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Fundamento: La nueva generación de materiales para implantes debe imitar las estructuras jerárquicas de la naturaleza. El carburo de silicio bioinspirado (bioSiC) es una cerámica producida a partir de madera, que presenta una estructura similar al hueso, con la propiedad única de una porosidad interconectada, que permite el crecimiento interno de los tejidos y favorece la angiogénesis. Objetivos: Valorar la biocompatibilidad y osteointegración del bioSiC en defectos óseos femorales en un modelo experimental en conejo. Material y métodos: Se obtuvieron 36 cilindros de bioSiC mediante pirólisis de madera de sapelli e infiltración con silicio fundido de la preforma de carbono resultante. Dieciocho cilindros se recubrieron con Si-HA por deposición con láser pulsado. Los cilindros se implantaron en cóndilos femorales de conejos que se sacrificaron a las 1, 4 ó 12 semanas. Las muestras se analizaron histológicamente mediante microscopía óptica y por microtomografía computarizada para evaluar el crecimiento de hueso. Resultados: Los implantes de bioSiC mostraron una buena osteointegración presentando tanto crecimiento hacia fuera (ongrowth) como hacia dentro (ingrowth). A las 4 semanas de la implantación la integración era casi completa, sin diferencias frente a las 12 semanas. El recubrimiento no mejora el valor de ningún parámetro con respecto a los implantes no recubiertos. Conclusiones: Las cerámicas de bioSiC fabricadas a partir de madera porosa presentan una buena osteointegración y su porosidad interconectada es colonizada por el tejido óseo. No requieren además la bioactividad de un revestimiento para mejorar la aposición de hueso neoformado. El bioSiC se erige como un material a tener en cuenta en aplicaciones biomédicas.

Objective: Our purpose was to investigate the advantages of laparoscopic myomectomy versus laparotomy.Study Design: A prospective, randomized trial was performed on 40 women, 22 to 44 years old, undergoing myomectomy. Patients were randomized to have laparoscopy (n=20) or laparotomy (n=20). The intensity of pain was assessed by a visual analog scale at 0, 1, 2, and 3 days postoperatively. The proportions of patients who were analgesic free on day 2, discharged from the hospital by day 3, and feeling fully recuperated on day 15 were also compared.Results: The intensity of postoperative pain was lower (p<0.05) after laparoscopy than after laparotomy. A higher (p<0.05) proportion of patients was analgesic free on day 2, discharged from hospital by day 3, and feeling fully recuperated on day 15 after laparoscopy compared with laparotomy.Conclusion: Laparoscopic myomectomy may offer the benefits of lower postoperative pain and shorter recovery time in comparison with laparotomy. [ABSTRACT FROM AUTHOR]

Patients with a partial reduction of merosin due to mutations in the laminin-[alpha]2 chain gene usually present with a mild form of congenital muscular dystrophy or a limb-girdle-like muscular dystrophy. To our knowledge, cardiac impairment has never been reported in such patients. A longitudinal study of a patient with partial laminin-[alpha]2 deficiency secondary to mutations in the LAMA2 gene revealed dilated cardiomyopathy with ventricular arrhythmias. Is this a chance association or a novel phenotype? Muscle Nerve, 2011. [ABSTRACT FROM AUTHOR]

Abstract Background The Mediterranean island of Sardinia has a strikingly high incidence of the autoimmune disorders Type 1 Diabetes (T1D) and Multiple Sclerosis (MS). Furthermore, the two diseases tend to be co-inherited in the same individuals and in the same families. These observations suggest that some unknown autoimmunity variant with relevant effect size could be fairly common in this founder population and could be detected using linkage analysis. Methods To search for T1D and MS loci as well as any that predispose to both diseases, we performed a whole genome linkage scan, sequentially genotyping 593 microsatellite marker loci in 954 individuals distributed in 175 Sardinian families. In total, 413 patients were studied; 285 with T1D, 116 with MS and 12 with both disorders. Model-free linkage analysis was performed on the genotyped samples using the Kong and Cox logarithm of odds (LOD) score statistic. Results In T1D, aside from the HLA locus, we found four regions showing a lod-score ≥1; 1p31.1, 6q26, 10q21.2 and 22q11.22. In MS we found three regions showing a lod-score ≥1; 1q42.2, 18p11.21 and 20p12.3. In the combined T1D-MS scan for shared autoimmunity loci, four regions showed a LOD >1, including 6q26, 10q21.2, 20p12.3 and 22q11.22. When we typed more markers in these intervals we obtained suggestive evidence of linkage in the T1D scan at 10q21.2 (LOD = 2.1), in the MS scan at 1q42.2 (LOD = 2.5) and at 18p11.22 (LOD = 2.6). When all T1D and MS families were analysed jointly we obtained suggestive evidence in two regions: at 10q21.1 (LOD score = 2.3) and at 20p12.3 (LOD score = 2.5). Conclusion This suggestive evidence of linkage with T1D, MS and both diseases indicates critical chromosome intervals to be followed up in downstream association studies.

