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Biomedical subjects

D Halpern

Publications and source records attributed to D Halpern.

At least 19 recordsLinked to original sources

The effect of airway wall motion on surfactant delivery.

Soluble surfactant and airway surface liquid transport are examined using a mathematical model of Marangoni flows which accounts for airway branching and for cyclic airway stretching. Both radial and longitudinal wall strains are considered. The model allows for variation of the amplitude and frequency of the motion, as may occur under a variety of ventilatory situations occurring during surfactant replacement therapy. The soluble surfactant dynamics of the thin fluid film are modeled by linear sorption. The delivery of surfactants into the lung is handled by setting the proximal boundary condition to a higher concentration compared to the distal boundary condition. Starting with a steady-state, nonuniform, surfactant distribution, we find that transport of surfactant into the lung is enhanced for increasing strain amplitudes. However, for fixed amplitude, increasing frequency has a smaller effect. At small strain amplitudes, increasing frequency enhances transport, but at large strain amplitudes, increasing cycling frequency has the opposite effect.

Animals↗

Intestinal obstruction from midgut volvulus after laparoscopic appendectomy.

We present the case of a 30-year-old man who developed a small bowel obstruction from an acute midgut volvulus 8 days after undergoing a laparoscopic appendectomy. There was no evidence of congenital malrotation or midgut volvulus on the initial computed tomography (CT) scan or at laparoscopy. Subsequently, a midgut volvulus developed in the absence of congenital malrotation.

Abdominal Pain↗

The ethnic density effect: results from a national community survey of England and Wales.

Using data from a community survey of 5196 ethnic minority and 2867 white respondents, together with data on local group concentration from the 1991 Census, the hypothesis was tested that ethnic group concentration is associated with lower levels of reported psychiatric symptoms. The hypothesis was broadly confirmed, both for within- and between-group differences. However, the effect was found to be modest in size and in one group, the Pakistani sample, was reversed. The findings are inconsistent with an explanation based on selection or drift. Linguistic factors contributed to, but did not explain the effects. Evidence on victimisation and mutual support suggests that social causation, in the form of reduced exposure to direct prejudice and increased social support, is a likely cause of the effect.

England↗

Mathematical model of gas bubble evolution in a straight tube.

Deep sea divers suffer from decompression sickness (DCS) when their rate of ascent to the surface is too rapid. When the ambient pressure drops, inert gas bubbles may form in blood vessels and tissues. The evolution of a gas bubble in a rigid tube filled with slowly moving fluid, intended to simulate a bubble in a blood vessel, is studied by solving a coupled system of fluid-flow and gas transport equations. The governing equations for the fluid motion are solved using two techniques: an analytical method appropriate for small nondeformable spherical bubbles, and the boundary element method for deformable bubbles of arbitrary size, given an applied steady flow rate. A steady convection-diffusion equation is then solved numerically to determine the concentration of gas. The bubble volume, or equivalently the gas mass inside the bubble for a constant bubble pressure, is adjusted over time according to the mass flux at the bubble surface. Using a quasi-steady approximation, the evolution of a gas bubble in a tube is obtained. Results show that convection increases the gas pressure gradient at the bubble surface, hence increasing the rate of bubble evolution. Comparing with the result for a single gas bubble in an infinite tissue, the rate of evolution in a tube is approximately twice as fast. Surface tension is also shown to have a significant effect. These findings may have important implications for our understanding of the mechanisms of inert gas bubbles in the circulation underlying decompression sickness.

Atmospheric Pressure↗

Surfactant effects in model airway closure experiments.

The capillary instability that occurs on an annular film lining a tube is studied as a model of airway closure. Small waves in the film can amplify and form a plug across the tube. This dynamical behavior is studied using theoretical models and bench-top experiments. Our model predicts the initial growth rate of the instability and its dependence on surfactant effects. In experiments, an annular film is formed by infusion of water into an initially oil-filled glass capillary tube. The thickness of the oil film varies with the infusion flow rate. The instability growth rate and closure time are measured for a range of film thicknesses. Our theory predicts that a thinner film and higher surfactant activity enhance stability; surfactant can decrease the growth rate to 25% of its surfactant-free value. In experiments, we find that surfactant can decrease the growth rate to 20% and increase the closure time by a factor of 3.8. Functional values of a critical film thickness for closure support the theory that it increases in the presence of surfactant.

