The Relationship Between HRCT and Pulmonary Function in Behcet’s Disease

The purpose of this study was to compare the pulmonary functions in female Behcets patients with or without pathological pulmonary lesions using high resolution computerized tomography (HRCT). Twenty-nine female patients aged 19–54 yrs and 20 healthy females aged 19–50 yrs (control group) were accepted into the study. HRCT images were taken and according to HRCT patients were divided into HRCT (+) and HRCT (–) groups (18 patients in each). Pulmonary function tests (PFT) through a spirometer were performed and FVC, FEV₁, FEF_25–75%, PEF, VC, RV, FRC, DLCO and DLCO/VA were determined. No statistically significant difference was observed when the PFT values were compared between HRCT (+) and HRCT (–) patients for the obtained results and the percentage of the expected values. When the PFT values were compared for both HRCT (+) and HRCT (–) patients with the control group separately there was no statistical difference between the best values. A statistically low DLCO/VA value was observed between the percentage of the expected values. It is concluded that though there is a pulmonary restriction in Behcets disease, this restriction has no relation to pulmonary functions. It would be useful to perform pulmonary function tests in the patients with Behcets disease both with or without any pathological findings in HRCT for obtaining information about pulmonary functions. We suggest that even when the results of the pulmonary function tests are normal, considering some pathological changes in HRCT, HRCT investigations may be useful for following up the disease.     

Expression of α-Defensins,CD20+ B-lymphocytes,and Intraepithelial CD3+ T-lymphocytes in the Intestinal Mucosa of Patients with Liver Cirrhosis: Emerging Mediators of Intestinal Barrier Function

Aim

The present study investigates the role of innate and adaptive immune system of intestinal mucosal barrier function in cirrhosis.

Methods

Forty patients with decompensated (n?=?40, group A), 27 with compensated cirrhosis (n?=?27, group B), and 27 controls (n?=?27, group C) were subjected to duodenal biopsy. Expression of α-defensins 5 and 6 at the intestinal crypts was evaluated by immunohistochemistry and immunofluorescence. Serum endotoxin, intestinal T-intraepithelial, and lamina propria B-lymphocytes were quantified.

Results

Cirrhotic patients presented higher endotoxin concentrations (p?<?0.0001) and diminished HD5 and HD6 expression compared to healthy controls (p?=?0.000287, p?=?0.000314, respectively). The diminished HD5 and HD6 expressions were also apparent among the decompensated patients compared to compensated group (p?=?0.025, p?=?0.041, respectively). HD5 and HD6 expressions were correlated with endotoxin levels (r?=?-0.790, p?<?0.0001, r?=???0.777, p?<?0.0001, respectively). Although intraepithelial T-lymphocytes were decreased in group A compared to group C (p?=?0.002), no notable alterations between groups B and C were observed. The B-lymphocytic infiltrate did not differ among the investigated groups.

Conclusions

These data demonstrate that decreased expression of antimicrobial peptides may be considered as a potential pathophysiological mechanism of intestinal barrier dysfunction in liver cirrhosis, while remodeling of gut-associated lymphoid tissue as an acquired immune response to bio-pathogens remains an open field to illuminate.

     

γ-Glutamyl Transpeptidase in Men and Alanine Aminotransferase in Women are the Most Suitable Parameters Among Liver Function Tests for the Prediction of Metabolic Syndrome in Nonviral Hepatitis and Nonfatty Liver in the Elderly

Background/Aims:

Nonalchoholic fatty liver disease (NAFLD) has been reported as a hepatic manifestation of metabolic syndrome (MetS); it is common and accounts for 80% of the cases with abnormal liver function tests (LFTs). In addition, several studies have proved that there is a correlation between abnormal LFTs and MetS. Therefore, LFTs may represent the abnormal metabolic status of livers in the patients with MetS. To identify the early state of metabolic dysfunction, we investigate the value of LFTs for the future MetS development in the relatively healthy (non-NAFLD) elderly.

