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Biomedical subjects

Tae Sung Park

Publications and source records attributed to Tae Sung Park.

At least 19 recordsLinked to original sources

Inactivation of SMAD4 tumor suppressor gene during gastric carcinoma progression.

PURPOSE: Mothers against decapentaplegic homologue 4 (SMAD4) is a tumor suppressor gene associated with gastrointestinal carcinogenesis. The aim of the present study is to more precisely characterize its role in the development and progression of human gastric carcinoma. EXPERIMENTAL DESIGN: The expression of SMAD4 was investigated in 283 gastric adenocarcinomas and related lesions, as well as in 9 gastric carcinoma cell lines. We also analyzed the methylation status of SMAD4 gene by using methylation-specific PCR, examined loss of heterozygosity (LOH) of this gene locus by using a vicinal marker, and detected exon mutation of SMAD4 through exon-by-exon amplification. Moreover, we assessed whether MG132, a proteasome inhibitor, affected the SMAD4 protein level. RESULTS: We found loss of SMAD4 protein expression in the cytoplasm (36 of 114, 32%) and in the nucleus (46 of 114, 40%) of gastric cancer cells. The loss of nuclear SMAD4 expression in primary tumors correlated significantly with poor survival, and was an independent prognostic marker in multivariate analysis. We also found a substantial decrease in SMAD4 expression at both the RNA and protein level in several human gastric carcinoma cell lines. In addition, we found that LOH (20 of 70, 29%) and promoter hypermethylation (4 of 73, 5%) were associated with the loss of SMAD4 expression. SMAD4 protein levels were also affected in certain gastric carcinoma cell lines following incubation with MG132. CONCLUSION: Taken together, our results indicate that the loss of SMAD4, especially loss of nuclear SMAD4 expression, is involved in gastric cancer progression. The loss of SMAD4 in gastric carcinomas was due to several mechanisms, including LOH, hypermethylation, and proteasome degradation.

Aged↗

A review of orthopedic surgeries after selective dorsal rhizotomy.

Selective dorsal rhizotomy (SDR) is an evidence-based treatment for cerebral palsy (CP) spasticity. During their lifetime, patients with CP spasticity may require orthopedic surgery for muscles and joints to correct physical deformities and provide a better quality of life. In this review, the authors discuss the timing of such orthopedic surgery, its necessity, and whether it is influenced by the performance of SDR. A review of findings from the authors' 19 years of experience yields the following conclusions: 1) that SDR reduces orthopedic surgery requirements when compared with historical controls; 2) that SDR performed in patients at a young age (2-4 years) can reduce future orthopedic surgery requirements; 3) that independent walkers and diplegic patients will have the smallest amount of orthopedic surgery post-SDR; and 4) that patients who need assistance walking and those with quadriplegia will have the greatest amount, although the frequency of orthopedic surgery for quadriplegic patients is not as high as popularly believed.

Cerebral Palsy↗

Surgical techniques of selective dorsal rhizotomy for spastic cerebral palsy. Technical note.

Selective dorsal rhizotomy is a well-established surgical procedure for improving lower-extremity spasticity in children with cerebral palsy. The standard technique requires an L1-S1 laminectomy or laminoplasty for visualization of all dorsal nerve roots exiting at their respective foramina. The authors describe a rhizotomy procedure that requires a single-level laminectomy at the level of the conus, with the advantages of decreased operating time and postoperative pain as well as a minimal risk of progressive lumbar instability. This procedure is both effective and well tolerated in appropriately selected children and adults, and has had one cerebrospinal fluid lead requiring operative repair in more than 1500 patients treated at the authors' institution since 1991.

Adolescent↗

Simultaneous image-guided and endoscopic navigation without rigid cranial fixation: application in infants: technical case report.

