Homer-dependent cell surface expression of metabotropic glutamate receptor type 5 in neurons

The metabotropic glutamate (mGlu) receptors are a family of receptors involved in the tuning of fast excitatory synaptic transmission in the brain. Experiments performed in heterologous expression systems suggest that cell surface expression of group I mGlu receptors is controlled by their auxiliary protein, Homer. However, whether or not this also applies to neurons remains controversial. Here we show that in cultured cerebellar granule cells, the group I mGlu receptor subtype, mGlu5, transfected alone is functionally expressed at the surface of these neurons. Transfected Homer1b caused intracellular retention and clustering of this receptor at synaptic sites. Recombinant Homer1a alone did not affect cell surface expression of the receptor, but in neurons transfected with Homer1b, excitation-induced expression of native Homer1a reversed the intracellular retention of mGlu5 receptors, resulting in the receptor trafficking to synaptic membranes. Transfected Homer1a also increased the latency and amplitude of the mGlu5 receptor Ca2+ response. These results indicate that Homer1 proteins regulate synaptic cycling and Ca2+ signaling of mGlu5 receptors, in response to neuronal activity.     

Phase IV study of liposomal daunorubicin (DaunoXome) in AIDS-related Kaposi sarcoma

The purpose of this article was to study the efficacy and tolerance of liposomal daunorubicin (DaunoXome) in the treatment of AIDS-associated Kaposi sarcoma (KS) as prescribed in France between September 1996 and September 1997. All patients with a positive HIV serology, histologically proven KS, and having received at least one daunorubicin treatment cycle during the study period were eligible for entry. Ninety-four patient files from 13 university hospital departments were retrospectively studied. Of 94 patients, 80% received cytostatic treatment before the first daunorubicin treatment cycle. Initial mean CD4 lymphocyte count was 114/microl. Ninety percent of the patients received highly active antiretroviral treatment (HAART) during daunorubicin treatment. Daunorubicin was administered as single chemotherapy to 70% of the patients. The total number of treatment cycles was 1,422, with a mean number of 16.1 treatment cycles (1-68) per patient and a mean cumulative daunorubicin dose of 674 mg/m2 (40-2,749). According to the AIDS Clinical Trial Group criteria, partial and complete response rates were 26.5% and 11.5%, respectively. A hematopoietic growth factor was prescribed in 29% of the treatment cycles. At the final evaluation, 71% of the patients were alive. No severe cardiotoxic event was observed despite high cumulative drug doses and prolonged follow-up. Since the introduction of HAART, this study constitutes the only evaluation of daunorubicin in a wide population. Our study confirms that daunorubicin is effective in patients with advanced KS. Daunorubicin is well tolerated over the long term in association with HAART.     

Guiding the study of brain dynamics by using first-person data: Synchrony patterns correlate with ongoing conscious states during a simple visual task

Even during well-calibrated cognitive tasks, successive brain responses to repeated identical stimulations are highly variable. The source of this variability is believed to reside mainly in fluctuations of the subject's cognitive "context" defined by his/her attentive state, spontaneous thought process, strategy to carry out the task, and so on...As these factors are hard to manipulate precisely, they are usually not controlled, and the variability is discarded by averaging techniques. We combined first-person data and the analysis of neural processes to reduce such noise. We presented the subjects with a three-dimensional illusion and recorded their electrical brain activity and their own report about their cognitive context. Trials were clustered according to these first-person data, and separate dynamical analyses were conducted for each cluster. We found that (i) characteristic patterns of endogenous synchrony appeared in frontal electrodes before stimulation. These patterns depended on the degree of preparation and the immediacy of perception as verbally reported. (ii) These patterns were stable for several recordings. (iii) Preparatory states modulate both the behavioral performance and the evoked and induced synchronous patterns that follow. (iv) These results indicated that first-person data can be used to detect and interpret neural processes.     

Recurrent myocardial infarction due to obstruction of the RCA ostium by an aortic papillary fibroelastoma

A 69-year-old healthy woman was hospitalized twice within a few weeks for management of acute inferior myocardial infarction with thrombolysis and stenting of the right coronary artery (RCA) ostium. After the second myocardial infarction, follow-up angiography showed subocclusion of the proximal RCA, and transesophageal echocardiography and chest computed tomography revealed the presence of a mobile, 2-cm diameter spherical mass partially adherent to the RCA ostium and penetrating the stent. A benign papillary fibroelastoma was surgically excised, the stent was removed, and vein bypass grafting of the RCA was performed. The literature relevant to this case report is reviewed.     

