Prognosis of patients with previous myocardial infarction, coronary slow flow, and normal coronary angiogram.

BACKGROUND: There is a common assumption that patients with coronary slow flow (CSF) have an excellent prognosis in the absence of coronary artery stenoses. Little is known about whether a history of previous coronary events affects the long-term survival in this population. In this retrospective, observational study, we assessed the possible association of a previous coronary event and long-term prognosis in patients with CSF but without significant coronary artery stenoses. METHODS: A total of 141 patients (70 male; median age: 59 years, range: 33-78 years) with CSF and normal coronary angiograms were included in the study. Patients were followed up for all-cause mortality during a period of 47 ± 22 months. RESULTS: Previous myocardial infarction (MI) was reported by 16 (11%) patients who had similar left ventricular ejection fraction (LVEF) as those without previous MI (51 ± 16 vs. 53 ± 16%, p = 0.595). Patients with previous MI more often had an abnormal resting electrocardiogram (69 vs. 40%, p = 0.03), while there were no significant differences in other baseline clinical characteristics (p > 0.05 for age, gender, risk factors, pharmacological treatment). In univariate Cox analysis, only previous MI was associated with unfavorable long-term survival (log-rank p = 0.012), while an abnormal electrocardiogram, LVEF, and other clinical variables were not (log-rank p > 0.05, for all). Kaplan-Meier analysis revealed unfavorable long-term survival in patients with CSF and a history of previous MI. CONCLUSION: In patients with CSF and an otherwise normal coronary angiogram, a history of a previous MI is associated with unfavorable long-term outcomes.

Ischemic preconditioning vs adenosine vs prostaglandin E1 for protection against liver ischemia/reperfusion injury.

Ischemia/reperfusion injury is still a major cause of morbidity and mortality during liver surgery and transplantation. A variety of surgical and pharmacological therapeutic strategies have been investigated to minimize the effects of ischemia/reperfusion. The aim of our study was to analyze and compare preventive influences of ischemic preconditioning, adenosine and prostaglandin E1 in the experimental model of hepatic ischemia/reperfusion injury. Adult chinchilla rabbits were divided into four groups: 10 rabbits subjected to liver ischemic preconditioning (3-min period of inflow occlusion followed by a 5-min period of reperfusion) followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of adenosine followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of prostaglandin E1 followed by 45 min of Pringle maneuver; and control group of 10 rabbits subjected to 45 min of inflow liver ischemia without any preconditioning. On the second postoperative day, blood samples were obtained and biochemical parameters of liver function were measured and compared. Liver tissue samples were also obtained and histopathological changes were compared. Based on biochemical and histopathological parameters, it was demonstrated that ischemic preconditioning provided the best protection against hepatic ischemia/reperfusion injury. This was probably due to a wider range of mechanisms of action of this method oriented to reduce oxidative stress and inflammation, and restore liver microcirculation and hepatocyte energy compared to the examined pharmacological strategies.

Ischemic preconditioning vs adenosine vs prostaglandin E1 for protection against liver ischemia/reperfusion injury

Ischemia/reperfusion injury is still a major cause of morbidity and mortality during liver surgery and transplantation. A variety of surgical and pharmacological therapeutic strategies have been investigated to minimize the effects of ischemia/reperfusion. The aim of our study was to analyze and compare preventive influences of ischemic preconditioning, adenosine and prostaglandin E1 in the experimental model of hepatic ischemia/reperfusion injury. Adult chinchilla rabbits were divided into four groups: 10 rabbits subjected to liver ischemic preconditioning (3-min period of inflow occlusion followed by a 5-min period of reperfusion) followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of adenosine followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of prostaglandin E1 followed by 45 min of Pringle maneuver; and control group of 10 rabbits subjected to 45 min of inflow liver ischemia without any preconditioning. On the second postoperative day, blood samples were obtained and biochemical parameters of liver function were measured and compared. Liver tissue samples were also obtained and histopathological changes were compared. Based on biochemical and histopathological parameters, it was demonstrated that ischemic preconditioning provided the best protection against hepatic ischemia/reperfusion injury. This was probably due to a wider range of mechanisms of action of this method oriented to reduce oxidative stress and inflammation, and restore liver microcirculation and hepatocyte energy compared to the examined pharmacological strategies.

Gender disparities in mortality from infectious diseases in Serbia, 1991-2014: a time of civil wars and global crisis.

