Role of proinflammatory cytokines in the pathophysiology of osteoarthritis

Osteoarthritis (OA) is associated with cartilage destruction, subchondral bone remodeling and inflammation of the synovial membrane, although the etiology and pathogenesis underlying this debilitating disease are poorly understood. Secreted inflammatory molecules, such as proinflammatory cytokines, are among the critical mediators of the disturbed processes implicated in OA pathophysiology. Interleukin (IL)-1β and tumor necrosis factor (TNF), in particular, control the degeneration of articular cartilage matrix, which makes them prime targets for therapeutic strategies. Animal studies provide support for this approach, although only a few clinical studies have investigated the efficacy of blocking these proinflammatory cytokines in the treatment of OA. Apart from IL-1β and TNF, several other cytokines including IL-6, IL-15, IL-17, IL-18, IL-21, leukemia inhibitory factor and IL-8 (a chemokine) have also been shown to be implicated in OA and could possibly be targeted therapeutically. This Review discusses the current knowledge regarding the role of proinflammatory cytokines in the pathophysiology of OA and addresses the potential of anticytokine therapy in the treatment of this disease.     

Should heart,lung, and liver transplant recipients receive immunosuppression induction for kidney transplantation?

Ranney DN, Englesbe MJ, Muhammad W, Al‐Holou SN, Park JM, Pelletier SJ, Punch JD, Lynch RJ. Should heart, lung, and liver transplant recipients receive immunosuppression induction for kidney transplantation?
Clin Transplant 2010: 24: 67–72. © 2009 John Wiley & Sons A/S. Abstract: As the outcomes of heart, liver, and lung transplantation continue to improve, more patients will present for subsequent renal transplantation. It remains unclear whether these patients benefit from induction immunosuppression. We retrospectively reviewed induction on solid organ graft recipients who underwent renal transplant at our center from January 1, 1995 to March 30, 2007. Induction and the non‐induction groups were compared by univariate and Kaplan–Meier analyses. There were 21 patients in each group, with mean follow‐up of 4.5–6.0 years. Forty‐seven percent of patients receiving induction had a severe post‐operative infection, compared with 28.6% in the non‐induction group (p = NS). The one yr rejection rate in the induction group was 9.5% compared with 14.3% for non‐induction (p = NS). One‐yr graft survival was 81.0% and 95.2% in the induction and non‐induction group (p = NS). In summary, there is a trend toward lower patient and graft survival among patients undergoing induction. These trends could relate to selection bias in the decision to prescribe induction immunosuppression, but further study is needed to better define the risks and benefits of antibody‐induction regimens in this population.     

Value of echotomography for the diagnosis of lithiasis of the common bile duct

The accuracy of ultrasonography (US) for the diagnosis of cholelithiasis and for dilatation of the intra- and extra-hepatic biliary tree is well known. However, the value of US for the diagnosis of common bile duct stones remains poorly defined. We performed a prospective study in 100 patients who were referred for endoscopic retrograde cholangiopancreatography (ERCP); all the examinations were carried out by the same sonographist in the 24 h preceding the ERCP. Fifty patients had choledocholithiasis, 20 patients had obstruction of the bile ducts without lithiasis and the common bile duct (CBD) was free in 30 patients. The sensitivity of US for the diagnosis of choledocholithiasis was 40 p. 100, the specificity 90 p. 100. The positive and negative predictive values of the "CBD stone" sign was 80 p. 100 and 60 p. 100 respectively. In a total of 30 false negatives, the CBD could not be explored in 4 cases, dilatation of the CBD was missed in one case, and obstruction of the CBD by an other disease was diagnosed in 2; in all the other cases, US was able to appreciate the CBD size as well as the ERCP. In the 20 patients with an obstructed CBD but without choledocholithiasis, US diagnosed a stone in 5 cases. Age, serum bilirubin, existence of a previous cholecystectomy, technical difficulties, stone size were comparable in patients with true positive tests and in patients with false negative tests. However the diagnosis of choledocholithiasis was more frequently achieved in patients with dilated CBD over 10 mm (p less than 0.05) and in patients with multiple stones.(ABSTRACT TRUNCATED AT 250 WORDS)     

Balloon catheter dilation of ureteroenteric strictures: long-term results

Balloon catheter dilation of benign ureteroenteric anastomotic strictures has been proposed as an alternative to either surgical revision or chronic ureteral stenting, with moderately successful short-term results reported by several groups in a limited number of patients. However, the authors' experience with 29 patients exhibiting 37 benign ureteroenteric strictures treated over the past 7 years revealed that in the majority of cases (23 patients, 26 strictures [70%]), strictures recurred within 6 months of balloon catheter dilation/ureteral stent therapy. Furthermore, of the 11 strictures that appeared to have been successfully dilated at a follow-up interval of 6 months, five restenosed within 1 year. Therefore, only six of 37 (16%) ureteroenteric stricture dilations could be considered successful when viewed at least 1 year after interventional therapy. Furthermore, repeat dilations have often been required to maintain ureteral patency in these patients.     

The Incorporation of an Advanced Donation Program Into Kidney Paired Exchange: Initial Experience of the National Kidney Registry

The continued growth of kidney paired donation (KPD) to facilitate transplantation for otherwise incompatible or suboptimal living kidney donors and recipients has depended on a balance between the logistics required for patients and the collaborating transplant centers. The formation of chains for KPD and the shipping of kidneys have permitted networks such as the National Kidney Registry (NKR) to offer KPD to patients over a transcontinental area. However, over the last 3 years, we have encountered patient requests for a more flexible experience in KPD to meet their individual needs often due to rigid time constraints. To accommodate these requests, we have developed an Advanced Donation Program (ADP) in which the donor desires to donate by a specific date, but their paired recipient has not yet been matched to a specific donor or scheduled for surgery. After obtaining careful informed consent from both the donor and paired recipient, 10 KPD chains were constructed using an ADP donor. These 10 ADP donors have facilitated 47 transplants, and thus far eight of their paired recipients have received a kidney within a mean of 178 (range 10–562) days. The ADP is a viable method to support time limited donors in a KPD network.     

