Itô versus Stratonovich white-noise limits for systems with inertia and colored multiplicative noise.

We consider the dynamics of systems in the presence of inertia and colored multiplicative noise. We study the limit where the particle relaxation time and the correlation time of the noise both tend to zero. We show that the limiting equation for the particle position depends on the magnitude of the particle relaxation time relative to the noise correlation time. In particular, the limiting equation should be interpreted either in the Itô or Stratonovich sense, with a crossover occurring when the two fast-time scales are of comparable magnitude. At the crossover the limiting stochastic differential equation is neither of Itô nor of Stratonovich type. This means that, after adiabatic elimination, the governing equations have different drift fields, leading to different physical behavior depending on the relative magnitude of the two fast-time scales. Our findings are supported by numerical simulations.

Clinical efficacy and safety of fluticasone propionate 250 microg twice daily administered via a HFA 134a pressurized metered dose inhaler to patients with mild to moderate asthma. French study group.

This study compared the efficacy and safety of the fluticasone propionate 125 microg pressurized metered dose inhaler (pMDI) propelled by either hydrofluoroalkane (HFA) 134a or chlorofluorocarbon (CFC) propellants, in adult patients with asthma. HFA 134a is a non-ozone depleting propellant used as a replacement for the CFC propellants 11 and 12 which are being phased out in accordance with the Montreal Protocol. Three hundred and eighty patients with mild to moderate asthma and 'room for improvement' in their treatment were randomized to receive fluticasone propionate 250 microg twice daily via pMDIs propelled by either CFC propellants 11 and 12 (n = 195) or HFA 134a (n = 185). Fluticasone propionate significantly improved lung function over the 4-week treatment period in both treatment groups. The improvement in mean morning peak expiratory flow (PEF) after 7 days of treatment was approximately 12 l min(-1) in both groups, rising to approximately 22 l min(-1) at the end of the 4-week treatment period. The adjusted mean difference between the two formulations over weeks 1-4 was -1 l min(-1) (90% confidence interval: -7, 5 l min(-1)), confirming their equivalence. Clinical comparability was also demonstrated with respect to secondary efficacy variables, including daily symptom scores, evening PEF and clinic visit expiratory measurements. There were no clinically relevant differences in adverse events or serum cortisol levels between the two groups. The fluticasone propionate 125 microg HFA 134a pMDI is an effective and well tolerated product and is a suitable replacement for the fluticasone propionate 125 microg CFC pMDI at a microgram equivalent dose.

A model mechanism for the chemotactic response of endothelial cells to tumour angiogenesis factor.

In order to accomplish the transition from avascular to vascular growth, solid tumours secrete a diffusible substance known as tumour angiogenesis factor (TAF) into the surrounding tissue. Endothelial cells which form the lining of neighbouring blood vessels respond to this chemotactic stimulus in a well-ordered sequence of events consisting, at minimum, of a degradation of their basement membrane, migration, and proliferation. A model mechanism is presented which includes the diffusion of the TAF into the surrounding host tissue and the response of the endothelial cells to the chemotactic stimulus. The model accounts for the main observed events associated with the endothelial cells during the process of angiogenesis (i.e. cell migration and proliferation); the numerical results compare very well with experimental observations. The situation where the tumour (i.e. the source of TAF) is removed and the vessels recede is also considered.

Inhaled salmeterol in the treatment of patients with moderate to severe reversible obstructive airways disease--a 3-month comparison of the efficacy and safety of twice-daily salmeterol (100 micrograms) with salmeterol (50 micrograms).

