Screening of 23 candidate genes by next-generation sequencing of patients with permanent congenital hypothyroidism: novel variants in TG, TSHR, DUOX2, FOXE1, and SLC26A7.

PURPOSE: To date, many genes have been associated with congenital hypothyroidism (CH). Our aim was to identify the mutational spectrum of 23 causative genes in Turkish patients with permanent CH, including thyroid dysgenesis (TD) and dyshormonogenesis (TDH) cases. METHODS: A total of 134 patients with permanent CH (130 primary, 4 central) were included. To identify the genetic etiology, we screened 23 candidate genes associated with CH by next-generation sequencing. For confirmation and to detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. RESULTS: Possible pathogenic variants were found in 5.2% of patients with TD and in 64.0% of the patients with normal-sized thyroid or goiter. In all patients, variants were most frequently found in TSHR, followed by TPO and TG. The same homozygous TSHB variant (c.162 + 5G > A) was identified in four patients with central CH. In addition, we detected novel variants in the TSHR, TG, SLC26A7, FOXE1, and DUOX2. CONCLUSION: Genetic causes were determined in the majority of CH patients with TDH, however, despite advances in genetics, we were unable to identify the genetic etiology of most CH patients with TD, suggesting the effect of unknown genes or environmental factors. The previous studies and our findings suggest that TSHR and TPO mutations is the main genetic defect of CH in the Turkish population.

Idiopathic Pulmonary Hypertension After Liver Transplantation.

Pulmonary hypertension is one of the problems that can be encountered before liver transplantation. It is not expected in cases with no additional disease in postoperative period. Herein, we report on a 43-year-old woman who developed idiopathic pulmonary hypertension in the early postoperative period. Further investigation both pathologically and clinically is needed in patients undergoing living donor liver transplantation that may help to solve the problems such as pulmonary arterial hypertension before it occurs and manage complex hemodynamic changes successfully in the future.

Varicella-Zoster Virus-Induced Hepatitis in a Liver Transplant Recipient: A Case Report.

Infections after solid organ transplantation are a major cause of mortality and morbidity. Varicella-zoster virus (VZV) infection after solid organ transplantation is rare. Here we present a case presenting with acute hepatitis and shingles after a liver transplantation (LT). A 36-year-old male patient underwent a liver transplantation; 7 months later his liver function tests increased. An examination and test results revealed that he had VZV-induced hepatitis. After VZV treatment, his test results returned to normal levels. Hepatic involvement of VZV infection is rare, but it may be fatal in immunocompromised individuals. Early diagnosis and early initiation of antiviral therapy is important in the control of hepatitis and rare hepatotropic viruses in immunocompromised individuals.

Physical activity in women with subclinical hypothyroidism.

PURPOSE: Physical activity is associated with many health-related benefits. However, there is a shift towards inactive lifestyles around the world. Subclinical hypothyroidism (SCH) may have adverse effects similar to hypothyroidism. The presence of symptoms and reduced physical performance in SCH may contribute to an inactive lifestyle. Therefore, the present study aimed to compare physical activity levels (PALs) between women with subclinical hypothyroidism and healthy controls. METHODS: Thirty-two women with newly diagnosed SCH and 28 healthy women were enrolled in this cross-sectional study. Arterial stiffness was evaluated by pulse wave velocity (PWV). Neuromuscular symptoms were questioned. Participants wore a physical activity monitor (SenseWear® Armband) for 4 consecutive days. Handgrip and quadriceps muscle strength were assessed by dynamometer. Functional exercise capacity was assessed by 6-minute walk test (6MWT). RESULTS: There was no significant difference in sociodemographic variables between the groups. PWV was significantly higher in the SCH group (P = 0.006). Physical activity duration and number of steps were significantly lower in the SCH group (P < 0.05). There was significant difference in neuromuscular symptoms, handgrip and quadriceps muscle strength, and 6MWT distance between the groups (P < 0.05). CONCLUSIONS: This study demonstrates that women with SCH had lower PALs compared to healthy controls. Women with SCH should participate in exercise programs to increase physical activity and muscle strength to achieve adequate PALs.

