Does mean platelet volume/lymphocyte count ratio associate with frailty in type 2 diabetes mellitus?

OBJECTIVES: Frailty is a common problem in patients with type 2 diabetes mellitus (T2DM). It is considered to be associated with inflammation. Novel markers derived from hemogram, such as neutrophil/lymphocyte ratio (NLR) and mean platelet volume/lymphocyte ratio (MPVLR), are proposed as inflammatory markers. In present study, we aimed to compare NLR and MPVLR levels of frail patients with T2DM to non­frail diabetic subjects. METHODS: Diabetic subjects were grouped in frail and non-frail groups according to the Edmonton Frail Scale. General characteristics and laboratory data of the frail and non-frail groups were compared. RESULTS: The MPVLR of the frail (3.9 [1.4-13.2] %) group was significantly higher than that of the non-frail (3.4 [1.5-6.9] %) group (p = 0.02). MPVLR was positively and significantly correlated with Edmonton Frail Scale score (r = 0.21, p = 0.03). A MPVLR level greater than 3.41 % has 71 % sensitivity and 51 % specifity in predicting frailty. CONCLUSION: We suggest that elevated MPVLR could be a finding that marks frailty in diabetic subjects. Inexpensive and easy­to­assess nature of the MPVLR may be useful in predicting frailty in type 2 diabetic population (Tab. 2, Fig. 1, Ref. 32).

THE ASSOCIATION BETWEEN VITAMIN D LEVELS AND HANDGRIP STRENGTH IN ELDERLY MEN.

CONTEXT: Vitamin D is a steroid hormone that acts by binding to the vitamin D receptor (VDR) found in many tissues. According to the long-term mechanism, vitamin D causes the proliferation and differentiation of muscle cells by gene transcription. OBJECTIVE: We aimed to evaluate the relationship between muscle strength and serum vitamin D levels in elderly men. DESIGN: Cross-sectional study. SUBJECTS AND METHODS: Male patients over age 50 were included in the study. Study population was divided into 2 groups with handgrip strength according to body mass index, either as subjects with weak or with normal handgrip strength test (HGST). Vitamin D levels and other variables compared between weak and normal groups. RESULTS: Vitamin D level of weak and normal groups were 7.5 (3-19.9) µg/L, and 11.6 (11.6-34.9) µg/L, which means significant reduced vitamin D levels in weakness group (p=0.01). Vitamin D levels were significantly correlated with HGST levels (r:0.362, p=0.001). Vitamin D levels were found to be an independent predictor of weakness according to HGST in logistic regression analysis (OR: 0.453, 95% Cl:0.138-0.769, p=0.05). CONCLUSIONS: Low vitamin D level is an independent risk factor for muscle weakness in men aged more than 50 years. Therefore, vitamin D levels should be screened and early replacement should be initiated for the sake of improvement of muscle strength in elderly subjects that vulnerable for frailty.

Combined antihypertensive treatment is better than mono-therapy in hypertensive patients.

BACKGROUND: Hypertension (HT) is a chronic condition associated with serious complications. In the present cross-sectional study, we aimed to analyse factors that contribute to blood pressure control in subjects with HT. METHODS: Subjects with HT admitted to outpatient internal medicine clinics of the institution were enrolled in the study. According to the Joint National Committee (JNC) VIII criteria, subjects with a mean blood pressure above target levels were defined as poorly-controlled hypertensive patients and others were grouped as well-controlled hypertensive patients. Clinical and laboratory parameters were compared between study groups. RESULTS: Smokers were more prevalent in the poorly-controlled HT group compared to the well-controlled HT group (p = 0.001). The number of patients who adhered to dietary and exercise recommendations were greater in well-controlled HT group than poorly-controlled HT group (p < 0.001 for both). The rate of combined therapy was greater in well-controlled HT group compared to poorly-controlled HT group (p = 0.04). CONCLUSIONS: We suggest that, in addition to dietary and exercise recommendations and smoking cessation, treatment with combination therapy could be better in reaching blood pressure targets in patients with HT.

Kidney transplantation in immunologically high-risk patients.

