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Biomedical subjects

S T Li

Publications and source records attributed to S T Li.

At least 37 records · Page 2Linked to original sources

Bovine type I collagen as an endovascular stent-graft material: biocompatibility study in rabbits.

PURPOSE: To study the biocompatibility of a bovine type I collagen preparation as a material for small-vessel stent-grafts in rabbits. MATERIALS AND METHODS: A composite nitinol-collagen endovascular stent-graft with a 4-mm inner diameter was deployed in the abdominal aorta in nine rabbits. Angiography was performed, and the rabbits were sacrificed at 1, 2, and 7 days and at 1 and 3 months. The portion of the aorta containing the stent-graft was excised and was histologically evaluated. RESULTS: All stent-grafts were patent at all time points. On days 1, 2, and 7 after implantation, scattered red and white blood cells adhered to the stent-graft. At 1 month, the stent-graft was endothelialized and was infiltrated with fibroblasts that deposited collagen within the interstices of the implanted collagen material. At 3 months, there was additional collagen deposition within the interstices of the stent-graft that did not narrow the lumen of the stent-grafts. CONCLUSION: Type I collagen as a intravascular stent-graft material is biocompatible for at least 3 months in rabbits. It is rapidly endothelialized and does not cause reactive stenosis. As a versatile and biocompatible polymer, collagen is potentially useful in the construction of endovascular stent-grafts for use in human arteries.

Alloys↗

Sympathetic innervation and function in reflex sympathetic dystrophy.

Patients with reflex sympathetic dystrophy have posttraumatic pain disproportionate to the injury and spreading beyond the distribution of any single peripheral nerve. We examined sympathetic neurocirculatory function and the role of sympathetic postganglionic nerve traffic in maintaining the pain in 30 patients with reflex sympathetic dystrophy. Most had had the condition for more than 1 year, and 14 had undergone sympathectomy for the pain. Positron emission tomographic scanning after administration of 13N-ammonia was used to assess local perfusion, and 6-[18F]fluorodopamine was used to assess sympathetic innervation. Rates of entry of norepinephrine in the regional venous drainage (spillovers) and regional plasma levels of L-dihydroxyphenylalanine (the immediate product of the rate-limiting enzymatic step in norepinephrine biosynthesis) and dihydroxyphenylglycol (the main neuronal metabolite of norepinephrine) were measured with and without intravenous trimethaphan for ganglion blockade. 13N-Ammonia-derived radioactivity was less on the affected side than on the unaffected side, whereas 6-[18F]fluorodopamine-derived radioactivity was symmetrical. Thus, perfusion-adjusted 6-[18F]fluorodopamine-derived radioactivity was higher on the affected side. Norepinephrine spillover and arteriovenous increments in plasma levels of L-dihydroxyphenylalanine and dihydroxyphenylglycol did not differ significantly between affected and unaffected limbs, although 4 patients had noticeably less norepinephrine spillover and smaller arteriovenous increments in plasma dihydroxyphenylglycol on the affected side. Trimethaphan decreased the pain in only 2 of 12 nonsympathectomized patients. The results indicate that patients with chronic unilateral reflex sympathetic dystrophy have decreased perfusion of the affected limb, symmetrical sympathetic innervation and norepinephrine synthesis, variably decreased release and turnover of norepinephrine in the affected limb, and failure of ganglion blockade to improve the pain in most cases. These findings suggest augmented vasoconstriction, intact sympathetic terminal innervation, possibly impaired sympathetic neurotransmission, and pain usually independent of sympathetic neurocirculatory outflows.

Adult↗

Modulation of long-term potentiation induction in the hippocampus by N-methyl-D-aspartate-mediated presynaptic inhibition.

