Biomedical subjects
Publications and source records attributed to L W Lee.
Results of Monte Carlo simulations of XY and Heisenberg spin glass models in three dimensions are presented. A finite-size scaling analysis of the correlation length of the spins and chiralities of both models shows that there is a single, finite-temperature transition at which both spins and chiralities order.
We demonstrate the use of an algorithm called the Flat Histogram sampling algorithm for the simulation of two-dimensional lattice polymer systems. Thermodynamic properties, such as the average energy or entropy and other physical quantities such as the end-to-end distance or radius of gyration can be easily calculated using this method. The ground-state energy can also be determined. We also explore the accuracy and limitations of this method.
PURPOSE: To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. RESULTS: Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg/m(2) for MC versus 480 mg/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. CONCLUSION: Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.
OBJECTIVES: To test the hypothesis that reduced hip extension range during walking, representing a limiting impairment of hip tightness, is a consistent dynamic finding that (1) occurs with increased age and (2) is exaggerated in elderly people who fall. DESIGN: Using a 3-dimensional optoelectronic motion analysis system, we compared full sagittal plane kinematic (lower extremity joint motion, pelvic motion) data during walking between elderly and young adults and between elderly fallers and nonfallers. Comparisons were also performed between comfortable and fast walking speeds within each elderly group. SETTING: A gait laboratory. PARTICIPANTS: Twenty-three healthy elderly subjects, 16 elderly fallers (otherwise healthy elderly subjects with a history of recurrent falls), and 30 healthy young adult subjects. MAIN OUTCOME MEASURES: All major peak joint angle and pelvic position values. RESULTS: Peak hip extension was the only leg joint parameter measured during walking that was both significantly lower in elderly nonfallers and fallers than in young adult subjects and was even lower in elderly fallers compared with nonfallers (all p <.05). Peak hip extension +/- standard deviation during comfortable walking speed averaged 20.4 degrees +/- 4.0 degrees for young adults, 14.3 degrees +/- 4.4 degrees for elderly nonfallers, and 11.1 degrees +/- 4.8 degrees for elderly fallers. Peak hip extension did not significantly improve when elderly subjects walked fast. CONCLUSION: An isolated and consistent reduction in hip extension during walking in the elderly, which is exaggerated in fallers, implies the presence of functionally significant hip tightness, which may limit walking performance. Overcoming hip tightness with specific stretching exercises is worthy of investigation as a simple intervention to improve walking performance and to prevent falls in the elderly.
In this study, Gram-positive Staphylococcus aureus lipoteichoic acid (LTA) dose dependently (0.1-1.0 microg/mL) and time dependently (10-60 min) inhibited platelet aggregation in human platelets stimulated by agonists (i.e., thrombin and collagen). LTA also dose dependently inhibited intracellular Ca(2+) mobilization in human platelets stimulated by collagen. In addition, LTA (0.5 and 1.0 microg/mL) dose dependently increased the formation of cyclic AMP but not cyclic GMP in platelets. LTA (0.5 and 1.0 microg/mL) did not significantly increase the production of nitrate within a 10-min incubation period. Rapid phosphorylation of a platelet protein of M(r) 47,000, a marker of protein kinase C activation, was triggered by PDBu (0.03 microM). This phosphorylation was dose dependently inhibited by LTA (0.5 and 1.0 microg/mL) within a 10-min incubation period. Furthermore, LTA (0.5 and 1.0 microg/mL) also inhibited platelet aggregation induced by PDBu (0.03 microM) in human platelets. These results indicate that the antiplatelet activity of LTA may be involved in the increase of cyclic AMP, leading to inhibition of intracellular Ca(2+) mobilization and protein kinase C activity. Therefore, LTA-mediated alteration of platelet function may contribute to bleeding diathesis in septicemic and endotoxemic patients.
