Importance of arterial stiffness in predicting cardiovascular events.

INTRODUCTION: Cardiovascular events represent an important cause of morbidity and mortality in the entire population. Arterial stiffness is currently considered one of the most important risk factors for the development of cardiovascular events. The gold-standard for evaluating arterial stiffness is pulse wave velocity (PWV). Recent studies have demonstrated that PWV is an independent risk factor regarding the development of cardiovascular events, especially in certain categories of patients. MATERIAL AND METHODS: The development of cardiovascular events was assessed in 174 patients admitted in the Center of Internal Medicine, Fundeni Clinical Institute, between January 2011 - May 2012. Arterial stiffness was evaluated by measuring PWV using the Sphygmocor system (AtCor, Australia), which is based on the principle of applanation tonometry. The patients were monitored for the development of cardiovascular events (ischemic heart disease, heart failure, stroke, acute myocardial infarction) and for death of cardiovascular cause, over a median period of 51.5 months (43-60 months). RESULTS: Of the 174 patients, 81 (46.6%) were women and 93 (53.4%) were men. Mean age was 55.96 years. 93 of the 174 patients had chronic kidney failure in different stages (47.3% in stage V). Regarding PWV in the patient group, we obtained a mean score of 9.382. We observed a significant difference regarding the PWV level only for acute myocardial infarction and death between patients who developed these events and those who did not. CONCLUSIONS: Our study demonstrates that PWV increase can be positively associated with the occurrence of cardiovascular events, particularly in certain groups of patients.

The effect of caffeine on cerebral asymmetry in rats.

EEG recordings reflect the gross electrical activity emanating from synaptic currents of individual neurons across large cortical areas. During periods of cortical activation, waking, and higher EEG frequencies, neurons display increased excitability and exhibit more asynchronous discharge. The activity of a number of subcortical neurotransmitter systems from several brain regions outside the thalamus can directly affect cortical activity patterns. These neurotransmitter systems are generally targets of pharmacological intervention or participate in neurological disease states. The EEG trace comprises 4 primary rhythms: alfa (α), beta (ß), theta (θ) and delta (δ), which differ in frequency and amplitude. Caffeine effect on brain asymmetry will be studied in this work. The study was realized by means of Fourier spectral frequency analysis (Fast Fourier Transformation) of the EEG signal on anesthetized rats. All 3 doses of caffeine increased the global wave power of brain activity compared to the control group. All 3 doses of caffeine reduced the number of peaks for the 0.5-4 Hz frequency band, with the intermediate dose of caffeine having such an effect in the 4-7 Hz frequency band and the high dose of caffeine for the 23-33 Hz frequency band. The group that received high doses of caffeine showed an increase of the percentage of delta waves, with a concurrent decrease of the percentage of alpha1, alpha2, beta and theta 2 compared to the control group. Low-dose caffeine produced positive values of left-right difference in brain electrical activity (left predominance) for the 0.5-5 Hz and 7.8-10.3 Hz frequency intervals. The group that received high-dose caffeine exhibited a left hemisphere dominance for the 0.5-1.5 Hz; 13.9-14.1 Hz and 19-20 Hz frequency ranges while right dominance was present in the 1.7-13.9 Hz, 15-19 Hz and 21-25 Hz frequency ranges. In conclusion, all doses of caffeine modified the global power of the brain as well as the number of peaks on the frequency range of 0.5-4 Hz. The higher dose of caffeine modified the percentage of alpha 1, alpha2, beta, delta and theta2 waves compared to the control group. The group that received 150 mg caffeine/ kg.b.w. recorded a reversal in the cerebral asymmetry of rats in the 1.7-13.9 Hz, 15-19 Hz and 21-25 Hz frequency ranges.

Efficacy of long-term low-dose sulodexide in diabetic and non-diabetic nephropathies.

