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Biomedical subjects

L M Chen

Publications and source records attributed to L M Chen.

At least 55 records · Page 3Linked to original sources

Endometrial cancer: recent developments in evaluation and treatment.

Endometrial carcinoma is the most common gynecologic malignancy in the United States. Most cases are diagnosed at an early stage. However, the outcome for women diagnosed with advanced-stage disease remains poor. The etiology of most endometrial carcinomas stems from the effects of excess estrogen, whether this comes from exogenous or endogenous sources. Differences in epidemiology and presentation suggest the existence of two forms of endometrial cancer: those related to and those unrelated to hormonal stimulation. Most women with endometrial cancer present with abnormal uterine bleeding; endometrial sampling is essential to exclude endometrial carcinoma in such patients. Endometrial cancer is surgically staged, and staging usually includes a hysterectomy and bilateral salpingooophorectomy. Lymphadenectomy also should be performed in selective cases to better assess disease spread and to evaluate the need for adjuvant therapy. Adjuvant treatment may include the use of radiation, progestins, or cytotoxic chemotherapeutic agents. Several clinical trials are underway to compare these treatment modalities, as well as to determine the optimal combination of active chemotherapeutic agents, such as doxorubicin, platinum agents, and paclitaxel (Taxol).

Endometrial Neoplasms↗

Effects of tea polyphenols on cerebral lipid peroxidation, liver and renal functions in rats after repeated +Gz stress.

OBJECTIVE: To observe the effects of repeated +10 Gz stress on cerebral lipid peroxidation, liver and renal function in rats and the prophylactic effects of antioxidant tea polyphenols (TP). METHOD: Twenty-four male Wistar rats were randomly divided into three groups (n = 8, each): group A (control), group B (+10 Gz), and group C (TP). Group B and C were exposed to repeated +10 Gz stress (each for 30s, onset rate about 0.5 G/s, 3 times/d with +1 Gz 1 min intervals, 3 d/wk, 4 weeks in total), but group A was only submitted to +1 Gz. TP (200 mg/kg) was given orally in group C about 1 h prior to the +Gz experiment, while distilled water was given in group A and B. Lipid peroxidation in the brain, liver and renal functions and serum lipids were determined. RESULTS: As compared with the control, lipid peroxidation in rat cerebral homogenate, mitochondria and cytoplasm was significantly increased (P < 0. 05), and serum creatinine concentration was markedly elevated after repeated +10 Gz stress (P < 0. 01). But, TP had significant inhibitory effect on +10 Gz stress induced peroxidative injury in rat brain and reduced the serum creatinine level. There were no differences of serum triglyceride and total cholesterol concentrations and glutamic-pyruvic transaminase activity among the three groups. CONCLUSION: These results indicated that repeated high +Gz stress could bring about peroxidative injury in brain and harmful effect on renal function, and natural antioxidant TP had significant protective effects.

Acceleration↗

Identification and analysis of the regulatory region R&R* with the cnf1 gene encoding the cytotoxic necrotizing factor type 1 that closely links to the lux regulon of Vibrio fischeri.

Nucleotide sequence of the regulatory region R&R* and the partial 5'-end of the cnf1 gene (GenBank Accession No. AF023157) of Vibrio fischeri ATCC 7744 has been determined, and the cytotoxic necrotizing factor 1 (CNF1) encoded by the cnf1 gene is deduced. Alignment and comparison of the cytotoxic necrotizing factor 1s of V. fischeri and E. coli show that they are homologous. Nucleotide sequence reveals that the cnf1 gene is closely linked to the lux regulon in genome; the gene order of the cnf1 gene and the lux regulon is <--cnf1-R&R*<--rrn-<--luxR-R&R-luxI-luxC-luxD -luxA-luxB-luxE-luxG-omega-->, whereas R&R is the regulatory region of the lux regulon, and R&R* is the regulatory region of the cnf1 gene; the sequence approximately 2 kb lay between the luxR gene of the lux regulon and the cnf1 gene is an rrn-like operon. It is unexpected to find the cnf1 gene in V. fischeri, since the CNF1 protein enables necrosis; the marine luminous bacterium V. fischeri is never to be identified as a pathogenic microbe. The cnf1 gene might be concerned with symbosis of the luminous bacteria and host fishes.

