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Background: Cluster analysis is a robust tool for exploring the underlining structures in data and grouping them with similar objects. In the researches of Functional Magnetic Resonance Imaging (fMRI), clustering approaches attempt to classify voxels depending on their time-course signals into a similar hemodynamic response over time. Objective: In this work, a novel unsupervised learning approach is proposed that relies on using Enhanced Neural Gas (ENG) algorithm in fMRI data for comparison with Neural Gas (NG) method, which has yet to be utilized for that aim. The ENG algorithm depends on the network structure of the NG and concentrates on an efficacious prototype-based clustering approach. Methods: The comparison outcomes on real auditory fMRI data show that ENG outperforms the NG and statistical parametric mapping (SPM) methods due to its insensitivity to the ordering of input data sequence, various initializations for selecting a set of neurons, and the existence of extreme values (outliers). The findings also prove its capability to discover the exact and real values of a cluster number effectively. Results: Four validation indices are applied to evaluate the performance of the proposed ENG method with fMRI and compare it with a clustering approach (NG algorithm) and model-based data analysis (SPM). These validation indices include the Jaccard Coefficient (JC), Receiver Operating Characteristic (ROC), Minimum Description Length (MDL) value, and Minimum Square Error (MSE). Conclusion: The ENG technique can tackle all shortcomings of NG application with fMRI data, identify the active area of the human brain effectively, and determine the locations of the cluster center based on the MDL value during the process of network learning.

AbstractA multiclass c-server retrial queueing system in which customers arrive according to a class-dependent Markovian arrival process (MAP) is considered. Service and retrial times follow class-dependent phase-type (PH) distributions with the further assumption that PH distributions of retrial times are acyclic. A necessary and sufficient condition for ergodicity is obtained from criteria based on drifts. The infinite state space of the model is truncated with an appropriately chosen Lyapunov function. The truncated model is described as a multidimensional Markov chain, and a Kronecker representation of its generator matrix is numerically analyzed.

Markovian systems with multiple interacting subsystems under the influence of a control unit are considered. The state spaces of the subsystems are countably infinite, whereas that of the control unit is finite. A recent infinite level-dependent quasi-birth-and-death model for such systems is extended by facilitating the automatic representation and generation of the nonzero blocks in its underlying infinitesimal generator matrix with sums of Kronecker products. Experiments are performed on systems of stochastic chemical kinetics having two or more countably infinite state space subsystems. Results indicate that, even though more memory is consumed, there are many cases where a matrix-analytic solution coupled with Lyapunov theory yields a faster and more accurate steady-state measure compared to that obtained with simulation.

The study objective of this prospective, double-blind randomised controlled study was to evaluate the efficacy of ultrasound guided transversus abdominis plane (TAP) block and bupivacaine infiltration of the skin and subcutaneous tissue of the wound in patients undergoing hysterectomy. Patients were randomly allocated to three groups: a control group (n=18) and TAP block group (n=18) received bilateral TAP blocks with saline and bupivacaine respectively, and an infiltration group (n=19) received skin and subcutaneous wound tissue infiltration with bupivacaine at the end of surgery. After surgery patients received patient-controlled intravenous tramadol and were assessed for pain and tramadol consumption at 1, 2, 4, 6 and 24 hours.Both the TAP and infiltration groups had lower movement and rest pain scores than the control group, with lower scores in the TAP group than the infiltration group at 6 and 24 hours. Total tramadol consumption was significantly lower in the TAP group than in the other groups at all time points. We concluded that ultrasound-guided TAP block reduced rest and movement pain after total abdominal hysterectomy and was more effective than superficial wound infiltration for postoperative pain management.

