Factors influencing time to seeking medical advice and onset of treatment in women who are diagnosed with breast cancer in Serbia.

OBJECTIVE: Streamlining the diagnosis is a key factor in improving the treatment outcomes for breast cancer. The aim of this study was to determine factors influencing time to seeking medical advice and treatment onset in women who are diagnosed with breast cancer in Serbia. METHODS: The study was a multicenter, cross-sectional national survey, performed at 10 oncology centers in Serbia. Time intervals spent throughout the complex diagnostic pathway were evaluated using a validated questionnaire administered to women with breast cancer (n = 800). Total interval (TI) was determined using predefined time scales, including one referring to patient interval (PI), and several related to health care system interval (SI). RESULTS: Mean PI, SI, and TI were 4.5, 9.2, and 12.9 weeks, respectively; 20% of patients had a PI>12 weeks. Based on the multivariate regression model, longer PI was associated with perceived lack of time and personal disregard or trivialization of detected symptoms and signs. Women who were supported by family members or friends and had at least a secondary level education tended to have a shorter PI. Longer PI was correlated with a longer SI, while regular self-examination, having been diagnosed by an oncologist, and living in a major city were associated with shorter SI. CONCLUSIONS: Several factors, related to psychological, demographic, behavioral, and health system characteristics, determined both the time to seeking medical advice and treatment onset for breast cancer. These findings support review and refining of national strategies and policies to promote early detection, diagnosis, and treatment of breast cancer.

Preclinical atherosclerosis at the time of pre-eclamptic pregnancy and up to 10 years postpartum: systematic review and meta-analysis.

OBJECTIVES: Pre-eclampsia (PE) is a pregnancy-specific hypertensive disorder that has been associated with cardiovascular risk factors and vascular changes, such as acute atherosis in placental blood vessels, similar to early-stage atherosclerosis. The objective of this study was to determine whether women with PE have increased atherosclerotic burden, as determined by the carotid intima-media thickness (CIMT), compared with women without PE. METHODS: We conducted a systematic review and meta-analysis of studies that reported CIMT, a non-invasive, ultrasound-based measure of subclinical atherosclerosis, in women who did vs those who did not have PE. Studies were eligible if they had been conducted during pregnancy or during the first decade postpartum, and if CIMT was measured in the common carotid artery. Studies published before 7 March 2016 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full-text screening, data abstraction and quality assessment. Heterogeneity was assessed using the I2 statistic. Standardized mean difference (SMD) was used as a measure of effect size. RESULTS: Fourteen studies were included in the meta-analysis. Seven studies were carried out during pregnancy complicated by PE, 10 were carried out up to 10 years postpartum and three included measurements obtained at both time periods. Women who had PE had significantly higher CIMT than did those who did not have PE, both at the time of diagnosis (SMD, 1.10 (95% CI, 0.73-1.48); P < 0.001) and in the first decade postpartum (SMD, 0.58 (95% CI, 0.36-0.79); P < 0.001). CONCLUSIONS: Atherosclerotic load is present at the time of PE and may be a mechanism associated with the disease. Measurement of CIMT may offer an opportunity for the early identification of premenopausal women with atherosclerotic burden after a PE pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Resumen Objetivos: La preeclampsia (PE) es un trastorno hipertensivo específico del embarazo que ha sido asociada con factores de riesgo cardiovascular y cambios vasculares, tales como aterosis aguda en los vasos sanguíneos de la placenta, similares a las primeras etapas de la aterosclerosis. El objetivo de este estudio fue determinar si las mujeres con PE han aumentado la carga aterosclerótica, según lo determinado por el espesor del complejo íntima-media de la arteria carótida (CIMT, por sus siglas en inglés), en comparación con las mujeres sin PE. MÉTODOS: Se realizó una revisión sistemática y un metaanálisis de estudios que reportaron el CIMT, una medida no invasiva de la aterosclerosis subclínica obtenida mediante ecografía, comparando mujeres con PE y mujeres sin ella. Solo se incluyeron estudios llevados a cabo durante el embarazo o durante la primera década después del parto, y en los que se midió el CIMT en la arteria carótida común. Se usaron las bases de datos de PubMed, EMBASE y Web of Science para identificar estudios publicados antes del 7 marzo de 2016. Dos revisores utilizaron formularios y protocolos preestablecidos para evaluar de forma independiente la elegibilidad de los estudios, a partir de los títulos y los resúmenes, y para realizar un cribado del texto completo, un resumen de los datos y una evaluación de calidad. La heterogeneidad se evaluó mediante el test estadístico I2 . Se usó la diferencia de medias estandarizada (SMD, por sus siglas en inglés) como una medida de la magnitud del efecto. Resultados: En el metaanálisis se incluyeron catorce estudios. Siete de los estudios se llevaron a cabo durante embarazos complicados por PE, 10 se realizaron hasta 10 años después del parto y tres incluyeron mediciones tomadas en ambos períodos. Las mujeres con PE tuvieron un CIMT significativamente mayor que aquellas que no la tenían, tanto en el momento del diagnóstico (SMD 1,10 (I 95%, 0,73-1,48), P <0,001) como en la primera década después del parto (SMD 0,58 (IC 95%, 0,36-0,79), P <0,001). Conclusiones: La carga aterosclerótica está presente en el momento de la PE y podría ser un mecanismo asociado con esta enfermedad. La medición del CIMT puede ofrecer una oportunidad para la identificación temprana de mujeres premenopáusicas con carga aterosclerótica después de un embarazo con PE. : (pre-eclampsia,PE),,,。-(carotid intima-media thickness,CIMT),PEPE,。 : PEPECIMTmeta,CIMT、。:10CIMT。PubMed、EMBASEWeb of Science,201637。,,、。I2 。(SMD)。 : meta14。7PE,1010,3。PEPE,[SMD,1.10(95% CI,0.73~1.48);P<0.001]10[SMD,0.58(95% CI,0.36~0.79);P<0.001] CIMT。 : PE,。CIMT,PE。.

