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Biomedical subjects

M Perrin

Publications and source records attributed to M Perrin.

At least 55 records · Page 3Linked to original sources
PubMed1998

Pattern of HCV antibodies with special reference to NS5A reactivity in HCV-infected patients: relation to viral genotype, cryoglobulinemia and response to interferon.

BACKGROUND/AIMS: We aimed to compare the anti-hepatitis C virus reactivity in confirmatory assays (RIBA 3.0 Ortho Diagnostic and INNO-LIA HCV Ab III Innogenetics) among patients infected with different hepatitis C virus genotypes, with or without cryoglobulinemia, and in patients treated with interferon. METHODS: One hundred and three patients followed in our hepatogastroenterology unit were included in the study and compared to 320 consecutive patients tested using RIBA 3.0. Seventy-nine of the 103 patients were treated with interferon. Long-term responders to interferon were defined as having normal alanine aminotransferase levels and being HCV RNA negative 6 months after the end of treatment. Initial responders were defined as having normal alanine aminotransferase levels at the end of interferon therapy but abnormal alanine aminotransferase levels and/or detectable HCV RNA during the following 6 months. Non-responders were defined as still having elevated alanine aminotransferase during and after interferon. Serological tests (RIBA and INNO-LIA) were performed according to the manufacturers' instructions. HCV RNA was detected by nested polymerase chain reaction. Hepatitis C virus genotype was determined by using a Line Probe Assay (Innogenetics). RESULTS: There was no significant difference in the pattern of hepatitis C virus reactivity according to the hepatitis C virus genotype or presence of cryoglobulinemia. Twenty-three patients were classified as non-responders, 35 as initial responders, 21 as long-term responders. NS5 reactivity was significantly different (p<0.01) between these three groups: 34% of non-responders (8/23) had RIBA 3.0 NS5 reactivity and 13% (3/23) were reactive in the INNO-LIA III. Almost all long-term responders (95%) had NS5 reactivity by both RIBA 3.0 and INNO-LIA III. CONCLUSION: We conclude that patients who respond to interferon have stronger reactivity against NS5 antigens than non-responders. Molecular changes in the NS5A region may be responsible for such differences, as recently suggested.

Antiviral Agents↗
PubMed1998

Dendritic cell-based vaccines in the setting of peripheral blood stem cell transplantation: CD34+ cell-depleted mobilized peripheral blood can serve as a source of potent dendritic cells.

We are investigating the use of tumor-pulsed dendritic cell (DC)-based vaccines in the treatment of patients with advanced cancer. In the current study, we evaluated the feasibility of obtaining both CD34+ hematopoietic stem/ progenitor cells (HSCs) and functional DCs from the same leukapheresis collection in adequate numbers for both peripheral blood stem cell transplantation (PBSCT) and immunization purposes, respectively. Leukapheresis collections of mobilized peripheral blood mononuclear cells (PBMCs) were obtained from normal donors receiving granulocyte colony-stimulating factor (G-CSF) (for allogeneic PBSCT) and from intermediate grade non-Hodgkin's lymphoma or multiple myeloma patients receiving cyclophosphamide plus G-CSF (for autologous PBSCT). High enrichment of CD34+ HSCs was obtained using an immunomagnetic bead cell separation device. After separation, the negative fraction of mobilized PBMCs from normal donors and cancer patients contained undetectable levels of CD34+ HSCs by flow cytometry. This fraction of cells was then subjected to plastic adherence, and the adherent cells were cultured for 7 days in GM-CSF (100 ng/ml) and interleukin 4 (50 ng/ml) followed by an additional 7 days in GM-CSF, interleukin 4, and tumor necrosis factor alpha (10 ng/ml) to generate DCs. Harvested DCs represented yields of 4.1+/-1.4 and 5.8+/-5.4% of the initial cells plated from the CD34+ cell-depleted mobilized PBMCs of normal donors and cancer patients, respectively, and displayed a high level expression of CD80, CD86, HLA-DR, and CD11c but not CD14. This phenotypic profile was similar to that of DCs derived from non-CD34+ cell-depleted mobilized PBMCs. DCs generated from CD34+ cell-depleted mobilized PBMCs elicited potent antitetanus as well as primary allogeneic T-cell proliferative responses in vitro, which were equivalent to DCs derived from non-CD34+ cell-depleted mobilized PBMCs. Collectively, these results demonstrate the feasibility of obtaining both DCs and CD34+ HSCs from the same leukapheresis collection from G-CSF-primed normal donors and cancer patients in sufficient numbers for the purpose of combined PBSCT and immunization strategies.

