Biomedical subjects

R Lee

Publications and source records attributed to R Lee.

At least 73 records · Page 4Linked to original sources

PubMed2001

The neuropsychopharmacology of criminality and aggression.

Although the idea that aggression has biological components is not a new one, recent research in genetics, neuropsychopharmacology, and neuroimaging has helped clarify the biological contributions to aggression. Studies to date have focused on serotonergic function and impulsive aggression. Reduced levels of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) are associated with impulsive aggression. Pharmacochallenge studies have found decreased serotonergic responsiveness associated with impulsive aggression. Neuroimaging studies suggest a role for the prefrontal cortex, along with other regions of the brain, in the expression of aggression. Serotonin is not the only aspect of brain function implicated in impulsive aggression, and further work is being done on other neurotransmitters and neuropeptides.

Aggression↗

PubMed2001

Contact mechanics of a novel metal-on-metal total hip replacement.

The contact mechanics of a novel metal-on-metal total hip replacement (THR) were investigated in this study. The metal-on-metal prosthesis considered consists of a cobalt-chrome acetabular insert connected to a titanium shell through a taper contact, articulating against a cobalt-chrome femoral head. Both the experimental measurement of the displacement of the acetabular insert and the contact area between the two bearing surfaces, and the corresponding numerical predictions using the finite element method have been conducted. Excellent agreement has been demonstrated between the experimental measurement and the finite element prediction under various loads up to 3 kN. The maximum contact pressure at the articulating surfaces has been predicted to be about 31 MPa from a simple axisymmetric finite element model, significantly lower than that of a similar cup but with a monoblock construct. This has been mainly attributed to the flexibility of the insert, leading to an increase in the conformity between the femoral head and the acetabular insert. In addition, the predicted maximum contact pressure is only slightly increased to 37 MPa, from a more realistic three-dimensional anatomical finite element model. The design features on metal-on-metal THRs have been shown to reduce contact stresses and may improve tribological performances of these hard-on-hard bearing couples.

Biomechanical Phenomena↗

PubMed2001

Evaluating the performance of the Lee-Carter method for forecasting mortality.

Lee and Carter (LC) published a new statistical method for forecasting mortality in 1992. This paper examines its actual and hypothetical forecast errors, and compares them with Social Security forecast errors. Hypothetical historical projections suggest that LC tended to underproject gains, but by less than did Social Security. True e0 was within the ex ante 95% probability interval 97% of the time overall, but intervals were too broad up to 40 years and too narrow after 50 years. Projections to 1998 made after 1945 always contain errors of less than two years. Hypothetical projections for France, Sweden, Japan, and Canada would have done well. Changing age patterns of mortality decline over the century pose problems for the method.

Age Factors↗

PubMed2001

Medical management of a large aortic thrombus in a young woman with essential thrombocythemia.

Aortic thrombus formation is rare in the patients with essential thrombocytosis (ET); therefore, no guidelines for its management have been established. Embolism from ET-associated large vessel thrombi is potentially lethal and has been managed surgically in a few reported cases. We describe herein a 45-year-old black woman with ET found to have a 3.5-cm, pedunculated intra-aortic thrombus at the thoracoabdominal junction. How to treat this potentially devastating aortic thrombus was a management dilemma. We believed, based on the patient's diagnosis of ET and the histology of similar thrombi in 1 reported series, that the aortic thrombus was a "white thrombus" consisting primarily of aggregated platelets with a minimal fibrin network and almost no entrapped erythrocytes. The patient was treated with aspirin, 325 mg daily, as a platelet antiaggregating agent and hydroxyurea, 1,500 mg daily, to reduce the platelet count to less than 450 x 10(9)/L. The thrombus resolved without severe thromboembolic events. To our knowledge, this is the first reported case of a large intra-aortic thrombosis associated with ET that has been successfully managed with medical therapy alone.

Aorta, Abdominal↗

PubMed2001

Case report: catheter-related epidural abscess.

