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Biomedical subjects

G L Brown

Publications and source records attributed to G L Brown.

At least 55 records · Page 3Linked to original sources

Muramyl dipeptide protects decomplemented mice from surgically-induced infection.

Muramyl dipeptide (MDP) is a natural product of bacterial cell-wall breakdown, which can now be produced synthetically; it is the smallest component of the mycobacterial cell wall capable of reproducing the adjuvant activities of Freund's complete adjuvant. We tested the well-documented, protective effect of MDP to increase survival in a murine model simulating surgically-induced bacteremia. The protocol involved the bacterial innoculation of control and decomplemented mice in the presence and the absence of pretreatment with MDP. Bacteremia in both the control and decomplemented groups pretreated with MDP was decreased statistically at 24 h (P less than 0.01) as compared to controls. Likewise, survival was increased significantly at 24 h (P less than 0.05), 48 h (P less than 0.001), and 72 h (P less than 0.001) using the same group comparisons. We conclude, therefore, that MDP maintains its protective effect in the absence of complement, supporting the view that the mechanism of action of MDP is complement independent.

Acetylmuramyl-Alanyl-Isoglutamine↗

Stimulants, urinary catecholamines, and indoleamines in hyperactivity. A comparison of methylphenidate and dextroamphetamine.

Children with attention deficit disorder with hyperactivity were given either methylphenidate hydrochloride or dextroamphetamine sulfate to compare the effects on urinary excretion of catecholamines, indoleamines, and phenylethylamine (PEA). Methylphenidate's effects were distinctly different from those of dextroamphetamine. After methylphenidate administration, both norepinephrine (NE) and normetanephrine (NMN) concentrations were significantly elevated, and there was a 22% increase in excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG). In contrast, after dextroamphetamine treatment, MHPG excretion was significantly reduced and NE and NMN values were unchanged. Excretion of dopamine and metabolites was unchanged by either drug. Urinary PEA excretion was not significantly changed after methylphenidate treatment, but increased 1,600% in response to dextroamphetamine. Methylphenidate treatment did not significantly alter serotonin or 5-hydroxyindoleacetic acid excretion. Effects of dextroamphetamine were not tested.

3,4-Dihydroxyphenylacetic Acid↗

Characterization of neutrophil iodination for the assessment of phagocytic and opsonic function in septic patients.

To increase our understanding of the nature of surgical infection, further studies on the host defense abilities of infected patients are required. Therefore, a more thorough investigation of the iodination method for the measurement of polymorphonuclear leukocyte function and serum opsonic activity was undertaken to characterize its application in surgical infection. A significant relationship was found between the phagocytic indices derived from different standard neutrophils or sera measured on the same day. When expressed as a value of normal phagocytic indices minus abnormal phagocytic indices, this relationship was constant from day to day despite wide variations in the absolute phagocytic index values. This finding enables direct comparisons to be made between the values obtained both from the same patient and from different patients during the course of their illness by reference to daily control values. We also found that the system was sufficiently sensitive to detect, in a dose-responsive manner, the changes induced in normal neutrophil phagocytosis and serum opsonic activity by a specific bacterial challenge with either K. pneumoniae or E. coli. In addition, zymosan, which is utilized in the iodination reaction but also has immunoadjuvant properties, was found to enhance neutrophil function but depress serum opsonic activity in the face of such bacterial challenges. We conclude that the iodination technique is a credible method for the indirect measurement of polymorphonuclear phagocytosis and serum opsonic function in the face of a bacterial challenge and can be reliably employed in studies of septic patients provided these findings are taken into account.

Blood Bactericidal Activity↗

Muramyl dipeptide and polymorphonuclear leukocyte chemotaxis in vitro.