Comparison of the effects of the L-dopa and insulin tolerance tests on cortisol secretion.

PURPOSE: The aims of the present study are to evaluate the effect of L-dopa on the secretion of cortisol and adrenocorticotropic hormone (ACTH) in short children and compare the performance of this test with the insulin tolerance test (ITT) in a large number of patients. METHODS: A total of 29 short but otherwise healthy children [mean age 9.5 ± 3.1 years (range 3.7-14.9 years)] who had inadequate growth hormone (GH) responses to ITT, which was performed as the first test, were consecutively enrolled in this study. GH, cortisol, and ACTH levels were measured just before administration of L-dopa and then at 30-min intervals afterward over a total time of 120 min. Peak concentrations of cortisol and ACTH exceeding 18 µg/dL (496 mmol/L) and 46 pg/mL (10.2 pmol/L), respectively, were defined as an adequate response. RESULTS: While the L-dopa test revealed that 26 of the 29 children (89.7%) had peak serum cortisol levels of > 18 µg/dL, the ITT revealed that only 23 children (79.3%) had adequate cortisol responses. The L-dopa test revealed normal ACTH responses (> 46 pg/mL) in 24 (82.8%) patients. Peak cortisol levels were higher in children with normal ACTH responses than in those with subnormal ACTH responses (25.6 ± 6.2 vs. 19.5 ± 6.4 µg/dL, p = 0.054), but the difference observed was statistically insignificant. CONCLUSION: The results of the current study confirm that the L-dopa test is a reliable test of cortisol secretion. As such, this test may be applicable to assessments of the hypothalamic-pituitary-adrenal axis.

Liver Transplantation for Polycystic Liver Disease Due to Huge Liver With Related Complications: A Case Report.

Polycystic liver disease is characterized by multiple cystic lesions on the liver. It is an uncommon autosomal dominant disease. The cysts' diameters range from 20 to 30 cm to small microscopic nodules. Generally, more than half of the liver parenchyma is covered. The mass effect of the liver created by the large cysts can cause life-threatening symptoms such as weight loss, reduction of oral intake, and malnutrition. Liver transplantation is the best treatment option in symptomatic patients. We present a patient who had polycystic liver and kidney disease, and we performed liver transplantation because of his life-threatening symptoms.

Value of ultrasound shear wave elastography in the diagnosis of adenomyosis.

BACKGROUND: The aim of the study was to assess the accuracy of ultrasound shear wave elastography in the diagnosis of adenomyosis. METHODS: One hundred and fifty three patients were examined. Ninety-seven patients were with suspected adenomyosis and 56 patients were with unremarkable myometrium. Adenomyosis was confirmed in 39 cases (A subgroup) and excluded in 14 cases (B subgroup) in the main group based on morphological examination. All patients underwent ultrasound examination using an Aixplorer (Supersonic Imagine, France) scanner with application of shear wave elastography during transvaginal scanning. Retrospective analysis of the elastography criteria against the findings from morphological/histological examination was performed. RESULTS: The following values of Young's modulus were found in subgroup A (adenomyosis): Emean - 72.7 (22.6-274.2) kPa (median, 5-95th percentiles), Emax - 94.8 (29.3-300.0) kPa, SD - 9.9 (2.6-26.3) kPa; in subgroup B (non adenomyosis) - 28.3 (12.7-59.5) kPa, 33.6 (16.0-80.8) kPa, 3.0 (1.4-15.6) kPa; in the control group - 24.4 (17.9-32.4) kPa, 29.8 (21.6-40.8) kPa, 2.3 (1.3-6.1) kPa, respectively (P < 0.05 for all comparison with subgroup В and the control group). The Emean cut-off value for adenomyosis diagnosis was 34.6 kPa. The sensitivity, specificity, positive predictive value, negative predictive value and area under curve (AUC) were 89.7%, 92.9%, 97.2%, 76.5% and 0.908. The Emax cut-off value was 45.4 kPa (89.7%, 92.9%, 97.2%, 76.5% and 0.907, respectively). CONCLUSION: This study showed a significant increase of the myometrial stiffness estimated with shear wave elastography use in patients with adenomyosis.

