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Biomedical subjects

D Chang

Publications and source records attributed to D Chang.

At least 19 recordsLinked to original sources
PubMed2001

A regulatory region rearranged BK virus is associated with tubulointerstitial nephritis in a rejected renal allograft.

A renal allograft transplant patient with high serum creatinine presented clinical symptoms of rejection. Sections of renal biopsy tissue showed mononuclear leukocyte infiltration in the tubulointerstitium and nuclear enlargement with inclusions in the tubular epithelium. The morphological characteristics resembled polyomavirus-induced interstitial nephritis. Electron microscopy of the nuclear inclusions showed paracrystalline arrays of naked viral particles with a diameter of 45 nm. Molecular studies revealed that a new variant of BK virus (BKV) with rearrangement at the regulatory region was involved in the nephritis. The BKV regulatory region contained a tandem repeat from the P-block to the Q-block causing duplication of several important transcriptional elements or transcriptional factor binding motifs. This is the first report to show a naturally occurring BKV variant with regulatory region rearrangement associated with tubulointerstitial nephritis.

Adult↗
PubMed2001

Apoptosis of ventricular and atrial myocytes from pacing-induced canine heart failure.

OBJECTIVE: Rapid ventricular pacing in dogs results in a low output cardiomyopathic state similar to idiopathic dilated cardiomyopathy in man. Cell death by apoptosis may play an important role in the loss of cardiac function. This study investigates the molecular pathways involved in the regulation of apoptosis in dogs with pacing-induced heart failure. METHODS: Apoptosis was identified by terminal transferase nick end-labelling (TUNEL) in the ventricles and atria of dog hearts affected by rapid-ventricular pacing. Western blots were used to determine expression of the components involved in the initiation (Fas, Fas-Ligand, FADD), regulation (Bcl-2, Bax) and execution (caspase-2 and caspase-3) of apoptosis. RESULTS: Pacing-induced heart failure resulted in a significant increase in the number of ventricular and atrial myocyte nuclei undergoing apoptosis as measured by TUNEL. Compared to the samples from control hearts (n=6) the expression of Bcl-2, an inhibitor of apoptosis, was significantly reduced in ventricles from five dogs with pacing-induced heart failure. No change in the expression of the apoptotic inducer Bax was detected. Fas and FADD were significantly elevated in all paced ventricles, and Fas-L was only detected in the paced hearts. Both caspase-2 and caspase-3 were elevated following ventricular pacing. CONCLUSIONS: We have identified components of the signalling pathways along which apoptosis proceeds following the induction of heart failure in dogs. Apoptosis was also detected in the atria raising the possibility that, like human dilated cardiomyopathy, the molecular changes are global.

Animals↗
PubMed2001

Efficacy of a proximal occlusion catheter with reversal of flow in the prevention of embolic events during carotid artery stenting: an experimental analysis.

OBJECTIVE: The role of percutaneous angioplasty and stenting of carotid bifurcation lesions has been limited by its potential for producing embolic debris. We evaluated the efficacy of a proximal occlusion catheter (POC) in the prevention of embolic events during carotid artery stenting. In addition, pressure measurements relevant to the clinical application of this device were obtained from 10 patients undergoing carotid endarterectomy. METHODS: The POC is a guiding catheter with an occlusion balloon attached on the outside of the catheter at its distal end. Occlusion of the common carotid artery (CCA) was achieved by inflating the balloon while access to carotid bifurcation lesions was obtained through the inner lumen. The POC was inserted in the CCA of 10 dogs via the femoral artery. The side port of the POC was connected to a sheath placed in the femoral vein, thereby creating an external arteriovenous shunt. Ten artificial radiopaque particles simulating embolic particles and contrast agent were introduced in the CCA and monitored fluoroscopically. As a control, the same procedure was performed with a standard guiding catheter without an occlusion balloon. In 10 patients undergoing carotid endarterectomy, the internal carotid artery (ICA) and external carotid artery stump pressures and the pressure in the internal jugular vein were measured. RESULTS: Without the external arteriovenous shunt, in all animals there was prograde flow in the distal CCA despite CCA occlusion. This flow was derived from the thyroid artery. However, once the arteriovenous shunt was activated, reversal of flow in the distal CCA was achieved in each animal, and all the artificial particles were recovered from the side port of the POC. In the control group, each particle embolized to the brain (100%, P <.01). In the patients, the mean stump pressures in the ICA and external carotid artery and the jugular vein pressure were 51.8 +/- 14.2, 62.2 +/- 15.1, and 6.5 +/- 3.5 mm Hg, respectively. In each case, the jugular vein pressure was the lowest among the three. CONCLUSIONS: Obtaining proximal CCA control by inflating the POC does not sufficiently prevent embolization. However, reversal of flow in the ICA can always be created with the external shunt, which effectively prevents embolization. Thus, POC may markedly lower procedural stroke rates during carotid artery stenting. The ability of POC to prevent embolization before crossing the lesion with a guidewire may be an important advantage over other distal protection devices.

