Age-dependent alteration in muscle regeneration: the critical role of tissue niche

Although adult skeletal muscle is composed of fully differentiated fibers, it retains the capacity to regenerate in response to injury and to modify its contractile and metabolic properties in response to changing demands. The major role in the growth, remodeling and regeneration is played by satellite cells, a quiescent population of myogenic precursor cells that reside between the basal lamina and plasmalemma and that are rapidly activated in response to appropriate stimuli. However, in pathologic conditions or during aging, the complete regenerative program can be precluded by fibrotic tissue formation and resulting in functional impairment of the skeletal muscle. Our study, along with other studies, demonstrated that although the regenerative program can also be impaired by the limited proliferative capacity of satellite cells, this limit is not reached during normal aging, and it is more likely that the restricted muscle repair program in aging is presumably due to missing signals that usually render the damaged muscle a permissive environment for regenerative activity.     

Hepatitis E Virus Genotype 4 Outbreak,Italy, 2011

During 2011, 5 persons in the area of Lazio, Italy were infected with a monophyletic strain of hepatitis E virus that showed high sequence homology with isolates from swine in China. Detection of this genotype in Italy parallels findings in other countries in Europe, signaling the possible spread of strains new to Western countries.     

Ionized serum calcium levels during acute renal failure: intermittent hemodialysis vs. Continuous hemodiafiltration

BACKGROUND: Achieving "adequacy of dialysis" includes the maintenance of normal serum ionized calcium concentrations and is an important therapeutic goal in the treatment of acute renal failure (ARF). It is unknown whether this goal is best achieved with intermittent or continuous renal replacement therapy. METHODS: We compared the effects of continuous veno-venous hemodiafiltration (CVVHDF) and intermittent hemodialysis (IHD) on serum ionized calcium concentrations using daily morning blood tests in 88 consecutive intensive care patients of which half were treated with IHD and half with CRRT. RESULTS: Mean patient age was 54 +/- 14 years for IHD and 60 +/- 14 years for CVVHDF (NS). However, patients who received CVVHDF were significantly more critically ill (mean APACHE II scores: 24.4 +/- 5.1 for IHD vs. 29.2 +/- 5.7 for CVVHDF, p < 0.003). Before treatment, the mean ionized calcium concentration was 1.177 +/- 0.03 mmol/l for IHD and 1.172 +/- 0.04 mmol/l for CVVHDF (NS), with abnormal values in 51.6% of IHD patients and in 68% of CVVHDF patients (NS). During treatment, hypocalcemia was significantly more common among CVVHDF patients (24.5% vs. 14.9%; p < 0.011) while hypercalcemia was more frequent during IHD (36.1% vs. 25.6%; p < 0.019). CONCLUSIONS: Abnormal serum ionized calcium concentrations are frequent in ARF patients before and during renal replacement. Once dialytic therapy is applied, CVVHDF is more likely to lower serum calcium concentrations, while IHD is more likely to induce hypercalcemia. Appreciation of these different biochemical effects may assist clinicians in adjusting dialytic therapy in selected patients.     

Perioperative management in children with sickle cell disease undergoing laparoscopic surgery.

OBJECTIVE: The aim of this study was to evaluate our experience with laparoscopic surgery in children with sickle cell disease. METHODS: A retrospective chart review was performed to analyze the indication for surgery, perioperative management, surgical technique, complications, duration of hospitalization, and outcome. One pediatric surgeon performed all procedures. RESULTS: Thirteen children underwent laparoscopic surgery for the following indications: symptomatic cholelithiasis/cholecystitis in 9; recurrent splenic sequestration in 3; and hypersplenism/symptomatic cholelithiasis in 1. The 7 boys and 6 girls had a median age of 7.8 years. Patients undergoing splenectomy only were younger than those undergoing cholecystectomy (median age, 3.6 years versus 11.5 years, respectively). Four children underwent endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy because of common bile duct dilatation and stones. Twelve patients received packed red blood cell transfusions prior to surgery. The median operative time was 150 minutes, and the median hospitalization was 3 days. Four patients suffered postoperative complications (2 with acute chest syndrome, 1 with recurrent abdominal pain, and 1 with priapism). The patient with abdominal pain was found to have a retained stone in the common bile duct, which was retrieved via endoscopic retrograde cholangiopancreatography and sphincterotomy. All complications resolved with medical management. CONCLUSIONS: Laparoscopic surgery is safe in children with sickle cell disease. Meticulous attention to perioperative management, transfusion guidelines, and pulmonary care may decrease the incidence of acute chest syndrome.     

