Microencapsulated islet allografts in diabetic NOD mice and nonhuman primates.

OBJECTIVE: Our goal was to assess the efficacy of encapsulated allogeneic islets transplanted in diabetic NOD mice and streptozotocin (STZ)-diabetic nonhuman primates (NHPs). MATERIALS AND METHODS: Murine or NHP islets were microencapsulated and transplanted in non-immunosuppressed mice or NHPs given clinically-acceptable immunosuppressive regimens, respectively. Two NHPs were treated with autologous mesenchymal stem cells (MSCs) and peri-transplant oxygen therapy. Different transplant sites (intraperitoneal [i.p.], omental pouch, omental surface, and bursa omentalis) were tested in separate NHPs. Graft function was monitored by exogenous insulin requirements, fasting blood glucose levels, glucose tolerance tests, percent hemoglobin A1c (% HbA1c), and C-peptide levels. In vitro assessment of grafts included histology, immunohistochemistry, and viability staining; host immune responses were characterized by flow cytometry and cytokine/chemokine multiplex ELISAS. RESULTS: Microencapsulated islet allografts functioned long-term i.p. in diabetic NOD mice without immunosuppression, but for a relatively short time in immunosuppressed NHPs. In the NHPs, encapsulated allo-islets initially reduced hyperglycemia, decreased exogenous insulin requirements, elevated C-peptide levels, and lowered % HbA1c in plasma, but graft function diminished with time, regardless of transplant site. At necropsy, microcapsules were intact and non-fibrotic, but many islets exhibited volume loss, central necrosis and endogenous markers of hypoxia. Animals receiving supplemental oxygen and autologous MSCs showed improved graft function for a longer post-transplant period. In diabetic NHPs and mice, cell-free microcapsules did not elicit a fibrotic response. CONCLUSIONS: The evidence suggested that hypoxia was a major factor for damage to encapsulated islets in vivo. To achieve long-term function, new approaches must be developed to increase the oxygen supply to microencapsulated islets and/or identify donor insulin-secreting cells which can tolerate hypoxia.

Scanning electron microscopy and microbiological approaches for the evaluation of salivary microorganisms behaviour on anatase titanium surfaces: In vitro study.

Implantology research framed the implant surface as a key element for a good and sustainable osseointegration of an implant fixture. The aim of this study was to analyze the antibacterial properties of anatase-coated titanium healing screws through microbiological and scanning electron microscopy. The comparison of the bacterial colonies growth between the anatase-coated titanium healing screws and non-coated titanium healing screws showed comparable antibacterial properties, without significant statistical differences. The scanning electron microscopy observations confirmed the microbiological study. These data, also considering previous reports on the positive effects on osteoblasts genetic expressions, might suggest a use of the anatase-coated titanium healing screws to preserve the tissues surrounding implants from microbial attacks.

[Addiction]. / Addictions.

What's new in addiction medicine in 2012? The news are presented according three axes: first, in the field of neuroscience, the process of extinction of addiction memories. Then in the clinical field, a reflexion is reported on how to treat addiction in psychiatric hospitals. At last, in the area of teaching, an e-learning development with a virtual patient shows a great interest in addiction psychiatry.

[Addiction]. / Dépendances.

The news in addiction medicine for 2011 include new knowledges coming from the neurosciences, but also new clinical concepts, as the role of hospital addiction units in an integrated network of care. The issue of cocaine vaccination is discussed from an ethical point of view. Finally, the integration of mindfulness techniques is introduced as a useful approach in the treatment of the addictions.

Feasibility of 3.0T pelvic MR imaging in the evaluation of endometriosis.

