Role of Ghrelin and Leptin in Predicting the Severity of Acute Pancreatitis

Ghrelin and leptin are the hormones that influence endocrine and exocrine functions of the pancreas and regulate feeding behaviors and energy metabolism. The aim of this study was to investigate the levels of ghrelin and leptin in pancreatitis of different severities and the relation of these hormones with blood glucose level and proinflammatory cytokines. The study was performed on 90 Wistar Albino rats. Three experimental groups composed of 30 rats were established: control group, 0.9% NaCl solution was injected intraperitoneally (i.p); acute edematous pancreatitis (AEP) group, 1 μg/100 g cerulein was injected i.p. five times, at 1-hr intervals; and acute necrotizing pancreatitis (ANP) group, 500 mg/100 g l-arginine was injected i.p. Ten animals in each group were sacrificed under anesthesia 12, 24 and 48 hr after the last injection. After blood withdrawal, the pancreas was totally excised. The levels of blood sugar, lipase, serum tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), ghrelin, and leptin were investigated and histopathologic examination was performed. Following pancreatitis induction, serum ghrelin levels increased at 24 hr and reached the peak level at 48 hr. Its level in the AEP group was higher than in the ANP group. Serum leptin levels in the AEP and ANP groups increased after 12 hr and stayed at high levels until 48 hr compared with the control group. Similarly to ghrelin and leptin, blood glucose levels increased in both pancreatitis groups, but the increase was more prominent in the ANP group, with levels >200 mg/ml at 48 hr. The levels of TNF-α and IL-1β in the AEP and ANP groups reached the peak level at 24 hr and then decreased to a level close to that of the control group at 48 hr. We conclude that serum leptin and ghrelin levels increase in the first 48 hr of AEP and ANP. As the serum ghrelin levels in ANP are higher than in AEP, it can be used as a marker to show the severity of pancreatitis. While TNF-α and IL-1β can be used as a prognostic factor in the first 24 hr, ghrelin and leptin can be used subsequently.     

Factors Predicting Mortality in Severe Acute Pancreatitis

Acute pancreatitis (AP) is a common disorder in which ensuing serious complications may lead to a fatal outcome in patients. Background/Aims: To describe a large series of patients with severe AP (SAP) who were admitted to our hospital and to identify factors predicting mortality.Patients and Methods: In a retrospective study, all patients with SAP diagnosed between February 1996 and October 2000 according to the Atlanta criteria were studied.Results: Out of a total of 363 AP patients, 67 developed SAP. The mean age of the patients was 69; the commonest etiology was biliary; 55.2% developed necrosis; the commonest systemic complication was respiratory failure (44.7%), followed by acute renal failure (35.8%) and shock (20.9%). A total of 31.3% of the patients died. Factors significantly related to mortality were age, upper digestive tract bleeding, acute renal failure, respiratory failure and shock by univariate analysis. However, pseudocysts seemed to have a protective effect. By multivariate analysis, independent prognostic factors were age, acute renal failure and respiratory failure.Conclusions: Patients with SAP mainly died due to systemic complications, especially acute renal failure and respiratory failure. Necrosis (in the absence or presence of infection) was not correlated with increased mortality. A pseudocyst was found to be a protective factor, probably because the definition itself led to the selection of patients who had survived multiorgan failure.     

Useful Markers for Predicting Severity and Monitoring Progression of Acute Pancreatitis

Background: The main problem in staging acute pancreatitis is the lack of accurate predictors of disease severity and of markers for progression of acute pancreatitis.Methods: We reviewed the literature for all candidate markers of acute pancreatitis and graded their usefulness and practicability for prediction of severe pancreatitis and for monitoring disease progression.Results: Several markers can differentiate mild and severe cases of acute pancreatitis with a high positive predictive value. Trypsinogen activation peptide and procalcitonin show significant differences in patients with mild and severe disease already on admission. While most parameters peak early and decrease rapidly thereafter, C-reactive protein (CRP), phospholipase A ₂ , procalcitonin and serum amyloid A are reliable predictors with persistently elevated levels in severe disease. CRP is still the reference parameter of all predictors indicating severe disease and pancreatic necrosis. So far, no single parame-ter has been developed which is suitable for early prediction of infected pancreatic necrosis.Conclusion: Of all markers available today, CRP is the 'gold standard' in predicting the severity of acute pancreatitis, but procalci-tonin seems to be a promising tool to monitor the progression of the disease. CRP has already been established in clinical routine. For procalcitonin, a practicable assay is also available and could easily be adopted into clinical routine.     