Angioplasty, Balloon↗
PubMed2001

Surfactant protein D enhances phagocytosis and killing of unencapsulated phase variants of Klebsiella pneumoniae.

Pulmonary surfactant protein D (SP-D) is a collagenous C-type lectin (collectin) that is secreted into the alveoli and distal airways of the lung. We have studied the interactions of SP-D and alveolar macrophages with Klebsiella pneumoniae, a common cause of nosocomial pneumonia. SP-D does not agglutinate encapsulated K. pneumoniae but selectively agglutinates spontaneous, unencapsulated phase variants, such as Klebsiella strain K50-3OF, through interactions with their lipopolysaccharides (LPS). These effects are calcium dependent and inhibited with maltose but not lactose, consistent with involvement of the SP-D carbohydrate recognition domain. Precoating of K50-3OF with SP-D enhances the phagocytosis and killing of these organisms by rat alveolar macrophages in cell culture and stimulates the production of nitric oxide by the NR-8383 rat alveolar macrophage cell line. SP-D similarly enhances the NO response to K50-3OF LPS adsorbed to Latex beads under conditions where soluble LPS or SP-D, or soluble complexes of SP-D and LPS, do not stimulate NO production. Our studies demonstrate that interactions of SP-D with exposed arrays of Klebsiella LPS on a particulate surface can enhance the host defense activities of alveolar macrophages and suggest that activation of macrophages by SP-D requires binding to microorganisms or other particulate ligands. Because unencapsulated phase variants are likely to be responsible for the initial stages of tissue invasion and infection, we speculate that SP-D-mediated agglutination and/or opsonization of K. pneumoniae is an important defense mechanism for this respiratory pathogen in otherwise healthy individuals.

Agglutination↗
PubMed2000

MHC recognition in thymic development: distinct, parallel pathways for survival and lineage commitment.

The molecular events triggered by MHC recognition and how they lead to the emergence of mature CD4 and CD8 lineage thymocytes are not yet understood. To address these questions, we have examined what signals are necessary to drive the development of CD8 lineage thymocytes in TCRalpha(-) mice in which TCR/MHC engagement cannot occur. We find that the combination of constitutive Notch activity and constitutive Bcl-2 expression are necessary and sufficient to allow the appearance of mature CD8 lineage thymocytes in TCRalpha(-) mice. In addition, Notch activity alone in TCRalpha(-) mice can induce the up-regulation of HES1, suggesting that thymocytes are competent to respond to Notch signaling in the absence of MHC recognition. These data indicate that survival and lineage commitment represent distinct, parallel pathways that occur as a consequence of MHC recognition, both of which are necessary for the development of mature CD8 lineage T cells.

Animals↗
PubMed2000

Preparation of (S)-N-substituted 4-hydroxy-pyrrolidin-2-ones by regio- and stereoselective hydroxylation with Sphingomonas sp. HXN-200.

[reaction: see text] Enantiopure (S)-N-substituted 4-hydroxy-pyrrolidin-2-ones have been prepared for the first time by regio- and stereoselective hydroxylation of the corresponding pyrrolidin-2-ones by use of a biocatalyst. Hydroxylation of 6 and 8 with Sphingomonas sp. HXN-200 afforded 68% of (S)-7 in >99.9% ee and 46% of (S)-9 in 92% ee, respectively. Simple crystallization increased the ee of (S)-9 to 99. 9% in 82% yield.

