Modulation of input-output curves by low and high frequency repetitive transcranial magnetic stimulation of the motor cortex.

OBJECTIVES: Exploring the modulatory effects of different frequencies of repetitive transcranial magnetic stimulation (rTMS) on the excitability of the motor cortex as measured by the input-output curve technique (I-O curve). METHODS: Sixteen healthy subjects participated in this experiment. On two different sessions, conducted 1 week apart, rTMS was applied either at a frequency of 20 or 1 Hz at 90% of individual motor threshold (MT) for a total of 1600 pulses each. Before and after rTMS, the cortical excitability was assessed by measuring MT and the size of motor evoked potentials (MEPs) collected at different intensities of stimulation. RESULTS: The analysis on the whole population showed a significant decrease of cortical excitability after 1 Hz rTMS and an increase after 20 Hz rTMS. A subsequent cluster analysis pointed out the presence of two distinct groups of subjects with opposite responses at the same frequency of stimulation. Significant variations on MT were found for both groups only for the facilitatory effect irrespective of the frequency of stimulation. CONCLUSIONS: The results provide further insight into interindividual differences in the effects of rTMS and suggest the existence of subpopulations with specific patterns of response to rTMS.     

Nonlinear sensory cortex response to simultaneous tactile stimuli in writer's cramp.

Writer's cramp is a task-specific dystonia that leads to involuntary hand postures during writing. Abnormalities of sensory processing may play a pathophysiological role in this disorder. Electrophysiology studies in a monkey model of focal dystonia have revealed de-differentiation of sensory maps and the existence of single cells in hand regions of area 3b with enlarged receptive fields that extend to the surfaces of more than one digit. These changes may lead to abnormal processing of simultaneous sensory inputs. To study abnormal processing of simultaneous sensory information in adult humans with writer's cramp, we used functional magnetic resonance imaging to compare the response in primary sensory cortex with simultaneous tactile stimulation of the index and middle finger, with the response to stimulation of each finger alone. We tested five patients with writer's cramp and seven unaffected (normal) subjects. In the normal subjects, a linear combination of the activation patterns for individual finger stimulation predicts the pattern of activity for combined stimulation with 12% error. In writer's cramp patients, the linear combination predicted the combined stimulation pattern with 30% error. Results indicate a nonlinear interaction between the sensory cortical response to individual finger stimulation in writer's cramp. This altered interaction may contribute to the motor abnormalities.     

Conduction of nervous impulses in spinal roots and peripheral nerves of dystrophic mice

Conduction was studied in the sacral ventral roots and ventral tail nerves of dystrophic mice (dy/dy) and phenotypically normal littermates. In myelinated ventral root fibers of normal mice, conduction velocity was uniform with internodal conduction time45 ± 5 μsec (26 °C). In ventral root fibers of dystrophic mice, conduction velocity was decreased and strikingly non-uniform; both saltatory and continuous conduction were observed in different portions of the same nerve fiber. Continuous conduction with velocity <2 m/sec (26 °C) was characteristically observed in mid-root where the axons are bare; conduction was saltatory close to the exit from the spinal canal and near the spinal cord where the axons are myelinated.Maximum conduction velocity in ventral tail nerves was21 ± 3 m/sec for dystrophic mice and31 ± 4 m/sec for littermate controls (37 °C). Internodal lengths were somewhat decreased in the dystrophic peripheral nerves but there was no significant difference in maximum fiber diameters, myelin thickness or nodal morphology between dystrophic and normal nerves.     

Anti-CCP in systemic lupus erythematosus patients: a cross sectional study in Brazilian patients

