Mustafa Kılıç

Mucopolysaccharidosis: Otolaryngologic findings, obstructive sleep apnea and accumulation of glucosaminoglycans in lymphatic tissue of the upper airway

OBJECTIVE The aim of this study is to evaluate otolaryngologic problems (upper airway obstruction, obstructive sleep apnea, restriction of mouth opening, middle ear effusion, hearing and breathing problems) and their treatments on mucopolysaccharidoses (MPS) patients and to investigate accumulation of glucosaminoglycans (GAG) in the upper airway biochemically and pathologically. METHODS 76 MPS patients were evaluated. Forty-two MPS patients underwent polysomnography (PSG) for obstructive sleep apnea (OSA). Pre- and postoperative PSG results of 18 patients were compared. The success and complications of treatments for OSA in MPS were evaluated. Biochemical and histopathological accumulation of GAG in tonsil and adenoid tissue and middle ear effusion were analyzed and compared with the control group. RESULTS Forty patients out of 42 tested with PSG had OSA (95%). Adenoid grade, Mallampati grade, restricted mouth opening, rate of difficult intubation were significantly different among MPS subtypes. MPS types III and IV had significantly lower Mallampati scores; type VI had significantly worse mouth opening; and type III had significantly better mouth opening and higher rate of easy intubation when compared to other MPS types. There was no significant difference between MPS subtypes according to tonsil grade, adenoid grade, rate of otitis media with effusion and OSA severity. Statistically significant difference was found between GAG accumulation in adenoid tissue and middle ear effusion of MPS and control group (p<0.05). However, GAG accumulation in tonsil was not significantly different between MPS and control group. There was a statistically significant improvement in postop Apnea-Hypopnea Index (AHI) compared to preop AHI (p<0.05). CONCLUSIONS Most MPS patients have airway obstruction and OSA due to adenotonsillar hypertrophy. Most of these children benefit from adenotonsillectomy, after which OSA significantly improves. They experience high recurrence rate after adenoidectomy; though this is not clinically problematic. They also suffer from conductive hearing loss due to OME, which has to be treated with ventilation tube insertion. However, such operations are usually complicated by difficult endotracheal intubation and restricted mouth opening. Sometimes tracheotomy may be necessary. Tracheotomy is also highly complicated in MPS patients. Significant accumulation of GAG in middle ear fluid and adenoid tissue is present; however, GAG appears not to accumulate in tonsillar tissue.

Increased mean platelet volume (MPV) indicating the vascular risk in Alzheimer's disease (AD)

Vascular risk factors play a significant role in the pathogenesis and progression of AD. MPV is an index of platelet activation and may be a potential marker of inflammation to demonstrate the vascular damage in AD. The aim of the present study is to assess whether platelet volume would be useful in predicting vascular damage in AD. A total of 126 patients with AD (male/female: 44/82, mean age 76.2 ± 6.8 years) and 286 patients as controls with normal cognitive function (male/female: 123/163, mean age 75.2 ± 6.3 years) were enrolled in this cross-sectional study. MPV values were determined for all study participants. Mini-Mental State Examination (MMSE) and clock drawing tests (CDT) were performed for cognitive assessment, DSM-IV and NINCDS-ADRDA criteria were used for diagnosis of AD. The mean MPV values were significantly higher in AD group (8.46 ± 1.15 vs. 8.17 ± 0.90; p=0.011). In this study, significantly higher MPV values in patients with AD have been detected. Since increased MPV levels are usually considered as a vascular risk factor, the results of this study suggested the role of platelet activation in the vascular pathogenetic basis of AD.

The impact of IQ and EQ on pre-eminent achievement in organizations: implications for the hiring decisions of HRM specialists

In this study, IQ and EQ determinants of pre-eminent achievement in organizations were explored to help HRM specialists in selecting more appropriate job applicants, having potential for outstanding performance in their career paths. Several EQ elements were proved the most important in the achievement. However, IQ elements still play a very important role in superior performance. Results also exhibit that correlation of IQ and EQ levels of superior performers is significant and strong. In conclusion, HRM specialists have to test both IQ and EQ in the hiring process, to create a high-performing workforce in their organizations.