Assessment of Severity in Acute Pancreatitis

Assessment of severity of acute pancreatitis (AP) is a key determinant in the management of a patient. This review evaluates the various methods of assessment: clinical assessment, biochemical tests, Ranson's and Imrie's multiple prognostic criteria, simplified prognostic criteria, APACHE II, peritoneal lavage, and computed tomography. Although all of the above criteria can identify most of the seriously ill patients, each has some drawbacks. Individual preference and available institutional facilities greatly influence the method used for prognostic assessment in AP. However, some type of predictive assessment is possible in any hospital, and should be used in the management of patients with AP.     

Value of Early Blood Th-1 Cytokine Determination in Predicting Severity of Acute Pancreatitis

Background: Early evaluation of the severity of acute pancreatitis (AP) requires measurement of many variables within 48 h after admission. Septic complications (SC) are frequent, and preliminary studies have highlighted the value of prophylactic antibiotherapy; however, single and reliable predictive markers of sepsis are not yet available. The aim of this study was to assess the value of determining early blood Th-1 cytokines and their natural antagonists (interleukin-6 (IL-6), IL-1, IL-1ra, and the soluble form of tumor necrosis factor (sTNF) receptors RI and RII) to predict the severity and SC during AP. Methods: Thirty-seven patients with AP were prospectively included; 25 of them had severe AP, including 8 with SC. Serum cytokines were measured 48 h and 72 h after the onset of AP with an enzyme-linked immunosorbent assay. The optimal severity or SC diagnostic thresholds was determined using receiver operative curves. Results: Severe AP in accordance with the Atlanta criteria were better predicted by C-reactive protein and IL-6 serum determination, albeit these levels could not predict absolutely the death of two patients. In severe AP cases (n     

The Relationship of Heart Rate Variability with Severity and Prognosis of Cirrhosis

Many studies have demonstrated that cirrhosis is frequently associated with autonomic dysfunction. The aim of this study was to test autonomic dysfunction in cirrhotic patients by analyzing heart rate variability (HRV), to determine whether or not the degree of autonomic dysfunction is correlated with the severity of disease, and, also, to compare the changes of HRV between survivor and nonsurvivor groups after 2-year follow-up periods. HRV was analyzed using 24-hr ECG recording in 30 cirrhotic patients and 28 normal controls. The changes in HRV parameters including mean normal-to-normal (N-N) interbeat intervals (mean NN), standard deviation of all N-N intervals (SDNN), standard deviation of the average of N-N intervals for each 5-min period over 24 hr (SDANN), root mean square succesive differences (r-MSSD; msec), and percentage of adjacent N-N intervals that are >50 msec apart (pNN50), all as time domain parameters, were evaluated. The cirrhotic patients were also evaluated according to Child-Pugh classification scores as markers of the disease severity. The time-domain measures of HRV in cirrhotic patients were significantly reduced compared with those in the control group (for all parameters; P < 0.001). The severity of disease was associated with reduced HRV measures (for all parameters; P < 0.001). After the 2-year follow-up periods, HRV measurements in cirrhotic patients were significantly much lower in nonsurvivors than in survivors (P < 0.001 for all). We conclude that increasing severity of cirrhosis is associated with a reduction in HRV. This finding may be an indicator of poor prognosis and mortality for cirrhosis.     

