Le labétalol : nouvel agent hypotenseur en chirurgie de l'oreille moyenne: Etude hémodymanique per-opératoire

The hypotensive effects of an alpha and beta blocker, labelatol, were studied. It was used to reduce the bleeding in 15 patients undergoing ear surgery under narconeuroleptanalgesia (droperidol, fentanyl and Althesin). Haemodynamic measurements included systolic and diastolic blood pressure, heart rate, cardiac output, stroke volume, total peripheral resistances and left ventricular work. These measurements were carried out before the injection of labetalol, then every five minutes during its administration, and at the end of the anaesthetic period. The total peripheral resistances fell from 134 ± 36 to 112 ± 27 kPa . 1^?1 . s (?13 p. 100, p <0.001), giving a fall in the systolic arterial blood pressure from 13.8 ± 1.6 to 12 ± 0.4 kPa (?13.5 p. 100, p <0.001) and in the diastolic arterial blood pressure, from 9.1 ± 1.1 kPa to 7.6 ± 1.2 kPa (?16 p. 100, p <0.001). The heart rate changed from 1.6 ± 0.3 Hz to 1.5 ± 0.1 Hz (?8 p. 100, p <0.05). The cardiac and systolic indices varied little, and the left ventricular work diminished from 0.12 ± 0.04 to 0.09 ± 0.03 J . s^?1 (?14 p. 100, p <0.01); the bleeding was reduced satisfactorily. The arterial blood pressure returns to normal at the end of the operation, and the heart rate after about an hour. This study shows that labetalol is hypotensive by alpha and beta blockade. These are manifest about five minutes after the first injection; the alpha block predominates, but it disappears more rapidly than the beta block.     

Constrictive fibrous endocarditis. Surgical treatment]

An anatomo-clinical entity, fibrous constrictive endocarditis can betreated srugically, and we carried out this procedure for the first time in 1971, since when we have used it seven times; it consists of an internal stripping of one or both centricles, with removal of one or both the mitral and tricuspid valves. The results were encouraging in the first two cases, and so good in the succeeding ones that this endocardial resection could be put forward as the treatment of choice for a condition whose aetiology is still unclear.     

Cholecystokinin-2 receptor modulates cell adhesion through beta 1-integrin in human pancreatic cancer cells

Several lines of evidence suggest that gastrin and the CCK-2 receptor (CCK2R) could contribute to pancreatic carcinogenesis by modulating processes such as proliferation, cell adhesion or migration. In the current study, we used a 'cancer gene array' and identified beta1-integrin subunit as a new gastrin-regulated gene in human pancreatic cancer cells. We also demonstrated that Src family kinases and the phosphatidylinositol-3-kinase (PI-3-kinase) pathway play a crucial role in the expression of beta1-integrin induced by gastrin. Our results also showed that gastrin modulates cell-substrate adhesion via beta1-integrin. Indeed, using blocking anti-beta1-integrin monoclonal antibodies, we completely reversed the increase in cell-substrate adhesion induced by gastrin. In addition, we observed that in response to gastrin, beta1-integrin is tyrosine phosphorylated by Src family kinases and associates with paxillin, a scaffold protein involved in focal adhesion and integrin signalling. This mechanism might be involved in gastrin-induced cell adhesion. Moreover, we showed in vivo that targeted CCK2R expression in the pancreas of Elas-CCK2 mice leads to the overexpression of beta1-integrin. This process may contribute to pancreatic tumour development observed in these transgenic animals.     

Improved therapeutic efficacy of doxorubicin through conjugation with a novel peptide drug delivery technology (Vectocell)

Improvement in the therapeutic index of doxorubicin, a cytotoxic molecule, has been sought through its chemical conjugation to short (15-23 amino acid) peptide sequences called Vectocell peptides. Vectocell peptides are highly charged drug delivery peptides and display a number of characteristics that make them attractive candidates to minimize many of the limitations observed for a broad range of cytotoxic molecules. The studies reported here characterized the in vitro and in vivo efficacy of a range of Vectocell peptides conjugated to doxorubicin through different linkers. These studies show that the in vivo therapeutic index of doxorubicin can be improved by conjugation with a specific Vectocell peptide (DPV1047) through an ester linker to C14 of doxorubicin, in both colon and breast tumor models. This conjugate was also shown to have significant in vivo antitumoral activity in a model resistant to doxorubicin, suggesting that this conjugate is able to circumvent the multidrug resistance (MDR) phenotype. These experiments therefore provide support for the use of the Vectocell technology with other cytotoxic agents.     

Household exposure to pesticides and risk of childhood acute leukaemia

Objectives

To investigate the relation between childhood acute leukaemia and household exposure to pesticides.

Methods

The study included 280 incident cases of acute leukaemia and 288 controls frequency matched on gender, age, hospital, and ethnic origin. The data were obtained from standardised face to face interviews of the mothers with detailed questions on parental occupational history, home and garden insecticide use, and insecticidal treatment of pediculosis. Odds ratios were estimated using unconditional regression models including the stratification variables parental socioeconomic status and housing characteristics.

Results

Acute leukaemia was observed to be significantly associated with maternal home insecticide use during pregnancy (OR = 1.8, 95% CI 1.2 to 2.8) and during childhood (OR = 1.7, 95% CI 1.1 to 2.4), with garden insecticide use (OR = 2.4, 95% CI 1.3 to 4.3), and fungicide use (OR = 2.5, 95% CI 1.0 to 6.2) during childhood. Insecticidal shampoo treatment of pediculosis was also associated with childhood acute leukaemia (OR = 1.9, 95% CI 1.2 to 3.3).

Conclusion

The results reported herein support the hypothesis that various types of insecticide exposure may be a risk factor for childhood acute leukaemia. The observed association with insecticidal shampoo treatment of pediculosis, which has never been investigated before, requires further study.     

Efficacy of a combination of pemetrexed and multiple redo-surgery in an 11-year-old girl with a recurrent multifocal abdominal mesothelioma

We report the case of an 11-year-old girl with a recurrent progressive locally advanced abdominal mesothelioma. First, there was an incomplete surgical resection without any complementary chemotherapy, followed by a slow progression of the disease. Three years later, after two macroscopically complete surgical resections of peritoneal and ovarian tumors, she failed to respond to treatment with gemcitabin-carboplatin and gemcitabin-cisplatin, and developed splenic tumors and large multicystic hepatic tumors. She was then treated with pemetrexed. The schedule of chemotherapy was pemetrexed 400 mg intravenously plus cisplatin 60 mg once every 3 weeks associated with folic acid and vitamin B12. The tumor reduction was evaluated with positron emission tomography scan and tomodensitometry every three courses. Chemotherapy tolerance was good apart from a grade III neutropenia at the second course, a fever of unknown origin at the fifth course and a grade III thrombocytopenia at the sixth course. As tolerance and clinical responses were good, pemetrexed posology was increased up to 10%. After six courses, hepatic and splenic lesion tumors were initially diminished and then stablilized. Thus, a surgical resection was attempted: a first surgery followed by a second one 3 days later allowed completion of a difficult left hepatectomy, and resection of the hilum and splenic tumors. Fourteen months after the surgery, the girl remained in partial remission with stable disease. So far, pemetrexed associated with cisplatin revealed a good tolerance and promising results regarding its antitumoral efficacy in a progressive metastatic abdominal mesothelioma in childhood.