Infectious diseases remain one of the leading causes of death worldwide. The aim of this descriptive epidemiological study was to analyse the trends in mortality from infectious diseases in Serbia (excluding the Autonomous Province of Kosovo & Metohia) from 1991 to 2014 using joinpoint regression analysis. The mortality rates from infectious diseases were found to have increased markedly from 1991 to 1994 (+12·4% per year), followed by a significant decline from 1994 to 2009 (-4·6% per year) and then another increase from 2009 to 2014 (+4·3% per year). Throughout the study period, mortality rates were consistently higher in men than in women. Although a substantial decline was observed for young people of both sexes, no consistent pattern was evident for the middle-aged nor the elderly. Since 1991, septicaemia has emerged as a leading cause of infectious disease mortality, particularly in older men. The Yugoslav civil wars in the 1990s and the global financial crisis in 2008 corresponded with changes in the trends in mortality from infectious diseases in Serbia, with the elderly showing particular vulnerability during those time periods. Data presented in this study might be useful to improve control of infectious diseases in Serbia.

Suicide in Serbia.

BACKGROUND: Suicide remains a significant public health problem worldwide. The aim of this study was to assess the mortality trend of suicide in Serbia for the years 1991-2014. METHODS: Data on persons who died of suicide and self-inflicted injury (site codes E950-E959 revision 9 and X60-X84 revision 10 of the International Classification of Diseases to classify death, injury and cause of death) were obtained from the Statistical Office of the Republic of Serbia. The age standardized rate was calculated by direct method (per 100,000 persons, using Segi's World population as standard population). Average annual percentage change (AAPC) with the corresponding 95% confidence interval (CI) was computed for trend using the joinpoint regression analysis. RESULTS: Total 33,930 (24,016 men and 9914 women) suicide deaths occurred in Serbia during the observed period, with the average annual age-standardized mortality rate being 12.7 per 100,000 inhabitants (19.5 per 100,000 in men and 6.7 per 100,000 in women). Suicide mortality in all age groups was higher among men than women. In both genders, suicide rates were highest in the oldest age group. Significantly decreased trend in suicide mortality was recorded continuously from 1991 to 2014 (AAPC=-1.9%, 95%CI -2.2 to -1.6). The most frequently used suicide method in both genders was hanging, strangulation or suffocation with 61.2% off all suicides. Changes in mortality rates were significant both for suicide by firearms, air guns and explosives (AAPC=-1.5% (AAPC=-1.5% in men and -3.1%-3.1% in women) and for suicide by hanging, strangulation, and suffocation (AAPC=-1.2% (AAPC=-1.2% in men and -3.0%-3.0% in women). In men, nonsignificant increase in suicide by firearms, air guns and explosives observed during the period 1991-1997 (by +6.1% per year) was followed by a significant decrease until 2014 (by -3.1% per year). The significantly increased mortality in suicide by firearms, air guns, and explosives was observed in older men (aged 40-69 years and 80 years and over). LIMITATIONS: The low rate of autopsies in Serbia, as well as the accuracy, reliability and comparability of the suicide mortality data is always a question. CONCLUSIONS: Downward trend in suicide mortality occurred in Serbia in last two decades. However, suicide rates are still very high in Serbia compared with the rates of suicides in developed countries. Particularly worrisome is the increase in mortality in older men, especially due to firearm suicides, air rifles, and explosives. Thus, additional efforts in the prevention of suicide are very important.

[ASSOCIATION OF SKIN PHOTOTYPE AND UV EXPOSURE WITH EXPRESSION OF HER RECEPTORS, Ki67 AND p53 IN PATIENTS WITH CUTANEOUS SQUAMOUS CELL CARCINOMA].

