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Biomedical subjects

M A Lee

Publications and source records attributed to M A Lee.

At least 19 recordsLinked to original sources
PubMed2005

Association of the metabolic syndrome with intracranial atherosclerotic stroke.

To investigate the impact of metabolic syndrome (MetSD) on the development of intracranial atherosclerotic stroke, the authors evaluated the components of the MetSD in 512 patients with stroke. The MetSD was observed most frequently in patients with intracranial atherosclerosis (p = 0.007). In multiple regression analysis, the MetSD, but not conventional risk factors, was independently associated with intracranial atherosclerosis (p = 0.005). The results suggest that treatment of metabolic abnormalities may be an important prevention strategy for intracranial atherosclerosis.

Aged↗
PubMed2005

Inflammatory markers, rather than conventional risk factors, are different between carotid and MCA atherosclerosis.

BACKGROUND: The apparent differences in risk factors for intra- and extracranial atherosclerosis are unclear and the mechanisms that underlie strokes in patients with intracranial atherosclerosis are not well known. We investigated the conventional vascular risk factors as well as other factors in stroke patients with large artery atherosclerosis. METHODS: Using diffusion weighted imaging (DWI) and vascular and cardiologic studies, we selected patients with acute non-cardioembolic cerebral infarcts within the middle cerebral artery (MCA) territory. Patients were divided into two groups: those with atherosclerotic lesions on the carotid sinus (n = 112) and those with isolated lesions on the proximal MCA (n = 160). Clinical features, risk factors, and DWI patterns were compared between groups. RESULTS: There were no differences in conventional risk factors, but markers for inflammation were significantly higher in patients with carotid atherosclerosis than in those with isolated MCA atherosclerosis (p < 0.01 for both). After adjustments for age/sex and the severity of stroke, an inverse correlation was observed between C-reactive protein levels and MCA atherosclerosis (odds ratio 0.57 per 1 mg/dl increase; 95% confidence interval 0.35 to 0.92; p = 0.02). Internal borderzone infarcts suggestive of haemodynamic causes were the most frequent DWI pattern in patients with MCA occlusion, whereas territorial infarcts suggesting plaque ruptures were most common in those with carotid occlusion. CONCLUSIONS: Our results indicate that inflammatory markers, rather than conventional risk factors, reveal clinical and radiological differences between patients with carotid and MCA atherosclerosis. Plaques associated with MCA atherosclerosis may be more stable than those associated with carotid atherosclerosis.

Acute Disease↗
PubMed2005

Measurements of plasma oxycodone, noroxycodone and oxymorphone levels in a patient with bilateral nephrectomy who is undergoing haemodialysis.

The use of opioid analgesics in renal dysfunction is potentially problematic and many patients with end stage renal disease are unable to tolerate these medications. A greater understanding of the pharmacokinetics of opioid analgesics is vital in informing safe and effective practice. Using pharmacokinetic analysis, this case study demonstrates for the first time that oxycodone and its metabolites are removed by haemodialysis. As such, care should be taken when using oxycodone in patients undergoing haemodialysis.

Analgesics, Opioid↗
PubMed2005

Brain transplantation of neural stem cells cotransduced with tyrosine hydroxylase and GTP cyclohydrolase 1 in Parkinsonian rats.

Neural stem cells (NSCs) of the central nervous system (CNS) recently have attracted a great deal of interest not only because of their importance in basic research on neural development, but also in terms of their therapeutic potential in neurological diseases, such as Parkinson's disease (PD). To examine if genetically modified NSCs are a suitable source for the cell and gene therapy of PD, an immortalized mouse NSC line, C17.2, was transduced with tyrosine hydroxylase (TH) gene and with GTP cyclohydrolase 1 (GTPCH1) gene, which are important enzymes in dopamine biosynthesis. The expression of TH in transduced C17.2-THGC cells was confirmed by RT-PCR, Western blot analysis, and immunocytochemistry, and expression of GTPCH1 by RT-PCR. The level of L-DOPA released by C17.2-THGC cells, as determined by HPLC assay, was 3793 pmol/10(6) cells, which is 760-fold higher than that produced by C17.2-TH cells, indicating that GTPCH1 expression is important for L-DOPA production by transduced C17.2 cells. Following the implantation of C17.2-THGcC NSCs into the striata of parkinsonian rats, a marked improvement in amphetamine-induced turning behavior was observed in parkinsonian rats grafted with C17.2-THGC cells but not in the control rats grafted with C17.2 cells. These results indicate that genetically modified NSCs grafted into the brain of the parkinsonian rats are capable of survival, migration, and neuronal differentiation. Collectively, these results suggest that NSCs have great potential as a source of cells for cell therapy and an effective vehicle for therapeutic gene transfer in Parkinson's disease.

