Insulin resistance in children with chronic hepatitis C and its association with response to IFN-alpha and ribavirin. / Resistencia a la insulina en niños con hepatitis C crónica y su asociación con la respuesta al IFN-alfa y ribavirina.

OBJECTIVE: The aim of our study was to evaluate the association between insulin resistance and the response to IFN-alpha and ribavirin in pediatric patients with chronic hepatitis C. METHODS: Twenty-six patients with chronic hepatitis C (mean age: 12.5 ± 1.96 years, M/F:3.33) were included in the study. Fasting glucose, insulin, and C-peptide levels, together with HOMA-IR, HOMA-B, and QUICKI values, were assessed. The association between those parameters and treatment response was determined. RESULTS: Five (19.2%) of the 26 patients analyzed (2 [21.4%] with treatment response and 3 [16.6%] with no treatment response) had insulin resistance (p=1.00). There were no significant differences between the patients with and without treatment response with respect to fasting glucose, insulin, and C-peptide levels or HOMA-IR, HOMA-B, and QUICKI values (p>0.05). CONCLUSIONS: No significant association was establihed between insulin resistance and response to IFN-alpha and ribavirin, in children with chronic hepatitis C.

Defying gravity: Drops that climb up a vertical wall of their own accord.

Drops that move uphill on a gradient surface have been introduced in the past. In this paper, however, we present drops that climb a surface that does not have a gradient to begin with. In our study, Octadecylamine in Tetradecane (ODA/TD) drops were placed on either vertical or horizontal mica surfaces, and both the cases show spreading and retraction that initiate the motion of the ODA/TD drops. On horizontal surfaces, initially, the drop spreads in all directions. Then, after some time, which is a function of the solute concentration, the rear edge of the drop jerks in the direction opposite to spreading with a retraction that reminds breaststroke swimming motion: the front sides keep spreading while the back retracts, followed by the sides closing on themselves and pushing all the liquid forward which is the only place that never retracts. The front side of the drop then spreads faster in a way that reminds the circle that the arms make during breaststroke. The back and front sides of the drop continue to shrink and expand, respectively, with a net result of moving forward. The reason this motion can happen, is that the drop self-creates a local interfacial gradient at its surrounding. The direction of this self-induced interfacial gradient is against the gravity for inclined surfaces and is random if the surface is horizontal. Tilting the surface results in a local gradient that is preferentially opposite to the direction of gravity, hence the drop's motion results in climbing up. The drop leaves behind it a surfactant covered, but otherwise dry, surface. To the best of our knowledge such a system has not been explored before.

Drops That Change Their Mind: Spontaneous Reversal from Spreading to Retraction.

A liquid drop may spread faster on surfaces when surfactants are added. Here we show that after some time the spreading in such systems can, under certain conditions, spontaneously reverse to retraction and the droplet pulls itself back, receding from areas it has just recently wetted, elevating its center of mass in a jerklike motion. The duration from drop placement to the onset of retraction ranges from hours to less than a second primarily as a function of surfactant concentration. When the retraction is asymmetric, it results in drop motion, and when it is symmetric, the mass of the drop collects itself on its spot. This phenomenon, which was predicted theoretically in 2014, is apparently a general one for drops with surfactants; however, other factors, such as evaporation and contamination, prevented its observance so far.

Reply to Comment on "Solid-Liquid Work of Adhesion".

Extrand's interpretation in his "Comment on "Solid-Liquid Work of Adhesion" by Tadmor and Coworkers" may lead to an important discussion and physical understanding of the problem. Below, we compare the two approaches and elucidate the differences to put them in the right perspective.

Evaluation of paediatric patients with protein losing enteropathy a single centre experience.

OBJECTIVE: The aim of the study is to evaluate paediatric patients with protein losing enteropathy (PLE). METHODS: Fourteen cases diagnosed as PLE were evaluated in terms ofaetiologies, diagnostic methods, laboratory findings, treatment procedures and long-term prognosis. RESULTS: Four of the cases had coeliac disease, three intestinal lymphangiectasia, three giardia infection, one H pylori infection and three cytomegalovirus (CMV) infection. Histopathological examinations of duodenum specimens revealed total villous atrophy in four cases, lymphatic dilatation in three cases, severe nodular appearance in four cases and no pathology in four cases. All of the cases except patients with intestinal lymphangiectasia were controlled by the appropriate treatment given for the underlying disease. The cases with CMV infection were treated with only supportive treatment and gancyclovir therapy was not needed. CONCLUSION: When proteinuria is not detected in well-appearing children admitted with oedema, PLE must be considered.

