Biomedical subjects

John J Leddy

Publications and source records attributed to John J Leddy.

11 recordsLinked to original sources

PubMed2006

Management of concussion and post-concussion syndrome.

Concussion and mild traumatic brain injury (mTBI) are common clinical problems. However, the literature is not consistent in defining how concussion and mTBI are related. Although most patients with concussion recover within days to weeks, approximately 10% develop persistent signs and symptoms of post-concussion syndrome (PCS). There are no scientifically established treatments for concussion or PCS and thus rest and cognitive rehabilitation are traditionally applied, with limited effectiveness. This article presents a clinical model to suggest that concussion evolves to become mTBI after PCS has developed, representing a more severe form of brain injury. The basic pathophysiology of concussion is presented, followed by a recommended approach to the clinical evaluation of concussion in the emergency department and the physician's office. We evaluate the limited evidence-based pharmacologic treatment of acute concussion symptoms and PCS symptoms and also discuss return to activity recommendations, with an emphasis on athletes. Lastly, we suggest a promising new direction for helping patients recover from PCS.

Journal Article↗

PubMed2006

A proposal for an evidenced-based emergency department discharge form for mild traumatic brain injury.

PRIMARY OBJECTIVE: To examine and compare a sample of head injury care instruction forms available in hospital emergency departments (EDs) against evidence-based factors predictive of haemorrhage or traumatic lesions and to propose an easy-to-understand discharge instruction form for patients with concussion or mild traumatic brain injury (MTBI). RESEARCH DESIGN/METHODS: Fifteen hospital discharge instruction forms were reviewed for inclusion of six factors known to be associated with the presence of haemorrhage after MTBI. ED instruction forms were also evaluated for readability. RESULTS: The 15 hospital ED instruction forms varied in what patients' caretakers were instructed to observe. Some but not all important factors associated with haemorrhage were included. The mean Flesch-Kincaid reading grade level of the discharge instruction forms was 8.2 with a mean Reading Ease score of 59.9%. CONCLUSION: EDs use discharge instruction forms listing signs and symptoms that are highly variable, confusing, not all evidence-based and often not easy to understand. This review proposes a discharge instruction form containing the six best evidence-based variables (according to the current literature) as being useful and understandable to patients and their families for home observation after MTBI.

Brain Injuries↗

PubMed2005

Food reinforcement.

The reinforcing value of food, measured by how hard someone is willing to work to obtain food, is influenced by food palatability, food deprivation and food variety, and may be a more powerful determinant of food intake than hedonics or liking. The reinforcing value of food is mediated in part by dopaminergic activity. Genotypes that influence dopamine transport and the density of dopamine D2 receptors interact with food reinforcement to influence eating behavior, and D2 receptor genotypes may influence food reinforcement and weight gain after smoking cessation. Inhibition of dopamine transport increases brain dopamine concentrations, which may influence weight gain after smoking cessation and can reduce energy intake in obese adults.

Dopamine↗

PubMed2005

Alternative splicing generates a CaM kinase IIbeta isoform in myocardium that targets the sarcoplasmic reticulum through a putative alphaKAP and regulates GAPDH.

We report the isolation of a full length cDNA from cardiac muscle that encodes a approximately 73 kDa calcium/calmodulin (CaM) dependent kinase IIbeta isoform (CaMKIIbeta(C)) that was generated by alternative splicing of the CaMKIIbeta gene. Antipeptide antibodies raised to specific regions of the kinase identified a 73 kDa kinase polypeptide in cardiac SR. Anti-alpha kinase anchoring protein (alphaKAP) antibodies identified a 25 kDa polypeptide in cardiac SR and RT-PCR followed by sequence analysis confirmed the presence of a full length alphaKAP encoding transcript in myocardium. Protein interaction assays revealed that the 73 kDa CaMKIIbeta(C) binds GAPDH to modulate the production of NADH in a Ca2+/CaM dependent reaction. The presence of a CaMKIIbeta isoform that can target the SR presumably via its membrane anchor alphaKAP defines a previously unrecognized Ca2+/CaM regulatory system in myocardium.

Alternative Splicing↗

PubMed2005

Kinetic changes with fatigue and relationship to injury in female runners.

PURPOSE: This research examined how ground reaction forces (GRF) changed with fatigue induced by an exhaustive treadmill run in female runners. A separate retrospective and prospective analysis correlated initial magnitude of GRF and fatigue-induced changes in GRF with lower-extremity injury. METHODS: Ninety adult female runners had vertical GRF measured before and after an exhaustive treadmill run. Subjects initially were questioned about previous running injuries, and were contacted during the following year and asked to report any additional running injuries. RESULTS: Fatigue induced by the exhaustive treadmill run resulted in decreased impact peak and loading rates in all runners by an average of 6 and 11%, respectively. The changes in GRF were attributed to altered running cadence, step length, and lower-extremity joint kinematics. It is unclear whether these changes were attempts by the runners to minimize impact forces and protect against injury, or represented a fatigue-induced loss of optimal performance capabilities. An interaction between injury in the previous year and change in impact loading rate with fatigue was observed, suggesting previously injured runners are exposed to relatively higher impact forces over time. CONCLUSION: Habitual female runners appear to adapt their running style with fatigue, resulting in altered GRF. Changes in GRF with fatigue may be associated with lower-extremity running injuries.

