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Biomedical subjects

E Y Cheng

Publications and source records attributed to E Y Cheng.

At least 37 records · Page 2Linked to original sources

Synovial sarcoma. Large size predicts poor outcome.

A consecutive series of 38 patients with synovial sarcoma diagnosed and treated in a consistent fashion from 1976 to 1994 was reviewed for prognostic variables. The histologic specimens were reviewed and confirmed by one pathologist. There was a minimum 4-year followup for all surviving patients and no patients were lost to followup. The treatment protocol consisted of surgical excision with a wide or radical margin and limb preservation when possible. In those patients in whom the surgical margin was undefined or was less than a wide margin, perioperative radiation therapy was used. Four patients presented with metastatic disease and all died of their disease. Thirty-four patients had localized disease at presentation. Variables considered in stratifying outcomes included histologic grade, histologic subtype, surgical margin, presence or absence of local recurrence, age, and size of tumor. Of the 34 patients without metastasis there was a strong statistical association between size of tumor and survival: 17 patients with tumors less than 5 cm indiameter had a 100% survival, 12 patients with tumors 5 cm to 10 cm had a 75% survival, and five patients with tumors greater than 10 cm had a 20% survival. The authors urge that a multicenter trial for neoadjuvant chemotherapy be initiated for patients presenting with a synovial sarcoma greater than 10 cm in diameter.

Adolescent↗

Injectable small intestinal submucosa: preliminary evaluation for use in endoscopic urological surgery.

PURPOSE: We evaluated the possible use of small intestinal submucosa in endoscopic urological surgery by assessing the smooth muscle regenerative capabilities and physical response of various forms of injectable small intestinal submucosa in the canine model. MATERIALS AND METHODS: In blinded fashion we injected small intestinal submucosa in 12 dogs submucosally under direct vision using a 20 gauge endoscopic needle. The 4 small intestinal submucosa formulations varied in harvesting method and sterilization technique. Animals were divided into groups of 3 and sacrificed 2 weeks, 6 weeks, 3 months and 6 months after surgery. Each injection site was analyzed grossly and histologically. Smooth muscle regeneration was identified by alpha-smooth muscle actin immunohistochemical staining. RESULTS: We identified 2 injectable small intestinal submucosa formulations that induced progressive smooth muscle regeneration at the site of submucosal injection compared with controls. De novo smooth muscle cells appeared in single cell aggregates as early as 6 weeks and in globular aggregates at 3 months. By 6 months early muscle bundle formation was noted. These 2 injectable small intestinal submucosa formulations also had the best submucosal volume preservation of about 25% of injected material during the study period. CONCLUSIONS: Injectable small intestinal submucosa promotes progressive submucosal smooth muscle regeneration in the canine bladder. The combined regenerative and bulking abilities of injectable small intestinal submucosa make this compound unique and novel. The clinical usefulness of injectable small intestinal submucosa for endoscopic correction of reflux and incontinence deserves further investigation.

Animals↗

Lumbosacral chordoma. Prognostic factors and treatment.

