Search PubMed⌕ Search

Biomedical subjects

A Y Lee

Publications and source records attributed to A Y Lee.

At least 19 recordsLinked to original sources

Gallbladder cancer presenting with acute cholecystitis: a population-based study.

BACKGROUND: The role of laparoscopic cholecystectomy (LC) in acute cholecystitis remains controversial. The aim of the present study was to determine the incidence, clinicopathological characteristics, and outcome of patients with gallbladder cancer presenting with acute cholecystitis. METHODS: We performed a retrospective analysis of patients with gallbladder cancer who presented with acute cholecystitis and were treated at the public hospitals in Hong Kong between 1998 and 2002. RESULTS: Among 2,700 patients with acute cholecystitis managed with cholecystectomy (1,347 open and 1,353 LC), 63 patients (2.3%) were found to have gallbladder cancer. There were 44 women and 19 men with a mean age of 74.7 (+/-12.8) years. Adenocarcinoma (90.5%) was the most common cancer. The overall median survival was 5 months (95% CI = 2.6-7.4). The 5-year survival rate was 20.8%. Laparoscopic cholecystectomy was attempted in 11 patients and was completed successfully in six of them. There was no difference between the LC and open groups in the complication rate, hospital mortality rate, or survival rate. CONCLUSIONS: In the ethnic Chinese population of Hong Kong, the incidence of gallbladder cancer presenting with acute cholecystitis is higher than the same finding in patients undergoing elective cholecystectomy for cholelithiasis. Long-term survival is possible because such patients may be diagnosed at an early stage of the disease.

Acute Disease↗

From Trousseau to targeted therapy: new insights and innovations in thrombosis and cancer.

Venous thromboembolism (VTE) commonly occurs in patients with malignant disease. At the 1997 ISTH meeting, cancer and thrombosis was discussed in a state-of-the-art symposium. Since then, there have been many new developments on this topic. Tumors, through expression of tissue factor can activate coagulation. Furthermore, local peritumor activation of coagulation may have important effects on the biology of cancer. A randomized trial has been conducted which evaluated extensive screening to detect underlying malignancy vs. no screening in patients presenting with idiopathic VTE. No statistically significant difference was detected in cancer-related mortality between the two groups. A trial has evaluated extended prophylaxis in patients undergoing surgery for abdominal malignancy. There was a statistically significant reduction in venographically detected deep vein thrombosis in favor of 4 weeks of treatment. In contrast, there is clearly a need for more information on the use of thromboprophylaxis in medical cancer patients. Low molecular weight heparin (LMWH) has replaced unfractionated heparin as the first line treatment in the majority of patients with acute VTE. Many cancer patients with acute VTE can be treated safely at home with subcutaneous LMWH without admission to hospital. The results of a recent trial demonstrated that long-term low molecular weight heparin administered over a 6-month period substantially reduced the rate of recurrent VTE compared with oral anticoagulant therapy with no increase in bleeding. Finally, the first trial specifically designed to evaluate the anticancer effect of long-term LMWH in cancer patients has been conducted and will no doubt stimulate future research.

Anticoagulants↗

Treatment of venous thromboembolism in cancer patients.

The management of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with cancer can be a clinical dilemma. Comorbid conditions, warfarin failure, difficult venous access, and a high bleeding risk are some of the factors that often complicate anticoagulant therapy in these patients. In addition, the use of central venous access devices is increasing but the optimal treatment of catheter-related thrombosis remains controversial. Unfractionated heparin (UFH) is the traditional standard for the initial treatment of venous thromboembolism (VTE) but low molecular weight heparins (LMWHs) have been shown to be equally safe and effective in hemodynamically stable patients. For long-term treatment or secondary prophylaxis, vitamin K antagonists remain the mainstay treatment. However, the inconvenience and narrow therapeutic window of oral anticoagulants make extended therapy unattractive and problematic. As a result, LMWHs are being evaluated as an alternative for long-term therapy. New antithrombotic agents are being tested in clinical trials and may have the potential to replace conventional treatment. The role of inferior vena cava filters in cancer patients remains ill defined but these devices remain the treatment of choice in patients with contraindications for anticoagulant therapy.

