Prognostic significance of increased serum bilirubin levels coincident with cardiac decompensation in chronic heart failure.

BACKGROUND: The aim of this study was to analyze the relationship between abnormal liver function tests (LFTs) coincident with heart failure (HF) exacerbation and subsequent long-term outcome in patients with chronic HF. METHODS AND RESULTS: The study population consisted of 183 consecutive patients admitted for HF exacerbation with left ventricular ejection fraction < or =40%. Cox proportional hazard analysis revealed that serum total bilirubin (T-Bil) levels on admission (hazard ratio 1.896, p<0.001, 95% confidence interval 1.323-2.717), but not T-Bil at discharge or other LFTs, was an independent predictor of subsequent cardiac events after hospital discharge (cardiac death or readmission for HF exacerbation) The cardiac-event-free rates significantly decreased according to increasing tertiles of T-Bil stratified by the level of 0.7 and 1.2 mg/dl (p<0.001). T-Bil on admission had significant correlations with simultaneously-measured central venous pressure (CVP) (r=0.42, p<0.01) and cardiac index (CI) (r= -0.50, p<0.01). The patients demonstrating high CVP together with low CI showed significantly increased T-Bil compared with any other group. CONCLUSIONS: Increased T-Bil coincident with cardiac decompensation predicts a worse long-term prognosis of CHF, presumably through the potential liability to both congestion and tissue hypoperfusion simultaneously when HF deteriorates.     

Contribution of caveolin protein abundance to augmented nitric oxide signaling in conscious dogs with pacing-induced heart failure

Myocardial NO signaling appears elevated in heart failure (HF). Whether this results from increased NO production, induction of the high-output NO synthase (NOS)2 isoform, or changes in NOS regulatory pathways (such as caveolae) remains controversial. We tested the hypothesis that increased abundance of caveolin-3 and/or sarcolemmal caveolae contribute to increased NO signaling in pacing-induced HF. Abundance of caveolin-3 (0.59+/-0.08 versus 0.29+/-0.08 arbitrary units, P = 0.01) but not caveolin-1 was increased in HF compared with control conditions, assessed by Western blot. Additionally, transmission electron microscopy revealed increased caveolae (2. 7+/-0.4 versus 1.3+/-0.3 per micrometer myocyte membrane, P<0.005). The association between caveolin-3 and NOS3 at the sarcolemma and T tubules was unchanged in HF compared with control myocytes. The impact of NOS inhibition with L-N(G)-methylarginine hydrochloride (L-NMMA) on beta-adrenergic inotropy was assessed in conscious dogs before and after HF. In control dogs, dobutamine (5 microg. kg(-1) x min(-1)) increased +dP/dt by 36+/-7%, and this was augmented to 66+/-24% by 20 mg/kg L-NMMA (P = 0.04 versus without L-NMMA, n = 8) but not affected by 10 mg/kg L-NMMA (34+/-10%, P = NS; n = 8). In HF, dobutamine +dP/dt response was depressed (P<0.001 versus control), and increased concentrations were required to match control inotropic responses (10 to 15 microg. kg(-1) x min(-1), 48+/-7%). L-NMMA enhanced +dP/dt responses similarly at 10 mg/kg (61+/-17%, P = 0.02; n = 4) and 20 mg/kg (54+/-7%, P = 0.04; n = 7). Caveolin-3 abundance positively correlated with L-NMMA augmentation of dobutamine inotropic responses in HF (r = 0.9, P = 0.03; n = 4). Thus, in canine pacing-induced HF, expression of caveolin-3 and of sarcolemmal caveolae is increased. This increase is associated with augmented agonist-stimulated NO signaling, likely via a compartmentation effect.     

The etiology of 'smoker's paradox' in acute myocardial infarction with special emphasis on the association with inflammation

Despite increased risk for coronary artery disease and acute myocardial infarction (AMI), prior studies have found that smokers with AMI have lower mortality rates than nonsmokers, a phenomenon often termed 'smoker's paradox'. The present study was designed to examine the etiology of 'smoker's paradox', especially with respect to the association with inflammation. The subjects included 528 consecutive AMI patients who were admitted within 24 hours of onset and underwent successful coronary intervention. Of the 528 subjects, 232 (44%) were smokers. The cardiac mortality rates over a 6 month period was significantly lower in the smoking group than the nonsmoking group (3% versus 9%, P = 0.01). There were significantly more male patients in the smoking group, and the smoking group was significantly younger than the nonsmoking group (P < 0.0001). The value of high sensitivity C-reactive protein (hs-CRP) on admission and 24 hours after onset, and serum amyloid A protein (SAA) were significantly higher, and acute phase BNP was significantly lower (hs-CRP on admission 1.36 +/- 1.03 mg/dL versus 0.75 +/- 0.82 mg/dL, P = 0.02, hs-CRP at 24 hours 3.86 +/- 4.32 mg/dL versus 2.90 +/- 3.46 mg/dL, P = 0.008, SAA; 288 +/- 392 microg/dL versus 176 +/- 206 microg/dL, P < 0.05, BNP; 248 +/- 342 pg/mL versus 444 +/- 496 pg/mL, P = 0.0002) in the smoking group than in the nonsmoking group. The early ST-segment resolution rate was higher in the smoking group compared with the nonsmoking group (80% versus 66%, P = 0.003). The reason why smokers with AMI have lower mortality rates than nonsmokers, the so-called 'smoker's paradox', is believed to be because smoking induces inflammation and smokers may have less damage to microvascular function after primary percutaneous coronary intervention.     

