Clinical characteristics of Crouzon syndrome.

Crouzon syndrome (CS) is an genetic disorder with autosomal dominant inheritance caused by mutation of the gene for fibroblast growth factor receptor 2 (FGFR2) was described as one of the varieties of craniosynostosis. In this presented case, premature closure of the sutures had caused restricted skull growth and lack of space for the growing brain resulted to shallowed eyes and cranial and ophthalmic deformities and impairment in tooth development. Management of a patient of CS has two components. First is the release of prematurely fused sutures based on evidence of raised intracranial pressure. Surgery is mainly carried out early after 3-6 months. Second is the craniofacial reconstructive surgery including advancement of the maxilla and frontonasal complex; and other surgeries depending upon the deformities. An increased intracranial pressure impairs brain development and can lead to mental retardation. Because of the delayed diagnosis and treatment in this case, visual and hearing loses and decreased mental capacity and mild retardation.

Noninvasive assessment of subclinical atherosclerosis in normotensive gravidae with gestational diabetes.

AIM: Carotid artery intima-media thickness (CIMT), hyperhomocysteinemia, microalbuminuria, and nitric oxide reflect subclinical atherosclerosis and predict the risk of future cardiovascular events. We aimed to evaluate the presence of subclinical atherosclerosis and endothelial dysfunction in normotensive patients with gestational diabetes mellitus (GDM) noninvasively. PATIENTS AND METHODS: We enrolled 41 normotensive patients with GDM and 44 healthy gravidae in the study. Serum homocysteine and nitric oxide levels, urinary albumin excretion (microalbuminuria), and CIMT were evaluated along with lipid parameters and anthropometric measurements. RESULTS: Patients with GDM had significantly higher levels of serum homocysteine, urinary albumin excretion, and increased CIMT (p < 0.001, p=0.005, and p < 0.001, respectively). Nitric oxide levels were significantly reduced in the patient group (p < 0.001). There was a significant difference between groups in terms of low-density lipoprotein (LDL) but not of high-density lipoprotein (HDL) and triglyceride levels. A significant correlation was observed between CIMT and serum LDL, HDL, homocysteine, nitric oxide levels, and urinary albumin excretion. Microalbuminuria was significantly correlated with serum homocysteine levels (p=0.03) but not with nitric oxide. CONCLUSION: Independent of elevated blood pressure, subclinical atherosclerosis and endothelial dysfunction exist in normotensive patients with GDM. Further studies with a large number of participants are required to clarify these data.

Evaluation of hepatitis B viraemia levels in patients with HBeAg-negative chronic hepatitis B virus infection.

OBJECTIVES: To evaluate patients with chronic hepatitis B virus (HBV) infection and low-level viraemia in terms of determining HBV DNA cut-off values and levels of alanine aminotransferase (ALT) and other possible markers for discriminating between chronic hepatitis B e-antigen (HBeAg)-negative patients and hepatitis B surface antigen (HBsAg) inactive carriers. METHODS: HBV-infected patients who were HBeAg-negative with undetectable HBV DNA by standard hybridization assay and high (HBeAg-negative group, n = 81) or normal (HBsAg inactive carrier group, n = 77) ALT levels were enrolled. Quantitative polymerase chain reaction assay using a COBAS Amplicor HBV monitor test was performed to detect low HBV DNA levels. RESULTS: The HBV DNA level was found to be significantly higher in the HBeAg-negative chronic HBV group (mean ± SD 94,477 ± 167,528 copies/ml) compared with the HBsAg inactive carrier group (mean ± SD 19,215 ± 57,970 copies/ml). CONCLUSIONS: A low level of viral replication may persist in chronic HBV-infected patients who are HBeAg-negative, and the level of HBV DNA was higher in the HBeAg-negative group than in the inactive HBsAg carrier group. Necroinflammation also persisted in the HBeAg-negative group and these patients had a higher level of ALT than the inactive HBsAg carriers.

The role of homocysteine, asymmetric dimethylarginine and nitric oxide in pre-eclampsia.

