IL-33 is induced in undifferentiated, non-dividing esophageal epithelial cells in eosinophilic esophagitis.

The molecular and cellular etiology of eosinophilic esophagitis (EoE), an emerging tissue-specific allergic disease, involves dysregulated gene expression in esophageal epithelial cells. Herein, we assessed the esophageal expression of IL-33, an epithelium-derived alarmin cytokine, in patients with EoE. IL-33 protein was markedly overexpressed within the nuclei of a subpopulation of basal layer esophageal epithelial cells in patients with active EoE compared to control individuals. IL-33 exhibited dynamic expression as levels normalized upon EoE remission. IL-33-positive basal epithelial cells expressed E-cadherin and the undifferentiated epithelial cell markers keratin 5 and 14 but not the differentiation marker keratin 4. Moreover, the IL-33-positive epithelial cells expressed the epithelial progenitor markers p75 and p63 and lacked the proliferation markers Ki67 and phospho-histone H3. Additionally, the IL-33-positive cells had low expression of PCNA. IL-33 expression was detected in ex vivo-cultured primary esophageal epithelial cells in a subpopulation of cells lacking expression of proliferation markers. Collectively, we report that IL-33 expression is induced in an undifferentiated, non-dividing esophageal epithelial cell population in patients with active EoE.

A retrospective review of 4767 consecutive spinal anesthetics: central nervous system complications. Perioperative Outcomes Group.

Serious neurologic complications rarely occur after spinal anesthesia. Historically, the reported frequency of persistent sensory or motor deficits has ranged from 0.005% to 0.7%. However, the introduction of small-gauge needles and new local anesthetics and intrathecal adjuvants makes it necessary to reevaluate the frequency of neurologic complications after spinal anesthesia. This study is a retrospective review of 4767 consecutive spinal anesthetics performed between June 1987 and June 1990. Mean patients age was 65 +/- 15 yrs. There were 3560 (74.7%) men and 1207 (25.3%) women. A preexisting neurologic condition was present in 481 (10.1%) cases. The surgical procedures were genitourinary and lower extremity orthopedic in 4348 (91.2%) cases. A paresthesia was elicited during needle placement in 298 (6.3%) cases. Six patients reported pain upon resolution of the spinal anesthetic (persistent paresthesia). Four persistent paresthesias resolved within 1 wk; the remaining two resolved in 18-24 mo. The presence of a paresthesia during needle placement significantly increased the risk of persistent paresthesia (P < 0.001). There, were also two infectious complications. One patient with recent (treated) urosepsis underwent a urologic procedure under spinal anesthesia and subsequently developed a disc space infection. The second patient developed a paraspinal abscess. Both were treated with surgical drainage and antibiotics and remained neurologically intact. There were 62 (1.3%) patients with a postdural puncture headache, including 23 (0.5%) who underwent an epidural blood patch. These results are similar to those of previously published reviews and demonstrate the continued safety of spinal anesthesia.

Neurologic complications of 603 consecutive continuous spinal anesthetics using macrocatheter and microcatheter techniques. Perioperative Outcomes Group.

Recent case reports of cauda equina syndrome after continuous spinal anesthesia have led to a reevaluation of the indications and applications of this regional anesthetic technique. However, few large studies have formally investigated the frequency of neurologic complications using macro- and microcatheter (smaller than 24 gauge) techniques. This retrospective review examines 603 continuous spinal anesthetics, including 127 administered through a 28-gauge microcatheter, performed between June 1987 and May 1992. The surgical procedure was orthopedic in 397 of 476 (83.4%) macrocatheter patients. All microcatheter patients were parturients. Three patients reported pain (persistent paresthesia) postoperatively. In two patients, the symptoms resolved in 4 days; the other patient was discharged 8 days postoperatively with residual foot pain. There was also one patient with aseptic meningitis and one patient with a sensory cauda equina syndrome (still present after 15 mo). There were 58 (9.6%) patients with a postdural puncture headache (PDPH), including 42 of 127 (33.1%) patients in the microcatheter group. An epidural blood patch was performed in 41 (6.8%) patients. The frequency of neurologic complications, excluding PDPH, is similar to those in published reviews. However, PDPH in microcatheter patients is more frequent than previously reported.

Comparison of screening methods in the detection of bladder cancer.

PURPOSE: We prospectively evaluate and compare the sensitivity and specificity of urine cytology, BTA stat, NMP22, fibrin/fibrinogen degradation products (FDP), telomerase, chemiluminescent hemoglobin and hemoglobin dipstick to detect bladder cancer. MATERIALS AND METHODS: Single voided specimens were obtained from 57 patients with bladder cancer, and 139 without evidence of bladder malignancy on cystoscopy or a negative biopsy of indeterminate lesions. A cytology report was available for 125 patients and interpreted independently. BTA stat, NMP22 and FDP were analyzed according to manufacturer specifications. The telomerase assay was performed on cells collected from urine by centrifugation in preparation for polymerase chain reaction based amplification using the telomeric repeat amplification protocol assay. The chemiluminescent screening assay for hemoglobin in urine uses the pseudoperoxidase activity of hemoglobin on hydrogen peroxide and subsequent oxidation of 7-dimethylaminonaphthalene-1,2-dicarbonic acid hydrazide to generate chemiluminescence emission. Hemoglobin dipstick was interpreted as positive if the hemoglobin content in the urine was trace or greater. RESULTS: Overall sensitivity with urine cytology, BTA stat, NMP22, FDP, telomerase, chemiluminescent hemoglobin and the hemoglobin dipstick was 44, 74, 53, 52, 70, 67 and 47%, respectively. Specificity with cytology, telomerase and FDP was high (95, 99 and 91%, respectively) but BTA stat, NMP22 (optimized), chemiluminescent hemoglobin (optimized) and the hemoglobin dipstick demonstrated lower specificity of 73, 60, 63 and 84%, respectively. Stepwise logistic regression analysis revealed that for all tumors, and within each tumor grade and stage telomerase had the strongest association with bladder cancer among all tests (69% overall concordance). Telomerase was also positive in 91% of the patients (10 of 11) with carcinoma in situ. CONCLUSIONS: Urinary telomerase had the highest combination of sensitivity and specificity (70 and 99%, respectively) for bladder cancer screening in these patients. It was the strongest predictor with superior accuracy in patients with grade 1 and noninvasive tumors (pTa), and extremely useful in patients with carcinoma in situ. Telomerase appears to be promising and outperformed cytology, BTA stat, NMP22, FDP, chemiluminescent hemoglobin and hemoglobin dipstick in the prediction of bladder cancer.