Search PubMed⌕ Search

Biomedical subjects

C Chan

Publications and source records attributed to C Chan.

At least 127 records · Page 7Linked to original sources
PubMed1998

Occlusion of Fontan fenestrations using the Amplatzer septal occluder.

OBJECTIVE: To evaluate the efficacy and safety of the Amplatzer septal occluder device for occlusion of Fontan fenestrations. SUBJECTS: Five children aged 5-10 years who had undergone a fenestrated Fontan operation. SETTING: Tertiary paediatric cardiology centre. METHODS: Each patient had right and left heart catheterisation to assess haemodynamic suitability for fenestration closure. Sizing of the defect was achieved with a balloon wedge catheter and transoesphageal echocardiography. Transcatheter occlusion of the fenestration was accomplished using a 4 mm device in three patients, and 5 mm or 9 mm devices in the other two patients. Residual shunting following occlusion was assessed using angiography and echocardiography. RESULTS: 100% occlusion rate of the fenestration was achieved in all patients. No complications or device failures were seen during the three month follow up period. CONCLUSION: The Amplatzer septal occluder device is safe, and effectively occludes the Fontan fenestration.

Angiography↗
PubMed1998

EGF-Receptor phosphorylation and signaling are targeted by H2O2 redox stress.

Inflammation of the respiratory tract is associated with the production of reactive oxygen species, such as hydrogen peroxide (H2O2) and superoxide (O2-), which contribute extensively to lung injury in diseases of the respiratory tract. The mechanisms and target molecules of these oxidants are mainly unknown but may involve modifications of growth-factor receptors. We have shown that H2O2 induces epidermal growth factor (EGF)-receptor tyrosine phosphorylation in intact cells as well as in membranes of A549 lung epithelial cells. On the whole, total phosphorylation of the EGF receptor induced by H2O2 was lower than that induced by the ligand EGF. Phosphorylation was confined to tyrosine residues and was inhibited by addition of genistein, indicating that it was due to the activation of protein tyrosine kinase (PTK). Phosphoamino acid analysis revealed that although the ligand, EGF, enhanced the phosphorylation of serine, threonine, and tyrosine residues, H2O2 preferentially enhanced tyrosine phosphorylation of the EGF receptor. Serine and threonine phosphorylation did not occur, and the turnover rate of the EGF receptor was slower after H2O2 exposure. Selective H2O2-mediated phosphorylation of tyrosine residues on the EGF receptor was sufficient to activate phosphorylation of an SH2-group-bearing substrate, phospholipase C-gamma (PLC-gamma), but did not increase mitogen-activated protein (MAP) kinase activity. Moreover, H2O2 exposure decreased protein kinase C (PKC)-alpha activity by causing translocation of PKC-alpha from the membrane to the cytoplasm. These studies provide novel insights into the capacity of a reactive oxidant, such as H2O2, to modulate EGF-receptor function and its downstream signaling. The H2O2-induced increase in tyrosine phosphorylation of the EGF receptor, and the receptor's slower rate of turnover and altered downstream phosphorylation signals may represent a mechanism by which EGF-receptor signaling can be modulated during inflammatory processes, thereby affecting cell proliferation and thus having implications in wound repair or tumor formation.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

H2O2 acts on cellular membranes to generate ceramide signaling and initiate apoptosis in tracheobronchial epithelial cells.

Hydrogen peroxide (H2O2) is an inflammatory oxidant which contributes to the pathogenesis of chronic diseases such as lung injury of the respiratory tract, atherosclerosis and cancer. The mechanisms and target sites of this reactive oxidant are mainly unknown. So far there are opposing reports as to whether reactive oxidants inhibit or promote apoptosis. We activated the death pathway in primary tracheobronchial epithelial (TBE) cells with H2O2 (20-200 microM) and observed the morphological changes, DNA laddering patterns, and DNA fragmentation associated with apoptosis. Elevation of ceramide with exogenous ceramide analogs was sufficient for apoptosis induction with the same characteristics and in the same time frame. H2O2 induced rapid sphingomyelin hydrolysis to ceramide, the elevation of which paralleled the induction of apoptosis. Furthermore, H2O2 acted directly on TBE cells membrane preparations devoid of nuclei, stimulating sphingomyelin hydrolysis through a neutral Mg2+ dependent sphingomyelinase (SMase). These data suggest that the formation of ceramide from sphingomyelin in the plasma membrane is a key event in H2O2-induced apoptosis in tracheobronchial epithelial cells.