Nitric oxide (NO) contributes to vasodilatation that is observed during normal pregnancy. Hyperhomocysteinaemia (HHcy) is a vascular risk factor associated with placental microvascular diseases and pre-eclampsia. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (NOS) has been linked to endothelial dysfunction. Maternal ADMA has been reported to be higher in women with pre-eclampsia and HHcy leads to accumulation of ADMA. The aim of this presented study is to evaluate the alterations of plasma homocysteine, ADMA and NO levels in mild pre-eclampsia. A total of 40 pre-eclamptic women and 40 healthy controls were included into the study. Mean systolic and diastolic blood pressure, mean serum homocysteine and ADMA levels were significantly higher and NO level was lower in patients. Serum homocysteine, ADMA and NO levels found to be correlated among them and with blood pressure. In conclusion, we found that homocysteine and ADMA levels were increased and NO levels decreased in pre-eclampsia.

Hirsutism score and the severity of hyperandrogenism associated with polycystic ovary syndrome in the southeastern region of Turkey.

This study investigated the severity of hirsutism and its correlation with serum total testosterone (tT) levels in 87 patients with polycystic ovary syndrome (PCOS) and 85 healthy control subjects from the south-eastern region of Turkey. A wide range of variability exists in both hirsutism and modified Ferriman-Gallwey (mFG) scores. Similar mFG scores and serum tT levels were found compared with previous studies of general populations, but lower scores than those previously reported from Turkey. The incidence of hirsutism was lower in hyperandrogenic PCOS patients compared with non-hyperandrogenic PCOS patients. There was no correlation between serum tT levels and the rate of hirsutism in patients with PCOS. Heritability, testosterone receptor sensitivity, 5α reductase activity or environmental/socioeconomic factors may play a role in the development of clinical hirsutism. Larger scale studies are needed to clarify which other factors may be responsible and to confirm these results.

Morphologic and functional vascular alterations in patients with polycystic ovary syndrome.

BACKGROUND: We aimed to investigate morphologic and functional alterations of common carotid arteries (CCA) and femoral arteries and the anteroposterior diameter of the abdominal aorta in patients with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: Fifty consecutive females with the complaint of oligoamenorrhea, infertility or hirsutismus, diagnosed with PCOS and 50 healthy females admitted to the Department of Gynecology and Obstetrics, Ergani State Hospital between January 2010 and January 2011 were included in the study. RESULTS: The mean BMI of 50 patients with PCOS was higher than control subjects (CS) (25.89 +/- 3.3 vs 22.52 +/- 2.7 kg/m2, p < 0.0001). The mean arterial blood pressure was 88.93 +/- 6.4 mmHg in the patient group and was it 85.73 +/- 7.6 mmHg in CS (p = 0.02). The mean plasma glucose level (74.04 +/- 6.7 vs 70.5 +/- 6.4 mg/dl), total cholesterol level (167.88 +/- 30.1 vs 153.38 +/- 27.8 mg/dl), low density lipoprotein level (101.28 +/- 27.0 vs 79.56 +/- 25.5 mg/dl) and triglyceride level (121.22 +/- 49.2 vs 102.54 +/- 36.6 mg/dl) were higher; also the mean high density lipoprotein level (44.56 +/- 8.1 vs 50.90 +/- 12.3 mg/dl) was lower in patients with PCOS than CS (p = 0.009, p = 0.014, p < 0.0001, p = 0.034 and p = 0.003, respectively). CCA-IMT (0.63 +/- 0.2 vs 0.52 +/- 0.1 mm), and CCA-PI (1.44 +/- 0.3 vs 1.28 +/- 0.22) were higher in patients with PCOS (p = 0.018 andp = 0.005, respectively). Femoral-IMT (0.62 +/- 0.6 vs 0.41 +/- 0.1 mm) and anteroposterior diameter of the infrarenal aorta (12.34 +/- 1.5 vs 11.4 +/- 1.0 mm) were higher in patients with PCOS (p = 0.024 and p = 0.001, respectively). CONCLUSION: The present study showed that IMT and PI of CCA, and anteroposterior diameter of the infrarenal abdominal aorta and femoral-IMT were higher in patients with PCOS. These results are probably related with increased androgens, their effects on insulin resistance and lipid profile, increased BMI and blood pressure. Detection of these functional and/or structural abnormalities are important in predicting prognosis. Larger scale prospective studies are needed to determine the effects of PCOS on the mortality and morbidity, and to clarify the relation between the duration of the disease and development of these alterations.

