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Biomedical subjects

S W Chiu

Publications and source records attributed to S W Chiu.

At least 37 records · Page 2Linked to original sources

Simulation study of a gramicidin/lipid bilayer system in excess water and lipid. II. Rates and mechanisms of water transport.

A gramicidin channel in a fluid phase DMPC bilayer with excess lipid and water has been simulated. By use of the formal correspondence between diffusion and random walk, a permeability for water through the channel was calculated, and was found to agree closely with the experimental results of Rosenberg and Finkelstein (Rosenberg, P.A., and A. Finkelstein. 1978. J. Gen. Physiol. 72:327-340; 341-350) for permeation of water through gramicidin in a phospholipid membrane. By using fluctuation analysis, components of resistance to permeation were computed for movement through the channel interior, for the transition step at the channel mouth where the water molecule solvation environment changes, and for the process of diffusion up to the channel mouth. The majority of the resistance to permeation appears to occur in the transition step at the channel mouth. A significant amount is also due to structurally based free energy barriers within the channel. Only small amounts are due to local friction within the channel or to diffusive resistance for approaching the channel mouth.

Biological Transport, Active↗

Surgical management of blunt traumatic rupture of the descending thoracic aorta.

Acute rupture of the descending thoracic aorta following blunt trauma is a life-threatening injury that requires emergent operative intervention. From February 1989 to January 1997, 4 patients with multiple injuries including traumatic rupture in the region of the aortic isthmus were surgically treated at our institution. Diagnosis was confirmed in all patients by aortogram prior to aortic repair. One patient had preoperative paraplegia secondary to an unstable spinal fracture. All patients underwent repair under cardiopulmonary bypass (3 partial, 1 total with hypothermic arrest). The site of rupture was resected and replaced with an interposition artificial graft. There was no perioperative mortality and no additional occurrence of paraplegia. Our experience and a review of the literature indicate that for survivors of traumatic aortic rupture, excellent outcomes can be achieved only if the diagnosis is made early and the surgical treatment is prompt.

Acute Disease↗

Lung and heart-lung transplantation in Hong Kong.

OBJECTIVE: To review the donor and recipient selection criteria, surgical techniques, perioperative and post-operative management, and complications of lung/heart-lung transplantation. DATA SOURCES: Medline and non-Medline search of the relevant English literature, local data, and personal experience. STUDY SELECTION: Studies containing supporting evidence were selected. DATA EXTRACTION: Data were extracted and analysed independently by the authors. DATA SYNTHESIS: Lung/heart-lung transplantations are considered only for patients who have progressively disabling and end-stage disease. Numerous investigations of the recipient and rigorous matching between the donor and recipient are required. Factors such as maintaining the donor's haemodynamic stability, graft preservation, effective perioperative immunosuppression, and careful postoperative monitoring are key to a successful transplantation. Follow-up should include the home-monitoring of body weight, temperature, and spirometry, as well as regular chest X-rays, pulmonary function tests, and blood tests. So far, two double and two single lung transplantations, and one heart-lung transplantation have been performed in Hong Kong. CONCLUSION: Lung transplantation is an invaluable treatment modality for patients with end-stage lung disease.

Journal Article↗

Repair of ruptured sinus of valsalva aneurysm: determinants of long-term survival.

BACKGROUND: Ruptured sinus of Valsalva aneurysm is a rare cardiac anomaly and long-term survival after surgical treatment is not well established. This study was designed to investigate the determinants of long-term survival after repair of ruptured sinus of Valsalva aneurysm. METHODS: From April 1978 to April 1996, 53 patients underwent operation for ruptured sinus of Valsalva aneurysm. The incidence among our cardiac surgical population was 0.56%. Long-term survival was investigated in 46 patients (13 to 65 years) who survived the operation, with 96.2% follow-up completeness (mean+/-standard deviation, 6.5+/-4.9 years; maximum, 17.2 years), by univariate and multivariate analyses. RESULTS: There was no early operative death and no recurrence after the initial repair. Actuarial survival was 83.8%+/-8.4% at 15 years. Reoperation, aneurysm draining into the left ventricle, aortic prosthetic dehiscence, bacterial endocarditis, and aortic cross-clamp time (<70 minutes) were significant factors in long-term survival (p < 0.05). Multivariate analysis revealed that only aortic prosthesis dehiscence was the significant factor influencing late survival (p = 0.0001). CONCLUSIONS: Surgical treatment for ruptured sinus of Valsalva aneurysm is safe and has satisfactory results. Aortic prosthesis dehiscence is the independent determinant for long-term survival. Other factors including bacterial endocarditis, concomitant ventricular septal defect repair, and aortic valve replacement did not independently influence long-term survival.

Adolescent↗

Health-care reforms in the People's Republic of China--strategies and social implications.