Animals↗
PubMed1998

The clinical impact of platelet glycoprotein IIb/IIIa receptor blockade in cardiovascular medicine.

Several of the adverse events that occur in acute coronary syndromes and after percutaneous coronary revascularization procedures are believed to be mediated by platelets. Recently, using molecular biology techniques, the platelet glycoprotein IIb/IIIa receptor was identified as the final common pathway for platelet aggregation. Thus, blocking the action of this receptor would seem to be an attractive proposition for reducing ischemic complications. A monoclonal antibody was the first agent in this new pharmacological family to be designed, but several peptide and peptide-like substances have subsequently been developed. This paper reviews the development of this class of agents and the various preclinical and clinical trials that have been undertaken. Early studies evaluated such agents during percutaneous coronary revascularization procedures. Because of the overwhelming benefits observed in such patients, together with the current limitations of treatments for acute coronary syndromes, the scope of investigations has been extended. Preliminary reports have been encouraging.

Blood Platelets↗
PubMed1998

Discovery of MC-02,331, a new cephalosporin exhibiting potent activity against methicillin-resistant Staphylococcus aureus.

A systematic approach toward building activity against methicillin-resistant staphylococci into the cephalosporin class of beta-lactam antibiotics is described. Initial work focused on finding the optimal linkage between the cephem nucleus and a biphenyl pharmacophore, which established that a thio linkage afforded potent activity in vitro. Efforts to optimize this activity by altering substitution on the pharmacophore afforded iodophenylthio analog MC-02,002, which although highly potent against MRSA, was also highly bound to serum proteins. Further work to decrease serum protein binding showed that replacement of the iodo substituent by the positively-charged isothiouronium group afforded potent activity and reduced serum binding, but insufficient aqueous solubility. Solubility was enhanced by incorporation of a second positively-charged group into the 7-acyl substituent. Such derivatives (MC-02,171 and MC-02,306) lacked sufficient stability to staphylococcal beta-lactamase enzymes. The second positive charge was incorporated into the cephem 3-substituent in order to utilize the beta-lactamase-stable aminothiazolyl(oximino)acetyl class of 7-substituents. These efforts culminated with the discovery of bis(isothiouroniummethyl)phenylthio analog MC-02,331, whose profile is acceptable with respect to potency against MRSA, serum binding, aqueous solubility, and beta-lactamase stability.

Animals↗
PubMed1998

Laparoscopic adhesiolysis for subfertility.

AIM: Laparoscopic adhesiolysis has been associated with pregnancy rates of 12% to 58%. This study looks at our experience with laparoscopic adhesiolysis in the management of subfertile patients. METHOD & RESULTS: Between January 1992 and March 1995, 27 subfertile patients who had laparoscopic adhesiolysis done were studied. Four patients (15%) had a second look laparoscopy. The overall pregnancy rate (after excluding 6 patients with bilateral tubal blockage or severe male factor) was 33% (7/21). The take home baby rate was 14.3% (3/21) and the ectopic pregnancy rate was 4.7% (1/21). CONCLUSION: Laparoscopic adhesiolysis still remains a useful and effective procedure for infertile couples with pelvic adhesions.

Adnexal Diseases↗
PubMed1997

Crystals of the carotenoid protein from Arthrospira maxima containing uniformly oriented pigment molecules.

Crystals of a carotenoid protein from the cyanobacterium Arthrospira maxima have been grown in space group C2 with unit-cell dimensions a = 219.6, b = 40.3, c = 75.5 A and beta = 95.5 degrees. The crystals diffract X-rays to 2.3 A resolution and display unusual optical properties in polarized light that suggest that all of the carotenoid molecules in the crystals are oriented similarly. A slight increase in the concentration of a crystallization additive in the mother liquor induces macroscopic twinning, which is also visible when the crystals are illuminated with polarized light.

