Management of low back pain in primary care prior to multidisciplinary functional restoration: a retrospective study of 72 patients.

OBJECTIVE: Chronic low back pain is a major socioeconomic health issue, due to the high direct (healthcare) and indirect (sick leave) costs. The aim of the present study was to describe the primary care management of low back pain patients prior to their inclusion in a multidisciplinary functional restoration network. METHODS: A descriptive, retrospective, questionnaire-based survey of the general practitioners dealing with 72 low back pain patients. RESULTS: Patients had been monitored by their general practitioner for an average of four years, with a mean frequency of eight appointments per year per patient. Ninety-three percent and 60% of the patients had been referred to a rheumatologist and a surgeon, respectively. Ninety-eight percent had had lumbar radiographies, 80% had undergone a computed tomography scan and 64% had undergone magnetic resonance imaging. The most commonly prescribed medications were anti-inflammatories and first- or second-line analgesics. Thirty percent had already received morphine analgesics and 50% had taken antidepressants. Thirty-two percent had undergone lumbar surgery. Physiotherapy was frequently reported and, indeed, 6% of patients had participated in over 100 sessions. Total sick leave averaged 8.25 months over the study's follow-up period. CONCLUSION: The time interval before referral to a multidisciplinary care team is long and so GPs should be encouraged and helped to organize this process earlier. It is also essential to determine factors which predict progression to chronic LBP.

Study of the correlation between MEIA and ELISA methods for FK 506 determination in liver transplant recipients.

BACKGROUND AND OBJECTIVES: FK 506 is an immunosuppressive macrolide advocated for prevention of graft rejection. Plasma or blood FK 506 levels must be determined to strike a balance between FK 506 toxicity and graft rejection. The first aim of this study was to compare an automated microparticle enzyme immunosorbent assay (MEIA) method (on whole blood) with the reference enzyme-linked immunosorbent assay (ELISA) method (on plasma). A second aim was to compare the two methods for prediction of FK 506 nephrotoxicity. PATIENTS AND METHODS: Forty-seven patients were studied comprising 128 samples. All were treated with FK 506 on a compassionate basis. For each patient, the concentrations of FK 506 were determined in plasma by means of ELISA and in whole blood by MEIA. RESULTS: The repeatability and the reproducibility of these two methods were similar. The inter-patient correlation coefficient between MEIA and ELISA, determined on 128 samples from 47 liver recipients, was satisfactory (r = 0.82). From these 47 patients, the intra-patient correlation coefficients were calculated for 17 of them. The intra-patient correlation coefficients were between 0.63 and 0.98 for 15 patients, and between 0.26 and 0.55 in the remaining two cases. Mean creatinine plasma levels in the 55 samples below the median FK 506 value in the MEIA method and in the 55 with values above the median (120 and 134 mumol/litre, respectively) were significantly different (P < 0.05), as were those using the reference ELISA methods (115 and 139 mumol/litre, P < 0.01). In contrast, there was no significant difference between the mean creatinine plasma levels in the 55 samples with FK 506 levels below the median using both methods or between those above the median. CONCLUSION: The automated MEIA method, being simpler and more rapid than the ELISA method, should now be preferred for therapeutic monitoring of FK 506.

Modulation of energy status and cytotoxicity induced by FK506 and cyclosporin A in a renal epithelial cell line.

FK506 and cyclosporin A (CsA) are two potent immunosupressants with similar toxicity profile. Nephrotoxicity is the main adverse effect of both compounds. The aim of this study is to compare the in vitro nephrotoxic effects on renal epithelial cell line LLC-PK1 by measuring cell viability and energy status as evaluated by concentrations of ATP and ATP metabolites. Cell viability (expressed as IC50 was assessed via thiazolyl blue (MTT) assay after incubation for 4-24 h with FK506 or CsA. ATP and its metabolites were determined by HPLC after 4 and 6 h incubation with FK506 or CsA alone at the respective IC50. Both FK506 and CsA decreased cell viability to similar extents, in a dose- and time-dependent manner. After 4 h incubation, both drugs decreased ATP levels (-25%) and increased uric acid levels. However, the latter percentage increase was twofold higher with CsA (18%) than with FK506 (9%). The energy charge, calculated according to levels of adenine nucleotides, was decreased by 10% in FK506-treated cells and by 27% in CsA-treated cells. At the end of 6-h incubation, FK506-treated cells maintained ATP levels coupled with energy charge at near control levels whereas the levels were 32% lower in CsA treated cells. Compared to the 4 h-incubation, the increase in uric acid was similar for FK506 but was doubled with CsA. The decrease in cell integrity and ATP depletion induced by CsA in LLC-PK1 cells was only transiently observed with FK506. By preserving energy status, FK506 leads to fewer metabolic disturbances than CsA in the renal epithelial cell line LLC-PK1, demonstrating a minor potential nephrotoxicity.

Comparative evaluation of in vitro and in vivo immunosuppressive potential of cyclosporin G with cyclosporin A and FK-506.

