Dimitrios Tzilves

Increased Cerebrospinal Fluid Helicobacter Pylori Antibody in Alzheimer’s Disease

Background: Helicobacter pylori (H. pylori) infection may play a role in Alzheimers disease (AD). Aim: A prospective, nonrandomized, comparative study was car- ried out to examine the levels of anti-H. pylori-specific IgG antibodies in the cerebrospinal fluid (CSF) and serum of AD patients, compared with those of age-matched cognitively normal controls. Patients: CSF was aspirated from 27 AD patients and 27 age-matched cognitively normal patients with prostate hyperplasia or long-bone fractures necessitating surgery after epidural anesthesia. Serum samples were obtained from AD patients and the day before surgery from controls. Methods: CSF and serum anti-H. pylori IgG concentrations were measured by means of an enzyme-linked immunosorbent assay. Results: The mean concentration of anti-H. pylori-specific IgG was significantly greater in (a) the CSF of AD patients (10.53 ± 12.54 U/mL) than in controls (8.63 ± 8.01 U/mL, p = 0.047), and (b) the serum of AD patients (30.44 ± 33.94 U/mL) than in controls (16.24 ± 5.77 U/mL, p = 0.041). CSF anti-H. pylori IgG antibodies correlated with the degree of severity of the disease. Conclusion: H. pylori-specific IgG antibody levels are significantly increased in CSF and serum of AD; its titer in CSF might reflect the AD severity, thereby supporting a role for this common infection in the pathobiology of the disease.

Helicobacter pylori infection and Parkinson's disease: apoptosis as an underlying common contributor.

Nielsen et al. [1] state that Helicobacter pylori infection (Hp-I) may play an important role in the pathogenesis of Parkinson s disease (PD) by triggering microglia activation through the humeral or vagal afferent pathways. In this regard, apoptotic rather than necrotic microglia-associated nerve cell death appears to underlie a number of common neurological conditions including PD, Alzheimer s disease (AD), glaucoma or multiple sclerosis [2]. The latter diseases are also associated with Hp-I [2–4]; likewise, an association of glaucoma with neurodegenerative diseases (PD and AD) via apoptotic cell death has been reported. Hp, apart from Fas–FasL apoptotic pathway [2], is capable of inducing apoptotic effects through the mitochondrial apoptotic pathway involving the activation of the pro-apoptotic proteins Bax and Bak, activation of certain caspases, or through inducible nitric oxide (NO);NO is a rapidly diffusing gas and a potent neurotoxin that may contribute to apoptotic neuronal cell death in degenerative neuropathies [4], including PD. In particular, increased endothelin-1 (a potent constrictor of arterioles and venules), NO and inducible nitric oxide synthase (iNOS) levels are associated with Hp-I [2]. Relative data in AD indicate that endothelin-1-like immunoreactivity in the AD brains is significantly more increased in frontal and occipital cortex than that in the control brains, thereby explaining the decreased cerebral blood flow in patients with AD. Besides, the synthesis of NO, the peroxynitrite reactive production and the protein tyrosine nitration are activated over the entire chronic course of AD, and the presence of Abeta increases the presence of neuronal NOS and iNOS isoforms over the chronic course of AD in pyramidal-like neurons [2]; NO contributes to mitochondrial fragmentation via S-nitrosylation of dynamin-related protein 1, a protein involved in mitochondrial fission. These findings might provide a new target for drug development in AD.Moreover, redox reactions triggered by excessive levels of NO can contribute to protein misfolding, the hallmark of a number of neurodegenerative disorders, including PD andAD [5]. Finally, apart from humeral and vagal afferent pathways, mentioned by the authors [1], Hp might access brain via oral-nasal-olfactory pathway or by circulating monocytes (possibly infected with Hp owing to defective autophagy) through disrupted blood–brain barrier, leading to neurodegeneration [3].

Low dose of bevacizumab is safe and effective in preventing bleeding episodes in hereditary hemorrhagic telangiectasia.

Low Dose of Bevacizumab Is Safe and Effective in Preventing Bleeding Episodes in Hereditary Hemorrhagic Telangiectasia

Helicobacter pylori might contribute to nonalcoholic fatty liver disease–related cardiovascular events by releasing prothrombotic and proinflammatory factors

ur Tropenmedizin, Infektionskrankheiten und Sektion Nephrologie, Universit€atsmedizin Rostock, Rostock, Germany; Gastroenterologische Schwerpunktpraxis, Cottbus, Germany; Hepatologische Schwerpunktpraxis, Magdeburg, Germany; Klinik f€ ur Gastroenterologie und Infektiologie, E.-v.-Bergmann Klinikum, Potsdam, Germany, III. Medizinische Klinik, Krankenhaus DresdenFriedrichstadt, Dresden, Germany; Klinik f€ur Gastroenterologie und Hepatologie, Klinikum St. Georg GmbH, Leipzig, Germany, Klinik und Poliklinik f€ ur Innere Medizin I, Martin-Luther-Universit€at Halle-Wittenberg, Halle, Germany for the East German HCV Study Group.

