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Biomedical subjects

C Thibault

Publications and source records attributed to C Thibault.

At least 37 records · Page 2Linked to original sources
PubMed1997

Anorectal melanoma--an incurable disease?

PURPOSE: This study was designed to describe recurrence and survival rates after operative treatment for anorectal melanoma and to identify predictive factors for recurrence. METHODS: Records of 50 patients with anorectal melanoma from 1939 to 1993 were reviewed. RESULTS: Overall five-year survival and disease-free survival were 22 and 16 percent, respectively. At the time of diagnosis, 26 percent of patients had metastatic disease, and all died within 12 (mean, 6.3) months. Five-year survival and recurrence rates were identical after either abdominoperineal resection (APR) or wide local excision, both with curative intent. Gender, size of tumor, presence of melanin, positive perirectal lymph nodes, or treatment were not predictive of recurrence. Anorectal melanoma was found incidentally after hemorrhoidectomy or polypectomy in five patients. Three other patients underwent an excisional biopsy of a lesion measuring less than 2 cm. Of these eight patients, five underwent APR and three underwent wide local excision with no microscopic residual tumor at pathology. All developed regional or systemic recurrence at a mean of 21 (range, 4-88) months, and all died of their disease at a mean of 29 (range, 5-98) months. CONCLUSION: Prognosis for anorectal melanoma is poor, irrespective of surgical treatment performed. No predictive factors for recurrence were identified in this series. Wide local excision with a negative margin of a least 1 cm is suggested as the treatment of choice. APR should be reserved for tumor not amenable to local excision or for palliative treatment of large obstructive lesion until effective adjuvant therapies are available.

Adult↗
PubMed1996

Tumor-infiltrating lymphocytes can be activated in situ by using in vivo activants plus F(ab')2 bispecific antibodies.

In vitro-activated T lymphocytes can be retargeted with anti-CD3 x anti-tumor bispecific antibodies (BsAb) to kill tumor cells in vitro and in vivo. The purpose of the present study was to examine the systemic and intra-tumor effects of in vivo T-cell activation with BsAb, staphylococcal enterotoxin B (SEB), and beta-glucan in combination with BsAb as a retargeting agent. CL-62 melanoma cells were injected subcutaneously into C3H/ HeN mice. Mice were subsequently treated with BsAb alone or with SEB or beta-glucan plus BsAb. Fresh splenocytes, lymph-node cells and tumor-infiltrating lymphocytes (TIL) were tested for their proliferative response using incorporation of 3H-thymidine, and for their ability to lyse CL-62 cells in the presence or absence of BsAb in 4-hr 51Chromium release assays. Toxicity of treatments was assessed in a D-galactosamine model. BsAb, alone or combined with beta-glucan, had essentially no effect on systemic T-cell cytotoxicity, and essentially no effect on systemic proliferation, unless exogenous IL-2 was provided. At the tumor site, BsAb alone, BsAb plus beta-glucan, and SEB plus BsAb all significantly increased BsAb-mediated TIL cytotoxicity. In contrast to the TIL-limited effects of BsAb and of BsAb plus beta-glucan, SEB plus BsAb markedly increased both systemic and intra-tumor T-lymphocyte activation. Toxicity correlated with measures of systemic activation, with limited effects from BsAb alone and from beta-glucan plus BsAb, and with marked lethality from SEB plus BsAb. Overall, these results suggest moderate intra-tumor activation of TIL, but no measurable systemic activation after in vivo treatment with BsAb or beta-glucan plus BsAb. SEB plus BsAb results in complete T-cell activation in both systemic and intra-tumor compartments, but at the expense of increased systemic toxicity. In conclusion, TIL can be activated in situ with different combinations of in vivo activants. In vivo-activated TIL can be retargeted with bispecific antibodies to lyse tumor cells, and may be an alternative to ex vivo T-cell activation and adoptive transfer therapy.

Animals↗
PubMed1995

Anti-CD3 x anti-tumor F(ab')2 bifunctional antibody activates and retargets tumor-infiltrating lymphocytes.

