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Biomedical subjects

D K Lee

Publications and source records attributed to D K Lee.

At least 127 records · Page 7Linked to original sources

Withdrawing care. Experience in a medical intensive care unit.

OBJECTIVE: To describe the process and outcomes of withdrawing life-sustaining interventions in a medical intensive care unit (MICU). DESIGN: Retrospective case series. SETTING: Medical intensive care unit in a community teaching hospital. PATIENTS: Consecutive series of 28 patients in whom mechanical ventilation, dialysis, and/or vasopressors were withdrawn. We distinguished physiological, neurological, and functional rationales for care withdrawal. MAIN OUTCOME MEASURES: Duration of discussions, MICU length of stay, and hospital survival. RESULTS: Mean +/- SD Acute Physiology and Chronic Health Evaluation (APACHE II) score was 27.1 +/- 7.3 on MICU admission, and average +/- SD predicted hospital mortality was 61% +/- 22%. Discussions leading to withdrawal of care occurred over an average +/- SD of 5.2 +/- 5.5 days, with decisions achieved soonest in cases with poor neurological prognosis. Average +/- SD MICU length of stay was 1.4 +/- 1.8 days following a decision to withdraw MICU care, and only four patients received more than 48 hours of additional MICU care. Four patients were discharged alive from the hospital. CONCLUSIONS: Patients and their surrogates willingly considered outcomes in addition to mortality when considering withdrawal of life-sustaining interventions. Finding an accommodation between physician judgments and patient preferences took time and effort but was an effective means of limiting ineffective life-sustaining efforts. Withdrawing futile or unwanted care was not always fatal.

Decision Making↗

Analysis of thymidine kinase gene expression in preimplantation mouse embryos.

Thymidine kinase (TK) activity was examined during the development of preimplantation mouse embryos. TK activity was increased approximately 20-fold from day 2 embryos (2-cell) to day 5 embryos (late blastocyst). TK activity did not change along with the progression into S-phase of the first and the second cell cycles but increased sharply at S-phase of the third cell cycle. Analysis of TK mRNA with a reverse transcription-polymerase chain reaction (RT-PCR) method showed that the level of TK mRNA was low in ovulated eggs and 1-cell embryos and was hardly detectable in day 2 embryos (2-cell), but sharply increased in day 3 embryos (mixture of 5- to 8-cell and morula). The functional role of 5'-flanking sequence of TK gene was also investigated in preimplantation embryos after microinjection with the DNA construct of 5'-flanking sequence of TK (2.4 kb) linked to bacterial lacZ gene (TK2.5lacZ) into the pronucleus of 1-cell and subsequently by histochemical staining with X-gal. beta-Galactosidase activity was first detected in day 3 embryos (8-cell), and 30% of embryos were stained with X-gal in day 4 and day 5 embryos, respectively. These results show that an increase in TK activity occurred after 2-cell stage, and this increase was primarily due to the embryonic activation of TK gene expression. Also, it appears that the 5'-flanking sequence of TK may directly regulate the TK gene expression at the transcriptional level during preimplantation murine development.

Animals↗

Adult presentation of congenital cystic adenomatoid malformation of the lung: a case report.

Adult presentation of congenital cystic adenomatoid malformation(CCAM) of the lung is so rare that only 5 cases have been reported in the literature to date. We report the case of a 19-year-old female with CCAM in the left lower lobe. Computed tomography showed a multilobulated cystic lesion with multiple air-fluid levels and also showed focal enhancement of the solid component in the eccentrical portion of the lesion. Thoracic aortogram and selected bronchial arteriograms show a slightly enlarged and tortuous bronchial artery feeding the multilobulated cystic lesion. We present the clinical and radiological features of our case with a brief review of the literature.

Adult↗

Respiratory failure in the elderly. Analysis of outcome after treatment with mechanical ventilation.

