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Biomedical subjects

T Pham

Publications and source records attributed to T Pham.

118 records · Page 7Linked to original sources

ICAM-1 antisense oligodeoxynucleotide improves islet allograft survival and function.

Expression of intercellular adhesion molecule-1 (ICAM-1) and its ligand, leukocyte function antigen-1 (LFA-1), after pancreatic islet transplantation may affect both nonspecific and alloantigen-specific phases of graft destruction. We examined the effects of ICAM-1/LFA-1 blockade on the survival of islet allografts. Fresh C57BL/10 (H2h) pancreatic islets were transplanted under the renal subcapsular space (KC) or embolized into the liver after portal vein (PV) injection to C3H (H2k) mice. Recipients remained untreated or were treated for 7 days by i.p. administration of: ICAM-1 antisense phosphorothioate oligodeoxynucleotide (oligo) alone; anti-1CAM-1 (alphaICAM-1) monoclonal antibody (mAb) alone: alphaLFA-1 mAb alone; ICAM-1 oligo/alphaLFA mAb combination; alphaICAM-1 mAb/alphaLFA-1 mAb combination; or control oligo IP-8997 or IP-1082. In some experiments, donors were pretreated with ICAM-1 oligo. Inhibition of single ligand with 5.0 mg/kg ICAM-1 oligo (25.1 +/- 10.3), 100 microg/daily alphaICAM-1 mAb (24.2 +/- 8.0 days), or 50 microg/daily alphaLFA-1 mAb (42.8 +/- 25.9 days) prolonged the survivals of KC islet allografts in comparison with untreated controls (11.9 +/- 1.0 days; all p < 0.01). However, dual ICAM-1/LFA-1 blockade with either ICAM-1 oligo/alphaLFA-1 mAb (78.3 +/- 16.5 days) or (alphaICAM-1 mAb/aLFA-1 mAb (65.2 +/- 31.3 days) was the most effective therapy. Although pretreatment of donors with ICAM-1 oligo alone was ineffective (12.2 +/- 0.8 days; NS), a combination of donor pretreatment and recipient treatment started 1 day prior to grafting with ICAM-1 oligo (39.2 +/- 14.0 days) was more effective than the recipient treatment alone (24.6 +/- 8.8 days). Furthermore, ICAM-1/LFA-1 blockade improved islet function as evaluated by glucose tolerance test, and decreased inflammation in comparison with untreated controls. Similar in vivo results were obtained following PV administration of islet allografts. Thus, ICAM-1/LFA-1 blockade prolongs the survival of pancreatic islet allografts and improves their early function.

Animals↗

Research review.

Explore the source record for details and available documents.

Amlodipine↗

HLA DRB1*01 and DRB1*04 phenotyping does not predict the need for joint surgery in rheumatoid arthritis. A retrospective quantitative evaluation of 300 French patients.

OBJECTIVE: To determine if the presence of HLA-DR disease-associated epitopes predicts the need for total joint arthroplasty or joint fusion in rheumatoid arthritis (RA). METHODS: Tertiary-referral, monocenter study. Three hundred RA patients (1987 ACR criteria) were retrospectively evaluated; outcome measure was recourse to total joint arthroplasty, joint fusion or bone resection. HLA-DR1 and DR4 were considered as the disease-associated epitopes (subtypes were not available for analysis). Analysis was performed using the lifetable method (Kaplan-Meyer technique). RESULTS: Of the 300 patients included, 78% were women, mean age: 56+/-14 years, mean RA follow-up: 12+/-9 years. Phenotyping: 73% of patients carried one (52%) or two (21%) disease-associated epitopes. Surgery was performed on 24% of the patients during follow-up. The most frequent surgery was total hip arthroplasty (13% of patients). According to lifetable analysis, 13% of patients had surgery (total joint arthroplasty or joint fusion) after 10 years of follow-up, 34% after 20 years. years of follow-up, There was no statistically significant difference in recourse to surgery according to absence or presence (single or double-dose) of disease-associated epitopes. Similar results were observed if the event was the second surgical procedure on a given patient. CONCLUSION: This study failed to demonstrate a relation between HLA phenotyping and the severity of RA defined by the requirement for surgery.

Adolescent↗

Leflunomide in rheumatoid arthritis in daily practice: treatment discontinuation rates in comparison with other DMARDs.

