Search PubMed⌕ Search

Biomedical subjects

J M Fabre

Publications and source records attributed to J M Fabre.

At least 19 recordsLinked to original sources

Laparoscopic vertical banded gastroplasty. A multicenter prospective study of 200 procedures.

BACKGROUND: The commonest surgical procedure for management of morbid obesity in Europe is laparoscopic adjustable gastric banding (LAGB), even though laparoscopic vertical banded gastroplasty (LVBG) is still considered to be a gold standard restrictive option in bariatric surgery. A multicenter prospective study was designed to to assess the efficacy of LVBG in terms of weight loss and complication rates for obese patients who have indications for a restrictive procedure. PATIENTS AND METHODS: Two-hundred morbidly obese patients (84.5% female) with a mean age of 41 years and mean body mass index (BMI) of 43.2 kg/m(2) underwent LVBG as described by MacLean. Five trocars were placed in standard positions as per laparoscopic upper gastrointestinal surgery. A vertical gastric pouch (30 ml) was created with circular (21 or 25mm) and endolinear stapling techniques, enabling definitive separation of the two parts of the stomach. The gastric outlet was calibrated with either a polypropylene mesh (5.5 cm in length and 1cm in width) or a nonadjustable silicone band. The median follow-up period was 30 months (range, 1-72 months). RESULTS: One case had to be converted to open surgery (gastric perforation) and there was one death secondary to peritonitis of unknown etiology. The morbidity rate was 24%, comprising the following complications: gastric outlet stenosis (8%); staple line leak (2.5%); food trapping (1.5%); peritonitis (1%); thrombophlebitis (1.5%); pulmonary embolism (0.5%); and gastroesophageal reflux (9%). The excess weight loss achieved was 56.7% (1 year), 68.3% (2 years), and 65.1% (3 years). CONCLUSIONS: Laparoscopic vertical banded gastroplasty is an effective procedure for the surgical management of morbid obesity, especially for patients who present hyperphagia but are unable to manage the constraints of adjustable gastric banding. Laparoscopic vertical banded gastroplasty is safe, as demonstrated by an acceptable complication rate, of which gastric outlet stenosis, staple line leakage, and gastroesophageal reflux predominate.

Adult↗

Migration of adjustable gastric banding from a cohort study of 4236 patients.

BACKGROUND: Experience was gained management of intra-gastric migration of adjustable gastric banding. METHODS: From July 1996 to January 2003, 4236 patients who underwent laparoscopic adjustable gastric banding were proposed for routine follow-up. Gastrograms were performed in case of band adjustment. Radiological controls and endoscopy were performed according to symptoms. RESULTS: A total of 45 cases of band migration (1.6%) were diagnosed during follow-up. All but one of the migrated bands were removed laparoscopically either by a dissection outside the stomach or through a short gastrotomy. Mortality was 0% and morbidity 8% (n = 4). CONCLUSION: The risk of an intragastric band migration remains low in the literature but could grow on account of the longer follow-up of patients. The retrieval of the band is the gold standard and must be planned promptly or delayed according to symptoms.

Adolescent↗

[Evaluation of inguinal hernia management in ambulatory surgery].

AIM: To evaluate the prospects of ambulatory surgery for inguinal hernia. PATIENTS AND METHODS: From January 1995 to June 2001, 599 operations on inguinal hernias were performed. Patients were composed of 554 men and 45 women. The average age was 58 years (7-95). All patients were examined by their primary doctor on the first and the third day, and by the surgeon on the 10th day. RESULTS: Four hundred and eighty-one patients were operated on by ambulatory surgery (80.3%). The "Tension-free" technique was carried out among 495 patients (82.6%). Loco-regional anaesthesia was used for 499 patients (83.3%). The postoperative rate of complications was 10.4% (62 patients). Only 201 patients presented postoperative painful symptomatology (33.6%), 341 a discomfort (56.9%), and 57 (10%) experienced no pain. The overall satisfaction rate was 92.9%. CONCLUSION: Use of the "Tension-free" technique under loco-regional anaesthesia for inguinal hernias allows ambulatory surgery with a low rate of complications and high satisfaction for the patients.