急性心肌梗死窦性心律震荡和心率变异性的研究

目的探讨急性心肌梗死(AMI)伴室性期前收缩患者窦性心律震荡和心率变异性(HRV)的变化和临床意义。方法随机选取本院AMI合并室性期前收缩的患者58例(心梗组)和体检健康者52例(对照组)。收集所有受检者24h平均心率、R-R间期标准差、窦性心律震荡的初始值(TO)、窦性心律震荡的斜率(TS)、肌钙蛋白I(TNI)峰值、左室射血分数(LVEF)。比较两组24h平均心率、R-R间期标准差、TO、TS。并研究窦性心律震荡和HRV指标与TNI峰值和LVEF的相关性。结果心梗组的心律震荡和HRV指标弱于对照组,差异有统计学意义(P<0.05)。心梗组的R-R间期标准差与TNI峰值呈负相关(r=-0.52,P<0.01),与LVEF呈正相关(r=0.25,P<0.05)。TO与TNI峰值呈正相关(r=0.68,P<0.01),TO与LVEF呈负相关(r=-0.49,P<0.01)。TS与TNI峰值呈负相关(r=-0.79,P<0.01),TS与LVEF呈正相关(r=0.55,P<0.01)。死亡组的R-R间期标准差、TS低于存活组,TO高于存活组,差异有统计学意义(P<0.05)。结论窦性心律震荡和HRV减弱是反映AMI严重程度和预后的有用指标。     

Heart Rate Variability in Heart Failure

The autonomic nervous system has an important role in the development and progression of the heart failure syndrome. Increased sympathetic, reduced parasympathetic, and impaired baroreceptor activity are well-documented features of heart failure. The analysis of heart rate variability can give insight into these autonomic abnormalities. A number of techniques now exist for assessing heart rate variability, and in general they reflect the known autonomic abnormalities. Power spectral analysis of RR variability has been claimed to reflect sympathovagal balance, but the reduced or absent low-frequency component in heart failure is paradoxical. It is likely that the absent low-frequency component in heart failure reflects impaired baroreceptor function. Although these various techniques of heart rate variability may be useful, reliability and reproducibility are problematic in this area. Better, more refined techniques for the noninvasive assessment of autonomic and baroreceptor function are still needed.     

Heart Rate Variability in Chronic Heart Failure and Its Role in Prognosis of the Disease

Aim. To assess role of 24 hour heart rate variability (HRV) for prognosis of patients with chronic heart failure (CHF) and systolic dysfunction in the era of wide use of b-adrenoblockers. Material. Patients (n=135) with symptomatic CHF and ischemic (68%) or nonischemic cardiomyopathy (32%) with systolic left ventricular (LV) dysfunction and sinus rhythm (age 52+/-11.9 years; 42, 40 and 18% with NYHA class II, III and IV, respectively; mean LV ejection fraction 30.1+/-6.7%) At study entry 89 and 78% of patients received angiotensin converting enzyme inhibitors and b-adrenoblockers, respectively. Methods. Holter ECG monitoring with HRV temporal and spectral analysis. Results. During average follow-up of 2.4 years 60 patients (44.4%) died of cardiac causes (92.3% of all deaths). Other deaths were due to surgical pathology (n=1) and stroke (n=2). All standard HRV values with the exception of high frequency power were lowered, this lowering correlated with functional severity of heart failure. According to multifactorial analysis the following characteristics were independent predictors of all cause death: NYHA class III-IV (RR=1.9, 95% confidence interval 1.1-9.6, p=0.002), and SDNN value 90 ms (RR=1.5, 95% confidence interval 1.2-2.5, p=0.001). Conclusion. In CHF parameters of HRV are lowered compared to normal values and correlate with functional heart failure severity. NYHA class III-IV and lowered HRV (SDNN 90 ms) allow to identify patients with high risk of death.     

Interaction between Heart Rate and Heart Rate Variability

Heart rate variability (HRV) is significantly associated with average heart rate (HR), therefore, HRV actually provides information on two quantities, that is, on HR and its variability. It is difficult to conclude which of these two plays a principal role in the HRV clinical value, or in other words, what is the HR contribution to the clinical significance of HRV. Moreover, the association between HRV and HR is both a physiological phenomenon and a mathematical one. The physiological HRV dependence on HR is determined by the autonomic nervous system activity, but the mathematical one is caused by the nonlinear relationship between RR interval and HR. By employing modification methods of the HRV and HR relationship, it is possible to investigate the HR contribution to the HRV clinical value. Recent studies have shown that the removal of the HR impact on HRV makes HRV more predictive for noncardiac death, however, the enhancement of this impact causes HRV to be a better predictor of cardiovascular mortality. Thus, HR seems to constitute a cardiovascular factor of the HRV predictive ability. HR also influences the reproducibility of HRV, therefore, HR changes should be considered when one compares HRV measurements in a given patient. This review summarizes methodological aspects of investigations of the HRV and HR interaction as well as latest observations concerning its clinical utility. The issues discussed in this article should also refer to any other heart rate dynamics analysis which indices are significantly associated with HR.     

