Effect of anticoagulation on the occurrence of deep venous thrombosis associated with temporary transvenous femoral pacemakers.
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Aged↗
Biomedical subjects
G D Young
Publications and source records attributed to G D Young.
Intravenous magnesium sulfate for acute termination of sustained monomorphic ventricular tachycardia associated with coronary artery disease.
The efficacy of intravenous magnesium in terminating sustained monomorphic ventricular tachycardia was examined in this study. This therapy was found to be ineffective in aborting monomorphic ventricular tachycardia induced in the electrophysiology laboratory.
Anti-Arrhythmia Agents↗
Arteether-induced brain injury in Macaca mulatta. I. The precerebellar nuclei: the lateral reticular nuclei, paramedian reticular nuclei, and perihypoglossal nuclei.
Malaria poses a threat across several continents: Eurasia (Asia and parts of Eastern Europe), Africa, Central and South America. Bradley (1991) estimates human exposure at 2,073,000,000 with infection rates at 270,000,000, illnesses at 110,000,000, and deaths at 1,000,000. Significant mortality rates are attributed to infection by the parasite Plasmodium falciparum, with an estimated 90% among African children. A worldwide effort is ongoing to chemically and pharmacologically characterize a class of artemisinin compounds that might be promising antimalarial drugs. The U.S. Army is studying the efficacy and toxicity of several artemisinin semi-synthetic compounds: arteether, artemether, artelinic acid, and artesunate. The World Health Organization and the U.S. Army selected arteether for drug development and possible use in the emergency therapy of acute, severe malaria. Male Rhesus monkeys (Macaca mulatta) were administered different daily doses of arteether, or the vehicle alone (sesame oil), for a period of either 14 days, or 7 days. Neuropathological lesions were found in 14-day arteether treated monkeys in the precerebellar nuclei of the medulla oblongata, namely: (1) the lateral reticular nuclei (subnuclei magnocellularis, parvicellularis, and subtrigeminalis), (2) the paramedian reticular nuclei (subnuclei accessorius, dorsalis, and ventralis), and the perihypoglossal nuclei (n. intercalatus of Staderini, n. of Roller, n. prepositus hypoglossi). The data demonstrate that the simina meduallry precerebellar nuclei have a high degree of vulnerability when arteether is given for 14 days at dose levels between 8mg/kg per day and 24 mg/kg per day. The neurological consequences of this treatment regimen could profoundly impair posture, gait, and autonomic regulation, while eye movement disorders might also be anticipated.
Animals↗
An unusual cause of arrhythmic syncope: the Brugada syndrome.
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Antidepressive Agents↗
An intranasal challenge model for testing Japanese encephalitis vaccines in rhesus monkeys.
Placebo-controlled field efficacy trials of new Japanese encephalitis (JE) vaccines may be impractical. Therefore, an animal model to evaluate efficacy of candidate JE vaccines is sought. Previous work has shown that exposure of monkeys to JE virus (JEV) via the intranasal route results in encephalitis. Here we report the further development of this model and the availability of titered virus stocks to assess the protective efficacy of JE vaccines. To determine the effective dose of our JE challenge virus, dilutions of a stock JEV (KE-93 isolate) were inoculated into four groups of three rhesus monkeys. A dose-dependent response was observed and the 50% effective dose (ED50) was determined to be 6.0 x 10(7) plaque forming units (pfu). Among animals that developed encephalitis, clinical signs occurred 9-14 days postinoculation. Infection with JEV was confirmed by detection of JEV in nervous tissues and IgM to JEV in the cerebrospinal fluid. Viremia with JEV was also detected intermittently throughout infection. Validation of the model was performed using a known effective JE vaccine and saline control. One ED90 of virus (2.0 x 10(9) pfu) was used as a challenge dose. Four of four animals that received saline control developed encephalitis while one of four monkeys administered the JE vaccine did so. This study demonstrates that the virus strain, route of inoculation, dose, and the outcome measure (encephalitis) are suitable for assessment of protective efficacy of candidate JE vaccines.
