Cortical and hippocampal volume deficits in temporal lobe epilepsy

PURPOSE: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE). METHODS: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA). RESULTS: As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe. CONCLUSIONS: Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.     

Data stability in an application of a software reliability model

The Goel-Okumoto (1979) model of reliability growth is applied to the failure data for a large software development project. This is done by fitting the model parameters to the error counts and test times, which are periodically tabulated. In the early phases of system testing, the problem of inaccurate estimation due to insufficient reliability growth occurs. A simple test is devised to measure the stability of the data with respect to this problem. In practice, such a test on the data can be used to determine when system testing has sufficiently progressed to allow one to expect reasonable estimates from reliability growth models     

Serial measurements of body composition in obese subjects during a very-low-energy diet (VLED) comparing bioelectrical impedance with hydrodensitometry

Bioelectrical impedance analysis (BIA) is a convenient, inexpensive, and noninvasive technique for measuring body composition. BIA has been strongly correlated with total body water (TBW) and also has been validated against hydrodensitometry (HD). The accuracy and clinical utility of BIA and HD during periods of substantial weight loss remain controversial. We measured body composition in moderately and severely obese patients serially using both methods during a very-low-energy diet (VLED). Mean initial weight in these patients was 116 (+/-30) kg (range, 74-196 kg). Mean weight loss was 24 (+/-13) kg with a decrease in fat mass (FM) by HD of kg (p < 0.001) and a decrease in fat-free mass (FFM) of 3.6 kg (p < 0.05). Loss of FFM is best predicted by the rate (kg/wk) of weight loss (r2 = 0.86, p < 0.0001). FFM, as predicted from BIA equations, was highly correlated with FFM as estimated by HD during all testing sessions (r = 0.92-0.98). Although highly correlated, BIA overestimated FFM relative to HD and this difference appeared to be more pronounced for taller patients with greater truncal obesity. Although the discrepancy was no greater during weight-loss treatment, the level of disagreement was considerable. Therefore, the two methods cannot be used interchangeably to monitor relative changes in body composition in patients with obesity during treatment with VLED. The discrepancy between BIA and HD may be caused by body mass distribution considerations and by perturbations in TBW which affect the hydration quotient for FFM (BIA) and/or which affect the density constants for FFM and FM (HD).     

Giant cell arteritis in Lugo, Spain, is associated with low longterm mortality

OBJECTIVE: To assess the longterm survival of patients with giant cell arteritis (GCA) in a well defined area in Northwestern Spain. METHODS: A followup study of consecutive biopsy proven patients with GCA diagnosed in Lugo, Spain January 1, 1982-March 31, 1996 was performed. Patients were followed from time of diagnosis until either their death or October 1, 1996. Time and cause of death were reviewed. Statistical methods included standardized mortality ratio (SMR), and Kaplan-Meier product-limit survival analysis. Cox proportional hazard models were used to identify clinical features and laboratory findings associated with survival. RESULTS: By October 1, 1996, full information about 109 biopsy proven patients with GCA (59 men/50 women) was available. The mean age +/- SD at the time of diagnosis was 73.9 +/- 7.3 years for women and 74.1 +/- 5.8 for men (p = NS). After a median followup of 54 months, 22 patients (20.2%) had died. Three died within the first month after diagnosis due to either vascular complications related to GCA or therapy complications. Apart from a history of severe underlying diseases (comorbid condition unrelated to GCA), neither sex nor any clinical features of GCA were significantly associated with an increase in mortality. As in the general population of the same age in Lugo, the majority of deaths were due to cardiovascular and cerebrovascular complications. SMR was 0.80 (95% CI 0.47-1.13). One, 2, 5, and 10 year survival rates were 95, 91, 81, and 62%, respectively. Hazard function was 1.8% at Day 30 after diagnosis and remained low until the end of the first year of treatment. Thereafter, mortality increased slightly. As this function was constant, we applied an exponential model. The estimated risk of death with this model was 5.3% per year. CONCLUSION: Longterm mortality of GCA in our area is low. However, it may be possible to further lower the mortality rate through early diagnosis and careful followup.     