Animals↗

A theoretical study of surfactant and liquid delivery into the lung.

A computational study is presented for the transport of liquids and insoluble surfactant through the lung airways, delivered from a source at the distal end of the trachea. Four distinct transport regimes are considered: 1) the instilled bolus may create a liquid plug that occludes the large airways but is forced peripherally during mechanical ventilation; 2) the bolus creates a deposited film on the airway walls, either from the liquid plug transport or from direct coating, that drains under the influence of gravity through the first few airway generations; 3) in smaller airways, surfactant species form a surface layer that spreads due to surface-tension gradients, i.e., Marangoni flows; and 4) the surfactant finally reaches the alveolar compartment where it is cleared according to first-order kinetics. The time required for a quasi-steady-state transport process to evolve and for the subsequent delivery of the dose is predicted. Following fairly rapid transients, on the order of seconds, steady-state transport develops and is governed by the interaction of Marangoni flow and alveolar kinetics. Total delivery time is approximately 24 h for a typical first dose. Numerical solutions show that both transit and delivery times are strongly influenced by the strength of the preexisting surfactant and the geometric properties of the airway network. Delivery times for follow-up doses can increase significantly as the level of preexisting surfactant rises.

Algorithms↗

Intrauterine levels of human decidua-associated protein (hDP) 200 in normal pregnancy and missed abortion.

Levels of human decidua-associated protein (hDP) 200 were measured in amniotic fluid samples, obtained from 32 induced and 21 missed abortions at 9-20 weeks of pregnancy. A 3-fold decrease in the hDP 200 level was observed between 9 and 20 weeks of normal pregnancy. Moreover, no significant difference was observed comparing the level of hDP 200 and the pattern of its decrease in missed and induced abortions. Thus, according to our results, hDP 200, being a monoclonal rheumatoid factor, is probably not required for the continuation of normal pregnancy.

Abortion, Missed↗

Tolerance of suicide, religion and suicide rates: an ecological and individual study in 19 Western countries.

BACKGROUND: Negative associations between religion and suicide, in individuals and countries, may be mediated by the degree to which suicide is tolerated. METHODS: Linear regression was used to examine ecological associations between suicide tolerance, religion and suicide rates in 19 Western countries in 1989/90. Logistic regression was used to study associations between suicide tolerance and strength of religious belief in 28085 individuals in these countries. The concept of effect modifying function was used to examine whether the strength of the association between suicide tolerance and religious belief in individuals depended on the extent of religious belief in their country. RESULTS: Higher female suicide rates were associated with lower aggregate levels of religious belief and, less strongly, religious attendance. These associations were mostly attributable to the association between higher tolerance of suicide and higher suicide rates. In the 28085 subjects suicide tolerance and the strength of religious belief were negatively associated even after adjustment for other religious and sociodemographic variables and general tolerance levels (odds ratios: men 0.74 (95% CI 0.58-0.94), women 0.72 (95% CI 0.60-0.86)). This negative individual-level association was more pronounced in more highly religious countries but this modifying effect of the religious context was apparent for men only. CONCLUSIONS: Ecological associations between religious variables and suicide rates are stronger for women than men, stronger for measures of belief than observance and mediated by tolerance of suicide. In individuals, stronger religious beliefs are associated with lower tolerance of suicide. Personal religious beliefs and, for men, exposure to a religious environment, may protect against suicide by reducing its acceptability.

Adult↗

Interaction of exogenous and endogenous surfactant: spreading-rate effects.

