Search PubMed⌕ Search

Biomedical subjects

A Lee

Publications and source records attributed to A Lee.

At least 271 records · Page 15Linked to original sources
PubMed1999

Measurement of cerebral blood volume using near-infrared spectroscopy and indocyanine green elimination.

Methods for measuring cerebral blood volume (CBV) have traditionally used radioisotopes. More recently, near-infrared spectroscopy (NIRS) has been used to measure CBV by using a technique involving O(2) desaturation of cerebral tissue, where the observed change in the concentration of oxygenated hemoglobin is a marker of the volume of blood contained within the brain. A new integration method employing NIRS is described by using indocyanine green (ICG) as the intravascular marker. After bolus injection, concentration-time integrals of cerebral tissue ICG concentration ([ICG](tissue)) measured by NIRS are compared with corresponding integrals of the cerebral blood ICG concentrations ([ICG](blood)) estimated by high-performance liquid chromatography of peripheral blood samples with allowance for cerebral-to-large-vessel hematocrit ratio. It is shown that CBV = integral [ICG]tissue/[ICG]blood. Measurements in 10 adult volunteers gave a mean value of 1.1 +/- 0.39 (SD) ml/100 g illuminated tissue. This result, although lower than previous NIRS estimations, is consistent with the long extracerebral path of light in the adult head. Scaling of results is required to take into account this component of the optical pathlength.

Adult↗
PubMed1999

The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on postoperative renal function: a meta-analysis.

The aim of this systematic review was to assess the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on post-operative renal function. Eight randomized placebo-controlled double-blinded trials (n = 345) were identified from searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register databases. The summary effect size and 95% confidence intervals (95% CI) were calculated by a weighted mean difference analysis using a random-effects model. The NSAIDs (diclofenac, ketorolac, indomethacin, ibuprofen) were used for up to three-days after surgery. There were no reported cases of postoperative renal failure requiring dialysis. NSAIDs reduced creatinine clearance by 22 ml.min-1 (95% CI: 7 to 37), sodium output by 54 mmol.day-1 (95% CI: 5 to 103) and potassium output by 38 mmol.day-1 (95% CI: 19 to 56) on Day 1 but not on Day 2. Serum creatinine increased on Day 2 by 15 mumol.l-1 (95% CI: 2 to 28). Urine volume did not change significantly at any time. There was therefore a clinically unimportant transient reduction in renal function. NSAIDs should not be withheld from patients with normal preoperative renal function because of concerns about postoperative renal impairment.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Development of the Drosophila mushroom bodies: sequential generation of three distinct types of neurons from a neuroblast.

The mushroom bodies (MBs) are prominent structures in the Drosophila brain that are essential for olfactory learning and memory. Characterization of the development and projection patterns of individual MB neurons will be important for elucidating their functions. Using mosaic analysis with a repressible cell marker (Lee, T. and Luo, L. (1999) Neuron 22, 451-461), we have positively marked the axons and dendrites of multicellular and single-cell mushroom body clones at specific developmental stages. Systematic clonal analysis demonstrates that a single mushroom body neuroblast sequentially generates at least three types of morphologically distinct neurons. Neurons projecting into the (gamma) lobe of the adult MB are born first, prior to the mid-3rd instar larval stage. Neurons projecting into the alpha' and beta' lobes are born between the mid-3rd instar larval stage and puparium formation. Finally, neurons projecting into the alpha and beta lobes are born after puparium formation. Visualization of individual MB neurons has also revealed how different neurons acquire their characteristic axon projections. During the larval stage, axons of all MB neurons bifurcate into both the dorsal and medial lobes. Shortly after puparium formation, larval MB neurons are selectively pruned according to birthdays. Degeneration of axon branches makes early-born gamma neurons retain only their main processes in the peduncle, which then project into the adult gamma lobe without bifurcation. In contrast, the basic axon projections of the later-born (alpha'/beta') larval neurons are preserved during metamorphosis. This study illustrates the cellular organization of mushroom bodies and the development of different MB neurons at the single cell level. It allows for future studies on the molecular mechanisms of mushroom body development.

Animals↗
PubMed1999

Hyperlactatemia and pulmonary lactate production in patients with fulminant hepatic failure.

