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Biomedical subjects

M W Chang

Publications and source records attributed to M W Chang.

At least 19 recordsLinked to original sources

Topical tretinoin and 5-fluorouracil in the treatment of linear verrucous epidermal nevus.

Treatment of a linear verrucous epidermal nevus using topical 0.1% tretinoin cream and 5% 5-fluorouracil in a young patient is described. In 1994, successful topical therapy using this combination was described in the management of an inflammatory linear verrucous epidermal nevus. We report another case in which treatment of a noninflamed epidermal verrucous nevus with 0.1% tretinoin and 5% 5-fluorouracil resulted in significant improvement. An updated summary of the literature discussing management of epidermal nevi is presented.

Antimetabolites↗

Contour tracking using a knowledge-based snake algorithm to construct three-dimensional pharyngeal bolus movement.

Videofluorography (VFG) using a barium-mixed bolus is in wide clinical use for assessing patients with swallowing disorders. VFG is usually done with both lateral (LA) and anterior-posterior (AP) views, most commonly in two separate sittings. A real-time, three-dimensional (3-D) representation of the evolution of a pharyngeal bolus and its volumetric information can potentially help clinicians analyze and visualize the kinematics of swallowing, dysphagia, and compensatory therapeutic strategies. Active contour models, also known as "Snakes," have been used to solve various image analysis and computer vision problems. We applied a Snake algorithm to automate in part the contour tracking and reconstruction of VFG images to visualize and quantitatively analyze the 3-D evolution of a pharyngeal bolus. To improve the accuracy of the Snake search, we provided the additional "knowledge" of the pharyngeal image itself, which served as an extra constraint to push the Snake curve toward the desired contour. VFG of pharyngeal bolus transport in a normal subject was recorded by using barium-mixed boluses (viscosity: 185 centipoise, density: 2.84 g/cc) with volumes of 5, 10, and 20 ml. The resulting LA and AP video images were digitally captured and matched frame by frame. The knowledge-based Snake search algorithm was used to generate Snake points to satisfy both internal (i.e., smoothness) and external (i.e., boundary fitting) constraints. Using these Snake points, we traced the 3-D bolus movement at each time instant, assuming elliptic geometry in the cross-section of the pharyngeal bolus. By concentrating the 3-D images for each time instant, we developed a 3-D movie representing pharyngeal bolus movement. The efficiency, reproducibility, and accuracy of this algorithm in tracing pharyngeal bolus boundaries and estimating front/tail velocities were assessed and found satisfactory. We conclude that 3-D pharyngeal bolus movement can be traced both accurately and efficiently by using a knowledge-based Snake search algorithm.

Algorithms↗

Update on juvenile xanthogranuloma: unusual cutaneous and systemic variants.

Juvenile xanthogranuloma (JXG) is a well-recognized benign disorder of infancy and early childhood characterized by yellowish cutaneous nodules that spontaneously regress over months to years. In the vast majority of children, JXG is limited to the skin and requires no treatment. Over the past two decades, unusual cutaneous and systemic forms of JXG have been increasingly reported. JXGs have been discovered, usually unexpectedly, in every organ system of the body. Correct diagnosis is crucial to prevent unnecessary invasive diagnostic and therapeutic procedures. Unusual clinical and histological variants of JXG often require immunohistochemical studies and/or electron microscopy to establish the diagnosis. Nonlipidized, giant, intramuscular, subcutaneous, and clustered JXG are but some of the variants that are discussed in this article. The immunohistochemistry of JXG, current nosology, and hypotheses regarding the origins of JXG are also reviewed.

Diagnosis, Differential↗

Advances in the management of dysphagia caused by stroke.

This article reviews the advancements that have occurred, primarily in the last decade, in the management and treatment of swallowing disorders related to stroke. An overview of swallowing physiology is given, and interventions, both indirect and direct, are explored. Expanding knowledge, applying techniques from other scientific disciplines, and developing new technologies provide hope for stroke patients who experience dysphagia.

Biofeedback, Psychology↗

Mucocutaneous manifestations of the hyper-IgM immunodeficiency syndrome.

