A Volume Challenge Reveals the Diagnosis of Pediatric Restrictive Cardiomyopathy.

A healthy 11-year-old girl presented with exercise intolerance of unclear etiology, and her physical exam was notable for a 3/6 systolic ejection murmur at the left upper sternal border with radiation to the back. Extensive noninvasive workup consisted of ECG, transthoracic echocardiogram, and cardiac MRI/MRA, which were all nondiagnostic. She was ultimately referred for cardiac catheterization. Baseline invasive hemodynamics demonstrated a normal cardiac index and pulmonary vascular resistance but was notable for mildly elevated right and left end-diastolic pressures. A diagnosis remained elusive, so a 500 mL volume challenge was performed, which unmasked right and left ventricular waveform transformations to reveal the pathognomonic "square root sign" of restrictive cardiomyopathy with concordant RV/LV respirophasic variation. These findings and her clinical history allowed for the rare pediatric diagnosis of restrictive cardiomyopathy early in her clinical course, prior to the development of overt signs of pathologic myocardial remodeling, such as pulmonary hypertension and biatrial enlargement.

Glycerol Improves Skin Lesion Development in the Imiquimod Mouse Model of Psoriasis: Experimental Confirmation of Anecdotal Reports from Patients with Psoriasis.

Glycerol is used in many skin care products because it improves skin function. Anecdotal reports by patients on the National Psoriasis Foundation website also suggest that glycerol may be helpful for the treatment of psoriasis, although to date no experimental data confirm this idea. Glycerol entry into epidermal keratinocytes is facilitated by aquaglyceroporins like aquaporin-3 (AQP3), and its conversion to phosphatidylglycerol, a lipid messenger that promotes keratinocyte differentiation, requires the lipid-metabolizing enzyme phospholipase-D2 (PLD2). To evaluate whether glycerol inhibits inflammation and psoriasiform lesion development in the imiquimod (IMQ)-induced mouse model of psoriasis, glycerol's effect on psoriasiform skin lesions was determined in IMQ-treated wild-type and PLD2 knockout mice, with glycerol provided either in drinking water or applied topically. Psoriasis area and severity index, ear thickness and ear biopsy weight, epidermal thickness, and inflammatory markers were quantified. Topical and oral glycerol ameliorated psoriasiform lesion development in wild-type mice. Topical glycerol appeared to act as an emollient to induce beneficial effects, since even in PLD2 knockout mice topical glycerol application improved skin lesions. In contrast, the beneficial effects of oral glycerol required PLD2, with no improvement in psoriasiform lesions observed in PLD2 knockout mice. Our findings suggest that the ability of oral glycerol to improve psoriasiform lesions requires its PLD2-mediated conversion to phosphatidylglycerol, consistent with our previous report that phosphatidylglycerol itself improves psoriasiform lesions in this model. Our data also support anecdotal evidence that glycerol can ameliorate psoriasis symptoms and therefore might be a useful therapy alone or in conjunction with other treatments.

A Comparison of the Clinical Presentation of Ovarian Hyperstimulation Syndrome in a Partial Molar Pregnancy Case Versus a Fertility Treatment Case.

Ovarian hyperstimulation syndrome (OHSS) is ovarian enlargement secondary to hormones overstimulating ovarian growth. It can be associated with a spectrum of other clinical findings, including ascites, hemoconcentration, hypercoagulability, and electrolyte imbalances. OHSS most commonly occurs as a complication of treatment with in vitro fertilization medications, such as human chorionic gonadotropin (hCG) or gonadotropin-releasing hormone agonists. OHSS has infrequently been reported to be caused by high hCG levels in complete, partial, or invasive molar pregnancies. The classic signs and symptoms of OHSS include nausea, vomiting, bloating, abdominal pain, tachycardia, tachypnea, and dyspnea. Further positive diagnostic studies for OHSS include enlarged ovaries, ascites, hemoconcentration, hyponatremia, hyperkalemia, and oliguria. OHSS due to molar pregnancies is extremely rare. Suziki et al. performed a literature review in 2014 and describe the eight ever-reported molar pregnancy-associated OHSS cases, three of which were partial molar pregnancies. We present a two-case comparison that first examines an exceptionally rare OHSS case presentation of a 19-year-old female with a partial molar pregnancy that was also complicated by hCG-induced thyrotoxicosis. Following this, we discuss a case of the more classic presentation of OHSS caused by fertility treatments. This case report is of novel interest because we present a case comparison that emphasizes a rare, paradoxical association between OHSS and dilation-evacuation procedures that is important for physicians to be aware of - OHSS is not an adverse event of molar pregnancies that can be eliminated by declining hCG levels after a dilation and evacuation procedure; rather, in a molar pregnancy, OHSS occurs after the dilation and evacuation.

Phosphatidylglycerol Inhibits Toll-Like Receptor-Mediated Inflammation by Danger-Associated Molecular Patterns.

Psoriasis is a common skin disorder characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes and inflammation. We previously showed that phosphatidylglycerol (PG) can regulate keratinocyte function and suppress skin inflammation. Based on data suggesting that PG can inhibit toll-like receptor (TLR) activation induced by microorganisms and their components, we determined whether PG can inhibit TLR activation in response to antimicrobial peptides. These peptides, which are up-regulated in psoriasis, are known to function as danger-associated molecular patterns (i.e., DAMPs) to activate TLRs and the innate immune system. Because S100A9 is elevated in psoriatic skin and in animal models of psoriasis, we selected S100A9 as a representative antimicrobial peptide DAMP. We showed that in primary keratinocytes and a macrophage cell line, PG suppressed inflammatory mediator production induced by recombinant S100A9 functioning through both TLR2 and TLR4. In addition, PG, but not phosphatidylcholine, inhibited downstream S100A9-elicited TLR2 and NF-κB activation. These results, to our knowledge previously unreported, show PG's ability to inhibit DAMP-induced TLR activation, thereby reducing inflammatory signals. In addition, topical PG ameliorated skin lesions and inflammation in a mouse model of psoriasis. Together, these results suggest the possibility of developing PG as a therapy for psoriasis.