The kinetics of immune reconstitution after human marrow transplantation

Human marrow transplantation for the treatment of malignant and nonmalignant disorders is becoming an established modality of therapy. As in any aggressive therapeutic modality, the benefits must be balanced with the risks of the therapy. The aggressive chemoradiotherapy used to prepare patients for marrow transplantation creates a transient immunodeficiency disorder postgrafting until the transferred donor marrow reestablishes a competent immune system. Immune reconstitution posttransplant follows a general pattern developing from immature to mature immune functions. Immune reactivity during the first month postgrafting is extremely low. Cytotoxic and phagocytic functions recover by day 100, while more specialized and cooperative functions of T and B cells remain impaired up to one year or more postgrafting. After the first year postgrafting, the various components of the immune systems of most healthy marrow recipients begin to work synchronously, whereas the immune systems of recipients with chronic graft-v-host disease (GVHD) remain crippled. Recent evidence shows that transfer of specific immunity from marrow donors to marrow recipients plays a role in reestablishing immunocompetence. Transferred antigen-specific immunity may explain why more recipients do not die from overwhelming infections.     

Inadvertent ligation of the left pulmonary artery

In five patients, aged 4 days to 20 months, the left pulmonary artery was inadvertently ligated at the time of attempted closure of the patent ductus arteriosus. The complication was recognized in these patients between 1 day and 5 years later from findings of chest radiography, two-dimensional echocardiography with spectral analysis of Doppler shifted echoes, and angiography. In three patients, the presence of asymmetric pulmonary blood flow on chest radiographs obtained after surgery initially suggested the diagnosis. In the other two patients with bronchopulmonary dysplasia, the diagnosis was made by means of two-dimensional echocardiography and Doppler spectra in one and angiography in the other. On angiograms, the left pulmonary artery distal to the ligation was visualized by delayed opacification from aortic collaterals in three patients and by means of pulmonary venous wedge injection in one. Radiographic and echocardiographic examination with Doppler spectra may permit prompt diagnosis and early correction of this complication.     

Meniscus tears of the knee: prospective evaluation with CT

A total of 209 patients underwent prospective axial computed tomography (CT) examinations of the knee to evaluate the ability of this technique to identify and characterize knee menisci in patients believed to have meniscus tears. Of the 359 knees examined, 105 subsequently underwent arthrography, arthroscopy, or arthrography and arthroscopic surgery. In this group, the sensitivity of CT was 88.5%, specificity was 95.5%, and accuracy was 91.5%. Although axial CT is a sensitive and effective method for the detection and characterization of tears involving the medial and lateral menisci, purely horizontal or nondisplaced peripheral tears may be difficult to demonstrate.     

Keine irreführende wettbewerbswidrige Werbung eines Medizinischen Versorgungszentrums mit der Bezeichnung “Rheumazentrum”

1. Der Begriff “Zentrum” ist im Zusammenhang mit der St?tte ?rztlicher Berufsausübung einem Bedeutungswandel unterlegen. 2. Im Bereich der ambulanten ?rztlichen Berufsausübung gilt der überkommene Zentrumsbegriff zumindest nicht mehr, wenn die ?rztliche Berufsausübung im Rahmen eines Medizinischen Versorgungszentrums erfolgt. (Leits?tze der Bearbeiterin)     

Autoantibodies against bactericidal/permeability-increasing protein in patients with cystic fibrosis

Cystic fibrosis (CF), a genetic disorder, is characterized by chronic pulmonary infection/inflammation which leads to respiratory failure. The presence of anti-neutrophil cytoplasmic autoantibodies (ANCA) has previously been observed in the sera of patients with CF. In view of the known relationship of ANCA with primary vasculitis and of their putative pathogenetic role in these disorders, we studied the presence, specificity and isotype of ANCA and their clinical associations in 66 adult CF patients. None of the 66 CF samples had autoantibodies to the major ANCA antigens, proteinase 3 or myeloperoxidase. However, 60/66 (91%) CF samples contained IgG and 55/66 (83%) IgA, autoantibodies to bactericidal/permeability increasing protein (BPI), a recently characterized ANCA specificity. All the IgA anti-BPI-positive samples were also IgG anti-BPI-positive. The autoantibody specificity was confirmed by inhibition assay and immunoblotting of CF sera against a neutrophil granule preparation. Furthermore, in this cross-sectional study, anti-BPI levels were inversely correlated with the observed reductions in FEV1 and FVC (IgA anti-BPI and FEV1: r = 0.508, <it>p</it> &lt; 0.0001), and both IgG and IgA anti-BPI levels were higher in CF patients with secondary vasculitis (<it>n</it> = 6) than in those without (<it>p</it> &lt; 0.05). ANCA with specificity for BPI were present in the majority of CF sera in this study and autoimmune processes may be associated with the development of pulmonary injury in CF.      

Tobacco smoke affects expression of peroxisome proliferator-activated receptor-γ in monocyte/macrophages of patients with coronary heart disease

Background and purpose:

Tobacco smoke represents a relevant risk factor for coronary heart disease (CHD). Although peroxisome proliferator-activated receptor (PPAR)γ activation reduces inflammation and atherosclerosis, expression of PPARγ in cells and its modulation by smoking are poorly investigated. We previously reported that monocyte/macrophages from healthy smokers exhibited an enhanced constitutive expression of PPARγ. Here, we evaluated PPARγ expression and basal cytokine release in monocytes and monocyte-derived macrophages (MDMs) from 85 CHD patients, classified by their smoking habit (smokers, non-smokers and ex-smokers), and assessed the role of PPARγ ligands in this context.

