Optical mapping of ventricular defibrillation in isolated swine right ventricles: demonstration of a postshock isoelectric window after near-threshold defibrillation shocks.

BACKGROUND: Investigators who studied ventricular defibrillation by use of optical mapping techniques failed to observe an initial defibrillation event (isoelectric window or quiescent period) shown by electrode mapping studies. This discrepancy has important implications for the mechanisms of defibrillation. The purpose of the present study was to demonstrate an optical equivalent of an isoelectric window after a near-threshold defibrillation shock. Methods and Results-- We studied 10 isolated, perfused swine right ventricles. Upper limit of vulnerability was determined by shocks on T waves. A 50% probability of successful defibrillation (DFT50) was determined with an up-down algorithm. Immediately after unsuccessful defibrillation shock, new wavefronts were generated. When the shock strength was low, immediate reinitiation of reentry and ventricular fibrillation might occur without a postshock isoelectric window. However, if the shock strength was within 50 V of DFT50 (near-threshold), a synchronized activation occurred, followed by organized repolarization that ended 64+/-18 ms after shock. After a period of quiescence (18+/-24 ms), activation recurred 83+/-33 ms after shock and reinitiated ventricular fibrillation. Similar patterns of activation, including a quiescent period, were observed after shock was applied on the T wave of the paced beat that induced ventricular fibrillation. Upper limit of vulnerability correlated well with DFT50. CONCLUSIONS: In isolated swine right ventricles, an optical equivalent of an isoelectric window exists after near-threshold defibrillation shocks. These findings support the idea that a near-threshold defibrillation shock terminates all activation wavefronts but fails to halt ventricular fibrillation because the same shock reinitiates ventricular fibrillation after an isoelectric window.

Patterns of wave break during ventricular fibrillation in isolated swine right ventricle.

Several different patterns of wave break have been described by mapping of the tissue surface during fibrillation. However, it is not clear whether these surface patterns are caused by multiple distinct mechanisms or by a single mechanism. To determine the mechanism by which wave breaks are generated during ventricular fibrillation, we conducted optical mapping studies and single cell transmembrane potential recording in six isolated swine right ventricles (RV). Among 763 episodes of wave break (0.75 times x s(-1) x cm(-2)), optical maps showed three patterns: 80% due to a wave front encountering the refractory wave back of another wave, 11.5% due to wave fronts passing perpendicular to each other, and 8.5% due to a new (target) wave arising just beyond the refractory tail of a previous wave. Computer simulations of scroll waves in three-dimensional tissue showed that these surface patterns could be attributed to two fundamental mechanisms: head-tail interactions and filament break. We conclude that during sustained ventricular fibrillation in swine RV, surface patterns of wave break are produced by two fundamental mechanisms: head-tail interaction between waves and filament break.

Measuring complete diagnostic evaluation in colorectal cancer screening.

Complete diagnostic evaluation, or CDE (i.e., a colonoscopy or combined barium enema X-ray and flexible sigmoidoscopy) is recommended for individuals who have an abnormal screening fecal occult blood test result. Accurate measures of CDE use are needed in colorectal cancer (CRC) screening programs. This study compares the sensitivity and specificity of different methods for measuring CDE recommendation and performance. We identified 17 primary-care practices with 120 patients who had a positive fecal occult blood test result in a CRC screening program operated by a managed-care organization. Approaches used to measure CDE recommendation and performance included external chart audit (ECA) only; internal chart audit (ICA) only; administrative data review (ADR) of electronic claims data; ICA plus ADR; and ECA plus ADR (the "gold standard"). Sensitivity and specificity of each method were assessed relative to CDE recommendation and performance as measured by ECA plus ADR. For CDE recommendation, sensitivity measures were ECA only, 0.926; ICA only, 0.790; ADR only, 0.617; and ICA plus ADR, 0.901. The specificity of each method for CDE recommendation was no less than 0.95. In terms of CDE performance, sensitivity measures were ECA only, 0.877; ICA only, 0.790; ADR only, 0.877; and ICA plus ADR, 0.965. The specificity of each method for CDE performance was 1.0. The ICA-plus-ADR method was a highly sensitive and specific measure of CDE use. This method should be considered in situations that involve primary-care physician follow-up of patients with abnormal CRC screening test results.

Mechanisms of ventricular fibrillation induction by 60-Hz alternating current in isolated swine right ventricle.

BACKGROUND: The mechanisms by which 60-Hz alternating current (AC) can induce ventricular fibrillation (VF) are unknown. METHODS AND RESULTS: We studied 7 isolated perfused swine right ventricles in vitro. The action potential duration restitution curve was determined. Optical mapping techniques were used to determine the patterns of activation on the epicardium during 5-second 60-Hz AC stimulation (10 to 999 microA). AC captured the right ventricles at 100+/-65 microA, which is significantly lower than the direct current pacing threshold (0.77+/-0.45 mA, P:<0.05). AC induced ventricular tachycardia or VF at 477+/-266 microA, when the stimulated responses to AC had (1) short activation CLs (128+/-14 ms), (2) short diastolic intervals (16+/-9 ms), and (3) short diastolic intervals associated with a steep action potential duration restitution curve. Optical mapping studies showed that during rapid ventricular stimulation by AC, a wave front might encounter the refractory tail of an earlier wave front, resulting in the formation of a wave break and VF. Computer simulations reproduced these results. CONCLUSIONS: AC at strengths less than the regular pacing threshold can capture the ventricle at fast rates. Accidental AC leak to the ventricles could precipitate VF and sudden death if AC results in a fast ventricular rate coupled with a steep restitution curve and a nonuniform recovery of excitability of the myocardium.

