Induction of ovulation using repeated doses of sulpiride, a dopamine antagonist, in ewe lambs.

This study aimed to test the hypothesis that sulpiride can increase the concentration of circulating gonadotropin that can promote puberty in pre-pubertal ewe lambs. Here, 12 1-3-year-old Merino rams and 60 7-9-month-old Merino sheep were included in the study. The sheep were randomly divided into sulpiride (n = 30) and control (n = 30) groups. The sulpiride group was subcutaneously injected with 0.6 mg/kg sulpiride twice daily (morning and evening) for 9 days. During these 9 days, blood samples were taken from the sheep before drug administration and at 4 h after every drug administration. The number of ovulating animals in the sulpiride group was significantly higher than that in the control group (90% vs. 32%). No oestrous signs were observed in either group during ram release. Further, there were no differences in the levels of mean follicle-stimulating hormone in the two groups based on treatment (p = .2), time (p = .3) or treatment-by-time interaction (p = .3). After sulpiride administration, the luteinizing hormone (LH) levels of the sulpiride group rapidly increased and remained stable for a long time, whereas physiological LH fluctuations in the control group remained unchanged. Within-group changes in terms of LH concentrations were significant for both groups (p < .001), whereas LH pulse frequency was significantly different between the sulpiride group (p = .03). Therefore, it is concluded that sulpiride can be used as a non-steroidal alternative to stimulate pre-pubertal ewe lambs and sheep during anoestrus.

A comparison of patients who have appendectomy during the COVID-19 pandemic period with the period before the pandemic.

BACKGROUND: This study aims to compare the waiting and operating times of the patients who applied to our hospital with the diagnosis of acute appendicitis (AA) during the pandemic, how the process was managed in terms of AA and other data of the patient compared to the pre-pandemic period. METHODS: A retrospective cohort analysis was performed among patients who were hospitalized in the Fatih Sultan Mehmet Training and Research Hospital General Surgery Clinic with a pre-diagnosis of AA. For this purpose, two groups were formed. Group 1: It comprised patients who were operated between March 11 and June 1, 2020; Group 2: It comprised patients who were operated between March 11 and June 1, 2019, with a pre-diagnosis of AA. RESULTS: Forty-six patients in Group 1 and 79 patients in Group 2 were operated with the pre-diagnosis of AA. There was no difference between groups in terms of pre-operative symptom durations or surgery waiting times. CONCLUSION: During the COVID-19 pandemic, significant decrease observed in the number of patients operated because of AA can be interpreted as the avoidance of patients from applying to the hospital with the concern of infection. Moreover, it may suggest that uncomplicated cases undergo spontaneous resolution; however, there is a requirement for further research to support this assumption and define the criteria for this condition by including a level of scientific evidence.

The pharmacokinetics of letrozole and its effect on gonadotropins in anestrous ewes.

The aim of this study was to determine the pharmacokinetics of letrozole and its effect on FSH and LH concentrations after single (IV, IM, SC) and repeated IV doses in anestrous ewes. This study was conducted in experiments 1 and 2 by randomly dividing 24 healthy Akkaraman ewes in anestrus into two equal groups. In experiment 1, the pharmacokinetics of letrozole following single IV, IM, and SC administration at 1 mg/kg dose and its effect of a single IV dose on plasma FSH and LH concentration were determined. In experiment 2, the effect of repeated IV doses of letrozole on FSH and LH concentrations was established. Plasma concentration of letrozole was measured using high-performance liquid chromatography, and pharmacokinetic parameters were calculated by non-compartmental analysis. FSH and LH concentrations were quantified using ELISA. The elimination half-life (t1/2ʎz) for IV, IM, and SC routes were 9.94, 37.29, and 41.07 h, respectively. The IV route for letrozole had a total clearance of 0.11 L/h/kg and a volume of distribution at a steady state of 1.50 L/kg. The peak plasma concentration was 0.11 µg/mL for the IM route and 0.14 µg/mL for the SC routes. The bioavailability was 55.18% for the IM route and 75.34% for the SC route. Letrozole following single and repeated (every 24 h for 3 days) IV administrations at 1 mg/kg dose did not affect LH concentration in anestrous ewes but caused an increase in the FSH concentration. This increase in FSH concentration may create a potential for the use of letrozole in ovarian superstimulation protocols. Favorable pharmacokinetic properties (long t1/2ʎz and good bioavailability) of letrozole for IM and SC routes require further investigation before use in estrus induction or estrus synchronization protocols in sheep.

