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Biomedical subjects

T S Li

Publications and source records attributed to T S Li.

At least 19 recordsLinked to original sources

Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity and quality of life in a cohort of survivors.

OBJECTIVE: To examine the impact of severe acute respiratory syndrome (SARS) on pulmonary function, exercise capacity, and health-related quality of life (HRQoL) among survivors. METHODS: 110 survivors with confirmed SARS were evaluated at the Prince of Wales Hospital, HK at the end of 3 and 6 months after symptom onset. The assessment included lung volumes (TLC, VC, RV, FRC), spirometry (FVC, FEV1), carbon monoxide transfer factor (TLCO adjusted for haemoglobin), inspiratory and expiratory respiratory muscle strength (Pimax and Pemax), 6 minute walk distance (6MWD), chest radiographs, and HRQoL by SF-36 questionnaire. RESULTS: There were 44 men and 66 women with a mean (SD) age of 35.6 (9.8) years and body mass index of 23.1 (4.8) kg/m2. Seventy (64%) were healthcare workers. At 6 months 33 subjects (30%) had abnormal chest radiographs; four (3.6%), eight (7.4%), and 17 (15.5%) patients had FVC, TLC, and TLCO below 80% of predicted values; and 15 (13.9%) and 24 (22.2%) had Pimax and Pemax values below 80 cm H2O, respectively. The 6MWD increased from a mean (SD) of 464 (83) m at 3 months to 502 (95) m (95% CI 22 to 54 m, p<0.001), but the results were lower than normal controls in the same age groups. There was impairment of HRQoL at 6 months. Patients who required ICU admission (n = 31) had significantly lower FVC, TLC, and TLCO than those who did not. CONCLUSION: The exercise capacity and health status of SARS survivors was considerably lower than that of a normal population at 6 months. Significant impairment in surface area for gas exchange was noted in 15.5% of survivors. The functional disability appears out of proportion to the degree of lung function impairment and may be related to additional factors such as muscle deconditioning and steroid myopathy.

Adult↗

Prolonged survival of xenograft fetal cardiomyocytes by adenovirus-mediated CTLA4-Ig expression.

BACKGROUND: Experimental allografting of fetal cardiomyocytes has been performed successfully. In this study, we attempted to transplant rat fetal cardiomyocytes into the hearts of mice by blocking the CD28/B7 costimulatory pathway via CTLA4-Ig gene transfer. METHODS: Fetal cardiomyocytes derived from Dark Agouti rat were infected with CTLA4-Ig-expressing adenovirus vectors (AdCTLA) and injected directly into the normal myocardium of C3H/He mice (n=15). For control, cells infected with beta-Gal-expressing adenovirus vector (AdRL) and cells without infection were injected into additional mice (n=30). Mice were killed at 2 (n=5), 4 (n=5), and 8 (n=5) weeks after xenotransplantation. Transplanted fetal cardiomyocytes were examined for survival by immunostaining with anti-rat atrial natriuretic peptide and anti-CTLA4-Ig antibodies. RESULTS: Fetal cardiomyocytes were successfully infected by AdCTLA and AdRL. The cardiomyocytes infected with AdCTLA expressed CTLA4-Ig and survived to 8 weeks after xenotransplantation in all of these mice. However, cardiomyocytes infected with AdRL and noninfected cells were not detected even 2 weeks after xenotransplantation. CONCLUSION: Survival of xenografted fetal cardiomyocytes is prolonged by adenovirus-mediated CTLA4-Ig expression.

Abatacept↗

Autologous bone marrow implantation induced angiogenesis and improved deteriorated exercise capacity in a rat ischemic hindlimb model.