Validation of Katz index of independence in activities of daily living in Turkish older adults

OBJECTIVE Katz Index of Independence in Activities of Daily Living Scale (Katz ADL) is a widely used tool to assess the level of independency in older adults. The objective of this study was to assess the validity and reliability of the Turkish version of the six item Katz ADL in geriatric patients aged 65 years and older. METHODS The participants were recruited in a geriatric medicine outpatient clinic (n=211). The Katz ADL was translated to Turkish and it was administered with the Barthel index (BI) and SF-36 physical functioning subscale (SF-36 PF) which are already validated in Turkish. Reliability was assessed by internal consistency, interrater and test-retest analysis. Construct validity was assessed by Spearman correlations between the Katz ADL and other functional status indices. RESULTS The internal consistency was high (Cronbachs α=0.838). The test-retest reliability and inter-rater reliability were excellent (ICC 0.999 [0.999-1.000 95% CI]). Regarding the convergent validity strong associations between Katz ADL, BI and SF-36 PF were demonstrated (rs=0.988, p<0.001 and rs=0.674, p<0.001). CONCLUSION Validating an instrument, which has originally been developed in a different culture, is a complex but neccessary task. It provides an opportunity for comparison of information across different cultures. To our knowledge, this is the only study to demonstrate reliability and validity of the Katz ADL-six item version in the geriatric population living in Turkey. Turkish version of the Katz ADL is a valid and reliable scale to detect the disability status in the basic activities of daily living in older adults.

Identification of Mutations and Evaluation of Cardiomyopathy in Turkish Patients with Primary Carnitine Deficiency

Primary systemic carnitine deficiency (SCD) is an autosomal recessive disorder caused by defective cellular carnitine transport. Patients usually present with predominant metabolic or cardiac manifestations. SCD is caused by mutations in the organic cation/carnitine transporter OCTN2 (SLC22A5) gene. Mutation analysis of SLC22A5 gene was carried out in eight Turkish patients from six families. Six patients presented with signs and symptoms of heart failure, cardiomyopathy, and low plasma carnitine levels, five of them with concurrent anemia. A patient with dilated cardiomyopathy had also facial dysmorphia, microcephaly, and developmental delay. Tandem MS analyses in siblings of the patients revealed two more cases with low plasma carnitine levels. SCD diagnosis was confirmed in these two cases by mutation screening. These two cases were asymptomatic but echocardiography revealed left ventricular dilatation in one of them. Carnitine treatment was started before the systemic signs and symptoms developed in these patients. Mean value of serum carnitine levels of the patients was 2.63±1.92μmol/L at the time of diagnosis. After 1year of treatment, carnitine values increased to 16.62±5.11 (p<0.001) and all responded to carnitine supplementation clinically. Mutation screening of the OCTN2 gene study in the patients revealed two novel (p.G411V, p.G152R), and four previously identified mutations (p.R254X, p.R282X, p.R289X, p.T337Pfs12X). Early recognition and carnitine supplementation can be lifesaving in this inborn error of fatty acid oxidation.

Phenotypic and genotypic spectrum of Turkish patients with isovaleric acidemia.

We aim to investigate the genetic basis of isovaleryl-CoA dehydrogenase (IVD) gene mutations and genotype-phenotype correlations in Turkish patients. Accordingly, bi-directional sequencing was performed to screen 26 patients with isovaleric acidemia (IVA). Nine novels (c.145delC, c.234 + 3G > C, c.506_507insT, p.Glu85Gln, p.Met147Val, p.Ala268Val, p.Ile287Met, p.Gly346Asp and p.Arg382Trp) and six previously reported (c.456 + 2T > C, p.Arg21His, p.Arg21Pro, p.Arg363Cys, p.Arg363His p.Glu379Lys) pathogenic mutations were identified. Pathogenicity of the novel mutations was supported using computational programs. No clear genotype-phenotype correlation could be determined. One of the cases with the novel c.234 + 3G > C mutation has portoseptal liver fibrosis, the clinical condition that was first reported for IVA. This study is the first comprehensive report from Turkey related to IVA genetics that provides information about the high number of disease-causing novel mutations.

