Biomedical subjects
Publications and source records attributed to P T Cheng.
A series of N-(4-hydroxy-3-methylsulfonanilidoethanol)arylglycinamides were prepared and evaluated for their human beta3 adrenergic receptor agonist activity. SAR studies led to the identification of BMS-201620 (39), a potent beta3 full agonist (Ki = 93 nM, 93% activation). Based on its favorable safety profile, BMS-201620 was chosen for clinical evaluation.
OBJECTIVE: To identify what influence the various features of spinal deformity have on pulmonary function in persons with idiopathic and the postpoliomyelitic scoliosis. DESIGN: Prospective, cohort, observational study with clinical and radiologic evaluations. SETTING: Hospital-based rehabilitation units. PATIENTS: Forty-four patients with idiopathic scoliotis and 16 with postpoliomyelitic scoliotis. Each group was divided into subgroups: normal and abnormal pulmonary function. INTERVENTION: Clinical and radiologic evaluation of spinal deformity, full pulmonary functional test and respiratory muscle strength were performed. Presence of dyspnea on exertion and low back pain (LBP) was recorded. MAIN OUTCOME MEASURES: Pulmonary function: spirometry, lung volume test, and diffusing capacity. Respiratory muscle strength: maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). Presence of dyspnea on exertion (DOE), and LBP were also recorded. Characteristics of spinal deformity: direction of convexity, uppermost vertebra, number of involved vertebrae, Cobb angle, the apical vertebra, degree of rotation at the apical vertebra, type of scoliotic curve, and presence of balanced spine and pelvic obliquity. Chi-square analyses and Mann-Whitney U test for between-groups comparisons. Spearman's rho correlation coefficient to determine the existence and magnitude of a relationship. RESULTS: We found significant differences between the idiopathic and postpoliomyelitis groups in the degree of rotation at the apical vertebra, MIP, average percentage of predicted vital capacity, residual volume/total lung capacity, presence of double or triple curves, pelvic obliquity, and DOE. Between the idiopathic scoliotis subgroups we found significant differences in the uppermost vertebra and number of vertebrae in the scoliotic curve. Between the subgroups of the postpoliomyelitis group were significant differences in the location of the apical vertebra and the uppermost vertebral body of scoliotic curve. In the idiopathic group, pulmonary function was mostly related to scoliotic angle, number of vertebrae in the scoliotic curve, location of the uppermost vertebra, and the patients' age; MIP and MEP were negatively related to the scoliotic angle and degree of rotation of apical vertebra. In the postpoliomyelitis group, pulmonary function was mostly related to scoliotic angle, kyphotic angle, location of the uppermost vertebra of the scoliotic curve, and age. CONCLUSION: No single factor can predict the severity of impairment in scoliotic patients' pulmonary function. In both groups, severity of pulmonary impairment was related to the combined features of the spinal deformity. However, uppermost vertebra, scoliotic angle, and patient's age may play important roles influencing pulmonary function in both groups.
OBJECTIVE: To determine the role of symmetrical body-weight distribution training in preventing falls among patients with hemiplegic stroke. DESIGN: A prospective study using a standing biofeedback trainer. SETTING: Hospital-based rehabilitation units. PATIENTS: Fifty-four patients with hemiplegic stroke (30 in the training group, 24 in the control group). INTERVENTIONS: Conventional stroke rehabilitation program, plus symmetrical standing training and repetitive sit-to-stand training, with a standing biofeedback trainer. Training effect was evaluated by assessing the sit-to-stand performance and comparing the occurrence of falls in the 2 groups at a 6-month follow-up. MAIN OUTCOME MEASURES: Occurrence of falls, sit-to-stand performance, including body-weight distribution, rate of rise in force, and sway in center of pressure (COP). RESULTS: Significant improvement in sit-to-stand performance was found in patients in the training group. Body weight was distributed more symmetrically in both legs, with less mediolateral sway in the COP when rising and sitting down. The mean difference in body-weight distribution between the left and right legs while subjects were rising from a chair significantly decreased, from 49.5% +/- 18.9% to 38.6% +/- 15.8% of body weight (BW) (p < .005). The rate of rise in force while rising from a chair significantly increased, from 28.3% +/- 13.5%BW/s to 53.6% +/- 20.5%BW/s (p < .001). At the 6-month follow-up, 10 of 24 patients (41.7%) in the control group had fallen, compared with only 5 of 30 patients (16.7%) in the training group (p < .05). CONCLUSIONS: Symmetrical body-weight distribution training may improve sit-to-stand performance and, consequently, decrease the number of falls by stroke patients.
