Successful lung transplant in a child with cystic fibrosis and persistent Blastobotrys rhaffinosifermentans infection.

Fungal respiratory infections in patients with CF are a significant concern both pre- and post-lung transplantation (LTx). Fungal infection is associated with increased mortality post-LTx, and in the past decade, the prevalence of fungal colonization in Canadian pediatric patients with CF has increased. The emergence of novel fungal pathogens is particularly challenging to the transplant community, as little is known regarding their virulence and optimal management. We present a case of a successful double-lung transplant in a pediatric patient with CF who was infected pretransplantation with a novel yeast, Blastobotrys rhaffinosifermentans. This patient was treated successfully with aggressive antifungal therapy post-transplantation, followed by extended fungal prophylaxis. The significance of fungal colonization and infection in children with CF pre- and post-LTx is reviewed.

Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy.

Muscle contraction results from the force generated between the thin filament protein actin and the thick filament protein myosin, which causes the thick and thin muscle filaments to slide past each other. There are skeletal muscle, cardiac muscle, smooth muscle and non-muscle isoforms of both actin and myosin. Inherited diseases in humans have been associated with defects in cardiac actin (dilated cardiomyopathy and hypertrophic cardiomyopathy), cardiac myosin (hypertrophic cardiomyopathy) and non-muscle myosin (deafness). Here we report that mutations in the human skeletal muscle alpha-actin gene (ACTA1) are associated with two different muscle diseases, 'congenital myopathy with excess of thin myofilaments' (actin myopathy) and nemaline myopathy. Both diseases are characterized by structural abnormalities of the muscle fibres and variable degrees of muscle weakness. We have identified 15 different missense mutations resulting in 14 different amino acid changes. The missense mutations in ACTA1 are distributed throughout all six coding exons, and some involve known functional domains of actin. Approximately half of the patients died within their first year, but two female patients have survived into their thirties and have children. We identified dominant mutations in all but 1 of 14 families, with the missense mutations being single and heterozygous. The only family showing dominant inheritance comprised a 33-year-old affected mother and her two affected and two unaffected children. In another family, the clinically unaffected father is a somatic mosaic for the mutation seen in both of his affected children. We identified recessive mutations in one family in which the two affected siblings had heterozygous mutations in two different exons, one paternally and the other maternally inherited. We also identified de novo mutations in seven sporadic probands for which it was possible to analyse parental DNA.

Small intestinal transplant mucosal necrosis associated with enteral sodium polystyrene sulfonate administration.

Diarrhea is a common manifestation of disease in recipients of intestinal transplants. Sodium Polystyrene Sulfonate administration has been associated with significant bowel injury. Recognizing the diagnosis requires clinical awareness and comprehensive review of intestinal biopsies. We present an illustrative case and discussion. It is the first reported case in a pediatric intestinal transplant patient with serial intestinal biopsies documenting the evolution of disease.

A multimetric approach to evaluate offshore mussel aquaculture effects on the taxonomical and functional diversity of macrobenthic communities.

A multimetric approach was used to detect structural, compositional, and functional shifts in the underlying macrobenthic communities of an offshore mussel (Mytilus galloprovincialis) farm in a Portuguese Aquaculture Production Area. Sampling stations distributed inside and outside this area were used to evaluate sediment descriptors and macrobenthic samples collected before (April and September 2010) and after (June and September 2014) the initiation of mussel farming. Sediment fine fraction, organic matter content, and trace element concentrations were found to increase with depth, independently from the mussel farm. Moreover, the structure and composition of the macrobenthic communities were likewise structured by depth. Turnover was the dominant temporal and spatial pattern of beta diversity for all communities. Furthermore, the functional diversity of these communities was unaffected by the mussel farm. These results suggested that an offshore profile allowed hydrodynamic conditions to weaken the impact of mussel farming and highlighted the importance of conducting an integrative multimetric analysis when studying aquaculture impacts on benthic communities.

Childhood Köhlmeier-Degos disease with atypical skin lesions.

We report clinical and pathologic findings in a 16-year-old boy whose disease began in infancy with maculopapular skin lesions, followed by cyclic nodular cutaneous eruptions, intermittent enlargement of liver and spleen, episodic abdominal pain, and sporadic unexplained fever. Subsequently, various ophthalmologic disturbances, along with a multitude of neurologic signs and symptoms, dominated the clinical picture. The CNS bore the brunt of pathologic changes, characterized by widespread leptomeningeal fibrosis, ventricular enlargement, and multiple brain infarcts. Striking intimal thickening led to narrowing or occlusion of almost all the medium-sized and small extraparenchymal arteries.

Tubulointerstitial nephritis induced by the leukotriene receptor antagonist pranlukast.

