Biomedical subjects
Publications and source records attributed to C Lee.
We report here a case of vulvar adhesion that was difficult to cure by estrogen only. We used amniotic membrane to be a barrier and after the operation, the symptoms of vulvar adhesion were resolved.
PURPOSE: Ascorbic acid was administered to patients with chronic hepatitis C to elucidate the mechanism of onset of retinopathy during interferon (IFN) therapy, and its prevention. METHODS: The subjects were 62 patients with chronic hepatitis C who had been admitted to our hospital. For the IFN therapy, 6 MIU of natural IFN-alpha, or 10 MIU of recombinant human IFN-alpha 2b was administered every day for the first 2 weeks, followed by administration three times a week for 22 weeks. The patients were randomly assigned to a group receiving 600 mg/day of ascorbic acid or a group not receiving ascorbic acid (control group). The optic fundi were examined by ophthalmologists before the IFN therapy began and subsequently at weeks 2 and 4 and then every 4 weeks during the IFN therapy. RESULTS: Retinopathy was found in 9 of the 31 patients (29%) in the ascorbic acid-treated group and in 11 of the 31 patients (35%) in the control group. The cumulative incidence of hemorrhage in the ascorbic acid-treated group was lower than that in the control group during the IFN therapy, but the difference between the two groups was not significant (P = 0.186). The cumulative incidence of cotton-wool spots in the ascorbic acid-treated group was almost same as that in the control group during the IFN therapy. The median platelet counts before the therapy was begun were 11.8 x 10(4)/mm2 in the group with hemorrhage and 16.6 x 10(4)/mm2 in the group without, and the lowest platelet counts during IFN therapy were 7.3 x 10(4)/mm3 in the group with hemorrhage and 9.5 x 10(4)/mm3 in the group without, indicating significantly lower values in the group with hemorrhage (P = 0.018 and P = 0.020, respectively). The lowest platelet counts during IFN therapy were 7.4 x 10(4)/mm3 in the group with cotton-wool spots and 9.7 x 10(4)/mm3 in the group without, indicating a significantly lower value in the group with cotton-wool spots (P = 0.036). CONCLUSIONS: Ascorbic acid was not considered to be useful for the prevention of the retinopathy associated with IFN therapy in patients with chronic hepatitis C.
BACKGROUND: The use of neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer. METHODS: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy (EBRT; median, 4500 cGy) with 5-flourouracil-based chemotherapy. Tumors were defined as potentially resectable (PR, n = 53) in the absence of arterial involvement and venous occlusion and locally advanced (LA, n = 58) with arterial involvement or venous occlusion by CT. RESULTS: Five patients (4.5%) were not restaged due to death (n = 3) or intolerance of therapy (n = 2). Twenty-one patients (19%) manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors (53%) and 11 patients with initially LA tumors (19%) were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months. CONCLUSIONS: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant (postoperative) CRT.
BACKGROUND: Up to 30% of patients with locally advanced rectal cancer have a complete clinical or pathologic response to neoadjuvant chemoradiation. This study analyzes complete clinical and pathologic responders among a large group of rectal cancer patients treated with neoadjuvant chemoradiation. METHODS: From 1987 to 2000, 141 consecutive patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative 5-fluorouracil-based chemotherapy and radiation. Clinical restaging after treatment consisted of proctoscopic examination and often computed tomography scan. One hundred forty patients then underwent operative resection, with results tracked in a database. Standard statistical methods were used to examine the outcomes of those patients with complete clinical or pathologic responses. RESULTS: No demographic differences were detected between either clinical complete and clinical partial responders or pathologic complete and pathologic partial responders. The positive predictive value of clinical restaging was 60%, and accuracy was 82%. By use of the Kaplan-Meier life table analysis, clinical complete responders had no advantage in local recurrence, disease-free survival, or overall survival rates when compared with clinical partial responders. Pathologic complete responders also had no recurrence or survival advantage when compared with pathologic partial responders. Of the 34 pathologic T0 tumors, 4 (13%) had lymph node metastases. CONCLUSIONS: Clinical assessment of complete response to neoadjuvant chemoradiation is unreliable. Micrometastatic disease persists in a proportion of patients despite pathologic complete response. Observation or local excision for patients thought to be complete responders should be undertaken with caution.
