Neutropenia following IVIG therapy in pediatric patients with immune-mediated thrombocytopenia

It has been observed that some children with immune-mediated thrombocytopenia (ITP) who are treated with intravenous immunoglobulin (IVIG) experience a decline in their absolute neutrophil count (ANC). The aim of this study was to investigate the incidence of neutropenia following IVIG therapy in a large cohort of children with ITP. This retrospective comparative cohort study determined the incidence of neutropenia in 104 patients (110 treatment courses) admitted for ITP to the Children's Hospital of Philadelphia from January 2000 to October 2003. Post-treatment ANCs were compared between patients who received IVIG and patients who received anti-D immunoglobulin. The incidence of neutropenia in each group was analyzed using the Fisher exact test. Pretreatment ANCs were not significantly different between the two treatment groups (P = 0.72). Neutropenia (ANC < 1,500/microL), developed during 18 of 64 (28%) treatment courses with IVIG, compared with 0 of 46 (0%) treatment courses with anti-D immunoglobulin (P < 0.001). This study suggests that IVIG may cause neutropenia commonly in children with ITP. While this is likely to be a transient condition, its recognition may affect clinical decisions such as the need for a bone marrow examination.     

An evaluation of the breastfeeding support skills of midwives and voluntary breastfeeding supporters using the Breastfeeding Support Skills Tool (BeSST)

The promotion of breastfeeding has been established as a global public health issue. Despite this global agenda, breastfeeding initiation and duration rates remain low in many countries. The lack of provision of adequate support to the breastfeeding mother is an important contributory factor to shorter duration of breastfeeding. Health professionals and voluntary breastfeeding supporters are in a prime position to work collaboratively to provide comprehensive support to the breastfeeding mother. However, a comparative evaluation of the breastfeeding support skills of voluntary breastfeeding supporters and health professionals has never been conducted. This study aimed to assess the breastfeeding support skills of midwives and Breastfeeding Network (BfN) supporters. Breastfeeding support skills were assessed using a between-subjects design conducted with 15 midwives and 15 BfN supporters in the north-west of England. Support skills were measured using the prevalidated Breastfeeding Support Skills Tool (BeSST), a questionnaire and video tool. Total scores on the BeSST were significantly higher in the BfN group (mean = 42.5 +/- 6.4 SD) than in the midwife group (mean = 30.7 +/- 8.2 SD) [t (26.5) = 4.4, P < 0.0001]. The BfN group has the breastfeeding support skills necessary to provide adequate assistance for breastfeeding mothers. An interagency and interdisciplinary collaborative model is crucial to developing a coherent and cohesive approach to the support infrastructure for breastfeeding women.     

Tophaceous gout: quantitative evaluation by direct physical measurement

OBJECTIVE: The absence of accepted standardized methods for monitoring tophaceous gout limits the ability to track tophus progression or regression. This multicenter study assessed intra- and interrater reproducibility of a simple and direct physical measurement. METHODS: The quantitative evaluation was the area (mm2) of each measurable tophus and was determined independently by 2 raters on 2 occasions within 10 days. Intra- and interrater reproducibilities were determined by calculating mean differences and average percentage differences (APD) in measurements of areas for the same tophus at each of 2 visits and by each rater, respectively. RESULTS: Fifty-two tophi were measured in 13 subjects: 22 on the hand/wrist, 16 on the elbow, and 14 on the foot/ankle. The mean (+/- SD) difference in tophus areas between visits was -0.2 +/- 835 mm2 (95% CI -162 to 162 mm2) and the mean (+/- SD) APD was 29% +/- 33%. The mean (+/- SD) APD between raters was 32% +/- 27%. The largest variations in measurements were noted for elbow tophi and variations were least for well demarcated tophi on the hands. CONCLUSION: This simple and reproducible method can be easily utilized in clinical trials and in practice as a measure of efficacy of urate-lowering treatment in tophaceous gout. Among factors contributing to variability in these measurements were the anatomic site of tophi and rater experience with the method. Restriction of measurements to well circumscribed hand or foot tophi could improve reliability, but major changes, as expected with effective therapy, can clearly be documented with this simple technique.     