BACKGROUND: Bone marrow possesses endothelial progenitor cells that secrete several growth factors and can contribute to the formation of new capillaries. In the present study, we investigated the extent of angiogenesis induced by implantation of autologous bone marrow cells (BMCs) in a rat ischemic hindlimb model and studied whether the increased collateral vessels can improve deteriorated physical function. MATERIALS AND METHODS: Ischemic hindlimb was created by ligation of the femoral artery and its branches in Dark Agouti (DA) rats. BMCs (1 x 10(7)) were injected percutaneously at six points into the gastrocnemius muscle. To assess angiogenesis, histologic evaluation and microangiography were performed at 2 weeks postligation. Severity of the ischemic insult was evaluated by measuring blood flow in the adductor and gastrocnemius muscles using nonradioactive colored microspheres and by determining the femoral arteriovenous oxygen difference (AVDO(2)) at 2 weeks postligation. Running time on a motor-driven treadmill was used to represent exercise capacity. RESULTS: The histologic evaluation and microangiogram showed that the implanted BMCs induce angiogenesis. Blood flow to the adductor muscle on the treated side in the bone marrow cell implantation (BMI) group was significantly restored to 77.3 +/- 19.3% of that of the normally perfused limb in comparison to that in control groups (P < 0.05). AVDO(2) in the BMI group significantly decreased when compared with AVDO(2) in control groups. Rats in the BMI group ran approximately 1.5 times longer than rats in control groups at 2 and 4 weeks postligation (P < 0.01). CONCLUSIONS: Implantation of autologous BMCs induced angiogenesis and improved deteriorated exercise capacity in our rat ischemic hindlimb model.

Angiography↗

Digitonin enhances the antitumor effect of cisplatin during isolated lung perfusion.

BACKGROUND: The antitumor effect of isolated lung perfusion with cisplatin was limited because the intracellular platinum concentration did not increase sufficiently. To solve this problem, digitonin, a detergent, was chosen to increase cell permeability and enhance intracellular uptake and antitumor effect. This study was designed to investigate toxicity, pharmacokinetics, and efficacy of isolated lung perfusion with the combined use of digitonin and cisplatin in Fischer 344 rats. METHODS: Systemic and local toxicities of isolated lung perfusion treatment were evaluated on the basis of body weight change, survival rate, and histologic findings. The maximal tolerated dose of digitonin was determined by assessing survival on day 21 after contralateral pneumonectomy, body weight change, and histologic findings. Pharmacokinetics were observed in a solitary lung tumor nodule model by measuring platinum concentration in tumor and normal lung tissue. The antitumor effect was evaluated by the number of tumor nodules in the left lung 21 days after isolated lung perfusion. Isolated lung perfusion was performed 7 days after 1.0 x 10(6) methylcholanthrene sarcoma cells were injected into the external jugular vein. RESULTS: The maximal tolerated dose of digitonin was 20 micromol/L. Platinum concentration of tumor nodules in the digitonin-cisplatin-treated rats was 20% higher than in the cisplatin-only group (5.48 +/- 0.64 microg/g tissue versus 4.50 +/- 1.09 microg/g tissue; p = 0.067). The number of pulmonary nodules decreased significantly by digitonin use (1.3 +/- 1.5 versus 9.7 +/- 2; p < 0.0001). CONCLUSIONS: Isolated lung perfusion with digitonin and cisplatin in combination was performed safely and enhanced the antitumor effect. These drugs in combination show promise for enhancing the effect of clinical isolated lung perfusion.

Animals↗

The influence of tumour resection on angiostatin levels and tumour growth--an experimental study in tumour-bearing mice.

The phenomenon of primary neoplasms inhibiting the growth of their metastatic lesions is thought to be related to endogenous angiogenesis inhibitors. The aim of this experiment was to investigate the influence of tumour resection on angiostatin levels and tumour growth using a tumour-bearing mouse model. A primary Lewis lung cancer tumour model was established in C57BL/6 mice and these mice were divided into two groups 10 days after the tumour cells were inoculated. In the surgical resection group (S group) the tumour was resected, but in the control group (C group) a sham operation was performed. The level of angiostatin in the sera was analysed 5 days after the operation by western blotting. To observe tumour growth, four Lewis lung cancer models were established in these mice from both the S and C groups. An immunohistochemical analysis of the tumour tissues was conducted to estimate the proliferation and apoptotic rates of the tumour cells, as well as the amount of neoangiogenesis in the tumours. Angiostatin was observed in the tumour-bearing mice, but disappeared within 5 days after the tumour had been resected. Increased tumour growth was observed in all of the tumour models in the S group compared with the C group and the differences were significant. A significantly higher intratumour vessel density and proliferation cell index, but a significantly lower apoptotic index were also found in the S group compared with the C group. These findings demonstrated that angiostatin was generated directly from the tumour tissue. Furthermore, tumour resection accelerates the growth of other tumours and this is probably related to multiple factors including increased neoangiogenesis, increased tumour cell proliferation, and decreased apoptosis.