Amino Acid Sequence↗

S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells.

S. typhimurium stimulates signaling pathways leading to membrane ruffling, actin cytoskeleton rearrangements, and nuclear responses. The stimulation requires a protein secretion system (type III) that translocates bacterial proteins into the host cell. We show that SopE, a substrate of this secretion system, stimulates cytoskeletal reorganization and JNK activation in a CDC42- and Rac-1-dependent manner. A lambda gt11 cDNA library screen for proteins that interact with SopE identified Rac-1 and CDC42. Furthermore, purified SopE was shown to stimulate GDP/GTP nucleotide exchange in several Rho GTPases in vitro, including Rac-1 and CDC42. These findings establish a paradigm for microbial stimulation of cellular responses in which the pathogen induces signaling events by directly engaging the signaling machinery within the host cell.

Animals↗

Ventilatory care in a selection of Ontario hospitals: bigger is not necessarily better! Critical Care Research Network (CCR-Net).

OBJECTIVE: To determine whether there is variability in the structure and process of ventilatory care in intensive care units (ICUs) of the hospitals of Southwestern Ontario. DESIGN: Self-administered questionnaire-based survey. SETTING: ICUs of selected community and teaching hospitals of Southwestern Ontario. PARTICIPANTS: Head of respiratory therapy service of respective hospitals; in those hospitals without respiratory therapists, the ICU nurse manager. INTERVENTION: Self-administered questionnaire. OUTCOME MEASURE(S): The availability of different models of ventilators and respiratory therapist and physician coverage were assessed. In addition, the use of clinical practice guidelines, respiratory therapists, and the nursing role in ventilatory care were determined. RESULTS: In general, the structure of ventilatory care, including availability of different modes of ventilation, and coverage by respiratory therapists and physicians was more comprehensive in larger hospitals. However, the availability of some modes of ventilation varied more than expected among hospitals of comparable size. Similarly, variability in the process of ventilatory care, defined by the availability of clinical practice guidelines and the roles of respiratory therapists varied both within and among hospitals of different size. CONCLUSIONS: The structure and process of ventilatory care in this sample of Southwestern Ontario ICUs was found to be variable. Not all this variability could be accounted for by hospital size, suggesting a potential for improvement in overall ventilatory care. Further study is required before any specific recommendations can be considered.

Critical Care↗

Prediction of equilibrated postdialysis BUN by an artificial neural network in high-efficiency hemodialysis.

In urea kinetic modeling, postdialysis blood urea nitrogen (BUN) is usually underestimated with an overestimation of the Kt/V especially in high-efficiency hemodialysis (HD). Thus, an artificial neural network (ANN) was used to predict the equilibrated BUN (Ceq) and equilibrated Kt/V (eKt/V60) by using both predialysis, postdialysis, and low-flow postdialysis BUN. The results were compared to a Smye formula to predict Ceq and a Daugirdas' formula (eKt/V30) to predict eKt/V60. Seventy-four patients on high-efficiency or high-flux HD were recruited. Their mean urea rebound was 28.6+/-2%. Patients were divided into a "training" set (n = 40) and a validation set (n = 34) for the ANN. Their status was exchanged later, and the two results were pooled. In the prediction of Ceq, both Smye formula and low-flow ANN were equally highly accurate. In patients with a high urea rebound (>30%), although Smye formula lost its accuracy, low-flow ANN remained accurate. In the prediction of eKt/V60, both Daugirdas' formula and low-flow ANN were equally accurate, although the Smye formula was not so accurate. In patients with a high urea rebound, although both Smye and Daugirdas' formulas lost their accuracy, low-flow ANN remained accurate. We concluded that low-flow ANN can accurately predict both Ceq and eKt/V60 regardless of the degree of urea rebound.

