Long-term results of arthroscopic repair of type II SLAP lesions in sports: assessment of return to pre-injury playing level and critical risk factors for complication.

PURPOSE: The management of isolated SLAP lesions is still debated especially in athletes. Aims of the study were: 1. to analyse our algorithm to treat SLAP lesions starting from the selection of patients for surgery and 2. to correlate the familiarity for diabetes and hypothyroid disorders with post-operative results. METHODS: Seventy-eight patients with isolated SLAP lesion were arthroscopically treated using knotless anchors and microfractures. All patients had a pre-operative and post-operative clinical examination according to Walch-Duplay, Constant, Rowe and Dash scores and interviewed for familiarity to diabetes and hypothyroid disorders. RESULTS: About 68.8% of patients solved pain with rehabilitation. About 29% of patients returned to the sports activities. About 32% of patients were no responder to physiotherapy and were arthroscopically treated. About 53.9% of patients responded excellent, 34.7% good, 3.8% medium and 7.6% poor results according to Walch-Duplay score. The Constant score increased from 64 to 95, the Rowe score from 48 to 96. The outcomes were significantly worse in patients with familiarity for diabetes. CONCLUSIONS: Microfractures and knotless anchor give long-term good results for the treatment of SLAP lesions in athletes. The familiarity for diabetes is an important risk factor that can lead to decreased outcomes.

Adiponectin profile at baseline is correlated to progression and severity of multiple sclerosis.

BACKGROUND AND PURPOSE: Adiponectin is a cytokine linking energy metabolism and immune system. After being assembled, adiponectin circulates as oligomers of different molecular weight, i.e. low, medium and high (HMW) molecular weight. These have the most potent biological effects. Multiple sclerosis (MS) is an autoimmune disease of the human central nervous system. The aim of this study was to characterize the expression levels of both total adiponectin and its oligomerization state in the serum from 99 patients with MS at baseline (i.e. not influenced by therapies). We also investigated the potential relationships between adiponectin and disease progression and severity. METHODS: Adiponectin was quantified and visualized by enzyme-linked immunosorbent assay, western blotting and fast protein liquid chromatography. During the follow-up (3.6 ± 2.20 years), the patients were evaluated using total annualized relapse rate and Expanded Disability Status Scale score. RESULTS: Total adiponectin is statistically higher in patients with MS compared with matched controls (12.18 vs. 10.02 µg/mL, P = 0.001). Interestingly, the adiponectin oligomerization state is altered in MS, with an increase of HMW oligomers. In addition, patients with MS with higher levels of adiponectin at baseline have significantly higher risk of progression and severity (Multiple Sclerosis Severity Score, 3.84 vs. 2.44, P = 0.001). No statistical difference in adiponectin expression was found between active and inactive patients with MS and among the different forms of disease. CONCLUSIONS: This study demonstrated that adiponectin and its HMW oligomers are greatly involved in MS autoimmune disorder representing a potential biomarker to predict worse MS prognosis and severity. Further studies are required to clarify the molecular mechanisms underlying the properties of adiponectin and HMW oligomers in MS.

Adiponectin and colon cancer: evidence for inhibitory effects on viability and migration of human colorectal cell lines.

Adiponectin (Acrp30) is an adipokine widely studied for its beneficial metabolic and anti-inflammatory properties. Colorectal cancer is among the most common cancers worldwide. The aim of present study was to explore the effects of Acrp30 on both CaCo-2 and HCT116 colorectal cancer cells in terms of viability, oxidative stress, and apoptosis. In addition, since colorectal cancer represents a typical inflammation-related cancer, we investigated whether Acrp30 treatment modifies the migration and the expression of crucial proteins in the EMT transition. Finally, we analyzed the expression of cytokines in CaCo-2 cells. We found that Acrp30 reduces the survival rate of both CaCo-2 and HCT116 cells through induction of apoptosis and oxidative stress already after 24 h of treatment. In addition, wound-healing assay indicated that Acrp30 exposure statistically inhibits CaCo-2 and HCT116 cell migration. Western blot analysis performed on E-cadherin and vimentin, two EMT crucial markers in carcinogenesis, indicated that Acrp30 does not influence EMT transition. Finally, we found a reduction of mRNA levels corresponding to the anti-inflammatory IL-10 cytokine together with an increase of the pro-inflammatory IL-6 and IL-8 cytokines. This study provides new insight into Acrp30 molecular effects on colorectal cancer cells. Indeed, even if further studies are necessary to clarify the precise role of Acrp30 in colorectal cancer, our data strongly suggest that Acrp30 negatively regulates cell survival and migration in association with induction of oxidative stress and regulation of cytokines expression in both CaCo-2 and HCT116 colorectal cells.

