Role for interferon-gamma release assays in latent tuberculosis screening before TNF-α antagonist therapy

TNF-α antagonist therapy is associated with a risk of severe, extrapulmonary, disseminated tuberculosis, which is fatal in 10% of cases. The risk of tuberculosis is increased four-fold in patients on TNF-α antagonist therapy. The main risk factors are a history of untreated or inadequately treated primary tuberculosis, recent contact with a tuberculosis patient, and residence in or travel to a high-endemicity region. Infection surveillance agencies throughout the world have issued recommendations to ensure the detection and treatment of latent tuberculosis before TNF-α antagonist initiation. These recommendations have returned the incidence of tuberculosis to the level seen before the introduction of TNF-α antagonists. Nevertheless, there is still room for improvement. Recommendations about latent tuberculosis screening include the use of tuberculin skin tests. However, these tests are positive in individuals vaccinated with the BCG vaccine, which leads to overuse of tuberculosis chemoprophylaxis and, therefore, to unnecessary patient exposure to hepatotoxic effects. Furthermore, tuberculin skin tests may be falsely negative in immunosuppressed patients, leading to underuse of tuberculosis prophylaxis. These shortcomings of tuberculin skin tests have generated interest in interferon-gamma release assays (IGRAs). In patients with overt tuberculosis, IGRAs are more sensitive and more specific than tuberculin skin tests. However, the accuracy of IGRAs for diagnosing latent tuberculosis remains unknown, because no reference standard is available. In addition, patients taking immunosuppressant agents to treat systemic disease may exhibit anergia, which complicates the interpretation of IGRAs. Until additional data become available, caution requires that IGRAs be used only when a positive or negative result, as assessed on a case-by-case basis, will help to decide whether tuberculosis chemoprophylaxis is in order.     

Single-level anterior cervical discectomy and interbody fusion using PEEK anatomical cervical cage and allograft bone

Background  

In an effort to avoid the morbidity associated with autogenous bone graft harvesting, cervical cages in combination with allograft bone are used to achieve fusion. The goal of the current study was to assess the reliability and efficacy of anterior cervical discectomy and interbody fusion (ACDF) using a PEEK anatomical cervical cage in the treatment of patients affected by single-level cervical degenerative disease.     

Covered Stents in the Treatment of Peripheral Arterial Aneurysms: Procedural Results and Midterm Follow-Up

Purpose: To evaluate initial and midterm results of percutaneous treatment of peripheral aneurysms using covered stents. Methods: Between June 1994 and December 1997 we used covered stents (EndoPro System or Passager) on 19 patients with peripheral aneurysms (7 iliac, 5 subclavian, 3 femoral, 3 popliteal, 1 carotid). Results: Successful aneurysm exclusion was achieved in 18 of 19 patients (95%). In the short term (<30 days), one patient died of puncture site hemorrhage complicated by myocardial infarction; two femoral stents were surgically removed because of leakage. At subsequent follow-up (mean 20 months) two further unrelated deaths occurred. At 1 year (intention-to-treat) the stent was patent in 13 of 19 patients (68%) and the aneurysm was excluded in 17 of 19 (89%). Conclusion: Treatment of peripheral aneurysms with covered stents has a high rate of immediate procedural success. Continued exclusion of the aneurysms is achieved in a large proportion of patients but there is a relatively high rate of stent thrombosis.     

Assessment of intrathoracic blood volume as an indicator of cardiac preload: single transpulmonary thermodilution technique versus assessment of pressure preload parameters derived from a pulmonary artery catheter.