Bifunctional Abs (BFA) with specificity for the TCR/CD3 complex of T cells and tumor Ag can bridge T lymphocytes and tumor cells and, thereby, trigger activation events. The ability of intact and F(ab')2 anti-CD3 (500A2) x anti-p97 (96.5) BFA to induce activation of T lymphocytes in the presence of murine melanoma tumor cells (CL-62) expressing human melanoma-associated Ag (p97) was investigated in vitro and in vivo. Intact and F(ab')2 BFA induced significant proliferation of T lymphocytes in the presence of p97+ tumor cells. Incubation of splenocytes with intact or F(ab')2 BFA and p97+ tumor cells increased BFA-mediated cytotoxicity against relevant tumor cells. Intact BFA, in contrast to F(ab')2 BFA, induced some activation of T cells in vitro even in the absence of p97+ target cells. In nontumor-bearing mice, administration of F(ab')2 BFA, in contrast to intact BFA, did not increase cytotoxic activity of lymph node (LN) cells and splenocytes. However, when F(ab')2 BFA was administrated into CL-62-bearing mice, an increase of BFA-mediated cytotoxicity of tumor-infiltrating lymphocytes, but not splenocytes nor LN cells, was observed. Moreover, in D-galactosamine-sensitized mice, injection of intact BFA (1 microgram/mice) induced 100% lethality, whereas the same dose of F(ab')2 BFA was not toxic. These results demonstrate that F(ab')2 BFA can induce activation of cytotoxic lymphocytes only in the presence of relevant tumor cells, both in vitro and in vivo. That these activated lymphocytes can be redirected to lyse relevant tumor cells by the same BFA has important implications for the clinical application of BFA anti-tumor therapies.

Animals↗
PubMed1995

Laparoscopic splenectomy.

We describe the clinical course of 23 patients considered for laparoscopic splenectomy. One patient was excluded on the basis of preoperative angiography findings, and two (9%) were converted to open surgery. In the remaining 20 patients who successfully underwent laparoscopic splenectomy, no mortality was reported; four postoperative complications (20% morbidity) occurred. Mean operating time was 3 h 35 min (135-300 min). After a mean postoperative stay of 3.9 days (2-9 days), all patients except two were back to normal activities within 2 weeks of hospital discharge. Preoperative splenic artery embolization, begun with the third patient, helped to reduce operative blood loss and made the procedure easier to perform. Laparoscopic splenectomy has become our procedure of choice for elective removal of normal-sized (< 11 cm long) or moderately enlarged (11-20 cm long) spleens.

Adolescent↗
PubMed1995

Lobectomy in the treatment of the scimitar syndrome.

The scimitar syndrome is a congenital anomaly that consists mainly of total or partial anomalous venous drainage of the right lung to the inferior vena cava. We report the case of an 8-year-old girl diagnosed at birth as having a scimitar syndrome and who presented with recurrent right lower lung infections. She underwent resection of the lower half of her right lung without diversion of the anomalous venous drainage of the upper portion of the lung. She improved rapidly postoperatively and the shunt fraction diminished.

Child↗
PubMed1995

Bifunctional antibody retargeting in vivo-activated T lymphocytes: simplifying clinical application.

For antitumor x anti-CD3 bifunctional antibody (BFA) therapy to be clinically relevant in solid tumors, activated lymphocytes must be present within tumors. Toward that end, three uniquely different in vivo activation approaches were investigated in a p97 human antigen expressing syngeneic murine melanoma model. beta-Glucan (200 micrograms), staphylococcal enterotoxin B (SEB) (50 micrograms), and F(ab')2 BFA (10 micrograms) were tested for their ability to activate lymphocytes, neutralize pulmonary metastases, and treat established tumors. Systemic activation, measured as the ability of splenocytes to lyse tumor cells in vitro in the presence of BFA, was enhanced by the in vivo administration of SEB but not by beta-glucan or F(ab')2 BFA. Despite lacking a systemic effect, F(ab')2 BFA increased both direct and BFA-mediated cytotoxicity in fresh tumor infiltrating lymphocytes. beta-Glucan did not increase systemic or intratumor T cell activation. However, it significantly enhanced the ability of splenocytes to lyse NK-sensitive YAC-1 cells. When tested in a pulmonary metastases model, all three forms of immune modulation combined with F(ab')2 BFA significantly reduced the number of metastases. BFA were more effective at tumor neutralization when combined with SEB compared with adoptively transferred, in vitro-activated splenocytes. These studies demonstrate that immune modulators when combined with F(ab')2 BFA can provide effective antitumor therapy. Several clinical obstacles may be overcome by the application of these reagents.