Utility of superior mesenteric artery Doppler and maternal pancreatic size for predicting gestational diabetes mellitus.

AIM: The aim of this study was to assess the relationship between the maternal superior mesenteric artery Doppler, pancreatic size and gestational diabetes mellitus (GDM). METHODS: Two hundred and fifty-eight consecutive, pregnant women between 20 and 22 weeks of gestation underwent routine fetal anomaly screening. All subjects underwent maternal superior mesenteric artery Doppler and pancreatic size measurement of head, corpus and tail during screening. Screening was done with 50 g glucose challenge test (GCT) at gestational age 24-28 weeks. The patients who were having an abnormal GCT were subjected to 100 g GCT. Subjects were divided into two groups such as pregnancies with gestational diabetes and normal pregnancies. Relationship between Doppler and pancreatic measurements with GDM was analyzed. RESULTS: Out of 258 screened pregnancies, 28 (10.9 %) were diagnosed as GDM. There were significant differences between GDM positive and negative cases in terms of pancreatic body size (17.5 vs. 14.4 mm, p = 0.05), superior mesenteric artery Doppler systolic/diastolic ratio (S/D) (4.2 vs. 3.4) and resistance index (RI) (0.72 vs. 0.68) values. Superior mesenteric artery Doppler S/D (AUC = 0.761, p < 0.001) and RI (AUC = 0.762, p < 0.001) indices were significant predictors for GDM. CONCLUSION: Superior mesenteric artery Doppler and pancreatic size evaluation may be utilized to detect abnormal glucose metabolism during pregnancy care.

Effects of ELF magnetic field in combination with Iron(III) chloride (FeCl3) on cellular growth and surface morphology of Escherichia coli (E. coli).

This study investigated the effects of extremely low frequency (ELF) magnetic field with/without iron(III) chloride (FeCl3) on bacterial growth and morphology. The ELF exposures were carried out using a pair of Helmholtz coil-based ELF exposure system which was designed to generate 50 Hz sinusoidal magnetic field. The field was approximately uniform throughout the axis of the coil pair. The samples which were treated or non-treated with different concentrations FeCl3 were exposed to 50 Hz, 2 millitesla (mT) magnetic field for 24 h. ELF effect on viability was assessed in terms of viable colony counts (in colony-forming unit per milliliter) with the standard plate count technique. Scanning electron microscopy was used to investigate the magnetic field effect on surface morphology of Escherichia coli. No significant results were seen in terms of cell viability between ELF and sham-exposed bacterial strains. Similarly, FeCl3 treatment did not change cell viability of E. coli samples. However, we observed some morphological changes on E. coli cell surfaces. Pore formations and membrane destruction were seen on the surface of 24 h ELF field-exposed cells. We concluded that ELF magnetic field exposure at 2 mT does not affect cell viability; however, it may affect bacterial surface morphology.

Serum osteopontin and CD44 levels in lymphoreticular malignancies in children.