The effect of cardiac rehabilitation on quality of life, anxiety and depression in patients with congestive heart failure. A randomized controlled trial, short-term results.

AIM: One of the major treatment goals in congestive heart failure (CHF) is to preserve the functional level of the patient and to improve psychosocial factors. For these purposes, exercise training is recommended for the management of CHF. With this background, the aim of this study is to investigate the effects of aerobic exercise on quality of life, depression and anxiety levels in a Turkish patient population with CHF. METHODS: Sixty patients with CHF in stage II-III according to NYHA were included. Patients were randomly assigned either to a cardiac rehabilitation group or to a control group. Twenty-seven patients were allocated to a weekly aerobic walking program on treadmill, thrice a week for 8 weeks, and 26 patients did not receive any exercise training. Both groups were assessed by an ergospirometric exercise test, Hacettepe Quality of Life Questionnaire (HQoL), Beck Depression Inventory (BDI), Spielberger Trait Anxiety Inventory (STAI) at baseline and at the end. RESULTS: Forty-four patients (treatment group: 23) completed the study. In the treatment group, significant increases in peak oxygen consumption, exercise time and metabolic equivalents (MET) levels were attained (P=0.001, P=0.001, P=0.003, respectively). Significant decreases in BDI (P=0.004) and STAI subgroups (P=0.049, P=0.023, respectively) were observed, whereas there was no change in HQoL scores. In the control group, there was no difference between baseline and 8th week evaluation in all parameters. CONCLUSIONS: Patients with CHF tolerated aerobic exercise programs well. This resulted with improvement in both physical and psychologic wellbeing, but not in quality of life in the short term.

Efficacy and safety of extended-release fluvastatin in Turkish patients with hypercholesterolaemia: TULIPS (Turkish Lipid Study).

OBJECTIVE: The efficacy and safety of extended-release fluvastatin (fluvastatin XL), 80 mg once daily, was assessed in Turkish patients with primary hypercholesterolaemia (low-density lipoprotein cholesterol (LDL-C) 3.37-5.70 mmol/l and triglyceride (TG) < 4.52 mmol/l). RESEARCH DESIGN: In this open-label, prospective, multi-centre study, 154 patients were given fluvastatin XL 80 mg once daily and lipid levels were assessed after 2 and 12 weeks. RESULTS: Fluvastatin XL 80 mg once daily significantly reduced LDL-C levels by 38.8 and 38.1% at weeks 2 (n = 140) and 12 (n = 116), respectively (p < 0.001 vs. baseline). Treatment with fluvastatin XL for 2 and 12 weeks significantly reduced total cholesterol levels by 30.2 and 27.4%, respectively (p < 0.001 vs. baseline) and reduced TG levels by 14.9 and 7.5%, respectively (p < 0.001 vs. baseline). Following stratification by risk factors for coronary heart disease (CHD) according to the National Cholesterol Education Program Adult Treatment Panel III guidelines, 87.3% of patients with > or = 2 risk factors, and 67.4% of patients with existing CHD or CHD risk equivalents achieved target LDL-C levels (< 3.37 mmol/l and < 2.59 mmol/l, respectively) with fluvastatin XL. Fluvastatin XL reduced high-density lipoprotein cholesterol by 8.9 and 4.7% at weeks 2 and 12 weeks, respectively. fluvastatin XL 80 mg once daily was generally well-tolerated. CONCLUSIONS: This open-label study indicates fluvastatin XL 80 mg once daily is an effective and well-tolerated lipid-lowering therapy for the reduction of CHD risk in Turkish patients.

Epidural magnesium reduces postoperative analgesic requirement.

