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Biomedical subjects

J Atsmon

Publications and source records attributed to J Atsmon.

At least 19 recordsLinked to original sources

Safety of pyridostigmine in hypertensive patients receiving beta blockers.

In the last decade, pyridostigmine, a quaternary carbamate that reversibly inhibits the enzyme acetylcholinesterase, was proposed for pretreatment of nerve gas (organophosphate) poisoning. The objective of this study was to assess the cardiovascular effects of pyridostigmine in patients treated with beta blockers. Eight hypertensive patients receiving regular treatment with beta blockers were randomized in a double-blind crossover study to receive pyridostigmine (30 mg 3 times daily) or placebo for 2 days. Heart rate and blood pressure in the supine and standing positions were recorded every 2 hours during the day, and 24-hour Holter monitoring was performed. In addition, a symptom-limited exercise test was performed, and plasma catecholamine levels were determined at rest and at peak exercise. Pyridostigmine, as compared with placebo, did not induce any significant effect on heart rate, plasma catecholamine levels or resting blood pressure. Both systolic and diastolic blood pressures increased in accordance with exercise intensity (p less than 0.01), although a significantly lower diastolic blood pressure was observed when pyridostigmine was used (average decrease 5 mm Hg compared with placebo; p less than 0.01). No clinical adverse reactions were observed, confirming the relative safety of the combination of low-dose pyridostigmine with beta-adrenergic blocking agents.

Adrenergic beta-Antagonists

Functional adaptation of rat remnant colon after proximal hemicolectomy.

Functional adaptation of the remnant intestine after extensive resection of small bowel is well documented. The effects of partial resection of large bowel on the remaining colon have not been characterized. Transepithelial potential (VT), tissue resistance (RT), and short-circuit current (Isc) were measured in vitro across distal colonic tissue of rats three weeks after proximal hemicolectomy with ileotransversotomy and compared to the same parameters measured in the distal colon of control animals. In a second series of experiments, an in vivo perfusion technique was used to measure changes in sodium, potassium, and water transport in distal colon following proximal hemicolectomy. A 2.5-fold increase in VT (P less than 0.01), a 62% increase in RT (P less than 0.001), and a 35% increase in Isc (P less than 0.05) were observed three weeks following hemicolectomy when compared to control animals. A 64% increase in net sodium absorption (P less than 0.025), no significant change in net potassium transport, and a 115% increase in net water absorption (P less than 0.01) were demonstrated in hemicolectomized animals when compared to control. It is concluded that in the rat the distal colon is capable of functional adaptation to increase net sodium and water absorption within three weeks after proximal hemicolectomy. The mechanism responsible for this adaptive process has yet to be defined. Our findings may explain the lack of chronic diarrhea in patients undergoing right hemicolectomy.

Animals

The effects of powered air supply to the respiratory protective device on respiration parameters during rest and exercise.

The common chemical warfare protective masks impose an excessive respiratory load on the wearer due to elevated breathing resistance and increased dead space. For patients with severe respiratory disease, the excessive respiratory effort may be intolerable. Besides, the substantial negative pressure created within the mask during inspiration may result in an inward leakage in individuals having difficulties with proper facial fitting of the mask. The purpose of the current investigation was to evaluate the effects of a blower, actively driving air, through the mask's filter, at a flow (mean +/- SD) of 42 +/- 2 L/min, on respiratory parameters during rest and moderate exercise. Ten healthy subjects of either sex participated in two experimental sessions, wearing the mask with and without the blower. Each session included 6 min of sitting at rest and 6 min of walking on a treadmill (3.2 mph, and 10 percent grade). In nine of the subjects, the active air supply produced a positive inspiratory pressure at rest (5 +/- 4 vs -24 +/- 9 mm H2O peak inspiratory pressure with and without the blower, respectively, p < 0.0001). Inspiratory carbon dioxide concentration (FICO2) at rest was diminished (0.4 +/- 0.4 vs 1.3 +/- 0.7 percent with and without the blower, respectively; p < 0.01) while FIO2 increased from 19.5 +/- 0.7 percent to 20.6 +/- 0.4 percent with the device (p < 0.01). These changes were associated with a significant decrease in respiratory rate (15 +/- 2 vs 18 +/- 3 per minute, p < 0.01). During exercise the blower barely decreased the negative inspiratory pressures, had no effect on other respiratory parameters measured, but significantly shortened the inspiratory/cycle-length time ratio (0.46 +/- 0.03 vs 0.53 +/- 0.03, p < 0.005). The effects of active air supply were not different between male and female subjects. We conclude that the blower is expected to be a useful accessory to respiratory protective devices for patients with pulmonary disease.

