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C Smadja

Publications and source records attributed to C Smadja.

At least 37 records · Page 2Linked to original sources

Behavioural and biochemical evidence for signs of abstinence in mice chronically treated with delta-9-tetrahydrocannabinol.

Tolerance and dependence induced by chronic delta-9-tetrahydrocannabinol (THC) administration were investigated in mice. The effects on body weight, analgesia and hypothermia were measured during 6 days of treatment (10 or 20 mg kg(-1) THC twice daily). A rapid tolerance to the acute effects was observed from the second THC administration. The selective CB-1 receptor antagonist SR 141716A (10 mg kg(-1)) was administered at the end of the treatment, and somatic and vegetative manifestations of abstinence were evaluated. SR 141716A administration precipitated several somatic signs that included wet dog shakes, frontpaw tremor, ataxia, hunched posture, tremor, ptosis, piloerection, decreased locomotor activity and mastication, which can be interpreted as being part of a withdrawal syndrome. Brains were removed immediately after the behavioural measures and assayed for adenylyl cyclase activity. An increase in basal, forskolin and calcium/calmodulin stimulated adenylyl cyclase activities was specifically observed in the cerebellum of these mice. The motivational effects of THC administration and withdrawal were evaluated by using the place conditioning paradigm. No conditioned change in preference to withdrawal associated environment was observed. In contrast, a conditioned place aversion was produced by the repeated pairing of THC (20 mg kg(-1)), without observing place preference at any of the doses used. This study constitutes a clear behavioural and biochemical model of physical THC withdrawal with no motivational aversive consequences. This model permits an easy quantification of THC abstinence in mice and can be useful for the elucidation of the molecular mechanisms involved in cannabinoid dependence.

Analysis of Variance↗

[Results of laparoscopic treatment of abdominal emergencies].

The purpose of this retrospective study was to evaluate the results of the laparoscopic surgical treatment of abdominal emergencies. From May 1991 to September 1995, 200 patients operated by laparoscopy for an acute abdomen were included in this study. The decision to treat the patient by laparoscopy was taken by the surgeon on duty. There were 101 males and 99 females with a mean age of 41 +/- 20 years (range 11-90 years). The main indications for operation were: acute appendicitis (109 patients), acute cholecystitis (52 patients), small bowel obstruction (14 patients) and perforated duodenal ulcer (14 patients). There was no hospital mortality. One per cent of patients experienced an operative complication which was treated by laparotomy. Conversion to laparotomy was needed in 13% of cases. The morbidity rate was 9% and reoperation by laparotomy for acute generalized peritonitis secondary to small bowel perforation was necessary in two cases. Mean postoperative hospital stay ranged from 4 to 7 days. The authors conclude that surgical laparoscopic treatment of the common abdominal emergencies is safe. The conversion rate is low as is the complication rate. These conclusions should be confirmed by a prospective study.

Abdomen, Acute↗

[Treatment of hepatic recurrence after resection of hepatocellular carcinomas].

Between October 1990 and December 1995, 86 patients underwent hepatic resection for hepatocellular carcinoma (HCC). All resections were carried out with the aim of achieving complete cure. Fifty one (60%) of these patients subsequently developed recurrent HCC. Only twenty patients could be treated in our hospital. There were 18 men and 2 women, with a mean age of 61 years at the time of recurrence. Six patients had a normal liver. Fourteen patients had associated liver cirrhosis. using Pugh's classification, 7 patients were Pugh A, 6 Pugh B and 1 Pugh C. The initial hepatic resection had consisted of major hepatectomy in 9 cases and segmentectomy in the remaining 11 patients. The mean time to recurrence was 17 months. There were 3 recurrences on the resection margin and 17 recurrences away from the hepatic stump. The therapeutic choice after hepatic recurrence was based on the number of tumors, hepatic function and the size of the liver remnant. Six patients were treated by tamoxifen due to poor hepatic function; median survival after recurrence was 6 months. Four patients with a single recurrent tumor on an atrophied liver remnant were treated by percutaneous ethanol injection with a median survival after recurrence of 15 months. Five patients with multiple diffuse lesions and good hepatic function were treated by transarterial chemoembolisation with a median survival after recurrence of 30 months. Five patients with a solitary tumor and good hepatic function underwent a second hepatic resection with a median survival after recurrence of 35 months. The overall median survival after diagnosis of recurrence was 20 months. These results suggest that an active treatment should be carried out in cases of recurrence of HCC. A second resection, if technically possible, offers the best chance of survival.

