A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma.

BACKGROUND: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear. METHODS: We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP 'group 1'; R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX 'group 2'; dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX 'group 3'. RESULTS: Overall, 217 patients were identified (49, 125 and 43 in groups 1-3, respectively). With median follow-up of 3.4 (range 0.2-18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1-3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5-33.1%), 6.9% (3.5-13.4%) and 2.3% (0.4-15.4%) in groups 1-3, respectively (P=0.009). CONCLUSIONS: The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.

The fluid mechanics of root canal irrigation.

Root canal treatment is a common dental operation aimed at removing the contents of the geometrically complex canal chambers within teeth; its purpose is to remove diseased or infected tissue. The complex chamber is first enlarged and shaped by instruments to a size sufficient to deliver antibacterial fluids. These irrigants help to dissolve dying tissue, disinfect the canal walls and space and flush out debris. The effectiveness of the procedure is limited by access to the canal terminus. Endodontic research is focused on finding the instruments and clinical procedures that might improve success rates by more effectively reaching the apical anatomy. The individual factors affecting treatment outcome have not been unequivocally deciphered, partly because of the difficulty in isolating them and in making the link between simplified, general experimental models and the complex biological objects that are teeth. Explicitly considering the physical processes within the root canal can contribute to the resolution of these problems. The central problem is one of fluid motion in a confined geometry, which makes the dispersion and mixing of irrigant more difficult because of the absence of turbulence over much of the canal volume. The effects of treatments can be understood through the use of scale models, mathematical modelling and numerical computations. A particular concern in treatment is that caustic irrigant may penetrate beyond the root canal, causing chemical damage to the jawbone. In fact, a stagnation plane exists beyond the needle tip, which the irrigant cannot penetrate. The goal is therefore to shift the stagnation plane apically to be coincident with the canal terminus without extending beyond it. Needle design may solve some of the problems but the best design for irrigant penetration conflicts with that for optimal removal of the bacterial biofilm from the canal wall. Both irrigant penetration and biofilm removal may be improved through canal fluid agitation using a closely fitting instrument or by sonic or ultrasonic activation. This review highlights a way forward by understanding the physical processes involved through physical models, mathematical modelling and numerical computations.

The effects of gas flow on granular currents.

Currents of particles have been quite successfully modelled using techniques developed for fluid gravity currents. These models require the rheology of the currents to be specified, which is determined by the interaction between particles. For relatively small slow currents, this is determined primarily through friction, which can be controlled and reduced by fluidizing the particles, so that they may become much more mobile. Recent results cannot be predicted using many of the proposed models, and may be defined by the interaction between the particles and the fluid through which they are passing. However, in addition, particles that are only initially fluidized also form currents that are also mobile, but otherwise are different from continuously fluidized currents. The mobility of these currents appears not to be connected to the time taken for them to degas. This suggests that defining the continuous stresses on the particle current may not be sufficient to understand its motion and that a challenge for the future is to understand the structure of these flows and how this affects their motion.

Kimberlite ascent and eruption.

Wilson and Head model kimberlite ascent and eruption by considering the propagation of a volatile-rich dyke. Wilson and Head's model has features in common with Sparks et al., but it is inconsistent with geological observations and constraints on volatile solubility. Here we show that this may be due to erroneous physical assumptions.

Community health profile of Windsor, Ontario, Canada: anatomy of a Great Lakes area of concern.