OBJECTIVES: To determine if joint kinetic gait alterations in fallers persist when they attempt to walk at a faster speed that is more comparable with nonfallers' comfortable walking speed. DESIGN: Retrospective, case-control study. Stereophotogrammetric and force platform data were collected. SETTING: A gait laboratory. PARTICIPANTS: Sixteen elderly subjects who had at least 2 falls in the last 6 months from an unclear cause and 23 elderly subjects with no history of repeated falls. MAIN OUTCOME MEASURES: Differences in all major peak joint kinetic (moment and power) values during the gait cycle between elderly nonfallers walking at comfortable speed and elderly fallers walking at (1) comfortable and (2) fast speed. RESULTS: Statistically significant differences present at both comfortable and fast walking speeds were present in 4 sagittal plane parameters. There was an increase in peak external hip flexion moment in stance, a reduction in peak hip extension moment, a reduction in knee flexion moment in preswing, and a reduction in knee power absorption in preswing. CONCLUSION: The presence and persistence of 4 specific alterations in sagittal plane joint kinetics at both comfortable and fast walking speeds imply specific intrinsic pattern differences and allow for new insights into the mechanics of gait in elderly people who fall. The presence of these alterations also suggests they may serve as potential identifiable markers to detect those who may be at risk for falls.
Several endocrine changes have been reported in patients with tetraplegia after spinal cord injury (SCI). These changes should be considered when prescribing medications that influence the endocrine pathways. Megestrol acetate has gained acceptance as a way to promote weight gain in cachectic patients without significant adverse effects. We present a case of a 51-year-old man with C5-C6 tetraparesis who was only 67% of his ideal body weight and was placed on megestrol acetate 5 months before admission for a urologic procedure. Postoperatively, the patient had severe hypotension and tachycardia that was interpreted as a septic or cardiac event. Further workup revealed subnormal levels of 8AM cortisol. An adrenocorticotrophic hormone stimulation test demonstrated results consistent with adrenal suppression. Hydrocortisone supplementation was started, and 6 months later cortisol levels were within normal limits. Cachexia, hypotension, and mild tachycardia are not uncommon in patients with SCI. When severe hypotension and tachycardia are seen in patients with tetraplegia, the diagnosis of adrenal insufficiency should be considered.
In this study, specific platelet activating factor (PAF) receptor antagonist ginkgolide B (BN52021) was tested for its antiplatelet activity in zymosan activated polymorphonuclear neutrophil-induced platelet aggregation. Triflavin was also tested for its antiplatelet activity compared with PAF receptor antagonist. Triflavin, an Arg-Gly-Asp-containing disintegrin purified from venom peptide inhibited platelet aggregation by interfering with the interaction of fibrinogen with the glycoprotein IIb/IIIa complex. Furthermore, we also report an efficient high resolution method for quantitative analysis of PAF using high-performance capillary electrophoresis (HPCE). The supernatant of polymorphonuclear neutrophils after their activation by opsonized zymosan induces the aggregation of washed rabbit platelets. In rabbit platelets, BN52021 (100-1000 microM) only partially inhibited activated polymorphonuclear neutrophil-induced platelet aggregation, and its maximal inhibition was estimated to be about 79%. Triflavin also partially inhibited platelet aggregation about 82% induced by activated polymorphonuclear neutrophils. Furthermore, after treatment with a combination of triflavin (0.26 microM) with various concentrations of BN52021 (4-1000 microM), the inhibitory effect of platelet aggregation was almost completely. This inhibition was greater than that produced by the individual drugs alone. These results indicate that a combination of glycoprotein IIb/IIIa complex and PAF receptor antagonist could completely inhibit activated polymorphonuclear neutrophil-induced platelet aggregation. In addition, the amount of PAF released from zymosan (6 mg/ml)-activated polymorphonuclear neutrophils was accurately calculated about 11.8+/-1.5 ng/10(6) cells, and did not further increase even at a high concentration of zymosan (10 mg/ml). These results suggest that PAF play a major role in the interaction between platelets and polymorphonuclear neutrophils. This interaction may be important in the pathogenesis of thrombosis and inflammatory diseases. Our present findings support the hypothesis that combination therapy with glycoprotein IIb/IIIa complex antagonists and PAF receptor antagonists may represent a new approach to the treatment of ischemic disorders.
