Age-related reference data of bone microarchitecture, volumetric bone density, and bone strength parameters in a population of healthy Brazilian men: an HR-pQCT study.

In a cross-sectional cohort of 340 healthy Brazilian men aged 20 to 92 years, data on density, structure, and strength of the distal radius and tibia were obtained using high-resolution peripheral quantitative computed tomography (HR-pQCT) to develop age- and site-specific reference curves. Age-dependent changes differed between the sites and bone compartments (trabecular and cortical). INTRODUCTION: The aim of this study was to establish age-related reference curves for bone densities, microarchitectural properties, and estimated failure load measured by HR-pQCT (distal radius and tibia) in men. Also, to correlate bone stiffness with the other HR-pQCT parameters, areal bone mineral density (BMD) by DXA and trabecular bone score (TBS). METHODS: Healthy Brazilian men (n = 340) between the ages of 20 and 92 years were recruited. Non-dominant radius and left tibia were scanned using HR-pQCT (Xtreme CT I). Standard and automated segmentation methods were performed, and bone strength estimated by FE analysis. Bone mineral density at lumbar spine, total hip, femoral neck, and TBS were measured using DXA (Hologic, QDR4500). RESULTS: Age-related reference curves were constructed at the distal radius and tibia for volumetric bone density, morphometry, and estimated bone strength parameters. There was a linear relationship with age only for thickness measurements of distal radius (trabecular: R2 0.108, p<0.001; cortical: R2 0.062, p=0.002) and tibia (trabecular: R2 0.109, p<0.001; cortical: R2 0.063, p=0.010), and bone strength at distal radius (R2 0.157, p<0.001). The significant correlations (p <0.05) found by Pearson's correlations (r) between bone stiffness and all other variables measured by HR-pQCT and DXA showed to be stronger at the tibia site than the distal radius. CONCLUSION: The current study expands the HR-pQCT worldwide database and presents an adequate methodology for the construction of reference data in other populations. Moreover, the correlation of bone strength estimated by FEA with other bone microstructural parameters provided by HR-pQCT helps to determine the contribution of each of these variables to fracture risk prediction in men.

Distal radius and tibia bone microarchitecture impairment in female patients with diffuse systemic sclerosis.

Radius and tibia bone microarchitecture, analyzed through a high-resolution peripheral quantitative computed tomography, were significantly impaired in female patients with diffuse systemic sclerosis compared with healthy controls. Acroosteolysis, quality of life-grip strength, hand disability, and disease duration were significantly associated with this bone deterioration. INTRODUCTION: The effect of diffuse systemic sclerosis (dSSc) on the bone is not completely understood. The objective of this study was to analyze the volumetric bone mineral density (vBMD), microarchitecture, and biomechanical parameters at the distal radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT, XtremeCT) in female patients with dSSc and identify clinical and laboratory variables associated with these parameters. METHODS: Thirty-eight women with dSSc and 76 healthy controls were submitted to HR-pQCT at the distal radius and tibia. Clinical and laboratory findings, bone mineral density(BMD), nailfold capillaroscopy (NC), total passive range of motion(ROM), and quality of life (health assessment questionnaire-HAQ) were associated with HR-pQCT (Scanco Medical AG, Brüttisellen, Switzerland) parameters. Multiple linear regression models adjusted for clinical and laboratory variables, ROM and HAQ, were performed. RESULTS: Density, microarchitecture, and biomechanical parameters at the distal radius and tibia were significantly impaired in dSSc patients compared with healthy controls (p < 0.001). Multiple linear regression models showed that lower trabecular density (Tb.vBMD) (radius R2 = 0.561, p = 0.002; and tibia R2 = 0.533, p = 0.005), and lower trabecular number (Tb.N) (tibia R2 = 0.533, p = 0.005) were significantly associated with acroosteolysis. Higher trabecular separation (Tb.Sp) was associated with disease duration and higher HAQ-grip strength (radius R2 = 0.489, p = 0.013), while cortical density (Ct.vBMD) was associated with ROM (radius R2 = 0.294, p = 0.002). CONCLUSION: Bone microarchitecture in patients with dSSc, analyzed through HR-pQCT, showed impairment of trabecular and cortical bone at distal radius and tibia. Variables associated with hand involvement (acroosteolysis, quality of life-grip strength, and ROM) and disease duration may be considered prognostic factors of this bone impairment.

A randomized double-blind placebo-controlled trial of vitamin D supplementation in juvenile-onset systemic lupus erythematosus: positive effect on trabecular microarchitecture using HR-pQCT.

