Geographical Variations in the Prevalence of COPD in Spain: Relationship to Smoking,Death Rates and other Determining Factors

BackgroundThe EPI-SCAN study (Epidemiologic Study of COPD in Spain), conducted from May 2006 to July 2007, determined that the prevalence of COPD in Spain according to the GOLD criteria was 10.2% of the 40 to 80 years population. Little is known about the current geographical variation of COPD in Spain.ObjectivesWe studied the prevalence of COPD, its under-diagnosis and under-treatment, smoking and mortality in the eleven areas participating in EPI-SCAN. COPD was defined as a post-bronchodilator FEV₁/FVC ratio <0.70 or as the lower limit of normal (LLN).ResultsThe ratio of prevalences of COPD among the EPI-SCAN areas was 2.7-fold, with a peak in Asturias (16.9%) and a minimum in Burgos (6.2 %) (P<.05). The prevalence of COPD according to LLN was 5.6% (95% CI 4.9–6.4) and the ratio of COPD prevalence using LLN was 3.1-fold, but with a peak in Madrid-La Princesa (10.1%) and a minimum in Burgos (3.2%) (P<.05). The ranking of prevalences of COPD was not maintained in both sexes or age groups in each area. Variations in under-diagnosis (58.6% to 72.8%) and under-treatment by areas (24.1% to 72.5%) were substantial (P<.05). The prevalence of smokers and former smokers, and cumulative exposure as measured by pack-years, and the age structure of each of the areas did not explain much of the variability by geographic areas. Nor is there any relation with mortality rates published by Autonomous Communities.ConclusionThere are significant variations in the distribution of COPD in Spain, either in prevalence or in under-diagnosis and under-treatment.     

Independent clinical validation of a Canadian FRAX tool: Fracture prediction and model calibration

A FRAX model for Canada was constructed for prediction of osteoporotic and hip fracture risk using national hip fracture data with and without the use of femoral neck bone mineral density (BMD). Performance of this system was assessed independently in a large clinical cohort of 36,730 women and 2873 men from the Manitoba Bone Density Program database that tracks all clinical dual‐energy X‐ray absorptiometry (DXA) test results for the Province of Manitoba, Canada. Linkage with other provincial health databases allowed for the direct comparison of fracture risk estimates from the Canadian FRAX model with observed fracture rates to 10 years (549 individuals with incident hip fractures and 2543 with incident osteoporotic fractures). The 10‐year Kaplan‐Meier estimate for hip fractures in women was 2.7% [95% confidence interval (CI) 2.1–3.4%] with a predicted value of 2.8% for FRAX with BMD, and in men the observed risk was 3.5% (95% CI 0.8–6.2%) with predicted value of 2.9%. The 10‐year estimate of osteoporotic fracture risk for all women was 12.0% (95% CI 10.8–13.4%) with a predicted value of 11.1% for FRAX with BMD, and in men, the observed risk was 10.7% (95% CI 6.6–14.9%) with a predicted value of 8.4%. Discrepancies were observed within some subgroups but generally were small. Fracture discrimination based on receiver operating characteristic curve analysis was comparable with published meta‐analyses with area under the curve for osteoporotic fracture prediction of 0.694 (95% CI 0.684–0.705) for FRAX with BMD and for hip fractures 0.830 (95% CI 0.815–0.846), both of which were better than FRAX without BMD or BMD alone. Individual risk factors considered by FRAX made significant independent contributions to fracture prediction in one or more of the models. In conclusion, a Canadian FRAX tool calibrated on national hip fracture data generates fracture risk predictions that generally are consistent with observed fracture rates across a wide range of risk categories. © 2010 American Society for Bone and Mineral Research.     