Adult↗

[Liver resection in patients with polycystic liver disease].

OBJECTIVES: Polycystic liver disease is sometimes responsible for chronic symptoms linked to hepatomegaly which can result in acute complications such hemorrhage or infection of cysts. The aim of this retrospective study was to evaluate the results of partial hepatic resection in patients with symptomatic or complicated polycystic liver disease. METHODS: Twelve patients (11 women and one man, mean age 49) with diffuse polycystic liver disease were treated by partial liver resection (left lateral lobectomy in 7, left hepatectomy in 4, and extended right hepatectomy in 1). Four patients had terminal renal failures and three had chronic haemodialysis. Median follow-up was 34 months. RESULTS: Ascites occurred postoperatively in 10 patients (83%) and was long-lasting (> 2 weeks) in 5; all patients with end-stage renal failure had long-lasting ascites. One of them died on the 40th postoperative day of ascites infection. Another patient with end-stage renal failure died two years postoperatively from chronic disabling ascites and malnutrition while awaiting kidney transplantation. The 10 other patients were markedly improved after partial liver resection, including a marked decrease in hepatomegaly, and the disappearance of chronic symptoms and cystic complications. This beneficial effect was incomplete in the two surviving patients with end-stage renal failure until kidney transplantation was performed. CONCLUSION: These results suggest that partial liver resection is a highly effective treatment in patients with symptomatic polycystic liver disease, preferably before the onset of end-stage renal failure.

Adult↗

The attenuation of morphine-conditioned place preference following chronic mild stress is reversed by a CCKB receptor antagonist.

Chronic exposure to mild unpredictable stress has been found to abolish the acquisition of preference for a distinctive environment paired with morphine, whereas morphine induced conditioning place preference in non-stressed rats. Chronic treatment for 21 days with the tricyclic antidepressant imipramine reversed the motivational effects produced by chronic mild stress, and animals showed a place preference for the morphine-paired compartment. When the CCKB receptor antagonist PD-134,308 was co-administered with morphine in stressed animals during the conditioning period, the preference for the morphine-paired compartment was also re-established. The CCKB receptor antagonist given alone did not induce rewarding effects in this paradigm. These findings indicate that the administration of a CCKB receptor antagonist reversed the effects of chronic mild stress on opiate rewarding properties.

Animals↗

CCK-B receptors in the limbic system modulate the antidepressant-like effects induced by endogenous enkephalins.

Systemic administration of RB 101, a complete inhibitor of enkephalin catabolism, has been reported to induce antidepressant-like responses in mice which were potentiated by an ineffective dose of a CCK-B antagonist. The aim of this study was to investigate the neuroanatomical substrate involved in the facilitatory effects induced by CCK-B antagonists on RB 101 behavioural responses. Thus, the CCK-B antagonist PD-134,308 was locally administered into different brain structures (anterior nucleus accumbens, central amygdala and caudate nucleus) and its effects on the antidepressant-like response induced by systemic administration of RB 101 were evaluated in the conditioned suppression of motility (CSM) test in rats. RB 101 administered alone by the IV route decreased the CSM in rats, as previously obtained in mice. Systemic administration of a non effective dose of PD-134,308 facilitated the antidepressant-like effect induced by RB 101. Local injection of PD-134,308 into the anterior nucleus accumbens, the central amygdala or the caudate nucleus did not modify CSM. The antidepressant-like effects elicited by RB 101 in this test were potentiated by PD-134,308 after microinjection in the anterior nucleus accumbens and central amygdala, but not in the caudate nucleus. All these effects were observed only in shocked animals. The present results suggest that the mesolimbic system, particularly the anterior nucleus accumbens and the central amygdala, seems to play an important role in the interaction occurring between the endogenous CCK and opioid system in the control of behavioural responses.

Amygdala↗

Preoperative predictors of blood transfusion in liver resection for tumor.

