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Biomedical subjects

A Constantin

Publications and source records attributed to A Constantin.

At least 19 recordsLinked to original sources
PubMed2006

Chronic morphine administration results in tolerance to delta opioid receptor-mediated antinociception.

Delta opioid receptor agonists produce only a moderate degree of antinociception, possibly reflecting the predominantly intracellular location of delta opioid receptor. However, recent studies suggest that short term morphine pretreatment can increase delta opioid receptor-mediated antinociception by promoting the translocation of delta opioid receptor to the cell surface. Even more striking sensitization has been reported after long term morphine pretreatment and withdrawal in locomotor tests. In the present study we therefore examined the effects of longer term morphine pretreatment and withdrawal on delta opioid receptor-mediated antinociception in the formalin test. Male adult rats were pretreated daily with morphine (10 mg/kg s.c.) or saline for 10 days, and were tested acutely with the delta opioid receptor agonist [D-Ala2,Glu4]-deltorphin (intrathecal) at 0, 7 and 14 days of withdrawal. Unexpectedly, chronic morphine pre-exposure resulted in tolerance to [D-Ala2,Glu4]-deltorphin-induced antinociception, and this occurred at 0 and 7 but not 14 days of morphine withdrawal. Morphine challenge at withdrawal day 7 confirmed the presence of tolerance to the antinociceptive effects of this drug. Chronic morphine pretreatment also resulted in tolerance to the locomotor stimulant effect of [D-Ala2,Glu4]-deltorphin (given i.c.v.), contrary to a previous report of sensitization. However, consistent with previous reports, short term (2 day) pretreatment with morphine did result in sensitization to [D-Ala2,Glu4]-deltorphin. Subsequent in vitro analysis, using [125I][D-Ala2,Glu4]-deltorphin or guanosine 5'(gamma-35S-thio) triphosphate autoradiography, did not reveal any changes in delta opioid receptor binding or function resulting from chronic morphine pretreatment. In conclusion, chronic morphine pretreatment caused tolerance to delta opioid receptor-mediated behavioral effects with no clear change at the receptor level.

Analgesics↗
PubMed2006

Comparison of the analgesic efficacy of pamidronate and synthetic human calcitonin in osteoporotic vertebral fractures: a double-blind controlled study.

Our aim was to compare the analgesic efficacy of pamidronate (PAM) and synthetic human calcitonin (CT) in intravenous infusion for recent painful benign vertebral compression in a randomised prospective double-blind study. Twenty-seven patients aged 49-85 years with painful benign non-traumatic vertebral compression were included in the study. They received either PAM (1 mg/kg) or synthetic human CT (1.5 mg) as an intravenous infusion. Pain and functional disability were evaluated before infusion, and 4 and 30 days afterwards. The pain score assessed on a visual analogue scale at day 0 was 5.94+/-2.47 in patients treated with PAM and 6.27+/-2.50 in patients treated with CT (p=0.74); at day 4, 4.8+/-2.80 with PAM vs 3.9+/-2.68 with CT (p=0.37); and at day 30, 3.6+/-3.13 with PAM vs 3.10+/-2.76 with CT (p=0.70). Spinal function scores were 18.21+/-3.17 at day 0 in patients treated with PAM vs 17.23+/-4.42 in patients treated with CT (p=0.69) and at day 30, 13.7+/-5.36 with PAM vs 12.33+/-3.22 with CT (p=0.68). We found no advantage of PAM over CT in a single intravenous infusion for the treatment of painful recent benign vertebral compression. Since CT is ten times less costly, its use should be preferred.

Aged↗
PubMed2006

Microsatellite typing of the human leucocyte antigen region: analytical approach and contribution to rheumatoid arthritis immunogenetic studies.

