Use of fibrin sealant in hypospadias surgical repair reduces the frequency of postoperative complications

INTRODUCTION: Urethrocutaneous fistulas (UCF) and flap dehiscence (FD) are the most common postoperative complications after hypospadias (HS) surgical repair. The aim of this study was to evaluate whether the application of fibrin sealant over the site of surgery and suture lines reduces these complications. MATERIALS AND METHODS: A prospective cohort of consecutive patients was treated over a 3-year period. 30 patients were submitted to HS surgical repair plus application of fibrin glue over the suture line and surgical site; for comparison, another 56 subjects made up the control group which was submitted to surgical repair only. Variables assessed included: age, type of HS, fibrin sealant used, complications and number of surgical procedures required to treat recurrences. RESULTS: In general, the frequency of complications was 10 vs. 41% for UCF (p = 0.002), 13 vs. 50% for FD (p = 0.001), and for flap necrosis (FN) 6.7 vs. 28.6% (p = 0.01) for the treatment and control groups respectively. The number of surgical reinterventions to treat recurrences was higher in the control group than in the study group (p = 0.04). CONCLUSION: The incidence of UCF after HS surgical repair can be reduced by applying fibrin sealant over the site of surgery and the suture lines.     

Altered beta-amyloid precursor protein isoforms in Mexican Alzheimer's Disease patients

Objective: To determine the β-amyloid precursor protein (βAPP) isoforms ratio as a risk factor for Alzheimer’s Disease and to assess its relationship with demographic and genetic variables of the disease. Methods: Blood samples from 26 patients fulfilling NINCDS-ADRDA diagnostic criteria for AD and 46 healthy control subjects were collected for Western blotting for βAPP. A ratio of βAPP isoforms, in optical densities, between the upper band (130 Kd) and the lower bands (106–110 Kd) was obtained. Odds ratios were obtained to determine risk factor of this component. Results: βAPP ratio on AD subjects was lower than that of control subjects: 0.3662 ± 0.1891 vs. 0.6769 ± 0.1021 (mean ± SD, p<0.05). A low βAPP ratio (<0.6) showed an OR of 4.63 (95% CI 1.45 ± 15.33). When onset of disease was taken into account, a βAPP ratio on EOAD subjects of 0.3965 ± 0.1916 was found vs. 0.3445 ± 0.1965 on LOAD subjects (p>0.05). Conclusions: Altered βAPP isoforms is a high risk factor for Alzheimer’s disease, although it has no influence on the time of onset of the disease.     

Familial clustering of autoimmune diseases in patients with type 1 diabetes mellitus

We investigated the familial aggregation of autoimmune diseases (AIDs) among first-degree relatives (FDR) of patients with type 1 diabetes mellitus (T1D). Relatives of 98 T1D patients defined according to the guidelines diagnosis of the American Diabetes Association and 113 matched controls without any AID, were interviewed using a questionnaire that sought information about demographic and medical characteristics including a list of 18 AIDs. Genetic analysis was performed using the program ASSOC and by calculating recurrent risk ratios. In cases, 25.5% of the families had at least one member having an AID, while in controls there were 9% (odds ratio [OR]: 3.96, 95% confidence interval [CI]=1.74-9.0, p=0.0006). An AID was registered in 8.3% of 312 FDR of patients as compared with 2.4% of 362 FDR in controls (OR: 3.56, 95% CI=1.64-7.73, p=0.0008). The most frequent AIDs registered in FDR of cases were autoimmune thyroid disease (AITD) and T1D, which disclosed coefficients of aggregation. These results indicate that AIDs cluster within families of T1D patients adding further evidence to consider that clinically different autoimmune phenotypes may share common susceptibility gene variants, which may act pleiotropically as risk factors for autoimmunity.     

