DICER1 Hotspot Mutations in Pleuropulmonary Blastoma: A Case Series From a Tertiary Center.

Pleuropulmonary blastoma (PPB) is a potentially aggressive, rare childhood neoplasia. We investigated histopathological features, survival, and DICER1 hotspot mutations among PPB patients. Archive records at our institution were reviewed, covering a 20-year period. Thirteen children (6 males and 7 females) with a mean age of 30.5 (range 6-83) months were included. The tumor subtypes were type I in 6 (46%), type II in 4 (31%), and type III in 3 (23%). Only tumors with type II and type III histology showed anaplasia (4/7, 57%). Median follow-up was 28 (range 9-216) months. Three-year overall survival rate was 83.3% and 3-year progression-free survival rate was 25%. Progression was seen in 60% (3/5) of type I and 66.7% (4/6) of type II and type III cases. Two patients died of disseminated disease at 9 and 44 months. Hotspot missense mutations on DICER1 gene were detected in all 11 patients with available tumor tissue. We found an additional novel germline loss-of-function mutation (c.5436dupT; p.E1813*) in 1 case. To the best of our knowledge, this is the first study to investigate hotspot missense mutations on DICER1 gene among the largest series of Turkish children with PPB.

Which cognitive dual-task walking causes most interference on the Timed Up and Go test in Parkinson's disease: a controlled study.

BACKGROUND: There is evidence that cognitive load has a negative effect on the gait of patients with Parkinson's disease (PD). However, it is not clear which type of cognitive activities are more likely to affect dual-task abilities in this patient group. AIMS: To compare the cognitive dual-task abilities in patients with PD and control subjects and to analyze the effect of different cognitive activities on the walking ability of patients with PD. METHODS: The Hoehn and Yahr scale, the Freezing of Gait Questionnaire (FOGQ), Montreal Cognitive Assessment (MoCA), and the Functional Reach Test were used to include and exclude the patients. The Timed Up and Go (TUG) test was applied under single and dual-task conditions. RESULTS: The completion time of TUG was found to be increased in the PD group compared with the healthy controls under single- and dual-task conditions (p < 0.05). The completion time of TUG was significantly increased in dual-task conditions with complex attention activity (serial subtractions test) compared with other dual-task conditions in patients with PD (p < 0.001). DISCUSSION: The gait performance of both healthy subjects and patients with PD was impaired with cognitive activity during walking, and patients with PD showed more impairment under different cognitive dual tasks. Among the other cognitive tasks, the 'serial sevens' test, a measure of complex attention, significantly increased the completion time of TUG. CONCLUSIONS: While assessing the dual-task ability of patients with early-stage PD, tasks that increase the demand for complex attention seem to be more sensitive to showing impaired dual-task ability.

An assessment of Movement Disorder Society Task Force diagnostic criteria for mild cognitive impairment in Parkinson's disease.

BACKGROUND AND PURPOSE: Cognitive impairment is one of the most disabling non-motor symptoms of Parkinson's disease. Mild cognitive impairment constitutes a major risk for the development of Parkinson's disease dementia in the course of the disease. A Movement Disorder Society Task Force proposed diagnostic criteria for mild cognitive impairment in Parkinson's disease (PD-MCI), comprising two operational levels: Level I and Level II. The objective of our study was to test the accuracy of Level I versus Level II diagnostic criteria. METHODS: Eighty-six consecutive patients with Parkinson's disease were screened and 68 patients without dementia or depression were included in the study. We used the Montreal Cognitive Assessment, Mini-Mental State Examination and Addenbrooke's Cognitive Evaluation-R screening tools for Level I and an extensive neuropsychological battery for Level II assessment. We first diagnosed PD-MCI on the basis of Level II assessment and then calculated sensitivity, specificity and area under the receiver-operator characteristics curve, comparing the performance of the three screening batteries. RESULTS: None of the three screening batteries proposed for Level I assessment provided satisfactory combined sensitivity and specificity for detecting PD-MCI, and their performance was similar. Using the Level II criteria, 29 patients (43%) were diagnosed as having PD-MCI. Lowest cut-off levels that provided at least 80% sensitivity were 24 for the Montreal Cognitive Assessment, 29 for the Mini-Mental State Examination and 87 for the Addenbrooke's Cognitive Evaluation-R. However, specificity levels were below 80% at these cut-off levels. CONCLUSIONS: We conclude that Level I assessment alone using screening batteries is not sufficiently sensitive/specific to detect PD-MCI.

