Four new cases of congenital secondary hypothyroidism due to a splice site mutation in the thyrotropin-beta gene: phenotypic variability and founder effect

Isolated TSH deficiency is a rare cause of congenital hypothyroidism. We here report four children from two consanguineous Turkish families with isolated TSH deficiency. Affected children who were screened at newborn age had an unremarkable TSH result and a low serum TSH level at diagnosis. Age at diagnosis and clinical phenotype were variable. All affected children carried an identical homozygous splice site mutation (IVS2 + 5 G--> A) in the TSHbeta gene. This mutation leads to skipping of exon 2 and a loss of the translational start codon without ability to produce a TSH-like protein. However, using specific monoclonal antibodies, we detected a very low concentration of authentic, heterodimeric TSH in serum, indicating the production of a small amount of correctly spliced TSH mRNA. By genotyping all family members with polymorphic markers at the TSHbeta locus, we show that the mutation arose on a common ancestral haplotype in three unrelated Turkish families indicating a founder mutation in the Turkish population. These results suggest that this TSHbeta mutation is among the more common TSHbeta gene mutations and stress the need for a biochemical and molecular genetic workup in children with symptoms suggestive of congenital hypothyroidism, even when the neonatal TSH screening is normal.     

A multicenter retrospective study defining the clinical and hematological manifestations of brucellosis and pancytopenia in a large series: Hematological malignancies, the unusual cause of pancytopenia in patients with brucellosis

The aim of the study is to review the clinical manifestations and the hematological findings of brucellosis and pancytopenia, with or without hematological malignancies. The records of 202 patients with brucellosis were evaluated retrospectively. Among these cases of brucellosis seen in a 6 year period between April 1999 and June 2005, 30 patients with pancytopenia were identified. The most common manifestation was fever, followed by weight loss, anorexia, malaise, arthralgia, and hepatosplenomegaly. Bone marrow biopsies revealed hypercellularity or normocellularity. The most common findings in the bone marrow evaluation were histiocytic hemophagocytosis and granulomas. Among all cases, we diagnosed 5 hematological malignancies (1 acute myelogenous leukemia, 2 acute lymphoblastic leukemia, and 2 multiple myeloma) concurrently with brucellosis. The clinical symptoms and findings were similar in patients with and without malignancies. In cases with malignancies, the bone marrow biopsy revealed predominant primary disease involvement. Significant increases in ESR and CRP, severe anemia and thrombocytopenia were observed in patients with malignancies. Peripheral blood counts in patients without malignancies returned to normal after antibiotic treatment for brucellosis. However, pancytopenia in two patients with malignancies did not recover because of primary resistant disease. We conclude that while histiocytic hemophagocytosis may be considered as a major cause of pancytopenia, leukemic infiltration can also be an extreme and unusual cause of pancytopenia in patients in whom brucellosis was concurrently diagnosed with hematological malignancies.     

Efficacy and safety of pegylated-interferon α-2a in hemodialysis patients with chronic hepatitis C

AIM： To evaluate the efficacy and safety of pegylated- interferon alpha-2a in hemodialysis patients with chronic hepatitis C. METHODS： Thirty-six hemodialysis patients with chronic hepatitis C were enrolled in a controlled and prospective study. All patients were treatment naive, positive tested for anti-HCV antibodies, and positive tested for serum HCV-RNA. Twenty-two patients received 135 μg peglyated-interferon α-2a weekly for 48 wk （group A）. The remaining patients were left untreated, eleven refused therapy, and three were not candidates for kidney transplantation and were allocated to the control group （group B）. At the end of the treatment biochemical and virological response was evaluated, and 24 wk after completetion of therapy sustained virological response （SVR） was assessed. Side effects were monitored.
RESULTS： Of 22 hemodialysis patients, 12 were male and 10 female, with a mean age of 35.2 ± 12.1 years. Virological end-of-treatment response was observed in 14 patients （82.4%） in group A and in one patient （7.1%） in group B （P = 0.001）. Sustained virological response was observed in 11 patients （64.7%） in group A and in one patient in group B （7.1%）. Biochemical response parameters normalized in 10/14 patients （71.4%） at the end of the treatment. ALT levels in group B were initially high in six patients and normalized in one of them （25%） at the end of the 48 wk. In five patients （22.7%） therapy had to be stopped at mo 4 due to complications of weakness, anemia, and bleeding.
CONCLUSION： SVR could be achieved in 64.7% of patients on hemodialysis with chronic hepatitis C by a treatment with peglyated-interferon α-2a. Group A had a significantly better efficacy compared to the control group B, but the side effects need to be concerned.     

Increased neopterin level and chitotriosidase activity in pregnant women with threatened preterm labor

Objectives: To determine whether the cellular inflammatory markers of activated macrophages, neopterin (NEO), chitotriosidase activity and the acute-phase inflammatory marker C-reactive protein (CRP) are elevated in pregnancy with threatened preterm labor (TPL).

Methods: Thirty-two pregnant women with TPL and 32 women with uncomplicated pregnancy (UP) were included this study. The primary aim was to compare the NEO, chitotriosidase activity and CRP levels between women with TPL and women with UP.

Results: NEO levels were all significantly elevated in patients with TPL compared to UP (median 25–75%; 9.61 [8.47–12.29] versus 4.46 [3.59–6.92], respectively; p?p?=?0.036). However, CRP levels were not different in women with TPL compared to UP (p?=?0.573). Furthermore, a significant moderate negative correlation was found between delivery week and NEO level (r?=??0.557, p?=?0.001). However, a significant correlation was not seen between delivery week and chitotriosidase activity (r?=??0.042, p?=?0.741).

