Ectopic Calcification and Hypophosphatemic Rickets: Natural History of ENPP1 and ABCC6 Deficiencies

Generalized arterial calcification of infancy (GACI) is a rare disorder caused by ENPP1 or ABCC6 variants. GACI is characterized by low pyrophosphate, arterial calcification, and high mortality during the first year of life, but the natural course and possible differences between the causative genes remain unknown. In all, 247 individual records for patients with GACI (from birth to 58.3 years of age) across 19 countries were reviewed. Overall mortality was 54.7% (13.4% in utero or stillborn), with a 50.4% probability of death before the age of 6 months (critical period). Contrary to previous publications, we found that bisphosphonate treatment had no survival benefit based on a start-time matched analysis and inconclusive results when initiated within 2 weeks of birth. Despite a similar prevalence of GACI phenotypes between ENPP1 and ABCC6 deficiencies, including arterial calcification (77.2% and 89.5%, respectively), organ calcification (65.8% and 84.2%, respectively), and cardiovascular complications (58.4% and 78.9%, respectively), mortality was higher for ENPP1 versus ABCC6 variants (40.5% versus 10.5%, respectively; p = 0.0157). Higher prevalence of rickets was reported in 70.8% of surviving affected individuals with ENPP1 compared with that of ABCC6 (11.8%; p = 0.0001). Eleven affected individuals presenting with rickets and without a GACI diagnosis, termed autosomal recessive hypophosphatemic rickets type 2 (ARHR2), all had confirmed ENPP1 variants. Approximately 70% of these patients demonstrated evidence of ectopic calcification or complications similar to those seen in individuals with GACI, which shows that ARHR2 is not a distinct condition from GACI but represents part of the spectrum of ENPP1 deficiency. Overall, this study identified an early mortality risk in GACI patients despite attempts to treat with bisphosphonates, high prevalence of rickets almost exclusive to ENPP1 deficiency, and a spectrum of heterogenous calcification and multiple organ complications with both ENPP1 and ABCC6 variants, which suggests an overlapping pathology. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.     

带血管蒂阔筋膜张肌及腱膜转位修补巨型腹股沟疝的应用解剖

目的:为带血管蒂阔筋膜张肌及腱膜转位修补巨型腹股沟疝提供解剖学基础。方法:在30例成人下肢标本上解剖观测了阔筋膜张肌的动脉血管分布,神经支配,肌腹和肌腱的长度等。结果:阔筋膜张肌动脉来源有旋股外侧动脉和臀上动脉,该肌由臀上神经支配,肌腹长度为112.31±3.13mm,髂经束的长度为315±6.8mm,额前上棘水平至腹肌外侧缘的距离,男性为168±7.5mm,女性为176±6.8mm。结论:阔筋膜张肌血供丰富,肌腱膜长,位置邻近腹股沟区,可作为巨型腹股沟疝修补的供体。     

pSV-VEGF165肌内原位注射促进兔缺血后肢侧支血管形成

目的 为临床探索一种更简便安全的下肢动脉缺血性疾病的基因治疗途径。方法 建立兔后肢缺血动脉模型,将体外构建的重组质粒ｐＳＶ－ＶＥＧＦ１６５注射于缺血肌群,３０ｄ后行动脉造影并切取标本,测定毛细血管密度和毛细血管／肌肉数比值。结果 经ｐＳＶ－ＶＥＧＦ１６５治疗后,缺血肢体毛细血管密度和毛细血管／肌肉数比值显著增加,小腿部位比大腿部位增加明显,动脉造影显示部分缺血肢体侧支动态明显增多。结论 肌肉内原位     

Periventricular- intraventricular hemorrhage in the premature infant- A historical perspective

The objective of this chapter is to trace the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow changes in the genesis of hemorrhage, clinical factors that increase the bleeding risk, and potential preventative strategies. In 1976, neuropathological studies demonstrated capillary rupture within the germinal matrix as the precursor of hemorrhage. In 1980, introduction of cranial ultrasound facilitated diagnosis of intraventricular hemorrhage. In 1979, loss of cerebral autoregulation in sick newborn infants was demonstrated. In the 1980’s, studies demonstrated the importance of intravascular factors in provoking hemorrhage. In 1983, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. In 1994, antenatal steroids use to accelerate lung development was recommended. This was associated with an unanticipated reduction in hemorrhage. In the mid 1990’s early indomethacin administration was associated with a reduction of severe hemorrhage.     

Aortopulmonary collateral artery embolization during postoperative extracorporeal membrane oxygenation after arterial switch procedure

Aortopulmonary collateral arteries sometimes complicate cyanotic congenital heart defects. Combined with a relevant left-right shunt, this could result in massive airway bleeding during and after corrective surgery. A preoperatively diagnosed 1.2 mm small aortopulmonary collateral artery in a newborn suffering from transposition of the great arteries caused life-threatening airway bleeding during surgery. Postoperative extracorporeal membrane oxygenation (ECMO) was necessary, and coil embolization was performed on ECMO to terminate pulmonary bleeding.     

