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Biomedical subjects

D Halpern

Publications and source records attributed to D Halpern.

At least 19 recordsLinked to original sources

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

Muscular hypertonia: quantitative analysis.

By a statistical method of analysis, the force applied to move a limb passively can be translated into physiologically relevant parameters relating to the muscle. The parameters identified and measured are the dynamic and static activity of the muscle and their interactions with the varying length of the muscle during stretch. This method of analysis has been shown to be of assistance in evaluating the reflex status of persons with central nervous system disorders in preparation for treatment and in measuring the effects of treatment.

Humans

Intramuscular neurolysis for spasticity in children.

Intramuscular neutrolysis with phenol has been used for 10 years in the management of spasticity in children. Best results depend on fastidious technique and realistic use of the procedure. Sedation or anesthesia was used in all cases -- 5% phenol in water was used for all procedures. The main indications were spasticity which interfered with function, either actual or potential, or with care. Where uninhibited vestibular or tonic neck reflexes affect muscle tone, or there is dystonia or athetosis, the procedure is less effective than where spasticity alone is present. Duration of relief of spasticity ranged from 1 month to more than 2 years. About one half of the lower extremity muscle treated required tenotomy later. Generally training was required after the procedure to obtain improved function. A representative sample of muscles treated, repeat procedures, and later surgery is discussed. The procedure is recommended for use in the management of spasticity in children as a way of improving function and/or care.

Adolescent

Electromyographic feedback and physical therapy for neuromuscular retraining in hemiplegia.

Electromyographic feedback was compared with physical therapy for its relative effectiveness in training motor activity in patients with hemiplegia. A cross over design was used, so that each patient served as his own control. Strong reinforcement for attentional direction and for successful response to established criteria was used with both modalities. Electromyography through auditory and visual display was found effective in improving electromyographic activity, but more limited in training effective function as measured by active range of motion. In some cases it was counterproductive. Using an instrumental modality permits attention to only a limited number of motor elements involved in a motion, and is even more limited with respect to the interplay of activation and inhibition of those components. The activity of physical therapy, using tactile, proprioceptive, visual and communicative modalities, has the capacity for attending and drawing attention to many motor elements, as well as to the complexities of activation of some components concomitantly with the inhibition of others during the training process. Electromyographic feedback was felt to be especially useful in its ability to enhance figure-background discrimination and bypass possible areas of sensory obtundation.

Aged