Patients and Methods:

A total of 16,912 subjects met the criteria for analysis. In the first stage of this study, subjects were enrolled in the cross-sectional study in order to find out the optimal cutoff value in different LFTs with higher chances to have MetS. In the second stage of the present study, subjects with MetS at baseline were excluded from the same study group, and a median 5.6-year longitudinal study was conducted on the rest of the group.

Results:

Among all LFTs, only aspartate aminotransferase in both genders and the α-fetal protein in women failed to show the significance in distinguishing subjects with MetS by the receiver operating characteristic curve. In the Kaplan–Meier plot, only γ-glutamyl transpeptidase (γ-GT) in men and the alanine aminotransferase (ALT) in women could be used to successfully separate subjects with higher risk of developing the MetS from those with lower risk. Finally, in the multivariant Cox regression model, similar results were identified. Still, the hazard ratio (HR) to have future MetS, γ-GT in men, and ALT in women showed significance (HR = 1.511 in men and 1.504 in women).

Conclusion:

Among all the different LFTs, γ-GT (>16 U/L) in male and ALT (>21 U/L) in female were the best predictors for the development of MetS in healthy elderly. These two liver markers could be an ancillary test in predicting future MetS development/diagnosis. Elevation of the LFTs without underlying liver diseases should be treated as a warning sign of the possible MetS development in the elderly.     

High Ascitic Fluid Leptin Levels in Patients with Decompensated Liver Cirrhosis and Sterile Ascites: Relationship with TNF-α Levels

Leptin is an adipocyte-derived hormone involved in the homeostasis of body composition. An imbalance in leptin regulation has been observed in patients with liver cirrhosis. We aimed to assess serum and ascitic leptin levels in a group of patients with decompensated liver cirrhosis and to evaluate the relationship of these levels with tumor necrosis factor alpha (TNF-alpha). We assessed both serum and ascitic fluid leptin levels in a series of 16 consecutive patients with liver cirrhosis. We calculated the body mass index (BMI) and assessed body fat (BF) of all patients by means of bioelectric impedence analysis. Leptin levels were analyzed in relationship to biochemical indexes, TNF-alpha levels, and body composition. None of the patients had spontaneous bacterial peritonitis. Both serum and ascites leptin levels were correlated with BMI and BF. On average, ascitic fluid leptin levels (13.1 +/- 10.9 ng/ml) were twice as high as serum levels (7.0 +/- 6.4 ng/ml), and the ascitic fluid/serum ratio of leptin was > 1 in all patients. Serum and ascites leptin levels were positively correlated (rS = 0.675, P = 0.009), while no correlation was observed between leptin and TNF-alpha levels, both in serum and in ascites. Serum and ascites TNF-alpha were not correlated. The ascitic fluid leptin levels of cirrhotic patients with sterile ascites are on average two times higher than circulating levels of this hormone. Noteworthily, they correlate significantly with body composition. These findings seem to suggest that in patients with decompensated liver cirrhosis, intraabdominal production of leptin may contribute to the metabolic picture.     

Child–Pugh Versus MELD Score for the Assessment of Prognosis in Liver Cirrhosis: A Systematic Review and Meta-Analysis of Observational Studies