OBJECTIVE: To analyze the clinical value of a new device (PiCCO) for cardiac output measurement and volume preload parameter assessment, based on transpulmonary thermodilution technique, as an alternative to the pulmonary artery thermodilution technique and assessment of pressure preload parameters derived from the pulmonary artery catheter. DESIGN: Prospective, controlled, clinical study. SETTING: University hospital. PARTICIPANTS: Eighteen patients with ejection fraction >50% undergoing coronary artery bypass graft surgery. INTERVENTIONS: A baseline measurement was performed after induction of anesthesia under clinical steady-state conditions (T1). Hypovolemia, defined as central venous pressure (CVP) <10 mmHg and pulmonary capillary wedge pressure (PCWP) <12 mmHg, was treated by infusion of 6% hydroxyethyl starch 200/0.5 (7 mL/kg). After 10 minutes, a second measurement (T2) was performed. MEASUREMENTS AND MAIN RESULTS: The mean difference (bias) between transpulmonary thermodilution cardiac output and pulmonary artery thermodilution cardiac output did not differ at the 2 sample points. Changes in pressure preload parameters of the pulmonary artery catheter (CVP, PCWP) did not correlate with changes in cardiac output or stroke volume, whereas changes in volume preload parameter intrathoracic blood volume (ITBV) of the PiCCO correlated significantly with changes in cardiac output and stroke volume (r = 0.55, p < 0.05; r = 0.62, p < 0.01). CONCLUSION: These results suggest that increased cardiac preload is more reliably reflected by ITBV than by CVP or PCWP. The assessment of ITBV by the transpulmonary single indicator dilution technique is an interesting alternative to the pressure preload parameters.     

Wegener's granulomatosis: inflammatory cells and markers of repair and fibrosis in renal biopsies--a clinicopathological study.

OBJECTIVE: This study aimed to quantitate inflammatory cells in renal biopsies from patients with Wegener's granulomatosis (WG) and to identify cells participating in early fibrogenesis. The goal was to determine whether these cells correlated with the severity of renal disease and whether their presence had a bearing on renal prognosis. MATERIAL AND METHODS: Sixty-one patients with WG who had a renal biopsy taken at the time of diagnosis were included in the study. Immunostaining with monoclonal antibodies towards macrophages (CD68), T- and B-lymphocytes, alpha-smooth muscle actin (alpha-SMA) and vimentin was done. RESULTS: The dominating intraglomerular leucocytes were macrophages (29.9 +/- 15 cells/glomerular cross-section) and to a lesser extent T-cells (2.57 +/- 1.8 cells/glomerular cross-section). No B-lymphocytes were detected in the glomeruli. More than two-thirds of the T-cells were CD8+ (cytotoxic) cells. Macrophages and T-lymphocytes were distributed equally in the renal interstitium and were numerous around crescentic glomeruli. Glomerular and interstitial macrophages and interstitial T-cells correlated significantly with serum (S-) creatinine at the time of biopsy but not after 1 year. S-creatinine at the time of biopsy and after 1 year differed significantly among the three levels of interstitial alpha-SMA staining. S-creatinine at biopsy was highest when tubular vimentin staining was strongest, and tubular vimentin staining was strongest in patients with acute tubular damage. CONCLUSIONS: Evidence was found for a cellular type IV immune response in WG, with CD8+ T-lymphocytes and macrophages dominating the cellular infiltrate. The detection of interstitial alpha-SMA, probably staining myofibroblasts implicated in renal fibrogenesis, indicated a low glomerular filtration rate 1 year after renal biopsy.     

Influence of preservation solution on human islet isolation outcome

BACKGROUND: The influence of the preservation solution used for in situ perfusion of the donor and pancreas storage on islet isolation has received little attention. METHODS: In this prospective controlled trial, we compared the outcome of human islet isolation from pancreata perfused with University of Wisconsin (UW) solution or Celsior, an alternative colloid-free extracellular solution. RESULTS: At the 1-year interim analysis, the viability and insulin secretion of islets isolated from donors perfused with UW (n=19) or Celsior (n=5) were identical. However, total islet recovery (IEQ) and isolation yield (IEQ/g) were 1.8-fold and 2.1-fold inferior in the Celsior group (P<0.05 vs. UW). Overall, 13 (68%) of islet preparations were effectively transplanted from the UW group vs. none from the Celsior group (P=0.01). The clinical study was discontinued and the causes of these differences were further explored in the pig (n=14). In contrast to UW, Celsior induced cell swelling and pancreas edema after only four hours of cold storage. These abnormalities were delayed when the donor was perfused with Solution de Conservation d'Organes et de Tissus (SCOT), an extracellular solution containing polyethylene glycol. CONCLUSIONS: Our results suggest that colloid-free preservation solutions might be suboptimal for pancreas perfusion and cold storage prior to islet isolation and transplantation. Because pancreata are now frequently recovered for islet transplantation, preliminary experimental and clinical data about islet isolation should be obtained prior to the routine implementation of new preservation solutions for abdominal perfusion during multiorgan recovery.     

