The heterogeneity of amyotrophic lateral sclerosis: a possible explanation of treatment failure

Amyotrophic lateral sclerosis (ALS) is a severe clinical condition characterized by upper and lower motor neuron degeneration for which there is no truly effective treatment. The absence of an effective treatment can be explained in part by the complex and heterogeneous genetic, biochemical, and clinical features of ALS. While ALS accounts for the majority of the motor neuron diseases, the recognition of disease variants and mimic syndromes may lead to further insights into possible causes for the generality of ALS. From a biochemical perspective, the process of motor neuron degeneration is complex and the multifactorial influences and potential biomarkers of ALS have never been assessed in the light of the clinical heterogeneity of ALS. Several genes and environmental influences have been suggested as possible risk factors of ALS. A better understanding of interactions between these risk factors, potential biomarkers and heterogeneous clinical features may lead to more clearly defined pathological profiles among individuals or groups of ALS patients and in turn lead to more focused therapeutic trials.     

A case of Stevens-Johnson syndrome possibly induced by amifostine during radiotherapy

Skin reactions to amifostine are considered to be rare. Here we describe the case of a patient who developed a severe skin eruption (Stevens-Johnson syndrome) during radiotherapy probably due to amifostine. As in most of the patients described so far, the worst lesions were located in the skin areas previously treated with radiotherapy.     

Insulin-like Growth Factor-Binding Protein 3 and Hemoglobin Concentration in Older Persons Living in the Community

A decreased hemoglobin concentration is a common clinical condition in elderly subjects, and in at least 20% of the cases it is not possible to directly attribute the anemia to specific factors. The aim of the present study was to evaluate the relationship of different levels of insulin-like growth factor-binding protein 3 (IGFBP-3) with the blood concentration of hemoglobin in persons aged 80 years and older. Data are from a baseline evaluation of the Aging and Longevity in the Sirente Geographic Area (ilSIRENTE) study (n=253). Analysis of covariance was used to examine the effect of different IGFBP-3 levels on hemoglobin concentration. After adjustment for potential confounding variables, which included age, sex, number of diseases, renal failure, cancer, gastric ulcer, albumin, and iron concentrations, individuals in the group with higher IGFBP-3 concentrations showed a significantly higher mean hemoglobin concentration than participants in the group with lower IGFBP-3 concentrations (13.4 +/- 1.4 g/dL versus 12.9 +/- 1.9 g/dL, respectively; P=.03). In conclusion, the present study has shown that a higher IGFBP-3 level is associated with a higher hemoglobin concentration among older people living in the community. This finding suggests that the growth hormone/IGF axis may play an important role in hematopoiesis, and it may be implicated in the age-related decline in hemoglobin concentration.     

Isolation and characterization of mesenchymal stem cells from the fat layer on the density gradient separated bone marrow

The density gradient centrifugation method was originally designed for the isolation of mononuclear peripheral blood cells and rapidly adapted to fractionate bone marrow (BM) cells. This method involves the use of gradient density solutions with low viscosity and low osmotic pressure that allows erythrocytes and more mature cells gravitate to the bottom at a density fraction superior to 1.080?g/dL; mononuclear cells (MNCs) held in the plasma-solution to interphase at a density between 1.053 and 1.073?g/dL; plasma, dilution medium and anticoagulant to occupy a density less than 1.050?g/dL and the fat cells to float due to their very low density. BM-mesenchymal stem cells (MSCs) are usually obtained after the separation and cultures of BM-MNCs from the plasma-solution interphase, which is traditionally considered the only source of progenitor cells (hematopoietic and nonhematopoietic). In this study evidences that MSCs could be isolated from the very low-density cells of the fat layer are presented. In addition, we demonstrated that the MSCs obtained from these cells have similar immunophenotypic characteristics, and similar proliferative and differentiation potential to those obtained from the MNCs at plasma-solution interphase. The method represents a simple and cost effective way to increase the MSCs yield from each BM donor, without the need to look for other sources, additional manipulation of cells, and risks of contamination or disturbances of the potential of differentiation. These cells might serve as a complementary source of MSCs to facilitate preclinical and clinical application in tissue engineering and cell therapy.     