Within the major histocompatibility complex (MHC), the human leucocyte antigen (HLA)-DRB1 locus is clearly associated with rheumatoid arthritis (RA). Using a microsatellite (MSat) typing approach, we aimed to identify other loci associated with RA susceptibility and/or severity within the MHC. A panel of nine MSat HLA loci [D6S291, D6S2876 (G51152), D6S1666 (DQCAR II), D6S273, D6S2789 (TNFd), D6S2810 (MIB), D6S265, D6S2222, D6S2239], and HLA-A, -B and -DRB1 genes were typed in 170 RA cases and 282 controls. For susceptibility analysis, MSat and HLA allele distribution were compared between cases and controls, before and after stratification on HLA-DRB1*04. Haplotype frequencies were estimated using an expectation-maximization algorithm in a permutation test procedure. For severity analysis, we compared the distribution of structural damage score at onset and after 4 years of follow-up in RA cases carrying susceptibility alleles. Two MSat polymorphisms were positively associated with RA susceptibility: allele*136 of D6S265 [odds ratio, OR (confidence interval, CI) = 1.55 (1.11-2.17), P= 0.007], allele*116 of D6S2239 [OR = 1.34 (1-1.79), P= 0.03] and HLA-A2 [OR = 1.46 (1.08-1.98), P= 0.01]. Two MSat polymorphisms were negatively associated with RA susceptibility: allele*133 of D6S273 [OR = 0.3 (0.1-0.75), P= 0.005] and allele*177 of D6S291 [OR = 0.72 (0.53-0.96), P= 0.02]. The association between allele*136 of D6S265 and RA susceptibility remained unchanged after stratification on HLA-DRB1*04. The haplotypic analysis showed an overrepresentation of D6S265*136/HLA-A*02 haplotype, which suggests an effect independent of HLA-DRB1 locus in RA susceptibility. While HLA-A2 and HLA-DR4 were associated with RA severity, no MSat polymorphism was associated with structural damage score.

Arthritis, Rheumatoid↗
PubMed2005

Do new therapeutic approaches (autotransplants, thalidomide, dexamethasone) improve the survival of patients with multiple myeloma followed in a rheumatology department?

Survival of patients with multiple myeloma (MM) showed no improvement between the 1960s and 1990s. During the last decade, new therapeutic approaches seemed likely to offer hope of prolonging survival. The aim of this study was to examine if this survival increased with the usage of new treatments. The method involves a retrospective study of 123 patients with MM, diagnosed between 1975 and 1999, all receiving treatment. They were divided into two groups: group 1 included 55 patients given the so-called "old treatments" [melphalan-prednisone, cyclophosphamide-prednisone, polychemotherapy (vincristine, melphalan, cyclophosphamide, prednisone (VMCP), VMCP-VBAP)], and group 2 included 68 patients receiving at least one of the so-called "new treatments" (dexamethasone, thalidomide, high-dose chemotherapy followed by autotransplants, bisphosphonates, interferon). The two groups were similar in terms of age, sex ratio and renal impairment, and the percentage of light-chain MM was identical in both groups. Patients who had been given a "new" treatment (group 2) had longer median survival than the patients in group 1 (54 vs 42 months). Independent analysis of each treatment modality showed increased median survival in MM patients treated using autotransplantation compared with untreated patients (125 vs 45 months). Survival was also longer in MM patients treated with thalidomide than in untreated patients (72 vs 42 months). On the other hand, neither bisphosphonates, interferon-alpha nor dexamethasone result in improved survival. Our findings emphasize the increased survival of the MM patients treated with new therapeutic approaches.

Adult↗
PubMed2001

Interferon gamma gene polymorphism and susceptibility to, and severity of, rheumatoid arthritis.

A strong association between an interferon gamma (IFN-gamma) gene polymorphism and rheumatoid arthritis susceptibility and severity has been reported in a case-control study. We investigated this polymorphism in 103 patients with early rheumatoid arthritis and 130 controls. Severity of rheumatoid arthritis was measured after 4-year follow-up with a validated radiographic score. The median radiographic score in patients increased from 1 (IQR 0-4) to 11.5 (2-35) over the 4-year follow up. The distribution of IFN-gamma alleles did not differ between patients and controls, and the distribution of radiographic scores did not differ among patients carrying the different IFN-gamma alleles. We have failed to confirm the association between the IFN-gamma gene polymorphism and rheumatoid arthritis susceptibility or severity.