A 7-year-old boy with asthma was receiving the leukotriene receptor antagonist pranlukast (Ultair; SmithKline Beecham; Pittsburgh) as part of an open-label clinical trial. The patient's asthma improved, and he remained asymptomatic; but routine study evaluations 9 to 12 months into therapy showed microhematuria, proteinuria, glucosuria, anemia, and renal insufficiency. Renal biopsy demonstrated changes classic for acute allergic tubulointerstitial nephritis (ATIN), with mixed interstitial inflammatory infiltrate including eosinophils. Within 6 months of pranlukast withdrawal, anemia resolved and urinary sediment and renal function normalized. The case demonstrates that hypersensitivity reaction to pranlukast and resultant ATIN is possible, and that periodic urine testing in patients receiving pranlukast should be considered.

Rapid autologous marrow recovery and eradication of infectious mononucleosis despite severe immunosuppression following second transplantation for aplastic anemia.

A patient with aplastic anemia failed to respond to immunosuppressive therapy and first marrow transplantation (BMT). Recovery of autologous hematopoiesis was rapid following a second stem cell transplant with a non-myeloablative preparatory regimen. The autologous immune response to infectious mononucleosis (IM) 4 weeks post-transplant was normal despite recent and ongoing severe immunosuppression.

Peliosis of the spleen.

Peliosis of the spleen is a rare condition that accompanies peliosis hepatis. Two cases are presented, and a detailed morphologic description is given. The lesions are confined to the red pulp and appear to arise by progressive distention of splenic sinuses, with eventual thrombosis and organization. Peliotic involvement of the spleen is probably more common than realized and can have serious clinical implications.

Secondary massive ovarian edema with Meig's syndrome.

Primary massive ovarian edema is uncommon, particularly when it involves both ovaries before puberty. Ovarian edema secondary to a preexisting ovarian lesion is one of the postulated mechanisms. A prepubertal girl presented with bilateral massive ovarian edema with stromal hyperthecosis, which may have predisposed both ovaries to undergo partial torsion. The associations with Meig's syndrome, greatly elevated hormone levels and presence of omental and retroperitoneal nodules, raised a suspicion of malignancy.

Autosomal recessive, fatal infantile hypertonic muscular dystrophy among Canadian Natives.

We describe eleven mid-western Canadian aboriginal infants with a unique, progressive muscle disorder. All except one had muscle biopsy and/or autopsy. The infants were normal newborns who rapidly developed rigidity of all skeletal muscles, with early, respiratory insufficiency. Death occurred before 18 months of age. Electromyography showed increased insertion activity and profuse fibrillation potentials; motor unit potentials and interference pattern are normal until late in the course. Pathologic features include progressive, granular to powdery Z-band transformation, myofibrillar loss, and muscle regeneration. SDS-gel electrophoresis of one muscle sample revealed increased 54kDa and reduced 80kDa protein fractions. This disease differs from other conditions with Z-band alterations because of continuous muscle activity and relentless clinical progression. The clinical features, elevated serum creatine kinase, electromyographic and muscle biopsy findings suggest a dystrophic process. The recognition of this condition as an autosomal recessive disorder allows appropriate genetic counselling.

Congenital endodermal sinus tumor of the penis.

Congenitally occurring endodermal sinus tumors are very rare and frequently occur in association with teratomatous growths. The most common location for these tumors in infancy is the gonads. Tumors of the penis are rare in any age group. As far as we know, this tumor has never been reported in the penis. A 17-month-old baby boy was noted to have a pimple-like lesion at the corona of the glans penis. This was stationary and ignored for a year. At this point, the lump began increasing in size. A further delay of 6 months elapsed before a definitive diagnosis was made. This case emphasizes that any nodule in this area in the neonate is ignored with jeopardy.

Familial coarctation of the aortic arch with bilateral ptosis: a new syndrome?

A Newfoundland family with the apparently unique syndrome of complex coarctation of the aortic arch, bilateral stenoses of the subclavian arteries, bilateral ptosis, sensorineural deafness, and bronchial asthma is reported. This syndrome appears to have affected at least four generations, and has the characteristics of autosomal dominant inheritance.

Peripheral neuropathy in the first 2 years of life: diagnostic evaluation including molecular genetics.

Inherited polyneuropathies present in the first 2 years of life are discussed with emphasis on clinical, pathologic, and molecular data. Early-onset polyneuropathies are relatively rare, sometimes life-threatening conditions that demand early recognition by clinical and pathologic examination. Histologic and ultrastructural overlaps among the various conditions are sometimes resolved by molecular genetic analysis. The growth in disease identification by genetic localization allows a more comprehensive understanding of the clinical and morphologic heterogeneity involving rearrangements of the same gene. Molecular mechanisms explaining the acquisition of such gene rearrangements are beginning to be unraveled. Peripheral myelin disorders may be confused with primary axonal disorders, and electrophysiologic examination often helps to distinguish between these two. Furthermore, early-onset central nervous system disorders may present as peripheral polyneuropathies and confound the clinical picture. A tentative diagnosis can often be offered by pathologic examination and confirmed by biochemical enzyme analysis later. The differential clinical diagnostic considerations of early-onset polyneuropathies are offered, to help clinicians sort out these diseases in the most efficient manner.