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Biomedical subjects

T C Lee

Publications and source records attributed to T C Lee.

At least 127 records · Page 7Linked to original sources

Ischemic colitis complicating abdominal aortic aneurysm surgery in the U.S. veteran.

Ischemic colitis (IC) is an infrequent but serious complication of abdominal aortic surgery. Prior reports have generally described small, selected populations. The aim of this paper is to evaluate characteristics of clinically diagnosed IC in a large non-referral-based population. Using national Veterans Affairs (VA) computer data sets, we identified all patients with the diagnostic codes for both prosthetic replacement of aorta for abdominal aortic aneurysm and subsequent vascular insufficiency of the intestine in the entire VA population from 1987 to 1991. Clinical information on these patients was then requested from the VA Medical Centers where they received care. Patients demographics, clinical data regarding both the aortic surgery and IC, and survival data were extracted from patient charts and computer records. Of 4957 patients who underwent surgery of the abdominal aorta for infrarenal abdominal aortic aneurysm, 58 (1.2%) also had the code for subsequent IC. In 49/58 (74%), sufficient chart-derived and computer-derived data were available for analysis. The mean age was 69 (range 57-95); all were males. Bloody diarrhea was the most frequent symptom and colonoscopy the most common means of diagnosis. Mean time to diagnosis of IC was 5.5 days after aortic surgery (range 1-21 days). Aneurysmal rupture or perioperative hypotension were present in 35/49 patients. Bowel resection with fecal diversion was required in 32/49 (65%). The overall mortality was 54% but it was 89% if bowel resection for bowel infarction was required. Only 2/12 (16%) of those who required fecal diversion and survived underwent eventual stoma closure. Among 7 patients who received second-look laparotomy for IC, additional bowel resection was required in 6. No patient had aortic graft infection diagnosed during the index hospitalization. The overall mean hospitalization duration after the diagnosis of IC was 38 days (range 1-164). IC following aortic aneurysm surgery in this national patient population is infrequently diagnosed. Emergency aneurysm operation and perioperative hypotension are common in patients who develop IC. The majority of patients diagnosed receive surgical intervention. Most patients who undergo fecal diversion retain their stomas.

Aged↗

Biosynthesis of N-acetylsphingosine by platelet-activating factor: sphingosine CoA-independent transacetylase in HL-60 cels.

We have previously identified a novel CoA-independent transacetylase in the membrane fraction of HL-60 cells that transfers the acetate group from platelet activating factor (PAF) to a variety of lysophospholipid acceptors (Lee, T.-c., Uemura, Y., and Snyder, F. (1992) J. Biol. Chem. 267, 19992-20001). In the present study, we demonstrate that a similar transacetylase can transfer the acetate group from PAF to sphingosine forming N-acetylsphingosine (C2-ceramide). The chemical structure of the reaction product, C3-ceramide, was established by its identical Rf value with authentic C2-ceramide standard on thin-layer plate, sensitivity to acid treatment, resistance to alkaline hydrolysis, and ability to form the C2-ceramide dibenzoate derivative. Nonspecific transfer of the acetate from PAF to sphingosine in the absence of enzyme and nonlinearity of the reaction rates were rectified by complexing sphingosine to bovine serum albumin in a 1:1 molar ratio. Under these conditions, the apparent Km for PAF is 5.4 microM, which is in the same range as the Km (12.0 microM) when lysoplasmalogen is the acetate acceptor. PAF:sphingosine transacetylase has a narrow substrate specificity and strict stereochemical configuration requirements. Ceramide, sphingosylphosphocholine, stearylamine, sphingosine 1-phosphate, or sphingomyelin are not substrates, whereas sphinganine has a limited capacity to accept the acetate from PAF. Also, only the naturally synthesized D-erythroisomer but not the synthetic L-erythro-, D-threo-, or L-threosiomers of sphingosine can serve as a substrate. PAF transacetylase activity is widely distributed among several tissues and may involve histidine and cysteine for its catalytic activity due to inhibitory effects to the enzyme by diethyl pyrocarbonate and N-ethylmaleimide, respectively. C2-ceramide is produced via PAF:sphingosine transacetylase, and physiological levels of C2-ceramide are detected in both undifferentiated and differentiated intact HL-60 cells. Collectively, because C2-ceramide has many biological activities that differ from that of PAF and sphingosine, the CoA-independent, PAF-dependent transacetylase serves as a modifier of PAF, and sphingosine functions by generating a variant lipid mediator, C2-ceramide.

