[Correlation between radiologic and ultrasonographic patterns and clinical manifestations in symptomatic hip osteoarthritis]. / Correlazione tra quadro clinico e patterns radiologici ed ecografici in pazienti affetti da artrosi sintomatica dell'anca.

Increasing amounts of data have recently been published regarding ultrasonographic (US) findings of osteoarthritic joints, but very few data concern hip joints. In the current study we described US patterns concerning 490 patients affected by symptomatic hip osteoarthritis (OA) who underwent to intra-articular injections of hyaluronic products under US guidance. All patients were studied by US and X-ray of hip, clinical evaluation was assessed by the followings indexes: Lequesne, pain VAS, ICED, Global Physician Assessment and Global Patient Assessment. US findings were summarized in four main patterns, effusion and synovial proliferation were also detected. The aim of this study was to correlate US findings with clinical assessment and radiographic findings (according to Kellgren-Lawrence classification). Pearson's r correlation coefficient were computed and come out significant and positive between X ray and US patterns and between clinical indexes and US patterns. Also the correlation between K-L score and US patterns showed a significant positive correlation indicating that higher K-L scores are associated with increasing abnormal US findings. Our data suggest that ultrasonography of the hip may give useful information about the state of synovial membrane, synovial fluid, joint margins and bone profile in hip OA. Further studies are needed to evaluate their prevalence in hip OA symptomatic and not-symptomatic patients and their correlation to treatment outcome.

Sjogren's syndrome in a celiac patient: searching for environmental triggers.

In the last few years many studies have shown the potential role of different triggers in the pathogenesis of several autoimmune diseases. In particular, in Sjogren's syndrome the presence of a genetic background is considered determining, but environmental factors have recently been described as triggers or precipitators. In this report, we describe the case of a young woman affected by celiac disease in which an Ascaris lumbricoides infestation and estrogen therapy could have played a role in the development of Sjogren's syndrome.

Pharmacological and clinical basis of treatment of Familial Mediterranean Fever (FMF) with colchicine or analogues: an update.

Familial Mediterranean Fever (FMF), an autosomal recessive disorder, is characterised by recurrent attacks of fever and serositis, lasting 24-72 hours. Since 1972 colchicine has become the drug of choice for prophylaxis against FMF attacks and amyloidosis FMF-associated. Colchicine, an alkaloid neutral, is absorbed in the jejunum and ileum. It metabolised by liver and only small amounts are recovered unchanged in the urine. Really plasma half-life is prolonged in patients with liver or renal failure. Colchicine is able to prevent activation of neutrophils, binding beta-tubulin and making beta-tubulin-colchicine complexes; this way inhibits assembly of microtubules and mitotic spindle formation; moreover its mode of action includes modulation of chemokines, prostanoids production, inhibition of neutrophil and endothelial cell adhesion molecules. The minimal daily dose in adults is 1.0 mg/die, but in children there is not a definite dose. Since in vitro high dosages of colchicine stop mitosis, this drug might interfere with male and female fertility and with children growth, but, according to current guidelines and because of rare side effects of the drug, FMF patients are recommended to take colchicine. Since colchicine treatment is often complicated by frequent gastrointestinal side effects, by our experience, in order to improve colchicine tolerance we recommend: lactose-free diet and treatment of intestinal bacterial overgrowth and/or Hp-infection, assessed by breath tests. Since our data showed that 10-15% of FMF patients seem are non-responders or intolerant to colchicine, today we are working in the design of colchicine analogues which may have lesser toxicities and a larger therapeutic window.

Synergy between cyclosporine and anti-IL-2 receptor monoclonal antibodies in rats. Functional studies of heart and kidney allografts.

Although cyclosporine has improved results of organ transplantation, treatment regimens using multiple agents are being evaluated both experimentally and clinically in attempts to diminish its often profound nephrotoxicity; some therapies act synergistically by differential inhibition of distinct steps of the rejection cascade. The effects on graft function of a full dose or a subclinical dose of CsA, ART-18, a monoclonal antibody (mAb) directed against the IL-2 receptor expressed on activated host cells, and a combination of low-dose CsA and ART-18, have been tested in rat recipients of both heart and kidney allografts. Renal graft function was assessed by several classic techniques; heart function by isolated perfusion methods. Full-dose CsA and combination treatment were most effective in both organ graft systems, with at least one-third of grafts surviving indefinitely. At seven days after transplantation, glomerular filtration rates and renal plasma flow of all grafted recipients were decreased as compared with normal; at 14 days, function in the best treatment groups had improved toward that of isografts. Similarly, cardiac output and stroke work index of best treatment groups were comparable to that of isografts. These functional studies complement previously reported immunological and immunohistological findings stressing that synergy occurs between subclinical doses of CsA and anti-IL-2-R mAb in two rat organ graft systems.

Cardioplegia for the immature myocardium. A comparative study in the neonatal rabbit.

