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Biomedical subjects

T Petit

Publications and source records attributed to T Petit.

At least 73 records · Page 4Linked to original sources

[Rectal resection for cancer in Lower-Normandy. Loco-regional recurrences and survival. Results of a regional survey (1988-1993)].

OBJECTIVES AND METHODS: A retrospective regional study was set up to identify the determinants of loco-regional recurrences and those of survival after rectal resection for cancer. The studied population was constituted of 505 patients with resection for carcinoma of the rectum in Lower-Normandy from 1988 to 1993. RESULTS: The actuarial rate of loco-regional recurrence was 17.3 +/- 4% at 3 years. The only significant predictive factor of survival free of loco-regional recurrence was the Dukes' stage. Actuarial survival rate was 52.0 +/- 4% at 5 years, the corresponding relative survival rate being 64.6 +/- 6%. The only two independent prognostic factors were the sphincter-saving procedure and adjuvant radiotherapy. COMMENTARIES: The loco-regional recurrence rate after resection for rectal cancer is still high. Sphincter-saving procedure and adjuvant radiotherapy increase over the time. Since the study was retrospective, no definitive conclusions could be drawn. Nevertheless, they incite us to set up larger prospective regional studies including quality control of surgical procedures, radiotherapy protocols and histopathological reports.

Actuarial Analysis↗

[Indications and results of mucosal proctectomy with colo-anal anastomosis in villous disease of the rectum].

The objective of this study was to define the indication for proctectomy and colo-anal anastomosis in large rectal villous adenomas. The study population consisted of 20 patients (12 men and 8 women; mean age 63.6) who underwent rectal excision and colo-anal anastomosis from 1990 to 1997. The average size of tumors was 59.8 mm; 18 tumors were located in the lower third of the rectal ampulla; 8 patients had prior treatment (surgical or medical) before proctectomy. There were 13 straight colo-anal anastomoses and 7 constructed with colonic J pouch. Eighty percent of the anastomoses were defunctioned by a temporary stoma. The overall morbidity included one case of pelvic sepsis, two anastomotic strictures and one colonic trans-anal prolapse. One patient experienced persistent mild fecal incontinence and two others developed urogenital. The mean hospital stay was 14.4 days and 8.5 days for stoma closure. 8 tumors contained malignancy: 3 Tis, 4 T1 and 1 T2. In our opinion the extension, natural history or potential of occult malignancy of large rectal villous adenomas may requires rectal excision with colo-anal anastomosis with low morbidity and good functional results.

Adenocarcinoma↗

A phase I and pharmacological study of protracted infusions of crisnatol mesylate in patients with solid malignancies.

This Phase I and pharmacological study was performed to assess the feasibility of administering the polycyclic aromatic hydrocarbon crisnatol in increasingly prolonged continuous i.v. infusions to patients with advanced solid malignancies. The study also sought to characterize the-principal toxicities of crisnatol on this schedule, to recommend doses for subsequent disease-directed studies, and to characterize possible associations between pharmacological parameters and toxicity. Sixteen patients were treated with 40 courses of crisnatol administered as a continuous i.v. infusion. The initial dose-schedule was 750 mg/m2/day for 6 days, and the duration of the infusion was to be progressively increased by 3-day increments to 9, 12, 15, 18, and 21. Courses were to be repeated every 4 weeks. Moderate to severe central nervous system (CNS) toxicity precluded the administration of crisnatol 750 mg/m2/day for longer than 6 days, and, therefore, the dose of crisnatol was reduced to 600 mg/m2/day. At this dose, three of five patients receiving a 12-day infusion experienced dose-limiting toxicity, which consisted of pulmonary thromboembolism (two patients) and grade 4 thrombocytopenia (one patient). None of the six patients completing a 9-day infusion at 600 mg/m2/day developed dose-limiting toxicity during the first or second course of crisnatol. At this dose level, the plasma concentrations at steady state (Css) averaged 1607.8+/-261.1 ng/ml, which exceeds minimal inhibitory concentrations for most tumors in vitro (1000 ng/ml). In fact, the administration of crisnatol at a dose of 600 mg/m2/day for 9 days resulted in the longest duration that biologically relevant plasma crisnatol concentrations have been sustained. Plasma Css values were significantly higher in patients who experienced severe CNS toxicity compared with those who did not (2465.3+/-1213.5 versus 1342+/-447.3 ng/ml; P = 0.04). There were no relationships evident between the clearance of crisnatol and indices reflecting renal and hepatic functions. One patient with a glioblastoma multiforme experienced a partial response lasting 14 months. The relative lack of intolerable CNS toxicity at the recommended dose for Phase II studies of crisnatol, 600 mg/m2/day for 9 days, as well as the magnitude of the Css values achieved and the antitumor activity observed at this dose, are encouraging. However, the mechanisms for the apparently increased thrombogenicity observed in this trial are unclear and require further elucidation.

