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Biomedical subjects

V W Lee

Publications and source records attributed to V W Lee.

At least 19 recordsLinked to original sources

Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients.

BACKGROUND: Target of rapamycin inhibitors (TOR-I) (sirolimus, everolimus) are immunosuppressive agents with a novel mode of action but an uncertain clinical role. OBJECTIVES: To investigate the benefits and harms of immunosuppressive regimens containing TOR-I when compared to other regimens as initial therapy for kidney transplant recipients. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library, issue 2, 2005), MEDLINE (1966-June 2005), EMBASE (1980-June 2005), the specialised register of the Cochrane Renal Group (June 2005)., and contacted authors and pharmaceutical companies to identify relevant studies. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs where drug regimens containing TOR-I were compared to alternative drug regimens in the immediate post-transplant period were included, without age restriction, dosage or language of report. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for eligibility and quality, and extracted data. Results are expressed as relative risk (RR) or weight mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: Thirty three trials (142 reports) were included (sirolimus (27), everolimus (5), head-to-head (1)). When TOR-I replaced CNI there was no difference in acute rejection, but serum creatinine was lower (MD -18.31 micromol/L, -30.96 to -5.67), and bone marrow more suppressed (leucopenia: RR 2.02 1.12 to 3.66; thrombocytopenia: RR 6.97 2.97 to 16.36; anaemia: RR 1.67, 1.27 to 2.20). When TOR-I replaced antimetabolites, acute rejection (RR 0.84, 0.71 to 0.99) and cytomegalovirus infection (CMV) (RR 0.49; 0.37 to 0.65) were reduced, but hypercholesterolaemia was increased (RR 1.65, 1.32 to 2.06). For low versus high-dose TOR-I, with equal CNI dose, rejection was increased (RR 1.23, 1.06 to 1.43) but calculated GFR higher (MD 4.27 mL/min, 1.12 to 7.41), and for low-dose TOR-I/standard-dose CNI versus higher-dose TOR-I/reduced CNI, acute rejection (RR 0.67, 0.52 to 0.88) and calculated GFR (MD -9.46 mL/min, -12.16 to -6.76) were reduced. There was no significant difference in mortality, graft loss or malignancy risk for TOR-I in any comparison. AUTHORS' CONCLUSIONS: TOR-I have been evaluated in four different primary immunosuppressive algorithms; as replacement for CNI and for antimetabolites, in combination with CNI at low and high dose and with variable dose of CNI. Generally, surrogate endpoints for graft survival favour TOR-I (lower risk of acute rejection and higher GFR) and surrogate endpoints for patient outcomes are worsened by TOR-I (bone marrow suppression, lipid disturbance). Long-term hard-endpoint data from methodologically robust RCTs are still needed.

Everolimus↗

Retention of endothelium on ovine collagen biomatrix vascular conduits under physiological shear stress.

This study evaluates the adhesion of endothelial cells to 4 mm internal diameter, ovine collagen biomatrix vascular conduits. The biomatrix conduit is formed in a living animal and the wall consists of a complete, naturally produced matrix reinforced with polyester mesh. We propose that the microarchitecture of the matrix lining the lumen may promote endothelial cell attachment without pretreatment with adhesive proteins or extra cellular matrix components. Endothelial cell adhesion to the biomatrix surface was assessed by subjecting conduits seeded with ovine aortic endothelial cells (OAEC) to physiological range shear stresses of 16 and 32 dyn/cm2 in vitro. OAECs were isolated, cultured and seeded (1 x 10(6) cells/ml) by rotation onto the luminal surface of 20 cm lengths of biomatrix vascular conduits (n = 36). The seeded conduits were divided into three groups and cultured either for 24 h (n = 12), 48 h (n = 12) or 72 h (n = 12). Following culture, the conduits from each group were subjected to flow rates of either 240 ml/min (n = 6) or 480 ml/min (n = 6) with heparinized sheep blood for 1 h. Luminal surface cell cover was determined pre- and post-flow from Datura stramonium lectin labeled en face preparations. Histological analysis demonstrated that OAECs attach to the luminal surface of biomatrix conduits and form confluent monolayers within 24-48 h. Flow testing revealed that, for both flow rates and independent of the time in culture, there was no significant decrease in cell cover after flow (p = 0.13). The results support the hypothesis that a vascular conduit, engineered from a naturally formed biomatrix, provides a suitable substrate for the formation of flow resistant endothelium.

Animals↗

Synechial angle closure pattern in Chinese chronic primary angle-closure glaucoma patients.