INTRODUCTION: Endometriosis represents an important clinical problem in women of reproductive age with high impact on quality of life, work productivity and health care management. The aim of this study is to define the role of 3T magnetom system MRI in the evaluation of endometriosis. MATERIALS AND METHODS: Forty-six women, with transvaginal (TV) ultrasound examination positive for endometriosis, with pelvic pain, or infertile underwent an MR 3.0T examination with the following protocol: T2 weighted FRFSE HR sequences, T2 weighted FRFSE HR CUBE 3D sequences, T1 w FSE sequences, LAVA-flex sequences. Pelvic anatomy, macroscopic endometriosis implants, deep endometriosis implants, fallopian tube involvement, adhesions presence, fluid effusion in Douglas pouch, uterus and kidney pathologies or anomalies associated and sacral nervous routes were considered by two radiologists in consensus. Laparoscopy was considered the gold standard. RESULTS: MRI imaging diagnosed deep endometriosis in 22/46 patients, endometriomas not associated to deep implants in 9/46 patients, 15/46 patients resulted negative for endometriosis, 11 of 22 patients with deep endometriosis reported ovarian endometriosis cyst. We obtained high percentages of sensibility (96.97%), specificity (100.00%), VPP (100.00%), VPN (92.86%). CONCLUSION: Pelvic MRI performed with 3T system guarantees high spatial and contrast resolution, providing accurate information about endometriosis implants, with a good pre-surgery mapping of the lesions involving both bowels and bladder surface and recto-uterine ligaments.

Fetal MRI as a complement to US in the evaluation of cleft lip and palate.

PURPOSE: The aim of our study was to investigate the role of fetal magnetic resonance imaging (MRI) as a complement to ultrasound (US) in the evaluation of cleft lip and palate (CLP), whether isolated or in association with syndromic conditions. MATERIALS AND METHODS: We enrolled 24 pregnant women (27 fetuses) (mean gestational age 23.7 weeks) with a level-two US diagnosis of cleft lip (CL) or CLP with or without associated central nervous system (CNS) or facial-bone anomalies. All individuals underwent a fetal MRI examination to study the facial skeleton, CNS and fetal body. For each fetus, the main anatomical facial landmarks and biometric parameters [anteroposterior diameter (APD), biparietal diameter (BPD), inferior facial angle (IFA), frontomaxillary angle (FMA), bi-orbital diameter (BOD), intraorbital diameter (IOD)] were measured. RESULTS: Twenty-five of 27 fetuses had a US diagnosis of CL or CLP. MRI confirmed the diagnosis in 16/25 fetuses and added information about the extent of the cleft and the degree of involvement of the anterior and posterior palate in 8/25 fetuses. MRI ruled out the diagnosis in 1/25 fetuses and identified an alteration of the parameters IFA, FMA and IOD in 6/24 fetuses. CONCLUSIONS: In the study of CLP fetal, MRI is able to define the degree of involvement of the posterior palate and the lateral extent of the cleft with higher diagnostic accuracy than US. Furthermore, MRI provides a complete study of the fetal head and biometric development of the facial bones, thus enabling early detection of potential syndromic conditions.

[Addiction]. / Dépendances.

The news in addiction medicine for 2010 include somatic, neuroscientific as well as psychotherapeutic aspects. First are considered the risks of cardiac arythmy with methadone as long as the racemate form is prescribed in Switzerland. Then the neurosciences bring their usual novelties in the field of the addictions, this year in relational neuroscience and in the relationship between trauma and addiction. At last a contribution bridges the notion of low threshold treatment with the psychodynamic approach.

Role of fetal MRI in the diagnosis of cerebral ventriculomegaly assessed by ultrasonography.

PURPOSE: To evaluate the additional diagnostic value of fetal MRI to evaluate cerebral ventriculomegaly assessed by ultrasonography (US) for the possibility to change the diagnosis, the counseling and the management of pregnancy. MATERIALS AND METHODS: From february 2006 to october 2008, we studied 55 pregnant women by fetal MRI (mean age 28 years), 4 with twin pregnancy, for a total of 59 fetuses with mean gestational age of 27 weeks. The number of fetuses affected by ventriculomegaly assessed by US was 55. All fetuses had a US diagnosis of ventriculomegaly: 29 fetuses with isolated ventriculomegaly and 26 fetuses with ventriculomegaly associated with CNS (central nervous system) abnormalities (18) and with no CNS abnormalities (8). RESULTS: The findings showed that the two techniques are substantially in agreement in defining the degree of VM, with the exception of some cases in which the disagreement could be attributed to the possible progression of the dilatation between the US and MRI examinations, which sway between two days and two weeks. We proved a low correlation between US and MRI in the evaluation of ventriculomegaly associated either with CNS or non-CNS anomalies: in fact while fetal MRI detected 26/55 (47,3%) VM associated with CNS anomalies, US demonstrated only 18/55(32,7%). Referring to VM associated with non-CNS anomalies, MRI diagnosed 10/55 cases (18,2%) compared to 8/55 fetuses (14,5%) showed by US. CONCLUSIONS: Our experience demonstrated that fetal MRI has an important role as adjunctive tool to sonography in the evaluation of cerebral ventriculomegaly for the additional informations given to parents and for the possibility to change the diagnosis, the counseling and the management of pregnancy.