BACKGROUND: The recurrent pyogenic infections of patients with hyper-IgM syndrome are controlled by intravenous gamma globulin administration, but patients may suffer from early-onset oral ulcerations and warts. OBJECTIVE: We have characterized the mucocutaneous manifestations associated with this condition to allow physicians to more readily identify it. METHODS: Three male patients with the mucocutaneous manifestations of the hyper-IgM syndrome are described. In one, histopathologic examination of the oral mucosal lesion was performed. RESULTS: Recurrent large, painful oral ulcerations can occur that are not necessarily associated with neutropenia nor do they respond to granulocyte colony-stimulating factor administration. Histopathologic examination of an ulcer showed a heavy infiltrate of mixed inflammatory cells. Warts tend to be widespread and resistant to traditional therapy. CONCLUSION: Physicians should consider this uncommon condition when examining a male patient with severe oral ulcers or recalcitrant widespread warts.

Adult↗

Mathematical modeling of normal pharyngeal bolus transport: a preliminary study.

Dysphagia (difficulty in swallowing) is a common clinical symptom associated with many diseases, such as stroke, multiple sclerosis, neuromuscular diseases, and cancer. Its complications include choking, aspiration, malnutrition, cachexia, and dehydration. The goal in dysphagia management is to provide adequate nutrition and hydration while minimizing the risk of choking and aspiration. It is important to advance the individual toward oral feeding in a timely manner to enhance the recovery of swallowing function and preserve the quality of life. Current clinical assessments of dysphagia are limited in providing adequate guidelines for oral feeding. Mathematical modeling of the fluid dynamics of pharyngeal bolus transport provides a unique opportunity for studying the physiology and pathophysiology of swallowing. Finite element analysis (FEA) is a special case of computational fluid dynamics (CFD). In CFD, the flow of a fluid in a space is modeled by covering the space with a grid and predicting how the fluid moves from grid point to grid point. FEA is capable of solving problems with complex geometries and free surfaces. A preliminary pharyngeal model has been constructed using FEA. This model incorporates literature-reported, normal, anatomical data with time-dependent pharyngeal/upper esophageal sphincter (UES) wall motion obtained from videofluorography (VFG). This time-dependent wall motion can be implemented as a moving boundary condition in the model. Clinical kinematic data can be digitized from VFG studies to construct and test the mathematical model. The preliminary model demonstrates the feasibility of modeling pharyngeal bolus transport, which, to our knowledge, has not been attempted before. This model also addresses the need and the potential for CFD in understanding the physiology and pathophysiology of the pharyngeal phase of swallowing. Improvements of the model are underway. Combining the model with individualized clinical data should potentially improve the management of dysphagia.

Deglutition↗

The risk intraocular juvenile xanthogranuloma: survey of current practices and assessment of risk.

BACKGROUND: Juvenile xanthogranuloma (JXG) is an uncommon, usually uncomplicated disease of childhood. Ocular involvement, however, can result in glaucoma and blindness if left untreated. The incidence of ocular complications and how best to screen for their occurrence is unknown. OBJECTIVE: We attempted to ascertain management and referral practices among ophthalmologists and dermatologists and to characterize the risk for ocular complications in children with JXG. METHODS: A total of 431 dermatologists and 438 ophthalmologists were surveyed. In addition, the literature was reviewed. RESULTS: The response rate were 28% (dermatologists) and 44% (ophthalmologists). Most believed screening was important, but referral and surveillance practices varied widely. The survey incidence of ocular complications in patients with cutaneous JXG was approximately 0.3% (7 of 2371). The literature incidence was 0.4% (1 of 260). Children at maximum risk were 2 years of age or younger, had multiple skin lesions, and had newly diagnosed JXG. CONCLUSION: Ophthalmologic screening of patients with JXG should be particularly targeted to patients with risk factors of multiple skin lesions, new diagnosis, and age of 2 years or younger.

Age Factors↗

Sudoriferous acrosyringeal acantholytic disease. A subset of Grover's disease.

Three selected cases of transient acantholytic dermatosis were studied because of their definitive correlation with sweating due to fever and/ or bed-ridden situations. Biopsy specimens were serially sectioned and acantholysis was found in the acrosyringium or traced to connect to the acrosyringium in all biopsy specimens. Carcinoembryonic antigen (CEA) and eccrine gland-specific monoclonal antibody, IKH-4, were positive in acantholytic cells. Electron microscopy revealed electron dense material filling the lumen of intraepidermal eccrine ducts. This material leaked into lateral intercellular spaces of the luminal cells, passing tight junctions. Marked edema and numerous lysosomes were reminiscent of those found when eccrine acrosyringium is formed in the embryo; this suggested that an occluded and damaged eccrine intraepidermal duct was being rebuilt via lysosomal digestion.