In this study, Escherichia coli LPS dose-dependently (100-500 microg/ml) and time-dependently (10-60 min) inhibited platelet aggregation in human and rabbit platelets stimulated by agonists. LPS also dose-dependently inhibited the intracellular Ca2+ mobilization in human platelets stimulated by collagen. In addition, LPS (200 and 500 microg/ml) significantly increased the formation of cyclic GMP but not cyclic AMP in platelets. LPS (200 microg/ml) significantly increased the production of nitrate within a 10-min incubation period. Furthermore, LPS also dose-dependently inhibited platelet aggregation induced by PDBu (30 nmol/l), a protein kinase C activator. These results indicate that the antiplatelet activity of E. coli LPS may be involved in the activation of a nitric oxide/cyclic GMP pathway in platelets, resulting in inhibition of platelet aggregation. Therefore, LPS-mediated alteration of platelet function may contribute to bleeding diathesis in septicemic and endotoxemic patients.
PURPOSE: To determine the efficacy and safety profile, including the risk for cardiac toxicity, of liposome-encapsulated doxorubicin (TLC D-99), fluorouracil (5-FU), and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-one women were registered in this phase II study. All patients had measurable disease and no previous chemotherapy for MBC. Treatment consisted of TLC D-99 60 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 and 5-FU 500 mg/m2 on days 1 and 8 every 3 weeks. Serial cardiac monitoring, including endomyocardial biopsies, was performed. RESULTS: The overall response rate was 73% (95% confidence interval, 57% to 86%). The median duration of response was 11.2 months, the median time to treatment failure was 8.1 months, and the median overall survival duration was 19.4 months. The median number of cycles per patient was 10. The median cumulative dose of TLC D-99 was 528 mg/m2. Ten patients required hospitalization for febrile neutropenia. Nausea/vomiting, stomatitis, and fatigue higher than grade 2 occurred in 12%, 15%, and 41% of patients, respectively. Twenty-one patients reached a cumulative doxorubicin dose greater than 500 mg/m2. Three patients (7%) were withdrawn from the study due to protocol-defined cardiac toxicity, two because of a decrease in left ventricular ejection fraction to < or = 40%, and one because her endomyocardial biopsy result was grade 1.5. One patient had congestive heart failure that was probably nonanthracycline related. CONCLUSION: This chemotherapy regimen, including TLC D-99, was highly active against MBC and associated with low cardiac toxicity despite high cumulative doses of doxorubicin.
Magnetic resonance cholangiopancreatography (MRCP) is an emerging imaging technique for direct visualization of biliary and pancreatic ducts without the need for an invasive procedure, ionizing radiation, or iodine contrast media administration. The purpose of this study was to evaluate the efficacy of non-breath-hold MRCP in depicting normal and diseased biliary and pancreatic ducts. A retrospective analysis of 162 patients who underwent MRCP was performed, and a comparison between MRCP and direct cholangiography was made. The overall accuracy of MRCP in diagnosing malignant and benign pancreaticobiliary diseases was also calculated. MRCP depicted more than three hepatic segments in 99% of patients with dilated intrahepatic ducts and in 63% of patients with nondilated intrahepatic ducts. MRCP demonstrated the main hepatic duct, gallbladder, and cystic duct in 100%, 89%, and 72% of patients, respectively. The dilated extrahepatic duct, nondilated extrahepatic duct, dilated pancreatic duct, and nondilated pancreatic duct were visualized in 100%, 98%, 95%, and 77% of patients, respectively. The accuracy of MRCP in diagnosing hepatolithiasis, cholecystolithiasis, and choledocholithiasis was 96%, 97%, and 96%, respectively. The obstruction levels and characteristics determined by MRCP were in agreement with those determined from direct cholangiography in 98% of malignant obstructions and 89% of benign obstructions. The overall accuracy of a combination of MRCP and conventional magnetic resonance imaging in diagnosing pancreaticobiliary diseases was 81% for malignant diseases, 86% for benign diseases, and 82% for stone diseases. We conclude that non-breath-hold MRCP can reliably depict normal and diseased pancreaticobiliary ducts except for cystic ducts and nondilated pancreatic ducts.