Specific binding of paraprotein to platelet receptors as a cause of platelet dysfunction in monoclonal gammopathies.

The study included 48 untreated patients with monoclonal gammopathies (MG). Paraprotein was isolated from the serum of 10 patients with decreased platelet aggregation. Platelet aggregation was measured before and after the addition of the isolated paraprotein to platelet-rich plasma (PRP) from 10 healthy donors, in vitro. Expression of platelet von Willebrand factor (vWF) receptor glycoprotein (GP)Ib and platelet collagen receptor GPVI was determined by flow cytometry in the PRP of healthy donors before and after the addition of isolated paraprotein using the monoclonal antibodies, CD42b (for GPIb) and CD36 (for GPVI). Flowcytometry showed that expression of CD42b and CD36 positive cells was reduced after the addition of isolated paraprotein to PRP from healthy donors (p < 0.001). These investigations demonstrated that paraprotein causes platelet dysfunction in patients with MG due to specific binding to the platelet vWF receptor GPIb and platelet collagen receptor GPVI.

Liver steatosis in celiac disease: the open door.

Non-alcoholic fatty liver disease (NAFLD) is a common disease of unknown origin characterized by histological features similar to alcoholic-like liver injury but in the absence of significant alcohol intake. Non-alcoholic fatty liver disease refers to a spectrum of diseases of the liver ranging from simple steatosis (i.e., fatty infiltration of the liver) to nonalcoholic steatohepatitis (i.e., steatosis with inflammation and hepatocyte necrosis) to cirrhosis. Non-alcoholic fatty liver disease is frequently associated with disorders such as insulin resistance, obesity, type 2 diabetes mellitus, hyperlipidemia and protein-calorie malnutrition. However, in a subgroup of NAFLD patients, the true relevant cause remains undetermined. Celiac disease (CD) is a common immune-mediated disorder and develops in genetically susceptible subjects after the ingestion of gluten proteins. Celiac disease has been found in about 10% of patients with unexplained abnormal liver tests, and in about 3.5% of patients with NAFLD as the only manifestation of the disease. The frequency of subclinical or silent presentations in older children and adults highlights the importance of CD screening in patients with unexplained chronic abnormal liver function tests and NAFLD without any specific etiology. The pathogenesis of liver steatosis in CD is uncertain. The aims of this review are to describe the possible mechanisms involved in the occurrence and progression of liver steatosis in CD patients.