Administration, Intranasal↗
Production of lethal infection that resembles fatal human disease by intranasal inoculation of macaques with Japanese encephalitis virus.
Twelve rhesus macaques (Macaca mulatta) challenged intranasally with a wild-type Japanese encephalitis virus (JEV) developed clinical signs 11-14 days later. Tissues from the cerebral cortex, cerebellum, brainstem, thalamus, meninges, and all levels of the spinal cord were stained for JEV antigen with hyperimmune mouse ascitic fluid and streptavidin-alkaline phosphatase; immunofluorescent staining was also done on frozen sections. Viral antigen was found in all cell layers of the cerebellum, the gray matter of the thalamus and brainstem, and the ventral horn of all levels of the spinal cord. Staining was limited to neurons and their processes. Histopathologic changes were limited to the nervous system and characterized by nonsuppurative meningoencephalitis. These results were comparable with those of previous studies done with human autopsy tissues. Intranasal inoculation of rhesus monkeys with JEV was effective in producing clinical disease comparable with natural disease in humans and may serve as a model to evaluate protective efficacy of candidate JEV vaccines.
Administration, Intranasal↗
Safety, immunogenicity, and protective efficacy of NYVAC-JEV and ALVAC-JEV recombinant Japanese encephalitis vaccines in rhesus monkeys.
Two poxvirus-vectored vaccines for Japanese encephalitis (JE), NYVAC-JEV and ALVAC-JEV, were evaluated in rhesus monkeys for safety, immunogenicity, and protective efficacy. The vaccines were given to four monkeys each on study days 0 and 28 along with saline placebo on day 7. For controls, the licensed BIKEN JE vaccine and a saline placebo were given to other groups of four monkeys on days 0, 7, and 28. No systemic effects were observed. All injection site reactions were mild. All vaccines elicited appreciable JE-specific neutralizing antibody responses. However, a more rapid increase and higher peak level of antibody were seen in the BIKEN group as compared with the NYVAC-JEV and ALVAC-JEV groups. The peak neutralizing antibody level in the NYVAC-JEV group was higher than that of the ALVAC-JEV group. Antibody persisted in all four BIKEN recipients through 273 days of follow-up, whereas, the antibody level decreased to the threshold of detection in two NYVAC-JEV and all four ALVAC-JEV recipients by day 120. On day 273, all monkeys were given a booster dose. A rapid increase in neutralizing antibody was seen in all vaccine recipients by seven days. Two months after the booster dose, all monkeys were challenged intranasally with one 90% effective dose of JE virus. Four recipients of saline, three of ALVAC-JEV, one of NYVAC-JEV, and one of BIKEN experienced encephalitis. This study suggests that the NYVAC-JEV and ALVAC-JEV vaccines are safe and immunogenic in monkeys and that the NYVAC-JEV and BIKEN vaccines are effective in protecting monkeys from encephalitis.
Administration, Intranasal↗
Safety and efficacy of DEET and permethrin in the prevention of arthropod attack.
Many preventable diseases affecting troop strength are directly attributed to disease-carrying insects. The first line of defense against arthropod vectors is the use of personal protective measures. The concurrent application of DEET (N,N-diethyl-m-toluamide) repellent on the skin and permethrin [(3-phenoxy-phenyl)methyl(+/-)cis,trans-3-(2,2-dichloroethenyl)-2, 2- dimethylcyclopropane-carboxylate] insecticide on the battle dress uniform, while the uniform is worn properly, is a personal protective strategy officially known as the DOD Insect Repellent System. It is important for troop commanders and field leaders to enforce the use of personal protective measures to prevent insect-borne infectious diseases and to ensure troop and soldier readiness. DEET is a safe and effective repellent. Permethrin is a synthetic pyrethroid insecticide and repellent. Used in conjunction with proper clothing and other personal protective equipment, these repellents provide the best known protection available and are critical in minimizing the occupational health threat of arthropod-borne diseases to troops in the field.
DEET↗
Arteether: risks of two-week administration in Macaca mulatta.
