Spondylocostal dysostosis with tetralogy of Fallot and herniation of the spleen through the diaphragm

Spondylocostal dysostosis (SCD) is a very rare syndrome characterized by vertebral malformation and rib deformity. Some of the patients with SCD have other birth defects in the central nervous system, the genitourinary tract, diaphragm or heart and so forth. There have been reported SCD with complex congenital heart disease, such as pulmonary atresia, double outlet right ventricle, and d‐transposition of great arteries. However, there have been no reported SCD patients with confirmed tetralogy of Fallot (TOF). Here, a patient with SCD having a very rare combination of rib defects on the right side and left‐sided scoliosis, tetralogy of Fallot, and diaphragmatic spleen herniation, which had not been reported before, was described.     

Lysophosphatidic Acid Rescues Human Dental Pulp Cells from Ischemia-induced Apoptosis

Introduction

Dental pulp is particularly susceptible to ischemic conditions (hypoxia and serum deprived) because it is commonly exposed to trauma, inflammation, chronic caries injury, and pulpitis. We investigated the apoptotic response of human dental pulp cells (HDPCs) to varying levels of oxygen and serum to mimic different degrees of ischemia, tested whether lysophosphatidic acid (LPA) could reverse ischemia-induced apoptosis, and investigated the possible mechanisms of LPA.

Methods

HDPCs were cultured under conditions mimicking serum deprivation and ischemia for 2 days with or without LPA at 25 μg/mL. Flow cytometry and JC-1 fluorescence were used to detect any apoptotic change. Western blotting was used to measure the expression of the apoptosis regulators B-cell lymphoma 2 (Bcl-2) and Bax, focal adhesion kinase (FAK), Src, extracellular signal-regulated kinase (ERK), and Akt.

Results

Flow cytometry and JC-1 immunofluorescence showed that ischemia could induce apoptosis of HDPCs in 2 days and treatment with LPA could reduce cell death significantly. To clarify the molecular mechanisms, Western blot results showed up-regulation of both proapoptotic Bax and antiapoptotic Bcl-2 during apoptosis. LPA functioned as an antiapoptotic cytokine by activation of the phosphorylation of FAK and ERK. No statistically significant difference was found in the activation levels of p-Src or p-Akt.

Conclusions

A self-defense mechanism functioned during cell apoptosis. LPA could effectively rescue HDPCs from ischemia-induced apoptosis via regulation of Bax and Bcl-2 and the activation of phosphorylated FAK and phosphorylated ERK. LPA is a potent candidate for biological therapy of chronic pulpal inflammatory diseases.     

The role of RAS in the pathogenesis of preeclampsia

Preeclampsia is a hypertensive disorder that is unique to pregnancy, with consistent involvement of the kidney. The renin-angiotensin system (RAS) has been implicated in the pathogenesis of preeclampsia. In the gravid state, in addition to the RAS in the kidney, there is a tissue-based RAS in the uteroplacental unit. Increased renin expression in human preeclampsia and in transgenic mouse models with a human preeclampsia-like syndrome shows that activation of the uteroplacental RAS, with angiotensin II entering the systemic circulation, may mediate the pathogenesis of preeclampsia. Vascular maladaptation in preeclampsia with increased vasomotor tone, endothelial dysfunction, and increased sensitivity to angiotensin II and norepinephrine in manifest preeclampsia may be explained on the basis of angiotensin II-mediated mechanisms through angiotensin receptor type I (AT1) activation. Recently, novel angiotensin II-related biomolecular mechanisms have been described in preeclampsia. These include AT1 and bradykinin B2 receptor heterodimerization and the production of autoantibody against AT1. Various organ systems with predilection for involvement in preeclampsia are sites of tissue-based RAS. Angiotensin II-mediated mechanisms may explain the primary clinicopathologic features of preeclampsia. In this review, these various aspects are critically examined and an integrated concept on the role of RAS in preeclampsia is presented.     

Redefining and Redesigning Hospital Discharge to Enhance Patient Care: A Randomized Controlled Study

BACKGROUND  Patients are routinely ill-prepared for the transition from hospital to home. Inadequate communication between Hospitalists and primary care providers can further compromise post-discharge care. Redesigning the discharge process may improve the continuity and the quality of patient care. OBJECTIVES  To evaluate a low-cost intervention designed to promptly reconnect patients to their “medical home” after hospital discharge. DESIGN  Randomized controlled study. Intervention patients received a “user-friendly” Patient Discharge Form, and upon arrival at home, a telephone outreach from a nurse at their primary care site. PARTICIPANTS  A culturally and linguistically diverse group of patients admitted to a small community teaching hospital. MEASUREMENTS  Four undesirable outcomes were measured after hospital discharge: (1) no outpatient follow-up within 21 days; (2) readmission within 31 days; (3) emergency department visit within 31 days; and (4) failure by the primary care provider to complete an outpatient workup recommended by the hospital doctors. Outcomes of the intervention group were compared to concurrent and historical controls. RESULTS  Only 25.5% of intervention patients had 1 or more undesirable outcomes compared to 55.1% of the concurrent and 55.0% of the historical controls. Notably, only 14.9% of the intervention patients failed to follow-up within 21 days compared to 40.8% of the concurrent and 35.0% of the historical controls. Only 11.5% of recommended outpatient workups in the intervention group were incomplete versus 31.3% in the concurrent and 31.0% in the historical controls. CONCLUSIONS  A low-cost discharge–transfer intervention may improve the rates of outpatient follow-up and of completed workups after hospital discharge.     

Caco-2 cell metabolism of oxygen-derived radicals

Reactive oxygen metabolites have been associated with gastrointestinal injury and may play a role as mediators of inflammation. The effect of oxygen metabolites on Caco-2 cell viability (trypan blue exclusion and⁵¹Cr release), hexose monophosphate shunt activity, and glutathione was assessed. Caco-2 cells were incubated with amino acid oxidase, xanthine oxidase, menadione, andt-butylhydroperoxide in the presence and absence of superoxide dismutase, catalase, mannitol, and butylated hydroxytoluene. With amino acid oxidase, trypan blue exclusion decreased (P<0.01) and⁵¹Cr release, oxidized glutathione, and shunt activity increased (P<0.05). The addition of catalase attenuated these changes. Trypan blue exclusion decreased (P<0.005) and⁵¹Cr release, oxidized glutathione, and shunt activity increased (P<0.01) with xanthine oxidase. The addition of superoxide dismutase caused a further increase in⁵¹Cr release, oxidized glutathione, and shunt activity (P<0.01), which was prevented by the addition of catalase or mannitol.t-Butylhydroperoxide did not effect⁵¹Cr release or trypan blue exclusion, but oxidized glutathione and shunt activity increased (P<0.01). The increase in shunt activity was prevented by preincubation with butylated hydroxytoluene (P<0.01). Menadione did not alter trypan blue exclusion or⁵¹Cr release, but caused an increase in oxidized glutathione and shunt activity (P<0.001). The increase in shunt activity was attenuated by preincubation with butylated hydroxytoluene (P<0.001). Menadione also caused a depletion of total glutathione. Thus, Caco-2 cells are sensitive to oxidant injury and in all four systems increase in shunt activity and oxidized glutathione occurred at concentrations lower than those that caused cell injury, suggesting the shunt via the glutathione cycle is important in Caco-2 cell metabolism of oxidant species.S. Baker was supported by a grant from the Crohns and Colitis Foundation of America and the USDA, #9000763.