Impact of postnatal nutrition on neurodevelopmental outcome in rat model of intrauterine growth restriction.

OBJECTIVE: There are limited data on nutritional management of infants with intrauterine growth restriction (IUGR). Postnatal protein supplementation for promoting growth is a common clinical practice in neonatology. The present study aims to investigate the consequences of protein supplementation on long-term growth, brain and body weight, brain histology and behavioral outcome in a rat model of IUGR. MATERIALS AND METHODS: Twenty-four IUGR-formed rat puppies and 12 healthy puppies were included in the study. IUGR model was established by low (10%) protein diet throughout pregnancy together with intraperitoneal injection of lipopolysaccharide (LPS). Pups were started to be fed with either standard protein (SP), or high protein (HP) diet until postnatal day (PN) 35. Puppies in the control group were given SP diet for 35 days. Six pups from each group were sacrificed at PN7, remaining six were evaluated by Morris water maze test between PN 30 to 35 days and then sacrificed at PN35. Histologic evaluation of brain tissue was performed at PN7 and PN35. RESULTS: IUGR group displayed lower body and brain weights at PN7 when compared with control. At PN35, SP group achieved similar brain/body weight ratios with control, whereas HP group displayed lowest brain/body weight ratio. The number of TUNEL positive cells was significantly higher and myelin basic protein and oligodendrocyte marker O4 immunoreactivity were significantly lower in HP group when compared with SP at PN35. Neuronal density in prefrontal cortex and hippocampus at PN7 were similar among SP and HP groups, but significantly lower in HP group when compared with SP at PN35. SP group displayed better results in the Morris water maze test when compared with HP group. CONCLUSIONS: Although postnatal HP support is associated with increase in body weight at PN35, it did not result in better brain/body weight ratios in the rat model of IUGR. In IUGR rats, HP diet was associated with increased apoptosis in brain tissue with lower neuronal density and decreased myelination when compared to SP. Furthermore, better neurodevelopmental scores were achieved by SP diet rather than HP support in IUGR.

Topiramate and darbepoetin alpha ameliorate bilirubin-induced neuronal cell damage.

OBJECTIVE: The aim of this study was to determine whether prophylactic darbepoetin alpha and/or topiramate administration could prevent bilirubin neurotoxicity (BNTx) in experimental model of kernicterus. MATERIALS AND METHODS: A total of 60 Wistar albino rat puppies with experimental kernicterus model were included in the study. The Kernicterus was established administering a bilirubin injection via a cisterna magna puncture 30 minutes after ip drug injection. The puppies were divided into five groups with 12 in each group as shown below: a control group, bilirubin group, darbepoetin alpha group, topiramate group and darbepoetin alpha+ topiramate group. Darbepoetin alpha and/or topiramate were administered on day 5 intraperitoneally (ip). At the 6th and 24th hours, bilirubin induced neurological dysfunction (BIND) score was used to assess behavioral changes. Hearing functions were evaluated on days 10 and 28. On day 30, the Water Maze water tank test was implemented to evaluate spatial memory. The rats were sacrificed on days 6 and 34 and apoptosis in the globus pallidus and hippocampus was examined. RESULTS: The BIND score was improved following darbepoetin alpha treatment. Neither darbepoetin alpha nor topiramate therapy ameliorate spatial memory. There were no significant differences between groups in terms of the auditory brainstem response (ABR). The combined use of darbepoetin alpha and topiramate lead to slight decrease in apoptosis. CONCLUSIONS: Darbepoetin alpha or topiramate administration ameliorates bilirubin induced neurological dysfunction in experimental model of kernicterus.

Metallic stent in the endoscopic treatment of pancreatic fluid collections.

BACKGROUND AND AIMS: The endoscopic treatment of pancreatic fluid collections (PFCs) has become the preferred first-line approach. Fully covered self-expandable metal stents (FCSEMS) were considered as an alternative to multiple double pigtail stents. The aim of this study was to evaluate the results of the endosonography guided drainage (EUS-GD) of PFCs with FCEMS. MATERIALS AND METHODS: A total of 33 consecutive patients were included. Cystogastrostomy and cystoduodenostomy were created with a linear echoendoscope under endosonographic and fluoroscopic control. Procedures were performed in a standard way of, puncture with a 19 gauge needle, bougie dilation and insertion of FCSEMS. RESULTS: A total of 33 patients (mean age 52 years, 21 men, range: 18-77 years), were included. PFCs were 22 non-infected symptomatic pseudocyst and 11 walled-off necrosis or abscess. EUS-GD was successful in 30 (90.9%) patients. Stent insertion failed in one patient. Two patients needed surgery. Complications were observed in 8 (25%) patients (stent dislocation in 3, perforation in 2, bleeding in 2 and pneumoperitoneum in 1 patient). Procedure related mortality was not seen. The mean cyst size was 11.3 cm (5-22). FCSEMS were successful in the treatment of pseudocysts (after 1 month mean cyst size is 6.2 cm, range: 0-15 cm, with 54.8% decrement rate). During a mean follow-up of 15 months complete resolution was 66.6% (20 patients) and recurrence due to stent malfunction was 10%. All these cases were submitted to a new session of endoscopic drainage. CONCLUSIONS: EUS-GD, FCSEMS insertion provides an effective, minimally invasive, and safe approach in the management of PFCs.

