Granulocyte colony stimulating factor in HCV genotype-1 patients who develop Peg-IFN-alpha2b related severe neutropenia: a preliminary report on treatment, safety and efficacy.

Dose reductions of Peg-IFNa because of severe neutropenia may affect the virologic response in patients with hepatitis C infection (HCV). Granulocyte colony-stimulating factor (G-CSF) has been used occasionally but studies addressing its safety and efficacy in the current treatment of HCV infection are missing. The database of 232 naïve patients with HCV genotype-1 who received PEG-IFNalpha2b 1.5 mcg/kg/week plus Ribavirin 800-1,400 mg/day and completed the treatment was examined. Nineteen patients who exhibited significant neutropenia and received 150-300 microg G-CSF (Group A) with 19 matched control patients who had dose reductions of Peg-IFNalpha according to the standard recommendations (Group B) were examined. None of the patients had treatment modifications due to thrombocytopenia or anemia. The mean decline of the neutrophils was similar in groups A and B (1,760 +/- 1,030/mm(3) at 11 +/- 8.6 weeks and 1,630 +/- 890 at 12.3 +/- 6.1, respectively). Nadir neutrophil values were also not statistically different. Patients who received G-CSF two before IFNalpha, maintained neutrophils between 1,400/mm(3) and 2,700/mm(3) and remained on G-CSF for 29 weeks (2-40). Virologic response at the end of treatment was observed in 12/19 (63%) patients and at 6 months follow-up in 6/19 (32%) in group A as compared to 9/19 (47%) and 4/19 (21%) in group B, respectively. No side effects related to G-CSF were encountered. Administration of G-CSF 2 days before Peg-IFNalpha is safe, maintains sustained neutrophil count, improves adherence to treatment and seems to increase the virologic response in patients infected with HCV genotype 1 who develop Peg-IFN-alpha2b related severe neutropenia.

Resolution of symptoms and serum peptides of collagen type I turnover in acute heart failure patients.

OBJECTIVES: Myocardial collagen content as a fundamental component of extracellular matrix, is altered in pathological states including heart failure (HF). Serum peptides related to myocardial collagen synthesis and degregation can be measured and may be used as indices of myocardial collagen turnover. The present study was undertaken to assess the hypothesis that resolution of acute decompensation of chronic HF is associated with changes in serum peptides related to collagen synthesis and degregation. METHODS AND RESULTS: Serum concentrations of the amino-terminal propetide of procollagen type I (PINP) and the carboxy-terminal telopeptide of collagen type I (CITP), indices of collagen type I synthesis and degradation, respectively, were determined at the time of admission and discharge in 156 patients (100 men, 68 +/- 10 years) with acute decompensation of chronic HF. A significant decrease (-3.5 ng/ml 95% CI -5.3/-1.6 ng/ml, P < 0.001) of PINP was observed whereas CITP levels were significantly increased (+ 0.04 ng/ml 95% CI 0.01-0.08 ng/ml, P = 0.031) at discharge compared to admission. CONCLUSIONS: Findings of the present study showed that serum indices of myocardial collagen turnover were changed significantly in a short period of time during the improvement of acute decompensation of chronic HF.

Serum levels of collagen type-I degradation markers are associated with vascular stiffness in chronic heart failure patients.

BACKGROUND: Chronic heart failure (CHF) induces peripheral vasoconstriction, endothelial dysfunction and arterial stiffness by activation of various neurohormonal pathways. The abnormal collagen turnover observed in CHF may be attributed not only to myocardial remodelling, but also to vascular remodelling. However, the effect of collagen metabolism on progressive large artery stiffening in the setting of CHF is understudied. AIMS: The present study was undertaken to investigate the association between circulating markers of collagen turnover and vascular stiffness in patients with CHF. METHODS: Eighty patients (mean age 65+/-11 years, 68 men) with stable CHF and in sinus rhythm, were studied. Serum concentrations of carboxy-terminal telopeptide of collagen type I (CITP) and amino-terminal propetide of procollagen type I (PINP), markers of collagen type I degregation and synthesis respectively, were measured in all patients. Pulse wave velocity (PWV) and augmentation index (AIx) of aortic pulse wave form, markers of arterial stiffness, were also determined by applanation tonometry. RESULTS: Peripheral PWV was inversely associated with serum CITP levels (r=-0.585, p<0.001). AIx although weakly was negatively correlated with serum CITP levels (r=-0.285, p=0.01). Multiple regression analysis showed that peripheral PWV remained independently associated with serum CITP levels after adjustment for all confounding variables. CONCLUSIONS: Findings from the present study imply a possible link between altered collagen metabolism and peripheral vascular stiffness in CHF.

Natural history of chronic hepatitis B virus infection in children of different ethnic origins: a cohort study with up to 12 years' follow-up in northern Greece.

