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Biomedical subjects

C J Flynn

Publications and source records attributed to C J Flynn.

14 recordsLinked to original sources
PubMed1999

Phenylalanine kinetics are associated with tardive dyskinesia in men but not in women.

RATIONALE: An association between tardive dyskinesia (TD) and severely impaired metabolism of the large neutral amino acid (LNAA), phenylalanine (Phe) was defined in a group of mentally retarded patients. Subsequently, an altered kinetics of Phe was associated with TD in men with schizophrenia based on plasma analyses subsequent to the ingestion of a protein meal. METHODS: In the present study, a standardized oral challenge of pure Phe (100 mg/kg in 170 ml orange juice) was administered to psychiatric patients of both sexes (n = 312), with and without TD after an overnight fast. Plasma LNAA levels were assayed both fasting and 2 h subsequent to the ingestion of the challenge. The extent of the increase in plasma Phe levels 2 h following a standardized challenge is determined by the sum of the kinetic processes of plasma absorption, tissue distribution, metabolism and elimination. RESULTS: The study hypothesis, that TD would be associated with significantly higher post-challenge plasma Phe indices of an absolute plasma Phe level and plasma Phe/LNAA ratio (a brain availability measure), was verified for the study men (n = 209), but not for the study women (n = 103). CONCLUSIONS: The demonstrated altered kinetics of Phe in men with TD indicates a greater availability of Phe to the brain in these men. We suggest that the disorder may be related to the effects of this greater availability. Such effects could be the direct neurotoxic effects of Phe and its metabolites and/or the modulating effects of these compounds on the synthesis of the monoamine neurotransmitters. The fact that TD (Yes/No) group differences in post-challenge plasma Phe indices were not seen for the study women suggests the possibility of a sex difference in the biology of TD that we propose may be reflective of the young age of the study sample.

Absorption↗
PubMed1999

Branched chain amino acids decrease tardive dyskinesia symptoms.

RATIONALE: Prior studies had suggested (a) that a lessened ability to clear ingested forms of the large neutral amino acid (LNAA), phenylalanine (Phe), was associated with having tardive dyskinesia (TD), and (b) that greater availability of a group of LNAA, the branched chain amino acids (BCAA), concomitant with the lower availability of Phe to the brain are associated with a decrease in TD symptoms. The present study was then conducted to test whether increasing the daily intake of the BCAA would decrease the symptoms of TD. METHODS: A 2-week trial of a BCAA medical food administered three times a day was conducted in nine men with long neuroleptic treatment histories. Frequency counts of TD movements were collected by videotape throughout the trial and these tapes were analyzed in blind random sequence for both patient and time for TD symptom level changes subsequent to completion of the trial. Plasma levels of the LNAA were also collected throughout the trial. RESULTS: A statistically significant decrease in the level of TD symptoms was observed for the sample. The symptom changes were also clinically significant in that six of the nine subjects had symptom decreases of at least 58%, with all subjects having a decrease of at least 38%. BCAA administration increased plasma BCAA concentrations and BCAA/LNAA ratios and decreased plasma Phe concentrations and the Phe/LNAA ratio. Analyses indicated a strong significant correlation between the percent increase in the plasma BCAA values at the first administration and the percent improvement in TD over the trial in eight of the nine subjects. CONCLUSIONS: The BCAA show promise as a treatment for TD. The decrease in TD symptoms seen in the trial may have been modulated by the BCAA treatment-induced increased availability of the BCAA and decreased availability of Phe to the brain.

Amino Acids, Branched-Chain↗
PubMed1997

Law enforcement K-9 dog bites: injuries, complications, and trends.