Abstract Background Multiple sclerosis (MS) is consistently associated with particular HLA-DRB1-DQB1 haplotypes. However, existing evidence suggests that variation at these loci does not entirely explain association of the HLA region with the disease. The MOG locus is a prime positional and functional candidate for such additional predisposing effects but the analysis is complicated by the strong, albeit labyrinthine pattern of linkage disequilibrium in the region. Here we have assessed the association of MOG variation with MS in the Sardinian population to see if it represents an independent contributor to MS predisposition. Results After re-sequencing the MOG gene in 21 healthy parents of MS patients we detected 134 variants, 33 of which were novel. A set of 40 informative SNPs was then selected and assessed for disease association together with 1 intragenic microsatellite in an initial data set of 239 MS families. This microsatellite and 11 SNPs were found to be positively associated with MS, using the transmission disequilibrium test, and were followed up in an additional 158 families (total families analysed = 397). While in these 397 families, 8 markers showed significant association with MS, through conditional tests we determined that these MOG variants were not associated with MS independently of the main DRB1-DQB1 disease associations. Conclusion These results indicate that variation within the MOG gene is not an important independent determinant of MS-inherited risk in the Sardinian population.

Mutations on the LMNA gene are responsible for an heterogeneous group of diseases. Overlapping syndromes related to LMNA gene alterations have been extensively reported. Study scope is to perform a systematic analysis of the overlapping syndromes so far described and to try to correlate the clinical features to the associated genetic alterations. We evaluated all the dominant overlapping syndromes reported by means of a PubMed search and by the analysis of the main databases containing the pathogenic LMNA gene variations and the associated diseases. Metabolic alterations in association to skeletal and/or cardiac alterations proved to be the most frequent overlap syndrome. Overlapping syndromes are mostly associated to inframe mutations in exons 1, 2, 8 and 9. These data further improve the understanding of the pathogenesis of laminopathies.

Introduction: LMNA gene mutations are associated with cardiac and skeletal muscle alterations., Methods: A cohort of 21 mutated individuals was assessed with clinical and instrumental investigations over the years., Results: The median observation period was 6 years. Cardiac compromise was detected in 16 patients. Bradyarrhythmias were the most frequent manifestations, followed by supraventricular arrhythmias. Two individuals suffered from nonsustained and 1 from sustained ventricular tachyarrhythmias. Dilated cardiomyopathy was detected in 3 patients. Evaluation of the frequencies of the clinical expressions showed a high probability of suffering from analogue heart compromise in study subjects bearing the same LMNA gene mutation., Conclusions: Cardiac involvement represents a very common phenotypic expression of LMNA gene mutation. Subjects sharing common genetic background seem to suffer from analogue pattern of cardiac manifestation., (Copyright © 2012 Wiley Periodicals, Inc.)

The following is a report on a large family with 5 males affected by the X-linked recessive form of Emery-Dreifuss muscular dystrophy with mutation in the STA gene. A detailed longitudinal cardiological evaluation and muscle imaging studies allowed for the assessment of intrafamilial variability of cardiac and muscle involvement. Long term cardiological follow up in the 5 affected males and in 7 female carriers revealed different degrees of severity, ranging from tachycardia-bradycardia syndrome and variable biatrial and left ventricle dilatation, to an episode of isolated symptomatic sustained ventricular tachycardia requiring a device implantation. Muscle imaging in the affected males showed involvement of the soleus and medial head of gastrocnemius on leg muscles and variable involvement on thigh muscles that have not been previously reported. In some cases, imaging showed clear signs of muscle involvement even when no overt signs of weakness could be detected during clinical examination., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Introduction: Familial dilated cardiomyopathy with conduction system defects variably associated with skeletal muscle abnormalities is frequently caused by LMNA gene mutations., Methods: A family affected by cardiac abnormalities, either isolated or variably associated with skeletal muscle compromise, was identified. LMNA gene analysis was applied to all family members., Results: A novel intron 5 (c.937-11 C > G) mutation was identified. mRNA transcription analysis was subsequently performed, and cDNA was obtained from mutated patients. It displayed an aberrant splice product featuring the insertion of 40 nucleotides from intron 5, leading to a frameshift. Computational predictions identified a cryptic splice site 40 bp upstream from the canonical site; this alternative splicing event was elicited by intronic mutation, which seems to interfere with the polypyrimidine tract of the canonical site., Conclusions: We have described the first mutation on the LMNA gene interfering with the polypyrimidine tract. Our findings underline the importance of including introns in the search for mutations., (Copyright © 2011 Wiley Periodicals, Inc.)