Antigens, CD34↗
PubMed1997

The inhibitory effect of glucose on growth hormone secretion is lost in obesity but not in hypertension.

In obesity there is a clear reduction of both spontaneous and stimulated GH secretion. Furthermore, in obese patients the somatotrope responsiveness to provocative stimulation is selectively refractory to the inhibitory effect of glucose load. It has been hypothesized that hyperinsulinism of obese patients could play a role in the pathogenesis of these alterations. Aim of the present study was to verify the GH response to GHRH and the ability of glucose load to inhibit it in patients with essential hypertension in whom hyperinsulinism and insulin resistance are frequently present. To this goal, 7 patients with essential hypertension (HP, age, mean +/- SE: 29.6 +/- 2.4 yr, 3 females and 4 males, BMI: 21.7 +/- 1.2 kg/m2), 7 obese (OB, 4 females and 3 males, 31.9 +/- 4.1 yr, 35.6 +/- 2.0 kg/m2) and 7 normal subjects (NS, 4 females and 3 males, 28.3 +/- 3.9 yr, 21.0 +/- 1.6 kg/m2) underwent the following tests: GHRH (1 microgram/kg i.v. at time 0) alone and preceded by oral glucose load (OGTT, 100 g po at -45 min). Basal insulin levels were similar in HP and OB (11.3 +/- 0.5 and 12.7 +/- 2.2 microU/ml, respectively); these, in turn, were higher (p < 0.005) than those in NS (6.8 +/- 0.8 microU/ml). Basal plasma glucose levels in HP were similar to those in OB and NS (80.3 +/- 3.6, 86.9 +/- 6.7 and 84.4 +/- 1.7 mg/dl, respectively). In HP and OB and NS basal GH (1.0 +/- 0.5, 1.0 +/- 0.6 and 0.3 +/- 0.1 micrograms/l, respectively) and IGF-I levels (132.6 +/- 14.8, 137.3 +/- 13.2 and 138.8 +/- 12.2 micrograms/l, respectively) were similar. In HP the GH response to GHRH (AUC: 1058.8 +/- 347.8 micrograms/l/min) was similar to that observed in NS (959.0 +/- 167.8 micrograms/l/min) and higher than that in OB (344.8 +/- 67.2 micrograms/l/min, p < 0.01). OGTT clearly blunted (p < 0.01) the GHRH-induced GH response in HP as well as in NS (401.8 +/- 104.4 and 521.6 +/- 76.6 (g/l/min, respectively) but not in OB (387.4 +/- 78.8 (g/l/min). The OGTT-induced insulin levels in HP did not differ from those of OB, both being higher (p < 0.05) than those recorded in NS. Glucose levels after OGTT were similar in the three groups. In conclusion, this study demonstrates that, like in normal subjects but differently from in obese patients the GH response to GHRH is normal in patients with essential hypertension and it is normally inhibited by oral glucose load even when these patients show high insulin levels. Thus, it is unlikely that the low somatotrope secretion and its refractoriness to inhibition by glucose load in obesity is due to hyperinsulinism.

Adult↗
PubMed1997

Effects of cirrhosis, interferon and azathioprine on adverse events in patients with chronic hepatitis C treated with ribavirin.