Evaluation of acute kidney injury (AKI) with RIFLE, AKIN, CK, and KDIGO in critically ill trauma patients.

PURPOSE: The aim of our study was to evaluate the effects of AKI development on mortality with four different classification systems (RIFLE, AKIN, CK, KDIGO) in critically ill trauma patients followed in the intensive care unit. METHODS: A retrospective review of 2034 patients in our intensive care unit was conducted between July 2010 and August 2013. A total of 198 patients with primary trauma were included in the study to evaluate the development of AKI. RESULTS: When the presence of AKI was investigated according to the four criteria (RIFLE, AKIN, CK, and KDIGO), the highest incidence of AKI was found according to the KDIGO classification (74.2%), followed by AKIN (72.2%), RIFLE (69.7%), and CK (59.1%). It was observed that more AKI developed according to KDIGO in patients with multiple trauma and thoracic trauma (p = 0.031, p = 0.029). Sixty-two (31%) of the 198 trauma patients monitored in the intensive care unit died; mortality was frequently found high in AKI stage 2 and 3 patients. According to the CK classification, there was a significant increase in mortality in patients with AKI on the first day (p = 0.045). AKI classifications by RIFLE, AKIN, CK, and KDIGO were independently associated with the risk of in-hospital death. CONCLUSION: In this study, the presence of AKI was found to be an independent risk factor in the development of in-hospital mortality according to all classification systems (RIFLE, AKIN, CK, and KDIGO) in critically traumatic patients followed in ICU, and the compatibility between RIFLE, AKIN, and KDIGO was the highest among the classification systems.

SYNE1 related cerebellar ataxia presents with variable phenotypes in a consanguineous family from Turkey.

SYNE1 related autosomal recessive cerebellar ataxia type 1 (ARCA1) is a late-onset cerebellar ataxia with slow progression originally demonstrated in French-Canadian populations of Quebec, Canada. Nevertheless, recent studies on SYNE1 ataxia have conveyed the condition from a geographically limited pure cerebellar recessive ataxia to a complex multisystem phenotype that is relatively common on the global scale. To determine the underlying genetic cause of the ataxia phenotype in a consanguineous family from Turkey presenting with very slow progressive cerebellar symptoms including dysarthria, dysmetria, and gait ataxia, we performed SNP-based linkage analysis in the family along with whole exome sequencing (WES) in two affected siblings. We identified a homozygous variant in SYNE1 (NM_033071.3: c.13086delC; p.His4362GlnfsX2) in all four affected siblings. This variant presented herein has originally been associated with only pure ataxia in a single case. We thus present segregation and phenotypic manifestations of this variant in four affected family members and further extend the pure ataxia phenotype with upper motor neuron involvement and peripheral neuropathy. Our findings in turn established a precise molecular diagnosis in this family, demonstrating the use of WES combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes.

INCIDENTAL PAGET'S DISEASE DISGUISED AS BONE METASTASIS IN A PATIENT WITH ENDOMETRIUM CARCINOMA.

Paget's disease is a disorder of aging bone which occurs in the setting of accelarated bone remodelling. In the presented case we discuss the difficulties in the diagnosis of Paget's disease in a 77 year old patient with coexisting endometrium carcinoma. The patient was initially diagnosed with metastatic bone disease due to endometrium adenocarcinoma when she was admitted to oncology clinic with pelvic pain. Bone scintigraphy with Tc99 and (18)F fluorodeoxyglucose positron emission tomography/CT revealed an increased uptake on the bone lesions which were reported as metastatic bone involvement. Although the (18)F-FDG uptake was much higher than the levels that would generally be anticipated in a case with Paget's disease, high levels of bone turnover markers indicated further evaluation in the differential diagnosis and the definitive diagnosis of Paget's disease was established with the pathological evaluation of bone biopsy.

Genetic bases and phenotypes of autosomal recessive Parkinson disease in a Turkish population.