Acetyltransferases↗

Cellular uptake of trivalent arsenite and pentavalent arsenate in KB cells cultured in phosphate-free medium.

Trivalent arsenite (As(III)) and pentavalent arsenate (As(V)) have been shown to have differential uptake mechanisms. In regular RPMI 1640 medium, As(III) was about 40-fold more toxic to KB oral epidermoid carcinoma cells. However, the cytotoxicity and intracellular accumulation of As(V) were dramatically enhanced, equalling those of As(III) when cells were grown in phosphate-free RPMI medium, As(V) uptake was dose-dependently inhibited by phosphate, mersalyl acid (a membrane sulfhydryl agent), and energy poisons, such as sodium azide and potassium cyanide. These results suggest that As(V) and phosphate share a common transport system. In contrast, As(III) uptake was not affected by the above agents. However, the initial uptake rates of As(III) were linearly correlated with its extracellular concentrations, suggesting that As(III) uptake is probably accomplished through simple diffusion. Our results also show that As(III) and As(V) are excreted from KB cells at a comparable rate, and at least half of As(V) is reduced to the more toxic As(III) prior to excretion into the medium. Therefore, the toxicity of As(V) may in part result from its reduction to As(III).

Arsenates↗

Arsenite efflux is inhibited by verapamil, cyclosporin A, and GSH-depleting agents in arsenite-resistant Chinese hamster ovary cells.

We have previously demonstrated that arsenite-resistant SA7 cells can extrude arsenite more effectively and completely than their parental Chinese hamster ovary cells. Our present results show that arsenite efflux from SA7 cells is inhibited by chemosensitizing agents to multidrug resistant-associated protein: verapamil and cyclosporin A and by glutathione-depleting agents: dinitrofluorobenzene and diethyl maleate. These results suggest that arsenite extrusion in SA7 cells may be mediated by a GSH-dependent and verapamil- and cyclosporin A-sensitive membrane transport system. Since arsenite extrusion was found dose-dependently inhibited by energy poison [potassium cyanide (KCN)] and an ATPase inhibitor (sodium vanadate), ATP is apparently required for arsenite extrusion in SA7 cells.

Animals↗

Aneurysm of superior branch of anterior choroidal artery mimicking carotid bifurcation aneurysm--case report.

Aneurysm of the superior branch of anterior choroidal artery is very rare. We report this rare case with unique angiographic findings mimicking an internal carotid bifurcation aneurysm. A 35-year-old woman was admitted to our hospital because of severe headache. Lumbar puncture disclosed numerous red blood cells. Computed tomography revealed an enhanced circular area in the left basal cistern with moderate hydrocephalus. Cerebral angiography showed a saccular aneurysm near the left internal carotid bifurcation. During operation, the aneurysm was not found at the internal carotid bifurcation, but located deeper budding from the superior branch of the anterior choroidal artery. The aneurysm was successfully clipped. The postoperative course was favourable without any neurological deficit. The postoperative angiogram showed that the aneurysm was clipped well with preservation of the main trunk of the anterior choroidal artery. Computed tomography of the brain did not show any infarction area, 3 months after the surgery. The uniqueness of this case is the favourable outcome after sacrificing the superior branch of the anterior choroidal artery. The role of collaterals of the anterior perforating substance is emphasized.

Adult↗

Transpedicular reduction and stabilization for postlaminectomy lumbar instability.

This study retrospectively reviewed the outcomes of 17 patients with postlaminectomy lumbar instability treated by transpedicular reduction and stabilization. The criteria of instability were defined strictly by both the clinical symptom of "instability catch" and the radiological findings that fulfilled Nachemson's criteria. Low back pain and/or sciatica that interfered largely with the patients' work or quality of life were the indications for this treatment. All the operations were performed by one surgeon with the same spinal instrumentation system-"AO internal fixator". The follow-up period was between 16 and 36 months (mean 24 months). Face to face questionnaire revealed that this treatment modality is encouraging. Fourteen patients (82%) had complete or nearly complete relief from all the pre-operative symptoms. Two (12%) had partial relief of the symptoms that required a subsequent discectomy or wider laminectomy. Only one case (6%) with osteoporosis remained unchanged after the operation. On the follow-up radiographs, sixteen patients (94%) showed good alignment and solid arthrodesis of the treated motion segment. These radiological findings correlated quite well with the absence of the clinical symptom of "instability catch". A common, but acceptable, complication found in this series was a variable degree of low back stiffness secondary to the instrumentation. Fracture of the screw was found in one patient and pull out of the screw was found in another patient. However, they did not elicit detectable symptoms. Osteoporosis, concomitant disc herniation and persistent spinal stenosis at/or adjacent to the operated level were the three main factors that may contribute to unsatisfactory results secondary to this treatment. These problems remain to be resolved in the future.