OBJECTIVE: Osteopontin (OPN) is an adhesive glycoprotein that interacts with a variety of cell surface receptors, including several integrins and CD44. OPN is expressed and secreted by numerous human malignancies. CD44 play an important role in tumor growth and metastasis. We aimed to evaluate serum levels of osteopontin and CD44 in patients with lymphorethicular malignancies in childhood. METHODS: We studied serum levels of CD44 and OPN levels of 54 patients (26, 18 and 10 patients with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL) and acute lymphoblastic leukemia (ALL), respectively) at the diagnosis. RESULTS: The mean levels of OPN were significantly higher in patients (5.42±8.24 ng/ml) than in controls (3.89 ±1.96 ng/ml). The mean levels of CD44 levels were also significantly higher in patients (3.82±2.31 ng/ml) than in controls (1.96±0.62 ng/ml), and significantly higher in the advanced stages than in early stages. The mean levels of the CD44 in NHL, HL and ALL were 3.49±2.00, 3.56±1.74, and 5.15±3.50 respectively. OPN and CD44 levels were found to be increased in parallel (p=0.003). A more advanced disease and/or poor prognostic factors were seen in 9 patients who had both serum CD44 and OPN levels higher than 2SD of the control. CONCLUSION: Elevated levels of both CD44 and OPN at the diagnosis may predict an unfavorable outcome in childhood leukemias and lymphomas (Tab. 2, Fig. 3, Ref. 44).

Immunologic and psychosocial status in chronic fatigue syndrome.

OBJECTIVE: The aim of the study was to investigate the immunologic functions and psychosocial status in patients with chronic fatigue syndrome (CFS). METHODS: Twenty-five patients with CFS diagnosed by the international CFS definition criteria and 20 age- and gender-matched healthy controls were recruited. Depression was assessed by Beck Depression Inventory (BDI) and health status was assessed by Nottingham Health Profile (NHP). Monoclonal antibodies (MAbs) were measured to identify the following NK cell subsets: CD3, CD4, CD8 and CD56 and cytokine measurements were performed for IL2r, IL6 and IL8 in both patients and control subjects. RESULTS: The BDI and NHP scores of CFS group were found to be significantly higher than in the control group. The absolute numbers of CD56 cell were also significantly decreased in the patients with CFS compared with the healthy controls. There were no other significant differences of NK cell activity (CD3, CD4 and CD8) and there were significant differences in IL6 and IL2r levels between patients and controls. There were significant correlations between serum IL-6 level and sleep, social isolation and physical ability NHP subscores, and betweenCD56 NK cell activity and emotional reaction NHP sub score in CFS patients. CONCLUSION: Significantly higher ratios of psychological and physical disturbances were found in patients with CFS. Decreased CD56 NK cell activity and increased IL2r levels seem to be important immunopathologic changes in CFS. IL-6 and CD 56 NK cell activity may play an important role in sleep, physical, social, and physicological manifestations of CFS (Tab. 3, Fig. 1, Ref. 36). Full Text in free PDF www.bmj.sk.

Is nerve stimulation needed during an ultrasound-guided lateral sagittal infraclavicular block?

BACKGROUND: The objective of the study was to evaluate the influence of ultrasound (US) guidance alone vs. neurostimulation (NS) and US (NSUS) guidance techniques on block performance time and block success rate for the lateral sagittal infraclavicular block (LSIB). METHODS: In a randomized and prospective manner, 110 adult patients scheduled for distal upper limb surgery were allocated to the US or the NSUS groups. In the US group, a local anesthetic (LA) was administered only with US guidance to produce a 'U'-shaped distribution around the axillary artery. In the NSUS group, LA was administered under US guidance only after electrolocation of one of the median, ulnar or radial nerve-type responses. A total of 30 ml of LA (10 ml of levobupivacaine 5 mg/ml and 20 ml of lidocaine 20 mg/ml) was administered in both groups. Sensory block was tested at 10 min intervals for 30 min. Successful block was defined as analgesia or anesthesia of all five nerves distal to the elbow. RESULTS: Block success rate was 94.5% in both groups. Block performance time was significantly shorter in the US than the NSUS group (157 +/- 50 vs. 230 +/- 104 s) (P=0.000). Block onset time was similar in both groups (12.5 +/- 4.8 in the US vs. 12.8 +/- 5.4 min in the NSUS groups). There were two arterial punctures in the NSUS group. CONCLUSIONS: During LSIB performance US guidance alone produces block success rate identical to both US and NS guidance yet with a shorter block performance time.