Downstaging of advanced rectal cancer following combined preoperative chemotherapy and high dose radiation.

PURPOSE: To assess the potential downstaging of advanced rectal cancer with combined preoperative chemoradiation. METHODS AND MATERIALS: Thirty-one patients with fixed rectal cancers (stage > or = cT3) were treated with concomitant preoperative chemotherapy and high-dose radiation in an effort to improve resectability. Three (10%) patients had partially fixed low rectal cancers, 24 (77%) patients had fixed tumors, and 4 (13%) had advanced fixation with pelvic sidewall invasion. Radiation was delivered to the whole pelvis using shaped anterior and posterior and lateral fields to 45 Gy followed by a boost to the tumor. Median total radiation dose was 55.8 Gy. Chemotherapy consisted of low dose continuous infusion of 5-FU (200-300 mg/m2/day) for the duration of radiation treatment. All 31 patients underwent surgical resection of tumor 6-8 weeks following treatment. Median follow up is 24 months (range 9-60). RESULTS: Twenty-three (74%) of the tumors were clinically downstaged following preoperative treatment. Of 24 fixed cancers, 11 (46%) became mobile, 6 (25%) became partially fixed, and 7 remained fixed. Of the four tumors with advanced fixation, two (50%) became mobile and two (50%) no longer had tumor extension to the pelvic sidewall. Two of the three initially partially fixed cancers became mobile and one remained partially fixed. Following surgery, the pathologic postradiation T-stages were as follows: T0: 10%, T1: 0%, T2: 32%, T3: 42%, and T4:16%. Seven patients (23%) were also node-positive (T0-2: 2, T3: 4, T4: 1), and two patients (6%) had liver metastases at surgery. Preoperative chemoradiation was well tolerated. There was no significant hematological toxicity. Acute grade 3 gastrointestinal toxicity was seen in six patients requiring a short hospitalization for dehydration and/or abdominal discomfort. No patient developed grade 4 toxicity. Five patients (16%) developed local recurrence of disease (T0-2: 0/13, T3: 1/13, and T4: 4/5). The actuarial 3-year survival is 68%. CONCLUSIONS: Concomitant preoperative chemoradiation using low dose continuous infusional 5-FU for advanced rectal cancer is relatively safe with acceptable morbidity. This approach is associated with considerable clinical and pathologic downstaging of cancer. Tumor resectability is improved with potential for improved local control of disease and survival.

Immunotherapy of lung cancer.

Review of the literature on immunotherapies in lung cancer provides hope that an impact on the natural history of this disease can be achieved. Although the various trials of adjuvant nonspecific immunostimulation with BCG, levamisole, and C parvum are not sufficiently detailed to permit meta-analysis, in aggregate the data suggest a slight improvement in disease-free survival for treated patients. Perhaps these adjuvants combined with more immunogenic TAAs could be formulated into a vaccine that would be effective in preventing recurrence of lung cancer after surgical excision. Ongoing research in molecular technology may provide adequate quantities of such products so that this hypothesis can be tested in appropriate patient populations.

Nodular regenerative hyperplasia: a cause of ascites and hepatomegaly after chemotherapy for leukemia.

Tender hepatomegaly and ascites occurred in a young woman receiving cytosine arabinoside and daunorubicin for acute myelogenous leukemia. Whereas veno-occlusive disease was suspected clinically, liver biopsy showed nodular regenerative hyperplasia with no evidence of hepatic vein abnormalities. It is postulated that nodular regenerative hyperplasia can be initiated by hepatotoxicity of chemotherapy agents used to treat leukemia and/or that these agents exacerbate clinical manifestations of this histological abnormality. Nodular regenerative hyperplasia should be added to the list of liver problems occurring in patients with leukemia.

A case of group B streptococcal pyomyositis.

The group B streptococcus is an opportunistic pathogen that causes a variety of serious infections including bacteremias, puerperal sepsis, and neonatal meningitis. Group B streptococcal infections of muscle are rare. We report here an unusual case of group B streptococcal pyomyositis. Pyomyositis arises predominantly from infections caused by Staphylococcus aureus and, occasionally, Streptococcus pyogenes. Because of the rarity of pyomyositis in temperate climates, the common lack of localizing signs or symptoms, and the frequently negative blood cultures, considerable delay often precedes the diagnosis of pyomyositis; in fact, the infection has been initially misdiagnosed as muscle hematoma, cellulitis, thrombophlebitis, osteomyelitis, or neoplasm. Diagnosis may be greatly aided by radiologic techniques that can demonstrate the sites of muscle enlargement and the presence of fluid collections. The response to antibiotics is usually rapid, but resolution of the infection may require aspiration of deeply situated muscle abscesses. This report describes a diabetic patient with an unusual presentation of pyomyositis that mimicked an acute abdomen.