Blood Urea Nitrogen↗

The role of conventional cytology, immunocytochemistry, and flow cytometric DNA ploidy in the evaluation of body cavity fluids: a prospective study of 52 patients.

Fifty-two specimens of body cavity fluids from 52 patients were analyzed with conventional cytology, immunocytochemistry, and flow cytometric DNA ploidy methods to evaluate the most appropriate way of applying and interpreting immunocytochemistry and to evaluate the contribution of DNA ploidy analysis to conventional cytology in the diagnosis of body cavity fluids. The results suggest that conventional cytology still has an important role in the diagnosis of body cavity fluids. MOC 31 is the most sensitive monoclonal antibody for distinguishing benign mesothelial cells from malignant epithelial cells. Immunocytochemistry with the combination of cytokeratin, desmin, and MOC 31 with or without epithelial membrane antigen is suggested as a helpful ancillary method for the differential diagnosis of body cavity fluids. Flow cytometric DNA ploidy analysis also provides additional information in some difficult cases. Appropriate integration of clinical information and results of conventional cytology, immunocytochemistry, and flow cytometry are necessary to achieve the most accurate diagnosis in patients with effusion involving a body cavity.

Adult↗

Postoperative analgesia by intra-articular neostigmine in patients undergoing knee arthroscopy.

BACKGROUND: Recently, the spinal administration of neostigmine was shown to produce a dose-dependent analgesia. However, this analgesia is limited by adverse effects. The purpose of this study was to examine the analgesic action of peripheral muscarinic receptors by administering intra-articular neostigmine after operation in patients undergoing knee arthroscopy. METHODS: Sixty patients (classified as American Society of Anesthesiologists status I or II) having arthroscopic meniscus repair during general anesthesia were randomized to receive, in a double-blind manner, after operation 125, 250, or 500 microg intra-articular neostigmine; 2 mg intra-articular morphine; or as control groups intra-articular saline or 500 microg neostigmine given subcutaneously (s.c.). Visual analog pain scores (VAS), duration of analgesia as defined by first demand for patient-controlled analgesia by morphine, and subsequent 48-h consumption of morphine were evaluated. RESULTS: Intra-articular (500 microg) neostigmine resulted in significant VAS reduction 1 h after injection compared with patients given intra-articular saline and with those given intra-articular morphine. Analgesia lasted longer after 500 microg intra-articular neostigmine (350 +/- 126 min) compared with intra-articular morphine (196 +/- 138 min; P < 0.05) or with the control groups (intra-articular saline, 51 +/- 11 min; s.c. neostigmine, 46 +/- 8 min; P < 0.05). The need for supplementary analgesia was significantly higher in control groups than for patients given intra-articular morphine or 500 microg intra-articular neostigmine. No significant analgesic effects were observed for the two lower doses of intra-articular neostigmine. Among all study groups, no adverse effects were observed. CONCLUSIONS: Intra-articular injection of the acetylcholinesterase inhibitor neostigmine produced a moderate but significant analgesic effect. Several mechanisms such as the hyperpolarization of neurons, reduction in the release of pronociceptive neurotransmitters, or activation of the nitric oxide-cyclic guanosine monophosphate pathway might mediate this peripheral cholinergic antinociception by elevating endogenous acetylcholine.

Adult↗

Progress in ovarian cancer.

The management of advanced ovarian cancer relies on appropriate surgical cytoreduction in conjunction with appropriate adjuvant chemotherapy. In the past year several studies have continued to support aggressive cytoreduction at the initial operation, including for stage IV disease, as well as in a second-look setting. Ongoing research has identified several agents active in ovarian cancer, yet the optimal first-line regimen has yet to be developed.

Antineoplastic Combined Chemotherapy Protocols↗

Withdrawal and withholding of life support in the intensive care unit: a comparison of teaching and community hospitals. The Southwestern Ontario Critical Care Research Network.