Child–Pugh and MELD scores have been widely used for the assessment of prognosis in liver cirrhosis. A systematic review and meta-analysis aimed to compare the discriminative ability of Child–Pugh versus MELD score to assess the prognosis of cirrhotic patients.PubMed and EMBASE databases were searched. The statistical results were summarized from every individual study. The summary areas under receiver operating characteristic curves, sensitivities, specificities, positive and negative likelihood ratios, and diagnostic odds ratios were also calculated.Of the 1095 papers initially identified, 119 were eligible for the systematic review. Study population was heterogeneous among studies. They included 269 comparisons, of which 44 favored MELD score, 16 favored Child–Pugh score, 99 did not find any significant difference between them, and 110 did not report the statistical significance. Forty-two papers were further included in the meta-analysis. In patients with acute-on-chronic liver failure, Child–Pugh score had a higher sensitivity and a lower specificity than MELD score. In patients admitted to ICU, MELD score had a smaller negative likelihood ratio and a higher sensitivity than Child–Pugh score. In patients undergoing surgery, Child–Pugh score had a higher specificity than MELD score. In other subgroup analyses, Child–Pugh and MELD scores had statistically similar discriminative abilities or could not be compared due to the presence of significant diagnostic threshold effects.Although Child–Pugh and MELD scores had similar prognostic values in most of cases, their benefits might be heterogeneous in some specific conditions. The indications for Child–Pugh and MELD scores should be further identified.     

Concordance Between Mechanical and Electrical Dyssynchrony in Heart Failure Patients: A Function of the Underlying Cardiomyopathy?

Background: Cardiac resynchronization therapy (CRT) improves heart failure (HF) symptoms through a reduction of cardiac mechanical dyssynchrony. Mechanical dyssynchrony is currently estimated by electrical dyssynchrony (QRS duration). It is known that electrical and mechanical dyssynchrony are not well correlated in HF patients. However, there is limited information about whether this relationship might be influenced by the underlying cardiomyopathy.
Methods: Doppler echocardiography was performed in 88 patients presenting with heart failure due to ischemic (n = 42) or nonischemic (n = 46) heart disease, left ventricular ejection fraction <40%, New York Heart Association class II–IV, regardless of their QRS duration. Interventricular dyssynchrony was assessed by the time interval between preaortic and prepulmonary ejection times. Intraventricular dyssynchrony was ascertained by (1) the delay between the earliest and the latest peak negative longitudinal strain recorded in the basal and mid-segments of the lateral and septal walls (TMinMax) and (2) the standard deviation of time-to-peak in the same segments (SDdys).
Results: The correlation coefficient between QRS duration and mechanical interventricular dyssynchrony was r = 0.47 (P < 0.001) in patients with nonischemic disease and nonsignificant in patients with ischemic disease. Similarly, the correlation coefficient between QRS duration and mechanical intraventricular dyssynchrony was significant in patients with nonischemic disease (r = 0.37, P = 0.01 for TMinMax; r = 0.42, P = 0.003 for SDdys) and nonsignificant in patients with ischemic disease.
Conclusion: The concordance between electrical dyssynchrony assessed by QRS duration and mechanical dyssynchrony assessed by myocardial strain is dependent upon the underlying cardiomyopathy. This observation may improve our understanding of the various responses observed in CRT patients.     

Liver Disease in α1-Antitrypsin Deficiency: Aspects of Incidence and Prognosis

The influence of the prokinetic drug cisapride on the release of gastrointestinal hormones was studied in volunteers. First, acute effects of single doses of cisapride compared with saline were investigated. Cisapride at doses of 8mg and 20 mg intravenously significantly increased plasma concentrations of pancreatic polypeptide (hPP) by 145% and 146%, respectively. Cholecystokinin (CCK) levels were increased by 176% at 8 mg cisapride, whereas gastrin and insulin levels remained unchanged. Enhancement of PP and CCK secretion was almost completely abolished by pre-treatment with 1 mg atropine. Carbachol (250 ug subcutaneously) increased PP release by 62% but did not affect the other hormones. Second, the influence of a 1-week treatment (10 mg three times daily, given orally) on plasma hormone levels was studied. After 1 week the postprandial CCK release was diminished by 58%. Basal levels and postprandial responses of gastrin, PP, and insulin were not altered by prolonged cisapride administration. It is concluded that acute application of cisapride stimulates secretion of PP and CCK via atropine-sensitive mechanisms and that chronic treatment with cisapride diminishes CCK release by an unknown mechanism.     