BACKGROUND: Hepatic resection remains a hemorrhagic procedure. The purpose of this study was to investigate the preoperative predictive factors of intraoperative blood transfusion. METHODS: One hundred consecutive patients who underwent hepatic resection for tumor were included in this retrospective study. Resection was performed for primary malignancies (n = 52), metastases (n = 18), and benign tumors (n = 30). Liver resection was performed under intermittent clamping of the portal triad. Seventeen variables were analyzed. RESULTS: The operative blood loss was 1,872 mL (mean 1,104; range 650 to 4500) for the 22 transfused patients. The mean blood transfusion was 5.5 units (mean 3.2; range 2 to 12) of packed red cells. Multivariate analysis demonstrated that the size of liver resection (P <0.001) and the prothrombin rate (P <0.001) were independently correlated with blood transfusion. CONCLUSIONS: Patients undergoing extended resection or with abnormal coagulation could be considered for autologous blood transfusion.

Adolescent↗

Social interaction increases the extracellular levels of [Met]enkephalin in the nucleus accumbens of control but not of chronic mild stressed rats.

Chronic application of various mild stress has been shown to decrease the responsiveness to reward in rats. This effect, which was suggested to mimic anhedonia, one of the main symptoms observed in depressive patients, can be measured by various tests. Thus chronic mild stress was shown to reduce the consumption of a palatable sucrose solution, and to decrease the acquisition of preferences for a distinct environment paired with a variety of reinforcing substances. These negative responses could be prevented by chronic treatment with tricyclic or atypical antidepressants. The behavioural changes, induced by exposure to chronic mild stress, were shown to be associated with a number of changes in dopaminergic neurotransmission in the mesolimbic system, especially in the nucleus accumbens. The nucleus accumbens contains a large number of enkephalinergic cell bodies giving rise to local collaterals and axons projecting to the globus pallidus-ventral pallidum region (for review see Ref. 9). Furthermore, there is evidence that this structure is instrumental in mediating the reward effects of exogenous and endogenous opioids (for reviews see Refs 5,7,17). This study was carried out to analyse the possible contribution of the enkephalinergic system in the anhedonic-like state induced by chronic mild stress. Microdialysis was used to study the extracellular levels of [Met]enkephalin-like material in the rostral part of the nucleus accumbens of freely moving rats exposed or not to chronically mild stress. In both groups, the basal levels of [Met]enkephalin-like material were found to be similar. Exposure of the two groups to a congener, increased the extracellular levels of [Met]enkephalin in the controls but not in chronic mild stressed rats. This suggests that the reactivity of the endogenous opioid system could be reduced in stress induced model of anhedonia.

Animals↗

Aprotinin reduces blood loss in patients undergoing elective liver resection.

Ninety-seven patients undergoing elective liver resection through a subcostal incision were assigned to large-dose aprotinin treatment or placebo in a double-blind, prospective, randomized fashion. Randomization was stratified by diagnosis: (a) cancer in cirrhosis, (b) cancer in healthy liver, and (c) benign tumor in healthy liver. Intraoperative blood loss, percentage of transfused patients, and total transfusion requirement per group were significantly lower in the aprotinin group than in the placebo group (1217 +/- 966 mL vs 1653 +/- 1221 mL, P = 0.048; 17% vs 39%, P = 0.02; 30 vs 77 red blood cell packs, P = 0.015, respectively). Assessment of hematological markers (a) prior to surgery, (b) at the end of surgery, and (c) 24 h after surgery showed an identical intraoperative increase in thrombin-antithrombin III complexes in patients of both groups (P = 0.86), which indicates a similar activation of coagulation. Intraoperative hyperfibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group (P = 0.0002 and P = 0.004 for D-dimers and fibrinogen, respectively). No adverse drug effects were detected (circulatory disturbances, deep venous thrombosis, increase in serum creatinine). These results suggest that aprotinin significantly reduces blood loss and transfusion requirement in patients undergoing elective liver resection through a subcostal incision.

Adult↗

Comparison of a modified Sugiura procedure with portal systemic shunt for prevention of recurrent variceal bleeding in cirrhosis.

