Diagnosing acute appendicitis using a nonoral contrast CT protocol in patients with a BMI of less than 25

The objective of this study was to compare the accuracy for the diagnosis of appendicitis in patients presenting to the emergency department (ED) with acute, nontraumatic abdominal pain and a body mass index (BMI) of less than 25 before and after the implementation of a nonoral contrast computed tomography (CT) protocol with intravenous contrast. The IRB approved this HIPAA-compliant retrospective study; informed consent was waived. This study included 736 adult patients with a BMI of less than 25 presenting to our ED with acute, nontraumatic abdominal pain over two distinct 6-month time periods. An oral and intravenous contrast-enhanced protocol was utilized in the first cohort (group A), and an intravenous contrast-enhanced protocol without oral contrast was utilized in the second cohort (group B). Three abdominal fellowship-trained readers retrospectively reviewed all CT studies and electronic medical records, including surgical/pathology reports that served as reference standards. Group A consisted of 359 patients; 41 patients had surgically proven appendicitis. The sensitivity and specificity of the readers for diagnosing appendicitis in group A ranged from 95.2–100 and 98.1–99.5 %, respectively. Group B consisted of 372 patients; 39 had surgically proven appendicitis. The sensitivity and specificity of the readers in group B ranged from 92.0–100 and 98.6–100 %, respectively. There were no statistically significant differences in sensitivity or specificity for CT scans performed in groups A and B. In patients with a BMI of less than 25, an intravenous contrast-enhanced CT protocol without oral contrast demonstrates similar accuracy to an intravenous contrast-enhanced protocol with oral contrast for diagnosing acute appendicitis.     

Multifunctional role of Erk5 in multiple myeloma

Multiple myeloma is characterized by the accumulation of terminally differentiated B cells in the bone marrow, due to increased proliferation and restricted apoptosis of the myelomatous clone. Here we have studied the participation of a novel mitogen-activated protein kinase (MAPK) route, the extracellular signal-regulated kinase 5 (Erk5) pathway, in the regulation of myeloma cell proliferation and apoptosis. Erk5 was expressed in cells isolated from patients and in myeloma cell lines. The myeloma growth factor interleukin 6 (IL-6) activated Erk5, and this activation was independent of Ras and Src. Expression of a dominant-negative form of Erk5 restricted the proliferation of myeloma cells and inhibited IL-6-dependent cell duplication. This dominant-negative form also sensitized myeloma cells to the proapoptotic action of dexamethasone and PS341. The latter compound caused a profound decrease in the amount of endogenous Erk5 and was less effective in inducing apoptosis when the level of Erk5 was increased by transfection of Erk5. These results place the Erk5 route as a new regulatory signaling pathway that affects multiple myeloma proliferation and apoptosis.     

Human colonic myogenic dysfunction induced by mucosal lipopolysaccharide translocation and oxidative stress

Background

Impairment of gastrointestinal motility is frequently observed in patients with severe infection.

Aim

To assess whether exposure of human colonic mucosa to pathogenic lipopolysaccharide affects smooth muscle contractility.

Methods

Human colonic mucosa and submucosa were sealed between two chambers, with the luminal side facing upwards and covered with Krebs solution, with or without lipopolysaccharide from a pathogenic strain of Escherichia coli (O111:B4; 1000 ng/mL), and with the submucosal side facing downwards into Krebs. The solution on the submucosal side was collected following 30-min mucosal exposure to Krebs without (N-undernatant) or with lipopolysaccharide (lipopolysaccharide undernatant). Undernatants were tested for lipopolysaccharide and hydrogen peroxide levels and for their effects on smooth muscle cells in the presence of catalase, indomethacin or MG132.

Results

Smooth muscle cells incubated with N-undernatant had a maximal contraction of 32 ± 5% that was reduced by 62.9 ± 12% when exposed to lipopolysaccharide undernatant. Inhibition of contraction was reversed by catalase, indomethacin and MG132. Lipopolysaccharide levels were higher in the lipopolysaccharide undernatant (2.7 ± 0.7 ng/mL) than in N-undernatant (0.45 ± 0.06 ng/mL) as well as hydrogen peroxide levels (133.75 ± 15.9 vs 82 ± 7.5 nM respectively).

Conclusions

Acute exposure of colonic mucosa to pathogenic lipopolysaccharide impairs muscle cell contractility owing to both lipopolysaccharide mucosal translocation and production of free radicals.     