Clinical approach to patients admitted to the emergency room due to acute cholecystitis during the COVID-19 pandemic and percutaneous cholecystostomy experience.

BACKGROUND: Acute cholecystitis (AC), a common complication of gallstones, is responsible for a significant part of emergency applications, and cholecystectomy is the only definitive treatment method for AC. Early cholecystectomy has many reported advantages. Operation-related morbidity and mortality have increased during the COVID-19 pandemic. In this study, our aim is to present our general clinical approach to patients who were diagnosed with AC during the pandemic and our percutaneous cholecystostomy experience during this period. METHODS: This study included 72 patients who were presented to our hospital's emergency room between March 11 and May 31, 2020, with AC. Patients were divided into three groups based on their treatment: outpatients (Group 1), inpatients (Group 2) and patients undergoing percutaneous cholecystostomy (Group 3). These three groups were compared by their demographic and clinical characteristics. RESULTS: There were 36 (50%) patients in Group 1, 25 (34.7%) patients in Group 2, and 11 (15.3%) patients in Group 3. The demographic characteristics of the patients were similar. The CRP and WBC levels of the patients in Group 3 were significantly higher compared to the other groups. Moreover, the wall of the gallbladder was thicker and the size of the gallbladder was larger in Group 3. Patients had percutaneous cholecystostomy at the median of 3.5 days and the length of hospital stay was longer compared to Group 2 (3.9 days versus 9.2 days, p=0.00). The rate of re-hospitalization after discharge was similar in Group 2 and Group 3, but none of the patients in Group 1 required hospitalization. None of 72 patients developed an emergency condition requiring surgery, and there was no death. CONCLUSION: Although many publications emphasize that laparoscopic cholecystectomy (LC) can be performed with low morbidity at the first admission in acute cholecystitis, it is a clinical condition that can be delayed in the COVID-19 pandemic and other similar emergencies. Thus, percutaneous cholecystostomy should be effectively employed, and its indications should be extended if necessary (e.g., younger patients, patients with lower CCI or ASA). This approach may enable us to protect both patients and healthcare professionals that perform the operation from the risk of COVID-19.

Comparison of the effectiveness of two treatment modalities for chronic anal fissure: Botox versus sphincterotomy.

OBJECTIVES: Anal fissure is a common health problem that affects the quality of life of young patients. The aim of our study was to benchmark results of lateral internal sphincterotomy (LIS) and botulinum toxin injection in the treatment of chronic anal fissure. MATERIAL AND METHODS: This multi-center, retrospective study used data from 135 chronic anal fissure patients. Patients' demographic features, clinical findings, fissure characteristics, post-defecation pain score, rectal bleeding or pruritus, and treatment satisfaction scores were recorded. Patients' data were collected from the hospital records and patients with all of this data available were called and invited to the hospital for examination. RESULTS: Seventy-four LIS and 61 botulinum toxin applied patients were included. Symptom duration, hospitalization period, and duration of remission of complaints after the treatment were significantly higher in the LIS group (p<0.001). However, pruritus in anus and relapses were found to be higher in the botulinum toxin group (p=¬ 0.04 and p= 0.043, respectively). Abscess and fistula were observed in one patient's perianal region in the LIS group, and an abscess was observed in one patient in the botulinum toxin group. There was no significant difference in treatment satisfaction rates and postoperative complications. CONCLUSION: Botulinum toxin yields satisfying results that are comparable to LIS. Patient selection may help mitigate this disease and allow it to be considered a good alternative option to surgery.

First platinum(II)-based metal-organic linker technology (Lx®) for a plug-and-play development of antibody-drug conjugates (ADCs).