Haemophagocytic syndrome associated with mucormycosis infection.

Several clinical forms of mucormycosis are recognized. The tendency of mucoraceous zygomycetes to invade the blood vessels often produces a disseminated infection. A case of disseminate mucormycosis complicated by a haemophagocytic syndrome (HS) in a 32-year-old Caucasian male is reported in this article. Few cases of infection-associated HS (IAHS), involving infections caused by fungi, have been reported. In all the recorded cases, the fungal infection coexists with malignant lymphoma, immunodeficiency and a long-term steroid therapy for renal transplant or Crohn's disease. This is the second described case of the HS due to mucormycosis.

Histological determination of skin thickness in farmed Australian Crocodylus porosus.

This descriptive study examined the variation in ventral Crocodylus porosus (saltwater crocodile) belly skin. The study is the first to determine both intra and inter variation of C. porosus skin, epidermis and dermis thickness across the ventral belly region. Standardised ventral scales from across the belly region of a Hatchling (< 12months), Yearling (1-2 years) and Grow Out (>2 years) animals were examined using histological measurements for the stratum (s.) corneum, a combined measure for the remainder of the epidermis; the s. granulosum, s. spinosum and s. basale, and the dermis. This study determined that there was a thinning across all layers of the belly skin, from the head to the cloaca, and a decrease in thickness scales in lateral scales compared to midline scales. Variation within a scale was found predominately in the s. corneum and can be related to the change in keratin type from beta- to alpha- in the hinge (inter-scalar) region and the integumentary sensory organs. Future studies should utilise a larger sample size and consider less invasive imaging techniques.

Obesity and metabolic syndrome during the menopause transition in Serbian women.

BACKGROUND: Abdominal obesity and metabolic syndrome are known to increase in prevalence from premenopause to postmenopause. Both are well recognized predictors of cardiovascular disease and diabetes in women. Aims The primary objective of this study was to assess the presence of obesity and metabolic syndrome during the menopause transition in Serbian women who attended health-care centers. The secondary objective was to evaluate the prevalence of ischemic heart disease, stroke and diabetes in this group. METHODS: Our results present a part of the national epidemiological cross-sectional study assessing prevalence of metabolic syndrome and obesity in Serbia. In all, 1076 women attending 20 health-care centers were assessed. Women were divided into five groups: premenopausal, perimenopausal, early and late postmenopausal and geripausal. Medical history, waist circumference, blood glucose, lipids, and blood pressure were recorded. RESULTS: The mean body mass index of all women was 28.5 ± 4.9 kg/m(2). The mean waist circumference of all women was 92 ± 12.5 cm. Both were significantly lower in premenopausal women than in other women. Metabolic syndrome was present in 72% of women, with a significant difference in prevalence between premenopausal women and other groups. High triglyceride levels and hypertension were the most commonly present components of metabolic syndrome. Ischemic heart disease, stroke and diabetes occurred significantly more often in postmenopausal and geripausal women. CONCLUSION: The majority of Serbian women attending health-care centers have abdominal obesity and metabolic syndrome which significantly increase in prevalence in the perimenopausal years. This indicates that preventive measures should be focused on diabetes and cardiovascular disease in the perimenopause.

Systematic review supports the role of DNA methylation in the pathophysiology of preeclampsia: a call for analytical and methodological standardization.