To determine adverse events of ribavirin in the treatment of chronic hepatitis C, 41 patients (18 with cirrhosis), treated with ribavirin at an initial dose of 600-1200mg day(-1), were analysed retrospectively (six patients were treated twice because adverse effects during the first treatment necessitated cessation of ribavirin). Indications for ribavirin included a contraindication (n = 15) an intolerance (n = 11) or a non-response (n = 15) to interferon (IFN). Ribavirin was combined with IFN 3 million units (MU) three times weekly for 15 patients and with azathioprine for six patients (five of whom were transplant patients). No cirrhotics and only one patient treated with ribavirin + IFN received azathioprine. The mean duration of treatment was 5 months (range 1-18 months). Sixteen of 47 treatments (34%) with ribavirin were stopped: four because of vomiting (8.5%), two for psychiatric disorder, one for dry cough, one for an unrelated cause, and eight (at 1-2 months) because of a fall in the level of haemoglobin (Hb) of 4.6 g dl(-1) (range 2.7-5.9 g dl[-1]); however, according to the rules of international protocol, we would have expected only four treatments (two in patients receiving azathioprine) with Hb < 8.5 g dl(-1) to be stopped. The decrease in Hb level occurred more slowly in patients treated with IFN plus ribavirin than in patients treated with ribavirin alone and was of lower clinical significance in patients with cirrhosis than in patients without cirrhosis. After exclusion of patients receiving azathioprine, there was no significant difference in the fall of Hb level between cirrhotic and non-cirrhotic patients and between patients treated with IFN plus ribavirin and patients treated with ribavirin alone. Interestingly, the platelet count of patients treated with IFN plus ribavirin fell less than in patients treated with IFN alone. The most important and expected adverse event associated with ribavirin was haemolysis. Anaemia < 8.5 g dl(-1), requiring cessation of ribavirin therapy, was present in 9% of patients and was worsened by azathioprine. Abdominal discomfort and dry cough were other, potentially important, clinical adverse events found in our study.

Adult↗
PubMed1997

[Recurrent varicose veins in the groin after surgery].

Recurrence of varicose veins following surgery of the long saphenous system are common. It is important to differentiate several causes. These, in fact, dictate the therapeutic decision. Physiopathologically, there are different types of recurrences: persistent reflux from the femoral veins into the superficial varicose network due to: an incomplete long sapheno-femoral high ligation (crossectomy), a neoangiogenesis at the level of the previous sapheno-femoral junction. separate termination of an incompetent long saphenous vein (LSV) into the common femoral vein or the superficial femoral vein (antero lateral or postero medial tributaries of LSV); persistent reflux from perineal and (or) paricto-abdominal veins into the varicose network of the thigh. Dynamic popliteal phlebography was, until the advent of echo-doppler, the author's method of choice for investigation as it was easier to interpret than varicography. At the present time it is only requested on the rare occasions where doubt persists even after echo-doppler. Additionally, with this investigation, the reflux (major or minor) can be analysed at its point of origin and a map of the underlying varicose network can be drawn. Therapeutically, we make the following suggestions: in the presence of a site of major reflux (incomplete crossectomy, high flow neoangiogenesis, separate termination of the saphenous tributaries), a further operation would be justified. The removal of the site of reflux can be associated with the placing of a PTFE patch on the common femoral vein. in the presence of a site of minor reflux, sclerotherapy or, preferably, echosclerotherapy would appear to be the treatment of choice. Elimination of the site (s) of reflux must be associated with suppression of the underlying varicose network by sclerotherapy or phlebectomy.

Combined Modality Therapy↗
PubMed1997

[Pre- and postoperative contribution of Doppler ultrasonography in superficial venous surgery of the popliteal fossa].