Adult↗

[Results and indications of lateral ileostomy functionally terminated in colorectal surgery].

UNLABELLED: Loop ileostomy (LI) ensures fecal diversion to protect an anastomosis or anatomic colorectal or ano-perineal damage. The aim of this retrospective study was to evaluate loop ileostomy morbidity in emergency and planned colorectal surgery. PATIENTS AND METHODS: From 1991 to 1996, 145 loop ileostomies were performed in 139 patients, 77 men and 62 women with a mean age of 48.7 years (15-82). The etiology was a rectal tumor (cancer or large villous tumor n = 47), inflammatory bowel disease (n = 47, ulcerative colitis = 37 and Crohn's disease = 10) Familial Adenomatous Polyposis (n = 13) and other diseases (n = 32). 80% LI (n = 116) protected ileo-anal anastomoses (n = 46) colo-anal anastomoses (n = 45, 26 with colonic pouch), ileo-rectal anastomoses (n = 11) and other anastomoses (n = 15). 20% LI (n = 29) dysfunctional ano-perineal lesions (n = 8), anastomosis leak (n = 4) or distal bowel without intestinal resection (n = 17). RESULTS: 7 deaths were not stoma-related. 91% LI were closed after a mean diversion time of 3.6 months. LI closure was performed by a parastomal (n = 128) or laparotomy procedure (n = 4). Morbidity during LI diversion was observed in 24 patients (16.5%) 12 of whom (8.3%) were operated for small bowel obstruction (n = 6; 4.2%) stoma revision (n = 5; 3.5%) and prolapse (n = 1; 0.7%). 2 patients had peristomal skin excoriations, and 5 patients required readmission for dehydration due to high LI output. Morbidity after LI closure was observed in 12 patients (8.6%) 5 of whom were operated for anastomotic leak (n = 4) or small bowel obstruction (n = 1). Low morbidity and defunctioning efficiency confirm the indications for LI. LI is our first-line stoma in planned or emergency colorectal surgery.

Adenomatous Polyposis Coli↗

A mutation Ser213/Asn in the hexokinase 1 from Schizosaccharomyces pombe increases its affinity for glucose.

Alignment of amino acids of the region implicated in glucose binding from a series of hexokinases showed that Schizosaccharomyces pombe hexokinase 1 had a Ser residue in a place where all other kinases had an Asn. We changed an AGT codon to AAT to place an Asn in the Ser213 position. This mutation decreased Km for glucose from 9.4 mM to 1.6 mM and the ratio Vmax (Fructose)/Vmax (Glucose) from 5 to 2.5. Also the Km for 2-deoxyglucose decreased from 2.7 mM to 0.8 mM. A mutation in the similar position of S. pombe hexokinase 2 (Asn196/Ser) increased the Km for glucose from 0.16 mM to 0.56 mM. Fermentation of glucose is not detectable in a S. pombe mutant with only hexokinase 1 activity but expression of the hxk1(S213/N) gene conferred ability to ferment the sugar. While the mutated hexokinase 1 partially mimicked S. cerevisiae hexokinase II in catabolite repression of invertase, the wild type one could not substitute for it.

Amino Acid Sequence↗

Mitoguazone induces apoptosis via a p53-independent mechanism.

Mitoguazone (methylglyoxal bisguanylhydrazone, methyl-GAG or MGBG) is a synthetic polycarbonyl derivative with activity in patients with Hodgkin's and non-Hodgkin's lymphoma, head and neck cancer, prostate cancer, and esophageal cancer. Mitoguazone has also recently been documented to have activity in patients with AIDS-related lymphoma. Among anticancer drugs, mitoguazone has a unique mechanism of action via interference with the polyamine biosynthetic pathway. Polyamines stabilize DNA structure by non-covalent cross-bridging between phosphate groups on opposite strands. In addition, mitoguazone causes uncoupling of oxidative phosphorylation. In this study, the ability of mitoguazone to induce apoptosis by inhibiting the polyamine pathway was assessed in three Burkitt's lymphoma cell lines (Raji, Ramos and Daudi) and one prostate carcinoma cell line (MPC 3). Additional evaluations were performed in two human breast cancer cell lines (MCF7 with wild-type p53 and VM4K with mutated p53) to determine whether the p53 tumor suppressor gene was required for efficient apoptosis induction. The present study demonstrated that mitoguazone induces apoptosis in all the different human cancer cell lines tested in a concentration- and time-dependent way, and triggers a p53-independent programmed cell death in the human breast cancer MCF7 cell line.

Antineoplastic Agents↗

The value of endoscopic treatment for ureteroceles during the neonatal period.