OBJECTIVES: To compare the incidence of withdrawal or withholding of life support (WD/WHLS), and to identify similarities and differences in the process of the withdrawal of life support (WDLS) between teaching and community hospitals' intensive care units (ICUs). DESIGN: Prospective cohort study, with some data obtained by retrospective chart review. SETTING: The ICUs of three teaching hospitals and six community hospitals. PATIENTS: All patients who died in these nine ICUs over a 6-mo period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on admitting diagnosis, cause of death, mode of death (death despite active treatment, withdrawal or withholding of life support), those initiating and involved in WDLS, and modalities of life support withdrawn were gathered for patients dying in the ICU over a 6-mo period. One hundred sixty patients in community hospitals and 292 in teaching hospitals died in their respective ICUs over the 6-mo period. We found a difference in the distribution of mode of death between community hospitals and teaching hospitals, resulting from a greater proportion of patients dying as a result of withholding life support in community hospitals (11.9% vs. 3.8% withheld, respectively, p = .004). Among the six community hospitals and three teaching hospitals, we found a difference in the proportion of patients dying despite active treatment compared with those dying as a result of WD/WHLS (p = .042 and p = .044, respectively). Initiation of WDLS by physicians was more frequent at teaching hospitals (81% vs. 61%, p = .0005), while families more commonly initiated WDLS at community hospitals (34% vs. 19%, p = .005). A greater proportion of patients in teaching hospitals were receiving mechanical ventilation (99% vs. 89%) and vasopressors (76% vs. 65%) before WDLS. Similar proportions had mechanical ventilation withdrawn (68% and 74%, community hospitals and teaching hospitals, respectively), while there was a trend for fewer patients in community hospitals to have vasopressors withdrawn (56% vs. 70%, p = .082). The time to death after WDLS had begun was longer in community hospitals compared with teaching hospitals (0.74 +/- 1.38 days vs. 0.27 +/- 0.79 [SD] days, p = .0028). CONCLUSIONS: The incidence of WD/WHLS was similar in community hospitals and teaching hospitals; however, withholding of life support was more common in community hospitals. The process of WDLS appears to differ between community hospitals and teaching hospitals.

Adult↗

Patients readmitted to the intensive care unit during the same hospitalization: clinical features and outcomes.

OBJECTIVE: To determine the clinical features and outcomes of patients readmitted to the intensive care unit (ICU) during the same hospital stay and the causes for these readmissions. DESIGN: Multicenter, cohort study. SETTING: Three ICUs from two teaching hospitals and four ICUs from four community hospitals. PATIENTS: All ICU admissions were collected prospectively for a registry database in the seven ICUs. We retrospectively analyzed ICU admissions between January 1, 1995 and February 29, 1996. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the study period, 236 (4.6%) of the patients discharged alive from the ICU were readmitted to the unit. Patients with gastrointestinal (GI) and neurologic diagnoses had the highest readmission rate. Of the readmissions, 45% had recurrence of the initial disease, 39% experienced new complications, and 14% required further planned operation. Among patients readmitted for the same illness, cardiovascular and respiratory problems were the most frequent diagnoses. Of patients readmitted with a new diagnosis, 30% initially had GI diseases, while respiratory diseases accounted for 58% of the new complications. Readmissions within 24 hrs occurred in 27% of all readmissions. Patients requiring readmission had a higher hospital mortality rate (31.4%) compared with those not requiring readmission (4.3%, p < .001), even after adjustment for disease severity score (odds ratio = 5.93, p < .001). CONCLUSIONS: Patients with GI and neurologic diseases are at greatest risk of requiring ICU readmission. Respiratory diseases are the major reason for readmission due to new complications. Readmitted patients have a high risk of hospital death that may be underestimated by the usual physiologic indicators on either initial admission or readmission. Further studies are required to determine if patients at risk for readmission can be identified early to improve the outcome.

APACHE↗

Genetic analysis, using P22 challenge phage, of the nitrogen activator protein DNA-binding site in the Klebsiella aerogenes put operon.