Fetal MRI of the cardiovascular system: role of steady-state free precession sequences for the evaluation of normal and pathological appearances.

PURPOSE: This study aimed to evaluate the feasibility of fetal magnetic resonance imaging (MRI) with steady-state free precession (SSFP) sequences to visualise the normal and pathological appearances of the cardiovascular system. MATERIALS AND METHODS: This is a prospective observational study of 83 pregnant women who underwent fetal cardiac MRI: 43 patients (cases) had echocardiographic suspicion of congenital heart disease; 40 patients (controls) did not. Fetal cardiac MRI consisted of a static phase with multiplanar SSFP sequences and a dynamic phase with real-time SSFP sequences. Two radiologists evaluated the diagnostic quality of the SSFP images in both the controls and cases, the MRI morphological and functional features in the controls and the MRI signs of congenital heart disease in the cases. RESULTS: In both groups, SSFP sequences produced goodquality MR images and good visualisation of morphological features. Functional data appeared to be unavailable due to the current small temporal resolution and the technical impossibility of fetal cardiac triggering. MRI detected direct signs of congenital heart disease in 21 fetuses, indirect signs in six and both signs in 15. CONCLUSIONS: SSFP sequences are effective in demonstrating the morphological features of the cardiovascular system, whereas dynamic SSFP cine-MRI sequences may provide adjunctive albeit suboptimal functional information.

Fetal MRI with diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) assessment in the evaluation of renal development: preliminary experience in normal kidneys.

PURPOSE: The study aimed to investigate the correlation between apparent diffusion coefficient (ADC) and gestational age by applying diffusion-weighted imaging (DWI) in the study of normal fetal kidneys. MATERIALS AND METHODS: We performed magnetic resonance (MR) imaging on 88 fetuses (gestational age range 17-40 weeks) after ultrasound had ruled out urinary system malformations. A multiplanar study of the urinary system was obtained by using conventional T2-weighted sequences and echoplanar imaging (EPI). DW sequences with ADC maps were subsequently acquired, and kidney ADC values were correlated with gestational age by diving the fetuses into six groups according to age. RESULTS: We found a correlation between ADC values and gestational age. The ADC values, ranging from 0.99 to 1.62x10(-3) mm(2)/s [mean 1.22; 95% confidence interval (CI) 1.19-1.25, standard deviation (SD) 0.147], showed a tendency to decrease with increasing gestational age. The relationship between ADC values and gestational age was expressed by a linear regression equation: ADC (mm(2)/s)=1.69-0.0169 (GA) (R(2)=37.7%, R(2) ADJ=37.0%, p<0.005, Pearson correlation=-0.614). CONCLUSIONS: DWI with ADC mapping provides functional information on fetal renal parenchyma development and may thus become a useful tool in the management of pregnancy and treatment of the newborn child.

Assessment of congenital heart disease (CHD): is there a role for fetal magnetic resonance imaging (MRI)?