BACKGROUND AND AIMS: Sulodexide has been reported to have antiproteinuric and nephroprotective properties. We investigated the effects of long-term low-dose Sulodexide on proteinuria and renal function in patients with chronic kidney disease (CKD) caused by diabetic nephropathy (DN), hypertensive nephropathy (HN) and primary glomerulonephritis (GN). MATERIAL AND METHODS: 100 patients with CKD received low-dose Sulodexide 50 mg/day for 12 months. Treatment efficacy was evaluated as proteinuria reduction compared to baseline; response was defined as a decline in proteinuria below 0.3 g/d. Renal function evolution was assessed by eGFR variation from baseline. RESULTS: All patients presented reduction of proteinuria, with global mean value of proteinuria decrease of 0.85 +/- 1.34 g/d (p<0.0001). Patients with HN had the highest mean percentage of proteinuria reduction (73 +/- 29%) and the lowest mean time period to achieve responder status (6.6 +/- 2.4 months), compared to patients with DN (57 +/- 29%, 8 +/- 2.9 months) and GN (63 +/- 24%, 10.7 +/- 1.2 months). Renal function as mean eGFR remained stable or improved during the study; significant increase was found only in HN group (3.41 +/- 6.38 ml/min/1.73 m2, p=0.043). Multivariate regression analysis identified that responder status was significantly associated with gender, baseline eGFR, baseline proteinuria and etiology of CKD. Concomitant administration of ACEIs or/and ARBs did not influence the response to Sulodexide therapy. CONCLUSIONS: Independently of ACEIs or/and ARBs therapy, long-term low-dose Sulodexide is efficient as antiproteinuric and renoprotective therapy in patients with CKD caused by DN, GN and HN. Better response is achieved in patients with lower degree of renal dysfunction.

Dermatoscopic and Histopatological Aspect of Preneoplasia and Skin Cancers - Study on 74 Patients.

Dermoscopy is an important in-vivo, non-invasive diagnostic technique that allows visualization of morphological features not macroscopic visible. It has a major contribution in enhancing the diagnostic accuracy for pigmented skin lesions. Recent studies have shown that it also aids in the diagnosis of non-pigmented keratinizing skin lesions, including actinic keratosis and Bowen's disease. We performed a retrospective study in Dermamed Clinic Craiova, between January and June 2014, with the aim to correlate the dermoscopic and histopathological aspect of skin tumors. This study included a total of 74 patients, aged between 16 and 76 years. The dermatoscopic examination revealed 12 skin cancers, 51 precancerous lesions and 11 benign tumors. Those 12 subjects diagnosed with malignant tumors by dermatoscopic examination, had also histopathological examination and confirmation of the diagnosis, also 11 patients identified with benign tumors with dermatoscopic examination were subsequently confirmed by histopathological assesment. Out of the 51 patients with premalignant tumors, 48 patients had histopatological confirmation of it, and for 3 patients the result was squamous cell carcinoma. Thus dermatoscopic examination identified the malignant lesions with a specificity of 100% and a sensitivity of 80% with a positive predictive value of 100% and a negative predictive value of 94.12%, p<0.000.

Molecular and pharmacodynamic interactions between caffeine and dopaminergic system.

Many drugs targeting dopaminergic system were developed for treating schizophrenia (antagonists of D2 dopaminergic receptors, e.g. antipsychotics) or Parkinson' disease (agonists of dopaminergic receptors, e.g. L-DOPA). Because many of the patients treated with these drugs consume caffeine based beverages, pharmacodynamics and pharmacokinetics interactions between caffeine and dopaminergic system or drugs influencing this system are possible. The present review is assessing the current available scientific data on pharmacodynamics interactions between the dopaminergic and adenosinergic system but also on caffeine and dopaminergic system interactions. Caffeine can significantly improve Parkinson's disease symptoms but also the extrapyramidal syndrome induced by antipsychotics via dopaminergic pathways. No study so far has directly evaluated the influence of caffeine in schizophrenia, but there is growing evidence that adenosine dysfunction may contribute to the neurobiological and clinical features of schizophrenia. Caffeine has also effects on the reward system but it seems that this effect does not involve dopaminergic system. Caffeine has some endocrine effects via dopaminergic system such as decreasing the milk production in lactating women or other potential reproductive and nutritional consequences.

Current therapies in hepatorenal syndrome.

Hepatorenal syndrome (HRS) is a serious complication of liver cirrhosis with critically poor prognosis. The pathophysiologic hallmark is severe renal vasoconstriction, resulting from complex changes in splanchnic and general circulations as well as systemic and renal vasoconstrictors and vasodilators. Rapid diagnosis and management are important, since recent treatment modalities including vasoconstrictor therapy can improve short-term outcome and buy time for liver transplantation, which can result in complete recovery.

