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Biomedical subjects

John Smith

Publications and source records attributed to John Smith.

29 records · Page 2Linked to original sources

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↗

Efficacy and time-efficiency of a "sonographer-driven" contrast echocardiography protocol in a high-volume echocardiography laboratory.

BACKGROUND: Contrast echocardiography (CE) has not gained widespread use despite numerous studies demonstrating its efficacy in the assessment of left ventricular (LV) function. METHODS: We sought to determine whether CE could be used in a high-volume echocardiography laboratory in a clinically effective and time efficient manner. We implemented a protocol with a feasibility phase and an established phase. Cost-benefit analyses were done on the basis of time use. RESULTS: During the feasibility and established phases, data on 119 and 672 patients, respectively, were obtained. After a "sonographer-driven" protocol, contrast studies represented 7% to 8% of the total number of routine transthoracic and stress studies. Stress studies accounted for only 15% of the total number of contrast studies. Obesity was the most common indication for contrast use. LV visualization indices and wall thickening assessment, as evaluated by 2 blinded readers, were significantly improved with CE compared with second harmonic imaging alone. The time to make the decision to use CE and the time taken to administer contrast decreased significantly from the feasibility phase to the established phase (8.3 +/- 5 vs 7.6 +/- 5 min, P <.01, and 13.4 +/- 10 vs 10.2 +/- 5 min, P <.001, respectively). On the basis of time use only, a cost analysis indicated that savings were obtained at a 10-minute reduction in study time. CONCLUSIONS: A "sonographer-driven" CE protocol for LV assessment is feasible in high-volume echocardiography laboratories. It is clinically effective because it significantly improves LV global and regional wall motion visualization. A "sonographer-driven" CE protocol can reduce decision and administration times substantially, thus making CE time-efficient.

Albumins↗

Cutoff frequencies and cross fingerings in baroque, classical, and modern flutes.

Baroque, classical, and modern flutes have successively more and larger tone holes. This paper reports measurements of the standing waves in the bores of instruments representing these three classes. It presents the frequency dependence of propagation of standing waves in lattices of open tone holes and compares these measurements with the cutoff frequency: the frequency at which, in an idealized system, the standing waves propagate without loss in such a lattice. It also reports the dependence of the sound field in the bore of the instrument as a function of both frequency and position along the bore for both simple and "cross fingerings" (configurations in which one or more tone holes are closed below an open hole). These measurements show how "cross fingerings" produce a longer standing wave, a technique used to produce the nondiatonic notes on instruments with a small number of tone holes closed only by the unaided fingers. They also show why the changes from baroque to classical to modern gave the instruments a louder, brighter sound and a greater range.

Humans↗

Mycophenolate mofetil decreases antibody production after cardiac transplantation.

New immunosuppressive drugs are extensively being investigated for their effect on T-cell immunity, with far less being known about their effect on the humoral immune response. In view of the experimental and clinical evidence that humoral immunity contributes to acute and chronic rejection, we investigated post-transplant production of anti-vimentin and anti-HLA antibodies in 86 patients who were part of a worldwide clinical trial for mycophenolate mofetil in cardiac transplantation. The results demonstrate that patients taking MMF instead of azathioprine generated significantly fewer de novo anti-vimentin antibodies.

Antibody Formation↗

Epstein-Barr virus myeloradiculitis and encephalomyeloradiculitis.

