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Objectives: This study assessed stroke knowledge and the need for stroke education among children with sickle cell disease (SCD) and their caregivers., Methods: A cross-sectional study was conducted and includes: (1) structured interviews of 44 children with SCD and their 50 caregivers, and (2) a self-administered survey completed by medical directors of 22 SCD centers. The participants were interviewed regarding stroke knowledge and stroke educational materials., Results: Among the caregivers, only 34% named stroke as a complication associated with SCD, 36% were aware that their children were at higher risk, and 46% were not able to identify any warning signs of stroke. Only 11% of the children could accurately describe a stroke. Although 82% of the medical directors provided stroke information to caregivers, only 50% provided stroke educational materials to children. Caregivers and children were interested in receiving information about stroke. The preferred format for the educational material was a pamphlet for adults and a video for the children., Conclusions: Children with SCD, caregivers, and healthcare providers need and desire educational materials about stroke. Educational materials to improve knowledge about stroke may be an important strategy to increase completion of stroke screening tests.

Objective: To test the hypothesis that children with sickle cell disease (SCD) who have an initial stroke temporally unrelated to another medical event are at higher risk for recurrent stroke than are children who had strokes temporally related to medical events., Methods: A retrospective cohort study of children with SCD and stroke who received regularly scheduled blood transfusions for a minimum of 5 years was conducted. Medical records were examined for the documentation of antecedent or concurrent medical events (hypertension, acute chest syndrome, aplastic crisis, fever associated with infection, exchange transfusion) associated with physician contact within 14 days before the initial stroke., Results: A total of 137 pediatric patients from 14 centers were studied. Mean age at first stroke was 6.3 years (1.4 to 14.0 years) with mean follow-up of 10.1 years (5 to 24 years). Thirty-one (22%) patients had a second stroke (2.2 per 100 patient years); 26 patients had an identified medical or concurrent event associated with their initial stroke. None of these patients had recurrent stroke 2 or more years after the initial event. The remaining 111 patients had an ongoing risk of recurrent stroke (1.9 per 100 patient-years) despite long-term transfusions (P =.038)., Conclusions: The absence of an antecedent or concurrent medical event associated with an initial stroke is a major risk factor for subsequent stroke while receiving regular transfusions.

Objectives: Although hydroxyurea is effective in treating adults with sickle-cell anemia (SCA), there is concern that it may adversely affect growth in children. We report the growth characteristics of patients in the Phase I-II pediatric hydroxyurea trial (HUG-KIDS) before and during treatment at the maximum tolerated dose for one year., Study Design: Children and adolescents with SCA (n = 68), aged 5 to 16 years at baseline, reached the maximum tolerated dose and had serial height, weight, and Tanner stage measurements. Data from the Cooperative Study of Sickle Cell Disease (CSSCD) were used for comparison. Mixed-effects models were used to compare serial measurements as a function of age and group., Results: In girls, there were no significant differences in height or weight among the pretreatment, on-treatment, and CSSCD groups. Compared with the CSSCD group, HUG-KIDS boys were heavier starting at age 9 years, and pretreatment HUG-KIDS boys were taller starting at age 7 years. The Tanner stage transitions took place at appropriate ages., Conclusions: Hydroxyurea treatment had no adverse effect on height or weight gain or pubertal development in school-aged children with SCA.

In the phase I/II pediatric hydroxyurea safety trial (HUG-KIDS), school-aged children with sickle cell anemia receiving hydroxyurea at the maximally tolerated dose (MTD) had variable increases in the percentage of fetal hemoglobin (%HbF). To identify predictors of the HbF response to hydroxyurea therapy, baseline clinical and laboratory values (age, sex, hemoglobin concentration, %HbF, reticulocytes, white blood cell [WBC], platelets, and serum chemistries), as well as treatment variables (number of toxicities, noncompliance, MTD dose, and MTD blood counts) were analyzed in 53 HUG-KIDS children who achieved MTD. Baseline %HbF values (P =.001), baseline hemoglobin concentration (P =.01), MTD dose (P =.02), and compliance (P =.02) were significantly associated with a higher %HbF at MTD; in contrast, age, sex, number of toxicities, and other baseline hematologic parameters were not. After adjusting for variations in baseline %HbF, the baseline reticulocyte count (P =.05) and baseline WBC count (P =.05) were also significantly associated with a higher %HbF at MTD. Hydroxyurea-induced increases in the hemoglobin concentration and mean corpuscular volume (both higher absolute values at MTD and larger positive changes from baseline values), as well as hydroxyurea-induced decreases in reticulocytes and WBC count, were significantly associated with a higher %HbF at MTD. These data suggest that selected baseline laboratory parameters, a higher MTD dose with attention to compliance, and greater therapy-related changes in blood counts may predict the HbF response to hydroxyurea therapy for children with sickle cell anemia. The HbF response to hydroxyurea is variable and complex, however, and even children with low baseline %HbF values can develop substantial increases in %HbF at MTD.