Role of zinc in subclinical hepatic encephalopathy: comparison with somatosensory-evoked potentials

BACKGROUND AND AIM: The purpose of the present paper was to determine the role of zinc in subclinical portosystemic encephalopathy (SPSE). METHODS: The serum zinc levels were studied for 10 cirrhotic patients who did not suffer SPSE and for 10 patients who did, and the results compared with those deriving from 10 healthy volunteers. The nutritional evaluation included serum prealbumin, albumin, and transferrin levels, body mass index (BMI), mid-arm muscle circumference (MAMC), and tricep skin-fold (TSF). The occurrence of SPSE was defined as a situation when the N20-N65 interpeak latencies of median nerve-stimulated somatosensory-evoked potentials (SEP) exceeded 2.5 SD of the control mean value. RESULTS: Cirrhotic patients suffering SPSE (57.5 +/- 10.5 microg/dL) had lower serum zinc levels than those not experiencing SPSE (69.5 +/- 16.6 microg/dL, P = 0.03) and controls (77.7 +/- 6.8 microg/dL, P < 0.001). Four of the non-SPSE and nine SPSE patients had zinc levels less than the lower normal limit. Cirrhotic patients suffering SPSE had lower levels of albumin (2.8 +/- 0.4 g/dL vs 3.8 +/- 0.4 g/dL, P < 0.001), prealbumin (9.0 +/- 4.3 mg/dL vs 14.3 +/- 6.0 mg/dL, P = 0.02), and transferrin (158 +/- 56 g/L vs 218 +/- 50 g/L, P = 0.01), but a greater total bilirubin level (1.2 +/- 1.5 mg/dL vs 0.9 +/- 0.4 mg/dL, P = 0.005) than those not suffering SPSE. The serum zinc levels correlated with N20-N65 interpeak latencies (P = 0.03), serum albumin (P = 0.006), prealbumin (P < 0.001), and total bilirubin (P = 0.02) levels. CONCLUSIONS: The data show that zinc deficiency is common in cases of non-alcoholic cirrhosis with SPSE. The early assessment of malnutrition and zinc deficiency are important.     

Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis

PURPOSE: To compare the efficacy and safety of subcutaneous insulin lispro with that of a standard low-dose intravenous infusion protocol of regular insulin in patients with uncomplicated diabetic ketoacidosis. METHODS: In this prospective, randomized open trial, 20 patients treated with subcutaneous insulin lispro were managed in regular medicine wards (n=10) or an intermediate care unit (n=10), while 20 patients treated with the intravenous protocol were managed in the intensive care unit. Patients treated with subcutaneous lispro received an initial injection of 0.3 unit/kg followed by 0.1 unit/kg/h until correction of hyperglycemia (blood glucose levels <250 mg/dL), followed by 0.05 to 0.1 unit/kg/h until resolution of diabetic ketoacidosis (pH > or =7.3, bicarbonate > or =18 mEq/L). Patients treated with intravenous regular insulin received an initial bolus of 0.1 unit/kg, followed by an infusion of 0.1 unit/kg/h until correction of hyperglycemia, then 0.05 to 0.1 unit/kg/h until resolution of diabetic ketoacidosis. RESULTS: Mean (+/- SD) admission biochemical parameters in patients treated with subcutaneous lispro (glucose: 674 +/- 154 mg/dL; bicarbonate: 9.2 +/- 4 mEq/L; pH: 7.17 +/- 0.10) were similar to values in patients treated with intravenous insulin (glucose: 611 +/- 264 mg/dL; bicarbonate: 10.6 +/- 4 mEq/L; pH: 7.19 +/- 0.08). The duration of treatment until correction of hyperglycemia (7 +/- 3 hours vs. 7 +/- 2 hours) and resolution of ketoacidosis (10 +/- 3 hours vs. 11 +/- 4 hours) in patients treated with subcutaneous lispro was not different than in patients treated with intravenous regular insulin. There were no deaths in either group, and there were no differences in the length of hospital stay, amount of insulin until resolution of diabetic ketoacidosis, or in the rate of hypoglycemia between treatment groups. Treatment of diabetic ketoacidosis in the intensive care unit was associated with 39% higher hospitalization charges than was treatment with subcutaneous lispro in a non-intensive care setting ($14,429 +/- $5243 vs. $8801 +/- $5549, P <0.01). CONCLUSION: Treatment of adult patients who have uncomplicated diabetic ketoacidosis with subcutaneous lispro every hour in a non-intensive care setting may be safe and more cost-effective than treatment with intravenous regular insulin in the intensive care unit.     