The nac gene product is a LysR regulatory protein required for nitrogen regulation of several operons from Klebsiella aerogenes and Escherichia coli. We used P22 challenge phage carrying the put control region from K. aerogenes to identify the nucleotide residues important for nitrogen assimilation control protein (NAC) binding in vivo. Mutations in an asymmetric 30-bp region prevented DNA binding by NAC. Gel retardation experiments confirmed that NAC specifically binds to this sequence in vitro, but NAC does not bind to the corresponding region from the put operon of Salmonella typhimurium, which is not regulated by NAC.

Amino Acid Transport Systems, Neutral↗

Underregistration of neonatal deaths: an empirical study of the accuracy of infantile vital statistics in Taiwan.

STUDY OBJECTIVE: The accuracy of the official statistic on infant deaths in Taiwan has been questioned. This study aimed to survey infant deaths nationwide, to measure associated vital statistics, and compare them with the official statistics to assess accuracy. DESIGN AND PARTICIPANTS: A nationwide survey of all gestational outcomes occurring at > or = 20 weeks' gestation over a three day study period (15-17 May 1989) was conducted to collect data from 23 counties and cities nationwide using a two stage data collection procedure. MAIN RESULTS: The survey derived infant death rate was 9.72 per 1000 live births, which was higher than the reported official statistic of 5.71 per 1000 live births. A more detailed examination of data on infant deaths showed that the estimated neonatal death rate of 6.68 per 1000 live births (95% confidence intervals: 3.33, 11.96 per 1000 live births) was significantly higher than the published official statistic of 1.94 per 1000 live births, while the postneonatal mortality of 3.04 per 1000 live births was comparable to the reported statistic of 3.37 per 1000 live births. CONCLUSIONS: This study empirically documented the underregistration of infant deaths in Taiwan, particularly those occurring during the first 27 days of life.

Data Collection↗

[Apamin sensitive component of Ca(2+)-activated K+ current of afterhyperpolarization, IAHP, in dorsal root ganglion neurons in rat].

Whole-cell voltage clamp technique was used to record the tail current in freshly isolated dorsal root ganglion (DRG) neurons of rat with an aim to investigate whether these neurons possess an apamin sensitive component of Ca(2+)-activated K+ current, IAHP. The results are as follows: (1) the amplitudes of the tail currents increased from 9.3 +/- 2.8 pA to 64.1 +/- 3.4 pA (P < 0.001) when the depolarizing duration was increased from 1 ms to 180 ms; (2) the amplitudes of the tail current were reduced when repolarizing pulses were applied, with a reversal potential of about -63 mV; (3) the amplitude of the tail current was significantly depressed or even almost completely blocked by extracellularly applied 500 mumol/L Cd2+ or intracellularly applied 11 mmol/L EGTA; (4) the amplitudes of the tail currents were decreased by about (26.32 +/- 3.9)% (P < 0.01) after 200 nmmol/L apamin was extracellularly applied; and (5) the fast component of the tail current was sensitive to 10 mmol/L TEA while the slow component was insensitive. These results suggest that an apamin sensitive component of Ca(2+)-activated K+ current may be present in afterhyperpolarization of DRG neurons.

Animals↗

Regional differences in the rise in blood levels of antigenic keratan sulfate and hyaluronan after chymopapain induced knee joint injury.

OBJECTIVE: Results from several recent studies suggest that the levels of antigenic keratan sulfate (agKS) and hyaluronan (HA) in serum provide useful information about changes taking place in injured or diseased synovial joints. To improve our understanding of the significance of such changes, we investigated the points of entry of these molecules into the blood circulation and their subsequent clearance after experimentally induced injury to rabbit knee joint. METHODS: Chymopapain was injected into knee joints of 8 young adult rabbits to induce aggrecan degradation in articular cartilage within the injected joint. Levels of agKS and HA in serum from various blood vessels were measured before and 5 h after the injury. The statistical significance of injury related changes and differences among the different vessels were evaluated. RESULTS: After the injury, the level of agKS rose most significantly in the popliteal vein draining the injected knee joint and dropped rapidly by the time the blood reached the femoral vein. The level of agKS was similar, although lower, in other blood vessels but, in each case, it was significantly higher than before the injection. The level of HA showed a different pattern of changes after injection. While highest in the popliteal vein draining the injected knee, HA was markedly elevated in the cranial vena cava, close to the entry of lymph into the circulation, and was 50% lower in the hepatic than in the portal vein. CONCLUSION: (1) Measurement of agKS and HA in a blood vessel draining or close to an injured/diseased knee joint may provide more specific information about degradative changes taking place in that joint than measurement of levels of these markers in other blood vessels; (2) some HA molecules but no measurable amounts of agKS enter the blood circulation via the lymphatic system: and (3) HA but not agKS is very rapidly cleared from the blood by the liver.