Evaluation of serum cystatin-C in dogs with visceral leishmaniasis.

Serum Cystatin C (sCys-C) is one of the most important serum markers of renal function assessment in dogs. The purpose of this study was to determine the sCys-C concentration in dogs with visceral leishmaniasis (VL). In the study, 16 dogs with VL and 10 clinical healty dogs (control) were used. Mean sCys-C concentration of the infected dogs was significantly higher than that of the control group (p < 0.05). Mean serum creatinine concentration was lower and mean blood urea nitrogen, albumin and globulin concentrations were higher in dogs with VL; however, these changes were not statistically significant. Mean total protein and phosphorus concentrations were found to be higher in dogs with VL than healthy dogs (p < 0.05). No significant correlation had been determined between sCys-C and other variables. Visceral leishmaniasis in dogs has increased sCys-C concentration indicating a possible renal impairment; however, further studies are needed to be performed together with renal biopsies in the investigation sCys-C in dogs with VL.

Clinical significance of elevated antinuclear antibody test in patients with Hodgkin's and Non-Hodgkin's lymphoma: a single center experience.

AIM: There is an increased risk of lymphoma subsequent to autoimmune conditions. Autoimmune disorders may occur in the course of lymphomas. In this study, the association of autoimmunity and related autoantibodies within non-Hodgkin's (NHL) and Hodgkin's lymphoma (HL) patients has been investigated. METHODS: The study enrolled 119 patients affected by NHL and 60 patients affected by HL for the presence of autoantibodies and autoimmune diseases. Afterwards, the results between the two lymphoma groups have been confronted. RESULTS: Autoimmune diseases were diagnosed in eight (6.7%) patients with NHL and three patients with HL (5%) (P=0.651). Thirty-four (28.5%) patients with NHL and 14 (23.3%) patients with HL displayed autoantibody positivity (P=0.083). As regards HL cases, antinuclear antibodies (ANA) were detected in 12 (20%) and anti PM-Scl in two patients (3.3%). None the patients had anti Jo-1, anti Scl-70, anti Sm, anti nRNP/Sm, anti single-stranded DNA (anti-ssDNA), anti double-stranded DNA (anti-dsDNA), antihistones, antinucleosomes, anti SS-A, anti SS-B or anti CENP-B autoantibodies. In patients affected by NHL ANA was detected in 16 (13.4%), anti SS-A and anti SS-B in two (1.7%), anti CENP-B in eight (6.7%) and anti PM-Scl in eight patients (6.7%). None of the patients had anti Jo-1, anti Scl-70, anti Sm, anti nRNP/Sm, anti ssDNA, antihistones or antinucleosome antibodies. There was a statistically significant difference between patients with HL and NHL in terms of anti CENP-B positivity (P=0.040). CONCLUSION: In conclusion, ANA and related autoantibodies can frequently be detected during lymphoma treatment. However, the majority of lymphoma patients with positive ANA did not display autoimmune diseases, demonstrating the lack of a strict correlation between the presence of ANA and autoimmune diseases.

Sequence specific peptidomimetic molecules inhibitors of a protein-protein interaction at the helix 1 level of c-Myc.

