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Biomedical subjects

L Fleming

Publications and source records attributed to L Fleming.

At least 19 recordsLinked to original sources
PubMed2003

Identification of developmentally regulated genes in the somatic cells of the mouse testis using serial analysis of gene expression.

To identify genes developmentally regulated in the somatic cells of the testis, serial analysis of gene expression (SAGE) has been used to generate gene expression profiles from these cells in the fetal and adult mouse. To avoid germ cell transcripts, a fetal SAGE library was generated from germ cell-free fetal Wv/Wv mice, and an adult SAGE library was generated from adult testes depleted of germ cells with busulfan. The combined SAGE libraries contained 147570 tags identifying 12976 unique transcripts. Of these transcripts, 3607 were present in only the fetal library and 3941 were present in only the adult library. Most of the abundant differentially expressed tags in the adult testis library were from characterized genes, whereas 3' rapid amplification of complementary ends was required to identify most differentially expressed tags in the fetal library. These fetal tags were mostly associated with uncharacterized UniGene clusters. These data provide a comprehensive and quantitative analysis of gene expression in the somatic cells of the fetal and adult testis (including unknown transcripts) and identify genes differentially expressed in these cells during testis development. These differentially regulated genes are likely to provide insight into mechanisms regulating testis function both during development and in the adult animal.

Animals↗
PubMed2002

[Extracorporeal shockwave therapy in symptomatic heel spurs. An overview].

Extracorporeal shock wave application (ESWA) has been successfully used for years in routine clinical management of plantar fasciitis. So far no clinical trails have shown the efficiency in placebo-controlled protocols. This paper presents an overview of conservative and operative treatment modalities with respect to their efficacy. Results of a prospective randomized placebo-controlled double-blind multicenter trial to show efficiency and safety of ESWT are presented. In patients treated conservatively without success, a single shock wave application can improve the condition significantly compared with placebo treatment (p = 0.0149). The Roles and Maudsley score also showed a significant improvement between the groups, with 61.6% good or excellent results in the verum group and 39.7% in the placebo group (p = 0.0128). Therapy-related side effects (local swelling, petechia) are rare. The data presented in this study led to FDA approval in January 2002 of the shock wave device used.

Adult↗
PubMed2001

Lithium intercalation into opened single-wall carbon nanotubes: storage capacity and electronic properties.

The effects of structure and morphology on lithium storage in single-wall carbon nanotube (SWNT) bundles were studied by electrochemistry and nuclear magnetic resonance techniques. SWNTs were chemically etched to variable lengths and were intercalated with Li. The reversible Li storage capacity increased from LiC(6) in close-end SWNTs to LiC(3) after etching, which is twice the value observed in intercalated graphite. All the nanotubes became metallic upon intercalation of Li, with the density of states at the Fermi level increasing with increasing Li concentration. The enhanced capacity is attributed to Li diffusion into the interior of the SWNTs through the opened ends and sidewall defects.

Journal Article↗
PubMed2000

Electronic structures of single-walled carbon nanotubes determined by NMR

Single-walled carbon nanotubes were studied by (13)C nuclear magnetic resonance (NMR). Two types of (13)C nuclear spins were identified with different spin-lattice relaxation rates. The fast-relaxing component, assigned to metallic tubes, followed the relaxation behavior expected in metals, and the density-of-states at the Fermi level increased with decreasing tube diameter. The slow-relaxing component has a significantly lower density-of-states at the Fermi level. Exposure to oxygen has a substantial effect on relaxation rates of both components.

Journal Article↗
PubMed2000

Causes and severity of ischemic stroke in patients with internal carotid artery stenosis.

