Deep neurological phenotyping in oculo-dento-digital syndrome.

OBJECTIVES: Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant congenital malformation syndrome characterized by high penetrance and great phenotypic heterogeneity. Neurological manifestations are thought to occur in about one third of cases, but systematic studies are not available. We performed deep neurological phenotyping of 10 patients in one ODDD pedigree. METHODS: Retrospective case series. We analyzed in depth the neurological phenotype of a three-generation family segregating the heterozygous c.416 T > C, p.(Ile139Thr) in GJA1. Clinical and neuroradiological features were retrospectively evaluated. Brain MRI and visual evoked potentials were performed in 8 and 6 cases, respectively. RESULTS: Central nervous system manifestations occurred in 5 patients, the most common being isolated ataxia either in isolation or combined with spasticity. Furthermore, sphincteric disturbances (neurogenic bladder and fecal incontinence) were recognized as the first manifestation in most of the patients. Subclinical electrophysiological alteration of the optic pathway occurred in all the examined patients. Neuroimaging was significant for supratentorial hypomyelination pattern and hyperintense superior cerebellar peduncle in all examined patients. CONCLUSION: The neurological involvement in ODDD carriers is often missed but peculiar clinical and radiological patterns can be recognized. Deep neurological phenotyping is needed to help untangle ODDD syndrome complexity and find genotype-phenotype correlations.

Time trends (2006-2015) of quality indicators in EUSOMA-certified breast centres.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006-2015. MATERIALS AND METHODS: Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006-2015. RESULTS: On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor-negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015. CONCLUSION: The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time.

Agreement between Dietary Intake of Older Adults and Proxy Respondents Assessed by a Food Frequency Questionnaire.

OBJECTIVE: To evaluate the degree of agreement of dietary intake reported by the patient subject with the dietary intake reported by a respondent (a next-of-kin or a caregiver), collected by a validated Food Frequency Questionnaire (FFQ). METHODOLOGY: 126 adults, both sexes, the average age was 65.9 years for patients and 54.4 years for respondents. They were recruited from the General Practice Clinic at the Clinical Hospital of São Paulo (AGD-FMUSP). The agreement between the responses given by patients and respondents was assessed using Spearman, weighted Kappa and Bland Altman tests. RESULTS: The analysis for accuracy between responses (Spearman test) showed a moderate degree of agreement (0.31-0.39) for Energy, Total fat, Total Saturated Fatty Acids (SFA), Total Monounsaturated Fatty Acids (MUFA). Regarding food groups a moderate agreement was found for the majority of the foods (fruits (0.30), dairy products (0.50), natural juices (0.45), beans (0.48), butter/margarine (0.55), coffee (0.41) and soda (0.45), with the exception of vegetables (0.12) and rice (0.63). The ingestion differences did not exceeded the limit of the two standard deviations for the majority of the pairs (Bland Altman). A respondent subsample composed only of husband/wives (N = 36) revealed a moderate agreement concordance for most macronutrients studied (0.30 - 0.58), except polyunsaturated fats (0.25). CONCLUSION: The results of this study show that, the FFQ may be used in cases where is impossible to get the answers directly from the patients.

Fiber reinforced composites orthodontic retainers.

AIM: Retention is the phase of orthodontic treatment that attempts to hold teeth in their corrected positions after orthodontic therapy is completed. The aim of this study was to consider fiber-reinforced composites (FRC) as a possible alternative to conventional multistranded stainless steel wire for retention through SEM analysis. METHODS: Two different FRC orthodontic retainers were investigated, i.e. Everstick® (Stick Tech Ltd, Turku, Finland) (type A, 24 samples), with a diameter of 0.76 mm made of glass fibers and a Young's modulus of elasticity of 28 gpa, and Ribbond® (Ribbond, Inc., Seattle, Washington, WA, USA) (type B, 24 samples), with ultra high molecular weight and with an high Young's modulus of elasticity by polyethylene fibers cold treated with plasma gas. Six groups were created: control groups A1 and B1, composed by 8 type A and 8 type B samples without impregnation and only with fluid resin before curing; groups A2 and B2, composed respectively by 8 type A and 8 type B samples impregnated with fluid resin Heliobond for 6 seconds; groups A3 and B3, composed respectively by 8 type A and 8 type B samples impregnated with fluid resin Heliobond for 6 minutes before curing. RESULTS: Cross- and lengthwise SEM analysis of the sectioned samples made showed that fiber without impregnation with fluid resin, before curing, showed interwoven and straight directed cylindrical fibers. The SEM analysis denoted that the two types of fiber shows structural characteristics differing in dimension, number, diameter and orientation of FRC without a preliminary treatment through impregnation of the fibers with fluid resin. CONCLUSION: An impregnation time of 6 seconds could considerably reduced voids, crazes and microcracks of the fibers, making them more resistant to the other oral and bacterial agents. A larger time of impregnation (6 minutes), with fluid resin before hardening, further enhances the morphological characteristics of the FRC.