Helicobacter pylori infection as an environmental familial clustering risk factor for primary open‐angle glaucoma

thought to reside. Indeed, its benefit remains theoretical. In addition, by using topical antibiotics, their side-effect profile is limited to the local ocular surface to which it is applied. Further studies comparing the long-term effect of prophylactic systemic antibiotic treatment verses prophylactic topical antibiotic treatment in a selection of patients who have a strong history of recurrent chalazia or existing meibomianitis would help to address this question. Furthermore, long-term systemic antibiotic treatment of P. acnes for acne vulgaris has been associated with antibiotic resistance. This problem was found to be more prevalent the longer the antibiotic course. Antibiotic resistance is therefore also likely to become an issue with long-term systemic antibiotic therapy for chalazia.

Association between Helicobacter pylori burden and Alzheimer's disease

Keywords: Alzheimers disease; bacterial infections; cognitive disorders and dementia; infections; mild cognitive impairment; neurological disorders

Helicobacter pylori might be a potential therapeutic target in epilepsy

predict AIS development. Cartilage oligomeric matrix protein (COMP) is essential for the normal development of cartilage and for its conversion to bone during growth. It is expressed at high levels during skeletal development and long bone growth. Mutations in COMP produce clinical phenotypes of pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) [2,3]. These disorders are characterized by disproportionate short stature, brachydactyly, joint hypermobility, earlyonset osteoarthritis, and scoliosis [4]. Interestingly, the phenotypes in PSACH/MED cartilage disorders is not caused by the reduced amount of COMP but rather due to dysfunctional mutated COMP. Abnormal COMP protein cannot be transported out of the cell but rather builds up inside the chondrocyte and it ultimately leads to early chondrocytes death preventing normal bone growth [5]. Recently, in a microarray approach evaluating primary human osteoblasts, we found that COMP is one of the most differentially regulated genes in AIS compared to unaffected individuals [6]. COMP was found to be significantly down-regulated by 4-fold in AIS [6]. Consistent with the microarray analysis, relatively low levels of COMP mRNA transcripts in AIS were detected by RT-qPCR analysis. Altogether, these data suggest that low expression of COMP is associated with AIS. This is the first down-regulated gene described in AIS. Thus, we hypothesized COMP down-regulation would result to a low COMP serum level in AIS patients and this could be an important and novel biomarker in predicting scoliosis development. Supported by The Yves Cotrel Foundation, Institut de France.

Hpn protein as a mediator between Helicobacter pylori infection and Alzheimer’s disease in sub-populations worldwide

Gout is defined as a disorder in which monosodium urate monohydrate (MSU) crystals are deposited in soft tissues, joints, bone, or renal collecting systems, often aggregated into tophi [1]. When these crystals are deposited in synovium they initiate the immune response which causes the severe joint pain and inflammation of a gout flare. Sometimes they are encased in externally visible or palpable subcutaneous tophi, or they cause urolithiasis. In these situations, the gout is termed symptomatic. But the formation of tophi is known to occur in tissue that is not externally visible or palpable. In some cases, their presence has been found to interfere with the proper function of organs, such as the heart [2] and the spine [3]. Symptomatic gout has been reported to occur in 2% of the sleep apnea (SA) population [4]. The hypothesis of this correspondence is that gout occurs in a much larger percentage of the sleep apnea population, but in most cases it is asymptomatic gout, in which the tophi are not visible externally or palpable, and there is no gouty joint pain or sign of urilithiasis.

Greek and Israeli patterns of Helicobacter pylori infection and their association with glaucoma: similarities or diversities?

