Oxaliplatin: available data in non-colorectal gastrointestinal malignancies.

Oxaliplatin is a third-generation platinum compound which has proven its efficacy alone or in combination with 5-fluorouracil (5-FU) and/or new anticancer drugs in advanced colorectal cancer. Compared to the amount of available data in this cancer, little is known about the use of oxaliplatin in non-colorectal gastrointestinal malignancies. (1) The preclinical activity of the drug alone or in combination; (2) the phase I studies (oxaliplatin alone or in combination with irinotecan, raltitrexed, gemcitabine, folinic acid and 5-FU); (3) the phase II studies developed in gastric, pancreatic, biliary tract, hepatocellular carcinoma and malignant mesothelioma; and (4) some of the ongoing trials with regard to non-colorectal gastrointestinal malignancies are reviewed in this paper. To date, oxaliplatin appears as a real candidate for clinical development in this field.

Activation of haptoglobin gene expression by cAMP involves CCAAT/enhancer-binding protein isoforms in intestinal epithelial cells.

CCAAT/enhancer-binding protein (C/EBP) isoforms are expressed in rodent intestine and in the rat intestinal epithelial cell line IEC-6 but their role remains to be determined. Treatment of IEC-6 cells with the adenylate cyclase activator forskolin led to coordinate induction of C/EBP isoforms alpha, beta and delta at the mRNA and protein levels. Transient transfection assays showed that their expression is controlled at the transcriptional level. Forskolin treatment induced haptoglobin mRNA levels. Electrophoretic mobility shift and supershift assays demonstrated an increase in DNA-binding activities of the three C/EBP isoforms to the haptoA and haptoC C/EBP DNA-binding sites of the proximal haptoglobin promoter. Site-specific mutations of both sites led to a decrease in transcriptional induction by forskolin, suggesting that C/EBP isoforms are involved in the cAMP-dependent regulation of the acute-phase protein gene haptoglobin in intestinal epithelial cells.

Primary angiosarcoma of bone in Paget's disease.

We report here a case of a primitive angiosarcoma of the bone occurring in Paget's disease. Only one case has been previously described in the literature. We review other types of tumours occurring in Pagetic bone and discuss medical and surgical management.

[Adult's anaplastic CD30+ large cell lymphomas]. / Lymphomes anaplasiques T ou nuls à grandes cellules CD30+ (Ki-1) de l'adulte.

Anaplastic large-cell lymphomas were recognized by Stein in 1985. Less than fifteen years were necessary to confirm this entity, as well as her phenotype and to characterize the t(2;5) (p23;q35) chromosomal abnormality. This rare subgroup of non-Hodgkin's lymphomas (15% of peripheral T cell lymphomas and 8% of all diffuse aggressive lymphomas) is individualized in the Real classification. This disease, which had a bimodal age distribution, is clinically characterized by a diffuse nodal involvement and the frequency of extranodal involvement, especially skin and lungs. Primitive cutaneous anaplastic large cell lymphomas belong to the cutaneous CD30+ lymphoproliferative diseases spectrum. Among peripheral T cell and diffuse aggressive lymphomas, they have the better prognosis. We present in this paper a review of the recent advances in the knowledge, treatment and prognosis of this peculiar entity.

Reversible pulmonary hypertension presenting simultaneously with an atrial septal defect and angiostrongylosis in a dog.

A one-year-old female neutered beagle was presented with marked abdominal effusion. Echocardiography showed marked dilatation of the right cardiac chambers, an atrial septal defect and severe tricuspid insufficiency. Systolic pulmonary arterial pressure (sPAP), evaluated by continuous wave Doppler echocardiography, was very high (80 mmHg), with a right to left interatrial shunt. The radiographic images were compatible with widespread pneumonitis. Numerous larvae of Angiostrongylus vasorum were visible on direct faecal examination. The animal was given fenbendazole for 15 days, combined with diuretics, an antibiotic and a vasodilator. Two weeks later, the dog showed a marked improvement. The treatment, except the anthelmintic, was continued for seven weeks and then stopped. At that stage, Doppler echocardiography revealed that the sPAP had returned to normal (20 mmHg) and the interatrial shunt had reversed (left to right). Eighteen months later, clinical and Doppler echocardiographic examinations were normal.

[Rupture of the left bronchus during intubation by Carlens tube]. / Rupture de la bronche souche gauche lors d'une intubation par sonde de Carlens.

The authors report a case of left main bronchus rupture following endotracheal intubation with a Carlens double-lumen tube. The bronchus rupture occurred during a cure of gastro-oesophageal-reflux and resection of oesophageal diverticula through a left thoracotomy. The patient was a 65-year-old woman treated with corticosteroids for an Addison's disease. The weakness of the bronchial wall initiated by the steroid hormones was an important factor contributing to the perforation. There is also a higher risk of rupture during oesophageal surgery because of surgical dissection and stretch on the tracheobronchial airway. This case demonstrates that such a complication can occur without ventilatory failure. A rupture must be recognized and treated surgically very rapidly. Recommendations regarding the use of double-lumen endotracheal tubes are reviewed in order to decrease the occurrence of such a complication.

Protective effect of melatonin and catalase in bovine neutrophil-induced model of mammary cell damage.