INTRODUCTION: Catheter-related spinal epidural abscesses are rare but increasing in incidence. CLINICAL PICTURE: An elderly gentleman received 4 days of continuous epidural analgesia following multiple traumatic rib fractures. Five days subsequently, he developed an extensive epidural abscess accompanied by backache, lower limb weakness, fever, leukocytosis and Staphylococcal bacteraemia. TREATMENT: He received appropriate intravenous antibiotics and underwent an emergent decompressive laminectomy. OUTCOME: A good outcome was achieved because of prompt diagnosis, appropriate intravenous antibiotics and timely surgical intervention. CONCLUSIONS: It is important to be vigilant and continue to maintain good clinical practice and a high index of suspicion for this procedural-related complication.

Analgesia, Epidural↗

PubMed2001

A defect in HIV-1 transgenic murine macrophages results in deficient nitric oxide production.

HIV transgenic mice bearing multiple copies of a noninfectious (Deltagag/pol) proviral DNA were tested for the systemic production of nitric oxide (NO). Serum levels of NO metabolites were reduced about 50% in HIV transgenic mice compared with nontransgenic sibling mice. This difference persisted when NO production was induced with peritoneal injections of bacterial endotoxin (LPS). Peritoneal inflammatory macrophages, but not resident peritoneal macrophages, derived from HIV-1 transgenic mice and activated in vitro with LPS and IFN-gamma (or tumor necrosis factor alpha and IFN-gamma) also produced about 50% less NO than did macrophages harvested from nontransgenic littermates. Isogenic, transgenic mice bearing mutated nef or vpr genes had normal serum levels of NO metabolites and their macrophages produced normal levels of NO when stimulated. An explanation for the reduced NO response of HIV[Vpr+Nef+] macrophages was not apparent from measured levels of iNOS expression, viral gene expression, or arginase activity in activated macrophages. Inhibition of nitric oxide synthase (NOS) isoforms with L-NAME or aminoguanidine blocked time-dependent increases in HIV gene expression in activated macrophages cultured ex vivo. Inhibition with L-NAME occurred despite high levels of NO generated by iNOS, and exogenously supplied NO induced HIV gene expression only weakly, suggesting that cNOS had the greater influence on proviral gene induction. This system is presented as a model of HIV-1 proviral gene expression and dysfunction in macrophages.

Animals↗

PubMed2001

Combining decision support and image processing: a PROforma model.

This paper addresses two important problems in medical image interpretation:(1) integration of numeric and symbolic information, (2) access to external sources of medical knowledge. We have developed a prototype in which image processing algorithms are combined with symbolic representations for reasoning, decision making and task management in an integrated, platform-independent system for the differential diagnosis of abnormalities in mammograms. The prototype is based on PROforma, a generic technology for building decision support systems based on clinical guidelines. The PROforma language defines a set of tasks, one of which, the enquiry, is used as means of interaction with the outside world. However, the current enquiry model has proved to be too limited for our purposes. In this paper we outline a more general model, which can be used as an interface between symbolic functions and image or other signal data.

Algorithms↗

PubMed2001

Absorption of benzoic acid in segmental regions of the vascularly perfused rat small intestine preparation.

Oral bioavailability is a consequence of intestinal absorption, exsorption, and metabolism and is further modulated by the difference in activities among segmental regions. The influence of these factors on the net absorption of benzoic acid (BA), a substrate that is metabolized to hippurate and is transported by the monocarboxylic acid transporter 1, was studied in the recirculating, vascularly perfused, rat small intestine preparation. Metabolism of BA was not observed for both systemic and intraluminal injections into segments of varying lengths. But, secretion of BA into lumen was noted. Absorption of BA (0.166-3.68 micromol) introduced at the duodenal end for absorption by the entire intestine was complete (>95% dose at 2 h) and dose-independent, yielding similar absorption rate constants (k(a) of 0.0464 min(-1)). The extent of absorption remained high (92-96% dose) when BA was injected into closed segments of shorter lengths (12 or 20 cm), suggesting a large reserve length of the rat intestine. However, k(a) was higher for the jejunum (0.0519 and 0.0564 min(-1), respectively, for the 12- and 20-cm segments) and exceeded that for the duodenum (12-cm segment, 0.0442 min(-1)) and ileum (20-cm segment, 0.0380 min(-1)) at closed injection sites. The finding paralleled the distribution of monocarboxylic acid transporter isoform 1 detected by Western blotting along the length of the small intestine. Fits of the systemic and oral data (based on duodenal injection for absorption by the whole intestine) to the traditional, physiological model and to the segregated flow model (SFM) that describes partial intestinal flow to the enterocyte region showed a better fit with the SFM even though metabolite data were absent.

