Biomedical subjects

Robert Thompson

Publications and source records attributed to Robert Thompson.

6 recordsLinked to original sources

PubMed2025

Dual-vector rAAVrh8 gene therapy for GM2 gangliosidosis: a phase 1/2 trial.

The dual rAAVrh8-HEXA and rAAVrh8-HEXB vector can restore central nervous system hexosaminidase (Hex) enzyme activity, decrease GM2 levels in cerebrospinal fluid and rescue phenotypic consequences of GM2 gangliosidosis, Tay-Sachs and Sandhoff diseases in animal models following simultaneous bi-thalamic (BiT) injections. Following up on an n = 2 expanded access trial, we initiated a phase 1/2, single-dose, dose-escalation of combined BiT, intra-cisterna magna and intrathecal infusion in children with Tay-Sachs and Sandhoff diseases (six infantile, three juvenile). The BiT injection volume and vector dose were doubled between four cohorts, with the lowest dose matching the earlier expanded access trial. Cerebrospinal fluid HexA enzyme activity, serum total Hex activity and GM2 levels showed a dose-dependent biochemical correction of the disease. Serum Hex activity surpassed 40 nmol h-1 ml-1, two times the lower limit of normal, and neuroimaging demonstrated increased fiber tracts. Correction was greatest at 12 weeks, but in decline by 24 weeks postdosing. Infantile patients experienced global clinical stabilization and prolonged oral feeding without aspiration until 3-3.5 years. Seizures had a later onset, were less frequent, less severe and more responsive to anti-convulsant medication. Adverse events were rare in infantile patients, but worsening dystonia was observed in juvenile patients, who were excluded from ongoing enrollment. ClinicalTrials.gov registration: NCT04669535 and NCT06614569 .

Humans↗

PubMed2006

Immunopathology of schistosomiasis.

Waterborne parasitic diseases plague tropical regions of the world with the development of water resources often increasing transmission. Skin-penetrating cercariae (infectious stages of schistosome parasites) mature within their mammalian host, form sexual pairs and produce several hundred eggs per day. Many eggs are swept within the circulation and in the case of Schistosoma mansoni and S. japonicum, become lodged within hepatic sinusoids, invoking a fibrotic granulomatous response. Animal studies have identified a moderate type 1 helper (Th1) response to parasite antigens; however, a robust Th2 response to egg-derived antigens dominates and propagates fibrogenesis within the liver. Elegant T helper cell polarization studies have highlighted that critical control of Th1, Th2 and interleukin (IL)-17-secreting lymphocytes is necessary to prevent severe liver pathology. Alternatively activated macrophages develop in the Th2 milieu and upregulate Fizz1, Ym-1 and Arg-1. The possible contribution of macrophages to fibrogenesis and their role in immune regulation are discussed. Within the liver, natural (CD4(+)CD25(+) Forkhead box protein 3 (Foxp3)(+)) and inducible (CD4(+)Foxp3(-)) Treg's are recruited, providing an essential regulatory arm to stabilize the immune response and limit immunopathology. This review ties together current thinking of how the granulomatous response develops, causing much of the associated immunopathology, with extensive discussions on how regulatory cells and cytokine decoy receptors serve to limit the extent of immune-mediated pathology during schistosomiasis.

Animals↗

PubMed2003

Independent calculations to validate monitor units from ADAC treatment planning system.

Current standards of practice are based on the use of an independent calculation to validate the monitor units (MUs) derived from a treatment planning system. The ADAC PINNACLE treatment planning system has shown discrepancies of 10% or more compared to simple independent calculations for highly contoured areas such as tangential breast and chest wall irradiation. The ADAC treatment planning system generally requires more MUs to deliver the same prescribed dose. Independent MU calculation methods are based on full phantom conditions. On the other hand, the MUs from the ADAC treatment planning system are derived using realistic phantom scatter. As such, differences exist in TMR factors, off-axis wedge factors, and the phantom scatter factor. To systematically study the discrepancies due to phantom conditions, experimental measurements were performed with various percentages of tissue missing. The agreement between the experimental measurements and ADAC calculations was found to be within 2%. Using breast field geometry, a relationship between missing tissue and the dosimetric parameters used by ADAC was developed. This relationship, when applied, yielded independent MU calculations whose values closely matched those from the ADAC treatment planning system.

Algorithms↗

PubMed2002

Identification of paramyosin as a binding protein for calgranulin C in experimental helminthic keratitis.