Angiostatins↗

The induction of angiogenesis by the implantation of autologous bone marrow cells: a novel and simple therapeutic method.

BACKGROUND: Bone marrow contains many kinds of primitive cells that could differentiate to endothelial cells and secrete several growth factors. In the current study, we attempted to induce therapeutic angiogenesis by implanting autologous bone marrow cells (BMCs) and using a rat ischemic hind limb model. METHODS: BMCs were prepared by removing red blood cells. A rat ischemic hind limb model was made by the ligation of the left femoral artery and its branches. BMCs were injected into 7 points of the ischemic muscles. To assess angiogenesis, a microangiogram, laser Doppler, and histologic evaluation were performed after the surgical procedure. RESULTS: A microangiogram and histologic evaluation showed that angiogenesis was significantly induced in the ischemic hind limb by the implantation of BMCs. Laser Doppler imaging analysis showed that blood flow was significantly increased after implantation of BMCs. Some implanted BMCs were stained positively with CD31 and vascular endothelial-cadherin (VE-cadherin), which might have been incorporated into the vasculature. The condition of ischemia caused an elevation in the level of basic fibroblast growth factor in the ischemic muscle and also in interleukin-1beta derived from the implanted BMCs, which might contribute to angiogenesis. CONCLUSION: These findings indicate that autologous bone marrow implantation may be a novel and simple method for inducing therapeutic angiogenesis.

Animals↗

Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results.

A new therapy for severe ischemic heart disease has been developed; therapeutic angiogenesis induced by the local implantation of autologous bone marrow cells (BMC). After confirming that no detrimental changes were induced by this treatment in a canine heart model, a clinical trial was commenced in 1999. Thus far, 5 patients have been given this new treatment concomitant with coronary artery bypass grafting and all have been followed up for at least 1 year. Autologous BMC were implanted into the ungraftable area and postoperative cardiac scintigraphy showed specific improvement in coronary perfusion in 3 of the 5 patients. Postoperative chest radiography, electrocardiography, echocardiography and blood tests did not reveal any detrimental changes. In conclusion, this new therapy appears to be safe and could provide a treatment option for patients with otherwise untreatable ischemic heart disease.

Aged↗

Determinants of continuous positive airway pressure compliance in a group of Chinese patients with obstructive sleep apnea.

OBJECTIVE: To assess continuous positive airway pressure (CPAP) compliance and factors associated with CPAP compliance among Chinese patients with obstructive sleep apnea (OSA). DESIGN: A prospective study of 112 consecutive patients with newly diagnosed OSA commencing CPAP treatment. SETTING: A university teaching hospital. MEASUREMENTS AND RESULTS: The following factors were evaluated for any correlation with objective CPAP compliance (effective mask pressure [hours per day]) at 1 month and 3 months: age, baseline apnea-hypopnea index (AHI), common OSA symptoms, minimum arterial oxygen saturation (SaO(2)), mean SaO(2), arousal index (AI), Epworth sleepiness scale (ESS), education level, CPAP levels, satisfaction with CPAP, side effects, and machine cost. There were 101 male and 11 female patients, with a mean (+/- SD) age of 45.6 +/- 1.2 years; body mass index, 29.3 +/- 5.2 kg/m(2); AI, 60 +/- 18/h; AHI, 48 +/- 24/h; minimum SaO(2) of 70 +/- 17%; and mean SaO(2) of 86 +/- 7%. ESS fell from 12.9 +/- 4.0 (baseline) to 5.2 +/- 4.7 at 3 months (p < 0.001). Objective CPAP compliance was 5.4 +/- 1.6 h/d and 5.3 +/- 1.6 h/d, while 75% and 72% of our patients were using CPAP objectively for > or = 4 h/d and at least 70% of the nights per week at 1 month and 3 months, respectively. Following univariate analysis of variance, a high baseline AHI (p = 0.006 and p = 0.004) was associated with higher objective CPAP compliance at 1 month and 3 months, respectively. CONCLUSION: CPAP usage and compliance were high in this patient population. A high baseline AHI was the only significant independent predictor of better CPAP compliance.

