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Biomedical subjects

K C Chung

Publications and source records attributed to K C Chung.

At least 19 recordsLinked to original sources

Pharmacokinetics of meropenem in animals, healthy volunteers, and patients.

Meropenem is a carbapenem antibiotic that appears to be widely distributed in tissues and is eliminated by both excretion and metabolism. Approximately 70% of meropenem is excreted via the kidneys, thus dosage adjustments are required for patients with renal impairment. The pharmacokinetic parameters for meropenem are similar to those for imipenem/cilastatin, with the exception of meropenem's smaller volume of distribution. The urinary recovery of meropenem is as high as that of imipenem in combination with cilastatin, an inhibitor of renal dehydropeptidase. Therefore, unlike imipenem, meropenem can be used without dehydropeptidase inhibitors to obtain a consistently high concentration in the urine without nephrotoxic effects.

Adult

Efficacy of magnetic resonance angiography in the evaluation of vascular malformations of the hand.

Conventional arteriography has been the accepted standard technique for demonstrating the anatomic details in vascular malformations of the hand. The technique of magnetic resonance angiography provides detailed anatomy for vascular anomalies of the hand without the use of an invasive technique or contrast enhancement. When magnetic resonance angiography is combined with magnetic resonance imaging, the extent of the lesion with respect to the surrounding tissues and the flow characteristics of the lesion can be determined noninvasively. In our institution, magnetic resonance angiography has replaced conventional arteriography as the technique of choice for the evaluation of these lesions. This report evaluates the efficacy of magnetic resonance imaging/ magnetic resonance angiography in the management of vascular malformations of the hand. Ten consecutive patients over 30 months (median age 37 years) underwent magnetic resonance imaging/magnetic resonance angiography evaluation after the clinical diagnosis of a vascular malformation of the hand was made. Four patients in the group had conventional arteriography performed before referral. Magnetic resonance imaging/magnetic resonance angiography clearly defined the anatomic extent of the lesion, its relationship to surrounding tissues, and the flow characteristics in each patient. In the four patients in whom conventional arteriography had been performed, the magnetic resonance angiography findings matched the arteriographic findings. On the basis of the magnetic resonance imaging/magnetic resonance angiography findings, six patients were treated nonoperatively with compressive garments and four patients had operative treatment (resection of lesion n = 2, digital ray resection n = 2). In this series, magnetic resonance imaging/magnetic resonance angiography was efficacious in the management of vascular malformations of the hand. This technique provides detailed images of both the arterial and venous components of the lesions without the requirements of contrast enhancement, ionizing radiation, or an invasive procedure. Furthermore, the resectability can be determined based on the extent of involvement and the flow characteristics.

Adolescent

Differentiation of central nervous system neuronal cells by fibroblast-derived growth factor requires at least two signaling pathways: roles for Ras and Src.

To evaluate the role of mitogen-activated protein (MAP) kinase and other signaling pathways in neuronal cell differentiation by basic fibroblast-derived growth factor (bFGF), we used a conditionally immortalized cell line from rat hippocampal neurons (H19-7). Previous studies have shown that activation of MAP kinase kinase (MEK) is insufficient to induce neuronal differentiation of H19-7 cells. To test the requirement for MEK and MAP kinase (ERK1 and ERK2), H19-7 cells were treated with the MEK inhibitor PD098059. Although the MEK inhibitor blocked the induction of differentiation by constitutively activated Raf, the H19-7 cells still underwent differentiation by bFGF. These results suggest that an alternative pathway is utilized by bFGF for differentiation of the hippocampal neuronal cells. Expression in the H19-7 cells of a dominant-negative Ras (N17-Ras) or Raf (C4-Raf) blocked differentiation by bFGF, suggesting that Ras and probably Raf are required. Expression of dominant-negative Src (pcSrc295Arg) or microinjection of an anti-Src antibody blocked differentiation by bFGF in H19-7 cells, indicating that bFGF also signals through a Src kinase-mediated pathway. Although neither constitutively activated MEK (MEK-2E) nor v-Src was sufficient individually to differentiate the H19-7 cells, coexpression of constitutively activated MEK and v-Src induced neurite outgrowth. These results suggest that (i) activation of MAP kinase (ERK1 and ERK2) is neither necessary nor sufficient for differentiation by bFGF; (ii) activation of Src kinases is necessary but not sufficient for differentiation by bFGF; and (iii) differentiation of H19-7 neuronal cells by bFGF requires at least two signaling pathways activated by Ras and Src.

