Malnutrition risk in hospitalized patients measured with Nutrition Risk Screening 2002 tool and its association with in-hospital mortality.

OBJECTIVE: Malnutrition is related to increased morbidity, mortality, and costs. NRS-2002 is a practical malnutrition risk (MR) screening tool approved by the European Society for Clinical Nutrition and Metabolism (ESPEN) for inpatients. We aimed to reveal the inpatient MR using NRS-2002, and to examine the relationship between MR and in-hospital mortality. PATIENTS AND METHODS: The results of inpatient nutritional screening in a tertiary referral center university hospital were retrospectively analyzed. The NRS-2002 test was used for defining MR. Comorbidities, initial and follow-up anthropometric data, NRS-2002 score, food intake, weight status, and laboratory analysis were examined. In-hospital mortality was noted. RESULTS: Data from 5,999 patients were evaluated. On admission, 49.8% of the patients had MR, and 17.3% had severe MR (sMR). MR-sMR was higher in geriatric patients (62.0-28.5%). Those with dementia had the highest MR (71%), followed by stroke (66%) and malignancy (62%). Age and serum C-reactive protein (CRP) were higher, and body weight, BMI, serum albumin, and creatinine were lower in patients with MR. Multivariate analysis showed that age, albumin, CRP, congestive heart failure (CHF), malignancy, dementia, and stroke were independently associated with MR. The overall mortality rate during hospitalization was 7.9%. MR was associated with mortality regardless of serum CRP, albumin, body mass index (BMI), and age. Half of the patients received nutritional treatment (NT). NT resulted in preserved or increased body weight and albumin levels among patients and the geriatric group with MR. CONCLUSIONS: AMR revealed that NRS-2002 is positive in approximately half of the hospitalized patients, which is associated with in-hospital mortality independent of the underlying diseases. NT is related to weight gain and increased serum albumin.

THE RELATIONSHIP BETWEEN CONGENITAL HEART DEFECTS AND e-NOS GENE IN DOWN SYNDROME.

The aim of the study was to compare the effects of three eNOS gene polymorphisms associated with congenital heart defects, between Down syndrome patients with and without cardiac anomalies. Transthoracic echocardiographic examinations and eNOS single-nucleotide polymorphisms were investigated on seventy-five patients, prospectively. The frequencies of mutant alleles in the eNOS promoter (the -786T/C polymorphism) and exon 7 mutant alleles (the 894G--->T polymorphism) were significantly higher in Down syndrome patients with and without cardiac anomalies. The frequency of the intron GIOT polymorphism did not significantly differ between patients with and without cardiac anomalies. We found a significant relationship between eNOS gene polymorphisms and the congenital heart defects in patients with Down syndrome. Screening for the presence or absence of eNOS polymorphisms may be useful to obtain preliminary data on the risk of congenital heart defects in patients with Down syndrome.

The spectrum of MEFV gene mutations and genotypes in Van province, the eastern region of Turkey, and report of a novel mutation (R361T).

Familial Mediterranean fever (FMF) is the most common hereditary inflammatory periodic disease, characterized by recurrent episodes of fever and abdominal pain, synovitis, and pleuritis. The aim of this study was to determine the frequency and distribution of Mediterranean fever (MEFV) gene mutations in Van province of Eastern Anatolia and to compare them with the other studies from various regions of Turkey. Therefore, we retrospectively evaluated MEFV gene mutations in 1058 pediatric patients with suspected FMF. The MEFV gene mutations were investigated using Sanger sequencing and the multiplex minisequencing technique. We identified 37 different genotypes and 16 different mutations. The four most common mutations and allelic frequencies were M694V (36.50%), E148Q (32.77%), V726A (14.09%), and M694I (4.41%). M694V was the most common mutation, and the M694I frequency was found to be higher compared to studies from other regions of Turkey. In addition, we identified a novel missense mutation (R361T, c.1082G>C) in exon 3 of the MEFV gene in a 12-year-old boy, who had a typical FMF phenotype. In conclusion, this study evaluated the distribution of MEFV gene mutations in children with FMF as the first study conducted in Van province, Eastern Anatolia.

The interaction between actin and FA fragment of diphtheria toxin.