Three-hundred and fifty patients with moderate to severe reversible obstructive airways disease (forced expiratory volume in 1 s or peak expiratory flow rate < or = 50% predicted, a 15% reversibility to inhaled salbutamol and symptomatic) were recruited into a multi-centre, multinational, double-blind, parallel-group randomized study. Two-hundred and eighty-three patients were randomized to receive 50 micrograms salmeterol twice daily or 100 micrograms salmeterol twice daily administered from a metered-dose inhaler for 3 months. Salbutamol (100 micrograms per metered actuation) was provided for symptomatic relief. Morning and evening peak expiratory flow rate (PEFR), day-time and night-time asthma symptoms and additional bronchodilator usage were recorded by the patient on a daily basis. Lung function and patient/physician assessment of treatment efficacy were recorded at scheduled clinic visits. Safety was determined by monitoring adverse events and standard biochemical, haematological and cardiovascular parameters. Salmeterol 100 micrograms twice daily was consistently superior to salmeterol 50 micrograms twice daily in morning and evening PEFR measurements (mean differences between the treatments: 10-14 l min-1 for morning, 95% CI-0, 22 l min-1, P = 0.047; and 10-15 l min-1 for evening, 95% CI 2, 22 l min-1, P = 0.023). The improvement in PEFR was independent of concurrent steroid usage, with the most marked improvement being seen in the more severe asthmatics requiring concurrent oral corticosteroids (mean differences between the treatments: 27-31 l min-1, 95% CI: 3,55 l m-1, P = 0.027).(ABSTRACT TRUNCATED AT 250 WORDS)

A mathematical model for the diffusion of tumour angiogenesis factor into the surrounding host tissue.

Unless they are furnished with an adequate blood supply and a means of disposing of their waste products by a mechanism other than diffusion, solid tumours cannot grow beyond a few millimetres in diameter. It is now a well-established fact that, in order to accomplish this neovascularization, solid tumours secrete a diffusable chemical compound known as tumour angiogenesis factor (TAF) into the surrounding tissue. This stimulates nearby blood vessels to migrate towards and finally penetrate the tumour. Once provided with the new supply of nutrient, rapid growth takes place. In this paper, a mathematical model is presented for the diffusion of TAF into the surrounding tissue. The complete process of angiogenesis is made up of a sequence of several distinct events and the model is an attempt to take into account as many of these as possible. In the diffusion equation for the TAF, a decay term is included which models the loss of the chemical into the surrounding tissue itself. A threshold distance for the TAF is incorporated in an attempt to reflect the results from experiments on corneal implants in test animals. By formulating the problems in terms of a free boundary problem, the extent of the diffusion of TAF into the surrounding tissue can be monitored. Finally, by introducing a sink term representing the action of proliferating endothelial cells, the boundary of the TAF is seen to recede, and hence the position and movement of the capillaries can be indirectly followed. The changing concentration gradient observed as the boundary recedes may offer a possible explanation for the initiation of anastomosis. Several functions are considered as possible sink terms and numerical results are presented. The situation where the tumour (i.e. the source of TAF) is removed is also considered.

Pharmacological characterization of the voltage-dependent sodium channels of rainbow trout brain synaptosomes.

Batrachotoxin, aconitine, and veratridine, alkaloid activators of voltage-dependent sodium channels, stimulated 22Na+ uptake by rainbow trout brain synaptosomes. The potency and efficacy of activation by these compounds decreased in the following order: batrachotoxin greater than aconitine much greater than veratridine. Aconitine-stimulated sodium uptake was completely inhibited by tetrodotoxin, a specific blocker of voltage-dependent sodium channels. Polypeptide toxins in the venom of the scorpion, Leiurus quinquestriatus, and the insecticide DDT enhanced veratridine-dependent sodium uptake but had no effect on non-specific uptake. These studies identify appropriate conditions for measuring sodium channel-dependent 22Na+ uptake in trout brain synaptosomes and characterize some of the pharmacological properties of trout brain sodium channels. Trout sodium channels differed from those in rat and mouse brain in their responses to batrachotoxin, aconitine, veratridine, and DDT but not to tetrodotoxin and Leiurus venom toxins. These results suggest that the specificity of some of the neurotoxin-binding domains of the trout brain sodium channel may differ from those of sodium channels in mammalian brain.

A semi-quantitative atlas of 5-hydroxytryptamine-1 receptors in the primate brain.