BACKGROUND: There is concern that a hypercoagulable status is caused after coronary artery bypass grafting without cardiopulmonary bypass (off-pump coronary artery bypass grafting, or OPCAB) and may potentially endanger the patency of the anastomosis. The aims of this study were: (1) to compare 1-year graft patency after OPCAB with that of conventional coronary artery bypass grafting (CABG) and that of on-pump beating CABG; and (2) to demonstrate any differences in patency of various conduits among the three groups. METHODS: We analyzed the results of 122 consecutive OPCAB cases (group 1) compared with those of 65 consecutive conventional CABG cases (group II) and those of 19 consecutive on-pump beating CABG cases (group III). In group I, coronary angiography (CAG) was performed immediately postoperatively and 1 year after surgery. In groups II and III, CAG was performed 1 year after surgery. Graft patency was graded as grade A (excellent), grade B (fair), or grade O (occluded). RESULTS: The average number of distal anastomoses in groups I, II, and III were 3.1 +/- 1.1, 3.7 +/- 0.9, and 3.6 +/- 0.9, respectively. In group I, postoperative CAG was performed in 92% of patients (112/122) before discharge. The patency rate (grade A + B) was 96.4% (162/168) for arterial grafts, and 85.6% (160/187) for saphenous vein grafts (SVG). One-year follow-up CAG was performed in 74% of patients (90/122). The patency rate was 97.8% (132/135) for arterial grafts and 67.9% (106/156) for SVG. In group II, 1-year follow-up CAG was performed in 65% of patients (42/65). The patency rate (grade A + B) was 93.5% (43/46) for arterial grafts and 88.3% (98/111) for SVG. In group III, 1-year follow-up CAG was performed in 89% of patients (17/19). The patency rate (grade A + B) was 100% (19/19) for arterial grafts and 86.8% (33/38) for SVG. CONCLUSIONS: Our results demonstrate that the patency rate ot SVG after OPCAB was significantly lower than that of arterial grafts in the early postoperative CAG (p < 0.001), and was also significantly lower than those of SVG of group II (p < 0.001) and group III (p < 0.01) in the postoperative 1-year CAG, although there was no significant difference in 1-year patency of arterial grafts among the three groups. Our data suggest that a specific perioperative anticoagulant therapy may be advisable in patients undergoing OPCAB with SVG.
The phonological codes activated in visual word recognition can be thought of minimally as strings of discrete and unstructured phoneme-like units. We asked whether these codes might additionally express a letter string's phonological form at a featural or gestural level. Specifically, we asked whether the priming of a word (e.g. sea, film, basic) by a rhyming non-word would depend on the non-word's phonemic-feature similarity to the word. The question was asked within a mask--prime--target--mask sequence with both brief (57 ms in Experiments 1 and 2) and long (486 ms in Experiment 1) prime durations. Non-word primes that differed from their targets by a single phonemic feature (initial voicing as in ZEA, VILM, PASIC) led to faster target lexical decisions than non-word primes that differed by more than a single phonemic feature (e.g. VEA, JILM, SASIC). Visual word recognition seems to involve a sub-phonemic level of processing.
It is widely assumed that combining the eye movement vector with the motion vector of the retinal image is both sufficient and necessary for recovering the direction and speed of visual motion. Here, we report that execution of a saccadic (rapid) eye movement in the dark systematically biased subsequent perceptual judgment of the direction of visual motion in the direction opposite to the saccade. This non-veridical motion perception reached a maximum immediately after saccade offset and then decayed in approximately equal to 100 ms. These results suggest that the oculomotor signal interacts with central mechanisms related to motion and possibly form perception, as well as spatial vision, as documented with mislocalization of visual objects at the time of saccades.
