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Biomedical subjects

C H Chang

Publications and source records attributed to C H Chang.

At least 199 records · Page 11Linked to original sources

Video-assisted cardiac surgery: preliminary results in Chang Gung Memorial Hospital.

OBJECTIVE: To summarize the experience of utilization of video-assisted endoscopy in 91 patients operated on at Chang Gung Memorial Hospital, Taipei, China. METHODS: From October 1995, through August 1996, 91 patients (44 male and 47 female) received video-assisted cardiac surgery (VACS). Their ages ranged from 1 year to 79.5 years (25.7 +/- 21.7). Indications for surgery were atrial septal defect (59 patients), ventricular septal defect (15), coronary artery disease (4), severe mitral regurgitation (4), severe tricuspid regurgitation (3), thrombosis of mitral mechanical prosthesis (3), left atrial tumor (2), and left ventricular thrombus with dilated cardiomyopathy (1). The VACS was performed through right or left anterior minithoracotomy and guided by video-assisted endoscopic techniques by means of projected images on the video monitor under extracorporeal circulation. The aorta was not cross-clamped and the myocardium was protected by continuous coronary perfusion with hypothermic fibrillatory arrest (rectal temperature 22.6 +/- 4.0 degrees C). Conventional instruments were used. RESULTS: All lesions were corrected successfully. The bypass time was 27 to 335 minutes (72.8 +/- 52.7). The operative time was 1.3 to 8.5 hours (3.0 +/- 1.7). There were no operative deaths and 3 late deaths. Follow-up was complete in all survivors (6 to 16 months, mean 8.7). Most of them were found to be in NYHA functional I or II. CONCLUSION: Our preliminary experiences demonstrate that VACS is simple and effective in surgical correction of selected cardiac lesions. Short-term results show good outcomes.

Adolescent↗

Minimally invasive coronary surgery in women.

OBJECTIVE: To evaluate the minimally invasive surgery in coronary artery bypass grafting and the feasibility for revascularization of triple vessel coronary artery disease. METHODS: Nine female patients, aged 49.1 to 81.6 years (mean 64.3), were operated on for triple vessel disease through minimally invasive surgical techniques. The surgeries were performed through limited left parasternal incision under femorofemoral extracorporeal circulation. The myocardium was protected by antegrade infusion of cold blood cardioplegic solution while the aorta was cross-clamped. Under direct vision, the left saphenous vein grafts were connected sequentially to the diagonal branch, obtuse marginal branch and posterior descending branch, and the left internal thoracic arterial graft was anastomosed to the left anterior descending artery in each patient. RESULTS: The number of distal anastomoses was 3 to 4 with a mean of 3.7. The aortic crossclamp time was 52 to 130 minutes (82 +/- 25 minutes). The duration of extracorporeal circulation was 78 to 151 minutes (115 +/- 29 minutes). The postoperative course was uneventful in all patients. The postoperative length of stay was 4 to 12 days (7.2 +/- 2.0 days). Follow-up (4.2 to 8.7 months, mean 6.4) was complete in all patients and there were no late deaths or angina. Coronary angiography of 2 patients showed patent grafts. All patients were satisfied with the good cosmetic healing of the incision. CONCLUSION: Our experience demonstrates that minimally invasive surgery in coronary artery bypass grafting is technically feasible and may be an alternative approach in surgical revascularization of triple vessel coronary artery disease, especially in female patients.

Aged↗

Endothelium-dependent relaxation of canine pulmonary artery endothelium after prolonged preservation.

OBJECTIVE: Experiments were designed to investigate the effect of Euro-Collins (EC) solution and University of Wisconsin (UW) solution on function of pulmonary arterial endothelium. METHODS: Third order canine pulmonary artery segments were preserved in cold (4 degrees C) UW (group 1, n = 8) or EC (group 2, n = 9) solutions for 16 hours. The preserved (group 1 and 2) and control (group 3, n = 7) pulmonary arterial segments with and without endothelium were studied in vitro in organ chambers to measure isometric tension. RESULTS: The endothelium-dependent relaxation to acetylcholine and adenosine diphosphate of group 1 and 3 were significantly better than those of group 2. CONCLUSIONS: We concluded that endothelium-dependent relaxation of canine pulmonary arterial endothelium to receptor-dependent acetylcholine and adenosine diphosphate were impaired after preservation with Euro-Collins solution. However, endothelium-dependent relaxation of pulmonary segments were well maintained after preservation with University of Wisconsin solution.