Animals↗
PubMed1995

Partial laparoscopic splenectomy for trauma: technique and case report.

We describe the course of a patient who underwent partial laparoscopic splenectomy after a fall while skiing. Computed tomography revealed intact liver and kidneys with fragmentation of the upper third of the spleen and a left upper quadrant hematoma. Splenic artery angiogram showed devascularization of the superior pole, and selective cannulation of the superior polar artery demonstrated extravasation of contrast media. The superior polar artery was embolized with three coils to control bleeding. After laparoscopic exploration, the patient underwent partial laparoscopic splenectomy of the superior pole, which consisted of ligating the short gastric vessels and incising the splenic parenchyma 6 to 8 mm above the ischemic demarcation line produced by embolization of the superior polar artery, where a deep transverse laceration was located. The specimen was retrieved in a plastic bag. Intraoperative blood loss was less than 50 ml, and the patient left the hospital on the 3rd postoperative day after an uneventful recovery. Partial laparoscopic splenectomy can be performed safely, and its role needs to be delineated.

Adolescent↗
PubMed1995

Laparoscopic splenectomy for massive splenomegaly: operative technique and case report.

Although laparoscopic splenectomy is the preferred technique for the elective removal of normal-sized and moderately enlarged spleens, its value in the management of massive splenomegaly has not been defined. A 33-year-old woman with massive splenomegaly was managed by laparoscopic splenectomy. The splenic vessels were embolized preoperatively to reduce operative blood loss. Laparoscopic surgery involved dissection of the suspensory ligaments at the lower pole of the spleen followed by dissection and ligation of all splenic branches near the splenic parenchyma. The operative field was explored manually through a 10-cm long Pfannenstiel incision at the public hairline, and under videoscopic control the remaining structures were safely secured. The spleen was delivered into the pelvis, fragmented and removed in large pieces. The incisions were closed after proper irrigation and laparoscopic inspection of the operative field. Further clinical evaluation is required to determine if the procedure is more efficacious than the open technique for massive splenomegaly.

Adult↗
PubMed1995

Total laparoscopic proctocolectomy and laparoscopy-assisted proctocolectomy for inflammatory bowel disease: operative technique and preliminary report.

We present the operative technique of laparoscopic proctocolectomy along with the clinical course of the first four patients to undergo this procedure. The operation was conducted through five 12-mm ports. In total laparoscopic proctocolectomy, the dissection began with the sigmoid, left colon, and rectum. The gastrocolic ligament was opened at the level of the midtransverse colon and dissected along with the transverse mesocolon toward the splenic flexure. The attachments and vessels of the right side of the gastrocolic ligament and the right colon were taken last. This sequence was followed because gradual mobilization of the colon displaced all structures in the middle of the abdomen and obscured vision. The specimen was extracted through the anus. In laparoscopy-assisted proctocolectomy, it was necessary to incise only the white line of Toldt of the ascending and descending colon, mobilize the hepatic and splenic flexures, and ligate the vessels of the gastrocolic ligament. Then the vessels of the mesentery were ligated near the bowel wall through a 6.5-cm midline subumbilical incision from which the abdominal colon was also extracted. The rectum was then completely dissected and sectioned at 10-15 cm from the anus, everted, and resected at the dentate line. Mean operative time was 7 h, 18 min, and average blood loss was 493 ml. One patient had urinary retention. Return to liquid diet took a mean of 4 days. Average postoperative stay, which depended on full return of bladder function and teaching of stoma care, was 10 days.

Adult↗
PubMed1994

Effect of ionizing dose rate on the radioresistance of some food pathogenic bacteria.