BACKGROUND AND PURPOSE: To evaluate the phenotype and the frequencies of mutations in PRKN, DJ1 and PINK1 genes in patients with Parkinson disease (PD) in Turkey. METHODS: Eighty-six patients from 77 PD families participated in the study. Seventy-four families were originating from Turkey, two families from Greece and one family from Bulgaria. All patients underwent detailed neurological examination. PRKN, PINK1 and DJ1 genes were sequenced, and dosage analysis was performed by multiplex ligation-dependent probe amplification. RESULTS: Sixteen patients with PD were found to carry homozygous (n = 14) or compound heterozygous (n = 2) PRKN mutations. We identified exon rearrangements, three point mutations and one new point mutation in exon 2 (p.K27del). In two families, two new PINK1 point mutations (L31X and P416L) were identified. No pathogenic mutations were found in DJ1 gene. Clinical phenotypes of PRKN patients were comparable to previously described features, but only in four of 13 families, the pedigree structure was clearly consistent with an autosomal recessive (AR) mode of inheritance in comparison with nine families where also different pattern of transmission could have been possible. CONCLUSIONS: Our data suggest that the PRKN gene mutation is the most frequent form of ARPD in Turkey. The proportion of mutations with regard to the age of onset in our population is in the range of those previously described, but our pedigrees are characterized by high rate of consanguinity, which might explain the high proportion of families with homozygous mutations and of patients in more than one generation. Pathogenic DJ1 mutations do not seem to play a major role in Turkey.

Osteoblastoma of the temporal bone: a case report.

Benign osteoblastoma is an unusual primary bone tumor. It affects usually long bones or the vertebral column. Osteoblastoma affecting the calvarium is extremely rare. A 23-year-old man presented with a two-month history of swelling and tenderness in the right temporal region. Computed tomography revealed an expansile, lytic lesion in the left temporal bone. T1- and T2-weighted magnetic resonance (MR) images demonstrated an isointense lesion in the temporal bone. After gadolinium DTPA injection, MR images revealed dense enhancement. The histopathological findings proved that the lesion was a benign osteoblastoma. To date, very few cases of the benign osteoblastoma arising in the calvarium have been reported in the literature. We discuss diagnostic and management aspects of this uncommon tumor.

The prevalence of dementia in an urban Turkish population.

A cross-sectional, population-based, 2-stage prevalence study was conducted in a sample of 1019 community-dwelling persons over the age of 70 years living in Istanbul. In the first phase, participants were screened with the Mini-Mental State Examination for evidence of cognitive impairment. In the second phase, 79% of those who screened positive (n = 322) and 9% of screen-negatives (n = 63) underwent a standardized diagnostic workup. Diagnosis of dementia and Alzheimer's disease (AD) was made according to established criteria. Ninety-three cases of dementia were identified, 58 of whom were diagnosed with probable AD. Based on these numbers, the prevalence rates of probable AD and dementia were calculated to be 11.0% (95% CI, 7.0% to 15.0%) and 20.0% (95% CI, 14.0% to 26.0%), respectively, in this population. Prevalence rates of dementia and AD in Istanbul, Turkey, are comparable with those seen in the Western world.

Large central osteoma of the maxillary antrum.

The aim of this report is to describe a case presenting with complaints of orbital pain, altered facial sensation, nasal obstruction and unilateral spontaneous nose bleeding. Panoramic radiography and computerized tomography disclosed a large pedunculated heterogeneous mineral opacity with two impacted molar teeth invading the maxillary sinus. The patient was operated on under general anaesthesia. Microscopic examination of the surgical specimen revealed relatively dense, compact bone with sparse marrow tissue that was diagnosed as osteoma. Clinical characteristics and biological behaviour of this lesion were evaluated with special regard to the reliability of imaging modalities and surgical procedures.

Effects of lipopolysaccharide on the blood-brain barrier permeability in prolonged nitric oxide blockade-induced hypertensive rats.