CONTEXT: Therapeutic trials generally have not distinguished outcomes of stroke according to cause. OBJECTIVE: To determine whether stroke and subsequent disability was of large-artery, lacunar, or cardioembolic origin in patients with different degrees of symptomatic and asymptomatic carotid stenosis. DESIGN: Observational study of prospective data collected from the North American Symptomatic Carotid Endarterectomy Trial between 1987 and 1997. SETTING AND PATIENTS: A total of 2885 patients from 106 sites in the United States and abroad (median age, 67 years; 70% male) who had symptomatic internal carotid artery stenosis. MAIN OUTCOME MEASURE: Risk of stroke from each of the 3 causes at 5 years by territory and degree of stenosis. RESULTS: During an average follow-up of 5 years, 749 patients had 1039 strokes, including 112 of cardioembolic, 211 of lacunar, 698 of large-artery, 17 of primary intracerebral hemorrhage, and 1 of subarachnoid hemorrhage origin. The 5-year risk of first stroke after entry into the trial in any territory was 2.6% of cardioembolic cause, 6.9% of lacunar cause, and 19.7% of large-artery cause. The proportion of cardioembolic strokes in the territory of the symptomatic artery was 12.0% and 6.9% in 60% to 69% and 70% to 99% arterial stenosis, respectively; large-artery strokes predominated (78.4%) at 70% to 99% arterial stenosis. With 70% to 99% arterial stenosis, the proportion of strokes of cardioembolic and lacunar origin was 43.5% and 21.6% in asymptomatic and symptomatic arteries, respectively. A total of 67.6% of cardioembolic, 16.7% of lacunar, and 33.0% of large-artery strokes in the territory of the asymptomatic artery were disabling or fatal. CONCLUSIONS: Our data suggest that approximately 20% and 45% of strokes in the territory of symptomatic and asymptomatic carotid arteries with 70% to 99% stenosis, respectively, are unrelated to carotid stenosis. The cause of subsequent strokes in similar types of patients should be considered when making treatment decisions involving carotid endarterectomy for patients with asymptomatic carotid stenosis, since lacunar and cardioembolic strokes cannot be prevented by endarterectomy.

Aged↗
PubMed1998

Silent aspiration after coronary artery bypass grafting.

BACKGROUND: "Silent" aspiration was recognized to be a more frequent complication at this hospital in patients who have had coronary artery bypass grafting than in the general surgical population. METHODS: A case-control retrospective study covering a 4.5-year period was conducted to determine risk factors for pharyngeal dysfunction resulting in silent aspiration. RESULTS: Significant predictors of silent aspiration were age, history of cerebral vascular disease, insulin-dependent diabetes mellitus, myocardial infarction, and chronic obstructive pulmonary disease. Intraaortic balloon pump and number of units of fresh-frozen plasma were the only independent intraoperative factors associated with silent aspiration in a model using continuous variables directly. Cold fibrillation was used in 7 of 53 study cases but no control patients, so it could not be modeled. Postoperative complications occurring with greater frequency included neurologic complications, adverse pulmonary outcomes, repeat surgical interventions, infection, and death. Using an Aspiration Risk Profile developed from the retrospective study, in a detailed prospective study of 10 patients, 3 of 4 patients with postoperative dysphagia had objective evidence of stroke. CONCLUSIONS: These findings suggest that postoperative coronary artery bypass graft dysphagia may be the result of intraoperative cerebral injury, and that careful postoperative clinical evaluation of coronary artery bypass graft patients with risk factors may result in early diagnosis of pharyngeal dysfunction with the goals of preventing silent aspiration and reducing morbidity, mortality, and hospital cost.

Age Factors↗
PubMed1997

Epidemiology of hepatitis B vaccine acceptance among urban paramedics and emergency medical technicians.

BACKGROUND: The epidemiologic pattern of hepatitis B vaccination acceptance has not been thoroughly examined in medical first responders. METHODS: A blood-borne pathogen questionnaire was administered to 255 paramedics and emergency medical technicians (EMTs) in a large, urban fire department. RESULTS: The overall prevalence of hepatitis B vaccination was 78%. The most frequently cited reason for not getting vaccinated was fear of contracting the hepatitis B virus from the vaccination (26%). Vaccination scheduling difficulties (23%) and lack of time to get vaccinated (20%) were also cited. Increased age, being an EMT, and not having obtained the rank of officer were independently and significantly associated with not having been vaccinated. CONCLUSIONS: Educational campaigns for medical first responders are needed to increase vaccination compliance, with a special emphasis on older workers and EMTs. Administrative barriers, such as vaccination scheduling difficulties, should also be addressed.

Adult↗
PubMed1996

Duration of action of intranasal atropine on methacholine-induced nasal secretions.