BACKGROUND: Studies have recently examined the role of epigenetic mechanisms in preeclampsia pathophysiology. One commonly examined epigenetic process is DNA methylation. This heritable epigenetic marker is involved in many important cellular functions. The aim of this study was to establish the association between DNA methylation and preeclampsia and to critically appraise the roles of major study characteristics that can significantly impact the association between DNA methylation and preeclampsia. MAIN BODY: A systematic review was performed by searching PubMed, Web of Science, and EMBASE for original research articles published over time, until May 31, 2019 in English. Eligible studies compared DNA methylation levels in pregnant women with vs. without preeclampsia. Ninety articles were included. Epigenome-wide studies identified hundreds of differentially methylated places/regions in preeclamptic patients. Hypomethylation was the predominant finding in studies analyzing placental tissue (14/19), while hypermethylation was detected in three studies that analyzed maternal white blood cells (3/3). In candidate gene studies, methylation alterations for a number of genes were found to be associated with preeclampsia. A greater number of differentially methylated genes was found when analyzing more severe preeclampsia (70/82), compared to studies analyzing less severe preeclampsia vs. controls (13/27). A high degree of heterogeneity existed among the studies in terms of methodological study characteristics including design (study design, definition of preeclampsia, control group, sample size, confounders), implementation (biological sample, DNA methylation method, purification of DNA extraction, and validation of methylation), analysis (analytical method, batch effect, genotyping, and gene expression), and data presentation (methylation quantification measure, measure of variability, reporting). Based on the results of this review, we provide recommendations for study design and analytical approach for further studies. CONCLUSIONS: The findings from this review support the role of DNA methylation in the pathophysiology of preeclampsia. Establishing field-wide methodological and analytical standards may increase value and reduce waste, allowing researchers to gain additional insights into the role of DNA methylation in the pathophysiology of preeclampsia.

Public health preparedness for two mass gathering events in the context of pandemic influenza (H1N1) 2009--Serbia, July 2009.

Preparedness planning for two large mass gatherings events were considered in Serbia in the context of pandemic influenza (H1N1) 2009. Planning included approaches to prevention, detection and response in order to mitigate the situation at this early stage of the epidemic in Serbia. Cases of influenza A(H1N1)v were identified nationally immediately prior to the mass gatherings but also identified in association with both events, as expected in the context of the pandemic situation. This article describes the experiences of planning and the epidemiological situation during the period of the mass gathering events.

The impact of bowel management on the quality of life in children with spina bifida with overactive bladder and detrusor sphincter dyssynergia.

OBJECTIVE: The aim of the study was to assess the impact of bowel management on the quality of life in children with spina bifida with overactive bladder and detrusor sphincter dyssynergia. MATERIALS AND METHOD: The research was carried out over the 2014-2017 period, during which 70 patients with spina bifida with overactive bladder and detrusor sphincter dyssynergia were observed. The first group (group 1) consisted of 35 patients who were administered bowel management combined with anticholinergic medication therapy and CIC. The second group (group 2) consisted of 35 patients who were treated only with anticholinergic medication therapy and CIC. Bowel management included daily enema, laxative application, and a special diet, with a view of treating constipation and fecal incontinence that was estimated on the basis of Roma III criteria, the echosonographically determined transversal rectal diameter, and encopresis frequency. The effects of the administered bowel management on urinary incontinence were estimated on the basis of the average dry interval between two CICs. Regarding the quality of life, a KINDL questionnaire was used for children and parents to determine the overall quality of life, but also the various aspects of the quality of children's life (physical well-being, emotional well-being, self-confidence, family, friends, school, disease). The test score ranges from 0 to 100, where 0 is the lowest and 100 denotes the highest quality of life. The follow-up period of every patient was one year. RESULTS: At baseline, there was no significant difference between the groups regarding demographic and clinical features (p > 0.05). After one year, treatment by bowel management demonstrated significant improvement for both fecal constipation/incontinence and urinary incontinence (p < 0.001). The bowel management group showed improved overall quality of life in contrast to the group without bowel management 88.9 ± 7.1 vs. 55.4 ± 11.4 (p < 0.001, assessed by parents) and 84.5 ± 8.9 vs. 53.4 ± 12.5 (p < 0.001, assessed by children), respectively. Moreover, the positive impact of bowel management on quality of life was confirmed for all domains of the quality of life (physical well-being, emotional well-being, self-confidence, family, friends, school, disease), (p < 0.001 for all), both by the parents' and the children's assessment. CONCLUSION: Administering bowel management considerably alleviates the symptoms of fecal and urinary incontinence and considerably improves the quality of life. Bowel management should be considered as an integral part of treatment of children with spina bifida.

