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D Elias

Publications and source records attributed to D Elias.

At least 91 records · Page 5Linked to original sources
PubMed1999

The pathogenicity of islet-infiltrating lymphocytes in the non-obese diabetic (NOD) mouse.

The aim of the present study was to investigate the pathogenic properties of islet-infiltrating lymphocytes related to the severity of the autoimmune destruction of islet beta-cells in the NOD mouse. We analysed the development of insulin-dependent diabetes mellitus (IDDM) produced by adoptive transfer of islet lymphocytes from NOD into NOD.scid mice. Here we show that the transfer was most effective when both CD4+ and CD8+ T cells were present in the infiltrate, but CD4+ T cells alone were sufficient to cause the disease. Islet lymphocytes from both females and males transferred diabetes effectively, but the severity of IDDM was higher when female islet lymphocytes were used. Unexpectedly, the sensitivity of male islets to beta-cell damage was greater than that of female islets. Treatment of NOD females with a peptide of heat shock protein (hsp)60, p277, known to protect NOD mice from IDDM, reduced the pathogenicity of the islet lymphocytes. In contrast, administration of cyclophosphamide to males, a treatment that accelerates the disease, rendered the islet lymphocytes more pathogenic. More severe disease in the recipient NOD.scid mice was associated with more interferon-gamma (IFN-gamma)-secreting islet T cells of the NOD donor. The disease induced by islet lymphocytes was strongly inhibited by co-transfer of spleen cells from prediabetic mice, emphasizing the regulatory role of peripheral lymphocytes. Thus, the cellular characteristics of the islet infiltrate and the pathogenicity of the cells are subject to complex regulation.

Adoptive Transfer↗
PubMed1999

A shared TCR CDR3 sequence in NOD mouse autoimmune diabetes.

T cells involved in autoimmune diseases have been characterized by the genetic elements used to construct their autoimmune TCR. In the present study, we sequenced the alpha and beta chains of the TCR expressed by a CD4(+) T cell clone, C9, functional in NOD mouse diabetes. Clone C9 can adoptively transfer diabetes or, when attenuated, C9 can be used to vaccinate NOD mice against diabetes. Clone C9 recognizes a peptide epitope (p277) of the 60 kDa heat shock protein (hsp60) molecule. We now report that the C9 TCR beta chain features a CDR3 peptide sequence that is prevalent among NOD mice. This CDR3 element is detectable by 2 weeks of age in the thymus, and later in the spleen and in the autoimmune insulitis. Thus, a TCR CDR3beta sequence appears to be a common idiotope associated with mouse diabetes.

Amino Acid Sequence↗
PubMed1999

Regulation of NOD mouse autoimmune diabetes by T cells that recognize a TCR CDR3 peptide.

NOD mice spontaneously develop type I diabetes resulting from autoimmune destruction of their insulin-producing beta cells. Among the self-antigens targeted by NOD autoimmune T cells is a peptide, p277, from the sequence of the 60 kDa heat shock protein (hsp60). Common to the anti-p277 T cell populations of NOD mice is an idiotope, C9, that spans the CDR3 region of the C9 TCR. We now report: (i) that the C9 idiotope peptide can be presented directly to anti-C9 anti-idiotypic T cells by C9 T cells, (ii) that spontaneous anti-C9 anti-idiotypic T cell activity falls as disease progresses, but immunization can activate the anti-idiotypic T cells to regulate the autoimmune process, (iii) that the anti-idiotypic T cells secrete IFN-gamma, but appear to control the disease by down-regulating the IFN-gamma produced by the pathogenic population of anti-p277 T cells, (iv) that intrathymic administration of the C9 idiotope peptide at 1 week of age can accelerate the disease, and (v) that administering the p277 target peptide can up-regulate the anti-idiotypic T cells and arrest the disease process. Thus, the development of NOD diabetes can be regulated by a balance between anti-idiotypic and anti-target peptide autoimmunity, and anti-idiotypic regulation can lead to changes in the cytokine secretion of the autoimmune T cells involved in the disease process.

Amino Acid Sequence↗
PubMed1999

[Sufentanil in balanced anesthesia: need to predict concentrations for dose optimization].

