The purpose of this study was to characterize a large group of infants with complete DiGeorge anomaly and to evaluate the ability of thymus transplantation to reconstitute immune function in these infants. DiGeorge anomaly is characterized by varying defects of the heart, thymus, and parathyroid glands. Complete DiGeorge anomaly refers to the subgroup that is athymic (< 1%). The characteristics of 54 subjects at presentation and results from 44 consecutive thymus transplantations are reported. Remarkably, only 52% had 22q11 hemizygosity and only 57% had congenital heart disease requiring surgery. Thirty-one percent developed an atypical phenotype with rash and lymphadenopathy. To date, 33 of 44 subjects who received a transplant survive (75%) with post-transplantation follow-up as long as 13 years. All deaths occurred within 12 months of transplantation. All 25 subjects who were tested 1 year after transplantation had developed polyclonal T-cell repertoires and proliferative responses to mitogens. Adverse events developing after transplantation included hypothyroidism in 5 subjects and enteritis in 1 subject. In summary, diagnosis of complete DiGeorge anomaly is challenging because of the variability of presentation. Thymus transplantation was well tolerated and resulted in stable immunoreconstitution in these infants. (Blood. 2007; 109: [4539][4540][4541][4542][4543][4544][4545][4546][4547]

Background Paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia are recognized clinically when patients seek treatment for symptoms due to recurrent arrhythmias; atrial fibrillation also increases the risk of stroke. The frequency with which asymptomatic arrhythmias occur in patients with these arrhythmias is unknown.Methods and Results Twenty-two patients with paroxysmal atrial fibrillation (n=8) or paroxysmal supraventricular tachycardia (n=14) were studied for 29 days with two different ambulatory ECG-monitoring techniques to measure the relative frequency of asymptomatic and symptomatic arrhythmias. All class I antiarrhythmic drugs, calcium channel blockers, ,8-blockers, and digitalis were withheld. Sustained asymptomatic arrhythmia events (defined as lasting at least 30 seconds) were documented using continuous ambulatory ECG monitoring once weekly for a total of 5 of the 29 study days; symptomatic arrhythmia events were documented using transtelephonic ECG monitoring for all 29 days of the study. In the group of patients with paroxysmal atrial fibrillation, asymp-P aroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia are common arrhythmias that may be treated with antiarrhythmic drugs when patients have symptoms. Patients who are affected with these disorders have sinus rhythm that is punctuated by episodic recurrences of their arrhythmias. The sequence of these recurrent arrhythmia events can be described in mathematical terms as a "stochastic process," which is a series of events occurring in time in accordance with probabilistic laws.' In this study, we used methods developed to study stochastic processes to estimate the average rate of asymptomatic arrhythmia events in groups of patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia. MethodsThe study sample consisted of 22 ambulatory outpatients (7 men and 15 women with mean±SD age of 47±+17 years) who were being followed in the Clinical Research Unit Arrhythmia Clinic because they had a paroxysmal supraventricular ar- tomatic arrhythmia events occurred significantly more frequently than symptomatic arrhythmia events; the mean rates, expressed as events/100 d/patient (95% confidence interval), were 62.5 (40.4, 87.3) and 5.2 (2.7, 9.0) (P<.01); the ratio of the mean rates was 12.1 (5.8, 26.4). In contrast, in the group of patients with paroxysmal supraventricular tachycardia, asymptomatic arrhythmia events were significantly less frequent than symptomatic arrhythmia events; the mean rates were 0.0 (0.0, 5.3) and 7.4 (5.0, 10.6) (P=.02). The ratio of the mean rates was 0.0 (0.0, 0.8).Conclusions In a group of patients with paroxysmal atrial fibrillation, sustained asymptomatic atrial fibrillation occurs far more frequently than symptomatic atrial fibrillation. However, it is not known whether asymptomatic atrial fibrillation is a potential risk factor for stroke even when patients are not having symptomatic arrhythmias. (Circulton. 1994;89:.224-227.) Key Words * a...

Efforts to develop an effective vaccine against ricin are focused on the engineering of attenuated and stable recombinant forms of the toxin’s enzymatic A subunit (RTA). While several candidate antigens are in development, vaccine design and efficacy studies are being undertaken in the absence of a fundamental understanding of those regions of RTA that are critical in eliciting protective immunity. In this present study, we produced and characterized a collection of monoclonal antibodies (MAbs) directed against five distinct immunodominant regions on RTA, and used these MAbs to identify several key neutralizing epitopes on the toxin. Protective MAbs were directed against α-helices located in RTA folding domains 1 and 2, whereas non-neutralizing antibodies recognized random coils and loops that were primarily confined to folding domain 3. These data offer insights into the immunodominant and structural determinants on RTA that give rise to protective immunity, and for the first time provide an immunological rationale for ricin vaccine design.

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Introduction: In order to facilitate scale-up of antiretroviral therapy (ART) in Malawi, innovative and pragmatic models have been developed to optimize the efficiency of HIV service delivery. In particular, three models of differentiated care have emerged for stable patients: adjusted appointment spacing through multi-month scripting (MMS); fast-track drug refills (FTRs) on alternating visits; and community ART groups (CAGs) where group members rotate in collecting medications at the facility for all members. This study aimed to assess the extent to which ART patients in Malawi are differentiated based on clinical stability and describe the characteristics and costs associated with the models of differentiated care offered.Methods: A mixed methods process evaluation was conducted from 30 purposefully selected ART facilities. Cross-sectional data for this evaluation was collected between February and May 2016. The following forms of data collection are reported here: structured surveys with 136 health care workers; reviews of 75,364 patient clinical records; 714 observations of visit time and flow; and 30 questionnaires on facility characteristics.Results: Among ART patients, 77.5% (95% confidence interval [CI] 74.1–80.6) were eligible for differentiated models of care based on criteria for clinical stability from national guidelines. Across all facilities, 69% of patients were receiving MMS. In facilities offering FTRs and CAGs, 67% and 6% of patients were enrolled in the models, respectively. However, eligibility criteria were used inconsistently: 72.9% (95% CI 66.3–78.6) of eligible patients and 42.3% (95% CI 33.1–52.0) ineligible patients received MMS. Results indicated that patient travel and time costs were reduced by 67%, and the unit costs of ART service delivery through the MMS, FTR and CAG models were similar, representing a reduction of approximately 10% in the annual unit cost of providing care to stable patients that receive no model.Conclusions: MMS is being implemented nationally and has already generated cost savings and efficiencies in Malawi for patients and the health system, but could be improved by more accurate patient differentiation. While expanding FTRs and CAGs may not offer significant further cost savings in Malawi, future studies should investigate if such alternative models lead to improvements in patient satisfaction or clinical outcomes that might justify their implementation.