BACKGROUND: Concerns about rendering futile care, the financial costs of mechanical ventilation, and aging of the population make it important to analyze the benefit of aggressive therapy for respiratory failure in the elderly. METHODS: This study is a retrospective review of 1860 patients treated with mechanical ventilation in the medical intensive care unit for more than 3 hours between 1974 and 1985. Patients were assigned to one of nine diagnostic groups, and 10 premorbid chronic illnesses or organ system dysfunctions were recorded. Survival to discharge was determined for all patients, and the duration of survival after discharge was determined for patients aged 80 years and older. Two hundred eighty-two patients aged 80 years and older were compared with 1578 patients less than 80 years of age. RESULTS: Fifteen percent of patients treated with mechanical ventilation were 80 years of age or older. Forty-four percent of patients younger than 80 years, and 30.9% of patients aged 80 years and older survived to discharge. Patients aged 80 years or older with preexisting renal disease, liver disease, cancer, systemic illness, or chronic gastrointestinal disease with malnutrition had only a 7% survival compared with 29% for younger patients. For patients without these premorbid conditions (80% of both the younger and older groups) survival among the elderly was better, even though it was still poorer than for younger patients (38% vs 49%). Elderly patients requiring more than 15 days of mechanical ventilation had a 9% survival compared with 36% for younger patients. CONCLUSIONS: A subgroup of patients 80 years of age or older can be identified whose chance for survival from respiratory failure is so poor that withholding or withdrawing treatment with mechanical ventilation may be appropriate. For the majority of elderly patients, short-term survival is nearly as good as in younger patients. Further studies are needed that assess long-term survival and functional recovery after treatment for respiratory failure so that elderly patients and their physicians can better decide whether or not to choose treatment with mechanical ventilation.

Age Factors↗

Oxidative stress induced by glutamate receptor agonists.

The effect of various selective glutamate agonists upon the rate of generation of reactive oxygen species (ROS), was examined in an isolated synaptoneurosomal (microsac) fraction derived from rat cerebral cortex. The rates of ROS generation were determined by a fluorescent probe. Agonists specific for each of the three major glutamate inotropic receptor sites (NMDA, kainic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxalolpropionic acid, AMPA), were able to enhance rates of ROS generation. The metabotropic glutamate agonist trans-1-aminocyclopentane-1,3-dicarboxylic acid, (ACPD), was inactive in this regard. Stimulation of ROS was most pronounced in the case of kainate. Such results could not be replicated by use of ion-channel active agents, veratridine and A23817. Pretreatment with the kainate antagonist, 6-cyano-7-quinoxaline-2,3-dione (CNQX), was not able to block the kainate-induced elevation of ROS. Domoic acid, a kainate agonist, also enhanced microsac ROS generation. Neurological damage may result from generation of excess free radicals, and this may be effected by glutamate agonists acting by means independent of their ionotropic properties.

Animals↗

Effect of age and preoperative airway obstruction on lung function after coronary artery bypass grafting.

To determine whether age or obstructive lung disease affects pulmonary function changes caused by uncomplicated coronary artery bypass grafting, we measured pulmonary function before operation and then 3 or 4 days, 7 days, and 17 +/- 2.2 weeks after operation in elderly patients (age, 74.8 +/- 3.3 years) and patients with obstructive lung disease (ratio of forced expiratory volume in 1 second to forced vital capacity, 0.60 +/- 8.8) and compared the results with those of a "normal" group. In all three groups a severe restrictive defect developed on day 3 (vital capacity, 61% +/- 20% of the preoperative value). Vital capacity recovered to 76.4% +/- 18.5% of the preoperative value on day 7. Three months after coronary artery bypass grafting, lung function had recovered to preoperative baseline (p > 0.2). The percent change from baseline in vital capacity, forced expiratory volume in 1 second, total lung capacity, and diffusing capacity for carbon monoxide was the same in all three groups throughout the study. A severe, reversible restrictive pulmonary function change follows coronary artery bypass grafting. This change is not affected by age or preexisting moderately severe obstructive lung disease.

Age Factors↗

Vasorelaxant effect of the potassium channel activator, RWJ 29009, is tissue selective.

Potassium channel activators have potential cardioprotective properties, in part due to their ability to increase coronary blood flow. We compared the vasorelaxant properties of potassium channel activators, a calcium channel blocker (nicardipine) and a direct smooth muscle relaxant (sodium nitroprusside) in the canine coronary artery, the femoral artery and the saphenous vein precontracted with 0.03 microM endothelin-1. In the circumflex coronary artery, RWJ 29009, a novel and potent potassium channel activator, maximally relaxed the precontracted rings with an EC50 of 1.9 nM. Cromakalim (EC50 = 220 nM) and nitroprusside (EC50 = 109 nM) were also active. Nicardipine (EC50 = 16.6 nM) produced only a 70% relaxation at 1 microM concentration. In both femoral artery and saphenous vein, all agents relaxed the precontracted rings only at much higher concentrations, and the relaxations were only 75% of maximal relaxation. The results show that while all vasodilators preferentially relax the coronary artery, potassium channel activators appear to be the most selective and potent of these agents.

Animals↗

Effect of recombinant human erythropoietin on muscle energy metabolism in patients with end-stage renal disease: a 31P-nuclear magnetic resonance spectroscopic study.