PURPOSE: The aim of this retrospective clinical study is to investigate the pattern of synechial angle closure in a group of Hong Kong Chinese with chronic primary angle-closure glaucoma. METHODS: The anterior angle of the upper, lower, medial, and lateral quadrants of 84 eyes from Hong Kong Chinese patients with chronic primary angle-closure glaucoma were assessed by the same examiner using indentation gonioscopy. RESULTS: The incidences of synechial angle closure at the superior, nasal, inferior, and temporal quadrants were 98% (83/84), 77% (65/84), 31% (26/84), and 94% (79/84), respectively. The Fisher exact test showed that the incidence of synechial angle closure at the superior quadrant was significantly higher than the nasal (P = 0.005) and inferior (P < 0.001) quadrants, but not the temporal quadrant (P = 0.07). CONCLUSION: Synechial angle closure is circumferential with asymmetry in these Chinese patients with chronic primary angle-closure glaucoma. The superior and temporal quadrants of the anterior angle may be the earliest sites of the synechial angle closure. The anterior angle may close synechially at the superior and temporal quadrants with gradual extension on the nasal quadrant, until the angle may close at the inferior quadrant.

Anterior Eye Segment↗

Nerve fiber analyzer and short-wavelength automated perimetry in glaucoma suspects: a pilot study.

PURPOSE: To test the relationship between the results of short-wavelength automatic perimetry (SWAP) and retinal nerve fiber layer (RNFL) measurements with scanning laser polarimetry (Nerve Fiber Analyzer, NFA) in age-matched normal subjects, glaucoma suspects, and early glaucoma patients. DESIGN: Case-control study. PARTICIPANTS AND METHODS: Thirty-eight normal subjects, 32 glaucoma suspects, and 14 early glaucoma patients were recruited. All subjects underwent RNFL assessment by NFA, achromatic visual field testing (24-2 threshold), and repeated SWAP (24-2 threshold blue-on-yellow). MAIN OUTCOME MEASURES: Mean deviation (MD) of visual field testing and RNFL values were obtained. RESULTS: Glaucoma suspects were divided into two groups according to their SWAP results: high risk (with SWAP abnormalities) and low risk (with normal SWAP result). No statistically significant difference in SWAP MD and RNFL values were observed between normal and low-risk groups (P > 0.05), but these values were found to be significantly lower in high-risk and early glaucoma groups (P < 0.01). CONCLUSIONS: This study suggests that RNFL examination by NFA may be a useful test for the early detection of glaucomatous damage of glaucoma suspects. It appears to provide agreement with SWAP abnormalities and is more sensitive than conventional standard automated perimetry.

Case-Control Studies↗

Nerve fibre layer measurement of the Hong Kong Chinese population by scanning laser polarimetry.

PURPOSE: To obtain normal retinal nerve fibre layer (RNFL) measurements by scanning laser polarimetry in a local Hong Kong Chinese population and to identify the correlation of the measurements with age. METHODS: One hundred and fifty-nine normal Hong Kong Chinese volunteers of different ages were recruited for this study. RNFL values were measured using a Nerve Fibre Analyzer GDx (Laser Diagnostic Technologies, CA). RESULTS: Mean peripapillary RNFL measurements at the superior, inferior, temporal and nasal regions were 95.0 +/- 15.6, 97.0 +/- 16.3, 47.0 +/- 9.0 and 43.9 +/- 15.1 microns respectively (mean +/- SD). There was a highly significant negative correlation in average RNFL values with increasing age (approximately 1.9 microns per decade, p = 0.001). A significant negative correlation with increasing age was also identified in the RNFL values in all four regions and they decreased by similar amounts (p < 0.05). No correlation with age was observed for relative ratio parameters such as superior/nasal ratio, inferior/nasal ratio and max. modulation (p > 0.05). CONCLUSION: RNFL values of the Hong Kong Chinese population appeared to decrease over time cross-sectionally. Since they decreased by similar amounts at four regions, use of relative ratio parameters for analysis has an advantage over absolute values, as they were not affected by age.

Adolescent↗

Chest wall resection and reconstruction via a muscle-sparing minithoracotomy for lung cancer.

Five per cent of lung cancers involve the parietal pleura and chest wall. En bloc resections improve survival. Lung resections via muscle-sparing chest incisions have minimized complications and hospital stay. We present a case in which we performed an en bloc lobectomy with chest wall resection and reconstruction through a muscle sparing minithoracotomy in a 48-year-old woman. She was discharged in the fourth postoperative day and remains tumor free and asymptomatic after 4 years.

Female↗

Reconstitution of acid-denatured holomyoglobin studied by time-resolved electrospray ionization mass spectrometry.