Alleles↗
PubMed2001

Whole body and regional bone mineral density in ankylosing spondylitis.

OBJECTIVE: To study the regional distribution of bone mass and look for factors leading to bone loss in ankylosing spondylitis (AS). METHODS: Thirty-nine patients, all men, aged 20 to 55 years and presenting with AS were studied. Four hundred sixteen gendarmes, all men aged 20 to 55 years, formed an age matched control population used to define standard values for bone mineral density (BMD) in men. The patients with AS and the controls underwent measurement of whole body BMD and regional BMD by dual-energy x-ray absorptiometry. RESULTS: AS was associated with spinal bone loss, with lumbar spine BMD (LSBMD) 1.085 +/- 0.178 g/cm2 in the AS group compared with 1.232 +/- 0.136 g/cm2 in the control group (p < 0.01). Whole body BMD and regional BMD of head, whole spine, pelvis, and legs were reduced, although this was not statistically significant. Using standard values for LSBMD from the controls, we found that 46% (18/39) of patients with AS had Z score < -1.5 SD. Biological markers of disease activity were higher in the subgroup of patients with low LSBMD than in the subgroup with normal LSBMD, with an erythrocyte sedimentation rate of 29.4 +/- 23.4 mm/h versus 12.1 +/- 10.8 mm/h (p < 0.05) and C-reactive protein at 24.8 +/- 18 mg/l versus 12.7 +/- 14.2 mg/l (p < 0.05). CONCLUSION: AS is associated with bone loss, mainly concerning the lumbar spine, in patients whose disease is biologically most active.

Adult↗
PubMed1999

Interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: relationship to occurrence and severity of rheumatoid arthritis.

OBJECTIVE: To test if interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), IL-4, or IL-10 gene polymorphisms could be used as markers of susceptibility or severity in rheumatoid arthritis (RA). METHODS: The study included 108 patients with early RA followed up for 2 years and 128 healthy controls. From genomic DNA, 6 polymorphisms in genes for IL-1beta, IL-1Ra, IL-10, and IL-4 were typed. Allelic frequencies and carriage rates were compared between RA patients and controls, between patients with erosive and nonerosive RA, and between patients with or without sustained remission. RESULTS: The RP1 allele of the IL-4 gene was found with a significantly higher frequency in RA patients compared with controls. The combination of an RA-related HLA-DR allele expressing shared epitope and the presence of allele E2 in IL-1beta exon 5 was found to expose patients to an increased risk of erosive disease, with an odds ratio of 8.20 (95% confidence interval 2.59-25.84, P < 0.0001). No significant association was observed between polymorphisms and the occurrence of sustained remission. CONCLUSION: This report, for the first time, indicates an association between RA and a polymorphic IL-4 gene sequence located in 5q31-33. In addition, the results show the prognostic value of a polymorphism in IL-1beta exon 5, which allowed prediction of erosive disease with a specificity of 91.8% in 42.1% of patients. Although these observations are very interesting, they have to be considered preliminary and will need to be confirmed.

Arthritis, Rheumatoid↗
PubMed1999

Measurement of bone mineral density by dual X-ray absorptiometry in Paget's disease before and after pamidronate treatment.