To evaluate the effects of recombinant human erythropoietin (r-HuEPO) on muscle energy metabolism in patients with end-stage renal disease (ESRD), 10 patients receiving maintenance hemodialysis were given r-HuEPO (3,000 U three times a week for 8 weeks). Intracellular phosphocreatine to inorganic phosphate ratios and pH were measured with 31P-nuclear magnetic resonance spectroscopy before and after all-out handgrip exercise, before treatment and at 4 and 8 weeks after r-HuEPO treatment. The same measurements, from 14 normal individuals also were studied for comparison. The hematocrit increased significantly with r-HuEPO treatment, although the dose of r-HuEPO did not correct it to the normal level. The exercise capacity improved significantly. Intracellular pH was not different between the ESRD patients and controls or between before and after r-HuEPO treatment. The phosphocreatine to inorganic phosphate ratio at the resting state improved significantly with r-HuEPO treatment, reaching the same level as the normal subjects even before the low hematocrit normalized. The measurements immediately after exercise were the lowest levels obtained (the nadir state) and were not different between groups. In the state of maximum recovery, a pattern was noted that was similar to that found in the resting state. These results showed that r-HuEPO treatment improved the phosphorylation potential during the resting state and the maximum phosphorylation potential during the postexercise recovery phase, and suggest that the treatment improved the rate of oxidative phosphorylation in ESRD patients receiving hemodialysis.

Adult↗

Potential RNA polymerase II-induced interactions of transcription factor TFIIB.

The ubiquitous transcription factor TFIIB is required for initiation by RNA polymerase II and serves as a target of some regulatory factors. The carboxy-terminal portion of TFIIB contains a large imperfect direct repeat reminiscent of the structural organization of the TATA-binding component (TBP) of TFIID, as well as sequence homology to conserved regions of bacterial sigma factors. The present study shows that the carboxy-terminal portion of TFIIB, like that of TBP, is folded into a compact protease-resistant core. The TFIIB core, unlike the TBP core, is inactive in transcription but retains structural features that enable it to form a complex with promoter-bound TFIID. The protease-susceptible amino terminus appears to contain components responsible for direct interaction with RNA polymerase II (in association with TFIIF) either on the promoter (in association with TFIID) or independently. In addition, core TFIIB (but not intact TFIIB) extends the footprint of TBP on promoter DNA, suggesting that TFIIB has a cryptic DNA-binding potential. These results are consistent with a model in which TFIIB, in a manner functionally analogous to that of bacterial sigma factors, undergoes an RNA polymerase II-dependent conformational change with resultant DNA interactions during the pathway leading to a functional preinitiation complex.

Amino Acids↗

Metastatic involvement of the stomach secondary to lung carcinoma.

Blood-borne metastatic involvement of the stomach by cancer is a rare entity. According to the number of reports in the literature, the most common tumors that spread to the stomach through the blood stream are malignant melanoma, breast carcinoma and lung carcinoma. Recently, two cases of metastatic involvement of the stomach secondary to lung carcinoma were diagnosed by gastroscopy. The first patient was a 66-year-old man who had primary lung carcinoma with multiple bone and subcutaneous metastases. Gastroscopy showed multiple submucosal tumors with central umbilications in the fundus and in the upper body of the stomach. Pathologic examination revealed massive submucosal infiltration and conical shaped and scanty deep mucosal infiltration of undifferentiated small cell carcinoma suggestive of metastatic involvement. The second patient was a 68-year-old man who had primary lung carcinoma with brain metastasis. Gastroscopy showed a large fungating mass in the greater curvature side of the stomach. Pathologic examination revealed poorly differentiated squamous cell carcinoma. We report the two cases of metastatic gastric cancer from lung carcinoma with the literature review.

Aged↗

The thrombolytic effect of lumbrokinase is not as potent as urokinase in a rabbit cerebral embolism model.

The purpose of the present study is to determine whether lumbrokinase has an in vivo thrombolytic effect in a rabbit cerebral embolism model. In our previous studies, we found that lumbrokinase, an extract from Korean earth worms, has a strong in vitro fibrinolytic effect without the presence of plasminogen and significant in vivo thrombolytic effects of lumbrokinase in a rat human-clot-induced cerebral embolism model. We established the cerebral embolism model in rabbits by injecting a piece of human clot into the internal carotid artery via the external carotid artery and confirmed the occlusion with angiography. Twenty one rabbits were divided into three groups and 5cc of saline, urokinase of 50,000 u/ml, and equipotent LK were injected intraarterially for 30 minutes into each group of 7 animals. Ten minutes after the end of infusion, an angiogram was performed to confirm the recanalization. Clot lysis occurred in one, six, and one animals in the saline, urokinase and lumbrokinase treated groups respectively. With regard to its in vitro effect, lumbrokinase is not as potent in vivo. Further investigation should be performed to determine the cause of its weakened in vivo effect and to develop a method to potentiate it.