BACKGROUND: Magnesium has antinociceptive effects in animal and human models of pain. Our hypothesis was that the addition of magnesium to postoperative epidural infusion of fentanyl may decrease the need for fentanyl. METHODS: Fifty patients undergoing hip surgery were enrolled to receive either fentanyl (Group F) or fentanyl plus magnesium sulphate (Group FM) for 24 h for epidural analgesia. All patients were equipped with a patient-controlled epidural analgesia device and the initial settings of a demand bolus dose of fentanyl 25 microg. In Group FM, patients received 50 mg magnesium sulphate epidurally as an initial bolus dose followed by a continuous infusion of 100 mg day(-1). Ventilatory frequency, heart rate, blood pressure, pain assessment using a visual analogue scale (VAS), sedation scores and fentanyl consumption were recorded in the postoperative period. RESULTS: There was no significant difference between groups in the time to first analgesic requirement. Compared with Group F, patients in Group FM received smaller doses of epidural fentanyl (P < 0.05). The cumulative fentanyl consumption in 24 h was 437 (SD110) microg in Group F and 328 (121) microg in Group FM (P < 0.05). Patients in Group F showed a higher VAS score in the first hour of the postoperative period (P < 0.05). The groups were similar with respect to haemodynamic and respiratory variables, sedation, pruritus, and nausea. CONCLUSION: Co-administration of magnesium for postoperative epidural analgesia results in a reduction in fentanyl consumption without any side-effects.

Exogenous zinc improves blood fluidity but has no effect on the mechanisms of vascular response to acetylcholine iontophoresis in humans.

Recent findings in cellular signaling function of zinc through the mobilization intracellular calcium or by inducing ATP release suggest that extracellular zinc plays an important role in many physiological functions. However, such an extracellular signaling action of zinc for most cells is not known. Therefore, we investigated whether zinc plays any role in endothelium- dependent acetylcholine (ACh)-induced vasodilatation in microvascular beds. Transdermal iontophoresis was used to transport ACh through the forearm skin and cutaneous perfusion was measured using a laser Doppler flowmeter (LDF). Experiments were repeated using (1) zinc instead of ACh to test the effect of zinc ions alone and (2) concomitant iontophoresis of ACh and zinc to explore the effect of zinc on ACh-induced vasodilatation. Although zinc augments blood flow, curve-fitting to LDF signals indicate that zinc has no effect on the neural and endothelial component of ACh-induced vasodilatation. Additionally, no effect of Zn2+ on blood flow was found during its iontophoresis alone. Therefore, it is suggested from the Fourier analysis of LDF signals that the Zn+ might influence blood fluidity by its action on red blood cells deformability/ aggregability during a high-blood-flow condition, which might, in turn, decrease blood viscosity and improve blood flow in vivo.

Elevated levels of C-reactive protein are associated with impaired coronary collateral development.

BACKGROUND: In vitro studies have shown that C-reactive protein (CRP) attenuates nitric oxide production and inhibits angiogenesis, which may result in impaired collateral development. The aim of this study was to investigate the association between high sensitivity CRP (hsCRP) levels and the extent of coronary collaterals. MATERIALS AND METHODS: We investigated the association between hsCRP levels and the extent of coronary collaterals according to the Rentrop classification in a cohort of 185 patients who had high-grade coronary stenosis or occlusion on their angiograms. RESULTS: Mean age was 62 years and 80% were males. Subjects with a higher grade of collaterals were significantly less likely to have diabetes mellitus (OR; 0.48, 95% and CI; 0.28, 0.83) or acute coronary syndrome (OR; 0.58, 95% and CI; 0.33, 0.99), but they were more likely to have higher number of vessels with significant stenosis (OR; 1.41, 95% and CI; 1.03, 1.93) and to have received statins (OR; 1.84, 1.09, 3.13). The mean hsCRP values reduced significantly as the Rentrop grades increased (trend, P = 0.0006). After adjusting for age, gender, statin use, clinical presentation with acute coronary syndrome, diabetes mellitus and the number of vessels with significant stenosis, each 10-unit increase in hsCRP values corresponded to a 31% reduced odds of having a higher collateral score (OR; 0.69, 95% and CI; 0.53, 0.90). CONCLUSIONS: Our findings indicate that elevated hsCRP levels are associated with a significant impairment in coronary collateralization. These data suggest a previously unrecognized mechanism through which inflammation may worsen cardiovascular outcomes.

Effects of clonidine pre-treatment on bupivacaine and ropivacaine cardiotoxicity in rats.