Does the estradiol level on the day of human chorionic gonadotropin administration predict the clinical outcome of controlled ovarian hyperstimulation?

OBJECTIVE: To investigate the effect of serum estradiol (E2) levels on the day of human chorionic gonadotropin (hCG) administration on the outcome of controlled ovarian hyperstimulation (COH) in both long gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist protocols. MATERIALS AND METHODS: This study included 212 in vitro fertilization-embryo transfer (IVF-ET) cycles performed with either long GnRH agonist or GnRH antagonist protocols were classified into three groups according to serum E2 levels measured on the day of hCG injection: < 2,000 pg/ml, 2,000-4,000 pg/ml, and > 4,000 pg/ml. The three groups were compared according to age, number of retrieved oocytes, number of transferred embryos, and pregnancy rates for each of the stimulation protocols. RESULTS: The long and antagonist protocols were performed in 130 and 82 cycles, respectively. The pregnancy rates were 21.5% (28/130) and 23.2% (19/82) in the long- and antagonist-protocol groups, respectively. Serum E2 levels were measured on the day of hCG administration as < 2,000 pg/ml in 65 cycles, 2,000-4,000 pg/ml in 76 cycles, and > 4,000 pg/ml in 71 cycles. The number of retrieved oocytes increased in parallel to serum E2 levels (p = 0.001). However, there was no significant difference among groups in the pregnancy rates (p = 0.116). Similarly, the number of retrieved oocytes increased in parallel to serum E2 levels in both of the protocol groups (p value was 0.001 in both long GnRH agonist and antagonist protocols), but there was no correlation between the pregnancy rates and serum E2 levels (p value of long GnRH agonist protocol was 0.254 and thep value of antagonist group was 0.349). CONCLUSION: The serum E2 level on the day of hCG administration does not predict the pregnancy outcome in IVF with either long GnRH agonist or GnRH antagonist protocols.

Long-term paracorporeal ventricular support systems: a single-center experience.

BACKGROUND: The Berlin Heart EXCOR is a first-generation paracorporeal, pneumatic ventricular assist device that creates pulsatile flow. It can be used for long-term support of the left and/or right ventricule during end-stage heart failure. The aim of this study was to share our clinical experience in 54 patients. METHODS: Between April 2007 and August 2012, 54 patients with end-stage heart failure underwent Berlin Heart EXCOR ventricular assist device implantation, including 5 females and 9 children. Twenty-four patients (44%) were in Intermacs level 1, 11 (21%) in level 2, and 19 (35%) in level 3. Biventricular support was applied to 13 patients. Device implantation was performed with an "on pump" beating heart technique while 6 other patients underwent intervention operations while the aortic valve has under cross-clamp. Tricuspid annuloplasty was performed in 6 patients. RESULTS: There was no peroperative death. Nine patients (17%) underwent re-exploration because of hemorrhage in the early postoperative period. Heart transplantation was performed in 32 patients (59%), while 10 (19%) are still under pump support with a mean follow-up of 13 months. Although 1 was successfully weaned from the system, 11 patients (20%) died during the support. Pump-head exchange was required 19 times in 17 patients because of visible thrombus or fibrin deposit in the pump head or due to membrane rupture. DISCUSSION: The use of long-term paracorporeal assist devices has decreased in recent years because of the increased popularity of implantable devices that permit longer survival and a better quality of life. We believe that the Berlin Heart EXCOR has a special role because it can be used in pediatric patients and especially in critical conditions like Intermacs levels 1 and 2.

Left ventricular assist device implantation in heart failure patients with a left ventricular thrombus.