Chromatography, High Pressure Liquid↗
PubMed2000

Enhanced antiviral and opsonic activity of a human mannose-binding lectin and surfactant protein D chimera.

The carbohydrate recognition domains (CRDs) of human serum mannose-binding lectin (MBL) and pulmonary surfactant protein D (SP-D) have distinctive monosaccharide-binding properties, and their N-terminal and collagen domains have very different quaternary structures. We produced a chimeric protein containing the N terminus and collagen domain of human SP-D and the neck region and CRD of human MBL (SP-D/MBLneck+CRD) to create a novel human collectin. The chimera bound to influenza A virus (IAV), inhibited IAV hemagglutination activity and infectivity, and induced aggregation of viral particles to a much greater extent than MBL. Furthermore, SP-D/MBLneck+CRD caused much greater increases in neutrophil uptake of, and respiratory burst responses to, IAV than MBL. These results indicate that pathogen interactions mediated by the MBL CRD are strongly influenced by the N-terminal and collagen-domain backbone to which it is attached. The presence of the CRD of MBL in the chimera resulted in altered monosaccharide binding properties compared with SP-D. As a result, the chimera caused greater aggregation and neutralization of IAV than SP-D. Distinctive functional properties of collectin collagenous domains and CRDs can be exploited to generate novel human collectins with potential for therapy of influenza.

Animals↗
PubMed2000

Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice.

TALL-1/Blys/BAFF is a member of the tumor necrosis factor (TNF) ligand superfamily that is functionally involved in B cell proliferation. Here, we describe B cell hyperplasia and autoimmune lupus-like changes in transgenic mice expressing TALL-1 under the control of a beta-actin promoter. The TALL-1 transgenic mice showed severe enlargement of spleen, lymph nodes, and Peyer's patches because of an increased number of B220+ cells. The transgenic mice also had hypergammaglobulinemia contributed by elevations of serum IgM, IgG, IgA, and IgE. In addition, a phenotype similar to autoimmune lupus-like disease was also seen in TALL-1 transgenic mice, characterized by the presence of autoantibodies to nuclear antigens and immune complex deposits in the kidney. Prolonged survival and hyperactivity of transgenic B cells may contribute to the autoimmune lupus-like phenotype in these animals. Our studies further confirm TALL-1 as a stimulator of B cells that affect Ig production. Thus, TALL-1 may be a primary mediator in B cell-associated autoimmune diseases.

Animals↗
PubMed2000

Treatment with cytotoxic immunosuppression agents increases urinary excretion of JCV in patients with autoimmune disease.

Human JC virus is ubiquitous in human populations and is reactivated frequently in immunosuppressed patients. Fifty-one patients with autoimmune disease receiving immunomodulating therapy were evaluated to study the possible relationship between immunosuppression and JCV viruria. Patients were divided into cytotoxic and noncytotoxic treatment groups based on their prescription. The incidence of JCV viruria in the cytotoxic treatment group was significantly higher than that in the noncytotoxic group (67% vs. 28%; P < 0.05). Most patients with JCV viruria were receiving corticosteroid (P = 0.03 for any dose and P < 0.001 for higher-dose treatments) and cytotoxic agents (P = 0.02). Age, disease duration, and medication duration appeared not to be the precipitating factors of JCV viruria in this study. The results of clinical evaluation indicate that cytotoxic immunosuppression may play an important role in JC virus reactivation.

Adolescent↗
PubMed2000

Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies.

BACKGROUND: Corticosteroids are first-line drugs for the treatment of a variety of conditions in women of childbearing age. Information regarding human pregnancy outcome with corticosteroids is limited. METHODS: We collected prospectively and followed up 184 women exposed to prednisone in pregnancy and 188 pregnant women who were counseled by Motherisk for nonteratogenic exposure. The primary outcome was the rate of major birth defects. A meta-analysis of all epidemiological studies was conducted. The Mantel-Haenszel summary odds ratio was calculated for the pooled studies with 95% confidence intervals. A cumulative summary odds ratio was also calculated by combining studies in chronological order. Chi-squared for homogeneity was determined to establish the comparability of the studies. RESULTS: In our prospective study, there was no statistical difference in the rate of major anomalies between the corticosteroid-exposed and control groups. In the meta-analysis, the Mantel-Haenszel summary odds ratio for major malformations with all cohort studies was 1.45 [95% CI 0.80, 2.60] and 3.03 [95% CI 1.08, 8. 54] when Heinonen et al. ('77) was removed. This suggests a marginally increased risk of major malformations after first-trimester exposure to corticosteroids. In addition, summary odds ratio for case-control studies examining oral clefts was significant (3.35 [95% CI 1.97, 5.69]). CONCLUSIONS: Although prednisone does not represent a major teratogenic risk in humans at therapeutic doses, it does increase by an order of 3.4-fold the risk of oral cleft, which is consistent with the existing animal studies.