Long-term lowering of blood pressure after carotid and vertebrobasilar ischemic stroke

We followed up 107 patients experiencing a first-ever ischemic stroke after having been affected by essential hypertension for at least one year, in order to analyze the phenomenon of post-stroke blood pressure lowering. Of the 82 patients still surviving after three months of follow-up, 44 (54%) had normal arterial blood pressure values. There were no significant differences between these normotensive patients and the 38 with high blood pressure in terms of cerebrovascular risk factors or disability, but blood pressure normalized in 34 of the 54 patients experiencing a carotid stroke (63%) and in only 10 of the 28 experiencing vertebrobasilar stroke (36%) (p=0.035). These data may offer a starting point for further studies of the neurogenesis of arterial hypertension.

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Sommario Al fine di analizzare il fenomeno della normalizzazione della pressione arteriosa dopo ictus cerebrale in pazienti prima ipertesi, abbiamo osservato 107 soggetti con primo ictus ischemico, che erano già precedentemente affetti da ipertensione arteriosa da almeno un anno. Degli 82 (77%) sopravvissuti a tre mesi di follow-up, 44 (54%) hanno mostrato una normalizzazione della pressione arteriosa. L'incidenza di fattori di rischio per malattia cerebrovascolare e disabilità grave non è risultata significativamente diversa nel gruppo degli ipertesi rispetto ai normotesi. Tuttavia la normalizzazione della pressione arteriosa è stata osservata in 34 dei 54 pazienti con ictus carotideo (63%) e solo in 10 dei 28 con ictus vertebrobasilare (36%) (p=0.035). Riteniamo che tali dati offrano uno spunto per ulteriori ricerche sulla genesi neurogena dell'ipertensione arteriosa essenziale.

     

Biventricular Bypass: Alternative to Univentricular Bypass and Total Artificial Heart–Bridge

Left ventricular and biventricular bypasses (LVBs, BVBs) were performed in 102 experiments in sheep, goats, and donkeys. Biventricular bypass was performed in the assisted circulation mode or in the paracorporeal artificial heart bridge (PCAHB) mode when the natural heart fibrillates. During implantation of artificial ventricles instead of a heart-lung bypass, counterpulsation was used. Several types of connective conduits were developed and tested in experiments. The conduits included bifurcational connective pipes that permit "intake" of blood into artificial ventricles from atria and ventricles of the natural heart simultaneously and consequently provide effective blood flow through shunts not depending on the state of the natural heart (acute cardiac weakness or asystole). Monitoring gas content (PO2, PCO2, and pH) in the myocardium of both ventricles suggested development of right ventricular failure under conditions of LVB before hemodynamic changes occurred and confirmed the preferability of BVB over other methods of assisted circulation, as it is most effective and capable of normalizing short-term cardiac disturbances in the course of the 1st 2 days. Survival time of experimental animals (2-3 days for dogs, 5-12 days for sheep, goats, and donkeys) is sufficient to overcome acute cardiac insufficiency. This suggests that BVB in the assisted circulation mode or PCAHB mode can serve as a bridge for cardiac transplantation for the time of search for the available organ.     

Effects of Nd-YAG laser on platelet function in vitro: A comparative study using the spectraprobe, ‘hot tip’ and bare fibres

The effects of Nd-YAG laser irradiation on platelet function in vitro were studied using platelet rich plasma obtained from the blood of healthy volunteers. Laser delivery was effected via the bare optical fibre, thermal hot tip fibre and spectraprobe and the effects of these probes on platelet function were compared. Fall in platelet count and mean platelet volume (MPV) were proportional to increasing energy delivery with all three probes, the effect being maximal with the spectraprobe, moderate with the hot tip and least with the bare optical fibre. A significant decrease in percentage aggregation of platelets in response to added ADP, collagen and ristocetin with increasing energy delivery was also observed with all three probes. The formation of preformed aggregates, however, showed an increase proportional to energy delivery with all three probes.The differential effects of the various probes used in this study on platelet function may enhance our understanding of the complex role played by platelets in the pathogenesis of complications such as arterial thrombosis and re-occlusion after laser angioplasty.     

家兔延髓吻端腹外侧区在“人中”穴加压效应中的作用

延髓吻端腹外测区(Rostral ventrolateral medulla,RVL)微量注射红藻氨酸(Kainic acid,KA)前,分别用弱、强电刺激“人中”穴时可引起动脉血压(BP)显著升高,心率(HR)明显增快。一侧或双侧RVL注射KA后,再用弱、强电刺激“人中”穴时,BP、HR的反应基本消失。结果表明,RVL在“人中”穴加压效应中起关键性作用。