Biomedical subjects

D B Young

Publications and source records attributed to D B Young.

At least 91 records · Page 5Linked to original sources

PubMed1995

Opposing effects of plasma epinephrine and norepinephrine on coronary thrombosis in vivo.

BACKGROUND: It is well known that plasma catecholamines and myocardial infarction have a close relation and that coronary artery thrombosis is a major cause of myocardial infarction. In addition, epinephrine is known to be a prothrombogenic agent in vivo. However, the role of the other major circulating catecholamine, norepinephrine, in the development of coronary thrombosis is somewhat uncertain, although the role of norepinephrine is often considered analogous to the role of epinephrine. Therefore, the present study was designed to investigate the effect of norepinephrine and its interaction with epinephrine on coronary thrombosis. METHODS AND RESULTS: To compare the effects of epinephrine and norepinephrine on coronary thrombosis, we analyzed the frequency of cyclic blood flow reductions (CFRs) in an anesthetized canine model of coronary thrombosis (n = 25). Three experiments were used in the present study. In the first experiment with epinephrine infusion, plasma epinephrine was elevated from 0.46 +/- 0.25 to 27.7 +/- 1.85 nmol/L. The frequency of CFRs increased by more than 60%, from 7.1 +/- 0.5 to 11.5 +/- 0.7 in 40 minutes (P < .01). The second experiment included three experimental periods: control, norepinephrine infusion, and norepinephrine infusion plus epinephrine infusion. Norepinephrine was infused to raise plasma norepinephrine from 1.3 +/- 0.2 to 32.4 +/- 4.3 nmol/L. The frequency of CFRs in the dogs was markedly reduced, from 7.89 +/- 0.42 to 2.41 +/- 1.08 in 40 minutes (P < .01), whereas arterial pressure was elevated from 88 +/- 3 to 118 +/- 5 mm Hg (P < .01). However, when epinephrine infusion was added to the norepinephrine infusion, the frequency of CFRs increased from 2.41 +/- 1.08 to 7.74 +/- 1.12 in 40 minutes (P < .01). In the third experiment, a servocontrol device was used during the norepinephrine infusion to prevent rises in coronary arterial pressure. As a result of the norepinephrine infusion, the frequency of CFRs was reduced from 7.47 +/- 0.71 to 0.83 +/- 0.65 in 40 minutes (P < .01), even though the coronary arterial pressure was not altered. CONCLUSIONS: The present study demonstrated that infusion of epinephrine stimulated coronary artery thrombosis, whereas infusion of norepinephrine inhibited coronary artery thrombosis. In addition, the inhibitory effect of norepinephrine on coronary thrombosis is independent of increases in coronary arterial pressure. Therefore, the present findings suggest that epinephrine and norepinephrine have opposing effects on coronary thrombosis in dogs.

Animals↗

PubMed1995

Impairment of cardiac function by moderate potassium depletion.

A previous study found that potassium depletion in dogs that resulted in a reduction in plasma potassium from 4.1 to 3.2 mmol/L was associated with impairment of many aspects of left ventricular mechanical function, including a 51% reduction in the peak rate of left ventricular filling. To determine if potassium depletion had similar effects in humans, cardiac function was assessed by Doppler and two-dimensional echocardiography in 10 normal volunteers following a 7-day period of potassium depletion, and again 7 days of potassium repletion. Potassium concentration for the group averaged 3.49 +/- 0.12 mmol/L after the depletion period, and 4.57 +/- 0.14 mmol/L after repletion. Early peak mitral flow velocity was significantly less during depletion than during repletion. The values at rest were 89.5 +/- 6.6 and 77.0 +/- 4.9 cm/s during repletion and depletion, respectively (P < .01). Isovolomic relaxation time and deceleration time of flow through the mitral valve were also significantly increased during potassium depletion. No other measured indices of cardiac function were affected by potassium depletion. The results suggest that in normal volunteers, moderate potassium depletion may impair active relaxation of the left ventricle to a degree that is clinically significant.

Adult↗

PubMed1995

Death caused by an allergic reaction to ethanol.

Death as a result of anaphylaxis remains rare and is only occasionally related to ingestion of common substances. This article reports a death due to an allergic reaction to ethanol, as well as a review of the reported deaths in the literature attributed to ethanol. This report emphasizes the importance of awareness of such obscure allergies by forensic pathologists, the significance of antemortem testing, and the value of gathering accurate medical information, both antemortem and postmortem.