OBJECTIVE: To evaluate if resistive inspiratory muscle training (RIMT) can improve lung function in patients with complete tetraplegia within half a year after trauma. DESIGN: A prospective study. The experimental patients received training with a Diemolding Healthcare Division inspiratory muscle trainer for 15 to 20 minutes per session, twice per day, 7 days a week for 6 weeks. SETTING: Hospital-based rehabilitation units. PATIENTS: Twenty patients who were in their first 6 months of complete cervical cord injury were randomly enrolled into RIMT (10 patients) and control (10 patients) groups. MAIN OUTCOME MEASURE: Spirometry, lung volume test, maximal inspiratory pressure, maximal expiratory pressure, and modified Borg scale measurements at rest were performed before training and at the end of 6 weeks of training. RESULTS: Most of the pulmonary parameters showed statistically significant improvements within the RIMT and control groups, but the improvements were greater in the RIMT group. In addition, the improvements in total lung capacity, total lung capacity predicted percentage, vital capacity, minute ventilation, forced expiratory volume in 1 second predicted percentage, and the resting Borg scale in the RIMT group showed significantly greater improvement. CONCLUSION: RIMT can improve ventilatory function, respiratory endurance, and the perceived difficulty of breathing in patients with complete cervical spinal cord injury within half a year after trauma.
OBJECTIVE: To investigate the correlation between movement patterns, measured by polyelectromyography (PEMG), and clinical upper motor neuron (UMN) syndrome in stroke patients. DESIGN: PEMG patterns, recorded from pairs of flexor-extensor muscles during voluntary maneuvers, and motor outcomes were assessed approximately 1 month after stroke (early stage). Motor outcomes were reassessed 6 months later (late stage). PARTICIPANTS: Thirty-nine hemiplegic stroke patients and 18 healthy control subjects. MAIN OUTCOME MEASURES: Passive stretch reflexes (PSRs), Brunnstrom's stages, and walking ability. RESULTS: Six PEMG patterns, varying from complete reciprocal to complete synchrony, were identified. Higher PEMG pattern scores were associated with better Brunnstrom's stages (r > .80), walking ability (r > .39), and some PSRs (r < -.37). PEMG patterns could separate patterns 1 and 2 from patterns 3 and 4 for patients with early Brunnstrom's stages 1 and 2. Patterns 1 and 2 (reduced agonist electromyographic activities) indicated weakness and resulted in the worst motor outcomes. Patterns 3 and 4 (cocontraction and coactivation) indicated spasticity and associated synergistic movements. Patients with patterns of 5 and 6 (reciprocal electromyographic activities) had more selective motor control. CONCLUSIONS: PEMG patterns correlate with clinical UMN syndromes and may allow treatment strategy planning on the basis of underlying motor control, as well as the prediction of final motor outcomes soon after stroke, even in patients who cannot move their legs initially.
A prospective study with subjective evaluation of shoulder pain and objective evaluation of shoulder muscle strength by isokinetic testing and electromyographic and electroneurographic studies of spinal accessory nerve function was performed on patients who had undergone neck dissection procedures. Twenty-one patients with head and neck cancer were enrolled in this study. Three types of neck dissection were performed: 7 selective neck dissections, 9 modified radical neck dissections, and 5 radical neck dissections. All patients who underwent radical neck dissection had shoulder pain, and 80% of them had shoulder droop after the operation. In the patients who underwent selective neck dissection, the electromyographic findings of the spinal accessory nerve were relatively normal. Their shoulder strength was sometimes decreased at I month after operation, but it had returned to preoperative strength by the 6-month follow-up visit. These findings suggested that patients who underwent selective neck dissection had the least damage to spinal accessory nerve function and the least shoulder disability after neck dissection.
