Postprandial leptin and adiponectin in response to sugar and fat in obese and normal weight individuals.

PURPOSE: Adipokines produced by white adipose tissue are central in the development of lifestyle diseases. Individuals in industrialized countries spend a substantial part of life in the non-fasting, postprandial state, which is associated with increased oxidation and inflammation. The aim was to study postprandial adiponectin and leptin levels after an oral fat tolerance test (OFTT) and an oral glucose tolerance test (OGTT) in obese (OB) and healthy, normal weight individuals (NW). METHODS: Fifty adults with obesity (BMI ≥ 30) and 17 healthy, NW were included. Postprandial triglyceride (TG), adiponectin, and leptin levels were measured every second hour during an 8 h OFTT, and every half hour during a 2 h OGTT. RESULTS: Compared with the basal level, postprandial levels of adiponectin following OFTT showed a slight initial peak, followed by a significant decrease at 8 h, in the NW. In the OB these changes were abolished. Postprandial levels of leptin decreased significantly from basal levels in the OFTT, in the NW, whereas in the OB, leptin was unchanged except for a slight increase from 2 to 8 h. During the OGTT both adiponectin and leptin levels remained unchanged in the NW, but decreased significantly in the OB. In addition, the OB had delayed TG clearance at 6 h. CONCLUSIONS: A fatty meal gives postprandial changes in the secretion of adiponectin and leptin in NW, but not in OB. Our observations indicate that a potential postprandial regulatory role of adiponectin and leptin is impaired in OB, and of importance in a more comprehensive understanding of the delayed postprandial TG clearance in obese individuals.

Leptin to adiponectin ratio - A surrogate biomarker for early detection of metabolic disturbances in obesity.

AIM: To study if the leptin to adiponectin (L:A) ratio, can be a potential biomarker for postprandial triglyceride clearance, insulin resistance (IR) or leptin resistance (LR) in apparently healthy obese, and obese individuals with established metabolic disease. METHODS AND RESULTS: Fifty adult subjects with obesity (BMI ≥30); of which 36 metabolic healthy obese (MHO), and 14 metabolic dysregulated obese (MDO), with clinical and/or biochemical signs of metabolic disease were included. Seventeen healthy, normal weight subjects represented the control group. Postprandial triglyceride (TG) levels were measured in an 8 h oral fat tolerance test (OFTT). IR by HOMA-IR, L:A ratio and indirect LR were measured. In the MHO group, 71.4%, 69.4% and 86.1%, had delayed TG clearance, IR and LR, respectively; whereas in the MDO group this was detected in 85.7%, 71.4% and 91.7%, respectively. A combination of all three metabolic risk factors was found in 39.8% of the MHO and in 42.9% of the MDO patients. Receiver operating characteristics (ROC) analysis revealed that a cut-off value for the L:A ratio of >1.65 for the control group (PPV 1.0, NPV 0.91) and >3.65 for the obese subjects (PPV 0.86, NPV 0.48) predicted the delayed TG clearance with a good specificity and sensitivity. Detecting a combined risk with at least 2/3 metabolic risk factors, the ROC yielded the most suitable L:A ratio cut-off at >1.88. CONCLUSION: L:A ratio was able to detect early metabolic disturbances in obese individuals, and may be a potential useful clinical surrogate biomarker of metabolic disorders.

Adenomas with adenocarcinoma: a study evaluating the risk of residual cancer and lymph node metastasis.

BACKGROUND AND AIMS: The increasing number of cases with colorectal adenomas with adenocarcinoma necessitates renewed evaluation of classification systems and risk factors. The aim for this retrospective study was to evaluate the potential risk of residual cancer and lymph node metastasis in patients with colorectal adenomas with adenocarcinoma. MATERIAL AND METHODS: An investigation of adenomas with adenocarcinoma in 74 patients was performed on histological slides and compared with clinical characteristics. A total of 44 of the samples were from macroscopically and microscopically completely resected lesions, and cancer at extended surgery was compared with pathology reports, classifications, and histopathological features. RESULTS: In all, 26 cases of adenomas with adenocarcinoma in the rectum and rectosigmoid were among women and 11 in men while 22 men as opposed to 15 women had primary lesions in colon, giving a significant association between gender and localization (p = 0.01). For macroscopically and microscopically fully resected lesions, Haggitt classification or submucosal invasion did not correlate with cancer at extended surgery. The lack of information on resection margins in the primary pathology reports was found to correlate significantly with residual cancer at extended surgery (p < 0.001) with residual cancer in 3 out of the 10 cases with no information, 1 out of the 5 where the resection margins were uncertain, 1 out of the 4 where the resection margins were not free, and none of the 25 cases when the resection margins were reported as free. In colon, 1 case out of the 6 with extended surgery (16.7%) was diagnosed with residual cancer compared with 4 out of the 10 (40%) from rectum. CONCLUSIONS: Haggitt or submucosal classifications were not found to be predictors for residual cancer in the remaining bowel tissue or lymph node metastasis. The only significant factor indicating increased risk of residual cancer was the lack of information on resection margins in the pathology report. Surgeons should therefore be alert when adenomas with adenocarcinomas are not confirmed as microscopically free in the pathology report.