Is There a Relationship Between the pH and Volume of Saliva and Esophageal pH-metry Results?

There are several implications in the buffer capacity and in the protective role of saliva in gastroesophageal reflux disease (GERD) and other digestive disorders. The lack of knowledge about the production and quality of saliva and the fact that saliva plays an important role in digestive homeostasis motivated the authors to study the relationship between reflux measured by esophageal pH-metry and the pH and volume of saliva in individuals with GERD and its laryngopharyngeal manifestations (LPR). The study was designed as a randomized clinical trial. The studied population consisted of 39 adults with GERD and LPR confirmed by a positive 24-hour double-probe esophageal pH-metry. Unstimulated whole saliva was collected and its pH and volume were compared to pH-metry results. Patients were divided into four groups according to the number of distal episodes of reflux and two groups according to the presence or absence of proximal reflux. A highly significant difference was found between the groups with distal reflux when comparing salivary volume alone and salivary volume/salivary pH. The same occurred for the presence or absence of proximal reflux. These results suggest a direct correlation between salivary volume and “salivary pH × volume” with the number of distal and proximal episodes of reflux on the esophageal pH-metry. If larger studies confirm this finding, in the future it might be possible to diagnose GERD and LPR through a simple “spit test,” avoiding more costly and invasive procedures.     

Investigating Cortisol Production and Pattern as Mediators in the Relationship Between Shift Work and Cardiometabolic Risk

Background

Shift work is a risk factor for many diseases, including cardiovascular disease. Although the biological pathways are still unclear, it is hypothesized that cortisol disruption during night work is an intermediate. The objective of this study is to determine whether total cortisol production and cortisol pattern mediate the relationship between current shift work and cardiometabolic risk (CMR) among female hospital employees.

Association Between Catalase Gene Polymorphisms and Risk of Chronic Hepatitis B,Hepatitis B Virus-Related Liver Cirrhosis and Hepatocellular Carcinoma in Guangxi Population: A Case–Control Study

Reactive oxygen species (ROS) play critical roles in hepatocarcinogenesis. The catalase (CAT) enzyme is involved in the repair of ROS. Therefore, we investigate the association between CAT gene polymorphisms and the risk of hepatocellular carcinoma (HCC).A total of 715 subjects were divided into 4 groups: 111 chronic hepatitis B (CHB) patients, 90 hepatitis B virus (HBV)-related liver cirrhosis (LC) patients, 266 HBV-HCC patients, and 248 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect CAT gene rs1001179, rs769217, and rs7943316 polymorphisms.Binary logistic regression analyses adjusting for sex, age, ethnicity, smoking and alcohol consumption, and body mass index suggested that subjects carrying the rs769217 T allele were at marginally increased risk of CHB, LC, and HCC, with adjusted odds ratios (ORs) of 1.51 (95% confidence interval [CI] = 1.04–2.20, P = 0.029), 1.48 (95% CI = 1.03–2.14, P = 0.035), and 1.51 (95% CI = 1.14–1.98, P = 0.004), respectively. Similarly, those individuals carrying the rs769217 TT genotype had a moderately increased risk of CHB, LC, and HCC, with adjusted ORs of 2.11 (95% CI = 1.05–4.22, P = 0.035), 2.00 (95% CI, 1.01–3.95, P = 0.047), and 1.93 (95% CI = 1.14–3.28, P = 0.015), respectively. Moreover, subjects carrying the rs769217 CT genotype and at least 1 copy of the T allele (dominant model) were 1.78 times and 1.83 times more likely to develop HCC, respectively (OR = 1.78, 95% CI = 1.16–2.73, P = 0.009 and OR = 1.83, 95% CI = 1.23–2.71, P = 0.003). This association between CAT rs769217 T alleles and HCC risk is significantly strengthened among men, nonsmokers, nondrinkers, and among individuals <50 years of age. Furthermore, we found 1 high-risk haplotype GTA for CHB (OR = 1.45, 95% CI = 1.05–2.01) and 1 protective haplotype GCA for HCC risk (OR = 0.67, 95% CI = 0.52–0.87). We did not found any significant difference in CAT rs1001179 and rs7943316 polymorphisms between controls and cases.Our findings suggest that the CAT rs769217 T allele is associated with increased risk of CHB, HBV-LC, and HBV-HCC in Guangxi population.     