An increase in the incidence of cancer, in particular skin cancer, has been observed in the last few decades. Skin cancer represents a significant public health problem in Croatia and worldwide. Cutaneous squamous cell carcinoma (cSCC) is a malignant tumor arising in epidermal keratinocytes. Together with basal cell carcinoma it belongs to non-melanoma skin cancers, which are the most common cancers in humans. The lifetime risk of cSCC development in Caucasian population is nowadays estimated to about 15%, which makes it double compared to 20 years ago. The most probable causes are increased ultraviolet light (UV) exposure (exposure to artificial UV sources in suntan parlors, spending more time outdoors, changes in fashion, as well as ozone holes), and longer life expectancy. In its etiopathogenesis, important risk factors include genetic factors, fair-skin phototype, UV exposure, chronic degenerative and inflammatory conditions, chemical factors, oncogenic viruses, immunosuppression, ionizing radiation, as well as habitual risk factors. Human epidermal growth factor receptor (HER) family is involved in the control of multiple signal pathways. Their dysregulation is associated with development of many cancers such as breast carcinoma, non-small cell lung carcinoma, ovarian carcinoma, carcinoma of pancreas, head and neck carcinoma, as well as glioblastoma. The objective of our investigation was to establish if there is association of the skin phototype and UV exposure with the expression of HER receptors, Ki67 and p53 in patients with cSCC. Study group included 101 cSCC patients. Inclusion criteria were age >50, both sexes, histopathologically confirmed cSCC, no previous therapy, specimens sufficient for immunohistochemistry, and complete clinical data collected by a questionnaire. Material obtained by excisional biopsy was completely histopathologically evaluated and additional tissue slices were immunohistochemically analyzed. Statistical analysis of the sample included non-parametrical statistical methods and statistical reviews. Analysis was done using R statistical package. Statistical significance was set at p<0.05. The following skin phototypes (according to Fitzpatrick) were present in our study: 54 (53.47%) patients with phototype II and 47 (46.53%) patients with phototype III. The majority of patients (n=93; 92.08%) were exposed to increased UV radiation during lifetime. Forty (39.60%) patients had three or more sunburns during childhood. Study results showed a signifi cantly higher expression of EGFR receptors, Ki67 and protein p53 in patients with light skin phototype that had been exposed to increased UV light during lifetime or had acquired 3 or more sunburns in childhood, suggesting that UV exposure led to the induction of EGFR, Ki67 and protein p53, and consequently to development of cSCC.

Compaction properties of crystalline pharmaceutical ingredients according to the Walker model and nanomechanical attributes.

This study investigates the extent to which single-crystal mechanical properties of selected active ingredients (famotidine, nifedipine, olanzapine, piroxicam) influence their bulk compressibility and compactibility. Nanomechanical attributes of oriented single crystals were determined with instrumented nanoindentation, and bulk deformational properties were assessed with the Walker and Heckel models as well as the elastic relaxation index. Good correlations were established between bulk and single-crystal plasticity parameters: the Walker coefficient and indentation hardness. The Walker model showed more practical value for evaluating bulk deformational properties of the APIs investigated because their properties differed more distinctly compared to the Heckel model. In addition, it was possible to predict the elastic properties of the materials investigated at the bulk level because a correlation between the elastic relaxation index and compliance was established. The value of using indentation hardness for crystalline APIs was also confirmed because their compactibility at the bulk level was able to be predicted. Mechanically interlocked structures were characteristic of most polymorphic forms investigated, resulting in single crystals having isotropic mechanical properties. It was revealed that in such cases good correlations between single and bulk mechanical properties can be expected. The results imply that innate crystal deformational properties define their compressibility and compactibility properties to a great extent.

Consolidation trend design based on Young's modulus of clarithromycin single crystals.

The key aim of this study was to determine single mechanical properties of clarithromycin polymorphic forms in order to select some of them as more suitable for the tableting process. For this purpose, AFM single-point nanoindentation was used. The Young's moduli of clarithromycin polymorphs were substantially different, which was consistent with the structural variations in their packing motifs. The presence of the adjacent layers, which can easily slide over each other due to the low energy barrier (the lowest Young's modulus was 0.25 GPa) resulted in better bulk compressibility (the highest Heckel coefficient) of clarithromycin Form I. We also addressed the importance of tip geometry screening because the stress during the force mode often results in tip apex fracture. Even the initial manufacture of the diamond-coated tips can result in defects such as double-apex tips.

Observation of discrete gap solitons in one-dimensional waveguide arrays with alternating spacings and saturable defocusing nonlinearity.

We consider, both experimentally and theoretically, the existence and stability of localized, symmetric, and antisymmetric gap solitons (GSs) in binary lattices of identical waveguides but with alternating spacings. Furthermore, the properties of surface GSs at the boundary of the lattice are explored.

Linear and nonlinear light propagation at the interface of two homogeneous waveguide arrays.

We investigate linear and nonlinear light propagation at the interface of two one-dimensional homogeneous waveguide arrays containing a single defect of different strength. For the linear case and in a limited region of the defect size, we find trapped staggered and unstaggered modes. In the nonlinear case, we study the dependence of power thresholds for discrete soliton formation in different channels as a function of defect strength. All experimental results are confirmed theoretically using an adequate discrete model.

Multicolor counterstaining for immunohistochemistry -- a modified Movat's pentachrome.