111Indium-labelled lymphocytes do not image or label the pancreas of the BB/W rat

Summary Autologous transfusions of ¹¹¹indium-labelled peripheral blood lymphocytes reportedly image the pancreas of patients with Type 1 (insulin-dependent) diabetes at the time of onset. We attempted to apply this technique to the spontaneously diabetic BB/W rat. First, acutely diabetic BB/W rats, diabetes-prone BB/W rats, diabetes-resistant W-line BB/ W rats, and Wistar Furth rats were given autologous transfusions of labelled peripheral blood lymphocytes. Radioactivity recovered from the pancreas was similar in all groups. No correlation was found between the intensity of imaging and the presence or intensity of insulitis. To decrease non-specific intravascular radioactivity, acutely diabetic, diabetes-prone, and W-line rats were perfused 48 h after autologous transfusion of labelled lymphocytes. Again, the intensity of recovered activity was similar in all groups, using both macroautoradiography and numerical counting techniques. A second set of experiments studied diabetes and insulitis induced by passive transfer of concanavalin A-treated splenic lymphocytes from acutely diabetic donors. Activated lymphocytes were labelled with ¹¹¹Indium and given to groups of diabetes-prone and diabetes-resistant rats. There were no differences in pancreatic localization 72–96 h after injection. Groups of diabetes-prone and diabetes-resistant rats were also given concanavalin A-activated lymphocytes and then challenged 2–10 days later with autologous transfusions of labelled peripheral blood lymphocytes. Again, no differences in organ labelling or imaging were detected. We conclude that the autologous transfusions of ¹¹¹indium-labelled lymphocytes do not label or image the pancreas of the BB/W rat.     

Cartilage degradation by neutral proteoglycanases in experimental osteoarthritis. Suppression by steroids

In this study, we sought to determine the role of neutral proteases in cartilage matrix proteoglycan degradation, which occurs during the early stages of experimental osteoarthritis. The anterior cruciate ligament was transected in the right knees of 33 dogs. Their left knees served as sham operated controls. The animals were killed 2, 4, 8, and 12 weeks after surgery. Six dogs were treated with oral prednisone and then killed 4 weeks after surgery. Cartilage specimens from medial and lateral tibial plateaus were analyzed for DNA, proteoglycan content, and neutral proteoglycan degrading activity. No significant differences in cartilage DNA and proteoglycan content were observed among the dogs that had surgery, the controls, and the prednisone-treated animals. Total neutral metalloproteoglycan-degrading enzyme (NMPE) activity, determined by direct tissue assay, was significantly higher at all time points in osteoarthritic cartilage than in control cartilage. The active form of NMPE was significantly higher in osteoarthritic cartilage than in control cartilage at 2, 4, and 8 weeks in lateral plateaus and at 2 and 4 weeks in medial plateaus. Treatment for 4 weeks with prednisone (0.20-0.25 mg/kg/day) blocked the increased NMPE activity in osteoarthritic cartilage. The increase in the total and active neutral proteoglycanases supports the hypothesis that these enzymes are involved in early osteoarthritis. The synthesis of NMPE appears to be controlled by stimulating factors released by the synovium.     

Endocardite infectieuse à Actinobacillus actinomycetemcomitans: A propos de 2 cas et revue de la littérature

This work reports two cases of endocarditis caused by Actinobacillus actinomycetemcomitans. As noted in the medical literature, the mean clinical features are a subacute infection without know source of bacteremia, in a male patient aged 40 years or older and who is suffering from a heart disease. In our two presentations, the good response to single antibiotic treatment, although the optimal therapeutic approach is not yet defined, and the lack of embolism phenomena are of special interest. Spectrum of bacteria which can be responsible of infective endocarditis is widening rapidly; this study is an example of this trend.     

Effects of Active Versus Passive Recovery on Power Output During Repeated Bouts of Short Term,High Intensity Exercise

ATP repletion following exhaustive exercise is approximated to be 90-95% complete in 3 minutes, and is crucial in the performance of short duration, high intensity work. Few studies appear to have used this 3-minute interval in the investigation of recovery modes, blood lactate accumulation and power output. Thus, our aim was to investigate changes in peak power (PP), average power (AP) and blood lactate during repeated bouts of high intensity, short duration cycling, comprising active and passive recovery modes lasting 3 minutes. Seven male cyclists (age 21.8±3.3 yrs, mass 73.0±3.8kgs, height 177.3±3.4cm) performed both an active (3 min at 80rpm & 1kg resistance) and a passive recovery (no work between bouts) protocol. Following a warm-up, subjects performed six 15-second maximal sprints against a fixed workload of 5.5kg. Mean PP across the six trials was 775±11.2Watts (W) and 772±33.4W for active and passive protocols respectively; whereas mean AP was 671±26.4W and 664±10.0W, respectively. Neither was significantly different. There was a significant difference within trials for both peak power and average power (p<0.05), with both values decreasing over time. However, the decrease was significantly smaller for both PP and AP values during the active recovery protocol (p<0.05). In the current study, variation in power output cannot be explained by lactate values, as values did not differ between the active and passive protocol (p=0.37). Lactate values did differ significantly between trials within protocols (p<0.05). The results of this study suggest that an active recovery of 3 minutes between high intensity, short duration exercise bouts significantly increases PP and AP compared to a passive recovery, irrespective of changes in blood lactate levels.Key words: Anaerobic power, light exercise, lactate, power output