An increased number of sensitized patients await kidney transplantation (KTx). Sensitization has a major impact on patient mortality and morbidity due to prolonged waiting time and may preclude live donor transplantation. However, recent reports have shown that KTx can be performed successfully using novel immunosuppressive protocols. This study presents our experience with patients displaying donor-specific antibody (DSA) (+). We enrolled 5 lymphocyte cross-match (LCM) negative (complement-dependent cytotoxicity) and panel-reactive antibody (PRA) plus DSA-positive patients mean fluorescein intensity [MFI] > 1000) who underwent living kidney donor procedures. All subjects were females and their mean age was 36.7 years. In our protocol, we started mycophenolate mofetil (2 g/d), tacrolimus (0.01 mg/kg) and prednisolone (0.5 mg/kg) on day -6. We performed 2 sessions of total plasma exchange (TPE) with albumin replacement and administered 2 doses of IVIG (5 g/d). On day -1, we added rituximab (200 mg). On the operation day and on day +4, the patients received doses of basiliximab. Serum samples were taken on days -6, 0, and 30 as well as at 1 year after transplantation. All patients displayed immediate graft function. Mean basal DSA titer was 5624 MFI. After desensitization, the MFI titers decreased at the time of transplantation to 2753 MFI, and were 2564 MFI at the 1st month and 802 MFI at 1st year. Three patients experienced acute rejection episodes (60%). After treatment for rejection, the average follow-up was 17 months and last creatinine levels were 0.6-0.8 mg/dL (minimum-maximum). In conclusion, KTx can be succesfully performed in sensitized patients displaying DSA. However, there seems to be a greater acute rejection risk. There is no consensus regarding adequate doses of IVIG or plasmapheresis treatments; furthermore, more studies are needed to clarify the safe MFI titer of the DSA.

Changes in liquid emptying in migraine patients: diagnosed with liquid phase gastric emptying scintigraphy.

Gastric stasis is suspected mostly to be encountered during acute migraine attack. The aim of this study is to evaluate the liquid phase gastric emptying and motility in migraine patients in ictal and interictal periods in comparison to normal subjects with gastric emptying scintigraphy. Seven women with migraine and age, sex matched controls who applied to the Neurology Department from May 2009 to May 2010 were compared. Gastric emptying study with a standard liquid was performed one time in the non-migraineur group and two times in the migraineur group. Non-migraineur controls and migraineurs were compared. The mean T1/2 was longer in ictal period in migraineurs. The T1/2 of migraineurs interictally and the control groups were similar. The T1/2 of migraineurs ictally and migraineurs interictally were also compared. We also considered the percentage of the radioactive material remaining in the stomach. There were no significant differences between non-migraineurs and migraineurs interictally. However, increased amount of radioactive material remaining in the stomach was observed in migraineurs ictally. We concluded that the liquid emptying was delayed in spontaneous migraine attacks in migraine without aura, however in the interictal period the emptying of liquids did not differ between migraineurs and non-migraineurs.

Cytotoxic T lymphocyte-associated antigen-4 polymorphism in patients with rheumatic heart disease.

Acute rheumatic fever (ARF) is a systemic inflammatory disease occurring as a consequence of an exaggerated immune response to group A, beta haemolytic streptococcal pharyngitis. The molecular mimicry between human target organs/tissues and specific components of the infectious organism leads to the development of autoimmune reactions and cardiac tissue damage in rheumatic heart disease (RHD). Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation and proliferation during the immune response. CTLA-4 gene polymorphism has been shown to affect the inhibitory function of CTLA-4. We aimed to analyze the association of CTLA-4 gene locus at position 49 of exon 1 with susceptibility to ARF/RHD. This study included a total of 98 patients with RHD as a sequela of ARF, who fulfilled the revised classification criteria of Jones and 154 healthy unrelated controls. CTLA-4 +49 A/G polymorphism was genotyped by using PCR-RLFP technique. Data was analyzed by binary logistic regression models. The frequencies of GG, GA and AA genotypes were found to be 14%, 47% and 39%, respectively, in patients and 6%, 45% and 49%, respectively, in controls. The GG genotype was found to be significantly different between patients and controls (OR: 3.11; P = 0.016). GA and AA genotypes did not statistically differ between patients and controls. Our data showed a significant association of +49G /G polymorphism in a small patient group with RHD.

Peripheral nervous system involvement in patients with sickle cell disease.

BACKGROUND AND PURPOSE: Peripheral nervous system involvement is rare in sickle cell disease (SCD). The aim of this study is to determine the peripheral nerve involvement electrophysiologically in SCD patients without clinically evident neurological signs, symptoms and to determine the relationship between the frequency of sickle cell crisis and peripheral neuropathy. METHODS: Fifty-one patients with SCD and fifty-one healthy controls were enrolled to the study. Conventional electrophysiological studies of peripheral nerves were performed to all subjects. The data about the frequency of sickle cell crisis were obtained. RESULTS: Peripheral nervous system involvement was detected in ten (19.6%) patients. Five (9.8%) patients had sensorimotor axonal neuropathy, two (3.9%) sensory axonal neuropathy, one (2%) patient had ulnar sensory neuropathy and two (3.9%) had median sensory neuropathy. Sural nerve sensorial action potential was unobtainable in eight (15.7%) patients and prolonged F latencies were observed in three (5.9%). The frequency of neuropathy was higher in SCD patients when compared with the controls. The frequency of sickle cell crisis was not significantly correlated with peripheral neuropathy. CONCLUSION: Subclinical peripheral nerve involvement may be seen in SCD patients. Electrophysiological examinations are recommended in routine examination to diagnose early neuropathy in SCD patients without neurologic symptoms.