BACKGROUND: Decreased equilibrium in standing and walking is a common problem associated with hemiplegic stroke patients. Stroke patients with balance problems are prone to falls. In addition to spatial recognition, the appropriate pattern of muscle activity to preserve balance depends on sensory and motor processes. Previous reports have mentioned that the right posterior parietal cortex seems to be predominantly involved in spatial integration. We therefore wanted to conduct a study to quantify and compare the balance control between right hemispheric stroke and left hemispheric stroke patients. METHODS: Thirty hemiplegic stroke patients (14 right, 16 left) and 15 age-matched healthy subjects were included in this study. The objective measurement of the basic components of balance control was performed using the SMART Balance Master. The motor status of the hemiplegic limbs was evaluated by Brunnstrom staging. The functional outcome of the stroke patients was evaluated by the functional independence measure (FIM). RESULTS: The balance function of stroke patients was significantly worse as compared to that of the healthy subjects especially in dynamic stability. However, different from the other reports, our right hemispheric stroke patients had better balance function than our left hemispheric patients. The locomotion and mobility scores of the FIM were also better in the right hemispheric stroke patients. CONCLUSION: This result suggested that the motor function of the healthy limbs of stroke patients may play an important role in their balance function. The results of this study may provide a guide for prescribing a more efficient rehabilitation program for stroke patients.
OBJECTIVE: To use kinetic assessment of the sit-to-stand movement as a means of sorting out those stroke patients at risk for falling. DESIGN: A retrospective study, using a force platform to assess sit-to-stand performance and to determine its correlation with falls in stroke patients. SETTING: Hospital-based rehabilitation units. METHODS: Thirty-three stroke patients (18 fallers, 15 nonfallers) and 25 age-matched healthy subjects were included in this study. Subjects sat in an adjustable chair with their feet on two force plates and performed the standing up/sitting down movement at a self-paced, comfortable speed. RESULTS: The rate of rise in force (dF/dT) was significantly lower in stroke fallers than in stroke nonfallers and healthy subjects (23.78+/-17.38, 55.23+/-31.24, and 85.96+/-42.4 percent body weight per second, respectively [p < .005]). The center of pressure sway in mediolateral direction during rising/ sitting down was much greater in stroke fallers than in stroke nonfallers or healthy subjects (p < .05). Body weight distribution was asymmetric on the feet of stroke patients, with much more body weight on their sound side. CONCLUSIONS: The significantly lower rate of rise in force and greater postural sway while rising/sitting down may be useful in identifying stroke patients who are at risk for falling.
Eighty patients with spinal cord injury (SCI) and neurogenic bladder were studied. Among them, 28 (70%) cases in the control group and 32 (80%) cases in the electroacupuncture group achieved ultimately balanced voiding and were selected for further analysis. The acupuncture group received electroacupuncture at four acupoints: Chung Chi (Conception Vessel CV3), Kuan Yuan (CV4), and bilateral Tzu Liao (Urinary Bladder UB32), in addition to conventional intermittent catheterization program (ICP). Whereas the control group underwent conventional bladder training program with ICP only. The results revealed that the time of achieving balanced voiding was statistically significantly shorter with electroacupuncture than in the control group: 57.1 +/- 22.6 vs 85.2 +/- 27.4 days (P < 0.005) for upper motor neuron lesions, and 55.4 +/- 22.6 vs 83.4 +/- 26.1 days (P < 0.01) for lower motor neuron lesions. However, there was almost no difference between upper motor neuron lesions and lower motor neuron lesions. When acupuncture commenced was alos a factor to influence the results. Those who received acupuncture within 3 weeks after injury had significantly shortened the total days to achieve a balanced bladder, as compared to those who received acupuncture 3 weeks after injury (46.6 +/- 13.2 vs 65.8 +/- 15.4 days, P < 0.005). Our study implied that acupuncture might be beneficial in the management of neurogenic bladder of SCI, and the earlier the patient received electro-acupuncture therapy, the sooner the bladder balanced. On the other hand, we also found that complete spinal cord injury, either with pronounced detrusor-sphincter dyssynergia in upper motor neuron lesion or with persistent areflexic bladder in lower motor neuron-lesion, was not affected by acupuncture.
A series of novel aminodiol inhibitors of HIV protease based on the lead compound 1 with structural modifications at P1' were synthesized in order to reduce the cytotoxicity of 1. We have observed a high degree of correlation between the lipophilicity and cytotoxicity of this series of inhibitors. It was found that appropriate substitution at the para position of the P1' phenyl group of 1 resulted in the identification of equipotent (both against the enzyme and in cell culture) compounds (10l, 10m, 10n, and 15c) which possess significantly decreased cytotoxicity.
