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Increased circulating AC133+ CD34+ endothelial progenitor cells in children with hemangioma

Kleinman, Mark E; Tepper, Oren M; Capla, Jennifer M; Bhatt, Kirit A; Ceradini, Daniel J; Galiano, Robert D; Blei, Francine; Levine, Jamie P; Gurtner, Geoffrey C
Hemangioma is the most common soft-tissue tumor of infancy. Despite the frequency of these vascular tumors, the origin of hemangioma-endothelial cells is unknown. Circulating endothelial progenitor cells (EPCs) have recently been identified as vascular stem cells with the capacity to contribute to postnatal vascular development. We have attempted to determine whether circulating EPCs are increased in hemangioma patients and thereby provide insight into the role of EPCs in hemangioma growth. METHODS AND RESULTS: Peripheral blood mononuclear cells (PBMCs) were isolated from hemangioma patients undergoing surgical resection (N = 5) and from age-matched controls (N = 5) undergoing strabismus correction surgery. PBMCs were stained with fluorescent-labeled antibodies for AC133, CD34, and VEGFR2/KDR. Fluorescent-labeled isotype antibodies served as negative controls. Histologic sections of surgical specimens were stained with the specific hemangioma markers Glut1, CD32, and merosin, to confirm the diagnosis of common hemangioma of infancy. EPCs harvested from healthy adult volunteers were stained with Glut1, CD32, and merosin, to assess whether cultured EPCs express known hemangioma markers. Hemangioma patients had a 15-fold increase in the number of circulating CD34 AC133 dual-staining cells relative to controls (0.78+/-0.14% vs.0.052+/-0.017%, respectively). Similarly, the number of PBMCs that stained positively for both CD34 and KDR was also increased in hemangioma patients (0.49+/-0.074% vs. 0.19+/-0.041% in controls). Cultured EPCs stained positively for the known hemangioma markers Glut1, CD32, merosin. CONCLUSIONS: This is the first study to suggest a role for EPCs in the pathogenesis of hemangioma. Our results imply that increased levels of circulating EPCs may contribute to the formation of this vascular tumor
PMID: 15624558
ISSN: 1539-6851
CID: 49078

Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures

Tepper, Oren M; Galiano, Robert D; Capla, Jennifer M; Kalka, Christoph; Gagne, Paul J; Jacobowitz, Glen R; Levine, Jamie P; Gurtner, Geoffrey C
BACKGROUND: The recent discovery of circulating endothelial progenitor cells (EPCs) has altered our understanding of new blood vessel growth such as occurs during collateral formation. Because diabetic complications occur in conditions in which EPC contributions have been demonstrated, EPC dysfunction may be important in their pathophysiology. METHODS AND RESULTS: EPCs were isolated from human type II diabetics (n=20) and age-matched control subjects (n=20). Proliferation of diabetic EPCs relative to control subjects was decreased by 48% (P<0.01) and inversely correlated with patient levels of hemoglobin A1C (P<0.05). Diabetic EPCs had normal adhesion to fibronectin, collagen, and quiescent endothelial cells but a decreased adherence to human umbilical vein endothelial cells activated by tumor necrosis factor-alpha (TNF-alpha) (P<0.05). In a Matrigel assay, diabetic EPCs were 2.5 times less likely to participate in tubule formation compared with controls (P<0.05). CONCLUSIONS: These findings suggest that type II diabetes may alter EPC biology in processes critical for new blood vessel growth and may identify a population at high risk for morbidity and mortality after vascular occlusive events
PMID: 12451003
ISSN: 1524-4539
CID: 33172

Type-II diabetes alters endothelial progenitor cell characteristics important for blood vessel growth [Meeting Abstract]

Tepper, OM; Galiano, RD; Capla, J; Kalka, C; Gagne, PJ; Jacobowitz, GR; Levine, JP; Gurtner, GC
ISI:000179142702820
ISSN: 0009-7322
CID: 37206

Comparison of tensile strength and thrombus formation between mechanical microvascular anastomoses using a biodegradable ring device and sutured anastomoses - Invited discussion [Editorial]

Levine, JP; Ahn, CY
ISI:000173790700012
ISSN: 0743-684x
CID: 55326

Hyponatremia in the postoperative craniofacial pediatric patient population: a connection to cerebral salt wasting syndrome and management of the disorder [Case Report]