In this randomized double-blind placebo-controlled 24-week trial, cholecalciferol supplementation at 50,000 IU/week effectively improved bone microarchitecture parameters in juvenile-onset systemic lupus erythematosus (JoSLE) patients, as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at tibia site. An increase in the trabecular number and a decrease in the trabecular separation were observed, suggesting that vitamin D supplementation may be recommended for JoSLE patients with its deficiency. INTRODUCTION: Vitamin D has an important effect on bone but there are no trials that directly address the boosting of serum levels of 25-hydroxyvitamin D (25OHD) in bone microarchitecture in JoSLE patients. The aim of this study was to evaluate the effect of vitamin D supplementation on bone microarchitecture parameters using HR-pQCT in JoSLE patients. METHODS: This study was a randomized double-blind placebo-controlled 24-week trial. Forty female JoSLE patients were randomized (1:1) to receive oral cholecalciferol at 50,000 IU/week (JoSLE-VitD) or placebo (JoSLE-PL). The medications remained stable throughout the study. Serum levels of 25OHD were measured using a radioimmunoassay. The bone microarchitecture and volumetric bone density were analyzed using HR-pQCT at tibia site. RESULTS: At baseline, the groups were similar with respect to their age, body mass index, organ involvement, glucocorticoid dose, immunosuppressant use, serum 25OHD levels, and HR-pQCT parameters. After 24 weeks, higher 25OHD levels were observed in the JoSLE-VitD group compared to the JoSLE-PL group [31.3 (8.6) vs. 16.5 (5.8) ng/mL, p < 0.001]. An increase in the trabecular number [∆Tb.N 0.16 (0.24) vs. 0.03 (0.19) 1/mm, p = 0.024] and a decrease in the trabecular separation [∆ThSp -0.045 (0.067) vs. 0.001 (0.009) mm, p = 0.017] were found in the JoSLE-VitD group compared to the JoSLE-PL group at tibia site. No differences were observed in other structural parameters [trabecular (Tb.Th) or cortical thickness (Ct.Th)], volumetric bone mineral densities, cortical porosity, and biomechanical parameters (p > 0.05). CONCLUSION: This study suggests that cholecalciferol supplementation for 24 weeks effectively improved the bone microarchitecture parameters, mainly the trabecular number, in JoSLE patients. TRIAL REGISTRATION: NCT01892748.

Age-related reference curves of volumetric bone density, structure, and biomechanical parameters adjusted for weight and height in a population of healthy women: an HR-pQCT study.

In a cross-sectional cohort of 450 healthy women aged 20 to 85 years, data on the density, structure, and strength of the distal radius and tibia were obtained using high-resolution peripheral quantitative computed tomography (HR-pQCT) and were adjusted for age, weight, and height. Age-dependent patterns of change differed between the sites and between the trabecular and cortical compartments. In postmenopausal women, the trabecular bone remained relatively stable at the distal tibia, but the cortical compartment changed significantly. Cortical porosity exhibited a very weak correlation with stiffness. INTRODUCTION: The aim of this study is to provide information on age-related, weight-related, and height-related changes in the volumetric bone mineral density (vBMD), structure, and biomechanical parameters of the cortical and trabecular compartments in a healthy female population using HR-pQCT. METHODS: For a cross-sectional Brazilian cohort of 450 women aged 20 to 85 years, age-related reference curves of the vBMD, structure, and biomechanical parameters of the distal radius (DR) and distal tibia (DT) were constructed and adjusted for weight and height, and comparisons between premenopausal and postmenopausal women were performed. RESULTS: Reference curves were obtained for all parameters. At the DR, age-related changes varied from -8.68% (cortical thickness [Ct.Th]) to 26.7% (trabecular separation [Tb.Sp]). At the DT, the changes varied from -12.4% (Ct.Th) to 26.3% (Tb.Sp). Cortical porosity (Ct.Po) exhibited the largest percent changes: 342.2% at the DR and 381.5% at the DT. In premenopausal women, Ct.Th remained constant; in postmenopausal women, structural trabecular parameters (trabecular number (Tb.N), trabecular thickness (Tb.Th), Tb.Sp) did not change, whereas cortical parameters and stiffness were significantly altered. Cortical vBMD showed the greatest absolute decrease at both sites, and the slopes were highly negative after menopause. Pearson correlations between stiffness (S) and HR-pCT parameters revealed a significant correlation between the densities and structures of the trabecular and cortical compartments. A weak correlation was observed between S and Ct.Po (DR r = -0.162, DT r = -0.273; p < 0.05). CONCLUSIONS: These data provide reference curves from healthy women and demonstrate that density and structural and biomechanical parameters differ between the radius and tibia and between the trabecular and cortical compartments. In postmenopausal women, the trabecular bone remained relatively stable at the tibia site, whereas the cortical compartment changed significantly.

Evaluation of bone mineral density and microarchitectural parameters by DXA and HR-pQCT in 37 children and adults with X-linked hypophosphatemic rickets.

