Bleeding and non-bleeding phenotypes in patients with GGCX gene mutations

Functional limitations for the vitamin K cycle, caused either by mutations in gamma-glutamyl carboxylase or vitamin K epoxide reductase genes, result in hereditary deficiency of vitamin K-dependent coagulation factors (VKCFD1 and VKCFD2, respectively). Patients suffering from VKCFD often share several other anatomical irregularities which are not related to haemostasis. Here we report on nine patients, eight of them previously unreported, who presented with VKCFD1. All were examined with special attention to vitamin K-dependent coagulation factors as well as to bone and heart development and to other anatomical signs of embryonal vitamin K deficiency. In total, we detected ten mutations in the gamma-glutamyl carboxylase gene of which seven have not been previously reported. Most interestingly, additional non-bleeding phenotypes were observed in all patients including midfacial hypoplasia, premature osteoporosis, cochlear hearing loss, heart valve defects, pulmonary stenosis, or pseudoxanthoma elasticum-like phenotype. Undercarboxylated matrix Gla protein, osteocalcin, and periostin appear to be responsible for these defects which are also observed in cases of fetal warfarin syndrome.     

Effects of thrice weekly nocturnal hemodialysis on arterial stiffness

ObjectiveIn this study, we compared the changes in arterial stiffness in chronic hemodialysis patients treated with 8-h vs. 4-h thrice weekly in-center hemodialysis.MethodsSixty prevalent chronic hemodialysis patients assigned to 8-h nocturnal in-center thrice weekly HD (NHD) and 60 control cases assigned to 4-h thrice weekly conventional HD (CHD) were followed for one year. Radial–carotid pulse wave velocity, augmentation index and echocardiography were performed at baseline and 12^th month.ResultsMean age of the patients was 49 ± 11 years, 30.8% were female, 27.5% had diabetes mellitus and mean dialysis vintage was 57 ± 47 months. Baseline demographical, clinical and laboratory parameters were similar between groups. During a mean follow-up of 15.0 ± 0.1 months, blood pressure remained similar in both groups while the number of mean daily anti-hypertensive substances decreased in the NHD group. In the NHD group, time-averaged serum phosphorus and calcium–phosphorus product were lower than the CHD group. Pulse wave velocity and augmentation index decreased in the NHD group (from 11.02 ± 2.51 m/s to 9.61 ± 2.39 m/s and from 28.8 ± 10.3% to 26.2 ± 12.1%; p = 0.008 and p = 0.04, respectively). While augmentation index increased in the CHD group (28.0 ± 9.4 to 31.0 ± 10.7%, p = 0.02), pulse wave velocity did not change. Subendocardial viability ratio and ejection duration improved in the NHD group (from 135 ± 28 to 143 ± 25%, p = 0.01 and from 294 ± 34 ms to 281 ± 34 ms, p = 0.003, respectively), accompanied by regression of left ventricular mass index. In multiple stepwise linear regression analyses, NHD was associated with improvements in augmentation index, ejection duration and subendocardial viability ratio.ConclusionsThese data indicate that arterial stiffness is ameliorated by implementation of longer hemodialysis sessions.     

Increased inflammatory markers are associated with obesity and not with target organ damage in newly diagnosed untreated essential hypertensive patients

The aim of this study was to investigate whether inflammatory markers are associated with hypertensive end organ damage or obesity in patients with hypertension. Seventy newly diagnosed essential hypertensive patients (29 men and 41 women aged 49.6 ± 9.5 y) and 25 age-sex-matched normotensive subjects (12 men and 13 women aged 45.8 ± 7.3 y) were asked about their family history of hypertension and smoking habits, and body mass index (BMI) was recorded and blood samples were taken to measure fibrinogen, C-reactive protein (CRP), and homocysteine levels. In hypertensive patients, creatinine clearance, urinary albumin extraction, and left ventricular mass index were determined. Hypertensive patients had significantly higher BMIs and inflammatory markers when compared with normotensive healthy controls. The CRP was positively associated with BMI (P < .05), diastolic blood pressure (P < .05), fibrinogen (P < .01), urinary albumin extraction (P < .01), and left ventricular mass index (P < .05). The BMI and serum fibrinogen level were independently associated with CRP. The effect of inflammation on the development of hypertensive end organ damage may be associated with obesity, so that control of obesity may eliminate the inflammatory state in hypertensive patients and also hypertensive end organ damage.     

The Association of Metabolic Syndrome, Insulin Resistance and Non-alcoholic Fatty Liver Disease in Overweight/Obese Children

Background/Aim:

To study the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT).

Patients and Methods:

Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and liver biochemical profile, in addition to liver ultrasound and liver biopsy.

Results:

Twenty patients (60.6%) were labeled with MS. IR was present in 16 (48.4%). Fifteen (44%) patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001). Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05) and fitted more with the criteria of MS (80% vs. 44%). IR was significantly more common among NAFLD patients (73% vs. 28%).

Conclusion:

There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD.     