Time-resolved electrospray ionization (ESI) mass spectrometry (MS) is a new technique for studying the kinetics of protein folding reactions. It can monitor both changes in the protein conformation and the loss or binding of protein ligands as a function of time. Time-resolved ESI MS was previously used to monitor the acid-induced unfolding of holomyoglobin (hMb). The native form of this protein is characterized by a tightly folded conformation and a heme group that is noncovalently attached to the protein. Acid-induced denaturation induces substantial unfolding of the polypeptide chain and disruption of the heme-protein interactions. In this work, time-resolved ESI MS is used to study the reverse reaction, i.e., reconstitution of acid-denatured hMb. To examine the mechanism and the kinetics of this reaction, a continuous-flow setup with two sequential mixing steps was developed. The data presented in this work show that reconstitution involves the formation of various short-lived intermediates such as tightly folded myoglobin without a heme group and several nativelike forms of the protein that are bound to more than one heme. The occurrence of these transient states is most likely due to the rapid aggregation of free heme in solution.

Acetic Acid↗

Retinal nerve fiber layer measurement by nerve fiber analyzer in normal subjects and patients with glaucoma.

OBJECTIVE: To identify the pattern of retinal nerve fiber layer (RNFL) loss in glaucoma using the Nerve Fiber Analyzer (NFA). DESIGN: Case-control study. PARTICIPANTS: A total of 80 normal and 75 age- and race-matched chronic open-angle glaucoma subjects were recruited. INTERVENTION: The RNFL thickness was assessed with a scanning laser polarimeter (Nerve Fiber Analyzer GDX, Laser Diagnostic Technologies Inc., San Diego, CA). Analysis of variance was used to compare the corresponding RNFL measurement indices of the different groups. MAIN OUTCOME MEASURES: Superior/nasal (S/N) and inferior/nasal (I/N) ratios of NFA are sensitive parameters to differentiate between glaucoma and nonglaucoma subjects. RESULTS: Peripapillary RNFL measurements at the superior and inferior regions were significantly lower in the glaucoma group (P<0.001) but were similar in temporal and nasal regions (P>0.05). Using nasal value as reference, S/N and I/N ratios were significantly lower in the glaucoma groups (P<0.001) and also decreased with increasing severity of glaucoma. CONCLUSIONS: In glaucoma, RNFL was more susceptible to loss in the superior and inferior regions than in the nasal and temporal regions. The S/N and I/N ratio parameters provided by the NFA appeared to give further discriminating ability in early glaucoma.

Adult↗

Influences of surgical castration on the thymus of male rats.

In previous studies, we have shown that castration of Sprague-Dawley rats enhances thymic weight through puberty whilst sex steroids reduce the castration-induced hypertrophy. In the current study, we have confirmed that castration enhances thymic growth compared to age-matched intact controls. In addition, immunoassays were used to measure thymosin alpha1 and thymosin beta4 levels in sera from intact and castrate rats. Castrate animals displayed greater sera levels of thymosins compared to sera from intact animals. To test whether the enhanced thymic weight and increased levels of thymosins observed post-castration were able to influence immune function of castrate animals, concanavalin A was used in the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay to examine lymphocyte and thymocyte responses from both intact and castrate male rats. Responses of cells isolated from castrate rats demonstrated that lymphocytes and thymocytes were stimulated at low levels of concanavalin A (1.56-3.13 microg/ml for lymphocytes and 1.56 microg/ml for thymocytes) compared to the same cell types isolated from intact rats. Concentrations of concanavalin A ranging from 6.25 to 200 microg/ml produced no significant differences in response from intact and castrate animals.

Animals↗

Tono-Pen tonometer and corneal thickness.

PURPOSE: To compare the intraocular pressure (IOP) measurements taken at the central cornea with those taken at the mid-peripheral cornea using the Tono-Pen tonometer. METHODS: Forty-eight normal human subjects had their IOP measurements taken (i) with the Goldmann tonometer, (ii) with the Tono-Pen at the central cornea and (iii) with the Tono-Pen at the mid-peripheral cornea. The central and mid-peripheral corneal thickness at the site of IOP measurements were then determined by ultrasonic pachymetry. RESULTS: The mean IOP with the Goldmann tonometer was 15.7 +/- 3.1 mmHg. The mean Tono-Pen IOPs at the central and midperipheral cornea were 15.2 +/- 3.2 mmHg and 15.7 +/- 3.3 mmHg respectively. The mean midperipheral corneal thickness (578 microns) was significantly higher than the mean central thickness (538 microns) (p < 0.001). CONCLUSION: There was no significant difference between the IOP taken with the Tono-Pen and with the Goldmann tonometer. In addition, no clinically significant difference was observed between the IOP readings of central and mid-peripheral cornea measured by the Tono-Pen.

Cornea↗

The evaluation of cocaine-induced chest pain with acute myocardial perfusion imaging.