Coronary artery disease progression is associated with C-reactive protein and conventional risk factors but not soluble CD40 ligand

BACKGROUND: Coronary artery disease (CAD) is a major cause of death worldwide. Epidemiological studies have documented conventional risk factors; however, no studies to date have addressed the roles of soluble CD40 ligand (sCD40L) and monocyte chemoattractant protein-1 (MCP-1), and there have been few reports on other novel risk factors in CAD progression. The aim of the present study was to explore the roles of novel and conventional risk factors in CAD progression. METHODS: Patients with stable angina pectoris who underwent repeat coronary angiograms and had serum samples at the time of their first catheterization between March 1999 and January 2004 were enrolled. Those who had progression of coronary atherosclerosis were classified into the progression group (n = 66). Those who did not have CAD progression were classified into the nonprogression group (n = 124). RESULTS: There were more cases of diabetes mellitus (36% versus 20%; P = 0.024) and more men (92% versus 81%; P = 0.040) in the CAD progression group than in the nonprogression group, respectively. The progression group also had poorer lipid profiles than the nonprogression group, including higher total cholesterol (188+/-42 mg/dL versus 173+/-39 mg/dL, respectively; P = 0.014) and low density lipoprotein cholesterol (122+/-38 mg/dL versus 112+/-36 mg/dL, respectively; P = 0.025). In terms of inflammatory markers, progression patients had higher baseline high-sensitivity C-reactive protein (hs-CRP) concentrations (P = 0.018), which was also related to the subsequent angiographic severity score changes; however, sCD40L (6182+/-4352 pg/mL versus 6244+/-4602 pg/mL; P = 0.961), MCP-1 (427+/-540 pg/mL versus 341+/-128 pg/mL; P = 0.580) and adhesion molecules concentrations were indifferent between the progression group and the nonprogression group, respectively. Using a multivariate logistical regression model, the ORs for predicting progression were 2.19 for diabetes mellitus, 2.04 for hypercholesterolemia and 1.52 for hs-CRP (P < 0.05). CONCLUSION: In the present study, only conventional risk factors, and particularly hs-CRP, were markers for predicting CAD progression. Novel risk factors, such as concentrations of sCD40L, MCP-1 and adhesion molecules, did not play significant roles.     

The clinical significance of monitoring alkaline phosphatase level to estimate postoperative liver failure after hepatectomy

BACKGROUND/AIMS: To predict the occurrence of postoperative liver failure after hepatectomy, the clinical significance of monitoring alkaline phosphatase (ALP) has been studied, and the relationship between the change of total bilirubin and the level of ALP or gamma-glutamyl transpeptidase (gamma-GTP) after hepatectomy was evaluated. METHODOLOGY: The 163 patients, who underwent hepatectomy at our institute for the past 12 years, were divided into three groups according to the postoperative events. HF consisted of 5 patients with liver failure, HB showed the postoperative high bilirubinemia (over 5mg/dL) in 13 cases and GP were 145 cases without any postoperative problems. RESULTS: 1. The postoperative highest level of total bilirubin (T-Bil) correlated with the decreasing rate of ALP, prothrombin time (PT), total cholesterol (T-CHO) or gamma-GTP and total blood loss (p<0.01). 2. The level of ALP decreased after hepatectomy significantly and the decreasing rate was serious in HB and HF (p<0.05). 3. The recovering time to preoperative level of ALP was clearly shorter in GP than in HB and HF. 4. The level of ALP and gamma-GTP at the point where the level of T-Bil increased over 5mg/dL, was useful to distinguish between HF and HB. 5. The good correlation between postoperative level of ALP and gamma-GTP was noted. The decreasing levels of ALP and gamma-GTP were found to be critical below 80% and 55% after bisegmentectomy. Furthermore, the recovered levels of ALP and gamma-GTP were important to distinguish between HF and HB. CONCLUSIONS: Monitoring the ALP level was indicated to be useful to estimate the postoperative course of bilirubin.     