STUDY OBJECTIVE: To quantify the number of individuals bitten, the number of bites per patient, and the types of injuries and complications caused by law enforcement K-9 dog bites treated in the Jail Ward Emergency Department of the Los Angeles County-University of Southern California Medical Center. These variables were compared before and after a change in K-9 police policy from the "bite-and-hold" to the "find-and-bark" technique or stricter controls were instituted over the K-9 teams. METHODS: A retrospective chart review of all patients in police custody with K-9 dog bites who presented to the Jail Ward ED between January 1, 1988, and December 31, 1995, was conducted. Demographic data of patients with K-9 dog bites, the number and location of bites, complications, procedures performed, and management of bites were recorded and compared between the periods 1988-1991 (before the policy changes) and 1992-1995 (after the changes). RESULTS: Between 1988 and 1995 790 in-custody patients were treated for K-9 dog bites in the Jail Ward ED; 705 charts were available for review. Nearly all the patients (98.6%) were male, with a mean age of 25; 85.0% were Hispanic or black. More than half (57.2%) sustained three or more bites, mainly to the extremities. Complications ensued in 19.3%: vascular in 7.0%, infection in 5.0%, fracture or cortical violation in 4.0%, nerve injury in 1.9%, and tendon injury in 1.1%. Half (49.9%) were hospitalized, with a median stay of 3 days. After the change in K-9 policy, the number of patients with K-9 dogs bites presenting to the Jail Ward ED decreased from 639 (1988-1991) to 66 (1992-1995). The proportion of patients who sustained three or more bites decreased from 58.4% to 45.5%. The rate of vascular complications decreased from 7.5% to 1.6%, the rate of fractures decreased from 2.4% to 0, and the rate of cortical violations increased from 1.4% to 6.3%. The proportion of patients hospitalized decreased from 52.0% to 33.8%. CONCLUSION: K-9 dog bites are associated with significant injuries and complications. In this study, changes in law enforcement K-9 policy contributed to a significant decrease in the overall number of individuals bitten, the number of injuries and complications, and the proportion of patients hospitalized.

Adolescent↗
PubMed1996

Managing law enforcement (K-9) dog bites in the emergency department.

OBJECTIVE: To review the types of injuries due to law enforcement (K-9) dog bites and address related management issues. METHODS: A case series of law enforcement dog bite victims is reported and related literature reviewed. RESULTS: Law enforcement dogs are taught a bite-and-hold technique for subduing individuals suspected of felony crimes. This bite-and-hold technique's greater applied force results in a unique spectrum of injuries, including deep puncture wounds, severe crush injuries, large tissue avulsions and lacerations, wounds necessitating surgical débridement, bony injuries ranging from cortical violations to displaced fractures, neurovascular damage, and other wounds at high risk for infection. The four reported cases highlight the types of injuries and complications associated with law enforcement dog bites. CONCLUSION: Attention to potential deep injuries of nerves, vessels, and the musculoskeletal system is essential with law enforcement dog bites. Injuries associated both with pursuit and arrest and with the bites themselves must be identified and assessed. Guidelines for the ED treatment of patients with law enforcement dog bite injuries are proposed.

Adolescent↗
PubMed1995

Dietary calcium and lead interact to modify maternal blood pressure, erythropoiesis, and fetal and neonatal growth in rats during pregnancy and lactation.

We studied the effects of dietary calcium and lead exposure on lead toxicity, fetal and neonatal growth, erythropoiesis and blood pressure during pregnancy and lactation in rats. Pregnant Sprague-Dawley rats (n = 43) were randomly assigned to one of six treatment groups of 7-8 rats each. Half of the rats were fed diets of low (0.1%), normal (0.5%) or high (2.5%) calcium as calcium carbonate and exposed to 250 mg/L of lead in their drinking water for the duration of the pregnancy and for 1 wk of lactation. Three control groups were fed the same diets without lead exposure. Pups were studied at 1 d and 1 wk of age. Maternal and fetal blood and organ samples from the groups fed the low calcium diet had the highest lead concentrations, whereas the lowest lead concentrations were found in the groups fed the high calcium diet. Dam and pup hemoglobin concentrations, hematocrits, and body weights and lengths were reduced by lead exposure and by the high calcium diet. The latter also reduced organ iron concentrations and prevented lead-induced increases in free erythrocyte protoporphyrin. Dam systolic blood pressures during the third trimester of gestation were significantly higher in rats exposed to lead and fed the low calcium diet than in rats in the other five treatment groups. The results demonstrate that dietary calcium and lead exposure interact in rats to influence maternal blood pressure, erythropoiesis, and fetal and neonatal growth during pregnancy and lactation.