Animals↗

Necrotizing soft tissue infections. Surgical or conservative treatment?

BACKGROUND: Both surgeons and dermatologists are increasingly challenged with the prompt diagnosis and management of severe soft tissue infections. Although early surgical intervention appears to be for life-saving in many patients, especially those diagnosed as necrotizing fasciitis, some patients recover well with only conservative treatment. Because most of these infections have similar initial clinical presentations, there remains a need to find reliable clinical and/or laboratory parameters that can predict the prognosis and to accordingly judge the necessity and timing of operation. METHODS: We conducted a retrospective study of case records of patients with necrotizing soft tissue infections. The clinical presentation, laboratory findings, management, and therapeutic outcome of 34 cases with necrotizing soft tissue infections were reviewed. RESULTS: These infections were potentially life-threatening, with an overall mortality of 26.5%. Shock on admission was an extremely grave sign associated with a poor prognosis (P < 0.05). In this grave condition, most (80%) patients died regardless of the choice of treatment. Coagulation parameters, including platelet counts, prothrombin time (PT), and partial thromboplastin time (PTT), were available in 21 patients, of whom 16 had at least one abnormality at their initial presentation. In these 16 patients, those who underwent surgery had a significantly higher survival rate than those who were treated conservatively (P < 0.05). Prolonged PT was significantly associated with a higher mortality (P < 0.05). Surgery did seem to correct coagulopathies. However, in patients presenting with substantial alteration of all three coagulation parameters, there was no significant difference between medical treatment and surgical intervention in terms of mortality. In such cases, mortality was high (75%). On the other hand, the prognoses of patients who presented with normal coagulation profiles were rather good. Most of them recovered well despite the therapeutic option. Surgical treatment did not seem to increase additional benefits on chances of survival. Extent of tissue plane involvement, bacteriology, and site of infection had no significant influence on patients' survival. CONCLUSIONS: A comprehensive, well-organized, universal approach, regardless of classification, is essential for all suspected cases of necrotizing soft tissue infections. Prompt diagnostic studies are needed, and platelet counts, PT, and PTT are readily available parameters that provide substantial information on diagnosis and treatment, thus avoiding an unwarranted loss of life or unnecessary operative sequelae. Early diagnosis and, in most cases, prompt radical surgical, intervention remain the cornerstone of successful management in these infections.

Adolescent↗

Clubfoot deformity in congenital constriction band syndrome: manifestations and treatment.

Clubfoot deformity associated with congenital constriction band syndrome (CCBS) has different characteristics than classic idiopathic clubfoot, and is more difficult to treat. We describe the manifestations, treatment, and outcomes of nine patients treated for 11 CCBS-associated clubfoot deformities between 1980 and 1993. All but one of these children had an abnormal gestational or neonatal history. From an assessment of the correctability of the deformity and the associated secondary changes, the clubfoot severities were all classified as grade B (intermediate). The constriction bands in eight clubfeet were classified as type 0 (5 feet), II (2), or III (1), according to the location and depth of the band. Band types in three feet were unclassified because the band release was performed at other hospitals. We released the bands before correcting the clubfeet in the two patients with type II bands. The five patients with type 0 bands received casting first but with poor response. All clubfeet were corrected surgically; the procedures were posteromedial release in 10 feet, split tibialis anterior tendon transfer in five, and lengthening of the Achilles tendon in three. At an average follow-up of 3.8 years, seven of the 11 clubfeet were classified as having good results and four as fair. Among the six clubfeet with constriction bands on the ipsilateral leg, five were classified as having good results and one as fair. Two of the five clubfeet without constriction bands on the ipsilateral leg had good results and three had fair results. The presence of a band did not influence the final outcome of the clubfoot deformity (p > 0.05). In the five patients with forefoot varus deformity due to peroneal weakness, tibialis anterior tendon transfer successfully corrected the deformity. All the clubfeet treated in this series were plantigrade after treatment and had satisfactory results.