The rates of mortality, morbidity as hospitalizations, and congenital anomalies in the Windsor Area of Concern ranked among the highest of the 17 Areas of Concern on the Canadian side of the Great Lakes for selected end points that might be related to pollution in this relatively highly industrialized city. Mortality and morbidity rates from all causes were higher than in the rest of the province. Anomalously high rates of diseases included various cancers; endocrine, nutritional, metabolic, and immunity disorders; diseases of the blood and blood-forming organs, nervous system and sense organs, circulatory and respiratory systems, digestive system, genitourinary system, skin and subcutaneous tissue, musculoskeletal system and connective tissues; congenital anomalies, and infant mortality. Of particular concern was the early onset of the elevated rates of many of these diseases and conditions. Comparison of these incident rates with those in Hamilton, another industrial municipality in southern Ontario, suggested that in addition to a variety of local sources of industrial pollution from automobile manufacturing and use, transboundary air and water pollution from Detroit, Michigan, should be investigated as potentially important causes of these health outcomes in the Windsor Area of Concern. Some of the institutional and political trends of the past decade may need to be reversed before effective remedial programs are implemented for cleaning up contaminated sediments and for containment of leaking hazardous waste sites. This pilot project would seem to be a useful preliminary method of integrating human health concerns and of priority setting for the administration of the Great Lakes Water Quality Agreement and the Canada-United States Air Quality Agreement.

Weight control in the physician's office.

BACKGROUND: Lifestyle changes involving diet, behavior, and physical activity are the cornerstone of successful weight control. Incorporating meal replacements (1-2 per day) into traditional lifestyle interventions may offer an additional strategy for overweight patients in the primary care setting. METHODS: One hundred thirteen overweight premenopausal women (mean +/- SD age, 40.4 +/- 5.5 years; weight, 82 +/- 10 kg; and body mass index, 30 +/- 3 kg/m(2)) participated in a 1-year weight-reduction study consisting of 26 sessions. The women were randomly assigned to 3 different traditional lifestyle-based groups: (1) dietitian-led group intervention (1 hour per session), (2) dietitian-led group intervention incorporating meal replacements (1 hour per session), or (3) primary care office intervention incorporating meal replacements with individual physician and nurse visits (10-15 minutes per visit). RESULTS: For the 74 subjects (65%) completing 1 year, the primary care office intervention using meal replacements was as effective as the traditional dietitian-led group intervention not using meal replacements (mean +/- SD weight loss, 4.3% +/- 6.5% vs 4.1% +/- 6.4%, respectively). Comparison of the dietitian-led groups showed that women using meal replacements maintained a significantly greater weight loss (9.1% +/- 8.9% vs 4.1% +/- 6.4%) (P =.03). Analysis across groups showed that weight loss of 5% to 10% was associated with significant (P =.01) reduction in percentage of body fat, body mass index, waist circumference, resting energy expenditure, insulin level, total cholesterol level, and low-density lipoprotein cholesterol level. Weight loss of 10% or greater was associated with additional significant (P =.05) improvements in blood pressure and triglyceride level. CONCLUSIONS: A traditional lifestyle intervention using meal replacements can be effective for weight control and reduction in risk of chronic disease in the physician's office setting as well as in the dietitian-led group setting.

Multivariate assessment of explicit memory function in combat veterans with posttraumatic stress disorder.

Declarative memory impairment is a frequent complaint of patients suffering from posttraumatic stress disorder (PTSD). We assessed memory, attention, visual spatial skills, and executive function in Vietnam combat veterans with (n = 19) and without (n = 13) PTSD. Although PTSD subjects demonstrated a "generalized impairment" relative to non-PTSD subjects on a majority of tasks, only attention and memory provided unique and independent prediction of PTSD versus non-PTSD status. Our findings suggest that memory functioning represents a neurocognitive domain of specific relevance to the development of PTSD in trauma-exposed individuals, which can be distinguished from generalized attentional impairment as well as the effects of trauma exposure severity, IQ, comorbid depression, history of alcohol use, and history of developmental learning problems.

Influence of haloperidol on the relationship of frontal lobe function to psychomotor poverty and disorganization syndromes.