Anticoagulants↗

Induction of herpes simplex virus gB-specific cytotoxic T lymphocytes in TAP1-deficient mice by genetic immunization but not HSV infection.

Loading of most endogenous peptides on major histocompatibility complex class I molecules is conditional on their transport into the endoplasmic reticulum (ER) by the peptide transporter TAP. We describe an HSV-2/1 cross-reactive cytotoxic T-cell (CTL) epitope that is processed in a TAP1-independent manner in vivo following immunization of TAP1-/- mice with naked DNA or a recombinant vaccinia virus. These data indicated that TAP1-independent processing of endogenous proteins is sufficient to prime CTLs in vivo. TAP1-independent processing of this epitope was not due to ER targeting by signal sequences and exogenous loading of MHC-I molecules and was not influenced by the amino acids flanking this epitope. In contrast, TAP1-/- mice infected with HSV-2 or HSV-2 mutants did not mount a CTL response against this epitope.

Animals↗

Multicenter study of the frequency of contact allergy to gold.

Gold sodium thiosulfate (GSTS) is reputed to be the most reliable gold antigen, but control studies are still required. Although Koreans have more varied sources of contact with gold, such as herbal medicines with gold coatings and indwelling gold acupuncture needles, no epidemiological studies have been performed. This study examined the frequency and sources of contact allergy to gold in South Korea by a multicenter study. Patch testing with 0.5% GSTS in pet. was conducted in 255 eczema patients and 58 control subjects. Results were observed at 21 days (D) to ensure there were no undetected late reactions in 54 observed patients and 47 controls. 8 (3.1%) of the 255 patients reacted positively to GSTS, including 1 with a late reaction. 1 of the 58 controls showed a positive reaction to GSTS on D4 with a negative reaction on D14. Clinical relevance was lacking in the patients with positive reactions. Unexpectedly, the above particular sources of gold contact gave rise to few allergic reactions in our patients.

Adolescent↗

Left atrial and ventricular ball thrombi complicating rheumatic heart disease with combined mitral and aortic stenosis.

A 42-year-old woman with chronic mitral stenosis was admitted for progressive dyspnea, palpitation, and weakness of lower extremities. Echocardiography revealed rheumatic, thickened, and stenotic mitral and aortic valves, and two free-floating ball thrombi were detected in the left atrium and ventricle, respectively. She died suddenly the next day, probably due to mitral or aortic outflow obstruction by the ball thrombi. We believe that the occurrence of free-floating ball thrombi in both the left atrium and left ventricle concomitantly has never been reported.

Aged↗

Treatment of venous thrombosis in the cancer patient.

Venous thromboembolism is a common complication in patients with cancer. The management of deep vein thrombosis and pulmonary embolism can be a considerable challenge in patients with cancer. The cancer itself and associated treatments contribute to an ongoing thrombogenic stimulus, while cancer patients are thought to be at increased risk for anticoagulant-induced bleeding. Initial treatment of acute thromboembolism is with intravenous unfractionated heparin or subcutaneous low molecular weight heparin. Treatment at home with low molecular weight heparin is an attractive option in patients with malignant disease. Long-term treatment of acute venous thromboembolism has traditionally been with oral anticoagulants. However, the inconvenience and narrow therapeutic window of oral anticoagulants make such therapy unattractive and problematic in cancer patients. Low molecular weight heparins are being evaluated as an alternative for long-term therapy because their anticoagulant effects are more predictable and laboratory monitoring is unnecessary. Although many clinical issues remain unresolved in the treatment of cancer patients with venous thromboembolism, the future holds much promise as new antithrombotic agents, including factor Xa antagonists and oral thrombin inhibitors, are being tested in clinical trials.

Anticoagulants↗

Photopatch testing in seven cases of photosensitive drug eruptions.