In X-linked hypophosphatemic (XLH) rickets, dual-energy X-ray absorptiometry (DXA) measurements must be analyzed with caution. High-resolution peripheral quantitative computed tomography (HR-pQCT) analysis suggested that XLH primarily affects the cancellous compartment, with the tibia more affected than the radius. Effective treatment of XLH appears to positively affect bone mineralization, mainly in the bone cortex. INTRODUCTION: The purpose of this study is to evaluate bone mineral density (BMD) and microarchitecture in 37 patients (13 children and 24 adults) with XLH confirmed by PHEX mutations from a tertiary center compared to healthy controls. METHODS: Areal BMD (aBMD) was evaluated by DXA, whereas volumetric BMD (vBMD) and microarchitectural parameters were analyzed by HR-pQCT. RESULTS: Adult XLH patients had higher lumbar aBMD (p < 0.01) than the controls. At the radius, the vBMD was similar between XLH patients and controls. At the tibia, XLH patients had lower total vBMD (p = 0.04), likely resulting from decreased trabecular vBMD (p < 0.01), and this difference was observed in the children and adult groups. Analysis based on metabolic status showed that the adult XLH patients with non-compensated disease had lower cortical vBMD at the tibia than the compensated XLH patients (p = 0.03). The microarchitectural differences at the radius and tibia included lower trabecular number (p < 0.01), greater trabecular separation (p < 0.01), and higher trabecular network inhomogeneity (p < 0.01) in XLH patients compared to their controls. At the radius, adults exhibited greater trabecular deficits than were seen in children. CONCLUSIONS: In XLH patients, DXA measurements must be analyzed with caution due to the interference of anatomic and anthropometric factors. HR-pQCT analysis suggested that XLH primarily affects the cancellous compartment, with the tibia more affected than the radius. Effective treatment of XLH appears to positively affect bone mineralization, mainly in the bone cortex.

Risk factors associated with gastroesophageal reflux disease relapse in primary care patients successfully treated with a proton pump inhibitor. / Factores de riesgo asociados a recaída de enfermedad por reflujo gastroesofágico en pacientes de primer nivel de atención exitosamente tratados con inhibidor de la bomba de protones.

BACKGROUND: There are no studies on the factors associated with gastroesophageal reflux disease (GERD) relapse in primary care patients. AIM: To identify the risk factors associated with GERD relapse in primary care patients that responded adequately to short-term treatment with a proton pump inhibitor. PATIENTS AND METHODS: A cohort study was conducted that included GERD incident cases. The patients received treatment with omeprazole for 4 weeks. The ReQuest questionnaire and a risk factor questionnaire were applied. The therapeutic success rate and relapse rate were determined at 4 and 12 weeks after treatment suspension. A logistic regression analysis of the possible risk factors for GERD relapse was carried out. RESULTS: Of the 83 patient total, 74 (89.16%) responded to treatment. Symptoms recurred in 36 patients (48.64%) at 4 weeks and in 13 patients (17.57%) at 12 weeks, with an overall relapse rate of 66.21%. The OR multivariate analysis (95% CI) showed the increases in the possibility of GERD relapse for the following factors at 12 weeks after treatment suspension: basic educational level or lower, 24.95 (1.92-323.79); overweight, 1.76 (0.22-13.64); obesity, 0.25 (0.01-3.46); smoking, 0.51 (0.06-3.88); and the consumption of 4-12 cups of coffee per month, 1.00 (0.12-7.84); citrus fruits, 14.76 (1.90-114.57); NSAIDs, 27.77 (1.12-686.11); chocolate, 0.86 (0.18-4.06); ASA 1.63 (0.12-21.63); carbonated beverages, 4.24 (0.32-55.05); spicy food 7-16 times/month, 1.39 (0.17-11.17); and spicy food ≥ 20 times/month, 4.06 (0.47-34.59). CONCLUSIONS: The relapse rate after short-term treatment with omeprazole was high. The consumption of citrus fruits and NSAIDs increased the possibility of GERD relapse.

Bone impairment assessed by HR-pQCT in juvenile-onset systemic lupus erythematosus.