Analyses the features, strategies and characteristics of health-care reforms in the People's Republic of China. Since the 14th Central Committee of the Chinese Communist Party held in 1992, an emphasis has been placed on reform strategies such as cost recovery, profit making, diversification of services, and development of alternative financing strategies in respect of health-care services provided in the public sector. Argues that the reform strategies employed have created new problems before solving the old ones. Inflation of medical cost has been elevated very rapidly. The de-linkage of state finance bureau and health service providers has also contributed to the transfer of tension from the state to the enterprises. There is no sign that quasi-public health-care insurance is able to resolve these problems. Finally, cooperative medicine in the rural areas has been largely dismantled, though this direction is going against the will of the state. Argues that a new balance of responsibility has to be developed as a top social priority between the state, enterprises and service users in China in order to meet the health-care needs of the people.

China↗

Risk factors for development of acute renal failure (ARF) requiring dialysis in patients undergoing cardiac surgery.

Acute renal failure (ARF) is one of the major complications after cardiopulmonary bypass for open heart operations. The present study was undertaken to identify the risk factors for the development of ARF following cardiopulmonary bypass (CPB). Four hundred and forty-seven consecutive patients who underwent open heart procedures from July 1994 to June 1995 were analyzed retrospectively. Their mean age was 55.6 +/- 14.2 (SD) years (range, 18 to 80). Dialysis was instituted whenever a patient exhibited inadequate urine output (<0.5 mL/kg/hr) for 2 to 3 hours despite correction of hemodynamic status and diuretic therapy, especially if fluid overload, hyperkalemia, or metabolic acidosis were also present. Twenty variables were analyzed by univariate analysis; these included nine preoperative variables--age, sex, hypertension, atherosclerosis, diabetes mellitus, left ventricular end-diastolic dimension (LVEDD) >5 cm, preoperative congestive heart failure, renal insufficiency (serum creatinine > or =130 micromol/L on two occasions), and sepsis--10 intraoperative variables--duration of CPB, redo procedures, emergency surgery, use of intraaortic balloon pump (IABP) in operating room, use of gentamicin, use of ceftriaxone, use of sulbactam/ampicillin, requirement of deep hypothermic circulatory arrest, duration of low mean perfusion pressure (mean pressure <50 mmHg for more than 30 minutes), operation on multiple valves--and one postoperative variable--significant hypotension (systolic blood pressure less than 90 mmHg for more than 1 hour). Significant variables or the variables having a trend (p<0.1) to be associated with ARF were included in stepwise multiple logistic regression analyses. Three regression analyses were performed separately. The incidence of ARF requiring dialysis in the study period was 15.0%. Significant risk factors for whole group of patients (regression I) were preoperative renal insufficiency (p<0.0001), postoperative hypotension (p<0.0001), cardiopulmonary bypass time more than 140 min (p<0.005), preoperative congestive heart failure (p<0.01), and history of diabetes mellitus (p<0.01). The risk factors in the valve group of patients (regression II) were preoperative renal insufficiency (p<0.0001) and postoperative hypotension (p<0.05). Risk factors in the CABG patients (regression III) were postoperative hypotension (p=0.0001), CPB time more than 140 min (p<0.05), preoperative renal insufficiency (p<0.05), and age (p<0.05). The authors conclude that preoperative renal insufficiency and postoperative hypotension are the most important independent risk factors for ARF in postcardiac surgical patients. In addition, CPB time greater than 140 minutes and old age are also independent risk factors for ARF in CABG patients. CPB time more than 140 minutes, history of diabetes mellitus, and preoperative congestive heart failure are independent risk factors for development of ARF in our total group of patients. These findings may have important clinical implications in the prevention of ARF in postcardiac surgical patients.

Acute Kidney Injury↗

A non-fatal impalement injury of the thorax.

Impalement is an uncommon injury with only occasional reports in the literature. There are even fewer reports of impalement injuries limited to the thorax. We report herein the case of a 24-year-old man who survived impalement injury of the left side of the thorax with a steel rod while working at a construction site. The great vessels of the thorax were spared but the second thoracic vertebra was fractured resulting in complete paralysis of the left lower limb. The precise nature and extent of the injury were determined pre-operatively by computed tomography and aortography. The important principles of surgical management contributing to the successful outcome are described, these being minimal manipulation of the impalement object before and during transport, careful pre-operative planning and a multidisciplinary approach.

Accidents, Occupational↗

Chromosomal 11 alterations in non-small-cell lung carcinomas in Hong Kong.

