ILAE-defined epilepsy syndromes in children: correlation with quantitative MRI

PURPOSE: The role of quantitative magnetic resonance imaging (MRI) in evaluation of childhood epilepsy remains poorly defined, with minimal published data. Previous work from our center questioned the specificity of hippocampal asymmetry (HA) in an outpatient group whose epilepsy was defined by using clinical and interictal data only. By using childhood volunteer controls and defining epilepsy syndromes using video-EEG monitoring, we readdressed the utility of HA in differentiating mesial temporal lobe epilepsy (MTLE) from other partial and generalized epileptic syndromes in children. METHODS: Seventy children were enrolled; entry criteria were age younger than 18 years with predominant seizure type recorded on video-EEG telemetry with volumetric MRI in all cases. Thirty healthy child volunteers had volumetric MRI. Epilepsy syndrome classification was according to ILAE. RESULTS: Control data revealed symmetric hippocampi, mean smaller/larger ratio of 0.96 (0.95-0.97, 95% CI) with no gender or right/left predominance. Overall 23% of patients had significant HA. Mean hippocampal ratio for MTLE was 0.78 (95% CI, 0.70-0.86), significantly lower than controls and from all other epilepsy syndromes. HA was highly specific (85%) to the syndrome of MTLE. Other potential epileptogenic lesions were found in 27 (39%) patients, lowest yield in frontal and mesial temporal syndromes. Dual pathology was present in 10% of patients. There was no significant association between HA and risk factors. CONCLUSIONS: In this study, we found that HA in children with a well-defined epilepsy syndrome is highly sensitive and specific for MTLE. Whether this will correlate with surgical outcome, as in adults, is the subject of ongoing study.     

The effect of post-injury spinal position on canal occlusion in a cervical spine burst fracture model

STUDY DESIGN: The canal space of burst-fractured, human cervical spine specimens was monitored to determine the extent to which spinal position affected post-injury occlusion. OBJECTIVE: To test the null hypothesis that there is no difference in spinal canal occlusion as a function of spinal positioning for a burst-fractured cervical spine model. SUMMARY OF BACKGROUND DATA: Although previous studies have documented the effect of spinal positioning on canal geometry in intact cadaver spines, to the authors' knowledge, none has examined this relationship specifically in a burst fracture model. METHODS: Eight human cervical spine specimens (levels C1 to T3) were fractured by axial impact, and the resulting burst injuries were documented using post-injury radiographs and computed tomography scans. Canal occlusion was measured using a custom transducer in which water was circulated through a section of flexible tygon tubing that was passed through the spinal canal. Any impingement on the tubing produced a rise in fluid pressure that was monitored with a pressure transducer. Each spine was positioned in flexion, extension, lateral (and off-axis) bending, axial rotation, traction, and compression, while canal occlusion and angular position were monitored. Occlusion values for each position were compared with measurements taken with the spine in neutral position. RESULTS: Compared with neutral position, compression, extension, and extension combined with lateral bending significantly increased canal occlusion, whereas flexion decreased the extent of occlusion. In extension, the observed mechanism of occlusion was ligamentum flavum bulge caused by ligament laxity resulting from reduced vertebral body height. CONCLUSIONS: Increased compression of the spinal cord after injury may lead to more extensive neurologic loss. This study demonstrated that placing a burst-fractured cervical spine into either extension or compression significantly increased canal occlusion as compared with occlusion in a neutral position.     

The sizes of peptides generated from protein by mammalian 26 and 20 S proteasomes. Implications for understanding the degradative mechanism and antigen presentation

Knowledge about the sizes of peptides generated by proteasomes during protein degradation is essential to fully understand their degradative mechanisms and the subsequent steps in protein turnover and generation of major histocompatibility complex class I antigenic peptides. We demonstrate here that 26 S and activated 20 S proteasomes from rabbit muscle degrade denatured, nonubiquitinated proteins in a highly processive fashion but generate different patterns of peptides (despite their containing identical proteolytic sites). With both enzymes, products range in length from 3 to 22 residues, and their abundance decreases with increasing length according to a log-normal distribution. Less than 15% of the products are the length of class I presented peptides (8 or 9 residues), and two-thirds are too short to function in antigen presentation. Surprisingly, these mammalian proteasomes, which contain two "chymotryptic," two "tryptic," and two "post-acidic" active sites, generate peptides with a similar size distribution as do archaeal 20 S proteasomes, which have 14 identical sites. Furthermore, inactivation of the "tryptic" sites altered the peptides produced without significantly affecting their size distribution. Therefore, this distribution is not determined by the number, specificity, or arrangement of the active sites (as proposed by the "molecular ruler" model); instead, we propose that proteolysis continues until products are small enough to diffuse out of the proteasomes.     

Liposuction: procedure for focal volume reduction and body contour remodeling

Liposuction is the most commonly used procedure for focal reduction of body fat deposits and remodeling the body contour. The procedure consists in aspirating fat from lamellar deposits using a vacuum source connected to a cannula that is passed bluntly through fatty tissue. Adjuncts to the procedure include infiltration of solutions to aid in fat removal or to limit blood loss and the application of ultrasonic energy to lyse fat cells before suction aspiration. Surgical history, theory, procedures, indications, potential complications, and guidelines are discussed herein.     