During balanced anaesthesia sufentanil may be difficult to use, as the required doses change over time depending on the patient and the noxious stimuli. Patient adjustment may be improved by using pharmacokinetic simulations that predict the concentration achieved in the body. In the first case report, sufentanil was given manually as repeated boluses, then by infusion. As haemodynamic status remained unstable, a simulation of the sufentanil concentration time course was started during the case. It showed that instability had pharmacokinetic explanation and allowed to determine the adequate sufentanil concentrations (0.30-0.40 ng.mL-1 + N2O + isoflurane 0.8-1 vol% for abdominal surgery). However, adjusting the doses manually required numerous human actions. In the second case, sufentanil was given as a computer-controlled infusion. The adequate concentrations were determined (0.15-0.20 ng.mL-1 + N2O + isoflurane 0.4 vol% for peripheral surgery in an aged cardiac patient). They were maintained with a limited number of human actions and resulted in satisfactory haemodynamic stability.

Aged↗
PubMed1999

[Long-term oncological results of hepatectomy performed after selective portal embolization].

BACKGROUND: Preoperative selective portal vein embolization (PSPVE), usually of the right portal branch, allows some patients to undergo an hepatectomy which was initially impossible as it would have left an insufficient amount of liver parenchyma. PSPVE induces relative atrophy of the embolized part of the liver, inducing compensatory hypertrophy of the nonembolized part (future remaining liver). Its technical aspects, its tolerance, its immediate results and indications are currently well-known, but long-term results of PSPVE followed by hepatectomy are unknown. The objective of this retrospective study was to assess the long-term survival of this unusual therapeutic approach. PATIENTS AND METHODS: Forty-one patients with initially unresectable (for volumetric reasons) malignant lesions of the liver, underwent PSPVE followed by hepatectomy between September 1987 and September 1998. In two-thirds of cases, the primary tumor was a colorectal adenocarcinoma. The mean number of resected lesions was 4.6 per patient, the mean size of the free margin was 4.3 mm, and 26.8% of the patients presented a (resectable) extrahepatic tumor. RESULTS: Overall 5-year survival (including the two postoperative deaths) was 31.3%, and 5-year survival without recurrence was 24%. For the 27 patients with colorectal metastases (the only homogenous subgroup of the series), overall 5-year survival was 28.6%. Although this result was lower than those obtained with classical hepatectomy (34.4%), it can be considered to be satisfactory, due to the number and size of the lesions. CONCLUSION: In conclusion, it is justified to use PSPVE to make initially unresectable very large liver tumors resectable, in view of the good survival results.

Adenocarcinoma↗
PubMed1999

[5-fluorouracile and cisplatinum combination chemotherapy for metastatic squamous-cell anal cancer].

Anal cancers (AC) represent rare gastrointestinal tumors and there are only a few studies dealing with the treatment of AC at the metastatic stage. We report here the results of one chemotherapy regimen based on the experience of the Gustave-Roussy Institute. Between 1985 and 1996, 19 patients: 3 males, 16 females, have been treated with a combination of 5-fluorouracil (5FU) and cisplatinum (CDDP) (FUP regimen). Their median age was 58, their performance status (WHO grade: G) was G0-1 in 68% and G2 in 32% of the cases. Metastasis were synchronous in 6 cases and metachronous in 13 cases. Metastatic sites were the liver (10 cases), the lymph nodes 11 cases (paraaortic 5, iliac 4 and inguinal 2) and pulmonary in 3 cases; in 9 cases the lymph nodes metastasis were isolated, in 7 cases the liver metastasis were isolated. One patient received FUP as an adjuvant treatment has been only considered for toxicity and survival. The FUP regimen combined an IV 5FU continuous infusion (1 g/m2/d (5 days) and a short infusion of CDDP (100 mg/m2) on day 2, every 4 weeks: 10 patients received further local treatment. According to WHO criteria, 18 patients were evaluable for the efficacy and 19 for the tolerance. The median number of cycles was 4. The response rate was 66% (standard error : 22%) with 1 complete response and 11 partial response; there were also 4 stabilisations and 2 progressions. Toxicity rate was neutropenia grade (G) 3-4 in 13% of the patients without febrile neutropenia, G3 nausea in 30%, no G2 or 3 mucositis or diarrhoea, and 2 patients experienced a nephrotoxicity G1-2. The actuarial survival was 62.2% at 1 year and 32.2% at 5 years and the median survival was 34.5 months. Three patients are still alive at 4, 5 and 7 years and benefited from additional local treatment (the patient treated with adjuvant chemotherapy after hepatic resection and 2 patients treated after response to the FUP regimen, by surgery or radiotherapy). The FUP combination gave a high response rate with an acceptable toxicity in patients with metastatic anal cancer. Combined with local treatment it does allow prolonged survivals for some patients.

Actuarial Analysis↗
PubMed1999

[Percutaneous radiofrequency ablation of hepatic metastases. Preliminary experience].