Laminopathies are a heterogeneous group of LMNA-gene-mutation-related clinical disorders associated with alterations of cardiac and skeletal muscle and peripheral nerves, metabolic defects, and premature aging. Leg muscle imaging investigations were performed in a cohort of patients with LMNA gene alterations who were suffering from Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy type 1B, isolated cardiac disorders or a phenotype of cardiac disorders, and lipodystrophy, including one individual with peripheral neuropathy. Leg muscle imaging revealed varying degrees of alteration in the soleus and medial head of gastrocnemius in each subject. This study demonstrates that LMNA-gene-mutated patients devoid of any clinically detectable skeletal muscle involvement have the same pattern of leg muscle involvement as patients with overt skeletal muscle compromise. This finding suggests the presence of a continuum of skeletal muscle involvement among phenotypes of LMNA-gene-mutation-related skeletalmyopathy and cardiomyopathy.

The aim of this study is to report the evolution of a phenotype in members of a single family carrying the heterozygous exon 1 c.178 C/G, p.Arg 60 Gly LMNA gene mutation. All mutated family members underwent neurological and cardiological assessments for a period ranging from 10 to 20 years. At onset, 4 affected adult members presented a phenotype that required pacemaker implantation. Three subjects underwent cardiac transplantation leading to long-term survival in 2 of them. One of the 3 longest surviving relatives manifested late lipodystrophy, and the other 2 had lipodystrophy, insulin-resistant diabetes, and distal peripheral neuropathy. The findings demonstrate that the exon 1 c.178 C/G, p.Arg 60 Gly LMNA gene mutation is associated with a novel phenotype featuring cardiac involvement followed by late lipodystrophy, diabetes, and peripheral axonal neuropathy.

The case of a family in which several members displayed conduction defects inherited as a dominant trait is reported. The proband was a young woman with a 1st degree atrio-ventricular block and high serum creatine kinase. Several members of the family featured cardiologic symptoms. All adult family members were clinically evaluated and blood tests including serum creatine-kinase levels, standard and Holter ECG, echocardiogram and muscle MRI were performed. LMNA gene analysis was carried out and a novel missense mutation consisting in substitution of exon 4 c.799 T/C, p.Tyr267His was revealed. The mutation was present in seven family members, five of whom displayed cardiac defects alone with no involvement of the skeletal muscle. In all mutated individuals muscle MRI featured a pattern of skeletal muscle involvement similar to that observed in autosomal dominant Emery Dreifuss muscular dystrophy, suggesting that even patients bearing a LMNA gene mutation associated to an apparently selective cardiac phenotype may present subclinical skeletal muscle involvement.

Lamins are the principal components of the nuclear lamina, a network constituting the major structural framework of the nuclear envelope. Alterations in lamin A/C have been associated with a heterogeneous series of human disorders known as laminopathies. We report the finding of a novel deletion in the central rod domain of lamin A/C exon 3 gene in four members of the same family. This genetic alteration was likely responsible for the relatively homogeneous clinical phenotype observed in our three patients, represented by a prominent cardiac conduction-system disease necessitating permanent pacemaker implantation, and limited skeletal involvement manifested by spinal rigidity and contractures. The findings from these cases further expand the clinical spectrum associated with mutations in the LMNA gene.

A linkage and association of the CD45 (protein-tyrosine phosphatase, receptor-type C) C77G polymorphism and multiple sclerosis (MS) has been found in some studies but not in others. We analysed the C77G polymorphism in MS patients from the genetically homogeneous population of Sardinia. Using the transmission disequilibrium test, the mutation has been sought in 241 patients and 217 healthy sibs (HS) from singleton MS families and it was found in 5 (2.07 %) affected and 3 (1.38%) HS from 7 heterozygous parents (1.45 %). Transmission of the G77 allele was 71.4 % (TDT = 1.3, P = 0.26) in patients and 50% (TDT = 0, P = 1) in HS. Stratifying families according to carriage of MS-predisposing (DR+) or not-predisposing (DR-) HLA-DR-DQ genotype in patients, percentage of G77 transmission to DR+ patients was 33 (TDT = 0.33, P = 0.56, Pc = 1.12), while it was 100 (TDT = 4, P = 0.045, Pc = 0.09) in the DR-patients. We concluded that, despite the presence of CD45 G77 polymorphism in a few patients who did not carry the HLADR- DQ MS-predisposing molecules, CD45 did not contribute to development of the disease in Sardinian MS.