STUDY OBJECTIVES: To determine whether the lungs of patients with fulminant hepatic failure release lactate, and if so, whether this release relates to systemic lactate concentration or acid base status. Another objective was to examine the accuracy of lactate flux calculations in critically ill patients. DESIGN: Prospective observational study. SETTING: The ICU of a major teaching hospital. PATIENTS: Twelve patients with fulminant hepatic failure; 30 other critically ill patients in whom a pulmonary artery catheter was in place. INTERVENTIONS: None. MEASUREMENT AND RESULTS: The precision of whole-blood lactate measurements was assessed in 30 patients with critical illnesses of variable etiology who had a wide range of arterial lactate concentrations. The reliability of lactate measurements decreased with increasing lactate concentration. In each patient with liver failure, pulmonary lactate flux was calculated on three occasions using the Fick principle. Arterial blood lactate concentration was consistently higher than venous concentrations, indicating lactate release by the lungs (mean difference, 0.15 mmol/L; 95% confidence interval, 0.09 to 0.21; p<0.001). Mean pulmonary lactate production for the 12 patients was 83 mmol/h (range, 22 to 210 mmol/h). No patient had significant acute lung injury. Correlations were found among the arterial lactate concentration and both the arteriovenous (AV) lactate difference (p<0.025) and pulmonary lactate production (p<0.05), but not with acid-base status or cardiac output. The reliability of individual AV lactate difference calculations and pulmonary lactate flux calculations was poor. CONCLUSION: The lungs release lactate in patients with fulminant hepatic failure at a rate proportional to the degree of systemic hyperlactatemia. However, the measurement errors associated with pulmonary lactate flux calculations using the Fick principle are large, so individual measurements should be interpreted with caution.

Critical Illness↗
PubMed1999

Imitation and identification in autism.

This study was designed to test the prediction that adolescents with autism would have specific limitations in imitating the "style" of another person's actions. In a series of original tasks that tested the delayed imitation of novel nonsymbolic actions, 16 participants with autism and 16 nonautistic participants group-matched for age and verbal ability were proficient in copying goal-directed actions, but in 3 out of 4 tasks, strikingly fewer participants with autism imitated with style with which the demonstrator executed the actions. An additional finding was that on 2 conditions that involved copying self-orientated actions, only 5 of the participants with autism but 15 of the 16 nonautistic participants spontaneously adopted the orientation-to-self on at least 1 occasion. The results are discussed with reference to theories concerning imitation deficits in autism, and with regard to the proposal that autism involves an impairment in intersubjective contact between affected individuals and others (Hobson, 1989, 1993; Rogers & Pennington, 1991).

Adolescent↗
PubMed1999

TP53 tumor suppressor protein in normal human fibroblasts does not respond to 837 MHz microwave exposure.

The TP53 tumor suppressor protein (formerly known as p53) responds to a wide variety of environmental insults. To evaluate the safety of cellular telephones, TP53 responses in human fibroblast cells were studied after exposure to 837 MHz microwaves. Cells were exposed in a temperature-controlled transverse electromagnetic (TEM) chamber to a specific absorption rate (SAR) of 0.9 or 9.0 W/kg at 837 MHz continuous-wave (CW) microwave irradiation for 2 h. The TP53 protein levels were measured by Western blot at 2, 8, 24 and 48 h after treatment. The TP53 protein levels in microwave-treated cells, sham-treated cells, and untreated cells remained unchanged relative to each other at all times tested (Fisher test and Student-Newman-Keuls test, P > 0.05). No morphological alterations were observed in microwave-treated cells compared to sham-treated cells. We conclude that TP53 protein expression levels in cultured human fibroblast cells do not change significantly during a 48-h period after exposure to 837 MHz continuous microwaves for 2 h at SAR levels of 0.9 or 9.0 W/kg.

Cells, Cultured↗
PubMed1999

Changing hepatitis A epidemiology among Hong Kong Chinese adolescents: what are the implications?

OBJECTIVE: To study the sero-epidemiology of hepatitis A virus (HAV) among adolescents in Hong Kong and analyse the changing patterns of the infection rates. DESIGN: Cross sectional study. SETTING: Secondary school students. SUBJECTS: One thousand, five hundred and eighty students were randomly selected from 12 schools in four regions of Hong Kong. MAIN OUTCOME MEASURES: Anti-HAV status. RESULTS: The overall prevalence of anti-HAV is 7%. The sero-prevalence for age group 11-20 y has fallen compared with 44.8% in 1978, 17.1% in 1987 and 11.2% in 1989. Those adolescents born in mainland China, who are frequent travellers and had a longer period of residence in mainland China were shown to have a higher prevalence of anti-HAV. CONCLUSION: The changing epidemiology of HAV indicates that Hong Kong will have a large proportion of susceptible young adults. Because of its geographic situation and import of most its food supplies from less developed countries, for epidemiological purposes the inhabitants can be compared to western travellers staying in a five star hotel in a less developed country. The risk of an outbreak of HAV is to be expected. Vaccination has the potential to serve as an effective prevention for adolescents living in countries whose circumstances are similar to Hong Kong.