The authors investigated the effects of lipopolysaccharide (LPS) on the blood-brain barrier (BBB) integrity and the activity of astrocytes during the Nw-nitro-L-arginine methyl ester (L-NAME) hypertension followed by angiotensin (ANG) II in rats. They measured the changes in the BBB permeability using the Evans blue (EB) dye and concomitantly in the levels of TNF-a, IL-1b, and IL-6 in serum and nitric oxide in plasma. The authors performed two tight junction-specific proteins, zonula occludens-1 and occludin, and glial fibrillary acidic protein, by using immunohisto-chemical method. The serum levels of TNF-a, IL-1 IL-6, and the plasma level of nitric oxide significantly increased in LPS-treated rats (p<.01). The EB dye extravasation increased in cerebellum (p<.001) and diencephalon (p<.05) of L-NAME plus ANG II-treated animals. However, LPS reduced the increased EB dye extravasation in the brain regions of L-NAME-induced hypertensive rats treated with ANG II (p<.001). In L-NAME, there was a considerable loss of staining in both zonula occludens-1 and occludin. Staining for zonula occludens-1 and occludin was highly intensive in animals treated with LPS. Glial fibrillary acidic protein staining was seen in a few astrocytes in brains of L-NAME-treated animals. However, this staining showed an increased intensity in the brain sections of animals treated with LPS. This study indicates that, in L-NAME hypertensive rats, ANG II leads to an increase in the extravasation of EB dye to brain as a result of decreased activity of tight junction proteins and astrocytes, and LPS could significantly attenuate the EB dye transport to the brain through the increased activity of tight junction proteins and astrocytes.

Intra-articular injection of tenoxicam in rats: assessment of the local effects on the articular cartilage and synovium.

This study investigated the possible local adverse effects of intra-articular administration of tenoxicam in the rat knee joint. A total of 50 rats were given 0.25 ml of a standard preparation of tenoxicam by injection into the right knee joint and 0.25 ml of 0.9% saline solution by injection into the left knee joint as a control. Groups of 10 rats were killed 24 h, 48 h, 7 days, 14 days and 21 days after tenoxicam administration. Two rats were sham operated; one was killed on the first day and the other on the second day after this procedure. All the joints were prepared and sectioned for histological examination. Tissue loss and oedema were observed in the specimens obtained 24 h and 48 h after treatment with tenoxicam. No pathological changes were observed in the 7-day, 14-day and 21-day specimens, or in the control joints. Caution should be exercised when using intra-articular tenoxicam for post-operative analgesia.

Tumoral calcinosis infiltrating the biceps brachii tendon - excision and reconstruction with allograft: a case report.

Two patients with limited elbow motion due to tumoral calcinosis underwent resection of calcified masses around the elbow joints. This necessilated removal of the distal two thirds and three fourths of the biceps muscles. The resulting defects were reconstructed with homologous Achilles tendon grafts. Both patients regained M4 muscle power and no recurrences were observed.

Human immunodeficiency virus-negative tonsil Kaposi's sarcoma and Hodgkin's disease: case report and review of the literature.

Kaposi's sarcoma (KS) is a multicentric malignant neoplastic vascular disorder characterized by multiple violet-colored nodules of the skin. The coexistence of KS with other primary malignancies, especially of the lymphoreticular system, has been frequently noted. However, the association of Hodgkin's disease with KS is a rare occurrence. In this article we present the case of a 33-year-old man with human immunodeficiency virus (HIV)-negative KS of the tonsil, occurring in the radiotherapy field for Hodgkin's disease treated 20 years ago.

Comparison of four different suture materials in soft tissues of rats.

OBJECTIVES: The purpose of this in vivo study was to histopathologically evaluate the inflammatory reaction incited by Vicryl in rats and compare this material with various suture materials that are widely used in the clinic. SUBJECTS AND METHODS: Four different suture materials, catgut, silk, polypropylene, and Vicryl were used in soft tissues of 32 Sprague-Dawley rats. Incisions performed were sutured by a standard technique. Eight rats were killed at the first, third, fifth, and seventh days. Histopathological evaluation of the en bloc samples was performed by determining the density of seven cell-types. A numerical grading from one to three was used. The data were statistically analysed by Kruskal-Wallis one way ANOVA and Dunn's tests. RESULTS: Vicryl has produced the mildest tissue reaction among the test materials at all experimental periods (P<0.05). Total cell number value in Vicryl group was found to be significantly lower than the one in catgut group (P<0.05). CONCLUSION: Under the conditions of this study, the results demonstrated that Vicryl as a suture material produced the mildest tissue reaction during early healing period.

Radiologic and histomorphometric evaluation of maxillary sinus grafting with alloplastic graft materials.