UNLABELLED: High-resolution peripheral quantitative computed tomography (HR-pQCT) analysis of female juvenile-onset systemic lupus erythematosus (JoSLE) patients revealed trabecular/cortical bone damage and reduced bone strength primarily at the distal radius compared to healthy controls. We demonstrated for the first time that JoSLE patients with vertebral fracture (VF) present trabecular impairment at the distal radius. INTRODUCTION: This study investigated the volumetric bone mineral density (vBMD), microarchitecture, and biomechanical features at the distal radius and tibia using HR-pQCT and laboratory bone markers in JoSLE patients compared to controls to determine whether this method discriminates JoSLE patients with or without VF. METHODS: We compared 56 female JoSLE patients to age- and Tanner-matched healthy controls. HR-pQCT was performed at the distal radius and tibia. Serum levels of the amino-terminal pro-peptide of type I collagen, the C-terminal telopeptide of type I collagen, intact parathormone, sclerostin, and 25-hydroxyvitamin D (25OHD) were evaluated. VFs were analyzed using VFA-dual-energy X-ray absorptiometry (DXA) (Genant's method). RESULTS: Reduced density and strength parameters and microarchitecture alterations of cortical and trabecular bones were observed in JoSLE patients compared to controls, primarily at the distal radius (p < 0.05). Patients with VF exhibited a significant decrease in trabecular bone parameters solely at the distal radius (Total.BMD, p = 0.034; Trabecular.BMD [Tb.BMD], p = 0.034; bone volume (BV)/trabecular volume (TV), p = 0.034; apparent modulus, p = 0.039) and higher scores for disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI), p = 0.002). Bone metabolism markers were similar in all groups. Logistic regression analysis of parameters that were significant in univariate analysis revealed that Tb.BMD (OR 0.98, 95 % CI 0.95-0.99, p = 0.039) and SLICC/ACR-DI (OR 7.37, 95 % CI 1.75-30.97, p = 0.006) were independent risk factors for VF. CONCLUSION: In conclusion, this study is the first demonstration of bone microstructure and strength deficits in JoSLE patients, particularly at the distal radius. Our results demonstrated that VF was associated with trabecular radius alteration and emphasized the potential detrimental effect of disease damage on this condition.

Polar vectors as a method for evaluating the effectiveness of irritable bowel syndrome treatments: an analysis with pinaverium bromide 100mg plus simethicone 300mg po bid.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a disorder characterized by abdominal pain or discomfort associated with changes in bowel habit. Currently there are no objective outcome measures for evaluating the effectiveness of treatments for this disorder. AIMS: To determine the usefulness of a method of analysis that employs polar vectors to evaluate the effectiveness of IBS treatments. METHODS: Data from a Phase IV clinical study with 1677 active IBS-Rome III patients who received 100mg of pinaverium bromide+300mg of simethicone (PB+S) po bid for a period of four weeks were used for the analysis. Using the Bristol Stool Scale as a reference, the consistency and frequency of each type of bowel movement were recorded weekly in a Bristol Matrix (BM) and the data were expressed as polar vectors. RESULTS: The analysis showed a differential response to the PB+S treatment among the IBS subtypes: in reference to the IBS with constipation subtype, the magnitude of the vector increased from 10.2 to 12.5, reaching maximum improvement at two weeks of treatment (p<0.05, Scheffé). In the IBS with diarrhea and mixed IBS subtypes, the magnitude of the vector decreased from 19 to 14 (p<0.05) and from 16.5 to 13 (p<0.05), respectively, with continuous improvement for a period of four weeks. There was no definable vectorial pattern in the unsubtyped IBS group. CONCLUSIONS: Analysis with polar vectors enables treatment response to be measured in different IBS subtypes. All the groups showed improvement with PB+S, but each one had its own characteristic response in relation to vector magnitude and direction. The proposed method can be implemented in clinical studies to evaluate the efficacy of IBS treatments.

[IT-Knife-2 electroincision as primary treatment of anastomotic strictures]. / Electroincisión con IT-Knife-2 como tratamiento primario de las estenosis posquirúrgicas.

BACKGROUND: Dysphagia is a common problem after surgical stenosis (5% to 55%) and can be refractory to conventional endoscopic treatment in 22% of cases. It has been proposed that electro-incision is an alternative and effective treatment. OBJECTIVE: To evaluate the effectiveness of electro-incision with the insulation-tipped diathermic Knife-2 (IT-Knife-2) in the treatment of dysphagia produced by surgical anastomotic strictures. METHODS: Longitudinal and case-series study from August 2009 to June 2010. Eight consecutive patients with anastomotic stricture-associated dysphagia and naive to endoscopic treatment were included. We performed three or more radiated cuts in the stricture until passage of the gastroscope was achieved with IT-Knife-2 and electrocautery (ERBE IC 200) with a 70-100 W energy cut-off and 25 W coagulation. We carried out measurements at baseline and 15 days after the intervention, evaluating the dysphagia by the Atkinson grading scale and endoscopic changes. RESULTS: The majority of patients were at clinical stage IV with an Eastern Cooperative Oncology Group score of 1 - 3 and Karnofsky between 40 and 90. At the time of endoscopic diagnosis, patients had dysphagia grade II and III. Strictures in all of the cases were short in length and had a diameter of minor than 5 mm. At 15 days of the intervention, no patient demonstrated dysphagia (p = 0.0013) and the anastomotic diameters was more than 9.5 mm and without evidence of stenosis (p = 0.0001). None of our patients presented postincisional complications. CONCLUSIONS: Electro-incision with IT-Knife-2 is effective as primary treatment for the relief of benign dysphagia associated with postsurgical anastomotic stenosis."

Heartburn and other related symptoms are independent of body mass index in irritable bowel syndrome.

