Frailty of the elderly in orthopaedic surgery and body composition changes: the musculoskeletal crosstalk through irisin.

In recent years, scientific interest has been developed towards irisin, a novel molecule of the family of myokines, which is directly involved in body mass composition balance, chronic diseases susceptibility and physiologic resilience to stressful events, including surgery. In the context of musculoskeletal disease, the role of this molecule has been associated to the balance of lean and fatty mass, and the production of irisin is subordinated to a healthy lifestyle and exercise. The mechanism of action of irisin on tissues is complex, and several studies described the molecular pathways in animal model and human subjects. In particular, in adipose cells, the key-role of irisin is to stimulate the differentiation of white adipose tissue to brown adipose tissue, through the action on the uncoupling protein 1. Furthermore, in the bony tissue, irisin stimulates osteogenesis through expression of Sost and Opn genes. These features make irisin a suitable molecule to use as a biomarker of the overall musculoskeletal health of the elderly, before undergoing orthopaedic surgery. Further research on this topic should be carried out to highlight the possible clinical role and predictive value of irisin in a multidisciplinary approach to the elderly before musculoskeletal surgery.

Assessment of pN-GAL as a marker of renal function in elite cyclists during professional competitions.

Glomerular filtration rate (GFR) has been shown to be lower than physiological values during exercise with a strong negative correlation with exercise intensity. Among new markers of renal function, neutrophil gelatinase-associated lipocalin (NGAL) seems to be very promising. It is an early, sensitive and specific marker of acute kidney injury (AKI) with two isoforms: plasma NGAL (pNGAL) and urinary NGAL (uNGAL). The aim of the present study was to assess acute variations in NGAL plasma levels after performing high endurance physical exercise in a group of professional cyclists during the two major European professional cycling competitions (Giro D'Italia and Tour de France). Eighteen professional cyclistis were recruited for the study. A blood sample was collected during rest (after 8 hours fasting) and immediately after the competition (mountain stages) in order to assess the effect of very intense exercise on kidney function by measuring the variations of pNGAL. We also assessed plasma levels of creatinine, creatine-kinase (CK), LDH, transaminases and electrolytes. The results showed that Creatinine, CK and electrolytes levels remained almost stable between rest and post-competition. The levels of transaminases and NGAL showed a mild increase between rest and post-competition, with a significant difference between the two values only for transaminases (p=0.005). However, post-competition values of all investigated variables remained within the physiological range. The results of the present study suggest that even if NGAL values mildly rose after competition, no kidney injury occurred in these highly trained athletes during mountain stages of professional competitions. Other studies in literature confirmed that high endurance physical exercise seems not to cause renal injury in elite athletes. This is probably due to adaptive mechanisms of renal function and to the adaptation to physical stress gained with training.

Open Latarjet versus arthroscopic Latarjet: clinical results and cost analysis.

PURPOSE: The aim of this study was to compare the clinical results between open and arthroscopic Latarjet and perform a cost analysis of the two techniques. MATERIALS AND METHODS: A systematic review of articles present in PubMed and MEDLINE was performed in accordance with PRISMA guidelines. Studies concerning post-operative outcomes following Latarjet procedures for chronic anterior shoulder instability were selected for analysis. The clinical and radiographic results as well as the costs of the open and arthroscopic techniques were evaluated. RESULTS: Twenty-three articles, describing a total of 1317 shoulders, met the inclusion criteria: 17 studies were related to open Latarjet, and 6 to the arthroscopic technique. Despite the heterogeneity of the evaluation scales, the clinical results seemed very satisfactory for both techniques. We detected a statistically significant difference in the percentage of bone graft healing in favour of the open technique (88.6 vs 77.6 %). Recurrent dislocation was more frequent following open surgery (3.3 % after open surgery vs 0.3 % after arthroscopy), but this finding was biased by the large difference in follow-up duration between the two techniques. The direct costs of the arthroscopic procedure were double in comparison to open surgery (€2335 vs €1040). A lack of data prevented evaluation of indirect costs and, therefore, a cost-effectiveness analysis. CONCLUSIONS: The open and arthroscopic Latarjet techniques showed excellent and comparable clinical results. However, the much higher direct costs of the arthroscopic procedure do not seem, at present, to be justified by a benefit to the patient. LEVEL OF EVIDENCE: III.