BACKGROUND: There is no agreement on the management of patients with cirrhosis and recurrent variceal bleeding after failure of medical or endoscopic treatments or both. Portal systemic shunts are highly effective in preventing rebleeding but are associated with a high incidence of chronic encephalopathy. This study compared the results of a slightly modified Sugiura procedure (esophageal transection plus esophagogastric devascularization plus splenectomy) with those of nonselective portal systemic shunts in patients with previous variceal bleeding. METHODS: Fifty-four patients were included in this randomized controlled study between January 1984 and April 1989. The major end point was chronic encephalopathy. Secondary end points were recurrent variceal bleeding, survival, ascites, and hepatocellular carcinoma. RESULTS: Twenty-seven patients were assigned to each group. The rate of chronic encephalopathy was significantly (p = 0.002) lower after modified Sugiura procedure than after portal systemic shunt. Recurrent variceal bleeding was more frequent after modified Sugiura procedure than after portal systemic shunt, but the difference is not significant. One-, two-, and three-year survival rates were 93%, 81%, and 67%, respectively, in the modified Sugiura group and 78%, 66%, and 39%, respectively, in the portal systemic shunt group (p = 0.044). CONCLUSIONS: These results suggest that the modified Sugiura procedure is better overall than the nonselective portal systemic shunt in the management of patients with cirrhosis and recurrent variceal bleeding. Although the rebleeding rate is higher after the modified Sugiura procedure, this does not seem to affect mortality in these patients.

Carcinoma, Hepatocellular↗

Long-term hemodynamic effects of portocaval shunt and Sugiura procedure in patients with cirrhosis.

Systemic and splanchnic hemodynamics were studied before and six months after a portal systemic shunt (n = 6) or a Sugiura procedure (n = 9) in 15 patients with cirrhosis and a past history of variceal bleeding. Hepatic blood flow was estimated by hepatic extraction and clearance of continuous indocyanine green infusion. Azygos blood flow was measured with a continuous thermodilution catheter. After portocaval shunt, the cardiac index increased significantly from 4.0 +/- .4 to 5.4 +/- 0.8 l/min m2 (p < 0.05), the hepatic venous pressure gradient and hepatic blood flow were significantly decreased from 21 +/- 3 to 13 +/- 5 mm Hg (p < 0.05) and from 1.20 +/- 0.35 to 0.37 +/- 0.16 l/min (p < 0.05) respectively. The decrease in azygos blood flow was not significant (0.51 +/- 0.31 vs 0.25 +/- 0.33 l/min; p = 0.1). After Sugiura procedure, there was no significant change in cardiac index, hepatic venous pressure gradient, hepatic blood flow or azygos blood flow. This is the first study to show the long-term maintenance of splanchnic and systemic hemodynamics in patients with cirrhosis after Sugiura procedure. The absence of long-term hemodynamic alterations could explain the absence of encephalopathy after this procedure.

Azygos Vein↗

[Laparoscopic colectomy: technique and results].

Laparoscopic preparation before colectomy consists of freeing the colon laparoscopically followed by a small elective laparotomy for resection and anastomosis. From January 1993 to October 1994, we performed 86 consecutive planned colectomies including 16 (19%) which had laparoscopic preparation. In 3 of these cases (19%) the procedure was converted to laparotomy due to difficult dissection. The 13 patients with complete laparoscopically prepared colectomy were retained for this study. There were 9 men and 4 women, mean age 54 +/- 14 years (range 34-79). Indications for surgery were benign tumor (n = 4), metastatic cancer (n = 3), diverticulosis (n = 3), volvulus of the pelvic colon (n = 2), and endometriosis involving the sigmoid (n = 1). Operative procedures were: short segmentary colectomy (n = 6), sigmoidectomy (n = 5), right colectomy (n = 2). Surgery duration was 280 +/- 75 minutes (range 150-390). The post-operative period was uneventful in all patients. Bowel activity resumed on the second day after surgery in most patients. Mean hospitalization time was 7.4 +/- 1.4 days (range 5-10 days). Laparoscopically prepared colectomy is a reliable simple method providing good patient comfort post-operatively. This technique should find its place in surgery of the colon.

Adult↗

Opposite role of CCKA and CCKB receptors in the modulation of endogenous enkephalin antidepressant-like effects.

