[Evaluation of the prescription of furosemide in persons aged 75years and older in a geriatric acute-care unit]. / Évaluation de la prescription du furosémide chez la personne âgée de 75 ans et plus dans un service de gériatrie aiguë.

INTRODUCTION: Furosemide is very often prescribed in France. It may cause important adverse effects especially in elderly persons. In order to limit its misuse and excessive expenditure for health insurance organizations, the European Society of Cardiology drafted strict guidelines for its prescription. We conducted a study in this population to determine the rate of prescription of furosemide in elderly persons outside the guidelines. METHOD: This was a prospective, single-centre, observational study bearing on elderly persons aged 75years and more admitted to a geriatric acute-care unit over a period of 6months. The prevalence of furosemide prescription and the proportion of prescriptions outside guidelines were calculated. The sociodemographic and medical characteristics of patients treated with furosemide were studied as were the modalities of furosemide prescription. RESULTS: In the 818 patients hospitalized during the period of the study, 267 were taking furosemide at admission (32.6%). Among these prescriptions, 69.2% were outside the guidelines. Arterial hypertension was the leading indication for furosemide (38.2%), followed by chronic heart failure (24.3%). CONCLUSION: This study confirmed the high prevalence of furosemide prescription and its misuse. Furosemide is often re-prescribed with no medical re-evaluation.

Axillary irradiation omitting axillary dissection in breast cancer: is there a role for shoulder-sparing proton therapy?

The recent EORTC 10981-22023 AMAROS trial showed that axillary radiotherapy and axillary lymph node dissection provide comparable local control and reduced lymphoedema in the irradiated group. However, no significant differences between the two groups in range of motion and quality of life were reported. It has been acknowledged that axillary irradiation could have induced some toxicity, particularly shoulder function impairment. In fact, conventional breast irradiation by tangential beams has to be modified to achieve full-dose coverage of the axillary nodes, including in the treatment field a larger portion of the shoulder structures. In this scenario, alternative irradiation techniques were discussed. Compared with modern photon techniques, axillary irradiation by proton therapy has the potential for sparing the shoulder without detrimental increase of the medium-to-low doses to the other normal tissues.

Bi-tangential hybrid IMRT for sparing the shoulder in whole breast irradiation.

BACKGROUND AND PURPOSE: A bi-tangential technique is proposed to reduce undesired doses to the shoulder produced by standard tangential irradiation. PATIENTS AND METHODS: A total of 6 patients affected by shoulder pain and reduced functional capacity after whole-breast irradiation were retrospectively analysed. The standard tangential plan used for treatment was compared with (1) a single bi-tangential plan where, to spare the shoulder, the lateral open tangent was split into two half-beams at isocentre, with the superior portion rotated by 10-20° medially with respect to the standard lateral beam; (2) a double bi-tangential plan, where both the tangential open beams were split. The planning target volume (PTV) coverage and the dose to the portion of muscles and axilla included in the standard tangential beams were compared. RESULTS: PTV95 % of standard plan (91.9 ± 3.8) was not significantly different from single bi-tangential plan (91.8 ± 3.4); a small but significant (p < 0.01) decrease was observed with the double bi-tangential plan (90.1 ± 3.7). A marked dose reduction to the muscle was produced by the single bi-tangential plan around 30-40 Gy. The application of the double bi-tangential technique further reduced the volume receiving around 20 Gy, but did not markedly affect the higher doses. The dose to the axilla was reduced both in the single and the double bi-tangential plans. CONCLUSION: The single bi-tangential technique would have been able to reduce the dose to shoulder and axilla, without compromising target coverage. This simple technique is valuable for irradiation after axillary lymph node dissection or in patients without dissection due to negative or low-volume sentinel lymph node disease.

Could ADMA levels in young adults born preterm predict an early endothelial dysfunction?

BACKGROUND: Sporadic data present in literature report how preterm birth and low birth weight are risk factors for the development of cardiovascular diseases in later life. High levels of asymmetric dimethylarginine (ADMA), a strong inhibitor of nitric oxide synthesis, are associated with the future development of adverse cardiovascular events and cardiac death. AIMS: 1) to verify the presence of a statistically significant difference between ADMA levels in young adults born preterm at extremely low birth weight (<1000 g; ex-ELBW) and those of a control group of healthy adults born at term (C) and 2) to seek correlations between ADMA levels in ex-ELBW and anthropometric and clinical parameters (gender, chronological age, gestational age, birth weight, and duration of stay in Neonatal Intensive Care Unit). METHODS: Thirty-two ex-ELBW subjects (11 males [M] and 21 females [F], aged 17-29years, mean age 22.2 ± 2.3 years) were compared with 25 C (7 M and 18F). ADMA levels were assessed by high-performance liquid chromatography with highly sensitive laser fluorescent detection. RESULTS: ADMA levels were reduced in ex-ELBW subjects compared to C (0.606+0.095 vs 0.562+0.101 µmol/L, p<0.05), and significantly correlated inversely with gestational age (r=-0.61, p<0.00001) and birth weight (r=-0.57, p<0.0002). CONCLUSIONS: Our findings reveal a significant decrease in ADMA levels of ex-ELBW subjects compared to C, underlining a probable correlation with preterm birth and low birth weight. Taken together, these results may underlie the onset of early circulatory dysfunction predictive of increased cardiovascular risk.

Gender-specific aspects in primary and secondary prevention of cardiovascular disease.