Comparison of three algorithms of non-invasive markers of fibrosis in chronic hepatitis C.

BACKGROUND: Preliminary data suggest that performance of non-invasive markers for liver fibrosis in hepatitis C may improve when combined. Three algorithms based on the combination of Fibrotest, Forns' index and AST-to-platelet ratio (APRI) have been proposed: Sequential Algorithm for Fibrosis Evaluation (SAFE biopsy); Fibropaca algorithm; Leroy algorithm. AIM: To compare three algorithms to diagnose significant fibrosis (≥ F2 by METAVIR) and cirrhosis (F4). METHODS: A total of 1013 HCV monoinfected cases undergoing liver biopsy were consecutively enrolled in seven centres. Fibrotest, APRI and Forns' index were measured at the time of liver biopsy, considered the reference standard. RESULTS: Overall, performance of combination algorithms was significantly higher than the single non-invasive methods (P < 0.0001). SAFE biopsy and Fibropaca algorithm saved a significantly higher number of liver biopsies than the single methods (P < 0.0001). For ≥ F2, Fibropaca algorithm saved more biopsies than SAFE biopsy (51.7% vs. 43.8%, P = 0.0003), but with lower accuracy (87.6% vs. 90.3%, P = 0.05). Regarding F4, the number of saved liver biopsies did not differ between SAFE biopsy and Fibropaca algorithm (79.1% vs. 76.2%, P = 0.12). However, SAFE biopsy showed a lower accuracy when compared with Fibropaca algorithm (91.2% vs. 94%, P = 0.02). As to Leroy algorithm, although it showed a good performance for ≥ F2 (93.5% accuracy), it saved less liver biopsies than SAFE biopsy and Fibropaca algorithm (29.2% vs. 43.8% and 51.7% respectively, P < 0.0001). CONCLUSIONS: SAFE biopsy and the Fibropaca algorithm have excellent performance for liver fibrosis in hepatitis C, allowing a significant reduction in the need for liver biopsies. They can be useful in clinical practice and for large-scale screening.

The impact of liver disease aetiology and the stages of hepatic fibrosis on the performance of non-invasive fibrosis biomarkers: an international study of 2411 cases.

BACKGROUND: Performance of non-invasive fibrosis biomarkers may be influenced by aetiology of chronic liver disease (CLD) and the stages of hepatic fibrosis, but large-scale studies are pending. AIM: To investigate the effect of aetiogy and stages of hepatic fibrosis on the performance of fibrosis biomarkers. METHODS: A total of 2411 patients with compensated CLD (HCV=75.1%, HBV=10.5%, NASH=7.9%, HIV/HCV=6.5%) were consecutively enrolled in 9 centres. APRI, Forns'index, Lok index, AST-to-ALT ratio, Fib-4, platelets and Fibrotest-Fibrosure were tested against liver biopsy, considered the gold standard. The effect of the stages of hepatic fibrosis to diagnose significant fibrosis and cirrhosis (≥F2 and F4 respectively) was investigated through difference between advanced and non-advanced fibrosis stages (DANA). Performance was expressed as observed area under the ROC curve (ObAUROC) and AUROC adjusted for DANA (AdjAUROC). RESULTS: Performance of APRI and Fibrotest-Fibrosure was higher than other biomarkers. In all aetiologies, AdjAUROC was higher than ObAUROC. APRI showed its best performance in HCV monoinfected cases, with an AdjAUROC of 0.77 and 0.83 for ≥F2 and F4 respectively. In HBV and non-alcoholic steatohepatitis (NASH) patients, its performance was poor (AdjAUROC <0.70). Performance of Fibrotest-Fibrosure was good in all aetiologies for both ≥F2 and F4 (AdjAUROC >0.73), except for ≥F2 in NASH (AdjAUROC = 0.64). Performance of all biomarkers was reduced in HCV cases with normal ALT. CONCLUSIONS: Aetiology is a major factor influencing the performance of liver fibrosis biomarkers. Even after correction for DANA, APRI and Fibrotest-Fibrosure exhibit the best performance. However, liver biopsy is not replaceable, especially to diagnose ≥F2 and in HCV carriers with normal ALT.