Systemic administration of RB 101, a complete inhibitor of the enkephalin degrading enzymes, has been reported to induce naltrindole-reversed antidepressant-like effects in the conditioned suppression of motility (CSM) test in mice. The selective CCKB antagonist L-365,260 also elicits the same naltrindole-blocked responses on CSM. The aim of this study was therefore to investigate the possible modulation of RB 101 induced behavioral responses by activation or blockade of CCK receptors. Thus, the effects induced by RB 101 administered alone or associated with an ineffective dose of a selective CCKB agonist (BC 264), a CCKB antagonist (L-365,260) or a CCKA antagonist (L-364,718), were evaluated on the CSM in mice. RB 101 alone decreased the stress-induced loss of motility, as previously reported. The antidepressant-like effect of RB 101 was potentiated by L-365,260, and suppressed by BC 264 and to a lesser extent by L-364,718. The facilitatory effect induced by L-365,260 on RB 101 responses was blocked by the delta selective antagonist naltrindole. All these effects occurred only in shocked animals. The present results suggest that the activation of CCKA and CCKB receptors by endogenous CCK, could play an opposite role in the control of behavioral responses induced by endogenous enkephalins. Delta opioid receptors seem to be selectively involved in this interaction.

Analgesics↗

Phosphorus-containing peptides as mixed inhibitors of endopeptidase 3.4.24.15 and 3.4.24.16: effect on neurotensin degradation in vitro and in vivo.

1. We have examined several phosphorus-containing peptides as potential mixed inhibitors of two neurotensin-degrading zinc metallopeptidases, endopeptidase 3.4.24.15 and endopeptidase 3.4.24.16. 2. Among a series of 13 phosphonamide peptides, N-(2-(2-naphtyl)ethylphosphonyl-glycyl-prolyl-norleucine (phosphodiepryl 08) was found to inhibit potently the hydrolysis of neurotensin by purified endopeptidase 3.4.24.15 and 3.4.24.16 with an identical Ki value of 0.4 nM. 3. Phosphodiepryl 08 displayed a strong selectivity towards the two peptidases since it failed to inhibit several other zinc-containing peptidases such as endopeptidase 3.4.24.11, angiotensin-converting enzyme, aminopeptidase M, leucine aminopeptidase and carboxypeptidases A and B. 4. The protective effect of phosphodiepryl 08 on neurotensin degradation was examined in vitro and in vivo in central and peripheral bioassays. 5. Phosphodiepryl 08 virtually abolished neurotensin degradation by 4-day-old plated pure cultured neurones from mouse embryos and greatly potentiated neurotensin-induced antinociception in the mouse hot plate test. 6. In the periphery, phosphodiepryl 08 inhibited neurotensin degradation by membranes prepared from isolated longitudinal smooth muscle of guinea-pig ileum and greatly potentiated the neurotensin-induced contraction of the same longitudinal smooth muscle preparation. 7. Our study indicates that phosphodiepryl 08 behaves as a potent and selective mixed inhibitor of endopeptidase 3.4.24.15 and 3.4.24.16 and can be used as a powerful agent to prevent neurotensin degradation, in vitro and in vivo, in central and peripheral assays.

Animals↗

Primary lymphoplasmacytic lymphoma of the liver associated with a serum monoclonal peak of IgG kappa.

We report a case of primary lymphoma of the liver successfully treated by major liver resection. The tumor exhibited the immunohistological features of a B-cell low-grade lymphoma of the lymphoplasmacytic type. Tumoral plasmacytic cells showed cytoplasmic-positive staining for IgG and kappa light chains. In addition, we detected a serum monoclonal peak of IgG kappa, a finding that has not been reported previously. Clinical, pathological, and immunohistochemical data from the literature are reviewed.

Adult↗

[Giant hemangioma of the liver disclosed by fever and an inflammatory syndrome. Apropos of 3 cases].

Three cases of giant liver haemangioma were revealed by fever and biological inflammatory changes, which disappeared after resection of the haemangioma. These rare symptoms accompanying liver haemangioma may lead to misdiagnosis. Resection whenever possible results in the disappearance of symptoms. Anatomic necrotic changes inside the angioma seem to be the cause of these inflammatory patterns.

Aged↗