Purpose To study the frequency of exfoliation syndrome (XFS) and its association with intraocular pressure (IOP) and systemic diseases in patients with age-related cataract scheduled for surgery.Methods All 1480 cataract patients had a comprehensive systemic and eye examination, including slit-lamp biomicroscopy before and after mydriasis, IOP measurement, gonioscopy, and fundus examination.Results The percentage of XFS among patients scheduled for cataract surgery was 16.4, with no gender difference (p=0.833). The mean age of XFS patients (74.3±7.0 years) was significantly higher when compared to the ones without XFS (66.5±10.9 years) (p<0.001). XFS was unilateral in 41.3% of the subjects and bilateral in 58.7%. The number of subjects with XFS increased significantly with aging (p<0.001) (OR=1.093, 95% CI=1.073–1.14) (p<0.001). The most common type of cataract was nuclear in the XFS group (33.5%) and 24.6% of patients with mature cataract had XFS. In the XFS group, 11.2% of the subjects had glaucoma, which was statistically higher than the non-XFS group (4.6%) (p<0.001) (OR=2.67, 95% CI=1.65–4.32). Eighty-four patients had glaucoma and 27 of them (32.1%) had exfoliative glaucoma. The only systemic disease that was found to be associated with XFS was coronary heart disease with an OR of 1.49 (95% CI=1.068–2.072) (p=0.019).Conclusions XFS is a common problem in the aging cataract population of Turkey and increased IOP, glaucomatous optic neuropathy, and coronary heart disease occur more frequently in patients with XFS compared with subjects without XFS.

Purpose To evaluate serum allergen specific immunoglobulin E (IgE) levels in patients with various types of allergic conjunctivitis.Methods Twenty-five patients with seasonal allergic conjunctivitis (SAC), 17 patients with perennial allergic conjunctivitis (PAC), and 10 patients with vernal conjunctivitis (VC) were included in the study Specific IgE levels to Dermatophagoides pteronyssinus (Dp), Dermatophagoides farinae (Df), mixed grass pollens, and animal epithelia were measured using Pharmacia CAP system (Pharmacia Diagnostic AB, Uppsala, Sweden).Results The percentage of subjects with specific IgE against Dp and Df was statistically higher in VC (30%) compared to PAC (5.9%) and SAC (0%) (p=0.03). Specific IgE against mixed grass pollens was found in 30% of VC and 40% of SAC, whereas 10% of VC and 8% of SAC patients were found to be hypersensitive to animal epithelia.Conclusions Allergic reaction against house dust mites and pollens was common in VC, whereas specific IgE against grass pollens was remarkable in SAC. IgE levels specific to various antigens might be measured by UNICAP system, which is a rapid and practical technology.

Purpose To evaluate the results of short wavelength perimetry (SWAP) of ocular hypertensive (OHT) patients and correlate these findings with central corneal thickness (CCT) measurements.Methods Thirty-seven OHT patients with a mean age of 50.2±8.2 (SD) years and 30 control subjects with a mean age of 50.3±8.5 (SD) years were included in this study. A questionnaire was applied to patients to evaluate the demographic risk factors that may predict glaucoma development. After a detailed ophthalmologic examination, achromatic and short wavelength perimetries and ultrasonic pachymetry were performed and the results were compared between the two groups with Student t test and Mann-Whitney U test. A p value <0.05 is considered as statistically significant.Results Mean CCT was higher in the OHT group (right eye; 558.13±28.39 μm and left eye; 558.94±27.30μm) when compared with the control subjects (524.66±30.53 μm and 525.86±30.46 μm, respectively) (p<0.01). A significant positive correlation was found between CCT measurements and intraocular pressure (r=0.5, p<0.001). Four right eyes (10.8%) and five left eyes (13.5%) of OHT patients had defects in SWAP. OHT patients with SWAP abnormalities had significantly lower CCT measurements in right (527.25±17.34 μm) and left eye (528.80±13.60 μm) when compared with OHT patients without SWAP defects (561.87±27.29 μm and 563.65±25.92 μm, respectively) (p<0.05). Significant correlations were found between CCT and SWAP MD, PSD, and CPSD (p<0.05).Conclusions OHT patients with SWAP abnormalities had significantly lower CCT measurements than those without. CCT is considered as a risk factor for the development of glaucomatous damage in OHT patients.

Not Available

Purpose To measure the retinal nerve fiber layer thickness in patients with pigment dispersion syndrome (PDS) using scanning laser polarimetry and to compare these measurements with those of normal subjects and patients with pigmentary glaucoma (PG).Methods Age-, sex-, and refractive error-matched subjects – 18 patients with PDS, 18 patients with PG, and 20 healthy subjects – were evaluated by scanning laser polarimetry (Nerve Fiber Analyzer [NFA] GDx). The NFA did not have a compensator for corneal polarization. One randomly selected eye from each patient was included in the statistical analysis. The NFA measurements of patients with PDS and PG and healthy subjects were compared statistically using analysis of variance, Tukey multiple comparisons, chi-square, and independent t-tests.Results The mean values for average thickness, superior and inferior maximum, superior and inferior average, ellipse average thickness, and superior integral were found to be lower in the patients with PDS (p<0.02) and PG (p<0.005) compared to the normal subjects. The mean values for maximum modulation, superior ratio, inferior ratio, and superior/nasal ratio in PDS were in between those of the PG and control groups (p>0.05). The ellipse modulation was significantly lower in the PG group when compared to the other two groups (p<0.03).Conclusions Retinal nerve fiber loss is present to some extent in patients with PDS and this loss is not age or sex dependent. Parameters of modulation might be more representative of significant damage of the nerve fiber layer.

