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Biomedical subjects

L Stone

Publications and source records attributed to L Stone.

At least 19 recordsLinked to original sources
PubMed2005

MRI as a marker for disease heterogeneity in multiple sclerosis.

BACKGROUND: Whereas recent data from imaging studies challenge the prevailing notion that multiple sclerosis (MS) is purely an inflammatory disease, pathologic studies suggest differences in the disease processes between individual patients with MS. The ability to dissect the pathophysiologic disease heterogeneity, if it indeed exists, by methodologies that can be applied in vivo is important both for the development of new therapeutics and for the ability to identify the optimal therapy for an individual patient. OBJECTIVE: To design a stratification algorithm for patients with MS based on accepted MRI measurements reflective of inflammation and axonal damage/tissue loss and to assess if such MS subgroups retain their intergroup differences long term. METHODS: Mathematical modeling was used to select three discriminatory MRI measures for clinical outcome based on the cross-sectional analysis of 71 patients with untreated MS and tested general applicability of the stratification scheme on the independent longitudinal cohort of 71 MS patients. RESULTS: By consecutive employment of MRI measures reflective of inflammation and tissue loss, the authors were able to separate MS patients into four clinically meaningful subgroups. The analysis of the longitudinal confirmatory cohort demonstrated persistence of the intergroup differences in selected MRI measures for 8 years. CONCLUSIONS: The inflammatory activity and destructiveness of the multiple sclerosis process are to some degree independent of each other, and the successive evaluation of both of these variables can strengthen prediction of clinical outcome in individual patients.

Adult↗
PubMed2005

A randomized blinded trial of combination therapy with cyclophosphamide in patients-with active multiple sclerosis on interferon beta.

OBJECTIVE: To evaluate the efficacy and safety of combination therapy with pulse cyclophosphamide given with methylprednisolone (MP) and interferon beta (IFNbeta)-Ia in multiple sclerosis (MS) patients with active disease during IFNbeta monotherapy. METHODS: This was a randomized, single-blind, parallel-group, multicenter trial in MS patients with a history of active disease during IFNbeta treatment. Patients were randomized to either cyclophosphamide 800 mg/m2 plus methylprednisolone 1 g IV (CY/MP) or methylprednisolone once a month for six months and then followed for an additional 18 months. All patients received three days of methylprednisolone 1 g IV at screening and 30 mcg IFNbeta-Ia IM weekly for the entire 24 months. The primary endpoint was change from baseline in the mean number of gadolinium-enhancing (Gd+) lesions. Secondary clinical endpoints included time to treatment failure. RESULTS: Fifty-nine patients were randomized to treatment: 30 to CY/MP and 29 to MP Change from baseline in the number of Gd+ lesions was significantly different between treatment groups at three (P =0.01), six (P =0.04) and 12 months (P =0.02), with fewer lesions in the CY/MP group. The cumulative rate of treatment failure was significantly lower in the CY/MP group compared with the MP group (rate ratio =0.30; 95% confidence interval, 0.12-0.75; P =0.011). CY/MP treatment was well tolerated. CONCLUSION: Combination therapy with CY/MP and IFNbeta-Ia decreased the number of Gd+ lesions and slowed clinical activity in patients with previously active disease on IFNbeta alone.

Adjuvants, Immunologic↗
PubMed2004

Interferon-beta-1b slows progression of atrophy in RRMS: Three-year follow-up in NAb- and NAb+ patients.

OBJECTIVE: To determine the effect of interferon-beta-1b (IFNbeta-1b) treatment on total contrast-enhancing lesions (CEL), white matter lesion load (WMLL), and cerebral atrophy (CA) in patients with relapsing-remitting multiple sclerosis (RRMS) using serial monthly MRI. METHODS: An open-label baseline-vs-treatment crossover trial was conducted with 30 RRMS patients monitored during a 6-month baseline and up to 36 months on treatment with IFNbeta-1b. Monthly MRI exams and neurologic exams using the Expanded Disability Status Scale (EDSS) were performed. RESULTS: The percentage changes from baseline for years 1, 2, and 3 on IFNbeta-1b were as follows: brain volume (BV) = -1.35, -1.48, and -1.68%; CEL = -76.5, -60.1, and -54.7%; WMLL = -12.2, -9.8, and -10.4%. There was no difference in the BV, CEL, or WMLL for between-year comparisons, and the decrease in BV from year 1 to years 2 and 3 was less than the change from baseline to year 1. EDSS did increase (p < 0.001) when comparing the last 3 months of baseline (2.8 +/- 2.1) and the last 3 months on IFNbeta-1b (3.6 +/- 2.1). Eleven patients developed neutralizing antibody (NAb) during the study. The effect of IFNbeta-1b on CEL and WMLL was significantly reduced in NAb+ patients compared with NAb- patients (p < 0.003). CONCLUSION: IFNbeta-1b decreases contrast-enhancing lesions and white matter lesion load over 3 years on therapy and slows the progression in cerebral atrophy during years 2 and 3.