Short-term clinico-radiographic response to super-selective intra-arterial cerebral infusion of Bevacizumab for the treatment of vestibular schwannomas in Neurofibromatosis type 2.

Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome with a prevalence of approximately 1 in 30,000. NF 2 is characterized by bilateral vestibular schwannomas, as well as meningiomas, ependymomas and gliomas. Currently, surgical resection and radiotherapy represent the mainstay of treatment, although new studies suggest a role for certain chemotherapeutic agents. Intravenous administration of Bevacizumab (Avastin, Genetech Pharmaceuticals) has been shown to be active in the treatment of vestibular schwannomas. The IV route of administration, however, carries a risk of known systemic side-effects such as bowel perforation, wound dehiscence and pulmonary embolism. In addition, the percentage of drug that reaches the tumor site may be restricted by the blood tumor barrier. This report describes the super-selective intra-arterial infusion of Bevacizumab following blood brain barrier disruption for the treatment of vestibular schwannomas in three patients with Neurofibromatosis type 2. It represents the first time such a technique has been performed for this disease. Additionally, this method of drug delivery may have important implications in the treatment of patients with vestibular schwannomas associated with Neurofibromatosis type 2.

Maternal HIV Status and Infant Feeding Practices among Ugandan Women

To describe the infant feeding practices in the general population in Uganda; and to assess the impact of maternal HIV status on these practices; a questionnaire was administered to women attending the follow-up clinics for child vaccination. Among the mothers who were still breastfeeding at the time of interview (N=838); 61.4of the HIV-infected women had planned to breastfeed for a maximum of 6 months; compared with 12.1of the HIV-uninfected women (p0.001). Among the women who were not breastfeeding at the time of interview (Nof the HIV-infected women had stopped breastfeeding within 3 months; compared with 23.5of the HIV-uninfected women (p0.001). Only 2.1of HIV-infected women seen up to 14 weeks postnatally practised mixed feeding; compared with 23.6of HIV-uninfected women (p0.001). After 6 months; however; 30of the HIV-infected women and 55of the HIV-uninfected mothers were using mixed feeding; with no significant differences. Programmes for the prevention of motherto- child transmission of HIV should re-enforce counselling activities to address the issue of early weaning by HIV-infected women; and to support safe breastfeeding up to 6 months

Polarized gamma-ray emission from the crab.

Pulsar systems accelerate particles to immense energies. The detailed functioning of these engines is still poorly understood, but polarization measurements of high-energy radiation may allow us to locate where the particles are accelerated. We have detected polarized gamma rays from the vicinity of the Crab pulsar using data from the spectrometer on the International Gamma-Ray Astrophysics Laboratory satellite. Our results show polarization with an electric vector aligned with the spin axis of the neutron star, demonstrating that a substantial fraction of the high-energy electrons responsible for the polarized photons are produced in a highly ordered structure close to the pulsar.

Implementation of a programme for the prevention of mother-to-child transmission of HIV in a Ugandan hospital over five years: challenges, improvements and lessons learned.

To identify factors that may limit acceptance of HIV testing and enrolment in the programmes for the prevention of mother-to-child-transmission of HIV, we retrospectively assessed the performance of the service at St Francis Hospital, Nsambya in Kampala. Over five years, a total of 26,556 pregnant women were offered voluntary counselling and confidential HIV testing and, if HIV positive, enrolment in the programme. Acceptance of the HIV test increased in the last two years (from 72.7% in 2001-2002 to 79.9% in 2003-2004). Enrolment in the programme increased over time and was greater among older (64% in women older than 30 years and 44.8% in those aged less than 20 years) and highly educated women. HIV prevalence was associated with age and inversely associated with the level of education. The need for specific personnel for counselling, male partners' involvement and availability of antiretroviral drugs for those who needed treatment were identified as factors possibly affecting implementation.

Colonic epithelial cells are a major site of macrophage inflammatory protein 3alpha (MIP-3alpha) production in normal colon and inflammatory bowel disease.