We investigated mechanisms involved in the modulation of long-term potentiation by low concentrations of N-methyl-D-aspartate in the CA1 region of rat hippocampal slices. When applied for 5 min prior to and during tetanic stimulation, 1 microM N-methyl-D-aspartate inhibited long-term potentiation induction. Studies examining paired-pulse facilitation of non-N-methyl-D-aspartate receptor-mediated synaptic responses suggest that the effects of N-methyl-D-aspartate result in part from a presynaptic mechanism. This conclusion is supported by the observation that 1 microM N-methyl-D-aspartate failed to diminish N-methyl-D-aspartate receptor-mediated synaptic currents and that agents that enhance glutamate release, including high extracellular concentrations of calcium and an adenosine A1 receptor antagonist, overcome the long-term potentiation inhibition. Furthermore, the calcineurin inhibitors, FK-506 and cyclosporin A, as well as the phosphatase 1 and 2A inhibitor, okadaic acid, blocked the effects of N-methyl-D-aspartate on long-term potentiation suggesting a role for phosphatase activation in modulating the induction of long-term potentiation. These results show that the inhibition of long-term potentiation by untimely N-methyl-D-aspartate receptor activation is reversed by treatments that enhance glutamate release and suggest that adenosine release and diminished calcium influx during tetanic stimulation coupled with phosphatase activation contribute to the modulation of synaptic plasticity.

Adenosine↗

Facilitation of NMDAR-independent LTP and spatial learning in mutant mice lacking ryanodine receptor type 3.

To evaluate the role in synaptic plasticity of ryanodine receptor type 3 (RyR3), which is normally enriched in hippocampal area CA1, we generated RyR3-deficient mice. Mutant mice exhibited facilitated CA1 long-term potentiation (LTP) induced by short tetanus (100 Hz, 100 ms) stimulation. Unlike LTP in wild-type mice, this LTP was not blocked bythe NMDA receptor antagonist D-AP5 but was partially dependent on L-type voltage-dependent Ca2+ channels (VDCCs) and metabotropic glutamate receptors (mGluRs). Long-term depression (LTD) was not induced in RyR3-deficient mice. RyR3-deficient mice also exhibited improved spatial learning on a Morris water maze task. These results suggest that in wild-type mice, in contrast to the excitatory role of Ca2+ influx, RyR3-mediated intracellular Ca2+ ([Ca2+]i) release from endoplasmic reticulum (ER) may inhibit hippocampal LTP and spatial learning.

Animals↗

Evaluation of the efficacy of a hospital-based asthma education programme in patients of low socioeconomic status in Hong Kong.

BACKGROUND: Good asthma control requires optimal medical treatment in conjunction with appropriate self-management. In the West, the effectiveness of patient education on improving self-management has been well documented. However, data amongst Asian populations are lacking. We performed a pilot study to evaluate the efficacy of a hospital based education programme aimed at improving self-management skills and reducing morbidity in a Chinese population with low socioeconomic status and education level. METHODS: Our asthma education programme was a low-cost programme conducted in essence by specialist respiratory nurses. Patients attending our asthma clinic were instructed during a two-hour educational session on the pathophysiology of asthma, its potential triggers, the appropriate use of medications including proper inhaler techniques, and the self-management of their disease. These instructions were reinforced by video sessions at subsequent outpatient clinic attendance when patients' inhaler and peak flow techniques were checked by the same nurses and their self-management plan re-examined by the attending physicians. Asthma knowledge, inhaler technique, FEV1 and peak expiratory flow (PEF), and patients' self-rating of their asthma were determined at baseline, 6 months and 1 year after the intervention. Morbidity was assessed by the numbers of hospitalizations, unscheduled visits to family physicians and accident and emergency department attendance, courses of oral steroid used and days off work or school at baseline and 1 year. RESULTS: Two hundred and thirty patients were recruited for the study, 83% completing the entire assessment period. The group demonstrated significant improvements in lung function: the mean FEV1 +/- SD increased from 63.6 +/- 20.6% of predicted values at baseline to 68.5 +/- 22.3% at 6 months and 68.6 +/- 22.8% at 1 year (P < 0.05), and the mean PEF +/- SD increased from 64.6 +/- 23.0% of predicted values at baseline to 75.4 +/- 27.0% at 6 months and 76.8 +/- 24.5% at 1 year(P < 0.001). There were also significant improvements in inhaler technique (P < 0.01), asthma knowledge (P < 0.001), patients' self-rating of their asthma (P < 0.05), and reductions in the numbers of hospitalizations (P < 0.01), visits to family physicians (P < 0.001) and accident and emergency department attendance (P < 0.001) during the study period. Patients with moderate to severe asthma as defined by an FEV1 of < 80% of predicted values were most likely to benefit from the programme. CONCLUSIONS: We conclude that patient education is likely to be an essential component in the holistic approach to the management of asthma even amongst Asian populations of low socioeconomic status and education level. Further studies using randomised controlled trials are necessary to consolidate our findings.