Purpose Either autogenous or allograft fascia lata frontal sling procedures can be used for the treatment of severe ptosis. We retrospectively evaluated the late outcomes of both approaches.Methods Medical records of patients who underwent frontal sling ptosis surgery between 1978 and 2000, with a follow-up of one year or more were included in the study. Success rates and the complications of the surgery for autogenous and allograft fascia lata were recorded. The results were compared statistically.Results Surgeries were performed with 82 autogenous or 43 allograft fascia lata. At last follow-up there were 71 eyes (86.6%) with good, 8 eyes (9.7%) with moderate, 3 eyes (3.7%) with poor results after autogenous fascia lata and 35 (81.4%), 3 (7%) and 5 (11.6%) after the allograft fascia lata frontal sling procedure. There was no significant difference between the two groups. Repeat surgery was carried out on three patients after autogenous and five after allograft fascia lata surgery. Two cases of preseptal cellulitis were observed, one abscess after autogenous and one lagophthalmus after allograft fascia lata sling surgery. All patients had slight edema early after surgery which resolved in a few days. Only one patient developed a hematoma at the site of the leg incision.Conclusions Although the long-term success rate with the autogenous fascia lata is slightly higher and this remains the first choice, allograft fascia lata is a good alternative in patients in whom fascia could not be harvested.

Purpose To evaluate the effect on lacrimal function and ocular complications in patients with severe acne vulgaris during systemic treatment with 13-cis-retinoic acid (isotretinoin).Methods Forty patients with acne vulgaris were treated with systemic isotretinoin at dosages of 0.5-1 mg/kg per day for two months. Full ophthalmologic examination, Schirmer / test, fluorescein break-up (BUT) and microbiological investigations of the conjunctival flora were done before, during the second month and at least one month after the end of the treatment.Results The average Schirmer values before and after the treatment were 21.6 mm/5 minutes (SD ± 7.01) and 18.48 mm/5 minutes (SD ± 7.87) respectively. After the treatment BUT was less than 10 seconds in 50% of the patients and 55% had blepharitis. Subjective symptoms like dryness, itching and contact lens intolerance occurred in 42.5% and colonization of the conjunctiva byStaphylococcus aureus increased significantly during treatment (p = 0.031). All abnormal findings disappeared one month after the cessation of treatment.Discussion Isotretinoin causes signs and symptoms of dry eye, probably by reducing meibomian gland function, but ocular complications are generally not serious when low doses are used for a limited time, and are reversible after discontinuation.

Purpose To assess the thickness of the retinal nerve fiber layer (RNFL) in patients with different stages of glaucoma, in comparison with ocular hypertensive (OHT) and healthy subjects in a Turkish population.Methods Scanning laser polarimetry was done with a GDx Nerve Fiber Analyzer (NFA, GDx version, 1.0.08) on 270 eyes with glaucoma, 52 OHT eyes, and 81 normal eyes. The eyes were classified as having early (146 eyes), moderate (66 eyes) and severe (58 eyes) glaucoma based on the Humphrey Visual Field indices. We compared 14 NFA parameters by analysis of variance (ANOVA) and Scheffe multiple comparison analysis. Receiver operator characteristic curves (ROC) and Fisher linear discriminant analysis (LDF) were used to measure the sensitivity and specificity of the NFA parameters.Results Except for symmetry, all NFA parameters showed significant differences between the groups (p<0.05). The eyes with glaucoma had significantly thinner RNFL than healthy eyes (p<0.01). The RNFL retardation measurements of OHT eyes were lower than controls, but higher than the early glaucoma group. The sensitivity and specificity of the GDx System were 87% and 72.8%, respectively. Applying LDF, the group with the highest sensitivity and specificity (85.9% and 74.1%) was determined as inferior ratio, superior/nasal ratio, superior maximum and the Number.Conclusions Assessment of RNFL thickness with scanning laser polarimetry can distinguish glaucoma, OHT and normal subjects with relatively high sensitivity and specificity.

