Beta cell mass and growth after syngeneic islet cell transplantation in normal and streptozocin diabetic C57BL/6 mice

In islet transplantation, nonimmunological factors such as limited growth capacity or increased death rate could reduce the beta cell mass in the graft and lead to failure of the transplant. We studied the evolution of beta cell replication and mass after transplantation of insufficient, minimally sufficient, or excessive islet tissue. Streptozocin diabetic C57BL/6 mice received 150 or 300 syngeneic islets under the kidney capsule and normal mice received 300 islets. In streptozocin diabetic mice 300 islets restored normoglycemia; beta cell replication in transplanted islets was similar to replication in normal pancreas and beta cell mass in the graft remained constant. In contrast, 150 islets were insufficient to achieve normoglycemia; beta cell replication was increased initially but not by 18 or 30 d despite persistent hyperglycemia, and beta cell mass fell progressively. When islets were transplanted into normal recipients, beta cell replication remained normal but beta cells underwent atrophy and mass in the graft was substantially reduced. Therefore, with a successful islet transplant, in diabetic mice beta cell replication and mass remain constant. In contrast, when insufficient islet tissue is transplanted an initial increase in beta cell replication can not compensate for a decline in beta cell mass. When excessive islet tissue is transplanted, beta cell mass is reduced despite normal beta cell replication.

Clinical picture of the amyloid arthropathy in patients with chronic renal failure maintained on haemodialysis using cellulose membranes.

The clinical picture of 15 patients (10 male, five female) with amyloid arthropathy secondary to chronic renal failure treated with haemodialysis has been studied. The average period of haemodialysis was 10.8 years. Joint symptoms appeared between three and 13 years after starting haemodialysis. No patient had renal amyloidosis. Early symptoms were varied and often overlapped: knee swelling (seven patients), painful and stiff shoulders (seven), and carpal tunnel syndrome (six) were the most prominent. Follow up showed extension to other joints. Joint effusions were generally of the non-inflammatory type. Radiologically, geodes and erosions of variable sizes were seen in the affected joints, which can develop into a destructive arthropathy. Amyloid was found in abdominal fat in three of the 12 patients on whom a needle aspiration was performed. Four of 12 patients showed changes compatible with amyloid infiltration in the echocardiogram. One patient had amyloid in the gastric muscular layer, another in the colon mucus, and two of four in rectal biopsy specimens. Amyloid deposits showed the presence of beta 2 microglobulin in 10 patients. The clinical and radiological picture was similar to the amyloid arthropathy associated with multiple myeloma. These patients can develop systemic amyloidosis.

Synovial fluid examination for the diagnosis of synovial amyloidosis in patients with chronic renal failure undergoing haemodialysis

The diagnosis of synovial amyloidosis is based upon synovial biopsy. Synovial fluid (SF) in seven patients with amyloid arthropathy associated with chronic renal failure undergoing haemodialysis were studied. The SF and synovial samples of 10 consecutive patients with seronegative mono- or oligoarthritis served as controls. Six of the seven patients with amyloid positive synovial biopsy specimens showed amyloid in their SF. No amyloid was found in the synovial tissue or fluid of the 10 patients in the control group, the sensitivity being 87.7%. The finding of amyloid in SF was highly reproducible, showing its presence in the same joint on several occasions. The deposits were Congophilia resistant to potassium permanganate pretreatment, and the immunohistochemical analysis proved that they contained beta 2 microglobulin. The high sensitivity and good reproducibility of the method shows that the finding of amyloid in SF is sufficient for the diagnosis of synovial amyloidosis. It is possible to perform immunohis

Amyloid arthropathy in patients undergoing periodical haemodialysis for chronic renal failure: a new complication.

Seven patients (five male and two female) with chronic renal failure (CRF) treated by periodical haemodialysis presented with swelling and effusion of more than three months' duration in knees (four bilateral), shoulders (two, one of them bilateral), elbow (one), and ankle (one). Four had a carpal tunnel syndrome both clinically and electromyographically (three bilateral). All patients had hyperparathyroidism secondary to their CRF, which was not due to amyloidosis in any of them. The dialysis duration period varied from five to 14 years, with an average of 8.6 years. Amyloid deposits (Congo red positive areas with green birefringence under polarising microscopy) were shown in six of the seven synovial biopsy specimens of the knee, in five of the sediments of the synovial fluids, and in specimens removed during carpal tunnel syndrome surgery. No amyloid was found in the biopsy specimen of abdominal fat of six of the patients. The finding of amyloid only in the synovial membrane and fluid, and carpal tunnel, its absence in abdominal fat, and the lack of other manifestations of generalised amyloidosis (cardiomyopathy, malabsorption syndrome, macroglossia, etc.) and of Bence Jones myeloma (protein immunoelectrophoresis normal) raises the possibility that this is a form of amyloidosis which is peculiar to CRF treated by periodical haemodialysis.

