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Biomedical subjects

Peter Lee

Publications and source records attributed to Peter Lee.

36 records · Page 2Linked to original sources

Infusion-related reactions to infliximab in patients with rheumatoid arthritis in a clinical practice setting: relationship to dose, antihistamine pretreatment, and infusion number.

OBJECTIVE: We describe infusion-related reactions to infliximab (during infusion or within 1 hour postinfusion) in patients with active rheumatoid arthritis (RA) treated in a quaternary care center. METHODS: We followed 113 patients for a mean of 60.6 +/- 28.9 weeks, obtaining 10.5 +/- 4.9 infusions per patient. RESULTS: We observed 1183 infusions resulting in 104 infusion reactions (8.8%). All reactions resolved within several hours following cessation of the infusion and none was serious enough to warrant hospitalization. Reactions included allergic reactions (pruritus, urticaria) in 4.2% of infusions, cardiopulmonary (hypotension, hypertension, tachycardia) in 3.0%, and miscellaneous reactions (headache, nausea, vomiting) in 2.0%. Reactions occurred in 8.0% of 3 mg/kg infusions and in 10.3% of 5 mg/kg infusions. Reactions occurred in 13.2% of infusions that involved antihistamine pretreatment compared to only 7.5% of infusions that involved no pretreatment. At both infliximab doses, there was a similar frequency of infusion reactions in patients pretreated due to a previous infusion (12.6%) compared to those pretreated strictly based on infusion number (14.7%). A number of the reactions involving antihistamine pretreatment may be explained by known side effects of diphenhydramine, including headache, dizziness, nausea, and palpitations. CONCLUSION: Infusion-related reactions to infliximab were infrequent, rarely severe, and easily manageable. The frequency of reactions was equivalent in patients treated with 3 mg/kg compared to 5 mg/kg. Reactions were significantly more frequent in infusions where patients were pretreated with the antihistamine diphenhydramine, compared to those not involving pretreatment.

Adolescent↗

Tracking the acetate threshold using DO-transient control during medium and high cell density cultivation of recombinant Escherichia coli in complex media.

DO-transient nutrient controllers use the dissolved oxygen signal to attempt acetate threshold tracking during fed-batch cultivation of recombinant E. coli. Here we apply DO-transient control to the production of Jembrana disease virus protein in complex Super Luria medium and compare performance against a high-limit pH-stat controller. For induction at medium cell density (harvest between 31 and 32.5 g dcw L) a total productivity of 0.27 g L h was achieved as compared to 0.24 g L h with the high-limit pH-stat. For induction at high cell density (harvest at 60 g dcw L), decreased productivity (0.12 g L h) was attributed to the effect of acetate accumulation on recombinant protein formation and a concomitant lowering of the critical growth rate. Our results suggest that complex media provides a difficult environment for the application of acetate threshold tracking DO-transient control because of difficulties in re-oxidizing acetate, and apparent localized production of acetate below the production threshold (as detected by the DO-transient controller as SPOUR(crit)). Configuring the DO-transient controller to avoid aggressive threshold probing is suggested as a means to improve performance and reduce acetate accumulation in complex media.

Acetates↗

Phase I study of intranodal delivery of a plasmid DNA vaccine for patients with Stage IV melanoma.

BACKGROUND: Based on the likelihood of transfecting large numbers of local antigen-presenting cells, a Phase I study in patients with Stage IV melanoma was conducted to determine the practicality, toxicity of, and immune responses to repeated infusions into a groin lymph node of escalating doses of a DNA plasmid encoding tyrosinase epitopes. METHODS: Cohorts of 8 patients each received 200 microg, 400 microg, or 800 microg of DNA intranodally by pump over 96 hours every 14 days for 4 cycles. Blood was collected for immunologic assays and to measure plasmid in serum prior to treatment, 4 weeks later, and 8 weeks later. Scans and X-rays were performed at baseline and after 8 weeks. RESULTS: Treatment was tolerated well, with only five patients demonstrating Grade 1-2 toxicity. Vaccine delivery by 96-hour infusions of plasmid into a groin lymph node resulted in only 1 episode of catheter leakage in 107 cannulations. Detection of plasmid in serum was rare and transient in two patients. Immune responses by peptide-tetramer assay to tyrosinase 207-216 were detected in 11 of 26 patients. No clinical responses were seen. Survival of the heavily pretreated patients on this trial was unexpectedly long, with 16 of 26 patients alive at a median follow-up of 12 months. CONCLUSIONS: Infusion of a DNA plasmid vaccine into a groin lymph node was practical and well tolerated. Immune responses to a novel tyrosinase epitope were noted. Overall survival in this trial of heavily pretreated patients was unexpectedly long, with 16 of 26 patients alive after a follow-up of 12 months, favoring immune responders.

