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Biomedical subjects

H S Chan

Publications and source records attributed to H S Chan.

At least 73 records · Page 4Linked to original sources
PubMed1995

A prospective comparative study between conventional and laparoscopic cholecystectomy.

A prospective, comparative study was made between 371 patients undergoing laparoscopic cholecystectomy and 100 patients undergoing conventional cholecystectomy. Post-operative pain was assessed subjectively by a single observer using a visual analog score and objectively by assessment of parenteral analgesic used. Patients who underwent laparoscopic cholecystectomy required significantly less analgesia (46.7 mg vs 223.9mg mean pethidine dose, p < 0.01) and were observed to have mobilised earlier and had a shorter mean post-operative stay (3.5 days vs 5.9 days, p < 0.01). Laparoscopic cholecystectomy objectively reduces post-operative pain significantly and should be the new standard for treatment of gallstones.

Adult↗
PubMed1994

Does compactness induce secondary structure in proteins? A study of poly-alanine chains computed by distance geometry.

A few years ago, lattice model studies indicated that compactness could induce polymer chains to develop protein-like secondary structures. Subsequent off-lattice studies have found the amounts of induced structure to be relatively small. Here we use distance geometry to generate random conformations of compact poly-alanine chains of various chain lengths. The poly-alanine chains are subjected only to compactness and excluded volume constraints; no other energies or conformational propensities are included in the chain generation procedure. We find that compactness leads to considerable stabilization of secondary structure, but the absolute amount of secondary structure depends strongly on the criteria used to define helices and sheets. By loose criteria, much secondary structure arises from compactness, but by strict criteria, little does. The stabilization free energy of secondary structure provided by compactness, however, appears to be independent of criteria. Since real helices and sheets in proteins can be identified by strict criteria, we introduced small energy perturbations to compact poly-alanine chains using the AMBER force field. Small refinements produced good alpha-helices. For beta-sheets, however, larger refinements are necessary. Compactness appears to impart stability, but not much structural specificity, to secondary structures in proteins. Compactness acts more like diffusion as a force, a result of ensemble statistics, than like pair interactions such as hydrogen bonding.

Models, Chemical↗
PubMed1994

Effect of age and disease on two drug binding proteins: albumin and alpha-1- acid glycoprotein.

The influence of age and disease on serum albumin and alpha-1-acid glycoprotein was studied in 126 subjects (69 M, 57 F) presenting with tuberculosis and after recovery. Albumin concentration fell with age in both disease and healthy states, and alpha-1-acid glycoprotein concentration rose with age in the healthy state. Age-related differences were less marked in the disease state. During recovery from illness, serum albumin concentration rose and alpha-1-acid glycoprotein concentration fell. The mean concentration difference in the latter was lower in the older age groups. The clinical consequences of changes in binding protein concentrations as a result of ageing and disease need to be studied further for individual drugs.

Adult↗
PubMed1994

Recurrent acute pancreatitis induced by isoniazid.

A 31-year-old man on haemodialysis who developed recurrent attacks of acute pancreatitis during the treatment of pulmonary tuberculosis is presented. The pancreatitis rapidly subsided once isoniazid was withdrawn, but the problem recurred again upon reintroduction of the drug. There was no further recurrence during successful treatment with full doses of rifampicin and pyrazinamide for 1 year.

Acute Disease↗
PubMed1994

One hundred and sixty-three consecutive video thoracoscopic procedures: the Hong Kong experience.

Video-assisted thoracoscopy (VAT) offers a new approach to the diagnosis and treatment of many thoracic conditions. From September 1992 to August 1993, a total of 163 VAT procedures were successfully performed on 108 patients (87 male, 21 female; age range from 12 to 77) which consisted of 42 bleb eliminations and 64 mechanical pleurodesis for spontaneous pneumothorax, 11 wedge resections for pulmonary nodules, three wedge biopsies for diffuse pulmonary infiltrate, four thoracic sympathectomies, resections of two mediastinal masses, three pericardial windows, 10 guided pleural biopsies for undiagnosed effusions, six guided drainage of empyema and haemothorax, 16 staging of intrathoracic tumours and two explorations for penetrating thoracic trauma. There was no procedure-related mortality. Complications included one recurrence for spontaneous pneumothorax, one re-exploration for bleeding (also by VAT approach), one wound infection, and six persistent air leaks for more than 10 days. The median duration of postoperative chest tube drainage was 2 days and the median hospital stay was 4 days. It was concluded that VAT is a safe and effective approach in thoracic surgery and with further refinement in instrumentation even more procedures will be technically feasible. The long-term results of VAT are being awaited in order to define its true merits in thoracic surgery.