OBJECTIVE: To evaluate the duration of the inhibitory action of intranasal atropine on the secretory response to nasal challenge with methacholine. DESIGN: Double-blind, placebo-controlled, four-way crossover trial. SUBJECTS: Twelve volunteers with perennial allergic rhinitis. INTERVENTIONS: Subjects were treated intranasally with placebo or 100, 200, and 400 micrograms of atropine in each nostril. They were then challenged 30 minutes after administration of the nasal spray and hourly for 6 hours with 0.19 mg of methacholine. The weight of nasal secretions generated by methacholine challenge served as an indicator of the secretory response. The nasal challenges and the collection of nasal secretions were performed using filter paper disks. RESULTS: After placebo treatment, the response to methacholine was similar at each time point. In contrast, all doses of atropine significantly reduced the response to methacholine stimulation at the 30-minute, 1-hour, and 2-hour time points. CONCLUSIONS: Our data show that the anticholinergic activity of intranasal atropine lasts at least 2 hours with no significant difference in the duration of inhibitory action between the doses used. The results suggest that intranasal atropine could become a therapeutic modality for patients in whom glandular hypersecretion is a major symptom.

Administration, Intranasal↗
PubMed1994

Parkinson's disease and brain levels of organochlorine pesticides.

Epidemiological studies have suggested an etiologic relationship between pesticide exposure and Parkinson's disease (PD). Organochlorine pesticides were assayed in postmortem brain samples from 20 PD, 7 Alzheimer's disease (AD), and 14 nonneurological control cases. The three groups were similar in age at death, sex, and demographic variables. Only two of 16 pesticide residues screened were detected. A long-lasting residue of DDT (pp-DDE) was found in the majority of cases of PD and AD, as well as in all the control cases; pp-DDT was significantly more likely to be found in AD controls than the PD cases (Fisher's exact two-tailed, p = 0.04). Dieldrin was detected in 6 of 20 PD brains, 1 of 7 AD, and in none of 14 control samples. Despite the relatively small number of brains assayed, the association between Dieldrin and the diagnosis of PD was highly significant (p = 0.03). Dieldrin, a lipid-soluble, long-lasting mitochondrial poison, should be investigated as a potential etiological agent of Parkinsonism.

Age Factors↗
PubMed1992

Opioid and cannabinoid receptor inhibition of adenylyl cyclase in brain.

Both opioids and cannabinoids bind to G-protein-coupled receptors to inhibit adenylyl cyclase in neurons. These reactions were assayed in brain membranes, where maximal inhibitory activity occurred in the following regions: mu-opioid inhibition in rat thalamus, delta-opioid inhibition in rat striatum, kappa-opioid inhibition in guinea pig cerebellum, and cannabinoid inhibition in cerebellum. The inhibition of adenylyl cyclase by both cannabinoid and opioid agonists was typical of G-protein-linked receptors: they required GTP, they were not supported by non-hydrolyzable GTP analogs, and they were abolished (in primary neuronal cell culture) by pertussis toxin treatment. The immediate targets of this system were determined by assaying protein phosphorylation in the presence of receptor agonists and App(NH)p, a substrate for adenylyl cyclase. In striatal membranes, opioid agonists inhibited the phosphorylation of at least two bands of MW 85 and 63 kDa, which may be synapsins I and II, respectively. Other experiments determined the long-term effects of this second messenger system. In primary neuronal cultures, opioid-inhibited adenylyl cyclase attenuated forskolin-stimulated pro-enkephalin mRNA levels, thus providing a feedback regulation of opioid synthesis. Finally, in cerebellar granule cells, both cannabinoid and opioid receptors may exist on the same cells. In these cells, agonists which bind to different receptor types may produce similar biological responses.

Adenylyl Cyclase Inhibitors↗
PubMed1992

Expression of human alpha 1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes.

The liver represents an excellent organ for gene therapy since many genetic disorders result from the deficiency of liver-specific gene products. We have previously demonstrated that transgenic mouse hepatocytes can be heterologously transplanted into congenic recipients where they survived indefinitely and continued to function as hepatocytes. Here we demonstrate the autologous transplantation of retrovirally transduced canine hepatocytes. At least 1 x 10(9) hepatocytes or 5% of the liver mass can be transplanted by the portal vasculature. In two animals we have transplanted hepatocytes transduced with a retroviral vector containing the human alpha 1-antitrypsin cDNA under transcriptional control of the cytomegalovirus promoter. Both animals had significant human alpha 1-antitrypsin in the serum for 1 month. Although the serum levels of human alpha 1-antitrypsin eventually fell due to inactivation of the cytomegalovirus promoter, PCR analysis demonstrated that a significant fraction of transduced hepatocytes migrated to the liver and continued to survive in vivo. The results suggest that gene therapy of hepatic deficiencies may be achieved by hepatocellular transplantation after genetic reconstitution with the use of promoters of cellular genes that are active in the normal liver.

