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Biomedical subjects

M A Lee

Publications and source records attributed to M A Lee.

At least 37 records · Page 2Linked to original sources
PubMed2001

The blunted plasma cortisol response to apomorphine and its relationship to treatment response in patients with schizophrenia.

The adrenocorticotropic hormone (ACTH) and cortisol responses to apomorphine (APO), a direct acting dopamine (DA) agonist, have been reported to be significantly blunted in neuroleptic-free patients with schizophrenia (SCH). This study primarily examined the cortisol, but also the prolactin (PRL) and growth hormone (GH), response to APO in patients with SCH compared to normal controls, as well as the relationship between endocrine measures and response to antipsychotic drug treatment. APO, 0.01 mg/kg, or placebo was administered to 51-98 patients with SCH and 15-25 normal controls. Psychopathology was assessed at the baseline and six weeks after drug treatment. The plasma cortisol response to APO was markedly blunted in patients with SCH compared to normal controls. Patients who responded to six weeks of treatment with antipsychotic drugs had a higher cortisol response to APO compared to non-responders. The plasma GH, but not PRL, response to APO was blunted in male patients with SCH. Neither plasma GH nor PRL responses to APO were related to treatment response at six weeks. These results provide further evidence of dopaminergic dysfunction in SCH. Furthermore, the APO-stimulated cortisol response may be predictive of subsequent clinical response to antipsychotic drug treatment.

Adrenocorticotropic Hormone↗
PubMed2001

Children's access to dental care in Connecticut's Medicaid managed care program.

OBJECTIVE: To describe dental care utilization and access problems in Connecticut's Medicaid managed care program, using quantitative and qualitative research methods. METHODS: Using Medicaid managed care enrollment and encounter data from Connecticut, utilization rates for preventive care and treatment services are determined for 87,181 children who were continuously enrolled in Medicaid managed care for 1 year in 1996-97. Sociodemographic and enrollment factors associated with utilization are identified using bivariate and multivariate methods. Dental providers and practices where children received services are described. Qualitative methods are used to characterize problems experienced by families seeking dental care during the study period. RESULTS: Only 30.5% of children continuously enrolled in Medicaid managed care for 1 year received any preventive dental services; 17.8% received any treatment services. Children who received preventive care were eight times more likely to have received treatment services. Utilization was higher among (a) younger children, (b) children who lived in Hartford and in other counties served by public dental clinics, and (c) children enrolled in health plans that did not subcontract for administration of dental services. Just 5% of providers, primarily those in public dental clinics, performed 50% of the services. Families whose children needed care encountered significant administrative and logistical problems when trying to find willing providers and obtain appointments. CONCLUSIONS: Access to dental care is a problem for children in Connecticut's Medicaid managed care program. Several features of managed care have negatively affected access. Public dental clinics served many children across the state and contributed to higher utilization of preventive care and treatment services among children living in Hartford.

Adolescent↗
PubMed2001

Pretreatment with glycine reduces the severity of warm intestinal ischemic-reperfusion injury in the rat.

Free jejunal flaps may experience adverse effects immediately after revascularization because of ischemic-reperfusion injury. In this study the authors evaluated the ability of glycine to protect the small intestine against the effects of a warm ischemic-reperfusion injury. Male Wistar rats (N = 30) were randomized to either a baseline group (no intervention), a control group (local arterial infusion with normal saline), or a glycine group (local arterial infusion with 20% glycine). Pretreatment with 20% glycine increased significantly (p < 0.05) mucosal protein and deoxyribonucleic acid content, reduced intestinal myeloperoxidase activity, and maintained mucosal glutaminase activity. These results indicate that some of the indicators of ischemic-reperfusion injury are improved by pretreatment with a 20% glycine solution.

Animals↗
PubMed2001

Retrospective study of the use of hydromorphone in palliative care patients with normal and abnormal urea and creatinine.

An uncontrolled retrospective study was conducted looking at the use of oral controlled-release hydromorphone in palliative care patients. Over a 2-year period 55 patients were switched to hydromorphone therapy, and the efficacy and outcomes were assessed. Urea and electrolyte measurements were also recorded at the time of opioid switch and renal impairment defined as urea > 10.5 mmol/l and/or creatinine > or = 101 mmol/l. This group of 29 patients with abnormal urea and/or creatinine (Group 1) was compared with the remaining 26 patients (Group 2) who had normal urea and creatinine. The major reasons for change to hydromorphone were side-effects (cognitive/drowsiness/nausea) on previous therapy. Following a switch to hydromorphone these side-effects improved in over 80% of patients (n = 55). Comparison between Group 1 and 2 demonstrated a significant difference in renal function but no significant differences in reasons for change, dose of opioids or response to change (over 80% improvement following opioid switch). We conclude that hydromorphone is a flexible second-line alternative to morphine that is particularly useful when intolerable side-effects are experienced with other opioids. In renal impairment (including two patients with end-stage renal failure) we found hydromorphone to be safe and effective. Further clinical and pharmacokinetic studies are required.