Early virological response in 1220 patients with HCV (genotype lb) chronic hepatitis and cirrhosis treated with PegInterferon plus Ribavirin.

UNLABELLED: There are over 5000 patients with genotype 1b HCV chronic infection in Romania on national waiting lists. This allowed us to evaluate the complete and partial early virological response rates (EVRc and EVRp), as well as the factors influencing the response rates to treatment. PATIENTS: We studied 1220 treatment naive patients with HCV chronic hepatitis who started antiviral therapy during 2009. Mean age was 48 years and female gender was predominant (58%). Chronic hepatitis was documented by liver biopsy in 1129 patients (93%) or by non-invasive tests in 91 cases (7%). Most patients presented advanced liver disease (F3 + F4 Metavir = 62.3%). Viral load was over 400000 iu/mL in 61% patients and over 600000 iu/mL in 52% patients. Treatment was performed with peginterferon alpha-2a in 75.2% patients and with peginterferon alpha-2b in 24.8% patients, with comparative histology. The influence of histology, viral load, gender, age and type of peginterferon on the response rates to treatment was evaluated. RESULTS: EVRc was obtained in 76.6% patients, while 16.2% presented EVRp. From those with EVRp, 78.8% had undetectable viral load after 6 months of therapy. The nonresponder rate was 9.6%. EVRc was influenced by viral load and age, but not by fibrosis stage or type of interferon. CONCLUSIONS: We noticed a high rate of EVRc, which was not influenced by histology, gender or type of interferon. The number of nonresponders and of patients who interrupted therapy due to lack of compliance or adverse events was low.

Pneumoperitoneum--rare complication in end stage renal disease patient on automated peritoneal dialysis.

Peritoneal dialysis (PD) is the first option for patients in end stage renal disease (ESRD). Several complications such as peritonitis, exit-site or tunnels infections are encountered during PD. Other complications such as pain, proteic malnutrition, hyperglycemia, hypertension, cardiac failure are described in patients on continuous ambulatory peritoneal dialysis (CAPD) or APD (automated peritoneal dialysis). Rare complications are incapsulated sclerosing peritonitis, hemoperitoneum or pneumoperitoneum. We present the case of a female patient, 66 years old, on cyclic continuous peritoneal dialysis (APD-CCPD) admitted for pneumoperitoneum developed during a dialysis change from a CCPD schedule, due to an error in the Tenckhoff catheter and peritoneal dialysis manipulation. The treatment consisted in extracting the air during manual peritoneal dialysis changes, with the patient in Trendelenburg position and pressing on the abdominal wall, without any other complications.

Recurrent spontaneous pneumothorax in renal transplantation.

Renal transplantation could be associated with severe complications. Pneumothorax is a rare and severe complication among renal transplant recipients. The relationship between pneumothorax and post transplantation status, pulmonary infections or immunosuppressive treatment is controversial. We report the case of a young female with normal renal graft function who developed recurrent pneumothorax after three years of kidney graft.

Frequency and prognostic significance of QT prolongation in chronic renal failure patients.

Cardiovascular mortality and morbidity are high in chronic renal failure (CRF) patients. Previous studies on non-uraemic patients with heart failure (HF), hypertension or diabetes mellitus (DM) showed that QT and QTc prolongation and dispersion represent cardiovascular risk factors. The patients with long QT interval have more often ventricular premature beats and sudden death than those with normal QT interval. The aim of our study was to evaluate the frequency and predictive value of QT and QTc prolongation in CRF patients, included or not in a chronic dialysis programme. On 68 patients (M/F = 36/32, mean age = 47.6 years), with CRF we analyzed QT and QTc interval with a digital 12 lead electrocardiogram-CARDIAX. 8/68 patients (11.8%) had long QT interval (>0.45"). After having calculated QT corrected (QTc) interval according to the heart rate, 28/68 patients (41.2%) had QT prolongation (>0.45"). Multivariate statistical analysis of clinical factors, but also of biological, electrocardiographic, echocardiographic data and 24 hours of ECG and blood pressure monitoring showed that QT prolongation is statistically significant (p < 0.05) correlated with: number of years of renal failure (p = 0.0001), serum concentrations of potassium and calcium (p = 0.0001) and diastolic BP (p = 0.05). QT prolongation in CRF patients is not dependent on the level of uremia or the type of chronic renal substitution (hemodialysis or continuous ambulatory peritoneal dialysis). There were no statistically significant correlations between QT prolongation and serum concentrations of Mg, PO4, HCO3 and Hb. Long QT interval was not dependent either on the dipper/nondipper profile of mean BP values or ejection fraction of left ventricle. In our study long QT interval was not statistically significant correlated with arrhythmias or sudden death. Despite the high incidence of QT prolongation in CRF patients (41.2%), short-term consequences are not as severe as those in cardiac patients. This is possibly explained by the different pathogenic mechanisms of arrhythmia in CRF when electrolytic disorders are the main cause for the development of arrhythmia. During a mean follow-up of 3.8 months (3-5.5) there were no cases of sudden death on patients with QT prolongation, and arrhythmia incidence was not statistically significant higher than in subjects with normal QT interval.