Male rhesus monkeys (Macaca mulatta) were administered daily doses of the antimalarial drug arteether. The 14-day treated group received either 24 mg/kg/day, 16 mg/kg/day, or 8 mg/kg/day. The seven-day treatment group received either 24 mg/kg/day or 8 mg/kg/day. All control cases in each group received the sesame oil vehicle alone. Neurologic signs were absent for animals in the seven and 14-day treatment groups except for one monkey which showed diffuse piloerection on day 14, and another monkey receiving 24 mg/kg/day for seven days showed mild lethargy after the fourth day. Mild, sporadic anorexia was noted in all animals by day 14, and a single animal showed diffuse piloerection on day 14. Surgical anesthesia preceded killing by exsanguination and was accompanied by perfusion fixation of the central nervous system. Brain sections were cut and then stained for study by light microscopy. Evidence of neuronal pathology, both descriptive and numerical, was collected. The neuroanatomic and neuropathologic findings demonstrated that arteether produced extensive brainstem injury when administered for 14 days. The magnitude of brainstem neurotoxicity was dose-dependent, where injury was greatest at the 24 mg/kg/day dose level, less at the 16 mg/kg/day dose level, and least at the 8 mg/kg/day dose level. Arteether induced multiple systems injury to brainstem nuclei of 1) the reticular formation (cranial and caudal pontine nuclei, and medullary gigantocellular and paragigantocellular nuclei); 2) the vestibular system (medial, descending, superior, and lateral nuclei); and 3) the auditory system (superior olivary nuclear complex and trapezoid nuclear complex). The vestibular nuclei and the reticular formation were most severely injured, with the auditory system affected less. The cranial nerve nuclei (somatic and splanchnic) appeared to escape damage, with the exception of the abducens nerve nucleus. The same brainstem nuclear groups of seven-day treated monkeys appeared normal. The statistical data are concordant with the descriptive data in demonstrating neurotoxic effects. In summary, no neurologic deficits were detected in any of the vehicle control monkeys (14-day and seven-day cases). Monkeys in the 14-day treatment group were free of clinical neurologic signs throughout the first week. At day 14, fine horizontal nystagmus was seen in one monkey, and another monkey exhibited diffuse piloerection. Monkeys in the seven-day treatment group were free of clinical neurologic signs except for one case. This monkey was treated with 24/mg/kg/day of arteether and exhibited lethargy after the fourth day. These indications of dysfunction arose too late to be practical indicators of neurotoxicity.
Animals↗
Experimental infection of the laboratory rat with the hepatitis E virus.
To confirm an earlier report that laboratory rats are susceptible to infection with the hepatitis E virus (HEV), we inoculated 27 Wistar rats intravenously with a suspension of a human stool known to contain infectious HEV. Stool, sera, and various tissues were collected from three rats each on days 0 (preinoculation) and 4, 7, 11, 14, 18, 21, 25, 28, and 35 postinoculation. Stool and sera specimens were examined by reverse transcription-polymerase chain reaction for the presence of HEV genomic sequences. Tissues were examined by light microscopy for detection of histopathological changes and by direct immunofluorescence for detection of HEV antigens. We detected HEV RNA in stools on day 7 in all three animals and in serum intermittently between days 4 and 35. We found HEV antigens in liver, peripheral blood mononuclear cells, spleen, mesenteric lymph nodes, and small intestine. We detected histopathology attributable to the inoculum in liver, spleen, and lymph nodes. The results confirm that HEV can replicate in laboratory rats and suggest new tissue sites for HEV replication.
Adult↗
Pathogenesis of hepatitis A in orally inoculated owl monkeys (Aotus trivirgatus).