Animals↗
PubMed2004

Prediction of changes in memory performance by plasma homovanillic acid levels in clozapine-treated patients with schizophrenia.

RATIONALE: Cognitive dysfunction in schizophrenia has been demonstrated to be dependent, in part, on dopaminergic activity. Clozapine has been found to improve some domains of cognition, including verbal memory, in patients with schizophrenia. OBJECTIVES: This study tested the hypothesis that plasma homovanillic acid (pHVA) levels, a peripheral measure of central dopaminergic activity, would predict the change in memory performance in patients with schizophrenia treated with clozapine. METHODS: Twenty-seven male patients with schizophrenia received clozapine treatment for 6 weeks. Verbal list learning (VLL)-Delayed Recall (VLL-DR), a test of secondary verbal memory, was administered before and after clozapine treatment. Blood samples to measure pHVA levels were collected at baseline. RESULTS: Baseline pHVA levels were negatively correlated with change in performance on VLL-DR; the lower baseline pHVA level was associated with greater improvement in performance on VLL-DR during treatment with clozapine. Baseline pHVA levels in subjects who showed improvement in verbal memory during clozapine treatment ( n=13) were significantly lower than those in subjects whose memory performance did not improve ( n=14). CONCLUSIONS: The results of this study indicate that baseline pHVA levels predict the ability of clozapine to improve memory performance in patients with schizophrenia.

Adult↗
PubMed2004

Cognitive effects of olanzapine treatment in schizophrenia.

Improvement in some but not all domains of cognition during treatment with the atypical antipsychotic drugs clozapine, quetiapine, olanzapine, and risperidone has been reported in some but not all studies. It has been recently suggested that these reports are an artifact, related to lessening of the impairment due to typical neuroleptic drugs and anticholinergic agents. The purpose of this study was to further test the hypothesis that olanzapine, an atypical antipsychotic drug reported to have anticholinergic properties, improves cognition in patients with schizophrenia, including domains of cognition related closely to work and social function (ie, verbal learning and memory) and that this improvement is independent of improvement in psychopathology. Thirty-four patients with schizophrenia who were partial responders to typical antipsychotic drug treatment were evaluated with a comprehensive neurocognitive battery, including measures of executive functioning; verbal and visual learning and memory; working memory; immediate, selective, and sustained attention; perceptual/motor processing; and motor skills prior to and following treatment with olanzapine for 6 weeks. The Brief Psychiatric Rating Scale (BPRS) was used to assess psychopathology in patients treated with typical antipsychotic drugs. Subjects were switched to olanzapine (average dose 13.4 mg, range 5-20 mg) and reassessed following 6 weeks and 6 months of treatment. Significant improvement was noted in 9 of 19 cognitive tests, including measures of selective attention, verbal learning and memory, and verbal fluency. No cognitive test was worsened by olanzapine treatment. Improvements in the BPRS Total and Positive Symptom Subscale scores were noted. Improvements in verbal learning and memory, sustained attention, and psychomotor tracking were independent of improvement in psychopathology. These data suggest that olanzapine improved some but not all cognitive deficits in schizophrenia, including verbal memory, a cognitive domain impaired by anticholinergic drugs. The basis for the improvement in cognitive scores, which should lead to improvement in role functioning if real, is discussed.

Adult↗
PubMed2002

New strategies for the diagnosis and screening of malaria.

