Enhanced dispersion of atrial refractoriness as an electrophysiological substrate for vulnerability to atrial fibrillation in patients with paroxysmal atrial fibrillation.

Atrial electrical remodeling plays a part in recurrence of atrial fibrillation (AF). It has been related to an increase in heterogeneity of atrial refractoriness that facilitates the occurrence of multiple reentry wavelets and vulnerability to AF. AIM: To examine the relationship between dispersion of atrial refractoriness (Disp_A) and vulnerability to AF induction (A_Vuln) in patients with clinical paroxysmal AF (PAF). METHODS: Thirty-six patients (22 male; age 55+/-13 years) with > or =1 year of history of PAF (no underlying structural heart disease--n=20, systemic hypertension--n=14, mitral valve prolapse--n=1, surgically corrected pulmonary stenosis--n=1), underwent electrophysiological study (EPS) while off medication. The atrial effective refractory period (AERP) was assessed at five different sites--high (HRA) and low (LRA) lateral right atrium, high interatrial septum (IAS), proximal (pCS) and distal (dCS) coronary sinus--during a cycle length of 600 ms. AERP was taken as the longest S1-S2 interval that failed to initiate a propagation response. Disp_A was calculated as the difference between the longest and shortest AERP. A_Vuln was defined as the ability to induce AF with 1-2 extrastimuli or with incremental atrial pacing (600-300 ms) from the HRA or dCS. The EPS included analysis of focal electrical activity based on the presence of supraventricular ectopic beats (spontaneous or with provocative maneuvers). The patients were divided into group A--AF inducible (n=25) and group B--AF not inducible (n=11). Disp_A was analyzed to determine any association with A_Vuln. Disp_A and A_Vuln were also examined in those patients with documented repetitive focal activity. Logistic regression was used to determine any association of the following variables with A_Vuln: age, systemic hypertension, left ventricular hypertrophy, left atrial size, left ventricular function, duration of PAF, documented atrial flutter/tachycardia and Disp_A. RESULTS: There were no significant differences between the groups with regard to clinical characteristics and echocardiographic data. AF was inducible in 71% of the patients and noninducible in 29%. Group A had greater Disp_A compared to group B (105+/-78 ms vs. 49+/-20 ms; p=0.01). Disp_A was >40 ms in 50% of the patients without A_Vuln and in 91% of those with A_Vuln (p=0.05). Focal activity was demonstrated in 14 cases (39%), 57% of them with A_Vuln. Disp_A was 56+/-23 ms in this group and 92+/-78 ms in the others (p=0.07). Using logistic regression, the only predictor of A_Vuln was Disp_A (p=0.05). CONCLUSION: In patients with paroxysmal AF, Disp_A is a major determinant of A_Vuln. Nevertheless, the degree of nonuniformity of AERP appears to be less important as an electrophysiological substrate for AF due to focal activation.     

Conservative management of duodenal trauma: a multicenter perspective

The experience of eight trauma centers with duodenal injuries was analyzed to identify trends in operative management, sources of duodenal-related morbidity, and causes of mortality. During the 5-year period ending December 1988, 164 duodenal injuries were identified. Patient ages ranged from 5 to 78 years. There were 38 Class I, 70 Class II, 48 Class III, four Class IV, and four Class V injuries. Injury mechanism was penetrating in 102 (62%) patients and blunt in 62. Primary repair of the duodenal injury was performed in 117 (71%) patients, including 27 patients also managed with pyloric exclusion and 12 with tube duodenostomy. Duodenal resection with primary anastomosis was used in six (4%) patients and pancreatoduodenectomy was necessary in five (3%). There were 30 (18%) deaths. The cause of death was uncontrolled hemorrhage from severe hepatic or vascular injuries in 22 (73%) patients. In only two (1%) patients could death be attributed to the duodenal injury; each as the result of duodenal repair dehiscence and subsequent sepsis. Duodenal-related morbidity was documented in 29 (18%) patients, including 22 patients with intra-abdominal abscess, six with duodenal fistula, and five with frank duodenal dehiscence. In summary, this analysis demonstrated: 1) the great majority of duodenal injuries can be managed by simple repair; 2) tube duodenostomy is not a mandatory component of operative treatment; 3) pyloric exclusion is a useful adjunct for more complex injuries; 4) pancreatoduodenectomy is rarely necessary for civilian duodenal trauma; 5) morbidity following duodenal trauma is more dependent on associated intra-abdominal injuries than the extent of duodenal trauma; and 6) mortality following duodenal injuries is primarily related to associated vascular and hepatic trauma.     

