Pediatric valve replacement, 15 years experience in Oman

Background Despite improving surgical techniques, treatment of heart valve disease in children remains controversial. Somatic growth and adequate anticoagulation are of concern when children undergo valve replacement. We conducted this study to evaluate the performance of valves in this age group. Methods 42 children under the age of 13 years who underwent valve replacement were included in this study. Totally, 50 valves were implanted in 42 patients: 48 were mechanical prostheses, two were bioprosthetic both in pulmonary position. 37 (74%) valves were implanted in mitral position, 10 (20%) in aortic position, 1 (2%) in tricuspid position and 2 (4%) in pulmonary position. Preoperatively, 14 (33,3%) patients were in New York Heart Association (NYHA) class IV, while 27 (64.2%) were in NYHA class III. Results There were 2 (4.7%) hospital deaths and 2 (4.7%) late deaths while 2 (4.7%) patients were lost to follow up. The mean follow up period was 9.4 yrs. 35 (83.3%) patients are in NYHA Class I and free of all medications except warfarin. 3 (7.1%) patients have undergone 5 successful pregnancies. The median INR was 2.23. Major thrombo-embolic episode occurred in 1 (2.3%) patient. Conclusions In view of the problems of sizing, anticoagulation and need for re-operation at an early age, there is a reluctance to replace valves in children. This study shows that despite these problems, valve replacement can be undertaken safely and successfully in children, when repair has failed or not technically feasible.     

The B- to Z-DNA equilibrium in vivo is perturbed by biological processes.

Right-handed B and left-handed Z conformations coexist in equilibrium in portions of plasmids in Escherichia coli. The equilibria are influenced by the length of the sequences that undergo the structural transitions and are perturbed by biological processes. The composite results of three types of determinations indicate a supercoil density of -0.025 in vivo. The coexistence of alternative DNA conformations in living cells implies the potential of these structures or their transitions for important functions in genetic regulatory processes.     

Recombinant troponin I substitution and calcium responsiveness in skinned cardiac muscle

Using treatment with vanadate solutions, we extracted native cardiac troponin I and troponin C (cTnI and cTnC) from skinned fibers of porcine right ventricles. These proteins were replaced by exogenously supplied TnI and TnC isoforms, thereby restoring Ca²⁺-dependent regulation. Force then depended on the negative logarithm of Ca²⁺ concentration (pCa) in a sigmoidal manner, the pCa for 50% force development, pCa₅₀, being about 5.5. For reconstitution we used fast-twitch rabbit skeletal muscle TnI and TnC (sTnI and sTnC), bovine cTnI and cTnC or recombinant sTnIs that were altered by site-directed mutagenesis. Incubation with TnI inhibited isometric tension in TnI-extracted fibers in the absence of Ca²⁺, but restoration of Ca²⁺ dependence required incubation with both TnI and TnC. Relaxation at low Ca²⁺ levels and the steepness of the force/pCa relation depended on the concentration of exogenously supplied TnI in the reconstitution solution (range 20–150 μM), while Ca²⁺ sensitivity, i.e. the pCa₅₀, was dependent on the isoform, and also on the concentration of TnC in the reconstitution solution. At pH 6.7, skinned fibers reconstituted with optimal concentrations of sTnC and sTnI (120 μM and 150 μM, respectively) were more sensitive to Ca²⁺ than those reconstituted with cTnC and cTnI (difference in pCa₅₀ approx. 0.2 units). Rabbit sTnI was cloned and expressed in Escherichia coli using a high yield expression plasmid. We introduced point mutations into the TnI inhibitory region comprising the sequence of the minimal common TnC/actin binding site (-G¹⁰⁴-K-F-K-R-P-P-L-R-R-V-R¹¹⁵-). The four mutants produced by substitution of T for P¹¹⁰, G for P¹¹⁰, G for L¹¹¹, and G for K¹⁰⁵ were chosen, based on previous work with synthetic peptides showing that single amino acid substitution in this region diminished the capacity of these peptides to inhibit acto-S₁ ATPase or contraction of skinned fibers. Therefore, all amino acid residues of the inhibitory region are thought to contribute to biological activity of TnI. However, each of the recombinant TnIs could substitute for endogenous TnI. In combination with exogenous TnC, Ca²⁺ dependence could be restored when ^gly110sTnI, ^thr110sTnI or ^gly111sTnI was used for reconstitution. The mutant ^gly105sTnI, on the other hand, reduced the ability of skinned fibers to relax at low Ca²⁺ concentrations and it caused an increase in Ca²⁺ sensitivity. Received: 5 October 1995/Received after revision and accepted: 1 December 1995     

Prophylaxis against lipopolysaccharide-induced liver injuries by lipoic acid in rats