Functional and metabolic implications of biotin deficiency for the rat heart

The tricarboxylic acid (TCA) cycle is the main ATP provider for the heart. TCA carbons must be replenished by anaplerosis for normal cardiac function. Biotin is cofactor of the anaplerotic enzymes pyruvate and propionyl-CoA carboxylases. Here, we found that in biotin deficient rats, both carboxylases decreased 90% in adipose tissue, jejunum and spleen, but in heart they conserved about 60% residual activity. We then investigated if under biotin deficiency (BtDEF), the heart is able to maintain its function in vivo and in isolated conditions, and during ischemia and reperfusion, where metabolism drastically shifts from oxidative to mainly glycolytic. Neither glucose nor octanoate oxidation were severely affected in BtDEF hearts, as assessed by mechanical performance, oxygen uptake or high-energy metabolite content; however, myocardial hexokinase activity and lactate concentration were reduced in deficient hearts. When challenged by ischemia and reperfusion injury, BtDEF hearts did not suffer more damage than the controls, although they lowered significantly their performance, when changed to ischemic conditions, which may have clinical implications. Post-ischemic increase in ADP/ATP ratio was similar in both groups, but during reperfusion there was higher rhythm perturbation in BtDEF hearts. By being relatively insensitive to biotin deficiency, cardiac tissue seems to be able to replenish TCA cycle intermediates and to maintain ATP synthesis.     

Direct tandem duplication in chromosome 19q characterized by array CGH

Partial trisomy of the long arm of chromosome 19 is a rare aneusomy. Only six cases of pure duplications have been previously reported, two of which were prenatally detected. Here we describe the clinical manifestations in a 15-month-old girl with a de novo dup(19)(q12q13.2) and the application of array-based comparative genomic hybridization with a resolution of approximately 1 Mb to characterize the duplicated segment. Seven clones were found duplicated, and the size of the fragment was determined to be 10.8 Mb.

The scarce number of patients reported and the difficulty of accurately defining the duplicated segment when conventional cytogenetic methods are applied hamper the delineation of a clinical phenotype for duplication of chromosome 19q.

To our knowledge this is the fifth live born reported with a pure dup(19), and the first report in which the duplicated segment has been accurately characterized by means of array CGH.     

Differential effects of low glucose concentrations on seizures and epileptiform activity in vivo and in vitro

In vivo, severe hypoglycemia is frequently associated with seizures. The hippocampus is a structure prone to develop seizures and seizure-induced damage. Patients with repeated hypoglycemic episodes have frequent memory problems, suggesting impaired hippocampal function. Here we studied the effects of moderate hypoglycemia on primarily generalized flurothyl-induced seizures in vivo and, using EEG recordings, we determined involvement of the hippocampus in hypoglycemic seizures. Moderate systemic hypoglycemia had proconvulsant effects on flurothyl-induced clonic (forebrain) seizures. During hypoglycemic seizures, seizure discharges were recorded in the hippocampus. Thus, we continued the studies in combined entorhinal cortex-hippocampus slices in vitro. However, in vitro, decreases in extracellular glucose from baseline 10 mM to 2 or 1 mM did not induce any epileptiform discharges. In fact, low glucose (2 and 1 mM) attenuated preexisting low-Mg2+-induced epileptiform activity in the entorhinal cortex and hippocampal CA1 region. Osmolarity compensation in low-glucose solution using mannitol impaired slice recovery. Additionally, using paired-pulse stimuli we determined that there was no impairment of GABAA inhibition in the dentate gyrus during glucopenia. The data strongly indicate that, although forebrain susceptibility to seizures is increased during moderate in vivo hypoglycemia and the hippocampus is involved during hypoglycemic seizures, glucose depletion in vitro contributes to an arrest of epileptiform activity in the system of the entorhinal cortex-hippocampus network and there is no impairment of net GABAA inhibition during glucopenia.     

Task-dependent changes in brain activation following therapy for nonfluent aphasia: discussion of two individual cases.

The complex process of cortical reorganization of language-related brain regions during recovery from aphasia and the effects of therapeutic interventions on brain systems are poorly understood. We studied two patients with chronic aphasia and compared their functional neuroanatomical responses to a younger control group on two tasks, an oral-reading task involving overt speech and a "passive" audiovisual story-comprehension task. Following identical therapy, we re-examined behavioral (language) and functional neuroanatomical changes using the same functional magnetic resonance imaging (fMRI) tasks. We hypothesized that better recovery would be associated with brain activation patterns more closely resembling healthy controls, whereas positive responses to language treatment would be associated with increased activity in undamaged left perisylvian areas and/or right-hemisphere areas homologous to the damaged regions. For the participant with a frontal lesion who was most responsive to therapy, brain activation increased in the right hemisphere during oral-reading, but decreased bilaterally in most regions on story-comprehension. The other participant with a temporal-parietal lesion showed decreased activation, particularly in the right hemisphere, during oral-reading but increased activation bilaterally on story-comprehension. Results highlight individual variability following language therapy, with brain activation changes depending on lesion site and size, language skill, type of intervention, and the nature of the fMRI task.