BACKGROUND: increasing body mass index (BMI) is a risk factor for GERD but little is known about this association in the irritable bowel syndrome (IBS). AIMS: to determine the presence of heartburn and other related symptoms in relation with BMI in IBS. METHODS: volunteers (n = 483) answered the Rome II-Modular Questionnaire, and were divided into IBS and non-IBS (controls) groups. The frequency of heartburn, chest pain, epigastric pain, nausea, vomiting and belching was compared between the groups in the study sample and within three BMI categories. RESULTS: the IBS (23.7%) and controls (76.3%) were similar in gender (females: 68.1%), age (32.2 +/- 12.7 years), and BMI (25.4 +/- 4.4). Raw associations analysis showed that heartburn: OR: 1.62 (95%CI: 1.04-2.53), chest pain: 1.77 (1.13-2.77), epigastric pain: 1.75 (1.03-2.98) and nausea: 2.45 (1.10-5.32) were more frequent in IBS vs. controls. Meanwhile, according to BMI, in those with obesity, heartburn was more frequent in IBS and among those with overweight, epigastric pain and nausea were also more frequent in IBS. However, in an adjusted log linear model, no significant interaction was found between BMI and any other studied symptom and heartburn was found to be independent of IBS: 1,4 (0.9, 4.7). Finally, a logistic regression model found no interaction between BMI and the presence of heartburn or IBS. CONCLUSIONS: while heartburn and other reflux-related symptoms are more frequent in IBS than in controls, these associations are independent of BMI.

[Prevalence and clinical characteristics of the IBS subtypes according to the Rome III criteria in patients from a clinical, multicentric trial. A report from the Mexican IBS Working Group]. / Prevalencia y caracterización de los subtipos de SII según los criterios de Roma III, en un estudio clínico, multicéntrico. Informe del grupo mexicano de estudio para el SII.

BACKGROUND: In Mexico the prevalence of irritable bowel síndrome (IBS) using Rome II criteria varies between 16 and 35%. OBJECTIVE: To analyze the relative frequency of the IBS subtypes according to the Rome III criteria. METHODS: A multicentric study in 1677 IBS-Rome III patients that consulted private medical clinics. They all answered a structured interview by their physicians to determine the IBS subtype and to evaluate their symptoms intensity (Likert Scales). Patients self-evaluated their symptoms as well by using 10 cm visual analog scales for each one. RESULTS: Women represented 76.8% of the patients for a F:M ratio of 3.3:1. The relative frequencies of the IBS subtypes were IBS-M: 48.4%, IBS-E: 43.0%, IBS-D: 5.6% and IBS-U: 2.8% with females predominating among all. However, IBS-D included 1.7 to 2.4 times more men than any of the other subtypes. The IBS-M reported a higher frequency and intensity of halitosis and vomiting and a higher intensity of burping; while those with IBS-E reported a higher frequency and intensity of straining and the IBS-D more urgency for a bowel movement, fecal incontinence and mucous in the stools. CONCLUSIONS: In IBS-Rome III patients in Mexico, IBS-M is the most common subtype and is more commonly associated with dyspeptic symptoms while the IBS-E reported more outlet symptoms and the IBS-D fecal incontinence. There is a higher female predominance amongst all, however men are more likely to be in IBS-D.

[External validity of a relevant model for Irritable Bowel Syndrome (IBS) using chronic stress by water avoidance in Wistar rats]. / Validez externa de un modelo experimental para síndrome de intestino irritable (SII) mediante estrés crónico por evitación al agua en ratas Wistar.

BACKGROUND: Development of animal models has been one of the most remarkable achievements for Irritable Bowel Syndrome (IBS) research. These models need to exhibit face validity, construct and predictive validity, as well as internal (replicability) and external validity (generalizability). Among these models, chronic stress induced by water avoidance exposure (WA) has been validated in rats through increasing visceral hypersensitivity, motility impairment, anxiety and, colonic immune activity, all related to IBS. OBJECTIVE: To assess the external validity of WA indirectly on colonic motility in Wistar rats. METHOD: Ten male-Wistar rats were exposed to WA and compared with ten Wistar rats not exposed (controls). At the end of each exposure, the quantity of fecal pellets were determined and considered as a sign of autonomic regulation of colonic motility. Data was analyzed with a general linear model for repeated measures. RESULTS: Rats exposed to WA had higher number or pellets than controls: 7.46 ± 0.45 (95%CI: 6.51, 8.41) vs. 2.88 ± 0.45 (1.93, 3.83), p < 0.001. The higher number of pellets was related to WA exposure as there were no other significant interactions. In both groups, the number of pellets was higher during the first day and then decreased progressively. CONCLUSIONS: Chronic stress induced through WA in Wistar rats, exhibits external validity as an experimental model for IBS research and our findings of increased number of fecal pellets coincide with the appearance hypermotility related to IBS. The model is optimum for research studies on this disorder.

Young adult binge drinkers have immunophenotypical disarrangements in peripheral natural killer cells.