Amniotic Band Syndrome↗

Wrist arthrodesis using a slab bone graft from the dorsal radius.

Arthrodesis is a well-established procedure for the management of wrist deformity, instability, and arthritis resulting from various causes. Several techniques, with or without internal fixation or heterotopic bone grafting, have been described, but no single procedure has gained general acceptance. We present our results using a simple and reliable technique that employs a local bone graft and light internal fixation. From 1987 to 1996, eight consecutive patients with wrist lesions were treated using a modified Gill procedure for arthrodesis. The average age of patients was 62 years and the mean follow-up period was 4 years. A slab corticocancellous bone graft harvested from the dorsal aspect of the distal radius was turned about to cover the fusion mass from the distal radius to the third metacarpal bone. Kirschner wires and tension band wires were used to fix the wrist and compress the bone graft. A long arm cast was applied for 6 weeks, followed by a short arm cast until arthrodesis was achieved. The wrist position was well maintained by the tension band wire alone thereafter. Pain relief, grip strength, and assessment of daily activities were documented. Solid fusion was achieved smoothly in all cases and all patients were satisfied with the results. We recommend this simple and reliable technique for wrist arthrodesis.

Aged↗

Factor structure and dimensionality of the multidimensional health locus of control scales in measuring adults with epilepsy.

External locus of control has been implicated in the development of psychosocial problems in epilepsy, and adults with epilepsy exhibit scores that are more external than those of the normative sample of the Multidimensional Health Locus of Control (MHLC) scales. Although the MHLC scales has the potential to be quite useful in the assessment and treatment of adults with epilepsy, it has not been assessed psychometrically using data from persons with epilepsy. The present study examined the internal consistency, factor structure, and construct validity of the scales using data from a survey of 143 adults with epilepsy. Results from reliability analysis, confirmatory factor analysis, and Rasch analysis supported the hypothesized three-factor structure of the measure, which was internally reliable and factorially valid.

Adult↗

Airway compression by a biplane pediatric transesophageal echocardiography probe: case report.

Transesophageal echocardiography (TEE) has been extensively used in cardiac surgery to assess cardiac function and anatomical relationships in both adults and children. Newer monitoring devices, despite being labeled "noninvasive", often present significant risks. Physicians should be cautious with the use of TEE in infants and small children, recognizing that oversized probes may inadvertently compress vital structures, resulting in airway or vascular compromise. If severe compression of the airway or vascular structures occurs, TEE monitoring may need to be discontinued. Although technological progress has yielded smaller ultrasonic probes, the TEE probe is significantly larger than most other devices placed in the esophagus. We present in this report a case of airway compression using a small-sized biplane pediatric TEE probe in a child undergoing Blalock-Taussig shunt surgery. Pediatric patients may be more at risk for airway obstruction because of the over-size of the probe-distended esophagus in relation to adjacent airway structures.

Airway Obstruction↗

Central retinal vein occlusion associated with cryofibrinogenemia in a young adult--study of skin dynamic capillaroscopy.

A 26-year-old woman presented with a 2-month history of intermittent dim vision in her right eye and a diagnosis of central retinal vein occlusion (CRVO) was made. Investigations revealed Raynaud's phenomenon and cryofibrinogenemia. Skin capillaroscopy revealed tortuous vessels and decreased capillary blood-cell velocity in the capillaries of her finger nail fold which coincided with the CRVO attack. After treatment with oral aspirin for 3 months, the CRVO subsided, the capillary blood-cell velocity in the nail fold improved, and serum cryofibrinogen was undetectable. The time course of the cryofibrinogenemia and skin capillaroscopic findings correlated well with her ocular presentations. Study of cryofibrinogen should be included in the evaluation of young adults with CRVO.

