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Biomedical subjects

M E Newman

Publications and source records attributed to M E Newman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Epidemics and percolation in small-world networks.

We study some simple models of disease transmission on small-world networks, in which either the probability of infection by a disease or the probability of its transmission is varied, or both. The resulting models display epidemic behavior when the infection or transmission probability rises above the threshold for site or bond percolation on the network, and we give exact solutions for the position of this threshold in a variety of cases. We confirm our analytic results by numerical simulation.

Epidemiologic Methods↗
PubMed2000

Exact solution of site and bond percolation on small-world networks.

We study percolation on small-world networks, which has been proposed as a simple model of the propagation of disease. The occupation probabilities of sites and bonds correspond to the susceptibility of individuals to the disease, and the transmissibility of the disease respectively. We give an exact solution of the model for both site and bond percolation, including the position of the percolation transition at which epidemic behavior sets in, the values of the critical exponents governing this transition, the mean and variance of the distribution of cluster sizes (disease outbreaks) below the transition, and the size of the giant component (epidemic) above the transition.

Disease Outbreaks↗
PubMed2000

Illness, cytokines, and depression.

Various medical conditions that involve activation of the immune system are associated with psychological and neuroendocrine changes that resemble the characteristics of depression. In this review we present our recent studies, designed to investigate the relationship between the behavioral effects of immune activation and depressive symptomatology. In the first set of experiments, we used a double-blind prospective design to investigate the psychological consequences of illness in two models: (1) vaccination of teenage girls with live attenuated rubella virus, and (2) lipopolysaccharide (LPS) administration in healthy male volunteers. In the rubella study, we demonstrated that, compared to control group subjects and to their own baseline, a subgroup of vulnerable individuals (girls from low socioeconomic status) showed a significant virus-induced increase in depressed mood up to 10 weeks after vaccination. In an ongoing study on the effects of LPS, we demonstrated significant LPS-induced elevation in the levels of depression and anxiety as well as memory deficits. These psychological effects were highly correlated with the levels of LPS-induced cytokine secretion. In parallel experiments, we demonstrated in rodents that immune activation with various acute and chronic immune challenges induces a depressive-like syndrome, characterized by anhedonia, anorexia, body weight loss, and reduced locomotor, exploratory, and social behavior. Chronic treatment with antidepressants (imipramine or fluoxetine) attenuated many of the behavioral effects of LPS, as well as LPS-induced changes in body temperature, adrenocortical activation, hypothalamic serotonin release, and the expression of splenic TNF-alpha mRNA. Taken together, these findings suggest that cytokines are involved in the etiology and symptomatology of illness-associated depression.

Adolescent↗
PubMed1999

Venlafaxine: acute and chronic effects on 5-hydroxytryptamine levels in rat brain in vivo.

Venlafaxine is a dual serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline uptake inhibitor which has been claimed to have an onset of antidepressant action which is faster than for other comparable drugs. The effects of venlafaxine on brain 5-HT levels in vivo have not yet been examined. Acute administration of venlafaxine to rats by i.p. injection resulted in dose-dependent increases in cortical and hippocampal 5-HT levels, as measured by in vivo microdialysis, over the range 5-20 mg/kg. The effect of venlafaxine (10 mg/kg i.p.) was potentiated by prior administration of pindolol (10 mg/kg s.c.) in hippocampus but not in frontal cortex. Daily administration of venlafaxine (5 mg/kg i.p.) for 4 weeks did not change basal 5-HT levels in either brain area. The effect of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.2 mg/kg s.c.) to reduce 5-HT levels was unaffected by chronic venlafaxine at this dose, indicating that there was no change in sensitivity of presynaptic 5-HT1A autoreceptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Low doses of ipsapirone increase growth hormone but not oxytocin secretion in normal male and female subjects.

OBJECTIVE: The present study investigated whether administration of a 5-HT1A receptor agonist would increase growth hormone (GH) and oxytocin levels in normal human subjects, and whether the responses would be modified according to the age and gender of the subjects. METHODS: Ipsapirone (0.3 mg/kg body weight), or placebo was administered to 30 normal subjects (14 males, 19-74 years and 16 females, 22-69 years) using a randomized, double blind design. RESULTS: Stimulation of GH secretion by ipsapirone was significantly greater in male compared to female subjects, with no apparent effect of age. Oxytocin secretion was not stimulated by ipsapirone compared to placebo in any of the groups. CONCLUSIONS: The effects of gender and age on the degree of stimulation of GH secretion by 5-HT1A agonists in human subjects differ from their effects on secretion of the hormones ACTH and cortisol. A higher dose of ipsapirone is required to stimulate oxytocin secretion in normal human subjects.

Adult↗
PubMed1999

5-HT1A receptor function in normal subjects on clinical doses of fluoxetine: blunted temperature and hormone responses to ipsapirone challenge.