Food pathogenic bacteria including Listeria monocytogenes (1A1 and ATCC 19111), Staphylococcus aureus (GD13 and ATCC 13565), Escherichia coli O157:H7 (ATCC 35150), Salmonella typhimurium, Yersinia enterocolitica, Vibrio parahaemolyticus, and Campylobacter jejuni were exposed to various rates of ionizing radiation (0.78, 2.6, and 22 kGy/h) emitted by three different 60Co irradiators. D10 values (D10 is the radiation dose required to eliminate 90% of a bacterial population (one logarithmic cycle reduction)) were calculated for the various strains and growth conditions tested. A covariance analysis of these results revealed that the dose rates studied had no significant influence on the radiosensitivity of these bacteria. At all dose rates, the bacteria were more radiosensitive when irradiated in a saline solution (0.85% NaCl) than in a chicken breast meat suspension. The growth phase of the bacterial population had a variable influence on its radioresistance. For L. monocytogenes 1A1, Staphylococcus aureus ATCC 13565, E. coli O157:H7, Y. enterocolitica, and V. parahaemolyticus, radioresistance was not significantly different in the exponential and stationary phases. Populations of L. monocytogenes ATCC 19111 and Staphylococcus aureus GD13 were significantly more resistant in the stationary phase (D10 = 0.23 and 0.12 kGy, respectively) than in the exponential phase (D10 = 0.17 and 0.09 kGy, respectively). Among the pathogenic bacteria investigated in this study, the most radioresistant was L. monocytogenes (D10 = 0.16-0.38 kGy, Gram-positive bacilli) and the most radiosensitive was V. parahaemolyticus (D10 = 0.03-0.04 kGy, halophilic Gram-negative bacilli).

Animals↗
PubMed1994

Involvement of the autonomic nervous system in the in vivo memory to glucose of pancreatic beta cell in rats.

The fact that the potentiating effect of prolonged hyperglycemia on the subsequent insulin secretion is observed in vivo but not in vitro suggests the involvement of extrapancreatic factors in the in vivo memory of pancreatic beta cells to glucose. We have investigated the possible role of the autonomic nervous system. Rats were made hyperglycemic by a 48-h infusion with glucose (HG rats). At the end of glucose infusion as well as 6 h postinfusion, both parasympathetic and sympathetic nerve activities were profoundly altered: parasympathetic and sympathetic activities, assessed by the firing rate either of the thoracic vagus nerve or the superior cervical ganglion, were dramatically increased and decreased, respectively. Moreover, 6 h after the end of glucose infusion, insulin secretion in response to a glucose load was dramatically increased in HG rats compared to controls. To determine whether these changes could be responsible for the increased sensitivity of the beta cell to glucose, insulin release in response to glucose was measured in HG and control rats, either under subdiaphragmatic vagotomy or after administration of the alpha 2A-adrenergic agonist oxymetazoline. Both treatments partially abolished the hyperresponsiveness of the beta cell to glucose in HG rats. Therefore chronic hyperglycemia brings about changes in the activity of the autonomic nervous system, which in turn are responsible, at least in part, for the generation of enhanced beta cell responsiveness to glucose in vivo.

Action Potentials↗
PubMed1994

[Peritoneal pseudomyxoma with pleural metastases. A case report].

The authors report a case of a 69 year old man with a peritoneal pseudo-myxoma probably secondary to a mucocele of the appendix and complicated by pleural metastases which were nodular, unilateral and asymptomatic. These were discovered on computerised tomography during examination for the recurrence of the peritoneal disease. A study of the histology of the pleural fragments obtained by thoracotomy showed the presence of lesions which were identical to those found in the peritoneal masses.

Aged↗
PubMed1994

The Angelchik antireflux prosthesis: long-term clinical and technical follow-up.

