Significant Increase In Incidence Research Articles

The prevalence of fungal infections in a level I Iranian burn hospital

Background: With significant increase in incidence of fungal infections in burn victims, determination of patternof fungal infections and colonization is required to allow medical staff to begin proper empirical antibiotic therapyin early stages of septic episodes. Objective: To determine the current infection profile (especially fungal profile) of burn wounds in a level I burncare center in Tehran. Methods: A cross-sectional survey was conducted from January 2008 to September 2009 on burn wound patientsadmitted in Shahid Motahari Burn Hospital, Tehran, Iran. Wound swab cultures and tissue specimens from 869patients (634 male and 235 female) out 4083 were taken and cultured in Sabouraud dextrose agar. The fungalorganisms were then identified with macroscopic and microscopic structures. Results: The incidence of fungal infection (not colonization) among the patients of this study was 13%.Candida albicans was identified as the dominant fungal agent (45%) followed by Aspergillus fumigatus (35%),Penicillium (8%), Aspergillus niger (5%), and other fungal organisms (7%). Conclusion: With such high mortality rate and an increasing incidence of fungal wound infections, fungalinfections should be a top infectious complication of burn patients and should be managed immediately andaggressively. Keywords: Burn wound, Candida albicans, colonization, fungal infection, incidence

Seventeen‐year study shows rise in parapneumonic effusion and empyema with higher treatment failure after chest tube drainage

To evaluate epidemiology, pre-admission characteristics and management of paediatric parapneumonic effusions (PPEs) and empyema in a tertiary paediatric pulmonary centre between 1993 and 2010. Retrospective chart review study using paediatric and thoracic database searches, with particular emphasis on pre-admission characteristics, disease stage (simple or complex effusion or empyema), general management and surgical procedures. One hundred children were eligible, exhibiting a significant increase in incidence from 0.5 to 2.6 per 100000 across the study period. Baseline characteristics were similar across disease stages. Streptococcus pneumoniae was the most common pathogen. Surgical intervention beyond chest tube drainage (CTD) was required in 50%; this rate showed a particular increase in children aged 0-5years (OR, 3.1), but was otherwise not influenced by baseline characteristics, disease stage or use of intrapleural fibrinolytics. Length of hospitalisation did not differ across disease stages or primary interventional procedures. This study confirmed an increasing incidence of PPEs and empyema in a Scandinavian tertiary paediatric pulmonary centre. Young children exhibited higher treatment failure after CTD. Length of hospitalisation was similar across disease stages and was comparable to previous reports according to primary interventional procedure.

Incidence trend of malignant polyps through the data of a specialized colorectal cancer registry: clinical features and effect of screening

Objectives. The purposes of the study are to describe the incidence trend of malignant polyp of large bowel over a 25-year period in the District of Modena and to assess the effect of an organized colorectal cancer screening program. Material and methods. Through the data of a specialized colorectal cancer Registry, we evaluate the clinical and pathological features of the polyps. Trend analysis was assessed with the Joinpoint Regression Program. Results. A total of 172 patients with malignant polyps were diagnosed throughout the study (3.5% of 4.835 registered patients); their overall frequency during the registration period increased from zero cases in the initial years (1984–85) to 57 cases in the past 3 years (2006–2008). Crude incidence rate passed from 0.37 in 1986–89 to 10.2 in 2006. Joinpoint trend analysis of crude rates showed a significant increase of incidence during the study period, with percent of annual variation ranging between 38.6% (95% CI 12.5–70.7) and 7.3% (95% CI 2.6–12.1). During the screening period (2005–2008, the past 4 years of registration) there was a significant increase of sessile polyps (p < 0.001), while other clinical and morphological features, including the number of low- and high-risk malignant polyps, remained unchanged. The surgery (after polypectomy) tended to raise both in low- and high-risk subgroups. Conclusion. The incidence of malignant polyps increased significantly from the initial to the most recent periods of colorectal cancer registration. Screening was associated with changes in gross morphology of polyps and with an increased use of the surgery after endoscopic polypectomy.