Mitochondria of rapidly developing mungbean seedlings were fractionated into four populations: two density classes, each from a 1500S and a 150S pellet. Each of the four populations exhibited cytochrome c oxidase (COX) activity and contained mitochondrial DNA and cardiolipin; plastid and glyoxysome content were found to be relatively low. Five mitochondrial membrane proteins, COXII/III, ATPase alpha/beta and porin, and a matrix enzyme, manganese superoxide dismutase (MnSOD), were detected by immunoblots in all four populations. Another matrix enzyme, pyruvate dehydrogenase was detected only in the two respiratory-competent 1500S populations. The two 150S populations contained a previously unidentified organelle that lacked demonstrable respiratory capability. This organelle, which we have tentatively referred to as "slow-sedimenting (ss-) mitochondrion", was small in size (below light-optics resolution, 70-300nm, majority < or =200nm) and possessed a peculiar looking boundary membrane, ribosomes, and an occasional prominent electron-dense spot. Characteristically, ss-mitochondria were almost always in contact with a filament-aligned membrane-like structure of varying length. Cristae structure, while undetected in small ss-mitochondria, appeared in larger individuals. Typical mitochondria were found in the denser 1500S population, while the lighter 1500S population consisted of 300-800 nm mitochondria exhibiting a varying degree of size-dependent inner membrane folding. Using electron microscopy (EM) immunolocalization and serial sectioning, we have identified in situ organelles resembling in size and in fine structure the ss-mitochondria, which also exhibit a size-dependent folding of the inner membrane. These results suggest that small ss-mitochondria may undergo a progressive development in situ. Taken together, our findings demonstrate the existence of a pattern of structure-function-coordinated gross heterogeneity among mitochondria. This pattern of mitochondrial heterogeneity, characterized both in isolated mitochondria and in situ, implies that small ss-mitochondria may represent a type of "nascent mitochondria" derived from a yet unidentified mitochondria-propagation mode operating during rapid seedling growth. Mitochondrial division by binary fission, characterized by the appearance of dumbbell-shaped intermediates, was also detected.
In a well-designed instrument the noise level is reduced until it is dominated by the front end noise. In a hearing instrument this is the microphone noise. This paper examines the perception of noise in a hearing instrument by both normal-hearing and hearing-impaired listeners. The noise levels are specified as input-referred values in one-third octave bands. Two sets of measurements, the just-objectionable level (JOL) and the just-audible level (JAL), were assessed in third octave bands from 250 to 5000 Hz. The data indicated that the use of a subjectively described acceptability of noise, JOL, is an unreliable measure due to a very large variability across listeners. It is recommended that mean values for the noise threshold level, the JAL, be used as a guide in the optimization of microphone noise design.