Adult↗

PubMed1995

Spontaneous rupture of the spleen. A fatal complication of pregnancy.

Spontaneous splenic rupture in pregnancy is a rare and potentially catastrophic event. As many as 76 cases have been identified in the past 190 years by a variety of authors. This case report describes splenic rupture during the immediate postpartum period. The exact cause of the rupture could not be determined, and it was consistent with a spontaneous rupture.

Adult↗

PubMed1995

"There's death in the cup, so beware!".

The proper investigation of deaths due to poisoning and the determination of the manner of death often depend upon knowledge and investigative skills that may have been allowed to deteriorate with lack of use. These case reports illustrate a wide variety of substances that people can ingest. This collection of case reports includes the ingestion of two insecticides and three different organic chemicals. A concise review of literature is provided, along with symptoms exhibited by those who ingest these poisons, and methodologies recommended for their determination in this series of cases.

Accidents↗

PubMed1995

Using counselors in a multideath disaster.

In the worst possible situation, a disaster results in multiple deaths, requiring the involvement of coroner's and medical examiner's offices. Guidelines offered by the National Association of Medical Examiners and by a national funeral directors' association suggest the use of ministers and chaplains to offer "pastoral" care to family members who have lost a loved one in a disaster. This article offers an example of a disaster protocol based upon national guidelines, but using certified and licensed professional counselors to provide preventive outreach counseling to those family members. Furthermore, this protocol uses a counselor in a key position to provide psychological care to investigative and medical personnel involved in the recovery and identification portions of a disaster.

Cause of Death↗

PubMed1995

Prospects for new interventions in the treatment and prevention of mycobacterial disease.

Mycobacterium tuberculosis claims more lives each year than any other single human pathogen. Despite the availability of effective drugs, the incidence of tuberculosis is increasing in much of the developing world and has recently reemerged as a public health problem in industrialized countries. In the first section of this chapter, current understanding of the fundamental biology of mycobacterial infection is reviewed from the perspective of development of new tools for disease control. A second section describes strategies for identification of novel antimycobacterial agents, with particular emphasis on recent progress in defining biosynthetic pathways for unique mycobacterial cell wall components. The third section focuses on current approaches to the development of new vaccine candidates consisting of live attenuated bacteria or individual antigenic subunits.

Anti-Bacterial Agents↗

PubMed1995

Potassium's cardiovascular protective mechanisms.

High rates of potassium intake are associated with protection from cardiovascular diseases in populations consuming primitive diets and in vegetarians living in industrialized cultures. In studies in humans and in animals, a strong inverse association between potassium intake and hypertension and stroke has been described. However, acceptance of the putative protective effect has been limited by inadequate understanding of 1) long-term potassium regulation, and 2) mechanisms by which small changes in plasma potassium concentration may affect development of cardiovascular diseases. In this review, we present results from analyses of long-term potassium regulation that indicated 1) changes in potassium intake may result in potassium concentrations from 3.1 to 4.6 mmol/l, and 2) when the initial rate is below normal, potassium concentration is very sensitive to changes in potassium intake rate. In addition, we present results that provide bases for possible mechanisms by which potassium may protect against cardiovascular diseases: 1) increases in potassium inhibit free radical formation from vascular endothelial cells and macrophages; 2) elevation of potassium inhibits proliferation of vascular smooth muscle cells; 3) platelet aggregation and arterial thrombosis are inhibited by elevation of potassium; and 4) renal vascular resistance is reduced and glomerular filtration rate is increased by elevation of plasma potassium. We propose that elevation of dietary potassium intake increases plasma potassium concentration, thereby inhibiting free radical formation, smooth muscle proliferation, and thrombus formation. As a result, the rate of atherosclerotic lesion formation and thrombosis will be diminished. In addition, we propose the increase in glomerular filtration rate will cause a shift in the relationship between arterial pressure and sodium excretion that will lead to a reduction in arterial blood pressure. By these actions, high levels of dietary intake of potassium could provide the observed protection against the cardiovascular diseases that have plagued humankind since we began eating a modern high-sodium, low-potassium diet.

Animals↗

PubMed1994

Tuberculosis. Beating the bacillus.