Adolescent↗
PubMed1994

Circulating adhesion molecules in asthma.

There is increasing evidence that leukocyte-endothelial adhesion molecules are important in inflammatory airway disease because of their involvement in the primary steps of entrapment and migration of leukocytes to the site of inflammation. Recently, circulating forms of these adhesion molecules have been described, although their origin, fate, and function are still unknown. We have used an antigen capture ELISA to measure the concentrations of circulating intercellular adhesion molecule-1 (cICAM-1), E-selectin (cE-selectin), and vascular cell adhesion molecule-1 (cVCAM-1) in the peripheral blood of 13 atopic and 16 non-atopic normal subjects, 29 patients with stable asthma, and inpatients with acute asthma on Day 1 (n = 38), Day 3 (n = 29), and Day 28 (n = 13) of an asthmatic episode. Circulating ICAM-1 and E-selectin levels were significantly raised in acute asthma on all three study days when compared with those observed in stable asthma, atopic normal, or nonatopic normal volunteers with no significant differences among the latter three groups. Circulating VCAM-1 was not significantly increased in any of the groups studied. There were no correlations among the concentrations of these three circulating adhesion molecules. The elevated concentrations of cICAM-1 and cE-selectin in acute asthma may reflect the extensive inflammatory response occurring in the airways during acute exacerbations of the disease with airway obstruction. It is possible that the cytokine and mediator profiles in acute asthma lead to the preferential synthesis and expression of these two circulating adhesion molecules in comparison with cVCAM-1.

Acute Disease↗
PubMed1994

Effects of priority assignment of attentional resources, order of testing, and response sequence on tunnel vision.

The effects of relative priority of attentional resources allocated to simultaneous peripheral and foveal tasks, response sequence to the tasks, and order to testing with two levels of foveal cognitive loading on tunnel vision were studied with 32 Chinese undergraduates. Two levels of foveal condition were used for the foveal task while the peripheral task required a single-target detection. Performance decrement value and a significant interaction of levels x eccentricities indicated that tunnel vision was most prominent when the foveal task was primary. Greater magnitude of tunnel vision was obtained when the more difficult foveal task was tested prior to the no-foveal-load condition. Responding sequence to the tasks was nonsignificant.

Adult↗
PubMed1994

Multidrug resistance. Clinical opportunities in diagnosis and circumvention.

Increased P-glycoprotein expression has been shown to be the molecular cause of multidrug resistance in tumor cell lines. Sensitive immunohistochemical and molecular biologic techniques have been developed to detect P-glycoprotein/mdr1 mRNA expression in clinical samples of tumors. We have reviewed the tools now available for assessment of P-glycoprotein expression in the clinic, the current evidence for a relevant role of the protein in mediation of resistance to chemotherapy, and one strategy used to overcome therapeutic failures due to multidrug resistance. It is now recognized that low levels of increased P-glycoprotein/mdr1 mRNA can occur at diagnosis and during the course of treatment in some cases of acute myelogenous leukemia, non-Hodgkin's lymphoma, multiple myeloma, breast carcinoma, rhabdomyosarcoma and undifferentiated sarcoma of children, neuroblastoma, and retinoblastoma, and these relatively low levels of mdr1 overexpression appear to be associated with poor prognosis. In contrast, it has not been established whether a multidrug resistance mechanism is the rate-limiting factor in response to chemotherapy in carcinomas that arise from tissues normally expressing increased P-glycoprotein. Clinical trials have been initiated to determine whether pharmacologic chemosensitization improves the outcome of chemotherapy-treated malignancies. Preliminary results suggest that chemosensitizers can modulate the effects of increased P-glycoprotein in low-expressing tumors for which effective multiagent chemotherapy is available. Further research is needed for more potent chemosensitizers or combinations of agents that can be used more effectively. The successful circumvention of chemotherapy failure by chemosensitizers will ultimately establish the clinical relevance of the P-glycoprotein efflux mechanism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

A sensitive multilayer immunoalkaline phosphatase method for detection of P-glycoprotein in leukemic and tumor cells in the bone marrow.