Alterations in antral cytokine gene expression in peptic ulcer patients during ulcer healing and after Helicobacter pylori eradication.

Earlier studies have shown that the antral immune response in Helicobacter pylori infection has a mixed Th1-Th2-T-regulatory profile. After eradication, a chronic inflammation remains in some patients, but a follow-up study with a comprehensive cytokine profile in has not previously been published. Twelve patients with H. pylori positive peptic ulcer disease (five antral and seven duodenal) were enrolled and cytokine gene expressions in antral biopsies were determined (1) at entry, (2) after resolving the ulcer with proton pump inhibitor (PPI) treatment and (3) after eradication. The second endoscopy was performed 4 weeks after ending the PPI treatment, and the third endoscopy was performed after a mean of 10 months after eradication. Inflammation was graded according to the updated Sydney system. Interleukin (IL)1beta, IL8, IL12A, IL18, TNFalpha, IFNgamma, IL4, IL6 and IL10 expression levels were analysed by real-time RT-PCR. Mixed mononuclear and neutrophil infiltrates were seen at entry and after ulcer healing. After eradication, low-grade mononuclear infiltrates were found. The cytokine expression levels after ulcer healing (H. pylori positive gastritis) were not significantly different from the levels at entry (ulcer). After eradication, attenuation of the Th1 cytokines except for TNFalpha and a persisting increase of IL4 levels were observed, whereas the IL10 expression was markedly reduced. The present data did not indicate a specific ulcer promoting cytokine gene regulation profile. However, after eradication a chronic low-grade inflammation was seen with reduced Th1, prolonged Th2 and disappearance of the T-regulatory response.

Serum levels of glial fibrillary acidic protein correlate to tumour volume of high-grade gliomas.

OBJECTIVES: To investigate serum levels of glial fibrillary acidic protein (GFAP) and S-100B in patients with newly diagnosed high-grade gliomas. MATERIALS AND METHODS: GFAP and S-100B were measured by enzyme-linked immunosorbent assay techniques in preoperative serum from 31 patients with high-grade gliomas. A database with clinical, radiological and histological variables was created for statistical analyses. RESULTS: Mean serum levels of 239 ng/l (range 30-1210 ng/l) for GFAP and 58.3 ng/l (range 22-128 ng/l) for S-100B were found. Of the 31 patients, 16 had elevated levels of GFAP while only two showed increased S-100B concentrations. Tumour size was the only variable significantly associated with serum levels of GFAP (P < 0.0001) with a linear correlation coefficient of 0.67. CONCLUSIONS: Serum levels of GFAP demonstrated a linear correlation to tumour volume in patients with high-grade gliomas. GFAP seems to be a more reliable biomarker in patients with high-grade gliomas than the commercially available S-100B.

Increased frequency of antral CD4 T and CD19 B cells in patients with Helicobacter pylori-related peptic ulcer disease.

Only a fraction of Helicobacter pylori (HP)-infected individuals develop clinical disease. Recent research indicates that immunological mechanisms may be important for understanding the pathophysiology of HP infection. Differences in the individual cellular immune response may reflect the clinical diversity. The aim of the present study was to investigate the cellular immune response against HP in three clinically well-defined patient groups: HP-positive peptic ulcer, HP-positive and HP-negative gastritis. Biopsies from gastric mucosa were processed for analysis by flow cytometry and histology. The number of T lymphocytes (CD3+) was significantly higher in HP-positive peptic ulcer (13.8%) than in HP-positive nonulcer gastritis (6.3%). A nonsignificant increase for B lymphocytes (CD19+) was noted as well. Furthermore, a significant difference was seen in mucosal CD4/CD8 ratio between HP ulcer (2.4) and nonulcer HP gastritis (1.0) patients. Thus, B cells (CD19+) and T-helper cells (CD4+) were dominant in gastric mucosa from peptic ulcer patients, and cytotoxic T cells (CD8+) were relatively dominant in gastric mucosa from nonulcer patients. In conclusion, distinct differences in the T-cell subset distribution of mucosal lymphocytes were detected in patients with HP infection, strongly correlated with the presence or absence of peptic ulcer.

[Anemia and neutropenia in primary empty sella syndrome]. / Anemi og nøytropeni ved primaert tom sella-syndrom.

BACKGROUND: A 64-year-old man was admitted to our hospital with significant weight loss and symptoms of fatigue. He had normocytic anaemia and absolute neutropenia in peripheral blood. MATERIAL AND METHODS: Further haematological and endocrinological investigations were performed. RESULTS: Bone marrow aspiration and biopsy showed dysplastic signs. Immunophenotyping and cytogenetics did not provide evidence of primary haematological disease. Endocrinological testing demonstrated secondary adrenal insufficiency. Magnetic resonance imaging of the sella turcica showed an empty sella. Cortisol substitution eliminated the symptoms of the patient and normalised his peripheral blood values. The disturbed maturity and hypoplasia of the bone marrow were also normalised. INTERPRETATION: Normalisation of haematopoiesis after cortisol substitution indicates that cortisol plays an important role in the regulation of haematopoiesis. Primary empty sella syndrome with isolated ACTH cortisol deficiency is a very rare cause of disturbed haematopoiesis.