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Biomedical subjects

L M Chen

Publications and source records attributed to L M Chen.

At least 19 recordsLinked to original sources
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

Adenovirus-mediated delivery of human kallistatin gene reduces blood pressure of spontaneously hypertensive rats.

Human kallistatin, or human tissue kallikrein-binding protein (HKBP), is a serine proteinase inhibitor (serpin). Transgenic mice overexpressing rat kallikrein-binding protein are hypotensive. To elucidate therapeutic potentials of kallistatin in hypertension, the human kallistatin gene in an adenoviral vector was directly introduced into spontaneously hypertensive rats (SHR) through portal vein injection. The kallistatin cDNA construct (RSV-cHKBP) under the promoter control of Rous sarcoma virus 3' long terminal repeat (LTR) was incorporated into adenovirus (Ad.RSV-cHKBP). Recombinant kallistatin in 293 cells transfected with RSV-cHKBP or Ad.RSV-cHKBP was measured by ELISA and by its complex formation with tissue kallikrein. A single intraportal vein injection of Ad.RSV-cHKBP at a dose of 8 x 10(10) pfu results in a significant reduction of blood pressure of SHR for 4 weeks. Human kallistatin mRNA was detected in the liver, spleen, kidney, aorta, and lung of rats receiving gene delivery. Immunoreactive human kallistatin in rat serum was detected at the highest level 1 day post injection and at lesser amounts in rat tissues. This study shows that adenovirus harboring Ad.RSV-cHKBP produces functional kallistatin, and adenovirus-mediated transfer of the human kallistatin gene reduces blood pressures of SHR. The results suggest that kallistatin may function as a vasodilator in vivo and provide important information for a potential gene therapy approach to hypertension.

Adenoviridae↗
PubMed1997

Beneficial effects of kallikrein-binding protein in transgenic mice during endotoxic shock.

Rat kallikrein-binding protein (RKBP) is a negative acute phase protein. The potential role of RKBP in inflammation was evaluated in transgenic mice overexpressing the RKBP gene under the control of the mouse metallothionein metal-responsive promoter. Bacterial endotoxic lipopolysaccharide (LPS) was injected intraperitoneally into mice at a dose of 600 microg/25 g body weight. The death toll was recorded every 12 hours for 3 days. The survival rate of transgenic male mice (n=78) was 33.3% while that of control male mice (n=54) was 9.3% 3 days post LPS injection. In comparison, the survival rate of transgenic female mice (n=59) was 55.9% while that of control female mice (n=65) was 30.8%. Recombinant RKBP levels in the circulation of these mice increased by 3-fold after LPS treatment. The results show that RKBP transgenic mice have a higher survival rate than their non-transgenic control littermates after endotoxin shock and female mice are more resistant to lethality induced by endotoxin shock than male mice in both transgenic and control groups. These findings suggest that kallikrein-binding protein has a protective effect during acute phase inflammation.

Animals↗
PubMed1997

A retrospective review of a large cohort of patients undergoing the process of withholding or withdrawal of life support.