Ureterosciatic hernia: a rare cause of ureteral obstruction visualized by multislice helical computed tomography

Ureterosciatic herniation is an extremely rare cause of ureteral obstruction, of which few cases have been published. We describe a case revealed by pyelonephritis with acute renal failure in an 81-year-old woman. After percutaneous nephrostomy tube placement and antibiotic therapy, urography and multiplanar computed tomography reconstructions of the pelvis confirmed the diagnosis. The symptoms resolved, and the hernia was then corrected surgically.     

Detection of MDM2-CDK4 amplification by fluorescence in situ hybridization in 200 paraffin-embedded tumor samples: utility in diagnosing adipocytic lesions and comparison with immunohistochemistry and real-time PCR

Atypical lipomatous tumor/well-differentiated liposarcomas and dedifferentiated liposarcomas are characterized by the amplification of MDM2 and CDK4 genes. To evaluate the accuracy of fluorescence in situ hybridization (FISH) analysis in the differential diagnosis of adipose tissue tumors, we investigated MDM2-CDK4 status by FISH, real-time polymerase chain reaction (PCR) [quantitative PCR (Q-PCR)] and immunohistochemistry (IHC) in a series of 200 adipose tumors. First, we evaluated MDM2-CDK4 amplification and expression in a series of 94 well-defined adipose tissue tumors. Results showed that FISH was interpretable in 45 of 50 cases (90%), and was more specific and sensitive than Q-PCR and IHC. We then used the same techniques as complementary diagnostic tools in a series of 106 adipose and soft tissue tumors of unclear diagnosis to distinguish between (i) lipomas and atypical lipomatous tumor/well-differentiated liposarcomas, (ii) malignant undifferentiated tumors and dedifferentiated liposarcomas, and (iii) a variety of benign tumors and liposarcomas. Our results indicate that although helpful, IHC alone is often insufficient to solve diagnostic problems. FISH and Q-PCR methods gave concordant results and were equally informative in most cases. However, the proportion of noninterpretable cases was slightly higher with FISH than with Q-PCR. When tumor cells represented a minor component of the tumor tissue, such as with inflammatory tumors, FISH was more powerful than Q-PCR by allowing visualization of individual cells. In conclusion, we recommend that the evaluation of MDM2-CDK4 amplification using FISH or Q-PCR be used to supplement IHC analysis when diagnosis of adipose tissue tumors is not possible based on clinical and histologic information alone.     

Nephrogenic syndrome of inappropriate antidiuresis in adults: high phenotypic variability in men and women from a large pedigree

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a recently described genetic cause of hyponatremia in male infants. Whether this X-linked condition could be detected in the adult or also could affect women is unknown. A large five-generation family was identified in which the recently described arginine-vasopressin receptor type 2 (AVPR2) mutation that is responsible for NSIAD was segregated. The proband was a 74-yr-old patient who had a syndrome of inappropriate antidiuresis and whose hyponatremia resisted administration of two AVPR2 antagonists. The phenotype of family members who carry the mutation was investigated. Patients with normal serum sodium were subjected to a water-load test. The previously reported activating missense R137C mutation in the AVPR2 gene in three hemizygous male and four heterozygous female individuals was identified. Except in one woman, spontaneous episodes of hyponatremia or abnormal water-load test were identified in all patients with the mutation, whether male or female. Skewed X inactivation was evidenced in the blood of the asymptomatic woman, which is compatible with preferential inactivation of her mutated allele. NSIAD is not limited to male infants. The diagnosis also should be considered in both male and female adults.     

Bilateral dissection of external iliac artery

External iliac artery (EIA) dissection and especially bilateral involvement is very rare. We report the case of a 49-year-old male intense bicyclist who had presented a dissection of the left EIA responsible for claudication. He underwent an iliofemoral vein graft bypass. The histopathologic examination showed a dissection of the EIA with an otherwise normal arterial wall. Two years after he resumed his sporting activity, a dissection of the right EIA occurred with the onset of claudication. The patient underwent a right iliofemoral vein graft bypass. Histopathologic examination showed the same lesions as on the left side. Bilateral involvement of EIA dissection is possible especially when the mechanism leading to dissection is persistent. An attentive follow-up is thus to consider.