The pathogenesis of hepatitis A virus (HAV) infection was studied in owl monkeys following oral administration of the wild-type HM-175 strain of HAV. Stools were collected daily and blood and pharyngeal swabs twice weekly for viral isolation, and animals were necropsied at various intervals after inoculation. Organs were examined for the presence of virus by isolation in cell culture and for viral antigens by immunofluorescence. Monkeys excreted HAV in the stools for 1-4 days after inoculation, presumably due to the residual unabsorbed inoculum. No virus was found in stools for the next 2-3 days. HAV re-appeared on days 4-7 and then persisted through day 39. Viremia occurred on the 10th day and continued until day 35. Virus was isolated occasionally from throat swabs 1 or 2 weeks after it was detected in stools and blood, and there was no evidence that HAV replicated in the pharyngeal tissues. Animals acquired anti-HAV antibody by the 4th week, and alanine aminotransferase (ALT) was elevated 5-5.5 weeks after inoculation. HAV was isolated from liver 5 days after inoculation; however, viral antigens were first detected in Kupffer cells of the liver at 14 days and in hepatocytes at 21 days. HAV antigen was detected in epithelial cells of the intestinal crypts and in the cells of the lamina propria of the small intestine 3 days postinoculation and thereafter until the 5th week, suggesting that these cells might represent an additional site of HAV replication.
Administration, Oral↗
Acute toxicity of cyclohexylmethylphosphonofluoridate (CMPF) in rhesus monkeys: serum biochemical and hematologic changes.
Changes in serum biochemical and hematological parameters were studied in 20 male rhesus monkeys following acute poisoning by the organophosphate nerve agent cyclohexylmethylphosphonofluoridate (CMPF or GF). Animals were challenged with 5 x LD50 GF (233 micrograms/kg, IM) following pretreatment with pyridostigmine (0.3-0.7 mg/kg per 24 h) and treated with atropine (0.4 mg/kg, IM) and either 2-PAM (25.7 mg/kg, IM) or H16 (37.8 mg/kg, IM) at the onset of clinical signs or at 1 min after exposure. Muscle fasciculations, tremors, or convulsions occurred in 19 of 20 animals. Serum biochemical and hematologic parameters were analyzed 2 days and 7 days after exposure and compared to pre-exposure baseline values. Significant increases in creatine kinase (CK), lactate dehydrogenase (LD), aspartate transaminase (AST), alanine transaminase (ALT) and potassium ion (K+), associated with damage to striated muscle and metabolic acidosis, occurred in both oxime-treated groups 2 days after exposure. Total protein, albumin, red blood cell (RBC) count, hemoglobin concentration (Hb) and hematocrit (Hct), were decreased in both oxime-treated groups at 7 days. The results demonstrate that animals exposed to a single high dose of GF and treated with standard therapy exhibit changes in serum biochemical and hematological indices directly and indirectly associated with their clinical presentations.
Alanine Transaminase↗
Efficacy of sotalol guided by programmed electrical stimulation for sustained ventricular arrhythmias secondary to coronary artery disease.
Sotalol is a class III antiarrhythmic drug with additional beta-blocker activity that has been shown to be effective in supraventricular and ventricular arrhythmias. Its long-term efficacy for ventricular arrhythmias is not as well described. Patients with documented sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) who had their clinical arrhythmia inducible at baseline electrophysiologic study received sotalol 320 to 640 mg/day. Repeat programmed stimulation was performed after a minimum of 72 hours while receiving the final dose. Of 28 patients (25 men and 3 women) whose arrhythmias were inducible at baseline, 15 had their arrhythmias suppressed with sotalol. Sotalol had greater success in suppressing arrhythmias in those with VF (8 of 9, 89%) than in those with VT (7 of 19, 37%, p < 0.01). In patients with a history of coronary artery disease but no history of myocardial infarction the arrhythmia was suppressed in 7 of 8 (88%) compared with 8 of 20 (40%, p < 0.05) patients with a history of myocardial infarction. All 15 patients in whom ventricular arrhythmias were suppressed continued to take long-term sotalol, and at a follow-up of 10.3 +/- 6.4 months none has had arrhythmia recurrence. Thus, sotalol is an effective drug for the suppression of ventricular arrhythmias as judged by programmed electrical stimulation. It appears to be more effective in patients in whom the clinical arrhythmia is VF rather than VT.
Aged↗
Comparing matching ability, spatial memory, and ideational fluency in boys and girls.