Adult↗

Minimally invasive approach for coronary artery bypass surgery.

Forty-two patients, 33 male and 9 female, aged 35.7 to 81.6 years old (mean 62.7), were operated on for left main and/or triple vessel coronary artery disease by using minimally invasive cardiac surgical techniques. A myocardial infarction had occurred in 26 patients (61.9%). The left ventricular ejection fraction ranged from 17 to 83% (52+/-22). The surgeries were performed through left parasternal minithoracotomy (8 to 12 cm in length) under femoro-femoral or aorto-atrial cardiopulmonary bypass. The myocardium was protected by blood cardioplegic solution with the aorta crossclamped. Under direct vision, average 3.8 distal anastomoses were performed in each patient, with the saphenous vein grafts and the left internal thoracic arterial graft. The aortic crossclamp time was 62 to 137 min (80+/-15). The duration of cardiopulmonary bypass was 88 to 168 min (115+/-24). The postoperative course was uneventful in all patients. Follow-up (1.0 to 5.6 months, mean 2.9) was complete in all patients and there were no late deaths or angina. Coronary angiography of ten patients showed patent grafts. Our experience demonstrates that minimally invasive cardiac surgery during cardioplegic arrest is technically feasible and can be performed in coronary artery disease safely and effectively for complete revascularization.

Adult↗

Protective antibodies develop, and murine Lyme arthritis regresses, in the absence of MHC class II and CD4+ T cells.

Murine Lyme borreliosis is characterized by arthritis and carditis that are most severe at 2 to 3 wk, then regress during the course of persistent infection. Borrelia burgdorferi-specific Abs and CD4+ T cells have been implicated in the resolution phase of arthritis. Therefore, MHC class II transactivator (CIITA)-deficient mice that do not express conventional class II molecules and lack the normal CD4 repertoire were used to investigate the role of MHC class II-mediated responses in Lyme disease. The development of arthritis and carditis, and the resolution of arthritis, were similar in CIITA-deficient and control C57/BL6 mice. In contrast, the resolution of carditis was delayed in CIITA-deficient animals compared with controls. Moreover, CIITA-deficient mice developed B. burgdorferi-specific IgG2b Abs, and sera from these animals passively protected naive C3H/HeN mice from challenge inoculation and cleared B. burgdorferi from 2 day-infected C.B.17 SCID mice. These data suggest that CD4+ T cells and MHC class II-mediated responses are not required for the generation of protective Abs or the regression of arthritis, but may be important in the resolution of Lyme carditis in mice.

Animals↗

Overexpression of adenovirus-encoded transgenes from the cytomegalovirus immediate early promoter in irradiated tumor cells.

Efficient expression of therapeutic genes in irradiated tumor cells would facilitate the conversion of a malignant tumor nodule into a cancer vaccine in situ. We reported previously that transgene expression from an adenoviral vector could be markedly enhanced by treating transduced tumor cells with butyrate. In this study, we demonstrated that a similar butyrate effect could be achieved in irradiated tumor cells. In addition, irradiating cells at doses of 2-40 Gy prior to transduction could also amplify recombinant adenoviral transgene products in a cell-type-specific manner. This suggests that adenovirus-mediated gene therapy, radiation therapy, and butyrate-mediated cancer therapy may potentially be formulated into one synergistic protocol for cancer treatment.

Adenoviridae↗

HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer.