Therapeutic efficiency of continuous renal replacement therapy--experience of a single Romanian center.

We have studied 24 patients with acute renal failure (ARF) or acutization of chronic renal failure (CRF) caused by a variety of different disorders. A rapid decline in renal excretory function, fluid, electrolyte, and divalent ion disturbances determined us to initiate continuous renal replacement: continuous venovenous hemofiltration (CVVHF)--28 procedures in 15 patients and continuous venovenous hemodiafiltration (CVVHDF)--11 procedures in 11 patients. Mean duration of CVVHF was 21.6+/-6.9 h, with a mean blood flow rate of 116.9+/-16.4 ml/min and an ultrafiltration rate of 6.4+/-4.6 ml/min. Serum creatinine level decreased from 12.6 to 8.3 mg% and the concentration of urea from 237 to 166 mg%. Mean duration of hemodiafiltration was 24+/-8.5 h, with mean blood flow rate of 134+/-15.2 ml/min, mean dialysate flow of 35+/-7 ml/min and mean ultrafiltration rate of 5.6+/-2.1 ml/min. Serum creatinine level decreased from 11.6 to 6.36 mg% and the concentration of urea from 236 to 137 mg%. Survival rate was 79.2% (19/24 patients). Complete recover of renal function was achieved in 5 patients, partial recover in 5 patients and 9 patients were included in chronic dialysis. In 8/24 (30%) patients we encountered complications, such as hypotension in 2 cases, bleeding disorders in 5 cases or diselectrolithemias in 2 cases. As a consequence, continuous renal replacement therapy is efficient, having an acceptable rate of adverse effects in patients with ARF or acutization of CRF.

Therapeutic efficiency of continuous renal replacement therapy--experience of a single Romanian center.

We studied 24 patients with acute renal failure (ARF) or acutization of chronic renal failure (CRF) caused by a variety of different disorders. A rapid decline in renal excretory function, fluid, electrolyte, and divalent ion disturbances determined us to initiate continuous renal replacement: continuous venovenous hemofiltration (CVVHF) - 28 procedures in 15 patients and continuous venovenous hemodiafiltration (CVVHDF) - 11 procedures in 11 patients. The mean duration of CVVHF was 21.6+/-6.9 h, with a mean blood flow rate of 116.9+/-16.4 ml/min and an ultrafiltration rate of 6.4+/-4.6 ml/min. The serum creatinine level decreased from 12.6 to 8.3 mg% and the concentration of urea from 237 to 166 mg%. The mean duration of hemodiafiltration was 24+/-8.5 h, with a mean blood flow rate of 134+/-15.2 ml/min, a mean dialysate flow of 35+/-7 ml/min and a mean ultrafiltration rate of 5.6+/-2.1 ml/min. The serum creatinine level decreased from 11.6 to 6.36 mg% and the concentration of urea from 236 to 137 mg%. Survival rate was 79.2% (19/24 patients). The complete recover of renal function was achieved in 5 patients, partial recover in 5 patients and 9 patients were included in chronic dialysis. In 8/24 (30%) patients we encountered complications, such as hypotension in 2 cases, bleeding disorders in 5 cases or diselectrolithemias in 2 cases. As a consequence, continuous renal replacement therapy is efficient, having an acceptable rate of adverse effects in patients with ARF or acutization of CRF.

[Tears' immunology in acute eye diseases]. / Imunologia lacrimilor în afectiuni oculare acute.

