John P. Frawley

Bio: John P. Frawley is an academic researcher. The author has contributed to research in topics: Poison control & Excretion. The author has an hindex of 5, co-authored 7 publications receiving 61 citations.

Muscle metabolism and catabolism in combat casualties; systemic response to injury in combat casualties.

Abstract: It is generally accepted that creatinine produced by endogenous metabolism is derived from muscle creatine and phosphocreatine. The conversion is apparently the result of an irreversible process of normal metabolism which takes place at a constant rate, proportional to muscle mass and independent of muscular exercise.* The daily urinary excretion of creatinine is constant for the individual, ranging from 1.5 to 2.0 gm. for men and from 0.8 to 1.5 gm. for women. This corresponds to approximately 2% of the total body creatine, from which it is derived. This excretion rate is apparently independent of protein ingestion and is considered an index of muscle metabolism. It is not influenced by exercise or urine volume. Decreased creatinine excretion, with concurrent elevation in plasma level, is generally indicative of impaired renal function, since creatinine is freely filterable at the glomerulus. Decreased excretion in the absence of elevated plasma concentration is usually due

Adrenal function in the combat casualty.

Abstract: This study was part of a broad survey of the systemic response to injury, carried out at a forward surgical hospital on the Eastern Front in Korea during 1952. This was a time when the front lines were stable and the flow of casualties was usually limited. Evacuation time averaged three and one-half hours. Because the casualty load was seldom very heavy, patients could be held at the forward hospital until they were ready for evacuation. Intensive studies could be made during this period of relative quiescence. MATERIALS AND METHODS Twenty battle casualties were chosen for study during a period of 7 to 14 days immediately after injury. The study was designed to study adrenal function during this period of early convalescence. This was often a period of repeated traumas—initial injury, evacuation, anesthesia, operation, secondary dressings, and secondary debridement. All of the patients studied were critically injured. Several died

Investigations of serum protein changes in combat casualties; the systemic response to injury.

Abstract: Previous studies in the disturbance of protein equilibrium following surgery and injury in man and experimental animals have shown a catabolic phase, or period of negative nitrogen balance, followed by an anabolic phase, or period of positive nitrogen balance.* The serum protein changes during the catabolic phase were described by Cuthbertson and Tompsett 4 primarily as a loss of albumin and an increase in globulin. However, the procedure used was a salt precipitation technique that did not separate the a 1 and a 2 globulin fractions from the albumin. More recently, Hoch-Ligeti, Irvine, and Sprinkle, 5 using paper-strip electrophoresis, studied the serum protein changes in a group of 45 surgical patients. Their results indicated a significant decrease in the albumin fraction and an increase in a 1 and a 2 globulin fractions in 80% of patients within four days following operation. PURPOSE The massive trauma and extensive surgical procedures experienced

If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans.

Abstract: The notion that chronic stress fosters disease by activating the hypothalamic-pituitary-adrenocortical (HPA) axis is featured prominently in many theories. The research linking chronic stress and HPA function is contradictory, however, with some studies reporting increased activation, and others reporting the opposite. This meta-analysis showed that much of the variability is attributable to stressor and person features. Timing is an especially critical element, as hormonal activity is elevated at stressor onset but reduces as time passes. Stressors that threaten physical integrity, involve trauma, and are uncontrollable elicit a high, flat diurnal profile of cortisol secretion. Finally, HPA activity is shaped by a person's response to the situation; it increases with subjective distress but is lower in persons with posttraumatic stress disorder.

Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders.

Abstract: An extensive literature stretching back decades has shown that prolonged stress or prolonged exposure to glucocorticoids-the adrenal steroids secreted during stress-can have adverse effects on the rodent hippocampus. More recent findings suggest a similar phenomenon in the human hippocampus associated with many neuropsychiatric disorders. This review examines the evidence for hippocampal atrophy in (1) Cushing syndrome, which is characterized by a pathologic oversecretion of glucocorticoids; (2) episodes of repeated and severe major depression, which is often associated with hypersecretion of glucocorticoids; and (3) posttraumatic stress disorder. Key questions that will be examined include whether the hippocampal atrophy arises from the neuropsychiatric disorder, or precedes and predisposes toward it; whether glucocorticoids really are plausible candidates for contributing to the atrophy; and what cellular mechanisms underlie the overall decreases in hippocampal volume. Explicit memory deficits have been demonstrated in Cushing syndrome, depression, and posttraumatic stress disorder; an extensive literature suggests that hippocampal atrophy of the magnitude found in these disorders can give rise to such cognitive deficits.