Adult

Medical limitations of gas masks for civilian populations: the 1991 experience.

Using a gas mask (GM) may involve considerable inconvenience, impairment of respiration and communication, and serious psychological reactions. The medical literature is primarily focused on the occupational aspects of using the GM by young and healthy workers. In contrast, there is hardly any information concerning the use of GMs by large, unselected populations, including children, the elderly, and the sick. Issuing GMs to all residents of Israel prior to Operation Desert Storm created an urgent need to define the populations whose health might be jeopardized by using the standard GM. Adding an active air supply system (AASS) to a standard GM may ease the burden on this high-risk group. We evaluated the physiological aspects of breathing with a GM, with and without AASS, in respect to pathophysiology of diseases, and reached a set of criteria for identifying those who may be endangered by a GM and are expected to benefit from the AASS. The method used to sort and identify those entitled to the AASS is described.

Chronic Disease

Formation of thiol conjugates of 9-deoxy-delta 9,delta 12(E)-prostaglandin D2 and delta 12(E)-prostaglandin D2.

Albumin catalyzes the transformation of prostaglandin D2 to 9-deoxy-delta 9,delta 12(E)-prostaglandin D2 and to isomeric prostaglandin D2 compounds including delta 12(E)-prostaglandin D2. Both of these compounds are alpha,beta-unsaturated ketones, which should render them susceptible to nucleophilic addition. We therefore examined the ability of the compounds to form conjugates with thiols glutathione and cysteine. During incubation with excess glutathione, both 9-deoxy-delta 9,delta 12(E)-prostaglandin D2 and delta 12(E)-prostaglandin D2 formed a conjugate. Conjugation of 9-deoxy-delta 9,delta 12(E)-prostaglandin D2 occurred very rapidly; approximately 70% was conjugated within 2 min. In contrast, conjugation of delta 12(E)-prostaglandin D2 with glutathione proceeded at a much slower rate; only 38% was conjugated at 60 min. The formation of both conjugates was enhanced by glutathione S-transferase. Conjugation of both compounds with cysteine was found to occur more rapidly than with glutathione. This effect was more pronounced with delta 12(E)-prostaglandin D2 in which 60% conjugated with cysteine within 2 min. These differences are likely attributed to greater steric hindrance for conjugation across the delta 12 double bond compared to that across the delta 9 bond. Analysis by fast atom bombardment mass spectrometry confirmed the formation of the glutathione conjugate of 9-deoxy-delta 9,delta 12(E)-prostaglandin D2. Following prolonged incubation of 9-deoxy-delta 9,delta 12(E)-prostaglandin D2 with excess glutathione in the presence of glutathione S-transferase, a small quantity of a bis conjugate of this compound was also detected by mass spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins

Conjugation of 9-deoxy-delta 9,delta 12(E)-prostaglandin D2 with intracellular glutathione and enhancement of its antiproliferative activity by glutathione depletion.

The major dehydration product of prostaglandin D2, 9-deoxy-delta 9,delta 12(E)-prostaglandin D2, is a potent cytotoxic compound. Like other cytotoxic prostaglandins, this compound possesses an alpha, beta-unsaturated ketone group to which cytotoxic activity has been attributed. This prostaglandin was found to readily conjugate with glutathione (GSH) in vitro. When 9-deoxy-delta 9,delta 12(E)-prostaglandin D2 was incubated with Chinese hamster ovary or hepatoma tissue culture cells, it was rapidly taken up and was recovered in the cell lysate primarily as a GSH conjugate in which the keto group at C-11 and the delta 12 double bond had been reduced. Identification of the GSH conjugate was accomplished by analysis by fast atom bombardment mass spectrometry following purification by high performance liquid chromatography. This GSH conjugate and its cysteinylglycinyl and cysteinyl metabolites were also identified in the cell culture medium. 9-Deoxy-delta 9,delta 12(E)-prostaglandin D2 inhibited cell proliferation of these two cell lines in a concentration dependent manner. Depletion of intracellular glutathione by treatment with diethyl maleate and buthionine sulfoximine decreased the amount of intracellular conjugated prostaglandin recovered, and significantly enhanced the antiproliferative effect of 9-deoxy-delta 9-delta 12(E)-prostaglandin D2 on the growth of these cell lines in a concentration dependent fashion. We conclude that intracellular GSH may modulate the antiproliferative activity of 9-deoxy-delta 9,delta 12(E)-prostaglandin D2 and, possibly, of other cytotoxic prostaglandins.

Animals

Immunogenic capacity of macrophage hybridomas.