Adult↗

Prolonged, complete remission after 2-chlorodeoxyadenosine therapy in a patient with refractory essential mixed cryoglobulinemia.

Essential mixed cryoglobulinemia is a systemic disorder in which cutaneous vasculitis and frequently glomerulonephritis are associated with cryoprecipitable serum immune complexes. Typically, the treatment regimen consists of plasmapheresis, high-dose corticosteroids, and cytotoxic chemotherapy, as well as interferon alfa for hepatitis C virus-related cryoglobulinemia. Herein we describe a man with progressive, symptomatic cryoglobulinemia and multisystem organ dysfunction in whom corticosteroid and alkylating therapy failed; however, he had a complete and long-lasting remission after administration of 2-chlorodeoxyadenosine (cladribine).

Aged↗

Saliva as a valid alternative to serum in monitoring intravenous caffeine treatment for apnea of prematurity.

Caffeine is a potentially useful alternative to theophylline for the treatment and prevention of apnea of prematurity because of its lower toxicity and longer terminal half-life. Monitoring of salivary caffeine concentrations is less invasive than blood sampling, especially in very sick premature neonates. Caffeine citrate-3 mg/kg, 15 mg/kg, or 30 mg/kg-was administered once daily for 7 days in a randomized, parallel design to 59 newborn, premature infants with an initial loading dose of twice the maintenance dose. Serum and saliva samples (131 pairs) were collected and assayed by high-performance liquid chromatography (HPLC) for caffeine content. Measurable caffeine concentrations in serum ranged from 0.28 to 93.3 mg/L and in saliva from 0.35 to 91.5 mg/L. The mean ratio of the saliva-to-serum concentrations was 0.924. There was no significant difference in precision between the serum and salivary data. The mean serum caffeine concentration was 29.9 mg/L, and the mean salivary concentration was 27.7 mg/L, indicating a small negative bias for saliva versus serum monitoring. Salivary caffeine concentration monitoring is a satisfactory alternative to blood sampling across a wide range of caffeine doses used to treat apnea.

Apnea↗

Theophylline population pharmacokinetics from routine monitoring data in very premature infants with apnoea.

1. Theophylline is commonly used in neonatology for the treatment and prophylaxis of apnoea of prematurity, and during ventilator weaning. 2. NONMEM was used to study the population pharmacokinetics of intravenous and oral theophylline from retrospective drug monitoring data in 82 premature neonates, weighing < 1500 g at birth, and < or = 32 weeks gestational age. 3. Clearance (CL), volume of distribution (V), and oral bioavailability (F1) from liquid preparations were modelled alone, and under the influence of demographic and clinical covariates, assuming a 1-compartment model with first-order elimination. 4. The final population models with influential co-variates were as follows: CL (1h-1) = 0.0000123 *body weight (g) + 0.000377 *postnatal age (days); V (1) = 0.000937 *body weight (g); F = 0.918. 5. The CL was lower and V was higher than previously reported for less premature neonates, term babies, and older children. 6. Predictive performance of the population models was evaluated by Bayesian forecasting in a similar, but independent cohort of 30 infants. There was statistically insignificant bias and imprecision between measured and predicted serum theophylline concentrations. 7. Based on the validated population models, recommended maintenance theophylline dosages are provided for infants aged between 2 and 50 days, and weighing 700 to 2000 g.

Apnea↗

Transforming growth factor-beta (TGF-beta) in silicosis.