Serotonergic receptors of the 5-HT1A subtype have been suggested to play a pivotal role in the mechanism of action of antidepressant drugs, including specific serotonin reuptake inhibitors (SSRIs). We examined the effect of clinical doses of the SSRI, fluoxetine, on 5-HT1A receptor function in 15 normal volunteers. Hypothermic and hormone responses to the 5-HT1A receptor agonist, ipsapirone (0.3 mg per kg, per os) were examined after two weeks of placebo and again, after the subjects had been receiving fluoxetine for four weeks. On fluoxetine, the hypothermic response to ipsapirone was significantly blunted, as were ACTH, cortisol and growth hormone release. Ipsapirone plasma levels were significantly increased by fluoxetine but a pharmacokinetic effect could not have accounted for the observed blunting of 5-HT1A receptor mediated effects. These findings confirm and extend previous observations in rodents and humans and indicate that both post-synaptic 5-HT1A receptors in the hypothalamus, which mediate hormone responses to 5-HT1A agonists, and pre-synaptic 5-HT1A receptors which (putatively) mediate the hypothermic response, are rendered subsensitive by chronic SSRI administration. Since fluoxetine did not have significant effects on mood and other psychological variables in these subjects, alterations in 5-HT1A receptor function induced by SSRIs may have psychotropic relevance only in the context of existing perturbations of serotonergic function which underlie the psychopathological states in which these drugs are therapeutically effective.

Adrenocorticotropic Hormone↗
PubMed1999

Glassy dynamics and aging in an exactly solvable spin model.

We introduce a simple two-dimensional spin model with short-range interactions which shows glassy behavior despite a Hamiltonian which is completely homogeneous and possesses no randomness. We solve exactly for both the static partition function of the model and the distribution of energy barriers, giving us the equilibration time scales at low temperature. Simulations of instantaneous quenches and of annealing of the model are in good agreement with the analytic calculations. We also measure the two-time spin correlation as a function of waiting time, and show that the model has aging behavior consistent with the distribution of barrier heights. The model appears to have no sharp glass transition. Instead, it falls out of equilibrium at a temperature which decreases logarithmically as a function of the cooling time.

Journal Article↗
PubMed1999

Scaling and percolation in the small-world network model.

In this paper we study the small-world network model of Watts and Strogatz, which mimics some aspects of the structure of networks of social interactions. We argue that there is one nontrivial length-scale in the model, analogous to the correlation length in other systems, which is well-defined in the limit of infinite system size and which diverges continuously as the randomness in the network tends to zero, giving a normal critical point in this limit. This length-scale governs the crossover from large- to small-world behavior in the model, as well as the number of vertices in a neighborhood of given radius on the network. We derive the value of the single critical exponent controlling behavior in the critical region and the finite size scaling form for the average vertex-vertex distance on the network, and, using series expansion and Padé approximants, find an approximate analytic form for the scaling function. We calculate the effective dimension of small-world graphs and show that this dimension varies as a function of the length-scale on which it is measured, in a manner reminiscent of multifractals. We also study the problem of site percolation on small-world networks as a simple model of disease propagation, and derive an approximate expression for the percolation probability at which a giant component of connected vertices first forms (in epidemiological terms, the point at which an epidemic occurs). The typical cluster radius satisfies the expected finite size scaling form with a cluster size exponent close to that for a random graph. All our analytic results are confirmed by extensive numerical simulations of the model.

Disease Outbreaks↗
PubMed1999

Chronic clomipramine and triiodothyronine increase serotonin levels in rat frontal cortex in vivo: relationship to serotonin autoreceptor activity.

Augmentation of tricyclic antidepressant (TCA) treatment with triiodothyronine (T3) has been shown to potentiate the therapeutic effect of TCA drugs in depressed patients. We have attempted to elucidate the mechanism of this potentiation by determining the effects of T3 alone and together with a TCA on serotonin (5-HT) levels in living rats, using in vivo microdialysis. A single s.c. injection of T3 at 0.1 mg/kg had no effect on 5-HT levels in frontal cortex or hippocampus. Chronic administration of clomipramine (10 mg/kg i.p. daily for 4 weeks) to rats resulted in increased basal 5-HT levels in the frontal cortex. Administration of T3 daily for 7 days at 0.1 mg/kg s.c. also resulted in elevated 5-HT levels, whereas in rats administered both clomipramine and T3, cortical 5-HT levels were significantly elevated compared with the levels in rats that had received only one treatment. Basal levels in hippocampus were unaffected by these treatments. Subcutaneous injection of the 5-HT-1a receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (0.2 mg/kg) resulted in a decrease in 5-HT levels in both cortex and hippocampus. In frontal cortex of animals that had received T3 or a combination of clomipramine and T3, the extent of the decrease was significantly reduced compared to that seen in control animals. The extent of the decrease in hippocampus was not affected by any of the treatments. Subcutaneous injection of the 5-HT-1b/1d antagonist GR 127935 (5 mg/kg) resulted in an increase in 5-HT levels in both brain areas. The extent of the increase was not affected by any of the treatments in either brain area. It is concluded that the action of T3 in potentiating the clinical response to TCA drugs may be due to its effect on 5-HT levels in the frontal cortex, which is due to desensitization of the presynaptic 5-HT-1a autoreceptors.

Animals↗
PubMed1998

Role of serotonin in the amygdala in hypothalamo-pituitary-adrenocortical responses.