Animals↗

Botulinum a toxin treatment of hemifacial spasm and blepharospasm.

We studied the effects of botulinum A toxin in 101 patients with hemifacial spasm and 11 patients with blepharospasm in an open trial and double blind manner. All patients in the open trial and 6 patients in the double blind trial improved after the first injection of botulinum toxin. There was no improvement with placebo. The peak effect ranged from one to 6 days after injection and mean peak effect was 3.6 days in blepharospasm, and 4 days in hemifacial spasm. Of 144 treatments, 98.6% had excellent results, (below grade I). The duration of beneficial effect ranged 11 to 40 weeks (mean 16.5 weeks) in hemifacial spasm and 9 to 30 weeks (mean 14.2 weeks) in blepharospasm. Complications were encountered in 63.4% in hemifacial spasm and 72.7% in blepharospasm. The common side effects were dry eyes, mouth droop, ptosis and lid edema in order of frequency. These side effects were mild and resolved spontaneously in 1 to 3 weeks. Botulinum A toxin therapy is effective and convenient, and the treatment of choice for patients with hemifacial spasm and blepharospasm.

Adult↗

Left ventricular hypertrophy in black and white hypertensives. Standard electrocardiographic criteria overestimate racial differences in prevalence.

OBJECTIVE: To assess racial differences in the accuracy of standard electrocardiographic (ECG) criteria in the diagnosis of left ventricular hypertrophy (LVH). DESIGN: The sensitivity and specificity of standard ECG criteria were compared in blacks and whites using echocardiographic LVH as the reference standard. SETTING: Eight worksite-based hypertension clinics in New York, NY. PATIENTS: A sample of 122 black and 148 white hypertensive patients. RESULTS: The prevalence of ECG-LVH was two to six times higher in blacks than in whites, depending on the criteria used (range, 6% to 24% in blacks vs 1% to 7% in whites; P = .0005 to .19 for black-white comparisons). The difference in prevalence of echocardiographic LVH [corrected], however, was less striking and did not attain statistical significance (26% in blacks and 20% in whites; P greater than .2). The sensitivity of the ECG was low (range, 3% to 17%) and did not differ significantly between the two races for any of the conventional criteria; specificity, however, was lower in blacks for all criteria (range, 73% to 94% vs 95% to 100% for whites; P = .0001 to .09). The predictive value of a positive ECG was consistently, although not significantly, lower in the black subjects. Black race was the strongest independent predictor of decreased ECG specificity in multiple logistic regression analysis that also considered age, gender, body mass index, left ventricular mass index, and smoking. CONCLUSIONS: Commonly used ECG criteria for the detection of LVH have a poor sensitivity in both black and white hypertensives and a lower specificity in blacks than in whites; this may lead to a greater number of false-positive diagnoses in black patients, as well as to an overestimation of black-white difference in LVH prevalence.

Black People↗

Inhibitory effect of purines in meiotic maturation of denuded mouse oocytes.

The potential action of purines, such as hypoxanthine and adenosine, in meiotic arrest was examined using denuded mouse oocytes. The spontaneous meiotic maturation of denuded oocytes was significantly inhibited by hypoxanthine and/or adenosine in a dose-dependent manner. Germinal vesicle breakdown (GVBD) was inhibited even at a low concentration (1 nM) of hypoxanthine, when hypoxanthine was microinjected into the cytoplasm of denuded oocytes. This inhibitory action was potentiated by co-injection with allopurinol, a metabolic blocker of hypoxanthine that can block a metabolic pathway to uric acid. By contrast, a microinjection of adenosine was no longer effective in inhibiting GVBD. Inhibitory action of purines in meiotic maturation was correlated with sustaining intracellular cAMP levels. GVBD was resumed by econazole, one of the nitroimidazole derivatives which act as inhibitors of catalytic subunit of adenylate cyclase. This compound was effective in counteracting the effect of adenosine, but not the action of 3-isobutyl-1-methylxanthine (IBMX) on GVBD, indicating that adenosine is probably exerted at the level of oocyte plasmalemma. These data suggest that the inhibitory action of hypoxanthine and adenosine in oocyte meiotic maturation may be involved in the regulation of cAMP metabolism in a differential manner.

1-Methyl-3-isobutylxanthine↗