A randomized trial comparing wireless capsule endoscopy with push enteroscopy for the detection of small-bowel lesions

BACKGROUND & AIMS: Wireless capsule endoscopy is a new, painless method of imaging the entire small bowel. It has not been compared with push enteroscopy. We compared the sensitivity, specificity, and safety of capsule and push enteroscopy in detecting small-bowel lesions. METHODS: Nine to 13 radiopaque, colored beads (3-6 mm diameter) were sewn in random order inside 9 canine small bowels, half within the first meter, and confirmed on x-ray. After recovery, the number, order, and color of beads were assessed in 23 capsule enteroscopies and 9 push enteroscopies in a random order. The surgeons, push enteroscopists, capsule video interpreters, and pathologist were blinded to the others' findings. RESULTS: The capsules identified more beads than push enteroscopy (median, 6 [range, 2-9] vs. 3 [range, 2-6 beads]; P < 0.001). The sensitivity of the capsule was 64% compared with 37% for push enteroscopy. The specificity was 92% for capsule enteroscopy and 97% for push enteroscopy. The capsules identified significantly more beads beyond the reach of the push enteroscope (median, 4 [range, 2-7] vs. 0; P < 0.0001). Hair, ingested plastic, ulceration, submucosal swelling, and worms were clearly identified by the capsule. The capsules passed safely through the animals with no significant histologic findings. CONCLUSIONS: Wireless capsule endoscopy detected more abnormalities in the small bowel than push enteroscopy.     

Fragment D-dimer levels: an objective marker of vaso-occlusive crisis and other complications of sickle cell disease

Although abnormalities in coagulation tests have been reported during vaso-occlusive crises in patients with sickle cell disease, objective, readily performed laboratory tests that document the occurrence of this complication have not been available. We examined the relationship between fibrin D-dimer levels and the occurrence of complications in patients with sickle cell disease, using a commercially available latex bead agglutination assay. The patients were either asymptomatic, hospitalized for vaso-occlusive crisis, or had other complications of sickle cell disease including leg ulcers, chronic cholecystitis, aseptic necrosis, joint pain and infection. Fifty-seven percent of 187 samples on 96 patients had elevated levels of fibrin D-dimer. Ninety percent of 75 samples from asymptomatic patients were negative for fibrin D-dimer (less than 1 microgram/ml) but 97% of 29 samples from patients with vaso-occlusive crisis and 85% of 83 samples from patients with other complications of sickle cell disease were positive. In serial studies, worsening or amelioration in clinical complications were reflected in increasing or decreasing levels of fibrin D-dimer, respectively. The molecular species of fibrin identified by the latex agglutination test was shown to be fragment D-dimer by successive immunoprecipitation and protein blot analysis. We conclude that the complications of sickle cell disease, including vaso-occlusive crisis, result in the production of fibrin D-dimer, and its detection may be used as a marker for the presence of the complication.     

Proliferative and inflammatory factors in the vitreous of patients with proliferative diabetic retinopathy

Purpose:

The purpose was to measure the concentrations of various cytokines and growth factors (including vascular endothelial growth factor [VEGF] and pigment epithelium-derived factor [PEDF]) in the vitreous of patients with proliferative diabetic retinopathy (PDR) and to investigate interaction between inflammatory and proliferative factors in the genesis of PDR.

Materials and Methods:

Vitreous samples from 32 eyes with PDR and 25 eyes without diabetes mellitus and signs of DR (control) were collected. Vitreous concentrations of VEGF, PEDF, monocyte chemotactic protein-1 (MCP-1), interleukin-4 (IL-4), IL-6, IL-8, IL-10, IL-17A, and secretory immunoglobulin A (sIgA) were simultaneously measured using enzyme-linked immunoassay.

Results:

Vitreous levels of VEGF, PEDF, IL-17A, IL-6, IL-8, IL-4, and sIgA were significantly (Π < 0.05) higher in eyes with PDR compared to control. The concentration of VEGF was more than 17-times higher than in control, and the concentration of PEDF was not changed oppositely and was also higher (1.45-times) compared to control, that may indicate disturbances of compensatory mechanisms in angiogenesis regulation in PDR. Significant (P < 0.05) positive correlations were observed between vitreous concentrations of VEGF and IL-17A (r = 0.45), VEGF and IL-8 (r = 0.48), VEGF and IL-4 (r = 0.51), PEDF and IL-17A (r = 0.48), PEDF and IL-8 (r = 0.59), MCP-1 and PEDF (r = 0.72), MCP-1 and IL-8 (r = 0.45), IL-4 and IL-17A (r = 0.65), IL-4 and IL-8 (r = 0.71), IL-8 and IL-17A (r = 0.59).