Adolescent↗

Is laparoscopic left pancreatic resection justified?

BACKGROUND: We reviewed our experience of laparoscopic left pancreatectomy to establish the feasibility of this approach and the characteristics of the operating procedure. METHODS: Thirteen patients with a mean age of 60 years were deemed for a left pancreatectomy. Preoperative diagnoses were: nine mucinous cystadenoma and one insulinoma, intraductal mucinous ectasia, chronic pancreatitis with ductal stenosis, and distal pancreatic tumor. RESULTS: Operative mortality was nil. Two patients required conversion for bleeding from splenic vein injuries leading to a splenectomy in one case. The spleen was preserved in 10 cases. Postoperative course was uneventful in nine cases. Four patients experienced postoperative complications: one pancreatic fistula, two liquid cysts on the pancreatic margin, and one reoperation for bleeding from a trocar port. Length of stay ranged from 5 to 22 days. CONCLUSION: These preliminary results confirm that in selected cases laparoscopic resection of the left pancreas is feasible and safe.

Adult↗

Nocardiosis revealed by thyroid abscess in a liver--kidney transplant recipient.

Nocardiosis is a life-threatening infection, particularly among immunocompromised patients, which usually affects lungs, skin and central nervous system. We report a case of disseminated nocardiosis revealed by suppurative thyroiditis in a liver-kidney transplant recipient with poor nutritional status at the time of infection. Nocardia Asteroides was isolated from fine-needle aspiration material of the thyroid abscess. Clinical manifestations resolved after surgical drainage of the thyroid abscess, prolonged antibiotherapy and diminution of immunosuppressive regimen. Clinicians should be aware of this entity, as Nocardia Asteroides may need more than 5 days of culture to be isolated.

Abscess↗

Dual effect of dexamethasone on CYP3A4 gene expression in human hepatocytes. Sequential role of glucocorticoid receptor and pregnane X receptor.

Although CYP3A induction by dexamethasone has been extensively documented, its mechanism is still unclear because both the role of the glucocorticoid receptor and the ability of dexamethasone to activate the human pregnane X receptor have been questioned. In an attempt to resolve this problem, we investigated the response of CYP3A4 to dexamethasone (10 nm-100 microm) in primary human hepatocytes and HepG2 cells, using a variety of methods: kinetic analysis of CYP3A4 and tyrosine aminotransferase expression, effects of RU486 and cycloheximide, ligand binding assay, cotransfection of HepG2 cells with CYP3A4 reporter gene constructs and vectors expressing the glucocorticoid receptor, pregnane X receptor or constitutively activated receptor. In contrast to rifampicin (monophasic induction), dexamethasone produces a biphasic induction of CYP3A4 mRNA consisting of a low-dexamethasone component (nmol concentrations) of low amplitude (factor of 3-4) followed by a high-dexamethasone component (supramicromolar concentrations) of high amplitude (factor of 15-30). We show that the low-dexamethasone component results from the glucocorticoid receptor-mediated expression of pregnane X receptor and/or constitutively activated receptor which, in turn, are able to transactivate CYP3A4 in a xenobiotic-independent manner. At supramicromolar concentrations (>10 microm), dexamethasone binds to and activates pregnane X receptor thus producing the high-dexamethasone component of CYP3A4 induction. We conclude that, in contrast to the other xenobiotic inducers of CYP3A4, glucocorticoids play a dual role in CYP3A4 expression, first by controlling the expression of PXR and CAR under physiological conditions (submicromolar concentrations) through the classical glucocorticoid receptor pathway, and second by activating the pregnane X receptor under bolus or stress conditions (supramicromolar concentrations).

Animals↗

Patient-controlled epidural analgesia after abdominal surgery: ropivacaine versus bupivacaine.