PURPOSE: To review our experience with fetal magnetic resonance imaging (MRI) to evaluate congenital heart disease (CHD). METHODS: We performed fetal MRI in 32 fetuses with an echocardiographically assessed CHD. Both direct and indirect signs of CHD were investigated. Direct signs considered were: morpho-volumetric abnormalities of the heart; malrotations; ventricular and atrial septal defects; anomalies of the origin, size and course of the great arteries. Indirect signs considered were: difficulty to recognize a "normal" anatomical structures in the reference projections; increase of the vascular size before a stenosis; hypertrophy of the papillary muscles; cardiomegaly and pericardial effusion. All MRI findings were compared with postnatal or autoptic findings. RESULTS: MRI allowed the CHD to be visualised by direct signs in 17 fetuses, indirect signs in 5 and both direct and indirect signs in 9 fetuses, excluding the prenatal echocardiographic suspect of hypoplastic left heart syndrome in 1 fetus. Postnatal echocardiograms or autoptic findings confirmed a normal heart in 1 fetus and CHD in 31 fetuses including a single cardiac anomaly or syndrome in 19 fetuses, 2 associated cardiac abnormalities in 11 and 3 cardiac anomalies in 1 fetus. However, in 2 fetuses MRI detected a ventricular septal defect successively disclosed by gold standard. CONCLUSIONS: MRI is a promising method for further assessment of the cardiovascular pathologies diagnosed by echocardiography, and may be a valuable tool in assessing associated extracardiac anomalies.

Design, fabrication, and characterization of a composite scaffold for bone tissue engineering.

Poly(lactide-co-glycolide) (PLGA) scaffolds have been successfully used in bone tissue engineering, with or without hydroxyapatite (HA) and with a macroporosity given either by simple PLGA sphere packaging and/or by leaching out NaCl. The objective of this work was the optimization of the design parameters for bone tissue engineering scaffolds made by sintering microspheres of PLGA, HA nanocrystals for matrix reinforcement and osteoconduction, and salt crystals for macroporosity and control of matrix pore size. Microsphere fabrication by a single-emulsion and solvent evaporation technique was first optimized to obtain a high yield of PLGA microspheres with a diameter between 80 and 300 microm. The influence of the sintering process and matrix composition on the scaffold structure was then evaluated morphologically and mechanically. Three scaffold types were tested for biocompatibility by culturing with human fibroblasts for up to 14 days. The most important parameters to obtain microspheres with the selected diameter range were the viscosity ratio of the dispersed phase to the continuous phase and the relative volume fraction of the 2 phases. The Young's modulus and the ultimate strength of the sintered matrices ranged between 168-265 MPa and 6-17 MPa, respectively, within the range for trabecular bone. Biocompatibility was demonstrated by fibroblast adhesion, proliferation, and spreading throughout the matrix. This work builds upon previous work of the PLGA/HA sintering technique to give design criteria for fabricating a bone tissue engineered matrix with optimized morphological, functional, and biological properties to fit the requirements of bone replacements.

[Addiction]. / Dépendances.

This year review emphasizes four aspects coming from addiction psychiatry: 1. Initiation and maintenance of cannabis use. 2. Methadone and heart toxicity. 3. Suicidal behaviour in gambling. 4. Treatment of addictive disorders via internet: present and future perspectives.

Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief.

The pharmacokinetics and pharmacodynamics of morphine are under the control of several polymorphic genes, which can account for part of the observed interindividual variation in pain relief. We focused on two such genes: ABCB1/MDR1, a major determinant of morphine bioavailability, and OPRM1, which encodes for the mu-opioid receptor, the primary site of action for morphine. One hundred and forty-five patients of Italian origin undergoing morphine therapy were genotyped for the single-nucleotide polymorphism (SNP) C3435T of ABCB1/MDR1 and for the A80G SNP of OPRM1. Pain relief variability was significantly (P<0.0001) associated with both polymorphisms. Combining the extreme genotypes of both genes, the association between patient polymorphism and pain relief improved (P<0.00001), allowing the detection of three groups: strong responders, responders, and non-responders, with sensitivity close to 100% and specificity more than 70%. This study provides a good example of the possible clinical use of pharmacogenetics.

US evaluation and diagnosis of rupture of the medial head of the gastrocnemius (tennis leg).

