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Biomedical subjects

Mark Lee

Publications and source records attributed to Mark Lee.

26 records · Page 2Linked to original sources
PubMed2002

CD4(+) T cells from glutamic acid decarboxylase (GAD)65-specific T cell receptor transgenic mice are not diabetogenic and can delay diabetes transfer.

Glutamic acid decarboxylase (GAD)65 is an early and important antigen in both human diabetes mellitus and the nonobese diabetic (NOD) mouse. However, the exact role of GAD65-specific T cells in diabetes pathogenesis is unclear. T cell responses to GAD65 occur early in diabetes pathogenesis, yet only one GAD65-specific T cell clone of many identified can transfer diabetes. We have generated transgenic mice on the NOD background expressing a T cell receptor (TCR)-specific for peptide epitope 286-300 (p286) of GAD65. These mice have GAD65-specific CD4(+) T cells, as shown by staining with an I-A(g7)(p286) tetramer reagent. Lymphocytes from these TCR transgenic mice proliferate and make interferon gamma, interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, and IL-10 when stimulated in vitro with GAD65 peptide 286-300, yet these TCR transgenic animals do not spontaneously develop diabetes, and insulitis is virtually undetectable. Furthermore, in vitro activated CD4 T cells from GAD 286 TCR transgenic mice express higher levels of CTL-associated antigen (CTLA)-4 than nontransgenic littermates. CD4(+) T cells, or p286-tetramer(+)CD4(+) Tcells, from GAD65 286-300-specific TCR transgenic mice delay diabetes induced in NOD.scid mice by diabetic NOD spleen cells. This data suggests that GAD65 peptide 286-300-specific T cells have disease protective capacity and are not pathogenic.

Abatacept↗
PubMed2002

An outbreak of food-borne illness associated with methomyl-contaminated salt.

CONTEXT: On January 5, 1999, the California Department of Health Services was notified of the repeated occurrence (December 21, 1998, and January 2, 1999) of gastrointestinal tract illness among patrons at a Thai restaurant in central California. OBJECTIVE: To identify the source of the outbreak. DESIGN: Case-control study; microbiological and toxicological laboratory testing of samples of food, stool, and vomitus. SETTING: Thai food restaurant in central California. PARTICIPANTS: Patrons of the restaurant. A case (n = 107) was defined as dizziness, nausea, or vomiting occurring in a person who ate at the restaurant between December 20, 1998, and January 2, 1999, with onset of symptoms within 2 hours of eating. A control (n = 169) was a person who ate at the restaurant during the same period but reported no symptoms. MAIN OUTCOME MEASURES: Odds ratios (ORs) of illness associated with food exposures; ORs of shifts during which illness occurred associated with certain cooks; laboratory results. RESULTS: The median latency period was 40 minutes from beginning eating to first symptom and was 2 hours to onset of diarrhea. The median duration of symptoms was 6 hours. Twenty-six persons (24%) visited the emergency department or were treated by a physician; no person required hospitalization. Patients reported nausea (95%), dizziness (72%), abdominal cramps (58%), headache (52%), vomiting (51%), chills (48%), and diarrhea (46%). Fifty-one cases (48%) included dizziness, lightheadedness, or a feeling of disequilibrium as the initial symptom. Illness was statistically associated with several foods and ingredients, but no single dish or ingredient explained a substantial number of cases. The analysis of food exposures included salt added by cooks, as estimated by using the amount of salt in the recipe for each dish and the amount of each dish eaten by respondents. This association was stronger with increasing levels of salt: ORs for illness among persons who consumed more than 0.42 to 0.84, more than 0.84 to 1.25, and more than 1.25 tsp of salt added to foods in the kitchen were 1.9 (95% confidence interval [CI], 0.6-5.7), 3.0 (95% CI, 1.0-8.8), and 4.0 (95% CI, 1.3-13.5) compared with persons who consumed less than 0.42 tsp (P value for trend =.004). Methomyl, a highly toxic carbamate pesticide, was identified in a sample of vomitus (20 ppm) and in salt taken from containers in the storeroom (mean, 5600 ppm) and the stovetop (mean, 1425 ppm). The oral toxic dose causing illness in 50% of those exposed to methomyl was estimated to be 0.15 mg/kg of body weight (estimated range, 0.09-0.31 mg/kg of body weight). The presence of cook A was associated with shifts during which cases of illness occurred (OR, 10.4; 95% CI, 1.2-157.4). CONCLUSION: This outbreak of gastrointestinal illness was associated with the consumption of food seasoned with methomyl-contaminated salt. To allow rapid assessment for further investigational and control measures by health officials, physicians should report suspected outbreaks of illness to public health departments, however trivial the symptoms or cause may seem.