BACKGROUND: In this report, we share our experience with left ventricular assist device (LVAD) implantation in cases with a left ventricular (LV) thrombus. METHOD: Over the 3 years, more than 100 end-stage heart failure cases have been treated with LVAD implantation in our center, including 6 patients with a LV thrombus. Three were detected using preoperative transthoracic echocardiography. Fifty percent of the patients had dilated cardiomyopathy and the remaining cases had an ischemic etiology. Double inotropic support with dopamine and dobutamine was used in all, with 3 drugs with the addition of adrenaline in 2 patients. In 4 cases we implanted the HeartWare Ventricular Assist System (HeartWare, Inc., Miramar, Fla, United States) and in the remaining 2 patients, the Berlin Heart EXCOR ventricular assist device (Berlin Heart AG, Berlin, Germany) for biventricular support. In 1 patient the apical ventriculotomy was extended to remove an intertrabecular thrombosis and ventricular septal surface covered with a dacron patch to minimize the thrombogenic potential. RESULTS: Two patients died due to sepsis and multiorgan failure. None of the patients experienced a neurological event, pump thrombosis, or pump malfunction. Two subjects underwent re-explorations due to hemorrhage. Two candidates underwent successfull transplantation without any evidence of thrombosis in the explanted heart or device. CONCLUSION: We believe that patients with a LV thrombus and preserved right ventricular function are good candidates for implantation of a LVAD after removing the intracavitary thrombus.

Effect of aortic valve movements on gastrointestinal bleeding that occured in continuous flow left ventricular assist device patients.

BACKGROUND: Gastrointestinal (GI) bleeding is one of the recently reported complications with continuous flow left ventricular assist devices (LVAD). The pathophysiology and etiology are unclear. We sought to describe the relationship between aortic valve movements and GI bleeding among patients with a new generation of LVAD. METHODS: We evaluated the data of 30 patients who underwent LVAD (HeartWare VAD) implantation from December 2010 to September 2012. The most common etiologic diagnosis was dilated cardiomyopathy. Patients were considered to show GI bleeding if they had hematemesis, melena, or hematochezia. RESULTS: Among 3 patients, 2 displayed upper GI bleeding and 1 had lower GI bleeding based on endoscopic and colononoscopic examinations. Pathological reports showed arteriovenous malformations in patients diagnosed with upper GI bleeding. The absence of aortic valve movements and a history of previous GI bleeding were significant risk factors (P = .021 and P = .007, respectively). CONCLUSION: In addition to aortic valve movements, we believe that a GI bleeding history was an equally important factor predisposing to this complication.

Valvular procedures during ventricular assist device implantation.

BACKGROUND: Increased experience and success with ventricular assist devices (VAD) has permitted more aggressive use in patients formerly believed to be inappropriate for mechanical circulatory support (MCS). There is no clearly proven policy to manage end-stage heart failure patients with valvular pathologies. The aim of this report was to analysis our experience with combined approach of VAD implantation and valvular procedures among patients with valvular heart disease and end-stage heart failure. METHODS: We evaluated the clinical records of 67 patients who underwent MCS from April 2007 to September 2011. We identified 12 patients (17.9%) who received concomitant valvular procedures, four of whom had significant aortic insufficiency and received a simple coaptation stitch at the center to approximate the fibrous nodules of Arantius. The mechanical aortic valve was replaced with a stentless bioprosthesis in three patients. Mitral valve commissurotomy was performed in one patient with mitral stenosis and seven patients underwent tricuspit valve repair using an annuloplasty ring. RESULTS: All 12 patients were males, of mean age 50.3 ± 11.5 years (range = 25-66). Eleven of them (91.6%) survived the early and late postoperative periods. Ten subjects (83.3%) continue to be supported with VAD; 1 (8.3%) was successfully bridged to transplantation. Each study participant regression of the valvular pathologies by early echocardiography demonstrated. CONCLUSION: Concomitant valve surgery during VAD implantation appeared to be a reasonable option in end-stage heart failure patients with valvular heart disease.

Comparison of the detection of influenza A and B viruses by different methods.