Several studies have indicated that multiple sclerosis (MS) is associated and linked to the major histocompatibility complex (MHC)/human leukocyte antigen (HLA) region of chromosome 6p21.3, but the exact location and nature of the primarily associated locus within the HLA complex is still controversial and largely presumptive. By linkage disequilibrium mapping, we have systematically investigated this chromosome region in the founder population of Sardinia to determine the relative associations of the various loci with MS. An overall 11.4 Mb region, which encompasses the whole HLA complex, was scanned with 19 microsatellite markers and with single nucleotide polymorphisms within 12 functional candidate genes and assessed for MS association using the extended transmission disequilibrium test (ETDT). A peak of association represented by the three adjacent DRB1, -DQA1 and -DQB1 loci was detected in the class II region. Two additional less significant areas of association were detected, respectively, in the centromeric side of the class II region at the DPB1 locus and, telomeric of the classically defined class I loci, at the D6S1683 microsatellite. Conditional ETDT analysis indicated that these regions of association could be independent of each other. Within the main peak of association, DRB1 and DQB1 contribute to the disease association independently of each other whereas DQA1 had no detectable primary genetic effects. We evaluated the haplotype distribution at the region showing the strongest association and found five DQB1-DRB1 haplotypes positively associated with MS in Sardinia. These consistently included all the haplotypes previously found associated with MS in the various human populations, thus supporting a primary effect of the products of these loci in MS. Overall these results are consistent with a multilocus model of the MHC encoded susceptibility to MS.

The prevalence of multiple sclerosis in Sardinia is significantly higher than in neighbouring Mediterranean countries, suggesting that the isolated growth of the population has concentrated genetic factors which increase susceptibility to the disease. The distinct HLA association of multiple sclerosis in Sardinia supports this interpretation. We have performed a whole genome screen for linkage in 49 Sardinian multiplex families using 327 markers. Non parametric linkage analysis of these data reveal suggestive linkage in the region of Chr 1q31, Chr 10q23 and Chr 11p15.

Purpose: We have evaluated in vitro the effects of using plasma (group A) or PAS-2 (group B) in storing platelets, regarding as well the type of container (conventional polyolefin--PL732--or new oxygen permeable platelet containers--PL2410, Compoflex--), on the metabolism of platelet concentrates--PC--from pools of five buffy coats., Material and Methods: 87, A and B pools of PCs collected in two types of bags were studied. The samples were taken on days 2, 5 and 7, and cell counts, pH, glucose, platelet activation (% CD62) and aggregation response were measured., Results: In group A, when we compared the two types of bags, we observed a difference (p < 0.01) in values of pH and glucose on day 5. These values were more advantageous in new oxygen permeable platelet containers. The rest of the parameters analysed didn't show significant differences. When we compared the PL-2410 containers from groups A and B, we found a lower level of glucose (p < 0.01) in group B, although the levels of glucose in this group on days 5 and 7 of storage were sufficient to support the platelet metabolism., Conclusions: The use of new oxygen permeable polyolefin containers and additive solutions, PAS-2, allows us to obtain pools of PC with suitable metabolic parameters during storage.

Objective: To verify if a 6-month period of hypoestrogenism due to chronic treatment with GnRH analogue (GnRH-a) causes irreversible bone loss in young women., Design: Controlled clinical study in volunteer women., Setting: Department of Obstetrics and Gynecology, University of Cagliari, Cagliari, Italy., Patients: Twenty-eight women (mean age +/- SE 81.1 +/- 0.99 years) with endometriosis diagnosed by laparoscopy and 25 healthy, normally cycling women of the same age (28.3 +/- 1.14 years)., Interventions: In women with endometriosis, six SC implants of the GnRH-a compound, 3.6 mg goserelin acetate depot, were administered every 28 days starting within 15 days of laparoscopy. Compounds interfering with bone metabolism or hormonal formulations were not taken by control women during the entire period of the study., Main Outcome Measure: Evaluation of lumbar bone mineral density at the start of the study and 6, 12, and 30 months later., Results: At the onset of the study, lumbar bone mineral density did not differ in women with endometriosis and control women. Lumbar bone mineral density values significantly decreased after 6 months of GnRH-a treatment. This reduction was still evident 6 months after GnRH-a interruption. However, 24 months after treatment withdrawal, bone mineral density reduction disappeared and bone mineral density values were completely superimposable (+/- O.4 percent) to those observed before treatment. In contrast, control women lumbar bone mineral density values did not change during the entire period of observation., Conclusions: These data suggest that GnRH-a treatment for 6 months is not associated with long-term effects on lumbar bone density.

The Authors report the results of a study on 204 patients anesthetized with epidural administration of buprenorphine with bupivacaine. The data obtained were compared with a sample of 236 patients treated with local anesthetic alone. On the whole, the first group of patients presented better anesthesia, with a significantly longer anesthetic effect and more effective sedative and postoperative analgesic effects. Side effects observed were of acceptable entity and incidence.