Acantholysis↗

Vasomotor responses of newly developed coronary collateral vessels.

Well-developed coronary collateral vessels contain an abundant muscular media and can undergo active vasomotion. However, early after coronary occlusion, coronary collateral vessels are thin walled with little smooth muscle, suggesting that vasomotor capability might be limited. Consequently, this study determined whether newly developed coronary collateral vessels have active vasomotor activity and whether endothelial function in these newly developed vessels is impaired. Retrograde blood flow was measured as an index of coronary collateral blood flow approximately 2 wk after embolic occlusion of the anterior descending coronary artery of dogs. Agonists were administered into the left main coronary artery to reach collaterals originating from the left coronary system. Baseline retrograde blood flow was 25.1 +/- 2.7 ml/min and increased to 36.7 +/- 3.7 ml/min after nitroglycerin (6 micrograms.kg-1.min-1, P < 0.05). Cyclooxygenase blockade with indomethacin (5 mg/kg i.v.) decreased retrograde collateral blood flow to 16.8 +/- 2.3 ml/min (P < 0.05). Subsequent administration of acetylcholine increased retrograde flow to 29.4 +/- 3.7 ml/min (P < 0.05), indicating intact endothelium-mediated vasodilation. Inhibition of nitric oxide synthase with NG-nitro-L-arginine further decreased coronary collateral retrograde flow to 12.0 +/- 2.8 ml/min (P < 0.05) and markedly blunted the response to acetylcholine. These findings demonstrate substantial vasomotor capability even early during coronary collateral development and indicate that both nitric oxide and cyclooxygenase-dependent endothelial mechanisms are intact.

Animals↗

Gene therapy for vascular proliferative disorders.

Despite major advances in interventional techniques in recent years, restenosis remains an important late complication of percutaneous revascularization procedures. Vascular smooth muscle cell proliferation after arterial injury plays an important role in the pathogenesis of restenosis. Major progress has been made recently in elucidating the cellular and molecular mechanisms underlying this proliferative response. This in turn has led to the development of novel, gene-based approaches for the treatment and prevention of restenosis as well as other vascular proliferative disorders. Included among these are somatic gene therapy the ability to introduce and express recombinant genes in non-germ-line cells of a recipient organism in vivo. This article reviews specific genetic approaches that have recently been developed for the treatment of vascular proliferative disorders such as restenosis, focusing on the use of adenovirus-mediated arterial gene transfer strategies designed to suppress the vascular smooth muscle cell proliferative response associated with these diseases.

Adenoviridae↗

Cytostatic gene therapy for vascular proliferative disorders with a constitutively active form of the retinoblastoma gene product.

Vascular smooth muscle cell (SMC) proliferation in response to injury is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis after balloon angioplasty. The retinoblastoma gene product (Rb) is present in the unphosphorylated and active form in quiescent primary arterial SMCs, but is rapidly inactivated by phosphorylation in response to growth factor stimulation in vitro. A replication-defective adenovirus encoding a nonphosphorylatable, constitutively active form of Rb was constructed. Infection of cultured primary rat aortic SMCs with this virus inhibited growth factor-stimulated cell proliferation in vitro. Localized arterial infection with the virus at the time of balloon angioplasty significantly reduced SMC proliferation and neointima formation in both the rat carotid and porcine femoral artery models of restenosis. These results demonstrate the role of Rb in regulating vascular SMC proliferation and suggest a gene therapy approach for vascular proliferative disorders associated with arterial injury.

Adenoviridae↗

Decreased balance performance in cowboy boots compared with tennis shoes.