The identification of the target of isoniazid in the mycobacterial tuberculosis pathogen opens the way for the developoment of new drugs and diagnostic tests to combat drug-resistant pathogen strains.

Animals↗

PubMed1994

Immunoblot studies in the differential diagnosis of porcine brucellosis: an immunodominant 62 kDa protein is related to the mycobacterial 65 kDa heat shock protein (HSP-65).

Smooth Brucella spp. share certain lipopolysaccharide antigens with other bacteria, resulting in serological cross-reactions which can prevent the definitive diagnosis of brucellosis. To identify other antigens with serodiagnostic potential, immunoblot studies following sodium dodecyl sulphate-polyacrylamide gel electrophoresis were carried out. Sera from pigs experimentally infected with Brucella suis and naturally infected feral pigs, sera from pigs from a farm with a known history of Yersinia enterocolitica 0:9 infection, Brucella Complement Fixation Test (CFT) reactor pigs (aetiology unknown) and pigs from consistently Brucella CFT negative farms were examined. Although B. suis infected pigs recognized a total of nine B. melitensis antigens, individual pigs rarely recognized more than three antigens in the range. A 62 kDa antigen was recognized by the majority (73%) of the Brucella infected pigs, but only by 10 to 23% of pigs from the other groups. This antigen was shown to be the Brucella homologue of the ubiquitous 65 kDa heat shock protein (HSP-65) family by immunoblot studies with 14 monoclonal antibodies to the Mycobacterium leprae HSP-65. Only four of these monoclones (Y1.2, ML-30, D7C and IIIC8) identified the B. melitensis 62 kDa protein suggesting that unshared, potentially Brucella specific, regions exist. Sera from Y. enterocolitica 0:9 infected pigs, CFT reactor pigs (aetiology unknown), CFT negative pigs and hyperimmune pig serum raised to Y. enterocolitica 0:9 also recognized B. melitensis antigens, most notably a 17 kDa protein. This antigen appears to be a common cross-reactive protein.

Animals↗

PubMed1994

Potassium inhibits cultured vascular smooth muscle cell proliferation.

Increased dietary K+ increases plasma [K+] and is linked to or associated with reduced mortality from stroke and reduced blood pressure in humans and animals. We hypothesized that physiologic increases in extracellular [K+] ([K]o) directly inhibit cultured vascular smooth muscle cell (VSMC) proliferation. Studies were performed by stimulating quiescent cultured canine coronary artery and A7r5 VSMC with 5% serum at varying [K]o starting on day 0. When plated at 5,200 cells/cm2 A7r5 VSMC counts increased 121% by day 2 and 190% by day 6 in 3 mmol/L [K]o, but only 21% by day 2 and 45% by day 6 in 7 mmol/L [K]o; intermediate [K]o yielded intermediate proliferative rates. Serum caused a four- to fivefold increase in cell counts of cultured canine coronary artery VSMC in 7 days at 2 mmol/L [K]o of 2 mmol/L, and increasing [K]o to 7 mmol/L reduced proliferation by 68%. Uptake of [3H]thymidine by cultured canine coronary artery VSMC was inhibited by 50% between 2 and 7 mmol/L [K]o. Increased [K]o may act by decreasing intracellular Na+ ([Na]i). Exposure to serum for 24 h more than doubles canine coronary artery [Na]i, an effect previously associated with VSMC proliferation, and increased [K]o (from 2 to 7 mmol/L) reduces [Na]i by 74% before and 64% 24 h after serum. We conclude that physiologic increases in [K]o reduce [Na]i and proliferation of cultured VSMC. Similar effects occurring in vivo may help to account for the ability of increased dietary K+ to prevent vascular lesions.

Analysis of Variance↗

PubMed1994

Death investigations involving personal computers.

Three death investigations are reviewed in which personal computers owned by the deceased were used to provide information regarding their deaths. To obtain the information from computers, however, the death investigator or forensic pathologist must have the investigative skills to secure this evidence for examination by a computer expert. Unless the computer is handled carefully, the information could be lost or even destroyed. This article provides recommendations for the investigation of a death scene where a personal computer has been found, how to secure it, and where to obtain assistance for the examination of the information contained on the computer.

Adult↗

PubMed1994

Transformation of mycobacterial species using hygromycin resistance as selectable marker.