The spreading rate of an exogenous surfactant monolayer due to surface tension gradients is examined by using our previously reported theoretical analysis, with particular attention given to the effects of endogenous surfactant. It is found that the presence of an endogenous surfactant reduces the spreading rate of exogenous surfactant and that, in certain circumstances, the spreading may be halted. A recently published paper (F. F. Espinosa, A. H. Shapiro, J. J. Fredberg, and R. D. Kamm. J. Appl. Physiol. 75: 2028-2039, 1993) reaches the opposite conclusion about the effect of endogenous surfactant, i.e., that the presence of an endogenous surfactant increases the spreading rate of the exogenous surfactant. This communication discusses the relevant issues associated with these different results and what the implications may be for surfactant replacement therapy. It is found that the endogenous surfactant, which is ahead of the advancing exogenous surfactant front, undergoes a concentration increase due to surface area compression of the air-liquid interface. Hence the spreading exogenous surfactant can raise surfactant concentrations in regions distal to its own location, and this is a previously unrecognized potential therapeutic mechanism of instilled surfactants. After initial instillations of intratracheal boluses of exogenous surfactant, additional surfactant may better reach the desired target site if delivered by aerosol. Predictions of surfactant and piggy-backed drug-delivery times through the lung are also discussed.

Biofilms↗

Endogenous epidermal growth factor regulates limb development.

Mutations associated with genes of the EGF superfamily are implicated in limb malformations. To evaluate the potential role of EGF-mediated signal transduction in the control of early mammalian limb development, we developed a simple in vitro system which is permissive for morphogenesis and cytodifferentiation in serumless, chemically defined medium. Our experimental strategy was to ascertain if the EGF precursor gene was transcribed and translated into potentially bioactive growth factor. EGF mRNA transcripts are expressed in Swiss Webster mouse embryonic (42-44 somite pairs) forelimbs as determined by mRNA phenotyping. EGF transcripts are translated into precursor EGF polypeptides which were localized to limb covering epithelium and the chondrogenic mesenchymal cell lineages. EGF immunostaining patterns suggested a paracrine type of regulation for the cartilage blastema associated with forelimb development. To test whether EGF effects the timing and positional information required for limb-specific cartilage morphogenesis, we employed tyrphostin (RG 50864) which inhibits EGF receptor kinase activity in a concentration-dependent manner and severely retards limb development. These findings support our hypothesis that endogenous EGF or EGF-like proteins provide signaling for the size and shape of discrete forelimb cartilage formations during mouse embryonic morphogenesis.

Animals↗

Minorities and mental health.

It is argued that minority status, despite some recent evidence to the contrary, is a risk factor for mental ill-health. The evidence reviewed suggests that it is the experience at the local, rather than national, level that is critical. The effect appears to be due to the reduced exposure to prejudice and increased social support that a consonant group offers. The effect cannot be readily explained in terms of social selection.

Health Status Indicators↗

Surfactant effects on fluid-elastic instabilities of liquid-lined flexible tubes: a model of airway closure.

A theoretical analysis is presented predicting the closure of small airways in the region of the terminal and respiratory bronchioles. The airways are modelled as thin elastic tubes, coated on the inside with a thin viscous liquid lining. This model produces closure by a coupled capillary-elastic instability leading to liquid bridge formation, wall collapse or a combination of both. Nonlinear evolution equations for the film thickness, wall position and surfactant concentration are derived using an extended version of lubrication theory for thin liquid films. The positions of the air-liquid and wall-liquid interfaces and the surfactant concentration are perturbed about uniform states and the stability of these perturbations is examined by solving the governing equations numerically. Solutions show that there is a critical film thickness, dependent on fluid, wall and surfactant properties above which liquid bridges form. The critical film thickness, epsilon c, decreases with increasing mean surface-tension or wall compliance. Surfactant increases epsilon c by as much as 60 percent for physiological conditions, consistent with physiological observations. Airway closure occurs more rapidly with increasing film thickness and wall flexibility. The closure time for a surfactant rich interface can be approximately five times greater than an interface free of surfactant.

