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Biomedical subjects

D S Cohen

Publications and source records attributed to D S Cohen.

52 records · Page 3Linked to original sources

Pulmonary edema associated with salt water near-drowning: new insights.

In this case report we describe the clinical and laboratory findings of a man who nearly drowned after aspirating a large quantity of seawater. The aspiration of salt water, which is strongly hypertonic with respect to plasma, resulted in severe pulmonary edema, both from the quantity of aspirated seawater and the osmotically driven ultrafiltrate of plasma that accumulated in the air spaces. The initial concentration of protein in the edema fluid sample was very low, 0.7 g/dl, consistent with only a minimal increase in epithelial permeability. Approximately 4 h later, there was a marked increase in the concentration of protein in the residual alveolar fluid associated with improvement in several clinical indices, indicating that the excess alveolar fluid was reabsorbed very rapidly. In addition, the magnesium concentration was markedly elevated because of the aspiration of magnesium-containing seawater, which may have diagnostic importance for near-drowning in salt water. The data from this case provide evidence for well-preserved alveolar epithelial barrier function after aspiration of large quantities of hypertonic salt water.

Animals↗

Polarized regulation of fibronectin secretion and alternative splicing by transforming growth factor.

Fibronectin is a multifunctional protein that is synthesized in several different forms that result from alternative splicing of mRNA. Although expression of splicing variants appears to be both developmentally regulated and tissue-specific, the functional significance of these isoforms is largely unknown. We found that cultured airway epithelial cells vectorially secrete two distinct species of fibronectin, one which contains the alternatively spliced EIIIA region (EIIIA+) and one in which the EIIIA segment is spliced out (EIIIA-). Fibronectin containing the EIIIA region is preferentially secreted apically. Although both apical and basal stimulation with transforming growth factor beta 1 increased fibronectin synthesis, the secretory response differed depending on which surface was being stimulated. Apical secretion of fibronectin and expression of EIIIA+ fibronectin mRNA increased only after apical stimulation. These data demonstrate a novel mechanism for the polarized regulation of targeted secretion and alternative splicing of fibronectin and suggest that the EIIIA segment may act as a targeting signal for the vectorial secretion of fibronectin.

Amino Acid Sequence↗

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 1. (+/-)-(3-pyridinylbicycloheptyl)alkanoic acids.

The design, synthesis, and in vitro pharmacology of a new class of compounds exerting both thromboxane receptor antagonist and thromboxane synthase inhibitory activities is described. [(3-Pyridinyl)bicycloheptyl] alkanoic acid 9 and its analogues, designed with the help of molecular modeling, were synthesized and found to be inhibitors of thromboxane A2 (TxA2) biosynthesis in a human platelet microsomal preparation. The compounds were also found to antagonize both platelet and vascular TxA2 receptors. The compounds inhibited the U 46619 induced aggregation of human washed platelets and platelet-rich plasma and the U 46619 induced contraction of the dog saphenous vein.

Blood Platelets↗

The response of guinea pig airway epithelial cells and alveolar macrophages to environmental stress.

Cells lining the respiratory tract form an interface between the organism and the external environment and are repeatedly exposed to physical, chemical, and metabolic stresses. We examined the response of cultured guinea pig tracheal epithelial cells and alveolar macrophages to various forms of stress, including clinically and environmentally relevant metabolic stresses such as ozone and acid exposure. Classic stress treatments such as heat shock and sodium arsenite treatment induced the synthesis of 28, 32, 72, 73, 90, and 110 kD stress proteins similar to those observed in other cell types. In contrast, no significant changes in the pattern of protein synthesis were detected after exposure to ambient concentrations of ozone, although ozone exposure caused significant cytotoxicity to both cell types. Another potent oxidant, hydrogen peroxide, similarly did not induce appreciable stress protein synthesis. However, surface acidification of tracheal epithelial cells and alveolar macrophages caused the induction of 72 and 78 kD stress proteins. While stress proteins may play a role in the response of respiratory cells to certain injuries such as hyperthermia and surface acidification, they may not be important in the defense against ozone or other forms of oxidative injury.