Animals↗

Involvement of mitogen-activated protein kinase pathways in the nuclear responses and cytokine production induced by Salmonella typhimurium in cultured intestinal epithelial cells.

Central to the pathogenesis of Salmonella typhimurium is its ability to engage the host cell in a two-way biochemical interaction. As a consequence of this interaction, a dedicated protein secretion system, termed type III, is activated in these bacteria and directs the translocation of signaling proteins into the host cell. Secretion of these proteins stimulates host cell signal transduction pathways that lead to a variety of cellular responses. An important feature of S. typhimurium pathogenesis is the induction of a profound inflammatory response in the intestinal epithelium. In this report, we show that S. typhimurium induces host cell signal transduction pathways that lead to the activation of the transcription factors NF-kappaB and AP-1, resulting in the production of proinflammatory cytokines such as IL-8. We also show that S. typhimurium infection of cultured intestinal epithelial cells results in the activation of the mitogen-activated protein (MAP) kinases ERK, JNK, and p38. Induction of these signaling pathways and the synthesis of IL-8 was strictly dependent on the function of the invasion-associated type III protein secretion system encoded by S. typhimurium. Pretreatment of cells with the highly specific p38 MAP kinase inhibitor SB 203580 prevented S. typhimurium-induced IL-8 production. These results indicate that the inflammatory response induced by S. typhimurium may be due to the specific stimulation of MAP kinase signaling pathways leading to nuclear responses.

Calcium-Calmodulin-Dependent Protein Kinases↗

Kallistatin is a potent new vasodilator.

Kallistatin is a serine proteinase inhibitor which binds to tissue kallikrein and inhibits its activity. The aim of this study is to evaluate if kallistatin has a direct effect on the vasculature and on blood pressure homeostasis. We found that an intravenous bolus injection of human kallistatin caused a rapid, potent, and transient reduction of mean arterial blood pressure in anesthetized rats. Infusion of purified kallistatin (0.07-1.42 nmol/kg) into cannulated rat jugular vein produced a 20-85 mmHg reduction of blood pressure in a dose-dependent manner. Hoe 140, a bradykinin B2-receptor antagonist, had no effect on the hypotensive effect of kallistatin yet it abolished the blood pressure-lowering effect of kinin and kallikrein. Relaxation of isolated aortic rings by kallistatin was observed in the presence (ED50 of 3.4 x 10(-9) M) and in the absence of endothelium (ED50 of 10(-9) M). Rat kallikrein-binding protein, but not kinin or kallikrein, induced vascular relaxation of aortic rings. Neither Hoe 140 nor Nomega-nitro--arginine methyl ester, a nitric oxide synthase inhibitor, affected vasorelaxation induced by kallistatin. Kallistatin also caused dose-dependent vasodilation of the renal vasculature in the isolated, perfused rat kidney. Specific kallistatin-binding sites were identified in rat aorta by Scatchard plot analysis with a Kd of 0.25+/-0.07 nM and maximal binding capacity of 47.9+/-10.4 fmol/mg protein (mean+/-SEM, n = 3). These results indicate that kallistatin is a potent vasodilator which may function directly through a vascular smooth muscle mechanism independent of an endothelial bradykinin receptor. This study introduces the potential significance of kallistatin in directly regulating blood pressure to reduce hypertension.

Adrenergic beta-Antagonists↗