Endocrine disruptors found in food contaminants enhance allergic sensitization through an oxidative stress that promotes the development of allergic airway inflammation

In the past few decades, there has been a significant increase in incidence of allergic diseases. The hygiene hypothesis may provide some clues to explain this rising trend, but it may also be attributable to other environmental factors that exert a proallergic adjuvant effects. However, there is limited information on the risks of developing allergic asthma and related diseases through the ingestion of environmental chemicals found in food contaminants. In the present study, we have shown that oral administration of tributyltin, used as a model environmental chemical, induced oxidative-stress status in the bronchial lymph node, mesenteric lymph node and spleen, but not in the lung, where the initial step of allergic asthma pathogenesis takes place. Mice exposed to tributyltin exhibited heightened Th2 immunity to the allergen with more severe airway inflammation. Tributyltin also induced Treg cells apoptosis preferentially over non-Treg cells. All these effects of tributyltin exposure were canceled by the administration of glutathione monoethyl ester. Meanwhile, tributyltin did not affect airway inflammation of mice transferred with allergen-specific Th2 cells. Collectively, these results suggest that tributyltin exerts its pathological effect during the sensitization phase through oxidative stress that enhances the development of allergic diseases. The current study dissects the pathogenic role of oxidative stress induced by oral exposure to an environmental chemical during the sensitization phase of allergic airway inflammation and would be important for developing therapeutics for prevention of allergic diseases.

건강관련 2차 자료에 근거한 왜관 지역주민의 암 발생 현황

Objectives: As the suspicion was raised that ‘Agent Orange’ was reclaimed 30 years ago at Camp Carol, located in Waegwan, Gyeongsangbuk-do, the government conducted an investigation of the influence of environmental and health effects around Camp Carol through a public-private joint investigation team. As part of the investigation of population health effects, this study was carried out in order to observe changes and regional differences in diseases, particularly cancer, by year. Methods: We authors conducted an analysis of secondary health data, such as cancer registration data, mortality data, and health insurance data. We drew an age standardized incidence ratio (SIR), death rate (SDR), mortality ratio (SMR), and health care utilization rate using these data. Results: For gastric cancer in women, and other cancers in men, a significant increase in incidence was observed compared to the control area. For biliary tract cancer, gallbladder cancer, and thyroid cancer in women, and prostate cancer in men, a significant decrease in incidence was observed compared to the control area. In the national statistical analysis of data, such as health insurance data and mortality data, we did not observe a significant increase at the Waegwan region compared to other regions. Conclusions: We must consider the limitations of this study. Because thirty years have passed from the time of the estimated landfill of ‘Agent Orange’, recent national statistical data may not reflect the past real situation. Therefore, the monitoring of secondary data for health effects at the municipal level should be carried out continuously.

Is a hypothetical melanoma-like neuromelanin the underlying factor essential for the aetiopathogenesis and clinical manifestations of multiple sclerosis?

BackgroundMultiple sclerosis (MS) has undergone a significant increase in incidence in the industrialised nations over the last 130 years. Changing environmental factors, possibly infections or a lack of or altered timing of them, determine the prevalence of the disease. Although a plethora of aetiological factors, clearly evident in a group of children with MS, appear relevant, there may nevertheless be a single factor essential for the aetiopathogenesis and clinical manifestation of MS.Description and discussionThis hitherto unknown factor is postulated to be a ‘melanoma-like neuromelanin’ (MLN) dependent on the activation of a gene for syncytin-1. An involvement of MLN could explain the diverse findings in the epidemiology, immunology and pathology of MS, requiring a consideration of a complex infectious background, the human leucocyte antigens, as well as cosmic radiation causing geomagnetic disturbances, vitamin D deficiency, smoking, and lower levels of uric acid.SummaryIn principle, the MLN-based concept is a unifying one, capable of explaining a number of characteristics of the disease. To date, MLN has not been addressed in studies on MS and future work will need to be done on human patients, as there is little or no neuromelanin (the precursor of MLN) in the animals used as experimental models in the study of MS.