AIM: To investigate the mode of transmission and the natural history of chronic hepatitis B virus (HBV) infection in children of different ethnicities in Greece. This study was part of the Interreg I-II EC project. PATIENTS AND METHODS: One hundred seventy-three hepatitis B surface antigen (HBsAg)(+) carriers, median age 6.9 (5-12) y, were prospectively followed-up for a mean period of 5.3 (1-12) y for serological markers of HBV infection, serum alanine aminotransferase (ALT), HBV-DNA, alpha-fetoprotein levels and ultrasonography. RESULTS: Vertical transmission predominates (61.8%) in Moslem children and horizontal (44%) in those born in Russia. At entry, 73 of 173 (42%) HBsAg(+) genotype D children were hepatitis B e antigen (HBeAg)(+), ranging from 27% to 67% among ethnic groups; 55 of 173 (32%) had ALT > 2 x upper normal limit (UNL), ranging from 21% to 39%. Of 100 anti-HBe(+) children, 85 (85%) were inactive carriers. During the follow-up period, seroconversion to anti-HBe was observed in 40 of 73 (55%) children with an annual rate of 11%; 35 of 40 (87.5%) had biochemical remission, and 28 of 35 (80%) lost HBV-DNA. In the anti-HBe(+) group, 27 of 100 (27%) lost HBV-DNA and 9 of 100 (9%) lost HBsAg. The annual seroconversion rate for HBeAg was significantly lower: in children with vertical transmission compared with horizontal (7.7% vs 14.8%, respectively, P < 0.001) and in Muslim children compared with both Christian children and those born in Russia (8.6% vs 12%, respectively, P < 0.001). No differences were found among the ethnic groups after adjusting for the mode of infection. Two of 173 children had progression of liver disease. CONCLUSIONS: The differences in HBeAg(+) status and seroconversion rate among the ethnic groups are related to the time/mode of HBV infection. The majority of children who developed anti-HBe immunity had biochemical remission, and a substantial number of the inactive carriers lost viremia during the observation period of up to 12 y.

Angiogenic factor expression in hepatic cirrhosis.

The pathogenesis of fibrosis in hepatic cirrhosis remains obscure. This study examines the eventual role of angiogenic factors in the fibrotic process. A series of 55 cirrhotic livers was studied for the proliferation state of fibroblasts, and the expression of vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and the basic and acidic fibroblast growth factor (bFGF, aFGF) in both fibroblasts and hepatic cells. The angiogenic and/or fibrogenic factors VEGF, TP, bFGF, and aFGF were clearly expressed in regenerative hepatocytes, but not in fibroblasts of diffuse hepatic fibrosis. The immunohistochemical findings suggest that angiogenic factors and factors promoting oxidative stress (i.e., TP) produced by hepatocytes may contribute to the development of fibrous bands in hepatic cirrhosis.

Effects of Helicobacter pylori infection on gastric emptying rate in patients with non-ulcer dyspepsia.

AIM: The pathogenesis of delayed gastric emptying in patients with non-ulcer dyspepsia (NUD) remains unclear. We aimed to examine whether gastric emptying rate in NUD patients was associated with Helicobacter pylori (H pylori) infection and whether it was affected by eradication of the infection. METHODS: Gastric emptying rate of a mixed solid-liquid meal was assessed by the paracetamol absorption method in NUD patients and asymptomatic controls (n=17). H pylori status was assessed by serology and biopsy urease test. H pylori-positive NUD patients (n=23) received 10-day triple eradication therapy. H pylori status was re-assessed by biopsy urease test four weeks later, and if eradication was confirmed, gastric emptying rate was re-evaluated. RESULTS: Thirty-three NUD patients and 17 controls were evaluated. NUD patients had significantly delayed gastric emptying compared with controls. The mean maximum plasma paracetamol concentration divided by body mass (Cmax/BM) was 0.173 and 0.224 mg/L.kg respectively (P=0.02), the mean area under plasma paracetamol concentration-time curve divided by body mass (AUC/BM) was 18.42 and 24.39 mg.min/L.kg respectively (P=0.01). Gastric emptying rate did not differ significantly between H pylori-positive and H pylori-negative NUD patients. The mean Cmax/BM was 0.172 and 0.177 mg/L.kg respectively (P=0.58), the mean AUC/BM was 18.43 and 18.38 mg.min/L.kg respectively (P=0.91). Among 14 NUD patients who were initially H pylori-positive, confirmed eradication of the infection did not significantly alter gastric emptying rate. The mean Cmax/BM was 0.171 and 0.160 mg/L.kg before and after Hp eradication, respectively (P=0.64), the mean AUC/BM was 17.41 and 18.02 mg.min/L.kg before and after eradication, respectively (P=0.93). CONCLUSION: Although gastric emptying is delayed in NUD patients compared with controls, gastric emptying rate is not associated with H pylori status nor it is affected by eradication of the infection.