OBJECTIVES: To determine the proportion of patients who died as a result of the withdrawal or withholding of life support (WD/WHLS) in the intensive care units (ICUs) of three teaching hospitals and to describe the process involved by determining: a) why the decision was made to withdraw support (WDLS); b) when WDLS took place; and c) how the WDLS process was conducted. DESIGN: Retrospective cohort study. SETTING: Three university-affiliated ICUs. PATIENTS: Four hundred nineteen patients who died in one of three academic, tertiary care ICUs over a 1-yr period. INTERVENTIONS: Retrospective chart review. Data collected included age, gender, admitting diagnoses, comorbid disease, Acute Physiology and Chronic Health Evaluation II score, and mode of death (brain death, death due to withholding of life support, death due to WDLS, or death despite ongoing therapy). For those patients dying due to WDLS, the reason for WDLS, person initiating discussion, timing of WDLS, degree of organ dysfunction, order of withdrawal of life support modalities, and the use of sedatives and analgesics were recorded. MEASUREMENTS AND MAIN RESULTS: Seventy percent of patients died by WD/WHLS and 8.4% were brain dead. Patients undergoing WD/WHLS were older and had a longer length of stay than patients dying from other causes. Poor prognosis was the most common reason given for WDLS, reflected by significant organ dysfunction at the time of WDLS. Future quality of life was a less frequently cited reason. Most patients undergoing WDLS did so early in their ICU stay, although time to WDLS appeared to reflect diagnostic group. Few meetings occurred before WDLS and death occurred soon after initiating WDLS. There was a preference of withdrawing mechanical ventilation last and large amounts of morphine (mean 21 +/- 33 [SD] mg/hr) and benzodiazepines (mean 8.6 +/- 11 mg/hr) were used. Little variability in practice was apparent among the studied ICUs. CONCLUSIONS: Similar to other studies, WD/WHLS was the most common cause of death in academic ICUs and poor patient prognosis was considered the most important factor in deciding on WDLS. However, in contrast to other studies, future quality of life was not as frequently cited a reason for WDLS and larger amounts of morphine were used during WDLS. These discrepancies suggest areas for potential future research.

APACHE↗
PubMed1997

Underreporting and misclassification of maternal mortality in Taiwan.

BACKGROUND: Underreporting and misclassification of maternal deaths are universal. The purposes of this study were to quantify the level of underestimation of maternal mortality and to analyze possible factors that contribute to underreporting and misclassification of maternal mortality. METHODS: An interview census of all registered deaths that occurred during 1984-1988 in women of reproductive age was undertaken in Taiwan. Pregnancy-related deaths were screened from all collected questionnaires and death certificates by the researchers. The screened pregnancy-related deaths were then reviewed and evaluated by obstetrician-gynecologists; a cause of each death was assigned. RESULTS: For the five years, on average, the rate of underreporting of maternal mortality is 58.38% and the correct/confirmed rate of classification is 53.28%. Underreported and misclassified maternal deaths are more likely for women aged 20-24, with stillbirth and fetal death, care sought for non-obstetric reasons, care received in private hospitals and clinics, occurrence in the home, certification by non-obstetrician-gynecologists and court doctors, and death from non-obstetric causes. CONCLUSIONS: This study shows the limitations of official vital registration and concludes that dependence on death certificates alone to identify maternal deaths is incomplete and incorrect.

Adult↗
PubMed1996

Requirement of CDC42 for Salmonella-induced cytoskeletal and nuclear responses.

The bacterial pathogen Salmonella typhimurium triggers host cell signaling pathways that lead to cytoskeletal and nuclear responses required for pathogenesis. Here, the role of the small guanosine triphosphate (GTP)-binding protein CDC42Hs in these responses was examined. Expression of a dominant interfering mutant of CDC42 (CDC42HsN17) prevented S. typhimurium-induced cytoskeletal reorganization and subsequent macropinocytosis and bacterial internalization into host cells. Cells expressing constitutively active CDC42 (CDC42HsV12) internalized an S. typhimurium mutant unable to trigger host cell responses. Furthermore, expression of CDC42HsN17 prevented S. typhimurium-induced JNK kinase activation. These results indicate that CDC42 is required for bacterial invasion and induction of nuclear responses in host cells.

Animals↗
PubMed1996

Tissue kallikrein-binding protein reduces blood pressure in transgenic mice.

