Pilot Safety Evaluation of Varenicline for the Treatment of Methamphetamine Dependence.

Despite the worldwide extent of methamphetamine dependence, no medication has been shown to effectively treat afflicted individuals. One relatively unexplored approach is modulation of cholinergic system function. Animal research suggests that enhancement of central cholinergic activity, possibly at nicotinic acetylcholine receptors (nAChRs), can reduce methamphetamine-related behaviors. Further, preliminary findings indicate that rivastigmine, a cholinesterase inhibitor, may reduce craving for methamphetamine after administration of the drug in human subjects. We therefore performed a double-blind, placebo-controlled, crossover pilot study of the safety and tolerability of varenicline in eight methamphetamine-dependent research subjects. Varenicline is used clinically to aid smoking cessation, and acts as a partial agonist at α4β2 nAChRs with full agonist properties at α7 nAChRs. Oral varenicline dose was titrated over 1 week to reach 1 mg bid, and then was co-administered with 30 mg methamphetamine, delivered in ten intravenous infusions of 3 mg each. Varenicline was found to be safe in combination with IV methamphetamine, producing no cardiac rhythm disturbances or alterations in vital sign parameters. No adverse neuropsychiatric sequelae were detected either during varenicline titration or following administration of methamphetamine. The results suggest that varenicline warrants further investigation as a potential treatment for methamphetamine dependence

Generalized Information Equilibrium Approaches to EEG Sleep Stage Discrimination

Recent advances in neuroscience have raised the hypothesis that the underlying pattern of neuronal activation which results in electroencephalography (EEG) signals is via power-law distributed neuronal avalanches, while EEG signals are nonstationary. Therefore, spectral analysis of EEG may miss many properties inherent in such signals. A complete understanding of such dynamical systems requires knowledge of the underlying nonequilibrium thermodynamics. In recent work by Fielitz and Borchardt (2011, 2014), the concept of information equilibrium (IE) in information transfer processes has successfully characterized many different systems far from thermodynamic equilibrium. We utilized a publicly available database of polysomnogram EEG data from fourteen subjects with eight different one-minute tracings of sleep stage 2 and waking and an overlapping set of eleven subjects with eight different one-minute tracings of sleep stage 3. We applied principles of IE to model EEG as a system that transfers (equilibrates) information from the time domain to scalp-recorded voltages. We find that waking consciousness is readily distinguished from sleep stages 2 and 3 by several differences in mean information transfer constants. Principles of IE applied to EEG may therefore prove to be useful in the study of changes in brain function more generally

Psychometric Profiles of Patient Populations with Excessive Daytime Sleepiness

Patients with narcolepsy have more psychiatric symptoms than normal controls as measured by psychometric tests. However, it is unclear whether these findings are specific to narcolepsy, as some studies have suggested, or related to excessive daytime sleepiness (EDS) or to chronic illness. We compared a group of 56 narcoleptics to age- and sex-matched controls with EDS. A group of 48 individuals with normal sleep architecture was also used as an additional control group. Both the narcoleptic group and the EDS-control group had significantly greater scores on Minnesota Multiphasic Personality Inventory scales hut were not different from each other. Our data suggest that the psychopathology associated with narcolepsy is not specific and may be generalized among patients with disorders of excessive sleepiness

Familial Childhood Sleep Apnea

We report four siblings who had polysomnographically documented sleep apnea. Two presented with the typical clinical picture of sleep apnea syndrome including daytime somnolence and snoring, had repetitive obstructive apneic episodes during sleep, and were effectively treated with upper airway surgery. The other two were asymptomatic and showed infrequent apneic episodes during sleep. This family illustrates the distinction between the sleep apnea syndrome and infrequent apneic episodes during sleep. The sleep apnea syndrome is associated with daytime symptomatology and requires treatment. The presence of apneic episodes during sleep in all four siblings has implications regarding the predisposing factors (eg, upper airway anatomy and central nervous system dysfunction) versus precipitating factors (eg, obesity, upper airway infection, and central nervous system depressants) in sleep apnea

Sleep-Wake Complaints and Their Relation to Sleep Disturbance

This report is a comparison of patients presenting with 1) an insomnia complaint diagnosed as no objective findings. 2) insomnia diagnosed as being associated with a psychiatric disorder, and 3) daytime sleepiness diagnosed as no objective findings. The sleep of patients with insomnia diagnosed as no objective findings is comparable to that of patients with daytime sleepiness diagnosed as no objective findings and is significantly better than that of patients with insomnia associated with a psychiatric disorder. Significant differences were found in sleep induction, sleep maintenance, and overall sleep efficiency. No major differences were found among any of the groups in terms of sleep staging. All groups showed signs of psychological distress, but as expected this was significantly higher in the patients with insomnia associated with a psychiatric disorder. The fact that patients may present with sleep complaints (either insomnia or daytime somnolence) despite essentially normal sleep has clinical implications. Adequate evaluation of sleep complaints and symptomatic treatment plans are discussed