Journal Article↗
PubMed1997

A randomized controlled trial of verapamil on cyclosporine nephrotoxicity in heart and lung transplant recipients.

BACKGROUND: Cyclosporine (CsA) is a potent immunosuppressive drug widely used in organ transplantation and in the treatment of autoimmune diseases (1, 2). However, its common nephrotoxic effect is a major limiting factor. Short-term CsA treatment has been shown to cause reversible renal vasoconstriction, whereas long-term treatment can lead to an afferent arteriolopathy and chronic renal failure. METHODS: We performed a randomized controlled trial to examine the short-term renal effects of verapamil in 32 CsA-treated heart or lung transplant recipients. Sixteen patients each were randomized to receive a 6-week course of verapamil or control treatment (atenolol in hypertensive patients and placebo in normotensive patients) 1-2 months after transplantation. An 8-hr sequential clearance study of inulin and p-aminohippuric acid for estimating glomerular filtration rate and renal plasma flow, respectively, was performed at baseline and at completion of study. The integral area under the curve of the clearance parameter over 8 hr was then calculated to generate a clearance-time index. RESULTS: There was no difference in the clearance-time indices for inulin and p-aminohippuric acid between the two groups at baseline. However, at the completion of study, the within-group change in the glomerular filtration rate clearance-time index was different between the verapamil and control groups (48+/-20 vs. -35+/-17 ml/min/1.73 m2 x hr, respectively; P=0.0038). A similar trend was seen for renal plasma flow, but did not reach statistical significance. Mean arterial blood pressure and whole-blood CsA levels did not differ between the two groups during the study. Verapamil treatment was also associated with a decrease in CsA dose requirement (7.6+/-0.58 mg/kg/day at baseline vs. 4.6+/-0.40 mg/kg/day at completion; P<0.001) without any significant change in trough whole blood CsA levels. Rejection episodes did not differ between the two groups. CONCLUSIONS: The use of verapamil in the heart or lung transplant recipients may therefore provide both renal protective effects and cost savings.

Adult↗
PubMed1997

Agonist-activated alphavbeta3 on platelets and lymphocytes binds to the matrix protein osteopontin.

The phosphorylated acidic glycoprotein osteopontin is present in the extracellular matrix of atherosclerotic plaques and the wall of injured but not normal arteries. To determine if osteopontin could serve as a substrate for platelet adhesion, we measured the adherence of resting and agonist-stimulated human platelets to immobilized recombinant human osteopontin. Agonist-stimulated but not resting platelets bound to osteopontin by a process that was mediated primarily by alphavbeta3. alphavbeta3-mediated adherence occurred at physiologic concentrations of calcium and was inhibited by an alphavbeta3-selective cyclic peptide. Assays using phorbol myristate acetate-stimulated transfected B lymphocytes expressing both alphavbeta3 and alphaIIbbeta3 confirmed that activated alphavbeta3 not activated alphaIIbbeta3 was responsible for the cellular adherence we measured. These studies indicate that alphavbeta3 can reside on the cell surface in an inactive state and can be converted to a ligand binding conformation by cellular agonists. Moreover, they suggest that platelet adherence to osteopontin mediated by activated alphavbeta3 could play a role in anchoring platelets to disrupted atherosclerotic plaques and the walls of injured arteries. By inhibiting alphavbeta3 function, it may be possible to inhibit platelet-mediated vascular occlusion with a minimal effect on primary hemostasis.

Adenosine Diphosphate↗
PubMed1997

The pseudoazurin gene from Thiosphaera pantotropha: analysis of upstream putative regulatory sequences and overexpression in Escherichia coli.

The pseudoazurin gene from Thiosphaera pantotropha has been cloned and sequenced. The deduced amino acid sequence showed that the protein contains an unusually alanine-rich signal peptide, 22 amino acid residues in length, which targets the protein to the periplasm. This pseudoazurin was expressed in large amounts in the periplasm of Escherichia coli when the gene with its native ribosome-binding site was placed downstream of the lac promoter. Removal of a putative hairpin-forming structure upstream of the ribosome-binding site increased the yield of the purified protein to approximately 80 mg/l. The recombinant protein is indistinguishable from that purified from its natural host. A primer extension study indicated that the pseudoazurin structural gene (pazS) is under the control of the Fnr/Nnr regulatory system, but no promoter-binding sequence could be recognized. The amino acid sequence of pseudoazurin from Paracoccus denitrificans is also reported.