UNLABELLED: In this randomized, double-blinded study we sought to assess the analgesic efficacy of ropivacaine and bupivacaine in combination with sufentanil and the efficacy of ropivacaine alone after major abdominal surgery. Sixty patients undergoing major abdominal surgery received standardized general anesthesia combined with epidural thoracic analgesia. They were allocated to one of three groups: the BS group received postoperative patient-controlled epidural analgesia with 0.125% bupivacaine plus 0.5 microg/mL sufentanil; the RS group received 0.125% ropivacaine plus 0.5 microg/mL sufentanil; and the R group received 0.2% ropivacaine, with the patient-controlled epidural analgesia device set at bolus 2-3 mL and background infusion 3-5 mL/h. Visual analog scale scores were significantly lower during coughing in the BS group compared with the RS and R groups and in the RS group compared with the R group. The BS group required significantly less local anesthetic (milligrams per day) during the first three postoperative days compared with the RS and R groups, and the RS group, significantly less than the R group. No major side effects were noted in any group. We conclude that, after major abdominal surgery, thoracic epidural analgesia was more effective with bupivacaine than with ropivacaine when these two local anesthetics are used in a mixture with sufentanil. Ropivacaine alone was less effective than ropivacaine in combination with sufentanil. IMPLICATIONS: After major abdominal surgery, thoracic epidural analgesia was more effective with 0.125% bupivacaine than with 0.125% ropivacaine when these two local anesthetics were used in a mixture with 0.5 microg/mL sufentanil. Ropivacaine 0.2% alone was less effective than 0.125% ropivacaine combined with sufentanil.

Abdomen↗

Induction of CYP2C genes in human hepatocytes in primary culture.

The expression and inducibility of four CYP2C genes, including CYP2C8, -2C9, -2C18, and -2C19, was investigated in primary cultures of human hepatocytes. By the use of RNase protection assay and specific antibodies, each CYP2C mRNA and protein were quantified unequivocally. The four CYP2C mRNAs were expressed in human livers and cultured primary hepatocytes, but only the CYP2C18 protein was not detected. Compounds known to activate the pregnane X receptor (PXR) such as rifampicin, or the constitutively activated receptor (CAR) such as phenobarbital, induced CYP2C8, CYP2C9, and to a lesser extent CYP2C19 mRNAs and proteins. CYP2C18 mRNA was expressed but not inducible. The concentration dependence of CYP2C8 and CYP2C9 mRNAs in response to rifampicin and phenobarbital paralleled that of CYP3A4 and CYP2B6, the maximum accumulation being reached with 10 microM rifampicin and 100 microM phenobarbital. In contrast, dexamethasone produced maximum induction of CYP2C8 and CYP2C9 mRNAs at 0.1 microM while in these conditions neither CYP3A4 nor CYP2B6 was significantly induced. Moreover, the concentration dependence of CYP2C8 and CYP2C9 mRNAs in response to dexamethasone paralleled that of tyrosine aminotransferase. Furthermore, dexamethasone, which has been recently shown to up-regulate PXR and CAR expression through the glucocorticoid receptor, potentiated CYP2C8 and CYP2C9 mRNA induction in response to rifampicin and phenobarbital. Collectively, these results suggest the possible implication of at least three receptors in the regulation of CYP2C8 and CYP2C9 expression, i.e., glucocorticoid receptor, PXR, and/or CAR.

Adult↗

Calcium channel modulators of the dihydropyridine family are human pregnane X receptor activators and inducers of CYP3A, CYP2B, and CYP2C in human hepatocytes.

