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Biomedical subjects

D R Franz

Publications and source records attributed to D R Franz.

At least 19 recordsLinked to original sources
PubMed2001

Clinical recognition and management of patients exposed to biological warfare agents.

Concern regarding the use of biological agents (bacteria, viruses, or toxins) as tools of warfare or terrorism has led to measures to deter their use or, failing that, to deal with the consequences. Unlike chemical agents, which typically lead to severe disease syndromes within minutes at the site of exposure, diseases resulting from biological agents have incubation periods of days. Rather than a paramedic, it will likely be a physician who is first faced with evidence of the results of a biological attack. Provided here is an updated primer on 11 classic BW and potential terrorist agents to increase the likelihood of their being considered in a differential diagnosis. Although the resultant diseases are rarely seen in many countries today, accepted diagnostic and epidemiologic principles apply; if the cause is identified quickly, appropriate therapy can be initiated and the impact of a terrorist attack greatly reduced.

Biological Warfare↗
PubMed2000

Biological terrorism: understanding the threat, preparation, and medical response.

The thought of an outbreak of disease caused by the intentional release of a pathogen or toxin in an American city was alien just 10 years ago. Many people believed that biological warfare was only in the military's imagination, perhaps to be faced by soldiers on a far-away battlefield, if at all. Political factors--and possibly biotechnology--have changed that. As we enter the new millennium, national, state, and local governments in the United States are preparing for what is now called "not if, but when" biological terrorism. In contrast to the acute onset and first-responder focus with a chemical attack, in a bioterrorist attack, the physician and the hospital will be at the center of the fray. Whether the attack is a hoax, a small food-borne outbreak, a lethal aerosol cloud moving silently through a city at night, or the introduction of contagious disease, the physician who understands threat agent characteristics and diagnostic and treatment options and who thinks like an epidemiologist will have the greatest success in limiting the impact of the attack. As individual health-care providers, we must add the exotic agents to our diagnostic differentials. Hospital administrators must consider augmenting diagnostic capabilities and surveillance programs and even making infrastructure modifications in preparation for the treatment of victims of bioterrorism. Above all, we must all educate ourselves. If done correctly, preparation for a biological attack will be as "dual use" as the facility that produced the weapon. A sound public health infrastructure, which includes all of us and our resources, will serve this nation well for the control of disease, no matter what the cause of the disease.

Biological Warfare↗
PubMed1997

Clinical recognition and management of patients exposed to biological warfare agents.

Concern regarding the use of biological agents--bacteria, viruses, or toxins--as tools of warfare or terrorism has led to measures to deter their use or, failing that, to deal with the consequences. Unlike chemical agents, which typically lead to violent disease syndromes within minutes at the site of exposure, diseases resulting from biological agents have incubation periods of days. Therefore, rather than a paramedic, it will likely be a physician who is first faced with evidence of the results of a biological attack. We provide here a primer on 10 classic biological warfare agents to increase the likelihood of their being considered in a differential diagnosis. Although the resultant diseases are rarely seen in many countries today, accepted diagnostic and epidemiologic principles apply; if the cause is identified quickly, appropriate therapy can be initiated and the impact of a terrorist attack greatly reduced.

Anthrax↗
PubMed1992

Effects of palytoxin on porcine coronary artery rings.

Palytoxin, in concentrations as low as 100 fM, caused contractions of porcine coronary artery rings. Palytoxin concentrations of less than 1 nM caused slowly developing contractions which were not maximal even after 2 h. Rings contracted by 100 nM palytoxin achieved maximal tension by 10 min and relaxed to 53% of that maximum after 2 h. Verapamil (1 microM) reduced the rate of contractions induced by 10 nM palytoxin. Exposure of rings to greater than 10 nM palytoxin for 1-2 h reduced contractions to potassium 18 h later to 61% of the expected contraction and abolished those to palytoxin administered later. Both 10 and 100 nM palytoxin depleted potassium from coronary artery rings. Verapamil (10 microM) prevented potassium depletion by 10 nM palytoxin, but neither 10 microM verapamil nor 1 microM nifedipine prevented potassium depletion in rings exposed to 100 nM palytoxin. Thus, the contractile action and the potassium depleting action of palytoxin on the porcine coronary artery involve mobilization of nifedipine- and verapamil-sensitive calcium. Verapamil- and nifedipine-sensitive calcium was not required for depletion of potassium by the highest PTX concentration (100 nM), however.