Adolescent↗

PubMed2004

The muscle-specific calmodulin-dependent protein kinase assembles with the glycolytic enzyme complex at the sarcoplasmic reticulum and modulates the activity of glyceraldehyde-3-phosphate dehydrogenase in a Ca2+/calmodulin-dependent manner.

The skeletal muscle specific Ca(2)+/calmodulin-dependent protein kinase (CaMKIIbeta(M)) is localized to the sarcoplasmic reticulum (SR) by an anchoring protein, alphaKAP, but its function remains to be defined. Protein interactions of CaMKIIbeta(M) indicated that it exists in complex with enzymes involved in glycolysis at the SR membrane. The kinase was found to complex with glycogen phosphorylase, glycogen debranching enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and creatine kinase in the SR membrane. CaMKIIbeta(M) was also found to assemble with aldolase A, GAPDH, enolase, lactate dehydrogenase, creatine kinase, pyruvate kinase, and phosphorylase b kinase from the cytosolic fraction. The interacting proteins were substrates of CaMKIIbeta(M), and their phosphorylation was enhanced in a Ca(2+)- and calmodulin (CaM)-dependent manner. The CaMKIIbeta(M) could directly phosphorylate GAPDH and markedly increase ( approximately 3.4-fold) its activity in a Ca(2+)/CaM-dependent manner. These data suggest that the muscle CaMKIIbeta(M) isoform may serve to assemble the glycogen-mobilizing and glycolytic enzymes at the SR membrane and specifically modulate the activity of GAPDH in response to calcium signaling. Thus, the activation of CaMKIIbeta(M) in response to calcium signaling would serve to modulate GAPDH and thereby ATP and NADH levels at the SR membrane, which in turn will regulate calcium transport processes.

Animals↗

PubMed2004

Influence of methylphenidate on eating in obese men.

OBJECTIVE: Rapid synaptic dopamine transport or reduced brain dopamine receptor signaling may influence energy intake. Methylphenidate, a dopamine reuptake inhibitor, increases brain synaptic dopamine and produces anorexia, suggesting that it may reduce energy intake. We investigated the effects of two doses of short-acting methylphenidate on energy intake over one meal in obese adult males. RESEARCH METHODS AND PROCEDURES: Nine obese males (>85th BMI percentile) ingested a placebo or a moderate dose (0.5 mg/kg) or a high dose (1.0 mg/kg) of methylphenidate in a within-subject double-blind acute laboratory study. One hour after ingestion, pizza consumption was measured in a naturalistic laboratory setting. RESULTS: Participants reduced energy intake by 23% for the moderate dose vs. the placebo (p < 0.02), but there was no significant difference for the high dose vs. the moderate dose (p > 0.05). Participants consumed 34% fewer kilocalories after ingesting the lowest effective dose of methylphenidate compared with placebo (725.7 +/- 404.5 vs.1095 +/- 271.1 kcal, p < 0.01). Seven of nine subjects responded to the moderate dose. The increase in perceived drug effect above placebo was correlated with the reduction in energy intake for both the moderate (r = -0.85, p = 0.004) and the high (r = -0.75 p = 0.021) doses. Hunger scores were not different across drug doses or placebo before drug administration. DISCUSSION: Methylphenidate reduced energy intake of a highly palatable food over one meal by one-third in obese adult males. Dopamine transport inhibition may be an effective component of a comprehensive treatment for obesity.

Adult↗

PubMed2004

Effect of low and high fat diets on nutrient intakes and selected cardiovascular risk factors in sedentary men and women.

OBJECTIVE: The desired level of dietary fat intake is controversial. The effect of decreasing fat intake to 19% and increasing it to 50% from a control diet of 30% on nutritional status and cardiovascular risk factors in healthy individuals was studied. METHODS: Eleven healthy subjects (5 men and 6 women) were randomized to consume diets with 19% and 50% calories from fat. Each diet lasted 3 weeks, with a one-week washout. The habitual and washout diets were determined to be 30% fat. At the beginning and the end of each diet, fasting blood was collected to determine plasma lipoproteins, and physiological factors were measured. RESULTS: Total caloric expenditure was similarly balanced to intake on the 30% and 50% fat diets, but intake was significantly lower on the 19% fat diet and led to a loss of 0.6 kg body weight. Consumptions of essential fatty acids, vitamin E and zinc were improved with increased fat intake, but folate intake was compromised on the 30% and 50% fat diets. Compared with the 50% fat diet, subjects consuming the 19% fat diet had significantly lower HDL cholesterol (HDL-C) (54 +/- 3 vs. 63 +/- 3 mg. dL(-1), p < 0.05) and apolipoprotein A1 (ApoA1) (118 +/- 4 vs. 127 +/- 3 mg/dL, p < 0.05). Changing the levels of fat intake did not affect % body fat, heart rate, blood pressure, blood triglycerides, total cholesterol (TC), LDL cholesterol, apolipoprotein B (ApoB), TC/HDL-C and ApoA1/ApoB ratios. CONCLUSION: A low fat diet (19%) may not provide sufficient calories, essential fatty acids, and some micronutrients (especially vitamin E and zinc) for healthy untrained individuals, and it also lowered ApoA1 and HDL-C. Increasing fat intake to 50% of calories improved nutritional status, and did not negatively affect certain cardiovascular risk factors.