Lipopolysaccharide (LPS) is a major cell wall molecule of Gram-negative bacteria known to stimulate the synthesis and secretion of several metabolites, such as reactive oxygen species, from phagocytes that play an important role in the pathogenesis of tissue injuries. In this study, the prophylactic effect of the antioxidant lipoic acid was evaluated in an animal acute organ injury model. Animals were pre-treated intraperitoneally with lipoic acid (50 mg kg(-1) body weight) or saline; 3 h later, pretreated animals were challenged intravenously with LPS (Escherichia coli 0111:B4, 1.0 mg kg(-1) body weight) or saline and killed 21 h later. Saline-pretreated animals challenged with LPS were extensively damaged in the liver, as evidenced by an increase in plasma alanine and aspartate aminotransferase activities. Also, LPS injection to saline-pretreated animals resulted in significant increases in plasma tumour necrosis factor-alpha (TNFalpha) and nitric oxide (NO) concentrations, suggestive of activation of the proinflammatory response. The LPS challenge to saline-pretreated animals also increased hepatic myeloperoxidase activity as well as protease and chloramine levels, suggestive of neutrophil infiltration and activation of the inflammatory response. In addition, the involvement of oxidative stress was evident, because a significant increase in lipid peroxidation was observed in the livers of saline-pretreated animals challenged with LPS. The administration of lipoic acid prior to LPS challenge resulted in a significant alleviation of liver injuries, evidenced by a general reversal of the altered biochemical indices toward normal among treated animals. These results indicate that lipoic acid may serve as a potentially effective prophylactic pharmacological agent in alleviating LPS-induced tissue injuries.     

Systemic Lupus Erythematosus: Perinatal and Neonatal Implications

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can affect almost all organ systems in the body. It is most common in women of childbearing age and may cause multiple peripartum complications. This article reviews the pathophysiology of SLE and the effects of SLE on fertility and pregnancy. The complexities of managing a pregnant patient with SLE are reviewed, and the importance of interdisciplinary collaboration discussed, as well as the effects of SLE on the fetus and a review of neonatal lupus erythematosus. Finally, a case report of a pregnant patient with SLE with challenging clinical management issues is presented.     

腹腔镜下精索血管高位离断后大鼠睾丸的形态学改变

目的观察腹腔镜FowlerStephens(FS)手术对青春发育前、中、后期睾丸形态结构的影响。方法30d龄Wistar大鼠麻醉后建立CO2气腹,分别行右侧精索血管游离术(对照组)、右侧腹腔内精索血管离断术(FS组),术后将每大组大鼠再分成7个小组(对照组每小组5只;FS组每小组8～12只),分别在术后第9d(青春发育期前)、20d和45d(青春发育期)、90d和180d(性发育成熟期)、360d和540d(中年期),获取睾丸进行详尽的组织形态学研究。结果FS手术可以引起术后不同时期共85%手术侧睾丸出现轻度(血睾屏障受损为主)、重度(唯支持细胞综合征为主)和完全萎缩(丧失睾丸基本结构,无生殖细胞存活);当轻度或重度萎缩,对侧睾丸未受累;当完全萎缩(49%),对侧睾丸在手术45d后,100%出现轻度(青春发育期后)或重度(中年期)萎缩;间质细胞增生或腺瘤可发生于轻、重和完全萎缩睾丸中(P<0.001)。结论腹腔镜FS动物模型可用幼年大鼠建立;该手术可以引起从青春发育前期至中年期较高比例、不同程度的睾丸萎缩,其中完全萎缩可以影响到对(健)侧睾丸,而可能引起青春发育期后生殖力下降或丧失;睾丸间质肿瘤可以较高比例地发生于不同程度萎缩睾丸中。     

Impedance of Novel Therapeutic Technologies: The Case of Stem Cells

Embryonic stem cell (ES) technology has advanced considerably within the past three decades and has gained prominent distinction within the emerging field of regenerative medicine. As it now enters the nascent stages of clinical application, many hopes and expectations arise along with questions as to where the technology will go. This paper evaluates the technical and practical obstacles that must be overcome before it can fully translate into the clinical context, the existence of strong opposition to the technology, political and legal barriers that have impeded its progression, and the role of healthcare reform in creating new social and economic priorities. In contrast to the technological imperative, a driving force seeking to implement the most recent scientific advances into medical practice, we refer to such translational obstacles as “technological impedance.” Rather than expending inordinate effort to preserve existing systems that continue to possess major hurdles, we advocate fostering interdisciplinary approaches in the development of new generation platforms and embracing disruptive innovations that create solutions to technological impedance and move us forward in healthcare delivery. Clin Trans Sci 2012; Volume 5: 422–427     

Comparison between two-dimensional and midsagittal three-dimensional cephalometric measurements of dry human skulls

The aim of this study was to compare two- and three-dimensional cephalometric values by using a three-dimensional analysis based on the midsagittal plane. Spherical metal markers were fixed on to the anatomical landmarks of 10 human skulls, which were examined radiographically with conventional lateral cephalograms and cone-beam computed tomographic (CBCT) scans. Preprogrammed analyses calculated the 18 angular and linear two- and three-dimensional cephalometric values. An error study was made to assess the accuracy and reliability of the methods used. Both sets of values were compared using Wilcoxon's signed-rank test. Probabilities of less than 0.05 were accepted as significant. Reliability of the measurements was assessed by intraclass correlation coefficients (ICC) based on absolute agreement. The method error (ME) was tiny (mean ME < 0.61 measuring unit) and reliable (ICC > 0.97). Comparison of the two- and three-dimensional measurements showed that that they were reliable (ICC > 0.88) and that there were no significant differences (P = 0.41-1.00). The values from the cephalometric analyses were comparable and interchangeable when using the midsagittal three-dimensional approach as described.