Acrylamides↗
PubMed1991

Effects of lyngbyatoxin A from the blue-green alga Lyngbya majuscula on rabbit aorta contractions.

The contractile effects of the tumor promoter and protein kinase C activator, lyngbyatoxin A, were studied in rabbit aorta rings. Contractions to 1 microM lyngbyatoxin A developed slowly, becoming maximal in approximately 3 hr. Contractions were not altered by 1 microM indomethacin, 1 microM nordihydroguaiaretic acid, or by endothelium removal, indicating that they did not involve contracting or relaxing substances from the epithelium. The contractions were also unaltered by calcium deletion from the medium and by 1 microM verapamil. Removal of adventitia did not alter contractions to lyngbyatoxin A, indicating that they did not involve release of norepinephrine or other neural vasoconstrictors. Previous contraction by norepinephrine in calcium-free medium containing a calcium-sequestering agent did not reduce subsequent lyngbyatoxin A contractions, indicating that they did not utilize the easily depleted intracellular calcium pool utilized by norepinephrine. Partial contraction with lyngbyatoxin A did not prevent contraction of the rings to norepinephrine. Contractions to lyngbyatoxin A in calcium-free medium did not differ from those obtained in calcium-free medium with 80 mM potassium chloride, indicating the contractions involved pharmacomechanical coupling. Contractions to both 1 microM lyngbyatoxin A and to 3 microM norepinephrine were depressed 18 hr after greater than 2 hr exposure to 1 microM lyngbyatoxin A (44 and 27%, respectively). Thus, lyngbyatoxin A contracts the rabbit aorta by an extracellular and intracellular calcium-, endothelium- and neuron-independent mechanism similar to the protein kinase C activating phorbol esters.

Animals↗
PubMed1991

Effects of palytoxin on guinea pig tracheal strips.

The effects of palytoxin (PTX) on airway smooth muscle were investigated in opened rings of guinea pig trachea. Concentrations of PTX from 10 pM to 100 nM caused contractions of tracheal strips, with maximal contractions approximately 80% of those in response to 120 mM potassium. Tension increased to its maximum in approximately 5 min with 100 nM PTX, then decreased to or near resting tension over the next 60 min. Contractions were larger when the epithelium was removed. Exposure to high (100 nM) concentrations of PTX markedly reduced subsequent contractions to PTX but had less effect on potassium-induced contractions. In zero-calcium solution the rate of contraction was slowed but the maximal contraction was not reduced. The addition of a calcium channel blocker (verapamil) markedly reduced the contractions and a calcium chelator (EGTA) abolished them. Contractions to PTX in zero-calcium media suggested that tracheal cartilage was serving as a calcium source, as it has been previously reported to do. Potassium removal and sodium reduction also greatly reduced contractions. These data are consistent with other observations suggesting that PTX may form pores through which sodium leaks into the cell. PTX was also found to differ from ouabain in its mode of action.

Acrylamides↗
PubMed1990

Respiratory and cardiovascular effects of tetrodotoxin in urethane-anesthetized guinea pigs.

Cardiorespiratory effects of tetrodotoxin (TTX) (15 micrograms/kg, i.p.) were investigated in urethane-anesthetized guinea pigs acutely instrumented for the recording of medullary respiratory-related units (RRUs), diaphragm electromyogram (DEMG), electrocorticogram (ECoG), electrocardiogram (ECG), blood pressure (BP), endtidal CO2, and arterial O2 and CO2. Respiratory system responses showed a hyperventilatory profile during the initial stage of intoxication. This was followed by an abrupt onset of a progressive decrease in the respiratory frequency, and a respiratory rate depression-related respiratory failure. The average time to TTX-induced respiratory arrest and death was 10.3 +/- 4.2 min. Concurrently recorded inspiratory and expiratory RRU activities indicated that respiration invariably failed in an end-expiratory position as manifested by a sustained period of expiratory RRU discharge. The progressive rate depression prior to respiratory arrest was temporally correlated only to a concomitantly augmenting expiratory RRU discharge duration. Inspiratory RRU discharge duration, on the other hand, did not display any significant change throughout the course of intoxication. The asymmetry in RRU response patterns indicates either an expiratory network component's particular sensitivity to perturbation by TTX or a dissociative trend in some bulbar respiratory rhythmogenic mechanisms. Peripheral cardiorespiratory changes were also quite profound. These included a gradual and steadfast decline in BP, a steadily decreasing amplitude in DEMG oscillations, and a state of progressive hypercapnia and hypoxemia. Changes in heart rate and ECG waveform attributes prior to respiratory arrest were not appreciable. In conclusion, in addition to a variety of TTX-induced peripheral cardiorespiratory effects, findings from this study have revealed a central respiratory system component that appears to show an unusual sensitivity to perturbation by TTX. The significance of this unique phenomenon as it relates to the nature and extent of TTX-induced central respiratory depression is discussed.