OBJECTIVE: The most important goal in the management of photosensitive drug eruptions, as in other types of drug eruptions is identification of the causative drugs to prevent reexposure to them. CASE SUMMARIES: Seven patients whose lesions were mainly distributed on sun-exposed areas underwent laboratory tests, phototests, and photopatch tests with suspected drugs. Phototests were done with ultraviolet A (UVA), UVB, and visible light. Drugs used in the photopatch tests were usually prepared as 10% concentrations in petroleum base, which did not produce reactions in 10 control subjects, followed by irradiation of suberythema doses of UVA. Systemic provocation by oral administration of small doses of causative drugs with irradiation of suberythema doses of UVA was performed to confirm the results of skin tests in four patients. Two patients were not rechallenged with the causative drugs. None of the patients had systemic lupus erythematosus, porphyria, or pellagra. All showed positive reactions to photopatch testing. Systemic provocation confirmed the results of photopatch tests in four patients. The two patients who were not rechallenged had no recurrence of lesions. One patient ingested only one drug at the time of eruptions, and provocation or avoidance was not attempted. A photoallergic mechanism was considered in five cases. CONCLUSIONS: Although there is no information about the appropriate concentrations or vehicles for suspected drugs, photopatch testing could be reliable for identification of causes of photosensitive drug eruptions. Besides piroxicam (a well-known photosensitizer) and carbamazepine, isoniazid and triflusal were identified as the causes of the reactions.

Aged↗

Like fibrin, (DD)E, the major degradation product of crosslinked fibrin, protects plasmin from inhibition by alpha2-antiplasmin.

Plasmin generation is localized to the fibrin surface because tissue-type plasminogen activator (t-PA) and plasminogen bind to fibrin, an interaction that stimulates plasminogen activation over a hundred-fold. To ensure efficient fibrinolysis, plasmin bound to fibrin is protected from inhibition by alpha2-antiplasmin. (DD)E, a major soluble degradation product of cross-linked fibrin that is a potent stimulator of t-PA, compromises the fibrin-specificity of t-PA by promoting systemic activation of plasminogen. In this study we investigated whether (DD)E also protects plasmin from inhibition by alpha2-antiplasmin, facilitating degradation of this soluble t-PA effector. (DD)E and fibrin reduce the rate of plasmin inhibition by alpha2-antiplasmin by 5- and 10-fold, respectively. Kringle-dependent binding of plasmin to (DD)E and fibrin, with Kd values of 52 and 410 nM, respectively, contributes to the protective effect. When (DD)E is extensively degraded by plasmin, yielding uncomplexed fragment E and (DD), protection of plasmin from inhibition by alpha2-antiplasmin is attenuated. These studies indicate that (DD)E-bound plasmin, whose generation reflects the ability of (DD)E to stimulate plasminogen activation by t-PA, has the capacity to degrade (DD)E by virtue of its resistance to inhibition. This provides a mechanism to limit the concentration of (DD)E and maintain the fibrin-specificity of t-PA.

Antifibrinolytic Agents↗

Acute myocardial infarction after upper gastrointestinal gastroscopy.

We describe a patient with gastric ulcer confirmed by upper gastrointestinal endoscopy who developed an acute Q wave myocardial infarction involving both the anterior and inferior wall shortly after the procedure. This life-threatening complication of gastroendoscopy was clearly demonstrated through studies of electrocardiogram, cardiac enzymes, echocardiogram and cardiac catherterization. We suggest that preventive measures should be implemented so that endoscopy can be performed under optimal conditions, especially for elderly patients with history of heart disease.

Aged↗

A novel putative transcription factor protein MYT2 that preferentially binds supercoiled DNA and induces DNA synthesis in quiescent cells.

Myelin transcription factor 2 (MYT2), a putative transcription factor found in the human central nervous system, was cloned from an expression cDNA library from human T-cells. MYT2 shares weak similarity to bacterial type I topoisomerases and shares 63% sequence identity to a replicase from Leuconostoc mesenteroides. MYT2 preferentially binds supercoiled DNA (scDNA). Incubation of MYT2 and scDNA at or above equal molar ratios generated topoisomer-like patterns that were abolished by deproteination. Thus, MYT2 appears to relax scDNA via a non-enzymatic mechanism. The banding pattern of MYT2-scDNA complexes was shown to be quantisized, saturable and sequence-independent. Microinjection of MYT2 mRNA induced G(o) growth-arrested NIH 3T3 cells to enter the S phase of the cell cycle.