California↗
PubMed2002

Restricted islet-cell reactive T cell repertoire of early pancreatic islet infiltrates in NOD mice.

The mechanisms responsible for initiating autoimmune diabetes remain obscure. Here, we describe a method for identifying both the alpha- and beta-chains of the T cell receptor (TCR) from individual pancreatic islet-infiltrating T cells at the earliest stages of disease in nonobese diabetic mice (NOD). Analysis of the TCR repertoire of these early islet infiltrates reveals enrichment for a small subset of TCR sequences. Reconstitution of these TCR in vitro demonstrates that these receptors confer reactivity to islet cells but not to the well characterized autoantigens, glutamic acid decarboxylase (GAD65) and insulin. Thus, autoimmune diabetes in NOD may be initiated by a limited number of antigens distinct from GAD65 and insulin.

Amino Acid Sequence↗
PubMed2002

An in vitro system for Doppler ultrasound flow studies in the stenosed carotid artery bifurcation.

To investigate the correlation between disease severity and Doppler spectral measurements in the carotid artery bifurcation, a unique in vitro system has been developed that mimics the human vasculature with respect to both anatomy and flow perfusion. Agar-based carotid phantoms are perfused with a blood-mimicking fluid using a computer-controlled pump and realistic pulsatile flow waveform. A three-axis translational stage allows the lumen to be interrogated with a 0.6-microL Doppler sample volume at the desired spatial intervals using a semiautomated acquisition system, to collect 10 cardiac cycles of gated quadrature data at each site. Off-line analysis, including a 1024-point FFT, produces a 4-D (i.e., time-varying 3-D) Doppler velocity data set with 1.3-cm/s velocity resolution and 12-ms temporal resolution. Using this system, in vitro flow in bifurcations with both normal and stenosed lumen geometry (from 30% to 80% stenosis by NASCET criteria) can be studied, along with the effect of factors, such as stenosis geometry (concentric vs. eccentric) and flow rate, on the observed Doppler ultrasound (US) spectra and haemodynamic patterns.

Blood Flow Velocity↗
PubMed2002

An outbreak due to multiresistant Acinetobacter baumannii in a burn unit: risk factors for acquisition and management.

OBJECTIVES: To describe the investigation and management of an outbreak due to multiresistant Acinetobacter baumannii and to determine risk factors for acquisition of the organism. SETTING: A 14-bed regional burn unit in a Canadian tertiary-care teaching hospital. DESIGN: Case-control study with multivariate analysis of potential risk factors using logistic regression analysis. Surveillance cultures were obtained from the hospital environment, from noninfected patients, and from healthcare providers. RESULTS: A total of 31 (13%) of 247 patients with acute burn injuries acquired multiresistant A. baumannii between December 1998 and March 2000; 18 (58%) of the patients were infected. The organism was recovered from the hospital environment and the hands of healthcare providers. Significant risk factors for acquisition of multiresistant A. baumannii were receipt of blood products (odds ratio [OR], 10.8; 95% confidence interval [CI95], 3.4 to 34.4; P < .001); procedures performed in the hydrotherapy room (OR, 4.1; CI95, 1.3 to 13.1; P = .02); and increased duration of mechanical ventilation (OR, 1.1 per day; CI95, 1.0 to 1.1; P= .02). INTERVENTIONS: Improved compliance with hand hygiene, strict patient isolation, meticulous environmental cleaning, and temporary closure of the unit to new admissions. CONCLUSIONS: Acquisition of multiresistant A. baumannii was likely multifactorial, related to environmental contamination and contact with transiently colonized healthcare providers. Control measures addressing these potential sources of multiresistant A. baumannii were successful in terminating the outbreak. Ongoing surveillance and continued attention to hand hygiene and adequate environmental cleaning are essential to prevent recurrent outbreaks due to antibiotic-resistant bacteria in burn units.