Adolescent↗
PubMed1999

Vaccines.

Extensive research with mice has shown that animals can be protected from or cured of Helicobacter infection by immunization. A therapeutic effect has also been demonstrated in ferrets. The possibility of developing a vaccine against H. pylori-associated diseases that will work in humans has been the stimulus for intense research activity. A major subset of lymphocytes involved in immunity against invading pathogens is the CD4+ T-lymphocytes, divided into Th1 and Th2 phenotypes. Th1 cells are involved in cell-mediated immunity and Th2 cells are involved in antibody formation, particularly IgA and IgG, which are most active at mucosal surfaces and thus most likely to be protective against bacteria trying to colonize that surface. H. pylori can exist for the life of its human host, despite the vigorous immune response that is mounted against it. Most infected humans have a Th1 response, which does not eradicate H. pylori. A Th2 response would logically be more effective. Experiments with mice deficient in the cytokines that drive the Th responses are confusing and indicate that a change in the balance of the Th1/Th2 response may have a therapeutic effect In the next 2-5 years, a number of anti-Helicobacter vaccines will be studied in humans and this will open up a completely new approach to the management of gastroduodenal diseases.

Animals↗
PubMed1999

Care of the pregnant patient in the dental office.

Attention to a woman's dental health can and should continue throughout pregnancy. The treating dentist must be diligent to the special situations surrounding treating the pregnant patient and the risks involved for both fetus and mother. Undertaking the proper precautions with these patients not only provides the best dental care, but also helps avoid potential complications. Any complication or question that arises with a complicated pregnancy should prompt referral to the patient's obstetrician for further evaluation.

Abnormalities, Drug-Induced↗
PubMed1999

Swallowing impairment and feeding dependency in the hospitalised elderly.

A prospective study was carried out to determine the prevalence of swallowing impairment and feeding dependency in an acute geriatric medicine unit in Singapore and the co-morbidity associated with it. A total of 211 patients were assessed over a 3-month period. Only 7.1% of patients gave a history of swallowing impairment prior to hospitalisation. We found that 29.4% of patients on admission and 28.2% on discharge had swallowing impairment, with a mortality of 8.1%. The prevalence of feeding dependency, as defined by the need for feeding assistance or tube feeding, was 26.5% before admission and 27.8% on discharge. The mode of feeding between the time of admission and discharge was changed in 14.9% of patients in response to the evolving medical condition. Swallowing impairment was significantly associated with the presence of dehydration (RR = 2.82, CI = 1.74-4.57), chest infection on admission (RR = 2.85, CI = 1.85-4.41), development of nosocomial chest infection (RR = 6.75, CI = 2.60-17.5), discharge to institutional care (RR = 2.8, CI = 1.51-3.47) and increased mortality (RR = 3.77, CI = 1.45-9.70). We concluded that swallowing impairment and feeding dependency are common in the elderly admitted to an acute geriatric unit. As elderly patients seldom inform clinicians of any underlying swallowing impairment and in view of the increased morbidity and mortality associated with this disability, it is important to screen for swallowing impairment. The high prevalence of feeding dependency adds to the burden of care in the ill elderly.

Aged↗
PubMed1999

D-dimer testing in the diagnosis of acute venous thromboembolism.