Levine JP; Stelnicki E; Weiner HL; Bradley JP; McCarthy aJ JG
Hyponatremia after cranial vault remodeling has been noted in a pediatric patient population. If left untreated, the patients may develop a clinical hypoosmotic condition that can lead to cerebral edema, increased intracranial pressure, and eventually, to central nervous system and circulatory compromise. The hyponatremia has traditionally been attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH); however, in our patients the treatment has been resuscitation with normal saline as opposed to fluid restriction (the accepted treatment of SIADH), thus placing the diagnosis of SIADH in question. Patients who developed hyponatremia after intracranial injury or surgery were, until recently, grouped together as having SIADH. However, there are diagnosis and treatment differences between SIADH and another distinct but poorly understood disorder that is designated cerebral salt wasting syndrome (CSW). CSW is associated with increased urine output and increased urine sodium concentration and volume contraction, and it is frequently seen after a central nervous system trauma. We therefore developed a prospective study to evaluate the cause of the sodium imbalance.Ten consecutive pediatric patients who underwent intracranial surgery for various craniosynostotic disorders were postoperatively monitored in the pediatric intensive care unit for hemodynamic, respiratory, and fluid management. The first four patients were evaluated for electrolyte changes and overall fluid balance to determine the consistency with which these changes occurred. The remaining six patients had daily (including preoperative) measurement of serum electrolytes, urine electrolytes, urine osmolarity, serum antidiuretic hormone (ADH), aldosterone, and atrial natriuretic hormone (ANH). All patients received normal saline intravenous replacement fluid in the postoperative period.All of the patients developed a transient hyponatremia postoperatively, despite normal saline resuscitation. Serum sodium levels as low as 128 to 133 mEq per liter (normal, 137 to 145 mEq per liter) were documented in the patients. All patients had increased urine outputs through the fourth postoperative day (>1 cc/kg/h). The six patients who were measured had an increased ANH level, with a peak value as high as 277 pg/ml (normal, 25 to 77 pg/ml). ADH levels were low or normal in all but one patient, who had a marked increase in ADH and ANH. Aldosterone levels were variable. On the basis of these results, all but one patient showed evidence of CSW characterized by increased urine output, normal or increased urine sodium, low serum sodium, and increased ANH levels. The other patient had similar clinical findings consistent with CSW but also had an increase in ADH, thus giving a mixed laboratory picture of SIADH and CSW.The association of CSW to cranial vault remodeling has previously been ignored. This study should prompt reevaluation of the broad grouping of SIADH as the cause of all hyponatremic episodes in our postoperative patient population. An etiologic role has been given to ANH and to other, as yet undiscovered, central nervous system natriuretic factors. All of the patients studied required normal saline resuscitation, a treatment approach that is contrary to the usual management of SIADH. These findings should dictate a change in the postoperative care for these patients. After cranial vault remodeling, patients should prophylactically receive normal saline, rather than a more hypotonic solution, to avoid sodium balance problems
PMID: 11711918
ISSN: 0032-1052
CID: 24279

Auricular reconstruction: indications for autogenous and prosthetic techniques

Thorne CH; Brecht LE; Bradley JP; Levine JP; Hammerschlag P; Longaker MT
Learning Objectives: After studying this article, the participant should be able to: 1. Describe the alternatives for auricular reconstruction. 2. Discuss the pros and cons of autogenous reconstruction of total or subtotal auricular defects. 3. Enumerate the indications for prosthetic reconstruction of total or subtotal auricular defects. 4. Understand the complexity of and the expertise required for prosthetic reconstruction of auricular defects.The indications for autogenous auricular reconstruction versus prosthetic reconstruction with osseointegrated implant-retained prostheses were outlined in Plastic and Reconstructive Surgery in 1994 by Wilkes et al. of Canada, but because of the relatively recent Food and Drug Administration approval (1995) of extraoral osseointegrated implants, these indications had not been examined by a surgical unit in the United States. The purpose of this article is to present an evolving algorithm based on an experience with 98 patients who underwent auricular reconstruction over a 10-year period. From this experience, the authors conclude that autogenous reconstruction is the procedure of choice in the majority of pediatric patients with microtia. Prosthetic reconstruction of the auricle is considered in such pediatric patients with congenital deformities for the following three relative indications: (1) failed autogenous reconstruction, (2) severe soft-tissue/skeletal hypoplasia, and/or (3) a low or unfavorable hairline. A fourth, and in our opinion the ideal, indication for prosthetic ear reconstruction is the acquired total or subtotal auricular defect, most often traumatic or ablative in origin, which is usually encountered in adults. Although prosthetic reconstruction requires surgical techniques that are less demanding than autogenous reconstruction, construction of the prosthesis is a time-consuming task requiring experience and expertise. Although autogenous reconstruction presents a technical challenge to the surgeon, it is the prosthetic reconstruction that requires lifelong attention and may be associated with late complications. This article reports the first American series of auricular reconstruction containing both autogenous and prosthetic methods by a single surgical team
PMID: 11373570
ISSN: 0032-1052
CID: 20645