Arterial-wave reflections are increased in heart failure patients with a left-ventricular assist device

BACKGROUND: Chronic heart failure (HF) is associated with increased central arterial pulse-wave reflections, which may contribute to increased myocardial oxygen demand. Although the treatment of HF via left-ventricular assist device (LVAD) placement has recently become widespread, the effects of LVAD therapy on central arterial pulse-wave reflections are unknown. METHODS: Central aortic pulse-wave analysis was performed on patients with end-stage HF awaiting cardiac transplantation and on healthy age-matched controls using the SphygmoCor (Akor Medical, Sydney, Australia) system. Arterial pulse-wave data were compared between patients receiving LVAD support versus those receiving intravenous inotropic drugs and healthy control patients. RESULTS: Five patients on LVAD support were compared with 10 patients on inotropic drugs and 10 healthy control patients. Aortic augmented pressure and the aortic augmentation index (AI(a)) were higher in LVAD patients compared with inotrope and control patients, despite similar brachial and aortic blood pressures between groups. The AI(a) was significantly higher in LVAD patients than in patients on inotropic drugs (28.2% +/- 10% v 7.9% +/- 9%, P < or = .01). Additionally, there was a significantly higher aortic systolic tension time index, an index of left-ventricular myocardial oxygen demand, in the LVAD group compared with the inotrope group (2655 +/- 298 mm Hg/sec/min v 1748 +/- 303 mm Hg/sec/min, P < .01). CONCLUSIONS: Central arterial pressure-wave reflection is increased in end-stage HF patients on LVAD support compared with those on inotropic drugs, leading to an increase in aortic augmented pressure, AI(a), and systolic tension time index. The AI(a) is also higher in LVAD patients than in healthy controls. This increased central arterial-wave reflection places an additional hemodynamic load on the LVAD device and may have relevance to the medical management of patients after LVAD placement and to the longevity of the LVAD device itself.     

Long-term outcome and prognostic factors of patients with hilar cholangiocarcinoma

AIM: To evaluate the long-term outcome and prognostic factors of patients with hilar cholangiocarinoma. METHODS: Ninety-six consecutive patients underwent treatment for malignant hilar bile duct tumors during 1995-2005. Of the 96 patients, 20 were initially treated with surgery (n = 2 R0 / n = 18 R1). In non-operated patients, data analysis was performed retrospectively. RESULTS: Among the 96 patients, 76 were treated with endoscopic transpapillary (ERC, n = 45) and/or percutaneous transhepatic biliary drainage (PTBD, n = 31). The mean survival time of these 76 patients undergoing palliative endoscopic and/or percutaneous drainage was 359 +/- 296 d. The mean survival time of patients with initial bilirubin levels > 10 mg/dL was significantly lower (P < 0.001) than patients with bilirubin levels < 10 mg/dL. The mean survival time of patients with Bismuth stage II (n = 8), III (n = 28) and IV (n = 40) was 496 +/- 300 d, 441 +/- 385 d and 274 +/- 218 d, respectively. Thus, patients with advanced Bismuth stage showed a reduced mean survival time, but the difference was not significant. The type of biliary drainage had no significant beneficial effect on the mean survival time (ERC vs PTBD, P = 0.806). CONCLUSION: Initial bilirubin level is a significant prognostic factor for survival of patients. In contrast, age, tumor stage according to the Bismuth-Corlette classification, and types of intervention are not significant prognostic parameters for survival. Palliative treatment with endoscopic or percutaneous biliary drainage is still suboptimal, new diagnostic and therapeutic tools need to be evaluated.     

Long-term effect of imidapril hydrochloride compared with dilazep hydrochloride administration on blood pressure and renal function in patients with chronic glomerulonephritis

The objective of the present study was to compare the effects of imidapril hydrochloride, an angiotensin converting enzyme inhibitor, and dilazep hydrochloride, an antiplatelet agent, on urinary protein excretion and renal function in patients with chronic glomerulonephritis. Imidapril (2.5 or 5 mg/day) or dilazep (300 or 450 mg/day) was administered for 3 years. Blood pressure, proteinuria, and renal function were measured before and during the treatment. In the group administered imidapril (n = 11), urinary protein decreased by approximately 50% (2.16 +/- 1.57 versus 0.90 +/- 0.53 g/g Cr, P < 0.01) and blood pressure by 14/10 mmHg (139.6 +/- 17.4/93.6 +/- 8.7 mmHg versus 122.7 +/- 10.5/81.8 +/- 9.9 mmHg, P < 0.01) and both remained at low levels during the three years of treatment. No correlation was observed between the extent of blood pressure reduction and changes in urinary protein. Serum creatinine concentrations did not change significantly (1.3 +/- 0.3 versus 1.3 +/- 0.3 mg/dL, NS). In the dilazep group (n = 12), there were no significant changes in blood pressure, urinary protein, or serum creatinine. These findings demonstrate that imidapril reduces proteinuria and contributes to preserve renal function, suggesting its usefulness in the treatment of patients with chronic glomerulonephritis.     