. Purpose:
The aim of this study was to compare the RNFL thickness in eyes with myelinated retinal nerve fibers (MRNF) and age, sex-matched controls using scanning laser polarimetry.
Methods:
Seventeen patients with MRNF underwent a comprehensive ophthalmological examination including automated visual field testing, and scanning laser polarimetry with Nerve Fiber Analyser (NFA II). Twenty eyes with MRNF from 17 patients were available for the study. Sixteen healthy, age and sex-matched subjects were taken as controls. Retinal nerve fiber thickness measurements of the four sectors (superior, inferior, nasal, temporal) and along the whole circumference of the optic disc were obtained for affected and control eyes, and compared.
Results:
Inferior average and inferior integral parameters of the NFA revealed significantly thinner RNFL thickness measurements in eyes with inferiorly located MRNF compared to controls.
Conclusion:
Retinal myelination alters the birefringent property of the RNFL, and results in diminished thickness measurements. Hence, NFA measurements in patients with MRNF may not be reliable.

Purpose The aim of the study is to investigate whether tear ferning patterns change during different phases of the menstrual cycle.Methods The tear ferning test was performed on twelve normal women of childbearing age at three day intervals throughout one complete menstrual cycle. Serum hormone levels (progesterone, estrogen, testosterone) were measured.Results Eight women showed type I ferning, and the other four had type II ferning initially. These patterns did not change during the menstrual cycle. Serum hormone levels were all in the normal range. Since no change in ferning pattern was detected during the menstrual cycle, the ferning test can be done at any time in women.Conclusions This study showed no effect of different menstrual cycle phases on tear ferning patterns.

Purpose To compare topographic indices of surface regularity in dry eye patients and in normal subjects (controls) and to investigate the short-term effect of lacrimal punctal plugs on these indices in dry eye patients.Methods The surface regularity index (SRI) and surface asymmetry index (SAI) of the TMS-2 corneal topographic modelling system were used to evaluate corneal surface regularity in 20 eyes of 10 dry eye patients before and after the insertion of Herrick silicon lacrimal plugs (Lacrimedics, Rialto, CA, USA) and in 24 eyes of 12 normal subjects as controls.Results SRI and SAI were significantly lower in controls than dry eye patients (p=0.00). Median SRI was 1.72 in dry eye patients before punctal occlusion and 0.525 in the control group. Median SAI was 1.305 in dry eye patients and 0.240 in controls. After lacrimal punctal occlusion, Schirmer test results and fluorescein breakup time increased in nine patients and remained the same in one patient. After occlusion, the SRI decreased in 9 eyes, and increased in 11 (p=0.970); SAI decreased in 13 eyes and increased in 7 (p=0.135).Conclusions No significant change in topographic indices of corneal surface irregularity could be detected in severe dry eye patients with lacrimal punctal plugs in the short-term follow-up.

Purpose To investigate the effect of diltiazem on wound healing after the creation of conjunctival flaps in rabbit eyes. Also, to investigate the pharmacokinetics of diltiazem in rabbits after subconjunctival and topical administration.Methods For the histopathological study, a limbal-based flap was prepared and diltiazem was injected subconjunctivally for five days after the surgery. The rabbits were euthanised 20 days after surgery. The effectiveness of diltiazem on wound healing was evaluated by histopathological examination and measurement of the thickness of subconjunctival fibrous tissue. For the pharmacokinetic study, diltiazem was applied topically or injected subconjunctivally. Aqueous paracenteses were performed 0.5, 1, 2, 4 hours thereafter.Results The histopathological study found no difference in thickness of the subconjunctival fibrous tissue in control and diltiazem-treated eyes. No significant toxicity was observed in eyes treated with diltiazem. The peak aqueous concentration was 3.8 ± 0.4 μg/ml after topical application and 15.3 ± 1.1 μg/ml after subconjunctival injection. The peak aqueous concentration was achieved 1/2 hours after administration in both cases.Conclusions Diltiazem did not appear to affect wound healing at the dose tested. Topical and subconjunctival diltiazem successfully penetrated the aqueous humor of rabbit eyes.