This study examined the effect of hypothermia (15 degrees C) alone or combined with various cardioplegic solutions on functional recovery of the neonatal heart after 120 minutes of global ischemia in an isolated working rabbit heart model. Control hearts were preserved with hypothermia alone, and groups 1 to 6 were given different hyperkalemic crystalloid cardioplegic solutions. Each cardioplegic solution differed in Na+ and Ca++ content. Aortic flow, coronary flow, cardiac output, heart rate, peak systolic pressure, and stroke work were measured before ischemia and after 35 and 45 minutes of reperfusion. There were no statistical differences in hemodynamic recovery in the six groups in which cardioplegia was used. However, hearts preserved with multidose hyperkalemic cardioplegia showed significantly better recovery of cardiac output (86% versus 75%; p less than 0.05), coronary flow (88% versus 72%; p less than 0.05), and stroke work (86% versus 75%; p less than 0.05) than those preserved with hypothermia alone. These results suggest that hypothermic hyperkalemic cardioplegia improves preservation of the neonatal rabbit heart but that variations in Ca++ and Na+ content appear not to provide further myocardial protection.

The mechanism of heart failure caused by cardiac allograft rejection.

Rejection of the cardiac allograft is often associated with reversible myocardial failure, the mechanism of which is not understood. We have examined this phenomenon in a small animal model that provides the opportunity for multimodality study of the rejection process. Heterotopic cardiac transplantation was performed in the Lewis rat with Lewis X Brown-Norway (allografts) or Lewis (isografts) donors. Without immunosuppression, allografts are completely rejected in 6 to 8 days. At 3 days cardiac grafts were explanted and mounted on a modified Langendorff apparatus for functional measurements or submitted for pathologic examination and biochemical determination of high-energy phosphates. Three-day isografts (n = 9) had minimal histologic changes. Pathologic examination of 3-day allografts (n = 13) showed lymphocytic infiltrate and myocyte necrosis, histologic features for which antirejection treatment is usually given clinically. For grafts subjected to functional studies (n = 11), heart rate, cardiac output, coronary flow, and stroke work were determined at baseline and in response to isoproterenol (3 x 10(-8) mol/ml). Three-day allografts (n = 6) and isografts (n = 5) had similar baseline function. The chronotropic response to isoproterenol was similar in allografts and isografts, but allografts had diminished cardiac output and stroke work after isoproterenol. Adenosine triphosphate levels were normal (41.9 nmol/mg) in 3-day allografts (n = 4). We have evaluated functional, biochemical, and pathologic changes associated with myocardial dysfunction during heterotopic cardiac transplant rejection in a small animal. This model reproducibly demonstrates diminished contractile reserve in 3-day allografts with normal baseline function and high-energy stores but histologically significant rejection.

The dynamics of antegrade cardioplegia with simultaneous coronary sinus occlusion. Effects on aortic root infusion pressure, coronary sinus pressure, and myocardial cooling.

It has been suggested that antegrade cardioplegia with coronary sinus occlusion improves homogeneous myocardial cooling and reduces myocardial injury in the presence of coronary artery occlusion. Little data are available on the exact relationships among the basic elements or this intervention, including antegrade infusion rate, aortic root pressure, the degree of coronary sinus occlusion, coronary sinus pressure, and myocardial cooling. The purpose of this study was to determine these relationships and to provide some basic guidelines for better understanding of this intervention. Twenty-two sheep were placed on cardiopulmonary bypass, the distal left anterior descending artery was occluded, and the proximal coronary sinus was snared. Sixteen combinations of infusion rate (3, 5, 7, or 9 ml/kg/min) and coronary sinus occlusion (total, subtotal, or moderate occlusion or no occlusion) were adopted for each 2 minutes of antegrade cardioplegia, yielding 96 measurements. Myocardial temperatures in the occluded and nonoccluded regions, aortic root infusion pressure, and coronary sinus pressure were measured during each infusion of cardioplegic solution. Coronary sinus occlusion was then released, and the whole heart was reperfused for 30 minutes for another infusion of cardioplegic solution and measurements. Results showed good degrees of linearity between infusion rate and aortic root infusion pressure for all coronary sinus occlusion and noninfusion groups (p less than 0.01). A positive effect of coronary sinus occlusion on aortic root infusion pressure was observed. The graded increases in infusion rate with various degrees of coronary sinus occlusion were constantly associated with elevation of coronary sinus pressure (p less than 0.01). It was also noted that myocardial temperatures in the region of the occluded left anterior descending artery were significantly lower in coronary sinus occlusion groups than in nonocclusion groups (p less than 0.01 or 0.05). Myocardial temperature in the nonoccluded region decreased significantly with the stepwise increases in infusion rate (p less than 0.01), but not with the increases in coronary sinus occlusion (not significant). Based on this and previous studies, we recommend that the induced coronary sinus pressure be safely maintained in the range of 25 to 35 mm Hg and that further studies be focused on the infusion rate of 5 ml/kg/min with subtotal or total coronary sinus occlusion for the intervention of antegrade cardioplegia plus coronary sinus occlusion.

