Review: Molecular characteristics of long-term epilepsy-associated tumours (LEATs) and mechanisms for tumour-related epilepsy (TRE).

Brain tumours are the second most common cause of seizures identified in epilepsy surgical series. While any tumour involving the brain has the potential to cause seizures, specific subtypes are more frequently associated with epilepsy. Tumour-related epilepsy (TRE) has a profound impact on patients with brain tumours and these seizures are often refractory to anti-epileptic treatments, resulting in long-term disability and patient morbidity. Despite the drastic impact of epilepsy-associated tumours on patients, they have not traditionally enjoyed as much attention as more malignant neoplasms. However, recently a number of developments have been achieved towards further understanding of the molecular and developmental backgrounds of specific epilepsy-associated tumours. In addition, the past decade has seen an expansion in the literature on the pathophysiology of TRE. In this review, we aim to summarize the mechanisms by which tumours may cause seizures and detail recent data regarding the pathogenesis of specific developmental epilepsy-associated tumours.

Prospective Multicenter Observational Study of Overt Hepatic Encephalopathy.

BACKGROUND: Overt hepatic encephalopathy (OHE) is a frequent complication of decompensated cirrhosis. AIMS: A multicenter prospective observational study was performed to assess the most commonly recorded presenting manifestations of OHE and its associated health-care burden. METHODS: Qualifying patients must have experienced ≥1 OHE episode within 30 days of enrollment (qualifying OHE) and were followed for recurrence (on-study OHE). RESULTS: Two hundred and sixty-five patients were enrolled at 30 sites and followed for up to 9 months (mean 72 days). Seventy-two patients experienced 122 on-study episodes; with 72, 23, and 13 having ≥1, ≥2, or ≥3 on-study episodes with median days to occurrence of the 1st, 2nd, and 3rd episode of 34, 19, and 11, respectively. The most frequently recorded OHE manifestations included confusion (78 %), change in mental status (57 %), disorientation (48 %), lethargy (46 %), and asterixis (45 %). West Haven grade was used inconsistently and recorded for only 28 % of episodes. Most qualifying and on-study episodes occurred on rifaximin (60 and 82 %, respectively) and were associated with hospitalization (68 and 85 %, respectively). Twenty-three patients experienced ≥2 on-study episodes within 2 months of enrollment on average (median 45 days) and accounted for 60 % of on-study episodes. CONCLUSIONS: In this prospective study, OHE's most commonly recorded presenting manifestations included confusion, altered mental status, disorientation, lethargy, and asterixis. As reflected by frequent recurrence and hospitalizations, OHE, particularly the approximately 10 % of "high-resource-utilizing" patients with frequent recurrence, continues to pose a major unmet medical need and health-care burden despite the use of rifaximin.

Glutamine and hyperammonemic crises in patients with urea cycle disorders.

UNLABELLED: Blood ammonia and glutamine levels are used as biomarkers of control in patients with urea cycle disorders (UCDs). This study was undertaken to evaluate glutamine variability and utility as a predictor of hyperammonemic crises (HACs) in UCD patients. METHODS: The relationships between glutamine and ammonia levels and the incidence and timing of HACs were evaluated in over 100 adult and pediatric UCD patients who participated in clinical trials of glycerol phenylbutyrate. RESULTS: The median (range) intra-subject 24-hour coefficient of variation for glutamine was 15% (8-29%) as compared with 56% (28%-154%) for ammonia, and the correlation coefficient between glutamine and concurrent ammonia levels varied from 0.17 to 0.29. Patients with baseline (fasting) glutamine values >900 µmol/L had higher baseline ammonia levels (mean [SD]: 39.6 [26.2]µmol/L) than patients with baseline glutamine ≤ 900 µmol/L (26.6 [18.0]µmol/L). Glutamine values >900 µmol/L during the study were associated with an approximately 2-fold higher HAC risk (odds ratio [OR]=1.98; p=0.173). However, glutamine lost predictive significance (OR=1.47; p=0.439) when concomitant ammonia was taken into account, whereas the predictive value of baseline ammonia ≥ 1.0 upper limit of normal (ULN) was highly statistically significant (OR=4.96; p=0.013). There was no significant effect of glutamine >900 µmol/L on time to first HAC crisis (hazard ratio [HR]=1.14; p=0.813), but there was a significant effect of baseline ammonia ≥ 1.0 ULN (HR=4.62; p=0.0011). CONCLUSIONS: The findings in this UCD population suggest that glutamine is a weaker predictor of HACs than ammonia and that the utility of the predictive value of glutamine will need to take into account concurrent ammonia levels.