Antiplatelet Drugs Are a Risk Factor for Esophageal Mucosal Injury

Background: In esophagus whether antiplatelet drugs, such as low-dose aspirin (LDA) and clopidogrel, induce mucosal injury by pH changes or by acid reflux is unclear. We designed to clarify which mechanism was responsible. Methods: In study 1, 80 patients taking LDA and 80 age- and sex-matched subjects who underwent endoscopy for dyspeptic symptoms or for a health check-up were evaluated the endoscopic incidence of esophageal mucosal injury and severity. In study 2, 35 healthy subjects were treated with LDA 100 mg (regimen A), and then 20 randomly selected subjects were dosed clopidogrel 75 mg (regimen C), LDA/clopidogrel (regimen AC), or LDA/clopidogrel/rabeprazole 10 mg for 7 days. Subjects underwent endoscopy and 24-hour pH measurements on day 7. Results: In study 1, the prevalence of esophageal injury in LDA patients was 40.0%, significantly higher than in non-LDA subjects (25.0%, p = 0.042). In study 2, significant increases in incidence of injury were observed with regimens A (45.8%) and AC (50.0%), but not with C (20.0%), on day 7. Among subjects in whom pH was >5.0 and <4.0 for less than 40% of time, none developed esophageal injury. Conclusions: LDA caused esophageal injury in half of patients and volunteers. Acid-inhibitory drugs effectively prevented the development of LDA-induced, not clopidogrel, esophageal injury.

Active and passive smoking in relation to lung cancer incidence in the Women's Health Initiative prospective cohort study.

1504 Background: The relationship between both active and passive smoking and lung cancer incidence in post-menopausal women was examined in theWomen’s Health Initiative Observational Study (WHI-OS). Methods: The WHI-OS, a prospective cohort study conducted at 40 U.S. centers, enrolled women ages 50-79 from 1993-1998.Among 93,676 participants, 76,304 women with complete smoking and covariate data comprised the analytic cohort, in which the association of lung cancer incidence with active and passive (childhood, adult home, and work) smoking exposure was studied. Results: Over 10.5 meanyears of follow-up with 901 lung cancer cases, lung cancer incidence was higher in current smokers (HR 13.44, 95% CI 10.80-16.75) and former smokers (HR 4.20, 95% CI 3.48-5.08), compared to never smokers. This relationship was dose-dependent for both current and former smokers. Risk of all lung cancer subtypes, particularly small cell lung cancer (SCLC) and squamous cell carcinoma (SqCC), was higher in smokers. Among never smokers, any passive smoking exposure (HR 0.88, 95% CI 0.52-1.49) and most passive smoking categories did not significantly increase lung cancer risk, compared to no passive exposure; however, passive exposure as an adult at home for &gt;=30 years was associated with increased risk, of borderline significance (HR 1.61, 95% CI 1.00-2.58). Current smokers had an annualized lung cancer incidence rate of 472.9 cases/100,000 person-years, compared to 158.1 for former smokers and 36.2 for never smokers (112.3 overall). Conclusions: To our knowledge, this is the first study to examine both active and passive smoking in relation to lung cancer incidence in a complete prospective cohort of U.S. women. Active smoking is associated with significant increases in incidence of all lung cancer subtypes in post-menopausal women, particularly SCLC and SqCC. Smoking cessation decreases lung cancer risk. Prolonged exposure as an adult at home may be the strongest passive smoking contributor to lung cancer risk in this cohort. The findings support continued need for investment in smoking prevention and cessation, research on passive smoking, and understanding of lung cancer risk factors other than smoking.

Rak gruczołu krokowego o wysokim ryzyku progresji: skutki pominięcia zasad Evidence Based Medicine (EBM) i braku współpracy interdyscyplinarnej

Prostate cancer (PC) is currently a problem for urologists and oncologists because of the significant incidence increase which has been also reported in Poland (10,000 new cases). The biggest challenge for the therapeutic team is locally advanced PC because of its extra capsular extension and increased risk of metastases in pelvic lymph nodes. Treatment of PC should be considered with multidisciplinary approach (MTD). The benefits of therapeutic decision made by the MDT has been proven in many types of cancers, and for this reason in the United States and most EU countries this approach also for PC is a mandatory standard of treatment that contributes to better survival rates, higher satisfaction of patients and economic benefit.The medical history of a 61-year-old man with prostate cancer will be described. The cancer was diagnosed in April 2012, based on a biopsy of the prostate (Prostate Adenocarcinoma, Gleason score=6, PSA=32 ng/ml). The patient made a decision to be treated abroad. Patient was in the group of high risk disease progression and the standard treatment is radiation therapy combined with 2–3 years lasting hormonal therapy. Radical prostatectomy with extended lymph node dissection is recommended as an optional treatment for selected patients without fixation. Urologist made a choice to perform a robotic assisted radical prostatectomy. After surgery, there were indications in pathological report to perform adjuvant radiotherapy, however it was not considered. Nowadays a patient is prepared to receive a salvage treatment in the oncological centre in Poland but delay in treatment could have significant effect on his prognosis.The main conclusion is that even the most expensive and modern therapy such as robotic surgery without MTD approach and Evidence Based Medicine can result worse outcomes. In this case both the basic principles in oncology Evidence Based Medicine and MTD approach were not included.