Effects of erythropoietin on muscle O2 transport during exercise in patients with chronic renal failure.

Erythropoietin (rHuEPO) has proven to be effective in the treatment of anemia of chronic renal failure (CRF). Despite improving the quality of life, peak oxygen uptake after rHuEPO therapy is not improved as much as the increase in hemoglobin concentration ([Hb)] would predict. We hypothesized that this discrepancy is due to failure of O2 transport rates to rise in a manner proportional to [Hb]. To test this, eight patients with CRF undergoing regular hemodialysis were studied pre- and post-rHuEPO ([Hb] = 7.5 +/- 1.0 vs. 12.5 +/- 1.0 g x dl-1) using a standard incremental cycle exercise protocol. A group of 12 healthy sedentary subjects of similar age and anthropometric characteristics served as controls. Arterial and femoral venous blood gas data were obtained and coupled with simultaneous measurements of femoral venous blood flow (Qleg) by thermodilution to obtain O2 delivery and oxygen uptake (VO2). Despite a 68% increase in [Hb], peak VO2 increased by only 33%. This could be explained largely by reduced peak leg blood flow, limiting the gain in O2 delivery to 37%. At peak VO2, after rHuEPO, O2 supply limitation of maximal VO2 was found to occur, permitting the calculation of a value for muscle O2 conductance from capillary to mitochondria (DO2). While DO2 was slightly improved after rHuEPO, it was only 67% of that of sedentary control subjects. This kept maximal oxygen extraction at only 70%. Two important conclusions can be reached from this study. First, the increase in [Hb] produced by rHuEPO is accompanied by a significant reduction in peak blood flow to exercising muscle, which limits the gain in oxygen transport. Second, even after restoration of [Hb], O2 conductance from the muscle capillary to the mitochondria remains considerably below normal.

Functional renal failure and haemorrhagic gastritis associated with endotoxaemia in cirrhosis

Forty-three patients with cirrhosis and ascites, 21 with normal renal function, 10 with a progressive functional renal failure (FRF), and 12 with a steady FRF, were investigated for the presence of endotoxaemia by the Limulus lysate test. Endotoxaemia was found in nine patients with FRF and in none of the 21 with normal renal function (P less than 0-01). A positive Limulus test was almost exclusively associated with a progressive FRF (eight of 10 patients) and all but one of them died. Renal function improved as endotoxaemia disappeared in the survivor. Endotoxaemia was also associated with haemorrhage due to acute erosions of the gastric mucosa, being present in six of the seven patients who had this complication. Intravascular coagulation was not found in any patient. The Limulus test was positive in the ascitic fluid in 18 of 21 patients tested, although only two of them had peritonitis. These results suggest that endotoxaemia may play a critical role in the development of progressive renal failure and haemorrhagic gastritis in cirrhosis, and emphasise the potential risk of procedures involving reinfusion of ascitic fluid.

Abnormalities of sodium excretion and other disorders of renal function in fulminant hepatic failure

Renal function was evaluated in 40 patients with fulminant hepatic failure, They were divided into two groups on the basis of glomerular filtration rates greater than 40 ml/min or less than 25 ml/min. A number of patients in group 1 had markedly abnormal renal retention of sodium together with a reduced free water clearance and low potassium excretion which could be explained by increased proximal tubular reabsorption of sodium. The patients in group 2 had evidence that renal tubular integrity was maintained when the glomerular filtration rate was greater than or equal ml/min (functional renal failure), but evidence of tubular damage was present when this was less than 3 ml/min (acute tubular necrosis).

