Platelet function and fibrinolytic activity in patients with bronchial asthma.

Platelets have the capacity to release mediators with potent inflammatory or anaphylactic properties. Platelet factor-4 (PF4) and beta-thromboglobulin (BTG) are two of these mediators. On the other hand, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) are two important mediators of fibrinolysis. Both mediators are secreted mainly by vascular endothelium. Plasma levels of PF4, BTG, PAI-1, and tPA may show changes in chronic inflammatory diseases such as asthma. This study examined the role of thrombocytes and the function of the endothelium in asthmatic patients during an attack and during a stable phase. Eighteen patients with known allergic asthma who came to our emergency department with an asthma attack and 14 control subjects were included in the study. Blood samples were taken after starting therapy with salbutamol inhalation. Lung function tests were performed after receiving the first emergency therapy for asthma. Plasma levels of PF4, BTG, PAI-1, tPA were determined before starting steroid therapy and after receiving 1 week of steroid therapy. Plasma levels of PF4 among patients with an asthma attack were significantly higher than those of controls (150.5+/-8.92 IU/mL vs. 92.5+/-7.63 IU/mL, p<0.001). A further increase in plasma PF4 levels was detected after steroid therapy (163.5+/-9.16 IU/mL). Plasma BTG levels of patients on admission were not statistically different from those in the control group (140.4+/-6.34 IU/mL vs. 152.2+/-8.71 IU/mL). An increase was detected after therapy (171.6+/-7.27 IU/mL) and post-treatment plasma levels were statistically meaningful versus the controls. Plasma levels of tPA and PAI were statistically higher than those in controls in asthmatic patients on admission (6.01+/-2.72 vs. 5.4+/-2.3 ng/mL for tPA and 75.2+/-27.2 ng/mL vs. 32.7+/-14.3 ng/mL for PAI-1). Further increases were detected in two parameters after 1 week of therapy with steroids (tPA levels were 6.85+/-2.96 ng/mL and PAI-1 levels were 83.5+/-29.6 ng/mL). There seems to be an increased activity of platelets during an asthma attack. Elevated PAI-1 and tPA levels may also indicate the activated endothelium in asthma. Increases of plasma levels of PAI-1 and tPA after steroid therapy need further investigation because elevated PAI-1 levels enhance airway remodeling.     

Rosiglitazone Attenuates Liver Inflammation in a Rat Model of Nonalcoholic Steatohepatitis

Rosiglitazone is an insulin-sensitizing agent. We aimed to assess the effects of rosiglitazone on a methionine- and choline-deficient diet (MCDD) model of nonalcoholic steatohepatitis (NASH) in rats. Wistar rats were fed either MCDD or a control diet in the 4-week induction study; they were given saline or 4 mg/kg/day rosiglitazone. After the induction study period, the rats were divided into four groups and fed MCDD or given a control diet for an additional 8 weeks and received saline or rosiglitazone. Serum and tissue samples were obtained. Rosiglitazone improved inflammation in NASH and improved ALT, alkaline phosphatase, and interleukin-6 levels in the induction study and interleukin-1β, interleukin-6, and tumor necrosis factor-α levels in the treatment study. Our preliminary study is the first to show the anti-inflammatory effects of rosiglitazone in NASH. Rosiglitazone’s effect on cytokines may be a key mechanism of its anti-inflammatory effect in NASH.     

Ischemic preconditioning decreases laparoscopy-induced oxidative stress in small intestine