HER2/Neu is overexpressed in 25-30% of all human breast cancers as a result of both gene amplification and enhanced transcription. Transcriptional upregulation of HER2/neu leads to a 6-8-fold increased abundance of its mRNA per gene copy and likely results from the elevated activity of transcription factors acting on the HER2/neu promoter. Here we report that transcripts of PEA3, an ETS transcription factor implicated in oncogenesis, were increased in 93% of HER2/Neu-overexpressing human breast tumor samples. Analyses to uncover the molecular basis for elevated PEA3 transcripts in HER2/Neu-positive breast tumors revealed that the HER2/Neu receptor tyrosine kinase initiated an intracellular signaling cascade resulting in increased PEA3 transcriptional activity; transcriptionally-activated PEA3 stimulated HER2/neu and PEA3 gene transcription by binding to sites in the promoters of these genes. PEA3 also activates transcription of genes encoding matrix-degrading proteinases, enzymes required for tumor cell migration and invasion. These findings implicate PEA3 in the initiation and progression of HER2/Neu positive breast cancer, and suggest that PEA3 and signaling proteins affecting its regulation are appropriate therapeutic targets.

Animals↗

The H3/H4 tetramer blocks transcript elongation by RNA polymerase II in vitro.

We have investigated transcript elongation efficiency by RNA polymerase II on chromatin templates in vitro. Circular plasmid DNAs bearing purified RNA polymerase II transcription complexes were assembled into nucleosomes using purified histones and transient exposure to high salt, followed by dilution and dialysis. This approach resulted in nucleosome assembly beginning immediately downstream of the transcription complexes. RNA polymerases on these nucleosomal templates could extend their 15- or 35-nucleotide nascent RNAs by only about 10 nucleotides in 15 min, even in the presence of elongation factors TFIIF and SII. Efficient transcript elongation did occur upon dissociation of nucleosomes with 1% sarkosyl, indicating that the RNA polymerases were not damaged by the high salt reconstitution procedure. Since the elongation complexes were released by sarkosyl but not by SII, these complexes apparently did not enter the arrested conformation when they encountered nucleosomes. Surprisingly, elongation was no more efficient on nucleosomal templates reconstituted only with H3/H4 tetramers, even in the presence of elongation factors and/or competitor DNA at high concentration. Thus, in a purified system lacking nucleosome remodeling factors, not only the core histone octamer but also the H3/H4 tetramer provide an nearly absolute block to transcript elongation by RNA polymerase II, even in the presence of elongation factors.

Cell-Free System↗

Treatment and health outcomes of women and men in a cohort with coronary artery disease.

BACKGROUND: Women with coronary artery disease are treated differently than men. Although mortality has been studied, functional outcomes for women and men have not been prospectively compared. METHODS: The Manitoba Health Reform Impact Study used hospital databases to identify all residents aged 45 years and older in Manitoba who were hospitalized for a myocardial infarction between October 1, 1991, and September 30, 1992. Cohort members were interviewed twice, an average of 16 and 25 months after hospitalization. Baseline and follow-up measures included treatments (eg, physician visits, diagnostic testing, revascularization, and cardiac medications), physical health status (physical component summary [PCS] score derived from the Medical Outcomes Study Short Form 36), reinfarction, and mortality. RESULTS: Of the 820 patients who completed the initial survey, 31 died during the follow-up period, and 734 completed the follow-up survey. Data were complete for the primary outcome (PCS score) and all relevant covariates for the 677 patients who were included in this study Women constituted 34% of this cohort. Although women had more physician visits during follow-up, they were less likely to have undergone treadmill testing or angiography (odds ratio, 0.68; 95% confidence interval, 0.46-0.99). Women were equally likely to report taking beta-adrenergic blocking agents, but were less likely than men to report the use of aspirin (odds ratio, 0.69; 95% confidence interval, 0.48-0.98). After adjusting for baseline differences in PCS scores, age, income, social supports, and the levels of angina and dyspnea, the PCS score for women declined by 1.4 points, while the score for men improved by 0.2 points (P = .03). During the follow-up period, reinfarction and mortality rates were low overall, but were not different in men and women. CONCLUSIONS: In this cohort of patients with known coronary artery disease, we found less aggressive treatment of coronary artery disease and less use of aspirin among women than among men during 1 year of observation. After controlling for baseline differences, women with coronary artery disease experienced a more rapid decline in physical health status than did men during 1 year of follow-up.

Age Factors↗

Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis infection.

