNT/A) to detect a possible dose-toxic effect. RESULTS: In both groups, no statistically significant variations in MUNE counting or single motor unit potential size were detected after 4 months from injections, when it was evident a recovery from the BoNTs blockade. CONCLUSIONS: We conclude that BoNT/C, similarly to BoNT/A, is safe and effective in humans and it could be proposed for a clinical use.     

Evidence for anterograde transport and transcytosis of botulinum neurotoxin A (BoNT/A)

Botulinum neurotoxin type A (BoNT/A) is a metalloprotease that blocks synaptic transmission via the cleavage of SNAP-25 (synaptosomal-associated protein of 25 kDa). BoNT/A is successfully used in clinical neurology for the treatment of several neuromuscular pathologies and pain syndromes. Despite its widespread use, relatively little is known on BoNT/A intracellular trafficking in neurons. Using the visual pathway as a model system, here we show that catalytically active BoNT/A is capable of undergoing anterograde axonal transport and transcytosis. Following BoNT/A injection into the rat eye, significant levels of BoNT/A-cleaved SNAP-25 appeared in the retinorecipient layers of the superior colliculus (SC). Anterograde propagation of BoNT/A effects required axonal transport, ruling out a systemic spread of the toxin. Cleaved SNAP-25 was present in presynaptic structures of the tectum, but retinal terminals were devoid of the immunoreactivity, indicative of transcytosis. Experiments based on sequential administration of BoNT/A and BoNT/E showed a persistent catalytic activity of BoNT/A in tectal cells following its injection into the retina. Our findings demonstrate that catalytically active BoNT/A is anterogradely transported from the eye to the SC and transcytosed to tectal synapses. These data are important for a more complete understanding of the mechanisms of action of BoNT/A.     

Liver resection for noncolorectal and nonneuroendocrine metastases: results of a study on 56 patients at a single institution

The usefulness of surgical treatment for hepatic metastases of noncolorectal nonneuroendocrine (NCRNNE) tumors is not yet clear due to the natural history of these tumors, their frequent systemic dissemination and their histological heterogeneity. The aim of this study was to evaluate the long-term outcome of patients who underwent liver resection for NCRNNE metastases. For this purpose we retrospectively analyzed 202 patients who underwent liver resection for metastasis between January 1989 and December 2006 at the Department of Surgery of the University Hospital of Udine. Fifty-six patients underwent liver resection because of NCRNNE metastases. The preoperative assessment was based on hepatic ultrasonography and CT scan; PET was used in a few patients. All patients had intraoperative liver ultrasonography to evaluate the lesions and to define the resection. Gender, age, primary tumor site (gastrointestinal or nongastrointestinal), synchronous or metachronous metastasis, unilobar or bilobar localization, number and diameter of the lesion(s), type of resection, margin status, positive lymph nodes in the hepatoduodenal ligament, and time between surgery and diagnosis of liver metastases were evaluated as possible prognostic factors for survival. Univariate analysis showed that the location of the primary tumor and the disease-free interval since the treatment of the primary tumor were positive predictive factors for longer survival. Multivariate analysis showed that the only independent significant factor was gastrointestinal versus nongastrointestinal origin. Demographic data, the synchronous or metachronous appearance of metastases, their unilobar or bilobar location, number and size, the type of resection, the resection margin status and the involvement of lymph nodes did not prove to be prognostic factors.     

A randomised phase II study of docetaxel/oxaliplatin and docetaxel in patients with previously treated non-small cell lung cancer: an Alpe-Adria Thoracic Oncology Multidisciplinary group trial (ATOM 019)

Introduction

To date, no combination regimen has proven superior to single agent chemotherapy as a second-line treatment for non-small cell lung cancer (NSCLC).