Purpose An oil in water emulsion of 0.01% all-trans-retinoic acid (tretinoin) was prepared and clinically evaluated in dry eye patients.Methods The ophthalmic emulsion consisted of 10% of arachis oil and 90% of the hydro-gel of Carbopol 940. To evaluate retinoic acid emulsion clinically, a placebo-controlled, open-labeled, randomized study was performed with 22 dry-eye patients. Symptoms were recorded before and after the treatments. The Schirmer 112067210001000205l test, measurement of tear film break-up time (BUT), rose Bengal and fluorescein staining of cornea and conjunctiva, and mucus fern test were done.Results Retinoic acid did not improve the dryness, photophobia and foreign body sensation more than placebo. Schirmer test and BUT were significantly improved by retinoic acid treatment. Corneal and conjunctival epithelium maintained their characteristics during the use of retinoic acid, as indicated by rose Bengal and fluorescein staining.Conclusions Ophthalmic emulsion of retinoic acid can be suggested as a promising approach for the treatment of dry eye.

The Selcuk type headgear-timer (STHT) is described and tested under laboratory conditions first and then in a controlled patient study. The timing device was compared with real time measurements for 4 months. Accuracy was determined to be absolute (100%). The STHT was determined to be independent of force variables, easy to construct, rugged, and inexpensive. In the clinical test, 10 patients were instructed to wear the extraoral appliance for 16 hours a day. After a 2-month treatment period, the timing mechanisms were introduced to the patients and a subsequent 2-month treatment period was initiated. At the end of the second period, headgear wear was increased 26%. This significant improvement in patient compliance with the STHT timing device, attached to a standard breakaway type headgear, has the likelihood of enhancing treatment results. A foolproof method of assessing actual duration of wear is now available. (Am J Orthod Dentofac Orthop 1997;111:87-92.)

Purpose The pathogenesis of pterygium is still not completely understood and many environmental factors, including ultraviolet (UV) radiation, play an important role in its etiology. Chronic exposure to UV radiation causes mutations in the p53 tumor suppressor gene, eventually leading to tumor formation. We analyzed the immunohistochemical expression of p53 proteins in pterygial tissues to determine the role of the p53 tumor suppressor gene in the development of pterygium.Methods Pterygial specimens were studied immunohistochemically using antibodies against p53 protein.Results Out of 38 specimens studied, 35 (92.1%) had conjunctival epithelial cells without p53 specific nuclear staining. Only three specimens (7.9%) had a few p53 stained cells. The role of UV radiation in the pathogenesis of pterygium is supported by epidemiological, geographical and microscopic findings. However, our results are not consistent with these data on a genetic basis.Conclusions We conclude that defective p53 tumor suppressor gene function seems to have no role in the pathogenesis of pterygium.

Purpose To report a case of corneal neovascularization possibly associated with latanoprost therapy.Methods Case report: A 67-year-old man developed a progressive stromal corneal neovascularization in his right eye within eight months of a corneal trauma. At admission, he was receiving latanoprost 0.005% therapy. His topical medications were rearranged: latanoprost was replaced with carteolol hydrochloride 1% twice daily bilaterally and prednisolone acetate 1% was added twice daily in the right eye.Results One month later, he presented regression of the corneal neovascularization and an increase in visual acuity.Conclusions Latanoprost, an arachidonic acid derivative, could have directly or indirectly stimulated the corneal neovascularization in this patient with a history of nonpenetrating corneal trauma.

Purpose To compare conventional and endoscopic probing for congenital nasolacrimal duct obstruction in infants.Methods Conventional probing was performed in 22 eyes of 18 patients, age range 7–14 months (mean 11.4 months). Probing was done with intranasal endoscopic visualization in 18 eyes of 14 patients, age range 7–13 months (mean 11.2 months). All were primary probing cases.Results After conventional probing 2 of the 22 cases required reprobing. After endoscopic probing only 1 of the 18 cases required reprobing.Conclusions In most cases of congenital nasolacrimal duct obstruction endoscopy is not required; however, in failed cases direct visualization of the inferior meatus with endoscopic guidance may be helpful.