Patients with acute VTE require clinical assessment and objective testing to be accurately diagnosed. Almost all patients with acute VTE have an elevated D-dimer level. An elevated D-dimer is associated with many illnesses, and therefore, is not specific for VTE. D-dimer tests can have a high sensitivity, however, which is useful because a normal test excludes the diagnosis of VTE. D-dimer testing is most appropriate in the assessment of outpatients because the prevalence of disease and the likelihood of comorbid conditions are lower than in inpatient populations, making a test of exclusion particularly valuable. Accuracy studies using conventional ELISA assays have confirmed that a test with a high sensitivity can be used to exclude a diagnosis of VTE, but conventional ELISA testing is not practical. Studies of more practical D-dimer testing indicate that, for patients with suspected DVT or PE, the need for serial testing or further investigation can be reduced if normal results are obtained using assays with a high sensitivity. There are, however, many sources of variation in the test characteristics of D-dimer assays. Therefore there is no reassurance that results from one manufacturer's test are applicable to other tests and different investigators may obtain varied results when using the same manufacturer's product. In addition, the results of D-dimer accuracy studies lack generalizability. This lack of generalizability has led to the recommendation that clinicians await the results of management studies before adopting the routine use of D-dimer assays in the diagnosis of VTE. Further, it may be reasonable to perform an accuracy study when planning to adopt a specific D-dimer assay from a published management trial, to be confident of its characteristics can be reproduced. In the management of patients with suspected DVT, rapid ELISA tests show promise as a practical D-dimer test, in that they have a sensitivity similar to that of the conventional ELISA assay. Two management studies have recently confirmed that a normal D-dimer result (using the SimpliRED whole-blood assay or the Instant IA rapid ELISA) in combination with a noninvasive test or a clinical model can reliably exclude DVT in outpatients. Use of a clinical model can reduce the need for VU, and the combination of a clinical model and D-dimer testing could further reduce the number of VU procedures required. As noted by Wells et al, who recently published a clinical model, however, a normal D-dimer result was most accurate in the patients with a low pretest likelihood (NPV = 99.5%) and least accurate in patients with a high pretest likelihood (NPV = 85.7%) Patients with a low pretest likelihood and a normal D-dimer are the largest proportion of outpatients referred for testing, and considerable resources may be saved if additional management studies confirm the usefulness of D-dimer testing in such patients. In patients with suspected PE, there is a lack of published management trials despite a number of accuracy studies indicating that D-dimer testing may be useful as a method of PE diagnosis exclusion. Recent results, however, from an accuracy study of patients with suspected PE who had D-dimer testing complement the findings of Wells et al in patients with suspected DVT. Using a standardized clinical model of PE in combination with a SimpliRED D-dimer assay, Ginsberg and colleagues found that the combination of a low pretest likelihood and a normal D-dimer had a negative predictive value of 99%, whereas the negative predictive value was only 78% in patients with a high pretest likelihood and a normal D-dimer. Similar to the findings in DVT, these results indicate that D-dimer testing is most useful in patients with a low pretest likelihood for PE and raise the possibility that such patients may not require lung scans. This finding is currently being evaluated in a prospective management trial.

Acute Disease↗
PubMed1999

Should general practitioners refer patients with major depression to counsellors? A review of current published evidence. Nottingham Counselling and Antidepressants in Primary Care (CAPC) Study Group.

Major depression can be treated effectively with antidepressants. However, in the United Kingdom, patients with depression are often referred to counsellors, and surveys indicate that public opinion favours this approach. We carried out a literature review to determine the evidence for the effectiveness of counselling for depression in primary care. Because no studies were identified in which counselling had been evaluated specifically in relation to treating depression, we examined indirect evidence from studies evaluating the overall effectiveness of generic counselling in primary care, and studies evaluating the effectiveness of psychological treatments, other than counselling, for depression. Methodological problems influencing the interpretation of such studies are discussed. We conclude that, while specific psychological treatments have been shown to have equivalent effectiveness as antidepressants, there is currently insufficient evidence to recommend that generic counselling should be used alone in the treatment of patients with major depression.

Counseling↗
PubMed1998

Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain.

The HERG voltage-dependent K+ channel plays a role in cardiac electrical excitability, and when defective, it underlies one form of the long QT syndrome. We have determined the crystal structure of the HERG K+ channel N-terminal domain and studied its role as a modifier of gating using electrophysiological methods. The domain is similar in structure to a bacterial light sensor photoactive yellow protein and provides the first three-dimensional model of a eukaryotic PAS domain. Scanning mutagenesis of the domain surface has allowed the identification of a hydrophobic "hot spot" forming a putative interface with the body of the K+ channel to which it tightly binds. The presence of the domain attached to the channel slows the rate of deactivation. Given the roles of PAS domains in biology, we propose that the HERG N-terminal domain has a regulatory function.

Animals↗
PubMed1998

Specificity and promiscuity in phosphoinositide binding by pleckstrin homology domains.