Administration of PTH(1-34) at low intermittent doses stimulates bone formation in vivo. However, the new bone is quickly resorbed after drug withdrawal. Following the concept of lose, restore, and maintain, we studied the possibility of maintaining the PTH(1-34)-mediated new bone by APD post-treatment and the effect of a second PTH(1-34)-APD cycle in osteopenic ovariectomized (OVX) adult rats. Eighty OVX rats (6-months-old, 3 months after OVX) and 10 sham-operated rats were divided into nine groups. One OVX group was killed as baseline (BL). Five OVX groups were injected with PTH(1-34) (20 micrograms/kg/day, subcutaneously) for 3 weeks (5 days/week). The remaining two OVX groups and the sham group (S) were injected with saline as controls. One PTH(1-34) group (A) and one control group (B) were then killed. Three PTH(1-34) groups were post-treated with APD injections (250 micrograms/kg/day, subcutaneously) for 5 days; the remaining PTH(1-34) group, the other control group, and group S were injected with saline; and all these groups were left untreated for 3 weeks. At the end, one PTH-APD group (C), the PTH-saline group (D), and the saline-saline group (E) were killed. Another PTH-APD cycle was applied to the remaining two PTH-APD groups, with group F killed after the second PTH treatment and group G killed after two complete cycles. We found a 90% increase in cancellous bone volume (Cn.BV/TV) and a 28% increase in trabecular thickness (Tr.Th) in group A over group B.(ABSTRACT TRUNCATED AT 250 WORDS)
Successful prevention of bone loss in ovariectomized rats with 17 beta-estradiol (E2) at 10 micrograms/kg/d has been reported. Here we show that E2 dose twice that much is not enough to maintain PTH(1-34) mediated bone gain. Three-month-old female Wistar rats were ovariectomized and fed with regular rodent chow and water ad libitum. Three months later they were divided into 9 groups (5-8 per group) and treated cyclically with PTH(1-34) (20 micrograms/kg/d sc, 5d/w for 3w) and E2 (20 micrograms/kg/d sc, 5d/w for 4w). There were also a baseline group and five vehicle control groups. Cancellous bone volume (Cn.BV/TV) of distal femoral metaphyses was measured by computer-aided histomorphometry on trichrome stained thin sections, and 24-hour fasted urine was analyzed for pyridinoline/creatinine (PYR/CREA) by immunoassay. Histomorphometric results showed that PTH(1-34) progressively increased Cn.BV/TV but E2 failed to maintain them. Urinary PYR/CREA results showed that E2-treated groups had lower values. We conclude that E2 dose > 20 micrograms/kg/d is required to maintain the PTH mediated bone gain.
BACKGROUND AND PURPOSE: This study was designed to investigate the correlation between reflex sympathetic dystrophy syndrome (RSDS) in hemiplegic patients and spontaneous electromyographic (EMG) activity, as well as to determine the predictive value of spontaneous EMG activity in early diagnosis of RSDS. METHODS: An EMG and nerve conduction velocity study of the weak upper limb was conducted on 70 hemiplegic patients at 3 to 4 weeks after cerebrovascular disease (either cerebral hemorrhage or infarction). Clinical assessment for development of the RSDS was done during the following 6 months. The correlation of RSDS development with the presence of spontaneous EMG activity and certain clinical parameters (including sex, age, side affected, cause of stroke, sensory impairment, spasticity, and shoulder subluxation) was analyzed statistically. RESULTS: Of the 46 patients who exhibited spontaneous activity, 30 (65%) developed clinical RSDS in their hemiplegic upper extremity, whereas only 1 (4%) of the other 24 patients with no spontaneous EMG activity developed clinical RSDS within 6 months after the onset of hemiplegia (P < .001). The correlation of RSDS development with the presence of shoulder subluxation and sensory impairment in the hemiplegic side was statistically significant. Neither age, sex, severity of spasticity, nor etiology of stroke had a significant correlation with the development of clinical RSDS. CONCLUSIONS: There is significant correlation between the presence of spontaneous EMG activity and the development of clinical RSDS in the hemiplegic upper extremity after stroke. It is concluded that spontaneous EMG activity in the hemiplegic hands of stroke patients might be a good predictor of the future development of clinical RSDS.