BACKGROUND: Relatively low levels of the multidrug resistance P-glycoprotein have correlated with poor prognosis in rhabdomyosarcoma, neuroblastoma, acute myelogenous leukemia, lymphoma, myeloma and breast carcinoma. A sensitive, nonradioactive method, less costly and time-consuming than the present molecular biologic techniques, is desirable for direct measurement of P-glycoprotein in tumor cells versus normal cells. EXPERIMENTAL DESIGN: We have devised an immunoalkaline phosphatase method using four antibody layers to amplify the primary signal considerably and refined staining conditions to optimize the 'signal-to-noise' ratio. Immunoalkaline phosphatase is preferred to immunoperoxidase for testing leukemic and tumor cells in bone marrow, because it avoids myeloperoxidase staining in myeloblasts and myeloid progenitors that interferes with P-glycoprotein interpretation. RESULTS: Multilayer immunoalkaline phosphatase detected low levels of P-glycoprotein overexpression, that could not be identified by conventional immunoperoxidase or immunoblot, in a low-resistance (8-fold) cell line with a barely detectable transcript. Our technique also detected increased P-glycoprotein in malignant cells in bone marrow of relapsed acute lymphoblastic leukemia (10/11), acute myelogenous leukemia (2/2), lymphoma (1/1), neuroblastoma (7/7), and rhabdomyosarcoma (2/2). Increased P-glycoprotein was not identified at diagnosis in 6 patients with acute lymphoblastic leukemia, and two with stage IV and three with stage IVS neuroblastoma that remained relapse-free in the long-term, but was detected in 4 patients with stage IV neuroblastoma and three with rhabdomyosarcoma who ultimately relapsed. CONCLUSIONS: Our new technique is more sensitive than conventional immunoperoxidase and immunoblot for assaying P-glycoprotein in low-resistance cell lines. It may be potentially applicable for detecting low levels of P-glycoprotein overexpression in leukemic and tumor cells in bone marrow. Early identification of low levels of multidrug resistance may be clinically relevant by allowing poor-prognostic patients to receive alternative therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Cooperativity in protein-folding kinetics.

How does a protein find its native state without a globally exhaustive search? We propose the "HZ" (hydrophobic zipper) hypothesis: hydrophobic contacts act as constraints that bring other contacts into spatial proximity, which then further constrain and zip up the next contacts, etc. In contrast to helix-coil cooperativity, HZ-heteropolymer collapse cooperativity is driven by nonlocal interactions, causes sheet and irregular conformations in addition to helices, leads to secondary structures concurrently with early hydrophobic core formation, is much more sequence dependent than helix-coil processes, and involves compact intermediate states that have much secondary--but little tertiary--structure. Hydrophobic contacts in the 1992 Protein Data Bank have the type of "topological localness" predicted by the hypothesis. The HZ paths for amino acid sequences that mimic crambin and bovine pancreatic trypsin inhibitor are quickly found by computer; the best configurations thus reached have single hydrophobic cores that are within about 3 kcal/mol of the global minimum. This hypothesis shows how proteins could find globally optimal states without exhaustive search.

Amino Acid Sequence↗
PubMed1993

Extremity osteosarcoma in childhood: prognostic value of radiologic imaging.

PURPOSE: To evaluate previously described radiologic prognostic factors in extremity osteosarcoma. MATERIALS AND METHODS: In 47 pediatric patients, available images were evaluated for seven prognostic factors at diagnosis and seven additional factors after preoperative chemotherapy. These factors were correlated with histopathologic response and clinical outcome. The association of histopathologic response and outcome was also evaluated. RESULTS: Metastases at presentation and a > 20-cm-diameter soft-tissue mass were predictive of a poor outcome but occurred in few patients. Factors most predictive of < 90% tumor necrosis after chemotherapy included an increase or no change in soft-tissue mass size and increased bone destruction. Although a significant relationship (P < .05) was found between histopathologic response and outcome, no factors predictive of histopathologic response were also predictive of outcome. The accuracy of pathologic response in predicting outcome was 66%. CONCLUSION: Radiologic studies are of only limited use in predicting which patients with extremity osteosarcoma will have a poor response to chemotherapy or a poor outcome, and are not useful in predicting a good response or outcome.