Anesthesia, General↗
PubMed1990

Sequence of cardiorespiratory effects of soman altered by route of administration.

Dilute soman was administered to anesthetized guinea-pigs by slow infusion (30 micrograms/kg/10 min); intravenous (IV), subcutaneous (SC), intraperitoneal (IP), intratracheal (IT), and upper-airway (UAW) routes were used. Times to ventilatory failure were 8.8 +/- 1.3 min (IV), 10.5 +/- 1.2 min (I.T.), 17.3 +/- 2.8 min (IP), 34.8 +/- 5.1 min (UAW), and 36.0 +/- 4.4 min (SC) for the 5 routes of exposure. Atrioventricular (AV) block occurred before ventilatory failure with all routes of challenge except IT and IP; when it did occur, AV block typically began after one-half reduction in minute volume. The results reflect the effects of rate of absorption and noncritical-site binding of the organophosphorus compound when all routes are compared and suggest that the pathogenesis of intoxication in the anesthetized guinea-pig is different when soman is infused into regions heavily enervated by vagal afferents.

Administration, Intranasal↗
PubMed1990

Lack of an effect of saxitonin on the contractility of isolated guinea-pig trachea, lung parenchyma and aorta.

The effects of saxitonin were investigated in guinea-pig tracheal rings, lung parenchymal strips and aorta rings. Tracheal rings were used both with epithelium present and with it removed. Aorta rings were used both with endothelium present and with it removed. Saxitoxin, 1 pM to 0.1 microM, did not alter the resting tension of either airway tissues or aorta. Also 0.1 microM saxitonin did not reduce tension of tracheal rings contracted by 10 microM carbachol, parenchymal strips contracted by 100 microM acetylcholine or by 10 microM histamine, or aorta rings contracted by 10 microM norepinephrine. Responses of tracheal rings to 0.03-10 microM carbachol added cumulatively were not altered by 0.1 microM saxitoxin (EC50 with epithelium: 1.11 +/- 0.48 microM control, 2.01 +/- 0.71 microM with saxitoxin; EC50 without epithelium: 2.83 +/- 0.55 microM control, 2.05 +/- 0.58 microM with saxitoxin). Also, 1 microM saxitoxin did not alter contractions of parenchymal stirps to cumulatively added acetylcholine (EC50: 3.47 +/- 1.06 microM, control; 3.98 +/- 1.19 microM with saxitoxin), histamine (EC50: 0.83 +/- 0.24 microM, control; 0.60 +/- 0.13 microM with saxitoxin); or of aorta strips to norepinephrine with endothelium (EC50: 1.78 +/- 0.80 microM, control; 0.74 +/- 0.21 microM with saxitoxin) or without endothelium (EC50: 2.18 +/- 0.78 microM, control; 1.42 +/- 0.62 microM with saxitoxin). Thus, saxitoxin did not significantly alter contractile activity of airways of large arteries in vitro.

Acetylcholine↗
PubMed1989

Respiratory effects of brevetoxin and saxitoxin in awake guinea pigs.