Electroporation with shuttle plasmids carrying a kanamycin resistance gene as a selectable marker failed to generate transformants in two mycobacterial species currently being used in human vaccine trials (Mycobacterium w and Mycobacterium vaccae). In contrast, efficient transformation [10(3)-10(5) transformants (micrograms DNA)-1] was obtained using novel vectors with selection based on expression of resistance to hygromycin. The hygromycin resistance vector was also found to be more efficient than kanamycin resistance vectors for transformation of Mycobacterium smegmatis and Mycobacterium bovis BCG. The hygromycin resistance vector was used to overexpress superoxide dismutase of Mycobacterium tuberculosis in M. vaccae in a form suitable for detailed structural analysis. The potential use of this approach for generation of novel recombinant mycobacterial vaccines is discussed.

Bacterial Proteins↗

PubMed1994

Nerve and skin damage in leprosy is associated with increased intralesional heat shock protein.

Leprosy is frequently complicated by the development of reversal reactions in which peripheral nerve and skin lesions become inflamed and irreversible nerve damage may ensue. Increased expression of proteins belonging to the 70-kD heat shock family (hsp 70) occurs in cells of the central nervous system exposed to hyperthermia, physical damage or drug-induced trauma. In the present study we have used immunocytochemical staining to monitor hsp70 levels in peripheral nerves infected by Mycobacterium leprae. Hsp70 was detected in skin and nerve lesions from all leprosy patients, but was particularly prominent in lesions from patients undergoing reversal reactions. Hsp70 immunocytochemistry can thus be used as a marker of neural injury in the peripheral as well as in the central nervous system. The cellular dynamics of nerve damage in leprosy are currently poorly understood, and we postulate that the immunopathology of leprosy may be partly due to an autoimmune response to heat shock proteins.

Biopsy↗

PubMed1994

Effects of phenylbutazone on thiamylal disposition and anaesthesia in ponies.

Phenylbutazone given during the perisurgical period has been reported to increase the intensity and duration of thiamylal anaesthesia in horses. A possible mechanism of competitive plasma protein binding has been suggested. The purpose of the present study was to experimentally reproduce the phenomenon of increased intensity and/or duration of thiamylal anaesthesia and to determine if there is competitive displacement of plasma protein bound thiamylal by phenylbutazone. Six ponies each received one of three treatments, 11 mg/kg intravenous (i.v.) thiamylal; 8.8 mg/kg i.v. phenylbutazone; and 11 mg/kg i.v. thiamylal with 8.8 mg/kg i.v. phenylbutazone given 9 min later. Thirteen blood samples were collected from 0 time through 600 min following drug administration and plasma drug concentrations quantified by high performance liquid chromatography. The pharmacokinetics of thiamylal and phenylbutazone were best described by three- and two-compartment models, respectively. There were no significant differences in pharmacokinetic parameters for thiamylal in the presence of phenylbutazone. However, there were differences in phenylbutazone pharmacokinetics when preceded by thiamylal administration. Unbound phenylbutazone concentrations were increased at 171, 231 and 351 min when given with thiamylal, accompanied by decreases in per cent bound phenylbutazone (P < 0.05). There were also significant (P < 0.05) changes in per cent plasma protein binding of thiamylal and phenylbutazone between 120 and 360 min, when in combination. No changes in intensity or duration of anaesthesia were observed.

Anesthesia↗

PubMed1994

Interaction between plasma potassium and epinephrine in coronary thrombosis in dogs.

BACKGROUND: Both plasma potassium ([K]) and epinephrine concentrations have been known to increase during exercise and decrease rapidly shortly after exercise; in addition, it is also known that exercise can promote coronary thrombosis in human and animal subjects. Many studies have shown that epinephrine has a stimulatory effect on coronary thrombosis; however, little information is available concerning the effect of raising plasma [K] on coronary thrombosis. The present study was designed to investigate the effect of raising plasma [K] and its interaction with epinephrine infusion on coronary thrombosis. METHODS AND RESULTS: A canine model of coronary thrombosis was used, and the frequency of cyclic blood flow reductions (CFRs) resulting from thrombus formation in the circumflex artery was analyzed in the study. By acutely raising plasma [K] to approximately 6.0 mEq/L, the frequency of CFRs was reduced from 8.0 +/- 0.6 to 3.7 +/- 1.0 in 40 minutes (P < .01). Epinephrine infusion (0.5 microgram.kg-1 x min-1) stimulated the frequency of CFRs from 7.1 +/- 0.5 to 11.5 +/- 0.7 in 40 minutes (P < .01). However, if plasma [K] was raised to approximately 6.0 mEq/L while the epinephrine infusion was continued, the frequency fell from 11.5 +/- 0.7 to 7.7 +/- 1.1 in 40 minutes (P < .01). CONCLUSIONS: The present study demonstrated that acutely raising plasma [K] inhibited coronary thrombosis in dogs and also blocked the potentiating effect of epinephrine on coronary thrombosis. These findings may suggest that raising plasma [K] exerts a protective effect against coronary thrombosis and that a rapid decrease in plasma [K], such as that occurring shortly after exercise, facilitates coronary artery thrombosis when the artery has a preexisting pathological condition.