Adult↗
PubMed2001

Timing of endogenous activin-like signals and regional specification of the Xenopus embryo.

Signaling by activin-like ligands is important for induction and patterning of mesoderm and endoderm. We have used an antibody that specifically recognizes the phosphorylated and activated form of Smad2, an intracellular transducer of activin-like ligands, to examine how this signaling pathway patterns the early mesendoderm. In contrast to the simple expectation that activin-like signaling should be highest on the dorsal side of the gastrula stage embryo, we have found that while Smad2 phosphorylation is highest dorsally before gastrulation, signaling is attenuated dorsally and is highest on the ventral side by mid-gastrulation. Early dorsal initiation of Smad2 phosphorylation results from cooperation between the vegetally localized maternal transcription factor VegT and dorsally localized beta-catenin. The subsequent ventral appearance of Smad2 phosphorylation is dependent on VegT, but not on signaling from the dorsal side. Dorsal attenuation of Smad2 phosphorylation during gastrulation is mediated by early dorsal expression of feedback inhibitors of activin-like signals. In addition to regulation of Smad2 phosphorylation by the expression of activin-like ligands and their antagonists, the responsiveness of embryonic cells to activin-like ligands is also temporally regulated. Ectopic Vg1, Xnr1 and derrière all fail to activate Smad2 phosphorylation until after the midblastula transition, and the onset of responsiveness to these ligands is independent of transcription. Furthermore, the timing of cellular responsiveness differs for Xnr1 and derrière, and these distinct temporal patterns of responsiveness can be correlated with their distinctive phenotypic effects. These observations suggest that the timing of endogenous activin-like signaling is a determinant of patterning in the early Xenopus embryo.

Activins↗
PubMed2001

Lost-a-fin encodes a type I BMP receptor, Alk8, acting maternally and zygotically in dorsoventral pattern formation.

TGFbeta signaling pathways of the bone morphogenetic protein (BMP) subclass are essential for dorsoventral pattern formation of both vertebrate and invertebrate embryos. Here we determine by chromosomal mapping, linkage analysis, cDNA sequencing and mRNA rescue that the dorsalized zebrafish mutant lost-a-fin (laf) is defective in the gene activin receptor-like kinase 8 (alk8), which encodes a novel type I TGFbeta receptor. The alk8 mRNA is expressed both maternally and zygotically. Embyros that lack zygotic, but retain maternal Laf/Alk8 activity, display a weak dorsalization restricted to the tail and die by 3 days postfertilization. We rescued the laf dorsalized mutant phenotype by alk8 mRNA injection and generated homozygous laf/alk8 mothers to investigate the maternal role of Laf/Alk8 activity. Adult fish lacking Laf/Alk8 activity are fertile, exhibit a growth defect and are significantly smaller than their siblings. Embryos derived from homozygous females, which lack both maternal and zygotic Laf/Alk8 activity, display a strongly dorsalized mutant phenotype, no longer limited to the tail. These mutant embryos lack almost all gastrula ventral cell fates, with a concomitant expansion of dorsal cell types. During later stages, most of the somitic mesoderm and neural tissue circumscribe the dorsoventral axis of the embryo. Zygotic laf/alk8 mutants can be rescued by overexpression of the BMP signal transducer Smad5, but not the Bmp2b or Bmp7 ligands, consistent with the Laf/Alk8 receptor acting within a BMP signaling pathway, downstream of a Bmp2b/Bmp7 signal. Antibodies specific for the phosphorylated, activated form of Smad1/5, show that BMP signaling is nearly absent in gastrula lacking both maternal and zygotic Laf/Alk8 activity, providing further evidence that Laf/Alk8 transduces a BMP signal. In total, our work strongly supports the role of Laf/Alk8 as a type I BMP receptor required for the specification of ventral cell fates.

Activin Receptors↗
PubMed2000

Sequencing and characterization of a novel serine metalloprotease from Burkholderia pseudomallei.

Burkholderia pseudomallei, a Gram-negative bacterium is found in the soil and water, mainly in Southeast Asia and Northern Australia. It is responsible for melioidosis in human and animals. The bacteria produce several potential virulent factors such as extracellular protease, hemolysin, lipase and lecithinase. The isolation of virulence genes and the study of their functions will contribute to our understanding of bacterial pathogenesis. Previous studies have implicated protease as a contributing virulence factor in the pathogenesis of some bacteria. Three out of 5000 clones screened from a genomic DNA library of B. pseudomallei were found to express protease activity. The clones were found to have the same sequence. The nucleotide sequence revealed an open reading frame (designated as metalloprotease A, mprA) encoding a 500-amino acid protein, MprA, with an estimated molecular mass of 50241 Da. The predicted amino acid sequence shares homology with the subtilisin family of serine proteases.