Effects of the cold pressor test on short-term fluctuations of finger arterial blood pressure and heart rate in normal subjects

The effect of the cold pressor test on autonomic cardiovascular control was studied non-invasively by means of spectrum analysis of periodic heart rate and blood pressure fluctuations in ten normal subjects. Fast Fourier Transform algorithm based on a 256-point time series (sampling rate 2 Hz, i.e. 2-min and 8-s) was used to estimate the amplitude spectra of heart rate and blood pressure rhythmicity at the low frequency (70–140 mHz) and respiration related frequency (230–270 mHz) band. Respiration rate was controlled at 250 mHz. Auto- and cross-spectral techniques were used to determine the complex relationship between systolic blood pressure and heart rate fluctuations in the frequency domain. The spectral pattern of systolic and diastolic blood pressure showed a marked increment of the absolute and relative (100 multiplied with absolute value/total area under the curve of the amplitude spectrum from 15–500 mHz) low frequency component: control vs. cold pressor test—systolic blood pressure—absolute values (in [mmHg/Hz^1/2]): 634.4 ± 48.9 vs. 827.4 ± 69.9* relative values (in [%]): 26 ± 2 vs. 32 ± 2*; diastolic blood pressure —absolute values: 433.2 ± 42.3 vs. 537.2 ± 45.8* relative values: 35 ± 3 vs. 40 ± 2*, (average ± SEM, *P < 0.05). The cold pressor test induced no change in average heart rate; the absolute low frequency component in heart rate spectra increased clearly during the test: low frequency component (in [bpm/Hz^1/2]): 586.9 ± 89.9 vs. 712.0 ± 91.4*, while the relative low frequency component did not change: 29 ± 3 vs. 30 ± 3. There was no alteration in the respiration related frequency component in all time series and in the transfer gain and phase functions during cold pressor test. We conclude that the cold pressor test increases low frequency systolic blood pressure fluctuations which reflects an increase in sympathetic vasomotor control. Furthermore the cold pressor test does not induce change in the transfer gain and phase characteristics of modulation of heart rate by systolic blood pressure.     

Anemia and colorectal cancer

Colorectal cancers are classically revealed by a low digestive bleeding, which can be occult or exteriorized. They commonly present anemia at the diagnosis leading to particular outcomes. Perioperative blood transfusions are frequently indicated for the treatment of localized tumors and for hepatic resection of metastatic lesions but transfusions seem to have a negative impact on prognosis by increasing infections and potentially recurrence. In this context, various strategies aim at limiting the transfusional risk (autologous transfusion, preoperative use of erythropoietin...). Anemia associated with advanced colorectal cancers provides the same interest as for any metastatic tumor, as quality of life of patients is correlated to the hemoglobin's level.     

Access to, and outcome of, renal transplantation according to treatment modality of end-stage renal disease in France

BACKGROUND: Although peritoneal dialysis (PD) is recognized as one of the methods of treatment of end-stage renal disease (ESRD), there have been recurrent concerns about the access of patients treated by this modality to kidney transplantation (KTx), as well as reports showing increased complications of KTx in such patients, such as graft thrombosis and infections. METHODS: The aim of this study was to provide a comprehensive view of the impact on transplantation of pretransplant modality of treatment of ESRD using a multivariate analysis of the French database. From 1997 to 2000, after exclusion of pediatric patients, multiple transplantations, and living donors, 6420 were patients registered on the waiting list, and 3464 were transplanted. RESULTS: Using a Cox proportional hazard analysis, we found a shorter waiting time for PD patients (RR 0.71, P < 0.0001), which became equivalent to hemodialysis (HD) patients when taking into account the transplant center as a variable (RR 1.0, P= 0.95). Concerning graft survival, only preemptive transplantation had a significant impact, being associated to a decreased risk of graft failure (RR 0.46, P= 0.005). Conclusion. Our study supports the concept that the choice of any pretransplant dialysis modality does not influence waiting time for transplant or the results of transplantation.     