Animals↗

Mercury exposure from interior latex paint.

BACKGROUND: Many paint companies have used phenylmercuric acetate as a preservative to prolong the shelf life of interior latex paint. In August 1989, acrodynia, a form of mercury poisoning, occurred in a child exposed to paint fumes in a home recently painted with a brand containing 4.7 mmol of mercury per liter (at that time the Environmental Protection Agency's recommended limit was 1.5 mmol or less per liter). METHODS: To determine whether the recent use of that brand of paint containing phenylmercuric acetate was associated with elevated indoor-air and urinary mercury concentrations, we studied 74 "exposed" persons living in 19 homes recently painted with the brand and 28 "unexposed" persons living in 10 homes not recently painted with paint containing mercury. RESULTS: The paint samples from the homes of exposed persons contained a median of 3.8 mmol of mercury per liter, and air samples from the homes had a median mercury content of 10.0 nmol per cubic meter (range, less than 0.5 to 49.9). No mercury was detected in paint or air samples from the homes of unexposed persons. The median urinary mercury concentration was higher in the exposed persons (4.7 nmol of mercury per millimole of creatinine; range, 1.4 to 66.5) than in the unexposed persons (1.1 nmol per millimole; range, 0.02 to 3.9; P less than 0.001). Urinary mercury concentrations within the range that we found in exposed persons have been associated with symptomatic mercury poisoning. CONCLUSIONS: We found that potentially hazardous exposure to mercury had occurred among persons whose homes were painted with a brand of paint containing mercury at concentrations approximately 2 1/2 times the Environmental Protection Agency's recommended limit.

Adolescent↗

Quadrature and the development of orientation selective cortical cells by Hebb rules.

We describe a new theoretical scenario for the development of orientation selective cells in a self-organizing feedforward network with modifiable synapses. A suitable choice of Hebb rule leads to a system that develops symmetric and antisymmetric response fields (quadrature pairs) at the same time as directional selectivity occurs using inhibition between neighboring cells. Quadrature phase relationships between the response properties of adjacent cortical cells is suggestive of several highly efficient information processing strategies.

Animals↗

Spine fusion in cerebral palsy with L-rod segmental spinal instrumentation. A comparison of single and two-stage combined approach with Zielke instrumentation.

The benefits of achieving rigid internal fixation and eliminating the need for postoperative external orthotic support with L-rod spinal instrumentation made it desirable for use in the surgical treatment of neuromuscular scoliosis. From May 1981 to May 1985, 31 severely involved cerebral palsy patients with progressive spinal deformity underwent posterior fusion and L-rod instrumentation. All patients except one were nonambulatory. Surgical indications included prevention of curve progression, correction of pelvic obliquity, and achievement of balanced spinal alignment in order to improve sitting balance and tolerance without external spinal orthotic support. Ten patients (Group I), with an average age of 15.2 years, with double major or flexible paralytic C-curves or scoliosis measuring less than 70 degrees, underwent posterior fusion and L-rod instrumentation only. Twenty-one patients (Group II), with an average age of 22.1 years, with thoracolumbar, lumbar, or rigid paralytic C-curves or scoliosis measuring greater than 70 degrees, underwent initial anterior release, bone grafting, and Zielke instrumentation followed by second-stage L-rod instrumentation. In Group I, scoliosis averaged 57 degrees and postoperatively 27 degrees (53% correction). In Group II, scoliosis averaged 88 degrees and postoperatively 36 degrees (63% correction). Fifteen Group II patients had posterior fusion extend into the sacrum using the Galveston technique. Six Group II patients were not fused into the sacrum. Scoliosis and pelvic obliquity were corrected in both groups. Torso decompensation improved to 2.7 cm in the Galveston group, but increased to 5.6 cm at follow-up in the patients not fused into the sacrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

CGS 15435A, a thromboxane synthetase inhibitor with an extended duration of action: a comparison with dazoxiben.