Introduction: Compared to the antibody and drug components of an ADC, the linker part has been somewhat neglected. However, its importance for the reduction of failures in ADC approvals is increasingly recognized. Next of being a stable glue between drug and antibody, an ideal linker should improve the manufacturability and widen the therapeutic window of ADCs. Areas covered: The biopharmaceutical company LinXis started an ADC development program in which platinum(II) is the key element of the first metal-organic linker. The cationic complex [ethylenediamineplatinum(II)]2+, herein called 'Lx®', is used successfully for conjugation of drugs to antibodies. Expert opinion: Based on lessons learned from ADC development, Lx linker technology fulfills most of the desirable linker characteristics. Lx allows large-scale cost-effective manufacturing of ADCs via a straightforward two-step 'plug-and-play' process. First clinical candidate trastuzumab-Lx-auristatin F shows favorable preclinical safety as well as outstanding in vivo tumor targeting performance and therapeutic efficacy.

Report: Fast chromatographic screening method for 7 drugs of potential threat in drug facilitated crimes.

In cases where pharmaceuticals and pharmaceutical candidates are involved in drug facilitated crimes (DFC), like organ theft, robbery, rape and suicides, the analysis of drug powders or solution residues found in crime scenes may give idea on what the victims have ingested. An easy and fast simultaneous determination of 7 drugs; GHB (γ-hydroxybutyrate), GBL (γ-butyrolactone), norketamine, ketamine, fenobarbital, fenitoin and thiopental which have the potential to be used in DFC was performed. The method required no sample preparation and has 12 minutes elution time with a good chromatographic separation. The separation was carried out on a C18 monolithic column with UV detection at 215 and 237nm. All r2 values were ≥0.99 and the linear ranges were between 0.9956-1.0000. The LOD and LOQ values were between 0.56-5.55µgmL-1 and 1.69-16.82µgmL-1 respectively. The repeatability values were <7.35%. This is the first study in the simultaneous screening of the above mentioned drugs using HPLC.

The relationship between intoxication severity and blood interleukin 6, interleukin 10 and CRP levels in carbon monoxide-poisoned patients.

Carbon monoxide (CO) is one of the most common causes of death due to intoxications. No biochemical marker is available to evaluate the severity of CO intoxication. We measured high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and interleukin-10 (IL-10) levels in patients with different degrees of CO poisoning. We prospectively included 40 CO-poisoned patients admitted to emergency services. Blood samples were collected from the patients at admission (0 hour) and after treatment (six hours). While all patients received normobaric oxygen (NBO2) therapy, patients with severe CO poisoning received additional sessions of hyperbaric oxygen (HBO2) therapy. Blood samples were also collected from a group of healthy volunteers (n=40). Serum IL-6 and IL-10 levels were measured with the ELISA method while hs-CRP was quantified by turbidimetric analysis. At admission, IL-6 levels were significantly higher in the patient group compared to the control group (P=0.001), but IL-10 and hs-CRP levels were not significantly different between the groups. Compared to admission levels, IL-6 levels were higher at six hours (P=0.014). The patients were grouped according to treatment type (NBO2, HBO2) and history of syncope, but no significant differences were detected in patient subgroups regarding IL-6, IL-10 and hs-CRP levels. A weak positive correlation was found between COHb and lactate levels in patients (P=0.013; r=0.390).This study shows that IL-6 level increases in CO-poisoned patients, but it is not correlated with the severity of the intoxication.

The association of profilin-1 levels with survival in chronic kidney disease.

BACKGROUND: Profilin-1 is a ubiquitous, actin-binding protein that plays an important role in the regulation of actin polymerization and cytoskeleton remodelling and contributes to vascular dysfunction. We conducted this study to investigate the association of serum profilin-1 levels with fatal and nonfatal CVE in a cohort of patients with stage 1-5 CKD. MATERIALS AND METHODS: Serum concentrations of profilin-1 levels were determined by enzyme-linked immunosorbent assay. Endothelium-dependent vasodilatation (flow-mediated dilatation [FMD]) and endothelium-independent vasodilatation (nitroglycerine-mediated dilatation [NMD]) of the brachial artery were assessed noninvasively, using high-resolution ultrasound. RESULTS: Both fatal and nonfatal CVE were significantly higher in patients with high profilin-1 levels. Kaplan-Meier survival curves showed that patients with profilin-1 below the median value (114 pg/mL) had higher cumulative survival compared with patients who had profilin-1 levels above the median value (log-rank test, P < .001). CONCLUSIONS: This is the first study that demonstrates the serum profilin-1 is independently associated with endothelial dysfunction, cardiovascular events and survival in patients with CKD.