Actin protein has many other cellular functions such as movement, chemotaxis, secretion and cytodiaresis. Besides, it have structural function. Actin is a motor protein that it has an important role in the movement process of toxin in the cell. It is known that F-actin gives carriage support during the endosomal process. Actin is found in globular (G) and filamentous (F) structure in the cell. The helix of actin occurs as a result of polymerisation of monomeric G-actin molecules through sequential rowing, is called F-actin (FA). Actin interacts with a great number of cellular proteins along with cell skeleton and plasma membrane. It is also known that some bacterial toxins have ADP-ribosylation affect on actin. Diphteria toxin is the part which has the FA enzymatic activity corresponding the N-terminal section of the toxin, which inhibits the protein synthesis by ADP-ribosylating the elongation factor 2 in the presence of NAD. FA, taken into the cell by endocytosis inhibits protein synthesis by ADP-ribosyltransferase activity and breaks the cytoskeleton. In the studies both in vitro and in vivo, actin with interaction FA of diphteria toxin has been yet to be fully elucidated. The aim of this study was to determine the three dimensional structures of actin with interaction FA of diphteria toxin by the amprical methods and in paralel with the computing technology, theoretical methods have gained significant importance. In our study, actin with interaction FA of diphteria toxin has been determined as the most possible interaction area with the theoretical method; analogy modelling. This area has been closed in the presence of polypeptides and FA-actin interactions have been tested with the gel filtration chromatography techniques. As a result of the findings, we found that 15 amino acid artificial peptides (DAMYETMAQACAGNR) corresponding to 201-215 amino acid residues of FA interacts with G-actin and closes this area. Secondly, in the model formed with the analogy modelling, it appears that the most possible interaction area is between FA (tyr204) and G-actin (gly48). Results obtained from both theoretical and experimental data support the idea that the interaction occurs in this area.

Evaluation of children with neurobrucellosis.

BACKGROUND: Brucellosis is an endemic disease in many areas throughout the world. Central nervous system involvement is a serious complication of brucellosis with a ratio of 4-11% of all patients. AIM: to describe our experience in diagnosis, treatment, and outcome of 25 pediatric patients with neurobrucellosis. PATIENTS AND METHODS: This study included a review of medical records of patients who were diagnosed with neurobrucellosis between March 2001 and March 2009. Patients who had both clinical findings consistent with neurobrucellosis and positive microbiologic/serologic examinations of CSF with abnormal CSF findings were enrolled in the study. RESULTS: The study included 25 patients between 1 and 15 years of age (mean 8.8 years), while 15 were males and 10 were females. Most of the patients (52 %) were in the age group of 5-9 years with male predominance. The distribution of cases showed density in June and February. The most commonly presented complaints were headache, fever and sweating while the most commonly observed findings were fever and meningeal irritation signs. All patients had positive cerebrospinal fluid agglutination test for brucellosis. Four different regimens were used based on ceftriaxone, doxycycline, cotrimoxasole, streptomycin, and rifampicin. One patient died, three patients were discharged with sequel, and the remaining patients (84 %) were discharged with full recovery. CONCLUSION: Clinicians, especially those providing health services in endemic areas like Turkey, should keep in mind that neurobrucellosis can be involved in patients with unexplained symptoms like memory impairment or in patients diagnosed with meningitis (Tab. 5, Fig, 2, Ref. 39).

Clinical findings in children with cutaneous anthrax in eastern Turkey.

Anthrax is a zoonosis produced by Bacillus anthracis. The aim of this study was to evaluate the clinical findings, therapy, and outcome in children with cutaneous anthrax (CA). Data on age, gender, occupation, clinical symptoms and findings, location and type of lesions, clinical history, laboratory findings, treatment, and outcome were recorded from patients' medical records, retrospectively. The study included 65 patients between 1 month and 18 years old (9.0±4.0 years), 37 patients (56.9%) were male and 28 (43.1%) were female. Most of the patients (89.1%) were admitted in summer and autumn (p<0.001). Of the 65 patients, 20 patients (30.8%) had received antibiotherapy before admission to our hospital. All patients except one had a contact history with infected animals. A 1-month-old patient had a contact history with his mother who had CA. On clinical examination, anthrax edema was noted in 36 (55.3%) patients, anthrax pustule in 27 (41.5%), and anthrax edema and anthrax pustule in two (3%) patients. Gram staining and culture was positive for B. anthracis in 35 (53.8%) patients, and only Gram staining was positive in 10 (15.4%) patients. In the remaining 20 (30.8%) patients, the diagnosis was made by clinical findings. Because the anthrax outbreak in Turkey was associated with slaughtering or milking of ill cows, sheep, or goats, and handling raw meat without taking any protective measures, persons in the community must be educated about using personal protective equipment during slaughtering of animals and handling of meat and skins.