STUDY DESIGN: Retrospective analysis. OBJECTIVES: To analyze the prognostic factors in patients with chordomas, the success of various treatments, the diagnostic value of open versus needle biopsy, the neurologic impairment after sacral nerve resection, and the clinical presentation and site of origin. SUMMARY OF BACKGROUND DATA: Staging of chordomas has not been of much value, compared with other bone tumors, because for chordomas, grade is similar, metastasis is infrequent at presentation, and the prognostic significance of size is uncertain. METHODS: A review of patients with chordoma from 1965 through 1996 found 23 cases (mean age of patients, 55 years). The mean follow-up was 84 months. Mean tumor size was 81 mm (range, 35-135 mm), location was lumbar (n = 6), S1 (n = 4), S2 (n = 3), S3 (n = 7), S4 (n = 2), and S5 (n = 1). RESULTS: No tumors were found in the higher sacrum (S1-S2) alone, without involvement of the lower sacrum. Survival analysis at 5 years showed overall survival (OS) 86%, continuous disease-free survival (CDFS) 58%, and local recurrence-free survival (LRFS) 60%. The location of tumor, defined by highest level of involvement (lumbar vs. sacrum) was of prognostic significance for OS (P = 0.01; log-rank test), CDFS (P = 0.036), but not for LRFS (P = 0.189). Results of multivariate regression showed that location was significant for OS (P = 0.007), CDFS (P = 0.008), and LRFS (P = 0.001). For patients with positive margins (n = 16), initial radiation correlated with longer CDFS (P = 0.002; Mantel-Cox) and LRFS (P = 0.005, Mantel-Cox), but was not significant for OS (P = 0.41). For patients who received no radiation, a positive margin correlated with a shorter CDFS (P = 0.04), a trend to shorter LRFS (P = 0.08), but no difference in OS. Therefore, both a tumor-free margin and initial radiation correlated with a longer survival. No patients had urinary or bowel dysfunction when both S3 nerves were preserved. If one S3 nerve was preserved, 1 of 3 patients had partial urinary incontinence and 2 of 3 patients required bowel medications. If both S3 nerves were resected, all patients required intermittent urinary catheterization and bowel medications. If both S2 nerves were resected, there was complete urinary and bowel incontinence. CONCLUSIONS: The highest level of tumor involvement was prognostically significant for OS, CDFS, and LRFS. Radiation was of value when complete excision was not achieved. Bilateral S3 nerve preservation is necessary to ensure retention of normal urinary and bowel function.

Adult↗

HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, is overexpressed in colon carcinoma.

Using the palindromic PCR-cDNA display method, we have cloned a novel gene overexpressed by human colon carcinoma relative to normal colon. Among normal tissues examined, only testis expresses it at a high level. Sequence analysis revealed its extensive homology with checkpoint genes rad17 of Schizosaccharomyces pombe and RAD24 of Saccharomyces cerevisiae. This novel gene designated as hRad17 is localized to chromosome 5q12,13.1, a region known to be deleted in a variety of human cancers. Promoter region and one pseudogene of hRad17 have been identified. Whereas the increased expression of hRad17 by human colon carcinomas may be related to the known resistance of these cells to DNA-damaging agents during therapy, the deletion of hRad17 in a variety of cancers may predispose them to increased rate of mutation and heightened sensitivity to DNA-damaging agents, including radiation and anticancer drugs.

Animals↗

Role of angiotensin II in bladder smooth muscle growth and function.

Preliminary studies by our group and others indicate that angiotensin II may have an important role in the cellular regulation of smooth muscle growth and collagen production in the bladder. The exact mechanisms in which angiotensin II elicits its cellular effects are not known. Given the available information thus far, we hypothesize the following (see Figure 2): 1) Outlet obstruction of the bladder causes increased cell stretch/strain which in turn induces the local production of angiotensin II. Angiotensin II may also influence cell stretch/strain via its direct effects on bladder tone. 2) Angiotensin II then acts as a trophic factor in the bladder wall to cause smooth muscle cell hypertrophy/hyperplasia and increased collagen production via an autocrine and/or paracrine pathway. 3) The cellular effect(s) of angiotensin II may be mediated by secondary growth factors such as bFGF and TGFb Much more extensive research is certainly needed to reveal whether some part, or all of this hypothesis is correct. If angiotensin II is indeed active in regulating muscle and collagen changes in the pathologic bladder, then the clinical implications are extremely exciting since numerous pharmacologic agents are now available which can either inhibit angiotensin II production and/or block receptor mediated events. These agents may prove to be extremely useful in the clinical management of the neurogenic bladder in which obstructive changes may be prevented and potentially reversed. Despite this, caution must be exercised with regard to the potential use of any medications which alter the systemic renin-angiotensin system in the pediatric population since some research has suggested that an intact system may be necessary for the normal development of some organs, including the kidney.

