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.     

Naphthalimido derivatives as antifolate thymidylate synthase inhibitors

A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structurally related to the previously reported thymidylate synthase (TS) inhibitor naphthaleins 3, were synthesized and compounds tested for their inhibition of several species of TS. Moreover, their in vitro cytotoxicity together with antimycotic and antibacterial properties were assayed. While no activity was detected in the antibacterial tests, the m-nitro (4ae) and the p-nitro (4af) derivatives were found able to partially inhibit TS at low micromolar concentrations. Introduction of nitro or (substituted)-amino groups in position 4 of the naphthalic ring always led to less active compounds.     

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.     

Critical ovarian hyperstimulation syndrome in a coasted in-vitro fertilization patient

We report an instance of critical ovarian hyperstimulation syndrome in a highly responsive in-vitro fertilization patient despite the preventive measure of a 4 day 'coast' interval during which no gonadotrophins were administered while gonadotrophin-releasing hormone agonist therapy continued until serum oestradiol concentrations fell below 3000 pg/ml.