A Comparative Study of the Effects of α1-Adrenoceptor Antagonists on Sympathetic Function in Rats

α₁-Adrenoceptor antagonists were comparatively evaluated in terms of their acute and long-term effects on sympathetic function in rats.In the first study, the effects of α₁-adrenoceptor antagonists on cardiovascular sympathetic nerve activity were electrophysiologically determined in anesthetized normotensive rats. Intravenous administration of four α₁-antagonists—prazosin, bunazosin, SM-2470, and YM-617—produced no changes or decreases in heart rate, in spite of the expected reflex tachycardia resulting from their marked hypotensive effect. Among the α₁-antagonists examined, some also produced a significant decrease in inferior cardiac nerve activity. All except prazosin decreased renal nerve activity, while prazosin showed an opposite tendency to increase the renal nerve activity. On the other hand, preganglionic adrenal nerve activity, an index of central sympathoinhibitory activity, underwent a significant decrease after SM-2470 and YM-617 administration, and a dose-dependent increase was observed in response to prazosin and bunazosin.In the second study, the long-term (4 weeks) effects of α₁-antagonists on plasma and urinary catecholamine levels and urinary electrolyte excretions were evaluated in stroke-prone spontaneously hypertensive rats (SHRSP). Prazosin and bunazosin did not exert any consistent changes on plasma and urinary catecholamine concentrations. SM-2470, however, significantly decreased both plasma and urinary epinephrine concentrations. In addition, bunazosin and SM-2470 produced increases in urinary sodium and potassium excretions. Urine volume tended to increase after bunazosin administration. Prazosin, on the other hand, produced decreases in urinary sodium and potassium excretions as well as in urine volume.These findings demonstrate that α₁-antagonists differentially affected cardiovascular sympathetic tone in anesthetized rats. These varied sympathoinhibitory profiles might be in part explainable as different effects on urinary electrolyte metabolism after long-term administration of α₁-antagonists in SHRSP. Am J Hypertens 1996;9:160S–169S     

Elevated Serum Levels of Astroglial S100β in Patients with Liver Cirrhosis Indicate Early and Subclinical Portal-Systemic Encephalopathy

Portal-systemic encephalopathy is the prototype among the neuropsychiatric disorders that fall under the term Hepatic Encephalopathies. Ammonia toxicity is central to the pathophysiology of Portal-systemic encephalopathy, and neuronal ammonia toxicity is modulated by activated astrocytes. The calcium-binding astroglial key protein S100 is released in response to glial activation, and its measurement in serum only recently became possible. Serum S100 was determined by an ultrasensitive ELISA in patients (n=36) with liver cirrhosis and transjugular intrahepatic portosystemic stent-shunt. Subclinical portal-systemic encephalopathy and overt portal-systemic encephalopathy were determined by age-adjusted psychometric tests and clinical staging, respectively. Serum S100 was specifically elevated in the presence of subclinical or early portal-systemic encephalopathy, but not arterial ammonia. S100 levels elevated above a reference value (S100 110pg/ml) or the cut off value determined in our group of patients (112pg/ml) predicted subclinical portal-systemic encephalopathy with a specificity and sensitivity of 100 and 56.5%, respectively. Serum S100 was significantly dependent on liver dysfunction (Child-Pugh score), but was more closely related to cognitive impairments than the score. Serum S100 seems to be a promising biochemical surrogate marker for mild cognitive impairments due to portal-systemic encephalopathy.