Angiotensin II↗

Analysis of a paracentric inversion in human oocytes: nonhomologous pairing in pachytene.

A cytological analysis of the pairing configurations in meiosis in a 19-week human fetus with a de novo paracentric inversion of chromosome 7 (q11.23)(q21.1) is reported, using fluorescent in situ hybridization with a chromosome 7 DNA library, a DNA probe for the centromeric region of chromosome 7, and a probe for the William Syndrome Critical Region (WSCR) at 7q11.23. Of 1079 pachytene cells, 58% exhibited complete heterosynapsis of the inverted region while only 10.3% of cells exhibited the expected loop formation. Meiotic progression was observed to be normal.

Chromosome Inversion↗

Elevated bladder urine concentration of transforming growth factor-beta1 correlates with upper urinary tract obstruction in children.

PURPOSE: We evaluated urinary transforming growth factor-beta1 (TGF-beta1) concentration in children with upper urinary tract obstruction as a potential tool for supporting the diagnosis of clinically significant obstruction. MATERIALS AND METHODS: Renal pelvic and bladder urine samples were obtained for analysis from 30 patients a median of 5 months old who underwent surgery for obstruction at the ureteropelvic (29) and ureterovesical (1)junctions. Urinary TGF-beta1 concentration was measured using a quantitative sandwich enzyme-linked immunoassay technique. Bladder urine TGF-beta1 in patients with obstruction was compared with that in controls. In addition, we compared renal pelvic and bladder urine TGF-beta1 in patients with obstruction. RESULTS: Mean bladder urine TGF-beta1 plus or minus standard error of mean was 4-fold higher in patients with upper tract obstruction than in controls (195 +/- 29 versus 47 +/- 7 pg./mg. creatinine, p <0.001). In the obstructed group mean TGF-beta1 in the renal pelvic urine was 378 +/-86 pg./mg. creatinine, or twice that of the bladder urine (p = 0.02). CONCLUSIONS: Bladder urine TGF-beta1 in patients with upper urinary tract obstruction is significantly elevated compared with that in controls. To our knowledge our study is the first to identify a bladder urinary marker that correlates with upper urinary tract obstruction with greater than 90% sensitivity. Measuring TGF-beta1 in a voided bladder urine sample may provide an objective and noninvasive test for assisting in the diagnosis of upper urinary tract obstruction.

Adolescent↗

The mu-opioid receptor gene-dose dependent reductions in G-protein activation in the pons/medulla and antinociception induced by endomorphins in mu-opioid receptor knockout mice.

There appear to be different relationships between mu-opioid receptor densities and the acute and neuroadaptive mu-opioid agonist-induced responses of the multiple opioid neuronal systems, including important pons/medulla circuits. The recent success in creating mu-opioid receptor knockout mice allows studies of mu-opioid agonist-induced pharmacological and physiological effects in animals that express no, one or two copies of the mu-opioid receptor gene. We now report that the binding of mu-opioid receptor ligand, [3H][D-Ala2,NHPhe4,Gly-ol]enkephalin to membrane preparations of the pons/medulla was reduced by half in heterozygous mu-opioid receptor knockout mice and eliminated in homozygous mu-opioid receptor knockout mice. The endogenous mu-opioid agonist peptides endomorphin-1 and -2 activate G-proteins in the pons/medulla from wild-type mice in a concentration-dependent fashion, as assessed using [35S]guanosine-5'-o-(3-thio)triphosphate binding. This stimulation was reduced to half of the wild-type levels in heterozygous mice and eliminated in homozygous knockout mice. The intracerebroventricular injection of either endomorphin-1 or endomorphin-2 produced marked antinociception in the hot-plate and tail-flick tests in wild-type mice. These antinociceptive actions were significantly reduced in heterozygous mu-opioid receptor knockout mice, and virtually abolished in homozygous knockout mice. The mu-opioid receptors are the principal molecular targets for endomorphin-induced G-protein activation in the pons/medulla and the antinociception caused by the intracerebroventricular administration of mu-opioid agonists. These data support the notion that there are limited physiological mu-opioid receptor reserves for inducing G-protein activation in the pons/medulla and for the nociceptive modulation induced by the central administration of endomorphin-1 and -2.

