Reliability of blood eosinophil count in steady-state bronchiectasis.

RATIONALE: The baseline value of eosinophils in peripheral blood (BEC) has been associated with different degrees of severity, prognosis and response to treatment in patients with bronchiectasis. It is not known, however, if this basal value remains constant over time. OBJECTIVES: The aim of this study was to assess whether the BEC remains stable in the long term in patients with bronchiectasis. METHODS AND MEASUREMENTS: Patients from the RIBRON registry of bronchiectasis diagnosed by computed tomography with at least 2 BEC measurements one year apart were included in the study. Patients with asthma and those taking anti-eosinophilic drugs were excluded. Reliability was assessed using the intra-class correlation coefficient (ICC). A patient with a BEC of at least 300 cells/uL or less than 100 cells/uL was considered eosinophilic or eosinopenic, respectively. Group changes over time were also calculated. MAIN RESULTS: Seven hundred and thirteen patients were finally included, with a mean age of 66.5 (13.2) years (65.8 % women). A total of 2701 BEC measurements were performed, with a median number of measurements per patient of 4 (IQR: 2-5) separated by a median of 12.1 (IQR: 10.5-14.3) months between two consecutive measurements. The ICC was good (>0.75) when calculated between two consecutive measurements (approximately one year apart) but had dropped significantly by the time of the next annual measurements. Similarly, the change from an eosinophilic or eosinopenic patient to a non-eosinophilic or non-eosinopenic patient, respectively, was less than 30 % during the first year with respect to the baseline value but was close to 50 % in later measurements. CONCLUSIONS: Given the significant changes observed in the baseline value of the BEC over time, its monitoring is necessary in patients with bronchiectasis in order to more reliably assess its usefulness.

CIDEC/FSP27 and PLIN1 gene expression run in parallel to mitochondrial genes in human adipose tissue, both increasing after weight loss.

OBJECTIVE: FSP27 KO mice showed enhanced expression of mitochondrial genes, increased mitochondrial activity and smaller lipid droplets. Here, we aimed to investigate lipid droplet protein (CIDEC/FSP27 and perilipinA (PLIN1)) gene expression in human adipose tissue in association with obesity, insulin resistance and mitochondrial gene expression. DESIGN AND SUBJECTS: In cohort 1, CIDEC/FSP27, PLIN1, adipogenic (FASN, ACACA, PPARG, GLUT4) and mitochondrial (PPARGC1A, PPARGC1B, TFAM, MT-CO3) gene expression were analyzed in 171 adipose tissue samples (88 visceral adipose tissue (VAT) and 83 subcutaneous adipose tissue (SAT) depots) and in a time course experiment in human subcutaneous and visceral preadipocytes using real-time PCR. In cohort 2, the effects of bariatric surgery-induced weight loss were also evaluated in six caucasian morbidly obese women. Additionally, in cohort 2 FSP27 and PLIN1 protein levels were measured using western blotting. RESULTS: CIDEC/FSP27 (1.03±0.52 vs 0.49±0.23 relative gene expression unit (R.U.), P<0.0001) and PLIN1 (1.32±0.82 vs 0.63±0.42 R.U., P<0.0001) gene were significantly more expressed in SAT than in VAT. In VAT, CIDEC/FSP27 and PLIN1 gene expression decreased with body mass index, percent fat mass, fasting glucose, fasting insulin, HOMA and were positively associated with adipogenic (PPARG, GLUT4, FASN and ACACA) and mitochondrial biogenesis (PPARGC1A, PPARGC1B, TFAM and MT-CO3)-related genes. Mitochondrial gene expression increased during adipocyte differentiation in parallel to FSP27 and PLIN1 and other adipogenic genes. After bariatric surgery-induced weight loss, PLIN1 and CIDEC/FSP27 gene and protein expression in SAT increased significantly in parallel to adipogenic and mitochondrial genes. CONCLUSION: These findings suggest a positive functional interaction between CIDEC/FSP27, PLIN1 and mitochondrial biogenesis-related genes in human adipose tissue.

Inflammation and insulin resistance exert dual effects on adipose tissue tumor protein 53 expression.