Animals↗
PubMed1990

Clinical and pathological characteristics of hepatotoxicity associated with occupational exposure to dimethylformamide.

The clinical characteristics, laboratory results, and liver biopsy findings of seven workers with toxic liver injury associated with exposure to several solvents, including substantial levels of the widely used solvent dimethylformamide, are presented. Three patients had short exposure (less than 3 months), four long exposure (greater than 1 year). Among those with brief exposure, symptoms included anorexia, abdominal pain, and disulfiram-type reaction. Aminotransferases were markedly elevated with the ratio of alanine aminotransferase to aspartate aminotransferase always greater than 1. Liver biopsy showed focal hepatocellular necrosis and microvesicular steatosis with prominence of smooth endoplasmic reticulum, complex lysosomes, and pleomorphic mitochondria with crystalline inclusions. Among workers with long exposure, symptoms were minimal and enzyme elevations modest. Biopsies showed macrovesicular steatosis, pleomorphic mitochondria without crystalloids, and prominent smooth endoplasmic reticulum, but no evidence of persisting acute injury or fibrosis. Abnormal aminotransferases in both groups may persist for months after removal from exposure, but progression to cirrhosis in continually exposed workers was not observed. We conclude that exposure of these workers to solvents, chiefly dimethylformamide, may result in two variants of toxic liver injury with subtle clinical, laboratory, and morphological features. This may be readily overlooked if occupational history and biopsy histology are not carefully evaluated.

Adult↗
PubMed1990

Magnetic resonance imaging of knee menisci. Comparison of spin echo pulse sequences.

Magnetic resonance imaging (MRI) is accurate in evaluating meniscal tears using spin echo pulse sequences. The purpose of this study was to systematically compare T1-weighted pulse sequences to two echo proton density/T2 (2eT2)-weighted sequences. Menisci were separated into four grades based on signal characteristics. In addition, all menisci were graded as positive or negative for tear. Twenty-three patients (46 menisci) were studied with both pulse sequences and the results were compared with arthroscopic findings. Using T1 sequences, 14 of 18 torn menisci and 26 of 28 untorn menisci were identified. Using 2eT2 sequences, 13 of 18 torn menisci and 26 of 28 untorn menisci were correctly identified. There was high correlation between T1 and 2eT2 sequences for torn versus untorn menisci and for grade of injury (P = .99). There is very little difference between T1- and 2eT2-weighted pulse sequences in evaluation of meniscal tears.

Arthroscopy↗
PubMed1989

Crohn's disease (regional enteritis) in association with Hodgkin's disease.

It has long been known that Crohn's disease may occur in association with certain forms of malignancy, specifically adenocarcinoma and lymphoma of the bowel and carcinoma of the vulva and perianal area. Here, the authors report the rare occurrence of extraintestinal Hodgkin's disease in a patient with documented regional enteritis of five years' duration. They propose explanations for this unusual combination of disease, reported in the literature only once previously, and review the pathophysiology of lymphoma and regional enteritis.

Adult↗
PubMed1988

MR imaging diagnosis of rotator cuff tears.

Thirty-one symptomatic patients were studied with MR imaging to evaluate the sensitivity and specificity of shoulder MR in the diagnosis of rotator cuff tears. Correlative studies included arthroscopy in 19 patients and arthrography in 12 patients. Images were obtained on either a 0.5- or 1.5-T Philips superconducting magnet using spin-echo pulse sequences (650-850/30 [TR, TE], 2000/30, 100) with 5-mm slices oriented in an oblique coronal plane perpendicular to the glenohumeral joint. The MR studies were initially interpreted without knowledge of the results of other diagnostic procedures. The MR diagnosis of cuff tear was made when irregularity, discontinuity, and increased signal were identified in the rotator cuff. MR images showed tears in 10 patients (32%) and were negative for tear in 21 patients (68%). MR correlated with arthroscopy and arthrography in 17 of 18 normal patients, in eight of 10 patients with complete tears, and in one of three patients with partial tears. For complete rotator cuff tears, the sensitivity, specificity, and accuracy were 80%, 94%, and 89%, respectively. For all tears (partial and complete), the sensitivity, specificity, and accuracy were 69%, 94%, and 84%, respectively. These data suggest that MR imaging is an accurate procedure for the diagnosis of complete rotator cuff tears. The number of partial tears (three) in this series is too small to evaluate the value of MR imaging in the diagnosis of partial tears.

Adult↗