The association between high-density lipoproteins and estimated glomerular filtration rate in patients without severe kidney disease.

PURPOSE: Several studies investigated the association between the estimated glomerular filtration rate (eGFR) and the concentration of high-density lipoproteins (HDL) in patients without severely damaged kidney function. As results of those studies were inconclusive and contradictory, we wanted to investigate this association in multiple cardiovascular disease (CVD) risk patients without severe kidney disease or renal failure. METHODS: We enrolled a cohort of 187 patients with intermediate and high CVD risk without severe renal disease. We grouped them based on their eGFR into: group 1 (≥ 30 < 60 ml/min/1.73 m2), group 2 (≥ 60 < 90 ml/min/1.73 m2) and group 3 (≥ 90 ml/min/1.73 m2). We analyzed the difference between their HDL levels and assessed the association of HDL and eGFR in three regression models with the following predictors: model 1 (age and gender), model 2 (model 1 plus smoking status, hs-CRP and diabetes mellitus) and model 3 (model 2 plus excessive weight and obesity, hypertension, hypercholesterolemia, hypertriglyceridemia, family history of CVD and medications they used). RESULTS: Patients with the lowest eGFR had the lowest HDL values (P = 0.013). In multiple linear regression, HDL was an independent predictor of eGFR (ß = 0.189, P = 0.025) which was also shown in multinomial regression for all three models: model 1 [odds ratio (OR) 0.05; 95% confidence interval (CI) 0.007-0.331; P = 0.002], model 2 (OR 0.052; 95% CI 0.006-0.428; P = 0.006) and model 3 (OR 0.2; 95% CI 0.001-0.309; P = 0.005). CONCLUSIONS: Low HDL is an independent predictor of lower eGFR in intermediate and high CVD risk patients without severe kidney disease. In such patients, low HDL could be one of the early indicators of renal failure.

Ganglioside GM3 content in skeletal muscles is increased in type 2 but decreased in type 1 diabetes rat models: Implications of glycosphingolipid metabolism in pathophysiology of diabetes.

BACKGROUND: Ganglioside GM3 is found in the plasma membrane, where its accumulation attenuates insulin receptor signaling. Considering the role of skeletal muscles in insulin-stimulated glucose uptake, the aim of the present study was to determine the expression of GM3 and its precursors in skeletal muscles of rat models of type 1 and type 2 diabetes mellitus (T1DM and T2DM, respectively). METHODS: Diabetes was induced in male Sprague-Dawley rats by streptozotocin injection (55 mg/kg, i.p., for T1DM induction; 35 mg/kg, i.p., for T2DM induction), followed by feeding of rats with either a normal pellet diet (T1DM) or a high-fat diet (T2DM). Rats were killed 2 weeks after diabetes induction and samples of skeletal muscle were collected. Frozen quadriceps muscle sections were stained with a primary antibody against GM3 (Neu5Ac) and visualized using a secondary antibody coupled with Texas Red. The muscle content of ganglioside GM3 and its precursors was analyzed by high-performance thin-layer chromatography (HPTLC) followed by GM3 immunostaining. RESULTS: Muscle GM3 content was significantly higher in T2DM compared with control rats (P < 0.001). Furthermore, levels of the GM3 precursors ceramide, glucosylceramide, and lactosylceramide were significantly higher in T2DM compared with control rats (P < 0.05), whereas ceramide content was significantly lower in T1DM rats (P < 0.05). The intensity of the GM3 band on HPTLC was significantly higher in T2DM rats (P < 0.001) and significantly lower in T1DM rats (P < 0.05) compared with control. CONCLUSIONS: The expression patterns of GM3 ganglioside and its precursors in diabetic rats suggest that the role of glycosphingolipid metabolism may differ between T2DM and T1DM.

CD44 Immunoexpression is Unfavorable Predictor in Ovarian Serous Cancer.

The aim of this study was to clarify the clinical role of CD44 expression in ovarian serous cancer, and its relation to clinicopathologic prognostic factors, disease free survival and overall survival (OS). Immunohistochemical staining for CD44 was performed on 81 formalin-fixed, paraffin-embedded tumor sections. CD44 expression was found in 43% of ovarian carcinoma samples. Correlations between categorical variables were studied using the χ and the Mann-Whitney U test. For survival analysis, the Kaplan-Meier method, the log-rank test and the Cox proportional hazard regression model were used. We did not find any statistically significant difference in the distribution of respondents according to clinical stage of the disease, tumor grade or the presence of vascular invasion in relation to the expression of CD44. According to the results of uninominal analysis, early International Federation of Gynecology and Obstetrics (FIGO) stage of the disease (P=0.003) was associated with longer disease free survival, while the expression of CD44 (P<0.001), FIGO stage III and IV (P=0.009) and the finding of vascular invasion (P=0.005) was related to a shorter OS. In conclusion, we proved that positive CD44 immunoexpression is a independent prognostic indicator of shorter OS of patients with ovarian serous cancer.