Thin and thick blood film microscopy are the "gold standard" for malaria diagnosis. In recent years, there have been important developments in malaria diagnostic tests including fluorescence microscopy of malaria parasites stained with acridine orange, dipstick immunoassays that detect species-specific parasite antigens, and more recently, detection of parasite nucleic acids after amplification by PCR. With some of these methods, sensitivities and specificities approaching and even exceeding those of the thin and thick film can be attained. In particular, PCR-based tests for plasmodium DNA or RNA are more sensitive and specific than other tests for malarial parasites. A specific application for PCR diagnosis of malaria could be blood donor screening. Clinical trials of blood donor sreening for malarial parasites by PCR are being conducted, in which pooled donor samples are screened to increase efficiency and reduce costs. Some of the new diagnostic methods may have specific applications in particular settings, depending on the purpose and location of testing, and other factors such as cost, desired sensitivity and specificity, speed and ease of use.

Blood Donors↗
PubMed2002

Remacemide hydrochloride as an add-on therapy in epilepsy: a randomized, placebo-controlled trial of three dose levels (300, 600 and 800 mg/day) in a B.I.D. regimen.

Remacemide hydrochloride is a low-affinity, non-competitive NMDA receptor channel blocker under investigation for the treatment of epilepsy. This double-blind, placebo-controlled, multicentre study assessed the safety and efficacy of adjunctive remacemide hydrochloride or placebo, in adult patients with refractory epilepsy who were already taking up to three antiepileptic drugs (including an enzyme-inducer). Patients (n= 262) were randomized to one of three doses of remacemide hydrochloride (300, 600 or 800 mg/day) or placebo, in a B.I.D. regimen, for up to 14 weeks. Plasma concentrations of carbamazepine (CBZ) and phenytoin (PHT) were controlled throughout. Patients recorded their seizures on a diary card. There was an increase in the percentage of responders (defined as a reduction in seizure frequency from baseline > or = 50 %), from 15 % (9/60) with placebo, to 30 % (18/60) in the 800 mg/day group. A pairwise comparison between remacemide hydrochloride 800 mg/day and placebo was statistically significant (P = 0.049). Most reported adverse events (mainly CNS and gastrointestinal) were mild or moderate in severity and dose-dependent. Adjunctive remacemide hydrochloride treatment was associated with a higher, dose-related responder rate compared with placebo. The difference reached significance at the highest dose tested (800 mg/day). Remacemide hydrochloride was well tolerated.

Acetamides↗
PubMed2002

An expanded cortical representation for hand movement after peripheral motor denervation.

OBJECTIVES: Functional reorganisation of the motor or sensory cortex has been demonstrated in animals after section of mixed peripheral nerves. Here functional changes in the motor cortex specifically after peripheral motor denervation in humans are investigated. METHODS: Functional MRI (fMRI) was used to study brain activation during a finger flexion-extension task in patients with a late onset, acquired pure motor neuropathy (n=6), contrasting results with those from patients with pure sensory neuropathies (n=4) or healthy controls (n=7). RESULTS: Increases in the extent of activation in the motor cortex both ipsilateral and contralateral to the hand moved were found in the patients with motor neuropathy. The neuroanatomical localisation of the mixed contralateral sensorimotor cortex activation volume was more posterior for the patients with motor neuropathy than for the healthy controls (mean difference, 12 mm, p<0.05). The pure sensory neuropathy group by contrast showed no change in the extent of activation relative to healthy controls and a trend for more anterior primary sensorimotor cortex activation (p<0.06). To test whether the increased activation volumes found in patients with motor neuropathy were a result simply of factors such as increased effort with movement rather than the motor denervation, patients with hand weakness from inclusion body myositis (n=4) were studied while making similar hand movements. No differences in either the numbers of significantly activated voxels or in their localisation were found relative to healthy controls (n=10). CONCLUSIONS: These results provide a novel demonstration that peripheral denervation (as distinguished from factors related to weakness) leads to functional reorganisation of the sensorimotor cortex in the adult brain. This suggests that adaptive responses to motor denervation involve the central as well as the peripheral nervous system.

Adult↗
PubMed2002

Pain management services in palliative care: a national survey.