Silicosis is characterized by fibrosing nodular lesions that may eventually develop into progressive massive fibrosis (PMF). Cytokines (interleukin-1beta [IL-1beta], tumor necrosis factor-alpha [TNF-alpha] and growth factors insulin-like growth factor-1 [IGF-1] platelet-derived growth factor [PDGF]) have been implicated in the formation of these lesions. TGF-beta promotes extracellular matrix accumulation by upregulating collagen and fibronectin gene expression, and inhibits matrix degradation by decreasing secretion of proteases and increasing secretion of protease inhibitors. We hypothesized that TGF-beta is associated with matrix deposition and fibrosis in silicosis. To test this hypothesis we studied early and late nodular lesions and PMF (11 cases and two controls) with immunohistochemistry, using rabbit polyclonal antibody to the purified whole molecule of TGF-beta in Bouin's fixed lung tissue. This antibody is reactive with both intra- and extracellular forms of TGF-beta. In the control lungs, small amounts of TGF-beta were present in the bronchial epithelium, macrophages, bronchial and vascular smooth muscle, and bronchial glands. There was minimal to moderate staining in the early silicotic peribronchiolar lesions. In the nodular lesions of silicosis, central hyalinized areas contained the maximum staining for TGF-beta. Fibroblasts in the periphery of the nodular lesions were also positive. In acute silicosis, there was marked staining of hyperplastic alveolar epithelium. Macrophages were markedly positive. In the PMF lesions, large areas of scar tissue contained TGF-beta. These data suggest a major role for TGF-beta in silicosis, particularly in the formation of silicotic nodules and the development of PMF.

Adult↗

Hemifacial spasm caused by a venous angioma. Case report.

The authors describe the case of a 53-year-old woman who suffered from a hemifacial spasm caused by a venous angioma in the posterior fossa. At operation the parenchymal segment of the angioma was preserved and vascular decompression was performed by placing pieces of shredded Teflon between the vessel and nerve. After decompression the patient was completely free from spasm.

Cerebral Angiography↗

Seeing the wood for the trees--the early papers of Denis Burkitt.

Denis Burkitt's was a remarkable career. A surgeon in the Colonial Medical Service in Uganda, his keen observation of the incidence of jaw tumours in children led him to describe a new form of lymphatic cancer. He confirmed, for the first time in man, that a cancer was caused by a virus and, most remarkable of all, he discovered a cure--low-dose chemotherapy. The condition was named after him--Burkitt's lymphoma--and with this came membership of a select group of eponymous Irishmen, including Graves, Colles and Corrigan. His ability to link the incidence of disease with geographical distribution brought him, first to question and then to champion Peter Cleave's theory that lack of dietary fibre contributed to many of the diseases common in western civilisation. In the process, he changed the dietary habits of the Western world. Yet Denis Burkitt's early career in Trinity College, Dublin was not auspicious for, as a Junior Freshman engineer in 1929, his tutor despaired of him, writing to his father 'Don't blame me if he gets stuck'. A happy irony then, that the College made him an Honorary Fellow half a century later.

Burkitt Lymphoma↗

Extramedullary thoracic myxopapillary ependymoma--a case report of a rare tumour.

We report a case of thoracic exophytic myxopapillary ependymoma with imaging modality mimicking an intradural extramedullary tumour. This tumour showed hypointense relative to the spinal cord on T1-weighted (TR516/TE17) images and hyperintense on T2-weighted (TR4000/TE84) images. It revealed strong enhancement on T1-weighted (TR500/TE11) images. These findings were diagnosed as a meningioma by the radiologist. The tumour was proven to arise from the ventral side of the thoracic cord, and was totally excised. It was verified histopathologically as a myxopapillary ependymoma.

Diagnosis, Differential↗

Sodium arsenite induces chromosome endoreduplication and inhibits protein phosphatase activity in human fibroblasts.

Arsenic, strongly associated with increased risks of human cancers, is a potent clastogen in a variety of mammalian cell systems. The effect of sodium arsenite (a trivalent arsenic compound) on chromatid separation was studied in human skin fibroblasts (HFW). Human fibroblasts were arrested in S phase by the aid of serum starvation and aphidicolin blocking and then these cells were allowed to synchronously progress into G2 phase. Treatment of the G2-enriched HFW cells with sodium arsenite (0-200 microM) resulted in arrest of cells in the G2 phase, interference with mitotic division, inhibition of spindle assembly, and induction of chromosome endoreduplication in their second mitosis. Sodium arsenite treatment also inhibited the activities of serine/threonine protein phosphatases and enhanced phosphorylation levels of a small heat shock protein (HSP27). These results suggest that sodium arsenite may mimic okadaic acid to induce chromosome endoreduplication through its inhibitory effect on protein phosphatase activity.

Arsenites↗

Differential cytotoxicity of cadmium to rat embryonic fibroblasts and human skin fibroblasts.