Intradiscal Pressure Changes during Manual Cervical Distraction: A Cadaveric Study.

The objective of this study was to measure intradiscal pressure (IDP) changes in the lower cervical spine during a manual cervical distraction (MCD) procedure. Incisions were made anteriorly, and pressure transducers were inserted into each nucleus at lower cervical discs. Four skilled doctors of chiropractic (DCs) performed MCD procedure on nine specimens in prone position with contacts at C5 or at C6 vertebrae with the headpiece in different positions. IDP changes, traction forces, and manually applied posterior-to-anterior forces were analyzed using descriptive statistics. IDP decreases were observed during MCD procedure at all lower cervical levels C4-C5, C5-C6, and C6-C7. The mean IDP decreases were as high as 168.7 KPa. Mean traction forces were as high as 119.2 N. Posterior-to-anterior forces applied during manual traction were as high as 82.6 N. Intraclinician reliability for IDP decrease was high for all four DCs. While two DCs had high intraclinician reliability for applied traction force, the other two DCs demonstrated only moderate reliability. IDP decreases were greatest during moving flexion and traction. They were progressevely less pronouced with neutral traction, fixed flexion and traction, and generalized traction.

Microbicides for HIV/AIDS. 3. Observation of apparent dynamic protonation and deprotonization in CD4+ T-cell model systems.

New measurements of the electrophoretic mobility of T-cell model systems have been carried out and analyzed to obtain the dynamic variation in mobility in small titration increments during separate upscale and downscale sweeps in pH. We demonstrate that a plot of plambda vs p[NaCl] has been found essential in evaluating the consistency of electrophoretic mobility measurements at different (1:1) electrolyte concentrations and show, for the first time, that electrophoretic mobility measurements as a function of pH can reflect different rates of the respective ionization and association that occur in the surface functional groups as a consequence of the different changes in the hydration-dehydration reactions involved. Differences found between the upscale and downscale sweeps suggest that it is easier to protonate a protein cell surface than to deprotonate it. The effect is most pronounced at the highest salt concentration (similar to that which exists for the cells in their native state) and becomes less pronounced as the salt concentration is lowered. The effect is interpreted as a result of the different changes in the state of hydration as a proton moves from the bulk through the double layer to a surface group and the reverse. The effect occurs with both replicating and activated T-cells. This latter result may be of biological significance and particularly relevant to HIV-1 infection, since during male-to-female transmission, the environment where most infections occur supports this protonation effect.

Microbicides for HIV/AIDS. 2. Electrophoretic fingerprinting of CD4+ T-cell model systems.

New measurements of the dependence of the surface charge on the pH and electrolyte concentration for three living human white blood cell lines that are the principal targets of the HIV-1 virus are reported. Comparison of the electrophoretic fingerprint (EF) pattern, especially the line of zero mobility, with that of reference colloids establishes the separate individual identities and shows that all three exhibit a zwitterionic surface. With the EF results as a guide, preliminary biological infectivity measurements showed that small polyvalent cations modulate the negative charge on the T-cell surface in a way that strongly affects the infection kinetics. H9 cells were exposed to an infectious virus (X4), and the data showed that HIV interaction with target cells is enhanced by physiological fluids. The nondestructive methodology described is generally applicable to characterization of the surface charge and determination of the colloidal stability of any aqueous charged colloidal system without reference to any model of the double layer.

Microbicides for HIV/AIDS. 1. Electrophoretic fingerprinting the H9 cell model system.