Animals

Encephalitis and polyradiculoneuritis following rubella virus infection--a case report.

Amongst neurological complications of rubella virus infection, polyradiculoneuritis as well as encephalitis is very rare. Only one case of postrubella polyradiculoneuritis combined with encephalitis has been reported to our knowledge. A 17-years-old male presented with suspected meningoencephalitis in a recent epidemic of rubella in a southern district of Korea. He developed symmetrical hyporeflexic weakness of all four extremities with urinary disturbance several days later. Rubella IgM antibody titer (enzyme linked immunosorbent assay) was 58 AU/mL in serum and 12 AU/mL in cerebrospinal fluid. Electrophysiologic studies showed peripheral polyradiculoneuropathy with multifocal conduction block. Considering the involvement of the central nerve as well as the peripheral nerve in an adult patient, this case is thought to be valuable in view of the pathophysiology of neurologic complication in rubella virus infection.

Adolescent

Mutation of Di-leucine residues in the juxtamembrane region alters EGF receptor expression.

Di-leucine motifs have been implicated in the internalization or degradation of many membrane proteins. The epidermal growth factor receptor (EGFR) contains two di-leucine residues at 658 (TLRRLLQER) and 679 (NQALLRIL). To determine the role of these di-leucine motifs in regulating EGF receptor expression, activity, or ligand-induced degradation, the di-leucine residues at positions 658 or 679 were mutated to di-alanine residues, and the mutant receptors were stably expressed in CHO cells. The results indicate that mutation of either di-leucine motif generates and promotes cell surface expression of carboxy-truncated EGF receptors (M(r) 120, 140 kDa) that do not undergo EGF-induced autophosphorylation or degradation. In contrast, full-length EGF receptors (170 kDa) containing di-alanine substitutions resemble wild type receptors in that they respond to EGF by autophosphorylation, their tyrosine kinase activity is inhibited by protein kinase C, and they are degraded. The level of autophosphorylation of the 170 kDa mutant receptors and EGF-induced tyrosine phosphorylation of other cellular proteins is lower than that of the wild type receptor, consistent with formation of kinase-inactive heterodimers between the truncated and full-length mutant receptors. These results demonstrate that removal of either of the di-leucines leads to generation of inactivating carboxy-truncated receptors, suggesting that the two di-leucine motifs within the juxtamembrane region of the EGFR are important for ensuring normal receptor expression.

Alanine

Augmentation of tumor metastasis by platelet-activating factor.

The effect of platelet-activating factor (PAF) on experimental pulmonary metastasis by the B16F10 murine melanoma and the possible involvement of PAF in the activities of tumor necrosis factor alpha (TNF-alpha) and interleukin 1alpha (IL-1alpha) in tumor metastasis were investigated. i.p. injection of PAF enhanced the lung colonization in a dose- and time-dependent manner. PAF enhanced lung colonization when it was administered after, but not before, B16F10 inoculation. Multiple injections of PAF were more effective than a single injection. Neutralization of endogenous PAF with PAF antagonist BN50739 decreased lung colonization, suggesting that endogenous PAF plays an important role in pulmonary metastases. A single i.p. injection of TNF-alpha or IL-1alpha caused a marked enhancement in lung colonization. TNF-alpha- and IL-1alpha-mediated enhancement in lung colonies was significantly inhibited by BN50739. These results demonstrate that PAF has a metastasis-enhancing effect and is a mediator of the metastatic activities of TNF-alpha and IL-1alpha.

Animals

Wrist arthrography versus arthroscopy: a comparative study of 150 cases.

One hundred fifty patients with suspected wrist ligamentous injuries were studied with both triple injection wrist arthrography and arthroscopy. The diagnoses obtained by these two techniques were compared to determine the differences between these two modalities. All the patients in this study had both the clinical diagnosis of ligamentous injuries of the wrist and normal findings on x-ray films. Intercarpal abnormalities were found in 106 patients (71%) at wrist arthrography and in 136 patients (91%) at arthroscopy. There was only 42% agreement (63 patients) between the arthrographic and arthroscopic diagnoses. Eighty-seven patients (58%) had alterations of their arthrographic diagnoses following arthroscopy. For patients with normal arthrographic findings (44 patients), 88% underwent arthroscopy because there was insufficient correlation between the physical examination findings and the arthroscopic findings. Out of the 44 patients with normal arthrographic findings, 35 patients (80% of the subgroup) had injuries found at arthroscopy. Over half of the patients had alterations in their arthrographic diagnoses following arthroscopy. In a patient with suspected ligamentous injury of the wrist, wrist arthroscopy may be the most efficient method in arriving at a definitive diagnosis.