The Relationship Between Plasma Whole Blood Viscosity and Cardiovascular Events in Patients With Chronic Kidney Disease.

BACKGROUND: Plasma levels of estimated whole blood viscosity (eWBV) have been increased by endothelial inflammation. Because there were no consistent data for assessing the eWBV levels for prediction of cardiovascular event (CVE) in patients with chronic kidney disease (CKD). We aimed to investigate the relationship between plasma eWBV levels and CVEs in patients with CKD. MATERIALS AND METHODS: We conducted a prospective, cross-sectional, long-term follow-up study, assessing the relationship between plasma eWBV levels and CVE (either fatal or nonfatal) in patients with newly diagnosed CKD. We also evaluated estimated glomerular filtration rate (eGFR), pentraxin 3 (PTX3), high-sensitivity C-reactive protein (hsCRP), and flow-mediated dilatation (FMD). RESULTS: Study patients were divided into 2 groups: patients with CVE and patients without CVE. The eWBV levels were higher in patients with CVE. Additionally, PTX3 and hsCRP were higher, and FMD and eGFR were lower in patients with CVE compared to those without CVE. According to the Cox regression analysis, WBV, plasma asymmetric dimethylarginine levels, FMD, hsCRP, eGFR, systolic blood pressure, calcium, and history of diabetes were independent predictors of CVEs in patients with CKD. Kaplan Meier survival curves were generated to establish the impact of the WBV on the cumulative survival of the cohort. Patients with eWBV values higher than 5.2 centipoise (cP) had lower survival rates when compared to patients with eWBV values lower than 5.2 cP (log rank = 4.49 df = 1 P = .034). CONCLUSION: In conclusion, plasma eWBV levels may increase the presence of lower eGFR and affect CVE in patients with CKD independent of classical and unconventional risk factors.

Thyroid function and cardiovascular events in chronic kidney disease patients.

BACKGROUND AND AIMS: Abnormalities of thyroid function are commonly seen in chronic kidney disease (CKD) patients. They are associated with adverse clinical conditions such as atherosclerosis, endothelial dysfunction, inflammation and abnormal blood pressure variability. We investigated the association between thyroid disorders and endothelial function, assessed by flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT), and cardiovascular events (CVE) in CKD patients. MATERIALS AND METHODS: This observational cohort study included 305 CKD (stages 1-5) patients. Routine biochemistry, including free T3, free T4 and thyroid stimulating hormone, fibroblast growth factor-23 (FGF-23) and FMD, CIMT were measured. We divided patients into four groups according to thyroid hormone status: euthyroidism, subclinical hyperthyroidism, subclinical hypothyroidism, and euthyroid sick syndrome. Fatal and composite CVE were recorded for a median 29 months. RESULTS: Patients with subclinical hypothyroidism had a higher prevalence of hypertension and diabetes and also were more likely to have higher values of systolic CIMT, phosphorus, intact parathormone (iPTH), FGF-23, homeostasis model assessment-insulin resistance and lower levels of FMD than euthyroid patients. In the unadjusted survival analysis, subclinical hypothyroidism and euthyroid sick syndrome were associated with an increased risk for the outcome as compared with euthyroidism [hazard ratio 30.63 (95 % confidence interval 12.27-76.48) and 12.17 (3.70-39.98), respectively]. The effects of subclinical hypothyroidism and euthyroid sick syndrome were maintained even in fully adjusted models. CONCLUSION: We demonstrated that subclinical hypothyroidism and euthyroid sick syndrome are associated with increased CVE in CKD patients. Further studies are needed to explore these issues.

Chitotriosidase as a novel biomarker of early atherosclerosis in hemodialysis patients.