Advances in pemphigus research, signaling, and acantholysis.

Pemphigus is a family of human autoimmune blistering diseases in which pathogenic autoantibodies induce blistering in skin and mucosa. The mechanisms by which pemphigus autoantibodies induce disease in the skin is under active investigation. A large number of cellular events induced in the target keratinocytes by pemphigus IgG have been described and suggest that pemphigus IgG binding to desmogleins trigger a complicated cascade of intracellular signaling and regulatory events. Targeting these intracellular events may prove useful therapeutically.

Intracranial hemorrhage due to vitamin K deficiency in infants: a clinical study.

The hospital records of 30 infants with a diagnosis of intracranial hemorrhage (ICH) due to late onset of vitamin K deficiency, seen during a 5-year period (2001-2005) were retrospectively evaluated. Signs and symptoms of the patients were convulsions (80%), poor sucking (50%), irritability (40%), vomiting (47%), acute diarrhea (33%), and fever (40%). On physical examination there were bulging or full fontanel in 19 patients (63%), collapsed fontanel in one (3%), diminished or absent neonatal reflexes in 11 (37%), pallor in 14 (47%), and cyanosis in one (3%) patient. Gastrointestinal disorder, skin hemorrhagic findings, and epistaxis each were noted in two (7%) patients. All the infants had prolonged prothrombin time (PT) and seven had prolonged activated partial thromboplastin time (APTT), both of which were corrected by the administration of vitamin K. All the infants had ICH, with the most common being intraparenchymal hemorrhage, followed by multiple type ICH (27%). Neurosurgical intervention was performed in five patients (17%). The overall case fatality rate was 33%. In conclusion, we would like to stress that ICH due to vitamin K deficiency in infants is still an important health problem in Turkey resulting in high mortality rate.

A short course of add-on adefovir dipivoxil treatment in lamivudine-resistant chronic hepatitis B patients.

The aims of the study were to investigate the efficacy of rescue therapy with lamivudine (LAM) and adefovir (ADV) combination for 6 months followed by ADV monotherapy in lamivudine-resistant chronic hepatitis B (LAM-R CHB) patients, and to analyze the frequency of ADV resistance mutant development in such patients. A total of 170 consecutive LAM-R CHB patients (male/female: 130/40, mean age: 42.9+/-13.4 years) with viral breakthrough under LAM therapy were analyzed. A total of 68 had HBeAg-positive. Patients received rescue therapy with LAM [100 mg (qd)]+ADV [10 mg (qd)] for 6 months after which LAM was discontinued. HBV-DNA was assessed with the HBV-DNA 3.0 bDNA assay. ADV-resistant mutations were identified by sequencing the reverse transcriptase region. The median duration of rescue therapy was 24 months. Cumulative probability of becoming HBV-DNA undetectable was 33.8%, 59.6% and 68.2% after 24, 48 and 96 weeks of treatment, respectively. These figures were 43.2%, 58.0% and 73.1% for ALT normalization. Among 68 HBeAg-positive CHB patients, 10 patients had an e-antigen seroconversion. Low baseline HBV-DNA level (<10(7) copies/mL) was a significant predictor of response to ADV treatment (P<0.01). Cumulative probability of ADV resistance was 1.2%, 15.1% and 37.3% at 12, 24 and 36 months of therapy, respectively. By multivariate analysis, baseline high viral load and primary nonresponse to treatment at week 24 predicted ADV resistance. The data indicate that a time limited add-on strategy does not provide benefit over the switch strategy with respect emergence of ADV resistant mutants in LAM-R CHB patients.

Clinical trial: insulin-sensitizing agents may reduce consequences of insulin resistance in individuals with non-alcoholic steatohepatitis.