Gender differences in biological substrates of disease determine different clinical manifestations of CV disease with important implications for prevention, diagnosis and therapy in the two sexes. In women, the activity of sex hormones reduces the influence of CV risk factors during the reproductive age, and delays the onset of CHD of 2 decades compared to men. However, women as men suffer from CV events, and in women mortality from all CV causes and have greater than the sum of the others 7 causes of death together. Women are more likely than men to die of a first myocardial infarction a probability of developing heart failure or a second infarction than their male counterparts. The levels of lipid components vary in different ages of life and in the two genders. TC and LDL increase in men between 35 and 50 years of age. On the contrary LDL levels do not change significantly in fertile women in which they have a lower predictive value for CHD than in men, HDL levels are higher in premenopausal women than in men of the same age and their role in predicting CHD is considerably higher in women. High triglycerides and Lp(a) are more important as a risk factor in women than in men. Because of the greater incidence of cardiovascular diseases in men until the early 80s, the information about the importance of risk factors associated with an increased risk of cardiovascular events has been gathered mainly in men and transferred to women. Most studies on lipid-lowering therapy did not have the adequate statistical power to show significant reductions in CV events in women. Regarding the indications for use of statins in daily practice, current data suggest that in secondary prevention statins are equally effective in both genders while in primary prevention the CV benefits of lipid-lowering therapy in women are less clear than in men and therefore should be used according to the degree of risk calculated from the available score systems.

Triiodothyronine stimulates hepatocyte proliferation in two models of impaired liver regeneration.

OBJECTIVES: Liver regeneration is attenuated in old age and is substantially slower after 90% than after 70% partial hepatectomy (PH). We have previously demonstrated that the proliferative response to a primary mitogen is intact in aged mice, indicating that impaired liver regeneration is not due to loss of proliferative capacity. Here, we have investigated whether mitogenic effects of triiodothyronine (T3) could reverse the impaired regeneration of ageing or 90% hepatectomy, in the rat. MATERIALS AND METHODS: T3 (20 microg/100 g body weight) was administered to 14-month-old rats subjected to 70% PH or to young rats subjected to 90% PH. Cell-proliferative capacity was determined by bromodeoxyuridine incorporation and microscopy and changes of cell cycle-related proteins were analysed by Western blot analysis. RESULTS: Treatment of old intact rats with T3 increased cyclin D(1) expression that was followed by an enhanced proliferative response, the labelling index (LI), being 7.8% versus 1.3% of controls. T3 given before 70% PH stimulated regenerative response (LI was 10.8% versus 2.28%), and expression of cyclin D(1) and proliferating cell nuclear antigen (PCNA) 24 h after PH. Pre-treatment with T3 also improved the regenerative response of the liver after 90% hepatectomy (LI was 27.9% versus 14.2%). CONCLUSIONS: These findings show in principle that mitogen-induced hyperplasia could be applied to human therapy in patients with reduced regenerative capacity or massive loss of hepatocytes.

Phase II study of preoperative irradiation and chemotherapy with capecitabine in patients with locally advanced rectal carcinoma.

Preoperative chemoradiotherapy has demonstrated to improve resectability and local control in locally advanced rectal cancer (LARC). 5-fluorouracil (5FU) has traditionally been the drug of choice in combination with radiation therapy. Early studies of capecitabine (CAP) have shown its potential to replace 5FU. Between March 2002 and April 2005, 31 patients with newly diagnosed LARC (T2 N+ 2 cases, T3 N0-N+ 25 cases, T4 N0-N+ 4 cases) received the combined treatment. Surgery was planned 6-8 weeks after chemoradiation. Adjuvant chemotherapy with 5FU plus leucovorin for 6 courses was given in pN+ patients. All patients completed the planned treatment. Grade 3 acute toxicity was observed in 5 patients (16%). Nineteen patients (61%) had a downstaging. A complete pathological remission was observed in 3 cases (10%). Median follow-up is of 23 months (range; 6-36 months). The results of this experience confirm the data of the literature about the feasibility and efficacy of a neoadjuvant treatment with radiation and CAP in LARC.

Increased ROS generation and p53 activation in alpha-lipoic acid-induced apoptosis of hepatoma cells.

Alpha-lipoic acid (alpha-LA) is an antioxidant used for the treatment of a variety of diseases, including liver cirrhosis, heavy metal poisoining, and diabetic polyneuropathy. In addition to its protective effect against oxidative stress, alpha-LA induces apoptosis in different cancer cells types. However, whether alpha-LA acid induces apoptosis of hepatoma cells is unknown. Herein, we investigated whether alpha-LA induces apoptosis in two different hepatoma cell lines FaO and HepG2. The results showed that alpha-LA inhibits the growth of both cell lines as indicated by the reduction in cell number, the reduced expression of cyclin A and the increased levels of the cyclin/CDKs inhibitors, p27(Kip1) and p21(Cip1). Cell cycle arrest was associated with cell loss, and DNA laddering indicative of apoptosis. Apoptosis was preceded by increased generation of reactive oxygen species, and associated with p53 activation, increased expression of Bax, release of cytochrome c from mitochondria, caspases activation, decreased levels of survivin, induction of pro-apoptotic signaling (i.e JNK) and inhibition of anti-apoptotic signaling (i.e. PKB/Akt) pathways. In conclusion, this study provides evidence that alpha-LA induces apoptosis in hepatoma cells, describes a possible sequence of molecular events underlying its lethal effect, and suggests that it may prove useful in liver cancer therapy.