Intraperitoneal treatment with dimethylthioampal (DIMATE) combined with surgical debulking is effective for experimental peritoneal carcinomatosis in a rat model

The goal was to evaluate the efficiency of intraperitoneal administration of dimethylthioampal (DIMATE), a cellular apoptosis inducer, combined, or not, with cytoreductive surgery on rats with peritoneal adenocarcinomatosis. Peritoneal carcinomatosis was induced in rats by intraperitoneal injection of adenocarcinoma cell line DHD/K12/pro B. Intraperitoneal DIMATE was given at 17.3 mg/kg. Rats were randomized into five groups of eight animals, regarding the day of treatment (2 days or 20 days after peritoneal carcinomatosis induction) and the combination with cytoreductive surgery. All rats were killed at 30 days to evaluate carcinomatosis extent (quantitative score) and ascites volume. The quantitative score of carcinomatosis and the ascites volume were significantly reduced in the groups treated with DIMATE at day 2 (P = 0.005 and P < 0.001, respectively) and when DIMATE was used with cytoreductive surgery at day 20 (P = 0.009 and P < 0.001, respectively). Cytoreductive surgery or DIMATE used alone at day 20 had no significant influence. The intraperitoneal DIMATE administration at day 20, when not combined with surgery, had no significant influence on carcinomatosis extent or on ascites volume. Intraperitoneal DIMATE appeared to be an efficient drug in the prevention or treatment of peritoneal carcinomatosis when combined with cytoreductive surgery or when it was given by intraperitoneal route, before the development of macroscopic peritoneal carcinomatosis. It appears to be a promising therapeutic agent to be investigated in a human phase I trial in peritoneal carcinomatosis.     

Health promotion and disease prevention for older adults: Intervention themes and strategies used in Quebec local community health centres and seniors' day centres

OBJECTIVE: Despite the considerable potential of disease prevention and health promotion (DPHP) among older adults, extant data suggest that this field of intervention is still underdeveloped. To shed further light on this issue, this paper presents the results of an inventory of DPHP interventions for older adults conducted in local community health centres (CLSCs) and seniors' day centres in the province of Quebec. METHODS: All CLSCs (N=147) and day centres (N=124) were invited to participate (response rates: 74% and 79%). Data were collected through telephone interviews. Interventions were coded according to type of intervention strategies and target themes. RESULTS: Awareness-raising and health education strategies emerged as the most frequently-cited type of intervention strategies, reported by 77% of CLSCs and 95% of day centres, respectively. The two themes reported by a majority of CLSCs were physical health (87%) and community issues (58%). Lifestyle habits (92%) and social issues (92%) were the two most frequently-cited themes in day centres. DISCUSSION: DPHP for older adults is substantially well developed in terms of intervention offerings in the two types of organizations under study. However, the range of available interventions requires expansion to increase the potential of DPHP programs to tackle the numerous challenges posed by the aging of the population.     

Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure

Ischemic acute renal failure is characterized by damages to the proximal straight tubule in the outer medulla. Lesions include loss of polarity, shedding into the tubule lumen, and eventually necrotic or apoptotic death of epithelial cells. It was recently shown that peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) increases keratinocyte survival after an inflammatory reaction. Therefore, whether PPARbeta/delta could contribute also to the control of tubular epithelium death after renal ischemia/reperfusion was tested. It was found that PPARbeta/delta+/- and PPARbeta/delta-/- mutant mice exhibited much greater kidney dysfunction and injury than wild-type counterparts after a 30-min renal ischemia followed by a 36-h reperfusion. Conversely, wild-type mice that were given the specific PPARbeta/delta ligand L-165041 before renal ischemia were completely protected against renal dysfunction, as indicated by the lack of rise in serum creatinine and fractional excretion of Na+. This protective effect was accompanied by a significant reduction in medullary necrosis, apoptosis, and inflammation. On the basis of in vitro studies, PPARbeta/delta ligands seem to exert their role by activating the antiapoptotic Akt signaling pathway and, unexpectedly, by increasing the spreading of tubular epithelial cells, thus limiting potentially their shedding and anoikis. These results point to PPARbeta/delta as a remarkable new target for preconditioning strategies.