Abnormalities, Drug-Induced↗
PubMed2000

CT in the selection of patients with abdominal or pelvic sarcoma for reoperative surgery.

BACKGROUND: Retroperitoneal or visceral sarcoma may recur with disease limited to the abdomen and pelvis. In this clinical situation, further surgical treatments in an attempt to control the disease may be appropriate. CT is used to help select patients for additional surgical interventions. STUDY DESIGN: Preoperative abdominal and pelvic CT scans of 33 patients with recurrent sarcoma were reviewed retrospectively. All patients underwent reoperative surgery and, when appropriate, perioperative intraperitoneal chemotherapy. Patients were divided into two groups according to survival and disease status: alive with no evidence of disease (n = 7) and alive with disease or dead of disease (n = 26). Twenty-two CT indices were studied retrospectively for each patient and evaluated statistically. RESULTS: The presence of large (greater than 5 cm) tumor volume in 3 of the 13 abdominopelvic regions resulted in a significant difference in the prognosis between the groups of patients. These findings included tumor in the left lower quadrant (p = 0.032), tumor in the pelvis (p = 0.008), and tumor in the distal jejunum (p = 0.032). Two other CT indices that showed a significant difference in survival between the groups were involvement of five abdominopelvic regions or fewer (p = 0.008) and a peritoneal cancer index of 15 or less (p = 0.03). A statistical approach using a tree-structured diagram showed that patients with tumor diameter greater than 5 cm in the pelvis accompanied by tumor involvement of more than one segment of small bowel had a 0% probability of postoperative disease-free survival. In contrast, patients with tumor diameter less than 5 cm in the pelvis on CT had an 86% probability of disease-free survival. CONCLUSIONS: For patients with recurrent sarcoma, selection criteria were generated by a preoperative CT of the abdomen and pelvis. In this disease, CT was a reliable diagnostic test for predicting benefit from further surgical interventions and should be used in the future to help select patients for an aggressive versus a palliative approach.

Abdominal Neoplasms↗
PubMed2000

Experience of pancreaticoduodenectomy in a district general hospital

AIMS: Long-term survival after surgery for pancreatic cancer remains very low and it is particularly important that minimal surgery-related morbidity and mortality rates are achieved. It has been stated that centres performing small numbers of proximal pancreaticoduodenectomies are likely to have high morbidity and mortality rates. The results of pancreatic surgery in a district general hospital are reported. METHODS: This was a retrospective analysis of all pancreaticoduodenectomies over 4 years. RESULTS: Twenty-one selected patients underwent proximal pancreaticoduodenectomy and two patients total pancreatectomy over a 4-year period from 1995 to 1999. The operations were performed by two surgeons with a special interest in upper gastrointestinal surgery. The median age was 62 (38-83) years. There were 14 men and nine women. Fifteen patients had adenocarcinoma of the head of the pancreas, five had ampullary carcinoma, one duodenal carcinoma and there was one case of chronic pancreatitis. Six patients had pylorus-preserving pancreaticoduodenectomy (PPPD) and 15 had a standard Whipple procedure. The median stay in hospital was 20 (13-26) days. Two patients had a pancreatic leak, one of whom developed an intra-abdominal abscess which was treated successfully by percutaneous drainage. Six patients experienced delayed gastric emptying, two of whom had PPPD. Both the 30-day and in-hospital mortality rates were zero. The median number of lymph nodes dissected was 12 and in 11 patients no nodal metastasis was found. CONCLUSIONS: It is possible to perform pancreatic surgery in a district general hospital and achieve results that are comparable to those of specialist centres.