Adolescent↗
PubMed1993

Effects of cognitive foveal load on a peripheral single-target detection task.

This experiment investigated the effects of foveal cognitive load on a primary peripheral single-target detection task. Four levels of foveal task with cognitive loads involving identification and summation of numerals were used. Number of correct targets detected seemed unaffected by the foveal load in the near periphery but a decrement occurred beyond 7.7 degrees. Response times for correct responses showed large dispersion compared with that for correct locations. At a low cognitive load, foveal task performance showed no deterioration for all eccentricities tested, but at a higher cognitive load performance declined gradually across eccentricities. Mild evidence of tunnel vision was obtained as indicated by the significant interaction of cognitive loads x eccentricities. Resources theory accounted well for the results.

Adult↗
PubMed1993

Visual lobe area mapping for targets on a competing homogeneous background.

Binocular visual lobe areas for two subjects were mapped over part of the visual field. Overall, the lobe shapes were strikingly consistent over a period of 18 months with regard to boundary irregularities and regions of insensitivity. The ratio of eight-axis mapping area to eight-axis area based on complete mapping data was near unity for one subject but very much higher for the other. If these results are typical, the various methods of determining lobe area from measurements taken on a few axes can only give very approximate relative values. It was suggested that the irregular boundary and areas of insensitivity may partly account for the difficulty some subjects experience in locating targets during visual search, even after repeated scanning.

Adult↗
PubMed1992

Modeling the effects of mutations on the denatured states of proteins.

We develop a model for the reversible denaturation of proteins and for the effects of single-site mutations on the denatured states. The model is based on short chains of sequences of H (hydrophobic) and P (other) monomers configured as self-avoiding walks on the two-dimensional square lattice. The N (native) state is defined as the unique conformation of lowest contact energy, whereas the D (denatured) state is defined as the collection of all other conformations. With this model we are able to determine the exact partition function, and thus the exact native-denatured equilibrium for various solvent conditions, using the computer to exhaustively enumerate every possible configuration. Previous studies confirm that this model shows many aspects of protein-like behavior. The present study attempts to model how the denatured state (1) depends on the amino acid sequence, and (2) is changed by single-site mutations. The model accounts for two puzzling experimental results: (1) the replacement of a polar residue by a hydrophobic amino acid on the surface of a protein can destabilize a native protein, and (2) the "denaturant slope," m = partial delta G/partial c (where c is the concentration of denaturant--urea, guanidine hydrochloride), can sometimes change by as much as 30% due to a single mutation. The principal conclusion of the present study is that, under strong folding conditions, the denatured conformations that are in equilibrium with the native state are not open random configurations. Instead, they are an ensemble of highly compact conformations with a distribution that depends on the residue sequence and that can be substantially altered by single mutations. Most importantly, we conclude that mutations can exert their dominant effects on protein stability by changing the entropy of folding.

Amino Acid Sequence↗
PubMed1992

Chemotherapy and surgical resection combined with immediate reconstruction in a 1-year-old child with rhabdomyosarcoma of the maxilla.

Parameningeal head and neck rhabdomyosarcomas of childhood are often considered unresectable and are treated with irradiation and chemotherapy. High-dose radiation therapy has a very long-term detrimental effect on the developing face and also results in many other significant long-range complications. With the availability of advanced craniofacial surgical and free-tissue-transfer techniques, one-stage resection and immediate reconstruction, along with the use of effective preoperative and postresection chemotherapy instead of local radiation, may be the logical approach to the treatment of selected patients with chemosensitive parameningeal head and neck rhabdomyosarcomas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Teflon injection for unilateral vocal cord paralysis and its effect on lung function.

We present a prospective analysis of the lung function of 22 patients with unilateral vocal cord paralysis before and after Teflon injection. In the majority of patients the vocal cord paralysis was caused by an underlying malignant condition. Full spirometric and flow-volume loop studies demonstrated an increase in airway resistance after Teflon injection which was not clinically evident. The improvement in symptom score for aspiration was greater than that for dysphonia.

Adult↗