Structure-function relations of variant and fragment nisins studied with model membrane systems

Nisin, a 34 residue lantibiotic produced by strains of Lactococcus lactis subsp. lactis, exerts antimicrobial activity against Gram-positive bacteria at the cytoplasmic membrane. The structural aspects of nisin which facilitate membrane interaction and permeabilization have been investigated in planar lipid bilayers and liposomes with proteolytic fragments and site-directed variants. N-Terminal nisin fragments N1-12 and N1-20 had little effect on phospholipid mobility, on macroscopic electrical conductance, or on calcein release from liposomes. By contrast, the I30W nisin A variant induced a time-dependent reduction in lipid mobility, indicative of nisin-membrane surface interactions, as well as a decline in membrane capacitance, rise in conductance, and calcein release from liposomes. In these respects I30W nisin A is similar to native nisin. Charge substitutions were also engineered to generate K12L and H27K nisin A variants, both of which were similar to I30W nisin A with respect to an overall reduction in phospholipid mobility. While the K12L nisin A variant elicited a higher increase in membrane capacitance and electrical conductance than I30W nisin A, the H27K nisin A variant elicited weaker effects. These results point to a substantial role for intramembrane charged residues in controlling ion flow through nisin-doped membranes. Native nisin and variants elicit an enhanced release of calcein from liposomes composed of the negatively-charged phospholipids cardiolipin and phosphatidylserine, compared with phospholipid bearing no net charge, suggesting that an electrostatic attraction encourages the initial nisin-membrane association. The results are discussed in the context of other recently proposed models for nisin action.     

SnoRNAs as tools for RNA cleavage and modification

Eukaryotic small nucleolar RNAs (snoRNAs) influence rRNA synthesis at two stages: nucleolytic processing and selection of nucleotides to be ribose methylated (Nm) or converted to pseudouridine (psi). The two modification functions and some processing activities involve direct base pairing of snoRNA with rRNA. In addition to rRNA-targeting sequences, snoRNA function depends on the presence of conserved box elements involved in snoRNA synthesis and localization. The present investigation is directed at using snoRNAs as tools for two purposes: 1) introducing nucleotide modifications into novel sites in rRNA and other snoRNAs, and: 2) targeting nucleolar RNAs for destruction using snoRNA:ribozyme chimers ('snorbozymes'). Early results demonstrate that snoRNAs can be used for both applications.     

Suspected nutritional deficiency causing anaemia in llamas (Lama glama)

A case of poor condition and recumbency in a 14-month-old female llama and a case of poor condition and ataxia in a 23-month-old male llama are described. Both animals were anaemic and had low plasma copper levels. An increased intake of feed with a higher copper level and treatment with copper injections and an oral mineral solution resulted in a successful recovery. Two other young llamas also had low plasma copper levels. The problem was probably due to a nutritional, particularly copper, deficiency and the animals recovered as their copper levels increased.     

Long-term follow-up results of alpha-interferon-based regimens in patients with late chronic phase chronic myelogenous leukemia

The aim of this analysis was to evaluate the efficacy of alpha-interferon (alpha-IFN) regimens in late chronic phase (diagnosis >12 months) chronic myelogenous leukemia (CP-CML). Long-term follow-up results were evaluated in 137 patients with Philadelphia chromosome (Ph)-positive late CP-CML. The alpha-IFN programs were sequential studies with human leukocyte alpha-IFN (seven patients), recombinant alpha-IFN alone (15 patients) or with IFN-gamma (29 patients), hydroxyurea (HU) (19 patients), or low-dose cytarabine (Ara-C) (67 patients). Overall, 57% of the patients achieved complete hematological response (CHR), and 7% obtained partial hematological response. Nineteen patients (15% of the 123 evaluable patients) had a cytogenetic response which was major (Ph-positive <35%) in 10 patients (8%). A trend for better responses was observed with shorter disease duration. The median overall survival from start of therapy was 49 months, with an estimated 5-year survival rate of 41%. Some common pretreatment prognostic factors associated with response did not show statistical associations when applied in late CP-CML; however, characteristics such as smaller spleen size, and lower percentages of peripheral blood and marrow blasts and basophils were associated with better survival experience. When patients were subgrouped according to risk, no significant differences in the incidence of cytogenetic response and in survival outcomes were observed among various risk groups. This study confirms that alpha-IFN-based regimens have a modest activity in late CP-CML, and supports the need to develop investigational strategies aimed at improving patient prognosis in this phase.