Mesial temporal lobe epilepsy: Clinical and neuropathologic findings of familial and sporadic forms

Purpose: To evaluate the clinical and hippocampal histological features of patients with mesial temporal lobe epilepsy (MTLE) in both familial (FMTLE) and sporadic (SMTLE) forms. Methods: Patients with FMTLE (n = 20) and SMTLE (n = 39) who underwent surgical treatment for refractory seizures were studied at the University of Sao Paulo School of Medicine at Ribeirao Preto. FMTLE was defined when at least two individuals in a family had clinical diagnosis of MTLE. Hippocampi from all patients were processed for Nissl/HE and Timm`s stainings. Both groups were compared for clinical variables, hippocampal cell densities, and intensity of supragranular mossy fiber staining. Results: There were no significant differences between FMTLE and SMTLE groups in the following: age at the surgery, age of first usual epileptic seizure, history of initial precipitating injury (IPI), age of IPI, latent period, ictal and interictal video-EEG patterns, presence of hippocampal atrophy and signal changes at MRI, and postoperative outcome. In addition, no differences were found in cell densities in hippocampal cornu ammonis subfields (CA1, CA2, CA3, CA4), fascia dentata, polymorphic region, subiculum, prosubiculum, and presubiculum. However, patients with SMTLE had greater intensity of mossy fiber Timm`s staining in the fascia dentata-inner molecular layer (p < 0.05). Discussion: Patients with intractable FMTLE present a clinical profile and most histological findings comparable to patients with SMTLE. Interestingly, mossy fiber sprouting was less pronounced in patients with FMTLE, suggesting that, when compared to SMTLE, patients with FMTLE respond differently to plastic changes plausibly induced by cell loss, neuronal deafferentation, or epileptic seizures.

Influence of aging, tidal volume, and respiratory rate on Doppler echocardiographic indices of diastolic function in normal male subjects: A quantitative evaluation

Background: Although the influence of respiration on ventricular filling, as evaluated by Doppler technique, and the evaluation of diastolic velocities of mitral valve annulus (MVA), as measured by Doppler tissue imaging (DTI), can provide valuable information for the study of left ventricular (LV) diastolic function, the concomitant effects of aging, tidal volume (TV), and respiratory rate (RR) on these velocities have not been quantitatively investigated. Methods: We evaluated 12 normal male volunteers (Group I) aged 20-26 years (mean: 22.8) and 8 normal subjects aged 41 to 54 years old (mean: 45.9) (Group II). Using DTI we measured peak early (E-a) and late (A(a)) velocities of longitudinal axis expansion at lateral and medial MVA. Doppler mitral and tricuspid flow velocities were measured: peak early (E) and late (A) inflow velocity, early (E-i) and late (A(i)) flow integral, and deceleration time of peak early mitral flow velocity (DT). Respiratory cycles were simultaneously recorded at RR of 9, 12, 15, and 18 cycles/min and TV of 600 and 900 mL during respiration (RESP). Results and conclusions: (1) E, A, and A(i) in MV had negligible change during respiration, but E-i was significantly reduced during inspiration; (2) DT reduced slightly with inspiration, but the change was significant only with TV of 900 mL; (3) an important increase of E in right ventricular flow was observed during inspiration; (4) variations of RR and TV did not significantly influence right and left ventricular inflow in normal subjects, in the conditions of this investigation; (5) a significant increase of E-a at medial MVA was documented during inspiration only in young subjects; (6) a significant decrease of A(a) at medial MVA was observed during inspiration in both groups of volunteers; (7) RR and TV did not influence MVA velocities in young and adult subjects; (8) a consistent reduction in E-a and a significant increase in A(a) were observed with increasing age; (9) these changes were more conspicuous and consistent than those documented in ventricular filling when young and middle-age men are compared, suggesting that the DTI is more sensitive to detect changes in diastolic function; and (10) in addition, these data suggest that, for evaluation of diastolic function, in clinical context, it is not necessary to control rigorously RR or TV.