Comparison of nerve stimulation vs. ultrasound-guided lateral sagittal infraclavicular block.

BACKGROUND: A nerve stimulation-guided lateral sagittal infraclavicular block (LSIB) has been proven to be an effective block. The purpose of this study was to evaluate whether the use of ultrasound (US) guidance would further improve the block quality of LSIB. METHODS: In a prospective manner, 80 adult patients scheduled for hand, wrist and forearm surgery were randomly allocated to US or nerve stimulation (NS) groups. A needle was inserted into a sagittal plane, 20 degrees dorsally, until muscle twitches were observed in synchrony with the stimulation. In the US group, the block was performed using the same puncture site but under ultrasonic guidance. The final position of the needle was verified with the use of a nerve stimulator. A local anesthetic mixture of 20 ml of levobupivacaine, 5 mg/ml and 20 ml of lidocaine and 20 mg/ml with 5 microg/ml epinephrine (total 40 ml) was administered in both groups. RESULTS: The block was successful in 37 patients in the NS group and 38 patients in the US group. Block efficacy was better in the US group than the group NS in radial nerve distribution at 20 min (P<0.05). In the US group, there was a slight tendency toward better block density in other nerve areas also but these differences were not significant. Vascular puncture was noted in three patients in the NS group and none in the US group. CONCLUSIONS: The block success rate was high and comparable in both groups. There was a trend toward improved block quality in the US group, although not significant.

Electrocardiographic findings after 5-HT3 receptor antagonists and chemotherapy in children with cancer.

BACKGROUND: The antiemetic efficacy of serotonin-type 3 (5-HT3) receptor antagonists has been found to be superior to older antiemetic drugs in cancer patients. Following the administration of these agents, changes in ECG parameters and increased or decreased heart rates have been demonstrated, but there is no sufficient data in children with cancer who are treated with cytotoxic agents. The objective of this study is to evaluate the ECG changes after administration of 5-HT3 receptor antagonists and chemotherapeutic agents in children with cancer. PROCEDURE: Thirty-eight patients with an age range between 2 and 19 years receiving chemotherapy for solid tumors were included in the study. The patients received 5-HT3 receptor antagonists 30 min before antineoplastic agents in 83 chemotherapy days. Antiemetic therapy consisted of ondansetron in 43 and granisetron in 40 chemotherapy days. Twelve-leads ECGs were obtained four times at the first day of each chemotherapy: just before 30, 90 min, and 24 hr after 5-HT3 receptor antagonists were given. Rate, rhythm, PR interval, QRS duration, ST segment, the shortest (QTca) and the longest (QTcb) QTc intervals with QTc dispersion (QTcd) were all evaluated. RESULTS: We found a significant shortening of the PR interval and QRS complex durations in the granisetron group at 90th min and at 24th hr, respectively. Also, granisetron infusion caused a significant prolongation of the QTca interval at 90 min. CONCLUSION: Although we observed minor ECG changes after 5-HT3 receptor antagonists and chemotherapy, neither dangerous rhythm disturbances nor serious ECG changes were seen.

Arthroscopic-assisted percutaneous stabilization of patellar fractures.

The authors did percutaneous, arthroscopic-assisted osteosynthesis of patellar fractures associated with skin abrasions and lacerations in 11 patients. Skin problems did not delay the operation and the rehabilitation. The average followup was 2.8 years. All fractures healed without complications and good results were obtained in all patients using the criteria of Levack et al. This technique avoids the problems of patellar fractures with skin abrasions and may be adapted to other fractures of the patella.

Effects of various irrigating solutions on articular cartilage. An experimental study in rabbits.

The effect of six different solutions (normal saline, ringer's lactate, chlorhexidine, povidone iodine, ceftriaxone, chloramphenicol) on articular cartilage was investigated in an in vivo rabbit model study. The right knees were aspirated and injected with one of these solutions for five days and, three days later, the patellae of the rabbits were excised and investigated histologically. Left knees were used as controls. There was no difference between the groups and the controls with respect to structure, cell density, and nuclei-to-lacunae ratio. These results suggest that, these solutions have no noxious effects on articular cartilage when used as irrigating fluids in orthopaedic practice.