In order to identify why cadmium is differentially toxic to humans and rats, we compared cadmium-induced cytotoxic responses in rat embryonic fibroblasts (REF) and human skin fibroblasts (HFW). According to the values of the lethal concentration 50% for cadmium, REF were about 13-fold more sensitive than HFW to cadmium acetate (1.5 vs 25 microM). Furthermore, progression of S phase cells was more severely delayed by cadmium in REF than in HFW. At doses that killed 90% of REF or HFW (5 or 50 microM, respectively), 50% of DNA synthesis was inhibited in REF, whereas DNA synthesis was not apparently inhibited in HFW. The differential sensitivity to cadmium could not be simply due to different basal levels of metallothionein, since the cellular metallothionein content in HFW was only 1.6 times that in REF, and metallothionein was apparently induced by cadmium in both cells with similar synthesis rates. Furthermore, elevation of cellular metallothionein levels by zinc sulfate pretreatment decreased cadmium toxicity in both cell types, but did not alter their relative sensitivity to cadmium. The differential sensitivity was also not due to differences in cadmium accumulation, since HFW accumulated more cadmium than REF after a 24-hr exposure to 1 or 5 microM cadmium acetate. Although most of the cadmium remained in the cytoplasm, the nuclei of REF contained 12-fold more cadmium than nuclei of HFW (1.31 vs 0.11 micrograms Cd/mg nuclear protein). Therefore, our results indicate that a high level of cadmium accumulation in nuclei of REF may be responsible for cell killing through breakdown of nuclear functions.

Animals↗

Modulation of cellular antioxidant defense activities by sodium arsenite in human fibroblasts.

Many studies have shown that oxygen radicals can be produced during arsenic metabolism. We report here that in human fibroblasts (HFW cells) sodium arsenite exposure caused increased formation of fluorescent dichlorofluorescein (DCF) by oxidation of the nonfluorescent form. The enhanced DCF fluorescence was inhibited by a radical scavenger, butylated hydroxytoluene. The effects of sodium arsenite treatment on cellular antioxidant activities were then examined. Treatment of HFW cells with sodium arsenite resulted in a significant increase in heme oxygenase activity and ferritin level. Sodium arsenite-enhanced heme oxygenase synthesis was inhibited by co-treatment of cells with the antioxidants sodium azide and dimethyl sulfoxide. Furthermore, sodium arsenite treatment did not apparently affect glucose-6-phosphate dehydrogenase activity, but resulted in significantly increased glutathione levels and superoxide dismutase activity, slightly decreased glutathione peroxidase activity, and significantly decreased catalase activity. Sodium arsenite toxicity was partly reduced by addition of catalase to the culture medium. These results imply that arsenite can enhance oxidative stress in HFW cells.

Arsenites↗

Quantitative arteriography of apparently normal coronary segments with nearby or distant disease suggests presence of occult, nonvisualized atherosclerosis.

OBJECTIVES: The aim of this study was to evaluate, using quantitative arteriography, whether the diameter of visually normal coronary segments might be influenced by the relative proximity of visually apparent disease. BACKGROUND: Severity of coronary artery lesions is commonly referenced against a presumed normal nearby coronary segment with the presumption that visually smooth segments are relatively free of atherosclerotic disease. METHODS: Angiograms from 136 male patients with focal coronary disease were examined, and visually normal segments in the proximal portions of the major vessels were identified for measurement of mean segment diameters. Normal segments with immediately adjacent disease were compared with normal segments with distal disease in the same vessel and compared with normal segments in vessels for which the only other visible disease was in distant vessels. Angiograms with entirely normal findings from 26 age-matched men with atypical chest pain were used as controls. Segments were measured after nitroglycerin administration by means of computer-assisted quantitation. RESULTS: Mean diameters of visually normal segments with distant disease were smaller than those of control segments (p < 0.05). Normal left main and proximal left anterior descending coronary artery segments in patients with disease within the same vessel were significantly smaller than normal segments in patients with distant disease (p < 0.05). Normal segments with immediately adjacent disease had smaller mean diameters than normal segments with distal disease in the same vessel (p < 0.05). CONCLUSIONS: Visually normal coronary segments have progressively smaller lumen diameters, depending on the relative proximity of visible disease. Measurement of percent stenosis on the basis of the diameter of apparently normal adjacent reference segments can result in underestimation of coronary lesion severity.

Cardiac Catheterization↗