Adult↗

Erosion patterns in a sediment layer.

We report here on a laboratory-scale experiment which reproduces a rich variety of natural patterns with few control parameters. In particular, we focus on intriguing rhomboid structures often found on sandy shores and flats. We show that the standard views based on water surface waves do not explain the phenomenon, and we evidence a different mechanism based on mud avalanche instability.

Journal Article↗

Dynamic three-dimensional MR renography for the measurement of single kidney function: initial experience.

A three-dimensional magnetic resonance (MR) renographic method to measure single kidney glomerular filtration rate (GFR) and split renal function was developed that is based on renal signal intensity measurements during 2-3 minutes after intravenous injection of a low dose (2 mL or 0.01 mmol/kg) of gadopentetate dimeglumine. In nine subjects, single kidney MR GFR indices correlated well with technetium 99m (99mTc) diethylenetriaminepentaacetic acid (DTPA) clearance (r = 0.7-0.8) for GFR values of 7-48 mL/min. MR right kidney split renal function values (range, 32%-59%) also correlated well with 99mTc-DTPA radionuclide measurements (r = 0.76); differences between the two methods averaged 0.8% +/- 8. MR renography was performed along with contrast material-enhanced MR imaging of the kidneys and renal arteries and added 8 minutes or less to the total examination time.

Adult↗

Effects of weightlessness and movement restriction on the structure and metabolism of the soleus muscle in monkeys after space flight.

After humans and animals have been in conditions of real and modeled weightlessness, the most marked changes are seen in the "slow" tonic muscles, particularly soleus. Studies of the effects of weightlessness and movement restriction on the soleus muscle in monkeys demonstrated significant reductions in the sizes of slow and rapid fibers due mainly to the actions of real weightlessness (rather than movement restriction in the space capsule). Protein loss in soleus muscle fibers in monkeys following space flight was more marked than loss of other components, including water. The level of atrophy of soleus muscle fibers in these conditions was greater than the decrease in the number of capillaries. Succinate dehydrogenase activity in soleus muscle fibers decreased proportionally to the reduction in fiber size.

Animals↗

CPR effectiveness in microgravity: comparison of three positions and a mechanical device.

BACKGROUND AND OBJECTIVE: Cardiopulmonary resuscitation (CPR) in microgravity via closed chest compression is thought to be possible by several techniques. This study examined the handstand, side, and waist straddle maneuvers, and a bear hug technique in performing CPR and meeting American Heart Association (AHA) recommendations in microgravity. We also hypothesized that one rescuer using a CPR bellows adjunct device is equivalent to two rescuers. METHODS: A pre-intubated mannequin model resting on the crew medical restraint system from the International Space Station was instrumented with transducers to measure airway pressure and chest compression depth. Microgravity conditions were provided through repetitive parabolic flight on the KC-135A. On identifying the most effective position, standard two-rescuer CPR was compared with one-rescuer CPR augmented with a bellows-on-sternum CPR adjunct device (Kendall CardioVent, Kendall Medizinische Erzeugnisse GMBH, Neustadt/Donau, Germany). RESULTS: Handstand position compression depth was 1.58 in +/- 0.20 in SD (4.01 cm +/- 0.51 cm), side straddle was 0.78 in +/- 0.44 in SD (1.98 cm +/- 1.12 cm), and waist straddle was 1.21 in +/- 0.47 in SD (3.07 cm +/- 1.19 cm) across rescuers with heights of 164-174 cm. Rates of compression were 98.3 +/- 6.3 SD, 100.0 +/- 3.0 SD, and 102.6 +/- 12.1 SD compressions per minute, respectively. Compression depth for one rescuer utilizing the Kendall CardioVent device in the handstand position was 1.48 in +/- 0.14 in SD (3.76 cm +/- 0.36 cm). Compression depth for two rescuers was 1.58 in +/- 0.20 in SD (4.01 cm +/- 0.51 cm) (p < 0.01). CONCLUSION: CPR in microgravity is most reliably performed in the handstand position and meets AHA guidelines for closed chest compression depth. One-rescuer CPR incorporating the Kendall CardioVent device appears promising in microgravity. CPR adjunct devices would positively impact resuscitative procedures like CPR by small crews with inherent manpower requirements.