Restoration of abdominal wall integrity as a salvage procedure in difficult recurrent abdominal wall hernias using a method of wide myofascial release [Case Report]

Levine JP; Karp NS
The management of primary and recurrent giant incisional hernias remains a complex and frustrating challenge even with multiple alloplastic and autogenous closure options. The purpose of this study was to develop a reconstructive technique of restoring abdominal wall integrity to a subcategory of patients, who have failed initial hernia therapy, by performing superior and lateral myofascial release. Over a 1.5-year period, 10 patients with previously unsuccessful treatment of abdominal wall hernias, using either primary repair or placement of synthetic material, were studied. The patients had either recurrence of the hernia or complications such as infections requiring removal of synthetic material. The hernias were not able to be treated with standard primary closure techniques or synthetic material. The average defect size was 19 x 9 cm. Each patient underwent wide lysis of bowel adhesions releasing the posterior abdominal wall fascia to the posterior axillary line, subcutaneous release of the anterior abdominal wall fascia to a similar level, and complete removal of any synthetic material (if present). The abdominal domain was reestablished by releasing the laterally retracted abdominal wall. The amount of available abdominal wall tissue was increased by wide release of the cephalic abdominal wall fascia overlying the costal margin and the external oblique fascia and muscle laterally. If needed, partial thickness of the internal oblique muscle and its anterior fascia were also released laterally to perform a tension-free primary closure of the defect. All repairs were closed with satisfactory functional and aesthetic results. All alloplastic material was removed. Fascial release was limited so as to close only the hernia defect without tension. No significant release of the rectus sheath and muscle was needed. Good, dynamic muscle function was noted postoperatively. All repairs have remained intact, and no further abdominal wall hernias have been noted on follow-up
PMID: 11304595
ISSN: 0032-1052
CID: 21200

Growth restriction of cranial sutures in the fetal lamb causes deformational changes, not craniosynostosis

Bradley JP; Shahinian H; Levine JP; Rowe N; Longaker MT
Newborns with in utero cranial vault molding can present with severe forms of plagiocephaly. Intrauterine constraint has been proposed as one cause for craniosynostosis. The purpose of this experiment was to investigate whether rigid plate fixation across a fetal cranial suture, representing a severe form of growth restriction in utero, would lead to cranial suture fusion in a fetal lamb model. Six fetal lambs at 85 to 95 days gestation (term = 145 days) underwent laparotomy, hysterotomy, fetal coronal scalp incision, and miniplate screw fixation across the right coronal suture in utero. Two unoperated twins and four unoperated age-matched lambs were used as controls (n = 12). Animals were killed at both 4 and 8 weeks postoperatively. Fetal head analysis consisted of gross examination, photography, basilar and lateral radiographs, and three-dimensional computed tomographic scans. Cranial suture analysis consisted of imaging by computed tomographic scan (axial and sagittal cuts) and histology of experimentally plated coronal sutures, contralateral nonplated coronal sutures and twin control coronal sutures. Gross examination, radiographs, and three-dimensional computed tomographic analysis of heads with cranial suture plating showed ipsilateral forehead flattening, contralateral forehead bossing, superiorly displaced ipsilateral orbital rim, anterolateral projection of ipsilateral malar eminence, and anterior position of the ipsilateral ear point compared with the contralateral side of the same animal and normal controls. There was no change in nasal root, chin point, or predentition occlusal plane. Although analysis of the plated coronal sutures by computed tomographic scans showed diminished width or even stenosis, the histology revealed narrowed but patent experimental coronal sutures at 4 and 8 weeks. Contralateral, nonplated coronal sutures were not only patent, but widened compared with normal control sutures. This finding may have represented compensatory changes in the contralateral coronal suture caused by growth restriction at the plated suture. These data demonstrate that intrauterine growth restriction across a cranial suture caused by compression plate fixation resulted in deformational skull changes, not craniosynostosis. In addition, these data strongly support a role for in utero positional molding secondary to growth restriction in the maternal pelvis as a cause for nonsynostotic plagiocephaly seen in newborns
PMID: 10845296
ISSN: 0032-1052
CID: 11653

Softform for facial rejuvenation: historical review, operative techniques, and recent advances

Miller PJ; Levine J; Ahn MS; Maas CS; Constantinides M
The deep nasolabial fold and other facial furrows and wrinkles have challenged the facial plastic surgeon. A variety of techniques have been used in the past to correct these troublesome defects. Advances in the last five years in new materials and design have created a subcutaneous implant that has excellent properties. This article reviews the development and use of Softform facial implant
PMID: 11802342
ISSN: 0736-6825
CID: 25992

Managing the tension nose

Constantinides M; Levine J
ORIGINAL:0004284
ISSN: 1064-7406
CID: 26024