Efficacy of FEIBA for acute bleeding and surgical haemostasis in haemophilia A patients with inhibitors: a multicentre registry in Turkey

Long used in established industrialized nations to treat patients with haemophilia and inhibitors, factor eight inhibitor bypassing activity (FEIBA) has, in recent years, been introduced into more geographically diverse settings. Data are needed on how successfully FEIBA therapy has been implemented in new regions. To determine the efficacy and safety of FEIBA for the treatment of acute bleeding and surgical haemostasis in a newly industrialized country. A multicentre registry of haemophilia A patients with inhibitors receiving FEIBA treatment was established in Turkey. With a standardized case report form, data were collected retrospectively on: patient demographics; characteristics of acute bleeding episodes and surgical interventions; FEIBA regimen; and treatment outcomes. Thirty-seven patients received a total of 112 FEIBA treatment courses, 90 for acute bleeding and 22 for surgical haemostasis. The median FEIBA dose per infusion for acute bleeding was 50 IU kg(-1), and for surgery was 100 IU kg(-1). For both acute joint and muscle/soft tissue bleeding and in surgery, haemostasis was attained in a median of two FEIBA infusions. FEIBA was judged effective in 92% of treatment courses for acute bleeding, with a 95% confidence interval (CI) of 85-97%. Rates of haemostatic efficacy did not differ significantly between anatomical sites of acute bleeding. The haemostatic efficacy rate of FEIBA in surgery was 86% (CI, 65-97%). No thromboembolic complications or other adverse events occurred during any treatment course. FEIBA has been successfully integrated into clinical practice in Turkey, with rates of haemostatic efficacy comparable to those reported in countries with a longer history of FEIBA usage.     

Aortitis in a patient with psoriatic arthritis

Aortitis, inflammation of the aortic tissue, is most commonly caused by vasculitic rheumatic conditions, and less frequently infectious organisms. Involvement of the aorta is well defined in HLA-B27-associated spondyloarthropathies such as long-standing ankylosing spondylitis and Reiter's syndrome. However, unlike other spondyloarthropathies, aortic involvement or true aortitis is not a feature of psoriatic arthritis and has been reported in only a few cases. Herein, we report the case of a 22?year-old woman with psoriatic arthritis who developed descending aortitis while using tumor necrosis factor inhibitors.     

The effects of aging on the central nervous system steroid profiles and myelin basic protein in rats

The aim of this study was to investigate the effects of aging on the central nervous system steroid and myelin basic protein (MBP) profiles. Forty-seven male Sprague-Dawley rats (newborn, 1, 6, 12 and 24-monthsold) were studied. Tissues were obtained from the cerebellum and parietal, frontal, temporal cortex of the central nervous system of the rats for steroid extraction. The estradiol, progesteron, testosterone and dehydroepiandrosterone (DHEA) levels were measured by Enzyme Linked Immunosorbent Assay (ELISA). The average levels of estradiol (pg/g), progesteron (ng/g), DHEA (ng/g) and testosterone (ng/g) in the brain tissues were respectively 24.29, 4.59, 0.27, 0.92 in the newborn-rats; 4.18 ± 1.10, 1.54 ± 0.30, 0.28 ± 0.01, 0.57 ± 0.10 in the 1 month-old-rats; 11.02 ± 1.10, 2.96 ± 0.30, 0.27 ± 0.01, 0.61 ± 0.10 in the 6 month-old-rats; 15.80 ± 1.10, 4.80 ± 0.30, 0.28 ± 0.10, 0.67 ± 0.10 in the 12 monthold- rats; 20.07 ± 1.10, 4.12 ± 0.30, 0.28 ± 0.01, 0.55±0.10 in the 24 month-old-rats. The myelin basic protein levels were determined by immunohistochemical staining and an elevation was observed in conjunction with the aging process. The results of the study indicate that the alterations in MBP, DHEA, progesterone, testosterone and estrodiol concentrations in the central nervous system of the rats during aging can be considered fundamental for future animal and human studies.     

Chemisorption and sustained release of cefotaxime between a layered double hydroxide and polyvinyl alcohol nanofibers for enhanced efficacy against second degree burn wound infection

Zn–Al layered double hydroxides (LDHs) were synthesized by a chemical method, while polyvinyl alcohol (PVA) nanofibers were fabricated by an electrospinning approach; we also synthesized Zn–Al LDH/cefotaxime (cefotax), Zn–Al LDH@PVA, and Zn–Al LDH/cefotax@PVA (LCP). Characterizations were performed by X-ray diffraction, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, high-resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, Brunauer–Emmett–Teller analysis, thermogravimetric-differential thermal analysis techniques, dynamic light scattering, X ray-florescence, and carbon, hydrogen, and nitrogen (CHN) analyses. The adsorption isotherm of cefotax and its entrapment percentage, release, and kinetics were also investigated. The results confirmed the elemental constituents of the mentioned formulas, which exhibited different degrees of crystallinity and different morphologies. Besides, these formulas were tested in vitro as antimicrobial agents and applied in vivo against second-degree wound burns induced in rats'' skin. The adsorption of cefotax occurred chemically, and the experimental data were fitted with different isotherm models, where the Freundlich and Toth models gave the best fits. The entrapment percentage in LDH/cefotax was 77.41% and in LDH/cefotax@PVA, it was 67.83%. The sustained release of cefotax from LDH and LCP was attainable; the release percentages were 89.31% and 81.55% in up to 12 h, respectively. The release kinetics of cefotax from LDH fitted well with first-order kinetics, while that for LCP was parabolic. The formulas showed uneven antimicrobial effects against Gram-positive and Gram-negative bacteria; the best effect was exhibited by Zn–Al LDH/cefotax@PVA due to its sustained release. Finally, investigating the possibility of using these formulas in the clinical setting should be considered.

This study succeeded to formulate, characterize, and investigate cefotax release and kinetics, and to compare cetofax with other known antibacterial agents.