Pleckstrin homology (PH) domains are small protein modules involved in recruitment of signaling molecules to cellular membranes, in some cases by binding specific phosphoinositides. We describe use of a convenient "dot-blot" approach to screen 10 different PH domains for those that recognize particular phosphoinositides. Each PH domain bound phosphoinositides in the assay, but only two (from phospholipase C-delta1 and Grp1) showed clear specificity for a single species. Using soluble inositol phosphates, we show that the Grp1 PH domain (originally cloned on the basis of its phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding) binds specifically to D-myo-inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) (the PtdIns(3,4,5)P3 headgroup) with KD = 27.3 nM, but binds D-myo-inositol 1,3,4-trisphosphate (Ins(1,3,4)P3) or D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) over 80-fold more weakly. We show that this specificity allows localization of the Grp1 PH domain to the plasma membrane of mammalian cells only when phosphatidylinositol 3-kinase (PI 3-K) is activated. The presence of three adjacent equatorial phosphate groups was critical for inositol phosphate binding by the Grp1 PH domain. By contrast, another PH domain capable of PI 3-K-dependent membrane recruitment (encoded by EST684797) does not distinguish Ins(1,3,4)P3 from Ins(1,3,4,5)P3 (binding both with very high affinity), despite selecting strongly against Ins(1,4,5)P3. The remaining PH domains tested appear significantly less specific for particular phosphoinositides. Together with data presented in the literature, our results suggest that many PH domains bind similarly to multiple phosphoinositides (and in some cases phosphatidylserine), and are likely to be regulated in vivo by the most abundant species to which they bind. Thus, using the same simple approach to study several PH domains simultaneously, our studies suggest that highly specific phosphoinositide binding is a characteristic of relatively few cases.

Animals↗
PubMed1998

The pleckstrin homology domains of dynamin isoforms require oligomerization for high affinity phosphoinositide binding.

The dynamins are 100-kDa GTPases involved in the scission event required for formation of endocytotic vesicles. The two main described mammalian dynamins (dynamin-1 and dynamin-2) both contain a pleckstrin homology (PH) domain, which has been implicated in dynamin binding to (and activation by) acidic phospholipids, most notably phosphoinositides. We demonstrate that the PH domains of both dynamin isoforms require oligomerization for high affinity phosphoinositide binding. Strong phosphoinositide binding was detected only when the PH domains were dimerized by fusion to glutathione S-transferase, or via a single engineered intermolecular disulfide bond. Phosphoinositide binding specificities agreed reasonably with reported effects of different phospholipids on dynamin GTPase activity. Although they differ in their ability to inhibit rapid endocytosis in adrenal chromaffin cells, the dynamin-1 and dynamin-2 PH domains showed identical phosphoinositide binding specificities. Since oligomerization is required for binding of the dynamin PH domain to phosphoinositides, it follows that PH domain-mediated phosphoinositide binding will favor oligomerization of intact dynamin (which has an inherent tendency to self-associate). We propose that the dynamin PH domain thus mediates the observed cooperative binding of dynamin to membranes containing acidic phospholipids and promotes the self-assembly that is critical for both stimulation of its GTPase activity and its ability to achieve membrane scission.

Amino Acid Sequence↗
PubMed1998

Family concern.

Explore the source record for details and available documents.

Family↗
PubMed1998

Nasopharyngeal carcinoma in situ: two cases of an emerging diagnostic entity.

BACKGROUND: The association of Epstein-Barr virus (EBV) with the oncogenesis of nasopharyngeal carcinoma (NPC) is well established. Latent infection by EBV with clonal proliferation has also been demonstrated in preinvasive lesions of NPC. In situ hybridization for EBV-encoded RNA (ISH EBER) now serves as an ancillary test in the definitive diagnosis of these lesions. METHODS: Two cases of nasopharyngeal carcinoma in situ (NPCIS) are presented in this study. Their biopsies were studied by ordinary light microscopy, the ISH EBER technique, and immunostaining for bcl-2. Tissue samples from 100 high risk subjects negative for NPC and NPCIS, who served as controls, were also studied using the ISH EBER technique. RESULTS: NPCIS was characterized by abnormal light microscopic appearance as well as positive staining by the ISH EBER technique; these features were not observed in samples from the 100 high risk subjects. Immunostaining for bcl-2 protein was positive but less specific. Postradiotherapy biopsies of the two patients were negative for NPCIS. CONCLUSIONS: With the help of the ISH EBER technique, the diagnosis of NPCIS is now possible in routine surgical pathology. As this entity is rare, it is necessary to have a high degree of suspicion when evaluating biopsies from high risk individuals. Radiotherapy for patients with NPCIS is justified in view of the risk of cancer progression and the possibility of a coexisting invasive carcinoma.

Carcinoma in Situ↗