To the Editor: We read with considerable interest the paper by Kurtz et al that showed no association between Helicobacter pylori infection and the occurrence of glaucoma. Moreover, the possible explanation for the discrepancy of Dr Kurtz et al’s findings and those of our studies stemming from different H. pylori infection occurrence rates between Greece and Israel was attempted to be dispelled by epidemiologic studies that demonstrated that both countries share similar patterns. However, this conclusion is, at least partly, not correct. It has now become clear that the prevalence of H. pylori infection is decreasing owing to the wide use of eradication practices. Over a 10-year period, Apostolopoulos et al, who conducted one of the epidemiologic studies mentioned by Dr Kurtz, found a significant decrease in H. pylori infection in Greece. Likewise, in Tel Aviv, by using the C-urea breath test, broadly used as the noninvasive diagnostic test of choice, having a significantly higher diagnostic accuracy than serology particularly in older subjects, Niv et al also found a rather lower prevalence of H. pylori infection in 33% of the elderly people studied. Surprisingly, Dr Kurtz reported a much higher prevalence of H. pylori infection in his age-matched and ethnicity-matched controls (61.1%). The reason for this tremendous difference in the prevalence of H. pylori infection in the control groups between the studies of Dr Kurtz and Dr Niv may be explained by the extremely small number of subjects (n=36) included in the first study (n=36 vs. n=2128, respectively). More importantly, the authors of the present study observed, again in Tel Aviv, by using C-urea breath test, a seasonal variation in the prevalence of H. pylori infection. Specifically, they found a significant decrease in H. pylori prevalence during the summer (July-September) compared with winter (December-January) (42.3% vs. 60.9%, P<0.007; results from 371 H. pylori-positive participants). According to the results in the present study by Dr Kurtz, all their participants might have been recruited during the winter because they found such a high prevalence of H. pylori infection. On the other hand, had their subjects been recruited mainly in the summer (42.3%), a statistical difference in H. pylori prevalence between their glaucoma patient and controls might have been observed. In any case, the most significant limitation in this study is the very low number of patients enrolled. From another viewpoint, H. pylori positivity in Israel is also associated with ethnic variations [Sephardic (Asian and African origins) versus Ashkenazi (European and American origins)], which should have been taken into consideration to determine the prevalence of H. pylori infection in both glaucoma patients and control subjects. In view of the abovementioned data, the explanation offered by Dr Kurtz for the discrepancy between his and our studies stemming from different H. pylori infection occurrence rates between Greece and Israel was certainly not dispelled by some epidemiologic studies that demonstrated that both countries share similar patterns, as different patterns do exist. With regard to the potential argument that we also used a small number of patients, in our studies H. pylori infection wasmainly determined by histologic detection of the bacteria in mucosal biopsy specimens, considered to be the actual gold standard for the diagnosis of this infection. It is important to note that the serologic test has limitations because it does not discriminate between current and old infections. Such a distinction is essential because current H. pylori infection induces humoral and cellular immune (predominant H. pylori-specific TH1 response with a TH1-type cytokine production leading to gastric epithelial cell apoptotic damage) responses that, owing to the sharing of homologous epitopes (molecular mimicry), crossreact with components of nerves, thereby affecting or perpetuating neural tissue damage including glaucomatous optic neuropathy. Moreover, eradication of H. pylori infection seems to delay glaucoma progression, particularly at early disease stages. Although it was too difficult to obtain consent of our glaucoma patients to be submitted to an upper gastrointestinal endoscopy, we managed to recruit a number of 41 by using this gold diagnostic standard, and thus we consider this number as rather reliable for our conclusions. Similar results to ours were also reported by a study from neighboring Turkey, which also showed a possible relationship between glaucoma and H. pylori infection by using serology. Moreover, differences might exist particularly in the prevalence of pseudoexfoliation glaucoma between Greek and other populations, with a high incidence in Greece and Scandinavia. It would be of interest to know its incidence in Israel (Sephardic or Ashkenazi people) that might reveal further epidemiologic differences or similarities with the Greek glaucoma patients.

Large mesenteric gastrointestinal stromal tumor in a patient with familial adenomatous polyposis syndrome

ZusammenfassungWir stellen den Fall eines 30-jährigen männlichen Patienten vor, der eine ausgeprägte Schwäche, Anämie und Diarrhoe seit 2 Monaten hatte. Bei der Koloskopie fanden sich viele (> 100) Polypen (Familiäres Adenomatöses Polyposis-Syndrom – FAP-Syndrom). Das Abdomen-CT zeigte einen großen Tumorim linken oberen Bauchraum, in der Nähe der linken oberen Kolonflexur. Wir führten eine totale Kolektomie mit Entfernung des mesenterialen Tumors und des angrenzenden Dünndarms mit einer Ileostomie durch. Die Untersuchung des resezierten mesenterialen Tumors zeigte einen stromalen Tumor (GIST) mit seltenen Mitosen und Infiltration des anliegenden Dünndarms. Der vorliegende Fall ist die in der medizinischen Literatur erstmalige Beschreibung der gleichzeitigen Existenz von FAP-Syndrom und GIST bei einem 30-jährigen männlichen Patienten.SummaryWe report a case of a 30-year-old man who presented with severe debilitation, anemia and diarrhea over two months. Colonoscopy revealed many (>100) polyps (familial adenomatous polyposis syndrome). Abdominal CT scan showed a large mass at the left upper abdomen in conjunction with the splenic flexure. Total colectomy with mesenteric mass and adjacent small bowel removal and ileoanal pouch was performed. Examination of the resected mesenteric mass showed a gastrointestinal stromal tumor (GIST) with scarce mitosis and infiltration of the adjacent small bowel. We describe for the first time in medical literature the coexistence of familial adenomatous polyposis syndrome and GIST in a 30-year-old man.