Our work is focused in the broad area of strategies and efforts to inhibit protein-protein interactions. The possible strategies in this field are definitely much more varied than in the case of ATP-pocket inhibitors. In our previous work (10), we reported that a retro-inverso (RI) form of Helix1 (H1) of c-Myc, linked to an RI-internalization sequence arising from the third alpha-helix of Antennapedia (Int) was endowed with an antiproliferative and proapoptotic activity toward the cancer cell lines MCF-7 and HCT-116. The activity apparently was dependent upon the presence of the Myc motif. In this work, by ala-scan mapping of the H1 portion of our molecules with D-aa, we found two amino acids necessary for antiproliferative activity: D-Lys in 4 and D-Arg in 5 (numbers refer to L-forms). In the natural hetero-dimer, these two side chains project to the outside of the four alpha-helix bundle. Moreover, we were able to obtain three peptides more active than the original lead. They strongly reduced cell proliferation and survival (RI-Int-VV-H1-E2A,S6A,F8A; RI-Int-VV-H1-S6A,F8A,R11A; RI-Int-VV-H1-S6A,F8A,Q13A): after 8 days at 10 muM total cell number was approximately 1% of the number of cells initially seeded. In these more potent molecules, the ablated side chains project to the inside in the corresponding natural four alpha-helix bundle. In the present work, we also investigated the behavior of our molecules at the biochemical level. Using both a circular dichroism (CD) and a fluorescence anisotropy approach, we noted that side chains projecting at the interior of the four alpha-helix bundle are needed for inducing the partial unfolding of Myc-H2, without an opening of the leucine zipper. Side chains projecting at the outside are not required for this biochemical effect. However, antiproliferative activity had the opposite requirements: side chains projecting at the outside of the bundle were essential, and, on the contrary, ablation of one side chain at a time projecting at the inside increased rather than decreased biological activity. We conclude that our active molecules probably interfere at the level of a protein-protein interaction between Myc-Max and a third protein of the transcription complex. Finally, CD and nuclear magnetic resonance (NMR) data, plus dynamic simulations, suggest a prevalent random coil conformation of the H1 portion of our molecules, at least in diluted solutions. The introduction of a kink (substitution with proline in positions 5 or 7) led to an important reduction of biological activity. We have also synthesized a longer peptido-mimetic molecule (RI-Int-H1-S6A,F8A-loop-H2) with the intent of obtaining a wider zone of interaction and a stronger interference at the level of the higher-order structure (enhanceosome). RI-Int-H1-S6A,F8A-loop-H2 was less active rather than more active in respect to RI-Int-VV-H1-S6A,F8A, apparently because it has a clear bent to form a beta-sheet (CD and NMR data).

Clinical Hepatozoon canis infection in a dog in Turkey.

A five-year-old female dog was presented with a four-week history of inappetence, weight loss, and skin and gait abnormalities. Physical examination revealed weakness, depression, incoordination of the posterior limbs, emaciation, skin and hair coat alterations, peripheral lymphadenopathy, pale mucous membranes and fever. Laboratory analysis of samples revealed abnormalities which included anaemia, neutrophilic leucocytosis, thrombocytopenia, low serum glucose and albumin concentrations, and increased serum alkaline phosphatase activity. The diagnosis was confirmed microscopically, by demonstrating the presence of Hepatozoon canis gametocytes within neutrophils in Giemsa-stained peripheral blood smears. Treatment consisting of toltrazuril and a trimethoprim-sulfamethoxazole combination was effective in relieving the clinical signs and clearing the blood of H. canis gametocytes. To the authors' knowledge, this is the first detailed clinical description of H. canis infection in a dog in Turkey.

Oxidative stress and non-enzymatic antioxidative status in dogs with visceral Leishmaniasis.

Leishmaniasis is a potentially fatal chronic protozoan disease in human, canine and rodent species. The infection by Leishmania is endemic in the Mediterranean Sea region, Africa, Asia and South America. Canine visceral leishmaniasis (CanVL) is a systemic disease caused by Leishmania infantum and Leishmania chagasi from the Leishmania donovani complex group. The blood glutathione (GSH), plasma malondialdehyde (MDA), ascorbic acid (AA), beta-carotene, retinol and ceruloplasmin levels of dogs with CanVL were investigated to establish the status of the antioxidant defense mechanism in the infected animals. Dogs diagnosed as CanVL with amastigotes in lymph node smear examination and/or antibody titers > or = 128 were used as subjects, while those with no serological response against leishmaniasis were used as healthy controls. The glutathione and retinol amounts were decreased although not significantly (p > 0.05), but the MDA levels were significantly higher in dogs with VL, suggesting increased lipid peroxidation.

Polyglandular autoimmune syndrome type III accompanied by common variable immunodeficiency.

We identified polyglandular autoimmune (PGA) syndrome type III in a 24-year-old nurse with common variable immunodeficiency (CVID). An immune-mediated disorder, membranoproliferative glomerulonephritis, was diagnosed when she was 15 years old. Clinical examination and laboratory findings revealed a PGA syndrome due to the presence of hypergonadotropic hypogonadism, insufficient growth hormone response and thyroid autoimmunity. The patient had neither adrenal disease nor hypoparathyroidism. Therefore we concluded that this patient has PGA syndrome type III. This is an interesting case, because we could not find any previous report of such coexistence between PGA type III and CVID in a Medline search. Coexistence of these two entities may be a result of autoimmunity and the association of both conditions with human leukocyte antigen.