Acetaminophen↗

PubMed2000

Mental health. Wrong side of beds.

Bed occupancy in inner city mental health trusts varies widely. The number of admissions outside the patient's local trust also shows wide variations. There is no relationship between the number of acute beds in a trust and the number of admissions outside a trust. The study suggests that opening more beds is not by itself the answer to easing pressure on services.

Bed Occupancy↗

PubMed2000

Expression of cyclooxygenase-1 and cyclooxygenase-2 in the human prostate.

OBJECTIVES: To determine the cell-specific expression of the two major isoforms of cyclooxygenase (COX-1 and COX-2) in human noncancerous and cancerous prostatic tissues. METHODS: Thirty-one specimens of prostate carcinoma (CaP) and 10 specimens of benign prostatic hyperplasia (BPH) were stained with mouse antihuman COX-1 and COX-2 monoclonal antibodies. The stained specimens were analyzed both descriptively and in a semiquantitative manner by assigning an immunoreactive intensity score (0 to 4). The averaged results were compared for different histologic tissue types, including luminal and basal epithelium of BPH, the peripheral zone, high-grade prostatic intraepithelial neoplasia (PIN), and CaP of varying Gleason grades. RESULTS: COX-1 expression in noncancerous prostatic tissue was seen predominantly in the basal epithelial cells of BPH (90% positive staining). COX-1 expression was minimal in noncancerous luminal epithelial cells (0% to 10%) but was upregulated in CaP (63% of CaP specimens). Strong COX-2 expression was demonstrated in the smooth muscle cells of the prostate. COX-2 was also expressed in the basal epithelial cells (60% BPH, 94% peripheral zone, 75% PIN). Luminal epithelial cells derived from BPH, the peripheral zone, and PIN expressed COX-2 in 0%, 26%, and 86% of samples, respectively. COX-2 expression in CaP was intense and uniform, with 87% of samples demonstrating immunoreactivity. CONCLUSIONS: The results of the present study indicate that expression of both COX-1 and COX-2 in human CaP is increased. COX-2 expression is also increased in the basal and luminal epithelial cells of PIN. These data indicate that COX-1 and COX-2 (and/or their prostaglandin products) may play a role in the malignant transformation of the prostate.

Cyclooxygenase 1↗

PubMed2000

Determination of roxithromycin residues in the flounder muscle with electrospray liquid chromatography-mass spectrometry.

A highly sensitive and specific method for the determination of roxithromycin in the flounder muscle by LC-MS was developed and validated. A dichloromethane extract of the sample was separated on C18 reversed-phase column with acetonitrile-50 mM ammonium acetate (80:20, v/v) as the mobile phase and analyzed by LC-MS via atmospheric pressure ionization/electrospray ionization interface. The limit of detection and limit of quantitation were 0.01 and 0.1 ng/g, respectively. Mean recoveries from spiked muscles were 81.1% (ranged from 71.0 to 90.3%) for roxithromycin. The method has been successfully applied to determine roxithromycin in the flounder muscle.

Animals↗

PubMed2000

Intimate partner violence prevalence estimation using telephone surveys: understanding the effect of nonresponse bias.

To assess the effect of nonresponse bias in telephone prevalence studies of intimate partner violence, the authors asked women visiting a health center in Albany, New York, during 1998 about their willingness to participate in telephone surveys. Women physically victimized by a male partner were more likely than other women to say they would participate in telephone surveys (66.7% vs. 44.4%, p = 0.03). Among women severely victimized, those living with their partner were less willing to participate than those not cohabiting (45.5% vs. 91.7%, p = 0.03). Including questions about willingness to participate in telephone surveys in studies of other kinds may be a useful method of identifying nonresponse bias.