BACKGROUND AND AIM: Macrophage inflammatory protein 3alpha (MIP-3alpha) is a recently described lymphocyte directed C-C chemokine expressed predominately at extralymphoid sites, including the intestine. The aim of this study was to determine whether colonic epithelial cells produce MIP-3alpha and whether its expression is upregulated in inflammatory bowel disease. METHODS AND RESULTS: We found that interleukin 1beta and tumour necrosis factor alpha dose dependently stimulated MIP-3alpha production in Caco-2 and HT-29 intestinal epithelial cells. In cytokine treated Caco-2 and HT-29 cells, a significant increase in MIP-3alpha protein production was observed after three hours and continued for at least 24 hours. Analysis of colonic tissues by quantitative real time polymerase chain reaction and ELISA revealed significantly elevated MIP-3alpha mRNA levels (7.9-fold; p<0.05) and protein levels (8.9-fold; p<0.05) in Crohn's disease compared with controls or ulcerative colitis. MIP-3alpha immunoreactivity in normal colon and inflammatory bowel disease was principally associated with crypt and surface epithelial cells. Moreover, MIP-3alpha protein levels were elevated in primary epithelial cells isolated from patients with inflammatory bowel disease. CONCLUSIONS: These findings indicate that increased enterocyte MIP-3alpha production may play an important role in lymphocyte activation and recruitment to the colonic epithelium in Crohn's disease and ulcerative colitis.

Lidocaine inhibits secretion of IL-8 and IL-1beta and stimulates secretion of IL-1 receptor antagonist by epithelial cells.

Lidocaine and related local anaesthetics have been shown to be effective in the treatment of ulcerative colitis (UC). However, the mechanisms underlying their therapeutic effect are poorly defined. Intestinal epithelial cells play an important role in the mucosal inflammatory response that leads to tissue damage in UC via the secretion of pro-inflammatory cytokines and chemokines. The aim of this study was to evaluate the direct immunoregulatory effect of lidocaine on pro-inflammatory cytokine and chemokine secretion from intestinal epithelial cells. HT-29 and Caco-2 cell lines were used as a model system and treated with lidocaine and related drugs. The expression of IL-8, IL-1beta and the IL-1 receptor antagonist (RA) were assessed by ELISA and quantification of mRNA. In further experiments, the effect of lidocaine on the secretion of IL-8 from freshly isolated epithelial cells stimulated with TNFalpha was tested. Lidocaine, in therapeutic concentrations, inhibited the spontaneous and TNFalpha-stimulated secretion of IL-8 and IL-1beta from HT-29 and Caco-2 cell lines in a dose-dependent manner. Similarly, suppression of IL-8 secretion was noted in the freshly isolated epithelial cells. Other local anaesthetics, bupivacaine and amethocaine, had comparable effects. Lidocaine stimulated the secretion of the anti-inflammatory molecule IL-1 RA. Both the inhibitory and the stimulatory effects of lidocaine involved regulation of transcription. The results imply that the therapeutic effect of lidocaine may be mediated, at least in part, by its direct effects on epithelial cells to inhibit the secretion of proinflammatory molecules on one hand while triggering the secretion of anti-inflammatory mediators on the other.

Spontaneous rupture of hepatocellular carcinoma with haemoperitoneum: a rare condition in Western countries.

BACKGROUND: Haemoperitoneum secondary to non-traumatic liver rupture is a rare but potentially fatal condition. It may result from several neoplastic and non-neoplastic diseases such as primary benign or malignant tumours, peliosis hepatis, polyarteritis nodosa, systemic lupus erythematosus, pre-eclampsia and metastatic carcinoma. CASE OUTLINES: Three cases of spontaneous haemoperitoneum caused by rupture of hepatocellular carcinoma are described. All three patients (two men, one woman) had cirrhotic livers, and all were submitted to an urgent operation.One patient re-bled on a second occasion. Emergency operation was undertaken four times in three patients and was successful on all but one occasion. DISCUSSION: The prognosis for patients with haemoperitoneum is generally poor. Although this condition is relatively frequent in some regions of Asia and Africa, it has rarely been reported in Western countries.The present experience shows that emergency laparotomy can be life-saving.

Papillary cystic neoplasm of the pancreas.