OBJECTIVE AND IMPORTANCE: Infants and young children demonstrate a variety of intraventricular and periventricular lesions. Endoscopy has proven useful in the treatment of many of these lesions, but its benefit is limited if it is applied to complex loculated cysts or if the disease is concealed by normal ependymal boundaries. In adults and older children, endoscopy can be augmented by the simultaneous use of frameless stereotaxy, but this combined modality has not been possible in infants and young children without rigid cranial fixation. We describe a method of achieving simultaneous stereotactic and endoscopic navigation in infants and young children by using a pinless, frameless stereotactic assembly. CLINICAL PRESENTATION: The first patient was a 6-week-old boy with macrocephaly and a bulging fontanelle. Computed tomographic and magnetic resonance imaging revealed a complex arachnoid cyst and obstructive hydrocephalus. The second patient was a 7-month-old, ex-premature (27-wk gestational age) boy who developed posthemorrhagic hydrocephalus. He underwent multiple shunt revisions, one of which was complicated by enterococcal ventriculitis. Despite bilateral ventriculoperitoneal shunts, he developed increasing head circumference, listlessness, and irritability. Imaging revealed an enlarged, multiloculated, and asymmetric ventricular system. INTERVENTION: Simultaneous image-guided and endoscopic neuronavigation was implemented in both patients. Before the procedure, a cranial reference arc was secured to the outer table of the cranium through a small incision adjacent to the operative field. After the stereotactic apparatus was registered, the software was used to plan a trajectory for the approach. A burr hole was then made, and a rigid 6-mm endoscope was inserted for direct visualization. Once advanced past the endoscopic port tip, the electromagnetic coil stylet was used to stereotactically track position and identify areas for fenestration, biopsy, and catheter insertion. CONCLUSION: Endoscopic views of complex hydrocephalus and arachnoid cysts alone are often difficult to interpret. Simultaneous image-guided and endoscopic neuronavigation may be advantageous in the management of complex cases that are anatomically related to the ventricular system in infants for whom rigid cranial fixation could lead to increased procedure-related morbidity.

Brain Diseases↗

Pediatric neurosurgical injuries associated with all-terrain vehicle accidents: a 10-year experience at St. Louis Children's Hospital.

OBJECT: All-terrain vehicles (ATVs) have been characterized as inherently unstable and are associated with significant pediatric injuries in the US. The authors performed a study to analyze data obtained in pediatric patients who had sustained neurological injuries in ATV-related accidents, identify potential risk factors, and propose preventive measures. The study is based on a 10-year experience at the St. Louis Children's Hospital. METHODS: The authors retrospectively analyzed data obtained in all patients admitted to the St. Louis Children's Hospital between 1993 and 2003, limiting their focus to pediatric cases involving ATV-related accidents. A total of 185 patients were admitted with these criteria. Sixty-two patients (33.5%) suffered neurological injuries; there were 42 male and 20 female patients whose age ranged from 2 to 17 years. The most common injuries included skull fracture (37 cases) and closed head injury (30 cases). There were 39 cases of intracranial hemorrhage and 11 of spinal fracture. A total of 15 types of neurosurgical procedure were performed: six craniotomies for hematoma drainage, five craniotomies for elevation of depressed fractures, two procedures to allow placement of an intracranial pressure monitor, one to allow placement of an external ventricular drain, and one to allow the insertion of a ventriculoperitoneal shunt. Two patients had sustained spinal cord injury, and three procedures were performed for spinal decompression or stabilization. The duration of hospital stay ranged from 1 to 143 days (mean 6.6 days). Fifty-seven patients (30.8%) were eventually discharged from the hospital, three (1.6%) were transferred to another hospital, two (1.1%) died, and 123 (66.4%) required in-patient rehabilitation. CONCLUSIONS: Children suffered significant injuries due to ATV accidents. In passengers there was a statistically significant increased risk of neurological injury. The relative risk of neurological injury in patients not wearing helmets was higher than that in those who wore helmets, but the difference did not reach statistical significance. Further efforts must be made to improve the proper operation and safety of ATVs, both through the education of parents and children and through the creation of legislation requiring stricter laws concerning ATV use.

Adolescent↗

Effect of selective dorsal rhizotomy in the treatment of children with cerebral palsy.

OBJECT: In this investigation the authors compared impairment and functional outcomes between two groups of children with cerebral palsy (CP): one group underwent selective dorsal rhizotomy (SDR) followed by intensive physical therapy (PT), and the other group underwent the latter only (PT group). Data from an age-matched group of children without disability (nondisabled [ND] group) were also collected. METHODS: Data pertaining to the 68 children with CP were collected before any intervention and again 8 and 20 months afterwards. Data regarding the 40 children in the ND group were collected in a single session. CONCLUSIONS: Although patients in both groups with CP were weaker than those in the ND group, they did have strength gains. Gait speed in the SDR-PT group was slower than that in the ND group preoperatively but not at 20 months postoperatively. Gait speed in the PT group remained slower than that in the ND group. The pre- to postoperative change in the Gross Motor Abilities Estimate score was significantly greater in the SDR-PT group than in the PT-only group. An effective treatment for children with CP, SDR offers gains in strength, gait speed, and overall gross motor function.

Adolescent↗

Collagen nerve guides for surgical repair of brachial plexus birth injury.