Androgens and cardiovascular disease in postmenopausal women: a systematic review.

Androgens play a pivotal role in cardiovascular function and their effects differ between men and women. In postmenopausal women, testosterone replacement within physiological levels is associated with overall well-being. However, a definitive explanation as to how androgens have an impact on cardiovascular health in postmenopausal women and whether they may be used for cardiovascular treatment has yet to be established. With these aims, a systematic review of the existing studies on the link between androgens and cardiovascular disease and the effects of testosterone therapy on cardiovascular outcomes in postmenopausal women has been conducted. The few existing studies on cardiovascular outcomes in postmenopausal women indicate no effect or a deleterious effect of increasing androgens and increased cardiovascular risk. However, there is evidence of a favorable effect of androgens on surrogate cardiovascular markers in postmenopausal women, such as high density lipoprotein cholesterol, total cholesterol, body fat mass and triglycerides. Further studies are therefore needed to clarify the impact of therapy with androgens on cardiovascular health in postmenopausal women. The cardiovascular effect of testosterone or methyltestosterone with or without concomitant estrogens needs to be elucidated.

Functional repair in massive immobile rotator cuff tears leads to satisfactory quality of living: results at 3-year follow-up.

PURPOSE: The aim of this retrospective study was to report clinical results of a selective population undergone to arthroscopic functional repair of massive, contracted, immobile rotator cuff tears. METHODS: From 2005 to 2009, 311 patients with rotator cuff tears were treated at our institution. Of them, 26 shoulders in 25 patients with a mean age of 64 years that presented a massive, contracted immobile tear repaired using an interval slide technique, were included in this study. RESULTS: The mean postoperative follow-up period was 39 months (range 19-70 months). The mean postoperative disabilities of the arm, shoulder and hand (DASH) score and simple shoulder test (SST) score were, respectively, 20.91 and 8.8 (range DASH: 0.83-59.1; range SST: 2-12). Based on single assessment numeric evaluation score, the outcome of surgery was satisfactory with a mean of 76 % (range 0-100 %). The residual level of pain was low, as reported by a final mean visual analog scale score of 1.8 (range 0-8). The mean postoperative range of motion was 157.5° in forward elevation (range 90°-180°) and 55.3° in extra rotation (range 0°-90°). Eleven patients reached mid-back, in 7, the lower back and in 8 cases, upper back. CONCLUSION: Arthroscopic functional repair could be considered an appropriate treatment option in case of massive, contracted and immobile cuff tears. This treatment can provide improvement in pain and function that positively affects patients' quality of life without precluding other, more invasive, eventually consequent solutions.

Role of cardiovascular risk factors (CRF) in the patients with mild cognitive impairment (MCI).

Few therapeutic options are available nowadays to improve the prognosis of patients with Alzheimer's disease (AD). There are rather several evidences in literature that controlling vascular risk factors may be an effective intervention for modifying the course of this disease. The aim of our study was to investigate the role of CRF in 50 patients with MCI according to Petersens's criteria, and to evaluate their influence on cognitive and behavioral features of the disease and on the development of dementia. Statistical analysis of the data showed that the 60% of the patients with MCI and CRF developed dementia, while 40% maintained the same cognitive conditions at the end of the study. Only 32% of the subjects without cardiovascular comorbidities developed dementia. The results of the study suggest that CRF play a key role in cognitive decline of patients with MCI. Patients with MCI and CRF showed not only worse cognitive performances, but also behavioral disorders, depression and functional disability. Patients with CRF had higher conversion rate to AD than the other group, with a mean disease-free period 3 months shorter than the control group.

Ectodermal dysplasia with amastia: a case of one-step reconstruction.

Background. Female patients presenting amastia associated with ectodermal dysplasia are not frequently encountered, but they are of great clinical interest and surgically demanding. Traditionally, skin alterations related to Ectodermal Dysplasia have addressed plastic surgeons to perform a two-stage approach in amastia associated with this congenital pathologic condition. This article describes an alternative method for correcting this deformity trough a mammary reconstruction in one surgical stage. Materials and Methods. We report a case of 26-year-old female patient with bilateral amastia associated with ectodermal dysplasia. Amastia in this patient was treated with implantation of subpectoral silicone gel prostheses, without previously breast tissue expansion. Results. At 18 months of follow-up after surgey, there were no complications and excellent cosmetic results were achieved. Patient and surgeon satisfaction was high and the patient underwent a bilateral areola-tattoo. Conclusions. One-stage mammary reconstruction have showed to be a reliable and effective technique also when amastia is associated with Ectodermal Dysplasia, suggesting a still satisfying biomechanical performance of the skin in this pathology.