Adjuvants, Immunologic↗
PubMed2002

The two sides of man-induced changes in littoral marine communities: Eastern Mediterranean and the Red Sea as an example.

Over the last two centuries, the marine life of the Eastern Mediterranean has been influenced by two major factors: one is beneficial, and concerns species migration, such as the opening of the Suez Canal, which enriched the impoverished eastern Mediterranean Sea with over 300 species of fish and invertebrates of Red Sea origin; while the other, a negative and possibly wider-reaching factor, is that of man-made pollution, which has induced unpredictable changes, destabilizing the biological world in both magnitude and duration. Initially cryptic, the effects caused by pollutants first occur at the biochemical and cellular levels of an organism, causing alterations and deviations from the normal, strongly mobilizing its defense systems. Conventional methodologies of ecological analyses, based on species and specimen numbers, cannot detect such alterations. Studying several mollusk populations from polluted and reference sites of the Red Sea and Mediterranean littoral of Israel, we used specific markers for in vivo and in vitro studies to expose the state of micronucleation; levels of defense transport systems such as membrane transport system of organic anions (SATOA) and organic cations (OCT); the state of the multi-xenobiotic resistance-mediating transporter (MXRtr). Based on fluorescent microscopy and microfluorometry, these markers offer powerful tools to expose cryptic changes in the affected populations and provide data necessary for planning and management to protect animal communities and preserve their biological diversity. Comparative analysis of general gene-expression in polluted and reference sites indicates that stress factors have differentially affected the various biological taxa and separated phenotypic sub-populations, producing a novel type of punctuated selection. Such factors, although negative in their influences, in some instances altering the qualities of organisms, and establishing alterations in their hereditary information, pre-adapt them to survive and succeed in new situations.

Adaptation, Physiological↗
PubMed2001

Unexpected coherence and conservation.

The effects of migration in a network of patch populations, or metapopulation, are extremely important for predicting the possibility of extinctions both at a local and a global scale. Migration between patches synchronizes local populations and bestows upon them identical dynamics (coherent or synchronous oscillations), a feature that is understood to enhance the risk of global extinctions. This is one of the central theoretical arguments in the literature associated with conservation ecology. Here, rather than restricting ourselves to the study of coherent oscillations, we examine other types of synchronization phenomena that we consider to be equally important. Intermittent and out-of-phase synchronization are but two examples that force us to reinterpret some classical results of the metapopulation theory. In addition, we discuss how asynchronous processes (for example, random timing of dispersal) can paradoxically generate metapopulation synchronization, another non-intuitive result that cannot easily be explained by the standard theory.

Animal Migration↗
PubMed2001

Heterogeneity stabilizes reciprocal altruism interactions.

In considering the phenomena of reciprocal altruism few would dispute that there are differences in individual quality-in particular, that for some individuals, at least on occasion, the cost of doing favors will exceed the potential of future benefits. That is, at any given time, a typical population is heterogeneous with respect to the affordability of reciprocal altruism. However, methodological limitations of the traditional analytical framework-Single Type (symmetric) Evolutionary Game Theory-have restricted previous analytical efforts to addressing populations idealized in terms of their averages. Here we use the methods of Multitype Evolutionary Game Theory to analyse the role of individual differences in direct reciprocity interactions. Multitype analysis shows that non-idealized populations possess an ESS profile wherein individuals who cannot afford reciprocity (low-quality) defect, while individuals who derive net benefits from reciprocity (high-quality) cooperate. Furthermore, this cooperation is implemented via unmodified tit-for-tat (TfT) strategy. Hence, our results may help resolve a long-standing problem concerning the evolutionary stability of TfT in direct reciprocal altruism. Finally, this difference between idealized and real populations is not restricted to direct reciprocal cooperation. Previously (Lotem et al., 1999) we have demonstrated evolutionarily stable indirect reciprocal cooperation among high-quality individuals in heterogeneous populations.