Animals↗
PubMed1992

Isolation and characterization of periaxolemmal and axolemmal enriched membrane fractions from the rat central nervous system.

In this report, we describe the fractionation of crude axolemmal fractions from rat lower brainstem into subfractions enriched in markers for either periaxolemmal myelin or axolemma. These subfractions were isolated on density gradients as bands layering on 0.8M and 1.0M sucrose. Both subfractions consisted of unilamellar vesicles. Relative to myelin purified from the same starting material, the 0.8M subfraction was enriched in MAG, CNPase, carbonic anhydrase and Na+, K+ ATPase but was extremely low in PLP and MBP. In addition, this fraction exhibited a protein profile distinct from myelin. The 1.0M fraction was also highly enriched in Na+, K+ ATPase and had an overall composition similar to the 0.8M subfraction. However, it differed from the 0.8M subfraction by being low in MAG, CNPase, and carbonic anhydrase, but enriched in voltage-dependent Na+ channel, axon-specific fodrin, and MAP-1B. Based on these characteristics we concluded that the 0.8M and 1.0M subfractions were highly enriched in periaxolemmal myelin and axolemmal membrane, respectively. Plasmolipin10 was unique with equally high levels in myelin and in the 0.8M and 1.0M subfractions. Both subfractions were enriched, relative to myelin, in the alpha subunit of the GTP binding protein, Go, and the alpha subunit common to all G proteins, GA/1. Electrophysiology with membrane subfractions fused to lipid bilayers showed that both membranes contained sets of K+ and Cl- channels, which based on channel sizes and open times, are largely distinct from one another.

Animals↗
PubMed1991

The phylogenic expression of plasmolipin in the vertebrate nervous system.

Plasmolipin is a plasma membrane proteolipid is a major myelin membrane component (Cochary et al., 1990). In this study we report the phylogenic expression of plasmolipin in the vertebrate nervous system. Using Western blot analysis with polyclonal antibodies, we have analyzed membrane fractions, including myelin, from elasmobranchs, teleosts, amphibians, reptiles, birds and mammals. On the basis of immune detection, plasmolipin appears to be restricted to the mammalian nervous system. Comparison of the central and peripheral nervous systems of mammals showed only minor differences in the level of plasmolipin in these two regions. Within mammals, little quantitative differences were observed when rat, human and bovine membrane fractions were compared. The late evolutionary expression of plasmolipin which results in its restriction to mammals makes it unique among the (major) myelin proteins. The potential physiologic significance of these data are discussed.

Amphibians↗
PubMed1987

Concomitant increases in the levels of choline and free fatty acids in rat brain: evidence supporting the seizure-induced hydrolysis of phosphatidylcholine.

The main objective of this study was to determine whether the excitotoxic cholinesterase inhibitor soman increases the catabolism of phospholipids in rat brain. Injections of soman (70 micrograms/kg, s.c.), at a dose that produced toxic effects, increased the levels of both free fatty acids (175-250% of control) and free choline (250% of control) in rat cerebrum 1 h after administration. All fatty acids contained in brain phosphatidylcholine were elevated significantly including palmitic (16:0), stearic (18:0), oleic (18:1), arachidonic (20:4), and docosahexaenoic (22:6) acids. The changes observed were consistent with those reported to occur following ischemia and the administration of other convulsants. Pretreatment of rats with the anticonvulsant diazepam (4 mg/kg, i.p.) prevented both the signs of soman toxicity and the soman-induced increase of choline and free fatty acids. Diazepam alone did not affect the levels of choline or free fatty acids, cholinesterase activity, or soman-induced cholinesterase inhibition, suggesting that soman toxicity involves a convulsant-mediated increase in phosphatidylcholine catabolism. In addition, administration of the convulsant bicuculline, at a dose that produces seizures and increases the levels of free fatty acids in brain, significantly increased the levels of choline. Results suggest that excitotoxic events enhance the hydrolysis of phosphatidylcholine in brain as evidenced by a concomitant increase in the levels of choline and free fatty acids.