Loss of membrane localization and aberrant nuclear E-cadherin expression correlates with invasion in pancreatic endocrine tumors

Decrease in E-cadherin is considered a molecular event in dysfunction of the cell-cell adhesion system, triggering invasion and metastasis in many malignancies, including those of endocrine origin. In addition, alterations in the cadherin-catenin system may also be involved in tumorigenesis. E-cadherin and beta-catenin, components of the Wnt signal transduction pathway, may serve as a common switch in central processes that regulate cellular differentiation and growth. The purpose of this study was to examine if abnormalities of the Wnt signaling pathway, specifically, E-cadherin and beta-catenin, occur in pancreatic endocrine tumors (PETs) and correlate these with clinicopathologic parameters. Tissue microarrays were constructed from 57 cases with 4 to 14 cores measuring 1.0 mm from each case. Size of tumor, presence or absences of necrosis, gross invasiveness/demarcation, lymphovascular invasion, and lymph node involvement and liver metastasis were recorded. The mitotic count, expressed per 50 high power fields (HPF) and MIB-1 index of the entire tumor were assessed. All the tissue microarray blocks were stained with commercially available antibodies to E-cadherin (cytoplasmic and extracellular domains), beta-catenin, APC, and GSK-3beta. Twenty-seven were male patients and 30 female, ranging in age from 23 to 80 years (mean, 51.7 y). Six patients had MEN1 syndrome and 1 von Hippel Lindau disease. The tumors ranged in size from 0.8 to 9.8 cm with a mean of 3.4 cm. Sixteen patients had lymph node spread and 7 had liver metastasis. The Ki-67 labeling index ranged from 1% to 30% and the mitotic counts from 0 to 27 per 50 HPF. Thirty of 57 cases (52.6%) cases showed abnormal beta-catenin expression. Thirteen of the 16 cases with lymph node metastasis and all 7 cases with liver spread showed abnormalities of beta-catenin immunostaining. Only 2 cases showed nuclear beta-catenin. The average size of tumors with beta-catenin abnormalities was 4.8 cm. Thirty-four of the 57 (59.6%) cases showed loss of normal membranous immunoreactivity for both antibodies E-cadherin, including nuclear localization in 18 cases with the antibody that recognizes the cytoplasmic domain. E-cadherin decrease and/or loss was identical to beta-catenin with the same 13 cases showing nodal involvement and all 7 cases with liver metastasis displaying aberrant E-cadherin staining. Seven of the 18 cases with nuclear E-cadherin had lymph node spread and 3 liver metastases. The mean size of the 34 cases with abnormal E-cadherin expression was 4.4 cm, compared to the series mean of 3.4 cm. Interestingly, cases with nuclear E-cadherin had a mean size of 5.2 cm. beta-catenin and E-cadherin abnormalities did not correlate with other clinicopathological parameters. All 57 cases showed cytoplasmic immunoreactivity for APC, and cytoplasmic and nuclear positivity for GSK-3beta. APC and GSK-3beta did not show any correlation with beta-catenin or E-cadherin staining.Abnormalities of beta-catenin and E-cadherin immunoexpression are seen in the majority of PETs. Nuclear beta-catenin is rare in PET but nuclear E-cadherin, a previously unrecognized staining pattern in PETs was seen 18 of 57 cases with the antibody detecting the cytoplasmic fragment of E-cadherin. Aberrant expression of both beta-catenin and E-cadherin correlated strongly with lymph node spread and liver metastases.     

Transient urethral obstruction predisposes to ascending pyelonephritis and tubulo-interstitial disease: studies in rats

Chronic tubulo-interstitial disease, an important cause of end-stage renal disease, often results from the combined effects of a disturbed urinary outflow tract and urinary tract infection. Acute unilateral ureteral obstruction in rats rapidly induces foci of medullary necrosis, confined to the region of the papilla and fornices. This injury may provide a nidus for bacterial invasion and may invoke reactive and regenerative changes, ultimately leading to chronic pyelonephritis and tubulo-interstitial nephropathy. To explore this possibility, adult rats underwent renal morphological evaluation 2–7 days following transient 24-h unilateral ureteral obstruction. In some experiments the bladder was inoculated with bacteria (10⁸–10⁹ cfu/ml Escherichia coli in 0.5 ml) after release of ureteral obstruction, with subsequent cultures obtained from the pelvis of both kidneys and from the urinary bladder. Morphologic evaluation of perfusion-fixed kidneys, 2–7 days after the release of 24-h ureteral obstruction disclosed papillary necrosis, urothelial proliferation, marked inner-stripe interstitial expansion, and fibrosis and proximal tubular (S₃) dilatation. The lateral (perihilar region) was predominantly affected, with lesions spreading from the fornices. There was some progression of interstitial fibrosis during the postobstructive time course or following more prolonged ureteral obstruction. By contrast, infection hardly contributed to the tubulointerstitial changes. In rats subjected to infection, cultures were positive in all 15 postobstructive kidneys, as opposed to five contralateral kidneys (P < 0.0001). Viable counts from the postobstructive kidney were also higher than those from the contralateral side (79,000 ± 12,000 vs 2900 ± 1600 cfu/ml, mean ± SEM, P < 0.0001), and were comparable to those obtained from the bladder (77,000 ± 13,000 cfu/ml). We conclude that transient ureteral obstruction predisposes to ascending pyelonephritis and to tubulointerstitial disease. This vulnerability may relate to altered urodynamics and medullary tissue destruction. Received: 28 December 1999 / Accepted: 28 September 2000     