Journal Article↗
PubMed2000

Results of treatment of 33 patients with peritoneal mesothelioma.

BACKGROUND: Peritoneal mesothelioma is a rare peritoneal malignancy, representing approximately one-third of all mesotheliomas. It is regarded as a universally fatal cancer with few treatment options. METHODS: Records of 33 patients with peritoneal mesothelioma were reviewed retrospectively. Demographic, clinical and quantitative prognostic indicators were evaluated and analysed statistically using survival as endpoint. Patients were treated by a uniform strategy involving cytoreductive surgery with peritonectomy procedures and perioperative intraperitoneal chemotherapy (cisplatin, doxorubicin). RESULTS: There were ten women and 23 men; mean age was 53.0 years. Asbestos exposure was recorded in five patients and a family history of cancer in 13. Presentation was mainly abdominal distension and pain. Median survival was 31.0 months; overall projected survival at 3 years was 56 per cent. The most significant positive predictive factors of survival were: female sex (P= 0.003), low prior surgical score (P=0.002), completeness of cytoreduction (P=0.0002) and second-look surgery (P=0.019). The morbidity rate for this combined treatment was 33 per cent and the perioperative mortality rate was 3 per cent. CONCLUSION: Although peritoneal mesothelioma is rare, progress in its management has occurred. Survival has been extended and selection factors by which patients may be allocated to aggressive management strategies have been defined.

Adolescent↗
PubMed2000

Lattice intrahepatic doxorubicin with and without in-flow occlusion: a pharmacokinetic study of direct liver injection.

AIM: To assess possible improvements in drug delivery to unresectable liver tumours we investigated the pharmacokinetics of intrahepatic doxorubicin in the dog liver with and without inflow occlusion. METHODS: Using a lattice template, doxorubicin was injected into 16 sites (over a 9 cm2 area) in each of three lobes of the liver for a total of 48 sites. The total doses of doxorubicin used were 4.8 mg and 96 mg (0.1 and 2 mg/site). Dogs with intravenous and intra-arterial delivery of the same total doses of doxorubicin were used as controls. Experiments using intrahepatic injection were performed with and without a 30 min occlusion of the hepatic artery, common bile duct and portal vein (inflow occlusion). The studies with vascular stasis were performed to determine if drug clearance from the injection sites and their plasma levels were reduced. Also, it was observed that blood and drug loss along the needle tract was reduced when inflow occlusion was used. Plasma and liver samples were harvested over a 90-min period and analysed by high pressure liquid chromatography (HPLC). RESULTS: In plasma mean peak levels and mean area under the curve (AUC) were significantly lower with intrahepatic doxorubicin (P<0.05) than with intravenous or intra-atrial delivery. In the liver AUCintrahepatic/AUCintravenous ratios were 3.45 and 3.6 with 4.8 mg and 96 mg of doxorubicin respectively. The AUCintrahepatic/AUCintraarterial ratios were 1.97 and 1.65 respectively. The liver extraction ratio (AUCliver/AUCplasma) after intravenous administration with 4.8 mg and 96 mg of doxorubicin was 31.9 with both doses of doxorubicin. The corresponding extraction ratios were 107.6 and 51 for intra-arterial administration and 425.2 and 237.7 for intrahepatic administration for the two doses of doxorubicin. Intrahepatic injection with inflow occlusion minimized the leakage back along the needle-tracts. The liver visibly retained the injected drug more completely. However, there was a decrease in systemic clearance resulting in a reduction of the pharmacological advantage. CONCLUSION: These results indicate that lattice-intrahepatic administration of doxorubicin into the liver using a lattice template was associated with a significant increase in local and decrease in systemic exposure as compared to intravenous or intra-arterial administration of the same doses. Simultaneous occlusion of arterial and portal venous inflow was not shown to improve regional drug delivery. These pharmacokinetic studies may constitute a basis for palliative treatment of liver tumours by lattice intralesional injection when these cancers are found to be unresectable at the time of exploratory surgery.

Animals↗
PubMed2000

Acute enlargement and subsequent rupture of an abdominal aortic aneurysm in a patient receiving chemotherapy for pancreatic carcinoma.