OBJECTIVE: The purpose of this study was to investigate the expression of human adipose tissue protein 53 (p53) in subjects who varied widely in terms of obesity and insulin resistance. We also analyzed different in vivo and in vitro models to try to comprehend the associations found in humans. METHODS: p53 was analyzed in human adipose and isolated adipocytes, in high fat-fed and GLP-1R KO mice, during in vitro adipogenesis, and in adipocytes after high glucose, rosiglitazone and inflammatory conditions. The effects of surgery-induced weight loss and ex vivo metformin were also evaluated. RESULTS: Omental (OM) p53 gene expression (+27%, P=0.001) and protein (+11%, P=0.04) were increased in obese subjects and high fat diet-induced obese mice (+86%, P=0.018). Although the obesity-associated inflammatory milieu was associated with increased OM p53, this was negatively related to insulin resistance and glycated hemoglobin, and positively with biomarkers for insulin sensitivity. Multiple linear regression analyses revealed that glycated hemoglobin (P<0.0001) and body mass index (P=0.048) contributed independently to explain 13.7% (P<0.0001) of the OM p53 variance. Accordingly, the improvement of insulin sensitivity with surgery-induced weight loss (+51%, P=0.01) and metformin (+42%, P=0.02) led to increased adipose p53. While the glucose-intolerant GLP-1R KO mice showed decreased mesenteric p53 (-45.4%, P=0.017), high glucose led to decreased p53 in pre-adipocytes (-27%, P<0.0001). Inflammatory treatments led to increased p53 (+35%, P<0.0001), while Rs downregulated this expression (-40%, P=0.005) in mature adipocytes. CONCLUSION: Inflammation and insulin resistance exert dual effects on adipose p53, which seems to be the final result of these opposing forces.

The lung innate immune gene surfactant protein-D is expressed in adipose tissue and linked to obesity status.

BACKGROUND: Surfactant protein-D (SFTPD) is a component of the lung innate immunity that enhances clearance of pathogens and modulates inflammatory responses. An inverse association of putative, lung-derived circulating SFTPD with obesity has been reported but no information is available concerning possible SFTPD gene expression in human adipose tissue. METHODS: SFTPD gene expression was analyzed in human omental (OM; n=156) and subcutaneous (SC; n=106) adipose tissue, and in isolated fat cells (n=12) in association with measures of obesity and glucose tolerance. RESULTS: SFTPD gene was expressed in human adipose tissue and adipocytes. This expression was decreased in OM and SC adipose tissue from obese subjects with (-47%, P<0.0001; and -37%, P=0.048) and without (-34%, P=0.001; and -22%, P=0.08; respectively) type 2 diabetes when compared with the control group. Indeed, OM SFTPD was inversely associated with body mass index (r=-0.33, P<0.0001), percent fat mass (r=-0.36, P<0.0001), waist perimeter (r=-0.26, P=0.002), diastolic blood pressure (r=-0.21, P=0.018) and fasting glucose (r=-0.21, P=0.012); and positively linked to the expression of insulin receptor substrate 1 (IRS1; r=0.25, P=0.004), perilipin A (PLIN; r=0.38, P=0.007) and fatty acid synthase (FASN; r=0.36, P<0.0001). Accordingly, increased SFTPD (4.5-fold, P=0.02) was detected in isolated adipocytes when compared with the stromal-vascular cell fraction, in parallel to IRS1, FASN and PLIN. CONCLUSIONS: Both OM and SC adipose tissue (mainly mature adipocytes) express SFTPD. This expression decreases with obesity and impaired glucose tolerance.

Type I iodothyronine 5'-deiodinase mRNA and activity is increased in adipose tissue of obese subjects.

Differentiation and metabolism of adipose tissue are modulated by thyroid hormones (THs), but relatively little is known about the metabolism of THs in this tissue. Expression of the genes for type I iodothyronine 5'-deiodinase (D1), leptin (LEP) and stearoyl-CoA desaturase 1 (SCD-1) was evaluated in omental (OM) and subcutaneous (SC) fat using a cohort of 70 humans. Activities of iodothyronine deiodinases (D1, D2 and D3) were assessed in a randomly selected subpopulation of 19 subjects. D1 expression was upregulated in both OM (P=0.011) and SC (P=0.003) fat of obese subjects. Concomitantly, OM (P=0.002) and SC (P=0.028) LEP expression were increased in obesity, associated with both D1 mRNA (r=0.315, P=0.014) and activity (r=0.647, P=0.023) and inversely related to SCD-1 (r=-0.266, P=0.034) expression in SC fat. Also D1 (but not D2 and D3) activity was increased in OM (∼fourfold, P=0.010) and SC (∼eightfold, P=0.004) fat of obese when compared with non-obese subjects and correlated in both OM (r=0.528, P=0.036) and SC (r=0.749, P=0.005) fat with body mass index. Our results document increased D1 gene expression and activity in adipose tissue of obese humans and suggest a role of 3,5,3'-triiodo-L-thyronine formed by D1 in response to leptin in the modulation of adipose tissue metabolism.