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Successful management of pediatric cardiac emergencies requires an accurate diagnosis to institute an appropriate plan of therapy. The diagnosis, however, is not always straightforward, as evidenced by the nonspecific clinical picture that can be presented by congenital heart defects. Entertaining the possibility of a cardiac problem in neonates with pulmonary symptoms unresponsive to standard therapies is crucial for successful management of patients with congenital heart disease. In addition to ventilatory support, prostaglandin E1 infusions or emergency interventional cardiac catheterization is often a life-saving initial measure in patients with acutely decompensated congenital cardiac lesions that require a patent ductus arteriosus for survival. Pericardial tamponade is associated with various acquired and iatrogenic causes. Emergent pericardiocentesis is mandatory when cardiovascular compromise occurs. The goal of anesthetic management is to maintain cardiac output. With the increasing use of central venous catheters in neonatal ICUs and the high mortality rate for central venous catheter-related cardiac tamponade, the diagnosis must be considered in any patient with a central venous catheter in situ who acutely develops unexplained hypotension, bradycardia, and diminished pulses. Arrhythmias also can cause hemodynamic instability in infants and children. Supraventricular tachycardia is by far the most common emergently presenting arrhythmia in the pediatric population. Unstable patients require immediate intravenous adenosine or synchronized cardioversion. Complete heart block is rare, but it can lead to congestive heart failure and occasionally to cardiovascular collapse and sudden death. Emergency treatment of complete heart block includes pharmacologic support and temporary or permanent pacemaker placement as indicated. In infants, congestive heart failure usually is related to congenital heart disease, whereas in older children, it tends to be secondary to an acquired cause. Supportive measures, fluid restriction, and inotropic support are the principles of initial treatment. Prompt recognition and initiation of appropriate therapy in pediatric cardiac emergencies are essential for favorable outcomes.
BACKGROUND: The Veterans Administration (VA) identified patient safety as a high-priority issue in 1997 and implemented the Patient Safety Improvement (PSI) initiative throughout its entire health care system. In spring 1998 the External Panel on Patient Safety System Design recommended alternative methods to enhance reporting and thereby improve patient safety. REDESIGNING THE PSI INITIATIVE: The VA began redesigning the PSI initiative in late 1998. The dedicated National Center for Patient Safety (NCPS) was established. Using the panel's recommendations as a jumping-off point, NCPS began to identify known and suspected obstacles to implementation (such as possible punitive consequences and additional workload). NCPS adopted a prioritization scoring method, the Safety Assessment Code (SAC) Matrix, for close calls and adverse events, which requires assessing the event's actual or potential severity and the probability of occurrence. The SAC Matrix specifies actions that must be taken for given scores. Use of the SAC score permits a consistent handling of reports throughout the VA system and a rational selection of cases to be considered. A system for performing a root cause analysis (RCA) was developed to guide caregivers at the frontline. This system includes a computer-aided tool, a flipbook containing a series of six questions, and reporting of the findings back to the reporter. The final step requires that the facility's chief executive officer "concur" or "nonconcur" on each recommended corrective action. The RCA team outlines how the effectiveness of the corrective action will be evaluated to verify that the action has had the intended effect, and it ascertains that there were no unintended negative consequences. IMPLEMENTATION: Based on successful implementation in two pilots, full-scale national rollout to the 173 facilities began in April 2000 and was concluded by the end of August 2000. NCPS supplied 3 days of training for individuals at each facility. The training included didactic components, an introduction to human factors engineering concepts, and small- and large-group simulation exercises. Facility leaders were reminded of the necessity to reinforce the point that assignment to an RCA team was considered an important duty. DISCUSSION: It is essential to design and implement a system that takes into account the concerns of the frontline personnel and is aimed at being a tool for learning and not accountability. The system must have as its primary focus the dissemination of positive actions that reduce or eliminate vulnerabilities that have been identified, not a counting exercise of the number of reports.