Serum creatinine as an index of renal function: new insights into old concepts.

Abstract: The serum creatinine concentration is widely interpreted as a measure of the glomerular filtration rate (GFR) and is used as an index of renal function in clinical practice. Glomerular filtration of creatinine, however, is only one of the variables that determines its concentration in serum. Alterations in renal handling and metabolism of creatinine and methodological interferences in its measurement may have a profound impact on the serum concentration of creatinine. We review the fundamental principles of physiology, metabolism, and analytical chemistry that are necessary to correctly interpret the serum creatinine concentration. These principles are then applied to important clinical circumstances, including aging, pregnancy, diabetes mellitus, drug administration, and acute and chronic renal failure. Despite numerous limitations, serum creatinine remains a useful clinical tool, but more accurate measures of renal function are frequently necessary.

MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder.

Abstract: Patients with combat-related posttraumatic stress disorder (PTSD) clinically demonstrate alterations in memory, including nightmares, flashbacks, intrusive memories, and amnesia for war experiences. In addition, descriptions from all wars of this century document alterations in memory occurring in combat veterans during or after the stress of battle. These include forgetting one's name or identity and forgetting events that had just taken place during the previous battle (1, 2), as well as gaps in memory that continue to recur for many years after the war (3). Servicemen who had been prisoners of war during the Korean conflict were found to have an impairment in short-term verbal memory, as measured by the logical memory component of the Wechsler Memory Scale, in comparison with veterans of the Korean war who did not have a history of imprisonment (4). We also found deficits in short-term verbal memory, as measured by the logical memory component of the Wechsler Memory Scale, in Vietnam combat veterans with combat-related PTSD in comparison with healthy subjects who were matched for age, years of education, and alcohol abuse (5). Several lines of evidence suggest a relation between stress and damage to the hippocampus (6). The hippocampus and the adjacent perirhinal, parahippocampal, and entorhinal cortex play an important role in short-term memory (7). Studies in humans have shown that reductions in hippocampal volume secondary to either neurosurgery (8) or the pathophysiological effects of epilepsy (9) are associated with deficits in short-term memory as measured by the Wechsler Memory Scale. Monkeys exposed to the extreme stress of improper caging have shown increased glucocorticoid release as well as damage to the CA2 and CA3 subfields of the hippocampus (10). Studies in a variety of animal species suggest that direct glucocorticoid exposure results in a loss of neurons and a decrease in dendritic branching in the hippocampus (11, 12) with associated deficits in memory function (13). The mechanism of action of glucocorticoid toxicity is probably through an increase in the vulnerability of neurons to the toxicity of excitatory amino acids (14–16). Studies using computed tomography in human subjects who are exposed to high levels of glucocorticoids secondary to glucocorticoid steroid therapy (17, 18) or who have affective disorders (also felt to be related to stress) (19) have shown changes in brain structure, including ventricular enlargement and widening of the cortical sulci. Magnetic resonance imaging (MRI) studies in patients with affective disorders have shown a smaller right hippocampal volume (20) and temporal lobe volume (21) in bipolar disorder and abnormalities of the hippocampus, including alterations in T1 (22), but no change in hippocampal volume (23) in major depression. One MRI study (24) found a relation between deficits in short-term memory and smaller hippocampal volume, as well as higher plasma cortisol levels and smaller hippocampal volume, in patients with Cushing's disease. Stress in both healthy human subjects (25) and soldiers undergoing random artillery bombardment (26) results in an increase in urinary cortisol, suggesting the possibility that exposure to the extreme stress of combat may be associated with damage to the hippocampus. The purpose of this study was to use MRI to measure the volume of the hippocampus and comparison brain structures in patients with PTSD and in matched comparison subjects. We hypothesized that PTSD would be associated with smaller hippocampal volume in relation to that of the comparison subjects. We also hypothesized that smaller hippocampal volume would be associated with deficits in short-term verbal memory in patients with PTSD.