BACKGROUND: Sinus lifting procedures are widely used to obtain adequate bony support for implant placement at the atrophic maxillae. The aim of this study was to compare various sinus lifting and grafting techniques and materials. METHODS: Nine maxillae were treated with delayed and 46 maxillae with immediate implant placement techniques. A total of 104 implants were inserted. Panoramic radiographs were obtained prior to, after, and 6 to 8 months after surgery. Computed tomographies were also taken before and after surgery. The height of new bone was compared. Biopsy specimens were obtained during delayed implant placement and analyzed histomorphologically. RESULTS: There were no statistically significant differences between the panoramic radiographs for delayed and immediately placed implants, or between the graft materials. We observed correlations between the panoramic radiographs and computerized tomographies. CONCLUSION: Both delayed and immediate placement of implants can be used safely for sinus lifting. There were no statistically significant differences between the various graft materials.

Reactions of connective tissue to compomers, composite and amalgam root-end filling materials.

AIM: To evaluate the subcutaneous connective tissue reaction to compomers, composite and amalgam root-end filling materials. METHODOLOGY: This study was conducted in 30 Wistar albino rats. The materials were mixed or light-cured according to the manufacturer's directions and placed in polyethylene tubes. Group 1 - Dyract compomer (Dentsply); group 2 - F2000 compomer (3M); group 3 - Valux Plus composite (3M); group 4 - Oralloy high-copper amalgam (Coltene). The tubes containing the materials were implanted into the dorsal connective tissue of rats, which were killed 7, 15, 30, 60 and 90 days after the implantation procedure. Thirty extra empty tubes were also placed as controls. The implant sites were excised and prepared for histological evaluation. Sections of 6-microm thickness were stained with haematoxylin and eosin and assessed under light microscopy. The presence of inflammation, predominant cell type and thickness of fibrous connective tissue adjacent to each implant were recorded. Reactions were scored as: 0: none or few cells and no reaction; 1: less than 25 cells and mild reaction; 2: between 25 and 125 cells and moderate reaction; 3: 125 and more cells and severe reaction. Fibrous capsules were considered to be thin if their thickness was less than 150 microm and thick if it was more than 150 microm. Necrosis and formation of calcification were categorized as 'yes' or 'no'. RESULTS: All four materials caused moderate or severe inflammatory reactions in the first 7-day period, but these reactions decreased by the 60th and 90th days. No significant difference in inflammatory cell numbers between the materials could be detected at the 90th day. CONCLUSIONS: Valux Plus composite, Dyract and F2000 compomers and Oralloy amalgam were biocompatible.

Malignant triton tumour of the parapharyngeal space.

We report the clinical course in a 25-year-old male patient of neurofibromatosis with malignant triton tumour (MTT). Triton tumour is a peripheral nerve sheath tumour with rhabdomyoblastic differentiation. This is relatively rare tumour of head and neck region and only 26 cases have been reported to date. The present case is the first reported MTT of parapharyngeal space, one of the most aggressive course among all head and neck MTTs, resulting in the death of the patient within three months following surgical resection. The aggressive nature of this tumour necessitates adjuvant therapeutic measures in addition to radical surgery in order to obtain better survival rates.

Perioral myoclonia with absence seizures: a rare epileptic syndrome.

We present the clinical and video-EEG data on an epileptic boy whose absence seizures with marked perioral movements had started at the age of 1.5 years. From age 12 years, he experienced frequent episodes of typical absence status epilepticus (ASE) lasting 1-2 hours with marked perioral myoclonia and moderate confusion. Initial therapy with carbamazepine was substituted by valproate because of worsening of the absence seizures. At the age of 17, the patient was admitted to our clinic with his usual, but long lasting ASE attack, accompanied by 2 generalized tonic-clonic convulsions. ASE was confirmed with the EEG which showed continuous 3 Hz spike and wave paroxysms with occasional normal intervals of 1-5 seconds. IV injection of clonazepam improved the clinical and EEG findings immediately. Video- EEG examination performed after a few weeks demonstrated typical absence seizures with perioral myoclonia. Based on the characteristics of seizure semiology, other clinical data and EEG findings, the patient was diagnosed as having the syndrome of "perioral myoclonia with absence seizures" described by Panayiotopoulos.