Glucose metabolism during ghrelin infusion in patients with anorexia nervosa.

Anorexia nervosa (AN) is an eating disorder characterized by self-induced starvation due to fear of adiposity. Ghrelin, gastric peptide with potent orexigenic, adipogenic, GH-releasing and metabolic properties, is elevated in AN. We have previously shown that intervention with exogenous ghrelin is not effective in terms of inducing neuroendocrine and appetite responses in AN. In this arm of the same study protocol we investigated glucose metabolism responses to 5 h i.v. infusion of active ghrelin in a) 9 severely malnourished AN patients, b) 6 AN patients who partially recovered body weight (PRAN), c) 10 constitutionally thin female subjects with regular menstrual cycles. At baseline, no significant differences were observed in blood glucose, insulin, c-peptide, adiponectin, and homeostasis model assessment index values, between the studied groups. During ghrelin infusions, blood glucose levels significantly increased in all groups although significantly less in low-weight AN; insulin levels were not significantly affected, while c-peptide levels were significantly suppressed only in the constitutionally thin and PRAN subjects. In addition to our previous findings of impaired neuroendocrine and appetite responses in patients with AN, we conclude that metabolic responses to ghrelin are attenuated in these patients, which tend to recover with weight gain.

Total ghrelin levels during acute insulin infusion in patients with polycystic ovary syndrome.

Controversial data were reported concerning fasting ghrelin (decreased, normal or elevated) in polycystic ovary syndrome (PCOS). The aim of our study was to clarify ghrelin levels in non-obese, overweight, and obese PCOS patients; to investigate the effect of acute insulin infusion on ghrelin in PCOS as a chronic insulin-resistant state, with and without the impact of obesity, and to examine ghrelin-androgen interaction. In that order, we evaluated 1) ghrelin levels among 8 nonobese patients with PCOS [body mass index (BMI): 20.52+/-1.31 kg/m2], 8 overweight and obese patients with PCOS (BMI: 34.36+/-6.53 kg/m2) and their respective controls, 2) ghrelin suppression during euglycemic hyperinsulinemic clamp, and 3) ghrelin-androgen interrelationship. After overnight fast, 2-h euglycemic hyperinsulinemic clamp, was performed in all investigated women. Fasting ghrelin was significantly lower in non-obese PCOS than in controls (64.74+/-25.69 vs 108.36+/-52.60; p<0.05) as well as in overweight and obese PCOS in comparison with controls (38.71+/-14.18 vs 98.77+/-40.49; p<0.05). Insulin infusion significantly suppressed ghrelin in all subgroups of investigated women. Analysis of variance for repeatable measures confirmed that there was no significant difference in pattern of response between PCOS and controls. In conclusion, women with PCOS had lower fasting ghrelin and decreased insulin sensitivity independently of their BMI, compared to the controls. In addition, there were no differences between fasting ghrelin levels among non-obese, overweight, and obese women with PCOS. During euglycemic hyperinsulinemic clamp, ghrelin decreased in all studied groups to a similar extent, implying that, compared to chronic hyperinsulinemia, acute hyperinsulinemia reduces ghrelin levels independently of the degree of insulin resistance.

Ghrelin has partial or no effect on appetite, growth hormone, prolactin, and cortisol release in patients with anorexia nervosa.