The application of "histochemical" staining procedures has been substantially replaced by immunostaining of specific molecular tissue components. The limited range of colors resulting from routine immunohistochemistry, however, can limit assessment of the general microscopic tissue organization. Consequently we have adapted a polychromatic histochemical counterstaining procedure based on Movat's pentachrome staining sequence for use with immunohistochemical procedures. The value of Movat's original method when applied as an immunohistochemical counterstain is limited by its use of iron hematoxylin and by fact that the resulting color combination is difficult to distinguish from the colors of routine immunohistochemical staining. Our variant pentachrome stains the same tissue components as Movat's stain; however, owing to a modification of the acid fuchsin staining step, it provides a strong color contrast with the reaction product resulting from immunostaining using diaminobenzidine as the chromogen. Multicolor counterstaining for immunohistochemistry offers a new approach to tissue analysis, especially when stromal-epithelial relations of normal and neoplastic tissues are considered.

Diagnóstico prenatal de un hemangioma occipital de rápida involución / Prenatal diagnosis of a occipital rapidly involuting hemangioma

El hemangioma occipital es, tras los linfangiomas, el tipode tumoración más frecuente en cabeza y cuello. Su diagnósticoecográfico suele establecerse en el tercer trimestre o finalesdel segundo trimestre siendo útil la resonancia magnética(RM) prenatal para la confirmación del mismo. Posnatalmente,la gran mayoría de los casos regresan espontáneamente si bienpueden persistir y complicarse requiriendo exéresis quirúrgica.Presentamos el caso del hemangioma fetal de involuciónrápida (RICH, Rapidly Involuting Congenital Hemangioma) anivel occipital diagnosticado por ecografía en el tercer trimestrede gestación así como una revisión de la literaturadestacando los puntos clave para su diagnóstico diferencial,manejo prenatal, conducta obstétrica y tratamiento posnatal(AU)

Occipital hemangioma is one of the most frequentfetal head and neck tumors, second only to lymphangiomas.Diagnose is usually established in the third or inthe late second trimester of pregnancy. Prenatal MRIallowsdiagnosis confirmation. Vast majority of fetal hemangiomasregress spontaneously in the first year afterdelivery. However, persistence is a possibility, and theymight present complications, such as bleeding or ulcerations,in which case surgical treatment is warranted.We report a case of rapidly involuting congenitalhemangioma (RICH) in the occipital region of fetal craniumdiagnosed on a routine third timester fetal ultrasoundscan. We also present a review of available literature,outlining the key points to differential diagnosis,prenatal, obstetric and postnatal management(AU)

Microparticle size control and glimepiride microencapsulation using spray congealing technology.

Drug-free microparticles were prepared using a spray congealing process with the intention of studying the influence of processing parameters. By varying the atomizing pressure and liquid feed rate, microparticles with median sizes (d((0.5))) from 58 to 278 microm were produced, with total process yields ranging from 81% to 96%. An increased liquid feed rate was found to increase microparticle size, and higher atomizing pressures were found to decrease microparticle size. Greater change in microparticle size was achieved by varying atomizing pressure, which can be considered a dominant process parameter regarding microparticle size. In addition, microparticles with glimepiride, a model poorly water-soluble drug, were prepared by spray congealing using three different hydrophilic meltable carriers: Gelucire 50/13, poloxamer 188, and PEG 6000. Spherical microparticles with relatively smooth surfaces were obtained, with no drug crystals evident on the surfaces of drug-loaded microparticles. XRPD showed no change in crystallinity of the drug due to the technological process of microparticle production. All glimepiride-loaded microparticles showed enhanced solubility compared to pure drug; however, Gelucire 50/13 as a carrier represents the most promising approach to the dissolution rate enhancement of glimepiride. The influence of storage (30 degrees C/65% RH for 30 days) on the morphology of glimepiride/Gelucire 50/13 microparticles was studied, and the formation of leaf-like structures was observed (a "blooming" effect).

[Colonization of cental venous catheter in the Intensive Care Units at the Institute of Cardiovascular Disease "Dedinje"--one year study].