Adolescent↗

PubMed2000

Development of disulfide peptide mapping and determination of disulfide structure of recombinant human osteoprotegerin chimera produced in Escherichia coli.

Recombinant human osteoprotegerin chimera is a 90-kDa protein containing a human IgG Fc domain fused to human osteoprotegerin. The molecule is a dimer linked by two intermolecular disulfide bonds and contains eleven intramolecular disulfide bonds per monomer. A cysteine-rich region in osteoprotegerin contains nine disulfide bridges homologous to the cysteine-rich signature structure of the tumor necrosis factor receptor/nerve growth factor receptor superfamily. In this report, we have developed peptide mapping procedures suitable to generate disulfide-containing peptides for disulfide structure assignment of the fusion molecule. The methods employed included proteolytic digestion using endoproteinases Glu-C and Lys-C in combination followed by LC-MS analyses. Disulfide linkages of peptide fragments containing a single disulfide bond were assigned by sequence analysis via detection of (phenylthiohydantoinyl) cystine and/or by MS analysis. Disulfide bonds of a large, core fragment containing three peptide sequences linked by four disulfides were assigned after generation of smaller disulfide-linked peptides by a secondary thermolysin digestion. Disulfide structures of peptide fragments containing two disulfide bonds were assigned using matrix-assisted laser desorption ionization mass spectrometry with postsource decay. Both the inter- and intramolecular disulfide linkages of the chimeric dimer were confirmed.

Amino Acid Sequence↗

PubMed2000

Improved branching ratio measurement for the decay K(0)(L) --> &mgr;(+)&mgr;(-)

We report results from Experiment 871, performed at the BNL AGS, of a measurement of the branching ratio K(0)(L)-->&mgr;(+)&mgr;(-) with respect to the CP-violating mode K(0)(L)-->pi(+)pi(-). This experiment detected over 6200 candidate &mgr;(+)&mgr;(-) events, a factor of 6 more than that seen in all previous measurements combined. The resulting branching ratio gamma(K(0)(L)-->&mgr;(+)&mgr;(-))/gamma(K(0)(L)-->pi(+)pi(-)) = (3. 474+/-0.057)x10(-6) leads to a branching fraction B(K(0)(L)-->&mgr;(+)&mgr;(-)) = (7.18+/-0.17)x10(-9), which is consistent with the current world average, and reduces the uncertainty in this decay mode by a factor of 3.

Journal Article↗

PubMed2000

Acetochlor-induced rat nasal tumors: further studies on the mode of action and relevance to humans.

The herbicide acetochlor, and its analogue alachlor, have similar toxicological properties, the most significant being the induction of nasal adenomas in rats in 2-year feeding studies. Previous investigations have proposed a mode of action involving metabolism to a quinone-imine, the formation of protein adducts, cell death, and compensatory hyperplasia leading to the observed adenomas. Comparisons between rats and humans of the metabolic cascade leading to the quinone-imine indicate that these chemicals do not pose a threat to humans. Further investigations with acetochlor, presented here, have revealed an additional activation pathway in which a sulfoxide metabolite of acetochlor plays a key role. The sulfoxide was found to be the major plasma metabolite in rats dosed with acetochlor. Whole-body autoradiography studies established that this metabolite selectively accumulates and persists in the olfactory epithelium of rats. Radiolabeling of the sulfoxide molecule in the phenyl ring and in the sulfoxide side-chain demonstrated that the metabolite accumulating in nasal tissues retains the sulfoxide side-chain. The formation of a quinone-imine from the sulfoxide was facilitated by hydroxylation of the phenyl ring by a cytochrome P450 isoenzyme which was specific to the nasal epithelium in the rat. This metabolic conversion could not be detected in 33 fresh human nasal tissue samples, supporting the earlier view that the acetochlor-induced rat nasal tumors do not represent a hazard for humans.

Adenoma↗

PubMed2000

Improved efficiency of gene transfer to the transplanted lung by retrograde vascular gene delivery.