We report a case of ruptured abdominal aortic aneurysm (AAA) in a patient receiving chemotherapy for pancreatic cancer. We reviewed the literature on the effects of corticosteroids and chemotherapy on aaa formation and discuss possible mechanisms for drug action to promote aneurysm expansion and rupture. If cancer and AAA coincide and curative chemotherapy is possible, a potential impact of chemotherapy on AAA expansion should be considered.

Adenocarcinoma↗
PubMed2000

Does the endovascular repair of aortoiliac aneurysms pose a radiation safety hazard to vascular surgeons?

OBJECTIVES: Endovascular aortoiliac aneurysm (EAIA) repair uses substantial fluoroscopic guidance that requires considerable radiation exposure. Doses were determined for a team of three vascular surgeons performing 47 consecutive EAIA repairs over a 1-year period to determine whether this exposure constitutes a radiation hazard. METHODS: Twenty-nine surgeon-made aortounifemoral devices and 18 bifurcated devices were used. Three surgeons wore dosimeters (1) on the waist, under a lead apron; (2) on the waist, outside a lead apron; (3) on the collar; and (4) on the left ring finger. Dosimeters were also placed around the operating table and room to evaluate the patient, other personnel, and ambient doses. Exposures were compared with standards of the International Commission on Radiological Protection (ICRP). RESULTS: Total fluoroscopy time was 30.9 hours (1852 minutes; mean, 39.4 minutes per case). Yearly total effective body doses for all surgeons (under lead) were below the 20 mSv/y occupational exposure limit of the ICRP. Outside lead doses for two surgeons approximated recommended limits. Lead aprons attenuated 85% to 91% of the dose. Ring doses and calculated eye doses were within the ICRP exposure limits. Patient skin doses averaged 360 mSv per case (range, 120-860 mSv). The ambient (> 3 m from the source) operating room dose was 1.06 mSv/y. CONCLUSIONS: Although the total effective body doses under lead fell within established ICRP occupational exposure limits, they are not negligible. Because radiation exposure is cumulative and endovascular procedures are becoming more common, individuals performing these procedures must carefully monitor their exposure. Our results indicate that a team of surgeons can perform 386 hours of fluoroscopy per year or 587 EAIA repairs per year and remain within occupational exposure limits. Individuals who perform these procedures should actively monitor their effective doses and educate personnel in methods for reducing exposure.

Aortic Aneurysm↗
PubMed2000

Brachytherapy: reconstructive options and the role of plastic surgery.

The objectives of this study were to evaluate reconstructive methods for patients receiving brachytherapy after cancer ablation. This retrospective review evaluated 19 patients who received brachytherapy and reconstruction between 1991 and 1998. The average age of the patient was 61.9 years and the average follow-up was 2.9 years. Lesions were located in the upper extremity (N = 6), trunk (N = 2), and lower extremity (N = 11). In all patients, early postoperative brachytherapy was initiated 5 days after wound closure. The average radiation dose was 47 Gy (range, 45-50 Gy) and was delivered over a 3 to 5-day period. In each case, varying numbers of catheters were employed (average, 8 +/- 5 catheters). Free flap coverage was performed in 8 patients, and the latissimus dorsi was used most often. Pedicled regional flaps were employed in 11 patients (58%). Sixteen patients (84%) had additional external beam irradiation, and 10 patients (52%) underwent preoperative chemotherapy. All flaps survived with a demonstrated low complication rate (10%). In 2 patients, partial flap necrosis and infection occurred. Three donor site complications were observed and included wound dehiscence in 2 patients and hematoma in 1 patient. Cumulative effects of external beam radiation and brachytherapy did not affect the complication rate. Location of the defect did not alter the incidence of complications. Wound complications did not delay functional rehabilitation in these patients; however, hospital stay was longer. In 8 patients local recurrence occurred (42%) between 6 and 36 months after surgery whereas in 6 patients (32%) distant metastasis was observed. Ten patients are currently alive without evidence of disease. One of the most important concerns about early postoperative brachytherapy is wound healing. With careful planning and precise reconstructive techniques, the use of brachytherapy as a part of salvage or primary surgery does not lead to increased wound morbidity. Reconstructive procedures and a multidisciplinary approach have allowed the delivery of brachytherapy in these complicated patients with low morbidity.

Adult↗