Mutation Spectrum of Fumarylacetoacetase Gene and Clinical Aspects of Tyrosinemia Type I Disease

Tyrosinemia type I (OMIM 276700) is a rare, autosomal recessive disorder caused by a deficiency in the fumarylacetoacetate hydrolase (FAH) enzyme. This study examined the spectrum of FAH gene mutation in 32 patients with tyrosinemia type I. In addition, clinical and biochemical findings were evaluated to establish a genotype-phenotype relationship in the patients. Mutation screening was performed using a 50K custom-designed resequencing microarray chip (TR_06_01r520489, Affymetrix) and sequencing analysis. Of the 12 different mutations found, 6 are categorized as novel. Three of the mutations-IVS6-1G>A, D233V, and IVS3-3C>G-are the most common in Turkish patients, comprising 25%, 17.1%, and 12.5% of mutant alleles, respectively.Clinical evaluations suggest that the spectrum of symptoms observed in the patients with very early and early disease were of the more nonspecific form, whereas the patients with late-presenting disease had more of the distinctive form over the course of the disease. This study adds support to the notion that the D233V mutation is specific to the Turkish population.

Estimating Radiation Therapy Toxicity and Tolerability with Comprehensive Assessment Parameters in Geriatric Cancer Patients

Cancer prevalance and incidence is increasing with aging of populations and age is a critical factor in decision-making for anti-cancer treatment. However it is believed that chronological age is not enough to guide management in elderly cancer patients. Multidisciplinary evaluation and comprehensive geriatric assessment has gained importance regarding the treatment selection especially for definitive anti-cancer therapy recently. We here aimed to analyse the effect of the comprehensive geriatric assessment parameters on radiotherapy toxicity and tolerability in a series of geriatric cancer patients in Turkey.

Purpura fulminans in a newborn infant with galactosemia

An 11-day-old neonate presented with purpura fulminans and was subsequently diagnosed with galactosemia. Neonatal purpura fulminans occurs predominantly in patients suffering from inherited protein C deficiency or disseminated intravascular coagulation associated with septicemia. Hemostatic changes in patients with liver disease may result in bleeding or, rarely, thrombosis. We suppose that in the present patient, deficiency of protein C, secondary to liver disease, was responsible for the development of purpura fulminans. Treatment consisted of blood and blood products and galactose-free formula. The patient recovered with residual mild psychomotor retardation and the lesions with minimal scarring. In conclusion, galactosemia also should be kept in mind as an uncommon cause of purpura fulminans in newborn infants.

Validation of the Turkish Version of the Quick Mild Cognitive Impairment Screen

Background: The objective of this study was to validate the Turkish version of the Quick Mild Cognitive Impairment (Qmci-TR) screen. Methods: In total, 100 patients aged ≥65 years referred to a geriatric outpatient clinic with memory loss were included. The Qmci was compared to the Turkish versions of the standardized Mini-Mental State Examination and the Montreal Cognitive Assessment (MoCA). Results: The Qmci-TR had higher accuracy than the MoCA in discriminating subjective memory complaints (SMCs) from cognitive impairment (mild cognitive impairment [MCI] or dementia), of borderline significance after adjusting for age and education (P = .06). The Qmci-TR also had higher accuracy than the MoCA in differentiating MCI from SMC, which became nonsignificant after adjustment (P = .15). A similar pattern was shown for distinguishing MCI from dementia. Test reliability for the Qmci-TR was strong. Conclusion: The Qmci-TR is a reliable and useful screening tool for discriminating MCI from SMC and dementia in a Turkish population.