Outside the fiber: Endomysial stromal and capillary pathology in skeletal muscle may impede infusion therapy in infantile-onset Pompe disease.

The survival of infantile-onset Pompe disease (IOPD) patients has improved dramatically since the introduction of enzyme replacement therapy (ERT) with a1glucosidase alfa. However, long-term IOPD survivors on ERT demonstrate motor deficits indicating that current therapy cannot completely prevent disease progression in skeletal muscle. We hypothesized that in IOPD, skeletal muscle endomysial stroma and capillaries would show consistent changes that could impede the movement of infused ERT from blood to muscle fibers.

Phase I study of liver depot gene therapy in late-onset Pompe disease.

Gene therapy with an adeno-associated virus serotype 8 (AAV8) vector (AAV8-LSPhGAA) could eliminate the need for enzyme replacement therapy (ERT) by creating a liver depot for acid α-glucosidase (GAA) production. We report initial safety and bioactivity of the first dose (1.6 × 10 vector genomes/kg) cohort (n = 3) in a 52-week open-label, single-dose, dose-escalation study (NCT03533673) in patients with late-onset Pompe disease (LOPD).

Complex III deficiency due to an in-frame MT-CYB deletion presenting as ketotic hypoglycemia and lactic acidosis.

Complex III deficiency due to a MT-CYB mutation has been reported in patients with myopathy. Here, we describe a 15-year-old boy who presented with metabolic acidosis, ketotic hypoglycemia and carnitine deficiency. Electron transport chain analysis and mitochondrial DNA sequencing on muscle tissue lead to the eventual diagnosis of complex III deficiency.

Skeletal muscle microvasculature in the diagnosis of neuromuscular disease.

Blood vessels are often overlooked in analyses of skeletal muscle biopsies. However, there are many vascular features in skeletal muscle biopsies that, when interpreted in the context of other histologic patterns and clinical history, provide useful information that allows muscle pathologists to narrow their differential diagnoses and provide more accurate guidance to treating physicians. Here, we provide a review of normal skeletal muscle vasculature with details of the ultrastructure of vessel walls.

Characterization of pre- and post-treatment pathology after enzyme replacement therapy for Pompe disease.

In Pompe disease, a genetic deficiency of lysosomal acid alpha-glucosidase, glycogen accumulates abnormally in the lysosomes of skeletal, cardiac and smooth muscle, and contributes to clinically progressive and debilitating muscle weakness. The present study involved 8 infantile-onset Pompe patients, treated weekly with 10 mg/kg of recombinant human acid alpha-glucosidase (rhGAA). Muscle biopsies were obtained at baseline, 12 and 52 weeks post-treatment to establish an indicator of efficacy.

Magnetic resonance imaging of intramuscular myxoma with histological comparison and a review of the literature.

Objective: To evaluate the magnetic resonance (MR) features of intramuscular myxoma (IM) compared with its pathological findings.

Design: Two radiologists retrospectively reviewed records and imaging studies of patients with histologically proven IM. Two radiologists also analyzed by consensus all the MR studies (pre- and post-contrast T1-weighted and T2-weighted sequences) and a pathologist reviewed the available histological material.

Clinical Studies in Non-chromosome 4-Linked Facioscapulohumeral Muscular Dystrophy.

Objectives: To characterize clinically and molecularly a large, non-chromosome 4-linked facioscapulohumeral muscular dystrophy (FSHMD) family.

Methods: Neurological evaluations of affected (N = 55) and at-risk (N = 48) individuals were performed along with selected laboratory analyses, including creatine kinase testing, muscle biopsy, p13E-11 fragment analysis, and cytogenetic studies. Genetic analyses of the scapuloperoneal muscular dystrophy and scapuloperoneal muscular atrophy regions on chromosome 12 were performed using genetic markers flanking the intervals of interest and parametric LOD score analyses.

Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial.

Purpose: Infantile glycogen storage disease type II (GSD-II) is a fatal genetic muscle disorder caused by deficiency of acid alpha-glucosidase (GAA). The purpose of this study was to investigate the safety and efficacy of recombinant human GAA (rhGAA) enzyme therapy for this fatal disorder.

Methods: The study was designed as a phase I/II, open-label, single-dose study of rhGAA infused intravenously twice weekly in three infants with infantile GSD-II.

Diclofenac sodium (Voltaren) reduced exercise-induced injury in human skeletal muscle.

Purpose: To examine the effects of prolonged systemic administration of diclofenac sodium (Voltaren), a nonsteroidal anti-inflammatory drug, on objective indices of exercise-induced muscle damage in humans.

Methods: Fifty-four volunteers (mean age, 26.4 yr; range, 18-35) participated in this randomized double-blind, placebo-controlled trial.

