Microfluidic auto-alignment of protein patterns for dissecting multi-receptor crosstalk in platelets.

Cell adhesion plays a critical role in many cellular functions, such as the hemostatic/thrombotic process, inflammatory reactions, and adaptive immune response. Many cell adhesion processes involve crosstalk between multiple ligand-receptor systems through intracellular signaling. To elucidate such crosstalk requires analysis of the synergistic or antagonistic effects of binding and signalling of multi-receptor species. Current techniques for these analyses, e.g., atomic force microscopy (AFM) and biomembrane force probe (BFP) assays, are either labor-intensive, low-throughput, or limited in the types of ligands they can interrogate. Circumventing these limitations requires a technique for manipulating ligand interactions with and measuring the functional response of a population of cells. In this work, we have developed a microfluidic platform for studying the binding and signaling of multi-receptor species by separating their actions in space and time. The platform directs cells through a single channel and uses sequentially presented ligands for pre-processing and stimulating cells, followed by reporting of cell activation states and functional consequences. Our method precisely patterns multiple proteins in different spatial regions without gaps. We demonstrate the utility of our method by using this platform to analyze the crosstalk between platelet receptors, glycoprotein Ib and IIb-IIIa, in the context of platelet adhesion and signaling under flow. We show the clinical utility of this platform by applying it to analyze whole blood samples and to assess differences in the activation of platelets between healthy and diabetic patients.

Neonatal thyrotoxicosis and conjugated hyperbilirubinemia.

We report a case of neonatal thyrotoxicosis secondary to maternal Graves' disease. In addition to presenting with symptoms of hyperthyroidism, the infant developed conjugated hyperbilirubinemia, a finding not previously reported in children with this condition.

A newborn with a goiter and thyroid dyshormonogenesis.

The report presents a case of a full-term male infant born with an enlarged anterior neck mass, of a healthy woman with normal thyroid function and negative thyroid antibodies. After treatment, his free thyroxine and total triiodothyronine levels normalized. A defect in thyroid hormone synthesis was considered the cause of the hypothyroidism.

Improving management of diabetic ketoacidosis in children.

OBJECTIVE: The optimal fluid management for diabetic ketoacidosis (DKA) is uncertain. In an effort to simplify DKA therapy, we revised the treatment protocol in our institution to use a simpler method of calculating fluid needs, use fluids with higher sodium concentration, and allow glucose concentration to be adjusted easily. We performed a retrospective study to determine the effects of these revisions. DESIGN: We compared patients treated with traditional and revised protocols (~220 and ~300 patients, respectively, over consecutive 2.75-year intervals). Sixty patient records were randomly selected from the first group (30 treated with each of 2 protocol versions) and 30 from the second group. Biochemical and clinical parameters were analyzed. RESULTS: Patients selected for detailed analysis were similar in demographics and initial laboratory measurements. Patients treated under the revised fluid protocol received less total fluid, needed fewer intravenous fluid changes, were treated at less cost, and resolved acidosis more rapidly than patients treated under the original protocols. The rate of cerebral edema (0.3%-0.5%) was unchanged. CONCLUSION: A DKA protocol that necessitates less fluid delivery and fewer calculations simplifies therapy and is associated with more rapid correction of acidosis.

A variation of vitamin D deficiency in children.

We report three children presenting with hypocalcemia, hyperphosphatemia, elevated levels of parathyroid hormone, low concentrations of 25(OH)-vitamin D, normal to elevated concentrations of 1,25(OH)2-vitamin D, and normal radiographs. Although these findings led to consideration of parathyroid hormone resistance, clinical and biochemical findings remained normal after discontinuation of therapy, suggesting a variation of vitamin D deficiency.

Time course of recovery of adrenal function in children treated for leukemia.

OBJECTIVE: Many protocols for treating children with early B-cell lineage acute lymphoblastic leukemia use 28 consecutive days of high-dose glucocorticoids during induction therapy. We prospectively studied the effects of this therapy on adrenal function. STUDY DESIGN: Ten children with early B-cell lineage acute lymphoblastic leukemia were evaluated by cosyntropin (corticotropin (1-24)) stimulation testing before initiation of dexamethasone therapy and every 4 weeks thereafter until adrenal function returned to normal. RESULTS: All 10 patients had normal adrenal function before dexamethasone treatment and insufficient adrenal responses 24 hours after completing therapy. Each child felt ill for 2 to 4 weeks after completing therapy. Although 7 patients recovered normal adrenal function after 4 weeks, 3 patients did not have normal adrenal function until 8 weeks after discontinuing therapy. Statistically significant differences in both basal and corticotropin-stimulated cortisol levels were noted when comparing tests performed at baseline, 24 hours after completing therapy, and 4 weeks after completing therapy. CONCLUSION: High-dose dexamethasone therapy, a standard treatment for early B-cell acute lymphoblastic leukemia, can cause adrenal insufficiency lasting more than 4 weeks after cessation of treatment. This problem might be avoided by tapering doses of glucocorticoids and providing supplemental glucocorticoids during periods of increased stress.

Prepubertal gynecomastia: indirect exposure to estrogen cream.

OBJECTIVE: To describe the clinical course of 3 prepubertal boys who presented with gynecomastia resulting from indirect exposure to a custom-compounded preparation of estrogen cream used by each child's mother. METHODOLOGY: Each child was initially referred to the Children's Medical Center of Dallas' Endocrinology Center and followed for over 1 year. RESULTS: All 3 boys presented with gynecomastia and elevated estradiol levels. Two had accelerated growth and advanced bone ages. Within 4 months after each child's mother discontinued use of the topical estrogen preparation, each child's gynecomastia regressed and estradiol levels returned to normal. CONCLUSION: Indirect exposure to excessive amounts of topical estrogen may cause gynecomastia, rapid changes in growth, and advanced bone age in prepubertal children. Because custom-compounded topical estrogen preparations are not regulated by the Food and Drug Administration and may contain high concentrations of estrogen, we recommend that women requiring estrogen use an alternate form of estrogen delivery if they are in frequent close contact with children.

Acute flank pain: an unusual presentation of a spinal AVM.

The authors report the case of a 6-year-old boy with a spinal cord arteriovenous malformation (AVM) who presented with acute flank pain and a delayed onset of paraplegia. An early diagnosis of a spinal cord AVM was made difficult by the absence of neurological findings on initial evaluation. Included is a description of his clinical course, and the presentation of spinal AVMs to the emergency physician is discussed.

Subcutaneous granuloma annulare: a review of 47 cases.

OBJECTIVE: The purpose of this study was to review and provide information regarding characteristic findings, diagnostic work-up, course, and treatment associated with subcutaneous granuloma annulare (SGA). MATERIALS AND METHODS: The medical and surgical records of 47 patients with SGA, who were diagnosed and treated at our institution over the past 26 years, were reviewed. RESULTS: All patients presented with a painless soft tissue nodule(s) of the extremities or scalp. The mean age at presentation was 4.3 years, with 19% of the patients encountering one or more recurrences. The mean time of recurrence was 10 months. Definitive diagnosis in all patients was made by biopsy, and no patient progressed to any recognized systemic illness or connective tissue disorder. CONCLUSIONS: SGA is a benign inflammatory skin lesion that should be considered in the differential diagnosis of a subcutaneous nodule(s) of the scalp and/or distal extremities of an otherwise healthy child. Because the nodule(s) are benign and may recur with or without surgical biopsy, reassurance is the best management.