BACKGROUND: Melanocortin, through its distinct receptor subtypes, has many different effects. Receptor-selective ligands are required to reduce the undesirable effects of melanocortin. To investigate which conformation is preferable to a given melanocortin receptor subtype, a structural and functional analysis of the ligand-receptor interactions was made by studying the biological activity, the nuclear magnetic resonance structures, and the patterns of the ligand-receptor interaction for each receptor subtype by homology modeling analysis. RESULTS: Among the several analogues examined, [Gln(6)]alpha-melanocyte-stimulating hormone (MSH)-ND was found to have 10000 times less biological activity than alpha-MSH-ND for the MC1R, whereas, the potencies of both oligopeptides were comparable in both the melanocortin-3 receptor (MC3R) and MC4R. [Gln(6)]alpha-MSH-ND exhibited a type I' beta-turn that was similar to the type I beta-turn structure of alpha-MSH-ND. However, a remarkable structural difference was observed with respect to the side chain orientations of the sixth and seventh residues of [Gln(6)]alpha-MSH-ND, which were found to be mirror images of alpha-MSH-ND. By homology modeling analysis, the His(6) of alpha-MSH-ND was found to interact with the TM2 regions of all three receptors (Glu(94) of MC1R, Glu(94) of MC3R, and Glu(100) of MC4R), but [Gln(6)]alpha-MSH-ND did not. The phenyl ring of the D-Phe(7) residue of [Gln(6)]alpha-MSH-ND revealed an interaction with the TM3 regions of both the MC3R and MC4R (Ser(122) of MC3R or Ser(127) of MC4R). However, in the MC1R, these serine residues corresponded to Val(122), which contains two methyl groups that induce steric hindrance with D-Phe(7) of [Gln(6)]alpha-MSH-ND. This is a possible explanation for the biological activity of [Gln(6)]alpha-MSH-ND for the MC1R being significantly lower than that for either the MC3R or MC4R. CONCLUSIONS: Minimization of the MC1R selectivity whilst preserving its comparable potency for both the MC3R and MC4R could be achieved by modifying the D-Phe(7) orientation of alpha-MSH-ND, while maintaining the 'type I beta-turn'-like structure.
Protein unfolding is a key step in several cellular processes, including protein translocation across some membranes and protein degradation by ATP-dependent proteases. ClpAP protease and the proteasome can actively unfold proteins in a process that hydrolyzes ATP. Here we show that these proteases seem to catalyze unfolding by processively unraveling their substrates from the attachment point of the degradation signal. As a consequence, the ability of a protein to be degraded depends on its structure as well as its stability. In multidomain proteins, independently stable domains are unfolded sequentially. We show that these results can explain the limited degradation by the proteasome that occurs in the processing of the precursor of the transcription factor NF-kappaB.
Although nonhomologous end-joining (NHEJ) deficiency has been shown to accelerate lymphoma formation in mice, its role in suppressing tumors in cells that do not undergo V(D)J recombination is unclear. Utilizing a tumor-prone mouse strain (ink4a/arf(-/-)), we examined the impact of haploinsufficiency of a NHEJ component, DNA ligase IV (Lig4), on murine tumorigenesis. We demonstrate that lig4 heterozygosity promotes the development of soft-tissue sarcomas that possess clonal amplifications, deletions, and translocations. That these genomic alterations are relevant in tumorigenesis is supported by the finding of frequent mdm2 amplification, a known oncogene in human sarcoma. Together, these findings support the view that loss of a single lig4 allele results in NHEJ activity being sufficiently reduced to engender chromosomal aberrations that drive non-lymphoid tumorigenesis.
Fruits of Gardenia jasminoides contain geniposide which can be transformed to blue pigments by a simple modification. Colorless geniposide obtained from gardenia fruits by charcoal and silica gel column chromatographies was hydrolyzed with beta-glucosidase to yield genipin. The resulting genipin was transformed to blue pigments by reaction with amino acids (glycine, lysine, or phenylalanine). The stability of the blue pigments against heat, light, and pH was studied to examine the blue dye for possible use as a value-added food colorant. Thermal degradation reactions at temperatures of 60-90 degrees C were carried out at different pH levels within the range 5.0-9.0 (pH 5.0, acetate buffer; pH 7.0, phosphate buffer; and pH 9.0, CHES buffer). The blue pigments remained stable after 10 h at temperatures of 60-90 degrees C, and in some cases, more new pigments formed. The pigments were more stable at alkaline pH than neutral and acidic pH. Similarly, the pigments were stable under light irradiance of 5000-20 000 lux. In this case, pH effect was not significant.