Amino Acid Sequence↗
PubMed2000

Dual anticancer activity of 8-Cl-cAMP: inhibition of cell proliferation and induction of apoptotic cell death.

8-Cl-cAMP induces apoptotic cell death in human cancer cells. To look at this more closely, we examined the changes in the levels of Bcl-2 family proteins during 8-Cl-cAMP-induced apoptosis of SH-SY5Y human neuroblastoma cells. Following the treatment with 8-Cl-cAMP, Bcl-2 was transiently down-regulated and Bad was increased continuously up to day 5. In addition, overexpression of Bcl-2 efficiently blocked the 8-Cl-cAMP-induced apoptosis, suggesting Bcl-2 family proteins may be involved in the 8-Cl-cAMP-induced apoptosis. The contribution of the apoptotic cell death and the inhibition of cell proliferation in the 8-Cl-cAMP-induced growth inhibition was closely monitored in the Bcl-2-overexpressing cells. Though the apoptosis was reduced significantly, no significant difference was observed in the inhibition of cell proliferation up to day 2 of 8-Cl-cAMP treatment. These results suggest that 8-Cl-cAMP exerts anticancer activity by two distinct mechanisms, i.e. , through the inhibition of cell proliferation as well as the induction of apoptosis. Supporting this notion was the observations that (1) suppression of apoptosis by zVAD did not abrogate 8-Cl-cAMP-induced inhibition of cell proliferation, and (2) 8-Cl-cAMP did not show additive inhibition of cell proliferation in RIIbeta-overexpressing cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Physicians' experiences with the Oregon Death with Dignity Act.

BACKGROUND: Physician-assisted suicide was legalized in Oregon in October 1997. There are data on patients who have received prescriptions for lethal medications and died after taking the medications. There is little information, however, on physicians' experiences with requests for assistance with suicide. METHODS: Between February and August 1999, we mailed a questionnaire to physicians who were eligible to prescribe lethal medications under the Oregon Death with Dignity Act. RESULTS: Of 4053 eligible physicians, 2649 (65 percent) returned the survey. Of the respondents, 144 (5 percent) had received a total of 221 requests for prescriptions for lethal medications since October 1997. We received information on the outcome in 165 patients (complete information for 143 patients and partial for on an additional 22). The mean age of the patients was 68 years; 76 percent had an estimated life expectancy of less than six months. Thirty-five percent requested a prescription from another physician. Twenty-nine patients (18 percent) received prescriptions, and 17 (10 percent) died from administering the prescribed medication. Twenty percent of the patients had symptoms of depression; none of these patients received a prescription for a lethal medication. In the case of 68 patients, including 11 who received prescriptions and 8 who died by taking the prescribed medication, the physician implemented at least one substantive palliative intervention, such as control of pain or other symptoms, referral to a hospice program, a consultation, or a trial of antidepressant medication. Forty-six percent of the patients for whom substantive interventions were made changed their minds about assisted suicide, as compared with 15 percent of those for whom no substantive interventions were made (P<0.001). CONCLUSIONS: Our data indicate that in Oregon, physicians grant about 1 in 6 requests for a prescription for a lethal medication and that 1 in 10 requests actually result in suicide. Substantive palliative interventions lead some--but not all--patients to change their minds about assisted suicide.

Attitude of Health Personnel↗
PubMed2000

Axonal injury or loss in the internal capsule and motor impairment in multiple sclerosis.

OBJECTIVE: To test the hypothesis that axonal damage extending into primarily normal-appearing white matter is clinically important by comparing the concentrations of N-acetylaspartate (NAA) bilaterally within the internal capsule with lateralization of motor impairment in patients with multiple sclerosis (MS) and persistent asymmetrical motor deficit. DESIGN: We performed magnetic resonance spectroscopy and T2-weighted imaging of the internal capsule, calculated central motor conduction times, and related these results to measures of motor function asymmetry in 12 patients with MS. RESULTS: Levels of NAA from normal-appearing white matter of the internal capsule in patients with MS were significantly lower than those in control subjects (P = .05). Side-to-side differences in NAA levels were also significantly greater in patients with MS than in controls (P = .01). There was a correlation between asymmetry in motor function for the left and right limbs and asymmetry of internal capsule NAA concentrations (r = 0.60; P = .04). This correlation seemed slightly stronger when tests specifically of arm and hand motor asymmetry were considered alone. Central motor conduction times were abnormal in most patients with MS and showed a side-to-side difference that also correlated with asymmetry in motor function. CONCLUSION: Our demonstration of a graded association between NAA concentrations within primarily normal-appearing white matter of a specific tract and functional impairments referable to that tract suggests that axonal pathology distant from macroscopic lesions might be an important determinant of disability in MS.