BACKGROUND/AIMS: Laparoscopy is advantageous but its adverse effects have not yet been completely elucidated. Pneumoperitoneum performed to facilitate laparoscopy causes the organ perfusion decrease such as in the intestine. Oxidative stress reflects the tissue injury related to ischemia and reperfusion. We previously showed that laparoscopy causes oxidative stress in intestinal tissues. To assess whether the preconditioning phenomenon could be taken advantage of during laparoscopy we designed this randomized, controlled, experimental study with blind outcome assessment. We evaluated the effect of preconditioning, including sequential periods of pneumoperitoneum and desufflation on laparoscopy-induced tissue injury of small bowel with the help of two important markers of oxidative stress, thiobarbituric acid reactive substances and reduced glutathione. METHODOLOGY: Forty Sprague-Dawley male rats were used. After anesthesia, an intraperitoneal catheter was inserted. Pneumoperitoneum was created in all except controls, by CO2 insufflation under a pressure of 15 mmHg. The rats were randomized into the groups below: Group P was subjected to 60 minutes of pneumoperitoneum; Group P/D was subjected to 60 minutes of pneumoperitoneum followed by 45 minutes of desufflation; Group IP + P was subjected to 10 minutes of pneumoperitoneum, 10 minutes of desufflation and 60 minutes of pneumoperitoneum; Group IP + P/D was subjected to 10 minutes of pneumoperitoneum, 10 minutes of desufflation, 60 minutes of pneumoperitoneum and 45 minutes of desufflation; Group C (Control) was subjected to a sham operation, without pneumoperitoneum. Small bowel tissue malondialdehyde and reduced glutathione activities were measured, as applicable, by investigators blinded to the study design. The results were decoded and statistically analyzed with Kruskal-Wallis test. Mann-Whitney U test was used to compare the paired groups. p < 0.05 was considered significant. RESULTS: Small bowel tissue malondialdehyde levels were increased, whereas glutathione values were decreased in Groups P and P/D, as compared to Groups PRE/P and PRE/P/D; the latter two groups had results similar to the Control Group. CONCLUSIONS: Laparoscopic preconditioning may reduce the oxidative injury in intestine following laparoscopic procedures.     

The role of N terminal pro-brain natriuretic peptide in the evaluation of left ventricular diastolic dysfunction: correlation with echocardiographic indexes in hypertensive patients

The utility of N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) and Brain Natriuretic Peptide (BNP) for detecting left ventricular (LV) diastolic dysfunction in hypertensive patients without heart failure symptoms is unclear. In this study, we investigated the relation between NT-proBNP plasma levels and LV diastolic dysfunction in hypertensive patients without systolic dysfunction. Method: We studied 40 ambulatory patients (26 women, mean age 52 ± 5) with controlled hypertension. LV diastolic function was assessed with conventional Doppler, by means of mitral inflow and with tissue Doppler echocardiography by means of mitral annulus. The ratio of early diastolic transmitral E wave velocities to tissue Doppler mitral annulus early diastolic E' wave velocities (E/E′), was used to detect LV filling pressures. Patients were divided in three groups according to E/E′ ratios < 10 (group I), E/E′ ratios 'between' 10 and 15 (group II) and E/E′ ratios > 15 (group III). Plasma concentrations of NT-proBNP were measured by electro chemiluminescence's immunoassay. Results: The NT-proBNP blood levels were positively correlated significantly with E/E′ ratio (r = 0.80, P < 0.0001). Patients with elevated LV end diastolic pressure (LVEDP), defined as E/E′ > 15 (n = 8) had highest NT-proBNP (203 ± 75 pg/ml) levels. E/E′ 10 to 15 group (n = 16) had a mean NT-proBNP level of 71 ± 26 pg/ml, and those with E/E′ < 10 (n = 16) had 39 ± 20 pg/ml. A NT-proBNP value of 119 pg/ml had a sensitivity of 87%, a specificity of 100% for predicting E/E′ > 15. Conclusion: The assessment of the blood concentration of NT-proBNP is of potential value for identification of those patients with hypertension to detect early cardiovascular changes, especially LV diastolic dysfunction.     

Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene

Hereditary juvenile megaloblastic anemia due to vitamin B12 (cobalamin) deficiency is caused by intestinal malabsorption of cobalamin. In Imerslund-Grasbeck syndrome (IGS), cobalamin absorption is completely abolished and not corrected by the administration of intrinsic factor (IF); if untreated, the disease is fatal. Biallelic mutations either in the cubilin (CUBN) or amnionless (AMN) gene cause IGS. In a series of families clinically diagnosed with likely IGS, at least six displayed no evidence of mutations in CUBN or AMN. A genome-wide search for linkage followed by mutational analysis of candidate genes was performed in five of these families. A region in chromosome 11 showed evidence of linkage in four families. The gastric IF (GIF) gene located in this region harbored homozygous nonsense and missense mutations in these four families and in three additional families. The disease in these cases therefore should be classified as hereditary IF deficiency. Clinically, these patients resembled those with typical IGS; radiocobalamin absorption tests had been inconclusive regarding the nature of the defect. In the diagnosis of juvenile cobalamin deficiency, mutational analysis of the CUBN, AMN, and GIF genes provides a molecular characterization of the underlying defect and may be the diagnostic method of choice.     