Differentially expressed and activated proteins associated with non small cell lung cancer tissues.

BACKGROUND: Lung cancer is a leading cause of mortality. The most common cancer subtype, non small cell lung cancer (NSCLC), accounts for 85-90% all cases and is mainly caused by environmental and genetic factors. Mechanisms involved in lung carcinogenesis include deregulation of several kinases and molecular pathways affecting cell proliferation, apoptosis and differentiation. Despite advances in lung cancer detection, diagnosis and staging, survival rate still remains poor and novel biomarkers for both diagnosis and therapy need to be identified. In the present study, we have explored the potential of novel specific biomarkers in the diagnosis of NSCLC, and the over-expression/activation of several kinases involved in disease development and progression. METHOD: Lung tumor tissue specimens and adjacent cancer-free tissues from 8 NSCLC patients undergoing surgery were collected. The differential activation status of ERK1/2, AKT and IKBα/NF-κß was analyzed. Subsequently, protein expression profile of NSCLC vs normal surrounding tissue was compared by a proteomic approach using LC-MS MS. Subsequently, MS/MS outputs were analyzed by the Protein Discoverer platform for label-free quantitation analysis. Finally, results were confirmed by western blotting analysis. RESULTS: This study confirms the involvement of ERK1/2, AKT, IKBα and NF-κß proteins in NSCLC demonstrating a significant over-activation of all tested proteins. Furthermore, we found significant differential expression of 20 proteins (Rsc ≥ 1.50 or ≤ -1.50) of which 7 are under-expressed and 13 over-expressed in NSCLC lung tissues. Finally, we validated, by western blotting, the two most under-expressed NSCLC tissue proteins, carbonic anhydrase I and II isoforms. CONCLUSION: Our data further support the possibility of developing both diagnostic tests and innovative targeted therapy in NSCLC. In addition to selective inhibitors of ERK1/2, AKT, IKBα and NF-κß, as therapeutic options, our data, for the first time, indicates carbonic anhydrase I and II as attractive targets for development of diagnostic tools enabling selection of patients for a more specific therapy in NSCLC.

Serologic response to treatment of syphilis in patients with HIV infection.

BACKGROUND: Much controversy exists concerning the manifestations, therapy, and response to treatment of syphilis in patients coinfected with the human immunodeficiency virus (HIV). OBJECTIVE: To assess the effect of HIV infection on the serologic response to treatment of patients with syphilis. METHODS: Sixty-four HIV-seropositive patients with syphilis were matched with 64 patients with syphilis who were HIV negative. Matching criteria included age (+/- 5 years), sex, race, initial rapid plasma reagin (RPR) titer (+/- 1 dilution), and stage of syphilis at entry. There were 26 matched patients with early syphilis, 26 matched patients with late syphilis, and 12 matched patients with biological false-positive RPR. The HIV-positive patients with early syphilis received three doses of penicillin G benzathine. All other patients received treatment as recommended by the Centers for Disease Control and Prevention, Atlanta, Ga. Our study's major end points were clinical and serologic response to treatment. RESULTS: All 16 patients with symptomatic syphilis were cured. No patient developed clinical signs of neurosyphilis during the 12-month follow-up period. Twenty-nine (56%) of 52 HIV-positive patients with early or late syphilis did not have a fourfold decrease in RPR titer 6 months after treatment compared with 20 (38%) of 52 matched controls (P = .06). No unique characteristics identifying patients who did not respond serologically could be established. The HIV-positive patients with initial RPR less than 1:32 experienced a significantly slower decrease in RPR at 12 months than did the controls (P < .001). CONCLUSIONS: Patients with syphilis who are HIV positive are less likely to experience serologic improvement after recommended therapy than are patients with syphilis who are HIV negative. Patients with HIV infection who contract syphilis should receive intensive and prolonged follow-up, and consideration should be given to designing alternative regimens.