Evaluation of Severity in Patients with Acute Pancreatitis

We compared the multiple organ system failure (MOSF) score, the Acute Physiologic and Chronic Health Evaluation (APACHE) II, and Ranson and Imrie scores for their predictive value in evaluating severity of acute pancreatitis. Of the 259 patients, 73 (28%) had severe disease. Fifty-two (20%) patients had organ system failure (OSF) on admission, and 59% of patients with severe disease had OSF. Shortly after admission, only MOSF and APACHE II scores were available, and in patients with severe disease, these predictions were correct in 64% and 60%, respectively. Forty-eight hours later, the MOSF score was the most sensitive, and correctly predicted outcome in 67% of patients, compared with about 60% for other scores. Of four scoring systems, only MOSF and APACHE II scores allowed repetitive assessment to monitor the course of the disease. MOSF score is organ-specific and may be better than APACHE II in reflecting disease activity. Our results suggest that the MOSF score is valuable in early identification and close monitoring of high risk patients and in deciding on therapy in these patients.     

Faster Rate of Initial Fluid Resuscitation in Severe Acute Pancreatitis Diminishes In-Hospital Mortality

Background/Aims:We evaluated the impact of the initial intravenous fluid resuscitation rate within the first 24 h of presentation to the emergency room on important outcomes in severe acute pancreatitis. Methods: Patients presenting directly with a diagnosis of severe acute pancreatitis were identified retrospectively. Patients were divided into two groups — those who received ≥.33% (‘early resuscitation’) and <33% (‘late resuscitation’) of their cumulative 72-hour intravenous fluid volume within the first 24 h of presentation.The primary clinical outcomes were in-hospital mortality, development of persistent organ failure, and duration of hospitalization. Results: 17 patients were identified in the ‘early resuscitation’ group and 28 in the ‘late resuscitation’ group and there were no baseline differences in clinical characteristics between groups. Patients in the ‘late resuscitation’ group experienced greater mortality than those in the ‘early resuscitation’ group (18 vs. 0%,p<0.04) and demonstrated a trend toward greater rates of persistent organ failure (43 vs. 35%, p = 0.31). There was no difference in the total amount of fluid given during the first 72 h. Conclusions: Patients with severe acute pancreatitis who do not receive at least one third of their initial 72-hour cumulative intravenous fluid volume during the first 24 h are at riskfor greater mortality than those who are initially resuscitated more aggressively.     

The Role of Fas Expression on the Occurrence of Immunosuppression in Severe Acute Pancreatitis

Background

Severe acute pancreatitis (SAP) is a dangerous illness with high mortality where most patients do not die of excessive inflammation, but die of immunosuppression and multiple infections at a later stage. The mechanism of immunosuppression in SAP is unknown.

Aim

The purpose of this study was to analyze the role of Fas expression on the occurrence of immunosuppression in patients with SAP.

Methods

Forty-eight patients with pancreatitis were divided into two groups: 20 cases with SAP (7 cases with sepsis, 13 cases without sepsis) and 28 cases with mild acute pancreatitis (MAP). Twenty-eight healthy volunteers were selected as controls. Fas mRNA expression in peripheral blood was detected by qPCR and Fas protein of lymphocyte membranes; T lymphocyte subsets and expression of monocyte Human leukocyte antigen DR (HLA-DR) in peripheral blood were detected by flow cytometry.

Results

Compared with MAP and control groups, expression level of Fas mRNA and lymphocyte Fas protein in peripheral blood were significantly increased in the SAP group (all P < 0.01). There was a further significant increase in the SAP group with sepsis compared to those without sepsis (all P < 0.01). The CD4⁺ T cell ratio, CD4⁺/CD8⁺ ratio and monocyte HLA-DR expression in the SAP group were decreased significantly compared with MAP and control groups (all P < 0.01). Significant negative relationships were observed between Fas mRNA expression and CD4⁺ T-cell ratio, CD4⁺/CD8⁺ ratio, and monocyte HLA-DR expression in SAP patients with sepsis (all P < 0.05).