PURPOSE: Calgranulin C (CaGC) is a protein released by activated neutrophils and involved in host defense against filarial infections. This study involved the identification of binding protein(s) of the helminth Brugia malayi to CaGC and the ability of binding complexes to induce keratitis. METHODS: Parasitic extracts prepared from B. malayi microfilariae and adult worms were incubated with recombinant CaGC protein. Parasite binding protein-CaGC complex was isolated by affinity chromatography. A B. malayi microfilariae cDNA library was immunoscreened with antisera from rats immunized with the isolated parasitic CaGC-binding protein. All positive clones contained paramyosin sequences. Paramyosin was thus considered the major CaGC-binding protein in the parasite. To delineate the binding of CaGC to native and recombinant paramyosin, 125I-CaGC was used as a binding tracer in SDS-PAGE analysis to identify a CaGC-binding complex. To determine whether the complex of CaGC and its binding protein could induce keratitis mimicking the onchocercal human corneal disease, BALB/c mice preimmunized with the binding complex were challenged with intracorneal binding complex or live Brugia microfilariae. In addition, splenocytes harvested from the same animals were assessed for their ability to elicit cellular immune responses to the binding complex by [3H]thymidine assay. RESULTS: In vitro binding of CaGC to paramyosin was confirmed using recombinant paramyosin and 125I-CaGC. Test animals showed development of severe keratitis that mimicked, clinically and histopathologically, the human onchocercal corneal disease, demonstrating the antigenic specificity of the paramyosin-CaGG-binding complex. CONCLUSIONS: Paramyosin is identified as a CaGC-binding protein in B. malayi.

Animals↗

PubMed1995

Computerized ICU Orders Versus Handwritten ICU Orders: A Prospective, Pharmacy-Based Analysis.

OBJECTIVE: To compare computerized ICU order writing with handwritten ICU physician orders. DESIGN: Prospective study. SETTING: Medical and surgical Intensive Care Units and pharmacy of a Department of Veterans Affairs Medical Center. PATIENTS: Two hundred sixty-four individual sets of orders. INTERVENTIONS: A time study and problem analysis were performed in the pharmacy as orders were received and processed. MEASUREMENTS AND MAIN RESULTS: Two hundred sixty-four sets of orders were evaluated; MICU (handwritten; n = 133) and SICU (computerized; n = 131). Physician length of training are similar in both units. The patient age and number of major diagnoses per patient in the two ICU groups were similar. Significantly less time (min) (MICU 2.5 ± 0.3 versus SICU 1.84 ± 0.1, p < 0.05) is required to review SICU orders. The SICU had significantly fewer order problems (MICU 45 versus SICU 12, p < 0.05). Computerized SICU orders were corrected more rapidly. The majority of order problems in both groups were resolved by telephone. CONCLUSIONS: ICU orders by computer program are processed more rapidly, have fewer errors, and are corrected more rapidly than standard handwritten orders. We conclude that a dedicated ICU computerized order-writing system permits orders to be written with fewer errors and the pharmacy to process them more efficiently than handwritten orders.

Journal Article↗

PubMedDate not supplied

Glycohemoglobin assessment program: glycated hemoglobin and epidemiologic variables in patients with type 2 diabetes.

OBJECTIVE: To obtain data on glycated hemoglobin (HbA1c) levels and a variety of epidemiologic variables in patients with type 2 diabetes living in the western United States. METHODS: This study was a noncomparative, multicenter, epidemiologic survey. Data were collected from consecutively enrolled patients at nine separate primary-care sites. Patients were eligible for inclusion if they had type 2 diabetes, were between 35 and 70 years old, and had received oral antidiabetic therapy, insulin, or both for at least 3 months before enrollment. RESULTS: Of 602 patients enrolled in the study, 588 were included in the final univariate analyses. The overall mean HbA1c level was 8.2%; however, only 20.4% of patients achieved the American Diabetes Association (ADA) strict HbA1c target of <7.0%. On the other extreme, only 18.9% of patients had HbA1c levels of greater than or equal to 9.5%. Patients treated with insulin had the highest HbA1c levels. Combination therapies were used in 59% of patients, and only 12% were treated with insulin alone. CONCLUSION: The mean HbA1c level in this study is lower than in prior surveys. The use of combination therapy for the management of type 2 diabetes has increased, and the use of insulin as monotherapy has decreased. Although more patients need to reach the ADA HbA1c target of <7.0%, extremely high HbA1c levels are less common than they were in the past. This finding suggests that HbA1c levels are declining, although many patients still have values above 7.0%.

Adult↗