OBJECTIVE: This study was conducted to examine the relative balance performance of cowboy boots versus tennis shoes when the subject was challenged with different accelerations. The end point was the highest acceleration at which the subject could maintain full foot contact with the platform for each footwear type, ie, break acceleration. DESIGN: Crossover trial. SETTING: General community. PARTICIPANTS: Twenty-seven healthy women, 18 to 40 years old, with shoe sizes between 6 and 9, were selected in a convenience sample after their response to posted ads in a university medical center. INTERVENTION: Each subject was tested 3 times in the forward direction per acceleration on a Motionspec balance platform. A successful series was defined as keeping feet flat for 2 of 3 tests/level. MAIN OUTCOME MEASURE: The planned major outcome was the difference between the highest accelerations at which the subject was successful for each type of footwear. RESULTS: Subjects were found to have a highest sustainable acceleration in boots 10.66 +/- 6.20cm/s2 less than the highest acceleration in shoes. A period effect was found that improved the results of the second footwear tested by 7.2 +/- 6.20cm/s2. CONCLUSIONS: Cowboy boots have a decreased balance performance compared with tennis shoes. Further study should examine the specific features in the boot that contribute to this imbalance and examine the kinematic adaptations of the body to cowboy boots.

Adolescent↗

Initialization of warfarin dosages using computer modeling.

OBJECTIVE: Software incorporating warfarin pharmacokinetics and pharmacodynamics, as well as a Bayesian regression method, was evaluated for accuracy in predicting steady-state dosages of warfarin during initialization of anticoagulation therapy. DESIGN: A cohort study was used to compare computer predictions with physician-determined doses during a retrospective chart review of 42 patients. PATIENTS: Forty-two patient charts were selected for monitoring anticoagulation initialization therapy. Of the 42 patients reviewed, 22 were excluded on the following bases: uncontrolled congestive heart failure; ongoing treatment with medications that interfered with warfarin metabolism or displaced warfarin from protein binding sites; recent treatment with fresh frozen plasma or vitamin K; or any bleeding disorders, sepsis, malabsorption or significant changes in liver and/or renal function. MAIN OUTCOME MEASURES: Using physician-determined International Normalized Ratios (INRs) as target levels for the software, the number of INR feedbacks needed to stabilize blood drug levels during initialization were compared between physicians and computer forecasting. Population parameters and sequentially measured INRs were used for evaluation. RESULTS: Current oral anticoagulation protocols require significantly more measured INRs than computer forecasting to achieve steady-state dosages (9.5 v 4.4, respectively, p < 0.01). Physicians showed a statistically significant pattern of underdosing patients (4.3 v 1.7 subtherapeutic INRs, respectively, p < 0.01). Computer predictions tended to overdose patients but did not significantly increase the number of supratherapeutic INRs. This study showed that five INR inputs consistently gave accurate steady-state dosage predictions, and in many ways computer modeling was more effective than clinician-determined steady-state dosing in warfarin initialization. CONCLUSIONS: Computer modeling provides a reliable means of predicting initialization dosages for warfarin anticoagulation therapy with five INR inputs and therefore has merit in the clinical setting if used with sound clinical judgment.

Adult↗

Adenovirus-mediated over-expression of the cyclin/cyclin-dependent kinase inhibitor, p21 inhibits vascular smooth muscle cell proliferation and neointima formation in the rat carotid artery model of balloon angioplasty.

Vascular smooth muscle cell (VSMC) proliferation after arterial injury is important in the pathogenesis of a number of vascular proliferative disorders, including atherosclerosis and restenosis after balloon angioplasty. Thus, a better understanding of the molecular mechanisms underlying VSMC proliferation in response to arterial injury would have important therapeutic implications for patients with atherosclerotic vascular disease. The p21 protein is a negative regulator of mammalian cell cycle progression that functions both by inhibiting cyclin dependent kinases (CDKs) required for the initiation of S phase, and by binding to and inhibiting the DNA polymerase delta co-factor, proliferating cell nuclear antigen (PCNA). In this report, we show that adenovirus-mediated over-expression of human p21 inhibits growth factor-stimulated VSMC proliferation in vitro by efficiently arresting VSMCs in the G1 phase of the cell cycle. This p21-associated cell cycle arrest is associated both with significant inhibition of the phosphorylation of the retinoblastoma gene product (Rb) and with the formation of complexes between p21 and PCNA in VSMCs. In addition, we demonstrate that localized arterial infection with a p21-encoding adenovirus at the time of balloon angioplasty significantly reduced neointimal hyperplasia in the rat carotid artery model of restenosis. Taken together, these studies demonstrate the important role of p21 in regulating Rb phosphorylation and cell cycle progression in VSMC, and suggest a novel cytostatic gene therapy approach for restenosis and related vascular proliferative disorders.

Adenoviridae↗