Association of Asymmetric Dimethylarginine With Acute Pancreatitis-Induced Hyperglycemia.

OBJECTIVE: The objective of this study was to investigate the relationship between asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, oxidative-nitrosative damage, and glucoregulation in acute pancreatitis (AP). METHODS: The study evaluated serum levels of ADMA, nitrotyrosine, and urinary 8-hydroxydeoxyguanosine in 40 male patients hospitalized for AP at baseline and at 2 and 10 days of treatment, respectively. The patients were classified into a mild and a moderately severe AP group (MAP and MSAP, respectively) according to Atlanta classification criteria. Glycemic status was evaluated by a 75-g oral glucose tolerance test 1 month after AP onset. Forty age-matched healthy subjects served as control subjects. RESULTS: Significant decrease of ADMA and increased levels of nitrotyrosine and urinary 8-hydroxydeoxyguanosine were found in MSAP, but not in MAP at baseline, with ADMA correction toward control levels at the 10th day of treatment. Fructosamine was found to significantly influence ADMA levels (r = -0.362, P = 0.002). After AP recovery, either impaired glucose tolerance or diabetes was identified with the oral glucose tolerance test in 10.5% and 92.8% of patients with MAP and MSAP, respectively. CONCLUSIONS: Insufficient inhibition of nitric oxide synthesis, through reduced bioavailability of ADMA, might be a novel significant contributory factor to the severity of AP and subsequent development of hyperglycemia.

[Anticoagulant therapy in patients with permanent atrial fibrillation - evidence based medicine and clinical practice]. / Antikoagulantno lijecenje u bolesnika s trajnom fibrilacijom atrija - medicina utemeljena na dokazima i klinicka praksa.

Objective of study was to assess the concordance of the tromboprophylactic treatment in patients with permanent atrial fibrillation (pAF) with guidelines of the European Society of Cardiology. Prospective cross-sectional study consecutivelly included 674 patients (400 S59%C male) discharged from cardiology department with the diagnosis pAF. The thromboembolic risk (TE) has been established according to CHA2DS2-VASc score, whereas the bleeding risk has been assessed according to HAS-BLED score. 578 (86%) belonged to the group of high, 57 (8%) to the group of moderate, and 39 (6%) patients to the group of low TE risk. 601 (89%) patients received thromboprophylaxis: 310 (46%) warfarin, 258 (38%) acetylsalicylic acid, and 33 (5%) patients clopidogrel. Warfarin has been prescribed to 47% of patients with high, 49% of patients with moderate and to 26% of patients with low TE risk (P=0.03). Acetylsalicylic acid (ASA) has equally been prescribed to patients of all TE risk groups: low, moderate and high (39% vs. 39% vs.38%/o; P=0.998). ASA (P<0.001) and warfarin (P=0.007) have been used more frequently in the group of patients with high bleeding risk, in which the same incidence of warfarin and ASA administration has been registered (53% vs. 47%; P=0.416). Age > or =75 has been an independent predictor of non-administration (OR 1.7; 95% CI 1.2-2.4; P=0.003), whereas the history of stroke was for warfarin administration (OR 0.47; 95% CI 0.29-0.76; P-0.002). In prescribing thromboprophylaxis to patients with pAF, cardiologists do not observe the recommended clinical guidelines. Despite nonexistence of contraindications, a significant number of patients with high TE risk has not been administered warfarin. At the same time, warfarin has been administered to the patients with low TE risk, exposing them unnecessarily to the undesired effect of anticoagulant treatment.

[Thromboembolic and bleeding risk assessment in patients with non-rheumatic atrial fibrillation using CHA2DS2-VASc and HAS-BLED scoring systems]. / Procjena tromboembolijskog rizika i rizika od krvarenja u bolesnika s nereumatskom atrijskom fibrilacijom primjenom bodovnih sustava CHA2DS2-VASC i HASBLED.