Kidney and liver involvement in monoclonal light chain disorders

Monoclonal light chains (LCs) are responsible for a wide spectrum of renal and hepatic diseases, that above all include amyloid light-chain (AL) amyloidosis and light chain deposition disease (LCDD). Amyloid deposits stain for Congo red on light microscopy and have fibrillar aspect on electron microscopy, whereas deposits in LCDD are positive using monotypic LCs on immunofluorescence and have a granular aspect on electron microscopy. Sometimes fibrillar and granular deposits are observed in the same organ or in different organs of the same patient. Kidney and liver involvement is a frequent finding, both in primary amyloidosis (AL amyloidosis) or in LCDD. Renal manifestations include proteinuria, nephrotic syndrome, and progressive renal failure. End-stage renal disease requiring dialysis is observed in about 20% of patients with AL amyloidosis and in 70% of patients with LCDD. The mean survival time is about 12 to 18 months in AL amyloidosis and 34 months in LCDD. The most important prognostic factor is severe cardiac involvement, which reduces the mean survival to only 6 months. Hepatic manifestations include hepatomegaly, portal hypertension, ascites, intrahepatic cholostatic jaundice, and hepatic insufficiency. The mean survival of patients with liver damage is 14 months, but it is reduced to 5 months in patients with cholostatic jaundice. Contemporary kidney and liver involvement is usually observed on histologic examination, less frequently as clinical manifestation. No specific treatment exists for AL amyloidosis and LCDD, and the prognosis remains severe. The aim of treatment is to suppress proliferation of the abnormal clone of plasma cells and remove tissue deposits. The regimens, including melphalan-prednisone (MP) or vincristine-doxorubicin-dexamethasone (VAD), are used both in AL amyloidosis or in LCDD with some effectiveness. New approaches, especially the use of 4'-iodo-4'deoxydoxorubicin, could achieve better results. Dialysis seems to not worsen the outcome in both diseases because survival of patients on dialysis is not different from that of patients not reaching uremia. Also, kidney and liver transplantation is effective, though amyloidosis or LCDD may occur in transplanted organs. The most interesting therapeutic approach is autologous-blood stem-cell transplantation, which may produce a complete remission of the plasma-cell dyscrasia and a substantial improvement of clinical manifestations related to LC deposits.     

Physiology of erection

In these article we review the main mechanisms involved in human erection. We review and update in detail the biochemical (nitric oxide and Rho-kinase pathways), cellular (smooth muscle relaxation mechanisms), neural (autonomic and somatic pathways) and microscopic penile principles.     

A pathologic fracture of an intracortical chondroma masking as an osteoid osteoma

The differential diagnosis of a tibial intracortical diaphyseal lesion includes osteoid osteoma, periosteal chondroma, nonossifying fibroma, osteofibrous dysplasia, and adamantinoma. While osteoid osteomas represent 5% of all primary bone tumors, little is understood about intracortical chondromas. Intracortical chondroma was first described in 1990 and 7 reported cases have since been published. This article presents the first reported case of a pathologic fracture of an intracortical lesion in a child that shared radiographic and clinical features similar to those of osteoid osteoma, but on histopathologic examination revealed an intracortical chondroma. Our patient exhibited radiographic features of a poorly circumscribed cortical bone sclerosis, a centralized radiolucent nidus on computed tomography, and a hot bone scan of a lesion <1 cm in size that was consistent with an osteoid osteoma. An excision of the bone lesion was performed. The histopathology of the lesion revealed nodules of benign hyaline cartilage in cortical bone, consistent with an intracortical chondroma. Demarcated by cortical bone with mature Haversian systems rather than periosteum or cancellous bone, intracortical chondroma differs from the other 2 chondroma variants, periosteal chondroma and enchondroma, by its relationship to the surrounding bone. Enchondromas are characteristically understood to be asymptomatic. Intracortical chondromas along with periosteal chondromas have been found to present as painful lesions. The similarities with osteoid osteoma and intracortical chondroma in our patient make it circumspect in regards to ablating lesions (ie, needle radiofrequency ablation) without acquiring a biopsy in pediatric patients that both clinically and radiographically are presumably an osteoid osteoma.     

Human ventral parietal cortex plays a functional role on visuospatial attention and primary consciousness. A repetitive transcranial magnetic stimulation study

In this paper, we used repetitive transcranial magnetic stimulation (rTMS) in 18 normal subjects to investigate whether the ventral posterior parietal cortex (PPC) plays a causal role on visuospatial attention and primary consciousness and whether these 2 functions are linearly correlated with each other. Two distinct experimental conditions involved a similar visual stimuli recognition paradigm. In "Consciousness" experiment, number of consciously perceived visual stimuli was lower by about 10% after rTMS (300 ms, 20 Hz, motor threshold intensity) on left or right PPC than after sham (pseudo) rTMS. In "Attentional" Posner's experiment, these stimuli were always consciously perceived. Compared with sham condition, parietal rTMS slowed of about 25 ms reaction time to go stimuli, thus disclosing effects on endogenous covert spatial attention. No linear correlation was observed between the rTMS-induced impairment on attention and conscious perception. Results suggest that PPC plays a slight but significant causal role in both visuospatial attention and primary consciousness. Furthermore, these high-level cognitive functions, as modulated by parietal rTMS, do not seem to share either linear or simple relationships.