Prevalence of Tumours in Domestic Animals in the Lower Silesia (Poland) in 2009–2011

Abstract The study aimed at the analysis of prevalence frequency and localisation of tumours in domestic animals. The research material comprised 4,212 tumours developed in dogs, cats, horses, and exotic animals, isolated during surgery, autopsy or biopsy, performed for the purpose of histopathological diagnosis. The most numerous group involved canine tumours, including 3,585 cases (85.1%), followed by tumours in cats (532 cases, 12.6%), ferrets (34 cases, 0.81%), rats (19 cases, 0.45%), horses (15 cases, 0.36%), and rabbits (14 cases, 0.33%). A significant increase in incidence of tumours was noted, as compared to studies performed in the same region of Poland in 1957-1995 and 2000-2004 or in 2005-2008. This was particularly evident in exotic animals, in which 80 cases (1.9%) were detected in 2009-2011 but only 20 cases (1.2%) in 2005-2008. The most frequent localisation of neoplasia involved the skin, subcutaneous tissue, and mammary gland.

Temporal trends in the incidence of kidney stone disease

Recent reports show an increased occurrence of kidney stone disease worldwide. To further evaluate and quantify this observation, we examined recent trends in the incidence of kidney stone disease in the adult population of Iceland over a 24-year period. Computerized databases of all major hospitals and medical imaging centers in Iceland were searched for International Classification of Diseases, radiologic and surgical procedure codes indicative of kidney stones in patients aged 18 years and older. The time trends in stone frequency of 5945 incident patients (63% men) were assessed by Poisson regression analysis. The majority of patients (90.5%) had symptomatic stone disease. The total incidence of kidney stones rose significantly from 108 per 100,000 in the first 5-year interval of the study to 138 per 100,000 in the last interval. The annual incidence of symptomatic stones did not increase significantly in either men or women. There was, however, a significant increase in the annual incidence of asymptomatic stones over time, from 7 to 24 per 100,000 for men and from 7 to 21 per 100,000 for women. The increase in the incidence of asymptomatic stones was only significant for women above 50 years of age and for men older than 40 years. Thus, we found a significant increase in the incidence of kidney stone disease resulting from increased detection of asymptomatic stones. This was largely due to a more frequent use of high-resolution imaging studies in older patients.

147: Infective endocarditis in Tunisia: A changing profile?

Since the first description of infective endocarditis (IE), the profile of the disease has evolved continuously with stable incidence. To update information gained on the epidemiology profile of IE in a Tunisian high-volume tertiary care center This was a descriptive retrospective study of patients treated for IE from January 2001 to December 2010. The patients were divided in two groups according to the date of diagnosis of IE: group 1 (from January 2001 to June 2006) and group 2 (from June 2006 to December 2011). These groups were compared for epidemiologic factors and microbiological differences. A total of 297 patients admitted during the study period met the modified Duke criteria for IE. The comparison of demographic and microbiological characteristics of IE cases over time between the results of the two groups showed that the annual incidence of IE was stable. The sex incidence rates of IE, in particular, incidence among men was relatively stable across the study period and ranged from 60% in 2001-2006 to 58% in 2006-2010, also there was no significant increase in incidence among women (P=ns). Among incident cases, there was a significant increasing age on presentation, with median age increasing from 39.5 years in 2001-2006 to 51.5 years in 2006-2010 (P=0.05). There were no statistically significant decreases in the proportions of cases affecting the aortic valve (P=0.4) and in IE due to oral streptococci (P= ns) over time. Also there was no significant increase in the incidence of Staphylococcus IE. However, the incidence of IE with negative blood culture has remained stable and continues to be high, nearing 50%. The rate of rheumatic heart disease as an underlying heart disease was stable over time. However, the standardized incidence of IE has increased in patients with prosthetic valves (P= ns). Overall in-hospital mortality rate decreased from ((18.6% in 2001-2006 vs 14.6% in 2006-2010. This study has shown that the annual incidence of IE is stable in Tunisia. However, profound changes in the epidemiological profile of this disease have not been noted in our population.