The regional distribution of 5-hydroxytryptamine-1 receptors in the primate brain was studied by semi-quantitative autoradiographic analysis of tritiated ligand binding. Areas showing the highest density of 5-hydroxytryptamine-1 receptors (greater than 200 fmol [3H]5-hydroxytryptamine bound per mg tissue), included the cerebral cortex (laminae I-II), claustrum, posterior cell group of the basal nucleus of Meynert, the infracommissural part of the globus pallidus, cortical amygdaloid nucleus, hippocampal formation (CA1-subiculum region, the anterior CA2, CA3 and CA4 regions and the molecular layer of the dentate gyrus), thalamic nuclei (parafascicular, parataenial, paraventricular and superior central lateral nuclei), substantia nigra pars reticulata, dorsal raphe nucleus and choroid plexus. The distribution of 5-hydroxytryptamine-1 receptors is compared to the distribution of both 5-hydroxytryptamine receptors and terminal fields of serotonergic projections as previously described in subprimates.

The ultrastructure of the larval malpighian tubules of a saline-water mosquito.

The larval Malpighian tubules of the saline-water mosquito Aedes taeniorhynchus were examined using light and electron microscopy. The tubules contain two cell types; primary cells and stellate cells. Primary cells are characterized by their size (70 microns x 70 microns x 10 microns) and an abundance of intracellular membrane-bound crystals. Two types of microvilli are found on the luminal surface of the primary cells: (1) small microvilli containing core microfilaments and extensions of endoplasmic reticulum, and (2) larger microvilli (approximately equal to 3 microns in length) which in addition to the above components contain a mitochondrion along their entire length. Both microvillar types have abundant knobs lining the cytoplasmic surface of the microvillar membrane. These knobs, which are often found in insect ion transporting tissues, have been termed 'portasomes' by Harvey (1980). The possible role of these structures in ion transport and mitochondrial positioning is discussed. The stellate cells are much smaller than the primary cells, and lack intracellular crystals. Their microvilli are smaller as well (approximately equal to 0 x 6 microns in length) and contain no endoplasmic reticulum, mitochondria or knobs. The cells types found in the saline-water mosquito larva, Aedes taeniorhynchus, are identical to those found in Aedes aegypti, indicating that the unique capacity of saline-water mosquito larvae to transport Mg2+ and SO42 is not associated with the presence of an additional cell type.

Morphological and functional aspects of an insect epidermal gland.

The sternal gland of primitive termites of the genus Zootermopsis (Z. nevadensis or Z. angusticollus) (Hagen) seems more organized than that of higher termites, in being comprised of three cell layers. It is also studded with about 200 campaniform sensilla. Below the meshwork cuticle of the gland lies a layer of columnar epithelial cells whose apical surfaces form a brush border, and whose basal surfaces are sculptured into a basketwork into which the second layer fits. Below the brush border are small microtubule-associated pits and coated vesicles. No channels can be seen either within or, except for the sensilla, between the cells. The second cell layer probably secretes the trail-following pheromone. Numerous electron-lucent droplets and large channels containing lipid micelles are found in the cytoplasm here, but the channels cannot be traced out of the secretory layer. The third layer consists of large pyriform cells. The campaniform sensilla are composed of three cells: the sensory cell proper whose dendrite carries a modified 9 + 0 sensory process, an accessory supporting cell that secretes an electron-opaque sheath, and an enveloping cell. At the cell borders of the sensillum, regions of septate and tight junction appear. There are also septate junctions between columnar cells and possibly tight junctions between columnar and secretory cells that would open an intracellular and molecular pathway to the endocuticle. The campaniform sensilla may be part of a feedback control system that determines the amount of pheromone deposited during trail laying.

Alarm, defense, and construction behavior relationships in termites (Isoptera).

Evidence indicates that building behavior in termites is a direct consequence of low-level alarm stimuli and that its immediate function is defense. As in other forms of termite defense behavior, recruitment of nymphs and workers is accomplished by trail laying in conjuction with transmission of the alarm. The number recruited is related to the intensity of the input stimulus. Primary construction ceases when the original causal stimulus is eliminated by the effects of the actual building.