OBJECTIVES: The application of Central Venous Catheters (CVC) is associated with increased risk of microbial colonization and infection. The aim of present study was to assess the frequency of pathogens colonizing CVC and to determine their susceptibility pattern to various antimicrobial agents. MATERIALS AND METHODS: A total of 253 samples of CVC from intensive care units (ICU) patients were received for culture during 2003. All microorganisms were identified by standard microbiological methods and the susceptibility to antimicrobial agents was determined according to NCCLS recommendations. RESULTS: A total of 184 (72.7%) cultures were positive and 223 pathogens were isolated. Coagulase negative staphylococci (CNS) were the dominant isolates (24.7%), followed by Enterobacter spp. (12.1%), Pseudomonas spp. (11.7%), Enterococcus spp. (9.9%), Klebsiella spp. (8.6%), Candida spp. (7.6%), Acinetobacter spp. (7.6%), other Gram negative nonfermentative bacilli (5.8%), Serratia spp. (4.5%), Staphylococcus aureus (2.6%), Proteus mirabilis (2.2%), E. coli (1.8%) and Citrobacter spp. (0.9%). Meropenem (84.5%) and vancomycin (100%) remain the most effective antimicrobial agents against Gram negative and Gram positive bacteria, respectively. CONCLUSION: Gram negative bacilli and CNS are the commonest microorganisms colonizing CVC from ICU patients. The increasing resistance of the bacteria to antimicrobial agents is the major problem in spite of restricted policy of using antimicrobial agents in ICU.

[Meta-analysis on minimally invasive surgical therapy of sigmoid diverticulitis]. / Meta-analiza o minimalno invazivnoj hirurskoj terapiji divertikulitisa sigmoidnog kolona.

UNLABELLED: The bowel diverticulitis is a complication of diverticulosis, occuring in 35% patients in 20 years after diagnosis. The study purpose was analysis of the results published in world literature. METHOD: Double blind electronic search of several databases using key words: diverticulitis, laparoscopy. RESULTS: 11 studies with 415 patients that satisfy the criteria were selected. AGE: 62.7 + 14.2. Hinchey stadiums: I, IIa i IIb of these 44% I and 28% IIa i Iib each. Operative time: 197.4 +/- 49.6 min. Conversions: 11.7 +/- 10.1 (0 - 38.9%). Protective stoma: 5.5%. Bowel sounds: 2.3 - 3.2 postoperative day. Oral feeding: 2.6-5 postoperative day. Hospitalization: 6.1 2.1 dana. Anastomotic dehiscence: 2.8%, wound infection: 7.3%, iatrogen rectum perforation with stapler: 3.3%, bleeding: 3.5%, ileus: 4.4%, reoperation rate: 4.7%. CONCLUSION: Sigmoid resection with or without a protective "loop" ileostomy is technically feasable by minimally invasive surgical technique, with an acceptable ratio of benefits and complications.

Endothelium-dependent relaxation of canine uterine artery in response to acetylcholine: the possible involvement of alternative pathways.

The effect of acetylcholine on the isolated, pre-contracted, uterine artery of non-pregnant dog was investigated. Acetylcholine-induced concentration-dependent relaxation of isolated canine uterine artery with endothelium (pEC50 = 6.48 +/-0.01, n = 37) and was without effect on arterial segments denuded of endothelium. Indomethacin, 4-aminopyridine (10-5 m) and pre-contraction with K+-rich Krebs-Ringer bicarbonate solution had no effect on acetylcholine-induced relaxation. NG-nitro-l-arginine (l-NOARG) (10-5 m) inhibited relaxation evoked by acetylcholine. Indomethacin applied with l-NOARG led to further inhibition of acetylcholine-induced relaxation. In the presence of both l-NOARG and indomethacin, 4-aminopiridine did not provoke further inhibition of acetylcholine-induced relaxation of canine uterine artery. It is concluded that the acetylcholine-induced relaxation of canine uterine artery is probably mediated by endothelial production of nitric oxide (NO). However, if NO-synthase is inhibited, acetylcholine-induced vasorelaxation may be, in part, mediated through activation of cyclooxygenase pathway.

Entropies of coding and noncoding sequences of DNA and proteins.

The entropies of protein coding genes from Escherichia coli were calculated according to Boltzmann's formula. Entropies of the coding regions were compared to the entropies of noncoding or miscoding ones. With nucleotides as code units, the entropies of the coding regions, when compared to the entropies of complete sequences (leader and coding region as well as trailer), were seen to be lower but with a marginal statistical significance. With triplets of nucleotides as code units, the entropies of correct reading frames were significantly lower than the entropies of frameshifts +1 and -1. With amino acids as code units, the results were opposite: Biologically functional proteins had significantly higher entropies than proteins translated from the frameshifted sequences. We attempt to explain this paradox with the hypothesis that the genetic code may have the ability of lowering information content (increasing entropy) of proteins while translating them from DNA. This ability might be beneficial to bacteria because it would make the functional proteins more probable (having a higher entropy) than nonfunctional proteins translated from frameshifted sequences.