Clinical significance of troponin elevations in acute decompensated diabetes without clinical acute coronary syndrome

BackgroundElevation of cardiac troponin has been documented in multiple settings without acute coronary syndrome. However, its impact on long-term cardiac outcomes in the context of acute decompensated diabetes remains to be explored.MethodsWe performed a retrospective analysis of 872 patients admitted to Temple University Hospital from 2004–2009 with DKA or HHS. Patients were included if they had cardiac troponin I (cTnI) measured within 24 hours of hospital admission, had no evidence of acute coronary syndrome and had a follow up period of at least 18 months. Of the 264 patients who met the criteria, we reviewed the baseline patient characteristics, admission labs, EKGs and major adverse cardiovascular events during the follow up period. Patients were categorized into two groups with normal and elevated levels of cardiac enzymes. The composite end point of the study was the occurrence of a major cardiovascular event (MACE) during the follow up period and was compared between the two groups.ResultsOf 264 patients, 24 patients were found to have elevated cTnI. Compared to patients with normal cardiac enzymes, there was a significant increase in incidence of MACE in patients with elevated cTnI. In a regression analysis, which included prior history of CAD, HTN and ESRD, the only variable that independently predicted MACE was an elevation in cTnI (p = 0.044). Patients with elevated CK-MB had increased lengths of hospitalization compared to the other group (p < 0.001).ConclusionsElevated cardiac troponin I in patients admitted with decompensated diabetes and without evidence of acute coronary syndrome, strongly correlate with a later major cardiovascular event. Thus, elevated troponin I during metabolic abnormalities identify a group of patients at an increased risk for poor long-term outcomes. Whether these patients may benefit from early detection, risk stratification and preventive interventions remains to be investigated.

The measles outbreak in the French military forces – 2010–2011: Results of epidemiological surveillance

Since the start of 2010 there has been a flare-up of measles in France, following on the resurgence observed in 2008. The aim of this study was to present results of the epidemiological surveillance of measles in the French armed forces in metropolitan France and to describe the outbreak that occurred in 2010 and 2011. Criteria for report were those used for French national compulsory notification. The data, concerning active military personnel, were derived from epidemiological surveillance from 1992 to 2011 for the incidence rates and from notification forms completed in 2010 and 2011 by the military practitioners for the description of characteristics of cases. Between January 1992 and July 2010, 833 cases of measles were reported. Since 2002, the mean incidence rate had been 1 case p.100,000. A significant increase in incidence was observed in 2010 (10.1 p.100,000) and in 2011 (41.4 p.100,000). Clusters of cases accounted for 72.3% of cases. Rates were much higher among subjects under 30. Only 68.6% of cases had been previously vaccinated with at least one dose of MMR vaccine. The mean vaccine coverage among contacts of cases was approximated to 54.3%. The outbreak of measles observed in 2010 and 2011 in the French armed forces followed the same pattern as that observed nationally and at European level, and can be seen as the likely consequence of inadequate vaccination coverage.