To assess the prevalence of nocturnal enuresis in children and adolescents with sickle cell disease (SCD) and associated factors, structured telephone interviews were conducted with primary caregivers of 217 children and adolescents with SCD aged 5 years or older. Prevalence, perceived causes, interventions undertaken, and emotional impact were assessed. Nocturnal enuresis was significantly higher for males (28.2% of males) than for females (11% of females), p = .002, and compared with cited population prevalence rates, nocturnal enuresis was significantly higher for children with SCD, p < .01. SCD was the most common reason given by primary caregivers for enuresis. Primary caregivers used a wide range of interventions for nocturnal enuresis, but few used empirically supported treatments for enuresis or spoke with their health care team about the enuresis. These data suggest that systematic assessment and intervention for nocturnal enuresis must be implemented in the follow-up care of children and adolescents with SCD.

The purpose of this study was to evaluate the efficacy and toxicity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy in patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease (GSD) type 1b. Thirteen patients with neutropenia and/or neutrophil dysfunction secondary to GSD type 1b were treated with rhG-CSF. The effects of therapy on neutrophil numbers and in vitro neutrophil function and on bone marrow cellularity and morphology were studied. The clinical status of the patients and the occurrence of adverse events associated with rhG-CSF use were monitored. Use of rhG-CSF therapy was associated with a significant increase in circulating neutrophil numbers (P <. 01) and an improvement in neutrophil function as assessed in vitro. In addition, rhG-CSF therapy produced a significant increase in marrow cellularity and an increase in myeloid:erythroid (M:E) ratio, indicating stimulation of granulopoeisis. No adverse effects on marrow function were noted; in particular, no myelodysplasia or marrow exhaustion was seen. Use of rhG-CSF therapy was associated with objective and subjective improvements in infection-related morbidity. The therapy was well tolerated, although all patients developed splenomegaly, and 5 patients developed mild hypersplenism that did not require any specific treatment. rhG-CSF therapy is efficacious in the management of neutropenia and neutrophil dysfunction associated with GSD type 1b. Patients on this therapy need to be monitored for hypersplenism. Continued follow-up will be necessary to confirm long-term safety; however, no significant short-term toxicity was noted.

CD8 is a T cell surface glycoprotein that participates in recognition of peptide/MHC class I molecules by binding to their alpha 3 domains. In addition, the cytoplasmic domain of CD8 associates with the intracellular tyrosine kinase p56(lck) (lck) promoting recruitment of lck to the TCR signaling complex. Recent data have suggested also that CD8 may interact with the TCR to promote energetically favorable conformations which increase its ligand binding. We have used the techniques of co-capping and confocal microscopy to ask whether we can detect an association between CD8 and the TCR independently of their binding to MHC class I molecules. We show that capping CD8 heterodimers with antibodies to the CD8 beta polypeptide is significantly more efficient than antibodies to the CD8 alpha polypeptide at inducing co-localization of TCR molecules with CD8, suggesting that there may be preferred conformations of CD8 which stabilize interactions with the TCR. In addition, we show by microscopy that intracellular lck redistributes very efficiently to the area of a CD8 cap, suggesting that there is a stronger association between lck and CD8 than has been proposed from immunoprecipitation analyses.

Hydroxyurea (HU) is the first drug that, under well-organized clinical trials, has shown the potential for altering significantly the clinical severity of sickle cell disease (SCD). The placebo-controlled trial of HU in adult SS hemoglobinopathy patients (the Multicenter Study of Hydroxyurea in Sickle Cell Anemia) reported in May 1995 that HU therapy reduced significantly the frequencies of severe pain episodes, acute chest syndrome, and transfusion. Despite these impressive results, no guidelines have been developed to direct clinicians on the use of HU in adult SCD patients. Small-scale phase II studies in children have reported increases in fetal hemoglobin (HbF) and F-cell levels in response to HU therapy. A larger phase II study, the Pediatric Hydroxyurea Study Group (HUG-KIDS), is under way and is expected to be completed by March 1998. The need for a large-scale placebo-controlled trial in children will be doubtful if no unusual short-term toxicity is demonstrated by HUG-KIDS. Guidelines regarding patient selection, dosing schedules, treatment goals, and short- and long-term monitoring parameters need to be established. The case is made of the organization of a clinical network to register and follow SCD patients treated with HU for long-term toxicity.