Leukocyte perturbation associated with Fabry disease.

Fabry disease is an X-linked lysosomal storage disorder of glycosphingolipid catabolism due to the deficient activity of the enzyme alpha-galactosidase A. The non-degraded substrate, mainly globotriaosylceramide (Galα1-4Galß1-4Glcß1-1Cer; Gb(3)) accumulates progressively in the lysosome of various cells. The aim of this work was to analyse changes in leukocyte subpopulations and surface markers and to determine whether Gb(3) is increased in leukocytes of patients with untreated and treated Fabry disease. Blood samples obtained from 22 male Fabry patients (11 untreated and 11 on enzyme replacement therapy) and 22 normal controls were subjected to flow cytometric analysis of Gb(3) intracellular content, leukocyte subpopulations and cell markers. Based on the fluorescence intensity of bound monoclonal antibody, and relative to normal control leukocytes, Gb(3) appeared significantly increased in lymphocytes (but not in monocytes or granulocytes) from patients with Fabry disease. A significantly higher percentage of lymphocytes and CD19(+) cells and a reduced proportion of monocytes, CD8(+) cells and myeloid dendritic cells were detected in samples from Fabry patients compared with normal controls. CD1d expression was significantly lower and MHC class II surface expression was significantly higher in monocytes from Fabry patients than in normal controls. As previously observed for other adhesion molecules, the expression of CD31 (PECAM) was higher in leukocytes from Fabry patients. In conclusion, the differences recorded in this study reveal a leukocyte perturbation associated with the disease state in Fabry patients, whereas some abnormalities are less marked in treated patients.

Correction of cicatricial ectropion by autologous fat graft.

BACKGROUND: Over the past few years, treatment of burn scars with lipofilling has shown encouraging clinical results in terms of texture, color, softness, and quality of skin patterns. This clinical application has been widened to include treatment for scars resulting from surgical correction of cicatricial ectropion. In fact, although standard surgery with flaps and skin grafts can grant significant functional and cosmetic improvements, these often are not complete because of secondary surgical scars. METHODS: The case of a 43-year-old man with cicatricial outcomes from chemical burns and subsequent surgical repair of medial ectropion in the lower eyelid is reported. The scar area was treated with injection of adipose tissue harvested from abdominal subcutaneous fat and processed according to Coleman's technique. RESULTS: At the 1-year follow-up assessment after lipostructure, the patient no longer reported xeroftalmia and epiphora. He had experienced complete functional recovery with excellent cosmetic results. CONCLUSIONS: Lipostructure of cicatricial ectropion seems to complete and improve the results of the standard surgical approach, and its long-lasting benefits are in keeping with the theoretical basis of this procedure.

A successful approach for the detection of Fabry patients in Argentina.

Fabry disease is an X-linked lysosomal disorder caused by the deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-Gal A). In males, the laboratory diagnosis is based on the demonstration of decreased levels of alpha-Gal A activity, while in females, the disease is diagnosed by the identification of a mutation in alpha-Gal A gene. Fabry disease in Argentina is underdiagnosed. To date, no comprehensive screening study of Fabry disease in our country has been reported. The present study aimed at developing a targeted screening for the detection of Fabry patients from Argentina based on the set of typical signs and symptoms. We received 121 blood samples from probable Fabry patients for enzymatic and genetic assay. We diagnosed six Fabry patients from six unrelated families, representing a yield of detection of 4.96%. The mutations detected in five of the families analysed were missense mutations: p.Leu243Trp, p.Asp155His, p.Leu415Pro, p.Cys94Tyr and p.Leu191Pro. After the detection of a Fabry patient, his/her relatives were also screened. In the course of these family studies, other 64 Fabry patients, 29 males and 35 females, were detected. To our knowledge, this is the first comprehensive screening of Fabry disease in Argentina. We detected 70 patients in a period of 2.5 years. The development of targeted protocols and the constitution of interdisciplinary groups for the identification of patients with Fabry disease are recommended to obtain a higher yield in the process.