A series of HIV protease inhibitors containing a novel C2 symmetrical "aminodiol" core structure were prepared from amino acid starting materials. The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds. Optimization of the structure-activity in this series led to aminodiol 9a (Ki = 100 nM; ED50 (HIV-1) = 80 nM) containing P1/P1 benzyl and P2/P2 Boc substituents. Compound 9a is a selective inhibitor of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin. In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs. After i.v. and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40%) and a promising plasma elimination half-life (4 h).
To examine the factors and patient characteristics predisposing to formation of calcium oxalate monohydrate or calcium oxalate dihydrate kidney stones, we compared blood and 24-hour urine tests, gender distribution and patient age in 2 groups of patients with pure calcium oxalate monohydrate (422) and calcium oxalate dihydrate (68) stones treated at the lithotripsy unit of the Wellesley Hospital and University of Toronto during 4 years. The calcium oxalate monohydrate group included relatively more women (31% versus 16% in the calcium oxalate dihydrate group, chi-square 7.89, p = 0.005). Patients were older in the calcium oxalate monohydrate group (59 +/- 13 versus 51 +/- 13 years, p = 0.001). The calcium oxalate monohydrate group had lower urinary calcium (4.19 +/- 2.34 versus 7.19 +/- 3.38 mmol. per day, p < 0.0001), calcium oxalate relative saturation rate (6.9 +/- 3.9 versus 8.9 +/- 3.3, p = 0.001), brushite relative saturation rate (0.7 +/- 0.8 versus 1.2 +/- 0.9, p = 0.0001) and urinary pH (5.72 +/- 0.75 versus 5.93 +/- 0.72). When corrected for patient age and gender, the calcium oxalate dihydrate group still had higher urine calcium levels. Higher urine pH in the calcium oxalate dihydrate group was age-related. In summary, we present evidence that calcium oxalate dihydrate stones are relatively more common among younger male patients with higher urine calcium levels and higher urine pH.
We have reviewed 67 patients of electrical burns treated at Linkou Burn Center of Chang Gung Memorial Hospital from January 1988 to April 1992. There were 2086 acute burn admissions during this period with the proportion of electrical injuries being 3.2%. Their age ranged from 13 to 68 years, with 61% in the age group of 20 to 40 years. Sixty-two (92.5%) of our patients were males. Over 60% of these injuries were work-related. The proportion of high voltage electrical injuries was over 60% in our series. All deceased patients and those patients with major complications were in the high voltage electrical injuries group. Low voltage injuries did not leave any major sequelae. In a mean follow-up of 2 years, 83% of our patients could return to the previous job or change to another work. The overall mortality was 6%.
The concentration dependence of the fluoride ion spin-lattice relaxation rate has been observed by nuclear magnetic resonance experiments on samples of defatted and dried bone. The 19F spin-lattice relaxation rates increased linearly with the bone fluoride concentration. Different results were obtained from trabecular than from cortical bone. For the same macroscopic fluoride content per gram of bone calcium, the relaxation rate is significantly faster in cortical bone. Relaxation rates in cortical bone samples prepared from both rats and dogs were apparently controlled by the same species-independent processes. For samples from beagle dogs, the bulk fluoride concentrations measured by neutron activation analysis were 3.1 +/- 0.3 times greater in trabecular bone than in the corresponding cortical bone. The beagle spin-lattice relaxation data suggest that the microscopic fluoride concentrations in bone mineral were 1.8 +/- 0.4 times greater in trabecular bone than in cortical bone. It is concluded that the accumulation of fluoride impurities in bone mineral is non-uniform.
We conducted preliminary crystallographic investigations and biologic studies on 5 synthetically grown preparations of monosodium urate monohydrate (MSUM) crystals including one preparation of urate spherulites. The 5 crystal preparations exhibited wide variations in morphology, size, surface area, and ultrastructure, but only a few changes in their biologic effects. When injected intraarticularly, urate spherulites were less phlogistic than most acicular forms. Since crystal-cell interactions and inflammatory responses are influenced by crystal size, morphology, and surface characteristics, standardization of methods of preparing MSUM crystals is, therefore, important, particularly when analyzing and comparing results from different research laboratories.