Age Factors↗

Dynamics of HIV-specific CD8+ T lymphocytes with changes in viral load.The RESTIM and COMET Study Groups.

The influence of HIV burden variations on the frequencies of Ag-specific CD8+ T cell responses was evaluated before and during highly active antiretroviral therapy by analyzing the number, diversity, and function of these cells. The frequencies of HLA-A2-restricted CD8+ PBL binding HLA-A2/HIV-epitope tetramers or producing IFN-gamma were below 1%. A panel of 16 CTL epitopes covering 15 HLA class I molecules in 14 patients allowed us to test 3.8 epitopes/patient and to detect 2.2 +/- 1.8 HIV epitope-specific CD8+ subsets per patient with a median frequency of 0.24% (0.11-4. 79%). During the first month of treatment, viral load rapidly decreased and frequencies of HIV-specific CD8 PBL tripled, eight new HIV specificities appeared of 11 undetectable at entry, while CMV-specific CD8+ PBL also appeared. With efficient HIV load control, all HIV specificities decayed involving a reduction of the CD8+CD27+CD11ahigh HIV-specific effector subset. Virus rebounds triggered by scheduled drug interruptions or transient therapeutic failures induced four patterns of epitope-specific CD8+ lymphocyte dynamics, i.e., peaks or disappearance of preexisting specificities, emergence of new specificities, or lack of changes. The HIV load rebounds mobilized both effector/memory HIV- and CMV-specific CD8+ lymphocytes. Therefore, frequencies of virus-specific CD8 T cells appear to be positively correlated to HIV production in most cases during highly active antiretroviral therapy, but an inverse correlation can also be observed with rapid virus changes that might involve redistribution, sequestration, or expansion of these Ag-specific CD8 T cells. Future strategies of therapeutic interruptions should take into account these various HIV-specific cell dynamics during HIV rebounds.

Amino Acid Sequence↗

Relationship between the concentration of CDDP in tumor and tumor size after isolated lung perfusion treatment experimental study on a solitary pulmonary sarcoma model in rats.

BACKGROUND AND OBJECTIVES: Few investigations on the pharmacokinetics of isolated lung perfusion (ILP) regional chemotherapy in tumors have been conducted. The purpose of this study was to evaluate the pharmacokinetic character of ILP in tumor tissues. Materials and Methods A solitary tumor nodule model was established in Fisher 344 rats by inoculating 1.0 x 10(6) methylcholanthrene-induced sarcoma cells into the left lung. On 14-21 days after the inoculation of tumor cells, rats were randomized into groups subjected to 10, 20, 40 or 60 min ILP with cis-diamminedichloroplatinum (CDDP) at concentrations of 25, 50, or 100 microg/ml. Total platinum concentration in tumors was measured by a flameless atomic absorption spectrophotometer. RESULTS: The average tumor weights and total platinum concentrations were not significantly different among the perfusion groups. We found, however, that the total platinum concentrations in tumor nodules were significantly correlated inversely with the tumor weight (total platinum concentration in tumor = 1.167 x 1/tumor wt; R(2) = 0.981; P < 0.001). CONCLUSIONS: The concentration of total platinum in the tumor tissue was found to be dependent on the weight of the tumor in ILP. Higher concentrations of total platinum were expressed in smaller tumor nodules than larger ones, indicating that ILP may be more effective against small tumors than large ones. Therefore, we suggest that large tumor legions should be debulked before ILP in patients with an unresectable lung tumor.

Animals↗

Enhancement of angiogenesis by the implantation of self bone marrow cells in a rat ischemic heart model.