OBJECTIVE: To investigate the detection of influenza viruses by three different methods. METHODS: Nasopharyngeal swabs were collected from patients with influenza symptoms and examined for influenza A and B viruses using a rapid antigen test, a multiplex polymerase chain reaction (PCR) test and a shell vial cell culture test. RESULTS: Using the shell vial cell culture test, the rapid antigen test and the multiplex PCR test in 130 patients, 31 (23.8%), 24 (18.5%) and 24 (18.5%) samples, respectively, were positive for influenza A and 10 (7.7%), nine (6.9%) and four (3.1%) samples, respectively, were positive for influenza B. Compared with the shell vial test, the sensitivity, specificity, and positive and negative predictive values of the rapid antigen test were 77.4%, 93.3%, 80.0% and 93.1%, respectively, for influenza A, and 90.0%, 95.8%, 64.2% and 99.1%, respectively, for influenza B. The corresponding values for the multiplex PCR test were 77.4%, 95.9%, 85.7% and 93.1%, respectively, for influenza A, and 40.0%, 97.5%, 57.1% and 95.1%, respectively, for influenza B. CONCLUSIONS: The multiplex PCR test and the rapid antigen test are both effective in the detection of influenza A and B viruses.

Evaluation and comparison of three different anti-hepatitis C virus antibody tests based on chemiluminescence and enzyme-linked immunosorbent assay methods used in the diagnosis of hepatitis C infections in Turkey.

The routine diagnosis of hepatitis C virus (HCV) infection is based on the detection of anti-HCV antibodies by two main methods (enzyme immunoassay [EIA] and chemiluminescence immunoassay [CIA]) but false-positives are a problem. We investigated three anti-HCV tests: two CIAs (Cobas e 601 and Architect i2000SR); and one EIA (Ortho HCV 3.0). Two other anti-HCV tests were also performed as supplementary and confirmatory tests, respectively: a recombinant strip immunoblot assay (RIBA HCV 3.0 SIA) and a reverse transcriptase polymerase chain reaction-based assay for HCV-RNA. After discriminating the false-positive results, the true anti-HCV seropositivity rate in 7156 serum samples was 0.91%. The seropositivity and false-positive rates for the Cobas e 601, Architect i2000SR and Ortho HCV 3.0 anti-HCV tests were 1.9% and 0.99%, 1.2% and 0.29%, and 0.87% and 0.01%, respectively. The mean level of HCV-RNA was 3399 x 10(3) IU/ml. Critical levels for false-positivity for HCV-RNA were a cut-off index of 200 for Cobas e 601, a signal/cut-off (S/CO) of 5 for Architect i2000SR and an S/CO of 1.2 for Ortho HCV 3.0. Positive and negative results for the RIBA HCV 3.0 SIA assay all accorded with the HCV-RNA assay, except for 23 (17%) 'indeterminate' results, all of which were negative with the HCV-RNA assay. In conclusion, to eliminate doubts related to false-positive findings in the initial HCV screening tests, additional confirmatory HCV-RNA assay should be performed.

Effects of endometrial thickness and echogenic pattern on assisted reproductive treatment outcome.

PURPOSE: To assess the effects of endometrial thickness and echogenicity on pregnancy and implantation rates in cases using assisted reproductive technology (ART). METHODS: We retrospectively analyzed the data of 241 ART cycles performed at Istanbul Medical Faculty, Reproductive Endocrinology Unit. The cycles were classified into three groups according to ultrasonographic endometrial thickness measurements on the day of hCG application; 51 cases (group 1) < or =8 mm, 182 cases (group 2) between 8-14 mm, and eight cases (group 3) 14 mm. Also the cycles were grouped according to endometrial echogenicity as trilaminar, isoechogenic and hyperechogenic pattern. RESULTS: There was no significant difference in pregnancy rates between the three endometrial thickness groups and echogenic patterns. When conception and non-conception cycles were compared, no significant difference in endometrial thickness was observed (9.88 +/- 1.83 mm vs 9.84 +/- 1.89 mm). CONCLUSION: Ultrasonographic evaluation of endometrial thickness and pattern is not useful in predicting implantation and conception rates in ART cycles.

Clinical and molecular progress in hereditary paraganglioma.

Hereditary paraganglioma (PGL) is characterised by genetic predisposition to the development of highly vascular tumours of the paraganglionic tissues and caused by germ line inactivating mutations in the SDHB, SDHC and SDHD subunits of mitochondrial succinate dehydrogenase enzyme complex (SDH; mitochondrial complex II). Recent studies have demonstrated that SDH gene mutations in germ line occur in at least 11% of non-familial head and neck paragangliomas, 8% of non-familial pheochromocytomas, 28% of malignant pheochromocytomas and 33% of extra-adrenal pheochromocytomas. An increasing amount of data suggest that PGL mutations lead to constitutive activation of hypoxia signalling pathways. Genetic and structural models suggest that SDH mutations cause an accumulation of succinate and reactive oxygen species (ROS) which might act as downstream signalling molecules that activate hypoxia inducible pathways. However, many fundamental aspects of PGL pathogenesis, including the mechanism of ROS accumulation, the imprinted transmission pattern of SDHD mutations, and the precise role of SDH in regulation of oxygen homeostasis, remain poorly understood.