Serological prevalence of anti-latex IgE antibodies in unselected blood donors in Argentina.

The prevalence of specific IgE to natural rubber latex proteins in the general population remains uncertain. The purpose of this study was to determine the prevalence of sera containing specific IgE antibodies to latex proteins using immunoenzymatic methods. A population of 500 unselected adult voluntary blood donors was the source of the sera used in this study. Two different immunoenzymatic methods (EAST and CARLA) were used to analyze the presence of specific IgE antibodies. Confirmation assay was carried out by inhibition ELISA and immunoblotting. Sera from healthy nonatopic individuals were also used as control. Two hundred and twenty five sera showed higher than normal total IgE levels. Of those, three presented latex specific IgE antibodies, which could be inhibited in a dose-response manner with the natural rubber latex and glove extracts. Several latex allergens were recognized by the IgE antibodies from these positive sera. This low seroprevalence (0.66%) indicates that latex hypersensitivity is not an important problem in the general population. We believe that prevention of latex exposure is only necessary in high risk groups of patients.

Detection and identification of a soy protein component that cross-reacts with caseins from cow's milk.

Soy-based formulas are the most employed cow's milk substitutes in the treatment of cow's milk allergy in our country. Since adverse reactions have been reported in allergic patients as a consequence of exposure to soy proteins, we have investigated the possible cross-reactivity between components from soybean and cow's milk. A cow's milk specific polyclonal antiserum and casein specific monoclonal antibodies were used in immunoblotting and competitive ELISA studies to identify a 30-kD component from soybean that cross-reacts with cow's milk caseins. Its IgE binding capacity was tested by EAST, employing sera from cow's milk allergic patients, not previously exposed to soy proteins. The 30 kD protein was isolated and partially sequenced. It is constituted by two polypeptides (A5 and B3) linked by a disulphide bond. The protein's capacity to bind to the different antibodies relies on the B3 poly-peptide. These results indicate that soy-based formula, which contains the A5-B3 glycinin molecule, could be involved in allergic reactions observed in cow's milk allergic patients exposed to soy-containing foods.

Evaluation of the residual antigenicity and allergenicity of cow's milk substitutes by in vitro tests.

BACKGROUND: This study aimed the to investigate presence of residual allergenic cow's milk proteins (CMP) in some milk substitutes employed in the treatment of cow's milk allergy (CMA). These allergens may interfere with the treatment, and elicit allergic reactions in sensitized individuals. METHODS: The protein composition of the different extracts was evaluated by Lowry's method and tricine SDS-PAGE. Different immunoenzymatic methods were used (ELISA, EAST and immunoblotting) to quantify total serum IgE and specific serum IgE, as well as to detect the presence of antigenic and allergenic components. RESULTS: The results showed a higher protein content in mammalian milks (cow, sheep, mare, goat, and human) than in hydrolyzed substitutes (partially or extensively hydrolyzed casein or whey proteins). Residual native, processed, or contaminant polypeptides have been identified in the moderate hydrolysates, whereas extensive hydrolysates did not show the presence of residual components by immunoblotting. However, specific antibodies with capacity to bind to peptides have been detected by EAST and ELISA, suggesting that extensive hydrolysates contain residual peptides that preserve immunoreactive epitopes. We were unable to demonstrate either residual antigenicity or allergenicity in an amino-acid-based formula. CONCLUSIONS: Immunoenzymatic methods were used to detect the presence of cross-reactive components in mammalian milks. Residual allergenic components from cow's milk could be identified in both the moderate and extensive hydrolysates analyzed. This information may be relevant to the treatment of CMA.

Unusual presentation of Hodgkin's disease mimicking inflammatory bowel disease.