Adolescent

Use of modern craniofacial techniques for comprehensive reconstruction of the acromegalic face.

The severe acromegalic patient poses a difficult reconstructive dilemma to the craniofacial surgeon. Significant facial deformities can include frontal bossing, prominent supraorbital ridges, malar flatness, maxillary hypoplasia, mandibular prognathism with class III malocclusion, and macrogenia. Reports on the correction of these deformities are rare. Prior publications describe long hospital stays, weeks of intermaxillary fixation, requirement for a tracheostomy, as well as the need for multiple, staged procedures and interdisciplinary teams. In an effort to extend the advances of modern craniofacial techniques to this group of patients, we performed an extensive reconstruction on a 28-year-old acromegalic patient using a one-stage procedure without the use of intermaxillary fixation and without the added morbidity of a tracheostomy. The procedure addressed the skeletal deformities of the upper face, the midface, and the lower face. The operation was performed by a single plastic surgery team and the patient was extubated in 36 hours and discharged in 6 days. We believe that the use of rigid fixation and the judicious application of modern craniofacial principles can allow a complex yet safe one-stage procedure to reconstruct the acromegalic face. Such an approach showed decreased perioperative morbidity and provided an excellent functional and aesthetic result.

Acromegaly

Diagnosis of silicone gel breast implant rupture by ultrasonography.

To prospectively evaluate the efficacy of ultrasonography in the diagnosis of ruptured silicone gel breast implants, 98 patients (192 implants) underwent preoperative breast ultrasonography prior to silicone gel breast implant removal. The prevalence of implant rupture confirmed at surgery in this group of patients was 62 of the 192 implants (32 percent). Of the 60 implants diagnosed as ruptured by ultrasonography, 46 were confirmed as having visible defects at surgery (true positive) for a positive predictive value of 77 percent. Of the 132 implants diagnosed as intact by ultrasonography, 116 were confirmed as intact at surgery (true negative) for a negative predictive value of 88 percent. Overall, the sensitivity of ultrasonography for implant rupture was 74 percent, and the specificity was 89 percent. These findings demonstrate that ultrasonography is an effective imaging modality for the diagnosis of silicone gel breast implant rupture. Compared with mammography, ultrasonography appears to offer superior sensitivity and specificity without radiation exposure or discomfort. Although magnetic resonance imaging has shown considerable promise in the diagnosis of implant rupture, ultrasonography provides comparable sensitivity at a fraction of MRI's cost.

Breast

A system for the analysis of seat support surfaces using surface shape control and simultaneous measurement of applied pressures.

A system for the design and analysis of seat support and buttock tissue interfaces has been developed. It has the ability to control the seating surface shape while measuring the pressure applied to the buttocks by the surface. Pressures are measured over an 11 x 12 rectangular array of support elements using silicon pressure sensors mounted in a swiveling head atop each support element. Control of surface shape is mediated by selective linear translation of the support elements along their respective vertical axes. Closed-loop control of the system allows for the dynamic formulation of a support surface on the basis of programmable criteria. The system is intended to function as a research tool to facilitate the study of the relationships between support surface shape and interface pressure, and support surface shape and soft tissue distortion. The purpose of this paper is to present the system instrumentation and the rationale behind its design and development. The paper also presents the results of several tests to evaluate the accuracy and performance of the system. This evaluation included a pilot study on 10 able-bodied subjects. The results of these system evaluations indicate that the system is capable of making repeatable and precise measurements of pressure and surface element position and can formulate support surface shapes that satisfy specified optimization criteria.

Back

Pericardiectomy for pericardial constriction.