INTRODUCTION: Increasing evidence suggests that inflammation and increased macrophage activity have a central role in pathogenesis of atherosclerosis. It is shown that chitotriosidase (CHIT-1) is a marker of macrophage activity in atherosclerotic plaque, and is found associated with severity of atherosclerotic lesion. There is no data about CHIT-1 activity of hemodialysis patients in the literature. Thus, we hypothesized that in hemodialysis patients, CHIT-1 levels might be a novel biomarker in early atherosclerosis. METHODS: Forty-five hemodialysis patients were included in the study (age: 61.93 ± 13.34). Intima media thickness (IMT) was evaluated with high-resolution B-mode ultrasonography. Biomarker levels were measured in serum of patients. FINDINGS: We found positive correlation among IMT, age (R: 0.426, P: 0.004) and, CHIT-1 value (R: 0.462, P: 0.001) in spearman correlation analysis. When age, CRP, creatinine, P, Alb, CHIT-1 were chosen as measures that can effect IMT in multiple regression model, IMT level was related with CHIT-1 (Beta: 0,396, P: 0.012) and age (Beta: 0,313 P: 0,048) independently. DISCUSSION: In conclusion, this is the first report showing that serum CHIT-1 level was related independently with carotid IMT in hemodialysis patients. This biomarker might have an unknown role in the development of atherosclerosis during uremia.

The Relation Between No-Reflow Phenomenon and Complete Blood Count Parameters.

The no-reflow (NR) phenomenon represents an acute reduction in coronary blood flow without coronary vessel obstruction, coronary vessel dissection, spasm, or thrombosis. No reflow is an important complication among patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). The complete blood count (CBC) is one of the most frequently ordered laboratory tests in clinical practice. Various studies have evaluated the performance of CBC parameters to predict disease severity and mortality risk. Automated cell counters are routinely available in many clinical laboratories and can be used to determine red blood cell distrubiton width (RDW), platetecrit, platelet count, and and some ratios like the neutrophil-lymphocyte ratio and RDW-platelet ratio. These hematological markers have been reported to be independent predictors of impaired angiographic reperfusion and long-term mortality among patients with STEMI undergoing pPCI. In this context, we reviewed the role of admission CBC parameters for the prediction of NR in patients with STEMI undergoing pPCI.

The Protective Effect of Adalimumab on Renal Injury in a Model of Abdominal Aorta Cross-Clamping.

BACKGROUND: Adalimumab (ADA) is a potent inhibitor of tumor necrosis factor (TNF-α). ADA treatment suppresses proinflammatory cytokines, leading to a decrease or inhibition of the inflammatory process. OBJECTIVES: The aim of this study was to investigate the possible protective effects of ADA on oxidative stress and cellular damage on rat kidney tissue after ischemia/reperfusion (I/R). MATERIAL AND METHODS: A total of 30 male Wistar albino rats were divided into three groups: control, I/R, and I/R plus ADA (I/R + ADA); each group comprised 10 animals. The control group underwent laparotomy without I/R injury. After undergoing laparotomy, I/R groups underwent two hours of infrarenal abdominal aortic cross ligation, which was followed by two hours of reperfusion. ADA (50 mg/kg) was administered as a single dose, intraperitoneally, to the I/R + ADA group, 5 days before I/R. RESULTS: The I/R group's TNF-α (1150.9 ± 145.6 pg/mg protein), IL-1ß (287.0 ± 32.4 pg/mg protein) and IL-6 (1085.6 ± 56.7 pg/mg protein) levels were significantly higher than those of the control (916.1 ± 88.7 pg/mg protein, p = 0.003; 187.5 ± 37.2 pg/mg protein, p < 0.001; 881.4 ± 57.1 pg/mg protein, p < 0.001, respectively) and I/R + ADA groups (864.2 ± 169.4 pg/mg protein, p = 0.003; 241.4 ± 33.4 pg/mg protein, p = 0.010; 987.7 ± 66.5 pg/mg protein, p = 0.004, respectively). To date, a few histopathological changes have been reported regarding renal I/R injury in rats due to ADA treatment whereas I/R caused severe histopathological injury to kidney tissue. CONCLUSIONS: ADA treatment significantly attenuated the severity of kidney I/R injury, inhibiting I/R-induced oxidative stress and renal damage. Because of its anti-inflammatory and antioxidant effects, ADA pretreatment may have protective effects on experimental kidney injury.

Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival.