A case of a 32-years old man with a long lasting history of inflammatory bowel disease (IBD) is described. He was treated in the past with adequate medical therapy with considerable improvement of the symptoms. However, after the resolution of the last episode of abdominal pain and diarrhoea, because of multiple protruding masses and sub-stenotic regions found during a colonoscopy, the patient underwent a right enlarged hemicolectomy with jejunal resection. During the surgical procedure 16 enlarged lymphnodes were removed. The histological examination of the surgical specimen showed the presence of numerous Reed-Sternberg cells, compatible with a diagnosis of Hodgkin's disease (HD). None of the removed lymphnodes showed the presence of tumor cells, and in addition the systemic staging procedure was negative. After staging, the ABVD regimen was started, achieving a complete clinical and pathological response. This is a rare case of primary extranodal HD localized to the colon, in a patient with a long standing history of IBD, who showed an optimal response to chemotherapy. The case and the differential diagnosis with other pathological entities of the bowel is discussed.

Prevention of delayed emesis induced by moderately emetogenic chemotherapy in patients with acute emesis: a pilot study with ACTH-Depot plus tropisetron.

The rates of delayed nausea and vomiting by moderately emetogenic chemotherapy in patients with previous experience of acute emesis are usually quite high. This is a pilot study aiming to evaluate the safety of a new antiemetic schedule to prevent delayed emesis in this subset of patients. During 5 consecutive cycles of moderately emetogenic chemotherapy, we evaluated 50 patients (15 males) who experienced acute emesis in the first cycle of treatment. The regimen for prevention of delayed emesis consisted of daily tropisetron (5 mg orally from d 2 to d 6 of each chemotherapeutic cycle) associated to ACTH-Depot (1 mg intramuscularly 24 and 68 h after the initiation of chemotherapy). In 77% of chemotherapy cycles, there was a total elimination of nausea and vomiting, whereas in the remaining 23% of cycles, there was a major response defined as < or = 2 vomiting episodes per cycle or nausea grade 1 according to the WHO. The efficacy of the antiemetic regimen persisted during the entire treatment program without the appearance of toxic effects. The proposed antiemetic regimen is highly active in preventing delayed nausea and vomiting episodes in patients receiving moderately emetogenic chemotherapy. Moreover, no toxic effects were observed. These promising results require confirmation by a randomized trial.

[Platelet glycoprotein IIB-IIIA receptor inhibitors in patients with ischemic heart disease]. / Gli inibitori dei recettori glicoproteici IIB-IIIA delle piastrine nei pazienti con cardiopatia ischemica.

Glycoprotein IIb-IIIa receptor inhibitors are the newest anti-platelets drugs currently used in patients with coronary artery disease. We examined mechanisms of their action and different pharmacokinetic and pharmacodynamic characteristics of the four glycoprotein IIb-IIIa antagonists evaluated in randomized, controlled and multicenter trials. We reviewed results of these trials in the settings of percutaneous revascularizations procedures or unstable coronary syndromes. Platelet glycoprotein IIb-IIIa receptor inhibitors reduced incidence of cardiac death and myocardial infarction during the short- and midterm, and benefit was greater in: a) patients undergoing coronary angioplasty with or without stent implantation, particularly in the presence of unstable angina, diabetes or complex and diffuse coronary artery disease; b) as a direct therapy of unstable coronary syndromes, particularly in patients with refractory angina, diabetes and elevated Troponin; more recently they have been used as adjuvant therapy in acute myocardial infarction. Infusion of these drugs was not associated with higher rates of major bleedings.

Single-shot plasmid DNA intrasplenic immunization for the production of monoclonal antibodies. Persistent expression of DNA.

Monoclonal antibodies (Mc. Abs.) were generated against a 18-kDa protein from Brucella abortus 48 h and 25 days after a single intrasplenic injection of a DNA plasmid containing the expression vector for the protein. Hybridomas were also obtained from spleens injected 3, 5, and 10 days before fusion. Somatic cell fusion of spleen cells from mice, injected with the plasmid DNA, in saline, with the NS-0 myeloma cell line resulted in Mc. Abs of the IgG and IgM Isotypes. IgG antibodies were of the IgG2b and IgG1 subtype. Hybridoma tissue culture supernatants were strongly positive by ELISA at dilutions of up to 1/1200 and produced intense specific bands in immunoblotting. All these antibodies recognized the native recombinant protein (the screening antigen) and some of them also recognized the heat-denatured recombinant 18-kDa protein. When compared to standard procedures of immunization, as well as to intramuscular or gene gun DNA immunizations, this technique results in very early, time saving, strong Mc Abs. It is common knowledge that in order to generate specific hybridomas; spleen cells from immunized animals have to be fused no later than 5 days after the last boost. The fact that through single-shot intrasplenic immunization (SSI) specific hybridomas are generated 25 days after one single injection indicates that the gene coding the p18 protein is being expressed in the spleen for at least 20 days. We propose that plasmid DNA intrasplenic immunization can be a helpful tool for the production of specific hybridomas. This route of immunization could also be helpful in the further understanding of early events of the immune response to genetic immunization by naked DNA injection.