The expression of three cytochromes P450 (CYP3A4, CYP2C9, and CYP2B6) was investigated in primary human hepatocyte cultures following treatment with four calcium channel modulators (CCM) of the dihydropyridine family, three antagonists (nifedipine, nicardipine, and isradipine), and one agonist (BK8644). Induction of CYP3A4 was studied by Northern blot, Western blot, and enzymatic activity. Induction began between 1 and 10 microM CCM and was dependent on the presence of dexamethasone (100 nM) in the medium. CYP3A4 mRNA accumulation started only after 16 h of treatment because pregnane X receptor (hPXR) synthesis was needed. Cotransfection experiments showed that the proximal and the distal PXR response elements of the CYP3A4 promoter and hPXR (HepG2 cells) or dexamethasone-induced hPXR (primary hepatocytes) were necessary to obtain full induction. Furthermore, glutathione S-transferase pull-down assays demonstrated that the CCM tested can act as hPXR ligands. In addition, cotransfection experiments in CV1 cells showed that these compounds failed to reverse CAR (constitutively activated receptor) inactivation by androstenol. Finally, 10 microM CCM induced both CYP2C9 and CYP2B6, strengthening the evidence that hPXR is involved in the regulation of these genes. All together, these results widen the field of hPXR activators to a new class of ligand, namely the CCM of the dihydropyridine family.

Aryl Hydrocarbon Hydroxylases↗

Interleukin-6 negatively regulates the expression of pregnane X receptor and constitutively activated receptor in primary human hepatocytes.

The marked impairment of hepatic drug metabolism during inflammation and infections has been known for many years and shown to result from down-regulation of cytochrome P450s (CYP) by cytokines. However, the mechanism of this repression is unknown. Using primary cultures of human hepatocytes, we show here that interleukin-6 (IL-6) rapidly and markedly decreases the expression of PXR (pregnane X receptor) and CAR (constitutively activated receptor) mRNAs, but does not affect the levels of dioxin receptor and glucocorticoid receptor mRNA. In parallel, IL-6 decreases both rifampicin- and phenobarbital-mediated induction of CYP2B6, CYP2C8, CYP2C9, and CYP3A4. As the transcriptional activity of PXR and CAR is not affected by IL-6 in cell-based reporter assays, our data suggest that the loss of CYP2 and CYP3 inducibility results from the negative regulation of PXR and CAR gene expression by this cytokine.

Cells, Cultured↗

Natural killer cell and alphabeta and gammadelta lymphocyte traffic into the liver graft immediately after liver transplantation.

BACKGROUND: The persistence and migration of donor leukocytes has been well established, but cellular kinetics immediately after revascularization and the potential relevance of these different lymphocyte populations to spontaneous tolerance remain unclear. During the early hours of revascularization, there is a transitory "congestion" of the liver graft, which is evidence of an early phase that we have termed "first cellular contact." METHODS: We have carried out by flow cytometry a prospective comparative study of the peak kinetics of lymphocyte subpopulations contained in: (a) peripheral blood and liver grafts at the time of multi-organ extraction from 14 brain-dead donors, (b) recipient peripheral blood before transplantation, and (c) recipient peripheral blood and liver grafts after (t=2 h) declamping and vascularization of the liver graft. RESULTS: Before transplantation, the liver grafts contained large numbers of natural killer (NK) and NK-like cells with early lymphocyte activation. Immediately after revascularization, there was an influx of recipient NK and NK-like cells into the liver. CONCLUSIONS: NK and CD3+CD56+ (NK-like) cells flooding into the liver graft immediately after revascularization could rapidly destroy allogeneic cells. However, spontaneous tolerance and the persistence of donor lymphocytes after orthotopic liver transplant could be a result of donor TCRalphabeta NK1.1 liver graft lymphocytes, which may be involved in the destruction of CD8+ T lymphocytes that would have received the apoptosis signal, and to NK and NK-like cell inhibition via inhibitory NK receptors. The decrease in gammadelta T lymphocytes in the two compartments suggests a mechanism of recirculation and capture in other lymphoid organs.

Adult↗

[Elective laparoscopic colectomy for sigmoid diverticulitis. Prospective study of 56 cases].