It is estimated that approximately 1-2% of the world population are affected with non-rheumatic atrial fibrillation (nAF). The most frequent complications of this arrhythmia are thromboembolic events, primarly ischemic stroke. In comparison with patients in sinus rhythm, stroke affected nAF patients have more severe clinical course and significantly higher mortality rate, and the survivors have significantly lower recovery rate and more serious permanent mental and physical impairments. The administration of anticoagulants to patients with nAF significantly reduces the incidence of stroke, while those who were stroke affected during the anticoagulant therapy show better treatment outcomes. Therefore, professional associations guidelines recommend the anticoagulant treatment for the majority of patients with nAF. The fear of bleeding caused by anticoagulants results in their frequently unjustified omission from the therapy in patients with high thromboembolic risk. This paper presents CHA2DS2-VASc- and HAS-BLED systems recommended for thromboembolic and bleeding risk assessment when deciding on thromboprophylactic therapy in patients with nAF.

Influence of hypertension and type 2 diabetes mellitus on cerebrovascular reactivity in diabetics with retinopathy.

BACKGROUND AND OBJECTIVES: Cerebrovascular reactivity (CVR) provides information on the intracerebral arterioles capacity to react to vasodilatory stimuli. The current study aimed to investigate the influence of hypertension and type 2 diabetes mellitus on CVR in diabetics with retinopathy. DESIGN AND SETTING: Retrospective analysis of data prospectively collected over a 1-year period. SUBJECT AND METHODS: Subjects were classified into four groups each comprised of 30 participants: diabetic retinopathy with hypertension (DRH), diabetic retinopathy without hypertension (DR), hypertension without diabetes mellitus (H), and healthy controls without diabetes and hypertension (C). CVR was estimated in relation to the increase in the mean flow velocity compared with the basal velocity in both middle cerebral arteries during hypercapnia. RESULTS: In the DRH group, the mean (SD) increase in CVR was 8.8 (2.49) cm/s, in the H group 14.4 (2.59) cm/s and in the DR group 9.7 (2.97) cm/s. The analysis of variance showed significant differences among the groups in blood flow velocity after a breath-holding test (F=89.83; df=3.116; P < .001). CONCLUSIONS: Diabetes mellitus influences CVR more than hypertension.

Successful endoscopic removal of a lighter swallowed 17 months before.

The majority of ingested foreign bodies will pass safely through the gastrointestinal tract, but long and rigid foreign bodies are associated with an increased risk of gastrointestinal impaction, perforation and bleeding. However, large foreign bodies which have been swallowed can remain trapped in the stomach over a longer period of time without any significant symptoms. This case report describes the case of a 36-year-old man addicted to heroin who purposefully swallowed a lighter (double wrapped in cellophane) and presented with hematemesis and melena 17 months after the ingestion of the foreign body. The lighter was successfully removed via flexible endoscopy using a polypectomy snare. Swallowed long and rigid foreign bodies trapped in the stomach over a long period of time always represent a special clinical and endoscopic challenge. In cases where endoscopic removal fails, a laparoscopic surgical approach may be an alternative.

Gastroesophageal reflux disease and pulmonary function: a potential role of the dead space extension.

BACKGROUND: To evaluate the differences in the existence and size of dead space in patients with and without Gastroesophageal Reflux Disease (GERD and non-GERD) expressed through the size of intrapulmonary shunt (QS/QT). MATERIAL/METHODS: The study enrolled 86 subjects - 43 patients referred for endoscopy because of symptoms of GERD (heartburn, acid regurgitation, dysfagia) and 43 healthy subjects with similar anthropometric characteristics without GERD symptoms. Based on endoscopy findings, patients were classified into the erosive reflux disease (ERD) group and non-erosive reflux disease (NERD) group. Spirometry values, single-breath diffusing capacity of the lung for carbon monoxide (DLCO) and intrapulmonary shunt (venous shunt - QS/QT) determined by the oxygen method were measured in all participants. RESULTS: Statistically significant differences between GERD and non-GERD groups in FVC (p=0.034), FEV1 (p=0.002), FEV1/FVC (p=0.001), and PEF (p=0.001) were observed. There were no statistically significant differences in FEF 25% (p=0.859), FEF 50% (p=0.850), and FEF 75% (p=0.058). Values of DLCO (p=0.006) and DLCO/VA (p=0.001) were significantly lower and QS/QT was significantly higher (p=0.001) in the GERD group than in the non-GERD group. However, in both groups the average values of DLCO and DLCO/VA expressed as a percentage of predictive values were within normal range, while the value of QS/QT in the GERD group showed pathological (6.0%) mean value (normal value ≤ 5.0%). There were no significant differences in respiratory function test results between patients with ERD and NERD. CONCLUSIONS: Our results suggest that microaspiration of stomach contents may cause surfactant damage, development of microatelectasis, and dead space expansion with consequent increase of intrapulmonary (venous) shunt.