Outcome and Hepatic Hemodynamics in Liver Transplant Patients with Portal Vein Arterialization

Few cases of successful portal vein arterialization in orthotopic and auxiliary liver transplantation have been reported. AIM: To evaluate the effect of portal vein arterialization on hepatic hemodynamics and long-term clinical outcome in three patients undergoing liver transplantation. METHODS: Two patients with extensive splanchnic venous thrombosis received an orthotopic liver transplant and one with fulminant hepatic failure received an auxiliary heterotopic graft. Portal vein arterialization was performed in all cases. RESULTS: One patient died 4 months after transplant and two are still alive. Auxiliary liver graft was removed 3 months post-transplant when complete native liver regeneration was achieved. Immediate post-transplant liver function was excellent in all cases. Only one patient developed encephalopathy and variceal bleeding owing to prehepatic portal hypertension secondary to arterioportal fistula 14 months after transplant. He was successfully treated by embolization of the hepatic artery. Hepatic hemodynamic measurements demonstrated a normal pressure gradient between wedged and free hepatic venous pressures in all cases. Liver biopsy showed acceptable graft architecture in two cases and microsteatosis in one. CONCLUSIONS: Liver transplantation with portal vein arterialization is an acceptable salvage alternative when insufficient portal venous flow to the graft is present. The double arterial supply does not imply changes in hepatic hemodynamics, at least in the early months post-transplant.     

Rats Submitted to Gastric Banding are Leaner and Show Distinctive Feeding Patterns

Background: Bariatric surgery is expanding to meet the global epidemic of morbid obesity, because this surgery is successful in achieving sustained weight loss. After having recently established a rat model of gastric banding, our aim now was to investigate the relative fat mass content and the feeding patterns of gastric banded rats. Methods: Two groups of Wistar rats, submitted either to gastric banding or to sham surgery, were followed-up for 26 days regarding weight, daily food intake and feeding patterns both under resting conditions and when refed after fasting. Weight of the epididymal fat pad was used as a measure to evaluate changes in white adipose tissue in the rats. Results: 10 days after surgery and thereafter, rats submitted to gastric banding showed the same daily food intake that was observed in sham-operated rats. Nevertheless, gastric banded rats kept lower body weights and were leaner than controls. These differences were associated with distinctive feeding patterns, both under resting conditions and when refed after fasting, suggesting that gastric banded rats present a significant increase in feeding frequency when compared with controls. Conclusion: This data is the first experimental evidence that an increase in feeding frequency is associated with weight loss after gastric banding, even if there is no decrease in total energy intake. Thus, medical advice on the advantages of fractionating daily caloric intake into multiple meals is further supported by the herein new information obtained in an animal model of gastric banding.     

