Antiproliferative activity of taxol on human tumor and normal breast cells vs. effects on cardiac cells

The antiproliferative activity of the chemotherapeutic agent taxol was evaluated on 2 normal and 2 carcinoma human breast-cell lines and compared with its effects on newborn rat cardiac cells growing in vitro. Relatively little difference in ID₅₀ response (ranging from 0.6 to 2.0 ng/ml) to taxol was found between normal and tumorous breast epithelial cells. Arrhythmias and slowing of beat frequencies of cardiac cells were induced by taxol but at doses approximately 10 times higher than those necessary to inhibit proliferation in dividing cells. Microtubules assayed by immunostaining appeared to be similarly retracted around the nucleus in both breast and heart cells. Overall, our results suggest that taxol does not selectively inhibit the growth of tumor vs. normal human breast cells. They also support the hypothesis that effects on microtubule integrity are associated with effects on cardiac function and that the clinical cardiac activity of taxol already reported may be due, at least in part, to a direct effect of taxol on cardiac cells as demonstrated in these in vitro studies. Thus, caution is needed, in view of possible cardiac effects, when using taxol in future clinical protocols, especially when combined with other cardioactive agents such as Adriamycin.     

Exertional heatstroke and muscle metabolism: an in vivo 31P-MRS study.

An impairment of muscle energy metabolism has been suggested as a predisposing factor for, as well as a consequence of exertional heatstroke (EHS). Thirteen young men were investigated 6 months after a well-documented EHS using 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS). The relative concentrations of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), and the intracellular pH (pHi) were determined at rest, during a graded standardized exercise protocol (360 active plantar flexions) and during recovery. Also the leg tissue blood flow was determined by venous occlusion plethysmography during the MRS procedure. Sixteen age-matched healthy male volunteers served as control group. In resting muscle, there were no significant differences between the groups as regards pHi, Pi/PCr, and ATP/PCr+Pi+PME ratios. During steady state exercise conditions, effective power outputs were similar for both groups at each level of exercise: 20, 35, and 50% of maximal voluntary contraction (MVC) of the calf muscle. No significant differences were shown between the two groups in Pi/PCr, pHi, or changes of leg blood flow at each level of exercise. At 50% MVC, Pi/PCr was 0.48 +/- 0.08 vs 0.47 +/- 0.05 (P = 0.96), pHi was 6.94 +/- 0.03 vs 6.99 +/- 0.02, respectively (P = 0.13). Finally, the rate of PCr resynthesis during recovery was not significantly different between the two groups: t1/2 PCr = 0.58 +/- 0.07 vs 0.50 +/- 0.05 min, respectively (P = 0.35). Therefore, no evidence of an impairment of muscle energy metabolism was shown in the EHS group during a standardized submaximal exercise using 31P-MRS performed 6 months after an EHS.     

Nosocomial viral infections in a pediatric service: example of rotaviral gastroenteritis and respiratory syncytial viral bronchiolitis]

Nosocomial infections are a preoccupation in a pediatric hospital mainly during the winter with bronchiolitis and gastroenteritis epidemics. We have examined the risk factors of nosocomial infections. MATERIAL AND METHODS: A prospective study was conducted between November, 1999 and March, 2000 in the infants units of the Le Havre hospital. We systematically listed the admissions and contacted the family after their discharge by phone. A geographic information system was implemented to display the epidemiological data; this software is able to illustrate the sectors at risk. RESULTS: During the study, 687 infants were hospitalized of whom 458 for bronchiolitis and community-acquired gastroenteritis. Mean age was 5.4 months old. No nosocomial bronchiolitis occurred. Prevalence of nosocomial gastroenteritis was 10% (68 cases including nine after discharge). Infants with nosocomial infection were younger than those with community-acquired infection (6.6 months vs. 11.2 months, P < 0.01). The mean length of stay was longer in nosocomial infection (7.7 vs. 4.1 days, P < 0.05). Among the infants with bronchiolitis, 16% have developed nosocomial intestinal infections (RR = 2.65, IC: 1.59-4.4; P < 0.01). The geographic analysis pointed the area with nosocomial risk (bedroom without water, nearness of nurse office and games room). CONCLUSION: Geographic information system is a part of the quality control system and may have some interaction effect on final decision making. Incidence of nosocomial infections showed the need for a prevention strategy in a pediatric hospital.     

Medical treatments of hyperactive child]

Treatment of hyperactive child is multimodal, a combination of behaviour therapy and medication. Stimulant drugs are the most often prescribed medications. In France, we use methylphenidate (Ritaline); its efficacy was demonstrated with mild side effects. New formulations of methylphenidate with prolonged action, and non-psychostimulant treatment (atomoxetine) are available in some countries, but not yet in France.     

Cystic fibrosis mortality trends in France.

BACKGROUND: In 1992 France set up a national cystic fibrosis observatory (Observatoire national de la mucoviscidose, ONM) to monitor the state of health of patients on an annual basis. Using the ONM data, this study estimates the main indicators for life expectancy and assesses the total number of cystic fibrosis patients. METHODS: The data for the years 1994 to 2003 are divided into 3-year periods. Life tables are drawn up for these periods, from which mean and median lengths of life are determined. Using the most recent life table, the number of births in 2003 and the incidence of the disease, the total population of patients can be estimated, assuming a stationary population. RESULTS: In 2001-2003, life expectancy at birth of patients registered with the ONM was 39.1 years and median length of life was 36.4 years. These results, substantially better than those of 1994-1996, are linked to improved conditions of patient inclusion in the ONM database, to improvements in their healthcare, but also to the limitations of the life tables. Based on the 2003 data, the total theoretical number of patients is 6490, and coverage by the ONM database is thus 63.2%. CONCLUSIONS: These provisional results demonstrate the need to convert the ONM observatory into a registry providing exhaustive coverage of all patients.     

Selective hepatic artery ligation for hepatic haemangioendothelioma: case report and review of the literature.

Although benign, hepatic haemangioendotheliomas (HHE) are rare vascular tumours of the infant which have a high mortality rate secondary to high output congestive heart failure. The management of these tumours is still controversial and none of the different medical or surgical options has been unanimously accepted. We report the case of a neonate with congestive heart failure (CHF) due to a localized HHE, treated successfully by selective ligation of the left hepatic artery branch irrigating the tumour, under perioperative ultrasound Doppler control. A review of the literature showed 35 cases of HHE treated by hepatic artery ligation (HAL) with a survival rate of 80 %.     

On the subject of the cyclic vomiting syndrome]

The cyclic vomiting syndrome is defined by episodes of vomiting lasting from hours to days with free intervals between episodes. Various symptoms can be associated with vomiting: nausea, abdominal pain, photophobia, fever, pallor, dehydratation, excess salivation, social withdrawal. Some factors often precipitate the crisis: infection, psychological stresses, menstruation. Excluding a medical condition, especially a gastro-intestinal or a neurological disease is compulsory for the diagnostic of cyclic vomiting syndrome. The cyclic vomiting syndrome shares many common features with migraine including treatment. Due to negative paraclinical testing, a psychiatric disease is often suspected in these children. Pathophysiology of cyclic vomiting syndrome is unknown. As for migraine, mitochondrial and ionic channels abnormalities are thought to play a role. Overactivation of hypothalamic-pituitary-adrenal axis and autonomic dysfunction seem to be involved too. Three clinical vignets will illustrate these aspects.