Dacryoliths are uncommon causes of partial or complete obstruction of the nasolacrimal drainage apparatus. We report our findings of a dacryolith that we studied by culture, light microscopy, atomic absorption spectrophotometry, and scanning electron microscopy. Although no fungi were recovered by culturing, hyphae-like structures were observed. No inorganic material was detected by atomic absorption spectrophotometry. Scanning electron microscopy of ultrastructure showed the stone was composed of lobes and lobules built on an amorphous core material.

Some chemical carcinogens, such as urethane and diethylnitrosamine, have been shown to produce carcinogenic effects on the fetus in utero(1, 2). In the case of the polycyclic hydrocarbon carcinogens, the data are quite unclear. A number of investigations have demonstrated that administration of polycyclic hydrocarbon carcinogens to pregnant animals will result in an increased number of tumors in their progeny (3–7). However, in these experiments, the offspring have been allowed to nurse on their own mothers. Since polycyclic hydrocarbon carcinogens will appear in the milk, a distinction cannot be made between prenatal and postnatal exposures (8). The studies to be presented were designed to distinguish between these two possibilities. The progeny of female mice which had received subcutaneous injections of benzo(a)pyrene (BP) during the latter half of pregnancy were delivered by caesarean section and nursed on foster mothers from a control group which had not received injections of any type. Thus, any carcinogenic effect which resulted from administration of the carcinogen would have occurred during the prenatal period. In the experiments to be reported the presence and number of pulmonary adenomas have been determined. The mouse lung is highly sensitive to chemical carcinogens, and such exposures result in formation of pulmonary adenomas (9). A second tissue which has received special attention is the skin. Weak carcinogenic effects in the skin, such as initiation, can be elicited or accelerated by subsequent topical application of croton oil (10) and this procedure has been employed. In addition to the study of these two sensitive indices of a carcinogenic effect, the presence of tumors in other tissues was also searched for at autopsy.Materials and Methods. Female Ha/ICR mice obtained from Millerton Farms, N.Y. were used for the study of carcinogenesis.

Saydam: Novartis Pharmaceuticals Corporation, Turkey: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees.

Saydam: Novartis Pharmaceuticals Corporation, Turkey: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Yavuz:Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity's Board of Directors or advisory committees. Ali:Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity's Board of Directors or advisory committees. Guvenc:Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity's Board of Directors or advisory committees. Sonmez:Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity's Board of Directors or advisory committees. Akkaynak:Novartis Pharmaceuticals Corporation, Turkey: Employment. Dag:Novartis Pharmaceuticals Corporation, Turkey: Employment.

Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in Western countries, predominates in the elderly. In this retrospective multicenter study, we investigated the clinical, biological features, outcomes and prognosis in 418 patients with CLL (269 men, 149 women with median age 73.8 years, range from 65 to 91years), who were diagnosed in 10 university hospitals in Turkey from January 2002 to December 2012. Three groups of patients were distinguished: 65-69 years-old (n=121), 70-79 years-old (n=210) and ≥80 years-old (n=87). There were B symptoms in 32.9% of all patients and the rate of B symptoms increased with the increasing age (rate of B symptoms in 3 age groups: 28.9%, 31.9%, 40.7%, respectively) (p=0.189). Bulky disease was seen in 5% of all patients. However, the rate of bulky disease decreased with the increasing age (rate of bulky disease in 3 age groups: 6.7%, 5.2%, 2.3%, respectively) (p=0.189). There was no organomegaly in 49.2% of the patients. However, rates of isolated hepatomegaly, isolated splenomegaly and hepatosplenomegaly were 7.7%, 22.9%, 20.2%, respectively. There were co-morbid diseases in 50.4% of all patients (hypertension 34.6%, type 2 diabetes mellitus 14.3%, coronary heart disease 10%, carcinoma 4%, thyroid disease 0.4%, and other diseases 23.6%). However, co-morbidity rates did not differ in 3 age groups (p=0.517). The infection rate was 16.6% and infections were seen mostly in ≥80 years-old patient group (rates were as 16.7%, 16.2%, and 17.4%, respectively) (p=0.966). The most common infection was lower respiratory tract infection in elderly patients (12.4%). The other common infections were urinary tract (1.9%), skin (1.4%), upper respiratory tract (0.5%) and sepsis (0.2%). The mean hemoglobin level was 11.9 ± 2.5 gr/dL and decreased with increasing age (12.7 gr/dL, 12.1 gr/dL, 11.2 gr/dL in 3 age groups, respectively) and this was statistically significant (p=0.008). The mean platelet count was 158300/mcL, leukocyte count was 41.9 x109/L, and lymphocyte count was 32.3 x 109/L, and these values were similar in 3 age groups. Bone marrow infiltration was mostly in diffuse pattern (33.7%) instead of interstitial (9.5%) or nodular pattern (9.8%) in all ages (p=0.575). Mean LDH, ß2-microglobulin levels and sedimentation/h were similar in 3 age groups. There was autoimmune hemolytic anemia in 13.8% of the patients. No biological differences (17p del, 13q del by fluorescent in situ hybridization, CD38, ZAP-70) were found across age groups (p=0.994). ECOG score was 0, 1, 2, 3, 4 in 35.5%, 40.1%, 20.5%, 3.4%, and 0.5% of the patients, respectively and the score increased with increasing age with a statistically significant difference (p=0.001). Most of the patients presented with early stage of CLL (Rai 0-I-II: 66.7%, Rai III-IV: 33.3%), however, stage of the disease increased with the increasing age (Rai 0-I-II: 66.3%, Rai III-IV: 33.7% in first group; Rai 0-I-II: 70.2%, Rai III-IV: 29.8% in second group; Rai 0-I-II: 58.4%, Rai III-IV: 41.7% in third group; p<0.099). 47.4% of the patients had to be treated and the indications for treatment were stage III-IV disease (50.7%), B symptoms (30.5%), increased doubling time (7.7%), frequent infections (4.8%), bulky disease (3.7%), and immune cytopenias (2.6%). Patients were treated mostly with chlorambucil + methylprednisolone (26.3%) and chlorambucil (25.8%) alone. Rates of complete remission (CR), partial remission (PR), stabile and progressive disease after treatment are 43.3%, 39.8%, 4.1%, and 12.9%, respectively. In the advanced age group, CR rate was found to be less than the younger patients (CR rates in 3 age groups: 62.5%, 36.1%, and 28.1%, respectively). Remission time was 0-12 months in 39.5%, 13-24 months in 23.6%, and >24 months in 36.9% of the patients. However, the remission times did not differ according to the 3 age group (p=0.412). In addition, remission time after therapy did not differ according to the co-morbidity rates (p=0.709). 20.9% of the patients died and 76.4% of the deaths were CLL related sepsis and pneumonia. The cause of deaths did not differ according to the 3 age groups (p=0.612). In conclusion, patients with CLL in advanced ages present with higher ECOG score, higher stages, and more co-morbidities and infections are the most important mortality reason. This study highlights the importance of a comprehensive medical care, achieving specific management strategies for elderly patients with CLL.

Introduction

Low cholesterol levels can be detected in solid tumors and hematological malignancies such as muliple myeloma. Moreover chloesterol levels reduced in some experimental studies of patients with chronic lymphocytic leukemia (CLL). In this retrospective multicenter study, lipid levels were retrospectively evaluated in 420 (264 male and 256 female with mean age 64 ± 11 years) patients with newly diagnosed CLL, according to the International CLL study group. 71 (28 male and 43 female with mean age 55 ± 9 years) healthy subjects as control group were included to this study. Lipid parameters such as total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), very low-density lipoprotein-cholesterol (VLDL-C), and triglyceride levels were measured with enzymatic/ calorimetric method and Architect C800 instrument. Low-density lipoprotein-cholesterol (LDL-C) levels were calculated according to Friedwald formula. Lipid parameters between two groups were compared with Mann-Whitney U test. A value of p< 0.05 was accepted as statistically significant. According to Binet classification, 60% of patients were in stage A, while 25% of them were in stage C. In CLL patients, the levels of TC, HDL-C, and LDL-C were lower than those of control group (p=0.001). There was no significantly difference for triglyceride and VLDL-C levels between two groups (p>0.05) (Table-1). The levels of TC, LDL-C, and HDL-C in the patients with stage C were lower than those of both stage A and stage B (Table-2). Low cholesterol levels in patients with CLL may occur due to increased use of cholesterol by lymphocytes.Table-1Lipid parameters in control group and CLL patientsCLL (N:420)Control (N:71)P valueTC (mg/dl)175±41217±36<0.001HDL-C (mg/dl)37±1153±14<0.001LDL-C (mg/dl)108±30131±29<0.001Triglyceride (mg/dl)140±71147±68>0.05VLDL-C (mg/dl)31±1731±17>0.05

Nilotinib, a more potent and selective drug than imatinib, was approved by the FDA and EMA initially for the treatment of chronic and accelerated phase Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) patients resistant or intolerant to prior therapy including imatinib and subsequently for the treatment of newly-diagnosed Ph+ CML patients in the chronic phase (CML-CP). The aim of the present study was to investigate efficacy and safety profile of nilotinib in a Turkish population of newly-diagnosed Ph+ CML-CP patients and to evaluate the effects of these results on prognosis according to current treatment guidelines.