AIMS OF THE STUDY: Does preoperative Duplex Scan (DS) allow to determine anatomy of the ending of the short saphenous vein (SSV), gastrocnemius vein (GV) and reflux in popliteal vein (PV), SSV and GV. Postoperative DS was performed to detect deep vein thrombosis (DVT) and GV thrombosis. MATERIAL AND METHODS: From June 94 to November 95 one hundred and eighty lower limbs operated for SSV were included consecutively and prospectively. Mean age in these 154 patients was 52 yr (24-80) with a sex ratio 4F/1M. An anatomical classification was previously defined. Type A: separate termination of SSV and GV; Type B: common ostium of SSV and GV in the popliteal vein; Type C: common trunk of the SSV and GV; Type D: Others. Forty-eight limbs (26.10%) had ligation of GV: 21 (11.10%) for reflux and 27 (16%) for anatomical or surgical reasons. Ten type A with GV reflux (10/31 = 32%) were not treated. Eighty two patients (45%) received preventive low molecular weight heparin (LMWH) treatment including the 48 limbs whose GV were ligated. RESULTS: Anatomical correlation between DS and surgery findings were calculated. Positive predictive values of DS in the different types were: A, 77%; B, 68%; C, 90%; D, 79%. That gave a global predictive value of 80%. Two limited DVT were identified in group D by postoperative DS (2/10 = 1.1%). These two patients had complete recanalization of PV without reflux. In the group of limbs which had ligation of GV we identified 37.5% of GV thrombosis. In the group without ligation of GV we found 3% of GV thrombosis. CONCLUSION: Duplex scanning appears to be the investigation of choice before surgery for superficial vein incompetence in the popliteal fossa. It is a reliable investigation to determine termination patterns of SSV and GV (80%). It brings to the surgeon essential information which helps in the management of surgical procedure and particularly to ligation of gastrocnemius veins. But at this time there is no consensus on this point. The occurrence of DVT after SSV surgery including GV ligation was very low. Two questions remain: is anticoagulation necessary in all patients or selective after surgery of the SSV? is Duplex Scan mandatory during postoperative monitoring? On the basis of this study, one recommendation can be made: A routine postoperative DS is necessary after ligation of the GV or when the dissection of the popliteal fossa has been extensive (Type D).

Adult↗
PubMed1997

[Deep venous insufficiency and recurrent varicose veins after surgery of superficial venous insufficiency].

Combination of deep and superficial venous insufficiency is far from exceptional and often causes severe chronic venous insufficiency (CVI). Does this association increase the risk of recurrent varicose veins after surgery of superficial insufficiency? After brief clinical and instrumental considerations in this situation, four series on this topic are analysed. Those published by Almgren, Guarnera, Darke and our personal series in which valve repair in the deep system was the inclusion criteria. Among the sixty seven patients included (80 lower limbs), fifty had previous surgery for varicose veins before valvuloplasty. Recurrence rate has been evaluated in both saphenous territories: great saphenous vein: 51% and short saphenous vein: 38.5%. It appears difficult to determine whether varicose vein recurrence is related to technical error at the initial operative procedure or due to the Primary Deep Vein Incompetence (PDVI). Nevertheless recurrence of varicose vein would appear to be frequent in the four series analysed. Many questions remain unanswered in this situation.

Humans↗
PubMed1997

[Surgical repair of varicose veins of the lower limbs by saphenous vein stripping].

For a long time, high ligation and stripping of the saphenous trunk was the only technique used to deal with primary varicose veins when surgical treatment was recommended. Duplex ultrasound has demonstrated that this attitude is not well-founded in many cases. Alternative techniques have been proposed and performed. Some of them have not been submitted to randomised and prospective studies. Others, particularly high ligation and stab avulsion of collaterals with preservation of the long saphenous trunk, have been evaluated. The author indicates in which cases high ligation + stripping of the saphenous trunk remains justified and in which situations it is not. All indications must be based on clinical examination and duplex ultrasound.

Humans↗
PubMed1996

Antibody responses to hepatitis C envelope proteins in patients with acute or chronic hepatitis C.

Antibody responses to the hepatitis C virus (HCV) envelope proteins E1 and E2 were analyzed using two original assays in sera from 86 patients in different stages of disease. A Western blot assay and an immunofluorescence assay (IFA) were developed using envelope proteins produced, respectively, in Escherichia coli and in CV1 cells infected with a recombinant SV40. As a third method, the INNO-LIA HCV Ab III assay including E2 synthetic peptides was used. Of 38 chronically infected patients positive for anti-E2 antibodies by IFA, 26 were positive in the Western blot assay (68%) and 25 in the INNO-LIA test (66%). Thus, the detection of anti-envelope antibodies is highly dependent on the antigen formulation, and a native glycosylated form of the proteins is probably needed for their efficient detection. This study shows that the antibody response to HCV envelope proteins depends on the phase of infection. A few acutely infected patients displayed a response to E1 or E2 (36% by Western blot, 7% by IFA), and these antibodies seem to develop in patients evolving toward chronicity. The high prevalence in chronically infected subjects (62% to E2 by Western blot, 90% by IFA), particularly in subjects with essential mixed cryoglobulinemia (68% and 100%), confirms that the resolution of infection involves more than these antibodies. The antienvelope response in patients treated with interferon was investigated, but no significant relationship was found between antibody level prior to treatment and the evolution of hepatitis. The detection of anti-envelope antibodies, therefore, is not predictive of the response to antiviral therapy.