Peri-ovulatory putrescine to reduce aneuploid conceptions

Women experience diminished fertility, increased risk of miscarriages and congenital birth defects in their late 30s and early 40s, 10-15 years before reaching menopause. Egg aneuploidy (having an incorrect number of chromosomes) is the most important etiology for these reproductive problems in older women. Science correspondent Jon Cohen wrote a News piece in 2002 [1] on the quest to understand the mechanisms of maternal aging-related aneuploidies in humans, which is still applicable today. Although we have made impressive progress in understanding how aneuploidies arise, we know little about providing medical interventions to reduce them. “My Holy Grail is to deliver some sort of aneuploidy-reduction pill, …”, Dr. Terry Hassold, a leading geneticist in the field, is quoted as saying. Our recent study [2] may be a step towards developing such a pill. Aneuploid eggs result in aneuploid conceptions, most of which are lost either prior to clinical recognition of pregnancies or by miscarriages. The small proportion that survive inevitably carry major birth defects. Accurate egg aneuploidy rates in the general population are not known, but numerous analyses of IVF samples have revealed staggeringly high rates. Notably, a recent study of more than 20,000 IVF eggs revealed significant age-related aneuploidies, reaching >40% in the 40 year old age group [3]. Furthermore, this study [3] employs fluorescence in situ hybridization of polar bodies and is therefore limited in the number of chromosomes (five) that can be analyzed simultaneously. The true aneuploidy rates in older women, considering all 23 chromosomes, would be expected to be much higher. This unusually high egg aneuploidy rate in humans is likely due to a combination of our longevity and the peculiar oogenesis (the process of generating eggs) in all vertebrates including humans. Unlike vertebrate males that continuously generate mature sperm from germ line stem cells through adulthood, in vertebrates oogenesis begins during the embryonic stage when germ line stem cells initiate meiosis and develop into primary oocytes. By birth, the females have developed a finite number of primary oocytes arrested in meiotic prophase that comprises their lifetime egg supply. The prophase oocytes contain chromosome bivalents each having four chromatids linked together by a combination of sister chromotid cohesion and non-sister cross-over (Figure ​(Figure1),1), with this linkage persisting for decades in women. During ovulation the two sister chromatids are segregated to the same cell (egg or 1st polar body) in a process called oocyte maturation; in the subsequent fertilization, the sisters are segregated between the 2nd polar body and the haploid egg. As females age, chromosome cohesion becomes progressively weakened [4], predisposing the oocytes to greater risk of premature separation of sister chromatids (PSSC) during oocyte maturation [2-5] (Figure ​(Figure11). Figure 1 Premature separation of sister chromatids (PSSC) during oocyte maturation Given the great time lapse, it seems daunting that any measure can be found to keep these primary oocytes “fresh” while women age. Our study however suggests that a metabolic deficiency during ovulation in older females, which can be easily corrected, is an important compounding factor in age-related egg aneuploidies. It has been known for more than four decades [6] that during mammalian ovulation, the ovaries exhibit a transitory (i.e. a few hours) rise in the enzyme ornithine decarboxylase (ODC) and its product putrescine and yet its physiological function remains enigmatic. We found that inhibition of ODC during ovulation results in significant increase of incidence of PSSC in eggs of young mice. Interestingly, older mice exhibit a diminished ODC rise in the ovaries, and a corresponding increase of PSSC in eggs. Most remarkably, a combination of putrescine supplementation in mouse drinking water leading up to oocyte retrieval and in oocyte maturation medium reduced the incidence of PSSC in eggs by more than 50% [2]. Putrescine is a naturally occurring, small metabolite easily absorbed and distributed throughout the organism. A high dose of putrescine supplementation similar to that used in our study has been given safely to neonatal calves and pigs as an ingredient of soybean-based milk replacement [7]. However, post-conception putrescine supplementation in mouse drinking water compromises fetal development, likely due to excess reactive oxygen species produced by placental diamine oxidase oxidizing the exogenous putrescine [8]. In contrast, periovulatory putrescine supplementation is safe for gestation, because exogenous putrescine administered around ovulation is cleared long before placental development (Tao and Liu, in preparation). Nonetheless, further studies, including that employing primates, are required to formulate effective and safe putrescine supplementation protocols to reduce egg aneuploidies, both in IVF clinics and in natural conception.