Mitral valve reconstruction in sickle cell disease.

As survival improves in patients with sickle cell anemia, the prospects of performing cardiac surgical procedures on older patients with this genetic defect increase. We describe the successful management of a 52-year-old patient with sickle cell disease (homozygous for hemoglobin S) and a history of multiple sickle crisis undergoing cardiopulmonary bypass for mitral valve repair. Preoperative partial exchange transfusion followed by total exchange transfusion at the time of operation was performed to reduce the level of hemoglobin S to 5.4% during bypass. Other management strategies included high-flow normothermic bypass with aortic crossclamping, topical hypothermia, and cold crystalloid cardioplegia.

Psoriatic arthritis: a clinical, radiological and genetic study of 58 Italian patients.

It is well known that genetic heterogeneity and/or the complex interaction of several MCH-linked risk factors can explain the onset and the broad spectrum of Psoriatic Arthritis (PsA) from the clinical point of view. Fifty-eight patients with PsA (Moll and Wright criteria), 35 men and 23 women, mean age of 45, 14, were studied; all the patients were assessed by both clinical and radiological examination, with particular attention to the sacroiliac joints. HLA typing of the patients confirmed the association between PsA and HLA-B39 (p = 0.0008) and Cw6 (p = 0.0011). In addition a significant increase in DQ2 antigen (p = 0.004) has been found. No correlation of any particular HLA antigen with clinical subsets (oligo-polyarticular peripheral PsA, axial PsA and axial with peripheral PsA) or erosive incidence of joint involvement-generally related to the duration of the disease--was found.

Initial management of serious urinary tract infection: epidemiologic guidelines.

OBJECTIVE: To obtain information necessary for the development of initial antibiotic treatment guidelines for patients with serious urinary tract infections. DESIGN: Retrospective chart review. SETTING: The medical service of a 533-bed university-affiliated community hospital. PATIENTS: 253 unselected patients hospitalized between January 1985 and December 1987 given principal discharge diagnoses of urinary tract infection, pyelonephritis, or gram-negative rod bacteremia originating in the urinary tract. RESULTS: Three clinically distinct groups were identified: women under 50 years old, older women, and men. Escherichia coli was isolated from 93% of young women, 70% of older women, and 46% of men. Pseudomonas aeruginosa was isolated from 39% of men with one or more urinary tract risk factors, including recent or recurrent urinary tract infections and known genitourinary tract abnormality. The overall prevalence of Group D streptococci was only 1%. More than 20% of the patients in each group were bacteremic. In all groups, resistance to ampicillin and first-generation cephalosporins was common. Trimethoprim-sulfamethoxazole was active in 98% of young women and 85% of older women and men without urinary risk factors. CONCLUSIONS: Age and gender identify clinically important subgroups of patients with serious urinary tract infections. Pending culture results, all patients should be considered bacteremic, ampicillin alone should not be prescribed, and antibiotics effective against P. aeruginosa should be given to men, especially those with risk factors.

Apparently normal ankyrin content in unsplenectomized hereditary spherocytosis patients with the inactivation of one ankyrin (ANK1) allele.

The study of erythrocyte membrane protein concentration by polyacrylamide gel electrophoresis (PAGE) is the first step in approaching the primary molecular defect in hereditary spherocytosis (HS). Normal or greater than normal protein 2.1 levels were found in ten unrelated HS patients showing the inactivation of one ankyrin allele. Erythrocyte membranes from the same patients, once splenectomized, showed a homogeneous degree of protein 2.1 reduction. Thus protein 2.1 levels could misleadingly appear normal due to the high number of circulating reticulocytes. To calculate the true ankyrin level using PAGE and consequently to avoid mistakes in studying a mutated gene, a simple equation, based on the number of reticulocytes, was developed.