We examined 60 non-small-cell lung cancer (NSCLC) patients for evidence of genetic alterations on chromosome 11 with nine polymorphic markers by Southern blot and microsatellite marker analysis. These analyses detected genetic alterations at both the 11p and 11q arms. At the 11p15 Ha-ras locus, the loss of heterozygosity (LOH) occurred in three out of 11 (27.3%) of the informative cases; at the 11p11-q12 D11S149 locus, the LOH occurred in two out of nine (22.2%) of the informative cases; and at the 11q13 INT-2 locus, the LOH occurred in four out of 18 (22.2%) of the informative cases. Microsatellite markers in the 11q12-q13 region revealed genetic alterations for PYGM in eight out of 54 (14.8%) of the specimens studied and 10 out of 55 (18.2%) of the specimens for the INT-2 marker. The data suggest genetic alterations occur in some of the lung cancer patients in both the 11p and 11q regions.

Adult↗

Rat immunogenicity assay of inactivated poliovirus.

A rat immunogenicity assay for IPV potency was validated and applied to routine vaccine testing as a potential alternative to the CFR Monkey Potency Assay. Potencies of pure trivalent polio, various combinations and experimental vaccines were tested with a view of producing a single dilution assay.

Animal Testing Alternatives↗

Incorporation of surface tension into molecular dynamics simulation of an interface: a fluid phase lipid bilayer membrane.

In this paper we report on the molecular dynamics simulation of a fluid phase hydrated dimyristoylphosphatidylcholine bilayer. The initial configuration of the lipid was the x-ray crystal structure. A distinctive feature of this simulation is that, upon heating the system, the fluid phase emerged from parameters, initial conditions, and boundary conditions determined independently of the collective properties of the fluid phase. The initial conditions did not include chain disorder characteristic of the fluid phase. The partial charges on the lipids were determined by ab initio self-consistent field calculations and required no adjustment to produce a fluid phase. The boundary conditions were constant pressure and temperature. Thus the membrane was not explicitly required to assume an area/phospholipid molecule thought to be characteristic of the fluid phase, as is the case in constant volume simulations. Normal to the membrane plane, the pressure was 1 atmosphere, corresponding to the normal laboratory situation. Parallel to the membrane plane a negative pressure of -100 atmospheres was applied, derived from the measured surface tension of a monolayer at an air-water interface. The measured features of the computed membrane are generally in close agreement with experiment. Our results confirm the concept that, for appropriately matched temperature and surface pressure, a monolayer is a close approximation to one-half of a bilayer. Our results suggest that the surface area per phospholipid molecule for fluid phosphatidylcholine bilayer membranes is smaller than has generally been assumed in computational studies at constant volume. Our results confirm that the basis of the measured dipole potential is primarily water orientations and also suggest the presence of potential barriers for the movement of positive charges across the water-headgroup interfacial region of the phospholipid.

Crystallography, X-Ray↗

Evaluation of a histogenetic classification for thymic epithelial tumours.

We reviewed 87 thymic epithelial tumours from Chinese patients and typed them according to the Marino and Müller-Hermelink classification as updated by Kirschner and Müller-Hermelink in 1989. Related categories were grouped for statistical analyses: group 1, medullary thymoma and mixed thymoma; group 2, cortical predominant thymoma; group 3, cortical thymoma and well-differentiated thymic carcinoma; group 4, other thymic carcinomas; and group 5, unclassified. Group 3 tumours were more frequently associated with the myasthenia gravis syndrome compared with group 1 tumours (P = 0.001). They also presented at a more advanced stage. Groups 1 and 2 showed an excellent prognosis (100% survival at 10 years). The 10-year survival for groups 3 and 4 patients was 40% and 30% respectively. Pure medullary thymoma made up a higher proportion of our cases (10.3%) than those of a similar Caucasian study (5.3%). The eight thymic carcinomas (group 4) included two thymic lymphoepitheliomas. We conclude that the histogenetic classification evaluated shows a clear correlation with prognosis and clinical features, even when tested on separate geographic groups, where pathogenetic factors may be different. A common approach to classification of thymic epithelial tumours would greatly facilitate future studies on these possible differences.

Adult↗

The nature of ion and water barrier crossings in a simulated ion channel.