Adult↗

PubMed2004

Relation between food reinforcement and dopamine genotypes and its effect on food intake in smokers.

BACKGROUND: Food reinforcement and dopaminergic activity may influence food consumption, but research on whether they interact has not been performed. OBJECTIVE: We assessed the effects of food reinforcement and the interaction of food reinforcement with the dopamine transporter (SLC6A3) genotype and the dopamine D(2) receptor (DRD(2)) genotype on energy consumption. DESIGN: We studied food-consumption and reinforcing-value-of-food tasks in 88 smokers of European ancestry before they enrolled in smoking-cessation treatment. In the food-consumption task, subjects tasted and consumed 8 snack foods ad libitum. The reinforcing-value-of-food task assessed how hard subjects would work for food. RESULTS: Significant interactions between dopamine genotypes and food reinforcement were observed. Subjects high in food reinforcement who lacked an SLC6A3*9 allele consumed significantly more calories (>150 kcal; P = 0.015) than did subjects low in food reinforcement or those high in food reinforcement who carried at least one SLC6A3*9 allele. Similarly, subjects high in food reinforcement who carried at least one DRD(2)*A1 allele consumed >130 kcal more (P = 0.021) than did subjects low in food reinforcement or those high in food reinforcement who lacked a DRD(2)*A1 allele. There was also a main effect of food reinforcement on energy intake (P = 0.005), with subjects high in food reinforcement consuming 104 kcal (or 30%) more than did subjects low in food reinforcement. CONCLUSIONS: Food reinforcement has a significant effect on energy intake, and the effect is moderated by the dopamine loci SLC6A3 and DRD(2).

Adult↗

PubMed2002

Dopamine transporter genotype as a risk factor for obesity in African-American smokers.

OBJECTIVE: To assess the association between a polymorphism related to dopamine function, dopamine transport (SLC6A3), and obesity in smokers. RESEARCH METHODS AND PROCEDURES: Logistic regression was used to assess the relationship between this genetic polymorphism and obesity (body mass index > or = 30 kg/m(2)) from a sample of 510 smokers who smoked at least 10 cigarettes per day and who were participating in a study designed to examine genetic and nongenetic predictors of response to a pharmacological treatment. RESULTS: The likelihood of obesity in African Americans (N = 90) with the 10/10 SLC6A3 genotype was 5.16 times that of African Americans with 9/9 or 9/10 SLC6A3 genotypes (odds ratio = 5.16, confidence interval = 1.60 to 16.65). There was no association of the SLC6A3 genotype with obesity for non-Hispanic whites (N = 420). DISCUSSION: These results suggest that variants of the dopamine transporter gene may be related to obesity in African-American smokers. Possible mechanisms responsible for the association between dopamine transport and obesity in African-American smokers are discussed.

Adolescent↗

PubMed2002

Implementation of the Ottawa ankle rule in a university sports medicine center.

PURPOSE: The Ottawa ankle rule (OAR) is a clinical decision rule used in emergency departments to identify which patients with acute ankle/midfoot injury require radiography. The purpose of this study was to implement the OAR, with a modification to improve the specificity for identifying malleolar fractures (the "Buffalo rule"), in a sports medicine center and measure impact on physician practice and cost savings. METHODS: All pediatric and adult patients presenting to a university sports medicine walk-in clinic with acute (< or = 10 d old) ankle/midfoot injury had the rule applied by primary care providers. Exclusion criteria included pregnancy, isolated skin injury, > 10 d since injury, second evaluation for same injury, obvious deformity of ankle or foot, or altered sensorium. RESULTS: In 217 patients (mean age, 23.3 +/- 8.5 yr; range, 10-64 yr) there were 24 clinically significant (i.e., nonavulsion) fractures (fracture rate 3.7% per year for 3 yr), all of which were identified by the rule (100% sensitivity). In 193 patients with malleolar pain, the sensitivity for malleolar fracture (with 95% confidence intervals) was 100% (78-100%) and specificity was 45% (43-46%). In 24 patients with midfoot pain, sensitivity was 100% (65-100%) and specificity was 35% (21-49%). Thirty-five percent of radiographic series (76 of 217) were foregone for a cost savings of almost $6000. One hundred percent follow-up on those patients for whom x-rays were obtained found no missed fractures and they were subjectively satisfied with their care. CONCLUSION: The OAR reduced radiography in acute ankle/midfoot injury and saved money in relatively younger patients in the outpatient sports urgent care setting without missing any clinically significant fractures. The specificity of the Buffalo malleolar rule in the present implementation study, however, was not a significant improvement over the OAR malleolar rule. Widespread application of the OAR could save substantial resources without compromising quality of care.

Academic Medical Centers↗