BACKGROUND AND OBJECTIVE: Clonidine has cardiac and systemic effects that can modify the potentially lethal cardiovascular effects of local anaesthetics. We evaluated the effects of clonidine pre-treatment on cardiotoxicity induced by an infusion of bupivacaine or ropivacaine and the success rate of resuscitation in anaesthetized rats. METHODS: Thirty-two Sprague-Dawley rats (250-300 g) were anaesthetized with thiopental and ketamine. Lung ventilation was maintained mechanically, and the electrocardiograph and invasive blood pressure were recorded continuously. Two separate groups of rats were treated with intravenous clonidine 5 microg kg(-1) (n = 16) or saline (n = 16) in a randomized fashion. Fifteen minutes later, each group was randomly subdivided into two equal groups and an infusion of bupivacaine or ropivacaine, 3 mg kg(-1) min(-1), was given until cardiac arrest (asystole) occurred. The times when the cardiotoxic events (25%, 50% and 75% reduction of arterial pressure and heart rate, first dysrhythmia and asystole, respectively), induced by the local anaesthetic, occurred and the resuscitation outcome scores were recorded. RESULTS: Clonidine reduced heart rate and arterial pressure (P < 0.01). Clonidine did not alter cardiotoxicity or the success rate of resuscitation in bupivacaine-treated rats. In the ropivacaine group, clonidine increased the 25%, 50% and 75% reduction times of arterial pressure and the 50% and 75% reduction times of heart rate, times to first dysrhythmia and asystole (P < 0.05). Clonidine also increased the success rate of resuscitation in ropivacaine-treated rats (P < 0.05). CONCLUSIONS: Although pre-treatment with clonidine protects the effects of ropivacaine cardiotoxicity and increases the success rate of resuscitation, it does not affect bupivacaine toxicity.

The effect of intrathecal medetomidine on small bowel transit in the rat.

BACKGROUND AND OBJECTIVE: Gastrointestinal motility is influenced by abdominal trauma, laparotomy and particularly by intestinal ischaemia. The reflex inhibition of gastrointestinal motility is mediated mainly by the sympathetic nervous system. There are reports on the effects of systemically applied alpha2-adrenoceptor agonists on gastric emptying and recovery of bowel motility, but the effect of spinally applied alpha2-adrenoceptor agonists on intestinal motility has not been studied. The aim of this study was to investigate the effects of intrathecal medetomidine on gastrointestinal transit in rats after transient intestinal ischaemia. METHODS: Forty rats were randomly assigned to four groups of 10 each. Intrathecal catheter insertion and laparotomy were performed on each rat. Saline (10 microL) was injected intrathecally in Groups A and B. Medetomidine (10 microg in 10 microL) was injected intrathecally in Groups C and D. Intestinal ischaemia was induced in Groups B and D. Gastrointestinal transit was determined by measuring the length that a standardized marker meal of activated charcoal had travelled. Intrathecal medetomidine was compared to intrathecal saline in their effect on intestinal motility after 30 min period of bowel ischaemia. RESULTS: Laparotomy and intestinal ischaemia slowed gastrointestinal transit. Intrathecal medetomidine accelerated transit in both ischaemia and non-ischaemia groups. CONCLUSION: Intrathecal medetomidine markedly accelerated small intestinal transit and may also hasten the recovery from post-ischaemic paralytic ileus.

Antiangiogenic therapy with somatostatin receptor-mediated in situ radiation.

Tumor growth and the development of metastases require an angiogenic response. Angiogenic vessels uniquely express somatostatin subtype 2 (sst 2) receptors that can transport somatostatin or its analogs into the cell. We hypothesized that radiolabeled somatostatin analogs could inhibit the angiogenic response by selectively destroying proliferating endothelial cells. We evaluated the antiangiogenic effects of 111In-pentetreotide, an sst 2-preferring somatostatin analog in a human vessel model. Disks of human placental vein were embedded in fibrin gels in culture and observed for angiogenic sprouting for 14 days. Vein disks were treated with 111In-pentetreotide (1.5, 15, and 150 microCi/mL) on the day of implantation. Control groups included disks treated with nutrient medium alone, with 111In-chloride, and with unlabeled pentetreotide. The percentage of wells that initiated an angiogenic response and the overall length and density of neovessel sprouts were assessed on Day 14. 111In-pentetreotide treatment did not completely block initiation of the angiogenic response but significantly decreased the growth of neovessels after initiation. Both the receptor-specific Auger electron-induced and nonspecific gamma radiation-mediated effects contributed to the angiotoxicity.

Post-surgical ablation of thyroid remnants with high-dose (131)I in patients with differentiated thyroid carcinoma.