Cholesterol absorption and synthesis in pediatric kidney, liver, and heart transplant recipients

BACKGROUND: Hypercholesterolemia after organ transplantation is common. Previously, we observed higher serum total cholesterol (TC) concentrations in our pediatric kidney than liver or heart transplant recipients. To find an explanation to the observed difference, our kidney recipients' cholesterol synthesis and absorption efficiency was compared to those of liver and heart recipients. METHODS: Serum noncholesterol sterol ratios (10 x mmol to the mol of TC, surrogate estimates of hepatic cholesterol synthesis and intestinal absorption) were studied in 50 pediatric kidney, 25 liver and 12 heart transplant recipients without diabetes or cholestasis, and in 29 controls. RESULTS: The kidney recipients had lower Delta-cholesterol (P=0.031), similar lathosterol and higher desmosterol ratios (markers of cholesterol synthesis) (P=0.020), and similar campesterol and sitosterol ratios (markers of cholesterol absorption) when compared to the controls. The liver recipients had lower campesterol ratios than the kidney recipients and controls (P=0.002). Glomerular filtration rates were not associated with the ratios of noncholesterol sterols. Multivariate analysis showed markers of cholesterol synthesis to be lower and absorption to be higher in the kidney than the liver or the heart transplant recipients. Weight-adjusted dosages of immunosuppressive agents were associated with some ratios of noncholesterol sterols and cholestanol though these varied between the transplant recipient groups. CONCLUSIONS: Serum TC concentration in kidney recipients was not significantly associated with absorption efficiency or synthesis of cholesterol, though kidney transplantation was associated with low synthesis and high absorption efficiency of cholesterol. Immunosuppressive therapy with cyclosporine and methylprednisolone may modulate absorption efficiency and synthesis of cholesterol.     

Reconstruction of parietal bone defects with adiposederived mesenchymal stem cells. Experimental study

Purpose:This study assessed the regeneration potential of mesenchymal stem cells (MSC) from adipose tissue associated with platelet-rich plasma (PRP) in bone regeneration.Methods:Thirty Wistar rats (Rattus norvegicus albinos) were divided into five groups (according to the grafting material and time to euthanasia): (1) autograft - 14 days (control), (2) autograft - 28 days (control), (3) MSC + PRP - 14 days, (4) MSC + PRP + papaverine - 14 days and (5) MSC + PRP + papaverine - 28 days. After euthanasia, the graft was removed and histological slides were prepared. They were assessed by a blinded pathologist using a previously published histological scale as parameter.Results:There was some degree of neoformed bone trabeculae (NBT) in 93.3% of the samples, as well as osteoblastic activity (OA). The autograft groups (14 and 28 days) had higher levels in the formation of bone trabeculae. Nonparametric data were analyzed using the Wilcoxon-Mann-Whitney test and proved not to be statistically significant at p < 0.05.Conclusions:Experimental parietal bone reconstruction, combining MSC, PRP and papaverine presented regeneration in all groups with no significant difference among them.Key words: Bone Regeneration, Platelet-Rich Plasma, Tissue Engineering, Rats     

Mutations in the UBIAD1 gene on chromosome short arm 1, region 36, cause Schnyder crystalline corneal dystrophy

PURPOSE: Schnyder crystalline corneal dystrophy (SCCD; MIM 121800) is a rare autosomal dominant disease characterized by an abnormal increase in cholesterol and phospholipid deposition in the cornea, leading to progressive corneal opacification. Although SCCD has been mapped to a genetic interval between markers D1S1160 and D1S1635, reclassification of a previously unaffected individual expanded the interval to D1S2667 and included nine additional genes. Three candidate genes that may be involved in lipid metabolism and/or are expressed in the cornea were analyzed. METHODS: DNA samples were obtained from six families with clinically confirmed SCCD. Analysis of FRAP1, ANGPTL7, and UBIAD1 was performed by PCR-based DNA sequencing, to examine protein-coding regions, RNA splice junctions, and 5' untranslated region (UTR) exons. RESULTS: No disease-causing mutations were found in the FRAP1 or ANGPTL7 gene. A mutation in UBIAD1 was identified in all six families: Five families had the same N102S mutation, and one family had a G177R mutation. Predictions of the protein structure indicated that a prenyl-transferase domain and several transmembrane helices are affected by these mutations. Each mutation cosegregated with the disease in four families with DNA samples from both affected and unaffected individuals. Mutations were not observed in 100 control DNA samples (200 chromosomes). CONCLUSIONS: Nonsynonymous mutations in the UBIAD1 gene were detected in six SCCD families, and a potential mutation hot spot was observed at amino acid N102. The mutations are expected to interfere with the function of the UBIAD1 protein, since they are located in highly conserved and structurally important domains.