Fractional excretion of electrolytes during pre- and postpartum periods in cows.

In this study, fractional excretions (Fe) of sodium (Na), potassium (K), chloride (Cl), calcium (Ca), magnesium (Mg) and phosphorus (PO4) were examined with the aim to demonstrate interactions between fractional excretions of these electrolytes within each period and relate them to electrolyte metabolism in clinically normal cows at different stages of lactation and dry period. The material of this study consisted of 20 clinically healthy Holstein-Friesian cows of the same age and milk yield. Blood and urine samples were collected on 190-200th, 240-250th and 270-280th days of pregnancy and on days 1-7th, 35-45th and 75-85th after calving, altogether 6 times. An increase was observed in FeCa and FeMg during the transition from the lactation to the dry period (p < 0.05), and a decrease in FeCa (p < 0.05), FeMg (p < 0.01) in the 2nd month of the dry period. FePO4 and FeMg, respectively, increased on levels of p < 0.01 and p < 0.05, while FeCa decreased on a level of p < 0.05 after gestation compared to the level before gestation. FeNa and FeK showed a decrease of p < 0.001 and p < 0.01, respectively, between the 1st and 2nd months of the dry period, while after gestation this value showed an increase in FeNa (p < 0.05) and FeK (p < 0.01). FeCl increased significantly (p < 0.05) only from postpartum to the 1st month of lactation. There was a strong positive correlation between FeNa and FeCl in all of the periods. It was concluded that there were significant changes in the Fe of Na, K, Cl, Ca, PO4 and Mg before parturition and during lactation; these changes could have an important role in assessing renal function and electrolyte balance.

Real-ear measures in evaluation of frequency response and volume control characteristics of telephone amplifiers.

The spectral frequency response, frequency response range, and volume control linearity of five telephone amplifiers were examined using real-ear measures. All measurements were performed in KEMAR's (Knowles Electronics Manikin for Acoustic Research) ear canal using a composite speech-shaped waveform as the stimulus. Spectral frequency response and response range of each device was obtained at four volume control settings and compared to those of a standard telephone receiver. Only two of the amplifiers replicate the spectral frequency response of the standard receiver and show an increase in the amount of gain provided with increasing volume control rotation. The remaining three amplifiers show a more restricted spectral frequency response and response range when compared to those of the standard receiver. The volume control characteristics of the amplifiers were somewhat more uniform. Overall results indicate that the spectral frequency response and response range of telephone amplifiers can be objectively evaluated using real-ear measures, and these measures are essential in determining the usefulness of certain telephone amplifying devices.

Individualized correction factors in the preselection of hearing aids.

This study investigated three issues involving corrections for individual ear acoustics in hearing aid prescriptions: (a) the extent to which inconsistencies in the sound-field reference position can affect comparative corrections for the real-ear unaided response (REUR); (b) the extent to which individual variability in the real-ear-to-coupler level difference (RECD) supports the use of individual measurements as opposed to an average-ear estimate; and (c) the adequacy of using KEMAR estimates of the effects of the location of the hearing aid microphone. In Experiment 1, KEMAR REURs using over-the-ear and under-the-ear reference positions were compared with KEMAR REURs using a center-of-head reference position. Maximum differences of 4-9 dB were found in the 1500- to 5000-Hz range, depending on test conditions. In Experiment 2, the ear canal response of an insert earphone was compared to the 2-cc coupler response of the same earphone to calculate the RECD. Individual RECDs for a population of hearing aid candidates were compared to the RECD for KEMAR. For 8 of the 15 subjects (9 of 18 ears), the RECD was more than 4 dB different from KEMAR at two or more third-octave frequencies between 500 and 4000 Hz. In Experiment 3, the effect of the location of the hearing aid microphone for in-the-ear (ITE) and in-the-canal (ITC) locations was compared with the over-the-ear (OTE) location for 18 ears and for KEMAR. The effects varied across individual ears, but all ears and KEMAR showed positive gain in the high frequencies for the ITE and ITC locations. The relevance of these results to hearing aid prescription practices is discussed.