Analgesics, Opioid↗

Differential bronchodilatory effects of terbutaline, diltiazem, and aminophylline in canine intraparenchymal airways.

OBJECTIVES: Intraparenchymal airways are involved in air flow regulation. Relaxation of intraparenchymal airways to volatile anesthetics varied by topographic location. This study was conducted to determine whether other bronchodilators (terbutaline, diltiazem, and aminophylline) relax bronchiolus to a greater degree than bronchus, as seen with volatile anesthetics. DESIGN: In vitro, controlled, randomized study. SETTING: Animal research laboratory. SUBJECTS: Adult dogs (n = 9). INTERVENTIONS: Proximal (outer diameter, 4-6 mm) and distal (outer diameter, 0.8-1.5 mm) airway rings of dogs were contracted in tissue baths with the effective concentration of acetylcholine that produces half the maximum response. Airway relaxant dose-response curves were constructed to measure isometric tension after administration of terbutaline (concentration range, 10(-8) to 10(-4) M), diltiazem (concentration range, 3 x 10(-7) to 1 x 10(-4) M), and aminophylline (concentration range, 10(-7) to 10(-4) M). MEASUREMENTS AND MAIN RESULTS: All three bronchodilators caused relaxation of the proximal and distal airways. At the maximum dose, diltiazem (maximum relaxation, 95%+/-2% [proximal], 94%+/-6% [distal]; p > .05) was the most efficacious, followed by terbutaline (maximum relaxation, 72%+/-13% [proximal], 55%+/-9% [distal]; p < .05) and aminophylline (maximum relaxation, 32%+/-10% [proximal], 35%+/-18% [distal]; p > .05. At the concentrations tested, they were equally efficacious. No significant differences in relaxation between proximal and distal airways were noted with diltiazem or aminophylline in the entire dose range. However, terbutaline relaxed the distal airway more than the proximal airway in the entire dose range. CONCLUSIONS: The results demonstrate that only terbutaline showed a differential airway relaxant effect between proximal and distal airways, as seen with volatile anesthetics.

Aminophylline↗

Patients, diagnoses, and procedures in a military internal medicine clinic: comparison with civilian practices.

BACKGROUND: Our goal was to compare the demographic features, diagnoses, and procedures in civilian and military ambulatory internal medicine clinics. METHODS: One year (September 1996 to August 1997) of data from the Ambulatory Data System of the Adult Primary Care Clinic at Madigan Army Medical Center was extracted and compared with the most recent (1995) National Ambulatory Medical Care Survey. RESULTS: A total of 41,374 Madigan patient encounters were compared with civilian data from the National Ambulatory Medical Care Survey. The age distribution was similar, with military patients averaging 53.5 years of age and civilian patients averaging 54.5 years. Military patients were more likely to be female (71 vs. 60%) and were more ethnically diverse (military: 68% white, 17% African American, 7% Hispanic, 7% Asian American, and 1% Native American; civilian: 78% white, 10% African American, 6% Hispanic, 5.9% Asian American, and 0.3% Native American). There were similar rank orderings of the top 189 diagnostic groups seen in each setting (Spearman's rho = 0.87). There were also no differences in the type or rank order of procedures performed between military and civilian internists (p = 0.53). CONCLUSION: The practice content of military and civilian practices appears to be more similar than different.

Age Distribution↗

Characterization of cultured bladder smooth muscle cells: assessment of in vitro contractility.