Uncoupling protein-2 45-base pair insertion/deletion polymorphism: is there an association with severe obesity and weight loss in morbidly obese subjects?

BACKGROUND: Uncoupling proteins are attractive candidate genes for obesity and type 2 diabetes mellitus. Our aim was to investigate the potential association of the uncoupling protein-2 (UCP2) 45-bp insertion/deletion (ins/del) polymorphism with obesity, as well as the potential effect of this polymorphism on weight loss variability in severely obese subjects. METHODS: A total of 158 severely obese subjects (94 without and 64 with metabolic syndrome) and 91 age and sex-matched lean controls were recruited. A subgroup of 124 obese patients participated in a 3-month weight loss program. Anthropometric and metabolic variables were measured. Participants were genotyped for the UCP2 ins/del polymorphism. RESULTS: Allelic frequency differed neither between obese subjects and controls (P=0.56), nor between obese subjects with versus without metabolic syndrome (P=0.58). At 3 months, metabolically healthy subjects carrying the insertion allele had significantly greater reduction in body mass index (P=0.029) and fat-free mass (P=0.013) and a borderline significant improvement in the homeostatic model assessment index (P=0.048). CONCLUSION: There is no association of the UCP2 ins/del polymorphism with morbid obesity in our population, but this genotype appears to be linked with a favorable response to dietary changes in metabolically healthy obese subjects.

Aortocaval fistula formation due to ruptured abdominal aortic aneurysms: a 12-year series.

This study reports on the frequency and management of aortocaval fistulas (ACFs) in our department between 1998 and 2009. Overall frequency of ACFs among ruptured abdominal aortic aneurysms was 5.5%. Patients presented with low back pain (92.8%), abdominal tenderness (78.6%), hemorrhagic shock (28.6%), congestive heart failure (21.4%), dyspnea (42.8%), and palpitations (57.1%). The most reliable clinical sign was the presence of palpable pulsating abdominal mass (92.8%). Other clinical findings included increased central venous pressure (21.4%), lower extremity edema (71.4%), hematuria (21.4%), and scrotal edema (14.3%). Diagnosis was established preoperatively in 85.7% and intraoperatively in 14.3% of cases. Surgery was successful in promptly improving clinical signs and symptoms. Mortality rate was 7.1%. After a mean follow-up of 18.5 months, all surviving patients remained free from complications. In conclusion, ACFs represent a life-threatening emergency for vascular surgeons but can be successfully managed.

Characteristics of patients presenting to the vascular emergency department of a tertiary care hospital: a 2-year study.

BACKGROUND: The structure of health care in Greece is receiving increased attention to improve its cost-effectiveness. We sought to examine the epidemiological characteristics of patients presenting to the vascular emergency department of a Greek tertiary care hospital during a 2-year period. We studied all patients presenting to the emergency department of vascular surgery at Red Cross Hospital, Athens, Greece between 1st January 2009 and 31st December 2010. RESULTS: Overall, 2452 (49.4%) out of 4961 patients suffered from pathologies that should have been treated in primary health care. Only 2509 (50.6%) needed vascular surgical intervention. CONCLUSIONS: The emergency department of vascular surgery in a Greek tertiary care hospital has to treat a remarkably high percentage of patients suitable for the primary health care level. These results suggest that an improvement in the structure of health care is needed in Greece.

Association between foot temperature and sudomotor dysfunction in type 2 diabetes.

BACKGROUND AND AIMS: Increased foot skin temperature has been described as a feature of diabetic neuropathy. The aim of this present study was to investigate the association between foot temperature and sudomotor dysfunction in type 2 diabetes mellitus. PATIENTS AND METHODS: This study included 51 patients (group A: 25 men, mean age 61.14 +/- 6.11 years) without sudomotor dysfunction and 52 patients (group B: 25 men, mean age 59.54 +/- 6.18 years) with sudomotor dysfunction. Sudomotor dysfunction was defined as time until complete Neuropad color change from blue to pink exceeding 600 s in at least one foot. Time until complete color change of the test was also recorded. Foot skin temperature was measured with a handheld infrared thermometer on the plantar aspect of the foot at the level of the first metatarsal head. RESULTS: On both feet, temperature was significantly higher in group B than in group A (right foot, group A versus group B, 30.62 +/- 1.13 degrees C versus 32.12 +/- 1.06 degrees C, p < .001; left foot, group A versus group B, 30.65 +/- 1.06 degrees C versus 32.19 +/- 1.10 degrees C, p < .001). There was a significant positive correlation between time to complete Neuropad color change and foot skin temperature (right foot, r = 0.742, p < .001; left foot, r = 0.758, p < .001), which was confirmed in both groups. CONCLUSIONS: Patients with sudomotor dysfunction have significantly higher foot temperature than those without sudomotor dysfunction. Foot temperature is positively correlated with severity of sudomotor dysfunction, as evaluated by the time to complete Neuropad color change.

