Clinical Spectrum of Capillary Malformation–Arteriovenous Malformation Syndrome Presenting to a Pediatric Dermatology Practice: A Retrospective Study

Capillary malformation–arteriovenous malformation syndrome (CM‐AVM) is an autosomal dominant disorder caused by RASA1 mutations. The prevalence and phenotypic spectrum are unknown. Evaluation of patients with multiple CMs is challenging because associated AVMs can be life threatening. The objective of this study was to describe the clinical characteristics of children presenting with features of CM‐AVM to an academic pediatric dermatology practice. After institutional review board approval was received, a retrospective chart review was performed of patients presenting between 2009 and 2012 with features of CM‐AVM. We report nine cases. Presenting symptoms ranged from extensive vascular stains and cardiac failure to CMs noted incidentally during routine skin examination. All demonstrated multiple CMs, two had Parkes Weber syndrome, and two had multiple infantile hemangiomas. Seven patients had family histories of multiple CMs; three had family histories of large, atypical CMs. Six had personal or family histories of AVMs. Genetic evaluation was recommended for all and was pursued by six families; four RASA1 mutations were identified, including one de novo. Consultations with neurology, cardiology, and orthopedics were recommended. Most patients (89%) have not required treatment to date. CM‐AVM is an underrecognized condition with a wide clinical spectrum that often presents in childhood. Further evaluation may be indicated in patients with multiple CMs. This study is limited by its small and retrospective nature.     

The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

Nonocclusive mesenteric ischemia in renal patients: recognition and prevention of intestinal gangrene

Nonocclusive mesenteric ischemia (NOMI) is a disorder with an extremely high mortality. Salvage of affected patients requires early recognition and aggressive intervention to prevent intestinal gangrene. Dialysis patients represent a group at particularly high risk for this condition. Clinicians should develop a high index of suspicion for NOMI in dialysis patients to lessen the risk of death. A high interventional posture must be maintained due to the notoriously unreliable signs and symptoms of this disorder.     

Prevalence of hypocitraturia and hypopyrophosphaturia in recurrent calcium stone formers: as isolated defects or associated with other metabolic abnormalities

Several underlying metabolic abnormalities may be present in patients with recurrent calcium calculus disease (RCCD). The aim of this study was to determine the prevalence of deficiencies of 2 well-known potent inhibitors of crystal formation and growth, citrate and pyrophosphate, in the various metabolic subgroups and as single defects. In 107 patients with RCCD, urinary citrate was significantly decreased in all metabolic subgroups with 49% of patients having hypocitraturia (2.53 +/- 1.19 mmol/24 h) versus controls (3.44 +/- 0.96 mmol/24 h; p less than 0.001). Reduced pyrophosphate:creatinine ratios were present in all the patient subgroups, and 48% of all patients had reduced ratios (1.68 +/- 1.68 vs. 3.10 +/- 2.66 in controls; p less than 0.01). There was no correlation between citrate and pyrophosphate concentration. Isolated hypocitraturia was found in 11.2%, reduced pyrophosphate:creatinine ratios as the single defect in 11.2% and a combination of both in 12.1% of patients. Thus inhibitor defects play an important role in patients with RCCD and frequently occur as isolated biochemical defects.     

Long-term storage effects on canine osteochondral allografts.

We have studied long-term (to 60 days) effects of 4 degrees C storage in culture media on the histologic, mechanical, and chemical properties of the cartilage from osteochondral shell allografts from the dog. The structural integrity of the cartilage matrix was intact up to 60 days of storage, for the mechanical properties represented by the aggregate modulus and apparent permeability remained normal. These data are supported by normal safranin-O staining as well as normal glycosaminoglycan content and total collagen concentration. However, chondrocyte viability, as assessed by 35SO4 uptake and hematoxylin and eosin preparations, decreased dramatically with time. We believe that the longer storage to 60 days is not indicated, unless conditions can be modified to maintain cell viability.     

The heart in rheumatoid arthritis--a clinical and echocardiographic study

A clinical and echocardiographic study was carried out in a randomly selected group of 101 patients with rheumatoid arthritis to determine the prevalence of cardiac abnormalities. Adequate two-dimensional assessments were obtained in 84 patients and 77 patients had adequate M mode recordings. Thirty-one patients (37 per cent) had 45 echocardiographic abnormalities. Five patients (6 per cent) had a pericardial effusion. Eleven abnormalities of the mitral valve were noted in 10 patients (13 per cent). Three patients had mitral valve prolapse, one patient with aortic incompetence had flutter on the mitral valve, five patients had mitral annular calcium and one patient had hypertrophic obstructive cardiomyopathy and mitral annular calcification. A reduction in the E-F slope was noted in 12 patients, seven of whom had associated cardiac disease, one patient had a sinus tachycardia and four patients (5 per cent) had a mild reduction without any other cardiac abnormality. Apart from the presence of pericardial effusion in 6 per cent and minor abnormalities of the E-F slope in 5 per cent of patients, all the other significant echocardiographic abnormalities could be related to the presence of associated cardiac disease.     

Xylocandin: a new complex of antifungal peptides. I. Taxonomy, isolation and biological activity

Xylocandin is a complex of novel peptides with potent antifungal activity that is produced by Pseudomonas cepacia ATCC 39277. The complex was isolated from the fermentation broth by extraction with butanol-methanol, 9:1, followed by collection of the precipitate formed upon concentration of the solvent extract. Purification was effected by chromatography on reversed phase and size exclusion gels followed by TLC on silica gel. These techniques afforded eight components: A1, A2, B1, B2, C1, C2, D1 and D2. A mixture of the two closely related components, xylocandins A1 and A2, displayed potent anticandidal and antidermatophytic activities in vitro. The activity was diminished by the presence of serum or vaginal washings. No antibacterial activity was demonstrable.     

The role of growth hormone replacement in a growth hormone deficient patient with underlying cardiomyopathy and severe congestive heart failure.

It has been reported that growth hormone (GH) deficiency induced cardiomyopathy responds to growth hormone replacement therapy. We describe the case of a middle-aged male with cardiomyopathic heart failure and growth hormone deficiency of the adult secondary to surgical panhypopituitarism. We demonstrate clinical and hemodynamic improvement of cardiac function with growth hormone replacement therapy despite underlying structural heart disease.