PURPOSE: The contractile properties of in vitro cultured bladder smooth muscle cells (SMC) are unknown. This study characterized the in vitro contractile response of human and rat bladder SMC to several pharmacological agonists known to induce in vivo contraction of intact bladder muscle. MATERIALS AND METHODS: Human and rat bladder SMC were seeded separately within attached collagen lattices. Contractility of SMC was analyzed by measuring alterations in lattice diameter after exposure and release to the following contractile agonists: carbachol (10(-7)-10(-3) microM), calcium-ionophore (10 microM), lysophosphatidic acid (LPA) (1 microM), endothelin (0.1 microM), KCl (3.33 mmicroM) angiotensin II (10 microM), and serotonin (100 microM). Results were recorded as a mean reduction of the lattice diameter. In addition, immunohistochemical analysis for phenotypic markers of smooth muscle cell differentiation was performed on bladder SMC cultured within collagen lattices. Human palmar fascia fibroblasts, which have been previously well characterized by in vitro contractility and immunohistochemistry, were tested in parallel and used as controls for all the above experiments. RESULTS: Human SMC had significant contractile responses to calcium-ionophore (31% +/- 4 relative percent contraction, p <0.05), LPA (34% +/- 4, p <0.05), and endothelin (37 +/- 5%, p <05). There was no significant contraction in response to carbachol, angiotensin II, KCl, or serotonin. Rat bladder SMC had a similar contractile response but did not contract in response to endothelin. In contrast to human and rat bladder SMC, fibroblasts did not contract to calcium-ionophore. CONCLUSIONS: In vitro cultured bladder SMC demonstrate loss of contractile response to normal in vivo pharmacologic agonists. Both human and rat bladder SMC can be distinguished in vitro from fibroblasts based upon their lack of contractile response to calcium- ionophore. These results demonstrate the ability to further characterize cultured bladder SMC with in vitro contractility. Further characterization is essential if we are to advance our understanding of the clinical applicability of in vitro studies utilizing cultured bladder SMC.

Animals↗

Comparison of discharge diagnoses and inpatient procedures between military and civilian health care systems.

BACKGROUND: Our goal was to compare the demographics and discharge diagnoses between civilian and military health care systems. METHODS: One year (1997) of data from the Retrospective Case Mix Adjustment System from the Military Health Services System were compared with the most recent (1994) civilian National Hospital Discharge Survey data. RESULTS: Military and civilian inpatient age (52.5 and 52.9 years), gender (54% and 59% female), and ethnic distributions (military: 71% white, 16% African American, 3% Asian American, 10% other; civilian: 65% white, 12% African American, 2.6% Asian American, 1.2% Native American, 18% unclassified) were similar. There were similar rank orderings of diagnosis-related groupings (Spearman's rank correlation = 0.72) and procedures performed during hospitalization (Spearman's rho = 0.74), although the military inpatients yielded a higher proportion associated with pregnancy and strenuous activity (traumatic joint disorders and hernias) than their civilian counterparts. CONCLUSION: The practice content of military and civilian inpatients appear to be more similar than different.

Diagnosis-Related Groups↗

Axillary artery aneurysm in tuberous sclerosis: cross-sectional imaging findings.

A 10-month-old boy with a known diagnosis of tuberous sclerosis presented with axillary and brachial masses. Cross-sectional imaging with computed tomography, magnetic resonance, and ultrasound demonstrated unsuspected aneurysms of the axillary and brachial arteries. The results of these studies significantly changed the preoperative planning for this patient, who was scheduled for a biopsy of a presumed soft-tissue tumor. To our knowledge, this is the first description of the cross-sectional imaging findings in the extremity peripheral vascular manifestation of tuberous sclerosis; it has only been previously described on angiography in one case. The rare association of peripheral arterial aneurysms with tuberous sclerosis is important to recognize not only for clinical diagnosis but also for appropriate surgical treatment and genetic counseling.

Aneurysm↗