Experimental approach:

PPARγ protein was detected by Western blot and semi-quantified by PPARγ/β-actin ratio; cytokine release was measured by elisa and nuclear factor-kappaB (NF-κB) translocation by electrophoretic mobility shift assays.

Key results:

As compared to the other groups, MDMs from smoker CHD patients exhibited a reduced PPARγ/β-actin ratio and an increased spontaneous release of tumour necrosis factor-α (TNF-α) and interleukin-6, but with no major variations in monocytes. In cells from selected CHD patients, rosiglitazone inhibited TNF-α release and NF-κB translocation induced by phorbol-12-myristate 13-acetate. The selective PPARγ antagonist GW9662 reversed these effects, with some variations related to smoking habit.

Conclusions and implications:

In CHD patients, exposure to tobacco smoke profoundly affected PPARγ expression, and this was related to levels of secretion of pro-inflammatory cytokines. MDMs from CHD smokers showed the lowest PPARγ expression and released more inflammatory cytokines. Moreover, rosiglitazone''s ability to inhibit cytokine release and its reversal by GW9662 clearly indicated PPARγ involvement in these changes in CHD patients.     

Leukopenia complicates cytomegalovirus prevention after renal transplantation with alemtuzumab induction

BACKGROUND: Cytomegalovirus (CMV) is a major cause of morbidity after transplantation. Valganciclovir (VGCV) is commonly utilized for CMV prophylaxis but can cause leukopenia, with risk compounded by the use of myelosuppressive immunosuppression. By utilizing a preemptive therapeutic strategy with VGCV targeted only toward patients at risk for developing CMV disease, the rate and extent of leukopenia may be reduced. METHODS: VGCV prophylactic and preemptive strategies were compared in renal transplant recipients receiving alemtuzumab induction and prednisone-free maintenance with tacrolimus and mycophenolate mofetil (MMF). Patients were risk-stratified by CMV serologic status. All donor seropositive/recipient seronegative (D+/R-) patients, February 2002-January 2004 (n=32), received prophylaxis with VGCV 450 mg daily for 3 months. Outcomes of D+/-/R+ patients were compared. Patients in the first cohort, February 2002-October 2002 (n=61), received prophylaxis as described. In the second cohort, October 2002-January 2004 (n=110), patients were monitored by quantitative CMV-polymerase chain reaction (PCR) every 2 weeks for 3 months. If the CMV load was above laboratory threshold, VGCV 450 mg daily was initiated for 1 month or until viremia cleared. RESULTS: Comparing preemptive therapy versus prophylaxis in D+/-/R+ patients, there was a lower incidence of leukopenia (67% vs. 82%, P=0.039) and trend toward less granulocyte-colony stimulating factor (G-CSF) use (24% vs. 33%, P=0.196), but higher CMV disease rate (15% vs. 3%, P=0.02). One limitation was strategy compliance: 41% (7 of 17) of preemptive patients who developed CMV missed at least 1 CMV-PCR before diagnosis. One-year patient (98.2% vs. 98.4%) and death-censored graft (100% vs. 98.4%) survival was similar. CONCLUSIONS: Antiviral toxicity may be decreased with preemptive therapy, but effectiveness for CMV prevention seems dependent upon monitoring compliance.     

Duodenal hematoma: the ring sign in MR imaging

Proper management of duodenal hematoma requires that an accurate diagnosis be made using noninvasive radiological methods. Conventional imaging may be nonspecific if there is no history of trauma or coagulopathy. Two cases of duodenal hematoma that were imaged by magnetic resonance (MR) and computed tomography (CT) are described. In both cases the hematoma had a well-defined concentric ring configuration on MR images, a finding which helped establish the diagnosis. MR imaging may provide tissue-specific characterization of duodenal hematomas.     

CAT correlates positively with respiratory rate and is a significant predictor of the impact of COPD on daily life of patients: a cross sectional study

Background

The pathophysiological changes of COPD tend to worsen with progression, triggering limiting symptoms and implying the decrease in the activities of daily living and quality of life. The COPD Assessment Test (CAT) is a questionnaire designed to measure the impact of COPD on the health status. The aim of this study was to evaluate the impact of the disease through the CAT in a Brazilian sample of COPD patients and to correlate symptoms at rest with the CAT score in these patients.

Methods

Study of cases with COPD patients was conducted by pulmonary rehabilitation program (RP). Respiratory rate (RR) and symptoms (dyspnea by Modified Borg Scale Dyspnea Index; symptoms by CAT) were analyzed at the beginning of the RP.

Results

The study analyzed 28 COPD patients, both genders, age 65.93?±?7.84 years and many patients ranging from severe and very severe disease. The majority of patients were rated by CAT with low impact-disease (n?=?13/46, 4%);medium (n?=?11/39, 3%) and the high impact-diseases were observed in a few subjects (n?=?4/14.3%). The difference between all CAT scores was significant, p?=?0.000. There was a positive correlation between respiratory rate and CAT scores impact-level (r?=?0.585, p?=?0.001). The results obtained by the Borg Scale revealed a high presence of symptoms in these COPD patients but no association with CAT.

Conclusion

The CAT is a sensitive tool to assess the current health status of COPD patients, and in Southern Brazil it is positively correlated with respiratory rate.