Expression analysis of proteins involved in the non homologous end joining DNA repair mechanism, in the bone marrow of adult de novo myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are characterized by genetic instability which is associated with abnormal DNA repair mechanisms. The most lethal type of DNA damage are double strand DNA breaks (DSBs), which are mainly repaired by Non Homologous End Joining Mechanism (NHEJ), whose core enzyme components include the Ku70/Ku80 heterodimer, DNA–PKcs, XRCC4 and DNA Ligase IV. The aim of the present study was the analysis of expression of proteins required for NHEJ in bone marrow cells of adult de novo MDS and their association with clinical characteristics and prognosis. Our analysis included 48 cases of MDS; 19 RA, 5 RARS, 19 RAEB, 3 RAEB-T, 1 CMML, 1 transformation to AML according to FAB classification. The expression of the enzymes Ku70, Ku80, XRCC4, DNA-PKcs and Ligase IV was determined by Western Blotting. The mean Ligase IV expression value was significantly lower in MDS patients compared to normal controls (0.53 vs. 0.78, p?=?0.03). A negative correlation was found between karyotype risk group and Ligase IV values. (p?=?0.05). Moreover, Ku70 expression levels were significantly lower in patients with a good prognosis karyotype (p?=?0.04). Furthermore, a negative correlation between Ku70 expression values and Hb levels was observed (p?=?0.04). Finally, a positive correlation was observed between enzyme Ku70 expression values and level of blasts (p?=?0.04). Our findings suppor-t a potential role of NHEJ enzyme Ligase IV in the pathogenesis of MDS. Larger numbers of cases need to be screened in order to draw definite conclusion.     

A simple and sensitive GC/MS method for the determination of atropine during therapy of anticholinesterase poisoning in serum samples

Atropine is used in the daily clinical practice for the treatment of poisonings caused by anticholinesterase pesticides, due to its sympathomimetic action. The investigation of the cause of the adverse effects that appear during atropine administration showed the necessity for the development and validation of a simple, rapid, sensitive, and specific method for the determination of atropine levels in serum samples. The developed method includes liquid-liquid extraction with ethyl acetate: dichloromethane (3:1, v/v) and derivatization using N,O-bis(trimethylsilyl)-trifluoracetamide (BSTFA) with 1% trimethylchlorsilane (TMCS) in acetonitrile environment. The method was found to be selective, linear, accurate, and precise according to international guidelines. The recovery was higher than 85.9%, the limit of quantification was 2.00?ng/ml, and the calibration curve was linear within the range of 2.00-500?ng/ml (R(2) ≥?0.992). Accuracy and precision were also calculated and were found to be less than 5.2 and 8.7%, respectively. The developed method was applied in a real case of accidental poisoning with chlorpyrifos in order to determine the atropine serum levels of the patient. The proposed method proved to be useful for the investigation of adverse effects that appear during atropine treatment of patients poisoned by anticholinesterase pesticides and it can also be used for the investigation of poisonings caused after consumption of atropine containing plants.     

Capsule endoscopy retention as a helpful tool in the management of a young patient with suspected small-bowel disease

Capsule endoscopy is an easy and painless procedure permitting visualization of the entire small-bowel during its normal peristalsis. However, important problems exist concerning capsule retention in patients at risk of small bowel obstruction. The present report describes a young patient who had recurrent episodes of overt gastrointestinal bleeding of obscure origin, 18 years after small bowel resection in infancy for ileal atresia. Capsule endoscopy was performed, resulting in capsule retention in the distal small bowel. However, this event contributed to patient management by clearly identifying the site of obstruction and can be used to guide surgical intervention, where an anastomotic ulcer is identified.     