PURPOSE: The aim of this study is to demonstrate the diagnostic accuracy of ultrasonography (US) in the diagnosis of rupture of the medial head of the gastrocnemius muscle, also called "tennis leg" (TL). MATERIALS AND METHODS: Thirty-five consecutive patients with acute traumatic injury of the calf underwent US examination. There were 25 men and 10 women; mean age 47.5 years (range 35-60 years). All examinations were performed using a 5-12 MHz broadband electronic linear array probe. RESULTS: Thirty-three out of 35 patients had TL; 24 cases of partial rupture and nine cases of complete rupture were diagnosed. In the remaining two cases, both with symptoms suggesting TL, one patient had a tear of the proximal musculotendinous junction and one had a ruptured Baker's cyst. Fluid collections caused by the muscular rupture were visible as hypoechoic areas; in 80% of cases associated by a hyperechoic oval area due to hematoma and local inflammation. The degree of fluid collection in the patients with complete rupture (6-16 mm; mean: 9.7 mm) was significantly greater than the one seen in patients with partial rupture (4-8 mm; mean: 6.8 mm). CONCLUSIONS: US is the imaging modality of choice in clinical suspicion of TL, both in the initial workup of the patient and in the follow-up. US is easy to perform and is particularly useful to distinguish TL from other pathologies, especially ruptured Baker's cyst and deep vein thrombosis, which require a different therapeutic management.

High prevalence of chromosome 10 rearrangements in human lymphocytes after in vitro X-ray irradiation.

PURPOSE: To evaluate the chromosome symmetric or asymmetric rearrangement (CR) frequency for chromosome 10 compared to chromosomes 1 and 3 induced in vitro in human lymphocytes by low doses of X-rays. MATERIALS AND METHODS: Blood samples obtained from three young and healthy volunteers were irradiated in G0 with 0.25, 0.50 and 1 Gy X-rays. Chromosome painting analysis was used on preparations of peripheral lymphocytes for the identification of CR. RESULTS: It was found that radiation-induced CR levels were nonrandomly distributed among the three painted chromosomes. Chromosome 10 CR frequencies were significantly greater than those involving chromosomes 1 (at all the doses tested) or 3 (at 0.25 and 1 Gy), with frequency ratios ranging from 2.2 to 5.2. CONCLUSIONS: In comparison to chromosomes 1 and 3, chromosome 10 appeared to be involved in exchanging at a significantly greater extent than expected according to its DNA content.

Impact of routine infant and adolescent hepatitis B vaccination in Tuscany, Central Italy.

BACKGROUND: In Italy routine infant and adolescent immunization against hepatitis B was introduced in 1991. OBJECTIVE: Evaluation of (1) coverage with three doses of hepatitis B vaccine in infants and adolescents; (2) seroconversion to anti-hepatitis B surface antigen antibody (anti-HBs) in adolescents receiving three doses of vaccine; (3) concordance of coverage rates in infants with prevalence of neutralizing antibodies in sera from anonymous children; (4) trend of notified cases of acute hepatitis B. METHODS: A sample of infants and adolescents living in Tuscany was studied during 6 years (1992 through 1997) by matching birth records and immunization certificates. Sera from 139 adolescents who completed the vaccination course and from 159 anonymous children belonging to immunized cohorts (1 to 5 years) were tested with a quantitative anti-HBs assay. Incidence of acute hepatitis B by age was calculated from regional statistics on notified infectious diseases between 1992 and 1996. RESULTS: Overall 10,606/11,164 (95%) infants and 10,599/11,100 (95%) adolescents received 3 doses of vaccine. Seroconversion to anti-HBs was detected in 98% of adolescent vaccinees. Anti-HBs titers > or =10 IU/l were detected in 87% of children. A 49% decline of acute hepatitis B cases was registered between 1992 and 1996 in 15- to 24-year-olds living in Tuscany. No case occurred in vaccinated adolescents. CONCLUSIONS: Coverage against hepatitis B is excellent in cohorts subject to mandatory immunization. If efforts to vaccinate are maintained at these levels, elimination of hepatitis B virus transmission could occur within few decades in Italy.

Low prevalence of diphtheria immunity in the population of Florence, Italy.

A seroepidemiological study was conducted in 1994 on a representative sample of the population of Florence in order to verify the immunity coverage against diphtheria. Subjects were divided according to sex and age class. Sera from each selected class were at least 1.5/1000 of the residing population. Diphtheria antitoxin was titrated using a quantitative ELISA test. The results show an overall adjusted prevalence of diphtheria immunity (> or = 0.01 IU/ml) equal to 63.7%. Subjects of younger age classes have good protection levels (85.5% immune under 30 years), while only half individuals aged > or = 50 years have antibody titres > or = 0.01 IU/ml. Full protection (antibody titre > or = 0.1 IU/ml) was detected only in a very small proportion of those aged > or = 40 years. Our data show (1) how a recrudescence of diphtheria could theoretically take place in older subjects living in Italy, and (2) stress the importance of periodical re-vaccination of adults.