Cyclosporin G (CsG), a promising cyclosporin A (CsA) analogue, was examined and compared with two reference immunosuppressive drugs: CsA and FK-506, regarding their inhibitory effects on different lymphocyte activation pathways as well as on graft-versus-host reaction (GvHR) across differences at major or minor histocompatibility loci. The results showed that, at different concentrations, CsG efficiently inhibited proliferation induced by alloantigens (mixed lymphocyte culture), mitogens (concanavalin A, pokeweed mitogen) and the combination of phorbol myristate acetate + ionomycin, to the same extent as observed with CsA and FK-506. It was also shown that CsG exhibited the same strong inhibitory effects as the two other immunosuppressants upon stimulation triggered by viral (MLs-1a) or bacterial (staphylococcal enterotoxin B) superantigen. Determination of IL-2 activity in the supernatant of MLC also confirmed similar strong inhibitory effects, exerted by CsG compared to CsA and FK-506. In systemic and local GvHR across major or minor histocompatibility barriers, CsG as well as CsA and FK-506 presented an equivalent immunosuppressive potential. In conclusion, from various experiments involving different modes of activation, it was shown that CsG was as strongly immunosuppressive as CsA and FK-506.

Monoclonal antibodies directed against T cell epitopes presented by class I MHC antigens.

Monoclonal antibodies which recognize a synthetic peptide derived from influenza virus nucleoprotein in association with a murine class I MHC molecule (Kd) have been isolated. One such antibody has been characterized and shown to react neither with the peptide nor with the Kd molecule, but only with the Kd-peptide complex. Evidence is given that it recognizes the naturally processed peptide located in the peptide binding groove, i.e. the antigenic moiety presented to T cells.

In vitro and in vivo comparative studies on immunosuppressive properties of cyclosporines A, C, D and metabolites M1, M17 and M21.

Cyclosporine A (CsA) and its major metabolites: M1, M17 and M21 and two analogues: cyclosporines C (CsC) and D (CsD), were studied for their capacity to interfere with different in vitro activation pathways. Their inhibition potentials against the reaction of Graft-versus-Host (GvH) were also studied. The results showed: CsA, CsC and metabolite M17 were the most active compounds upon the inhibition of lymphocyte proliferation induced by different mitogens (ConA, PHA, PWM) and also on the proliferation of mixed lymphocyte cultures (MLC). The same results were observed concerning the direct activation by protein kinase C using a combined action of phorbol ester + calcium ionophore. In vivo using local GvH reaction, CsA and CsC proved more active than M17 in the two different combinations: H-2d --> (H-2b x H-2d)F1 and H-2k --> (H-2b x H-2k)F1 CsD and two metabolites M1 and M21 showed no or weak immunosuppressive effects. Overall, the immunosuppressive potency of six compounds could be schematized as: CsA > or = CsC > M17 > M1 > or = CsD > M21.

[Isolation and characterization of monoclonal antibody directed against antigenic peptide presented by class I histocompatibility molecule]. / Isolement et caractérisation d'un anticorps monoclonal dirigé contre un peptide antigénique présenté par une molécule d'histocompatilité de classe I.

We describe the isolation and several characteristics of a monoclonal antibody (X5.3.7) which recognizes a peptide derived from influenza virus nucleoprotein and presented by the murine class I major histocompatibility molecule Kd. X5.3.7 is thus an example of an antibody capable of recognizing an epitope normally recognized by T cells.

The Paul Brousse liver transplant series 1989 to 1992: new trends in the last four years.

In the last four years, 551 liver transplantations have been performed at the Paul Brousse center, for a total of 840 liver transplantations performed from 1984 to 1992. Several changes have been observed in the field of liver transplantation in the past years. The field of immunosuppression was marked mainly by the advent of FK506 as a preventive treatment of rejection and as a treatment of cortico-resistant rejection. Results are still under analysis. From the surgical viewpoint, the main modification was the advent of UW solution, which extends cold ischemic time. However, our policy was to maintain the cold ischemic time at less than 12 hours. Primary indications for liver transplantations have changed with an increase in the rate of patients transplanted for cirrhosis related to hepatitis virus infection: from 24% in the period 1984-1988 to 42% in the period 1989-1992. The difference was due mainly to HCV-related cirrhosis, which increased from 8% to 20%. Alcoholic cirrhosis was a rare indication in the period 1989-1992 (3.4%); however, it was an increasing indication in the last 2 years. In order to improve the long-term results, major attention was given to the recurrence of initial liver disease. In patients transplanted for HBsAg-positive liver disease, long-term passive anti-HBs immunoprophylaxis was administered, which reduced the rate of HBV recurrence in patients without HBV replication before transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential modulation of the in vitro lymphocyte activation pathways by soluble and solubilized placental substances.

Soluble and detergent-solubilized placental extracts were studied for their modulatory effects upon the proliferation of lymphocytes stimulated by various activating agents. It was shown that soluble placental extract (SPE) exerted an inhibitory effect on the lymphoproliferation triggered by alloantigen or LPS but not by Con A or the combined action of PMA + calcium ionophore A 23187. This effect was also observed with SPE precipitated by 30% of ammonium sulfate (SPE30). On the other hand, a solubilized placental extract (SzPE) that was obtained by using octyl-beta-D-glucopyranoside inhibited the stimulation triggered by alloantigen, LPS, and Con A but did not affect the protein kinase C pathway. The modulatory effects were observed not only when SPE (or SPE30) and SzPE were added at the time of culture initiation but also at 24 h before or after the activating agents. Preincubation with SPE30 or SzPE immobilized on plastic surface, however, transduced an enhanced lymphoproliferative response to alloantigen and mitogen Con A but not to LPS. The above results suggest that placental substances exerted their modulatory effects by interfering mainly with the antigen or mitogen lymphoproliferation pathways.