Background. Bone marrow contains various kinds of primitive cells which differentiate into endothelial cells and could secrete several growth factors. Therefore, we attempted to induce therapeutic angiogenesis using self bone marrow cells in a rat model. Materials and methods. Quantitative angiogenesis was examined using a sponge implantation assay that indicated whether the rat bone marrow cells had induced angiogenesis or not. Employing a rat ischemic heart model, bone marrow cells were injected directly into the ischemic area and the number of vessels was examined immunohistochemically using the anti-CD31 monoclonal antibody. The contributed growth factors revealed the levels present in the ischemic myocardium by an enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. Results. The sponge implantation assay showed that bone marrow cells induced angiogenesis. Light microscopic analysis of the vessel count positively stained by anti-CD31 in the ischemic area showed that angiogenesis had been induced to a significantly greater degree in the group implanted with bone marrow cells (BMI group) than in the group injected with phosphate-buffered saline (PBS group) 1 week after BMI. Levels of the inflammatory cytokines interleukin-1 (IL-1beta) and cytokine-induced neutrophil chemoattractant (CINC) in the BMI group were significantly elevated compared with those in the PBS group. Conclusions. Self bone marrow cell implantation induced angiogenesis in a rat ischemic heart model as a result of elevation of the levels of IL-1beta and CINC. Thus, bone marrow implantation could be a novel and simple method to induce therapeutic angiogenesis.

Animals↗

Prevalence of sleep disturbances in chinese patients with end-stage renal failure on continuous ambulatory peritoneal dialysis.

Patients with end-stage renal failure (ESRF) are reported to have a high prevalence of sleep disorders, such as daytime sleepiness, insomnia, restless legs syndrome (RLS), and obstructive sleep apnea syndrome (OSAS). However, there are few published data from Southeast Asia. A sleep questionnaire was administered to 201 patients (103 men) at the continuous ambulatory peritoneal dialysis (CAPD) outpatient clinic to assess sleep problems. Patients had a mean age of 56.7 +/- 12 (SD) years, with a mean body mass index (BMI) of 23.6 +/- 3.5 kg/m(2). Daytime sleepiness was the most frequent symptom (77.1%), and frequent awakening occurred in 69% of the patients. Sleep-onset insomnia and sleep-maintenance insomnia occurred in 73% and 60% of the patients, respectively. Sixty-two percent of the patients reported symptoms of RLS, which significantly correlated with sleep-onset insomnia (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.5 to 5.5; P = 0.001) and sleep-maintenance insomnia (OR, 2.1; 95% CI, 1.2 to 3.8; P = 0.014). The prevalence of OSAS was estimated by the frequency of the following symptoms: extremely loud snoring, 7 patients (3.5%); observed choking, 21 patients (10.5%); witnessed apnea, 11 patients (5.6%); snoring and witnessed apnea, 6 patients (3%); disruptive snoring, 29 patients (14.4%); and disruptive snoring and witnessed apnea, 3 patients (1.5%). This questionnaire survey confirmed a high prevalence of daytime sleepiness, insomnia, and RLS in patients with ESRF undergoing CAPD but showed a relatively low prevalence of OSAS of up to 14.4%, which may be related to the low BMI of these patients with ESRF compared with other populations. Whether this contributes to the overall better survival observed in some Asian patients with ESRF undergoing dialysis needs further investigation.

Adolescent↗

Effects of augmented continuous positive airway pressure education and support on compliance and outcome in a Chinese population.

OBJECTIVES: To study the effects of augmentation of continuous positive airway pressure (CPAP) education and support on compliance and outcome in patients with obstructive sleep apnea (OSA). DESIGN: A randomized, controlled, parallel study of basic vs augmented CPAP education and support. SETTING: A university teaching hospital. PATIENTS: A total of 108 OSA patients randomized into basic-support (BS) and augmented-support (AS) groups. INTERVENTIONS: Patients in the BS group (n = 54) were given educational brochures on OSA and CPAP, CPAP education by nurses, CPAP acclimatization, and were reviewed by physicians and nurses at weeks 4 and 12. Patients in the AS group (n = 54) received more education, including a videotape, telephone support by nurses, and early review at weeks 1 and 2. MEASUREMENTS: Objective CPAP compliance, Calgary sleep apnea quality of life index (SAQLI), and cognitive function after 1 month and 3 months; and Epworth sleepiness scale (ESS) after 3 months of CPAP treatment. RESULTS: At 4 weeks, CPAP usage was 5.3 +/- 0.2 h/night (mean +/- SEM) vs 5.5 +/- 0.2 h/night in the BS and AS groups, respectively (p = 0.4). At 12 weeks, CPAP usage was 5.3 +/- 0.3 h/night vs 5.3 +/- 0.2 h/night in the two groups, respectively (p = 0.98). There was greater improvement of SAQLI at 4 weeks (p = 0.008) and at 12 weeks (p = 0.047) in the AS group. There was no significant difference between BS and AS groups in terms of improvement of ESS and cognitive function. CONCLUSION: Augmentation of CPAP education and support does not increase CPAP compliance, but leads to a greater improvement of quality of life during the reinforced period.