We provide a comprehensive clinical, radiological and virological analysis of four patients with Epstein-Barr virus (EBV) infection of the nervous system. One patient developed acute myeloradiculitis, one had acute encephalomyeloradiculitis, one had acute meningoencephalomyeloradiculitis and one had a subacute meningomyeloradiculitis. The ability of EBV to affect multiple parts of the entire neuraxis from meninges and brain to the spinal cord and peripheral nerves was evidenced by combinations of stiff neck and mental status changes, as well as patterns of weakness and sensory loss due to transverse myelitis or peripheral nerve disease. The CSF of all four patients contained a pleocytosis, predominantly mononuclear with elevated levels of protein, but a normal glucose level. In the two patients with acute myeloradiculitis and subacute meningomyeloradiculitis, the MRI revealed an increased signal in the spinal cord and lumbosacral roots, but in the two patients with acute encephalomyeloradiculitis and acute meningoencephalomyeloradiculitis, the brain and spinal cord MRIs were normal. In all four patients, EBV DNA, but not cytomegalovirus (CMV), herpes simplex virus (HSV) or varicella-zoster virus (VZV) DNA, was found in the CSF. The antibody pattern in serum was consistent with recent infection, and both EBV immunoglobulin (Ig) M and IgG antibodies, but not antibodies to HSV, VZV or CMV, were found in the CSF. Finally, there were reduced serum/CSF ratios of antibody to EBV, but not to total IgG or albumin, consistent with intrathecal antibody synthesis. None of the four patients died and none had brain swelling or focal changes according to brain MRI. Residual neurological deficits were evident. The two patients with acute myeloradiculitis and acute meningomyeloradiculitis had residual lower extremity weakness, and one of these patients later developed optic neuritis. The patient with acute encephalomyeloradiculitis had a moderate flaccid paraparesis, and the patient with subacute meningomyeloradiculitis was left with sensory loss in the feet. Compared with neurological disease caused by other herpes viruses, the clinical features of acute EBV myeloradiculitis, encephalomyeloradiculitis, encephalomyeloradiculitis and subacute meningomyeloradiculitis are distinctive. Of the eight human herpesviruses, EBV and VZV produce the most protean neurological syndromes. The mechanism by which EBV produces neurological disease is unknown. More correlative pathological, virological and immunological studies are needed in EBV-associated neurological disease.

Adult↗

Development and analysis of a new certifying examination in perioperative transesophageal echocardiography.

UNLABELLED: A key element in developing a process to determine knowledge and ability in applying perioperative echocardiography has included an examination. We report on the development of a certifying examination in perioperative echocardiography. In addition, we tested the hypothesis that examination performance is related to clinical experience in echocardiography. Since 1995, more than 1200 participants have taken the examination, and more than 70% have passed. Overall examination performance was related positively to longer than 3 mo of training (or equivalent) in echocardiography and performance and interpretation of at least six examinations a week. We concluded that the certifying examination in perioperative echocardiography is a valid tool to help determine individual knowledge in perioperative echocardiography application. IMPLICATIONS: This report describes the process involved in developing the certifying transesophageal echocardiography examination and identifies correlates with examination performance.

Anesthesiology↗

Naturally acquired simian varicella virus infection in African green monkeys.

Simian varicella virus (SVV) infection of primates shares clinical, pathological, immunological, and virological features with varicella-zoster virus infection of humans. Natural varicella infection was simulated by exposing four SVV-seronegative monkeys to monkeys inoculated intratracheally with SVV, in which viral DNA and RNA persist in multiple tissues for more than 1 year (T. M. White, R. Mahalingam, V. Traina-Dorge, and D. H. Gilden, J. Neurovirol. 8:191-205, 2002). The four naturally exposed monkeys developed mild varicella 10 to 14 days later, and skin scrapings taken at the time of the rash contained SVV DNA. Analysis of multiple ganglia, liver, and lung tissues from the four naturally exposed monkeys sacrificed 6 to 8 weeks after resolution of the rash revealed SVV DNA in ganglia at multiple levels of the neuraxis but not in the lung or liver tissue of any of the four monkeys. This animal model provides an experimental system to gain information about varicella latency with direct relevance to the human disease.

Animals↗

A randomized, controlled trial comparing compression bandaging and cold therapy in postoperative total knee replacement surgery.

PURPOSE: To examine the difference between compression bandaging and cold therapy after total knee arthroplasty. SAMPLE: Eighty-four postoperative, unilateral, total knee replacement, surgical clients. PROCEDURE: Clients were randomized into two groups: those receiving compression bandaging, and those receiving cryo-pad technology. Subjects were assessed for total length of stay, blood loss, blood transfusion, swelling, flexion, pain, and opiate use. FINDINGS: Unlike other studies, the results of these data showed no significant differences between groups on the measured outcomes. A simple cost benefit analysis shows that the compression bandage is cheaper and more labor efficient than the cold therapy as delivered by cryo-pad technology.

Arthroplasty, Replacement, Knee↗