An electrophoretic fingerprint of a CD4+ T-cell (H9) has been produced for the first time. Samples were taken from three separate cultures prepared at different times to obtain a general characterization of the cells. The availability of commercial instrumentation equipped with an auto-titrator has made possible the application of both the 2-dimensional and 3-dimensional representation of electrophoretic fingerprinting. The 2-dimensional treatment has been used to assess the reliability of the data and has detected hysteresis as a possible second-order effect. The 3-dimensional representation has been used to explore the data needed for a reliable overall pattern that characterizes the conditions of pH and conductivity required for an effective microbicide. The dome negative maximum in the electrophoretic fingerprint at high pH, along with the line of zero mobility (LZM) and a dome positive maximum at low pH, are interpreted as evidence for surface carboxyl groups prominent in the alkaline regime and surface amino groups prominent in the acid regime, suggesting that the H9 cell surface is zwitterionic. This has important implications as to the choice and design of microbicide actives.

Congestive heart failure with preserved systolic function in a statewide sample of community hospitals.

BACKGROUND: The importance of congestive heart failure (CHF) in patients with preserved left ventricular systolic function is increasingly recognized, but most studies have been conducted at a single, usually academic, medical center. The aim of this study was to determine the prognosis, readmission rate, and effect of ACE inhibitor therapy in a Medicare cohort with CHF and preserved systolic function. METHODS AND RESULTS: We examined a statewide, random sample of 1,720 California Medicare patients hospitalized with an ICD-9 diagnosis of CHF confirmed by a decreased left ventricular ejection fraction (EF) or chest radiograph from July 1993 to June 1994 and January 1996 to June 1996. Among the 782 patients with confirmed CHF and an in-hospital left ventricular EF measurement, 45% had reduced systolic function (ReSF) (EF < 40%) and 55% had preserved systolic function (PrSF) (EF > 40%). The PrSF group had a lower 1-year mortality rate but similar hospital readmission rates for both CHF and all causes. In patients with ReSF, ACE inhibitor treatment was associated with a lower mortality rate (P =.04) and a trend toward a lower CHF readmission rate (P =.13). In contrast, ACE inhibition therapy was associated with neither a lower rate of mortality nor CHF readmission in PrSF patients (P =.61 and.12, respectively). In multivariate analyses treatment with ACE inhibitors in PrSF patients was not associated with either a reduction in mortality (hazard ratio, 1.15; 95% CI, 0.79-1.67) or CHF readmission (hazard ratio, 1.21; 95% CI, 0.92-1.58). CONCLUSIONS: CHF with PrSF seems to be associated with high mortality and morbidity rates, but ACE inhibitors may not produce comparable benefit in this group as in patients with ReSF.

Utilization of by-products from the tequila industry. Part 2: Potential value of Agave tequilana Weber azul leaves.

The leaves of the agave plant are left in the field after harvesting the heads for tequila production. Different types of agave leaves were isolated, classified, and their content in the total plant determined. The usable fractions were collected and their properties determined. Of the total wet weight of the agave plant, 54% corresponds to the agave head, 32% corresponds to materials which could be usable for sugar and fiber production which leaves 14% of the wet plant without apparent utility. The fractions with higher total reducing sugars (TRS) content were the fresh fraction of partially dry leaves stuck to the head and the leaf bases with a TRS content of 16.1% and 13.1%, respectively. The highest TRS concentration (16-28%) is in the agave head which is used for tequila production. The leaves are 90-120 cm long and 8-12 cm wide and contain fiber bundles that are 23-52 cm long and 0.6-13 mm wide. The ultimate fiber length is approximately 1.6 mm with an average width of 25 microns. There are several types of leaf fibers that can be utilized depending on what part of the plant they come from and what product is desired. Agave leaf fibers were pulped using a soda pulping process and the pulp was hand formed into test sheets. Test sheets made from pulped agave leaf fibers had a breaking length comparable to paper made from both pine and eucalyptus fibers, but the tear index and burst index were lower than the other two papers.

Utilization of byproducts from the tequila industry: part 1: agave bagasse as a raw material for animal feeding and fiberboard production.