Myxoid liposarcoma of the supraclavicular fossa.

Liposarcomas generally originate most often in the extremities or retroperitoneum, less frequently in the head and neck, and rarely in the thorax. We describe a particularly rare presentation of myxoid liposarcoma originating in the supraclavicular fossa. The mass was resected and has not recurred.

Acute pancreatitis in an infant with lactic acidosis and a mutation at nucleotide 3243 in the mitochondrial DNA tRNALeu(UUR) gene.

Unlabelled: The A to G point mutation at position 3243 of the mitochondrial DNA tRNALeu(UUR) gene is commonly found in patients with the syndrome of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). A male patient was referred at 7 months with failure to thrive, developmental delay, microcephaly and hypotonia since age 2 months. He had developed lactic acidosis and increasingly frequent seizures since age 5 months.

Mitochondrial myopathy with anemia, cardiomyopathy, and lactic acidosis: a distinct late onset mitochondrial disorder.

A 40-year-old woman presented with profound muscle weakness resulting in failure to wean from a ventilator and persistent lactic acidosis after having recovered from a pneumonia complicated by adult respiratory distress syndrome, myocardial infarction, renal failure and shock. She had a 28 year history of chronic anemia and exercise intolerance. Anemia and thrombocytopenia persisted after admission.

The management of desmoid tumors.

Purpose: To determine the efficacy of different treatment modalities for desmoid tumors.

Materials And Methods: We reviewed the treatment of 40 patients with histologically confirmed desmoid tumors seen at Duke University Medical Center between 1974 and 1990.

Results: Radiotherapy was administered to 16 patients (Group I)--14 with recurrent disease s/p surgery and in two as initial treatment.

Ipecac myopathy and cardiomyopathy.

Two cases of ipecac myopathy, one with associated cardiomyopathy are reported. Both patients were young women with eating disorders who came to medical attention because of diffuse muscle weakness. Clinical and electromyographic data suggested ipecac myopathy and muscle biopsies confirmed this diagnosis.

Micro-anastomosis of 0.3-0.4 mm vessels after cold ischemia using a rat model of toe-to-thumb transplantation.

Anastomoses of vessels of less than 0.5 mm in diameter remain a challenge from the technical aspect. Clinically such anastomoses are necessary for replantation of the distal digit in adults and whole digits in children.

Oncocytic differentiation in intrahepatic biliary cystadenocarcinoma.

An intrahepatic biliary cystadenocarcinoma in a 56-yr-old white man was characterized by pronounced oncocytic differentiation. Grossly the tumor was a well-demarcated cyst filled with numerous branching papillary fronds. Most tumor cells had abundant granular, intensely eosinophilic cytoplasm on light microscopic examination and large numbers of densely packed mitochondria by electron microscopy.

Nasopharyngeal teratomas.

Teratomas are the most common congenital tumors, but neoplasms of the nasopharynx are rare in neonates and children. Four histologic types of nasopharyngeal teratomas occur-dermoids, teratoids, true teratomas, and epignathi-of which dermoids comprise the vast majority. A case is presented of a neonate born at term exhibiting signs of respiratory difficulty, which were found to be caused by a true teratoma of the nasopharynx.

Adenoid cystic carcinoma of the breast metastatic to the kidney. A clinically symptomatic lesion requiring surgical management.

Adenoid cystic carcinoma (ACC) of the breast is a rare histologic type of breast cancer associated with a good prognosis. A woman who earlier had a pulmonary metastasis surgically resected 6 years postmastectomy developed clinically symptomatic bleeding from a renal metastasis 12 years postmastectomy. An atypical angiographic picture (moderate vascularization) for secondary renal neoplasms was observed.

The effect of acute denervation on the microcirculation of skeletal muscle: rat cremaster model.

Although tissue is denervated during replantation of a severed part, tissue transfer, or muscle transplantation, there are few studies concerning the effects of acute denervation on muscle microcirculation. We have described a surgical procedure that totally denervates the rat cremaster muscle. Histological examination of the denervated tissue has given convincing evidence of nerve degeneration and skeletal muscle atrophy, accompanied by electrophysiological evidence of total denervation.

To excite a heart: a bird's view.

Ultrastructural investigations of avian cardiac muscle, including ratite hearts, have provided great insights into the mechanisms as to how excitation leads to contraction in the heart. The geometry of the conduction fibers of ratite hearts confirms earlier observations on birds showing that the geometry of the conduction system and its component cells is adapted to hearts of different sizes and rates of contraction so as to maintain a differential in conduction velocities between the conduction system and the working fibers. The study of the ratite conduction fibers bears out the idea of an inverse relationship between the size of the gap junctions and the input resistance of cardiac cells.