The neuroprotective and anti-inflammatory effects of diltiazem in spinal cord ischaemia-reperfusion injury.

The protective effects of diltiazem were examined in a rabbit model of spinal cord ischaemia-reperfusion induced by infrarenal aortic occlusion for 30 min. In the diltiazem group (n = 6), an intravenous infusion (2 microg/kg per min) was started 10 min before ischaemia induction; normal saline solution was infused in the control group (n = 6). Neurological function was assessed using modified Tarlov criteria 24 h after surgery. Plasma samples were analysed for interleukin (IL)-6 and IL-10. Spinal tissue was analysed for malondialdehyde, nitric oxide and reduced glutathione activities. Tarlov scores of the diltiazem-treated rabbits indicated significantly improved hind-limb motor function compared with the control group. The diltiazem group also had better quantitative and qualitative histopathological findings. Diltiazem infusion significantly reduced IL-6 levels 3 and 24 h after reperfusion compared with the control group. The mean IL-10 level in the diltiazem group was significantly higher than in the control group 24 h after reperfusion. It is concluded that diltiazem has cytoprotective and anti-inflammatory properties, leading to reduced spinal cord injury.

A comparative ID migraine screener study in ophthalmology, ENT and neurology out-patient clinics.

Migraine is more likely to be misdiagnosed in patients with comorbid diseases. Not only primary care physicians, but also specialists might misdiagnose it due to the lack of diagnostic criteria awareness. The ID migraine test is a reliable screening instrument that may facilitate and accelerate migraine recognition. This study aimed to compare the prevalence and characteristics of migraine in a large sample of patients admitted to clinics of ophthalmology (OC), ear, nose and throat diseases (ENTC) and neurology (NC), as well as to validate the use of the ID migraine test in OC and ENTC settings. This was a multicentre (11 cites) study of out-patients admitting either to NC, ENTC or OC of the study sites during five consecutive working days within 1 week. From each of the clinics, 100 patients were planned to be recruited. All recruited patients were interviewed and those having a headache complaint received an ID migraine test and were examined for headache diagnosis by a neurologist, blinded to the ID migraine test result. A total of 2625 subjects were recruited. Only 1.3% of OC patients and 5.4% of ENTC patients have been admitted with a primary complaint of headache, whereas the percentage of NC patients suffering from headache was 37.6%. Whereas 138 patients (19.3%) in OC, 154 (17.3%) in ENTC and 347 (34%) in NC were found to be ID migraine test positive, 149 patients (20.8%) in OC, 142 (16%) in ENTC and 338 (33.1%) in NC were diagnosed with migraine. The sensitivity, specificity, and positive and negative predictive ratios of the ID migraine test were found to be similar in all clinics. An important fraction of the patients admitted to NC, as well as to OC and ENTC, for headache and/or other complaints were found out to have migraine by means of a simple screening test. This study validated the ID migraine test as a sensitive and specific tool in OC and ENTC, encouraging its use as a screening instrument.

Thymidylate synthase genotype and serum concentrations of homocysteine and folate in Behçet's disease.

The aim of this study was to assess whether thymidylate synthase (TYMS) genotype, serum homocysteine, and folate concentrations were related to venous thrombosis in Behçet's disease (BD) patients. The study included 104 BD patients fulfilling the International Study Group Criteria for the diagnosis of BD and 121 healthy individuals-controls. Out of 104 patients, 50 (48%) had vascular involvement: 34 had active-history of venous thrombosis, 16 had arterial involvement (aneurysm), and 11 of these patients had both venous and arterial lesions as confirmed by Doppler ultrasound and/or angiography. Genotype analysis of the TYMS promoter enhancer region was determined by polymerase chain reaction. The distribution of the TYMS genotypes 2R/2R, 2R/3R, 3R/3R, 4R/2R, and 3R/3R were not significantly different between BD patients and control group (p>0.05; 16.5% vs 8.3%, 49.0% vs 53.9%, 31.7% vs 38.0%, 1.9% vs 0%, and 1.0% vs 0%, respectively). TYMS genotypes were not associated with thrombosis and serum homocysteine concentration in BD patients. The mean serum homocysteine level in patients with thrombosis (14.87+/-8.99 micromol/L) was significantly higher than the level in patients without thrombosis (10.78+/-3.81 micromol/L; p<0.05). Serum folate concentrations were not different between the BD patients and the healthy controls. The study results suggest that the distribution TYMS genotype in BD was not different from that of healthy controls. There was no relationship between TYMS genotype and the homocysteine levels in BD patients with thrombosis or without thrombosis.