[Rehabilitation of lung cancer patients]. / Rehabilitation bei Patienten mit Lungenkarzinom.

In the industrial world incidence and prevalence of lung cancer are increasing. At the same time new drugs and new therapies can improve cure rates, prolong survival and procure better quality of life. Nowadays, oncology provides multimodal therapies which may cause psychological and physical stress in the often multimorbid patients. Furthermore, the tumour itself may cause pain and bring about special nutritional and coping problems. Patients may face fear and depression, nicotine withdrawal, socioeconomic problems and the risk of permanent disability. The sequelae of multimodal therapies can vary according to the chosen procedure such as surgery, radiotherapy, chemotherapy, and hormone or immune treatment. After the end of treatment, rehabilitation needs to address the never-ending fear of disease relapse, dyspnoea and suffocation feelings as well as the psychological problems associated with lung cancer. At the initiation of rehabilitation, physical performance is usually limited by the underlying disease as well as the different therapeutic modalities. In Germany, rehabilitation is mainly carried out as in-patient rehabilitation in specialised oncological or pneumological rehabilitation centres. The analysis of published data shows that in-patient rehabilitation has not been evaluated sufficiently for its efficiency so far. This also applies to out-patient rehabilitation, which is largely unavailable in Germany. Oncologists, pneumologists and patient groups agree that rehabilitation should be offered or even strongly recommended to all lung cancer patients.

Evaluation of serum hyaluronic acid level and hyaluronidase activity in acute and chronic hepatitis C.

Following major tissue injury, hyaluronic acid production increases as a rapid response survival mechanism. Increased hyaluronic acid production and turnover are often associated with increased hyaluronidase activity, the enzyme that degrades hyaluronic acid. We investigated whether hyaluronic acid and hyaluronidase can be used as non-invasive markers of acute disease activity in hepatitis C by studying 26 patients with acute hepatitis C, 89 with chronic hepatitis C and 32 healthy controls. Chronic hepatitis C subjects were classified into five subgroups according to the stage of liver fibrosis. Serum aspartate aminotransferase and alanine aminotransferase activities and hyaluronic acid levels were increased in hepatitis C patients compared with the controls. Serum hyaluronic acid elevation correlated with disease progression. Serum hyaluronidase activities were also increased in patients compared with the controls, but decreased with disease progression. We conclude that both hyaluronidase and hyaluronic acid may be useful as early non-invasive serum indicators of disease activity in acute hepatitis C.

Emotional distress of infertile women in Turkey.

OBJECTIVE: To determine the prevalence, severity and predictability of psychiatric symptoms of infertile women and the effects of infertility on marital and sexual relationships. METHODS: A semi-structured interview form, symptom check list, Beck Depression Inventory, State-Trait Anxiety Inventory and the Maudsley Marrital Questionnaire were utilized for 50 infertile women and 40 healthy women as a control group. RESULTS: Depression, anxiety and strength of psychological symptoms were significantly higher in the infertile group. Depression was decreased as the rate of employment, economic status and education increased. Infertility, infertility treatment, and marriage duration were positively correlated with depression and the strength of psychological symptoms. Sexual relationships were negatively affected the longer the duration of infertility treatment lasted. CONCLUSION: Special attention must be given to identifying psychiatric problems in infertile women. Relationship and sexual difficulties also appear central to infertility-related stress; targeting problems in these domains will have maximal therapeutic benefit.

Detection and evaluation of salivary antibodies to Helicobacter pylori in dyspeptic patients.

Helicobacter pylori infection is one of the most prevalent infections in humans. The high prevalence and the association with peptic ulceration and gastric cancer require simple and non-invasive methods for the diagnosis of the infection. Detection of salivary anti-H. pylori IgG antibodies has advantages compared with those on serum. In this study, salivary immunoglobulin G response to H. pylori was evaluated in 100 consecutive dyspeptic patients by enzyme-linked immunosorbent assay (ELISA), in comparison with culture and histopathologic examination of gastric biopsy specimens obtained at endoscopic procedures and assessed the accuracy of salivary diagnosis of the infection. The overall sensitivity and specificity of the test were 87 and 73%, respectively. These results suggest that saliva testing for H. pylori antibodies could be used reliably for screening dyspeptic patients in general practice, especially in children in whom venesection is more difficult.