The Impact of Preexisting Myocardial Remodeling on Ventricular Function Early after Tetralogy of Fallot Repair

Background: Twenty-three patients (median age 23 months) who underwent Fallot`s tetralogy repair were investigated prospectively to detect a possible association between histopathologic myocardial remodeling and echocardiographic findings of systolic or diastolic ventricular dysfunction. Methods: Intraoperatively resected infundibular bands and subendocardial biopsy samples from the right ventricle (RV) and left ventricle were obtained for histopathologic evaluation. Tissue Doppler echocardiographic interrogation of the ventricles was performed before surgery and in the postoperative period. Results: Histopathologic data revealed hypertrophy of the RV cardiomyocytes and increased interstitial collagen in both ventricles. Mean values of RV isovolumic acceleration decreased significantly at the third evaluation compared with the preoperative values (P = .006). RV myocardial fibrosis greater than 8.3% was associated with a probability of altered E` of at least 0.7 (odds ratio = 2.31). Conclusion: Preoperative histologic myocardial remodeling influenced the postoperative RV function in this group of patients with late repair. Further studies are necessary to evaluate the myocardium in younger patients and to define its influence in the long-term follow-up. (J Am Soc Echocardiogr 2010;23:912-8.)

Low mRNA Expression of the Apoptosis-Related Genes CASP3, CASP8, and FAS Is Associated With Low Induction Treatment Response in Childhood Acute Lymphoblastic Leukemia (ALL)

Background. Defects in apoptosis signaling have been considered to be responsible for treatment failure in many types of cancer, although with controversial results. The objective of the present study was to assess the expression profile of key apoptosis-related genes in terms of clinical and biological variables and of the survival of children with acute lymphoblastic leukemia (ALL). Procedure. The levels of mRNA expression of the apoptosis-related genes CASP3, CASP8, CASP9, FAS, and BCL2 were analyzed by quantitative real-time PCR in consecutive samples from 139 consecutive children with ALL at diagnosis treated by the Brazilian protocol (GBTLI-ALL 99). Gene expression levels and clinical and biological features were compared by the Mann-Whitney test. Event-free survival (EFS) was calculated by Kaplan-Meier plots and log-rank test. Results. A significant correlation was detected between CASP3, CASP8, CASP9, and FAS expression levels (P<0.01) in ALL samples. Higher levels of BCL2 were significantly associated with white blood cell (WBC) count <50,000/mm(3) at diagnosis (P=0.01) and low risk group classification (P=0.008). Lower expression levels of CASP3, CASP8 and FAS gene were associated with a poor response at day 7 according the GBTLI-ALL 99 protocol (P=0.03, P=0.02 and P=0.008, respectively). There was a relationship between FAS gene expression lower than the 75th percentile and lower 5-year EFS (P=0.02). Conclusion. These findings suggest an association between lower expression levels of the pro-apoptotic genes and a poor response to induction therapy at day 7 and prognosis in childhood ALL. Pediatr Blood Cancer 2010;55:100-107. (C) 2010 Wiley-Liss, Inc.

Audiological findings in pacients treated with radiotherapy for head and neck tumors

Radiotherapy has been widely used given its increase in the successful outcomes and cure of some cancers. Aim: To evaluate the functionality of the auditory system in patients who underwent radiotherapy treatment for head and neck tumors. Materials and Methods: From May 2007 to May 2008, otorhinolaryngological and audiological evaluation (Pure Tone Audiometry (air and bone conduction), Speech Audiometry, Tympanometry, Acoustic Reflex testing and Distortion Product Otoacoustic Emissions) were performed in 19 patients diagnosed with head and neck neoplasia and treated with radiotherapy. Prospective case series study. Results: 10.5% left ears and 26.3% right ears had bilateral hearing loss soon after radiotherapy according to ASHA criteria. Conclusions: Radiotherapy treatment for head and neck cancer has ototoxic effects. Early programs of auditory rehabilitation should be offered to these patients.