Acinetobacter Infections↗
PubMed2002

Computed tomography of the brain morphology of patients with first-episode schizophrenic psychosis.

OBJECTIVE: To report computed tomographic (CT) scan ratings of various aspects of brain morphology of a large representative sample of patients with a first episode of schizophrenic psychosis and to compare these ratings with those from a previously reported sample of patients with chronic schizophrenia. METHODS: A brain CT scan was performed on 114 patients with a diagnosis of first episode of schizophrenia or schizophreniform psychosis. Ratings on sulcal and ventricular enlargement and sylvian fissure were obtained using the Computed Tomographic Rating Scale for Schizophrenia. The influence of age, sex, age of onset, duration of illness and clinical psychopathology on CT ratings was assessed using bivariate correlations and multiple regression analyses. The CT ratings were also compared with those from a sample of patients with chronic schizophrenia. RESULTS: First-episode patients showed a modest enlargement of sulci and ventricles and a reversed asymmetry of the sylvian fissure. Age was the only independent predictor of these regional changes. Clinical symptoms, sex or duration of untreated psychosis showed no relation to CT ratings. A comparison of first-episode patients with chronically ill patients, with the effect of age covaried, revealed the sylvian fissure was significantly larger (right and left sides) in the chronically ill patients. CONCLUSIONS: Patients with a first episode of schizophrenic psychosis showed evidence of morphological changes generally associated with chronic schizophrenia. Such changes are not likely related to sex, clinical symptoms or duration of untreated psychosis, but are influenced by age. Changes in the ventricles and sulcal size are unlikely to be progressive, suggesting a neurodevelopmental origin, whereas changes in the area of the sylvian fissure may be of a more degenerative nature.

Adult↗
PubMed2002

Internal medicine resident satisfaction with a diagnostic decision support system (DXplain) introduced on a teaching hospital service.

OBJECTIVE: The objective of this study was to determine whether Internal Medicine residents would find the use of an expert system (i.e. Clinical Diagnostic Decision Support System) to be a satisfactory experience when used during a clinical rotation in the hospital setting. Resident willingness to use the instrument was considered to be of particular importance because of growing concerns regarding the educational experience of residents in the hospital. Thus, our first goal was to assess resident satisfaction with the tool, prior to widespread implementation. STUDY POPULATION: Residents on the General Medical Hospital Service at St. Mary's Hospital, Rochester, Minnesota STUDY TYPE: Prospective cohort study METHOD: We provided unrestricted access DXplain, a Web-based Clinical Diagnostic Decision Support System, to five general medical teams in St. Mary's Hospital, Rochester, MN. All residents were particularly encouraged to access the system during the evaluation of new admissions. Usage of the system was recorded electronically each time a user logged on. At the conclusion of the 2 month study period, a survey was sent electronically to each of the participating residents. RESULTS: During the study period, a total of 30 residents (G1 =20, G3= 10) rotated on the five medical services. 29/30 residents responded to the survey. 18/29 indicated that they had used the service, while 11/29 stated that they had not accessed the system. The resident's logged on 117 times to enter a case during the study period, with several entering more than one case per logon. The average number of log-ons per user was 2.4/week. Of the 18 who used the system, 15 found it useful (83.3%), 2 were unsure whether it was useful (11.1%), and 1 (5.6%) did not think it was helpful. However, when asked how often the system led the user to consider novel alternative diagnoses 13/18 (72.2%) responded "almost always to frequently" and 5/18 (27.8%) said "occasionally to sometimes". None of the users felt that the system "rarely" or "never" yielded additional diagnostic considerations. Seventeen out of eighteen users (94.4%) thought the system was "easy to use". When asked if they would like to have such a system regularly available 13/18 (72.2%) responded yes, while 4/18 (22.2%) were unsure. One resident said that they would not like to have DXplain available (5.6%). CONCLUSION: We believe the data reflect a significant level of satisfaction with the system among residents. Their recognition that it frequently led them to consider novel diagnoses suggests it had a positive educational impact.

Attitude of Health Personnel↗