Administration, Oral↗

A clinical study of collagen meniscus implants to restore the injured meniscus.

The meniscus performs critical functions within the knee, and its loss frequently leads to osteoarthritis and irreversible joint damage. Because prosthetic replacement of the meniscus has proven ineffective, the authors used tissue engineering techniques to develop a resorbable collagen scaffold (collagen meniscus implant) that supports ingrowth of new tissue and eventual regeneration of the lost meniscus. Eight patients underwent arthroscopic placement the collagen meniscus implant to reconstruct and restore the irreparably damaged medial meniscus of one knee. Seven patients had one or more prior meniscectomies, and one patient had an acute meniscus injury. Patients were observed with frequent clinical, serologic, radiographic, and magnetic resonance imaging examinations for at least 24 months (range, 24-32 months). All patients underwent relook arthroscopy and biopsy of the implant regenerated tissue at either 6 or 12 months after implantation. All patients improved clinically from preoperatively to 1 and 2 years postoperatively based on pain, Lysholm scores, Tegner activity scale, and self assessment. Relook arthroscopy revealed tissue regeneration in all patients with apparent preservation of the joint surfaces based on visual observations. Histologic analysis confirmed new fibrocartilage matrix formation. Radiographs confirmed no progression of degenerative joint disease. The collagen meniscus implant is implantable, biocompatible, resorbable, and supports new tissue regeneration as it is resorbed. This tissue seems to function similar to meniscus tissue by protecting the chondral surfaces.

Arthroscopy↗

Effects of theophylline, dexamethasone and salbutamol on cytokine gene expression in human peripheral blood CD4+ T-cells.

CD4+ T-cells are considered as pivotal in orchestrating the airway inflammation in asthma through the actions of their cytokines. Current hypothesis suggests that the anti-asthma effect of theophylline may be due to its anti-inflammatory actions, although the exact mechanisms remain unclear. The in vitro effect of theophylline on cytokine gene expression in peripheral blood CD4+ T-cells in normal subjects was compared with that of dexamethasone and salbutamol. CD4+ T-cells were cultured with phytohaemagglutin and phorbol myristate acetate in the presence of different concentrations of theophylline (10(-8)-10(-3) M or 0.0018-180 microg x mL(-1)) in one group of subjects (n=8), dexamethasone (10(-9)-10(-6) M or 0.39-390 ng x mL(-1)) in a second group (n=8) and salbutamol (10(-9)-10(-4) M or 0.00058-58 microg x mL(-1)) in a third group (n=8). Gene expression of interleukin (IL)-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN)-gamma was semiquantified by reverse transcription-polymerase chain reaction. Suppressed expression of IL-3 (36.9%), IL4 (38.8%), GM-CSF (24.6%) and IFN-gamma (37.7%), but not of IL-5, was only seen with theophylline at a concentration of 10(-3) M (180 microg x mL(-1)) (p<0.05) and not at lower concentrations. In contrast, dexamethasone caused a dose-dependent suppression of transcription of all cytokines, with 39.5% for IL-3, 84.4% for IL-4, 40.6% for IL-5, 50.9% for GM-CSF and 31.8% for IFN-gamma at 10(-6) M (390 ng x mL(-1)) (p<0.05-0.001). Salbutamol did not suppress gene expression of any of the cytokines at the concentrations examined. These data suggest that cytokine gene expression of CD4+ T-cells is not affected at therapeutic concentrations of theophylline and salbutamol, but its suppression is likely to be an important mechanism underlying the therapeutic effect of corticosteroids in asthma.