Expression and Immunohistochemical Detection of Leptin‐Like Peptide in the Gastrointestinal Tract of the South American Sea Lion (Otaria flavescens) and the Bottlenose Dolphin (Tursiops truncatus)

This study provides an immunohistochemical approach to the expression of leptin in the gastrointestinal tract of the monogastric South American sea lion (Otaria flavescens), and the poligastric bottlenose dolphin (Tursiops truncatus). The specific organization of the gastrointestinal tract is examined in relation to the neuroendocrine regulation of the gut exerted by leptin. In the South American sea lion some leptin‐like‐immunoreactive (ir) cells, and endocrine type cells, were found in the pit of gastric mucosal folds and in the epithelium of duodenum as well as numerous neurons were detected in the submucosal and myenteric plexuses of the stomach. In the bottlenose dolphin, many leptin‐like‐ir cells, and exocrine type cells, were identified in the mucosal layer of the main stomach as well as several neurons and nervous fibers were detected in nervous plexuses of main stomach, pyloric stomach, proximal, and middle intestine. Our data suggest that the distribution of leptin‐like peptides is similar in the two species, notwithstanding the different anatomical organization of the gastrointestinal apparatus of South American sea lion and bottlenose dolphin. These findings “suggest” the presence of a basal plan in the regulation of food intake, body weight, energy balance and of the gastrointestinal functions in general also in marine mammals with different and specific feeding habits. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

Laparoscopic conservative treatment of colo-vesical fistulas following trauma and diverticulitis: report of two different cases

Introduction

The standard treatment of colovesical fistula is the removal of fistula, suture of bladder wall, and then colic resection with or without temporary colostomy. The open approach is more commonly used because the laparoscopic approach seems to have high conversion rates and morbidity. We report two cases of colovesical fistula treated with a laparoscopic conservative approach. We also focus on the long term outcome. Case presentation 1. A 69-year-old male with colovesical fistula that appeared after endoscopic polipectomy in the sigmoid diverticulum underwent a totally laparoscopic conservative treatment without colic resection. Operative time was 210 minutes and blood loss was 300 ml. Time to bowel movement was 60 hours. No complications or fistula recurrence occurred at 48-month follow-up. Case presentation 2. A 34-year-old male with colovesical fistula secondary to diverticulitis underwent totally laparoscopic conservative surgery. Operative time was 160 minutes and blood loss was 150 ml. Time to bowel movement was 72 hours. Fistula reoccurred two weeks after discharge. We performed Hartmann’s procedure and defunctioning colostomy with an open approach. No recurrence or complications were found at 36 months follow up.

Conclusion

The laparoscopic conservative treatment of colovesical fistula is a safe and feasible technique. When there is no diverticular disease, the conservative approach is very effective.     

Randomised controlled monotherapy trials: which comparators to use?

As approximately 50% of patients with newly diagnosed epilepsy achieve seizure remission after initial monotherapy, the selection of the first-choice drug to be used as the gold standard in randomised clinical trials is critical. Several first and second generation drugs have been used in regulatory and pragmatic monotherapy trials with similar efficacy but differing pharmacokinetic, tolerability, and safety profiles. None of the available compounds has an ideal profile and second generation drugs do not appear to present unequivocal advantages in this regard. Compared to first generation drugs, some newer generation antiepileptic drugs may be preferred as they have similar efficacy but lower potential for idiosyncratic reactions and drug interactions. However, more recent antiepileptic drugs also have limitations, which include lack of superiority and, in some cases, unbearable adverse effects. In this light, there are no standard criteria as a reference for the selection of the best comparator for new monotherapy trials. However, according to the recommendations of evidence-based guidelines, carbamazepine still represents the first-choice drug for patients with partial epilepsy. Ethosuximide may be an option for absence epilepsy. In contrast, for the treatment of patients with other generalised epilepsies, there is no clear indication of preferred drug, as valproate, which has been found to prevail over other compounds, should be withheld in women of childbearing age due to its teratogenic potential, and there is insufficient evidence to choose an alternative drug.