Surgery for liver trauma

Hepatic injuries are found in 30 per cent of patients undergoing operation after penetrating abdominal wounds and in 15 to 20 per cent of patients undergoing operation after blunt trauma. Signs of blood loss, peritonitis, or peritoneal traverse by a missile prompt early operation in many patients. Stable patients who have suffered stab wounds in proximity to the liver may be safely evaluated by diagnostic peritoneal lavage, whereas CT evaluation is now used in stable patients suffering blunt trauma that may involve the liver. "Simple" techniques of repair such as suture hepatorrhaphy, application of topical agents, or application of fibrin glue suffice in 60 per cent (blunt trauma) to 90 per cent (penetrating trauma) of patients with hepatic injuries. The remainder require "advanced" techniques of repair such as extensive hepatorrhaphy, hepatotomy with selective vascular ligation, resectional debridement with selective vascular ligation, lobectomy or segmentectomy, selective hepatic artery ligation, or perihepatic packing. Using the techniques described, the mortality rate for all patients with hepatic injuries will be approximately 10 per cent, with 75 to 80 per cent of all deaths occurring in the perioperative period from shock or transfusion-related coagulopathies. The most common major complications in survivors are perihepatic abscesses and postoperative hemorrhage, both of which are frequently treated by the interventional radiologist.     

Predictive Value of DXA Appendicular Lean Mass for Incident Fractures,Falls, and Mortality,Independent of Prior Falls,FRAX, and BMD: Findings from the Women's Health Initiative (WHI)

In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX^®) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height²) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height² (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height² was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83–0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98–1.14). There were no associations between ALM/height² and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height², depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height² and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Tolerability of Leukotriene Modifiers in Asthma

The so called leukotriene antagonists or, more accurately, the leukotriene modifiers are a rather heterogeneous set of drugs that work by several mechanisms. Such mechanisms include: (i) 5-lipoxygenase enzyme inhibition (e.g. zileuton); (ii) 5-lipoxygenase-activating-protein inhibition (e.g. quiflapon, BAYx 1005); (iii) LTD4-receptor antagonism (e.g. zafirlukast, montelukast, MK-571, pranlukast). The first leukotriene modifiers tested (L-649,923 and tomelukast) had adverse gastrointestinal effects. Since then, several leukotriene modifiers have been marketed, including zafirlukast, zileuton and montelukast. Zafirlukast has been associated with 8 cases of Churg-Strauss syndrome, although these were probably not caused by zafirlukast. It is more likely that this syndrome is related to the underlying illness, which was masked by corticosteroids, and revealed after zafirlukast-mediated asthma treatment allowed steroid withdrawal and unmasking of underlying vasculitis. The main adverse effects of zileuton include liver function test abnormalities, while montelukast, the most recently marketed, has so far shown minimal adverse effects. Zafirlukast causes a decrease in warfarin clearance and a clinically significant increase in prothrombin time, probably by cytochrome P450 isoenzyme interactions. Moreover, terfenadine decreases zafirlukast maximum serum concentrations. Calcium antagonists, cyclosporin, cisapride and astemizole are metabolised via the cytochrome P450 system, and interactions with leukotriene modifiers can be expected.     

A rational screening and treatment strategy based on the electrocardiogram alone for suspected cardiac contusion.

The charts of 71 patients admitted to one teaching institution over a 4-year period with a primary or secondary diagnosis of "rule out cardiac contusion" and of another 62 admitted to a second institution with more severe injuries and suspicion of cardiac contusion were reviewed to determine if mortality or morbidity would have occurred if all patients with normal electrocardiograms (EKGs) in the emergency department (ED) were discharged (or admitted to unmonitored beds for other injuries). Only 13 patients developed cardiac problems: two elderly patients died in the ED, while the others experienced arrhythmias or, less commonly, pump failure requiring treatment or observation. All 13 had EKG changes present while still undergoing evaluation in the ED: 11 had a specific problem on arrival, 1 developed a problem while still being evaluated in the ED, and the 13th had what was probably an iatrogenic problem. Importantly, 5 of 12 patients had normal creatine phosphokinase-MB fractions, and 5 of 9 had normal echocardiograms. No patient with a normal EKG had subsequent cardiac problems. Operative intervention for other injuries was necessary in 26 patients overall, and there was no cardiac morbidity. We conclude that had the EKG been used as the sole screening tool, approximately 25% of these patients could have been discharged from the ED without missing problems. In addition, management would have been greatly simplified, and the hospital would have realized substantial savings, both in terms of direct costs and in the freeing of valuable and scarce resources.     

Microcystin production by Radiocystis fernandoi (Chroococcales, Cyanobacteria) isolated from a drinking water reservoir in the city of Belém, PA, Brazilian Amazonia region.

During the monitoring of toxic cyanobacteria in the Utinga Reservoir, which is the main drinking water supply for the city of Belém, PA, Brazil, a Radiocystis fernandoi strain (SPC714) was isolated. This non-axenic strain was submitted to a toxicity bioassay with mice and microcystin production analyzed by HPLC-DAD. The species was identified based on cultured and natural preserved material. Morphometric, developmental and reproductive characteristics were analyzed. The strain was cultured in liquid ASM-1 medium, at 25+/-1 degrees C, at an incident irradiance of 20 micromol photon m(-2)s(-1) and constant aeration. At the end of the exponential growth phase, cells were lyophilized and submitted to toxicity tests. The strain showed high toxicity to mice, by intraperitoneal route, with an approximate LD100 of 60 mg kg(-1) of body weight, producing characteristic symptoms of hepatotoxicity. Analyses performed by HPLC-DAD confirmed the production of microcystins, in a concentration of 3.83 microg mg(-1) of lyophilized cells. This is the first reference related to the toxicity of the genus Radiocystis.