Amifostine protects normal tissues from paclitaxel toxicity while cytotoxicity against tumour cells is maintained

The objectives of this study were to evaluate the protective effects of amifostine against paclitaxel-induced toxicity to normal and malignant human tissues. Haematopoietic progenitor colony assays were used to establish the number of CFU-GEMM and BFU-E colonies after incubation with WR-1065 alone, Amifostine alone, paclitaxel (2.5 or 5 microM) +/- WR-1065 or amifostine. MTT and alkaline elution assays evaluated the in vitro growth inhibitory and DNA damaging effects, respectively, of paclitaxel with or without amifostine against normal human fibroblasts and human non-small cell lung cancer (NSCLC) cells. This combination was also evaluated in vivo using severe combined immune deficient (scid) mouse models of early (non-palpable tumours) and advanced (palpable tumours) human ovarian cancer. Human 2780 ovarian cancer cells were inoculated subcutaneously while paclitaxel and amifostine were administered intraperitoneally. A brief exposure (15 min) to amifostine not only protected human haematopoietic progenitor colonies from paclitaxel toxicity, but stimulated the growth of CFU-GEMM and BFU-E beyond control values. Amifostine protected normal human lung fibroblasts from paclitaxel-induced cytotoxicity and DNA single-strand breaks. However, paclitaxel cytotoxicity and DNA single-strand breaks were actually enhanced by pretreatment with amifostine in the NSCLC model. Importantly, amifostine did not interfere with paclitaxel antitumour activity even with prolonged exposure (24.5 h) of the lung cancer cells to high concentrations (1.2 mM) in vitro or following five repetitive high doses (200 mg/kg) given to scid mice with human ovarian cancer xenografts. Indeed, under certain circumstances, amifostine resulted in sensitisation of tumour cells to paclitaxel. Our results confirm previous reports of the ability of amifostine to protect normal tissues from the toxic effects of chemotherapy drugs and now extend these observations to paclitaxel.     

Risk factors for a medically inappropriate admission to a Department of Internal Medicine

OBJECTIVE: To identify patient- and admission-related risk factors for a medically inappropriate admission to a department of internal medicine. METHODS: Cross-sectional study of a systematic sample of 500 admissions to the department of internal medicine of an urban teaching hospital. The appropriateness of each admission and reasons for inappropriate admissions were assessed using the Appropriateness Evaluation Protocol. Risk factors included the time (day of week and holidays) and manner (through emergency department or direct admission) of admission, patient age and sex, health status of patient and spouse, living arrangements, formal home care services, and informal support from family or friends. RESULTS: Overall, 76 (15.2%) hospital admissions were rated as medically inappropriate by the Appropriateness Evaluation Protocol. In multivariate analysis, the likelihood of an inappropriate admission was increased by better physical functioning of the patient (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1-2.1 [for 1 SD in Physical Functioning scores]), lower mental health status of the patient's spouse (OR, 2.6; 95% CI, 1.3-5.6), receipt of informal help from family or friends (OR, 3.3; 95% CI, 1.5-7.2), and hospitalization by one's physician (OR, 3.6; 95% CI, 1.7-7.5). Receiving formal adult home care was not associated with inappropriateness of hospitalization. CONCLUSIONS: Inappropriate admissions to internal medicine wards are determined by a mix of factors, including the patient's health and social environment. In addition, the private practitioners' discretionary ability to hospitalize their patients directly may also favor medically inappropriate admissions.     

Immunohistochemical identification of varicella-zoster virus gene 63-encoded protein (IE63) and late (gE) protein on smears and cutaneous biopsies: implications for diagnostic use

Early and specific recognition of varicella zoster virus (VZV) infection is of vital concern in immunocompromised patients. The aim of this study was to compare the diagnostic accuracy of histochemical and immunohistochemical identification of the VZV ORF63 encoded protein (IE63) and of the VZV late protein gE on smears and formalin-fixed paraffin-embedded skin sections taken from lesions clinically diagnosed as varicella (n = 15) and herpes zoster (n = 51). Microscopic examinations of Tzanck smears and skin sections yielded a diagnostic accuracy of Herpesviridae infections in 66.7% (10/15) and 92.3% (12/13) of varicella, and 74.4% (29/39) and 87.8% (43/49) of herpes zoster, respectively. Immunohistochemistry applied to varicella provided a type-specific virus diagnostic accuracy of 86.7% (13/15; IE63) and 100% (15/15; gE) on smears, and of 92.3% for both VZV proteins on skin sections. In herpes zoster, the diagnostic accuracy of immunohistochemistry reached 92.3% (36/39; IE63) and 94.9% (37/39; gE) on smears, and 91.7% (44/48; IE63) and 91.8% (45/49; gE) on skin sections. These findings indicate that the immunohistochemical detection of IE63 and gE on both smears and skin sections yields a higher specificity and sensitivity than standard microscopic assessments.     

Identification of a gene that causes primary open angle glaucoma

Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma (GLC1A) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.     

Structure and properties of the cell nucleus chromatin in the brain of rats exposed to gamma-radiation]

Exposure of rats to radiation in a dose of 1 Gy changes sensitivity of chromatin in the cerebral cortex cells to the action of DNAase 1, which promotes an increase of the DNA hydrolysis level and content of dissolved chromatin fractions. A day after irradiation the chromatin structure restores only partially and then (7-30 days after irradiation) it passes into a new, less compact state. The irradiation changes the chromatin ability to aggregation in the presence of Mg2+ and spermidine.