The aim of the study is to research the immunoglobulins' concentration into the tears liquid and into the blood serum at the patients with acute affections of the anterior ocular pole. The study was accomplished on two groups of patients: one group with herpetic Keratitis, the other with anterior uveitis, the second having a different etiology--that the viral one. Another group of patients with senile cataract was used like witness-group. The immunoglobulins concentration were detected into the serum and into the tears by the Mancini method of the radial immunodiffusion. The results indicate a general immunodefficiency signed by the decrease of IgG and IgM into the serum on the one hand, and the increase of local defense mechanisms reflected on the growing of IgA and IgG level into the tears, on the other hand.

[Treatment of alopecia areata with diphencyprone]. / Tratamentul alopeciei areata cu diphencyprone.

Topic immunotherapy in alopecia areata consist in a mild contact dermatitis with help of a chemical substances, with a high potency of sensitization, such as dinytroclorbenzenul (DNCB), squaric acid dibutylester (SADBE) and diphencypronil (DPCP). Eight patients with alopecia areata, 3 with mild form and 5 with severe form was treated with DPCP in acetone solution. We have obtained a positive result in 3 cases (37.5%), one with total regrows and 2 with partial regrows and a negative result in 5 cases, 3 with partial regrows and loss of the hair in other areas and 2 cases with no response after 24 weeks. We consider this method like an alternative therapy in severe alopecia areata resistant at other treatments.

Pre- and post-therapy blood lymphocyte levels in IgE-negative urticaria, associated with several parasitic or fungal diseases.

115 patients with non-immune (IgE-negative) urticaria, related to parasitic (lambliasis, oxyuriasis, ascaridiasis) or fungal (candidiasis) associations were investigated-both before and one month after specific and antihistaminic therapy-concerning different percentage levels of blood lymphocyte sets and subsets, by means of flow cytometry. Before therapy, three kinds of immune deficiency patients were obtained, one in lambliasis and oxyuriasis, the second in ascaridiasis, and the third in candidiasis, respectively. Clinical, biological and immunological recovering after therapy exhibited some differences related to the presumed non-allergic etiology, i.e. better in lambliasis and oxyuriasis and worse in ascaridiasis and candidiasis.

Transjugular intrahepatic portosystemic shunt.

The prevention and therapy of upper digestive hemorrhage due to rupture of esophageal varices in patients with liver cirrhosis are not yet effective enough. For their improvement, a transjugular intrahepatic portosystemic shunt (TIPS) is achieved by a new method which, without requiring general anesthesia, creates a shunt between a portal vein branch and the inferior vena cava. The indications, contraindications, outcome and eventual accidents of TIPS are analysed in the light of the latest data in the medical literature.

Comparative study on some systemic humoral and cellular immune markers in only HIV or HIV and hepatitis B infected children.

Three different groups of asymptomatic children, aged from 12 to 24 months (30 subjects per each group), i.e. controls, only HIV, or HIV/hepatitis B virus (HBV) double infected, were studied, as concerned the following systemic immune parameters: immunoglobulin (IgG, IgM, IgA, IgD) levels; absolute numbers of blood CD+4, CD+8, CD+16 and CD+19 cells; phytohaemagglutinin (PHA)-blast responsiveness of T lymphocytes; natural killer (NK) cell activity--as tested by means of cytotoxicity assays; per cent suppression of PHA-dependent T cell blastogenesis in the presence of concanavalin A (Con A) selected T suppressor (Ts) cells. On the other hand, in 15 ARC-shifting cases belonging to HIV, and HIV/HBV groups, respectively, a second serum sample was collected and searched comparatively with the corresponding first serum sample, as regarded: presence of total and anti-p24 HIV antibodies, patterns of Western Blot (WB), as well as amounts of free p24-HIV antigen. In asymptomatic double HIV/HBV infected subjects, some immune disorders occurred, at a more significant degree, as compared to only HIV-infected. Once the shift toward ARC being installed, in both infected groups a decrease of anti-p24 HIV antibody presence, disappearance of corresponding band in WB confirmation test, as well as presence of free p24 antigen in serum, were noticed. However, greater amounts of p24 antigen in HIV/HBV infected, as compared to only HIV infected patients, were found. Some considerations about diagnostic and predictive value of presented data are discussed.