Most inbred strains of mice are susceptible to Leishmania amazonensis infection. We have examined the mechanism(s) underlying this generalized susceptibility using mice deficient in T cell development or in the expression of either MHC class I or class II. In contrast to wild-type C57BL/6 (B6) mice that uniformly developed large ulcerating lesions, mice lacking functional CD4+ T cells (due to targeted disruption of genes for either MHC class II trans-activator or I-A beta) showed no signs of lesion development for up to 12 to 14 wk postinfection and contained significantly lower numbers of parasites in lesions. Similarly, both B6 nude and RAG2 -/- mice failed to develop lesions. However, RAG2 -/- mice reconstituted with naive wild-type CD4+ T cells and beta2m -/- mice did develop lesions. Lesions of MHC class II -/- mice contained minimal numbers of CD8+ T cells, a marked reduction of monocytes/macrophages, and evident extracellular parasites. The inability to mount an inflammatory response in MHC class II -/- mice correlated with the failure to produce lymphokines that lead to the recruitment of monocytes/granulocytes. These results demonstrate that CD4+ T cells are the primary lymphocyte subset that mediates cellular infiltration, lesion pathology, and therefore, susceptibility to L. amazonensis infection. The disease-promoting CD4+ T cells in L. amazonensis-infected mice have the characteristics of Th1 cells. The striking differences in the course of infection between MHC class II -/- mice infected with L. amazonensis and Leishmania major suggest that these parasites may have adapted different strategies regarding the CD4-dependent immune response.

Animals↗

Design, synthesis, and evaluation of tetrahydropyrimidinones as an example of a general approach to nonpeptide HIV protease inhibitors.

Re-examination of the design of the cyclic urea class of HIV protease (HIVPR) inhibitors suggests a general approach to designing novel nonpeptide cyclic HIVPR inhibitors. This process involves the inversion of the stereochemical centers of the core transition-state isostere of the linear HIVPR inhibitors and cyclization of the resulting core using an appropriate cyclizing reagent. As an example, this process is applied to the diamino alcohol class of HIVPR inhibitors to give tetrahydropyrimidinones. Conformational analysis of the tetrahydropyrimidinones and modeling of its interaction with the active site of HIVPR suggested modifications which led to very potent inhibitors of HIVPR (24 with a Ki = 0.018 nM). The X-ray crystallographic structure of the complex of 24 with HIVPR confirms the analysis and modeling predictions. The example reported in this study and other examples that are cited indicate that this process may be generally applicable to other linear inhibitors.

Binding Sites↗

Improved P1/P1' substituents for cyclic urea based HIV-1 protease inhibitors: synthesis, structure-activity relationship, and X-ray crystal structure analysis.

We present several novel P1/P1' substituents that can replace the characteristic benzyl P1/P1' moiety of the cyclic urea based HIV protease inhibitor series. These substituents typically provide 5-10-fold improvements in binding affinity compared to the unsubstituted benzyl analogs. The best substituent was the 3,4-(ethylenedioxy)benzyl group. Proper balancing of the molecule's lipophilicity facilitated the transfer of this improved binding affinity into a superior cellular antiviral activity profile. Several analogs were evaluated further for protein binding and resistance liabilities. Compound 18 (IC90 = 8.7 nM) was chosen for oral bioavailability studies based on its log P and solubility profile. A 10 mg/kg dose in dogs provided modest bioavailability with Cmax = 0.22 microg/mL. X-ray crystallographic analysis of two analogs revealed several interesting features responsible for the 3,4-(ethylenedioxy)benzyl-substituted analog's potency: (1) Comparing the two complexes revealed two distinct binding modes for each P1/P1' substituent; (2) The ethylenedioxy moieties are within 3.6 A of Pro 81 providing additional van der Waals contacts missing from the parent structure; (3) The enzyme's Arg 8 side chain moves away from the P1 substituent to accommodate the increased steric volume while maintaining a favorable hydrogen bond distance between the para oxygen substituent and the guanidine NH.

Animals↗