Vascular endothelial growth factor attenuates myocardial ischemia-reperfusion injury.

BACKGROUND: Hypoxic endothelial cell activation plays a key role in the myocardial dysfunction resulting from ischemia-reperfusion injury. Recent evidence suggests that vascular endothelial growth factor (VEGF) may, in addition to promoting angiogenesis, modulate various aspects of endothelial function and repair. We examined whether administration of VEGF in the cardioplegic solution might have a beneficial effect on myocardial ischemia-reperfusion injury in an isolated rat heart model. METHODS: Hearts from Sprague-Dawley rats were perfused with Krebs-Henseleit solution in a modified Langendorff apparatus. Percent recovery of cardiac output, coronary flow, stroke work, and percent increase in coronary vascular resistance were measured after 2 hours of global ischemia and 40 minutes of reperfusion. Coronary effluent was collected after ischemia and reperfusion for measurement of creatine kinase. RESULTS: Hearts receiving cardioplegia solution containing 125 microg VEGF showed significantly improved recovery of cardiac output, coronary flow, and stroke work, and significantly reduced coronary vascular resistance compared with hearts receiving hyperkalemic cardioplegia only (p < 0.05). Coadministration of a nitric oxide synthase inhibitor attenuated the VEGF-induced cardiprotective effects. Hearts treated with VEGF released significantly less creatine kinase compared with control hearts. CONCLUSIONS: Addition of VEGF to hyperkalemic cardioplegia protects against myocardial ischemia-reperfusion injury in the isolated rat heart.

Association of myasthenia gravis and antisynthetase syndrome: a case report.

Myasthenia gravis is a chronic disease of neuromuscular transmission caused by loss of acetylcholine receptors. It can be found in association with other autoimmune disorders. We report the case of a 47-yr-old woman affected by Myasthenia gravis who complained of fever, progressive weakness of proximal limb muscle, arthritis and Raynauds phenomenon and dyspnea. Chest X-rays and CT scan showed an interstitial lung disease; laboratory data indicated an inflammatory picture and increased serum muscle enzymes. Evaluation for infectious, metabolic, iatrogenic and neoplastic aetiologies was unrevealing. The patients clinical condition together with positive results on antisynthetase antibody assay lead to the diagnosis of antisynthetase syndrome. To our knowledge, this is the first report on the association of Myasthenia gravis with antisynthetase syndrome.

HIV-1: a case of RT67 deletion in a multi-treated non responder patient.

The early detection of mutations in the HIV-1 polymerase is a key point in the management of anti-retroviral therapy. While nucleotide substitutions and insertions have been well and frequently desribed in literature as linked to drug resistance, deletions have been rarely observed and desribed (ART67, Imamichi et al.). The aim of this study is to describe a case of deletion of three nucleotides in the RT gene (ART67) of a multi-treated HIV-1 infected patient. As this deletion has not been detected by the oligoprobe assay, the phenotyping test was used to support therapy but without an appreciable success in terms of viral load. Then a sequencing based genotyping system was used to analyse the viral polymerase and a novel deletion was found at codon 67 of RT gene.

Improved distribution of antegrade cardioplegic solution with simultaneous coronary sinus occlusion following acute coronary artery occlusion.

This study was designed to evaluate the distribution of cardioplegic solution infused antegradely with simultaneous coronary sinus occlusion. After 1 hr LAD occlusion, sheep were placed on cardiopulmonary bypass. Hearts were arrested with 300 ml of cold cardioplegia and replenished with two additional doses. In group I (n = 10), antegrade cardioplegia (ACP) was given alone; in group II (n = 9), ACP was given in combination with simultaneous coronary sinus occlusion. Microspheres were infused into the cardioplegic line to determine the antegrade distribution of the solution, while a different microsphere was injected into the anterior interventricular vein to detect the venous backflow of the solution. The data showed that myocardium distal to LAD occlusion in group II received more antegrade (0.17 +/- 0.02 versus 0.06 +/- 0.02 ml/g/min, P less than 0.01, in subendocardium; and 0.15 +/- 0.03 versus 0.09 +/- 0.02 ml/g/min, P = NS, in subepicardium) and retrograde (2181 +/- 455 versus 0 counts/g/min, P less than 0.01, in subendocardium; and 2,146 +/- 527 versus 0 counts/g/min, P less than 0.01, in subepicardium) distribution of cardioplegic solution in comparison to group I. We therefore conclude that simultaneous coronary sinus occlusion significantly improves the distribution of antegrade cardioplegic solution to the regionally occluded myocardium by increasing collateral flow as well as venous backflow.