Experiments were designed to evaluate the efficiency of antegrade compared to retrograde vascular gene transfection of donor lungs used for transplantation. Rat donor lungs (n = 5/group) were transduced with an adenoviral vector encoding for beta-galactosidase (AdbetaGal), either antegrade in the pulmonary artery (Group A, 3 x 10(8) pfu, Group B, 3 x 10(9) pfu) or retrograde into the pulmonary vein (Group C, 3 x 10(8) pfu), immediately after pneumoplegia. After storage at 4 degrees C for 1 h, the transduced lungs were transplanted orthotopically in syngeneic animals. The lungs were assessed for transgene expression by ELISA and X-Gal-staining at day 7 after operation. Inflammation was graded based on the extent of inflammatory cell infiltration. Transgene expression was similar between Groups A (1.7 +/- 0.7 ng/mg protein) and B (2.1 +/- 1.0 ng/mg protein). With retrograde delivery, there was a four-fold (8.3 +/- 2.6 ng/ mg protein) increase (P < 0.05) in transgene expression compared to either group A or B. In all groups, pneumocytes were transduced most frequently. The degree of inflammation correlated positively with the extent of transgene expression (r = 0.75, P < 0.01). The efficiency of vascular gene delivery to transplanted lungs can be improved by retrograde delivery of the vector via the pulmonary vein. Transgene expression predominates in pneumocytes following both antegrade and retrograde delivery. The severity of inflammation in the transplanted lung appears to correlate with the extent of transgene expression.

Adenoviridae↗

PubMed2000

Bezafibrate reduces blood glucose in type 2 diabetes mellitus.

The clinical efficacy of bezafibrate was examined with special reference to glucose metabolism in patients with type 2 diabetes mellitus (DM2). In protocol 1, 342 patients with DM2 and hyperlipidemias were randomly divided into 2 groups, 16-week bezafibrate treatment (n = 174) and no bezafibrate treatment (n = 168). In protocol 2, 20 DM2 patients were randomly divided into 2 groups, 8-week bezafibrate treatment (n = 10) and no bezafibrate treatment (n = 10), and a meal tolerance test (MTT) was performed. In protocol 1, bezafibrate treatment significantly reduced the fasting levels of triglyceride (TG) by 50% +/- 1.6%, total cholesterol (TC) by 12% +/- 1.1%, plasma glucose (PG) from 151.3 +/- 3.5 to 128.6 +/- 3.4 mg/dL, and hemoglobin A1c (HbA1c) from 7.2% +/- 0.1% to 6.9% +/- 0.1%, and significantly increased high-density lipoprotein cholesterol (HDL-C) by 20% +/- 0.8%. In protocol 2, fasting TG, PG, and insulin levels were significantly reduced by bezafibrate treatment. Moreover, in the MTT, postprandial increments of TG were significantly blunted after bezafibrate treatment, whereas postprandial PG and insulin levels were not significantly changed. Leptin levels were significantly decreased, while tumor necrosis factor alpha (TNF-alpha) levels were not changed. In conclusion, both hyperglycemia and hyperlipidemia can be improved by bezafibrate treatment in DM2.

Bezafibrate↗

PubMed2000

The natural history of bladder cancer. Implications for therapy.

Transitional cell carcinoma of the bladder is comprised of a variety of cancer diatheses that manifest a spectrum of distinct biologic potentials. Although these diseases have traditionally been classified as "superficial" and "muscle invasive" on the basis of their histologic appearance (depth of penetration of the "bladder wall" and corresponding prognosis) the pathways presumably followed by the various forms of these cancers imply an even greater complexity. These disparate pathways may reflect different events in carcinogenesis, which may determine subsequent development and risk for either recurrence or progression. In addition, biologic activity and malignant potential for each type of cancer may be associated with distinctive molecular and genetic alterations. These considerations may provide an opportunity to expand traditional staging systems in creating molecular profiles that may more precisely characterize the biologic potential of these tumor diatheses. Although there are far more questions than answers concerning how these alterations may effect the natural history of bladder cancer, molecular-based identification of bladder cancer patients at greatest risk for progression may ultimately improve clinical management.

Carcinoma in Situ↗