Adolescent↗

Gas dispersion in volume-cycled tube flow. I. Theory.

A mathematical theory is derived for the dispersion of a contaminant bolus introduced into a fully developed volume-cycled oscillatory pipe flow. The convection-diffusion equation is solved for a tracer gas bolus by expressing the local concentration field as a series expansion of derivatives of the area-averaged concentration. The local, as well as the area-averaged, concentration is determined for a uniform initial slug or Gaussian bolus. The effect of various flow parameters such as Womersley parameter, Schmidt number, and tidal volume is investigated. The overall dispersion is characterized by a time-averaged effective diffusion coefficient, which for long duration coincides with previous dispersion theories based on a constant linear axial concentration profile. The effective diffusion coefficient can be determined from the local time history of concentration, independent of the spatial location or the initial tracer bolus. Furthermore the local peaks of the concentration-time curve follow a decaying curve dictated by the time-averaged effective diffusion coefficient. Thus the theory is directly applicable for dispersion measurements in oscillatory tube flows, a basis for the pulmonary airways application, as shown by Gaver et al. (J. Appl. Physiol. 72: 321-331, 1992).

Bronchi↗

Gel electrophoresis of polystyrene particles in glutaraldehyde crosslinked polyvinyl alcohol.

Polystyrene sulfate and carboxylate particles (19-189 nm radius) were subjected to electrophoresis in glutaraldehyde crosslinked polyvinyl alcohol of molecular weight 25.000 and 650.000 Da at various concentrations. The degree of crosslinking is severely limited by the mechanical properties of the gels that deteriorate beyond a glutaraldehyde concentration which decreases with increasing polyvinyl alcohol chain length. The effective fiber radius of the short-chain and long-chain polymer fiber was 45 +/- 25 and 131 +/- 47 nm, respectively. Thus, these media do not significantly exceed the apparent fiber thickness of agarose, are more difficult to prepare--but are well-defined synthetic products rather than natural ones, and have the advantage of carrying no net charge and can therefore be expected to exhibit no electroendosmosis.

Cross-Linking Reagents↗

Leech therapy: when once is not enough.

Venous congestion is a constant threat in the survival of free flaps, pedicled flaps, tissue replantations and traumatized tissue. Leech therapy has proved effective in salvaging much of these compromised tissues. To be effective, leeches must be both readily available and hungry, requirements not always easily met. Our investigation seeks to establish a means to return sated leeches to their previous unfed, hungry state for reuse. Sated leeches were purged of their blood meals by placement in 3% hypertonic saline or by gentle finger pressure, then exposed to serotonin 0 microM (control), 10 microM, 30 microM or 90 microM for 20 min. Subsequent rebiting/refeeding was observed and analysed. Leeches bathed in serotonin rebit or reattached at nearly four times the rate of unexposed leeches; 30% vs 8% respectively. Biting, however, is not refeeding. Overall, 41 leeches were treated with serotonin with four (10%) refeeding. Those that refed consumed a significantly smaller blood meal than the initial feeding; 50% +/- 47% SD vs 348% +/- 143% SD of original body weight. None of the control group refed. As a method for routinely reusing leeches, serotonin bathing cannot be recommended. In the immediate postoperative period with the sudden emergence of venous congestion requiring leech therapy, but with an inadequate number available, this 20% [corrected] refeed rate after 10 microM serotonin exposure could potentially determine the success or failure of the flap/replantation until fresh leeches are made available.

Animals↗

Wrist subluxation in juvenile rheumatoid arthritis: pathophysiology and management.

Management principles in juvenile rheumatoid arthritis provide for long-term follow-up throughout all phases of disease activity, including apparent remission. Treatment is based on the stage of disease and anatomy and kinesiology of the joints. Palmar subluxation of the wrist requires proximal support by splints for prevention and correction. Small sphygmomanometer bags have been incorporated into splints for home stretching with demonstrated improvement in bony alignment.

Arthritis, Juvenile↗