Cardiopulmonary Resuscitation↗

A case study for demonstrating the application of U.S. EPA's monitored natural attenuation screening protocol at a hazardous waste site.

Natural attenuation assessment data, collected at a Superfund site located in Louisiana, USA, are presented. The study site is contaminated with large quantities of DNAPL waste products. Source characterization data indicated that chlorinated ethene and ethane compounds are the major contaminants of concern. This case study illustrates the steps involved in implementing the U.S. EPA's [U.S. EPA, 1998. Technical protocol for evaluating natural attenuation of chlorinated solvents in ground water, by Wiedmeier, T.H., Swnason, M.A., Moutoux, D.E., Gordon, E.K., Wilson, J.T., Wilson, B.H., Kampbell, D.H., Hass, P.E., Miller, R.N., Hansen, J. E., Chapelle, F.H., Office of Research and Development, EPA/600/R-98/128] monitored natural attenuation (MNA) screening protocol at this chlorinated solvent site. In the first stage of the MNA assessment process, the field data collected from four monitoring wells located in different parts of the plume were used to complete a biodegradation scoring analysis recommended by the protocol. The analysis indicates that the site has the potential for natural attenuation. In the second stage, a detailed conceptual model was developed to identify various contaminant transport pathways and exposure points. The U.S. EPA model and BIOCHLOR was used to assess whether the contaminants are attenuating at a reasonable rate along these transport paths so that MNA can be considered as a feasible remedial option for the site. The site data along with the modeling results indicate that the chlorinated ethene and chlorinated ethane plumes are degrading and will attenuate within 1000 ft down gradient from the source, well before reaching the identified exposure point Therefore, MNA can be considered as one of the feasible remediation options for the site.

Environmental Monitoring↗

Murine cytomegalovirus m02 gene family protects against natural killer cell-mediated immune surveillance.

The murine cytomegalovirus m02 gene family encodes putative type I membrane glycoproteins named m02 through m16. A subset of these genes were fused to an epitope tag and cloned into an expression vector. In transfected and murine cytomegalovirus-infected cells, m02, m04, m05, m06, m07, m09, m10, and m12 localized to cytoplasmic structures near the nucleus, whereas m08 and m13 localized to a filamentous structure surrounding the nucleus. Substitution mutants lacking the m02 gene (SMsubm02) or the entire m02 gene family (SMsubm02-16) grew like their wild-type parent in cultured cells. However, whereas SMsubm02 was as pathogenic as the wild-type virus, SMsubm02-16 was markedly less virulent. SMsubm02-16 produced less infectious virus in most organs compared to wild-type virus in BALB/c and C57BL/6J mice, but it replicated to wild-type levels in the organs of immunodeficient gamma(c)/Rag2 mice, lacking multiple cell types including natural killer cells, and in C57BL/6J mice depleted of natural killer cells. These results argue that one or more members of the m02 gene family antagonize natural killer cell-mediated immune surveillance.

Acute Disease↗

Cardiac function: MR evaluation in one breath hold with real-time true fast imaging with steady-state precession.

In 12 healthy volunteers and eight patients with cardiac disease, cine magnetic resonance (MR) imaging in the heart was performed with real-time true fast imaging with steady-state precession (FISP), which permitted evaluation of the entire left ventricle in one breath hold (91 msec per frame, 13 frames per section position, nine short-axis section positions per breath hold). Contrast-to-noise ratios (CNRs) and left ventricular mass and function measurements with this technique were compared in all subjects with single-section true FISP imaging and, in the volunteers only, with segmented fast low-angle shot (FLASH) MR imaging. Myocardium-to-blood CNR was significantly higher for both true FISP sequences compared with the FLASH sequence. Measurements of resting left ventricular function with real-time true FISP imaging were comparable with those derived from a series of separate breath-hold single-section true FISP acquisitions.

Adult↗

Relative cerebral blood volume measurements in intracranial mass lesions: interobserver and intraobserver reproducibility study.