Recently, it has been found that some lupus patients may have anti-cyclic citrullinated peptide antibodies (anti-CCP), although the clinical significance of such finding is not well established. Systemic lupus erythematosus (SLE) patients may have joint complaints that are very similar to those observed in rheumatoid arthritis (RA). In early stages of disease, this form of arthritis can be difficult to differentiate from RA, so it is not rare that some SLE patients are initially misdiagnosed to have this disease. This study aims to investigate the prevalence of anti-CCP in SLE patients from Southern Brazil and its association with clinical and serological profiles. One hundred nine SLE patients were studied for anti-CCP and compared with data of 156 RA patients and 100 healthy volunteers. Comparison of clinical and autoantibody profile of anti-CCP-positive and anti-CCP-negative SLE patients was done. All SLE patients positive of anti-CCP were submitted to hand and feet X-rays. Anti-CCP was positive in 15 of 109 SLE patients, and one of them had confirmed the diagnosis of rhupus. This prevalence was significantly higher than in healthy controls (p?=?0.0004) and lower than in RA patients (p?<?0.0001). No relationship could be found with clinical profile, including joint complaints. SLE patients with anti-CCP had higher prevalence of anti-Ro (p?=?0.02) and anti-La (p?=?0.004) autoantibodies, in comparison with those negative to anti-CCP. We found that 13.7 % of Brazilian patients with SLE have positive anti-CCP. Patients with anti-CCP showed higher prevalence of anti-Ro and anti-La autoantibodies than those negative for anti-CCP. Only a careful and prolonged follow-up will reveal the real clinical value of these markers in each patient individually.     

Audit of nutrition support for hematopoietic stem cell transplantation at a single institution

OBJECTIVE: To analyze experience with total parenteral nutrition (TPN) for hematopoietic stem cell transplantation (HSCT) at our institution compared with reports in the literature. PATIENTS AND METHODS: We reviewed medical records of 100 patients (53 men and 47 women) who underwent HSCT from 1992 to 2001. Data were abstracted on demographics, primary diagnosis, type of transplantation, myeloablative regimen, length of hospital stay, time to engraftment, 1- and 5-year survival, initiation and duration of TPN, and TPN-related complications. RESULTS: Seventy-one transplantations were autologous, 27 allogeneic, and 2 syngeneic. The median age of the patients was 51 years (range, 19-71 years). We initiated TPN when patients' oral caloric intake was less than 50% of their estimated needs (4 to 7 days after the start of myeloablative therapy; median, 1.2 days after HSCT; range, 8 days before HSCT to 13 days after HSCT). We discontinued TPN when oral intake was more than 50% of estimated needs (median duration, 16 days for autologous and 24 days for allogeneic transplantations, with the shortest duration in breast cancer patients and the longest duration in those treated with cyclophosphamide). Mean weight loss was less than 2%. No differences in patient characteristics, myeloablative regimen, or diagnosis were observed between patients who required and those who did not require TPN. Infection, hospital stay, time to engraftment, and mortality were comparable to published reports. CONCLUSION: In patients undergoing HSCT, TPN should not be initiated until oral caloric intake is less than 50% of estimated needs. During the period of inadequate oral intake, TPN maintains stable body weight with longer duration of support needed for patients undergoing allogeneic than for those undergoing autologous transplantations.     

Comparing bacterial genomes through conservation profiles

We constructed two-dimensional representations of profiles of gene conservation across different genomes using the genome of Escherichia coli as a model. These profiles permit both the visualization at the genome level of different traits in the organism studied and, at the same time, reveal features related to the genomes analyzed (such as defective genomes or genomes that lack a particular system). Conserved genes are not uniformly distributed along the E. coli genome but tend to cluster together. The study of gene distribution patterns across genomes is important for the understanding of how sets of genes seem to be dependent on each other, probably having some functional link. This provides additional evidence that can be used for the elucidation of the function of unannotated genes. Clustering these patterns produces families of genes which can be arranged in a hierarchy of closeness. In this way, functions can be defined at different levels of generality depending on the level of the hierarchy that is studied. The combined study of conservation and phenotypic traits opens up the possibility of defining phenotype/genotype associations, and ultimately inferring the gene or genes responsible for a particular trait.     

Review of the evidence on the management of blunt renal trauma in pediatric patients

Due to the size and location within the pediatric patient, the kidneys are susceptible to injury from blunt trauma. While it is clear that the goal of management of blunt renal trauma in children is renal preservation, the methods of achieving this goal have not been well established in the current literature. Therefore, we have set out to summarize and clarify the current published information on the management strategies for blunt renal trauma in children. While there is extensive literature available, it consists mostly of retrospective series documenting widely varied management styles. The purpose of this review is to display the current information available and delineate the role for future studies that may allow us to develop consistent management strategies of pediatric patients, who have sustained blunt renal trauma, in a safe and cost-effective manner.     