The aim of the study was to examine effects of haloperidol on the relationships between neuropsychological measures of frontal lobe functioning and the schizophrenia syndromes of psychomotor poverty and disorganization. Twenty-one participants with schizophrenia were initially evaluated when clinically stable and chronically treated with haloperidol, and 19 were evaluated again after a 3-week haloperidol-free period. Participants were evaluated with the Trail Making Test, the Wisconsin Card Sorting Test, the Purdue Pegboard, and psychiatric rating scales at each evaluation. There were significant correlations between schizophrenia syndromes and the tests sensitive to frontal lobe function when participants were medicated but not when drug-free. No significant changes in symptom severity or motor function occurred from the medication to the medication-free evaluation. The results indicate that haloperidol mediates the relationship between tests sensitive to frontal lobe function and the schizophrenia syndromes of psychomotor poverty and disorganization. This mediation effect was not attributable to changes in overall symptom severity or motor function.

Neurologic soft signs in chronic posttraumatic stress disorder.

BACKGROUND: Subtle neurologic impairment has been reported in several mental disorders. The goals of the present study were to evaluate neurologic status in patients of both sexes with chronic posttraumatic stress disorder (PTSD) from different traumatic experiences. METHODS: Twenty-one adult women who were sexually abused as children (12 with PTSD, 9 without) and 38 male Vietnam War combat veterans (23 with PTSD, 15 without) underwent examination for 41 neurologic soft signs, which were scored by the examiner as well as a blind rater observing videotapes. Subject history was obtained with special attention to neurodevelopmental problems. Psychometrics included the Wender Utah Rating Scale for symptoms of childhood attention-deficit/hyperactivity disorder and the Michigan Alcoholism Screening Test. Veterans also completed the Combat Exposure Scale and subtests of the Wechsler Adult Intelligence Scale-Revised. RESULTS: Average neurologic soft sign scores (interrater reliability = 0.74) of women with PTSD owing to sexual abuse in childhood (mean [SD], 0.77 [0.32]) and veteran men (0.72 [0.20]) with combat-related PTSD were comparable and significantly (P<.001) higher than those of women sexually abused as children (0.42 [0.10]) and combat veteran men (0.43 [0.17]) without PTSD. This effect could not be explained by a history of alcoholism or head injury. Subjects with PTSD reported more neurodevelopmental problems and more childhood attention-deficit/hyperactivity disorder symptoms and had lower IQs, all of which were significantly correlated with neurologic soft signs. CONCLUSION: Neurologic compromise is evident from subject history and findings from physical examination in both women and men with chronic PTSD who had experienced different kinds of traumatic events in childhood and adulthood.

Eco-toxicology: traditional and post-normal interpretations of the Great Lakes Water Quality Agreement.

Eco-toxicology is a potentially useful fusing of the two distinct disciplines of ecology and environmental toxicology. However, in applying an ambiguous "ecosystem approach," since the late 1970s, to the implementation of the Great Lakes Water Quality Agreement, there have been difficulties in delimiting the Great Lakes issues to be addressed under the Agreement and in ensuring that general biological resource management and conservation issues are dealt with separately under other existing mandates. There is a priority need for managers involved in the implementation of the Great Lakes Water Quality Agreement to decide whether the purpose remains one of maintaining and restoring Great Lakes water quality or whether it has already been transformed into a broad program to maintain and restore ecosystem integrity throughout the entire Great Lakes basin. Parts of this ambiguity may have arisen as a result of this fusing of ecology and environmental toxicology.

Construct validity of neuropsychological tests in schizophrenia.

Validity studies of neuropsychological tests have typically examined individuals with neurological disorders. The present study was designed to investigate the construct validity of neuropsychological measures in patients with schizophrenia. We used Wechsler Adult Intelligence Scale Revised (WAIS-R) factor scores that were generated from the population of interest as marker variables in the present analysis. The current study included 39 patients with schizophrenia who were evaluated with a battery of neuropsychological tests assessing attention, memory, and abstract reasoning abilities. Pearson correlations indicated significant relationships between (a) WAIS-R Verbal Comprehension factor and tests of sustained attention, verbal memory and remote memory; (b) WAIS-R Perceptual Organization factor and tests of visual memory and abstraction and problem solving; and (c) WAIS-R Freedom From Distractibility factor and neuropsychological measures of attention and concentration. These results provide support for the construct validity of the neuropsychological tests in patients with schizophrenia, and indicate that these tests evaluate essentially the same constructs in patients with schizophrenia as they do for patients with structural neurological disorders.