Methods

This multicenter, non-comparative randomised phase II trial evaluated the activity of docetaxel (75 mg/m² on day 1) with oxaliplatin (70 mg/m² on day 2) every 3 weeks in previously treated NSCLC patients; the reference arm was single-agent docetaxel (75 mg/m² on day 1 every 3 weeks). It was designed as a one-stage, three-outcome phase II trial; 21 evaluable patients were required in each arm. The primary end-point was response rate; secondary end-points were toxicity, progression free survival (PFS) and overall survival.

Results

Fifty patients were enrolled. Patient characteristics included male/female, 76/24%; median age 62 years; ECOG PS 0/1, 36/64%; previous platinum-based chemotherapy, 98%. Partial response was seen in 20% and 8%, stable disease in 52% and 32%, of patients treated with docetaxel/oxaliplatin and docetaxel, respectively. Main grade 3-4 toxicities were neutropenia 56% and 64%; febrile neutropenia 4% and 8%; diarrhoea 12% and 4% for docetaxel/oxaliplatin and docetaxel, respectively. Median PFS was 5.0 and 1.7 months, median survival 11.0 and 7.1 months, and 1-year survival 44% and 32% for docetaxel/oxaliplatin and docetaxel, respectively.

Conclusions

The study met its pre-defined study end-point; docetaxel/oxaliplatin and more generally platinum-containing doublets warrant further evaluation as second-line therapy for patients with NSCLC.     

Internal auditory canal metastasis

Metastasis of the inner auditory canal is a really rare event. Clinically, it usually presents with rapid worsening cranial nerve palsy. Authors present a review of the literature reporting clinical features, radiological findings, intraoperative aspects of an illustrative case. A 56-year-old female patient presented with a peripheral facial nerve palsy. MRI showed two left p-fossa tumors whose one into the inner canal. Rapid worsening of facial damage despite corticosteroid treatment and the possibility to remove both tumors in the same surgical step suggested authors to operated on the patient. Intraoperatively, inner canal tumor looked totally involving the VII-VIII nerve complex so surgical extirpation was only partially feasible. Posterior wall drilling of the meatus was performed which improved facial palsy. Leptomeningeal spinal seeding occurred and spinal irradiation was performed. The case highlights the importance of maintaining a high degree of awareness of the auditory canal metastasis in patients with a previous history of malignancy who develop a rapid progressive peripheral VII nerve palsy. Furthermore, our case and literature data suggest that inner canal metastasis is a distinct entity from temporal bone and ponto-cerebellar angle metastasis on the base of the peculiarity of clinical features, prognosis, therapeutic strategies. In fact, inner canal metastases usually arise in patients apparently cured, and they imply a better prognosis even if with an higher risk of leptomeningeal seeding. Moreover, surgery rarely allows the removal of the lesion, also if symptoms relief may be achieved, as in our case.     

The first 3 months after BCNU wafers implantation in high-grade glioma patients: clinical and radiological considerations on a clinical series

Purpose  

Carmustine (1,3-bis[2-chloroetyl]-1-nitrosurea (BCNU)) wafers are approved for the local treatment of newly diagnosed and recurrent malignant glioma. Reassuring data on both safety and efficacy of treatment have been previously reported by phase III studies. Although most of related adverse events are reported in the first few months after surgery, there is a lack in the literature of radiological data regarding this period. Few anecdotal experiences have been reported about surgical bed cyst occurrence. The aim of our study is to analyse the radiological course of patients treated with wafers implantation focusing on the relationship between radiological data, and in particular bed cyst occurrence, and safety data.     

