The ultrastructural localization of fibronectin in the lining layer of rheumatoid arthritis synovium: The synthesis of fibronectin by type B lining cells

The distribution of fibronectin in the lining layer of inflamed rheumatoid arthritis (RA) synovium has been ultrastructurally investigated using an anti-human plasma fibronectin antibody. The hyperplasia of lining cells was prominent in the lining layer of the inflamed RA synovium. A high level of fibronectin was localized in this region. Ultrastructurally the fibronectin was observed on the surface of both type A (type M) and type B (type F) cells, and in the extracellular fibrin-like material. This glycoprotein was detectable in rough endoplasmic reticulum (RER), some Golgi apparatus, and peripheral vesicles of type B cells. On the other hand, RER and Golgi apparatus of type A cells failed to be immunostained with the antibody. Type A cells occasionally contacted each other with interdigitation of cytoplasmic processes, and a high amount of fibronectin was localized in this region. These findings indicate that fibronectin is synthesized along the classic secretory pathway through RER and Golgi apparatus of type B cells. On the contrary, type A cells seem not to be associated with the local synthesis of the glycoprotein. Fibronectin may play a structural role in organizing these proliferated lining cells by promoting cell adhesion. The synthesis of fibronectin by proliferated type B cells may be responsible in part for the local increase of this glycoprotein in the lining layer of RA synovium.     

Comparison of red cell creatine level and reticulocyte count in appraising the severity of hemolytic processes.

In seeking a sensitive indicator for quantitative assessment of hemolytic disease, we found a close dependence of red cell creatine level on cell age. Studies in 21 patients with steady-state hemolysis showed high correlation (r=0.89, p less than 0.001) between reticulocyte counts and red cell creatine levels. Excluding elevation of the creatine level as a variable epiphenomenon of increased erythropoietic activity, density separation of normal red cells revealed distinctly higher creatine levels in younger cells. The reticulocyte counts and creatine levels as quantitative predictors of hemolytic processes were compared: in severe hemolytic anemias (T50Cr less than 11 days), erythrocyte survival (T50Cr) correlated well with creatine levels (r = -0.86, p less than 0.01) and, to a lesser degree, with reticulocyte counts (r = -0.72, p less than 0.05). In milder disease (T50Cr greater than 11 days), however, no correlation existed between reticulocyte counts and T50Cr, whereas the creating levels correlated closely with T50Cr (r = -0.84, p less than 0.001). Thus, on the basis of our regression equations, useful estimation of red cell survival may be obtained from single measurements of erythrocyte creatine.     

Implementing an Innovative Cardiac Assist System in a Nonuniversity Hospital—Feasibility,Complications, and First Results

To evaluate the feasibility of implementing a cardiac assist system in a nonuniversity hospital we analyzed 18 consecutive patients treated with venoarterial membrane oxygenation. The system was used electively in 5/18 (27.8%) patients during high‐risk interventions. Thirteen patients (72.2%) were treated in emergency situations. The extracorporal system could be initiated successfully in all patients. Periprocedural complications were hemolysis in 3/18 (16.7%), disseminated intravascular coagulation in 2/18 (11.1%), cerebral ischemia in 1/18 (5.6%), and local infection in 2/18 (11.1%) patients. None of these led to a discontinuation of the therapy. All electively treated patients were successfully weaned from the extracorporeal system. In 9/13 (69.2%) emergency patients the system was removed successfully. The 60‐day survival rate of the emergency patients was 53.8% (7/13). Our experience confirms that an innovative extracorporeal circulatory support system can be implemented in a nonuniversity hospital at a tolerable risk and a low complication and high procedural success rate.     

Cytomegalovirus post kidney transplantation: prophylaxis versus pre‐emptive therapy?

Cytomegalovirus is the most important pathogen causing opportunistic infections in kidney allograft recipients. The occurrence of CMV disease is associated with higher morbidity, higher incidence of other opportunistic infections, allograft loss and death. Therefore, an efficient strategy to prevent CMV disease after kidney transplantation is required. Two options are currently available: pre‐emptive therapy based on regular CMV PCR monitoring and generalized antiviral prophylaxis during a defined period. In this review, we describe those two approaches, highlight the distinct advantages and risks of each strategy and summarize the four randomized controlled trials performed in this field so far. Taken this evidence together, pre‐emptive therapy and anti‐CMV prophylaxis are both equally potent in preventing CMV‐associated complications; however, the pre‐emptive approach may have distinct advantages in allowing for development of long‐term anti‐CMV immunity. We propose a risk‐adapted use of these approaches based on serostatus, immunosuppressive therapy and availability of resources at a particular transplant centre.     

Multicentric Castleman’s disease as a cause for unclear febrile episodes in a 55-year-old HIV-infected man

Our case illustrates the difficulties involved in diagnosing multicentric Castleman’s disease (MCD) in a human immunodeficiency virus-infected man with febrile episodes and malaise. In the absence of well-established treatment protocols, we have chosen a new treatment algorithm with rituximab, etoposide, and valganciclovir, which led to the remission of clinical symptoms. Yet, we advocate focused exploration for MCD in immunosuppressed patients with unclear febrile episodes, as recent advances in treatment are promising.     

A stringent preemptive protocol reduces cytomegalovirus disease in the first 6 months after kidney transplantation

Background

The optimal strategy to prevent cytomegalovirus (CMV) disease after kidney transplantation continues to be open to debate. The preemptive approach requires regular determination of CMV viremia and prompt initiation of therapy.

Methods

We retrospectively compared the incidence of CMV disease during two periods at our center: A first phase (P1, n?=?84 kidney recipients), during which time the intensity of surveillance was determined by the responsible physician, was compared to a second phase (P2, n?=?74), when a stringent protocol of CMV surveillance was required for all patients. The preemptive approach was applied for all CMV risk groups; prophylaxis was optional in the case of treatment for rejection or delayed graft function in the intermediate- and high-risk group. Follow-up was truncated at 6?months after transplant surgery. CMV syndrome was differentiated from asymptomatic replication by the presence of at least one systemic symptom, while diagnosis of CMV end-organ disease required histological confirmation.

Results

Immunosuppression was similar in the two periods. CMV prophylaxis was used equally (26?%) in both periods. The probability for asymptomatic viremia episodes was not different for patients in P1 and P2 regardless of the prevention strategy. For patients following the preemptive strategy, the probability for CMV disease was increased during P1 (p?=?0.016), despite fewer PCR assays being performed in phase 2. Protocol violations were only observed during P1.

Conclusions

The probability of CMV disease episodes (CMV syndrome and CMV end-organ disease) was substantially reduced using a very stringent protocol. This study highlights the crucial importance of a stringent protocol with optimal adherence by all caregivers if the preemptive strategy is to be successful.