Altruism↗
PubMed2001

Multi-stage regulation, a key to reliable adaptive biochemical pathways.

A general "multi-stage" regulation model, based on linearly connected regulatory units, is formulated to demonstrate how biochemical pathways may achieve high levels of accuracy. The general mechanism, which is robust to changes in biochemical parameters, such as protein concentration and kinetic rate constants, is incorporated into a mathematical model of the bacterial chemotaxis network and provides a new framework for explaining regulation and adaptiveness in this extensively studied system. Although conventional theories suggest that methylation feedback pathways are responsible for chemotactic regulation, the model, which is deduced from known experimental data, indicates that protein interactions downstream of the bacterial receptor complex, such as CheAs and CheZ, may play a crucial and complementary role.

Bacterial Physiological Phenomena↗
PubMed2001

A case-control study of risk factors for asthma in New Zealand children.

OBJECTIVE: As in other English-speaking countries, asthma is a major and increasing health problem in New Zealand. This study examined the risk factors for asthma in children aged 7-9. METHODS: Cases and controls were randomly selected from participants in the Wellington arm of the International Study of Asthma and Allergies in Childhood (ISAAC). Cases were children with a previous diagnosis of asthma and current medication use (n=233), and controls were children with no history of wheezing and no diagnosis of asthma (n=241). RESULTS: After controlling for confounders, factors significantly associated with asthma were maternal (OR=3.36, 95% CI 1.88-5.99) and paternal asthma (OR-2.67, 95% CI 1.42-5.02), and male sex (OR=1.81, 95% CI 1.17-2.81). Children from social classes 5 and 6 or with unemployed parents (OR=2.32, 95% CI 1.22-4.44) were significantly more likely to have asthma than children in social classes 1 and 2. There was no significant association between having polio vaccination (OR=2.48, 95% CI 0.83-7.41), hepatitis B vaccination (OR=0.66, 95% CI 0.42-1.04) or measles/mumps/rubella vaccination (OR=1.43, 95% CI 0.85-2.41) and asthma. CONCLUSIONS: This study has confirmed the associations of family history and lower socio-economic status with current asthma in 7-9 year old children. The role of vaccinations requires further research.

Asthma↗
PubMed2000

Integrating counselling into general practice.

BACKGROUND: General practice counselling has many significant differences to counselling in other settings. General practitioners have long term relationships with their patients involving physical as well as mental health care. General practitioners are often the first point of contact for distressed patients who may not perceive their problem to have a psychological basis. There are barriers to counselling including time management and cultural expectations of the consultation. OBJECTIVE: To outline a practical biopsychosocial model for counselling in the general practice setting using the knowledge and skills unique to each GP. Theoretical and practical barriers to counselling commonly encountered in general practice are discussed. DISCUSSION: Assessing the problem in a biopsychosocial format highlights strengths and skills the patient already possesses and involves consideration of physical sensations, emotions, behaviours, key relationships, family, social roles and resources. Counselling in general practice requires flexibility and an ability to adapt available resources to address patient needs in an individually appropriate way.

Counseling↗
PubMed1999

Complex dynamics and phase synchronization in spatially extended ecological systems.

Population cycles that persist in time and are synchronized over space pervade ecological systems, but their underlying causes remain a long-standing enigma. Here we examine the synchronization of complex population oscillations in networks of model communities and in natural systems, where phenomena such as unusual '4- and 10-year cycle' of wildlife are often found. In the proposed spatial model, each local patch sustains a three-level trophic system composed of interacting predators, consumers and vegetation. Populations oscillate regularly and periodically in phase, but with irregular and chaotic peaks together in abundance-twin realistic features that are not found in standard ecological models. In a spatial lattice of patches, only small amounts of local migration are required to induce broad-scale 'phase synchronization, with all populations in the lattice phase-locking to the same collective rhythm. Peak population abundances, however, remain chaotic and largely uncorrelated. Although synchronization is often perceived as being detrimental to spatially structured populations, phase synchronization leads to the emergence of complex chaotic travelling-wave structures which may be crucial for species persistence.