The aims of this study were to evaluate the efficacy of an empirically determined "fixed" high ablative dose of radioiodine ((131)I) therapy and to determine the utility of ultrasonography (US) in dose determination. A retrospective analysis was performed of 242 thyroid cancer cases treated with "fixed" high-dose (131)I for ablation of thyroid remnants without a pre-ablative (131)I diagnostic scintigraphy or radioiodine uptake study. Treatment doses ranged from 1850 MBq (50 mCi) to 7.4 GBq (200 mCi). The selection of the treatment dose was based on the surgical and pathological findings as well as the remnant thyroid volume calculated by US. A successful ablation was defined as the absence of activity in the thyroid bed on subsequent imaging studies. Successful ablation was obtained in 218 of the 242 patients (90%). In 162 of the 218 patients (74.3%), successful ablation was achieved after a single (131)I treatment. The remnant thyroid volume calculated by US was significantly different (P=0.04) between those who were successfully ablated and those who were not. The total (131)I dose needed for successful ablation was significantly higher in males (P=0.003). Patients with higher post-operative thyroglobulin (Tgb) levels and patients with a higher stage of disease required higher doses (P=0.036 and P=0.021 respectively). Serum Tgb levels were under 10 ng.ml(-1) in 220 of the 242 patients (90%) following radioiodine ablation while not receiving L-thyroxine suppression. Nineteen patients (7.8%) showed metastases on post-therapy scan and successful treatment was achieved in 11 of 19 (57.8%). Four of the 19 patients with distant metastases (revealed on post-treatment scan) were found to have been given a treatment dose of less than 200 mCi based on the proposed empirical approach. These results indicate that "fixed" high-dose (131)I treatment is clinically feasible with an acceptable dose underestimation rate, and the utilization of US in the determination of the thyroid remnant volume provides more accurate and reproducible results.

Clinical utility of frozen section in sentinel node biopsy in breast cancer.

One hundred sixty-five breast cancer patients underwent a sentinel lymph node biopsy procedure over a period of 2 years. Sentinel node (SN) could be successfully localized in 157 (95%) of the patients. Complete axillary lymph node dissection was performed only if the frozen section (FS) revealed a positive SN. All SN specimens were further evaluated by hematoxylin and eosin on multiple sections and cytokeratin immunohistochemisty. The patients whose SNs were negative by FS but positive by permanent histopathologic evaluation underwent a delayed axillary lymph node dissection. SN was positive in 41 of 157 (26%) patients. Eighteen (44%) of the 41 patients with SN metastases were diagnosed intraoperatively by FS and underwent a one-stage definitive surgical treatment. The benefit of FS was most notable in patients with T1c and larger lesions.

Antitumor and antiangiogenic effects of somatostatin receptor-targeted in situ radiation with (111)In-DTPA-JIC 2DL.

INTRODUCTION: Expression of somatostatin receptor subtype 2 (sst 2) in angiogenic tumor vessels appears to be homogeneous, while tumor cell expression of this receptor is often heterogeneous. We have developed a novel in vitro three-dimensional tumor angiogenesis model to study the antitumor and the antiangiogenic effects of radiolabeled somatostatin analogs. We hypothesized that targeted in situ radiation with an Auger electron-emitting radiolabeled somatostatin analog would produce receptor-specific cytotoxicity in sst 2-expressing cells. MATERIALS AND METHODS: IMR-32 human neuroblastoma (sst 2-positive) and MDA MB-231 human breast cancer (sst 2-negative) xenografts were created in nude mice from monolayer cell cultures. Fragments of these tumors were embedded in three-dimensional fibrin gels supplemented with endothelial growth media and incubated for a period of 14 days. Tumor fragments were treated with 50 microCi/ml of (111)In-JIC 2DL, a sst 2-preferring somatostatin analog, or medium on Day 1. Initial angiogenic activity was determined at 48 h and the mean angiogenic score and tumoricidal responses were assessed on Day 14. RESULTS AND CONCLUSION: Tumoricidal effects of (111)In-JIC 2DL were seen only in sst 2-positive IMR-32 tumors. However, the angiogenic response was inhibited in both IMR-32 and MDA MB-231 tumors independent of the tumor cells' sst 2 status. Somatostatin receptor-mediated in situ radiation therapy has profound cytotoxic effects on angiogenic blood vessels and sst 2-expressing tumor cells.