BACKGROUND AND AIMS: Endostatin, generated from collagen XVIII, and endorepellin, possess dual activity as modifiers of both angiogenesis and endothelial cell autophagy. Plasma endostatin levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. Few data on endostatins are available for patients with chronic kidney disease (CKD). We tested whether serum endostatin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population. MATERIALS AND METHOD: A total of 519 CKD pre-dialysis patients were included. Baseline plasma endostatin levels were measured in all patients. All included patients were followed-up (time-to-event analysis) until occurrence of death, fatal or nonfatal CVEs. Fatal and nonfatal CVE including death, stroke, and myocardial infarction were recorded prospectively RESULTS: The mean age of the patients was 52.2±12.3years. There were 241 (46.4%) males, 111 (21.4%) had diabetes, 229 (44.1%) were smokers and 103 (19.8%) had a previous CVE. After a median follow-up of 46months, 46 patients died and 172 had a new CVE. In the univariable Cox survival analysis, higher endostatin levels were associated with a higher risk for both outcomes. However, after adjusting for traditional (age, gender, smoking status, diabetes, systolic blood pressure, HDL and total cholesterol) and renal-specific (eGFR, proteinuria and hsCRP) risk factors, endostatin levels remained associated only with the CVE outcome (HR=1.88, 95% CI 1.37-2.41 for a 1 SD increase in log endostatin values). CONCLUSION: Endostatin levels are independently associated with incident CVE in CKD patients, but show limited prediction abilities for all-cause mortality and CVE above traditional and renal-specific risk factors.

NFU1 gene mutation and mitochondrial disorders.

Mitochondrial respiratory chains consist of approximately 100 structural proteins. Thirteen of these structural proteins are encoded by mitochondrial DNA (mtDNA), and the others by nuclear DNA (nDNA). Mutation in any of the mitochondrial structural-protein related genes, regardless of whether they are in the nDNA or mtDNA, might cause mitochondrial disorders. In the recent past, new nuclear genes required for assembly, maintenance, and translation of respiratory chain proteins have been found. Mutation in these genes might also cause mitochondrial disorders (MD). NFU1 gene is one of such genes and has a role in the assembly of iron-sulfur cluster (ISC). ISCs are included in a variety of metalloproteins, such as the ferredoxins, as well as in enzymatic reactions and have been first identified in the oxidation-reduction reactions of mitochondrial electron transport. It is important to be aware of NFU1 gene mutations that may cause severe mitochondrial respiratory chain defects, mitochondrial encephalomyopathies and death, early in life.

High prevalence of chronic hepatitis D virus infection in Eastern Turkey: urbanization of the disease.

INTRODUCTION: Both hepatitis B virus (HBV) and hepatitis D virus (HDV) infection play an increasingly important role in liver diseases. The main objective of this study was to investigate the socio-epidemiological, laboratory and radiological aspects of both HBV and HDV infection near the Iranian border of Turkey. MATERIAL AND METHODS: The study included 3352 patients with HBV and HDV infection. Socioepidemiological, laboratory and radiological aspects of the study subjects were retrospectively examined. Comorbid metabolic diseases were not assessed due to the retrospective design of the study. RESULTS: Most of the study subjects were HBe antigen negative. No significant difference in terms of HBV-DNA levels or HBe antigen seropositivity was detected between the city centre and rural areas (p > 0.005). The mean HBV-DNA level in the anti-HDV-positive group was significantly lower than in the anti-HDV-negative group (p < 0.001). The rate of HDV-RNA positivity in women was higher than in their male counterparts (p = 0.017). Anti-HDV-IgG was detected in 18.4% of tested subjects who came from an urban area. In contrast, 12.5% of subjects of the rural group had a positive result for anti-HDV-IgG. Among 134 ultrasonographically evaluated delta hepatitis patients, 37.3% had liver cirrhosis. On the other hand, in 1244 patients with hepatitis B monoinfection, there were 90 patients with liver cirrhosis. Radiologically, the rate of hepatic steatosis in delta hepatitis patients was lower than in those with HBV monoinfection. CONCLUSIONS: Hepatitis D virus infection was particularly prevalent among the urban population as well as in female subjects. More broadly, the current observations are the first to suggest an inverse correlation between delta hepatitis and ultrasonography-proven hepatic steatosis.