Long-term outcomes of orthotopic liver transplantation in human immunodeficiency virus-infected patients and comparison with human immunodeficiency virus-negative cases

Human immunodeficiency virus (HIV) positivity is no longer a contraindication for orthotopic liver transplantation (OLT) due to the efficacy of antiretroviral therapy. The aim of this study was to compare OLT among HIV-positive and HIV-negative cohorts; the results were also stratified for hepatitis C virus (HCV) coinfection. Between 2004 and 2009, all HIV-infected patients undergoing OLT from heart-beating deceased donors (n = 27) were compared with an HIV-negative cohort (n = 27). The pure HCV infection rate was similar between HIV-positive and HIV-negative subjects (63% each). HIV-positive recipients were younger (P = .013). The CD4 count for HIV-positive subjects was 376 ± 156 at transplantation. The mean model for end-stage liver disease (MELD) score at transplantation was 15 ± 7 in both groups (P = .92). No differences were observed for donor age (P = .72) or time on the waiting list (P = .56). The median follow-up was 26 (range, 1-64) and 27 months (range, 1-48) for HIV and non-HIV recipients, respectively (P = .85). The estimated 1-, 3-, and 5-year patient and graft survival rates were 88%, 83%, and 83% versus 100%, 73%, and 73% (P = .95), and 92%, 87%, and 87% versus 95%, 88%, and 88% (P = .59) for HIV and non-HIV cases, respectively. HIV/HCV-coinfected patients were younger, namely 47 (range, 40-53) versus 52 years (range, 37-68; P = .003), and displayed lower MELD scores at transplantation compared with HCV-mono-infected patients 10 (range, 7-19) versus 17 (range, 8-30) (P = .008). For HIV/HCV-coinfected and HCV-mono-infected cases the estimated 1-, 3-, and 5-year patients and graft survival rates were respectively 93%, 76%, and 76% versus 100%, 70%, and 60% (P = .99) and 93%, 84%, and 84% versus 100%, 70%, and 60% (P = .64), respectively. No difference was observed in the histological severity of HCV recurrence. In conclusion, under specific, well-determined conditions, OLT can be a safe, efficacious procedure in HIV patients.     

The choice of recipient does not have a bearing on early outcome in liver transplant patients receiving grafts from non-heart-beating donors: a reappraisal?

INTRODUCTION: Donation after cardiac death has reemerged as a potential way of increasing the supply of organs for transplantation. We retrospectively reviewed the outcomes of non-heart-beating donor (NHBD) liver transplantation (OLT) experience and compared with standard heart-beating donation (HBD) at a single center. METHODS: From October 2003 to November 2006, 13/111 liver transplantations were performed in our institution with NHBD. Living donor liver transplantation, splitting procedures, combined, and pediatric liver transplantations were excluded from this analysis. RESULTS: Donor population was similar in both groups. The median warm ischemia time was 10 minutes (range 6 to 38). The median cold ischemia times 6 hours and 16 minutes (2.4 to 6.30 hours and 9 hours and 14 minutes (2.15 to 15.35 hours) for NHBD and HBD groups, respectively (P = .0002). In the NHBD groups, 4/13 (31%) grafts were retransplanted within 3 months, due to ischemic biliary lesions with severe cholestasis (n = 3) or due to the occurrence of primary nonfunction (n = 1). The retransplantation rate was significantly lower in the HBD group (11/98, 11%; P = .03). One-year patient and graft survivals were 62% and 54% versus 86% and 79%, respectively, for the NHBD and HBD groups (P = .107 and P = .003). CONCLUSION: Liver grafts procured from donors after cardiac death accounted for a significantly greater retransplantation rates, mainly due to nonanastomotic biliary strictures. This risk must be taken into account when transplanting such grafts. Based upon this experience, NHBD cannot rival HBD to be a comparable source of quality organs for liver transplantation.     

Seabather's eruption: report of case in northeast region of Brazil

Seabather's eruption is characterized by the occurrence of intensely itchy erythematous papules observed mainly in the region covered by swimwear. The dermatitis occurs due to the contact of planula larvae of scyphomedusae Linuche unguiculata with the skin. The swimsuit pressure triggers the action of the poisonous stinging structures carried by the larvae. The case described occurred in a child who, while bathing in the ocean waters of the Northeast coast of Bessa's Beach located in the city of Joao Pessoa, state of Paraiba, showed typical clinical signs of the disease. It was concluded that the report of the case showed clinical and therapeutic implications for doctors working in all of the Brazilian coastal areas.