Does pneumonectomy for lung cancer adversely influence long-term survival?

OBJECTIVE: The increased operative mortality associated with pneumonectomy has stimulated the use of lung-sparing operations such as sleeve lobectomy. Whether pneumonectomy adversely affects long-term outcome after lung resection is unknown. METHODS: We reviewed the cases of patients who underwent lobectomy/bilobectomy or pneumonectomy because of non-small cell lung cancer between January 1980 and June 1998. Survival curves were compared by the log-rank test. Covariates were determined for operative mortality and survival using logistic regression analysis and Cox proportional hazards estimation, respectively. RESULTS: There were 259 men and 183 women who underwent lobectomy/bilobectomy (340) or pneumonectomy (102). Operative mortality was 36 (8.1%) patients overall, 24 (7.0%) for lobectomy/bilobectomy and 12 (12%) for pneumonectomy. Mean follow-up was 41 months (range 0-222 months). Median survival was worse for pneumonectomy (stage II: 17.9 vs 36.3 months, log-rank P =. 05; stage III: 11.7 vs 21.3 months, log-rank P =.07). However, important covariates for survival were age, primary tumor status, regional nodal status, and forced expiratory volume in 1 second. After adjusting for these covariates, survival did not differ significantly between the types of operations (hazard ratio for pneumonectomy 1.21; 95% CI 0.88-1.68). CONCLUSIONS: We did not detect a significant long-term adverse influence of pneumonectomy on survival after adjusting for other prognostic factors, but randomized clinical trials would be needed to definitively address this issue.     

Factors associated with liver biopsy performance in HCV-HIV coinfected injecting drug users with HCV viremia: Results from a five-year longitudinal assessment

The last international consensus conference about hepatitis C virus (HCV) treatment emphasized the importance of treatment for persons coinfected with HCV and human immunodeficiency virus (HIV). As liver biopsy precedes treatment, we aimed to identify factors associated with the performance of liver biopsy among HIV-HCV coinfected drug users during a 5-year follow-up to study their access to HCV treatment. Of the 296 patients followed in the HIV hospital departments of Nice and Marseilles and with retrievable records about HCV diagnosis and care, 166 were eligible for analysis having had detectable HCV RNA at least once during the study period. Overall, 45.2% of patients underwent liver biopsy during follow-up. Using proportional hazard models, predictors of having had a liver biopsy were high social support, complete abstinence from drug injection, and lack of immunosuppression as well as male gender, no history of multiple incarcerations, more recent onset of drug use, and an increase of liver enzyme levels. These results suggest that specific efforts should be devoted to HIV-HCV coinfected drug users to assist with stabilizing these patients to optimize their access to HCV care whenever possible. The MANIF 2000 study group includes C. Boirot, A. D. Bouhnik, M. P. Carrieri, J. P. Cassuto, M. Chesney, P. Dellamonica, P. Dujardin, S. Duran, J. G. Fuzibet, H. Gallais, J. A. Gastaut, G. Lepeu, D. A. Loundou, C. Marimoutou, D. Mechali, J. P. Moatti, J. Moreau, M. Nègre, Y. Obadia, I. Poizot-Martin, C. Pradier, D. Rey, C. Rouzioux, A. Sobel, B. Spire, F. Trémolières, and D. Vlahov.     

The ontogeny of induction of c-fos in the rat SCN by a 5-HT(2A/2C) agonist

The induction of c-fos in the suprachiasmatic nucleus (SCN) by the 5-HT(2A/2C) agonist, DOI was studied at mid-dark in neonatal rats. The number of cells expressing c-FOS immunoreactivity following DOI was low 3 days after birth, but increased rapidly over the next 3 days. By contrast, light exposure stimulated cells throughout this period. These results are consistent with the arrival of serotonergic afferents at the SCN and their role in the entrainment of rhythms.     

The calcium receptor modulates the hyperpolarization-activated current in subfornical organ neurons

Here we report that neurons of the subfornical organ (SFO), a circumventricular structure devoid of a blood-brain barrier, show time-dependent, inward rectification indicative of the presence of a subthreshold, hyperpolarization-activated inward current (Ih). In whole-cell patch clamp experiments of isolated SFO neurons, we observed a Cs+-sensitive Ih in 47% of cells tested. Furthermore, we show that Ih is involved in the generation of evoked bursts in SFO neurons. An allosteric agonist of the extracellular calcium-sensing receptor (CaR) was found to potentiate Ih consistent with our previous observations of CaR-mediated bursting in SFO neurons. These studies indicate that a proportion of SFO neurons express Ih, and this may be one ionic mechanism through which bursting is regulated by various extracellular messengers.     

Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats.

Oral treatment with the anti-acne drug Accutane (isotretinoin, 13-cis-retinoic acid) has been associated with suicide ideation and depression. Here, depression-like behaviors (i.e., behavioral despair and anhedonia) were quantified in adult Sprague-Dawley rats gavaged daily beginning at postnatal day (PND) 82 with 13-cis-RA (7.5 or 22.5 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg ). Tested at PND 130-131 in the Forced Swim Test, 7.5 mg/kg 13-cis-RA marginally decreased immobility and slightly increased climb/struggle durations whereas neither all-trans-retinoic acid group differed from controls. Voluntary saccharin solution (0.03%) intake at PND 102-104 and PND 151-153 was not different from controls in any treated group, although all RA-treated groups had lower intakes. Swim speed in a water maze at PND 180 was similar across groups, indicating no RA-induced differences in physical ability. Open field activity was mildly decreased at PND 91 in 7.5 mg/kg-treated males only, but it was within the control range at PND 119, 147, and 175. Thus, at serum levels similar to those in humans receiving the drug, chronic 13-cis-RA treatment did not severely affect depression-like behaviors in rats. These data do not substantiate the hypothesis of 13-cis-RA-induced depression.     

Resistance to the tubulin-binding agents in renal cell carcinoma: no mutations in the class I beta-tubulin gene but changes in tubulin isotype protein expression.

PURPOSE: The primary purpose of this study was to determine whether mutations of the class I beta-tubulin gene may be implicated in the inherent resistance to tubulin-binding agents (TBA) in renal cancer, with a small number of samples and cell lines also being examined for class I and III beta-tubulin isotype protein expression. EXPERIMENTAL DESIGN: DNA was extracted from 90 renal tumors and the class I beta-tubulin gene analyzed for mutations. For each sample, eight PCRs were used to cover the complete coding sequence with intronic primers ensuring highly homologous pseudogenes were not coamplified. Additionally, expression levels of class I and III beta-tubulin isotypes in 17 matched normal and malignant renal samples and a panel of renal cell carcinoma cell lines with differing intrinsic resistance to the TBAs was examined by Western blotting. RESULTS: Four polymorphic sequence changes of the class I beta-tubulin gene were identified with no mutations. Class I protein expression levels were higher in tumor tissue versus normal tissue, whereas class III expression showed no consistent change. In renal cancer cell lines, a significant correlation between class III isotype expression and vinblastine sensitivity was observed. CONCLUSIONS: These results do not support a role for mutations in the class I beta-tubulin gene in the intrinsic resistance of renal cancer to TBAs. Class III isotype expression may be implicated in resistance in vitro but in vivo, changes in class I isotype expression in renal cell carcinoma tissue may support a role in resistance to the TBAs and warrants further investigation.     

Perceptions of commercial snack food and beverages for infant and young child feeding: A mixed‐methods study among caregivers in Kathmandu Valley,Nepal

Ensuring nutritious complementary feeding is vital for child nutrition. Prior research in Kathmandu Valley found high consumption rates of commercially produced snack foods among young children, which are often energy‐dense/nutrient poor. This mixed‐methods study was conducted to elicit Nepali caregivers' perceptions of commercial snack foods and beverages and factors influencing their use for young child feeding. Seven facilitated focus group discussions (FGD) were conducted with Kathmandu Valley caregivers of children 12–23 months, and a survey of 745 primary caregivers of children 12–23 months of age was then conducted. During the FGD, caregivers reported commonly providing commercial food and beverage products to their children as snacks, and 98.6% of caregivers participating in the survey reported feeding their child such a food in the previous week. Because of processing and packaging, snack foods were not trusted by many FGD participants and considered as “junk foods” and not healthy for children. However, commercial snack foods were consistently ranked highly on convenience, both because of minimal preparation and ease of feeding; 48.5% of all surveyed caregivers reported providing a snack food because of convenience. Other family members' diets or provision of snack foods as treats also influenced children's consumption of these snack foods and beverages. This study indicates that caregivers of young children prefer snack options that are nutrient rich; however, this may conflict with preferences for foods that require minimal preparation and are appealing to young children. Such findings carry programmatic implications for interventions aiming to address children's diet quality in urban Nepal.