Two clones, E2-7.7 and E2-10.50, derived from two macrophage(M phi)hybridomas, E2-7 and E2-10, have been studied. The first clone, E2-7.7, is Ia+ and Fc receptor (FcR) negative and manifests a strong antigen-presenting capacity. When we pulsed its cells in vitro with keyhole limpet hemocyanin (KLH) antigen and injected them into syngeneic animals, we found that as small a dose as 10(3) cells initiated an immune response in vivo. On the other hand, antigen-pulsed cells of the E2-10.50 clone, which are Ia- and FcR+, were almost incapable of triggering immunity, even when injected at a dose of 10(5) cells. Thus, the two clones differ in their immunogenic capacity (both cellular and humoral immunity). In experiments aimed at testing the stimulation in vitro of primed lymph node (LN) cells by antigen-pulsed cells of these two hybridoma clones, we observed that E2-7.7 stimulated the unfractionated population of LN cells and the LN-derived population of T cells. The E2-10.50 cells stimulated only the unfractionated population of LN cells, but not the T cell population. Subsequent tests indicated that the E2-10.50 cells require an intermediate Ia+ accessory cell to present the antigen to the T lymphocytes. Analyzing the molecular structure of the M phi hybridomas, we discovered that major histocompatibility complex (MHC) genes of the myeloma haplotype (H-2d), and of the splenic M phi used for fusion (H-2k), which were not expressed in the parental myeloma or in the E2-10.50, were expressed in the E2-7.7. Thus, somatic cell fusion of M phi resulted in the activation of suppressed genes of the myeloma partner. It appears that these antigens participate in controlling the immunogenic properties of the E2-7.7 clone. Testing the effects of interferons on the M phi hybridomas, we observed that interferon-gamma activated, at both the mRNA and the cell surface-antigen levels, the expression of H-2Dk, H-2Kd and H-2Dd in the E2-10.50 cells, but not in the E2-7.7. Consequently, interferon-gamma augmented significantly antigen presentation by E2-10.50 but not by E2-7.7 cells. These two hybridoma clones might represent two distinct subsets of normal M phi, manifesting two different sets of functional properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

[Tuftsin].

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Humans

Outline of hospital organization for a chemical warfare attack.

A plan for hospital organization in the event of chemical warfare is described. The basic principles are: a) isolation of the hospital receiving the casualties, b) several levels of triage, and c) treatment according to simple therapeutic protocols using appropriate treatment sites. Triage is based upon walking feasibility, respiratory status, age, and additional conventional injuries. The nurse's diagnostic and treatment authority is extended. Auxiliary staff (numbering hundreds of people) are needed for decontamination, stretcher bearing, artificial ventilation, etc. A nation-wide educational program on the prevention, decontamination and treatment of chemical warfare casualties is conducted in Israeli hospitals and drills are exercised frequently. This scheme is suitable for nerve gas poisoning, but can be easily modified for other chemical agents.

Chemical Warfare

Combined chemical and conventional injuries--pathophysiological, diagnostic and therapeutic aspects.

Chemical warfare (CW) agents may cause both conventional and chemical injuries. The effects of the two types of injuries may be reciprocal, leading to difficulties in assessing and treating such patients. Several aspects of the combined injury are discussed: increased exposure to CW agents following conventional trauma, owing to skin laceration or inability to use a gas mask (head, face or chest trauma); pathophysiological interactions between the two types of injuries; protection of medical personnel against CW intoxication; treatment limitations of personnel caused by their CW protection gear, when treating patients requiring urgent decontamination; and the influence of conventional trauma on the management of CW casualties. The Israel Defense Forces' recommendations for the treatment of combined injuries in a contaminated area include: a) airway maintenance, b) securing breathing and ventilation, c) circulation and hemorrhage control, d) antidote administration, e) decontamination with fuller's earth, f) dressing the wound, and g) evacuation to a noncontaminated area.

Antidotes

Mortality in Israel during the Persian Gulf war--initial observations.

During the 6-week-long 1991 Persian Gulf war, in which the civilian population was subjected to 18 separate missile attacks and the constant threat of nonconventional warfare, crude mortality rates in Israel were no higher than in the previous decade. Although the results are preliminary and need to undergo more sophisticated epidemiologic analysis, it appears that our population was able to tolerate the subacute period of psychological stress without excess mortality.

Cause of Death

Principles of respiratory protection.

This review describes the various types of respiratory protective devices used in Israel during the Persian Gulf war, and summarizes the relevant physiological concepts of respiratory protection. Physiological principles of modern devices with powered air supply are discussed in detail. Our experience may be useful in the evaluation of new respirators and in finding solutions for problematic subpopulations.

Adult