Clinical dimensions of auditory hallucinations in schizophrenic disorders

BACKGROUND: Auditory hallucinations occupy, along with delusional beliefs, the center stage of active or "positive" psychotic clinical psychopathology. During the last decade, several sets of auditory hallucinations' clinical features were subjected to multivariate statistical analyses to disclose major dimensions of psychotic patients' overall hallucinatory experience and behavior. However, these studies failed, to a large extent, to provide satisfactory external validations of the thereby extracted factors. METHODS: We investigated the major clinical dimensions of verbal auditory hallucinations in a sample of 100 inpatients with schizophrenic disorders. Patients (61 men and 39 women) were examined before the initiation of antipsychotic treatment and their assessment included 18 major clinical features of auditory hallucinations. Brief Psychiatric Rating Scale, Hamilton Depression Rating Scale, Global Assessment Scale, and Mini-Mental State Examination were used as external validators. RESULTS: Principal component analysis resulted in the extraction of 5 factors interpreted as the dimensions of severity of auditory hallucinations, emotional and behavioral impact, rate of their intrusion in self-consciousness, delusional elaboration, and similarity to ordinary auditory perception, respectively. The second and third factors extracted in our study correlated with short duration of illness, whereas the first, fourth, and fifth ones correlated with chronicity. Our second factor correlated with clinical severity of patients' current mental state, the fifth factor with severity of their cognitive impairment, and the first and fourth ones with lower clinical depression despite patients' chronicity. CONCLUSION: The findings of our study contribute to the further elucidation of the major clinical dimensions of auditory hallucinations and the testing of their external validity.     

Parallel manifestation of Crohn’s disease and acute pericarditis: a report of two cases

Pericarditis is an uncommon extraintestinal manifestation of inflammatory bowel disease (IBD), which may occur at any time during its natural course. Moreover, it may be associated with the medications used to treat IBD, especially mesalamine. We report on two patients with acute pericarditis who were subsequently diagnosed with Crohn’s disease. It is likely that mild, longstanding, virtually asymptomatic intestinal disease preceded the onset of pericarditis in both cases.     

Expression of ets-1 is not affected by N-ras or H-ras during oral oncogenesis

PURPOSE: To determine whether ras-activated cascades lead to activation of ets-1 expression in sequential histological stages of oral oncogenesis in an experimental animal model. METHODS: Thirty-seven Syrian golden hamsters were divided into three experimental groups (A, B, C) and one control group. The hamsters' buccal pouches in experimental groups were treated with 0.5% 9, 10-dimethyl-1, 2-benzanthracene (DMBA) for 14 weeks and were excised at 10, 14, 19 weeks, respectively. The biopsies were classified pathologically (normal mucosa, hyperkeratosis, hyperplasia, dysplasia, early invasion, well and moderately differentiated carcinoma) and studied immunohistochemically. The two-tailed Student's t test was performed for each animal group and for each histological category. RESULTS: The ets-1 expression increased in early stages of oral tumor formation and invasion. The expression of N-ras gradually decreased during oral oncogenesis, as previously observed with H-ras. CONCLUSIONS: Neither N-ras nor H-ras affects ets-1 expression in contrast to other types of cancer in which N-ras and ets-1 are implicated in the same signalling pathway. Therefore, the existing pathway implicating these proteins might be somehow altered in oral cancer. It seems that ets-1 is a good prognostic marker for invasiveness and progression of oral cancer.     

Two cases of synovitis, acne, pustulosis, osteitis--SAPHO syndrome

Synovitis, acne, pustulosis, osteitis (SAPHO) syndrome is rare with yet unknown prevalence. The difficulty in recognizing the syndrome is due to the very wide diversity of its signs and symptoms, the lack of skin manifestations in many cases and to confusion in medical terminology in describing this syndrome. In this paper, we present two cases with characteristic bone lesions in bone scan and in radiology images that are considered to be SAPHO syndrome. In the first case the characteristic bone single photon emission tomography scan findings in a patient with spine involvement supposed by bone biopsy but were not followed by characteristic skin manifestations. The point of interest of this case lies on the significant improvement of both symptoms and scintigraphic findings after treatment with biphosphonates. In the second case the diagnosis was also based on the characteristic bone scan findings, although the patient referred to us for staging of prostate cancer. Detailed history and clinical examination revealed skin manifestations of the syndrome.     

Strongyloides stercoralis in a bronchial washing specimen processed as conventional and Thin‐Prep smears: Report of a case and a review of the literature

Strongyloidiasis is an opportunistic infection which may result in a fatal hyperinfection syndrome in immunocompromised patients. We report the case of a pulmonary infection with Strongyloides stercoralis in a 61‐year‐old male with a history of a long‐term administration of corticosteroids. Cytologic examination of a bronchial washing specimen, processed both as conventional and as Thin‐Prep smears, revealed an abundance of the typical larvae of Strongyloides stercoralis, amidst a cellular population comprising several acute inflammatory cells as well as bronchial epithelial cells with features of basal cell hyperplasia or regenerative atypia. To the best of our knowledge there is only one previous report describing Strongyloides stercoralis in thin‐layer smears, and there are no previous studies comparing its morphology in conventional and thin‐layer preparations. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.