PURPOSE: To assess inter- and intraobserver reproducibility for different techniques of measuring relative cerebral blood volume (rCBV) in patients with intracranial mass lesions. MATERIALS AND METHODS: Three independent observers (neuroradiology fellows) who were blinded to the histopathologic diagnosis performed rCBV measurements in 50 patients with various intracranial mass lesions. Three different methods were compared. With method 1, placement of a single region of interest was guided by a color overlay map. With methods 2 and 3, the highest rCBV value and the mean of repeated rCBV measurements, respectively, were recorded. Calculations of the intraclass correlation coefficient, coefficient of variation (CV), and descriptive statistics were used to determine the levels of reproducibility. A multiple linear regression model was used to evaluate for possible explanatory factors for interobserver variance. RESULTS: Method 2 had, overall, the best reproducibility of all techniques, with an intraclass interobserver correlation coefficient of 0.71 (indicating good agreement), interobserver CV of 30%, and intraobserver CV in the range of 32%-41%. Measurement variations between observers correlated significantly (P <.001) with increasing rCBV values. CONCLUSION: In this study, interobserver and intraobserver reproducibility of rCBV measurements were clinically acceptable.

Adolescent↗

Planning and implementing HIPAA compliance activities.

This article reviews one healthcare network's HIPAA compliance management approach, detailing findings and trends from the assessment and presenting possible solutions derived from the remediation analysis activities, including fiscal and implementation timing considerations.

California↗

Characterization of long-term effector-memory T-cell responses in patients with resected high-risk melanoma receiving a melanoma Peptide vaccine.

The authors determined whether long-term memory T cells could be detected in patients who received a multipeptide vaccine for high-risk resected melanoma. Five HLA-A*0201 patients received a vaccine that included the gp100(209-217) (210M) peptide with Montanide ISA 51. Peripheral blood mononuclear cells were obtained before therapy, after 6 months of vaccinations, and from 18 months to 36 months later. The presence of gp100 antigen-specific cytolytic T cells was measured by ELISPOT, tetramer and chromium release assays. Tetramer-positive CD8 cells were phenotyped by flow cytometry for markers including CD44, CD45RA, and CCR7. T-cell avidity and its evolution over time were examined in selected patients. Epitope spreading was analyzed by assessment of gp100(280-288) (288V) T cells. All patients exhibited a significant increase in tetramer-positive gp100-specific CD8 T cells that decayed at different rates over 18 to 36 months after vaccinations. Cells from all patients exhibited an effector-memory phenotype and were generally CD45 RA low/CCR7 negative and CD44 positive. Tetramer-positive cells declined over time in four of the five patients, but the proportion of tetramer-positive CD8 cells that secreted gamma-interferon rose, suggesting enrichment for effector cells. Epitope spreading for the gp100(280-288) (288V) epitope was detected. One patient maintained a population of 2.5% circulating gp100 tetramer-positive cells over 36 months. Avidity analysis showed no changes over time after induction of antigen-specific T cells. Vaccination with a heteroclitic melanoma antigen peptide with Montanide ISA 51 generated populations of circulating functional effector-memory T cells that were specific for gp100 and long-lived in the circulation for periods of 18 to 36 months after vaccination.

Adult↗

Preoperative assessment of intracranial tumors with perfusion MR and a volumetric interpolated examination: a comparative study with DSA.

BACKGROUND AND PURPOSE: In evaluating intracranial tumors, a safe low-cost alternative that provides information similar to that of digital subtraction angiography (DSA) may be of interest. Our purpose was to determine the utility and limitations of a combined MR protocol in assessing (neo-) vascularity in intracranial tumors and their relation to adjacent vessels and to compare the results with those of DSA. METHODS: Twenty-two consecutive patients with an intracranial tumor who underwent preoperative stereoscopic DSA were examined with contrast-enhanced dynamic T2*-weighted perfusion MR imaging followed by a T1-weighted three-dimensional (3D) MR study (volumetric interpolated brain examination [VIBE]). The maximum relative cerebral blood volume (rCBV) of the tumor was compared with tumor vascularity at DSA. Critical vessel structures were defined in each patient, and VIBE images of these structures were compared with DSA findings. For full exploitation of the 3D data sets, maximum-intensity projection algorithms reconstructed in real time with any desired volume and orientation were used. RESULTS: Tumor blush scores at DSA were significantly correlated with the rCBV measurements (r = 0.75; P <.01, Spearman rank correlation coefficient). In 17 (77%) patients, VIBE provided all relevant information about the venous system, whereas information about critical arteries were partial in 50% of the cases and not relevant in the other 50%. CONCLUSION: A fast imaging protocol consisting of perfusion MR imaging and a volumetric MR acquisition provides some of the information about tumor (neo-) vascularity and adjacent vascular anatomy that can be obtained with conventional angiography. However, the MR protocol provides insufficient visualization of distal cerebral arteries.

Adult↗