Comparison of MB fraction of creatine kinase mass and troponin I serum levels with necropsy findings in acute myocardial infarction

Serum levels of troponin and heart-related fraction of creatine kinase (CK-MB) mass are used as diagnostic and prognostic criteria in myocardial infarction, but the relation between those levels and-the necropsy-determined size of necrosis has not been tested in human beings. In this retrospective study, 1-cm-thick transverse sections of the ventricles were cut from the base to the apex in the necropsy hearts of 27 patients aged 47 to 86 years (mean 66, median 69; 19 men). Total and necrotic areas were measured using a computer-linked image analysis system. The weights of the necrotic areas were also calculated. The correlations of the areas and weights of necrotic myocardium with the highest serum values of CK-MB mass and troponin 1, which had been quantified during life by chemiluminescence immunoassays, were verified by Pearson`s test; results were considered significant at p <= 50.05. Significant correlations were detected between CK-MB mass peak and infarct size (r = 0.63, p < 0.01) and weight (r = 0.69, p < 0.01) and between CK-MB mass and highest troponin level (r = 0.73, p < 0.01); however, the correlations between highest troponin level and myocardial infarct size (r = 0.31, p = 0.11) and weight (r = 0.35, p = 0.07) were small and nonsignificant. In conclusion, despite the well-established role of serum levels of troponin as a diagnostic tool for myocardial infarction, their highest values showed poor correlations with the extent of infarct. In contrast, the highest serum level of CK-MB mass was well correlated with myocardial infarct size. (c) 2008 Elsevier Inc. All rights reserved.

Low-intensity Treadmill Exercise-related Changes in the Rat Stellate Ganglion Neurons

Stellate ganglion (SG) represents the main sympathetic input to the heart. This study aimed at investigating physical exercise-related changes in the quantitative aspects of SG neurons in treadmill-exercised Wistar rats. By applying state-of-the-art design-based stereology, the SG volume, total number of SG neurons, mean perikaryal volume of SG neurons, and the total volume of neurons in the whole SG have been examined. Arterial pressure and heart rate were also measured at the end of the exercise period. The present study showed that a low-intensity exercise training program caused a 12% decrease in the heart rate of trained rats. In contrast, there were no effects on systolic pressure, diastolic pressure, or mean arterial pressure. As to quantitative changes related to physical exercise, the main findings were a 21% increase in the fractional volume occupied by neurons in the SG, and an 83% increase in the mean perikaryal volume of SG neurons in treadmill-trained rats, which shows a remarkable neuron hypertrophy. It seems reasonable to infer that neuron hypertrophy may have been the result of a functional overload imposed on the SG neurons by initial posttraining sympathetic activation. From the novel stereological data we provide, further investigations are needed to shed light on the mechanistic aspect of neuron hypertrophy: what role does neuron hypertrophy play? Could neuron hypertrophy be assigned to the functional overload induced by physical exercise? (C) 2008 Wiley-Liss, Inc.

Hypertrophy and neuron loss: structural changes in sheep SCG induced by unilateral sympathectomy

Recently, superior cervical ganglionectomy has been performed to investigate a variety of scientific topics from regulation of intraocular pressure to suppression of lingual tumour growth. Despite these recent advances in our understanding of the functional mechanisms underlying superior cervical ganglion (SCG) growth and development after surgical ablation, there still exists a need for information concerning the quantitative nature of the relationships between the removed SCG and its remaining contralateral ganglion and between the remaining SCG and its modified innervation territory. To this end, using design-based stereological methods, we have investigated the structural changes induced by unilateral ganglionectomy in sheep at three distinct timepoints (2, 7 and 12 weeks) after surgery. The effects of time, and lateral (left-right) differences, were examined by two-way analyses of variance and paired t-tests. Following removal of the left SCG, the main findings were: (i) the remaining right SCG was bigger at shorter survival times, i.e. 74% at 2 weeks, 55% at 7 weeks and no increase by 12 weeks, (ii) by 7 weeks after surgery, the right SCG contained fewer neurons (no decrease at 2 weeks, 6% fewer by 7 weeks and 17% fewer by 12 weeks) and (iii) by 7 weeks, right SCG neurons were also larger and the magnitude of this increase grew substantially with time (no rise at 2 weeks, 77% by 7 weeks and 215% by 12 weeks). Interaction effects between time and ganglionectomy-induced changes were significant for SCG volume and mean perikaryal volume. These findings show that unilateral superior cervical ganglionectomy has profound effects on the contralateral ganglion. For future investigations, it would be interesting to examine the interaction between SCGs and their innervation targets after ganglionectomy. Is the ganglionectomy-induced imbalance between the sizes of innervation territories the milieu in which morphoquantitative changes, particularly changes in perikaryal volume and neuron number, occur? Mechanistically, how would those changes arise? Are there any grounds for believing in a ganglionectomy-triggered SCG cross-innervation and neuroplasticity? (C) 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