OBJECTIVE: The aim of this prospective study was to assess the feasibility and postoperative advantages of the laparoscopic-assisted elective colectomy for diverticular disease. PATIENTS AND METHODS: From january 1989 to december 1997, among the 114 patients electively operated on for diverticulitis, 56 patients were treated by laparoscopic approach. Evaluated parameters included: gender, age, weight, size, ASA score, operating time, duration of hospital stay, of analgesic treatment, and of postoperative ileus, morbidity and mortality rate. RESULTS: The study group consisted of 35 women and 21 men. Mean age was 59 years (34-81 years); 29 patients were ASA 1 and 27 ASA 2. Overall postoperative mortality rate was 0% and morbidity rate 16% (n = 9). There were no complications directly related to laparoscopic technique. The conversion rate was 14% (n = 8). Mean operating time was 300 min (200-600 min). Mean duration of postoperative ileus was 2.4 days. Mean duration of hospital stay was 9.4 days. CONCLUSION: This study demonstrates the feasibility of elective laparoscopic-assisted colonic resection for diverticular disease in more than 80% of cases with a postoperative morbidity and mortality rate comparable to those of conventional surgery.

Adult↗

Dexamethasone induces pregnane X receptor and retinoid X receptor-alpha expression in human hepatocytes: synergistic increase of CYP3A4 induction by pregnane X receptor activators.

In this report we show that submicromolar concentrations of dexamethasone enhance pregnane X receptor (PXR) activator-mediated CYP3A4 gene expression in cultured human hepatocytes. Because this result is only observed after 24 h of cotreatment and is inhibited by pretreatment with cycloheximide, we further investigated which factor(s), induced by dexamethasone, might be responsible for this effect. We report that dexamethasone increases both retinoid X receptor-alpha (RXRalpha) and PXR mRNA expression in cultured human hepatocytes, whereas PXR activators such as rifampicin and clotrimazole do not. Accumulation of RXRalpha and PXR mRNA reaches a maximum at a concentration of 100 nM dexamethasone after treatment for 6 to 12 h and is greatly diminished by RU486. A similar pattern of expression is observed with tyrosine aminotransferase mRNA. Moreover, the effect of dexamethasone on PXR mRNA accumulation seems to be through direct action on the glucocorticoid receptor (GR) because the addition of cycloheximide has no effect, and dexamethasone does not affect the degradation of PXR mRNA. Furthermore, dexamethasone induces the accumulation of a RXRalpha-immunoreactive protein and increases the nuclear level of RXRalpha:PXR heterodimer as shown by gel shift assays with a CYP3A4 ER6 PXRE probe. This accumulation of latent PXR and RXRalpha in the nucleus of hepatocytes explains the synergistic effect observed with dexamethasone and PXR activators together on CYP3A4 induction. These results reveal the existence of functional cross talk between the GR and PXR, and may explain some controversial aspects of the role of the GR in CYP3A4 induction.

Adult↗

Dexamethasone enhances constitutive androstane receptor expression in human hepatocytes: consequences on cytochrome P450 gene regulation.

The barbiturate phenobarbital induces the transcription of cytochromes P450 (CYPs) 2B through the constitutive androstane receptor (CAR; NR1I3). CAR is a member of the nuclear receptor family (NR1) mostly expressed in the liver, which heterodimerizes with retinoid X receptor (RXR) and was shown to transactivate both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element. Because previous studies in rodent hepatocyte cultures have shown that the phenobarbital-mediated induction of CYP2B genes is potentiated by glucocorticoids, we examined the role of activated glucocorticoid receptor in this process. We show that submicromolar concentrations of dexamethasone enhance phenobarbital-mediated induction of CYP3A4, CYP2B6, and CYP2C8 mRNA in cultured human hepatocytes. In parallel, we observed that glucocorticoid agonists, such as dexamethasone, prednisolone, or hydrocortisone, specifically increase human car (hCAR) mRNA expression. Accumulation of hCAR mRNA parallels that of tyrosine aminotransferase: both mRNAs reach a maximum at a concentration of 100 nM dexamethasone and are down-regulated by concomitant treatment with the glucocorticoid antagonist RU486. Moreover, the effect of dexamethasone on hCAR mRNA accumulation appears to be of transcriptional origin because the addition of protein synthesis inhibitor cycloheximide has no effect, and dexamethasone does not affect the degradation of hCAR mRNA. Furthermore, dexamethasone increases both basal and phenobarbital-mediated nuclear translocation of CAR immunoreactive protein in human hepatocytes. The up-regulation of CAR mRNA and protein in response to dexamethasone explains the synergistic effect of this glucocorticoid on phenobarbital-mediated induction of CYP2B genes and the controversial role of the glucocorticoid receptor on phenobarbital-mediated CYP gene inductions.