A Double-Blind Trial of Protriptyline in the Treatment of Sleep Apnea Syndrome

Eight male subjects with sleep apnea syndrome were given placebo and protriptyline in a double-blind crossover design to evaluate the effects of protriptyline on respiration during sleep. Treatment with protriptyline produced significantly better oxygenation and significantly fewer arousals during sleep, but sleep staging was unchanged. The decreased number of respiratory events approached significance and was much greater in six of eight subjects. A rapid eye movement sleep-suppression explanation of the improvement in oxygenation is not supported. Alternative explanations of these findings are discussed

TO THE PROBLEM OF THE TREATMENT OF PANCREATONECROSIS

991 patient with, pancreatonecrosis was studied, in 2000—2011. 224 (22,6 %) of them. died. Males prevailed among all the patients (72,5 %). Average age was 46,9 yeaκ. 802 (85,3 %) patients had. 1—6 episodes of acute panaeatitis in past histoιγ. 51 (5,1 %) patient had. conseirwative treatment (all of them. died, of enzymatic toxemia. 940 (94,9 %) patients had. different operations, 173 (18,4 %) patients died. 6 patients had. 20—22-minutes intraoperational hypothemia of panaeas residuary tissues after nerectomy. Hypothermia was realized with help of either 20—30 ml of chlomethyl oг pieces of 1 kg of melting ice placed, in 2 thin polyethylene bags, and then it lasted for these patients through bursomentostoma during the firs 7—10 days after the opemtion and on the 12—14th and 16—18th days after it

A Dual Role of erbB2 in Myelination and in Expansion of the Schwann Cell Precursor Pool

Neuregulin-1 provides an important axonally derived signal for the survival and growth of developing Schwann cells, which is transmitted by the ErbB2/ErbB3 receptor tyrosine kinases. Null mutations of the neuregulin-1, erbB2, or erbB3 mouse genes cause severe deficits in early Schwann cell development. Here, we employ Cre-loxP technology to introduce erbB2 mutations late in Schwann cell development, using a Krox20-cre allele. Cre-mediated erbB2 ablation occurs perinatally in peripheral nerves, but already at E11 within spinal roots. The mutant mice exhibit a widespread peripheral neuropathy characterized by abnormally thin myelin sheaths, containing fewer myelin wraps. In addition, in spinal roots the Schwann cell precursor pool is not correctly established. Thus, the Neuregulin signaling system functions during multiple stages of Schwann cell development and is essential for correct myelination. The thickness of the myelin sheath is determined by the axon diameter, and we suggest that trophic signals provided by the nerve determine the number of times a Schwann cell wraps an axon

Hypothesis: primary antiangiogenic method proposed to treat early stage breast cancer

<p>Abstract</p> <p>Background</p> <p>Women with Down syndrome very rarely develop breast cancer even though they now live to an age when it normally occurs. This may be related to the fact that Down syndrome persons have an additional copy of chromosome 21 where the gene that codes for the antiangiogenic protein Endostatin is located. Can this information lead to a primary antiangiogenic therapy for early stage breast cancer that indefinitely prolongs remission? A key question that arises is when is the initial angiogenic switch thrown in micrometastases? We have conjectured that avascular micrometastases are dormant and relatively stable if undisturbed but that for some patients angiogenesis is precipitated by surgery. We also proposed that angiogenesis of micrometastases very rarely occurs before surgical removal of the primary tumor. If that is so, it seems possible that we could suggest a primary antiangiogenic therapy but the problem then arises that starting a therapy before surgery would interfere with wound healing.</p> <p>Results</p> <p>The therapy must be initiated at least one day prior to surgical removal of the primary tumor and kept at a Down syndrome level perhaps indefinitely. That means the drug must have virtually no toxicity and not interfere meaningfully with wound healing. This specifically excludes drugs that significantly inhibit the VEGF pathway since that is important for wound healing and because these agents have some toxicity. Endostatin is apparently non-toxic and does not significantly interfere with wound healing since Down syndrome patients have no abnormal wound healing problems.</p> <p>Conclusion</p> <p>We propose a therapy for early stage breast cancer consisting of Endostatin at or above Down syndrome levels starting at least one day before surgery and continuing at that level. This should prevent micrometastatic angiogenesis resulting from surgery or at any time later. Adjuvant chemotherapy or hormone therapy should not be necessary. This can be continued indefinitely since there is no acquired resistance that develops, as happens in most cancer therapies.</p