Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency

One of the severe combined immunodeficiencies (SCIDs), which is caused by a genetic defect in the signal transduction pathways involved in T-cell activation, is the ZAP70 deficiency. Mutations in ZAP70 lead to both abnormal thymic development and defective T-cell receptor (TCR) signaling of peripheral T-cells. In contrast to the lymphopenia in most SCID patients, ZAP70-deficient patients have lymphocytosis, despite the selective absence of CD8+ T-cells. The clinical presentation is usually before 2 years of age with typical findings of SCID. Here, we present three new ZAP70-deficient patients who vary in their clinical presentation. One of the ZAP70-deficient patients presented as a classical SCID, the second patient presented as a healthy looking wheezy infant, whereas the third patient came to clinical attention for the eczematous skin lesions simulating atopic dermatitis with eosinophilia and elevated immunoglobulin E (IgE), similar to the Omenn syndrome. This study illustrates that awareness of the clinical heterogeneity of ZAP70 deficiency is of utmost importance for making a fast and accurate diagnosis, which will contribute to the improvement of the adequate treatment of this severe immunodeficiency

ACE Inhibition and Endothelial Function: Main Findings of PERFECT, a Sub-Study of the EUROPA Trial

Background: ACE inhibition results in secondary prevention of coronary artery disease (CAD) through different mechanisms including improvement of endothelial dysfunction. The Perindopril-Function of the Endothelium in Coronary artery disease Trial (PERFECT) evaluated whether long-term administration of perindopril improves endothelial dysfunction. Methods: PERFECT is a 3-year double blind randomised placebo controlled trial to determine the effect of perindopril 8 mg once daily on brachial artery endothelial function in patients with stable CAD without clinical heart failure. Endothelial function in response to ischaemia was assessed using ultrasound. Primary endpoint was difference in flow-mediated vasodilatation (FMD) assessed at 36 months. Results: In 20 centers, 333 patients randomly received perindopril or matching placebo. Ischemia-induced FMD was 2.7% (SD 2.6). In the perindopril group FMD went from 2.6% at baseline to 3.3% at 36 months and in the placebo group from 2.8 to 3.0%. Change in FMD after 36 month treatment was 0.55% (95% confidence interval −0.36, 1.47; p = 0.23) higher in perindopril than in placebo group. The rate of change in FMD per 6 months was 0.14% (SE 0.05, p = 0.02) in perindopril and 0.02% (SE 0.05, p = 0.74) in placebo group (0.12% difference in rate of change p = 0.07). Conclusion: Perindopril resulted in a modest, albeit not statistically significant, improvement in FMD

mesenchymal stem cells

C-type natriuretic peptide (CNP) signaling has been implicated as an important regulator of chondrogenic differentiation during endochondral bone development. This preliminary study further investigated the putative effectors and/or targets of CNP signaling in transforming growth factor (TGF)-beta induced in vitro chondrogenic differentiation of mesenchymal stem cells (MSCs). Previously characterized human trabecular bone derived MSCs were induced either with only TGF-beta 1 or with a combination of TGF-beta 1 and CNP in micromass culture for 10 or 20 days. Genome wide gene expression profile changes in between these two groups were analyzed on day-10 or day-20 of culture. Results revealed that there were only 7 genes, whose expression change was fourfolds or higher in TGF-beta 1 and CNP fed group in comparison to only TGF-beta 1 fed group. The up-regulated genes included matrilin-3 (MATN3), engulfment and cell motility 1 (ELMO1), CD24, and DCN1, defective in cullin neddylation 1, domain containing 1 (DCUN1D1). The down-regulated genes, on the other hand, included LIM domain kinase 2 (LIMK2), Ewing sarcoma breakpoint region 1, and guanine nucleotide binding protein (G protein), gamma 12 (GNG12). The up-regulation of MATN3 was confirmed on the basis of RT-PCR. The known literature on both CNP signaling and MATN3 function in chondrogenesis match with each other and suggest MATN3 as a putative effector and/or target of CNP signaling during this process

Morbidity And Mortality Characteristics Of Infants Hospitalized In The Pediatrics Department Of The Largest Turkish Military Hospital In 2001

A descriptive study was conducted in the pediatric inpatient unit of Gulhane Military Medical Academy, to investigate the morbidity and mortality characteristics of 532 infants hospitalized between January 1 and December 31, 2001, for treatment purposes. Of the study participants, 55.8% were boys and 44.2% were girls. The most common cause of hospitalization was neonatal hyperbilirubinemia (19.7%). The most common admission month was January (12.4%). Of 532 infants, 510 (95.9%) were discharged, whereas 22 patients died in the hospital. Twenty-one patients died in the neonatal period, and respiratory distress syndrome and neonatal sepsis were identified as the most common causes of death. Our finding of associations between male gender and low birth weight and hospital death is consistent with previous knowledge. Despite the high frequencies of pneumonia and gastroenteritis as admission diagnoses, the finding of only one pneumonia-related death and no gastroenteritis-related deaths in the study population is pleasing.WoSScopu

patient-based survey

Although gout is potentially curable, the management of this disease is often suboptimal. In this study, we investigated the treatment of gout in Turkey and also compared the management approaches to gout in different clinical specialties. Three hundred and nineteen consecutive patients (mean age 58.60 +/- 12.8 years; 44 females, 275 males) were included in this multicenter study. A standardized form was generated to collect data about the patient's first admission to health care, the specialty of the doctor first diagnosed the gout, the treatment options for gout including attack management, patient referral, chronic treatment including medical treatment, and life style modifications. Forty patients were referred to another center without any treatment (12.8 %), and referral rate is most common among the primary care physicians (28.8 %). Colchicine was more commonly used for attack prophylaxis than allopurinol. Ninety-two patients had never been treated with allopurinol (28.8 %). Allopurinol prescription was less common among the primary care physicians and orthopedists, and highest among the rheumatologists. Recommendation of diet and life style modifications was less common among the primary care physicians and orthopedists, and highest among the rheumatologists. The rates of life style modification recommendation and long-term allopurinol prescription were 83.7 and 77.6 %, respectively, among the rheumatologists. Both acute and chronic management of gout is suboptimal in Turkey especially among the primary care physicians and orthopedists. Moreover, chronic treatment is even suboptimal among rheumatologists

Is relapse rate of giant cell arteritis in real-life experience lower

Congress of the European-League-Against-Rheumatism (EULAR) -- JUN 13-16, 2018 -- Amsterdam, NETHERLANDSWOS: 000444351003216European League Against Rheumatis