Prognostic Importance of the Cuse of Renal Failure in Patients With Cirrhosis

BACKGROUND & AIMS: The prognostic value of the different causes of renal failure in cirrhosis is not well established. This study investigated the predictive value of the cause of renal failure in cirrhosis. METHODS: Five hundred sixty-two consecutive patients with cirrhosis and renal failure (as defined by serum creatinine 1.5 mg/dL on 2 successive determinations within 48 hours) hospitalized over a 6-year period in a single institution were included in a prospective study. The cause of renal failure was classified into 4 groups: renal failure associated with bacterial infections, renal failure associated with volume depletion, hepatorenal syndrome (HRS), and parenchymal nephropathy. The primary end point was survival at 3 months. RESULTS: Four hundred sixty-three patients (82.4%) had renal failure that could be classified in 1 of 4 groups. The most frequent was renal failure associated with infections (213 cases; 46%), followed by hypovolemia-associated renal failure (149; 32%), HRS (60; 13%), and parenchymal nephropathy (41; 9%). The remaining patients had a combination of causes or miscellaneous conditions. Prognosis was markedly different according to cause of renal failure, 3-month probability of survival being 73% for parenchymal nephropathy, 46% for hypovolemia-associated renal failure, 31% for renal failure associated with infections, and 15% for HRS (P .0005). In a multivariate analysis adjusted for potentially confounding variables, cause of renal failure was independently associated with prognosis, together with MELD score, serum sodium, and hepatic encephalopathy at time of diagnosis of renal failure. CONCLUSIONS: A simple classification of patients with cirrhosis according to cause of renal failure is useful in assessment of prognosis and may help in decision making in liver transplantation.

Development of a population-based cost-effectiveness model of chronic graft versus host disease in Spain

Chronic graft-versus-host disease (cGvHD) is the leading cause of late nonrelapse mortality (transplant-related mortality) after hematopoietic stem cell transplant. Given that there are a wide range of treatment options for cGvHD, assessment of the associated costs and efficacy can help clinicians and health care providers allocate health care resources more efficiently. OBJECTIVE: The purpose of this study was to assess the cost-effectiveness of extracorporeal photopheresis (ECP) compared with rituximab (Rmb) and with imatinib (Imt) in patients with cGvHD at 5 years from the perspective of the Spanish National Health System. METHODS: The model assessed the incremental cost-effectiveness/utility ratio of ECP versus Rmb or Imt for 1000 hypothetical patients by using microsimulation cost-effectiveness techniques. Model probabilities were obtained from the literature. Treatment pathways and adverse events were evaluated taking clinical opinion and published reports into consideration. Local data on costs (2010 Euros) and health care resources utilization were validated by the clinical authors. Probabilistic sensitivity analyses were used to assess the robustness of the model. RESULTS: The greater efficacy of ECP resulted in a gain of 0.011 to 0.024 quality-adjusted life-year in the first year and 0.062 to 0.094 at year 5 compared with Rmb or Imt. The results showed that the higher acquisition cost of ECP versus Imt was compensated for at 9 months by greater efficacy; this higher cost was partially compensated for ( 517) by year 5 versus Rmb. After 9 months, ECP was dominant (cheaper and more effective) compared with Imt. The incremental cost-effectiveness ratio of ECP versus Rmb was 29,646 per life-year gained and 24,442 per quality-adjusted life-year gained at year 2.5. Probabilistic sensitivity analysis confirmed the results. The main study limitation was that to assess relative treatment effects, only small studies were available for indirect comparison. CONCLUSION: ECP as a third-line therapy for cGvHD is a more cost-effective strategy than Rmb or Imt.

Cost-effectiveness analysis of cardiac resynchronization therapy in patients with NYHA I and NYHA II heart failure in Spain

Objectives: The aim of the study was to combine clinical results from the European Cohort of the REVERSE study and costs associated with the addition of cardiac resynchronization therapy (CRT) to optimal medical therapy (OMT) in patients with mild symptomatic (NYHA I-II) or asymptomatic left ventricular dysfunction and markers of cardiac dyssynchrony in Spain. Methods: A Markov model was developed with CRT + OMT (CRT-ON) versus OMT only (CRT-OFF) based on a retrospective cost-effectiveness analysis. Raw data was derived from literature and expert opinion, reflecting clinical and economic consequences of patient"s management in Spain. Time horizon was 10 years. Both costs (euro 2010) and effects were discounted at 3 percent per annum. Results: CRT-ON showed higher total costs than CRT-OFF; however, CRT reduced the length of hospitalization in ICU by 94 percent (0.006 versus 0.091 days) and general ward in by 34 percent (0.705 versus 1.076 days). Surviving CRT-ON patients (88.2 percent versus 77.5 percent) remained in better functional class longer, and they achieved an improvement of 0.9 life years (LYGs) and 0.77 years quality-adjusted life years (QALYs). CRT-ON proved to be cost-effective after 6 years, except for the 7th year due to battery depletion. At 10 years, the results were 18,431 per LYG and 21,500 per QALY gained. Probabilistic sensitivity analysis showed CRT-ON was cost-effective in 75.4 percent of the cases at 10 years. Conclusions: The use of CRT added to OMT represents an efficient use of resources in patients suffering from heart failure in NYHA functional classes I and II.