CONTEXT: Anorexia nervosa (AN) is an eating disorder characterized by self-induced starvation. Gastric hormone ghrelin, potent orexigen, and natural GH secretagogue are increased in AN. Although exogenous ghrelin stimulates appetite, GH, prolactin, and cortisol release in humans, its effects have not been studied, during infusions, in AN patients. OBJECTIVE: The objective of the study was to determine the effects of ghrelin on appetite, sleepiness, and neuroendocrine responses in AN patients. DESIGN: This was an acute interventional study. SETTING: The study was based at a hospital. Investigated SUBJECTS: Twenty-five young women, including nine patients diagnosed with AN with very low body weight, six AN patients who partially recovered their body weight but were still amenorrheic, and 10 constitutionally thin female subjects, without history of eating disorder, weight loss, with regular menstrual cycles, were included in the study. INTERVENTION: Each patient received 300-min iv infusion of ghrelin 5 pmol/kg.min and was asked to complete Visual Analog Scale questionnaires hourly. MAIN OUTCOME MEASURES: Visual Analog Scale scores for appetite and sleepiness, GH, prolactin, and cortisol responses were measured. RESULTS: At baseline, AN patients had significantly higher ghrelin, GH, and cortisol levels and significantly lower leptin than constitutionally thin subjects. GH responses to ghrelin infusion were blunted in patients with AN. Ghrelin administration did not significantly affect appetite but tended to increase sleepiness in AN patients. CONCLUSIONS: Ghrelin is unlikely to be effective as a single appetite stimulatory treatment for patients with AN. Our results suggest that AN patients are less sensitive to ghrelin in terms of GH response and appetite than healthy controls. Ghrelin effects on sleep need further studies.

OC-07 - Decoding risk for thromboembolic events in lymphoma patients.

INTRODUCTION: There are few prediction tools for estimating the risk of thrombosis but they are based on studies performed on hospitalized medical patients without cancer or on hospitalized neutropenic cancer patients without special consideration to lymphoma patients. AIM: Aim of our study was to determine incidence of thromboembolic (TE) events in patients with non Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) who were hospitalized to the lymphoma department in the Clinic of hematology, Clinical Center Serbia, Belgrade and Clinic of hematology, Clinical Center Kragujevac. Also, we assessed 2 predictive models (Padua and Khorana score) and create new model for the identification of lymphoma patients at risk for thromboembolism. MATERIALS AND METHODS: We reviewed all medical records of patients with with NHL, HL and CLL/SLL diagnosed and treated at two previously mentioned institution between January 2006 and December 2014. RESULTS: The study population included 1820 eligible lymphoma patients. Of all the patients included in the study, 99 (5.4%) developed at least one TE during a follow-up period of 3 months from the end of therapy. In the final multivariate analysis, the following variables were independently associated with risk of TE: previous VTE and/or arterial events, reduced mobility (ECOG 2-4), obesity (BMI >30 kg/m(2)), extranodal localization, mediastinum involvement, development of neutropenia during therapy and hemoglobin level less than 100g/L. Subsequently, we assigned points for the risk model based on the regression coefficients obtained from the final model and developed Thrombosis Lymphoma (ThroLy) score consisting of all significant variables from the multivariate analysis. The Throly score was arrived at by assigning 2 points for all parameters with an OR >5 in multivariate regression analyses (e.g., previous VTE and arterial events, mediastinum involvement, and BMI) and 1 point for rest all other significant variables. Finally, population were divided into 3 risk categories for TE based on the score from the risk model: low (score 0-1), intermediate (score 2-3) and high (score >3). High risk score had a positive predictive value (probability of TE in those designated high risk) of 65.2%. CONCLUSIONS: Significance of our investigation is development of score that help phisicians to recruit lymphoma patients at risk for development of thromboembolic complications. Also, we can say that our score is dynamic allowing us to change approach during different phase of therapy and is not limited to outpatient settings or with some complicated laboratory analysis.

Incidence of acute pancreatitis and nucleoside reverse transcriptase inhibitors usage.