Structural, functional and immunological studies on a polymeric bacterial protein

The characterization of proteins from Brucella spp, the causative agent of brucellosis, has been the subject of intensive research. We have described an 18-kDa cytoplasmic protein of Brucella abortus and shown the potential usefulness of this protein as an antigen for the serologic diagnosis of brucellosis. The amino acid sequence of the protein showed a low but significant homology with that of lumazine synthases. Lumazine is an intermediate product in bacterial riboflavin biosynthesis. The recombinant form of the 18-kDa protein (expressed in E. coli) folds like the native Brucella protein and has lumazine-synthase enzymatic activity. Three-dimensional analysis by X-ray crystallography of the homolog Bacillus subtilis lumazine synthase has revealed that the enzyme forms an icosahedral capsid. Recombinant lumazine synthase from B. abortus was crystallized, diffracted X rays to 2.7-A resolution at room temperature, and the structure successfully solved by molecular replacement procedures. The macromolecular assembly of the enzyme differs from that of the enzyme from B. subtilis. The Brucella enzyme remains pentameric (90 kDa) in its crystallographic form. Nonetheless, the active sites of the two enzymes are virtually identical at the structural level, indicating that inhibitors of these enzymes could be viable pharmaceuticals across a broad species range. We describe the structural reasons for the differences in their quaternary arrangement and also discuss the potential use of this protein as a target for the development of acellular vaccines.

Determination of anti-omega-gliadin antibodies in serologic tests for coeliac disease.

BACKGROUND: Serologic detection of coeliac disease in the general population or in subjects belonging to risk groups implies the use of a test with high efficiency, large-scale use, and low cost. The enzyme-linked immunosorbent assay (ELISA) technique is the most appropriate assay for performing this kind of studies. Even though anti-gliadin determination has been the test most frequently used as the first step in screening procedures, many false-positive results produced a low-specificity test. In a previous work a selective recognition of omega-gliadins, mainly by IgA antibodies, was observed. Results also indicated that omega-gliadins can be useful as antigens in serologic detection of coeliac disease. We therefore wanted to analyse the anti-gliadin antibody reactivity by using purified gliadins and to evaluate the actual performance of the anti-omega-gliadin antibody test. METHODS: A population consisting of 105 coeliac patients, 81 healthy controls, and 73 subjects in a disease control group was analysed. Anti-endomysium (EMA), both IgG and IgA anti-omega-gliadins, and anti-tissue transglutaminase (tTG) antibodies were determined. RESULTS: Concordant results, positive and negative, in the EMA and IgG and IgA anti-gliadin determinations were observed in 220 of 259 samples from the total population analysed. The three assays showed high efficiency, being 96.9%, 90.7%, and 91.1% for EMA and anti-omega-gliadins IgG and IgA, respectively. Anti-tTG determination was performed on 103 samples (69 controls and 34 coeliac patients), finding 4 false results (2 false positive and 2 false negative), whereas anti-omega-gliadins showed 10 false results (5 false negative and 5 false positive), 3 of which were coincident with anti-tTG determination. To compare the reactivity of anti-gliadin antibodies, alpha-, beta-, gamma- and omega-gliadins were isolated under non-denaturing conditions by acid preparative electrophoresis and cation-exchange fast protein liquid chromatography (FPLC) and used in an indirect ELISA test. The composition of these fractions was analysed by means of capillary electrophoresis, showing no cross-contamination among them. CONCLUSIONS: The comparison of results using purified gliadins shows that omega-gliadins present a differential reactivity that has not previously been documented. Results using omega-gliadins isolated by either preparative electrophoresis or FPLC were similar. Tests using the purified omega-gliadin fraction present the best performance when anti-gliadin antibodies are evaluated.