Alcohol consumption is an issue of worldwide relevance and a problem of national scale in Mexico. The consumption pattern of large amounts of alcohol on the weekends is rapidly increasing in young adults between 18 and 29 years. Despite various studies that have focused on the noxious effect of alcohol in immunity, the changes in the immunoprofiles of peripheral blood cells have not been completely described. Natural killer cells (NKCs) are lymphoid-origin cells of the immune system that are responsible for defense against tumors, among other functions. In homeostatic conditions, they are found to be in a state of "dynamic balance" between activation and inhibition stimuli, which, if broken, may lead to immunosuppression or activation of cytotoxic mechanisms. In this study, we evaluated the immunoprofile of peripheral NKCs of 54 young adults, 29 of whom were binge drinkers and 25 of whom were low risk (LR), as classified by validated tools. Drinking habits were assessed. Blood samples were collected to perform hematic biometry and liver enzyme tests. Peripheral NKCs were identified by FACS, and stained for CCR2, CCR4, CCR5, CXCR4, CD69, CD127, CD137, TLR4, and Granzyme B. The data were analyzed using the t test and Mann-Whitney's U test for contrasts, and the effect size was obtained in order to evaluate the impact of each immunoprofile. The binge group showed increased expression of CCR5 and PD-1 in NKCs, respective to the LR group, and decreased expression of TLR4, along with fewer CCR4+ cells. Moreover, the increase found in CCR5 and PD-1 expression was correlated with the number of drinks in the last drinking session. Our findings show that young binge drinkers have different immunoprofiles that could suggest an early status of immunosuppression and trafficking of NKCs to the liver, which could be related to the onset of early liver damage, early in a subject's lifespan.

Lack of agreement between the World Health Organization Category of impaired glucose tolerance and the American Diabetes Association category of impaired fasting glucose.

OBJECTIVE: To study the concordance between the 1997 American Diabetes Association (ADA) impaired fasting glucose (IFG) category with the World Health Organization (WHO) impaired glucose tolerance (IGT) status in a population with a high prevalence of diabetes. RESEARCH DESIGN AND METHODS: We analyzed the oral glucose tolerance tests (OGTTs) carried out at the Instituto Nacional de la Nutrición Salvador Zubiran (INNSZ) central laboratory from June to December 1997. We included patients with fasting plasma glucose (FPG) between 60 and 160 mg/dl. The results from the glucose tolerance test were selected as the gold standard. RESULTS: Among the 1,802 glucose tolerance test results available for analysis, 1,706 fulfilled the requirements to be included. Diabetes and IGT were remarkably more frequently diagnosed when the WHO criteria were applied. The new ADA criteria failed to diagnose 69% of WHO diabetic patients and the vast majority of WHO glucose-intolerant subjects. Using the new criteria, 82% were considered normal. Of the IFG subjects, 39% were classified as diabetic and 23% were normal according to the 2-h postchallenge glucose values. Only 37% of the IFG patients were, in fact, glucose intolerant according to the WHO criteria. CONCLUSIONS: Our results clearly show that the 1997 ADA criteria are less sensitive for diagnosing diabetes than OGTT-based WHO criteria. Even more important, there is poor agreement between the WHO category of IGT and the ADA category of IFG.

A preponderance of circulating basic isoforms is associated with decreased plasma half-life and biological to immunological ratio of gonadotropin-releasing hormone-releasable luteinizing hormone in obese men.