Third-generation bisphosphonates are now currently used in the treatment of Paget's disease of bone. Dual X-ray absorptiometry may make it possible to quantify the action of these bisphosphonates on bone mineral density (BMD) in pagetic and nonpagetic bone. We used Lunar DPX, a total-body software program (automatic analysis and/or manual windows according to the site and bilateral or unilateral pagetic involvement) to study BMD in 28 patients (18 men, 10 women, mean age 69.8 years) with Paget's disease before and 6 months after infusions of 60 mg (alkaline phosphatase <350 IU) or 120 mg (ALP >350 IU) of pamidronate. Before treatment, in the 28 patients, the BMD of trabecular pagetic bone was 25% higher than that of nonpagetic bone; in cortical pagetic bone the BMD was 35% higher. After treatment, the BMD of trabecular pagetic bone increased by only 1.17%. the BMD of cortical pagetic bone increased by 1.37% whereas nonpagetic cortical bone lost 0.84%, independently of the levels of parathyroid hormone or the administration of calcium and vitamin D.

Absorptiometry, Photon↗
PubMed1999

Decreased peripheral blood T cell cytokine gene expression in rheumatoid arthritis.

Currently, few informations are available about spontaneous production of T cell cytokines in rheumatoid arthritis (RA) peripheral blood (PB), because these cytokines are generally under the detection threshold of ELISAs. Because the Th1/Th2 balance could help to determine the outcome of RA, we used a sensitive and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method to mesure spontaneous T cell production of IL-2, IL-4, IL-10, and IFN-gamma mRNAs using unstimulated PBMC from 25 active RA patients, not taking any DMARDs for at least 6 weeks, and 19 healthy controls. Spontaneous IL-2 and IL-4 mRNA expressions are significantly lower in RA patients compared to healthy controls. Levels of IL-10 and IFN-gamma are similar in the two groups. No correlation was found between cytokine mRNA levels and clinical parameters. Spontaneous IL-4 and IL-10 mRNA levels are respectively correlated to the number of CD4+ T cells and to the number of monocytes in PB. After in vitro stimulation, IFN-gamma mRNA production by RA PBMC is significantly decreased. Most of the patients cannot be classified as having a T cell cytokine type 1 or type 2 secretion pattern in PB. IL-2 and IL-4 mRNAs in PB of active RA are produced at a low spontaneous level and the response to in vitro activation by mitogen is weak.

Adult↗
PubMed1999

Eight years of experience in the first Romanian center of family planning and contraception.

This study describes 8 years of experience (1990-97) in the first Romanian center for family planning and contraception, which started in Bucharest at the Clinic Hospital of Obstetrics and Gynecology 'Prof. Dr. P. Sirbu' on 27 February 1990. A total of 14,258 women had attended the clinic by 1 January 1998. Trends in the use of contraceptives and the number of births and abortions at the center are described. During the 8 years, the induced abortions decreased by 65% and the uncompleted abortions (illegal abortions) by 45%. Hormonal contraception was the most commonly used contraceptive method (61.5%), followed by intrauterine devices (28.8%) and local contraception (barrier methods: condoms, diaphragms, spermicides) (9%).

Abortion, Induced↗
PubMed1999

Rheumatoid factor and antikeratin antibody are independent from presence of DR4 or DR1 in rheumatoid arthritis.

BACKGROUND: Presence of HLA-DR4, rheumatoid factor, and antikeratin antibody may predict severe rheumatoid arthritis. OBJECTIVE: To investigate potential associations between HLA DR4, rheumatoid factor and antikeratin antibody in rheumatoid arthritis patients. PATIENTS AND METHODS: Retrospective review of 169 patients followed at the Rangueil Teaching Hospital rheumatology department for rheumatoid arthritis. RESULTS: No differences in prevalences of DR4 and DR1 were found between patients with and without rheumatoid factor or between patients with and without antikeratin antibody, suggesting that the production of rheumatoid factor and/or antikeratin antibody is not dependent on genetic factors. Substantial overlap was seen between rheumatoid factor and antikeratin antibody. All three parameters can be identified at first evaluation of a patient with joint disease. CONCLUSION: It would be of interest to evaluate the cumulative predictive value of DR4 or DR1, rheumatoid factor and antikeratin antibody at disease onset.