Agave bagasse was successfully separated into fractions that were used in sheep feeding trials. Agave bagasse can be substituted for corn stubble in the sheep's diet which resulted in improved weight gain. Agave bagasse was also processed into long and short fiber fractions with a hammermill and fiberboards of medium and high specific gravities being produced. Medium specific gravity agave fiberboards had moisture and mechanical properties comparable to medium specific gravity fiberboards made using aspen fiber. All high specific gravity agave fiberboards made from short or long fibers were stronger in bending than the ANSI standard for hardboards.

Evaluating hypertension control in a managed care setting.

BACKGROUND: We conducted a retrospective cohort study on a random sample of adult patients with hypertension in a large health maintenance organization to assess the feasibility of documenting blood pressure (BP) control and to compare different measures for defining BP control. METHODS: Three criteria for BP control were assessed: systolic BP less than 140 mm Hg; diastolic BP less than 90 mm Hg; and combined BP control, with systolic BP less than 140 mm Hg and diastolic BP less than 90 mm Hg. Four methods of assessing hypertension control by the above criteria were examined: proportion of patients with BP under control at 75% and 50% or more of their office visits; the mean of all pressures during the study period; and the BP from the last visit during the study period. RESULTS: The proportion of patients meeting each criterion for control was similar whether we used the mean BP for all visits, the last recorded BP, or control at 50% or more of visits. Control rates were substantially lower when the more stringent assessment, 75% of visits, was used. The proportion of patients with combined BP control at 75% or more of their visits was half that of the other methods. CONCLUSIONS: In this health maintenance organization population, results with the use of the simplest approach, the last BP measurement recorded, were similar to results with the mean BP. Our findings indicate that evaluation of BP control in a large health maintenance organization will find substantial room for improvement, and clinicians should be encouraged to be more aggressive in their management of hypertension, especially with regard to the systolic BP, which until recent years has been underemphasized.

Congestive heart failure hospitalizations and survival in California: patterns according to race/ethnicity.

BACKGROUND: Congestive heart failure (CHF) disproportionately affects African Americans, but data are limited concerning CHF hospitalization patterns among Hispanic and Asian populations, the 2 fastest growing ethnic groups in the United States, and race/ethnic patterns of rehospitalization and survival among patients with CHF are unknown. We conducted a study to assess rates of CHF hospitalization, readmission, and survival among diverse populations in California. METHODS AND RESULTS: We used 2 study designs. First, we calculated the population-based incidence of CHF hospitalization in California in 1991. Next we conducted a retrospective cohort study that identified patients initially hospitalized for CHF in 1991 or 1992 and followed these patients for 12 months after their index hospitalization to determine their likelihood of rehospitalization or death. Data were analyzed with Cox proportional hazards models. African Americans had the highest rate of CHF hospitalization. Age-adjusted hospitalization rates were comparable among whites, Latinos, and Asian women and all lower than those in African American, whereas Asian men had the lowest rates. On adjusted analyses, African Americans were more likely than whites and Asians to be rehospitalized (relative risk 1.07; 95% confidence interval 1.04 to 1.10). However, they were less likely to die within the 12-month follow-up period (relative risk 0.86; 95% confidence interval 0.82 to 0.90). Whites, conversely, had the highest posthospitalization mortality rates. CONCLUSIONS: These findings demonstrate important racial-ethnic differences in CHF morbidity and mortality rates. The disparate findings of higher hospitalization and rehospitalization rates and lower mortality rates among African Americans than whites may represent differences in the underlying pathophysiology of CHF in these groups or differences in access to quality care. Further studies are needed to explain these seemingly paradoxical outcomes.

Containing incontinence in men: an extra dimension.

The prevalence and nature of incontinence means that all nurses will see patients who suffer from this condition. Many professionals remain unaware of products that can assist in the management of such patients. This article describes experience with some of the products available, highlighting their clinical usefulness and effectiveness.

Failure to detect circulating IgG or IgM antibodies to basal cell carcinoma by immunofluorescence.

Immunofluorescence techniques failed to reveal evidence of anti-tumour antibody in the sera of patients with basal cell carcinima. Although the presence of such antibodies has previously been associated with the absence of metastasis in malignant melanoma, other explanations for the low metaststic potential of basal cell carcinoma should be sought.