Oxidant status increased during fracture healing in rats.

We evaluated oxidant status during bone healing in 50 rats. In 40 rats, the right tibia was fractured and fixed intramedullarly (study leg) and the left tibia was pinned but not fractured (control leg). Rats were killed on days 1, 3, 7, 14, 28 and malondialdehyde (MDA) levels were determined in tibial bone tissue. The MDA levels of study and control legs were compared with basal MDA levels in bone in 10 rats. There was no apparent difference between the basal level and control legs, but the study legs showed a statistically significant increase in MDA levels on days 7 and 14. We conclude that no oxidative stress injury occurs during the ischemic period of fracture healing, but it may be significant during inflammation and the formation of callus.

Excimer laser photorefractive keratectomy (PRK) in myopic astigmatism.

UNLABELLED: To assess the visual and refractive results of excimer laser photorefractive keratectomy (PRK) in myopic astigmatism. METHODS: Excimer laser PRK was performed using an Aesculap Meditec MEL 60 laser in 46 myopic astigmatic eyes. Preoperative corneal astigmatism was -1.50 D. (+/- 0.50) in 7 eyes (15.2%); -2.50 D. (+/- 0.50 in 14 eyes (30.5%); -3.50 D. (+/- 0.50) in 13 eyes (28.3%); -4.50 D. (+/- 0.50) in 8 eyes (17.4%); and -5.50 D. (+/- 0.50) in 4 eyes (8.6%). Mean preoperative cylinder was -3.50 D. (+/- 2.50). Mean preoperative sphere was -4.50 D. (+/- 2.25). Pre and post-operative visual acuity, refraction, keratometer readings, corneal topography, intraocular pressure, and slit lamp findings were recorded. RESULTS: By one year of follow-up, postoperative cylinder was between +0.50 and -0.50 D. in 31 eyes (67.4%); between -0.50 and -1.50 D. in 11 eyes (23.9%); between -1.50 and -2.50 D. in 4 eyes (8.7%). Mean post-operative cylinder was -1.21 D. (+/- 1.70). Mean postoperative sphere was -1.09 D. (+/- 1.25). Myopic and astigmatic improvement was achieved in each patient (100%). Topography analysis showed 69.4% were within 0.5 mm, 96.8% within 1 mm, 97.8% within 1.5 mm of centration; 55% of the patients achieved uncorrected visual acuity of 10/10 (Snellen). One patient (2.2%) lost one line of best corrected vision due to decentration and change of axis. CONCLUSION: These preliminary results of myopic astigmatic excimer laser PRK procedures compare favorably in efficiency and safety with reports of PRK for myopia.

[The value of laboratory tests for the early diagnosis of newborn sepsis]. / Yenidogan sepsisinin erken tanisinda laboratuvar testlerinin degeri.

In our study, laboratory tests were evaluated in the early diagnosis of newborn sepsis. The study consisted of 53 newborn infants with the diagnosis of suspected sepsis. Of the 53 newborn infants twenty seven were excluded from the study, because of negative blood culture. Remaining 26 newborns with positive blood culture and 15 healthy newborns comprised the study (sepsis group) and control group respectively. Total mature neutrophil count, immature/total neutrophil and immature/matür neutrophil ratio, toxic granulation changes, serum level of C-reactive protein and haptoglobin were found statistically higher in sepsis group than control group. Thrombocyte count and serum level of IgG were significantly lower in sepsis group. Average total white blood cell count, result of nitroblue tetrazolium tests erythrocyte sedimentation rate and serum level of IgM was similar in both groups. We emphasized that hematological scoring system, serum level of C-reactive protein and haptoglobins can be used in the early diagnosis of newborn sepsis.