AIM: To evaluate the efficiency of percutaneous radiofrequency ablation in the treatment of liver metastases. METHODS: Eighteen patients with 31 liver metastases, mainly from colorectal cancer, 10 - 35 mm in diameter (m = 23), underwent 26 courses of percutaneous radiofrequency ablation. Fifteen patients had previously undergone hepatectomy, and 3 patients had contra-indications to surgery. Imaging guidance was ultrasound in 21 patients, CT in 4 (tumors not seen with ultrasound), and both in 1. A generator working at 450 KHz with a maximum output power of 150 W was used to treat each lesion for 18 - 20 min. Treatment was monitored with real time ultrasound. RESULTS: Among the 12 patients followed more than 3 months, only one of the 24 treated lesions recurred after a mean follow up of 259 ¿ 109 days. Liver disease was controlled in 8 of the 12 patients after 90 - 509 days (m = 306). Among these 8 patients, 3 were tumor free after 559, 378 and 90 days, respectively; 2 died tumor free of non-tumoral disease (pulmonary embolism, digestive bleeding); 3 developed lung metastases treated with chemotherapy (n = 2) or surgery (n = 1). Three of the 12 patients had widespread hepatic tumor occurrence, and one patient died of these metastases. Six patients experienced mild skin burns, but no major complication was observed. CONCLUSION: Radiofrequency ablation of hepatic metastases appears safe and promising in this preliminary experience. Further investigation is needed.

Adult↗
PubMed1999

[Pseudomyxoma peritonei. A review].

Pseudomyxoma peritonei is a rare disease characterized by the presence of a large mucin component within the abdomen. Recent pathological and genetic advances indicate that they originate from an appendiceal adenoma or adenocarcinoma. Their prognostic is worse than ovarian border-line mucinous tumors (with which they are frequently confused). Currently, the histologic aspect permits to separate the diffuse peritoneal adenomucinosis (DPAM) originating from adenomas, with a relatively benign course, from the mucinous peritoneal carcinomatosis (MPC) originating from adenocarcinomas, with a very poor prognosis. Paradoxically, the treatment of these two diseases are rather similar, with supra-radical surgery as frequently as possible. This type of surgery allows to reach a crude 5-year survival comprised between 50% and 70%, with very different results according to the DPAM-type or the MPC-type. The adjunction of an intraperitoneal chemo-hyperthermia is logical for these two types of disease and probably increases the survival rate.

Adenocarcinoma↗
PubMed1998

Results of 136 curative hepatectomies with a safety margin of less than 10 mm for colorectal metastases.

BACKGROUND AND OBJECTIVES: It is now established that liver resection is beneficial for metastases from colorectal cancer. Nevertheless, a surgical margin estimated at less than 10 mm at preoperative imaging is considered an absolute contraindication to surgery by some, and a relative contraindication by others. The true impact of the width of the margin on the prognosis is unclear. METHODS: From 1984 to 1996, 196 patients underwent curative hepatectomy for liver metastases and were studied prospectively. Surgery was to be curative (or a complete R0 resection) and mortality was to be avoided. Of these 196 patients, 136 had surgical margins of less than 10 mm. Sixty-eight percent had multiple liver metastases and 15% had extrahepatic metastatic lesions. Clinical and pathological factors were studied specifically and a multivariate analysis was carried out. RESULTS: Overall 5-year survival rate of these 136 patients (taking into account postoperative mortality which attained 1.5%) was 27.8% and the disease-free survival was 22.9%. The surgical margin was 0 mm in 30 cases. The sole prognostic factor was the discovery of unsuspected (resectable) extrahepatic lesions at laparotomy (P < 0.001) ; the width of the free margin had no significant effect. However, in the multivariate analysis of prognostic factors for the entire series (269 hepatectomies), three powerful parameters were identified : (1) the curative nature of resection (P = 0.0007), (2) less than 20% of liver involvement (P = 0.002), and (3) a free margin exceeding 9 mm (P = 0.02). A correlation was found between narrow margins and extensive disease (high number of metastases, bilateral sites, and extended hepatectomy). There was also a greater likelihood of microscopic satellite lesions within 10 mm around the metastases. CONCLUSIONS: The prognostic impact of the width of the surgical margin should not be overestimated. Hepatectomy for liver metastases can procure long-term survival, even in patients with supposedly poor prognostic factors. Resection is justified as long as it is complete and the risks are minimal.

Aged↗
PubMed1998

Islet T cells secreting IFN-gamma in NOD mouse diabetes: arrest by p277 peptide treatment.