Constrictive pericarditis is a pathologic condition that may lead to significant morbidity. Definitive management of constrictive pericarditis requires pericardiectomy. A retrospective review of pericardiectomy for constrictive pericarditis at the Ochsner Clinic was undertaken. Twenty-one patients (17 male, four female) underwent pericardiectomy for constrictive pericarditis between January 1969 and June 1994. Ages ranged from 15 to 66 years (mean 41.5 years). Pedal edema, dyspnea, fatigue, and chest pain were the most common symptoms. Fifteen patients had important comorbidities. Preoperative New York Heart Association (NYHA) class was I (2), II (8), III (6), IV (5). Mean preoperative catheterization data, available in 17 patients (81%), demonstrated elevated intracardiac pressures (right atrial 17.4 mm Hg, right ventricular end-diastolic 22.4 mm Hg, pulmonary artery 26.2 mm Hg, pulmonary capillary wedge 20.2 mm Hg, left ventricular end-diastolic 20.1 mm Hg). A total pericardiectomy was performed in nine patients (sternotomy 8, thoracotomy 1). Pericardiectomy limited anteriorly to the phrenic nerves was performed in 11 patients (sternotomy 9, thoracotomy 2). One partial pericardiectomy was performed through a sternotomy. Cardiopulmonary bypass was used in six patients (29%). Mean hospital stay was 12 days (preoperative 4.2, postoperative 7.67). All patients achieved NYHA Class I postoperatively. Sixteen patients were discharged in sinus rhythm. No early mortality (<30 days), or major postoperative complications were observed. Pericardiectomy for pericardial constriction can be performed safely low morbidity and mortality and can favorably impact the natural history of this debilitating condition.

Adolescent

Repletion of high energy phosphates in the postischemic neonatal heart.

Milrinone improves function in failing adult hearts, but it has not been examined in the immature myocardium. The purpose of this study was to characterize the effects of milrinone, a phosphodiesterase inhibitor, on immature hearts, and compare these to dobutamine, a commonly used catecholamine inotrope. One hundred isolated working neonatal rabbit hearts were used. Hearts were made ischemic (37 degrees C) for 1 hour and reperfused for 0, 10, 40, or 70 minutes. In separate groups, infusion of milrinone (1.0 microg/mL) or dobutamine (0.1 microg/mL) was begun after reperfusion for 10 or 40 minutes. High energy phosphates, total nondiffusable nucleotides, cyclic adenosine monophosphate (cAMP), and the percent recovery of cardiac output were determined. Cardiac output returned to normal, and adenosine triphosphate (ATP) and total nondiffusable nucleotide levels did not decline when dobutamine or milrinone were begun after 10 minutes of reperfusion. In hearts receiving inotropes after 40 minutes of reperfusion, when high energy phosphates were low, ATP increased, and total nondiffusable nucleotide repletion was observed. Cardiac output did not improve when inotropes were begun after 40 minutes. cAMP was higher in milrinone hearts compared to dobutamine, but there was no simple relation between cAMP and ventricular function. Inotropes may increase purine salvage pathway activity. Deriving maximum benefit from inotropes may depend on beginning infusions early, before the appearance of irreversible changes.

Adenosine Triphosphate

Stability of granisetron hydrochloride in a disposable elastomeric infusion device.

The stability and sterility of granisetron hydrochloride in 5% dextrose injection or 0.9% sodium chloride injection when stored in a disposable elastomeric infusion device were studied. Granisetron was diluted to 0.02 mg/mL (as the hydrochloride salt) in 5% dextrose chloride injection. The solution was placed in the drug reservoir of a disposable elastomeric infusion device and refrigerated at 4 degrees C for 14 days. A total of eight pumps were prepared, four containing granisetron 0.02 mg/mL in 5% dextrose injection and four containing granisetron 0.02 mg/mL in 0.9% sodium chloride injection. The solutions were assayed for granisetron concentration by stability-indicating high-performance liquid chromatography at 0 hours, 24 hours, 48 hours, 7 days, and 14 days. Each solution was inspected for clarity, color, and precipitation, and sterility testing was performed. Throughout the study, the mean concentration of granisetron remaining was more than 92% of the initial concentration both in 5% dextrose injection and in 0.9% sodium chloride injection. Individual solutions in 0.9% sodium chloride injection consistently maintained more than 90% of the initial drug concentration for only seven days. No microbial growth was detected. No precipitation, color change, or haziness was seen. Granisetron 0.02 mg/mL (as the hydrochloride salt) was stable and free of microbial growth in 0.9% sodium chloride injection for up to 7 days and stable and free of microbial growth in 5% dextrose injection for up to 14 days when stored at 4 degrees C in a disposable elastomeric infusion device.

Antiemetics