Recent and remote memory dissociation: medication effects and hippocampal function in schizophrenia.

Neuropsychological measures of recent and remote memory as well as general attention were administered to two groups of DSM-III-R schizophrenic patients in a within-subject repeated measures design across a 3-week interval. One group of patients (n = 12) was maintained on haloperidol for both test sessions, whereas a second group (n = 9) was tested first on haloperidol and again 3-weeks drug free. Patients received no adjunctive anticholinergic medication during the study. No differences were observed between the patient groups in level of psychotic symptomatology or general attention across the two test sessions. Patients withdrawn from haloperidol showed significant decreases in recent verbal memory function, while at the same time demonstrating significant increases in remote verbal memory. We speculate that the observed pattern of results is consistent with medial temporal lobe dysfunction particularly prominent in the left hemisphere as patients become drug free, and provides support for the existence of state-dependent cognitive changes in schizophrenia.

Neurological status of combat veterans and adult survivors of sexual abuse PTSD.

We found higher levels of positive soft neurological signs in PTSD participants than in participants who also experienced similar trauma but did not develop PTSD. This finding was replicated in two samples, that is, Vietnam combat veterans and adult female survivors of childhood sexual abuse, despite differences in gender, age, nature of trauma, and period of life when the trauma occurred. Past developmental history of participants and a substance abuse history of first-degree relatives also differentiated PTSD from non-PTSD groups in both combat and sexual abuse samples. Evidence for neurological impairment and compromised developmental history raises the possibility of pretrauma impairment as a risk factor for the development of PTSD.

Chronic haloperidol treatment does not affect structure of attention in schizophrenia.

Results of a number of investigations indicate attention is a multifactorial construct composed of four distinct cognitive factors including focus-execute, sustain, encode and shift abilities. While investigators have partially or fully replicated this attentional structure in a number of clinical and nonclinical populations, no study has adequately examined the structure of attention in patients with schizophrenia who are not treated with antipsychotics. In this study, we examined the four-factor theory of attention in patients with schizophrenia while they were stabilized on haloperidol (with no adjunctive antiparkinsonian/anticholinergic medications) and again when they were approximately 3 weeks drug free. Standard neuropsychological measures were used to assess attentional functions. Principal components analyses (varimax rotation) of neuropsychological test scores in medicated and drug-free conditions indicated that four factors accounted for 84.2 and 91.8 of total variance in medicated and unmedicated conditions, respectively. Based on these results, it appears that: (1) haloperidol does not appreciably affect structure of the attentional system in patients with schizophrenia; (2) unmedicated patients with schizophrenia exhibit a similar structure of attention as both medicated patients and controls, suggesting that attentional structure is 'normal' in schizophrenia; and (3) the four-factor attention theory is a useful and valid paradigm for evaluating attention in patients with schizophrenia, regardless of medication status.

Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder.

This study used quantitative volumetric magnetic resonance imaging techniques to explore the neuroanatomic correlates of chronic, combat-related posttraumatic stress disorder (PTSD) in seven Vietnam veterans with PTSD compared with seven nonPTSD combat veterans and eight normal nonveterans. Both left and right hippocampi were significantly smaller in the PTSD subjects compared to the Combat Control and Normal subjects, even after adjusting for age, whole brain volume, and lifetime alcohol consumption. There were no statistically significant group differences in intracranial cavity, whole brain, ventricles, ventricle:brain ratio, or amygdala. Subarachnoidal cerebrospinal fluid was increased in both veteran groups. Our finding of decreased hippocampal volume in PTSD subjects is consistent with results of other investigations which utilized only trauma-unexposed control groups. Hippocampal volume was directly correlated with combat exposure, which suggests that traumatic stress may damage the hippocampus. Alternatively, smaller hippocampi volume may be a pre-existing risk factor for combat exposure and/or the development of PTSD upon combat exposure.