Clinical, microbiological, and immunological characteristics in HIV-infected subjects at risk for disseminated Mycobacterium avium complex disease: an AACTG study

The clinical, microbiologic, and immunologic parameters in HIV-infected subjects first presenting with disseminated Mycobacterium avium complex (DMAC) were determined. Four HIV-positive groups not yet on DMAC treatment were enrolled: 19 subjects with CD4 lymphocyte counts < or =50/microl thought to have DMAC on clinical grounds; 18 subjects newly found to have a positive blood culture for MAC; 25 asymptomatic controls (CD4 cell counts < or =50); and 25 asymptomatic controls (CD4 counts 100-250/microl). Outcome measures include comparisons between groups for clinical characteristics; results of cultures from blood, marrow, and gastrointestinal and respiratory tracts; immunological markers from staining of marrow and flow cytometry of circulating lymphocytes; and cytokine production of PBMCs. Only 21% of the 19 patients entered on suspicion of having DMAC grew MAC from blood or marrow. Neither clinical presentation nor laboratory tests differentiated those culture-positive from those culture-negative patients. However, prior PCP or multiple other opportunistic infections were more common in the DMAC group. MAC was isolated from 82% of marrow and 50% of blood specimens from the DMAC group. Respiratory or gastrointestinal colonization was present in 36% of DMAC subjects, but only 5% of non-DMAC subjects with CD4 counts <50 cells/microl. CD8+ cells were more frequent in bone marrow, and CD4 cells recognizing MAC antigen were more frequent in blood from DMAC subjects vs. controls. Results suggest an early stage of tissue dissemination preceding persistent bacteremia, and mucosal entry without persistence of colonization. MAC-specific T cell responses apparently develop and persist during DMAC, but are dysfunctional or too infrequent to prevent persistence.     

Predictors of outcome in perinatal arterial stroke: a population-based study

Some infants with perinatal arterial ischemic stroke (PAS) experience development of cerebral palsy (CP), epilepsy, and cognitive impairment, whereas others have a normal outcome. Previous prognostic studies rarely have included all diagnosed cases of PAS within a population. Among 199,176 infants born within Kaiser Permanente from 1997 to 2002, we electronically identified head imaging reports and physician diagnoses suggesting stroke. The diagnosis of PAS was confirmed by review of brain imaging and medical records. Presentation of PAS was considered delayed if symptoms were only noted after 28 days. Outcomes were determined by chart review. Of 40 infants with PAS, 36 were observed over 12 months. Abnormal outcomes included CP (58%), epilepsy (39%), language delay (25%), and behavioral abnormalities (22%). A delayed presentation was associated with increased risk for CP (relative risk [RR], 2.2; 95% confidence interval [CI], 1.2-4.2). Radiological predictors of CP included large stroke size (RR, 2.0; 95% CI, 1.2-3.2) and injury to Broca's area (RR, 2.5; 95% CI, 1.3-5.0), internal capsule (RR, 2.2; 95% CI, 1.1-4.4), Wernicke's area (RR, 2.0; 95% CI, 1.1-3.8), or basal ganglia (RR, 1.9; 95% CI, 1.1-3.3). Among infants with PAS, specific radiological findings and a lack of symptoms in the newborn period are associated with increased risk for CP.     

Genetic linkage of autosomal dominant progressive supranuclear palsy to 1q31.1

Progressive supranuclear palsy (PSP) is a disorder of unknown pathogenesis. Familial clusters of PSP have been reported related to mutations of protein tau. We report the linkage of a large Spanish family with typical autosomal dominant PSP to a new locus in chromosome 1. Four members of this family had typical PSP, confirmed by neuropathology in one case. At least five ancestors had similar disease. Other members of the family have incomplete phenotypes. The power of the linkage analysis was increased by detecting presymptomatic individuals with 18F-fluoro-dopa and 18F-deoxyglucose positron emission tomography. We screened the human genome with 340 polymorphic markers and we enriched the areas of interest with additional markers. The disease status was defined according to the clinical and positron emission tomography data. We excluded linkage to the tau gene in chromosome 17. PSP was linked, in this family, to one area of 3.4 cM in chromosome 1q31.1, with a maximal multipoint < OD score of +3.53. This area contains at least three genes, whose relevance in PSP is unknown. We expect to further define the gene responsible for PSP, which could help to understand the pathogenesis of this disease and to design effective treatment.     