Prognostic Importance of the Cuse of Renal Failure in Patients With Cirrhosis

BACKGROUND & AIMS: The prognostic value of the different causes of renal failure in cirrhosis is not well established. This study investigated the predictive value of the cause of renal failure in cirrhosis. METHODS: Five hundred sixty-two consecutive patients with cirrhosis and renal failure (as defined by serum creatinine 1.5 mg/dL on 2 successive determinations within 48 hours) hospitalized over a 6-year period in a single institution were included in a prospective study. The cause of renal failure was classified into 4 groups: renal failure associated with bacterial infections, renal failure associated with volume depletion, hepatorenal syndrome (HRS), and parenchymal nephropathy. The primary end point was survival at 3 months. RESULTS: Four hundred sixty-three patients (82.4%) had renal failure that could be classified in 1 of 4 groups. The most frequent was renal failure associated with infections (213 cases; 46%), followed by hypovolemia-associated renal failure (149; 32%), HRS (60; 13%), and parenchymal nephropathy (41; 9%). The remaining patients had a combination of causes or miscellaneous conditions. Prognosis was markedly different according to cause of renal failure, 3-month probability of survival being 73% for parenchymal nephropathy, 46% for hypovolemia-associated renal failure, 31% for renal failure associated with infections, and 15% for HRS (P .0005). In a multivariate analysis adjusted for potentially confounding variables, cause of renal failure was independently associated with prognosis, together with MELD score, serum sodium, and hepatic encephalopathy at time of diagnosis of renal failure. CONCLUSIONS: A simple classification of patients with cirrhosis according to cause of renal failure is useful in assessment of prognosis and may help in decision making in liver transplantation.

Shaping urban traffic patterns through congestion charging : What factors drive success or failure?

Congestion costs are emerging as one of the most important challenges faced by metropolitan planners and transport authorities in first world economies. In US these costs were as high as 78 million dollars in 2005 and are growing due to fast increases in travel delays. In order to solve the current and severe levels of congestion the US department of transportation have recently started a program to initiate congestion pricing in five metropolitan areas. In this context it is important to determine those factors helping its implementation and success, but also the problems or difficulties associated with charging projects. In this article we analyze worldwide experiences with urban road charging in order to extract interesting and helpful lessons for policy makers engaged in congestion pricing projects and for those interested in the introduction of traffic management tools to regulate the entrance to big cities.

Graft materials in oral surgery: revision

Oral implantology is a common procedure in dentistry, especially for fully or partially edentulous patients. The implants must be placed in the best location from both the aesthetic and functional point of view. Because of this it is increasingly more frequent to resort to regeneration techniques that use substitutes of the bone itself, in order to be able to insert the implants in the most appropriate location. Material and Methodology: A review was performed on the literature from the last ten years based on the following search limitations: "graft materials', 'allograft', 'xenograft', 'autologous graft" and 'dentistry". Results: 241 works were obtained that after reading their respective summaries, they were reduced to 38, and 9 previous works were included in order to summarize the concepts. Discussion: Autologous grafts are the 'gold standard' of the bone regeneration. They have obvious advantages, but they also have drawbacks. This is why allogeneic and xenogeneic tissues are used. The former because of their clear similarity with the recipient's tissue and the latter due to their wide availability. Given that these grafts also have drawbacks, the industry has developed synthetic materials that have properties similar to those of human bone tissue. However, as of today, the ideal material to substitute human bone has not yet been found. In recent years the tendency has been to combine these synthetic materials with the patient's own bone, which is extracted during drilling in implant placement, with bone marrow aspiration, or with bone morphogenetic proteins. Thus the intention is to equip these substances with the osteogenic capacity. Conclusions: There is currently no ideal graft material, with the exception of those materials that come directly from the patient. We hope that in the coming years we will have products that will allow us to perform rehabilitations with better results and provide a better quality of life for our patients, especially those who have more complex situations to resolve, like the patients that are operated on for head and neck cancer