Esophagus-Related Symptoms in First-Degree Relatives of Patients with Achalasia: Is Screening Necessary?

Background: Despite an increasing understanding of the pathophysiology of achalasia, the etiology of this esophageal motility disorder remains largely unknown. However, the occurrence of familial achalasia, its association with well-defined genetic syndromes, the candidate gene approach, and recent presentation of the first systematic genome-wide association study on achalasia suggest the involvement of genetic factors.

Methods: In this study we analyzed the frequency with which symptoms associated with esophageal function (swallowing difficulties, regurgitations, retrosternal cramps/pain, heartburn) occur in first-degree relatives of patients with achalasia to determine if screening is useful and justified against the background of early diagnosis in a genetically predisposed population.

Comprehensive epidemiological and genotype-phenotype analyses in a large European sample with idiopathic achalasia.

Background And Aim: Although an eight-residue insertion in HLA-DQβ1 has been recently identified as a genetic risk factor for idiopathic achalasia, other risk factors are still unknown. In the present study, we carried out an epidemiological survey and a genotype-phenotype (G×P) analysis to gain further insights into the etiology of achalasia.

Methods: We obtained medical data from 696 achalasia patients and 410 controls, as well as their first-degree relatives (2543 of patients and 1497 of controls).

Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia.

Idiopathic achalasia is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. This ultimately leads to massive dilatation and an irreversibly impaired megaesophagus. We performed a genetic association study in 1,068 achalasia cases and 4,242 controls and fine-mapped a strong MHC association signal by imputing classical HLA haplotypes and amino acid polymorphisms.

Murine genetic deficiency of neuronal nitric oxide synthase (nNOS(-/-) ) and interstitial cells of Cajal (W/W(v) ): Implications for achalasia?

Background And Aim: Nitric oxide (NO) is an important inhibitory mediator of esophageal function, and its lack leads to typical features of achalasia. In contrast, the role of intramuscular interstitial cells of Cajal (ICC-IM) and vasoactive intestinal peptide (VIP) in lower esophageal sphincter (LES) function is still controversial. Therefore, we examined the function and morphology of the LES in vivo in NO-deficient (nNOS(-/-) ), ICC-IM-deficient (W/W(v) )-, and wild-type (WT) mice.

Achalasia: will genetic studies provide insights?

Despite increasing understanding of the pathophysiology of achalasia, the etiology of this esophageal motility disorder remains largely unknown. However, the occurrence of familial achalasia and its association with well-defined genetic syndromes suggest the involvement of genetic factors. Mutant mouse models display gastrointestinal disturbances that are similar to those observed in achalasia patients.

[Virus persistence in hepatitis C: lifelong infection despite therapy?].

Background: Chronic hepatitis C infection still represents a clinical and scientific challenge. Exciting progress has been achieved by the use of combined therapy regimens with pegylated interferon and ribavirin resulting in sustained virological response rates of 60-80%, depending on the genotype.

Virus Persistence Despite Successful Therapy: Despite favorable longterm data with regard to viremia, liver histology and serum liver enzymes in treated patients who comply with the criteria of sustained virological response, a complete elimination of the hepatitis C virus (HCV) is rarely observed.

Thalidomide induces apoptosis in human monocytes by using a cytochrome c-dependent pathway.

Thalidomide has been shown to be an effective treatment in various immunologic diseases such as Crohn's disease and rheumatoid arthritis. Its major effect is thought to be mediated by the inhibition of TNF-alpha, but the exact mechanism of action is still uncertain. Recent observations could demonstrate that the induction of monocyte apoptosis is a common feature of a variety of anti-inflammatory agents.

Angiogenic effects of interleukin 8 (CXCL8) in human intestinal microvascular endothelial cells are mediated by CXCR2.

Angiogenesis plays a critical role in metastasis and tumor growth. Human tumors, including colorectal adenocarcinoma, secrete angiogenic factors, inducing proliferation and chemotaxis of microvascular endothelial cells, eventually leading to tumor neovascularization. The chemokine interleukin 8 (IL-8; CXCL8) exerts potent angiogenic properties on endothelial cells through interaction with its cognate receptors CXCR1 and CXCR2.