PURPOSE: We report a series of 35 neonates presenting with ureterocele diagnosed during the antenatal period or during the first weeks of life. The first line treatment was an endoscopic incision. MATERIALS AND METHODS: Immediate postnatal evaluations detected 37 ureteroceles (bilateral in 2 cases), including 16 of the intravesical type and 21 that were ectopic. Endoscopic incision permitted decompression of the majority of ureteroceles and improvement in renal function in most cases. Secondary low grade vesicoureteral reflux appeared in 9 neonates (ectopic in 8 cases) and had already been present in 14 patients. RESULTS: Endoscopic treatment alone proved effective in 14 of the intravesical ureteroceles, while the other 2 cases requiring upper pole nephrectomy (1) and ureterovesical reimplantation using the Cohen technique (1). In contrast, among patients with the ectopic form additional surgery was necessary in 18 cases. Treatment comprised resection of the ureterocele with bladder reconstruction and ureteral reimplantation without remodeling according to the Cohen technique in 15 cases, total ureteronephrectomy in 1 and pole nephrectomy in 2. CONCLUSIONS: We suggest that early endoscopic incision be used for first line treatment of ureteroceles. The aim of this procedure is to ensure better urine drainage, preserve function of the parenchyma and reduce the risk of severe infection in the neonate. The principal complication remains secondary vesicoureteral reflux onset, which can be controlled well by antibiotic prophylaxis but requires regular radiological monitoring.

Endoscopy↗

A series of vectors to construct lacZ fusions for the study of gene expression in Schizosaccharomyces pombe.

We have constructed a series of plasmids to facilitate the fusion of promoters with or without coding regions of genes of Schizosaccharomyces pombe to the lacZ gene of Escherichia coli. These vectors carry a multiple cloning region in which fission yeast DNA may be inserted in three different reading frames with respect to the coding region of lacZ. The plasmids were constructed with the ura4+ or the his3+ marker of S. pombe. Functionality of the plasmids was tested measuring in parallel the expression of fructose 1,6-bisphosphatase and beta-galactosidase under the control of the fbp1+ promoter in different conditions.

Base Sequence↗

Detection of maternal cells in human fetal blood during the third trimester of pregnancy using allele-specific PCR amplification.

Using a highly sensitive allele-specific PCR amplification method, we have previously shown that maternal cells could be detected in all 10 cord bloods tested. This raised the question of whether maternal cells are released into cord blood during the process of delivery or whether they are already present during pregnancy. We have now used the same PCR method to detect the presence of maternal cells in nine fetal blood samples collected at different gestational ages. Maternal cells were detected in eight samples obtained between 24 and 35 weeks of gestation. They were estimated to amount between 10(-4) and 10(-5) of nucleated fetal blood cells. In two cases mononuclear and polymorphonuclear cell fractions were separated by Ficoll gradient centrifugation and maternal cells were detected as comparable levels in both fractions. Maternal cells could not be detected in the one fetal blood sample obtained at 20 weeks of gestation, suggesting that maternal cells could appear at detectable levels in fetal blood during the third trimester of pregnancy. These results are discussed in terms of materno-fetal immune tolerance and of transmission of viruses (and more specifically of the human immunodeficiency virus) from mother to child.

Female↗

A phase II study of cisplatin, 5-fluorouracil, leucovorin, and etoposide in advanced non-small-cell lung cancer.

The aim of this study was to define the efficacy of a combination of cisplatin, 5-fluorouracil (5-FU), leucovorin, and etoposide (VP-16) in locally advanced or metastatic non-small-cell lung cancer (NSCLC). From September 1991 to November 1994, 28 patients were treated with cisplatin, 100 mg/m2 i.v. on day 1; 5-FU and leucovorin, 500 mg/m2 on days 1, 2, 3, and 4 by i.v. continuous infusion; and VP-16, 70 mg/m2 i.v. on days 1, 2, 3, and 4 (combination, PFL-VP-16). Cycles were repeated every 3 weeks. There were 22 men and six women. The median age was 58 (range, 41-76). All had measurable diseases (one was stage IIIA, six were IIIB, and 21 were IV). None had previously received chemotherapy for metastatic disease. There was one complete response and six partial responses, for an overall response rate of 25% (95% confidence interval 9-41%). The median response duration and the overall survival were 8 and 9 months, respectively. Limiting toxicity was myelosuppression and oral mucositis. Grade 3 or 4 leucopenia was observed in 20% of all of the 95 cycles administered, and oral mucositis in 13%. No grade 3 or 4 renal toxicity occurred, and neurologic toxicities were limited (3% of the 28 patients experienced grade 3). PFL-VP-16 is active and can easily be administered to patients with advanced NSCLC. However, according to the results obtained with this schedule, VP-16 does not increase either response rate or survival compared with the regimen previously described by Vokes et al. (PFL).

Adult↗