3T3 Cells↗

Quantification of the number of cytotoxic T cells specific for an immunodominant HCV-specific CTL epitope primed by DNA immunization.

Priming of strong cellular immune responses to hepatitis C (HCV) is thought to be important for eradication of infection. Although productive infection of HCV occurs only reproducibly in humans and chimpanzees, definition of HCV-specific T cell epitopes in mice is necessary to screen efficiently HCV vaccine strategies for their ability to prime cellular immune responses. Out of seven strains of mice screened for immunodominant CTL epitopes against HCV-1a Core, E2, NS5a and NS5b, only one epitope (p214K9) in only one mouse strain was identified. Enumeration of p214K9-specific CD8+ cells by flow cytometry revealed that the number of epitope specific CTL primed by 'naked' DNA immunization was lower than that reported during viral infection. The p214K9 epitope described here, combined with analysis of CTL responses by flow cytometry, should be instrumental in ranking various HCV vaccine strategies for their ability to prime CTL responses.

Animals↗

The pleasures and pains of distinct self-construals: the role of interdependence in regulatory focus.

Regulatory focus theory distinguishes between self-regulatory processes that focus on promotion and prevention strategies for goal pursuit. Five studies provide support for the hypothesis that these strategies differ for individuals with distinct self-construals. Specifically, individuals with a dominant independent self-construal were predicted to place more emphasis on promotion-focused information, and those with a dominant interdependent self-construal on prevention-focused information. Support for this hypothesis was obtained for participants who scored high versus low on the Self-Construal Scale, participants who were presented with an independent versus interdependent situation, and participants from a Western versus Eastern culture. The influence of interdependence on regulatory focus was observed in both importance ratings of information and affective responses consistent with promotion or prevention focus.

Adult↗

Placement of intravenous cannulae prior to ambulatory phlebectomy.

BACKGROUND: Ambulatory phlebectomy (AP) is a popular outpatient procedure for the removal of varicose veins. One of the major obstacles of AP is the disappearance and shift of the veins to be removed when the patient is positioned horizontally. OBJECTIVE: We aimed to verify the usefulness of preoperative placement of intravenous cannulae. METHODS: Forty-three vein segments of four consecutive patients with varicose veins were treated by AP with preoperative placement of intravenous cannulae. The procedures including anesthesia, incision, and exteriorization of the veins were performed with intravenous cannula in situ. We compared the courses of cannula and preoperative conventional marking of the veins. The time spent with extracting a vein was also compared with that spent with conventional procedure. RESULTS: The preoperative cannulation provides excellent fixation of varicose veins to their original position, at least at the puncture sites. The disagreement of courses between cannula and preoperative conventional marking was noticed in 47.8% of the vein segments from the knees and thighs, and in 15% from the lower legs. The time spent for extracting a vein was reduced by more than half with our method. CONCLUSION: Intravenous cannulation prior to AP is a simple procedure, but significantly improves the technique of AP by more accurately guiding the site of anesthesia and incision.

Ambulatory Surgical Procedures↗

Priming of hepatitis C virus-specific cytotoxic T lymphocytes in mice following portal vein injection of a liver-specific plasmid DNA.

The immunology of hepatitis C virus (HCV) infection should be studied in the context of HCV antigen expression in the liver, because HCV primarily infects this organ. Indeed, the nature, function, and fate of T cells primed after antigen expression in the liver might differ from those primed when antigens are expressed systemically or in other organs, because the nature of the antigen-presenting cells (APCs) involved may be different. In addition, the normal liver contains a resident population of lymphocytes that differ from those present at other sites. Thus, we investigated whether HCV-specific CD8(+) cytotoxic T cells (CTLs) could be elicited following portal vein (PV) injection of plasmid DNA in mice whose hepatic veins were transiently occluded. We show that PV injection of mice with "naked" DNA expressing the HCV-NS5a protein, under the control of a liver-specific enhancer/promoter, resulted in NS5a expression in the liver and the priming of HCV-specific CTLs. These results suggested that such a model might be relevant to the study of HCV-specific immune responses primed during natural infection.

Animals↗