The role of serial measurement of serum HBV DNA levels in patients with chronic HBeAg(-) hepatitis B infection: association with liver disease progression. A prospective cohort study.

BACKGROUND/AIMS: To evaluate the fluctuating course of serum HBV-DNA levels during the natural history of chronic HBV infection in the general population of North-Eastern Greece, in association with liver disease progression. METHODS: Two hundred and sixty-three adults with chronic HBV, median 34 years of age, were randomly selected and prospectively followed-up for a maximum period of 12 years. Viral markers, liver biochemistry and physical examination were performed every 6 months, and liver biopsy/abdominal ultrasound every 2-4 years. RESULTS: At entry, 195/263 (76%) were HBeAg (-)/anti-HBe (+) inactive carriers: (a) almost all 195 individuals with undetectable or HBV-DNA levels <2000IU/ml had no liver disease at entry and at follow-up period by imaging or liver histology evaluation (b) only 4/195 (2%) showed HBV reactivation with HBV-DNA >2000IU/ml. At entry, 48/263 (18%) patients were chronic HBeAg(-); (a) 1/3 patients had intermittently HBV-DNA <2000IU/ml for at least one occasion and were misclassified as inactive carriers (b) 22/48 (46%) had moderate/severe histology at entry and 5/48 (10%) showed liver disease progression during follow-up. Logistic regression analysis was used to derive OR (95%CI) for factors associated with liver disease progression. CONCLUSIONS: Close monitoring of serum HBV-DNA levels is useful in the management of chronic HBeAg(-) patients, as associated with liver disease progression.

Effect of angiotensin-converting enzyme insertion/deletion genotype on collagen type I synthesis and degradation in patients with atrial fibrillation and arterial hypertension.

OBJECTIVE: The present study was undertaken to assess the impact of the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms on circulating markers of collagen type I synthesis and degradation, and also to study the effect of therapy with ACE inhibitors on these markers in hypertensive patients with atrial fibrillation (AF). RESEARCH DESIGN AND METHODS: ACE I/D genotypes were assessed in 158 hypertensive patients (71 +/- 9 years; 72 male) with AF and 174 patients with arterial hypertension in sinus rhythm (SR) (71 +/- 9 years; 88 male). Serum concentrations of amino-terminal propeptide of pro-collagen type I (PINP) and of carboxy-terminal telopeptide of collagen type I (CITP), indices of collagen type I synthesis and degradation, respectively, were measured. RESULTS: Of the 332 study participants, 74 (22.3%) were I/I, 158 (47.6%) were I/D and 100 (30.1%) were D/D carriers. Genetic variation in ACE significantly influenced serum CITP levels in AF patients (p = 0.011). CITP levels were lower in D allele carriers (DD and ID) compared with I/I carriers. There was no difference in PINP levels between the different ACE genotype groups (p = 0.302). Patients treated with ACE inhibitors had higher CITP levels compared with those not treated (p = 0.036). CONCLUSIONS: This study suggests that the presence of the D allele in hypertensive patients with AF is associated with attenuation of type-I collagen degradation, and that therapy with ACE inhibitors increases degradation of collagen type I. The data indicate a subgroup of patients with AF and arterial hypertension who may benefit to a greater extent from therapy with ACE inhibitors, thus, providing a basis for pharmacogenetics.

Thyroxine replacement dose in patients with Hashimoto disease: a potential role for interleukin-6.

OBJECTIVE: To investigate the potential association between serum inflammatory cytokine levels and thyroxine replacement dose in patients with Hashimoto disease. PATIENTS AND METHODS: The study included 40 patients (12 men) with a mean age of 56.52+/-6.12 years who had hypothyroidism due to Hashimoto disease. Serum interleukin-1b (IL-1b), tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels, as well as TSH, T(3) and T(4) were measured (ELISA). RESULTS: Serum IL-6 showed a significant positive correlation both with total thyroxine replacement dose (r=0.551, p=0.001) and with dose per kilogram of body weight (r=0.482, p=0.002). There was also a significant negative linear correlation between serum IL6 and T(3) (r=-0.322, p=0.043), as well as between serum IL6 and T(3)/T(4) ratio (r=-0.332, p=0.036). A further significant (r=0.419, p=0.007) positive association was demonstrated between IL6 and TNF-alpha. However, no association was found between T(3) or T(3)/T(4) ratio and TNF-alpha or IL1b. CONCLUSIONS: In patients with Hashimoto disease serum IL-6 levels are positively associated with thyroxine replacement dose and negatively associated with T(3) and T(3)/T(4) ratio. These results are possibly attributable to the inhibitory effect of IL6 on deiodination of T(3) and imply a role for IL6 in determining thyroxine replacement dose among these patients.