Sibutramine added to a behavior therapy program reduced BMI and body weight more than placebo and improved the profile of several metabolic risk factors in obese adolescents.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder characterized by multiple parathyroid, pancreatic, duodenal, and pituitary neuroendocrine tumors. Nonendocrine mesenchymal tumors, such as lipomas, collagenomas, and angiofibromas have also been reported. MEN1-associated neuroendocrine and some mesenchymal tumors have documented MEN1 gene alterations on chromosome 11q13. To test whether the MEN1 gene is involved in the pathogenesis of multiple smooth muscle tumors, we examined the 11q13 loss of heterozygosity (LOH) and clonality patterns in 15 leiomyomata of the esophagus, lung, and uterus from five patients with MEN1. Forty sporadic uterine leiomyomata were also studied for 11q13 LOH. LOH analysis was performed using four polymorphic DNA markers at the MEN1 gene locus; D11S480, PYGM, D11S449, and INT-2. The gene for multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant tumor syndrome, has been mapped to chromosome 11q13 1 and recently identified. 2 The MEN1 gene is thought to act as a tumor suppressor based on the presence of inherited inactivating mutations in the constitutional DNA of affected family members accompanied by the loss of the wild-type allele in associated tumors. 2-4 Somatic inactivation of the MEN1 gene has been also documented in a subset of sporadic counterpart parathyroid, enteropancreatic, and pulmonary endocrine tumors, and mesenchymal tumors. 5 MEN1 patients typically present first with primary hyperparathyroidism resulting from multiple parathyroid tumors caused by MEN1 gene alterations. 6 Neuroendocrine tumors of the pancreas, duodenum, anterior pituitary gland, stomach, and lung are other tumors that are an integral part of MEN1. 7,8 Nonendocrine mesenchymal tumors, such as lipomas, angiofibromas, and collagenomas, have also been shown to be associated with MEN1 and MEN1 gene alterations. 8 -10 Leiomyomata have been occasionally documented in MEN1 patients, 8,[11][12][13][14] and loss of heterozygosity (LOH) at the MEN1 locus was recently shown in two esophageal leiomyomata from one MEN1 patient. 15 MEN1 gene inactivation in lung or uterine leiomyomata, however, has not been studied. To test whether MEN1 gene alterations are involved in the development of multiple smooth muscle tumors in MEN1 patients, we analyzed 15 leiomyomata from five patients with documented MEN1 germline mutations for LOH at the MEN1 gene locus. To assess whether MEN1 gene alterations are present in sporadic smooth muscle tumors, we analyzed 40 sporadic uterine leiomyomata for MEN1 gene deletion for comparison. Furthermore, to evaluate whether MEN1-associated leiomyomata arise as independent clonal events at different anatomical sites within an organ, the patterns of 11q13 LOH in different tumors from individual patients

Objectives: Fear of opioid withdrawal syndrome (OWS) often dissuades opioid discontinuation. Lofexidine is an FDA-approved, alpha 2-adrenergic receptor agonist for treatment of OWS. Pivotal trial results from the per-protocol statistical analyses have been published. However, the FDA prescribing information presents these efficacy results using a different, standardized statistical approach that does not transform data or impute missing values. This analysis is easier to interpret and allows comparison across studies. This reanalysis is presented here. Methods: Studies were double-blind, placebo-controlled for 7 days in Study 1 and 5 days in Study 2. Opioid-dependent adults received placebo or lofexidine; efficacy was assessed using the Short Opioid Withdrawal Scale of Gossop (SOWS-G) daily. Results: Study 1 (N ¼ 602) mean SOWS-G scores were 6.1 (SE: 0.35), 6.5 (SE: 0.34), and 8.8 (SE: 0.47) over Days 1-7 for lofexidine 2.88 mg/day, 2.16 mg/day, and placebo, respectively (for 2.88, p < .0001; for 2.16 mg, p < .0001). Study 2 (N ¼ 264) mean SOWS-G scores were 7.0 (SE: 0.44) and 8.9 (SE: 0.48) over Days 1-5 for lofexidine 2.16 mg/day and placebo, respectively (p ¼ .0037). Median time to treatment discontinuation was approximately 2 days later with lofexidine treatment than with placebo and significantly more lofexidine-treated subjects completed the studies. Hypotension and bradycardia were more common with lofexidine. More placebo subjects withdrew prematurely for lack of efficacy. Conclusion: This simplified analysis confirmed previous per-protocol results, that lofexidine better reduces OWS severity and increases retention compared with placebo in opioid-dependent adults. These results are robust and comparable across studies using various methods of analysis.

Lucemyra® (lofexidine hydrochloride) has recently been approved by the US FDA for the mitigation of withdrawal symptoms to facilitate abrupt discontinuation of opioids in adults. Lofexidine is an alpha-2 adrenoceptor agonist. However, the clinical attributes of lofexidine differ in advantageous ways from the classical alpha-2 adrenoceptor agonist clonidine. In the present study, we measured the receptor binding profile of lofexidine and clonidine in an effort to gain an insight into the clinical difference(s).