Growth failure and outcomes in infants with biliary atresia: a report from the Biliary Atresia Research Consortium

Malnutrition is a significant clinical problem in infants with biliary atresia. The natural history of poor growth and its potential association with early transplantation or death in children with biliary atresia was determined. Serial weight- and length-for-age z-scores were computed as part of a retrospective study of 100 infants who underwent hepatoportoenterostomy (HPE) for biliary atresia at 9 U.S. pediatric centers between 1997 and 2000. Poor outcome was defined as transplantation or death by 24 months of age (n = 46) and good outcome was defined as survival with native liver at 24 months of age with total serum bilirubin less than 6 mg/dL (n = 54). Growth velocity was significantly slower in the poor outcome group compared to the good outcome group (P < 0.001 for both weight and length). Mean weight z-scores were significantly lower by 6 months after HPE in the poor outcome group (-2.1 +/- 1.4) compared to the good outcome group (-1.2 +/- 1.4) (P < 0.001). In a subgroup with total bilirubin between 2 and 6 mg/dL at 3 months after HPE (n = 28), the weight z-scores at 3 months after HPE were significantly lower in the poor outcome group (-2.0 +/-1.2) compared to the good outcome group (-1.0 +/- 1.2) (P = 0.04) despite similar bilirubin concentrations. CONCLUSION: Growth failure after HPE was associated with transplantation or death by 24 months of age. The combination of intermediate bilirubin concentrations and poor mean weight z-scores 3 months after HPE was also associated with poor clinical outcome.     

A case-control pilot study on n-3 polyunsaturated fatty acid as a negative risk factor for myocardial infarction

The relation between n-3 polyunsaturated fatty acid (PUFA) and nonfatal myocardial infarction is still controversial. A multicenter case-control pilot study on n-3 PUFA as a negative risk factor for myocardial infarction was performed in Niigata prefecture. Seventy-three patients with acute myocardial infarction (AMI) and age and gender matched controls (n = 84) were recruited. Serum leptin levels were significantly higher in patients with AMI than the controls (8.1 +/- 6.7 ng/mL versus 5.8 +/- 3.7 ng/mL, P < 0.01), and serum high-density lipoprotein cholesterol (HDLc) levels were significantly lower in patients with AMI than the controls (46 +/- 10.5 mg/dL versus 60 +/- 15 mg/dL, P < 0.00001). Statistically significant differences were preserved in leptin and HDLc when the data were analyzed separately by gender. Serum levels (%weight) of linolenic acid (C18:3:n3), eicosapentaenoic acid (C20:5:n3), docosapentaenoic acid (C22:5:n3), and total n-3 PUFA were significantly lower in patients with AMI than the control group (P < 0.000001, < 0.05, < 0.05, < 0.05, respectively). The serum n-3 PUFA/saturated fatty acid (SF) ratio and n-3 PUFA/n-9 monounsaturated fatty acid (MUFA) ratio were significantly lower in patients with AMI than the controls (P < 0.05 and < 0.01, respectively). When the subjects were separated into two categories according to an n-3/n-6 PUFA ratio below 0.3 or above 0.3, patients with AMI were more frequently in the former while the controls were more frequently in the latter (P < 0.05). N-3 PUFA may be a negative risk factor for AMI. The results suggest leptin is a risk factor for AMI irrespective of ethnicity and gender.     

The growth hormone (GH) response to the arginine plus GH-releasing hormone test is correlated to the severity of lipid profile abnormalities in adult patients with GH deficiency