Acute pancreatitis (AP) is a well-known adverse effect of nucleoside reverse transcriptase inhibitors (NRTIs). Therefore, we performed a prospective, cohort study to examine the incidence rates (IRs) and rate ratios (RRs) of AP for each NRTI. A total of 116 HIV patients were included in the final analysis comprising 445.6 person-years of follow-up. Twelve cases of AP were recorded. The lowest IR for AP was for didanosine (ddI) (IR=0.03 per 100 person-years, 95% confidence interval [CI] = 0.01-0.05), and the highest for ddI + stavudine (d4T) (IR = 0.08, 95% CI = 0.07-012). Compared with ddI alone, the RR of AP was 2.21 (95% CI = 1.32-9.31) for d4T, and 3.13 (95% CI = 1.43-12.56) for ddI + d4T. Other risk factors for AP were CD4 cell count <200 cells/mm(3) and female sex. Our results suggest that the use of d4T alone or combined with ddI should not be used as first-line therapy, especially in women or patients with CD4-cell count <200 cells/mm(3).

The effect of parathyroidectomy on insulin sensitivity in patients with primary hyperparathyroidism - an never ending story?

Previous studies demonstrated insulin resistance and increased prevalence of impaired glucose tolerance and type 2 diabetes mellitus in patients with primary hyperparathyroidism (PHPT). The effect of curative parathyroidectomy on insulin sensitivity was associated with conflicting results depending on which method for measuring the insulin sensitivity has been used. There was no improvement using HOMA and QUICKI while minimal model demonstrated significant improvement in insulin sensitivity. The aim of our study was to evaluate the insulin sensitivity before and after parathyroidectomy in patients with PHPT using a euglycemic clamp. 44 patients with PHPT and 11 age and body mass index matched healthy controls participated in study protocol. Before surgery M values and HOMA IR suggest insulin resistance in patients with PHPT. There was no difference in M index (3.74±1.89 vs. 4.62±2.27, p>0.05), HOMA IR (2.94±1.39 vs. 3.29±0.81, p>0.05), AUC glucose (863.0±261.3 vs. 842.3±165.5, p>0.05), AUC insulin (7068.7±4159.0 vs. 7229.6±2581.7, p>0.05), ISI (4.73±2.77 vs. 4.25±2.94, p>0.05) and AIR (47.89±32.05 vs. 38.96±21.20, p>0.05) between patients with PHPT and HC. There was significant improvement in insulin sensitivity after parathyroidectomy but both preoperative and postoperative M values were not significantly different in comparison to HC. There were no significant changes in HOMA IR, AUC glucose, AUC insulin, ISI and AIR before and after therapy. In conclusion, we observed significant improvement in insulin sensitivity after parathyroidectomy in patients with PHPT. There was no difference in parameters of insulin secretion before and after parathyroidectomy in patients with PHPT.

Immunohistochemical analysis of cyclin D1 and p53 in multiple myeloma: relationship to proliferative activity and prognostic significance.

Conflicting data are reported on the clinical significance of cyclin D1 deregulation in multiple myeloma. The aim of this study was to evaluate the incidence and prognostic significance of cyclin D1 expression and p53 mutations in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients with newly diagnosed multiple myeloma. Expression of cyclin D1 and p53 was analyzed using standard immunohistochemical method of B5-fixed and routinely processed paraffin-embedded bone marrow specimens. Cyclin D1 was overexpressed in 14/59 (27%) and p53 in 5/59 (8.5%) specimens. There was no significant correlation between cyclin D1 overexpression and age, gender, clinical stage (Durie-Salmon classification), extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, C-reactive protein, and beta2-microglobulin. No association was observed between the expression of cyclin D1 and the extent of bone marrow infiltration, histological grade, proliferative activity index (measured with Ki-67 immunoreactivity) and response to therapy. No significant difference was observed regarding overall survival between cyclin D1 positive and cyclin D1 negative patients (29 vs 36 mo, p = 0.76). Results of this study did not revealed prognostic significance of cyclin D1 overexpression in multiple myeloma. Mutations of p53 gene are rare events in myeloma, suggesting their limited role in the pathogenesis of the disease.