BACKGROUND: Currently, although only a few therapies normalize the liver test abnormalities with/without improving the liver histology, no pharmacologic therapy has proved to be effective for the treatment of non-alcoholic steatohepatitis. AIM: To investigate the role of insulin sensitizers in the treatment of individuals with non-alcoholic steatohepatitis (NASH). METHODS: A total of 74 individuals with NASH (male/female, 44/30; mean age, 47.2 +/- 9.0 years) were enrolled. Participants were divided into two distinct groups: group 1 (n = 25) participants were administered a conventional diet and exercise programme while those in group 2 (n = 49) were administered the diet and exercise programme plus insulin sensitizers. RESULTS: With respect to baseline metabolic, biochemical and histological parameters, no significant differences were observed between the two groups (P > 0.05). Insulin sensitizers significantly improved metabolic parameters (homeostasis model assessment-insulin resistance score, P < 0.05), serum aminotransferase levels [aspartate aminotransferase (AST): 45.9 +/- 24.2 to 33.3 +/- 17.7 IU/L, P < 0.01; alanine aminotransferase (ALT): 78.2 +/- 46.3 to 47.3 +/- 34.5 IU/L, P < 0.001] and histological features (median non-alcoholic fatty liver disease activity score: 5.0-3.0, P = 0.01), while diet and exercise improved serum aminotransferase levels (AST: 39.3 +/- 11.1 to 30.0 +/- 8.6 IU/L, P < 0.01; ALT: 66.9 +/- 28.9 to 42.0 +/- 16.2 IU/L, P < 0.001) at the end of the 48 weeks when compared to baseline. Insulin sensitizers improved the high-sensitivity C-reactive protein levels (P < 0.01). No serious adverse effects of insulin sensitizers were observed. CONCLUSION: Insulin sensitizers can lead to improvement in metabolic, biochemical and histological abnormalities of NASH as a result of improved insulin sensitivity.

Endogenous ADP-ribosylation of eukaryotic elongation factor 2 and its 32 kDa tryptic fragment

Eukaryotic elongation factor 2 (eEF-2) can undergo ADP-ribosylation in the absence of diphtheria toxin. The binding of free ADP-ribose and endogenous transferase-dependent ADP-ribosylation were distinct reactions for eEF-2, as indicated by different findings. Incubation of eEF-2 tryptic fragment 32/33 kDa (32F) with NAD was ADP-ribosylated and gave rise to the covalent binding of ADP-ribose to eEF-2. 32F was revealed to be at the C-terminal by Edman degradation sequence analysis. In our study, the elution of 32F from SDS-PAGE was ADP-ribosylated both in the presence and absence of diphtheria toxin. These results suggest that endogenous ADP-ribosylation of 32F might be related to protein synthesis. This modification appears to be important for the cell function.(AU)

Endogenous ADP-ribosylation of eukaryotic elongation factor 2 and its 32 kDa tryptic fragment

Eukaryotic elongation factor 2 (eEF-2) can undergo ADP-ribosylation in the absence of diphtheria toxin. The binding of free ADP-ribose and endogenous transferase-dependent ADP-ribosylation were distinct reactions for eEF-2, as indicated by different findings. Incubation of eEF-2 tryptic fragment 32/33 kDa (32F) with NAD was ADP-ribosylated and gave rise to the covalent binding of ADP-ribose to eEF-2. 32F was revealed to be at the C-terminal by Edman degradation sequence analysis. In our study, the elution of 32F from SDS-PAGE was ADP-ribosylated both in the presence and absence of diphtheria toxin. These results suggest that endogenous ADP-ribosylation of 32F might be related to protein synthesis. This modification appears to be important for the cell function.

The diagnostic value of on-site cytopathological evaluation and cell block preparation in fine-needle aspiration cytology of liver masses.

OBJECTIVE: The aims of this study were to evaluate the typing accuracy of conventional smear (CS), cell block (CB) preparations and combined use of both procedures (CS + CB) for the diagnosis of hepatic malignancies and to determine whether immediate on-site cytopathological evaluation improves the diagnostic yield of liver fine-needle aspiration cytology (FNAC). METHODS: Ultrasound-guided FNABs were performed on 323 consecutive cases with liver masses between December 2002 and December 2004. Histologically and/or clinically correlated 167 cases were included in the study. Preliminary FNAB results, results of CS, CB, and combined use of CS and CB were compared regarding diagnostic sensitivity, specificity, and accuracy for the diagnosis of malignancy. Subtyping accuracies of different methods were also compared. RESULTS: The sensitivity of on-site cytopathological examination and CS were both 92.8%. The sensitivity of CS + CB was slightly better than that of CB (93.5% versus 84.8%). Specificity of all procedures was achieved 100%. Diagnostic accuracy of on-site cytopathological evaluation, CS, CB, and CS + CB were 93.9%, 93.9%, 87.2%, and 94.5%, respectively. A specific subtype diagnosis of malignant tumours could be rendered accurately on the basis of preliminary diagnosis in 71%, CS in 75.4%, CB in 78.3% and combined approach in 92% of cases. In terms of typing accuracy, 87.5% of HCCs, 93.2% of adenocarcinomas, 92.3% of neuroendocrine carcinomas, 100% of lymphomas and 100% of other malignant tumours were correctly subclassified in the final cytopathological diagnosis. The agreement between preliminary diagnosis and final cytopathological diagnosis was 77.2%. CONCLUSION: With use of on-site cytopathological evaluation and combined use of CS and CB, the diagnostic accuracy of liver tumours approaches 100% and also significantly improve diagnostic and subtyping accuracy of liver malignancies.