In this report, we made use of sorbitol dehydrogenase (SDH)-deficient mutant mice (C57BL/LiA) to test whether there is a close correlation between the level of polyol accumulation and the degree of reduction in motor nerve conduction velocity (MNCV) associated with diabetes. The C57BL/LiA mouse has SDH deficiency due to a G-to-A mutation at the +1 position of intron 8, thus producing only aberrant SDH transcripts. These C57BL/LiA mice should have higher levels of polyol accumulation in the peripheral nerve because of the inability to further metabolize sorbitol to fructose. Here, we confirm by Western blot analysis and high-performance liquid chromatography that these mice lack SDH in the sciatic nerve and other various tissues, whereas normal mice possess SDH. These C57BL/LiA mice do not display any obvious phenotype that includes peripheral neuropathy in the normal laboratory environment and breed normally as described previously, although the tissues that normally contain SDH accumulate more sorbitol. This finding suggested that C57BL/LiA mouse strain is a valid model for studying the role in diabetic neuropathy of the polyol pathway, which consists of two enzymes-aldose reductase for converting glucose to sorbitol and SDH for converting sorbitol to fructose. Sorbitol levels in the sciatic nerve of diabetic C57BL/10N, nondiabetic, and diabetic C57BL/LiA mice were increased 4.3-, 16.6-, and 38.1-fold, respectively, above that of nondiabetic C57BL/10N. The fructose level in the sciatic nerve was increased 2.4-fold in diabetic C57BL/10N mice compared with that of nondiabetic and diabetic C57BL/LiA mice. Diabetic SDH-deficient mice showed an MNCV reduction similar in magnitude to that of diabetic C57BL/10N mice, despite greater nerve sorbitol accumulation and the lack of fructose in the former. The present data suggest that the levels of sorbitol and fructose in the sciatic nerve of mice do not correlate with the severity of MNCV deficit associated with diabetes.
Kingella denitrificans possess type-4 pili, and the type strain, ATCC 33394, contains at least four complete copies of type-4 pilin-encoding genes. Previously reported hybridization patterns of K. denitrificans chromosomal DNA seen using a Neisseria gonorrhoeae pilin gene region probe, had been interpreted as representing possible partial, silent gene loci. This now appears to be due to cross-reaction to multiple copies of 18-bp inverted repeat structures. Data are presented on a variety of colony variants which have changed from a spreading-corroding (SC) phenotype to a nonspreading-noncorroding (N) phenotype. Interestingly, while the SC to N transition is most often associated with loss of piliation in other bacteria containing type-4 pili, many of the K. denitrificans N variants still produce pilin, and some still produce pili.
In this study, naloxone was tested for its antiplatelet activity in human platelet suspensions. In platelet suspensions (4.5 x 10(8)/ml), naloxone (0.1-0.5 mM) significantly inhibited platelet aggregation and ATP-release stimulated by various agonists (i.e., thrombin, collagen, U46619, and ADP). Furthermore, naloxone (0.5 and 0.8 mM) dose-dependently inhibited the intracellular free Ca2+ rise of Fura 2-AM loaded platelets stimulated by collagen. Additionally, naloxone (0.5 and 1.0 mM) did not influence the binding of FITC-triflavin to platelet glycoprotein (GP) IIb/IIIa complex. On the other hand, naloxone (0.5 mM) markedly decreased the fluorescence of platelet membranes tagged with diphenylhexatriene (DPH). In addition, naloxone (0.1-0.5 mM) did not significantly affect cyclic-AMP levels in human washed platelets. It is concluded that the antiplatelet activity of naloxone may possibly be due to the induction of conformational changes in the platelet membrane and the inhibition of the intracellular Ca2+ ([Ca2+]i) mobilization as well as the release reaction of platelets stimulated by agonists.
The study aims to develop a Cantonese receptive vocabulary test to assess 2-6-year-old children in Hong Kong. The test consists of 100 test items. Each target item is accompanied by a phonological distractor, a semantic distractor and an unrelated distractor. A sample of 609 normal children from four Maternal and Child Health Centres and nine kindergartens was selected. The results show that there is a significant effect of age on the correct score. ANOVA was performed to look at the age effect on each distractor individually. It was found that the scores of the three distractors decrease in their own patterns as age increases. With strong content validity, strong construct validity and high correlation coefficients in the split-half reliability, this test could be used as a reliable measurement for the Cantonese-speaking population in Hong Kong.