CGS 15435A, a novel thromboxane (Tx) synthetase inhibitor (5-chloro-1-methyl-2-(3-pyridyl)-3-indolhexanoic acid HCl), had a selectivity for Tx synthetase 100,000-fold greater than that for cyclooxygenase, PGI2 synthetase and lipoxygenase enzymes. In conscious beagles, 1 h following a single 3 mg/kg p.o. dose, serum TxB2 was inhibited 95% by CGS 15435 and 82% by dazoxiben (DAZ). Unlike the short acting Tx synthetase inhibitor DAZ, CGS 15435A significantly inhibited TxB2 formation 4, 6, 12 and 24 h after dosing. Serum levels of 6-keto PGF1 alpha and PGE2 were significantly increased following the administration of either drug. CGS 15435A and DAZ were further examined in a model with known Tx involvement. Thrombotic sudden death, produced in anesthetized rabbits by injection of 0.75 mg/kg arachidonic acid (AA) i.v. resulted in a 45% fall in the platelet count and 0% survival. Pretreatment with DAZ (8.6 mumol/kg i.v.) at 0.25 or 2 h pre-AA resulted in 3 and 42% thrombocytopenia and 100 and 0% survival respectively. CGS 15435A (8.6 mumol/kg i.v.) prevented the increases in plasma TxB2 levels, thrombocytopenia and sudden death with pretreatment at 0.25 h (0% thrombocytopenia and 100% survival) or 24 h (11% thrombocytopenia and 83% survival) before AA. These data indicate that CGS 15435A is a potent and selective Tx synthetase inhibitor with a long duration of action, and suggest that the compound could be useful in chronic, non-symptomatic indications of Tx involvement.

6-Ketoprostaglandin F1 alpha↗

Bacterial lipopolysaccharides prime macrophages for enhanced release of arachidonic acid metabolites.

Preincubation of resident peritoneal macrophages with 10-100 ng/ml LPS for 60 min resulted in the cells becoming primed for enhanced (three-to eightfold higher) arachidonic acid (20:4) secretion in response to a variety of triggers. The half-maximal concentration of LPS required for priming was 10 ng/ml irrespective of whether the trigger was particulate (examples: zymosan or immune complexes) or soluble (such as PMA or A23187). Similarly, the time required for half-maximal priming of macrophages was 20 min irrespective of which trigger was used. The primed state persisted for at least 30 h. LPS-priming of macrophages also affected the kinetics of 20:4 metabolite secretion. The lag phase characteristically observed when 20:4 secretion is triggered was reduced in LPS-primed cells. Furthermore, LPS-primed cells secreted 20:4 metabolites when challenged with latex beads, while unprimed cells did not. These data suggest that stimuli such as zymosan, which elicit 20:4 secretion in macrophages, promote two signals, a priming signal and a triggering signal. LPS is capable of establishing the priming signal but not the triggering signal, while latex promotes the triggering signal but is unable to prime the cells for 20:4 release. LPS did not effect the profile of 20:4 metabolites secreted in response to any of the triggers, nor did it effect the profile of products synthesized from exogenously added 20:4, suggesting that it did not regulate the 20:4 cascade at the level of either the cyclooxygenase or lipoxygenase pathways. Macrophages respond to LPS without the intervention of T lymphocytes, since the macrophages from nude mice could be primed for enhanced 20:4 secretion.

Animals↗

Coping resources and parenting mentally retarded children.