Behçet's disease-like presentation of bullous pyoderma gangrenosum associated with Crohn's disease.

A 47-year-old woman presented with a 2-month history of generalized arthralgia and a 10-day history of oral aphthous ulcers. After hospitalization, papulopustular lesions and perianal ulcerations developed. Pathergy test was positive and ophthalmological examination was normal. The presence of oral aphthous ulcers, genital ulcerations, papulopustular lesions and arthralgia, and the positive pathergy test suggested the diagnosis of Behçet's disease (BD). In a few days, positive pathergy reactions and papulopustular lesions evolved into bullous lesions, which were diagnosed dermatopathologically as pyoderma gangrenosum. Two days after the presentation of papulopustular lesions, the patient experienced diarrhoea accompanied by bloody stools and mucus. Histopathological examination of biopsy specimens showed no vasculitis but revealed findings suggestive of Crohn's disease. The patient responded well to treatment with systemic steroids and 5-aminosalicylic acid. Our case demonstrates that the differential diagnosis of BD and inflammatory bowel disease may be perplexing and that these two diseases may be closely related.

Duodenal angiodysplasia: MR angiographic evaluation.

We describe a patient in whom endoscopy failed to determine the origin of gastrointestinal bleeding, and magnetic resonance angiography showed dilated inferior pancreaticoduodenal veins that were considered indirect signs of the duodenal angiodysplasia. Incidentally, a connection between the inferior vena cava and the inferior pancreaticoduodenal veins were also noted. Repeat endoscopy and catheter angiography confirmed the presence of the angiodysplasias.

Differential involvement of ceramide in TNFalpha-mediated activation of NF-kappaB in primary human keratinocytes and HaCaT keratinocytes.

The involvement of ceramide signaling in tumor necrosis factor alpha (TNFalpha) mediated nuclear transcription factor kappa B (NF-kappaB) activation was studied. The cell response modifier ceramide has been shown to modulate apoptosis, cell differentiation and cell proliferation in different cell populations. Sphingomyelin hydrolysis is one pathway generating intracellular ceramide increase. Previously, we could show that TNFalpha induces a ceramide increase in primary human keratinocytes and HaCaT keratinocytes and consequently apoptosis was initiated. It is well known that TNFalpha activates the transcription factor NF-kappaB, but there have been controversial reports on the role of ceramide in TNFalpha-mediated NF-kappaB activation. Here we show by different lines of experimental evidence that TNFalpha is a strong inducer of NF-kappaB in both cell types, whereas C2-ceramide failed to activate NF-kappaB in HaCaT keratinocytes in contrast to primary keratinocytes.

Sphingolipid signaling in epidermal homeostasis. Current knowledge and new therapeutic approaches in dermatology.

In the present review we have attempted to give an overview of the role of sphingolipids in skin homoeostasis. Sphingolipid metabolites are emerging as potent second messengers in diverse cellular signaling pathways. In the skin little is known about sphingolipids in signaling events. In various cell populations it has been shown that different sphingolipid metabolites have opposing effects on the biological outcome of a stimulus. Therefore, the term 'sphingolipid rheostat' has been established and has also been shown to exist in skin-derived cell populations. In many cells ceramide is a mediator of proliferation inhibition and apoptosis, whereas sphingosine-1-phosphate acts more like a growth factor and reverses ceramide effects. In keratinocytes extracellular and intracellular ceramides play important roles. Extracellular ceramides are necessary for the water retention capacity and for maintaining the permeability barrier of the skin. Intracellular ceramides cause differentiation of keratinocytes. Until now less is known about the effect of other sphingolipid metabolites in the skin.