Macrocephaly, corpus callosum morphology, and autism

Although the cause of autism is undetermined, a general consensus has been that some type of early aberrant neural development underlies the disorder. Given the increased prevalence of macrocephaly in autism, one theory of abnormal neural development implicates early brain growth resulting in larger brain and head size in autism. Surface area measurements of the midsagittal section of the corpus callosum can be used as an index of neural development and white-matter integrity because the corpus callosum is the major white-matter structure that interconnects the two cerebral hemispheres. The purpose of this study was to obtain corpus callosum surface area, shape, and contour in a sample of non-mentally retarded autistic subjects with macrocephaly (n = 12) and compare them with those of matched (n = 8), typically developing control subjects with benign macrocephaly. No significant differences were found in surface area, shape, or contour between groups, nor did corpus callosum surface area relate to measures of IQ or picture vocabulary. These findings suggest no unique difference in overall regional corpus callosum surface area in autism with macrocephaly.     

Video and CD-ROM as a training tool for performing neurologic examinations of 1-year-old children in a multicenter epidemiologic study

In lieu of traditional training of examiners to identify cerebral palsy on a neurologic examination at age 1 year, we proposed an alternative approach using a multimedia training video and CD-ROM we developed after a two-step validation process. We hypothesized that use of CD-ROM interactive training will lead to reliable and valid performance of the neurologic examination by both pediatric neurologists and nonpediatric neurologists. All examiners were asked to take one of six interobserver variability tests found on the CD-ROM on two occasions. In the first interobserver variability evaluation, 89% (531 of 594) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the two items that had a 60% correct rate, the correct response rate rose to 93% (114 of 123). In the second interobserver variability evaluation, 88% (493 of 560) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the four items that had a 70% correct rate, the correct response rate rose to 96% (104 of 108). Interactive CD-ROM examination training is an efficient and cost-effective means of training both neurologists and non-neurologists to perform structured neurologic examinations in 1-year-old children. It provides an effective means to evaluate interobserver variability, offers a route for feedback, and creates an opportunity to reevaluate variability, both immediately and at periodic intervals.     

Service use and outcomes of first-admission patients with psychotic disorders in the Suffolk County Mental Health Project

OBJECTIVE: The purpose of the study was to examine the inpatient and outpatient service use and 4-year outcomes of newly admitted psychotic patients during a period of rapid change in the provision of psychiatric services in a well-defined catchment area in New York State in the 1990s. METHOD: Subjects were 573 participants of the Suffolk County Mental Health Project. This group comprised patients with psychotic disorders first admitted between September 1989 and August 1995 to 12 inpatient facilities across Suffolk County, N.Y., and followed for up to 48 months. The subjects' service use, course of illness, symptomatic outcomes, suicide risk, homelessness risk, and satisfaction with care were compared across admission years. RESULTS: The length of inpatient stays decreased significantly across the years. However, the number of outpatient visits and therapy sessions did not vary. Although the patients admitted in later years were more symptomatic at admission to their first hospitalization, their course and outcomes over the follow-up period were not worse and they were not less satisfied with their care, compared with the patients admitted in earlier years. CONCLUSIONS: The clinical characteristics of patients and the role of inpatient care in the management of patients with psychotic disorders gradually changed during the 1990s. These changes, however, were not associated with changes in the use of outpatient services or outcomes. Nevertheless, shorter hospital stays and the presence of more severely ill patients highlight the need for more attention to linkage to aftercare and enhancement of support networks in the community.