OBJECTIVE: To evaluate the long-term clinical outcome and compare the rupture rate of the two generations of the silicone Angelchik antireflux prosthesis. DESIGN: A cohort study. Follow-up ranged from 61 to 119 months. SETTING: A university teaching hospital. PATIENTS: Sixty-three patients: 33 patients received the first generation Angelchik device (group 1) and 30 patients received a second generation design (group 2). The two groups were comparable for sex ratio, mean age and duration of symptoms. INTERVENTIONS: Implantation of the Angelchik prosthesis. MAIN OUTCOME MEASURES: Comparison of the rupture rate and migration of the prosthesis as assessed by patient questionnaire, telephone interview and radiography of the abdomen. RESULTS: The prosthesis remained in a good position in 53% of group 1 patients and 93% of group 2 patients. The prosthesis was removed in 40% of group 1 patients, most often for rupture, and in only 7% of patients in group 2, to relieve dysphagia (p < 0.01). Grading on a Visick scale demonstrated a good result in 37% of group 1 patients and 69% of group 2 patients. Long-term dysphagia was the most prevalent adverse effect, seen in 45% of patients whose prosthesis was in a good position, and symptomatic reflux recurred in 8%. CONCLUSIONS: The second generation of the Angelchik prosthesis, resulted in a reduced rupture rate of the prosthesis. Nevertheless the high complication and the failure rates militate against continued implantation of the prosthesis.

Adult↗
PubMed1993

In vivo and in vitro increased pancreatic beta-cell sensitivity to glucose in normal rats submitted to a 48-h hyperglycaemic period.

We investigated the importance of the level and the duration of glucose stimulation on the in vivo and in vitro insulin response to glucose in normal rats previously submitted to hyperglycaemia. Rats were made hyperglycaemic by a 48-h glucose infusion. Glucose-induced insulin secretion was investigated in vivo by a 20-min hyperglycaemic clamp and in vitro by the isolated perfused pancreas technique, 3 h after the end of the in vivo glucose infusion. In glucose-infused rats, as compared to controls, in vivo incremental plasma insulin values above baseline integrated over the 20-min hyperglycaemic clamp (delta I) were five times higher during 8 mmol/l glucose clamp, only two times higher in 11 mmol/l glucose clamp and no different in 16.5 mmol/l. Compared to the controls, in vitro incremental plasma insulin concentration above baseline integrated over a 20-min period (delta I) in glucose-infused rats was 16 times higher in response to 2.8 mmol/l glucose, two times higher in response to 5.5 mmol/l, similar in response to 8.3 mmol/l and significantly lower in response to 16.5 mmol/l. In conclusion, our data suggest that a 48-h hyperglycaemic period results in an increased response of the pancreatic beta cell to low glucose. The response is immediately maximal and can not be increased with higher glucose concentrations. This situation could explain the apparent minimal effect of high concentrations on in vitro insulin secretion in previously hyperglycaemic rats and may provide insights into the sequence of events leading to the impairment of beta-cell function in Type 2 (non-insulin-dependent) diabetes mellitus.

Analysis of Variance↗
PubMed1993

DOCA-salt hypertensive rat hearts exhibit altered expression of G-proteins.

We have recently demonstrated an alteration in the levels of G-proteins and their correlation with adenylyl cyclase in spontaneously hypertensive rats (SHR). In the present studies we examined if the other models of hypertensive rats, such as DOCA-salt hypertensive rats (HR), also exhibit the similar alterations in G-protein and in adenylyl cyclase activity. We have determined the adenylyl cyclase activity stimulated and inhibited by hormones, as well as the levels of G-proteins using specific antibodies and cDNA probes in the hearts from DOCA-salt HR and their sham-operated controls after 2 and 4 weeks of treatment. Adenylyl cyclase activity stimulated by GTP gamma S, isoproterenol, and glucagon was significantly decreased in heart sarcolemma from DOCA-salt HR as compared to their controls after 2 and 4 weeks of treatment. In addition, the inhibitory hormones inhibited the enzyme activity to a greater extent in hypertensive rats than controls. Furthermore, the levels of Gi alpha-2 and Gi alpha-2 mRNA, as determined by immunoblotting and Northern blotting techniques, respectively, were higher in hearts from DOCA-salt HR. However, the levels of G8 alpha 45 were decreased in these rats. These results indicate that, similar to SHR, the hearts from DOCA-salt HR exhibit the increased expression of Gi, however unlike SHR, the expression of G8 was decreased. It is suggested that the altered expression of G-proteins may partly be responsible for the decreased responsiveness of adenylyl cyclase to hormone stimulation and increased responsiveness to hormone inhibition in DOCA-salt hypertension.

Adenylyl Cyclases↗