A Rare Reason of Hyperinsulinism: Munchausen Syndrome by Proxy.

Hyperinsulinism, one of the most important causes of hypoglycaemia, can be congenital or acquired. Rarely, drug toxicity can be a reason for hyperinsulinism. In the context of Munchausen syndrome by proxy (MSP), toxicity usually occurs in children due to drug administration by a parent or caregiver. A 7-year-old girl was referred to our department due to a hyperglycaemic period and hypoglycaemic episodes. On admission, gliclazide was initiated due to her hyperglycaemia, which we attributed to maturity onset diabetes of the young. However, during follow-up, hypoglycaemic levels were detected. Despite cessation of gliclazide, hypoglycaemic seizures occurred. Even with the medications administered, hypoglycaemia could not be prevented. During follow-up, the mother's affect, characterized by anxiety and interest in her daughter's medical care, appeared discordant with the situation. Due to our suspicion of MSP, we discovered toxic levels of gliclazide in the blood and urine samples which had been sent to the toxicology laboratory to search for hypoglycaemic agents. The patient was isolated, and all medications were stopped. After isolation, her hypoglycaemia disappeared, and she became hyperglycaemic (250 mg/dl). Physicians should consider the possibility of MSP in hyperinsulinaemic patients with discordant laboratory results and clinical symptoms, even if the child's parents display great concern.

The relation between monocyte to HDL ratio and no-reflow phenomenon in the patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: No-reflow phenomenon is a prognostic value in ST-segment elevation myocardial infarction (STEMI). Monocyte to high density lipoprotein ratio (MHR) has recently emerged as a marker of inflammation and oxidative stress in the cardiovascular disease. PURPOSE: In this study, we aimed to investigate the relation between MHR and no-reflow phenomenon in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI). MATERIAL AND METHODS: A total of 600 patients with STEMI (470 men; mean age, 62 ± 12 years) admitted within 12 hours from symptom onset were included into this study. Patients were classified into 2 groups based on postintervention Thrombolysis in Myocardial Infarction (TIMI) flow grade: no-reflow-TIMI flow grade 0, 1, or 2 (group 1); angiographic success-TIMI flow grade 3 (group 2). RESULTS: According to admission whole-blood cell count results, the patients in the no-reflow group had significantly higher monocyte count and MHR values when compared with those of the reflow patients. After multivariate backward logistic regression, MHR remained independent predictors of no reflow after pPCI. Adjusted odds ratios were calculated as 1.09 for MHR (P< .001; confidence interval [CI], 1.07-1.12). Receiver operating characteristic curve analysis suggested that the optimum MHR level cutoff point for patients with no-reflow was 22.5, with a sensitivity and specificity of 70.2% and 73.3%, respectively (area under curve, 0.768; 95% CI, 0.725-0.811). CONCLUSION: In conclusion, MHR levels are one of the independent predictors of no reflow in patients with STEMI after pPCI.

Osteoprotegerin in Chronic Kidney Disease: Associations with Vascular Damage and Cardiovascular Events.

Vascular injury and dysfunction contribute to cardiovascular disease, the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor receptor superfamily that has been linked to atherogenesis and endothelial dysfunction. Elevated circulating OPG levels predict future cardiovascular events (CVE). Our aim was to evaluate the determinants of circulating OPG levels, to investigate the relationship between OPG and markers of vascular damage and to test whether OPG improves risk stratification for future CVE beyond traditional and renal-specific risk factors in a CKD population. 291 patients with CKD stage 1-5 not on dialysis were included in the study. In the multivariate analysis, OPG was a significant predictor for flow-mediated dilatation, but not for carotid intima media thickness levels. During follow-up (median 36 months, IQR = 32-42 months), 87 patients had CVE. In the Cox survival analysis, OPG levels were independently associated with CVE even after adjustment for traditional and renal-specific cardiovascular risk factors. The addition of OPG to a model based on commonly used cardiovascular factors significantly improved the reclassification abilities of the model for predicting CVE. We show for the first time that OPG improves risk stratification for CVE in a non-dialysis CKD population, above and beyond a model with established traditional and renal-specific cardiovascular risk factors, including estimated glomerular filtration rate and fibroblast growth factor 23.