Acute Disease↗
PubMed1996

[Forensic medical implications in surgery of chronic venous insufficiency of the legs].

Current literature and personal experience with these complications are discussed. Complications with medicolegal implications have been analyzed in three studies, in France by J. Natali and A. Rispoli (Marseille, 1994) and in Great Britain by W.G. Tennant and C.V. Ruckley. The incidences reported are certainly underestimated as only those complications leading to an official expert opinion were counted. We also report our personal experience with medicolegal implications after 15,340 limb operations performed from 1968 to 1994. The conclusions provide an overall view of how to reduce the number of complications and provide adequate therapeutic management.

Accidents↗
PubMed1995

Potent, structurally constrained agonists and competitive antagonists of corticotropin-releasing factor.

Predictive methods, physicochemical measurements, and structure activity relationship studies suggest that corticotropin-releasing factor (CRF; corticoliberin), its family members, and competitive antagonists (resulting from N-terminal deletions) usually assume an alpha-helical conformation when interacting with the CRF receptor(s). To test this hypothesis further, we have scanned the whole sequence of the CRF antagonist [D-Phe12,Nle21,38]r/hCRF-(12-41) (r/hCRF, rat/human CRF; Nle, norleucine) with an i-(i + 3) bridge consisting of the Glu-Xaa-Xaa-Lys scaffold. We have found astressin [cyclo(30-33)[D-Phe12,Nle21,38,Glu30,Lys33]r/ hCRF(12-41)] to be approximately 30 times more potent than [D-Phe12,Nle21,38]r/hCRF-(12-41), our present standard, and 300 times more potent than the corresponding linear analog in an in vitro pituitary cell culture assay. Astressin has low affinity for the CRF binding protein and high affinity (Ki = 2 nM) for the cloned pituitary receptor. Radioiodinated [D-125I-Tyr12]astressin was found to be a reliable ligand for binding assays. In vivo, astressin is significantly more potent than any previously tested antagonist in reducing hypophyseal corticotropin (ACTH) secretion in stressed or adrenalectomized rats. The cyclo(30-33)[Ac-Pro4,D-Phe12,Nle21,38,Glu30,Lys33++ +]r/hCRF-(4-41) agonist and its linear analog are nearly equipotent, while the antagonist astressin and its linear form vary greatly in their potencies. This suggests that the lactam cyclization reinstates a structural constraint in the antagonists that is normally induced by the N terminus of the agonist.

Adrenalectomy↗
PubMed1995

Identification of a second corticotropin-releasing factor receptor gene and characterization of a cDNA expressed in heart.

Corticotropin-releasing factor (CRF; corticoliberin) regulates the secretion of corticotropin (ACTH) and beta-endorphin and has a broad range of effects on the nervous, endocrine, reproductive, cardiovascular, gastrointestinal, and immune systems. Recently, human, rat, and mouse CRF receptors (CRF-R) have been cloned and functionally and anatomically characterized. We report here the cloning of a second CRF-R cDNA (CRF-RB), which encodes a protein of 431 amino acids, which is 16 amino acids longer and 68% similar to the previously cloned CRF-R, CRF-RA. When transiently expressed in COS-M6 cells, CRF-RB binds CRF with high affinity [Kd = 1.2 (0.57-2.5)nM] and transduces the CRF-stimulated signal of the accumulation of intracellular cAMP, which is inhibited by a CRF antagonist. Comparison of the amino acid sequences of CRF-RB and the previously cloned receptor reveals major differences in the N-terminal domain and in the extracellular loops, whereas the sequences of the intracellular loops are nearly identical. CRF-RB and related transcripts are expressed in the heart, as well as in other tissues, including the gastrointestinal tract, epididymis, and brain.

Amino Acid Sequence↗