The aim of the present study was to correlate the degree of the GH response to the combined arginine and GHRH (ARG+GHRH) test with clinical status in 157 adult hypopituitary patients and 35 healthy controls. On the basis of the GH response to ARG+GHRH, the 192 subjects were subdivided into 5 groups: group 1, very severe GH deficiency (GHD; 65 patients with GH peak <3 microg/L); group 2, severe GHD (37 patients with GH peak between 3.1-9 microg/L); group 3, partial GHD (25 patients with GH peak between 9.1-16.5 microg/L); group 4, non-GHD (30 patients with GH peak >16.5 microg/L); and group 5 (35 controls with GH peak >16.5 microg/L). Plasma insulin-like growth factor I (IGF-I) concentrations were lower (P < 0.001) in patients of group 1 (74.4 +/- 6.7 microg/L) and group 2 (81.4 +/- 6.8 microg/L) than in those of group 3, 4, and 5 (163.6 +/- 40.6, 185.9 +/- 21, and 188.8 +/- 11.1 microg/L, respectively). Plasma IGF-binding protein-3 concentrations were lower (P < 0.01) in group 1 (2.1 +/- 0.2 mg/L) and group 2 (2.0 +/- 0.2 mg/L) than in group 3 (3.4 +/- 0.7 mg/L) and group 5 (3.8 +/- 0.2 mg/L). In patients of group 1, total cholesterol (228.3 +/- 5.7 mg/dL) and triglycerides levels (187.4 +/- 15.3 mg/dL) were higher than those in group 3 (196.6 +/- 9.6 and 115.8 +/- 10.1 mg/dL, respectively), group 4 (176.8 +/- 11.3 and 101.4 +/- 12.5 mg/dL, respectively), and group 5 (160 +/- 6.9 and 99.3 +/- 5.4 mg/dL, respectively). High density lipoprotein cholesterol levels were lower in patients of group 1 (45.2 +/- 2.4 mg/dL) than in those of group 4 (54.7 +/- 3.5 mg/dL; P < 0.05) and group 5 (53.6 +/- 2 mg/dL; P < 0.001), whereas low density lipoprotein cholesterol levels were higher in patients of group 1 (127.3 +/- 7.9 mg/dL), group 2 (129.2 +/- 9.5 mg/dL), and 3 (133 +/- 9 mg/dL) than in those of group 5 (102.4 +/- 7.4 mg/dL; P < 0.05). Patients of group 2 had total cholesterol, high density lipoprotein cholesterol, and triglycerides levels at an intermediate level with respect to those in groups 1, 3, and 4. Among the five groups, no difference was found in fasting glucose concentrations, heart rate, or systolic and diastolic blood pressures. A significant increase in fat body mass and a decrease in lean body mass and total body water were found in all patients compared to controls. Disease duration was significantly shorter in patients of group 4 than in those of the remaining three groups (P < 0.001). A significant correlation was found between the GH peak after ARG+GHRH and disease duration (r = -0.401; P < 0.001), plasma IGF-I (r = 0.434; P < 0.001), total cholesterol (r = -0.324; P < 0.001), and triglycerides levels (r = -0.219; P < 0.05). A significant multiple linear regression coefficient was found between the GH peak after ARG+GHRH and plasma IGF-I levels (t = 2.947; P < 0.005), total cholesterol levels (t = -2.746; P < 0.01), and disease duration (t = -2.397; P < 0.05). In conclusion, the results of the present study indicate that the degree of the GH response to ARG+GHRH is correlated with the severity of lipid profile abnormalities and substantiate the reliability of the ARG+GHRH test for the diagnosis of GHD in adults. Because at present GH treatment is recommended only in adult patients with severe GHD, patients with a GH response below 9 microg/L to the ARG+GHRH test should be treated with GH, as should patients with a peak GH response to an insulin tolerance test below 3 microg/L.     

Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease

Autoimmune hepatitis may fail to respond to corticosteroid therapy, but the frequency and bases for this outcome are uncertain. We aimed to determine the frequency and nature of treatment failure in patients with type 1 autoimmune hepatitis, define features associated with its occurrence, and assess if the model for end-stage liver disease can predict this outcome. Patients failing conventional corticosteroid regimens were compared to patients who responded to similar regimens. Fourteen of 214 patients (7%) failed corticosteroid treatment. Patients who failed therapy were younger (33 +/- 3 years versus 48 +/- 1 years, P = 0.0008), had higher serum levels of bilirubin at accession (4.1 +/- 0.9 mg/dL versus 2.3 +/- 0.2 mg/dL, P = 0.02), presented acutely more frequently (43% versus 14%, P = 0.01), and had a higher frequency of HLA (human leukocyte antigen) DRB1*03 (93% versus 53%, P = 0.004) than did patients who achieved remission. An alternative disease (fatty liver disease) emerged in only 1 patient who failed therapy (7%). Scores determined by the model of end-stage liver disease at presentation of patients who failed treatment were higher than those of who achieved remission (16 +/- 1 versus 10 +/- 0.3 points, P < 0.0001), and score greater than 12 points had greater sensitivity (97%) and specificity (68%) for treatment failure than did HLA DRB1*03 or other features. CONCLUSION: Onset at an early age, acute presentation, hyperbilirubinemia, and presence of HLA DRB1*03 characterize patients who fail corticosteroid treatment. The model for end-stage liver disease may be a useful instrument for identifying patients prone to this outcome.     

Cardiac resynchronisation therapy: an option for inotrope‐supported patients with end‐stage heart failure?