OBJECTIVE: To evaluate the treatment discontinuation rate of leflunomide in rheumatoid arthritis (RA) in comparison with the discontinuation of other disease modifying anti-rheumatic drugs (DMARDs), in daily practice, in a single center and during the same period of time. METHODS STUDY DESIGN: 3-year, retrospective, monocenter. PATIENTS: RA patients for whom leflunomide or another DMARD was initiated between 1998 and 2001 (several DMARDs could be initiated for a given patient during this period). Collected data: For each patient, demographic and disease data. For each treatment course, date of initiation, if relevant date of discontinuation and reason for discontinuation. ANALYSIS: Percentage of patients discontinuing treatment over time (life table method; Kaplan-Meier), comparison between leflunomide and the "any other DMARD" or methotrexate groups using the Log-Rank test. RESULTS: During the study period, 515 DMARDs were initiated in 285 patients. Leflunomide was initiated in 161 patients who were older and had a longer disease duration than the other treated patients (59 +/- 13 years and 14 +/- 9 years versus 54 +/- 15 years and 11 +/- 10 years in the leflunomide group and other DMARDs group respectively). Discontinuation rate of leflunomide after 1 year was 56.7%, mainly because of adverse drug reactions (41.6%). The discontinuation rate whatever the reason and for toxicity was higher for leflunomide than for other DMARDs studied. However discontinuation for inefficacy was similar in both groups. CONCLUSION: This study conducted in conditions of daily practice when leflunomide was first available suggests a higher discontinuation rate of leflunomide because of adverse events when compared to other DMARDs.

Adjuvants, Immunologic↗

A practical cytogenetic protocol for in vitro cytotoxicity and genotoxicity testing.

In vitro cytogenetics has been established as a valid method for evaluating the genotoxic potential of chemical agents. Armstrong et al have described a simple, quantitative approach to in vitro cytotoxicity and genotoxicity testing by using Chinese hamster ovary (CHO) cells. This approach can also be sensitive and repeatable in an inter-laboratory setting, a prerequisite for routine testing of compounds suspected of having genotoxic properties. In the present study, cytotoxicity was evaluated by the parameter of mitotic index (MI). Genotoxicity is measured by the chromosome aberration (Abs) assay as described by Armstrong et al using CHO cells. The basic analytic principles proposed were extended to include human lymphocytes. Sister chromatid exchange (SCE) analysis was used to establish an additional endpoint. Mitomycin C (MMC), an established clastogen, was used as the model compound for protocol validation. Dose response curves for MI and Abs in CHO cells were found to be consistent with those reported by Armstrong et al. Results from our extended study on lymphocytes and using SCE analysis were analogous. Our experience is that this standardized approach is indeed sensitive and reliable and can serve as a basis for an inter-laboratory testing program.

Animals↗

Bone insufficiency fractures as an inaugural manifestation of primary hyperparathyroidism.

Primary hyperparathyroidism causes excessive bone resorption with a decrease in bone mineral density. Fractures of the vertebras and appendicular bones, however, seem uncommon, even in the long term. We report three patients who presented with bone insufficiency fractures as the inaugural symptom of primary hyperparathyroidism. The three patients were women, aged 62, 65 and 86 years, respectively, who presented with fractures of the medial tibial plateau, femoral neck of femoral neck and tarsus. Laboratory tests showed hypercalcemia, hypophosphatemia and elevated parathyroid hormone levels. Apart from confusion in the 86-year-old patient, there were no clinical manifestations. A bone biopsy obtained in one patient showed increased resorption parameters with no loss of bone trabecular volume; the two other patients underwent absorptiometry, which disclosed a marked decrease in bone mineral density at the spine and femoral neck. There were no risk factors for osteopenia apart from advanced age and female gender. A parathyroid adenoma was removed surgically in all three cases. Vitamin D deficiency was a concomitant abnormality that probably exacerbated the adverse effects of hyperparathyroidism on the skeleton.

Absorptiometry, Photon↗

[Psychopathy and evaluation of violent behavior in a psychiatric security milieu].

This study examines risks of violent behavior among 62 offenders in a belgian psychiatric security institution. Two variables were assessed as predictor of the subjects' history of violent behavior recorded in their medical files: (1) subjective classification as "violent" vs "non-violent" by care taking personnel; and (2) scores on Hare's (1991) Revised Psychopathy Checklist (PCL-R). The study assessed also the score of the Michigan Actuarial Scale of Violent Behavior (MARSS) which was not considered as predictor. The PCL-R, the subjective classification and the MARSS were found to be highly intercorrelated. Regression analysis suggest that the PCL-R is a significant predictor of violent behavior. The use of this instrument for the prediction of violent behavior is thus encouraged.

Adult↗

Small-area analysis: targeting high-risk areas for adolescent pregnancy prevention programs.

CONTEXT: Traditional methods of identifying areas in need of adolescent pregnancy prevention programs may miss small localities with high levels of adolescent childbearing. METHODS: Birthrates for 15-17-year-olds were computed for all California zip codes, and the zip codes with birthrates in the 75th percentile were identified. Panels of local experts in adolescent pregnancy reviewed these "hot spots" for accuracy and grouped them into potential project areas, based on their demographics, geography and political infrastructure. RESULTS: In all, 415 zip codes exceeded the 75th-percentile cut-off point of 62.8 births per 1,000, and 210 of them differed significantly from the state average of 44.5 per 1,000 for 15-17-year-olds. While all had high adolescent birthrates, they varied greatly in racial and ethnic mix, poverty and educational attainment, and certain perinatal measures such as inadequate prenatal care and repeat pregnancy. CONCLUSIONS: The use of zip code-level data holds promise for more effective program planning and intervention.

Adolescent↗