Amino Acid Sequence↗
PubMed1997

Selective shunts for portal hypertension: current role of a 21-year experience.

The results of treatment of hemorrhagic portal hypertension with selective shunts over a 21-year period in a selected patient population are reported. Patients selected for surgical treatment had good cardiopulmonary and renal function, and most also had adequate liver function (141 Child-Pugh class A, 59 class B). Among 734 patients treated surgically for bleeding portal hypertension, 221 had selective shunts (168 distal splenorenal and 53 splenocaval shunts). Global operative mortality (in the 21-year period) was 14% and 12% for Child-Pugh A patients. Operative mortality in Child-Pugh A patients in the last 5 years was only 5%. The rate of rebleeding was 6%, rate of incapacitating encephalopathy was 5%, and rate of survival was 65% at 15 years (last 5 years: 88% at 1 year and 85% at 5 years). Good quality of life was demonstrated in 80% of surviving patients. Shunt patency was 94%. Postoperative portal blood flow changes occurred in 23% of cases (8% diameter reduction, 14% thrombosis). Compared with other forms of therapy (pharmacotherapy, sclerotherapy, and transjugular intrahepatic shunting), only liver transplantation offers similar results for these patients. In countries in which liver transplantation is not routinely performed, shunting with selective shunts is the treatment of choice for patients with good liver function.

Angiography↗
PubMed1997

Responses of polycystic ovarian syndrome and related variants to low-dose follicle stimulating hormone.

OBJECTIVE: To determine whether patients with classical polycystic ovarian syndrome (PCOS) respond differently to low-dose FSH therapy in comparison with anovulatory patients (PCOS-like) where only some features of PCOS are present. METHODS: Two groups of patients were studied. The PCOS group (25 patients, 51 cycles) and the PCOS-like group (38 patients, 57 cycles) were treated with the same protocol of purified FSH, commencing with an initial dosage of 75 IU/day and increasing by 37.5 IU/day after 14 days, where necessary. Estradiol levels and ultrasonographic evidence of follicular development were used for monitoring. RESULTS: PCOS patients required more ampules of FSH, needed more days of gonadotropin stimulation, secreted higher levels of E2 and had increased numbers of intermediate follicles compared to the PCOS-like group. CONCLUSIONS: This study demonstrated significant differences between PCOS and other PCOS-like conditions when treated with low-dose FSH. Classification of the subvariants of PCOS may have therapeutic implications.

Adult↗
PubMed1997

Angioscopic evaluation of rotational atherectomy followed by additional balloon angioplasty versus balloon angioplasty alone in coronary artery disease: a prospective, randomized study.

OBJECTIVES: This study sought to compare, by angioscopy, the morphologic changes induced by rotational atherectomy, followed by additional angioplasty, with those observed after balloon angioplasty alone. BACKGROUND: Rotational atherectomy and balloon angioplasty act by different mechanisms, which could explain the difference in morphologic changes induced by these two techniques. METHODS: The study group included 50 patients with 50 lesions who were randomly assigned to undergo rotational atherectomy (n = 24) or balloon angioplasty (n = 26). Rotational atherectomy with a single burr (approximately equal to 70% of coronary diameter) was systematically followed by additional balloon angioplasty. Angioscopy was performed immediately after the procedure. Abnormal angioscopic findings were 1) flaps, graded from 1 to 3 (1 = intimal flap; 2 = flap protruding into < 50% of the lumen; 3 = flap protruding into > or = 50% of the lumen); 2) thrombi, graded from 1 to 3 (1 = flat deposits; 2 = protruding but nonocclusive thrombus; 3 = occlusive thrombus); 3) subintimal hemorrhage; 4) longitudinal dissection. The two groups were comparable for clinical and angiographic baseline data. RESULTS: On angioscopy, flaps were observed less frequently after rotational atherectomy followed by additional balloon angioplasty (8 [33%] of 24 lesions) than after balloon angioplasty alone (14 [54%] of 26 lesions, p = 0.08) and were also less severe (grade 1 in 6 lesions, grade 2 in 2 and grade 3 in none vs. grade 1 in 4 lesions, grade 2 in 5 and grade 3 in 5). Longitudinal dissections were also significantly less frequent: one versus six (p = 0.05). There was no difference in the incidence of angioscopic thrombi (p = 0.16) or subintimal hemorrhage (p = 0.15), but the power to detect a significant difference was low for these variables (37% and 26%, respectively). CONCLUSIONS: Rotational atherectomy followed by additional balloon angioplasty leads to fewer angioscopic dissections and a trend toward fewer intimal flaps than balloon angioplasty alone. However, our angioscopic differences did not lead to an outcome difference between the two groups.