The effect of several antioxidants and a proteinase inhibitor on bovine neutrophil-induced mammary epithelial cell damage was investigated using an in vitro model of co-culturing bovine neutrophils and MAC-T cells, a mammary epithelial cell line. Epithelial cell damages were evaluated by measuring lactate dehydrogenase activity in culture media and by morphological observations of cells after acridine orange staining. Activation of neutrophils with Escherichia coli lipopolysaccharide and phorbol 12-myristate 13-acetate caused superoxide and gelatinase release in media. Activated neutrophils damaged the epithelial cells, as demonstrated by an increase in lactate dehydrogenase release and the observation of morphological changes. The addition of melatonin or catalase reduced neutrophil-induced cytotoxicity in a dose-dependent manner, whereas superoxide dismutase and aprotinin had no effect on cytotoxicity. Melatonin has been reported to scavenge hydroxyl radical and peroxynitrite, whereas catalase and superoxide dismutase scavenge hydrogen peroxide and superoxide, respectively. Our results suggest that hydroxyl radicals released by activated bovine neutrophils cause damage to mammary epithelial cells and that antioxidants may be useful to protect the mammary tissue during bovine mastitis.

Induction of nitric oxide production by bovine mammary epithelial cells and blood leukocytes.

A recent study from our laboratory has shown that significant amounts of nitric oxide are released by somatic cells recovered during endotoxin-induced mastitis. The present study was undertaken to investigate which cell type(s) among milk somatic cell population can produce nitric oxide under inflammatory conditions. Nitric oxide release from mammary epithelial cell lines and from bovine neutrophils and monocytes extracted from blood was measured in response to cytokines and Escherichia coli lipopolysaccharides. An epithelial cell line isolated from bovine mammary gland, FbE cells, was found to release nitric oxide after exposure to interleukin-1beta. This nitric oxide production was completely abolished by addition of L-N6-(1-iminoethyl) lysine, a potent inducible nitric oxide synthase inhibitor. Bovine monocytes produced nitric oxide in response to recombinant bovine interferon-gamma alone or in combination with E. coli lipopolysaccharides. In these cells, nitric oxide release was reduced by the addition of inducible nitric oxide synthase inhibitors L-N6-(1-iminoethyl) lysine and aminoguanidine. Lipopolysaccharides and recombinant bovine interferon-gamma increased nitric oxide synthase mRNA in neutrophils, but nitric oxide release could not be detected under any of the experimental conditions used. These results show that bovine epithelial cells and mononuclear phagocytes produce nitric oxide under inflammatory conditions and suggest that these cell populations are responsible for nitric oxide release observed during mastitis.

Questioning the cardiocirculatory excitatory effects of opioids under volatile anaesthesia.

BACKGROUND: Opioid-induced hyperalgesia has been demonstrated in awake animals. We observed an increased haemodynamic reactivity in response to noxious stimuli in rats under sevoflurane anaesthesia treated with a very low dose of sufentanil. The aim of this investigation was to determine whether the two phenomena share a common origin: an opioid-induced excitatory reaction. To address this, we administered several drugs with proven efficacy in opioid hyperalgesia to rats presenting with haemodynamic hyper-reactivity. METHODS: The MACbar of sevoflurane was measured in controls and in animals treated with sufentanil 0.005 micro g kg(-1) min(-1) before and after administration of i.v. (0.25, 0.5 mg kg(-1)) and intrathecal (i.t.) (250 micro g) ketamine, i.v. (0.5, 1 mg kg(-1)) and i.t. (30 micro g) MK-801(NMDA antagonist), i.v. (0.1, 0.5 mg kg(-1)) naloxone, i.v. (10 mg kg(-1)) and i.t. (50, 100 micro g) ketorolac or i.t. (100, 150 micro g) meloxicam (COX-2 inhibitor). RESULTS: Sufentanil 0.005 micro g kg(-1) min(-1) significantly increased MACbar (3.2 (sd 0.3) versus 1.9 (0.3) vol%). With the exception of naloxone, all drugs displayed a significant MACbar-sparing effect (>50%) in controls. Naloxone completely prevented haemodynamic hyperactivity. Two patterns of reaction were recorded for the other drugs: either hyper-reactivity was suppressed and the MACbar-sparing effect was maintained (i.t. ketamine, i.t. MK-801, i.t. ketorolac [100 micro g], i.t. meloxicam [150 micro g]) or hyper-reactivity was blocked but MACbar-sparing effect was lost (i.v. ketamine [0.5 mg kg(-1)], i.v. MK-801 [0.5, 1 mg kg(-1)], i.v. ketorolac [10 micro g kg(-1)], i.t. ketorolac [50 micro g], i.t. meloxicam [100 micro g]). CONCLUSIONS: We have demonstrated that low-dose sufentanil-induced haemodynamic hyper-reactivity is an excitatory micro -opiate-related phenomenon. This effect is reversed by drugs effective in treating opiate-induced hyperalgesia.

Neoadjuvant tamoxifen for hormone-sensitive non-metastatic breast carcinomas in early postmenopausal women.

BACKGROUND: From 1984 to 1996, 1581 postmenopausal women aged 50-70 years old were treated at Institut Bergonié for an infiltrative non-metastatic breast carcinoma with a positive estrogen and/or progesterone receptor determination. PATIENTS AND METHODS: Among them, 199 were treated with first line tamoxifen. Ninety-seven had operable disease (T2 >30 mm, T3, N0/1) and 102 had T4 tumours. RESULTS: After a mean treatment duration of 5.3 months, 89 T2 and T3 (92%) and 93 T4 (91%) were treated by surgery (conservative or not) with or without irradiation, or by irradiation alone. Conserving treatment levels were 53.6% and 44%, respectively. The other women were treated with either second-line chemotherapy or another hormonotherapy; the remaining patients continued regularly with tamoxifen. Overall survival is analysed with a 83 month median follow-up. CONCLUSIONS: A comparison between neoadjuvant endocrine therapy and surgery seems feasible to assess the concept of neoadjuvant hormonotherapy.