Arthritis, Rheumatoid↗
PubMed1998

[Gammopathies of indeterminant significance and osteoporosis: association or coincidence?].

OBJECTIVES: Osteoporosis is common in subjects over 70 years of age. Likewise, the incidence of monogammapathies of undetermined signification (MGUS) increases with age. We conducted this study to determine whether the biological and histomorphometric characteristics of osteoporosis in patients with MGUS are different from those in primary osteoporosis and to ascertain whether any cause and effect relationships could exist between MGUS and osteoporosis, excluding signs of active myeloma. PATIENTS AND METHODS: Serum and urinary phosphorus and calcium, histomorphometric measurements, hormone levels and serum cytokines (IL1, IL6 and TNF alpha) were determined in 7 patients (mean age 71.8 years, 2 men and 5 women) with MGUS associated with osteoporosis with vertebral fractures (OP) and compared with those in 7 osteoporosis patients without MGUS matched for age, sex, and osteoporosis severity and 7 other age and sex matched patients with MGUS without OS. The MGUS + PS patients were followed for 9 years (4.5 to 20) so slowly progressive myeloma could be excluded. RESULTS: Cytokine levels were the same in the three groups of patients but MGUS + OP patients had higher urinary calcium levels (ca/cr = 0.21 +/- 0.08 vs 0.12 +/- 0.1 (OP) and 0.13 (MGUS); p = 0.04), decreased osteocalcin levels (7 +/- 4.6 ng/ml vs. 12 +/- 4 (OP) and 11.5 +/- 5 (MGUS); p = 0.01) and increased surface resorption (8 +/- 1.4 vs. 3.6 +/- 1.2 (OP) and 5.5 +/- 1.7 (MGUS); p = 0.05). DISCUSSION: It has been demonstrated that MGUS in patients with increased resorption and lower osteocalcin levels frequently progresses to active myeloma. The question is raised as to whether, in certain cases of MGUS, in situ stimulation of bone cells by monoclonal plasma cells could exist without ongoing transformation to active myeloma.

Aged↗
PubMed1998

Antiinflammatory and immunoregulatory action of methotrexate in the treatment of rheumatoid arthritis: evidence of increased interleukin-4 and interleukin-10 gene expression demonstrated in vitro by competitive reverse transcriptase-polymerase chain reaction.

OBJECTIVE: To look for in vitro modulation of the main immunoregulatory and antiinflammatory cytokines by methotrexate (MTX) during the course of rheumatoid arthritis (RA). METHODS: We quantified interleukin-2 (IL-2), IL-4, IL-10, and interferon-gamma (IFNgamma) gene expression by peripheral blood mononuclear cells ex vivo under basal conditions and in vitro after stimulation with phytohemagglutinin (PHA) or PHA plus MTX, by competitive reverse transcriptase-polymerase chain reaction (RT-PCR), in 12 patients with untreated active RA (group 1), 10 patients with MTX-treated disease in partial remission (group 2), and 11 healthy control subjects. Simultaneously, under the same experimental conditions, we quantified cytokine production by specific enzyme-linked immunosorbent assays (ELISAs). RESULTS: Under basal conditions, we found no differences in IL-2, IL-10, and IFNgamma gene expression in the 3 groups, while IL-4 gene expression was significantly decreased in RA patient group 1 compared with the control group. In vitro, under the action of MTX, IL-10 gene expression was significantly increased in the 3 groups, IL-4 gene expression was significantly increased in RA group 1 and in the control group, and IL-2 and IFNgamma gene expression was significantly decreased in RA group 1. Cytokine gene expression assessed by RT-PCR and cytokine production assessed by specific ELISAs were highly correlated. CONCLUSION: In vitro modulation of the cytokine network by MTX, increasing Th2 cytokines and decreasing Th1 cytokines, could explain its antiinflammatory and immunoregulatory actions in vivo during the treatment of RA.

Adult↗