Non-obese diabetic (NOD) mice spontaneously develop insulin-dependent (type 1) diabetes mellitus (IDDM) caused by T cells which destroy the insulin-producing islet beta-cells. Since cytokines are involved in this auto-immune beta-cell damage, we used an ELISPOT assay to enumerate the islet-associated T cells that secreted interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) or interleukin-4 (IL-4). We used mitogenic anti-CD3 antibody to activate all the T cells capable of responding, irrespective of their antigen specificity. We found that NOD females, more susceptible than males to IDDM, accumulated islet IFN-gamma producers more rapidly with age than did the males. Acceleration of male IDDM by cyclophosphamide led to a marked increase in IFN-gamma secreting islet T cells. In contrast, a decrease in IFN-gamma-producing islet T cells was associated with arrest of IDDM by administration of peptide p277 of the 60 kDa heat-shock protein (hsp60) to 12-week-old female NOD mice. The p277-treated mice later manifested a greater number of islets and fewer leukocytes per islet than did the mice treated with a bacterial hsp60 peptide. Thus, the development of diabetes could be correlated with the accumulation in the islets of T cells producing IFN-gamma, and destructive insulitis could be downregulated by the administration of a single peptide.

Age Factors↗
PubMed1998

Production and purification of a recombinant human hsp60 epitope using the cellulose-binding domain in Escherichia coli.

The heat shock protein hsp60 plays a functional role in insulin-dependent diabetes mellitus. The hsp60 epitope p277 (aa 437-aa 460) is effective in vaccinating mice against diabetes. A synthetic peptide gene (p277) that encodes the human hsp60 epitope was cloned to the 3' end of the cellulose-binding domain gene (cbd). CBD-p277 was overexpressed in Escherichia coli and purified on a cellulose column. A methionine at the C-terminal end of CBD enabled CNBr cleavage between CBD and p277. After CNBr cleavage, free CBD and residual uncleaved CBD-p277 were recovered by cellulose chromatography. The p277 peptide was further purified on a RPC-FPLC column. The molecular weight of the recombinant peptide was confirmed by electrospray mass spectrometry. The recombinant peptide was found to be biologically active in assays involving clone C9 T-cell proliferation, lymph-node cell proliferation, and antibody production. Thus the use of CBD as an affinity tag and the utilization of affordable cellulose matrices offers an attractive method for the production and purification of recombinant peptides.

Cell Division↗
PubMed1998

Circumferential pharyngolaryngectomy with total esophagectomy for locally advanced carcinomas.

BACKGROUND: Forty-nine cases of circumferential pharyngolaryngectomy with total esophagectomy (PLTE) done between 1982 and 1996 were studied retrospectively. These procedures were performed for advanced squamous cell tumors of the superior esophageal sphincter (n = 23), for hypopharyngeal tumors with synchronous esophageal carcinoma (n = 15), and for hypopharyngeal tumors extensively invading the cervical esophagus (n = 11). METHODS: Ninety-six percent of the patients had T3-4 lesions, and it was impossible to use a free jejunal graft reconstruction. Patients underwent primary surgery in 70% of the cases, and salvage surgery (after failure of chemoradiotherapy) in 30%. In most patients, esophagectomy was performed without thoracotomy (n = 45). Resection was curative (R0) in 70% of the cases, in spite of lymph node invasion in 94%. Reconstruction of the digestive tract was achieved with the stomach in 33 patients (67%) or with the colon in 16 patients (33%). RESULTS: Before 1989, postoperative mortality was high, was correlated with the high frequency of palliative surgery, and resulted in unsatisfactory survival results (overall 5-year survival rate of 7%). After 1989, as a result of better selection of patients and appropriate training of our team, postoperative mortality decreased from 33% to 10%, R1-2 resections decreased from 39% to 26%, and a 3-year overall survival rate of 28% was obtained for the last 25 patients, all of whom were able to eat without difficulty. These results are superior to the survival rates and functional results obtained with radiochemotherapy alone for such advanced tumors, even though the voice is preserved with radiochemotherapy alone. CONCLUSIONS: PLTE for advanced pharyngeal or cervical esophageal tumors is the best treatment currently available, but it is indicated only in very selected cases: when it is technically impossible to perform reconstruction with a free jejunal graft after circumferential pharyngolaryngectomy; as primary surgery, rather than as salvage surgery following chemoradiotherapy; after careful preoperative morphologic and endoscopic assessment of the extent of the tumor; and in patients able to tolerate a thoracotomy for an esophagectomy with lymphadenectomy. Selection according to these guidelines should improve results.

Adult↗
PubMed1998

[Preoperative portal embolization: an effective means for inducing hypertrophy of the healthy liver and increasing indications for hepatic resection].