Strengthening early warning function of surveillance in the Republic of Serbia: lessons learned after a year of implementation.

The Republic of Serbia, with WHO support, has implemented an early warning system (ALERT) for priority communicable diseases, to complement the routine surveillance system which notifies individual confirmed cases. The results of its evaluation, conducted one year after implementation is presented here. ALERT relies on notification of 11 syndromes by primary care facilities. Data is analysed weekly at district level and transmitted to national epidemiologists. ALERT is perceived to be a simple and flexible tool. Acceptability is higher at national level than at district level. Some districts perceive ALERT as a parallel system poorly connected to control measures. Sensitivity of ALERT in detecting cases of meningitis is 93%, and 37% for cases of hepatitis. Retrospective analysis of ALERT data identified 9 outbreaks, 5 of which had been recognized by epidemiologists. ALERT was the timeliest system for detecting 4 outbreaks identified by both systems. ALERT was useful for triggering timely investigation and control of outbreaks of hantavirus and salmonellosis and for detecting the start of the influenza season. However, ALERT did not detect clusters of brucellosis and tularaemia targeted by the unexplained fever syndrome. This evaluation underlined the need for a global review of surveillance activities when implementing new components such as ALERT. While control measures based on notification of individual confirmed cases are well understood and implemented, the investigation and verification process that should result from an increase in ALERT syndromes is not fully understood. Field epidemiology training programmes, such as the EPIET programme, are best suited to bring about this change of perspective.

Strengthening early warning function of surveillance in the Republic of Serbia: lessons learned after a year of implementation.

The Republic of Serbia, with WHO support, has implemented an early warning system (ALERT) for priority communicable diseases, to complement the routine surveillance system which notifies individual confirmed cases. The results of its evaluation, conducted one year after implementation is presented here. ALERT relies on notification of 11 syndromes by primary care facilities. Data is analysed weekly at district level and transmitted to national epidemiologists. ALERT is perceived to be a simple and flexible tool. Acceptability is higher at national level than at district level. Some districts perceive ALERT as a parallel system poorly connected to control measures. Sensitivity of ALERT in detecting cases of meningitis is 93%, and 37% for cases of hepatitis. Retrospective analysis of ALERT data identified 9 outbreaks, 5 of which had been recognized by epidemiologists. ALERT was the timeliest system for detecting 4 outbreaks identified by both systems. ALERT was useful for triggering timely investigation and control of outbreaks of hantavirus and salmonellosis and for detecting the start of the influenza season. However, ALERT did not detect clusters of brucellosis and tularaemia targeted by the unexplained fever syndrome. This evaluation underlined the need for a global review of surveillance activities when implementing new components such as ALERT. While control measures based on notification of individual confirmed cases are well understood and implemented, the investigation and verification process that should result from an increase in ALERT syndromes is not fully understood. Field epidemiology training programmes, such as the EPIET programme, are best suited to bring about this change of perspective.

The results of some cytochemical reactions in metastatic malignant tumor cells in pleural and peritoneal effusions.

The cytomorphologic and cytochemical investigation of 59 samples of pleural and peritoneal effusions with malignant tumor cells was performed and the results were compared. The diagnosis was confirmed histologically in most cases. The cytomorphologic method gave very good results not only in the determination of malignant tumor cells but also in the differentiation of various kinds of tumors. A diagnosis was made of differentiated carcinoma (adenocarcinoma and squamous carcinoma) in 40 cases, undifferentiated carcinoma in five, sarcoma or hemoblastosis in nine and undifferentiated malignant tumor in five cases. The results of cytochemical reactions investigated demonstrated a significant difference between the cells of carcinoma and sarcoma, and in various kinds of carcinoma the most important difference was found between the positive reaction of the alkaline phosphatase and negative reaction of the acid phosphatase in the cells of ovarina and uterine carcinoma. Although we consider the morphologic examination of effusions the most important for the diagnosis of malignancy, the cytochemical methods can sometimes be helpful in a more precise differentiation.