Widespread maculopapular rash due to intramuscular interferon beta-1a during the treatment of multiple sclerosis.

We describe a 41-year-old woman with multiple sclerosis, who presented erythematous maculopapular rash on the trunk and extremities after the second injection of interferon beta-1a. Histopathologic examination of the lesion revealed lymphocytic exocytosis and perivascular lymphocytic infiltrate in the dermis. Oral antihistamine and topical corticosteroid was started. After improvement of the lesions, the third injection was performed. However, the same reaction occurred. A prick test, which was performed 6 weeks after the eruption, also revealed positive reaction. Although injection-site reactions have been observed with interferon beta-1a, to our knowledge there have been no previous reports of interferon beta-1a-induced widespread cutaneous reaction.

QTc dispersion and P-wave dispersion during migraine attacks.

The aim of this study was to investigate increase of QTc dispersion and P-wave dispersion during migraine attacks. Fifty-five patients (16-65 years of age, 49 women, six men) with migraine were included in our study. Heart rate, QTc interval, maximum and minimum QTc interval, QTc dispersion, maximum and minimum P-wave duration and P-wave dispersion were measured from 12-lead ECG recording during migraine attacks and pain-free periods. ECGs were transferred to a personal computer via a scanner and then used for magnification of x400 by Adobe Photoshop software. Maximum QTc interval (454 +/- 24 ms vs. 429 +/- 23 ms, P < 0.001), QTc interval (443 +/- 26 ms vs. 408 +/- 22 ms, P < 0.001) and QTc dispersion (63 +/- 18 ms vs. 43 +/- 14 ms, P < 0.001) were found significantly higher during migraine attacks compared with pain-free periods. Maximum P-wave duration (107 +/- 11 ms vs. 100 +/- 11 ms, P < 0.001) and P-wave dispersion (45 +/- 13 ms vs. 35 +/- 13 ms, P < 0.001) were found higher during migraine attacks than pain-free periods. We concluded that migraine attacks are associated with increased QTc and P-wave dispersion compared with pain-free periods.

Frequency of mtDNA A1555G and A7445G mutations among children with prelingual deafness in Turkey.

UNLABELLED: Considerable differences on the frequencies of the mitochondrial 12S rRNA A1555G and tRNA(Ser(UCN)) A7445G mutations have been reported in different populations. Our screening of 168 patients coming from independent Turkish families with prelingual sensorineural non-syndromic deafness revealed three deaf children with A1555G (1.8%) but no examples of A7445G. One proband with the mitochondrial A1555G mutation has also evidence for right parietal infarct on a brain imaging study, for which common thrombotic mutations were found to be negative. CONCLUSION: This study shows that the mitochondrial A1555G mutation is among the significant causes of prelingual non-syndromic deafness in the Turkish population.

Moderate hearing loss and pseudodominant inheritance due to L90P/35delG mutations in the GJB2 (connexin 26) gene.

Mutations in the GJB2 (connexin 26-Cx26) gene are responsible for 20-50% of cases with prelingual non-syndromic deafness in a large part of the world including Turkey. Although most of the cases with Cx26 deafness have a recessive mode of inheritance, a small group of families demonstrated dominant or pseudodominant inheritance. In this report we present a Turkish family in which the proband had congenital profound deafness and was found to be homozygous for the 35delG mutation, whereas the father and a paternal uncle who had milder, late-onset sensorineural hearing loss had compound heterozygous 35delG and L90P mutations. This family and previous reports with the L90P mutation demonstrate that the hearing loss associated with the L90P/35delG genotype is consistently milder than that of 35delG homozygotes. GJB2 gene screening should be considered in families with seemingly dominant inheritance and late-onset moderate hearing loss.

Mutations of the 5alpha-steroid reductase type 2 gene in six Turkish patients from unrelated families and a large pedigree of an isolated Turkish village.