Adrenergic beta-Agonists↗

Regeneration of meniscal cartilage with use of a collagen scaffold. Analysis of preliminary data.

A collagen scaffold was designed for use as a template for the regeneration of meniscal cartilage and was tested in ten patients in an initial, Food and Drug Administration-approved, clinical feasibility trial. The goal of the study was to evaluate the implantability and safety of the scaffold as well as its ability to support tissue ingrowth. The study was based on the findings of in vitro and in vivo investigations in dogs that had demonstrated cellular ingrowth and tissue regeneration through the scaffold. Nine patients remained in the study for at least thirty-six months, and one patient voluntarily withdrew after three months for personal reasons. The collagen scaffold was found to be implantable and to be safe over the three-year period. Histologically, it supported regeneration of tissue in meniscal defects of various sizes. No adverse immunological reactions were noted on sequential serological testing. On second-look arthroscopy, performed either three or six months after implantation, gross and histological evaluation revealed newly formed tissue replacing the implant as it was resorbed. At thirty-six months, the nine patients reported a decrease in the symptoms. According to a scale that assigned 1 point for strenuous activity and 5 points for an inability to perform sports activity, the average score was 1.5 points before the injury, 3.0 points after the injury and before the operation, and 2.4 points at six months postoperatively, 2.2 points at twelve months, 2.0 points at twenty-four months, and 1.9 points at thirty-six months. According to a scale that assigned 0 points for no pain and 3 points for severe pain, the average pain score was 2.2 points preoperatively and 0.6 point thirty-six months postoperatively. One patient, who had had a repair of a bucket-handle tear of the medial meniscus and augmentation with the collagen scaffold, had retearing of the cartilage nineteen months after implantation. Another patient had debridement because of an irregular area of regeneration at the scaffold-meniscus interface twenty-one months after implantation. Magnetic resonance imaging scans demonstrated progressive maturation of the signal within the regenerated meniscus at three, six, twelve, and thirty-six months. These findings suggest that regeneration of meniscal cartilage through a collagen scaffold is possible. Additional studies are needed to determine long-term efficacy.

Adult↗

The value of Tc-99m MIBI SPECT during isosorbide dinitrate infusion in assessment of viable myocardium in patients with myocardial infarction.

Tc-99m MIBI myocardial SPECT has shown promise for evaluation of coronary artery disease. But its role in predicting myocardial viability is still under investigation. The purpose of this study was to evaluate the value of Tc-99m MIBI myocardial SPECT during isosorbide dinitrate (ISDN) infusion in the assessment of myocardial viability. Thirty-seven patients with previous myocardial infarction (the infarct age ranged from < or = 30 days to 900 days) were studied, of them 13 patients had Tc-99m MIBI studies before and after coronary artery bypass grafting (CABG). The results showed that out of 134 segments with hypoperfusion at resting SPECT, 56 segments (41.8%) had an increase in Tc-99m MIBI uptake during ISDN infusion. Among them, 17 segments (30.4%) were normalized, 6 segments (10.7%) were significantly improved and 33 segments (58.9%) were improved. The degree of improvement in perfusion was related to the age of the myocardial infarction. In 13 patients with CABG, of 31 segments with improvement in perfusion post CABG, 25 segments (80.6%) showed perfusion improvement during ISDN infusion, and of 28 segments with improved wall motion post CABG, 23 segments (82.1%) showed improvement in perfusion during ISDN infusion. Tc-99m MIBI SPECT during ISDN infusion may therefore be a useful approach for assessing myocardial viability.

Adult↗

[Synthesis of Achyranthes bidentata polysaccharide sulfate and its antivirus activity].