INTRODUCTION: The effective management of pain requires a multidisciplinary approach. Previous studies have suggested that around 8% of cancer patients will require interventional techniques from an anaesthetist with special interest in pain management to maximize pain control, although this percentage may increase in the cohort of patients with difficult pain syndromes under the care of specialist palliative care services. We wished to determine the experiences and views of other palliative care physicians with regard to input from specialists in pain management. METHOD: A postal questionnaire was sent to the consultant members of the Association of Palliative Medicine. RESULTS: Most respondents had access to 'as-required' anaesthetist consultations with 72% of respondents feeling that the frequency of consultation was adequate. However, over half of the respondents had used the services of a pain management specialist less than four times in the past year and a quarter of respondents had not been involved in a joint consultation with an anaesthetist in the past year. All respondents felt that the pain management specialist's role included advice on technical procedures but less than 25% felt that their role should extend to advice on prescribing analgesics. DISCUSSION: There are likely to be several reasons for this apparent underutilization of specialist anaesthetist/pain management services. This survey has identified possible factors including lack of formal arrangements, lack of suitable experience and the attitudes of palliative medicine consultants.

Anesthesiology↗
PubMed2001

5-HT(1A) receptor dysfunction in female patients with schizophrenia.

BACKGROUND: Serotonin (5-HT)(1A) receptors are of interest in the pathophysiology of schizophrenia (SCH) and the mechanism of action of atypical antipsychotic drugs. To test the hypothesis that 5-HT(1A) receptor responsivity is significantly different in patients with SCH compared to normal control subjects, the neuroendocrine study was performed using ipsapirone (IPS), a 5-HT(1A) partial agonist, as a probe. METHODS: Ipsapirone 0.5 mg/kg, p.o. or placebo were administered, in random order, to patients with SCH (n = 43; 32 male) and normal controls (n = 33; 21 male). Blood samples for plasma cortisol and body temperature were obtained from 30 min before to 180 min after administration of IPS or placebo. RESULTS: Female normal control subjects had markedly greater increases in plasma cortisol following IPS than did male control subjects. The placebo response-corrected plasma cortisol response to IPS was significantly blunted in female SCH compared to female normal control subjects (p =.0001). The IPS-stimulated plasma cortisol response in male SCH did not differ from that of male normal control subjects or female SCH. There were no significant differences in the IPS-induced hypothermia in men and women or between patients with SCH and normal control subjects. Behavioral responses to IPS, including nausea, dizziness, irritability, and feeling less well, did not differ between groups. CONCLUSIONS: These results suggest that the post-synaptic 5-HT(1A) receptor mediated endocrine response is diminished in female SCH compared to female normal control subjects, possibly secondary to an abnormality in intracellular signal transduction mechanism.

Adult↗
PubMed2001

Oregon physicians' attitudes about and experiences with end-of-life care since passage of the Oregon Death with Dignity Act.

CONTEXT: The Oregon Death with Dignity Act, passed by ballot measure in 1994 and enacted in October 1997, legalized physician-assisted suicide for competent, terminally ill Oregonians, but little is known about the effects of the act on clinical practice or physician perspective. OBJECTIVE: To examine Oregon physicians' attitudes toward and practices regarding care of dying patients since the passage of the Death with Dignity Act. DESIGN, SETTING, AND PARTICIPANTS: A self-administered questionnaire was mailed in February 1999 to Oregon physicians eligible to prescribe under the act. Of 3981 eligible physicians, 2641 (66%) returned the questionnaire by August 1999. MAIN OUTCOME MEASURES: Physicians' reports of their efforts to improve care for dying patients since 1994, their attitudes, concerns, and sources of information about participating in the Death with Dignity Act, and their conversations with patients regarding assisted suicide. RESULTS: A total of 791 respondents (30%) reported that they had increased referrals to hospice. Of the 2094 respondents who cared for terminally ill patients, 76% reported that they made efforts to improve their knowledge of the use of pain medications in the terminally ill. Nine hundred forty-nine responding physicians (36%) had been asked by a patient if they were potentially willing to prescribe a lethal medication. Seven percent of all survey participants reported that 1 or more patients became upset after learning the physician's position on assisted suicide, and 2% reported that 1 or more patients left their care after learning the physician's position on assisted suicide. Of the 73 physicians who were willing to write a lethal prescription and who had received a request from a patient, 20 (27%) were not confident they could determine when a patient had less than 6 months to live. CONCLUSION: Most Oregon physicians who care for terminally ill patients report that since 1994 they have made efforts to improve their ability to care for these patients and many have had conversations with patients about assisted suicide.

Adult↗
PubMed2001

Generation and characterization of immortalized human microglial cell lines: expression of cytokines and chemokines.