Rosetting of human T lymphocytes with goat red blood cells: Effect of treatment with 2-aminoethylisothiouronium bromide (AET) and comparison with AET treated sheep red blood cells

In vitro treatment of goat red blood cells (GRBCs) with the sulphydryl compound 2-aminoethylisothiouronium bromide (AET) increases their specific reactivity with human T lymphocytes without affecting the specificity of the reaction. AET-GRBCs bind to only part of T lymphocytes rosetting with AET-sheep red blood cells (SRBCs): the receptors for both types of RBCs are very similar if not identical, but display higher affinity for AET-SRBCs than for AET-GRBCs. Rosetting of T lymphocytes with AET-GRBCs may be useful to enumerate T lymphocyte subsets in patients with abnormality of the immune system and to fractionate T lymphocyte subpopulations.     

Oxidative stress response involving induction of protective enzymes in Candida dubliniensis.

Candida dubliniensis is a yeast species closely related to Candida albicans, but in contrast to C. albicans, limited information is available on the virulence factors of this important fungal pathogen. The objective of the present study was to determine if this species was able to evoke an adaptive response to oxidants. C. dubliniensis, treated with a low concentration of either H(2)O(2) or methyl viologen (a superoxide generating agent), mounts an adaptive response that results in increased survival against lethal doses of both oxidants. This response was characterized by the induction of enzymes with known antioxidant function. C. dubliniensis strains were less resistant to oxidants than C. albicans, displaying higher susceptibility to their toxic effects. The adaptive response described here might be responsible, among other factors, for the ability of this pathogen to cause infections in individuals with impaired immunity.     

In systemic sclerosis macrovascular damage of hands digital arteries correlates with microvascular damage

Objective

To assess morphology and blood flow of the proper palmar digital arteries (PPDA) by Color Doppler Ultrasonography (CDUS) and its relationship with nailfold videocapillaroscopy (NVC), skin blood perfusion and digital arteries pulsatility of hands in SSc patients and healthy controls.

Methods

CDUS, NVC, Laser Doppler Perfusion Imaging (LDPI) and photoplethysmography (PPG) were performed in 36 systemic sclerosis (SSc) patients and 20 healthy controls.

Results

CDUS was pathologic in 69% of patients with SSc and in none of healthy controls (p < 0.0001). SSc patients with low vascular damage (early capillaroscopic pattern) have a normal morphology of PPDA, but the blood flow, evaluated by peak systolic velocity (PSV) and end diastolic velocity (EDV), is reduced and vascular resistance, measured by resistive index (RI) and pulsatility index (PI), increased. At this stage the LDPI mean perfusion and digital artery pulsatility, evaluated by PPG, were reduced. The US changes appear with microvasculare damage progression (active and late capillaroscopic patterns), while the PPDA blood flow progressively decreases (PSV and EDV decreased, RI and PI increased). The macrovascular damage correlates with disease duration. Anti-topoisomerase I represents an independent predictive factor for macrovascular damage. We not observed any association between digital ulcer history, pulmonary fibrosis and US findings.

Conclusion

PPDA blood flow dysfunction is already present in early disease. Structural macrovascular damage progresses with worsening of SSc microangiopathy.     

Detection of coronary disease patients at high risk for recurrent myocardial infarction by elevated plasma inactive creatine kinase B protein levels

The diagnostic and prognostic significance of plasma inactive creatine kinase B protein (CK-Bi) levels measured by radioimmunoassay was determined in various ischemic myocardial syndromes. In 120 stable angina patients free of pain at time of blood sampling, mean CK-Bi level was 114 ± 42 (SD) μg-equiv/ml; 195 μg-equiv/ml (95% confidence interval) represented upper limit of normal. In seven coronary artery disease (CAD) patients atrial pacing-induced ischemia was not associated with increased coronary sinus CK-Bi. Of 201 consecutive patients with suspected acute infarction (AMI), 45 developed ECG criteria of transmural AMI with concomitant increased plasma CK-Bi levels (498 ± 133, range 372–718 μg-equiv/ml). Elevated CK-Bi levels in evolving transmural AMI were detected before raised CK enzyme activity. Elevated plasma CK-Bi levels also occurred in acute pericarditis and in unstable angina. In the 84 patients not developing ECG changes or elevated plasma CK activity, their plasma CK-Bi levels were also normal and no coronary events occurred in the next 6 months. The remaining 55 patients had nontransmural AMI, with 15 also having elevated plasma CK and CK-Bi levels, of whom six developed re-AMI in the next 3 months. In the other 40 nontransmural AMI patients, plasma CK-Bi levels (350 ± 65 μg-equiv/ml, range 228 to 445) increased significantly without associated CK activity rise, and 24 developed re-AMI (three fatal) in the next 6 months. These data suggest that: (1) plasma CK-Bi protein radioimmunoassay measurement provides a sensitive means for detecting myocardial necrosis or inflammation and (2) elevated plasma CK-Bi levels in coronary disease patients during myocardial ischemic pain may afford identification of a CAD clinical subset at high risk of subsequent AMI.