Tabaquismo / Smoking

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Thyroid hormone responsive Spot 14 increases during differentiation of human adipocytes and its expression is down-regulated in obese subjects.

CONTEXT: Very limited information is available regarding the function of human thyroid hormone responsive Spot 14 (human S14, hS14) in adipogenesis and human adiposity. OBJECTIVE: To evaluate hS14 levels during differentiation of human pre-adipocytes, in human fat depots and isolated fat cells. DESIGN: This was a cross-sectional study. SUBJECTS: A total of 161 omental (OM) and 87 subcutaneous (SC) adipose tissue samples obtained during elective surgical procedures from a population who varied widely in terms of obesity. MEASUREMENTS: hS14 gene expression and protein levels during adipogenesis were assessed by RT-PCR, western blot, and using an automated confocal imaging approach. RESULTS: hS14 gene expression levels were decreased in OM adipose tissue from overweight (-42.0%) and obese subjects (-56.5%) compared with lean subjects (P<0.05 and P<0.0001, respectively). hS14 mRNA (but not hS14-related) was inversely associated with obesity measures such as body mass index (P=0.001), percent fat mass (P=0.001), waist-to-hip ratio (P=0.020), and systolic blood pressure (P=0.031). hS14 gene expression and protein levels were up-regulated at the early stages of differentiation of human pre-adipocytes as well as for 3T3-L1 cells. That observation was most prominent in those individual cells exhibiting the more marked differentiation features. hS14 gene expression levels increased by approximately 45 000-fold in mature adipocytes. Increased hS14 levels were also found in stromal-vascular cells/pre-adipocytes (3.8-fold, P<0.05) and in adipose tissue samples (1.9-fold, P<0.0001) from SC compared with OM fat depots. CONCLUSIONS: These results suggest that hS14 is involved in human adipogenesis, but inversely related to obesity and OM fat accumulation.

Síndrome de Cushing suprarrenal / No disponible

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Obturator hernia: clinical analysis of 16 cases and algorithm for its diagnosis and treatment.

BACKGROUND: Obturator hernia is an uncommon but important cause of intestinal obstruction. METHODS: Retrospective study of 16 patients undergoing surgery for obturator hernia in a 20-year period. RESULTS: All patients were elderly women. Low body mass index and multiparity were predisposing factors. Mean time from onset of symptoms to consultation was 4.1 days. The preoperative diagnosis was intestinal obstruction of unknown etiology in 13 cases and intestinal obstruction due to obturator hernia in three (diagnosis by CT). The rate of strangulated hernias was 75% and the perforation rate was 56.3%. Intestinal resection was required in 12 cases. Hernia repair was performed using polypropylene mesh in 11 cases and by means of simple suture and apposition of the peritoneum in five. Morbidity was 75% and mortality was 18.8%. CONCLUSIONS: Early diagnosis--we recommend CT in thin, elderly, multiparous women with intestinal obstruction--and early treatment can reduce complications and mortality.

Surgically treated perforations of the gastrointestinal tract caused by ingested foreign bodies.

