Further insight on the hypoglycemic and nonhypoglycemic effects of troglitazone 400 or 600 mg/d: effects on the very-low-density and high-density lipoprotein particle distribution.

The effects of troglitazone 400 or 600 mg/d on the glycemic control, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) subclass concentrations and plasminogen-activator inhibitor 1 (PAI-1) levels were assessed in patients with type 2 diabetes that had not been controlled with dietary treatment. This was a multicenter, open-label, parallel-groups study. It included a run-in 4-week diet period and a 24-week randomized treatment. Fifty one patients received 400 mg/d and 55 patients 600 mg. The mean HbA(1c) concentration at the end of the study was similar for both doses. Troglitazone, regardless of dose, significantly improved insulin sensitivity assessed by the homeostasis model (HOMA). PAI-1 levels were significantly decreased in both groups by 13%. Higher HDL cholesterol concentrations and lower triglycerides levels were observed at the end of treatment. Triglyceride contents were reduced only in the lighter VLDL1. The change in HDL cholesterol concentration resulted from a combination of increased HDL3 cholesterol and lower HDL2 cholesterol levels. No differences were found in the effects of both treatment groups on the evaluated parameters. Our data provide new information about the actions of the drug on the lipid profile. Troglitazone reduces triglyceride levels by lowering the triglycerides content of the VLDL1 particles and increases HDL cholesterol concentrations by increasing HDL3 cholesterol levels.     

"Hyper-response" evaluated by 3D echocardiography after cardiac resynchronization therapy

Cardiac resynchronization therapy consists of a promising treatment for patients with severe heart failure, but about 30% of patients do not exhibit clinical improvement with this procedure. However, approximately 10% of patients undergoing this therapy may have hyperresponsiveness, and three-dimensional echocardiography can provide an interesting option for the selection and evaluation of such patients.     

Epiretinal membrane vitrectomy: outcomes with or without cataract surgery and a novel prognostic factor for cystoid macular edema

Graefe's Archive for Clinical and Experimental Ophthalmology - To assess the outcomes of vitrectomy with or without cataract surgery for the treatment of idiopathic ERM in phakic eyes and...     

Levetiracetam for the treatment of hot flashes: a phase II study

Goals of work The objectives of this pilot trial were to assess the potential efficacy and safety of levetiracetam for the treatment of hot flashes, a major cause of morbidity among breast cancer survivors. Patients and methods Women, aged 18 years or more, with a history of breast cancer or those who wished to avoid estrogen because of a perceived increased risk of breast cancer, who were experiencing bothersome hot flashes (more than or equal to 14 times per week, for more than or equal to 1 month before study entry), were included. During the baseline week, general demographic characteristics, hot flash information, and quality of life data were obtained. At the beginning of week 2, patients were started on levetiracetam for a total of 4 weeks. Information about hot flashes, quality of life, and toxicity were collected during these 4 weeks and compared with the baseline week. Main results After treatment with levetiracetam for 4 weeks (N = 19), mean hot flash scores (frequency times mean severity) were reduced by 57%, and mean hot flash frequencies were reduced by 53%, compared to the baseline week; both these reductions were greater than what would be expected with a placebo (20–25% reduction). There were significant improvements in abnormal sweating (p = 0.004), hot flash distress (p = 0.0002), and satisfaction of hot flash control (p = 0.0001), when comparing data from the fourth week of treatment to the baseline week. Twenty-nine percent of the subjects did not complete the study because of treatment-related adverse events, with the most frequently reported side effects being somnolence, fatigue, and dizziness, usually with mild to moderate intensity. Conclusion The results of this pilot trial suggest that levetiracetam might be an effective therapy for the treatment of hot flashes. Further data are needed to test this hypothesis, evaluating the efficacy and toxicity of this agent. Financial Disclosure: None     

Activation of the integrated stress response confers vulnerability to mitoribosome-targeting antibiotics in melanoma

The ability to adapt to environmental stress, including therapeutic insult, contributes to tumor evolution and drug resistance. In suboptimal conditions, the integrated stress response (ISR) promotes survival by dampening cytosolic translation. We show that ISR-dependent survival also relies on a concomitant up-regulation of mitochondrial protein synthesis, a vulnerability that can be exploited using mitoribosome-targeting antibiotics. Accordingly, such agents sensitized to MAPK inhibition, thus preventing the development of resistance in BRAF^V600E melanoma models. Additionally, this treatment compromised the growth of melanomas that exhibited elevated ISR activity and resistance to both immunotherapy and targeted therapy. In keeping with this, pharmacological inactivation of ISR, or silencing of ATF4, rescued the antitumoral response to the tetracyclines. Moreover, a melanoma patient exposed to doxycycline experienced complete and long-lasting response of a treatment-resistant lesion. Our study indicates that the repurposing of mitoribosome-targeting antibiotics offers a rational salvage strategy for targeted therapy in BRAF mutant melanoma and a therapeutic option for NRAS-driven and immunotherapy-resistant tumors.     

Optimal crown-rump length for measuring the nuchal translucency

PURPOSE: To determine the optimal crown-rump length (CRL) for obtaining nuchal translucency (NT) measurements. METHODS: Women undergoing NT measurements by NT-certified sonographers within a combined screening program over an 18-month period were included in the study if they had a living fetus with a CRL of 45-84 mm. NT measurement success and screen-positive rates, transvaginal sonography (TVUS) use, and reasons for failed NT measurements were compared in 3 groups by CRL corresponding to 11-0/7 to 11-6/7 weeks (45-54 mm), 12-0/7 to 12-6/7 weeks (55-66 mm), and 13-0/7 to 13-6/7 weeks (67-84 mm). RESULTS: Eight hundred thirty-seven women aged 34.9 +/- 4.9 years underwent 1 to 3 NT measurements at a mean CRL of 59.8 +/- 25.0 mm. NT measurements were more successful at 11 and 12 weeks (81.8% and 84.4%) than at 13 weeks (66.9%) (p < 0.001). Screen-positive and TVUS rates, and reasons for failed NT measurements did not vary by CRL. CONCLUSION: NT measurements are most successful at CRL 45-66 mm corresponding to sonographically determined gestational ages of 11-0/7 to 12-6/7 weeks.