We describe six Turkish patients with 5alpha-steroid reductase type 2 deficiency from unrelated Turkish families and a large pedigree of one of these patients who reside north-west of Anatolia. Patients NA, KS, BD and SY presented for evaluation of bilateral inguinal masses with female phenotypes. Patient ABE had penoscrotal hypospadias with male phenotype. Homozygous mutation of the 5alphaSR2 gene was identified in five of these patients by genomic DNA analysis. These mutations were Leu55Gln in exon 1 (in patients FG, BD and ABE), deltaMet157 in exon 3 (in patient NA), and splice junction abnormality in intron 1 (in patient SY). One individual (patient KS) was found to be a compound heterozygous carrier of two different mutations, Leu55Gln in exon 1 and Arg171Ser in exon 3. Patient FG had a large pedigree with the Leu55Gln mutation in exon 1. The pedigree of this family with marital consanguinity is remarkable, and possibly due to the isolation of this family because of economic and social problems. A further 85 individuals belonging to this family were analyzed for exon 1 Leu55Gln mutations in the 5alphaSR2 gene. Forty-two of these 85 individuals (49.41%) had this alteration; 11 were homozygous (8 genetic male, 3 genetic female) and 31 heterozygous (18 genetic male, genetic female) for this mutation. It was interesting to see asymptomatic homozygous female carriers. In conclusion, according to our results and those of other Turkish patients reported by different investigators, 5aSR2 gene mutation analysis, especially for Leu55Gln in exon 1 and deltaMet157 in exon 3, must be carried out in Turkish patients with male pseudohermaphroditism. Homozygous asymptomatic female carriers must be taken into consideration in this clinical entity, especially in a closed population, because of the risk of transmitting the disease to their offspring.

A multistep process for the dispersal of a Y chromosomal lineage in the Mediterranean area.

In this work we focus on a microsatellite-defined Y-chromosomal lineage (network 1.2) identified by us and reported in previous studies, whose geographic distribution and antiquity appear to be compatible with the Neolithic spread of farmers. Here, we set network 1.2 in the Y-chromosomal phylogenetic tree, date it with respect to other lineages associated with the same movements by other authors, examine its diversity by means of tri- and tetranucleotide loci and discuss the implications in reconstructing the spread of this group of chromosomes in the Mediterranean area. Our results define a tripartite phylogeny within HG 9 (Rosser et al. 2000), with the deepest branching defined by alleles T (Haplogroup Eu10) or G (Haplogroup Eu9) at M172 (Semino et al. 2000), and a subsequent branching within Eu9 defined by network 1.2. Population distributions of HG 9 and network 1.2 show that their occurrence in the surveyed area is not due to the spread of people from a single parental population but, rather, to a process punctuated by at least two phases. Our data identify the wide area of the Balkans, Aegean and Anatolia as the possible homeland harbouring the largest variation within network 1.2. The use of recently proposed tests based on the stepwise mutation model suggests that its spread was associated to a population expansion, with a high rate of male gene flow in the Turkish-Greek area.

The alpha2 Gene alleles of the platelet collagen receptor integrin alpha2 beta1 in Turkish children with cerebral infarct.

The possible role of point mutations in the platelet integrin alpha2 beta1 gene in Turkish children with ischemic stroke was evaluated in this study. The case-control study included 44 pediatric patients with cerebral infarct (age range, 10 months to 18 years) and 96 healthy unrelated individuals. Genotyping was performed according to previously described methods. Distribution of the three haplotypes were 36.4%, 45.3%, 10.4% and 31.8%, 50.0%, 13.6% for the controls and the patients, respectively. A new fourth haplotype was found which was 7.8% and 4.5% respectively. Our data indicated that these haplotypes are not risk factors in pediatric stroke group.

Superior cerebellar artery territory stroke.

OBJECTIVES: The purpose of this study was to clarify etiologic factors, prior symptoms and clinical features of isole superior cerebellar artery (SCA) territory infarcts. METHODS: All data were collected from consecutive 21 patients with isole SCA infarcts involved on computerized tomography. RESULTS: The risk factors including hypertension, cardiopathy and rhythm disturbances, hyperlipidemia, diabetes mellitus, abnormality in homeostasis, smoking, oral contraceptive have been identified. Headache, nausea-vomiting, vertigo, gait imbalance and diplopia were the most common complaints at onset. During the clinical course, the most common findings have been found as dysmetria and dysdiadochokinesia, dysarthria, ataxia and vertigo. Although 19 patients were improved in different degrees, 2 patients died because of cardiorespiratory arrest. Classical syndrome of SCA was only seen in 2 patients. CONCLUSION: According to our findings, SCA territory infarcts have multiple risk factors, and various clinical features as well as the syndrome of SCA are usually rare and incomplete.