The Relationship between Epicardial Adipose Tissue and Malnutrition,Inflammation, Atherosclerosis/Calcification Syndrome in ESRD Patients

Summary

Background and objectives

Malnutrition, inflammation, atherosclerosis/calcification (MIAC) and endothelial dysfunction are the most commonly encountered risk factors in the pathogenesis of cardiovascular disease in ESRD patients. Epicardial adipose tissue (EAT) is the true visceral fat depot of the heart. The relationship between CAD and EAT was shown in patients with high risk of coronary artery disease. In this study, we aimed to investigate the relationship between EAT and MIAC syndrome in ESRD patients.

Design, setting, participants, & measurements

Eighty ESRD patients and 27 healthy subjects enrolled in this cross-sectional study. EAT and coronary artery calcification score were measured by a multidetector computed tomography (MDCT) scanner. Patients with serum albumin <3.5 mg/dl were defined as patients with malnutrition; those with serum C-reactive protein level >10 ng/dl (normal range, 0–5 ng/dl) had inflammation; and those with CACS >10 had atheroscleosis/calcification.

Results

Total CACS and EAT measurements were significantly higher in ESRD patients when compared with healthy subjects. There was a statistically significant relationship between EAT and CACS in ESRD patients (r = 0.48). EAT measurements were higher in PD patients than HD patients. Twenty-four of the patients had no component, 31 had one component, 17 had two components, and nine had all of the MIAC components. EAT was found to be significantly increased when the presence of MIAC components increased. EAT was positively correlated with age, body mass index, and presence of MIAC. These parameters were also found as independent predictors of increased EAT.

Conclusions

We found a relationship between EAT and components of MIAC syndrome in ESRD patients.     

Prevalence of Hepatic Granulomas in Chronic Hepatitis B

An increasing frequency of hepatic granulomas, up to 10%, in chronic hepatitis C patients is reported, and their presence is considered to be a predictor of treatment success. However, there is only one prevalence study on granuloma in chronic hepatitis B, and its significance for treatment outcome is unknown. We aimed to determine the prevalence of hepatic granulomas in a larger group of chronic hepatitis B patients and to compare their presence with the response to interferon therapy. Biopsy specimens of chronic hepatitis B patients were reevaluated for the presence of hepatic granulomas. All patients with hepatic granuloma were screened for other granulomatous diseases by tuberculin skin test, chest X-ray and computed tomography, venereal disease research laboratory, Brucella agglutination tests, and exposure to hepatotoxic agents. We screened 663 cases of chronic hepatitis B. Hepatic granulomas were found in 10 cases (1.5%). The granulomas could not be ascribed to any other reason. Of the 10 patients with hepatic granulomas, 4 responded to interferon therapy, 2 dropped out, and 4 were nonresponders. We conclude that hepatic granuloma is a rare finding in chronic hepatitis B and its presence does not seem to predict the response to interferon therapy.     

In vivo effect of losartan on platelet aggregation in patients with hypertension

The angiotensin II receptor, losartan, has been found to inhibit platelet aggregability to some extent in in vitro experiments. There have been conflicting results about the in vivo effects of losartan. We sought to clarify the in vivo effect of losartan on platelet aggregation. Forty patients with grade I essential hypertension were treated with losartan for 3 weeks. Platelet aggregation tests with adenosine diphosphate (ADP) and ristocetin were analyzed and compared before and at the end of the study. Losartan effectively decreased systolic (SBP) and diastolic (DBP) blood pressure. Mean SBP before and after treatment was 159.6 ± 12.8 and 149.2 ± 17.3mmHg, respectively. Mean DBP decreased from 93.7 ± 8.2 to 87.7 ± 10.3mmHg after treatment. The results of the platelet aggregation tests with ADP and ristocetin were not significantly different when both rate and amplitude of maximal aggregation were included. Peak platelet aggregation with ADP regarding the lowest light transmission in the aggregometer was 59.8% ± 24.3% before and 58.3% ± 18.1% after the treatment. The same variables with ristocetin were 66.8% ± 21.6% and 60.8% ± 23.3%, respectively. In vivo effects of losartan on platelet aggregation with ADP and ristocetin were insignificant.     