Aged↗
PubMed1997

Characterization of renal ischemia-reperfusion injury in rats.

The purpose of this study was to characterize the time course of renal ischemia-reperfusion injury in the rat. Male Sprague-Dawley rats were subjected to bilateral renal clamping for 45 min. At reestablishment of blood flow, the rats were divided into nine groups (representing 0, 0.5, 1, 2, 4, 6, 9, and 24 h, and 1 week post-ischemia). At each time point, blood samples were taken for analysis of blood urea nitrogen (BUN) and creatinine, and both kidneys were harvested for histopathology and myeloperoxidase activity (MPO) assays. An intracellular adhesion molecular (ICAM-1) monoclonal antibody (IMAb) was tested in a separate group of animals (1 mg/rat) to confirm that it may provide renal protection previously reported by Kelly et al. (1994). Following renal ischemia, significant increases in serum BUN and creatinine were observed compared to levels in normal animals. Serum BUN and creatinine increased 2, 4, and 6 h post-ischemia leading to peak elevations 24 h post-ischemia. Values returned to normal at the 1 week time point. MPO activity was slightly increased 2 and 4 h following ischemia, with peak elevations occurring at the 6-h and 9-h time points. Histopathologic examination of kidneys revealed that the most severe damage occurred at the 24-h time point, which correlated with the peak elevations in serum BUN and creatinine. Evidence of renal injury was still evident histologically 1 week following ischemia, although renal function tests (BUN and creatinine) had returned to normal. In summary, renal injury following ischemia may be demonstrated as early as 4 h post-ischemia as judged by changes in renal function, MPO levels, and renal histopathology. However, based upon renal function tests and histology, peak injury is observed approximately 24 h following ischemia. The ICAM-1 monoclonal antibody, ICAM-Ab, provided some renal protection against ischemia-reperfusion injury in this study as measured by serum creatinine, BUN and renal histopathology. However, in contrast to the results reported by Kelly et al., the magnitude of the protective effects was not as dramatic in the present study, and furthermore, no reductions in renal MPO activity were observed.

Animals↗
PubMed1997

Sphenoid sinus mucocoele presenting with isolated oculomotor nerve palsy.

We describe two cases of sphenoid sinus mucocoele. Both presented with isolated oculomotor nerve palsy. Mucocoeles involving only the sphenoid sinus are uncommon. They are probably under-diagnosed as they may be asymptomatic or cause non-specific symptoms. Nasal symptoms occur infrequently but the close relationship of the sphenoid sinus to the orbital apex means that ocular symptoms including cranial nerve palsies are a common presenting feature. Involvement of the third cranial nerve in isolation is rare but has important neurosurgical implications which must be excluded before this symptom is attributed to the sphenoid sinus.

Adult↗
PubMed1997

The Chinese in Britain.

"This research note offers a brief historical perspective on the relationship between Hong Kong and Britain and describes the demographic profile of the Chinese community in Britain...[using] information obtained from the 1991 [UK] Census.... The data analysis shows that the Chinese population is widely dispersed and increasing rapidly, and is characterised by a high child-bearing capacity and a low rate of unemployment."

Acculturation↗