OBJECTIVE: To use myocardial perfusion imaging to determine the etiology of cocaine-induced chest pain in patients without ECG evidence of acute cardiac ischemia. METHODS: The authors conducted a prospective study of consecutive consenting patients aged 18-70 years with cocaine-induced chest pain who reported cocaine use within three days and presented with a chief complaint of chest pain occurring within three hours and lasting longer than 15 minutes with a normal or nondiagnostic ECG. Patients were excluded if they had a clear-cut noncardiac cause of chest pain, ECG evidence of acute cardiac ischemia, history of myocardial infarction, pregnancy, or lactation, required immediate hospitalization, or were unable to consent. Patients were injected with Tc-99m tetrofosmin and imaged. Perfusion scans were independently read by two nuclear radiologists. Clinicians blinded to scan results determined patient disposition. Patients with abnormal scans were asked to return for follow-up resting scans. RESULTS: Fourteen patients were enrolled. Twelve of the 14 patients had chest pain at the time of Tc-99m tetrofosmin injection. Ten of the 14 [(71%) 95% CI = 48% to 95%] scans were normal or within normal limits. Four of the 14 [(29%) 95% CI = 5% to 52%] were abnormal. Of the four patients with abnormal scans, two had follow-up scans that demonstrated an irreversible perfusion abnormality, and two who did not return for follow-up reported no subsequent hospitalizations for acute cardiac ischemia. CONCLUSION: Perfusion imaging did not demonstrate reversible ischemia in most patients (12/14, 86%) with cocaine-induced chest pain without ECG evidence of ischemia. These results suggest that cocaine-induced chest pain in most patients without ECG evidence of ischemia is not due to acute ischemia.

Adolescent↗

Radioaerosol scintigraphy in infants and children born to mothers with HIV disease. Pediatric Pulmonary and Cardiovascular Complications (of Vertically Transmitted Human Immunodeficiency Virus) Study Group.

PURPOSE: To determine the usefulness of technetium 99m diethyltriaminepentacetic acid (DTPA) radioaerosol inhalation-clearance scintigraphy for early detection of pulmonary complications of human immunodeficiency virus (HIV) disease in children. MATERIALS AND METHODS: A total of 301 studies were performed in 132 HIV-positive children (group 1; mean age, 46.6 months). In children born to HIV-positive mothers (group 2), 273 studies were performed in 160 children who eventually were proved to be HIV negative (mean age, 10.3 months), and 80 studies were performed in 47 HIV-positive children (mean age, 15.6 months). Radioaerosol studies were performed by using commercially available radioaerosol nebulizers. Pulmonary clearance half-time was measured by using conventional gamma camera computer systems. Radioaerosol results were correlated with indexes of pulmonary health and function. RESULTS: The HIV-negative, group 2 children had a mean radioaerosol clearance half-time (58.1 minutes; 162 studies in 108 children) similar to that reported in healthy adults. Group 1 children with pulmonary involvement exhibited a faster mean clearance half-time (28.6 minutes) than did children without evidence of pulmonary involvement from either group 1 or group 2 (P < .05). A faster pulmonary clearance rate did not simply reflect the presence of chest disease that also was detectable on radiographs (P = .3). CONCLUSION: Quantitative DTPA radioaerosol clearance studies may provide useful information about pulmonary involvement in selected children with HIV disease.

Administration, Inhalation↗

Intracranial mass lesions: sequential thallium and gallium scintigraphy in patients with AIDS.

PURPOSE: To determine the efficacy of sequential thallium and gallium scintigraphy to differentiate intracranial neoplasms (lymphoma and glioma) from other nonmalignant intracranial mass lesions among patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: The authors reviewed the cases of 40 patients with human immunodeficiency virus (HIV) who underwent thallium and gallium scanning to evaluate intracranial mass lesions from October 1991 through November 1997. There was a definitive final diagnosis of the nature of the mass lesions in 21 of these cases. In these 21 cases, the scintigraphic patterns were reviewed and were compared with the final diagnosis. RESULTS: On the basis of results at thallium and gallium scanning, the patients were divided into three groups. Group A included 13 patients (11 with brain tumors [lymphomas and gliomas] and two with progressive multifocal leukoencephalopathy [PML]) with thallium-positive, gallium-positive scans. Group B included five patients with intracranial infections (tuberculosis, Cryptococcus, bacteria) with thallium-negative, gallium-positive scans. Group C included three patients (one with PML and two with infarcts) with thallium-negative, gallium-negative scans. All patients with lymphomas were in group A. The sensitivity and specificity of the thallium-positive, gallium-positive pattern for intracranial malignancy were 100% and 80%, respectively. CONCLUSION: Sequential thallium and gallium scanning helped differentiate tumors from nonmalignant intracranial mass lesions and may help differentiate infections from PML or infarcts.

Acquired Immunodeficiency Syndrome↗