The purpose of our study was to examine whether girls and boys show patterns of problem-solving ability similar to those attributed by Kimura in 1992 to women and men, respectively. Subjects were 28 girls and 24 boys, aged 5-11 years, who were tested individually on matching ability, spatial memory, and ideational fluency, tasks on which women reportedly outperform men. No significant gender differences in these problem-solving abilities were found. On ideational fluency, the youngest girls were seven times more likely than young boys to give whimsical responses, but older girls were then times less likely than older boys to give whimsical responses. These results suggest that the patterns of visuospatial problem-solving abilities that Kimura ascribed to women and men are not present in preadolescent girls and boys.
Aptitude↗
Cryofibrinogenaemia: a case report.
A case of chronic acral ulceration is described in a 54-year-old man with cryofibrinogenaemia. Initial management with prednisolone and azathioprine was unsuccessful in controlling the disease. Introduction of a programme of plasmapheresis in addition to treatment with cyclophosphamide and prednisolone has brought about marked improvement.
Cryoglobulinemia↗
Enhancement of tissue plasminogen activator-induced fibrinolysis by activated protein C in endotoxin-treated rabbits.
Endotoxin-treated rabbits produce high levels of plasminogen activator inhibitor-1 (PAI-1), which inhibits fibrinolysis by neutralizing endogenous tissue-type plasminogen activator (t-PA). These animals will develop renal fibrin deposition when infused with ancrod, an enzyme that acts directly on fibrinogen. In normal rabbits with an intact fibrinolytic system, ancrod induces hypofibrinogenemia without fibrin deposition. Rabbit PAI-1 activity can be neutralized by recombinant human t-PA or by bovine activated protein C. The present study determined the efficacy of these two agents used alone or in combination in neutralizing increased PAI-1 activity and in preventing renal fibrin deposition in a rabbit model. Male New Zealand rabbits first received intravenous endotoxin to increase PAI-1 activity. Ancrod was infused intravenously during hour 4 to 5, and the kidneys were examined at hour 5.5. Renal fibrin deposition occurred in 100% (6 out of 6) of the endotoxin-treated rabbits that received ancrod; this was reduced to 14% (1 out of 7) for rabbits receiving t-PA (170 micrograms/kg) before and during the ancrod infusion. Fibrin deposition occurred in only 12% (1 out of 8) of the rabbits that received a 10-fold lower dose of t-PA (17 micrograms/kg) combined with activated protein C (1 mg/kg) before and during the ancrod. Activated protein C at this dose completely neutralized plasma PAI-1 activity. However, low-dose t-PA and activated protein C did not prevent fibrin deposition when used as single agents, with fibrin deposition occurring in 75% and 100% of rabbits, respectively. The data indicate that activated protein C can neutralize plasma PAI-1 activity in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Ancrod↗
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↗
Plasminogen activator inhibitor: a regulator of ancrod-induced fibrin deposition in rabbits.
Plasma levels of a fast-acting plasminogen activator inhibitor (PAI), which neutralizes both tissue plasminogen activator (t-PA) and urokinase, are markedly increased in endotoxin-treated rabbits. The ability of this inhibitor to prevent the fibrinolysis that occurs after a thrombogenic stimulus was investigated in a rabbit model. Normal and endotoxin-treated male New Zealand rabbits were infused with ancrod, an enzyme that causes noncrosslinked fibrin formation in vivo. Ancrod stimulated t-PA activity by 90% in normal rabbits and caused hypofibrinogenemia but did not increase PAI levels or induce fibrin deposition in target organs. Rabbits injected with endotoxin (10 micrograms/kg) showed an increase in PAI from less than 1 to 32 U/mL 4 hours later. When ancrod was infused at this time, 90% of the rabbits developed renal fibrin thrombi. Fibrin deposition was recorded in 40% of the rabbits that received a lower dose of endotoxin (1.0 microgram/kg) and had a PAI level of 14 U/ml at the time of ancrod infusion 4 hours later. Fibrin deposition did not occur in the endotoxin-treated rabbits that received normal saline. These data suggest that high levels of PAI inhibit fibrinolysis in vivo, thereby promoting fibrin clot deposition following a thrombogenic stimulus.
Ancrod↗