Laparoscopic mesh-augmented hiatoplasty without fundoplication as a method to treat large hiatal hernias

PURPOSE: Laparoscopic hiatal hernia repair with additional fundoplication is a commonly recommended standard surgical treatment for symptomatic large hiatal hernias with paraesophageal involvement (PEH). However, due to the risk of persistent side effects, this method remains controversial. Laparoscopic mesh-augmented hiatoplasty without fundoplication (LMAH), which combines hiatal repair and mesh reinforcement, might therefore be an alternative. METHODS: In this retrospective study of 55 (25 male, 30 female) consecutive PEH patients, the perioperative course and symptomatic outcomes were analyzed after a mean follow-up of 72 months. RESULTS: The mean DeMeester symptom score decreased from 5.1 to 1.8 (P < 0.001) and the gas bloating value decreased from 1.2 to 0.5 (P = 0.001). The dysphagia value was 0.7 before surgery and 0.6 (P = 0.379) after surgery. The majority of the patients were able to belch and vomit (96 and 92 %, respectively). Acid-suppressive therapy on a regular basis was discontinued in 68 % of patients. In 4 % of patients, reoperation was necessary due to recurrent or persistent reflux. A mesh-related stenosis that required endoscopic dilatation occurred in 2 % of patients. CONCLUSIONS: LMAH is feasible, safe and provides an anti-reflux effect, even without fundoplication. As operation-related side effects seem to be rare, LMAH is a potential treatment option for large hiatal hernias with paraesophageal involvement

Mysterious α6-containing nAChRs: function, pharmacology, and pathophysiology

Neuronal nicotinic acetylcholine receptors (nAChRs) are the superfamily of ligand-gated ion channels and widely expressed throughout the central and peripheral nervous systems. nAChRs play crucial roles in modulating a wide range of higher cognitive functions by mediating presynaptic, postsynaptic, and extrasynaptic signaling. Thus far, nine alpha (α2-α10) and three beta (β2, β3, and β4) subunits have been identified in the CNS, and these subunits assemble to form a diversity of functional nAChRs. Although α4β2- and α7-nAChRs are the two major functional nAChR types in the CNS, α6*-nAChRs are abundantly expressed in the midbrain dopaminergic (DAergic) system, including mesocorticolimbic and nigrostriatal pathways, and particularly present in presynaptic nerve terminals. Recently, functional and pharmacological profiles of α6*-nAChRs have been assessed with the use of α6 subunit blockers such as α-conotoxin MII and PIA, and also by using α6 subunit knockout mice. By modulating DA release in the nucleus accumbens (NAc) and modulating GABA release onto DAergic neurons in the ventral tegmental area (VTA), α6*-nAChRs may play important roles in the mediation of nicotine reward and addiction. Furthermore, α6*-nAChRs in the nigrostriatal DAergic system may be promising targets for selective preventative treatment of Parkinson's disease (PD). Thus, α6*-nAChRs may hold promise for future clinical treatment of human disorders, such as nicotine addiction and PD. In this review, we mainly focus on the recent advances in the understanding of α6*-nAChR function, pharmacology and pathophysiology

Modulation of hippocampus-dependent learning and synaptic plasticity by nicotine

A long-standing relationship between nicotinic acetylcholine receptors (nAChRs) and cognition exists. Drugs that act at nAChRs can have cognitive-enhancing effects and diseases that disrupt cognition such as Alzheimer's disease and schizophrenia are associated with altered nAChR function. Specifically, hippocampus-dependent learning is particularly sensitive to the effects of nicotine. However, the effects of nicotine on hippocampus-dependent learning vary not only with the doses of nicotine used and whether nicotine is administered acutely, chronically, or withdrawn after chronic nicotine treatment but also vary across different hippocampus-dependent tasks such as the Morris water maze, the radial arm maze, and contextual fear conditioning. In addition, nicotine has variable effects across different types of hippocampal long-term potentiation (LTP). Because different types of hippocampus-dependent learning and LTP involve different neural and molecular substrates, comparing the effects of nicotine across these paradigms can yield insights into the mechanisms that may underlie the effects of nicotine on learning and memory and aid in understanding the variable effects of nicotine on cognitive processes. This review compares and contrasts the effects of nicotine on hippocampus-dependent learning and LTP and briefly discusses how the effects of nicotine on learning could contribute to nicotine addictio