Using a combination of techniques, including molecular dynamics, time-correlation analysis, stochastic dynamics, and fitting of continuum diffusion theory to electrophysiological data, a characterization is made of thermally driven sodium, water, and D2O motion within the gramicidin A channel. Since the channel contents are constrained to move in a single-file fashion, the motion that corresponds to experimentally measurable rates of permeation of the membrane is the motion of the center of mass of the channel contents. We therefore emphasize channel contents center-of-mass motion in our analysis of molecular dynamics computations. The usual free energy calculation techniques would be of questionable validity when applied to such motion. As an alternative to those techniques, we postulate a periodic sinusoidal free energy profile (related to the periodic structure of the helical channel) and deduce the fluid dynamic diffusion coefficient and the height and spacing of the free energy barriers from the form of the mean-square-deviation function, using stochastic computations. The fluid dynamic friction in each case appears similar to that for aqueous solution. However, the diffusive motions are modulated by a spatially periodic free energy profile with a periodicity characteristic of an L-D pair of amino acids in the gramicidin helix, approximately 1.7 A in the model we use. The barrier height depends on which substance is moving in the channel, but in each case is several times thermal energy. For barriers of this width and height, the motion is intermediate between the low-friction (transition-state) and high-friction (Brownian) limits. Thus, neither of these formalisms that have been used commonly to describe membrane permeation gives an accurate picture of the underlying physical process (although the Brownian description seems closer to correct). The non-Markovian Langevin equation must be solved to describe properly the statistics of the process. The "channel state of matter" characteristic of the channel contents appears to have some properties typical of the solid and some typical of the liquid state. The magnitude of the local friction and nature of the ion solvation are similar to the liquid state, but the periodicities of structure, free energy, and dynamics are somewhat solid-like. The alignment of water dipoles in the channel bears some resemblance to the orientational ordering of a nematic liquid crystal, but unlike a nematic liquid crystal, the waters have a degree of translational order as well. Thus, the "channel state" is not adequately described by analogy to either the solid or liquid states or to liquid crystals but must be dealt with as its own characteristic type of condensed matter.

Biological Transport, Active↗

Time-correlation analysis of simulated water motion in flexible and rigid gramicidin channels.

Molecular dynamics simulations have been done on a system consisting of the polypeptide membrane channel former gramicidin, plus water molecules in the channel and caps of waters at the two ends of the channel. In the absence of explicit simulation of the surrounding membrane, the helical form of the channel was maintained by artificial restraints on the peptide motion. The characteristic time constant of the artificial restraint was varied to assess the effect of the restraints on the channel structure and water motions. Time-correlation analysis was done on the motions of individual channel waters and on the motions of the center of mass of the channel waters. It is found that individual water molecules confined in the channel execute higher frequency motions than bulk water, for all degrees of channel peptide restraint. The center-of-mass motion of the chain of channel waters (which is the motion that is critical for transmembrane transport, due to the mandatory single filing of water in the channel) does not exhibit these higher frequency motions. The mobility of the water chain is dramatically reduced by holding the channel rigid. Thus permeation through the channel is not like flow through a rigid pipe; rather permeation is facilitated by peptide motion. For the looser restraints we used, the mobility of the water chain was not very much affected by the degree of restraint. Depending on which set of experiments is considered, the computed mobility of our water chain in the flexible channel is four to twenty times too high to account for the experimentally measured resistance of the gramicidin channel to water flow. From this result it appears likely that the peptide motions of an actual gramicidin channel embedded in a lipid membrane may be more restrained than in our flexible channel model, and that these restraints may be a significant modulator of channel permeability. For the completely rigid channel model the "trapping" of the water molecules in preferred positions throughout the molecular dynamics run precludes a reasonable assessment of mobility, but it seems to be quite low.

Gramicidin↗

Molecular dynamics computations and solid state nuclear magnetic resonance of the gramicidin cation channel.

This paper reports on a coupled approach to determining the structure of the gramicidin A ion channel, utilizing solid state nuclear magnetic resonance (NMR) of isotopically labeled gramicidin channels aligned parallel to the magnetic field direction, and molecular dynamics (MD). MD computations using an idealized right-handed beta-helix as a starting point produce a refined molecular structure that is in excellent agreement with atomic resolution solid state NMR data. The data provided by NMR and MD are complementary to each other. When applied in a coordinated manner they provide a powerful approach to structure determination in molecular systems not readily amenable to x-ray diffraction.

Amino Acid Sequence↗

[Combined CA-125 test and ultrasonography in the presurgical evaluation of ovarian mass].

Clinicians are urgently searching for ways of differentiating a malignant from a benign ovarian mass. How to approach or what is the prognosis? Some have shown the CA-125 test combined with ultrasonography to be highly sensitive and specific, when compared to single parameter. We examined 238 patients who underwent laparotomy for adnexal mass. Of these 44 were found to suffer from malignant tumors and 194 from benign lesions. Before the operation, CA-125 level was measured; pelvic ultrasonography was performed on each patient and the sonographic data were evaluated on an echostructural scoring system. After a sophisticated computer assisted analysis, the results of the combined tests were CA-125 greater than or equal to 65 U/ml or US score greater than or equal to 8 with a sensitivity of 77.3%, a specificity of 81.4% and a diagnostic accuracy of 80.7%. Therefore we confirm that CA-125 may be considered as a useful adjunct to sonography in the differential diagnosis of adnexal mass.

Antigens, Tumor-Associated, Carbohydrate↗