Hormonal abnormalities of the reproductive axis have been described in obesity. In men, extreme obesity is associated with low serum testosterone (T) and high estrogen [estrone and estradiol (E(2))] levels. As changes in the sex steroid milieu may profoundly affect the carbohydrate heterogeneity and thus some of the biological and physicochemical properties of the LH molecule, we analyzed the relative distribution of LH isoforms circulating under baseline conditions (endogenous GnRH drive) as well as the forms discharged by exogenous GnRH stimulation from putative acutely releasable and reserve pituitary pools in overweight men. Secondarily, we determined the impact of the changes in LH terminal glycosylation on the in vitro bioactivity and endogenous half-life of the gonadotropin. Seven obese subjects with body mass indexes ranging from 35.7-45.5 kg/m(2) and seven normal men with body mass indexes from 22.5-24.2 kg/m(2) underwent blood sampling at 10-min intervals for a total of 10 h before and after the iv administration of 10 and 90 microg GnRH. Basally released and exogenous GnRH-stimulated serum LH isoforms were separated by preparative chromatofocusing and identified by RIA of eluent fractions. Serum pools of successive samples collected across 2-h intervals (five serum pools per subject) containing LH released under baseline and exogenous GnRH-stimulated conditions were tested for bioactivity employing a homologous in vitro bioassay. Mean serum T and E(2) levels were significantly lower and higher, respectively, in the obese men than in the control group [serum T, 13.5 +/- 2.4 vs. 19.4 +/- 1.4 nmol/L (mean +/- SEM; P: = 0.01); serum E(2), 0.184 +/- 0.01 vs. 0.153 +/- 0.01 nmol/L (P: < 0.05)]. Mean baseline serum LH levels were similar in obese subjects and normal controls (13.3 +/- 1.3 and 12.2 +/- 1.2 IU/L). Although multiple parameter deconvolution of the exogenous GnRH-induced LH pulses revealed that the magnitude of the pituitary response in terms of secretory burst mass, secretory amplitude, and half-duration of the LH pulses was similar in obese and control subjects, the apparent endogenous half-life of LH was significantly (P: < 0.05) shorter in the obese group (98 +/- 11 min) than in the normal controls (132 +/- 10 min). Under all conditions studied, the relative abundance of basic isoforms (those with pH >/=7.0) was significantly (P: < 0.05) increased in the obese subjects compared with the controls (percentages of LH immunoactivity recovered at pH >/=7.0: obese subjects, 34-57%; normal controls, 22-46%). The biological to immunological ratio of LH released in baseline and low dose (10 microg) GnRH-stimulated conditions were similar in obese subjects and normal controls, whereas LH released by obese subjects in response to the high (90 microg) GnRH dose exhibited significantly lower ratios than those detected in normal individuals (0.62 +/- 0.07 and 0.45 +/- 0.09 vs. 1.01 +/- 0.10 and 0.81 +/- 0.09 for LH released within 10-120 min and 130-240 min after GnRH administration in obese and controls, respectively; P: < 0.05). Collectively, these results indicate that the altered sex steroid hormone milieu characteristic of extreme obesity provokes a selective increase in the release of less acidic LH isoforms, which may potentially modify the intensity and duration of the blood LH signal delivered to the gonad. Altered glycosylation of LH may therefore represent an additional mechanism modulating the hypogonadal state prevailing in morbid obesity.

Effect of malnutrition during the first year of life on adult plasma insulin and glucose tolerance.

There is evidence linking intrauterine growth retardation with increased cardiovascular risk and diabetes mellitus (DM) later in life. However, little is known about the association between malnutrition during the first year of life and metabolic abnormalities in adulthood. The objective of this study was to assess the effect of documented malnutrition during the first year of life on glucose tolerance, plasma insulin, lipid profile, and blood pressure in early adulthood, as well as to assess the interaction between body mass index (BMI) and malnutrition on these variables. A study group of young men with a documented history of malnutrition during their first year of life was recruited from 4 pediatric hospitals in Mexico City and compared with a control group. Subjects included were 52 men, aged 20.2 +/- 3.6 years, with a mean birth weight of 3.0 +/- 0.7 kg and documented malnutrition in their first year of life; controls were 50 men, aged 23.3 +/- 1.8 years, with a mean birth weight of 3.2 +/- 0.5 kg. Insulin and glucose concentrations, fasting and in response to an oral glucose load, plasma lipids, blood pressure, and an insulin sensitivity index (ISI) were measured. The areas under the curves of glucose (AUCG) and insulin (AUCI) were significantly higher in cases (P =.012 and <.002, respectively), independent of birth weight, BMI, or age. BMI was significantly associated with fasting plasma insulin (FPI), AUCI, ISI, triglyceride, and high-density lipoprotein (HDL)-cholesterol concentrations in cases, but not in controls. These data suggest that early malnutrition in extrauterine life, independently of birth weight, has an adverse effect on insulin metabolism and glucose tolerance in young men, and it worsens as body mass increases even within the normal range of BMI. Therefore, it is advisable to prevent obesity in individuals exposed to early malnutrition.

Effect of major improvement in glycemic control on results of cardiovascular function tests in patients with insulin-dependent diabetes mellitus.

OBJECTIVE: To evaluate the effect of major improvement in glycemic control on cardiovascular function tests in patients with insulin-dependent diabetes mellitus (IDDM). METHODS: Eight men with chronic, poorly controlled IDDM (serum fructosamine >300 mmol/L and mean fasting blood glucose >200 mg/dL), who were 24 +/- 6 years of age and had a mean duration of diabetes of 8 +/- 1 years, were studied. No patient had microalbuminuria, was taking medication other than insulin, or had evidence of heart disease. Patients underwent baseline continuous ambulatory blood pressure monitoring, echocardiographic studies, and cardiovascular autonomic function tests, which were repeated after 4 weeks of an intensified insulin treatment program (IITP), during which they reached and maintained blood glucose concentrations and serum fructosamine levels in near-normal, nondiabetic ranges. RESULTS: Substantial changes in glycemic control had no significant influence on results of ambulatory blood pressure monitoring, cardiovascular autonomic function tests, and echocardiographic studies. CONCLUSION: Major improvement in glycemic control during a 1-month period in patients with IDDM had no significant influence on cardiovascular function tests. We cannot exclude the possibility that, after a longer duration of an IITP or in patients with clinically evident heart disease or evidence of major complications of diabetes, different responses might be observed.

