Urinary metabolites as noninvasive biomarkers of gastrointestinal diseases: A clinical review.

The diagnosis of gastrointestinal (GI) disorders is usually based on invasive techniques such as endoscopy. A key important factor in GI cancer is early diagnosis which warrants development of non- or less-invasive diagnostic techniques. In addition, monitoring and surveillance are other important parts in the management of GI diseases. Metabolomics studies with nuclear magnetic resonance and mass spectrometry can measure the concentration of more than 3000 chemical compounds in the urine providing possible chemical signature in different diseases and during health. In this review, we discuss the urinary metabolomics signature of different GI diseases including GI cancer and elaborate on how these biomarkers could be used for the classification, early diagnosis and the monitoring of the patients. Moreover, we discuss future directions of this still evolving field of research.

Alelo C del polimorfismo rs2209972 del gen de la enzima degradadora de insulina y enfermedad de Alzheimer en diabéticos tipo 2. Estudio de casos y controles / C allele of the rs2209972 single nucleotide polymorphism of the insulin degrading enzyme gene and Alzheimer's disease in type 2 diabetes, a case control study

Background and objective: In the last few decades we have witnessed an interesting transformation of the population pyramids throughout the world. As the population's life expectancy increases, there are more chronic diseases such as diabetes mellitus and dementias, and both of them have shown an association. General objetive: To determine the association between Alzheimer's disease in diabetic patients and the insulin degrading enzyme in outpatients of a second level Hospital in Monterrey, Mexico. Materials and methods: This was a case control study in which we included outpatients from the Geriatrics Clinic of a Hospital in Northeastern Mexico. Cases were patients with a Mini Mental Score Exam (MMSE) below 24 and DSM-IV criteria for Dementia. Controls were patients who had MMSE scores greater than 24. Results: Data from 97 patients were analyzed. Regarding physical examination and the results of laboratory tests, there were no differences between the two groups (p > 0.05). A 98% prevalence of the insulin degrading enzyme was documented in the sample studied. We found an association between a homozygous status for the CC genotype and Dementia with an estimated Odds Ratio (OR) of 2.5 (CI 95% 1.6–3.3) on the bivariate test, while, on the multivariate analysis, the OR was estimated 3.3 (CI 95% 1.3–8.2). Conclusions: Evidence shows that cognitive impairment is more frequent among those exposed to the C allele of the rs2209972 SNP of the insulin degrading enzyme gene (AU)

Fundamento y objetivo: En las últimas décadas se ha producido una transformación en las pirámides poblacionales, con un aumento en la expectativa de vida, lo que conlleva un mayor número de enfermedades crónico-degenerativas, como son la diabetes mellitus y la demencia, que han mostrado tener una asociación estrecha, pero cuya etiología aún está por discernir. El objetivo de este estudio fue determinar la asociación entre el alelo C de la enzima degradadora de insulina y la enfermedad de Alzheimer en pacientes con diabetes tipo 2. Material y métodos: Estudio de casos y controles, en el cual se incluyeron pacientes de la clínica de Geriatría del Hospital General del Noreste de México. Los casos fueron aquellos con una puntuación en el Mini-Mental State Examination (MMSE) menor de 24 y criterios para demencia de acuerdo con el DSM-IV. Los controles fueron pacientes con MMSE superior a 24. Resultados: Se analizaron datos de 97 pacientes. No hubo diferencias respecto a las características basales clínicas y de laboratorio entre los casos y los controles (p > 0,05). Se documentó una prevalencia de 98% del alelo C de la enzima degradadora de insulina. Encontramos una asociación entre homocigosidad para el genotipo CC de la enzima degradadora de insulina y enfermedad de Alzheimer, con una OR de 2,5 (IC 95% 1,6–3,3) en el examen bivariado, y en el examen multivariado se encontró asociación con una OR de 3,3 (IC 95% 1,3–8,2). Conclusiones: La evidencia muestra una asociación entre deterioro cognitivo y presencia del alelo C del polimorfismo rs2209972 del gen de la enzima degradadora de insulina (AU)

A diagnostic screening tool for identifying safe drivers among dialysis patients.

INTRODUCTION: Studies have shown that adverse effects of dialysis are associated with increased risk of driving impairment. While recommendations have been made that physicians should place an increased focus on detecting risks for driving impairment among patients on dialysis, there are currently no diagnostic tools designed to help physicians assess driving impairment among this patient population. In addition to driver self-assessment tools provided by AAA (American Automobile Association), one of the only tools specifically designed to help physicians assess driver safety is the "Am I a Safe Driver?" checklist, originally designed to assess for driving impairment among geriatric patients. This study aimed to determine the utility of this checklist in detecting dialysis patients at risk for driving impairment. METHODS: The checklist was administered to dialysis patients who were predetermined to either be at risk or not at risk for driving impairment. The checklist was used to identify patients who test positive for driving impairment. ROC (receiver operationg characteristic) analysis was done to identify the best cut off to consider as a positive test. RESULTS: The study found that the checklist is very good in detecting risk for driving impairment among dialysis patients. ROC analysis determined that answering “yes” to at least two statements in the "Am I a Safe Driver?" checklist gives the highest sensitivity and specificity combination (Youden's index = 0.42). DISCUSSION: Higher sensitivity and lower specificity of the "Am I Safe Driver" checklist implies that it is effective only as a preliminary screening test for ruling out risk of driving impairment among dialysis patients.