Microglia are a major glial component of the central nervous system (CNS), play a critical role as resident immunocompetent and phagocytic cells in the CNS, and serve as scavenger cells in the event of infection, inflammation, trauma, ischemia, and neurodegeneration in the CNS. Studies of human microglia have been hampered by the difficulty of obtaining sufficient numbers of human microglia. One way to circumvent this difficulty is to establish permanent cell lines of human microglia. In the present study we report the generation of immortalized human microglial cell line, HMO6, from human embryonic telencephalon tissue using a retroviral vector encoding myc oncogene. The HMO6 cells exhibited cell type-specific antigens for microglia-macrophage lineage cells including CD11b (Mac-1), CD68, CD86 (B7-2), HLA-ABC, HLA-DR, and ricinus communis agglutinin lectin-1 (RCA), and actively phagocytosed latex beads. In addition, HMO6 cells showed ATP-induced responses similar to human primary microglia in Ca2+ influx spectroscopy. Both human primary microglia and HMO6 cells showed the similar cytokine gene expression in IL-1beta, IL-6, IL-8, IL-10, IL-12, IL-15, and TNF-alpha. Using HMO6 cells, we investigated whether activation was induced by Amyloid-beta fragments or lipopolysaccharide (LPS). Treatment of HMO6 cells with Amyloid-beta 25-35 fragment (Abeta(25-35)) or Amyloid-beta 1-42 fragment (Abeta(1-42)) led to increased expression of mRNA levels of cytokine/chemokine IL-8, IL-10, IL-12, MIP-1beta MIP-1, and MCP-1, and treatment with LPS produced same results. Expression of TNF-alpha and MIP1-alpha was not detected in unstimulated HMO6 cells, but their expression was later induced by long-term exposure to Abeta(25-35) or Abeta(1-42.) ELISA assays of spent culture media showed increased protein levels of TNF-alpha and IL-8 in HMO6 cells following treatment with Abeta(25-35) or LPS. Taken together, our results demonstrate that treatment of human primary microglia and HMO6 immortalized human microglia cell line with Abeta(25-35), Abeta(1-42) and LPS upregulate gene expression and protein production of proinflammatory cytokines and chemokines in these cells. The human microglial cell line HMO6 exhibits similar properties to those documented in human microglia and should have considerable utility as an in vitro model for the studies of human microglia in health and disease.

Adenosine Triphosphate↗
PubMed2001

Cloning and sequence characterisation of falcipain-2 from Plasmodium falciparum Gombak A strain (Malaysia).

In this study, the genome of the Plasmodium falciparum Gombak A strain was examined for the presence of a gene encoding falcipain-2, a cysteine protease, using homology-based polymerase chain reaction cloning. The nucleotide sequence obtained from the gene cloned (designated pFG1) is approximately 99% homologous to other falcipain-2 genes from different strains. Comparatively, it is 69% homologous to falcipain-3 genes. Direct cloning of the falcipain-2 gene and its resemblance to the reported corresponding mRNA transcript suggests the absence of introns in this gene. Sequence alignment and comparison revealed four amino acid differences at positions 15, 51, 59 and 414 in the falcipain-2 from P. falciparum Gombak A as compared to other falcipain-2 proteins from different strains.

Amino Acid Sequence↗
PubMed2001

Development of a simplified assay for the detection of neutralizing antibodies to Japanese encephalitis virus.

Japanese encephalitis virus is a common cause of viral encephalitis in Asia with an estimated 45,000 cases annually. It causes significant morbidity and mortality. It is transmitted primarily by Culex mosquitoes between birds and animals, while man is thought to be an accidental, dead-end host. Since dengue is also prevalent usually in Japanese encephalitis-endemic areas, all Japanese encephalitis positive sera must be confirmed by detecting Japanese encephalitis specific neutralizing antibodies. The plaque reduction neutralization test is the gold standard for detecting and quantifying Japanese encephalitis neutralizing antibodies. This test, however, takes about a week and is carried out in 6 or 24-well plates, which limits its usage for large-scale screening. A simplified assay was developed for the detection and quantification of Japanese encephalitis neutralizing antibodies. The assay, which is carried out in 96-well plates, would be suitable for use in the mass screening of the population's immunity level as well as for use in vaccine efficacy studies.

Animals↗