Effects of Angiotensin-converting enzyme inhibition and statin treatment on inflammatory markers and endothelial functions in patients with longterm rheumatoid arthritis

OBJECTIVE: To investigate the effects of angiotensin-converting enzyme (ACE) inhibitors and statins (hydroxy-methyl-glutaryl-CoA reductase inhibitors) on inflammatory markers and endothelial functions in patients with rheumatoid arthritis (RA). METHODS: A total of 45 patients with longterm RA were randomized into 3 groups to receive 8 weeks of treatment with placebo (n = 15), simvastatin (20 mg/day, n = 15), or quinapril (10 mg/day, n = 15) as an adjunct to existing antirheumatic drug treatment. Factors with a role in the development of endothelial dysfunction, such as C-reactive protein (CRP), fibrinogen, nitric oxide (NO), and serum cytokine concentrations including interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured at baseline and in the posttreatment period. Brachial artery vasodilator responses were assessed by high resolution ultrasound to evaluate endothelial functions. RESULTS: Simvastatin treatment significantly decreased serum CRP and TNF-a [from 14 +/- 6 to 7 +/- 3 mg/l (p = 0.025) and 30 +/- 5 to 16 +/- 4 pg/ml (p = 0.012), respectively], while quinapril had no significant changes in these 2 measures. IL-1beta and IL-6 showed insignificant changes in patients in the 2 drug groups. Endothelium-dependent vasodilatation was improved significantly in the simvastatin group [from 5.3 +/- 1.1% to 8.9 +/- 1.4% (p = 0.025)], while there was no difference in endothelium-independent vasodilatation [9.0 +/- 1.8% to 11.2 +/- 2.5% (p = 0.17)]. The quinapril group showed no significant changes in both types of vasodilation although there was a tendency to an increase in endothelium-dependent vasodilatation [from 6.1 +/- 0.8% to 7.8 +/- 0.7% (p = 0.06)]. Treatment with the 2 drugs had no significant effects on resting arterial diameter. CONCLUSION: We show that simvastatin 20 mg daily improves endothelial function in patients with RA. Its beneficial effect may be attributed to lowering CRP and TNF-alpha concentrations. ACE inhibition with daily 10 mg quinapril was found to have no significant effects on inflammatory markers and endothelial vasodilator response.     

Impact of obstructive sleep apnea-related symptoms on surgical wound complications in breast cancer patients: pilot study in a tertiary health center in Turkey

Purpose

Wound healing is an important factor influencing morbidity following surgical procedures. The association of obstructive sleep apnea (OSA) with numerous postoperative complications has been previously reported. In this study, we report the impact of OSA-related symptoms on wound complications in breast cancer patients in the postoperative period.

Methods

Breast cancer patients were enrolled for a prospective observational study. Outcome measures included sociodemographic data, self-reported sleep-wake questionnaires (Berlin questionnaire, STOP-BANG, and Epworth sleepiness scale [ESS]) as well as type of surgery, smoking status, duration of anesthesia, the need for postoperative opioid drugs, and complications for surgical wounds. Patients’ general preoperative health status was quantified by using American Society of Anesthesiologists (ASA) scores.

Results

A total of 132 women were included in the study, of whom 61% (n?=?81) underwent mastectomy, and 39% (n?=?51) had breast conserving surgery. Mean ESS score of the study group was 7.7?±?0.5. Multivariant analysis identified, either being at medium high risk by STOP-BANG questionnaire (OR:1.77, p: 0.04) or being at high risk by Berlin questionnaire (OR:1.96, p: 0.04) as well as high BMI (OR:2.76 95% CI:1.73–4.65, p: 0.02), smoking history (OR:3.04 95% CI: 2.25–3.86, p: 0.01) and type of surgery (OR:2.64 95% CI: 1.63–2.89, p: 0.03) were independent factors for wound healing.

Conclusions

The study results suggest that patients with high risk for OSA have a tendency to develop postoperative wound complications after breast cancer surgery. This study lays groundwork for further scrutiny using more robust methodology.