C allele of the rs2209972 single nucleotide polymorphism of the insulin degrading enzyme gene and Alzheimer's disease in type 2 diabetes, a case control study.

BACKGROUND AND OBJECTIVE: In the last few decades we have witnessed an interesting transformation of the population pyramids throughout the world. As the population's life expectancy increases, there are more chronic diseases such as diabetes mellitus and dementias, and both of them have shown an association. GENERAL OBJETIVE: To determine the association between Alzheimer's disease in diabetic patients and the insulin degrading enzyme in outpatients of a second level Hospital in Monterrey, Mexico. MATERIALS AND METHODS: This was a case control study in which we included outpatients from the Geriatrics Clinic of a Hospital in Northeastern Mexico. Cases were patients with a Mini Mental Score Exam (MMSE) below 24 and DSM-IV criteria for Dementia. Controls were patients who had MMSE scores greater than 24. RESULTS: Data from 97 patients were analyzed. Regarding physical examination and the results of laboratory tests, there were no differences between the two groups (p>0.05). A 98% prevalence of the insulin degrading enzyme was documented in the sample studied. We found an association between a homozygous status for the CC genotype and Dementia with an estimated Odds Ratio (OR) of 2.5 (CI 95% 1.6-3.3) on the bivariate test, while, on the multivariate analysis, the OR was estimated 3.3 (CI 95% 1.3-8.2). CONCLUSIONS: Evidence shows that cognitive impairment is more frequent among those exposed to the C allele of the rs2209972 SNP of the insulin degrading enzyme gene.

Lessons from the profile of kidney diseases among Afghan refugees.

BACKGROUND: Due to a paucity of research on the profile of kidney diseases among refugee populations, specifically Afghan refugees in Iran, this study aimed to illustrate the pattern of kidney disease among Afghan refugees in Iran and create a database for evaluating the performance of future health services. MATERIAL AND METHODS: This was a retrospective cross sectional study, in which we collected the demographics and profile of kidney diseases among Afghan refugees between 2005 and 2010 from referrals to the United Nations High Commissioner for Refugees (UNHCR) offices in Iran. RESULTS: The total number of referrals in this group of diseases was 3193 out of 23 152 with 41.5% female and 58.5% male. Regarding age distribution, 10.5% were 0-14 years of age, 78% were 15-59, and 11.5% were ≥60. The most common health referral for females and males (0-14) was end-stage renal disease (ESRD), accounting for 34.6%. This was also the main reason of referrals for females and males aged 15-59, accounting for 73.5% and 66.6%, respectively, and in both sexes in the ≥60 age range it was 63.1%. CONCLUSIONS: The pattern of our renal clinic referrals may gradually change to ESRD, which is associated with a huge economic burden. The need to provide health insurance to everyone or reform the health care system to provide coverage for more of the population can be justified and would improve cost effectiveness.

Dilated cardiomyopathy secondary to chronic cocaine abuse: a case report.

BACKGROUND: Cocaine is a potent sympathomimetic agent associated with the development of possible fatal cardiovascular complications. Dysrhythmias, acute myocardial infarction, hypertension and dilated cardiomyopathy are just some of many cardiovascular effects related to the abuse of cocaine. CASE PRESENTATION: A 38-year-old Hispanic male with a past medical history of hypertension presented with a chief complaint of progressive shortness of breath. The patient confessed to the use of cocaine for almost 18 years once per week. On examination he was hypertensive and tachycardic with a systolic murmur over the 5th intercostal space at the level of the left mid-clavicular line. Laboratory workup revealed an elevated Brain natriuretic peptide; urine toxicology was positive for cocaine. 2D-echocardiogram showed dilated cardiomyopathy. Cardiac catheterization excluded angioischemic cause. He was managed medically and subsequently discharged with drug rehabilitation. On follow-up diagnostic evaluation after 5 months of cocaine cessation, his ejection function improved significantly. CONCLUSION: The exact incidence of cocaine related cardiomyopathy is unknown and likely underreported. The clinical course is abrupt and comparatively similar to other types of cardiomyopathy. The management is like other forms of cardiomyopathy; however ß-blockers should be avoided. The myocardial dysfunction is reversible with abstaining from additional cocaine ingestion. Non-invasive testing should be performed after several months to re-evaluate the treatment response.

Protein turnover and amino acid transport kinetics in end-stage renal disease.