Animals↗

PubMed1994

Potassium inhibits free radical formation.

We conducted this study to determine whether physiological changes in potassium concentration affect free radical formation by vascular cells. We assessed the effects of potassium on reactive oxygen species formed by cultured endothelial and monocyte/macrophage cells or freshly isolated human white blood cells by cytochrome c reduction or luminol chemiluminescence, respectively. Reducing potassium concentration of endothelial cell media (normally 5.1 to 6.1 mmol/L) to 3.0 mmol/L exponentially increased the rate of cytochrome c reduction, up to 8.4-fold at 2 hours; raising potassium concentration to 5.5 or 7.0 mmol/L at 1 hour reduced the maximal rate of cytochrome c reduction by 86% or 93%. Subsequent studies were done 30 to 75 minutes after media change. Potassium reduced the rate of cytochrome c reduction by 49% (endothelial cells) to 55% (monocytes/macrophages) between 3.0 and 7.0 mmol/L; the greatest decrement (20% to 26%) occurred between 3.0 and 4.0 mmol/L. Superoxide dismutase reduced the rate of cytochrome c reduction by 62% or 50% in endothelial or monocyte/macrophage cells. Potassium had no effect on the rate of cytochrome c reduction in the presence of superoxide dismutase. Increasing potassium concentration from 1.48 to 4.77 or 7.94 mmol/L also reduced luminol chemiluminescence in human white blood cells challenged by 1 to 10 mg/mL zymosan. We conclude that physiological increases in potassium concentration inhibit the rate of superoxide anion formation by cell lines derived from endothelium and from monocytes/macrophages and reactive oxygen species formation by human white blood cells.

Animals↗

PubMed1993

Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: a candidate Lyme disease vaccine.

The current vaccine against tuberculosis, Mycobacterium bovis strain bacille Calmette-Guerin (BCG), offers potential advantages as a live, innately immunogenic vaccine vehicle for the expression and delivery of protective recombinant antigens (Stover, C.K., V.F. de la Cruz, T.R. Fuerst, J.E. Burlein, L.A. Benson, L.T. Bennett, G.P. Bansal, J.F. Young, M.H. Lee, G.F. Hatfull et al. 1991. Nature [Lond]. 351:456; Jacobs, W.R., Jr., S.B. Snapper, L. Lugosi and B.R. Bloom. 1990. Curr. Top. Microbiol. Immunol. 155:153; Jacobs, W.R., M. Tuckman, and B.R. Bloom. 1987. Nature [Lond.]. 327:532); but as an attenuated intracellular bacterium residing in macrophages, BCG would seem to be best suited for eliciting cellular responses and not humoral responses. Since bacterial lipoproteins are often among the most immunogenic of bacterial antigens, we tested whether BCG expression of a target antigen as a membrane-associated lipoprotein could enhance the potential for a recombinant BCG vaccine to elicit high-titered protective antibody responses to target antigens. Immunization of mice with recombinant BCG vaccines expressing the outer surface protein A (OspA) antigen of Borrelia burgdorferi as a membrane-associated lipoprotein resulted in protective antibody responses that were 100-1,000-fold higher than responses elicited by immunization with recombinant BCG expressing OspA cytoplasmically or as a secreted fusion protein. Furthermore, these improved antibody responses were observed in heterogeneous mouse strains that vary in their immune responsiveness to OspA and sensitivity to BCG growth. Thus, expression of protective antigens as chimeric membrane-associated lipoproteins on recombinant BCG may result in the generation of new candidate vaccines against Lyme borreliosis and other human or veterinary diseases where humoral immunity is the protective response.

Animals↗