Sulfation of Achyranthes bidentata polysaccharide (Abps) with sulfuric acid or sulfur trioxide-pyridine or chlorosulfonic acid-pyridine was studied. A homogeneous sulfation method with good yield of 82.11% was obtained, using chlorosulfonic acid in an excess of pyridine. Sulfated Achyranthes bidentata polysaccharide was obtained as an amorphous sodium salt easily soluble in water. The UV and IR spectrum of Abps sulfate showed absorptions at 208, 268, 286 nm and 1232, 823.6 cm-1 respectively. The sulfur content of the products was found to be 20-22%. The degree of substitution varied from 2.8 to 3.2. It showed that the hydroxy group of Abps was almost completely esterified by chlorosulfonic acid. The Abps sulfate was shown to have high activity as anti-HBsAg and HBeAg. It is also effective on simple herpes virus type-I.

Antiviral Agents↗

[Effects of lidocaine on contraction of isolated rabbit aortic rings].

The mechanism of relaxing effects of lidocaine (Lid) on the contraction of isolated rabbit thoracic aortic rings was studied. Verapamil (Ver) was used for comparison. Lid and Ver showed obvious relaxing effect on contraction evoked by high K+ depolarization. In the study of contractions induced by noradrenaline (NA), both Lid and Ver were shown to suppress the component elicited by calcium release from the intra-cellular store, but not that induced by calcium influx. Lid shifted the dose-response curves for KCl and NA to the right nonparallelly and depressed their maximal responses. The inhibition to KCl was more potent than that to NA. This suggests that Lid has selective blocking effects on PDC channel, but not the ROC channel. Lid shifted the dose-response curve for CaCl2 to the right nonparallelly and depressed its maximal response. The results indicate that the calcium antagonistic property of Lid may be one of the mechanisms of its vascular smooth muscle relaxing effect.

Animals↗

Peripheral nerve repair with collagen conduits.

This paper describes the repair of peripheral nerves with a tubular conduit fabricated from collagen. The tubular collagen matrix was made semipermeable to permit nutrient exchange and accessibility of neurotrophic factors to the axonal growth zone during regeneration. In-vitro studies showed that the semipermeable collagen conduit allowed rapid diffusion of molecules the size of bovine serum albumin and was adequately cross-linked for controlled resorption in vivo. Studies on primates suggest that collagen conduits worked as effectively as nerve autografts in terms of physiological recovery of motor and sensory responses. The results of in-vitro and in-vivo studies of the collagen conduit represent a significant step towards our specific aim of developing suitable off-the-shelf prostheses for clinical repair of damaged peripheral nerves.

Animals↗

A new bioabsorbable intravascular stent: in vitro assessment of hemodynamic and morphometric characteristics.

Currently available intracoronary stents are permanent and their placement may be complicated by thrombosis and restenosis. We have developed a new bioresorbable stent constructed of type I collagen. This stent has a compliant tubular structure that is self expanding and carries a net negative surface charge to increase hemocompatibility. In vitro histologic and morphometric examination was performed by deploying the stent in six pressure fixed explanted porcine arteries. Morphometry revealed a close relationship between the stent external diameter 2.9 +/- 0.4 mm) and the arterial lumen diameter (3.0 +/- 0.4 mm). A relative reduction in arterial lumen diameter secondary to stent placement of 17% to 26% was observed. Folding of the stent wall was noted in those preparations where the stent external diameter was larger than the arterial lumen diameter. Polyvinyl chloride (PVC) tubing was used as a mock arterial segment for flow studies. Flow at baseline and following stent placement was determined at perfusion pressures of 10, 50, and 80 mmHg. A modest reduction in flow following stent placement of between 2% and 6% was observed. Thus, type I collagen may be used to construct a self expanding tubular stent. Morphometric and hemodynamic evaluation reveals a modest impact on arterial lumen dimensions and flow.

Absorption↗

A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates.

When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP amplitudes was not significantly different between the groups. In contrast, the SAP amplitude only recovered to the low normal range and there were no statistically significant differences between the two groups in terms of sensory recovery rates. The rodent and primate studies suggest that in terms of recovery of physiological responses from target muscle and sensory nerves, entubulation repair of peripheral nerves with a collagen-based nerve guide conduit over a short nerve gap (4 mm) is as effective as a standard nerve autograft.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