[Diagnosis of malignant and benign insulinoma. Experience of the National Institute of Nutrition]. / Diagnóstico de insulinomas malignos y benignos. Experiencia en el Instituto Nacional de la Nutrición.

INTRODUCTION: Insulinomas are uncommon tumors, their incidence is approximately one case for 1 million population per year. OBJECTIVE: To expose our experience in the diagnosis of these tumors at the Instituto Nacional de la Nutrición Salvador Zubirán. MATERIAL AND METHODS: All patients with histologic diagnosis of insulinoma were reviewed; the period was from 1959 to 1996. The methods used for diagnosis and localization as well as the clinical picture according to the benignity or malignity of the tumor were registered. RESULTS: Eighteen patients were included, four of them with malignant tumors. In two patients islet cell tumors occurred in association with MEN type I, one of them benign and the other malignant. The mean age of patients with benign tumor was 38.2 +/- 13.5 years, in those with malignant tumors it was 51.5 +/- 16.2 years. The median period between symptoms and diagnosis was 34.4 +/- 15 months for benign tumors and 6 +/- 1.1 months for those with malignant tumors (p = 0.02). Patients with increasing weight had benign tumors. The 24 hours fasting test was not done in patients with malignant tumors because of the severity of hypoglycemia. The insulin/glucose ratio in patients with a malignant tumor was 5.2 +/- 4.7, while in patients with a benign tumor it was 1.82 +/- 1.7. The imaging studies showed that three patients with malignant tumors had hepatic metastasis and one had lymph node metastasis. The low accuracy of localization by radiological methods is due to the size of the tumor (> 2 cm). CONCLUSIONS: Malignant insulinomas are more aggressive and the delay of diagnosis is shorter that in cases with benign tumors. Selective arteriography remains the best preoperative localization procedure.

[99m-Tc alendronate as a new option in bone gammagraphy]. / El 99mTc-alendronato como nueva opción en la gammagrafía ósea.

OBJECTIVE: To compare the quality of bone scans obtained with 99mTc-ABP, a new radiopharmaceutical, and 99mTc-MDP. MATERIAL AND METHODS: A comparative study within subjects was done in nine healthy volunteers, 5 female and 4 male, aged 23 to 39 years. The dose for both radiopharmaceuticals was 740 MBq; radiopharmacokinetic parameters were determined and a whole body bone scan was taken with a MultiSpect 2 gamma camera two hours post administration with a wash-out period of 72 hours between preparations. The images were independently evaluated by three nuclear medicine physicians by drawing of regions of interest (ROIs) on vertebrae, ribs, femur, sternum, joints and skull. Ratios bone/soft tissue were obtained drawing ROIs on several bones. The kappa test and the Wilcoxon rank test were used for statistical comparisons. RESULTS: The agreement on the quality of the images with Tc-ABP and Tc-MDP was fair (kappa 0.4). The femur/soft tissue ratio had a normal distribution and the Wilcoxon test showed no statistical difference between preparations. CONCLUSIONS: Even though bone uptake was higher and faster with Tc-ABP, the quality of the scans obtained with either radiopharmaceutical was similar. We recommend the use of Tc-ABP as a routine bone scan agent because of its less radiation exposure to the patient.

[Migration from a rural zone to an urban one is associated with android distribution of body fat in obese women]. / La migración de zona rural a urbana se asocia con la distribución androide de grasa corporal en mujeres obesas.

INTRODUCTION: Studies about migration to industrialized countries have shown an increased prevalence of diabetes, obesity and dyslipidaemias, all of them related to android body fat distribution. Migration status might be influence body fat distribution but it has not been sufficiently investigated. The aim of this study is to determine the relationship between body fat distribution and migration from rural to urban areas in Mexico. MATERIAL AND METHODS: This sequential sample of 433 women were seen in the outpatient obesity clinic of four federal states: Tabasco (n = 81), Mexico City (n = 166), Coahuila (n = 80), and Yucatan (n = 106). Migration history from rural to urban area, familial history of diabetes, ages of onset of obesity, height and weight circumferences were obtained. A regression logistic model was used and maintained as dependent variable body fat distribution. Age and federal state were considered as confounders and they adjusted the model. RESULTS: Migrating women from rural to urban area were 121 (27.9%). The waist circumference was higher in Tabasco (102.2 +/- 12 cm), and lesser in Yucatan (93.6 +/- 15 cm, p < 0.001); no differences were found for hip circumference. The logistic regression model showed that body fat distribution is associated to migration from rural to urban area, and also to diabetes of mother and age of onset of obesity. CONCLUSIONS: Migrating from rural to urban area is a risk factor for android body fat distribution and this risk increases with age, history of diabetes in mother and adulthood onset o obesity.