Sonmez: Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity’s Board of Directors or advisory committees.

Nilotinib, a more potent and selective drug than imatinib, was approved by the FDA and EMA initially for the treatment of chronic and accelerated phase Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) patients resistant or intolerant to prior therapy including imatinib and subsequently for the treatment of newly-diagnosed Ph+ CML patients in the chronic phase (CML-CP). The aim of the present study was to investigate efficacy and safety profile of nilotinib in a Turkish population of newly-diagnosed Ph+ CML-CP patients and to evaluate the effects of these results on prognosis according to current treatment guidelines.The study was planned as a multicenter, open-label, one-arm phase II clinical trial. All patients were planned to be treated with nilotinib (AMN107, Tasigna®) 300 mg BID for 24 months. Herein, efficacy results of the patients who completed the first year of the study are presented.Of the 112 patients included in the study, data for 94 patients who completed 12 months of the study up to April 29, 2013 were analyzed. Of these 94 patients, 16 were excluded within this period and 78 completed the first year of the study within the median 371 days (range, 339-401 days) or median 12.4 months (range, 11.3-13.4 months). General characteristics of the patients are presented in Table 1.Treatment-related characteristics of the patients are presented in Table 2.Data are presented as mean±standard deviation or number (%), where appropriate.MMR (Major molecular rate): BCR-ABL/control gene ratio of ≤%0.1 measured by RQ-PCR as %CCyR (Complete cytogenetic response): Patients with 0% Ph+ metaphasesCumulative MMR rates at 3rd, 6th 9th, and 12th months of the patients are shown in Figure 1.According to the results of interim analysis of this first prospective CML study conducted on Turkish population, the cumulative MMR rate by 12th month (primary endpoint) (61.7%) appears to be similar to that of the ENESTnd study. From the 3rd month, rapid and increasing MMR rates were reported and median time to MMR was 6.5 months. At both 6th and 12th month, high CCyR rates (both 90.5%) were also established. At all landmark evaluations, most of the patients rapidly achieved high rates of cytogenetic and molecular responses to nilotinib assessed by both 2009 and 2013 ELN optimal response criteria, and only one patient had disease progression. These results suggest that more rapid and greater efficacy was achieved with nilotinib during the 1st year of the study in comparison to historical data with imatinib and that nilotinib might improve short-term responses when started in the first-line setting.The rate of patients with BCR-ABL ≤10% at 3rd month, which is very important according to the current treatment guidelines, was 86.2%.The results of the present study revealed that efficacy of nilotinib, which is a licensed alternative for the treatment of newly diagnosed Ph+ CML-CP in Turkey, might provide a new standard of treatment.Saydam: Bristol-Myers Squibb: Membership on an entity’s Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation, Turkey: Consultancy, Membership on an entity’s Board of Directors or advisory committees. Haznedaroglu:Novartis Pharmaceuticals Corporation, Turkey: Honoraria, Research Funding. Yavuz:Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity’s Board of Directors or advisory committees. Ali:Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity’s Board of Directors or advisory committees. Guvenc:Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity’s Board of Directors or advisory committees. Sonmez:Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity’s Board of Directors or advisory committees. Akkaynak:Novartis Pharmaceuticals Corporation, Turkey: Employment. Dag:Novartis Pharmaceuticals Corporation, Turkey: Employment.

A simple injection device has been developed which allows the option of introducing either liquid or dry samples into gas chromatographic columns. The injector is compact, sturdy, and inexpensive. This device provides the gas chromatography user with the freedom to use liquid and dry injection methods interchangeably which greatly helps to resolve questions raised by use of either of the two methods of injection alone. The apparatus described has been employed routinely in this laboratory for more than two years, and our experience indicates that the injector is reliable and that accurate results can be obtained.