Conclusions: Inflammatory markers such as NEO and chitotriosidase activity, which are markers of macrophages, are more elevated in pregnant women with TPL than in women with UP. These data suggest that there are striking increases in inflammation and cellular immune activation in TPL.     

Pulsed Doppler tissue imaging can help to identify patients with right ventricular infarction

This study was planned to assess whether tissue Doppler imaging is a useful method for the detection of the right ventricular myocardial infarction. Forty-eight patients with acute inferior myocardial infarction and 24 age- and sex-matched healthy controls were included in this study. Twenty-four patients had electrocardiographic signs of inferior myocardial infarction without right ventricular infarction (group I), and the other 24 patients had electrocardiographic signs of inferior myocardial infarction with right ventricular infarction (group II). From the echocardiographic apical four-chamber view, peak systolic, early diastolic, and late diastolic velocities of the tricuspid annulus at the right ventricular free wall were recorded with the use of pulsed-wave Doppler tissue imaging. The tricuspid annular peak tissue Doppler imaging systolic velocity was significantly lower in group I (14.03 ± 2.57cm/s, P 0.005) and in group II (8.50 ± 0.84cm/s, P 0.005) than in controls (16.63 ± 2.31cm/s). The tricuspid annular peak systolic (8.50 ± 0.84cm/s vs 16.63 ± 2.31cm/s) and peak early diastolic (10.99 ± 3.28cm/s vs 19.39 ± 4.3cm/s) velocities were significantly lower in group II than in group I, as compared with controls (P 0.001). Peak early diastolic velocity of tricuspid annulus (10.99 ± 3.28cm/s vs 19.39 ± 4.3cm/s) was significantly lower in group I than in controls (P 0.001); however, late diastolic velocity was significantly lower in group II (15.98 ± 5.08cm/s, P 0.05) than in group I (18.21 ± 2.63cm/s, P 0.05) and in controls (19.02 ± 5.29cm/s). The results of this study indicate that tricuspid annular peak systolic and early diastolic velocities are reduced in patients with right ventricular infarction. The velocity of the tricuspid annulus by tissue Doppler imaging is simple and can be used to distinguish whether patients with inferior myocardial infarction have right ventricular infarction.This study was presented at the XXIII. Congress of the European Society of Cardiology, Stockholm, Sweden, 1–5 September 2001     

Alexithymia and anger in patients with fibromyalgia

Our objective was to delineate the relevance of the personality construct alexithymia and anger-in in patients with fibromyalgia syndrome. Fifty subjects with fibromyalgia syndrome were compared to 20 subjects with rheumatoid arthritis and 42 healthy controls on the measures of anxiety, depression, anger, alexithymia, pain intensity and disability. There was a significant difference on the measures of anxiety and anger between FMS and RA groups, and also between FMS patients and healthy controls. There was a significant difference between FMS patients and healthy controls on the measures of depression, difficulty in identifying feelings subscale of TAS (TAS-dif), and total alexithymia scores. When the severity of pain was controlled for, there was a significant difference on the measures of anger and alexithymia between the FMS and the RA groups. Fibromyalgia patients were more alexithymic than rheumatoid arthritis patients even when the level of depression was controlled for. Anger towards oneself, which is anger-in, was higher in patients with fibromyalgia patients than in the rheumatoid arthritis sample. A stepwise regression model showed that the anger-out scores and the anxiety scores predicted the level of pain severity, and this explained 32% of the variance in the fibromyalgia syndrome group. Although anger-in is consistently higher in fibromyalgia patients, it is the behavioral expression of anger, together with anxiety, that predicts the severity of the pain. The difficulty of identifying feelings, rather than other dimensions of alexithymia, seems to be associated with fibromyalgia.Abbreviations CLBP Chronic low back pain - FMS Fibromyalgia syndrome - RA Rheumatoid arthritis - VAS Visual analog scale     

Group eye movement desensitization and reprocessing interventions in adults and children: A systematic review of randomized and nonrandomized trials

This review systematically synthesized existing literature on group protocols of eye movement desensitization and reprocessing (EMDR) therapy for treating a range of mental health difficulties in adults and children. We conducted database searches on PsychINFO, EMBASE, MEDLINE, Web of Science, The Cochrane Library and Francine Shapiro Library up to May 2020, using PRISMA guidelines. Studies were included if they used at least one standardized outcome measure, if they present a quantitative data on the effect of group EMDR protocols on mental health difficulties and if they were published in English. Twenty-two studies with 1739 participants were included. Thirteen studies examined EMDR Integrative Group Treatment Protocol (IGTP), four studies examined EMDR Group Traumatic Episode Protocol (G-TEP), four studies EMDR Integrative Group Treatment Protocol for Ongoing Traumatic Stress and one study considered EMDR Group Protocol with Children. Of the 22 studies included, 12 were one-arm trials and 10 were two-arm trials. We assessed risk of bias using a revised Tool to Assess Risk of Bias in Randomized Trials (ROB 2) and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I). Overall, the results suggested that Group EMDR protocols might be an effective tool in improving a wide range of mental health-related outcomes including posttraumatic stress disorder (PTSD), depression and anxiety. However, the included studies are limited to methodological challenges. The limitations and future directions are discussed.     

Effects of micro-osteoperforations on intraoral miniscrew anchored maxillary molar distalization

Journal of Orofacial Orthopedics / Fortschritte der Kieferorthopädie - The aim was to study the effects of micro-osteoperforations (MOPs) on miniscrew-supported maxillary molar distalization....