Four broad dimensions of coping resources (utilitarian resources, energy/morale, general and specific beliefs, and social support) were assessed with a sample of 140 mothers of mentally retarded children. The dimensions were related to a measure of the adequacy of parental coping, i.e., Questionnaire on Resources and Stress-Friedrich Factor 1, Parent and Family Problems. Three of the four categories of coping resources were significant contributors in a regression analysis and contributed additional variance beyond that of behavioral and physical problems of the child. For validational purposes, 104 of these mothers were reexamined 10 months later. The original analysis was supported, and changes in marital satisfaction were related to an increase in parent and family problems over the elapsed time span.

Adolescent↗

Aggregation, release and desensitization induced in platelets from five species by platelet activating factor (PAF).

PAF-induced aggregation and dense granule release (ATP release) were investigated in human, primate, guinea pig, rabbit and rat platelet-rich plasma (PRP). Guinea pig PRP was most sensitive to PAF, followed by rabbit and then human. PRP from rats and primates did not aggregate or release when exposed to PAF. In guinea pig and rabbit PRP, release was independent of aggregatory response. In human PRP high doses of PAF (5 X 10(-7) M) caused maximum aggregation and a biphasic ATP release, whilst lower concentrations (3 X 10(-8) M) induced biphasic aggregation and one phase of ATP release concomitant with the second phase of aggregation. Aggregation and ATP release induced by PAF in guinea pig and rabbit PRP is dependent upon Ca++ levels, whilst the response of human platelets is relatively independent of the Ca++ level above a certain threshold concentration. The PRP from the three species which aggregated with PAF also demonstrate the phenomenon of desensitization.

Adenosine Triphosphate↗

Transport of radon through cracks in a concrete slab.

A model involving the use of line sources is developed to describe the transport of radon through the cracks or gaps which appear in concrete slabs used in building foundations. The strength of these sources is determined from the results of the diffusion model proposed by Landman in a previous work. Once the strength of the source is known, additional transport mechanisms can be treated in a simple manner. Pressure differences across the slab and in the underlying soil are discussed. The rate of exhalation through a portion of the cracked slab is determined and compared to the rate of exhalation from the same surface area of bare soil. In typical cases, their ratios vary from 0.25 to 0.50. Therefore, these transport mechanisms account for a larger portion of the levels of radon found in many houses than do previous models.

Background Radiation↗

Health food stores investigation.

In accordance with the New York City Department of Consumer Affairs' mandate to educate consumers and to prevent fraud and deception in the marketplace, the agency conducted a three-month investigation of city health food stores. Twenty-three health food businesses located throughout the five boroughs were visited from September through November 1982 in order to ascertain what those stores sold and how their merchandise compared, in quality and price, with items sold by other businesses.

Costs and Cost Analysis↗

The effect of metabolic inhibitors on retinal adhesion and subretinal fluid resorption.

Retinal adhesion and the resorption of subretinal fluid were studied in Dutch rabbits, with two experimental techniques. In the first, small local detachments were made in vivo by injecting a small amount of fluid under the retina with a micropipette, and the time for resorption of the detachment was monitored. In the second, strips of eyecup were maintained in a physiologic bathing medium, and the force required to peel retina from the pigment epithelium was measured. Using these techniques, we have found that both the mechanisms for removing subretinal fluid and for maintaining retinal adhesion in vitro are enhanced by exposure to ouabain, are inhibited by exposure to cyanide, and are inhibited by the replacement of the physiologic medium with normal saline. These data suggest that metabolic systems may simultaneously hydrate and dehydrate the subretinal space and that some factors which are important to the maintenance of normal adhesion are missing from normal saline.

Animals↗

Computerizing drug usage evaluation.

Drug usage evaluation (DUE) has been computerized at the Department of Veterans Affairs Medical Center in Coatesville, PA. This article describes the implementation of a simple, cost-effective process and provides examples of facility-wide and provider-specific reports that can be used at the time of reappointment for privileges. As a result of computerization and the involvement of all pharmacists, the number of drug reviews have increased dramatically, and there is more consistency in the reviews.

Clinical Pharmacy Information Systems↗