Active Transport, Cell Nucleus↗

Human hepatocytes in primary culture predict lack of cytochrome P-450 3A4 induction by eletriptan in vivo.

Eletriptan (Relpax) is a novel 5-hydroxytryptamine (serotonin)(1D/1B) agonist currently in development for the acute treatment of migraine. The aim of this work was to evaluate the relative induction potency of eletriptan in vitro compared with well characterized cytochrome P-450 (CYP) inducers with primary cultures of human hepatocytes and to relate this to the situation in vivo. Eletriptan was a weak inducer of CYP3A4 protein and cyclosporin A oxidation in four of the six cultures used, whereas rifampicin was a potent inducer in all cultures. Induction was concentration dependent and not detectable at eletriptan concentrations of 5 microM and lower. The amplitude of the increase in CYP3A4 protein and activity by 25 microM eletriptan was significantly lower, with a mean of 19 (P =.0015) and 26% (P =.0002), respectively, of that observed in response to 25 microM rifampicin. CYP2A6, a protein with minor pharmacological implication, also was induced by eletriptan and rifampicin in two cultures but was not detected in the others. The levels of other CYP proteins, including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, were not affected by eletriptan. Because the maximum blood concentration of eletriptan in humans after a therapeutic dose (maximum 80 mg) is 0.5 microM, the in vitro model would predict no clinically significant induction of CYP3A4 protein in vivo. This has been confirmed subsequently in a clinical study, with 6beta-hydroxycortisol/cortisol ratios as marker of CYP3A4 activity. Eletriptan is therefore not an inducer of CYP3A4 at clinical doses.

Adult↗

[Treatment of common bile duct stones with laparoscopy. Retrospective multicenter study with 612 patients].

OBJECTIVE: To analyse retrospectively the results of one-stage laparoscopic treatment for common bile duct stones in 19 surgical centers in France. PATIENTS: From January 1991 to July 1996, 612 patients with choledocholithiasis underwent laparoscopic treatment. RESULTS: Overall duct clearance was obtained in 489 of the 612 patients (80%): through the cystic duct in 222 of 380 patients (58.4%), by secondary choledochotomy (after unsuccessful transcystic duct extraction) in 77 of 96 (80%), and in 190 of 232 (82 %) by primary choledochotomy. The overall duct clearance rate increased from 65% in 1991 to 84% in 1996. The use of the choledochotomy approach increased from 43% in 1991 to 69% in 1996 (P<0.01), due to a substantial increase in primary choledochotomy. In contrast, the use of the transcystic approach decreased from 57% to 31% (P<0.01). The mean time for surgery was shorter for cystic duct exploration than for primary choledochotomy (101+/-51 vs. 155+/-62 min, P<0.0001). The mean hospital stay decreased from 7.7+/-3.6 days in 1991 to 4.1+/-2 days in 1996 (P<0.001). The main biliary complications were related to biliary drainage (2,8%) and retained stones (3.1%). CONCLUSION: This study confirms that laparoscopy is a good alternative with a low complication rate, a short hospital stay, and is an effective and safe option for the management of common bile duct stones.

Adolescent↗