Early Detection of Renal Dysfunction in Pediatric Sickle Cell Patients

AbstractAbstract 1017▪▪This icon denotes a clinically relevant abstractIn sickle cell disease, patients are predisposed to renal dysfunction and eventual renal failure as they reach adulthood. Many advances have been made within the field of sickle cell anemia, yet to this day sickle cell nephropathy remains an important cause of mortality in adult patients. Previous studies have determined that proteinuria and hematuria are two useful markers of sickle cell nephropathy. Currently, the best marker for detecting early renal dysfunction is proteinuria on urine dipstick due to its ease of use and efficiency. Our goal in this study is to determine the age at which the first signs of renal dysfunction appear.Pediatric patients with sickle cell disease were selected for a retrospective chart review to determine age of onset for renal abnormalities. The sickle cell pediatric roster was used from the Children’s Hospital University of Illinois to study a total of 175 patients within the age range of 0–31 years. Urinalysis was captured at patient’s baseline when available and possible risk factors for glomerular dysfunction were studied. Factors such as urine protein and blood on dipstick were recorded and proteinuria was further quantified by using the urine protein to creatinine ratio. Blood on dipstick was further analyzed by red blood cells on microscopic urinalysis. Patients with positive urine for blood on dipstick with <5 RBCs on microscopic UA were marked as patients with hemoglobinuria. Other factors such as sickle cell hemoglobin type, LDH, reticulocyte count, HbF, and hydroxyurea treatment were also recorded to look for correlation with predictors of early renal dysfunction. The Fisher’s exact test was used to compute the (two-tailed) probability.Urinalysis results were available for 141 of the 175 pediatric patients from the sickle cell roster. From the 141 patients that were studied 65% of the patients had urinalysis done at baseline, the other 35% had UA when acutely ill. The mean overall age was 9.9 years and a total of 25 of the 141 (17.7%) patients were observed to have proteinuria on dipstick. In the proteinuria group, 64% of the UA were obtained at baseline and the other 36% were during a sick visit. The majority (66%) of these ‘sick' patients were febrile under the age of 7. Obtaining a UA during an acute illness could skew our results since pediatric patients who are acutely ill may have transient proteinuria but none at baseline. In our pediatric sickle cell population, about 14% had hemoglobinuria. Analysis of only baseline UA showed that no patients under the age of 5 at baseline had proteinuria and there is a strong correlation between age and proteinuria (R2 = 0.81, p<0.02). Similarly there is a correlation between age and hemoglobinuria (R2 = 0.57). Hemoglobinuria is occasionally observed in 11.4% of children <5 years of age, and at 12.9% in the teenage group. A significant increase in incidence of hemoglobinuria is noted in the young adults (40%). Of the 16 patients with hemoglobinuria only 8 had concurrent proteinuria. A larger sample size is needed to determine whether proteinuria and hemoglobinuria are independent versus correlated markers of early renal dysfunction. Preliminary analyses of baseline UA found no correlations between proteinuria and Hb level, LDH, reticulocytes, serum creatinine, or creatinine clearance.From this retrospective chart review in this pediatric sickle cell disease population, it can be deduced that proteinuria becomes a concern in sickle patients in the adolescent years while hemoglobinuria appears in late teen to young adult years. It can be concluded that the first clinical signs of renal dysfunction which lead to nephropathy in sickle patients are more frequently seen in adolescent to late teen years and this is likely the marks the beginning of the deterioration of kidney function. Further studies are needed for multivariate analysis of other markers (GFR, Cr, Cr Clearance) of nephropathy and to improve early detection of renal dysfunction by conducting longitudinal studies. Our goal is to improve our current practice by routine screening in sickle patients to preserve renal function and improve the morbidity and mortality related to sickle cell nephropathy in the aging patient. [Display omitted] [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

P-0283 Characterisation of Colorectal Carcinoma in Uganda: is Ugandan Tumor Unique?

ABSTRACT Introduction Colorectal cancer (CRC) was thought to be uncommon in black Sub Saharan Africa. High fibre diet, low incidences of adenomas and low social economic class are postulated to give protection against CRC. The past two decades have, seen a significant increase in incidence of a unique early onset, non-polypoid type of tumor affecting principally the rural population of generally low socio-economy status and whose diet differ significantly from that of similar patients from the developed countries. There are some similarities between Uganda tumors and MSI-H CRC found principally in Black Americans. Is the Uganda tumor therefore a unique form of CRC with some similarities to CRC found mainly among black Americans? Aim To provide basic epidemiologic, pathological and clinical data on CRC in Uganda and identify characteristics of this tumor which differ from those of similar patients from the developed countries. Methods The data presented is from a large data-base of colorectal cancer patients established at Mulago hospital in Jan. 2003. This data-base is being continuously upgraded by the research team in our colorectal Unit. Presently the database consists of 448 fully documented CRC cases. Results Of 448 clinically diagnosed CRC, 386 had confirmed histological diagnosis. CRC constituted 3.8% of all malignancies and 19.8% of all GIT malignancies. Incidence has doubled from 1.7% in 1983 and is higher than 2.5% average for the entire African continent. Mean age was 52.4yrs and M : F=1.2 :1. 68% of patients were rural peasants feeding on Bananas, Maize, Millet, Cassava, Yams, Vegetables and Tropical fruits with very low meat consumption and over 60% did not smoke or consume alcohol. Mean duration of symptoms was 9.4 months. 62.2% of tumors were rectal and 78% occurred on the left side. 70.6% of staged patients had Duke's C and D tumors. Only 12 tumors were found in co-existence with colonic adenomas, five of which were confirmed to have arisen from pre-existing adenomas and no synchronous tumors were diagnosed. Tumor resection was carried out in 38.3% of patients while 28% of patients declined surgery. Only 42% of patients were followed-up for mean duration of 8.6 months. Conclusion CRC in Uganda, is unique early-onset, non-polypoid form of CRC occurring mainly in young rural peasants, of low socio-economic status, eating unprocessed high-fibre, high-carbohydrate, low-protein and fat, traditional diet rich in vegetables and tropical fruits and is distinct from that found in patients from developed countries, who are generally 2 to 3 decades older, are mainly affluent and of generally high socio-economic status and whose diet is rich in processed animal fats and proteins and low in vegetable fibres. Whereas majority of tumors from the developed countries do arise from pre-existing adenomatous polyps, the Uganda tumors do not arise from such polyps. Uganda tumors therefore appear to be a unique form of CRC.