OBJECT: Standard brachial plexus repair techniques often involve autologous nerve graft placement and neurotization. However, when performed to treat severe injuries, this procedure can sometimes yield poor results. Moreover, harvesting the autologous graft is time-consuming and exposes the patient to additional surgical risks. To improve surgical outcomes and reduce surgical risks associated with autologous nerve graft retrieval and placement, the authors use collagen matrix tubes (Neurogen) instead of autologous nerve graft material. METHODS: Between 1991 and 2005, the authors surgically treated 65 infants who had suffered brachial plexus injury at birth. During this time, seven patients were treated using collagen matrix tubes (Neurogen). This study is a retrospective analysis of the initial five patients who were treated using the tubes. Two patients underwent tube placement recently and were excluded from the analysis because of the inadequate follow-up period. Four of the five patients experienced a good recovery (motor scale composite [MSC] > 0.6), and three exhibited an excellent recovery (MSC > 0.75) at 2 years postoperatively. The MSC improved by an average of 69 and 78% at 1 and 2 years, respectively. The movement scores improved to greater than or equal to 50% range of motion in most patients, and the contractures were usually mild or moderate. Follow-up physical and occupational therapy evaluations confirm these patients' functional status. When last seen, four of five of these children could feed and dress themselves. CONCLUSIONS: Technically, the use of the collagen matrix tubes was straightforward and efficient, and there were no complications. The outcomes in this small series are encouraging.

Brachial Plexus↗

Constitutive nitric oxide synthase activity is required to trigger ischemic tolerance in mouse retina.

Profound morphologic and functional protection against retinal ischemic injury can be achieved if the tissue is 'preconditioned' one day earlier with a brief, noninjurious ischemic challenge. To begin to address the mechanistic basis of this 'ischemic tolerance', we used genetic and pharmacologic approaches to test the hypothesis that nitric oxide (NO) derived from one of the three NO synthase (NOS) isoforms was responsible for triggering the adaptive response to brief preconditioning ischemia. Retinae of adult mice were preconditioned with 5-min preconditioning ischemia and subjected to 45-min injurious ischemia 24 hr later. Some animals were treated with the constitutive NOS inhibitor L-nitroarginine (5 mg/kg, i.p.) 1 hr before preconditioning. Retinal layer thicknesses and cell counts were determined one week postischemia in 5-mum thin sections, and flash electroretinograms were obtained at 1 and 7 days postischemia. We confirmed that ischemic preconditioning afforded morphologic and functional protection in the strains of wild-type mice studied. Histopathologic analyses of inducible NOS (iNOS) knockout mice revealed that ischemic preconditioning was completely effective, whereas ischemic tolerance was not achieved in the retinae of endothelial NOS (eNOS) and neuronal NOS (nNOS) knockout mice. The participation of the constitutive NOS enzymes in preconditioning-induced tolerance was confirmed by the finding that administration of the NOS inhibitor L-NA to wild-type mice prior to ischemic preconditioning blocked the development of ischemic tolerance. These cross-validating genetic and pharmacologic findings indicate that NO derived from both eNOS and nNOS is a required molecular signal in the adaptive response to ischemic preconditioning in the retina.

Animals↗

Incidental pediatric intraparenchymal xanthogranuloma: case report and review of the literature.

Juvenile xanthogranuloma (JXG) is a specialized form of non-Langerhans cell histiocyte proliferation that occurs in children. The majority of cases present as a solitary cutaneous lesion with a predilection for the head and neck region; however, isolated lesions occasionally have been identified in the central nervous system. The cutaneous forms of JXG usually follow a benign course. Other physicians have reported surgery as the first line of treatment in symptomatic patients with accessible lesions. Adjuvant therapies may be indicated for multicentric or surgically inaccessible lesions. The authors describe an unusual case of isolated intraparenchymal JXG in an asymptomatic child with no cutaneous manifestations and provide a review of the literature.

Antigens, CD↗

Primary hypothyroidism in a 12-year-old girl with a suprasellar pituitary mass: rapid regression after thyroid replacement therapy: case report.

The authors report on a 12-year-old girl with a suprasellar mass and primary hypothyroidism in whom the lesion promptly regressed following initiation of thyroid replacement therapy. Based on this experience, it is suggested that secondary pituitary hyperplasia be included in the differential diagnostic considerations of a suprasellar lesion in a child and that resolution of the hyperplasia may occur in a matter of weeks rather than months as previously reported.

Child↗

Orthopedic surgery after selective dorsal rhizotomy for spastic diplegia in relation to ambulatory status and age.