BACKGROUND: Patients with refractory heart failure requiring inotropic support have a very poor prognosis. Cardiac resynchronization therapy (CRT) offers symptomatic and possibly a survival benefit for patients with stable chronic heart failure (CHF) and a prolonged QRS, but its role in the management of end-stage heart failure requiring inotropic support has not been evaluated. METHODS: We performed a retrospective observational study of patients undergoing CRT at our institution. RESULTS: We identified 10 patients who required inotropic support for refractory CHF and who underwent CRT while on intravenous inotropic agents. Patients had been in hospital for 30+/-29 days and had received inotropic support for 11+/-6 days prior to CRT. All patients were weaned from inotropic support (2+/-2 days post-CRT) and all patients survived to hospital discharge (12+/-13 days post-CRT). Furosemide dose fell from 160+/-38 mg on admission to 108+/-53 mg on discharge (p<0.01). Serum creatinine fell from 192+/-34 micromol/l prior to CRT to 160+/-37 micromol/l on discharge (p<0.05). Serum sodium was 131+/-4 mmol/l prior to CRT and remained low at 132+/-5 mmol/l on discharge. At short-term follow up (mean 47 days), all patients were alive; mean furosemide dose was 130+/-53 mg (p=0.056 versus pre-CRT). Serum creatinine was 157+/-36 micromol/l and serum sodium had increased to 138+/-6 mmol/l (p<0.05 and p<0.01, respectively, versus pre-CRT). CONCLUSION: CRT may offer a new therapeutic option for inotrope-supported CHF patients with a prolonged QRS.     

The effect of lamivudine therapy in hepatic decompensation during acute exacerbation of chronic hepatitis B

BACKGROUND/AIMS: Severe acute exacerbation (AE) of chronic hepatitis B (CHB) can lead to hepatic decompensation and death. The aim of this study was to investigate the effect of lamivudine therapy in hepatic decompensation during such AEs. METHODS: In a 10-month period, a total of 60 consecutive AE patients with jaundice and prolonged prothrombin time over 3s were treated with lamivudine 150 mg daily. As a historical control, another 31 CHB patients with AE resulting in hepatic decompensation hospitalized in an immediate past 6-month period were enrolled for comparison. RESULTS: Patients in both groups were comparable in clinical and biochemical features. After a median treatment period of 6 weeks (range 1-48 weeks), all of the 25 patients with pretherapy bilirubin level < 20 mg/dl in the treatment group survived, while five (25%) of 20 patients in the control group died (P=0.013; odds ratios, 2.667; 95% confidence interval, 1.787-3.979). However, the mortality rate was similar in patients with pretherapy bilirubin level > or =20 mg/dl in both groups. CONCLUSIONS: These results suggest that lamivudine may prevent fatality in CHB patients with hepatic decompensation if therapy starts early enough or before serum bilirubin level rise over 20 mg/dl, but helps little if serum level already risen over that level.     

Cardiac resynchronization therapy in patients with end-stage inotrope-dependent class IV heart failure

Although cardiac resynchronization therapy (CRT) is beneficial in patients with drug-refractory New York Heart Association (NYHA) class III/IV heart failure (HF) and left ventricular (LV) dyssynchrony, CRT efficacy is not well established in patients with more advanced HF on inotropic support. Ten patients (age 55 +/- 13 years) with inotrope-dependent class IV HF (nonischemic [n = 6] and ischemic [n = 4]) received a CRT implantable cardioverter-defibrillator device. QRS duration was 153 +/- 25 ms (left branch bundle block [n = 7], intraventricular conduction delay [n = 2], and QRS <120 ms [n = 1]). The indication for CRT was based on either electrocardiographic criteria (n = 9) or echocardiographic evidence of LV dyssynchrony (n = 1). Intravenous inotropic therapy consisted of dobutamine (n = 6; 4.3 +/- 1.9 microg/kg/min) or milrinone (n = 4; 0.54 +/- 0.19 microg/kg/min) as inpatient (n = 3) or outpatient (n = 7) therapy for 146 +/- 258 days before CRT. One patient required ventilatory support before and during device implantation. All patients were alive at follow-up 1,088 +/- 284 days after CRT. Three patients underwent successful orthotopic cardiac transplantation after 56, 257, and 910 days of CRT. HF improved in 9 patients to NYHA classes II (n = 5) and III (n = 4). Intravenous inotropic therapy was discontinued in 9 of 10 patients after 15 +/- 14 days of CRT. LV volumes decreased (end-diastolic from 226 +/- 78 to 212 +/- 83 ml; p = 0.08; end-systolic from 174 +/- 65 to 150 +/- 78 ml; p <0.01). LV ejection fraction increased (23.5 +/- 4.3% to 32.0 +/- 9.1%; p <0.05). No implantable cardioverter-defibrillator shocks were recorded, and antitachycardia therapy for ventricular tachyarrhythmias was delivered in 1 patient. In conclusion, patients with end-stage inotrope-dependent NYHA class IV HF and LV dyssynchrony may respond favorably to CRT with long-term clinical benefit and improved LV function.     