Ten new polyacetylenic alcohols (1-6, 8-11), along with a known compound, petrocortyne C (7), were isolated from the marine sponge Petrosia sp. The gross structures were established based on NMR and MS data, and the absolute configuration was determined by the modified Mosher's method. These compounds displayed considerable cytotoxicity against a small panel of human solid tumor cell lines. Compounds 1-11 were further evaluated for in vitro inhibitory activity on DNA replication.
Investigation of the whole plant of Isodon excisus resulted in the isolation of two new apoptosis inhibitors (1 and 2). Compounds 1 and 2 inhibited etoposide-induced apoptosis in U937 cells with IC50 values of 10.2 and 52.4 microg/mL, respectively. The structures of 1 and 2 were determined by spectral data interpretation.
BACKGROUND: Retrospective and correlation studies suggest that early-onset periodontal disease may be due to a deficiency in phagocyte function, a pathogenic oral biofilm, and/or dysregulated gingival cytokine expression. Increased susceptibility to periodontal disease is therefore thought to result from multiple risk factors. METHODS: We tested this hypothesis prospectively using P/E-selectin adhesion molecule deficient mice that mimic the human syndrome leukocyte adhesion deficiency II. RESULTS: Our studies demonstrate that, in comparison to wild type animals, P/E-/- mice exhibit: spontaneous, early onset alveolar bone loss which is significant by 6 weeks of age; a 10-fold elevation in bacterial colonization of their oral cavities; and elevated gingival tissue levels of the bone resorptive cytokine IL-1alpha. Alveolar bone loss is completely prevented by prophylactic antibiotic therapy. CONCLUSIONS: These experiments provide the first prospective evidence for the multiple risk factor hypothesis of periodontal disease, and validate the first animal model for early onset periodontitis in which both the microbiota and host response can be systematically manipulated. P/E-/- animals should be useful in testing the virulence of putative periodontal pathogens, in determining the role of host resistance factors in periodontitis, in exploring the proposed relationship(s) between infection mediated alveolar bone loss and systemic health disorders, and exploring their genetic relationships.
BACKGROUND: One-week triple regimens have been shown to be effective for the treatment of Helicobacter pylori-related peptic ulcer disease. AIM: To conduct an economic analysis of four triple regimens for the treatment of H. pylori-related peptic ulcer disease from the perspective of a public health organization in Hong Kong. METHODS: Records of 200 patients with H. pylori-related peptic ulcer disease, who had previously participated in a randomized comparison of ranitidine bismuth citrate (RBC) with amoxicillin and clarithromycin (RAC), omeprazole with amoxicillin and clarithromycin (OAC), RBC with metronidazole and tetracycline (RMT), or, colloidal bismuth subcitrate with metronidazole and tetracycline (BMT) in either in-patient or out-patient setting were reviewed. RESULTS: Fifty patients were excluded because of incomplete documentation or lack of peptic ulcer. In the out-patient group (n=72), the median direct costs of the RAC group (HK $ 5094) were lower those of the BMT (HK $ 5400), RMT (HK $ 5394), or OAC (HK $ 5440) groups, but the difference was significant only between the RAC and BMT groups (P < 0.05). In the in-patient group (n=78), the median direct costs of the RMT group (HK $ 8524) were significantly lower than those of the OAC (HK $ 13 871) and RAC (HK $ 12 092) groups (P < 0.05), but were similar to those of the BMT group (HK $ 8758). CONCLUSIONS: RAC and RMT are the least costly regimens for out-patient and in-patient treatment, respectively, of H. pylori-related peptic ulcer disease in Hong Kong.