OBJECT: A retrospective study was performed to determine the following: 1) whether children who walk independently after selective dorsal rhizotomy (SDR) undergo fewer subsequent orthopedic operations than those who walk with assistance; and 2) the effect of age at SDR on the rate of orthopedic operations. METHODS: The cases of 158 children with spastic diplegia who were 2 to 14 years of age when they underwent SDR were followed over a 5- to 9-year period. Patients were grouped by age at the time of SDR as follows: 2 to 3 years (Group 1), 4 to 7 years (Group 2), and 8 to 14 years (Group 3). Follow-up data showed that children in all age groups who walked independently after SDR underwent fewer orthopedic operations than did children who walked with assistance. Overall rates of orthopedic surgery 5 to 9 years after SDR at last follow up were 24% for independent walkers and 51% for assisted walkers. Two-way categorical analysis (age group by ambulation) yielded a highly significant effect of ambulation (p = 0.0003). Children in Group 1 needed the fewest orthopedic operations at follow-up evaluation. In the older age groups (Groups 2 and 3), those who walked independently at the time of SDR underwent fewer orthopedic operations after SDR than did walkers who required assistance (p = 0.01). CONCLUSIONS: These data are of value in advising parents about the likelihood of orthopedic surgery based on the child's gait status both at the time of SDR and at follow-up evaluation. Orthopedic surgery is more likely in patients destined to be nonambulators.

Activities of Daily Living↗

Use of rapid-sequence magnetic resonance imaging for evaluation of hydrocephalus in children.

OBJECT: The authors examine the use of rapid-sequence magnetic resonance (rsMR) imaging to make the diagnosis of malfunctioning and/or infected shunts in patients with hydrocephalus. Computerized tomography (CT) scanning is usually used in this context because it rapidly acquires high-quality images, yet it exposes pediatric patients to particularly high levels of radiation. Standard MR imaging requires longer image acquisition time, is associated with movement artifact, and, in children, usually requires sedation. Standard MR imaging provides greater structural resolution, yet visualization of ventricular catheters is relatively poor. METHODS: The authors analyzed a series of 67 rsMR imaging examinations performed without sedation in pediatric patients with hydrocephalus whose mean age was 4 years at the time of the examination. The mean study duration was 22 minutes. Catheter visualization was good or excellent in more than 75% of studies reviewed, and image quality was good or excellent in more than 60% of studies reviewed. The authors analyzed cancer risk with a model used for atomic bomb survivors. Fifty percent of their patients with hydrocephalus had undergone more than four brain imaging studies (CT or MR imaging) in their lifetimes. For the many patients who had undergone more than 15 studies, the total estimated lifetime attributable cancer mortality risk was calculated to be at least 0.35%. CONCLUSIONS: Rapid-sequence MR imaging yields reliable visualization of the ventricular catheter and offers superior anatomical detail while limiting radiation exposure. The authors' protocol is rapid and each image is acquired separately; therefore, motion artifact is reduced and the need for sedation is eliminated. They recommend the use of rsMR imaging for nonemergent evaluation of pediatric hydrocephalus.

Adolescent↗

Early programmable valve malfunctions in pediatric hydrocephalus.

OBJECT: The use of adjustable differential pressure valves has been recommended to improve ventriculoperitoneal (VP) shunt performance in selected patients; however, published data are scarce regarding their clinical reliability. Recently, the identification of a number of malfunctioning programmable valves during shunt revision surgery in children prompted a retrospective review of valve performance in this patient cohort. METHODS: The authors performed a retrospective chart analysis of 100 patients with programmable valve shunts and 89 patients with nonprogrammable valve shunts implanted at the St. Louis Children's Hospital between April 2002 and June 2004. They noted the cause of hydrocephalus, the type of shunt malfunction, and cerebrospinal fluid (CSF) protein levels. Regular clinical follow up ranged from 1 to 26 months, with a mean follow-up time of 9.75 months for patients with programmable valves and 10.4 months for patients with nonprogrammable valves. Patient ages ranged from 2 weeks to 18 years. One hundred patients had 117 programmable valves implanted, and 35 of these patients (35%) underwent shunt revision because of malfunction. The programmable valve itself malfunctioned in nine patients who had undergone shunt revision (11.1%/year of follow up). The nonprogrammable valve group had no valve malfunctions. The overall VP shunt revision rate in the nonprogrammable valve group was 20.2%. No significant differences were identified when CSF protein levels and specific malfunction types were compared within the programmable valve and nonprogrammable valve groups. CONCLUSIONS: In this study the authors demonstrated an annualized intrinsic programmable valve malfunction rate of 11.1%, whereas during the same period no intrinsic valve malfunctions were noted with nonprogrammable valve systems for similar causes of hydrocephalus. The CSF protein levels did not correlate with observed valve malfunction rates. Further evaluation in a prospective, randomized fashion will elucidate specific indications for programmable valve systems and better determine the reliability of these valves in the pediatric population.

Adolescent↗