Adult↗
PubMed2000

Correlating magnetic resonance imaging markers of axonal injury and demyelination in motor impairment secondary to stroke and multiple sclerosis.

The primary pathological mechanisms in stroke and multiple sclerosis (MS) are very different but in both diseases, impairment may arise from a final common pathway of axonal damage. We aimed to examine the relationship between motor impairment, magnetisation transfer ratio (MTR) (an index of demyelination), and N-acetyl aspartate (NAA) loss (an index of axonal injury) localised to the descending motor pathways in stroke and MS. Twelve patients between 1 and 10 months after first ischaemic stroke causing a motor deficit and 12 patients with stable MS with asymmetric motor deficit were examined. T(2)-weighted imaging of the brain together with MTR and proton (voxel 1.5x2x2 cm(3)) MRS localised to the posterior limb of the internal capsule were performed and correlated to a composite motor deficit score. MTR and NAA in the internal capsule were reduced in both stroke and MS patients compared to controls. NAA loss correlated with motor deficit score in both stroke and MS (p<0.001 and p = 0.04, respectively). Correlations were seen between MTR and motor deficit (p<0.001) MTR and NAA loss (p <0.001) in stroke patients but not in MS patients. Axonal injury in the descending motor tracts would appear to be an important determinant of motor impairment in both stroke and MS. In stroke, MTR measures of demyelination are closely related to axonal damage and thus also correlate with motor deficit. However in MS, MTR measures of demyelination do not correlate with NAA loss or motor deficit suggesting that demyelination and gliosis may occur independently of axonal damage and are less closely linked with functional impairment.

Adult↗
PubMed2000

Localizing and lateralizing value of epileptic symptoms in temporal lobe epilepsy.

The symptoms and signs associated with all stages of a temporal lobe seizure may be helpful in determining both the localization and lateralization of seizure onset. Auras, when present, may be very suggestive of temporal lobe onset and may further localize to a mesiobasal or lateral temporal lobe site of onset. During the ictus, automatisms and motor phenomena may be highly indicative of temporal lobe seizure activity and may even help lateralize the discharge. In the post-ictal period, motor paresis and aphasia are helpful in lateralization. Video E.E.G. data has provided extensive information on the utility of ictal symptomatology in seizure localization. Thus, the seizure semiology provides important adjunctive information in evaluating patients for epilepsy surgery and should be concordant with information obtained from ictal EEG, neuroimaging and neuropsychology.

Automatism↗
PubMed2000

Physician orders for life-sustaining treatment (POLST): outcomes in a PACE program. Program of All-Inclusive Care for the Elderly.

OBJECTIVES: To evaluate whether terminal care was consistent with Physician Orders for Life-Sustaining Treatment (POLST), a preprinted and signed doctor's order specifying treatment instructions in the event of serious illness for CPR, levels of medical intervention, antibiotics, IV fluids, and feeding tubes. DESIGN: Retrospective chart review. SETTING: ElderPlace, a Program of All-Inclusive Care for the Elderly (PACE) site in Portland, Oregon. PARTICIPANTS: All ElderPlace participants who died in 1997 were eligible (n = 58). Reasons for exclusion were no POLST (1), missing POLST (1), and insufficient documentation of care (2). MEASUREMENTS: POLST instructions for each participant and whether or not each of the treatments addressed by the POLST was administered in the final 2 weeks of life. RESULTS: The POLST specified "do not resuscitate" for 50 participants (93%); CPR use was consistent with these instructions for 49 participants (91%). "Comfort care" was the designated level of medical intervention in 13 cases, "limited interventions" in 18, "advanced interventions" in 18, and "full interventions" in 5. Interventions administered were at the level specified in 25 cases (46%); at a less invasive level in 18 (33%), and at a more invasive level in 11 (20%). Antibiotic administration was consistent with POLST instructions for 86% of 28 subjects who had infections in the last 2 weeks of life, and less invasive for 14%. Care matched POLST instructions in 84% of cases for IV fluids and 94% for feeding tubes. CONCLUSIONS: POLST completion in ElderPlace exceeds reported advance directive rates. Care matched POLST instructions for CPR, antibiotics, IV fluids, and feeding tubes more consistently than previously reported for advance directive instructions. Medical intervention level was consistent with POLST instructions for less than half the participants, however. We conclude that the POLST is effective for limiting the use of some life-sustaining interventions, but that the factors that lead physicians to deviate from patients' stated preferences merit further investigation.

Advance Directives↗