AIM OF THE STUDY: The aim of the preoperative portal embolization is a redistribution of the portal venous blood flow in an attempt to induce hypertrophy of the future remnant liver in order to perform a curative liver resection. MATERIAL AND METHODS: Preoperative portal embolization was performed in a group of 43 patients. The volumetric ratio (future remnant liver/total liver-tumor) was 20%. Liver metastases were present in 40 patients and primary liver tumor in three. Twenty-four patients had received chemotherapy prior to the preoperative portal embolization. Required operative procedures were right hepatectomy (n = 15), right hepatectomy extended to the segment IV (n = 24) or atypical resection (n = 4). Preoperative portal embolization was performed under percutaneous transhepatic approach with a Blue Histoacryl and Lipiodol Ultra Fluide mixture. Liver volumetric measurements were obtained with 3D color encoded computed tomography, before portal embolization and before surgery. RESULTS: Hypertrophy of the future remnant liver was 83 +/- 58% after a mean 32-day interval between portal embolization and surgery. The tolerance of portal embolization was excellent. Thirty-six hepatectomies were performed as initially planned; seven were cancelled for emergence of metastases (distant in six patients and intrahepatic in one). CONCLUSION: Pre-operative portal embolization is a safe and effective procedure which increases the possibilities of curative resection in the liver tumors.

Embolization, Therapeutic↗
PubMed1998

Surgical treatment of hepatic and pulmonary metastases from colorectal cancers.

BACKGROUND: Selected patients with double hepatic and pulmonary metastases from colorectal cancer may benefit from operation. METHODS: From 1970 to 1995, 239 patients underwent operation for resection of pulmonary metastases from colorectal cancer at two French surgical centers. Among these patients, 43 (18%) had previously undergone complete resection of hepatic metastases and constitute the subject of this retrospective study. RESULTS: The median interval time between hepatic and pulmonary resections was 18 months. Two pneumonectomies, 5 lobectomies, 3 segmentectomies, 6 wedge resections, and 27 metastasectomies were performed. No postoperative mortality was observed. Two patients had major postoperative complications. Seven patients (16%) underwent subsequent pulmonary resection for recurrences. Twenty-one patients were still alive, 14 free of disease. The median survival from pulmonary resection was 19 months and the 5-year probability of survival was 11%. Prethoracotomy carcinoembryonic antigen blood levels and the number of pulmonary resection were found to be significant prognostic factors; the interval time between hepatic and pulmonary resection (> 36 months) was borderline significant (p = 0.06). CONCLUSIONS: Selected patients with combined hepatic and pulmonary metastases from colorectal cancer should be considered for surgical resection. Patients with normal prethoracotomy carcinoembryonic antigen levels and late metachronous pulmonary metastasis, appear to be the best surgical candidates.

Adenocarcinoma↗
PubMed1998

Resection of liver metastases from colorectal cancer: the real impact of the surgical margin.

AIMS: The benefit of liver resection for metastatic colorectal cancer is now established. Nevertheless if the surgical margin on pre-operative imaging is considered to be less than 10 mm, this is considered an absolute contraindication to surgery by some, and a relative contraindication by others, so its real impact on prognosis is not clear. METHODS: From 1984 to 1996, 269 patients underwent hepatectomy for liver metastases and were prospectively studied. The only two objectives of this surgery were to be curative (or achieve complete R0 resection), and to avoid mortality. Of the 269, 187 patients had surgical margins inferior to 10 mm. Sixty per cent had multiple liver metastases, and 37% had extrahepatic metastatic sites. Their clinical and pathological factors were specifically studied. RESULTS: The crude 5-year survival of these 187 patients (including the 2% post-operative mortality) was 24.7%, and the disease-free survival was 18.8%. The surgical margin was 0 mm in 60 cases and was histologically invaded in 20 cases. The most important prognostic factor was whether the resection was considered palliative (R1-R2 resection according to UICC criteria) (P < 0.0001). When the cases with invaded margins were excluded, there was not prognostic difference between the 107 patients with a margin of 0-4 mm and the 143 patients with a margin greater than 4 mm. However, a surgical margin greater than 9 mm appears to be a second prognostic factor (P = 0.001), when these 187 patients are compared to others. The reasons behind this are that there is a close relationship between narrow margins and extensive disease (high number of metastases, bilateral localization and extended hepatectomy), and also an increased possibility of microscopic satellite lesions within 10 mm around the metastases. CONCLUSION: The real prognostic impact of the surgical margin must not be overestimated. Hepatectomy for metastases can provide long-term survival in patients with supposed poor prognostic factors. Resection is justified so long as it is complete and with minimal risk. An experienced, specialized centre can be a prognostic determinant.

Aged↗