Protein and amino acid metabolism is abnormal in end-stage renal disease (ESRD). Protein turnover is influenced by transmembrane amino acid transport. The effect of ESRD and hemodialysis (HD) on intracellular amino acid transport kinetics is unknown. We studied intracellular amino acid transport kinetics and protein turnover by use of stable isotopes of phenylalanine, leucine, lysine, alanine, and glutamine before and during HD in six ESRD patients. Data obtained from amino acid concentrations and enrichment in the artery, vein, and muscle compartments were used to calculate intracellular amino acid transport and muscle protein synthesis and catabolism. Fractional muscle protein synthesis (FSR) was estimated by the precursor product approach. Despite a significant decrease in the plasma concentrations of amino acids in the artery and vein during HD, the intracellular concentrations remained stable. Outward transport of the amino acids was significantly higher than the inward transport during HD. FSR increased during HD (0.0521 +/- 0.0043 vs. 0.0772 +/- 0.0055%/h, P < 0.01). Results derived from compartmental modeling indicated that both protein synthesis (118.3 +/- 20.6 vs. 146.5 +/- 20.6 nmol.min-1.100 ml leg-1, P < 0.01) and catabolism (119.8 +/- 18.0 vs. 174.0 +/- 14.2 nmol.min-1.100 ml leg-1, P < 0.01) increased during HD. However, the intradialytic increase in catabolism exceeded that of synthesis (57.8 +/- 13.8 vs. 28.0 +/- 8.5%, P < 0.05). Thus HD alters amino acid transport kinetics and increases protein turnover, with net increase in protein catabolism.

Hemodynamic changes during hemodialysis: role of nitric oxide and endothelin.

BACKGROUND: Etiology of dialysis induced hypotension and hypertension remains speculative. There is mounting evidence that nitric oxide (NO) and endothelin (ET-1) may play a vital role in these hemodynamic changes. We examined the intradialytic dynamic changes in NO and ET-1 levels and their role in the pathogenesis of hypotension and rebound hypertension during hemodialysis (HD). METHODS: The serum nitrate + nitrite (NT), fractional exhaled NO concentration (FENO), L-arginine (L-Arg), NGNG-dimethyl-L-arginine (ADMA) and endothelin (ET-1) profiles were studied in 27 end-stage renal disease (ESRD) patients on HD and 6 matched controls. The ESRD patients were grouped according to their hemodynamic profile; Group I patients had stable BP throughout HD, Group II had dialysis-induced hypotension, and Group III had intradialytic rebound hypertension. RESULTS: Pre-dialysis FENO was significantly lower in the dialysis patients compared to controls (19.3 +/- 6.3 vs. 28.6 +/- 3.4 ppb, P < 0.002). Between the experimental groups, pre-dialysis FENO was significantly higher in Group II (24.1 +/- 6.7 ppb) compared to Group I (17.8 +/- 5.6 ppb) and Group III (16.1 +/- 4.2 ppb; P < 0.05). Post-dialysis, FENO increased significantly from the pre-dialysis values (19.3 +/- 6.3 vs. 22.6 +/- 7.9 ppb; P=0.001). Pre-dialysis NT (34.4 +/- 28.2 micromol/L/L) level was not significantly different from that of controls (30.2 +/- 12.3 micromol/L/L). Serum NT decreased from 34.4 +/- 28.2 micromol/L/L at initiation of dialysis to 10.0 +/- 7.4 micormol/L/L at end of dialysis (P < 0.001). NT concentration was comparable in all the three groups at all time points. Pre-dialysis L-Arg (105.3 +/- 25.2 vs. 93.7 +/- 6.0 micromol/L/L; P < 0.05) and ADMA levels were significantly higher in ESRD patients (4.0 +/- 1.8 vs. 0.9 +/- 0.2 micromol/L/L; P < 0.001) compared to controls. Dialysis resulted in significant reduction in L-Arg (105.3 +/- 25.2 vs. 86.8 +/- 19.8 micromol/L/L; P < 0.005) and ADMA (4.0 +/- 1.8 vs. 1.6 +/- 0.7 micromol/L/L; P < 0.001) concentrations. Pre-dialysis ET-1 levels were significantly higher in ESRD patients compared to the controls (8.0 +/- 1.9 vs. 12.7 +/- 4.1 pg/mL; P < 0.002), but were comparable in the three study groups. Post-dialysis ET-1 levels did not change significantly in Group I compared to pre-dialysis values (14.3 +/- 4.3 vs.15.0 +/- 2.4 pg/mL, P=NS). However, while the ET-1 concentration decreased significantly in Group II (12.0 +/- 4.0 vs. 8.7 +/- 1.8 pg/mL, P < 0.05), it increased in Group III from pre-dialysis levels (12.8 +/- 3.8 vs. 16.7 +/- 4.5 pg/mL, P=0.06). CONCLUSION: Pre-dialysis FENO is elevated in patients with dialysis-induced hypotension and may be a more reliable than NT as a marker for endogenous NO activity in dialysis patients. Altered NO/ET-1 balance may be involved in the pathogenesis of rebound hypertension and hypotension during dialysis.