Ptychodiscus brevis toxin (brevetoxin) is associated with 'Florida red tide' and cause neurotoxic shellfish poisoning. Saxitoxin is the agent of paralytic shellfish poisoning. Clinical reports of human intoxication suggest that both toxins affect the respiratory system. The toxins were administered by slow intravenous infusion. The effects of the toxins on respiratory function of awake guinea pigs in a pressure plethysmograph were studied. Both toxins caused lactic acidosis of unknown etiology, which was compensated for by increased minute volume with brevetoxin (PbTx-3)- but not with saxitoxin-intoxicated animals. In general, brevetoxin increased ventilation, before respiratory failure, while saxitoxin had a depressive effect on ventilation. Airways resistance was not increased, nor was dynamic compliance decreased during intoxication, although the data suggest that respiratory system failure was the primary cause of death. The responses seen in these experiments are consistent with the dissimilar molecular actions of these toxins.

Animals↗
PubMed1988

No effect of modulators of reactive oxygen-induced pathology on microcystin-LR intoxication.

Because reactive oxygen species are formed during the metabolism of several toxins that cause similar pathologic changes, we hypothesized that compounds that alter the concentration of reactive oxygen species would alter the toxic effects of the peptide-hepatotoxin produced principally by Microcystis aeruginosa. Pretreatment with alloxan, butylated hydroxyanisole or desferrioxamine did not alter the severity of microcystin-LR intoxication in fed mice. Furthermore, fasting mice for 24 hr before testing, which unmasks lipid peroxidation in paracetamol intoxication, did not alter the effect of butylated hydroxyanisole pretreatment.

Alloxan↗
PubMed1988

Pathologic activity of Plasmodium berghei prevented but not reversed by dexamethasone.

Dexamethasone has recently been shown to block the production of cachectin (implicated in the pathogenesis of cerebral malaria) if administered prior to endotoxin induction of mouse macrophages. Using the hamster cheek pouch-cerebral malaria model, we tested the hypothesis that dexamethasone is effective as a therapeutic agent in severe malaria if given before some yet undefined trigger point in the disease. Infected hamsters were treated with dexamethasone (0.7 mg/kg) daily on days 7-12, 4-12, or 1-12 post-challenge. When treatment was started on day 1, whole body oxygen consumption (used as a measure of erythrocyte transport to sites of diffusion) on day 12 was greater than (P less than 0.05) that of infected control animals, though the degree of anemia was no different in treated and untreated groups. Furthermore, treatment produced a reduction in monocyte accumulation, capillary malfunction, and monocyte/red blood cell aggregate formation observable in the cheek pouch in vivo and a similar reduction in monocyte presence, capillary pathologic change, and multifocal hemorrhage in the brain on postmortem. These data suggest that mediator(s), whose production can be blocked by pretreatment with dexamethasone, are involved in the pathogenesis of disease leading to death of the Plasmodium berghei infected hamster.

Animals↗
PubMed1987

Peripheral vascular pathophysiology of Plasmodium berghei infection: a comparative study in the cheek pouch and brain of the golden hamster.

Four- to six-week-old hamsters were infected with 1.5 X 10(7) Plasmodium berghei-parasitized hamster red blood cells by intraperitoneal injection. Cheek pouch circulation was observed microscopically in the anesthetized animal; the brain and contralateral pouch were collected for histopathologic examination on days 3-12 post-challenge. Cheek pouch vascular lesions, observed in vivo, appear to involve three phenomena; early (beginning 3-4 days) adhesion of pigment-laden mononuclear cells to endothelium within venous vessels and loss of function of the small capillaries supplying the skeletal muscle fibers and, later (6-9 days), the apparent attraction of erythrocytes to venular and venous endothelium and to adherent monocytes. The aggregation of formed elements on endothelial walls leads to progressive occlusion of venules and small veins and contributes to the observed disruption of flow through capillary networks. Histopathology of the brain and pouch shows vascular changes similar to those seen in vivo; in addition, multifocal hemorrhages are seen commonly in the brain and occasionally in the pouch on postmortem. In severe disease, evidence of cerebral edema is seen in the brain. The data suggest that failure of capillary flow and disruption of venous outflow tracts by cell aggregates are central to vascular failure in both the cheek pouch and brain of the P. berghei infected hamster. This hamster model of human cerebral malaria allows the in vivo observation, still and video photomicrography, and manipulation of the peripheral vascular pathogenesis of a disease process similar to that seen in humans.

Animals↗