In view of the fact that the amygdala (AMG) and hypothalamic serotonin (5-HT) have an excitatory effect on the hypothalamo-pituitary-adrenal (HPA) axis, we have investigated the role of 5-HT in the AMG on this response. In intact freely moving rats, a mildly stressing short photic stimulation caused depletion of median eminence CRH-41, due to its release into the portal circulation and a rise in serum ACTH and corticosterone levels. This effect was significantly inhibited in rats in which 5-HT was depleted in the AMG following local 5,7-dihydroxytryptamine administration, which did not affect hypothalamic 5-HT content. Also, local pretreatment with ketanserin (a 5-HT2 receptor antagonist) in the AMG had the same inhibitory effect on the HPA axis response. These results indicate that AMG 5-HT has an important role in the activation of the HPA axis following neural stimulation and that 5-HT2 receptors are involved.

5,7-Dihydroxytryptamine↗
PubMed1998

Neurochemical mechanisms of action of ECS: evidence from in vivo studies.

Recent advances in receptor pharmacology and in the understanding of intracellular signal-transduction systems have given rise to new theories of the mechanism of action of antidepressant drugs. The relevance of these theories to the antidepressant mechanism(s) of electroconvulsive shock (ECS) is discussed, with a view to increasing understanding of the mechanism of electroconvulsive therapy (ECT). Particular attention is given to results obtained with in vivo methods both in experimental animals and in human subjects.

Animals↗
PubMed1998

Wernicke-Korsakoff amnestic syndrome secondary to malnutrition in a patient with schizoaffective disorder.

OBJECTIVE: The authors identify a rare case of Wernicke-Korsakoff amnestic syndrome and highlight its occurrence in the absence of alcohol dependence. METHOD: A longitudinal case history of a patient with schizoaffective disorder who developed Wernicke-Korsakoff syndrome secondary to malnutrition. RESULTS: Refusal to eat based on persecutory delusions in chronic psychotic patients can cause malnutrition and result in Wernicke-Korsakoff syndrome. CONCLUSIONS: With increasing managed-care demands for outpatient treatment of chronic psychotic patients, physicians may see more cases of Wernicke-Korsakoff syndrome in psychiatric populations.

Amnesia↗
PubMed1997

A model of mass extinction.

In the last few years a number of authors have suggested that evolution may be a so-called self-organized critical phenomenon, and that critical processes might have a significant effect on the dynamics of ecosystems. In particular it has been suggested that mass extinction may arise through a purely biotic mechanism as the result of "coevolutionary avalanches". In this paper we first explore the empirical evidence which has been put forward in favor of this conclusion. The data center principally around the existence of power-law functional forms in the distribution of the sizes of extinction events and other quantities. We then propose a new mathematical model of mass extinction which does not rely on coevolutionary effects and in which extinction is caused entirely by the action of environmental stress on species. In combination with a simple model of species adaption we show that this process can account for all the observed data without the need to invoke coevolution and critical processes. The model also makes some independent predictions, such as the existence of "aftershock" extinctions in the aftermath of large mass extinction events, which should in theory be testable against the fossil record.

Animals↗
PubMed1997

Chronic electroconvulsive shock and 5-HT autoreceptor activity in rat brain: an in vivo microdialysis study.

In vivo microdialysis was used to determine the effects of chronic electroconvulsive shock (ECS), given daily for 10 days, on basal 5-HT levels in rat frontal cortex and hippocampus and on the effect of systemic administration of the 5-HT-la receptor agonist, 8-OH-DPAT (0.2 mg/kg), to reduce 5-HT levels in these areas by activation of somatodendritic autoreceptors. Neither basal 5-HT levels nor the effects of 8-OH-DPAT on 5-HT levels were altered after chronic ECS. The effect of systemic administration of the 5-HT1A and 5-HT1B antagonist, (+/-)-pindolol (10 mg/kg), to increase 5-HT levels in hippocampus, was also not affected by chronic ECS.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

In vivo cyclic AMP responses in rat brain are not modified by chronic electroconvulsive shock.

In vivo microdialysis was used to determine the effects of chronic electroconvulsive shock (ECS), given daily for 10 days, on the cyclic AMP (cAMP) responses to noradrenaline (NA) and to forskolin in the cortex of freely-moving conscious rats. Microdialysis probes were inserted on the final day of ECS administration, and cAMP responses measured the following day. Chronic ECS did not modify the responses to either NA or forskolin. These results differ markedly from those previously obtained with incubated slices of rat brain. It is concluded that care is needed in interpreting results obtained by either ex vivo or in vitro methods.

Adrenergic alpha-Agonists↗
PubMed1996

A model for evolution and extinction.

We present a model for evolution and extinction in large ecosystems. The model incorporates the effects of interactions between species and the influences of abiotic environmental factors. We study the properties of the model by approximate analytic solution and also by numerical simulation, and use it to make predictions about the distribution of extinctions and species lifetimes that we would expect to see in real ecosystems. It should be possible to test these predictions against the fossil record. The model indicates that a possible mechanism for mass extinction is the coincidence of a large coevolutionary avalanche in the ecosystem with a severe environmental disturbance.

Animals↗