Comparative pilot study of repeated large volume paracentesis vs the combination on clonidine-spironolactone in the treatment of cirrhosis-associated refractory ascites

OBJECTIVES: To study the usefulness of the combination of clonidine--spironolactone in refractory ascites. METHODS: Twenty cirrhotic patients with refractory ascites were randomly assigned to receive repeated large volume paracentesis plus intravenous albumin (group 1), or a combination of clonidine (0.075 mg twice daily) and spironolactone (200 to 400 mg daily) (group 2). RESULTS: During the first hospitalisation,, the mean weight loss in group 1 was higher than in group 2 (12.4 +/- 3.2 versus 4.3 +/- 1.1 kg, P < or = 0.01). Mean stay in hospital was shorter in group 2 (20 +/- 1.5 versus 10 +/- 2.8 days; P < or = 0.01). Paracentesis did not induce changes in neuro-hormonal measurements. Oppositely, clonidine induced a decreased sympathetic activity, an increased glomerular filtration rate and a delayed reduction of the renin-aldosterone levels. During the follow-up in group 1, the number of rehospitalisations for ascites was higher than in group 2 (37 versus 3; P < or = 0.01), and the mean time to the first readmission was shorter (10 +/- 2.7 versus 23.7 +/- 5.6 days; P < or = 0.01). The total duration spent in hospital were similar in both groups. CONCLUSION: Paracentesis is more effective for short-term treatment of ascites but clonidine-spironolactone association might provide better long-term control.     

Changes in lipoprotein(a) concentration after orthotopic heart transplantation

BACKGROUND: Elevated concentrations of lipoprotein(a) have been considered an important risk factor in the development of premature cardiovascular disease and have been proposed as a risk factor in the development of accelerated cardiac allograft vasculopathy after orthotopic heart transplantation. METHODS: We prospectively measured lipoprotein(a), fasting cholesterol, and triglyceride concentrations before (n = 38), 6 months (n = 38), and 1 year (n = 21) after orthotopic heart transplantation. The mean age of the patients was 52 +/- 2 years. Eighty-seven percent of the patients were men, 82% were white, and 61% had ischemic cardiomyopathy. RESULTS: Mean lipoprotein(a) concentration was lower 6 months after transplantation than it was before the operation (23 +/- 3 mg/dL vs 17 +/- 3 mg/dL; P =.014) and remained low 1 year after transplantation (23 +/- 3 mg/dL vs 18 +/- 4 mg/dL; P = not significant). In contrast, mean cholesterol concentration was higher 6 months after transplantation (171 +/- 8 mg/dL vs 221 +/- 8 mg/dL; P <.001) and 1 year (171 +/- 8 mg/dL vs 205 +/- 10 mg/dL; P <.01) than it was before transplantation. Triglyceride concentration was higher 1 year after transplantation than it was before the operation (146 +/- 13 mg/dL vs 184 +/- 20 mg/dL; P =.017). CONCLUSIONS: Lipoprotein(a) concentrations decrease during the 6 months after transplantation and stay low for at least 1 year after the operation. Additional studies are needed to ascertain the effect these changes in lipoprotein(a) concentration on the development of cardiac allograft vasculopathy.     

Prognostic significance of hemoglobin levels in patients with heart failure

INTRODUCTION AND OBJECTIVES: To evaluate the prognostic significance of hemoglobin (Hb) levels in terms of 1-year mortality and hospital admissions due to heart failure (HF) during the first year of follow-up after the first visit to an outpatient HF unit. PATIENTS AND METHOD: Survival status and HF-related hospital admission rate at 1 year were analyzed for 337 patients admitted between August 2001 and March 2003. Plasma Hb level was measured at the first visit to the unit. RESULTS: 28 patients (8%) died and there were 158 HF-related hospital admissions in 66 patients. Plasma Hb level correlated strongly with survival at 1 year, and was 13.0 +/- 1.7 g/dL in patients who were alive after this time, versus 11.7 +/- 1.6 g/dL (P < .001) in patients who died. Plasma Hb level also correlated with HF-related need for hospital admission, and was 13.1 +/- 1.7 g/dL in patients who were not hospitalized, versus 12.2 +/- 1.7 g/dL (P < .001) in patients with at least one hospital admission. In the multivariate logistic regression analysis plasma Hb level remained statistically associated both with 1-year survival and with the need for HF-related hospital admission. On the basis of a cutoff value for anemia of Hb < 12 g/dL, 30% of the patients had anemia. One-year mortality was 17% in patients with anemia and 5% in patients without anemia (P < .001). Among patients without anemia, 31% had at least one HF-related hospital admission, whereas only a 15% of the patients without anemia needed to be hospitalized for HF (P = .001). CONCLUSIONS: Plasma Hb levels correlated inversely with mortality and with HF-related hospital admissions at 1 year. The prevalence of anemia (Hb < 12 g/dL) in the population with HF studied here was high and had independent prognostic value.