OBJECTIVE: Intestinal perforation due to foreign body (FB) ingestion is rare (1%). We describe our experience in treating these lesions surgically. METHOD: From 1995 to 2006, data were collected prospectively in 33 patients (18 women and 15 men; mean age 64 years) operated on for intestinal perforation due to an ingested FB. The type of object, preoperative diagnosis, perforation site, treatment, morbidity and mortality were reviewed. RESULTS: Foreign body ingestion was predominantly involuntary (88%). The mean time from ingestion to perforation was 10.4 days. The most frequently ingested objects were dietary FB (n = 21) and toothpicks (n = 6). The most frequent predisposing factors were dentures or an orthodontic appliance (73%). The most common preoperative diagnoses were acute abdomen of uncertain origin (n = 7), acute appendicitis (n = 7) and acute diverticulitis (n = 5). Pneumoperitoneum was observed in 10 cases. The diagnosis was reached during laparotomy in 30 (91%) cases. The most frequent perforation site was the colorectal region (n = 18, 54.5%), followed by the terminal ileum (n = 7, 21.2%); intraperitoneal perforation was the most common (n = 30, 91%). All cases had abdominal contamination and 22 (66.7%) had diffuse peritonitis. Treatment was always by surgery and antibiotics. Thirteen patients required a colostomy. Morbidity was 57.6% (n = 19) and mortality 6.1% (n = 2). CONCLUSION: Intestinal perforation by a foreign body is rare and normally affects the sigmoid colon, rectum or distal ileum. Dentures are a common risk factor. Patients are rarely aware of foreign body ingestion. Dietary FB and toothpicks are the most commonly ingested objects. Treatment consists of surgery and antibiotics. Appendicitis and acute diverticulitis should be considered in the differential diagnosis.

Management of foreign bodies in the rectum.

OBJECTIVE: The discovery of foreign bodies (FB) in the rectum is an infrequent clinical problem. Most commonly, FB are introduced through the anal passage or reach the rectum after oral ingestion. We describe our experience in the diagnosis and treatment of FB retained in the rectum. METHOD: From 1997 to 2004, data were collected prospectively in 30 patients (20 men and 10 women; median age 42.5 years). Extraction method, size and type of object, and postextraction evolution were reviewed. RESULTS: The FB was introduced anally in 16 cases and by oral ingestion in 14. Principal associated factors were: mental disorder in 11, penitentiary confinement in two, and drug and alcohol intake in two. Recent sexual activity had taken place in 14 cases. The size and nature of the FB were varied. The most frequent symptom was constipation with or without pelvic or anal discomfort (n = 23, 77%). Treatment consisted of spontaneous ejection (n = 2), digital extraction with or without enemas (n = 10), digital extraction under local/regional anaesthesia after fragmentation (n = 11) and regional exploratory laparotomy under general anaesthesia (n = 7). Grade I rectal trauma was the most common (n = 23, 77%). Six patients required colostomy. Four patients (13.5%) suffered complications and none died. Only 17 patients were hospitalized, with a mean stay of 6 days. All patients recovered without sequelae. CONCLUSION: The diagnosis of rectal FB should be suspected when faced with low pelvic or perianal abdominal pain and/or rectal haemorrhage within the context of an unconvincing story in patients without a history of recent instrumental rectal exploration for therapeutic or diagnostic purposes. Because of potential complications, FB in the rectum should be considered a serious condition that must be treated without delay.

Asymptomatic bilateral adrenal pheochromocytoma in a patient with a germline V804M mutation in the RET proto-oncogene.

UNLABELLED: A diagnosis of bilateral pheochromocytoma warrants exclusion of hereditary pheochromocytoma. OBJECTIVE: To describe the first case of a bilateral pheochromocytoma associated with V804M mutation in the RET proto-oncogene. PATIENTS: The index case was a 54-year-old man with bilateral adrenal masses discovered during a CT scan performed for other reasons. MEASUREMENTS: Genetic analysis included exons 8-11 and 13-17 in the RET proto-oncogene, all four exons and flanking intronic regions in the SDHD gene, all eight exons and flanking intronic regions in the SDHB, and all three exons in the VHL gene. RESULTS: Investigations revealed elevated urinary metanephrines (32.3 micromol/day), and laparoscopic bilateral adrenalectomy confirmed bilateral pheochromocytomas. A heterozygous V804M mutation in exon 14 of the RET was found in the index case and in four relatives. Total thyroidectomy, performed in four of five affected members in this kindred, disclosed a medullary thyroid carcinoma in the index case and in a 50-year-old woman, and nodular C-cell hyperplasia in the other two subjects. CONCLUSIONS: This clinical case suggests that individuals carrying the germline V804M mutation should be screened annually for the presence of pheochromocytoma.

Apendicitis del muñón: una rara patología / Stump appendicitis: A rare entity

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