T-cell activation Rho GTPase–activating protein expression varies with inflammation location and severity in Crohn's disease

Background

The T-cell activation Rho GTPase–activating protein (TAGAP) gene has a regulatory role in T cell activation. We have previously suggested a correlation between the TAGAP-associated single nucleotide polymorphism rs212388 and protection from anal sepsis in Crohn's disease (CD) patients. The present study sought to evaluate TAGAP's expression in colonic tissue of CD patients with varying disease severity and location.

Materials and methods

Five transverse, 17 left, and five sigmoid colectomy specimens from 27 CD patients with varying disease severity (16 male, mean age at diagnosis 26.4 ± 2.2 y) were evaluated for TAGAP messenger RNA expression. Fisher exact, Mann–Whitney, and Welch two-sample t-tests were used for statistical evaluation. Immunohistochemistry confirmed results.

Results

Patients with tissue demonstrating lower TAGAP messenger RNA expression (less than the overall mean) were younger at diagnosis (mean age 21.1 ± 6.3 versus 32.5 ± 13 y, P = 0.009). Increased TAGAP expression was seen in moderate or severely diseased tissue versus tissue with no or mild disease (RQ = 1.3 ± 0.34 versus 0.53 ± 0.09, P = 0.050). This was the most dramatic in the sigmoid colon (P = 0.041). TAGAP expression was increased in more distal tissue with a significant difference seen when comparing transverse versus sigmoid colon with moderate or severe disease (0.51 ± 0.14 versus 1.9 ± 0.37, P = 0.049).

Conclusions

Colonic expression of TAGAP in CD patients varied according to disease severity and location, being the most elevated in patients with severe disease in the sigmoid colon. Whether changes in TAGAP expression are a result of disease response or inherent to the disease pathophysiology itself remains to be determined. This gene warrants further investigation for its role in CD.     

Impact of clinical history on fracture detection with radiography

The effect of knowledge of localizing symptoms and signs in the detection of fractures was studied. Forty radiographs of the extremities were examined twice by seven radiologists; the sessions were separated by 4 months. In 26 cases, a subtle fracture was present; 14 cases were normal. In half of the cases at each session, the precise location of pain, tenderness, or swelling was provided. The observer was asked to determine if the case was normal or abnormal (provide the exact location of the fracture) and to indicate the degree of confidence in the diagnosis. Responses were converted to a numeric scale for analysis. Analysis of receiver operator characteristic parameters indicates that clues regarding location of trauma facilitate detection of fractures. The improvement is based largely on an increased true-positive rate without an increased false-positive rate, regardless of the decision criteria of the radiologist (overall willingness to "overread" or "underread"). This has direct clinical applicability and reinforces the plea of radiologists for precise clinical information.     

Lower extremity revascularization with in situ saphenous vein for critical ischemia

Over a 3 1/2 year period, 55 limbs were revascularized with in situ saphenous vein bypass grafts in 49 patients. Ninety-five percent of grafts were constructed in patients with critical ischemia for limb salvage, and 5 percent were constructed for debilitating claudication. The proximal anastomosis was performed in the groin in all patients. The distal graft was taken to the popliteal artery in 45 percent and to a tibial or isolated popliteal segment in 55 percent, with 55 percent of the grafts having single-vessel runoff. The perioperative mortality rate was 7 percent. The primary immediate patency rate was 91 percent and the secondary immediate patency rate was 98 percent at 1 month. The cumulative patency rate at 42 months was 85.4 percent overall, 86.6 percent for the tibial grafts, and 84 percent for the popliteal grafts. The cumulative limb salvage rate was 100 percent for the popliteal grafts, 90 percent for the tibial grafts, and 94.5 percent overall. All of the patients were followed and 3 required secondary revision. In situ vein bypass is a technically demanding procedure that can be performed successfully in high-risk patients with limbs with minimal runoff and can yield very high long-term patency and limb salvage rates in a community hospital setting.     

Membrane-associated sickle hemoglobin: a major determinant of sickle erythrocyte rigidity

Micropipette aspiration tests on single erythrocytes have previously shown that the static rigidity (membrane shear modulus) of oxygenated sickle cells increased with increasing hemoglobin concentration, whereas the rigidity of normal cells was independent of hemoglobin concentration. Moreover, it was observed that after mechanical extension, sickle cells exhibited persistent deformation more frequently and to a greater extent than normal cells. To ascertain if differences in association of normal and sickle hemoglobin with the membrane could account for these observations, we measured rheologic properties of normal membranes reconstituted with sickle hemoglobin and sickle membranes reconstituted with normal hemoglobin. The static rigidity of normal ghosts reloaded with sickle hemoglobin was higher than those of either normal ghosts reloaded with normal hemoglobin or native normal cells. On the other hand, the increased rigidity of native sickle cells decreased to near-normal values following reconstitution with normal hemoglobin. Furthermore, we observed that normal ghosts reconstituted with sickle hemoglobin exhibited persistent bumps after mechanical extension, but no bumps formed on normal ghosts reconstituted with normal hemoglobin. Moreover residual bumps were not produced on sickle cells reloaded with normal hemoglobin. Since mechanical characteristics peculiar to sickle cells could be induced in normal cells by incorporation of sickle hemoglobin, and since normal characteristics could be restored to sickle cells by incorporation of normal hemoglobin, we suggest that the interaction of sickle hemoglobin with the cell membrane is responsible for augmented static rigidity of oxygenated sickle erythrocytes.     

Validation of pulse dynamic blood pressure measurement by auscultation

BACKGROUND: The accurate measurement of arterial blood pressure is essential for the diagnosis and treatment of hypertension. The development of new automated methods of measurement that provide reliable determinations of blood pressure should be valuable in the assessment of hypertension not only in the clinic or hospital but also, in the home for self-monitoring. DESIGN: We evaluated a noninvasive method for the measurement of systolic and diastolic blood pressures in 132 subjects. METHODS: Measurements obtained using the pulse dynamic method of blood pressure determination were validated with simultaneous manual measurements. Two qualified nurses used Korotkoff sounds to determine systolic (phase I) and diastolic (phase IV) blood pressures according to the Association for the Advancement of Medical Instrumentation 1987 guidelines. RESULTS: Inter-nurse variability was 2.7 +/- 4.1 mmHg (mean +/- SD) for systolic blood pressure and 4.0 +/- 3.7 mmHg for diastolic blood pressure and correlations were r = 0.98 and 0.94, respectively. We observed excellent agreement between auscultatory and pulse dynamic methods for systolic (127 +/- 21 versus 132 +/- 20 mmHg; r = 0.97) and diastolic (72 +/- 10 versus 71 +/- 10 mmHg; r = 0.89) blood pressures. Bland-Altman analysis demonstrated that there was a mean difference (reference-device) between the two methods of - mmHg (pulse dynamic value higher) and SD of 5 mmHg for systolic blood pressure and a mean difference of 1 mmHg (pulse dynamic value lower) and SD of 5 mmHg for diastolic blood pressure. CONCLUSION: The results of this study demonstrate that this noninvasive method of measurement of blood pressure is accurate and reliable and should therefore be appropriate for the evaluation of hypertension both in the home and in clinical settings.