Adult↗

Obstructive sleep apnoea syndrome: treatment update.

Obstructive sleep apnoea syndrome is a common but underrecognised disorder with associated substantial morbidity and mortality. Excessive daytime sleepiness caused by the disorder leads to poor work performance and increases the risk of an individual having an automobile accident. The main objective of treatment for sleep apnoea is the relief of disabling daytime sleepiness and the improvement of quality of life. Conservative measures such as weight reduction and the avoidance of alcohol should be initiated when appropriate. Nasal continuous positive airway pressure devices have remained the standard treatment since it was first introduced in 1981. Oral appliances provide an alternative treatment choice in mild-to-moderate cases, whereas surgery is useful in selected cases.

Humans↗

EMG responses in humans during painful heterosegmentary stimulation.

The amplitude-temporal parameters of the nociceptive flexor reflex evoked in the upper and lower extremities by painful heterosegmentary electrical stimulation were studied in healthy volunteers. This reflex was detected bilaterally in the muscles of the upper and lower extremities independently of the site of painful stimulation. The maximum amplitude of the reflex was observed in the case, when the segmentary muscle innervation and the application site of painful stimulation coincided. The least latency of the nociceptive flexor reflex was observed after painful stimulation of the ear lobe. It was concluded that nociceptive flexor reflex is not an elementary polysynaptic spinal reaction, but involves also some supraspinal centers.

Adult↗

HIV-1 rebound during interruption of highly active antiretroviral therapy has no deleterious effect on reinitiated treatment. Comet Study Group.

BACKGROUND: Potent antiretroviral therapy (ART) with a protease inhibitor-based regimen is commonly used to treat HIV-1-infected patients. Transient treatment interruptions because of drug intolerance or other reasons are not uncommon. HIV-1 dynamics during therapy interruption and its consequences for the subsequent reinitiation of therapy have not been properly studied. METHODS: Ten antiretroviral-naive, HIV-1-infected subjects (mean baseline CD4 cell count of 414 cells/mm3 and plasma viral load of 4.8 log10 copies/ml) were treated with the triple drug ART regimen indinavir/zidovudine/lamivudine for 28 days. Therapy was then interrupted for 28 days, after which the same ART regimen was re-started. RESULTS: HIV-1 in plasma declined during the first 7 days of therapy with T1/2 of 1.5 days, and during days 7-28 with T1/2 of 8.9 days. Once therapy was interrupted, a delay of 4-7 days was observed in all subjects, preceding a rapid viral rebound with a mean doubling time of 1.6 days. Mean viral load after 28 days of interruption was 96% of baseline. Upon reinitiation of the same ART regimen, viral load declined at rates similar to those observed during the initial therapy (T1/2 of 1.6 and 8.0 days, respectively). No resistance-conferring mutations were observed in the HIV-1 reverse transcriptase (RT) and protease regions after the interruption of therapy. Plasma viral loads were maintained below 200 copies/ml in subjects continuing therapy for 4 (n = 9) to 12 (n = 5) months, with a mean CD4 cell count increase of 145 cells/mm3. CONCLUSIONS: The reintroduction of efficient ART therapy after a 1 month interruption shows viral kinetics similar to that of naive patients, and is not associated with the development of resistance. No deleterious effect on the reinitiated therapy was observed in patients who temporarily discontinued ART therapy. Nevertheless, because viral load rebounds back to baseline during treatment interruption, viral suppression is in effect put off by that period of time.

Anti-HIV Agents↗