Conclusions:

Significantly raised levels of inflammatory and proliferative factors and numerous positive correlations between them may demonstrate a significant role of activation of vascular proliferation and local inflammation in the pathogenesis of PDR.     

Indication of an involvement of interleukin-1 beta converting enzyme- like protease in intramedullary apoptotic cell death in the bone marrow of patients with myelodysplastic syndromes

Our previous studies using in situ end labeling (ISEL) of fragmented DNA revealed extensive apoptotic cell death in the bone marrows (BM) of patients with myelodysplastic syndromes (MDS) involving both stromal and hematopoietic cells. In the present report we show greater synthesis of interleukin-1 beta (IL-1 beta) in 4 hour cultures of density separated BM aspirate mononuclear (BMAM) cells from MDS patients as compared to the cultures of normal BM from healthy donors or lymphoma patients (1.7 +/- 0.37 pg/10(5) cells, n = 29 v 0.42 +/- 0.24 pg/10(5) cells, n = 11, respectively, P = .049). Further, these amounts of IL-1 beta in MDS showed a significant correlation with the extent of apoptosis detected by ISEL in corresponding plastic embedded BM biopsies (r = .480, n = 30, P = .007). In contrast normal BMs did not show any correlation between the two (r = .091, n = 12, P = .779). No significant correlation was found between the amounts of IL-1 beta and % S-phase cells (labeling index; LI%) in MDS determined in BM biopsies using immunohistochemistry following in vivo infusions of iodo- and/or bromodeoxyuridine. Neither anti-IL-1 beta antibody nor IL-1 receptor antagonist blocked the apoptotic death of BMAM cells in 4 hour cultures (n = 5) determined by ISEL (apoptotic index; AI%), although the latter led to a dose-dependent accumulation of active IL-1 beta in the culture supernatants. On the other hand, a specific tetrapetide- aldehyde inhibitor of ICE significantly retarded the apoptotic death of BMAM cells at 1 mumol/L in 5/6 MDS cases studied (AI% = 2.99 +/- 0.30 in controls v 1.58 +/- 0.40 with ICE-inhibitor, P = .05) and also reduced the levels of active IL-1 beta synthesized (5.59 +/- 2.63 v 2.24 +/- 0.93 pg/10(6) cells, respectively). In normal cells, neither IL-1 blockers nor the ICE inhibitor showed any effect on the marginal increase in apoptosis observed in 4 hour cultures. Our data thus suggest a possible involvement of an ICE-like protease in the intramedullary apoptotic cell death in the BMs of MDS patients.     

Method for High Accuracy Differential Pressure Measurements Using Fluid-Filled Catheters

The advantage of measuring differential pressure using fluid-filled catheters is that the system is relatively inexpensive, but the readings are not accurate and affected by the common mode pressure (CMP) distortion. High accuracy differential pressure measurements are required in various biomedical applications, such as in fluid-dynamic test rigs, or in the cath-lab, from cardiac valves efficacy to functional assessment of arterial stenoses. We have designed and built a unique system in which the pressure difference was measured along the fluid flow inside a rigid circular tube using a fluid-filled double-lumen catheter. The differential pressure measurements were taken across two side-holes near the catheter distal tip, spaced apart by 3 cm. The goal was to overcome the CMP error, which significantly distorted the output differential pressure signal and to formulate a restoration factor. A restoration formula was developed based on simultaneous gauge pressure measurements, and was tested in several different cases. Several representative cases are presented and show that the common mode artifact was reduced by factors of 12–27. The restored pressure gradient signal was validated using direct pressure drop measurements, and showed very good agreement.     

The area of the pressure-flow loop for assessment of arterial stenosis: a new index.

This study describes a novel method for assessing stenotic severity, based on simultaneous pressure and flow wave measurements. Pressure and flow measurements were performed in latex and rubber tubes, and in a clinically-used vascular graft. Pressure waves were recorded at several degrees of stenosis and at different distances proximal to the stenosis. Pressure wave versus flow wave was plotted. Internal pressure-flow loop area (PFLA), loop slope and pressure-axis intercept were calculated. Values of these three indices significantly increased with increasing degrees of stenosis P < 0.001). Similar phenomenon was observed during in-vivo experiments. Polynomial functions were fitted, resulting in an excellent PFLA variable/ percent stenosis correlation, independent of distance between sensor and stenosis (R2 > 0.96). In addition, tube compliance was measured and found to correlate with the polynomial coefficients (/R/ > 0.9). This innovative approach could significantly contribute to detecting and evaluating arterial stenoses, and to characterize the elasticity of the artery.