BACKGROUND: Papillary cystic neoplasm of the pancreas is a rare disorder that occurs most commonly in young women. It has a low potential for malignancy, and the prognosis following resection is favourable. CASE OUTLINE: An 18-year-old white girl presented with a palpable mass in the right hypochondrium on physical examination associated with epigastric pain, nausea and vomiting, but no fever. Upper gastro-intestinal endoscopy revealed extrinsic compression of the posterior wall of the antrum and duodenal bulb with no mucosal lesion. Computed tomography (CT) scan and then laparotomy revealed a large tumour adjacent to the hepatic hilum and originating from the head of pancreas. Pancreatoduodenectomy was performed, and a diagnosis of papillary cystic neoplasm of the pancreas was made.There was no evidence of recurrence after 6 years of follow-up. DISCUSSION: A radical surgical approach is justified for papillary cystic neoplasm of the pancreas because of its biological behaviour, local aggressiveness and low incidence of metastases.

[Boerhaave syndrome. A case report and review of the literature]. / La sindrome di Boerhaave. Descrizione di un caso e revisione della Letteratura.

Spontaneous esophageal perforation (Boerhaave's syndrome) remains a difficult diagnostic and management problem with controversial recommendations regarding its treatment. The clinical manifestations of the disease are variable, and may be misleading, thus delaying accurate recognition. On the other hand, in view of the rapid onset of severe complications, particularly mediastinitis, a prompt diagnosis is essential to a better prognosis, successful operative outcome and potential survival. A case of spontaneous perforation of the thoracic esophagus penetrating the left pleural space treated within 4 hours from admission to the Emergency Room, with minimal surgical intervention is presented. Despite negative chest X-ray, a thoracic TC showed a small right sided effusion with left sided hydropneumothorax, and the definitive diagnosis was obtained by contrast study with a water soluble medium which showed the leak communicating freely with the left pleural space. The patient underwent repair by thoracic approach, the rupture was closed with a primary suture without flap reinforcement and the pleural space drained with the placement of single chest thoracostomy tube. The recovery was uneventful. The analysis of this case report and of the appropriate literature reveals that a poor prognosis is correlated with the time elapsed between the perforation and treatment. In conclusion the importance of an early aggressive surgical treatment for the Boerhaave's syndrome is emphasized, because any perforation treated more than 24 hours after the onset of symptoms, irrespective of the procedure used, is associated with a significantly higher morbility and mortality.

[Sciatic and femoral nerve block with electro-neural stimulator (ENS) in surgery of the knee in day-care surgery]. / Blocco dei nervi sciatico e femorale con elettroneurostimolatore (ENS) nella chirurgia del ginocchio in regime di day hospital.

This study was designed to evaluate locoregional anesthesia (double block of sciatic and femoral nerves with ENS) for ambulatory knee arthroscopic surgery. A statistical evaluation was performed in 50 adult outpatients (41 males, 9 females, ASA class 1 or 2) undergoing ambulatory knee arthroscopic procedures. Basal and intraoperative BP, HR SaO2 were recorded and the intensity of analgesia was also assessed according to the patient's subjective evaluation. Extra sedative or analgesic requirements were also recorded. There were no statistical changes in hemodynamic parameters during the perioperative period. The effectiveness of the anaesthetic block was classified as very good in 84% of patients, good in 2%, sufficient in 6% and inadequate in 8%. All patients were discharged in four hours after surgery. Our study shows that in ambulatory arthroscopic surgery, sciatic and femoral block with ENS is a valuable alternative to general anaesthesia.

Effects on renal hemodynamics and tubular function of the contrast medium iohexol in renal patients.

Renal function was assessed in 20 (11 female and 9 male, age 21-76 years, mean 53) renal patients with a creatinine clearance 25-145 ml/min, mean 95, to evaluate the effects of iohexol, a non-ionic low-osmolar contrast medium. Intravenous urography was performed in 16 patients and computed body tomography in 4, using a dose of iohexol ranged between 0.6-3.3 (mean 1.17) g/kg b.w. Different parameters of renal function were determined in the week preceding and 1, 3 and 5 days after the administration of iohexol. The principal renal effect of iohexol was an increase of urinary alanine aminopeptidase, gamma-glutamyltransferase, lactate dehydrogenase, alkaline phosphatase and N-acetyl-beta-D-glucosaminidase. The maximum increase of enzymuria was observed on day 1 after the administration of iohexol. In most cases enzymes returned to base-line values within 3 days. No relevant variation of renal hemodynamics (glomerular filtration rate and effective renal plasma flow) was observed after iohexol. In conclusion, iohexol can increase of urinary enzymes, but the effect is rapidly reversible and is not accompanied by a clinically significant impairment of renal hemodynamics.