The kallikrein-kinin system participates in blood pressure regulation. One of the kallikrein-kinin system components, kallikrein-binding protein, binds to tissue kallikrein and inhibits its activity in vitro. To investigate potential roles of rat kallikrein-binding protein (RKBP) in vivo, we have developed transgenic mice that express an RKBP gene under the control of the mouse metallothionein metal-responsive promoter. Expression of the transgene, RKBP, was detected in the liver, kidney, lung, heart, pancreas, salivary glands, spleen, brain, testis, and adrenal gland at the mRNA and protein levels. Systolic blood pressures of homozygous transgenic mice were 88.5 +/- 0.8 mm Hg (mean +/- S.E., n = 19, P < 0.001) for one line and 88.8 +/- 1.6 mm Hg (mean +/- S.E., n = 19, P < 0.001) for another, as compared with 100.5 +/- 0.8 mm Hg (mean +/- S.E., n = 18) for control mice. Direct blood pressure measurements of these transgenic mice through an arterial cannula showed similar reductions of blood pressure. Intravenous injection of purified RKBP into mice via a catheter produced a dose-dependent reduction of the mean arterial blood pressure. Our findings suggest that RKBP may function as a vasodilator in vivo, independent of regulating the activity of tissue kallikrein.

Animals↗
PubMed1996

The cytosolic subunit p67phox contains an NADPH-binding site that participates in catalysis by the leukocyte NADPH oxidase.

The NADPH-dependent respiratory burst oxidase of human neutrophils catalyzes the reduction of oxygen to superoxide using NADPH as the electron donor and is essential for normal host defenses. To gain insight into the function of the various oxidase subunits that are required for the full expression of catalytic activity, we studied the interactions between the 2',3'-dialdehyde derivative of NADPH (NADPH dialdehyde) and neutrophil cytosol. NADPH dialdehyde treatment of cytosol resulted in the loss of the ability of the cytosol to participate in cell-free oxidase activation; this inactivation was blocked by NADPH but not by NAD, NADP, or GTP. Partial purification of neutrophil cytosol yielded a single peak which could restore the activity lost in cytosol treated with NADPH dialdehyde. This peak contained p67phox but not p47phox or Rac2. Purified recombinant p67phox was similarly able to restore the activity lost in NADPH dialdehyde-treated cytosol and bound [32P]NADPH dialdehyde in a specific fashion. The activity of recombinant p67phox in cell-free oxidase assays was lost on treatment with NADPH dialdehyde. Together, these data suggest p67phox contains the catalytic NADPH-binding site of the leukocyte NADPH oxidase.

Aldehydes↗
PubMed1996

Systemic and portal vein delivery of human kallikrein gene reduces blood pressure in hypertensive rats.

There is an inverse correlation between systemic blood pressure and urinary kallikrein levels in humans and hypertensive animal models, suggesting that the tissue kallikrein-kinin system plays an important role in blood pressure regulation. In this study, we explored the potential of human kallikrein gene delivery on blood pressure reduction in spontaneously hypertensive rats (SHR). The human tissue kallikrein gene or cDNA was placed under the control of following promoters: the metallothionein gene metal response-element (MRE-pHK), albumin gene (ALB-pHK), Rous sarcoma virus 3' long terminal repeat (LTR) (RSV-cHK), and cytomegalovirus (CMV-cHK). A single injection of these kallikrein DNAs results in a significant reduction of blood pressure in SHR, which lasts for 5-6 weeks. Systemic delivery of CMV-cHK, RSV-cHK, and MRE-pHK has a greater effect on blood pressure reduction than ALB-pHK, whereas intraportal vein gene delivery of ALB-pHK is more effective than the other kallikrein DNA constructs. The degree of blood pressure reduction depends on the amount of administered DNA and the age of the animals. Reduction of blood pressure was observed in adult, but not young, SHR. The expression of human tissue kallikrein in rats was identified by an ELISA that is specific for human tissue kallikrein. No antibodies to either human tissue kallikrein or its DNA were detected in rat sera after somatic gene delivery. These results show that somatic gene delivery of human tissue kallikrein causes a lowering effect of systolic blood pressure in genetically hypertensive rats and provide valuable information for kallikrein gene therapy in the treatment of hypertension.

Animals↗