Newborn Screening in Slovenia

Introduction

Newborn screening in whole Slovenia started in 1979 with screening for phenylketonuria (PKU). Congenital hypothyroidism (CH) was added into the programme in 1981. The aim of this study was to analyse the data of neonatal screening in Slovenia from 1993 to 2012 for PKU, and from 1991 to 2012 for CH.

Methods

Blood samples were collected from the heels of newborns between the third and the fifth day after birth. Fluorometric method was used for screening for PKU, CH screening was done by dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA).

Results

From 1993 to 2012, from 385,831 newborns 57 were identified with PKU. 184 newborns out of 427,396 screened from 1991 to 2012, were confirmed for CH. Incidences of PKU and CH in the periods stated are 1:6769 and 1:2323, respectively.

Conclusions

Successful implementation of newborn screening for PKU and CH has helped in preventing serious disabilities of the affected children. Adding screening for new metabolic diseases in the future would be beneficial.     

Acceleration of full-thickness wound healing in normal rats by the synthetic thrombin peptide, TP508

Thrombin is an essential factor in hemostasis, inflammation, and tissue repair. The synthetic thrombin peptide, TP508, binds to high-affinity thrombin receptors and mimics cellular effects of thrombin at sites of tissue injury. Treatment of full-thickness excisional wounds in normal rats with a single topical application of 0.1 microg TP508 (14 pmol/cm2) reproducibly accelerates wound closure, yielding wounds that on average close 39% more than controls by day 7 (p < 0.001). Wounds treated with 1.0 microg TP508 are 35% and 43% (p < 0.001) smaller than controls on day 7 and 10, respectively. The early rate of closure is approximately 40% greater in TP508-treated than vehicle-treated wounds (20 versus 14 mm2/day) and remains higher through day 7. Breaking strength after closure is slightly greater (15-23%) in wounds treated with TP508 than with saline alone. Histologic comparisons show that TP508 enhances recruitment of inflammatory cells to the wound site within 24 hours post-injury. TP508 treatment also augments revascularization of injured tissue, as evidenced at day 7 by the larger size of functional vessels in the granulation tissue and by the directed development of blood vessels to wounds. These studies raise the possibility that TP508 may be clinically useful in management of open wounds.     

Factors associated with renal dysfunction within an urban HIV-infected cohort in the era of highly active antiretroviral therapy

Background

Kidney disease remains a prevalent problem in HIV care. The contribution of highly active antiretroviral therapy (HAART), HIV disease factors and traditional factors needs further evaluation.

Methods

A cross‐sectional study of all patients seen at an HIV outpatient clinic during 2005 was performed. All data were collected from medical record review. Multivariate regression modelling was used to identify independent predictors of lower glomerular filtration rate (eGFR) and chronic renal failure (CRF) from factors significant in univariate analysis. eGFR was calculated using the simplified modification of diet in renal disease equation. Results were compared with those for persons from the National Health and Nutrition Examination Survey (NHANES) matched for age, race and gender.

Results

Of 845 HIV‐infected persons, 64% were men and 34% were Caucasian, and the mean age was 39.8 years. Thirty per cent of the patients had proteinuria and 43% had eGFR<90 mL/min/1.73 m². Persons on HAART (63%) had a lower mean eGFR than those not on HAART (92.0 vs. 101.6). In multivariate analyses, significant predictors of eGFR decline were diagnoses of hypertension, hyperlipidaemia, proteinuria, use of tenofovir or stavudine, and lower viral load. Compared with those in NHANES, HIV‐infected persons had a lower mean eGFR (94.9 vs. 104.2) and a higher prevalence of CRF (8%vs. 2%).

Conclusion

In this cohort, the prevalence of CRF is low, but remains higher than that of the general population. Clinicians should routinely screen for early asymptomatic kidney disease to address risk factors that can be treated.     

淋病流行特征与淋球菌药物敏感性的流行病学研究

目的 为控制淋病的增长，探讨淋病流行病特征与淋球菌对常用药物敏感性的流行病学关系。方法 完整收集淋病的流行病学资料，测定每年淋球菌对各种药物的敏感度及耐药率，药物包括青霉素，四环素，环丙沙星，壮观霉素和头孢三嗪。结果 性病流行在10年内稳定上升，但淋病则由1993年开始呈稳定的负增长，壮观霉素及头孢三嗪在4年间未发现耐药菌株；环丙沙星的耐药率显上升，由1998年的56.4%上升至2001年的71.4%，产青霉素的耐药菌株（PPNG）和四环素耐药菌株（TRNG）在4年内分别上升10%和16.3%，结论 随淋病的有效控制，淋球菌对常用药物的敏感性降低，PPNG和TRNG菌株的明显上升表明淋球菌的耐药趋势正逐渐增强，喹诺酮类药物的高耐药率表明该类药物已不再适宜被推荐用于治疗淋病的首选药物，头孢三嗪和壮观霉素尚没有耐药菌株，但必须强调规范使用，保证在性病防治工作中有足够可供选择有效药物。     

Target cell-induced apoptosis of interleukin-2-activated human natural killer cells: roles of cell surface molecules and intracellular events

We previously reported that natural killer (NK)-sensitive target cells, K562, kill interleukin-2-stimulated (lymphokine-activated killer [LAK]) but not unstimulated NK cells. We have now investigated the molecular basis of this phenomenon. Soluble monoclonal antibody (MoAb) to CD18 inhibited 75% of K562-induced DNA fragmentation and membrane disruption, whereas blocking MoAb to Fas partially inhibited only the DNA fragmentation. MoAbs to CD2, CD11a, CD11b, B7, or CD16 had limited or no effect on K562-induced death of LAK cells. Receptor ligation with either immobilized MoAb to CD18 or Fas induced membrane disruption and DNA degradation in LAK cells independently of K562, and MoAb to CD18, CD11a, or CD11b enhanced DNA fragmentation induced by anti-Fas. Fas-L- transfected Raji cells also killed LAK cells, but only if Fas-L expression was amplified. K562 cells rapidly triggered protein phosphorylation in LAK cells, and the tyrosine kinase inhibitor, Herbimycin A, inhibited DNA fragmentation and membrane disruption. Protease inhibitors strongly suppressed K562-mediated DNA fragmentation of LAK cells, but not membrane disruption. In conclusion, (1) K562- induced death of LAK cells involves primarily CD18, although other molecules, such as Fas, may also be involved; (2) K562-mediated apoptosis of LAK cells requires tyrosine phosphorylation and protease activity; (3) engagement of Fas by immobilized MoAb or Fas-L on target cells can also kill LAK cells; and (4) Fas-immobilized MoAb synergizes with coimmobilized MoAb to CD11a, CD11b, or CD18 for LAK cell killing. Activation-induced death of NK cells may represent a mechanism for NK cell regulation.