[Role of ultrasonography-guided fine-needle biopsy in the selection for surgical treatment in thyroid diseases. Multicenter retrospective study of 5,109 patients]. / Analisi del ruolo della citologia agoaspirativa ecoguidata quale criterio di selezione nella terapia chirurgica delle malattie tiroidee. Studio retrospettivo multicentrico su 5109 pazienti.

FNAB cytology is a very specific diagnostic tool for distinguishing benign from malignant lesions. It allows the histologic type to be diagnosed too. FNAB findings also help select the type of surgery. The value of FNAB cytology was investigated in 5,109 patients examined from 1987 through March 1993. 607 patients has surgical confirmation. 444 patients underwent cytology before surgery, while 163 patients were not submitted to FNAB. Histology diagnosed 116 malignant tumors (19.2%): 83 of them were papillary carcinomas (71.5%), 26 follicular carcinomas (2.6%), 1 primary thyroid lymphoma (0.9%) and 3 medullary carcinoma (2.6%). Seventy-nine of 116 cases had been diagnosed by FNAB cytology, while 37 of 116 were diagnosed at surgery. Aspiration biopsy under US guidance reduced the rate of thyroidectomies from 19.2% to 8.5% because true-positive cases were assessed before surgery. FNAB cytology should be used as a preliminary diagnostic tool, thanks to its high accuracy and to its capabilities of distinguishing benign from malignant lesions for proper medical or surgical treatment. Moreover, FNAB cytology allows potentially malignant lesions to be surgically explored.

[The role of ultrasonography in thyroid disease]. / Il ruolo dell'ecografia nella patologia tiroidea.

Ultrasound examination of the thyroid gland is widely used in the diagnosis of thyroid disease. This test is easy and rapid to perform, widely available and the results are readily interpreted. Using ultrasound the image of foci of disease within the gland are easily identified, especially using high frequency probes which enable solid nodules up to approx 3 mm to be revealed with 10 MHz probes. In non-nodular thyroid disease the ultrasonic structure guides the diagnosis (thyroiditis, Graves' disease). During the follow-up of thyroidectomised patients ultrasound can easily reveal postoperative anatomic variations and an early diagnosis can be obtained of any signs of local recurrence of the primary disease. Only hemiagenesia and hypoplasia can be accurately evaluated in congenital disease, whereas in the event of the persistence of the thyroglossal duct the latter can only be diagnosed if it presents a cystic evolution. Thyroid ectopia cannot be identified and must be studied using thyroscintigraphy, preferably performed using 131I as the isotope. The acquired pathology is classified into phlogistic processes, diffuse or nodular hyperplasia, benign and malignant neoplasia. This classification is widely accepted by virtually all authors. In thyroiditis, ultrasound may facilitate the diagnosis of De Quervain's non-suppurative sub-acute thyroiditis (TANS) and Hashimoto's chronic thyroiditis, although always in association with clinical and laboratory tests. The most frequent thyroid pathology is without doubt goitre. This disorder may occur in a non-nodular (widespread goitre with an endemic or sporadic pattern) or nodular form which may be single or multiple. The term goitre is used to indicate the increased volume of the thyroid gland independently of the causes which have provoked it. Common goitre is defined as being endemic when in some geographic area 10% of the general population or 20% of the school-aged population suffers from thyroid hyperplasia (areas of goitrogenic endemic disease). Graves' disease may be included in the group of thyroid hyperplasia diseases, although it is distinguished from the simple versions by the marked glandular hyperactivity which creates manifest hyperthyroidism. In this pathology ultrasonography must be supplemented by colour-Doppler wherever possible. Thyroid nodules are subdivided in terms of their echostructure into 5 types: liquid, mixed (prevalently solid or prevalently liquid), hyperechogenic solid, isoechogenic solid and hypoechogenic solid. The characteristics of benign nodules are: hypoechogenic structure, regular edges, complete and uniform hypoechogenic peripheral halo.(ABSTRACT TRUNCATED AT 400 WORDS)