Animals↗
PubMed1999

Effects of immigration on the dynamics of simple population models.

Many simple population models exhibit the period doubling route to chaos as a single parameter, commonly the growth rate, is increased. Here we examine the effect of an immigration process on such models and explain why in the case of one-dimensional ("single-humped") maps, immigration often tends to suppress chaos and stabilise equilibrium behaviour or cyclical oscillations of long period. The conditions for which an increase of immigration "simplifies" population dynamics are examined.

Animals↗
PubMed1999

Indoor environment, atopy and the risk of the asthma in children in New Zealand.

The objective of this study was to examine the relationship between the indoor environment, atopy and asthma in 7-9-year-old children. Cases and controls were randomly selected from children who participated in the International Study of Asthma and Allergies in Childhood (ISAAC) in Wellington, New Zealand. Cases were children with a previous diagnosis of asthma and current medication use (n = 233) and controls were children with no history of wheezing and no diagnosis of asthma (n = 241). Information was recorded about the indoor environment during the first year of life and currently. Dust was sampled from floors and beds and Der p 1 and Fel d 1 measured using enzyme-linked immunosorbent assays. Skin-prick tests were performed with eight common allergens. Sensitization to Dermatophagoides farinae (OR = 3.19; 95% CI 1.74-5.84), Dermatophagoides pteronyssinus (OR = 2.06; 95% CI 1.16-3.65) and cat (OR = 3.89; 95% CI 1.06-14.30) were independently associated with current asthma. The use of a sheepskin in the first year of life (OR = 1.91; 95% CI 1.11-3.33) was also independently associated with current asthma but current Der p 1 levels showed no association with current asthma. Exposures in early life may be more important than current exposures in determining asthma at age 7-9 years. Prospective studies are needed in New Zealand to determine the relative importance of early life exposures to Der p 1 and other risk factors for asthma.

Air Pollution, Indoor↗
PubMed1999

Can mirrors alleviate visual hemineglect?

Following right hemisphere stroke, many patients display an indifference to objects and events in the left side of the world ('neglect'). Here, we describe a new technique that might help accelerate recovery from neglect. The patient sits at a table and a mirror is propped vertically on the patient's right side in the parasagittal plane, so that when the patient rotates his head rightward and looks into the mirror, he sees the neglected side of the world reflected in the mirror. Our question was: since the sensory information was now coming from the non-neglected left side, would this somehow make him overcome the neglect? In pilot experiments, two types of responses were seen: (a) In one subset of patients the presence of the mirror seemed to enhance the patients' awareness of the neglected field, so that they reached correctly for an object that was shown in the neglected field. Will repeated practice with this task accelerate recovery from neglect? (b) The second group of patients kept reaching into the mirror to grasp the reflection or kept groping behind the mirror ('mirror agnosia'). If the mirror was placed in the coronal position and the object placed behind their head, then some of these patients (from group B) reached correctly for the object. Quite apart from its obvious theoretical implications, we believe this technique might provide a new approach for the treatment of visual hemineglect.

Brain↗
PubMed1998

Pulse vaccination strategy in the SIR epidemic model.

Theoretical results show that the measles 'pulse' vaccination strategy can be distinguished from the conventional strategies in leading to disease eradication at relatively low values of vaccination. Using the SIR epidemic model we showed that under a planned pulse vaccination regime the system converges to a stable solution with the number of infectious individuals equal to zero. We showed that pulse vaccination leads to epidemics eradication if certain conditions regarding the magnitude of vaccination proportion and on the period of the pulses are adhered to. Our theoretical results are confirmed by numerical simulations. The introduction of seasonal variation into the basic SIR model leads to periodic and chaotic dynamics of epidemics. We showed that under seasonal variation, in spite of the complex dynamics of the system, pulse vaccination still leads to epidemic eradication. We derived the conditions for epidemic eradication under various constraints and showed their dependence on the parameters of the epidemic. We compared effectiveness and cost of constant, pulse and mixed vaccination policies.

Computer Simulation↗