Subchronic Thyroid Toxicity Evaluation of 4,4′-Methylenebis(N,N′-Dimethyl)Aniline in Fischer 344 Rats

Female F344 rats were exposed to 4,4′-methylenebis(N,N′-dimethyl)aniline (MDA) by dietary feed at concentrations of 0, 50, 200, 375, 500, or 750 ppm for 5 d, 2 wk, 4 wk, and 13 wk duration. Endpoints evaluated included clinical observations, body weights, thyroid weights, serum thyroid hormones, blood MDA, gross pathology, and thyroid histopathology. There were no MDA exposure-related clinical signs of toxicity. Mean body weight decreased 5% compared to control in the 750 ppm group during study wk 6 through 13. Serum TSH increased and serum T4 and T3 levels decreased with increasing feed concentrations of MDA and time of exposure. Thyroid weight increases were both concentration- and exposure time-dependent and statistically significant at ≥375 ppm. Incidence and severity of decreased colloid, follicular cell hypertrophy and follicular cell hyperplasia were also related to MDA concentration and exposure time. A no-observed-adverse-effect level (NOAEL) of 200 ppm was selected based on the statistically significant increase in incidence of follicular cell hyperplasia at concentrations ≥375 ppm.

Effects of Thiazide Diuretics on Glucose Metabolism

Previous studies have shown a small but significant increase in incidence of type 2 diabetes in patients with hypertension treated with thiazide

Esophageal cancer incidence gender disparity.

1573 Background: Over the past 30 years, esophageal cancer incidence has been increasing more rapidly than any other solid neoplasm in the Western world. Globally, there is a large male predominance in both esophageal squamous and adenocarcinoma. The reasons for this gender difference and the possible role of estrogen are unclear. The objective of this study is to determine if estrogen exposure is consistent with the male predominance observed in esophageal cancer incidence. Methods: A database assessment of esophageal cancer incidence rates (age-adjusted) from 1975 to 2008 was conducted in the National SEER 9 Database and the Maryland Cancer Registry. Rates by gender and age were calculated. Gender-specific incidence rate ratios were compared across age groups. Annual percentage change (APC) was compared for each gender-age group. Results: In both national and state, male and female, adeno and squamous cell histologies, incidence rates increase with patient age. SEER data trends revealed the 50-64 aged female cohort as the only gender-age cohort APC decreasing between 1975-2008. Furthermore, a significant increase in incidence for females is observed in the 65+ age groups; whereas among males, the rates are rising in all age groups. Conclusions: Using age as a proxy for estrogen exposure, our findings suggest a hormonal component in the declining male: female esophageal cancer incidence rate ratios with increasing age and confirm gender differences in incidence long observed in esophageal cancer. Histological features may be predictive of a lower rate ratio. (Bodelon et al. 2011) Estrogen exposure may play a protective role in esophageal cancer which dissipates with time after age 60-69. Our data suggest possible future roles of estrogen as a chemopreventive agent in esophageal cancer (Barone et al. 2011). [Table: see text] [Table: see text]