Animals↗
PubMed1986

Elevated choline levels in brain. A non-cholinergic component of organophosphate toxicity.

The role of cholinergic and non-cholinergic mechanisms in mediating organophosphate cholinesterase (ChE) inhibitor-induced elevations in choline levels in brain was investigated. The nerve agents soman and sarin, when administered to rats at doses greater than the IC50 for acetylChE inhibition, significantly increased the levels of choline and acetylcholine in both the striatum and hippocampus. The elevation in choline levels was evident 1 hr after injection with a maximal increase at 2 hr. Levels of choline returned to control by 4 hr. In contrast, the administration of diisopropyl phosphorofluoridate at doses greater than the IC50 for acetylChE inhibition increased the levels of acetylcholine, but did not alter the concentration of choline during the first 3 hr. Between 4 and 24 hr after injection, however, a significant decrease in choline levels was apparent. This effect persisted for 48 hr. When rats were pretreated with the anticonvulsant diazepam, the sarin- and soman-induced increases in choline levels were attenuated significantly. Results indicate that the organophosphates differentially alter the levels of choline in brain and suggest that the effect of soman and sarin to elevate choline levels is not a reflection of excessive cholinergic activity, but rather may be a consequence of the excitotoxic actions of these compounds.

Acetylcholinesterase↗
PubMed1982

Choline availability: effects on the toxicity of centrally active drugs.

The effect of chronic choline supplementation was studied on the toxicity of various pharmacological agents in rats and mice. Choline prevented both the incidence of seizures and the consequent lethality of nicotine, paraoxon, pentylenetetrazol, and strychnine. Nicotine toxicity was most markedly affected, and the prophylactic effects of choline were present in both rats and mice following either dietary or parenteral supplementation. Results suggest that chronic choline availability may alter neuronal membrane excitability.

Animals↗
PubMed1982

Enhancement of antibody production and protection against systemic anaphylaxis by large doses of vitamin C.

Male and female guinea pigs receiving, respectively, 100 and 280 mg/day Vitamin C throughout the duration of immunization showed enhanced humoral antibody production to bovine serum albumin (BSA) and, in castrated females, to penicilloyl-coupled guinea pig gamma-globulin. A significant degree of protection was afforded against fatal anaphylactic shock in passively sensitized males. Under appropriate conditions of sensitization with rabbit anti-HGG and challenge with human gamma-globulin, 8 of 20 unsupplemented animals died of shock, whereas in the group receiving 280 mg Na ascorbate/day for 4 days preceding passive transfer and again 60' before challenge, only 2 of 18 died. The rate of dose-dependent mortality observed when groups of passively sensitized animals were challenged with increasing doses of antigen was reduced in animals supplemented as above. Actively immunized guinea pigs were not protected by 5 daily doses of 280 mg Na ascorbate given prior to challenge. There were no significant differences in the total hemolytic activity of the serum nor in the C3 and C4 components of complement in immunized animals. There was no change in the concentration of Cl esterase in non-immunized controls, but immunization with BSA was followed by a rapid decline in Cl concentration, the decrease being greater in the ascorbate-treated group than in the unsupplemented controls, possibly reflecting a higher level of circulating immune complexes in the former case.

Anaphylaxis↗