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.     

Characteristics of Acute Asthma Patients Attended Frequently Compared with Those Attended Only Occasionally in an Emergency Department

Asthma patients that depend on emergency department (ED) services are generally considered to have extremely poor disease control and prognosis. It is important to identify characteristics related to poor disease control and frequent visits to the ED to apply appropriate clinical management. This study comprised a cross-sectional survey of consecutive patients with asthma exacerbation (age ≥12 years) presenting at the adult ED of a large, tertiary care, university-affiliated hospital over a 2-month period. The frequent visitors (FV) were defined by ≥3 visits to the ED in the preceding year, and the occasional visitors (OV) by ≤2 visits. Eighty-six patients (61 females and 25 males) were included in the study (mean age 38 ± 18 years). Of these patients, 51.2% were FV and 48.8% were OV. Sixty-nine percent had annual income lower than A$3000 and 66.3% had ≤8 years of the formal education. Only 18.6% had used inhaled corticosteroids, 79.1% identified the asthma attack severity, 70.9% increased or initiated inhaled β-agonist, 20.9% increased or initiated steroid therapy, and 55.8% had an asthma action plan for attack. The number of hospital admissions in past year (OR 4.3, P = .02), use of home nebulizer (OR 3.6, P = .05) and the lack of a written asthma action plan (OR 3.3, P = .03) were independently associated with frequent visits to the ED. We conclude that a substantial proportion of the patients that visit the ED are FV. These patients are more likely to have hospital admission in the past year, to use a home nebulizer, and to lack a written asthma action plan. They should be considered the most important target for asthma education.     

The 1989 report of the North American Pediatric Renal Transplant Cooperative Study

This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1–5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6–12 and 12–17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live-donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1-year survival estimate is 0.94. There have been 9 malignancies.A list of all participating centers and the names of the investigators is printed on pages 552–553     

Endothelial Vascular Function in Hypertensive Patients After Renin—Angiotensin System Blockad

It is unclear whether single and combined pharmacologic inhibition of the renin-angiotensin-aldosterone system have similar effects on endothelial function and blood pressure (BP). The authors evaluated 63 hypertensive patients divided into 4 groups (hydrochlorothiazide 25 mg/d; irbesartan [IRBE] 150 mg/d; quinapril [QUIN] 20 mg/d; or IRBE 150 mg/d + QUIN 20 mg/d) and 25 healthy normotensive subjects (normal) followed for 12 weeks. Endothelium-dependent dysfunction measured as flow-mediated dilation at Weeks 0 and 12 were: normal, 11.5%±2.4% vs 13.5%±2.0%; hydrochlorothiazide, 7.3%±2.0% vs 12.8%±3.1%; QUIN, 7.2%±2.8% vs 13.2%±2.1%; IRBE, 7.1%±2.8% vs 13.0%±2.9%; and IRBE + QUIN, 7.5%±1.9% vs 12.8%±3.0%. Nitroglycerin-mediated responses were: normal, 26.0%±1.9% vs 24.0%±2.5%; hydrochlorothiazide, 17.0%±2.2% vs 18.3%±2.6%; QUIN, 17.8%±3.2% vs 23.4%±3.0%; IRBE, 16.8%±3.6% vs 24.7%±2.0%; and IRBE + QUIN, 17.3%±3.0% vs 25.1%±2.5%. Antihypertensive therapy restored BP to normal and improved the endothelium-dependent and -independent dysfunction after renin-angiotensin-aldosterone system blockade. In a further finding, the combined effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade was not superior to the action of either of these treatments separately.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.