An in vivo role for Trypanosoma cruzi calreticulin in antiangiogenesis

Angiogenesis leads to neovascularization from existing blood vessels. It is associated with tumor growth and metastasis and is regulated by pro- and antiangiogenic molecules, some of them currently under clinical trials for cancer treatment. During the last few years we have cloned, sequenced and expressed a Trypanosoma cruzi calreticulin gene (TcCRT). Its product, TcCRT, a 45 kDa protein, is more than 50% identical to human CRT (HuCRT). TcCRT, present on the surface of trypomastigotes, binds both C1q and mannan binding lectin and inhibits the classical activation pathway of human complement. Since TcCRT is highly homologous to a functional antiangiogenic fragment from HuCRT (aa 120–180), recombinant (r) and native (n) TcCRT were tested in their antiangiogenic effects, in the chick embryonic chorioallantoid membrane (CAM) assay. Both proteins mediated highly significant antiangiogenic effects in the in vivo CAM assay. This effect was further substantiated in experiments showing that the plasmid construct pSecTag/TcCRT also displayed significant antiangiogenic properties, as compared to the empty vector. Most likely, the fact that antiangiogenic substances act preferentially on growing neoplasic tissues, but not on already established tumors, is due to their effects on emerging blood vessels. The results shown here indicate that TcCRT, like its human counterpart, has antiangiogenic properties. These properties may explain, at least partly, the reported antineoplasic effect of experimental T. cruzi infection.     

Characterization of Polydimethylsiloxane (PDMS) Properties for Biomedical Micro/Nanosystems

Polydimethylsiloxane (PDMS Sylgard 184, Dow Corning Corporation) pre-polymer was combined with increasing amounts of cross-linker (5.7, 10.0, 14.3, 21.4, and 42.9 wt.%) and designated PDMS1, PDMS2, PDMS3, PDMS4, and PDMS5, respectively. These materials were processed by spin coating and subjected to common micro-fabrication, micro-machining, and biomedical processes: chemical immersion, oxygen plasma treatment, sterilization, and exposure to tissue culture media. The PDMS formulations were analyzed by gravimetry, goniometry, tensile testing, nano-indentation, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Spin coating of PDMS was formulation dependent with film thickness ranging from 308 microm on PDMS1 to 171 microm on PDMS5 at 200 revolutions per minute (rpm). Ultimate tensile stress (UTS) increased from 3.9 MPa (PDMS1) to 10.8 MPa (PDMS3), and then decreased down to 4.0 MPa (PDMS5). Autoclave sterilization (AS) increased the storage modulus (sigma) and UTS in all formulations, with the highest increase in UTS exhibited by PDMS5 (218%). PDMS surface hydrophilicity and micro-textures were generally unaffected when exposed to the different chemicals, except for micro-texture changes after immersion in potassium hydroxide and buffered hydrofluoric, nitric, sulfuric, and hydrofluoric acids; and minimal changes in contact angle after immersion in hexane, hydrochloric acid, photoresist developer, and toluene. Oxygen plasma treatment decreased the contact angle of PDMS2 from 109 degrees to 60 degrees. Exposure to tissue culture media resulted in increased PDMS surface element concentrations of nitrogen and oxygen.     

Prevalences, genotypes, and risk factors for HIV transmission in South America

HIV cross-sectional studies were conducted among high-risk populations in 9 countries of South America. Enzyme-linked immunosorbent assay screening and Western blot confirmatory testing were performed, and env heteroduplex mobility assay genotyping and DNA sequencing were performed on a subset of HIV-positive subjects. HIV prevalences were highest among men who have sex with men (MSM; 2.0%-27.8%) and were found to be associated with multiple partners, noninjection drug use (non-IDU), and sexually transmitted infections (STIs). By comparison, much lower prevalences were noted among female commercial sex workers (FCSWs; 0%-6.3%) and were associated mainly with a prior IDU and STI history. Env subtype B predominated among MSM throughout the region (more than 90% of strains), whereas env subtype F predominated among FCSWs in Argentina and male commercial sex workers in Uruguay (more than 50% of strains). A renewed effort in controlling STIs, especially among MSM groups, could significantly lessen the impact of the HIV epidemic in South America.