Conclusions

The results suggest that expression level of Fas is related to severity and immune status of pancreatitis. Overexpression of Fas may lead to the occurrence of immunosuppression and sepsis.     

The Acute Effects of Age and Particulate Matter Exposure on Heart Rate and Heart Rate Variability in Mice

Exposure to ambient particulate matter (PM) is associated with increased cardiac morbidity and mortality with the elderly considered to be the most susceptible. The purpose of this study was to determine if exposure to PM would cause a greater impact on heart regulation in older DBA/2 (D2) male mice as determined by changes in heart rate (HR) and heart rate variability (HRV). D2 mice at the ages of 4, 12, and 19 months were instilled with 100 µg of PM or saline by aspiration. Before and after the aspiration, 3-min echocardiogram (ECG) samples for HR and HRV were recorded at 15-min intervals for 3 h along with corresponding measurements of homeostasis, such as temperature, metabolism, and ventilation. PM exposure resulted in an increase in HRV, declines in HR, and altered measures of homeostasis for a subset of the 12-mo mice. The PM aspiration did not affect cardiac or homeostasis parameters in the 4- or 19-mo mice. Our results suggest that a select group of middle-age mice are more susceptible to alterations in their heart rhythm after PM exposure and highlight that there are acute age-related differences in heart rhythm following PM exposure.     

急性冠脉综合征心率变异性与QT离散度的分析

近年来心率变异性(HRV)与QT离散度(QTd)和心律失常、心肌缺血、心功能不全等之间的关系受到了国内外学者的广泛重视.本文测定64例急性冠脉综合征(ACS)患者的HRV与QTd,现报道如下.     

Heart Rate and Heart Rate Variability in Normal Young Adults

Heart Rate and Heart Rate Variability. Introduction: The relationships between heart rate (HR) and HR variability (HRV) are not simple. Because both depend on the autonomic nervous system (ANS), they are not independent variables. Technically, the quantification of HRV is influenced by the duration of the cardiac cycles. The complexity of these relationships does not justify ignoring HK when studying HRV, as frequently occurs. Methods and Results: Using spectral and nonspectral methods, the HR and various normalized and non-normalized indices of HRV were studied in 24-hour recordings of a homogeneous cohort of seventeen 20-year-old healthy males. The HR-HRV relationships were appraised by analyzing the same data in two different ways. The 24 mean hourly values provide consistent information on the circadian behavior of the indices, while the average 24-hour individual data show a wide spectrum of normality. Combined approaches allow assessment of the direct impact of RR interval on HRV evaluation. The correlations between HR and normalized indices of HRV arc weaker in 24-hour individual data than in pooled hourly data of the same individuals. These correlations are close to 1 in the latter case, which does not mean that measuring HRV is simply another method of evaluating HR, but that normal physiology supposes a harmonious behavior of the various indices. When considered individually without normalization, the specific indices of vagal modulation (high-frequency band of the spectrum, short-term HR oscillations of the nonspectral analysis) consistently increase at night and diminish during the day. However, the low-frequency power, which supposedly reflects sympathetic influences, also increases at night, whereas more logically the longer HR oscillations would predominate during the day. Moreover, the selective analysis of HR oscillations during HR acceleration or decrease indicates that their behavior differs accordingly. Conclusion: We recommend that closer attention be paid to the complex relationships between HR and HRV. The strong correlations found in healthy subjects may reflect either the physiological harmony of ANS functions or simple redundancy. Their tendency to deteriorate in diseased hearts suggests that redundancy is not the cause and that abnormalities of ANS functions are not demonstrated by HRV analysis alone.     

Sex Moderates the Relationship Between Nausea Severity and Heart Rate Variability in Adolescents and Young Adults

Digestive Diseases and Sciences - Nausea is a common complaint among children and is particularly prevalent in children with functional abdominal pain (FAP), with nearly half of children with FAP...     

肥大细胞在重症急性胰腺炎肠黏膜屏障功能损伤中的作用

肥大细胞(MC)是神经-免疫-内分泌系统中的关键细胞,参与调节机体多种病理生理过程。重症急性胰腺炎(SAP)发生时,大量MC被激活,释放多种细胞因子以及炎性介质,与SAP并发肠黏膜屏障功能损伤密切相关。本文就MC在SAP肠黏膜屏障功能损伤中的作用作一综述。