The aims of the present study were to determine whether nerves that contain nitric oxide synthase (NOS), calcitonin gene-related peptide (CGRP) or substance P (SP) are present in the human vagina and, if so, to determine the pattern of innervation relative to that of other neurotransmitters, particularly vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY). Surgical specimens of vaginal tissue (n = 10) from pre- and postmenopausal women were fixed and processed for immunohistochemistry of peptides and NOS and for histochemistry of NADPH-diaphorase. SP-immunoreactive nerves were very sparse, being absent from 9 of the 10 tissue samples. For other peptides and NOS, the innervation of the deep arteries and veins was greater than that of blood vessels in the propria. Capillaries in the epithelial papillae also appeared to be innervated by nerves containing NOS, CGRP, NPY and VIP. Beneath the epithelium nerve fibres formed a subepithelial plexus; no nerve cell bodies were seen. The relative density of innervation by immunoreactive fibres was PGP-9.5 > NPY > VIP >> NOS > CGRP > SP. These results imply that nerves that utilise nitric oxide or NPY, VIP or CGRP as a neurotransmitter may play a role in controlling blood flow and capillary permeability in the human vagina. The origin and function of all these nerves is discussed.

The p53 gene has been correlated with disease progression in a number of human malignancies, and p53 abnormalities are found in a high percentage of head and neck squamous cell carcinomas. The objectives of this study were 1. to correlate p53 expression with disease progression in squamous cell carcinoma of the head and neck (SCCHN), and 2. to determine whether there are site-specific differences in p53 expression. Primary lesions and/or lymph node metastases from 147 patients with invasive SCCHN were immunostained for p53 overexpression. Expression of p53 was similar (42% versus 43%) in primary lesions and lymph node metastases. Expression also did not vary significantly by site in the head and neck. In conclusion, increased p53 expression did not correlate with disease progression in our series of patients with invasive SCCHN. The finding of a lack of increased expression with disease spread to lymph nodes supports the belief that p53 alterations occur early in head and neck carcinogenesis.

A 48-year-old male patient underwent mitral annuloplasty for severe mitral regurgitation secondary to myxomatous degeneration of the mitral valve, with ruptured chordae. Intraoperative transesophageal echocardiography showed satisfactory repair. The patient developed postoperative atrial fibrillation and clinical and echocardiographic evidence of left ventricular outflow obstruction. Following conversion to sinus rhythm, the evidence for left ventricular outflow obstruction markedly improved. We suggest that postoperative atrial fibrillation may precipitate dynamic left ventricular outflow obstruction following mitral annuloplasty.

Acute glomerulonephritis is a syndrome characterized by the abrupt onset of hematuria often accompanied by proteinuria, hypertension, edema, and renal dysfunction. Acute glomerulonephritis can be subdivided into primary glomerular disease, postinfectious glomerulonephritis, and glomerulonephritis associated with systemic disease. With few exceptions, the underlying mechanism of acute glomerulonephritis is an immunologic one. To differentiate clinically the specific etiology of the glomerulonephritis, attention must be focused on the presence of signs or symptoms of systemic disease, changes in the environment of the patient, family history of renal disease, and recent history of infectious disease.

School health education has an important role to play in discouraging teenage smoking. However, it is likely that government, the general public and students themselves will be less favorable toward smoking education in major tobacco-producing states. To determine whether students whose families are involved in tobacco production hold more favorable attitudes toward smoking and smoke more than children whose families are not involved, 1,322 Kentucky public school students in grades five-12 were surveyed regarding smoking attitudes and behavior. Twenty-one percent (276) of the students reported that their families were involved in tobacco production. Tobacco family students held more favorable attitudes toward smoking and a larger percentage of these children smoked and smoked more than their nontobacco family peers. These differences were statistically significant at the 0.05 level. Tobacco family children appear to be at high risk for smoking-related disease and may prove resistant to some antismoking messages. Developing effective smoking education programs in major tobacco states in an important challenge for school health education.