A quantitative analysis of the nerve fibres of the acetabular periosteum of dogs

There are many techniques for the treatment of hip dysplasia, and novel research is currently being undertaken in the hope of obtaining more efficient and less traumatic techniques. The denervation of the hip joint capsule is a simple and effective technique that allows recovery of the functional activity of the affected limbs in significantly less time than other techniques. This surgical procedure consists of removing the acetabular periosteum, thus eliminating the nerve fibres with consequent analgesia. The aim of this investigation was to quantify the number of nerve fibres present in different regions of the acetabular periosteum. The knowledge of regional differences is potentially valuable for the refining of the denervation technique of the hip joint capsule. Thirty canine acetabular fragments were used to compare the nerve fibre density of the periosteum. The results showed a significant difference between the mean density of nerve fibres at the cranial and dorsal-lateral portion (approximately 75 fibres/mm(2)) and caudal lateral portion (approximately 60 fibres/mm(2)) of the acetabulum. Those fibres at the pedosteum are almost positioned in a sagittal plane, pointing towards the joint capsule, suggesting the some density in the latter region. These results indicate a new approach to the articular denervation technique, thus obtanining even better results for the treatment of hip dysplasia in dogs.

Quantitative CT analysis of the glabellar and anterior nasal spine regions for the placement of implants for nasal prosthesis retention

Objectives: The aim of this study was to determine the precision of the measurements of 2 craniometric anatomic points-glabella and anterior nasal spine-in order to verify their possibility as potential locations for placing implants aimed at nasal prostheses retention. Methods: Twenty-six dry human skulls were scanned in a high-resolution spiral tomography with 1-mm axial slice thickness and 1-mm interval reconstruction using a bone tissue filter. Images obtained were stored and transferred to an independent workstation containing e-film imaging software. The measurements (in the glabella and anterior nasal fossa) were made independently by 2 observers twice for each measurement. Data were submitted to statistical analysis (parametric t test). Results: The results demonstrated no statistically significant difference between interobserver and intraobserver measurements (P > .05). The standard error was found to be between 0.49 mm and 0.84 mrn for measurements in bone protocol, indicating a high /eve/ of precision. Conclusions: The measurements obtained in anterior nasal spine and glabella were considered precise and reproducible. Mean values of such measurements pointed to the possibility of implant placement in these regions, particularly in the anterior nasal spine.

MMP1 and MMP20 contribute to tooth agenesis in humans

Objective: Variations in genes that are critical for tooth formation may contribute to the tooth agenesis. MMPs are potential candidate genes for dental alterations based on the roles they play during embryogenesis. The aim of this study was to investigate the possible association between MMP1, MMP3, and MMP20 and tooth agenesis. Methods: One hundred sixty-seven nuclear families from two different populations were analysed, 116 from Brazil and 51 from Turkey. Probands had at least one congenitally missing tooth. DNA samples were obtained from blood or saliva samples and genotyping was performed using TagMan chemistry. In addition, Mmp20 was selected for quantitative real-time polymerase chain reaction analysis with SYBR Green I Dye in mouse tooth development. Results: Associations between tooth agenesis and MMP1 (p = 0.007), and MMP20 (p = 0.03) were found in Brazilian families. In the total dataset, MMP20 continued to be associated with tooth agenesis (p = 0.01). Mmp20 was not expressed during the initial stages of tooth development. Conclusion: Our findings provide evidence that MMP1 and MMP20 play a role in human tooth agenesis. (C) 2010 Elsevier Ltd. All rights reserved.