Muramyl dipeptide (MDP) is an immunostimulatory agent that has been shown repeatedly to provide protection against the effects of some forms of experimental surgical infection. The mechanisms of this protection are incompletely understood, and in order to further define them, the impact of MDP upon in vitro polymorphonuclear (PMN) leukocyte chemotaxis was examined in the presence of both normal and opsonic depleted serum. We have also evaluated the effect of MDP as a chemoattractant itself and the response of neutrophils along with MDP to a standard chemoattractant, n-formyl-L-methionyl-L-leucyl-L-phenyl-alanine (FMLP), using the agarose assay for chemotaxis. MDP has weak but significant chemotactic activity itself, with a peak effect at a concentration of 5 X 10(-8) micrograms/ml for neutrophils. These effects are enhanced by the addition of 10% serum. MDP more strongly enhances neutrophil chemotaxis to FMLP. The enhancement of chemotaxis may be a factor in the protection that MDP exerts against some experimental bacterial challenges.

Acetylmuramyl-Alanyl-Isoglutamine↗

Traumatic diaphragmatic hernia: a continuing challenge.

Traumatic diaphragmatic hernia is an uncommon but important problem in the patient with multiple injuries. Since diaphragmatic injuries are difficult to diagnose, those that are missed may present with latent symptoms of bowel obstruction and strangulation. From 1957 to 1982, we treated 41 patients with traumatic diaphragmatic hernias. In 39 patients (95%), diaphragmatic hernia followed blunt trauma. The herniation occurred on the right side in 14 patients and on the left side in 29; it was bilateral in 2. Twenty-four patients had diagnostic chest radiographs, and an additional 11 had abnormal but nondiagnostic studies. Peritoneal lavage was of little value in making the preoperative diagnosis. Twenty-three patients underwent laparotomy only, 13 required thoracotomy alone, and 5 had combined laparotomy and thoracotomy. There were 7 deaths (17%) from associated injuries. Only one missed injury was encountered; a second delayed hernia, initially treated elsewhere, was repaired 45 years after the original trauma. Traumatic diaphragmatic hernia should be suspected on the basis of an abnormal chest radiograph in the trauma victim with multiple injuries. Right-sided injuries occur more commonly than previously thought and often require dual incisions (laparotomy and thoracotomy) for diagnosis and treatment. The organization of emergency care for such patients is critical in avoiding the potential of long-term sequelae.

Abdominal Injuries↗

Comparison of prosthetic materials for abdominal wall reconstruction in the presence of contamination and infection.

Abdominal wall defects resulting from trauma, invasive infection, or hernia present a difficult problem for the surgeon. In order to study the problems associated with the prosthetic materials used for abdominal wall reconstruction, an animal model was used to simulate abdominal wall defects in the presence of peritonitis and invasive infection. One hundred guinea pigs were repaired with either polytetrafluorethylene (PTFE) or polypropylene mesh (PPM). Our experiments included intra-operative contamination with Staphylococcus aureus. We found significantly fewer organisms (p less than 0.05) adherent to the PTFE than to the PPM when antibiotics were administered after surgery, as well as when no antibiotics were given. In the presence of peritonitis, we found no real difference in numbers of intraperitoneal bacteria present whether PTFE or PPM was used. In all instances, the PTFE patches produced fewer adhesions and were more easily removed. From these experiments, it appears that PTFE may be associated with fewer problems than PPM in the presence of contamination and infection.

Abdominal Muscles↗

Mania resulting from brain stem tumor.

Mania usually represents one extreme of recurrent affective illness in patients with a genetic predisposition. Mania or hypomania is not generally known to signal the presence of an occult neoplasm; however, this possibility should be considered. The authors describe a 55-year-old man without personal or family history of affective disease whose manic behavior precipitated diagnosis of a metastatic mesencephalic tumor.

Bipolar Disorder↗

Muramyl dipeptide enhances in vitro peritoneal macrophage phagocytic activity.

There is little agreement as to the precise mechanism of action of muramyl dipeptide (MDP) despite a steadily unfolding series of experiments designed for clarification. This report further defines the role of MDP in nonspecific enhancement of host defenses by examining its effect on in vitro macrophage phagocytosis. Peritoneal macrophages were incubated in vitro with muramyl dipeptide. Phagocytic indices were determined using the iodination technique. The macrophages treated with MDP had a significant increase in their phagocytic function compared to control cells, adding to the understanding of the mechanism of action of MDP and raising the possibility of a trial peritonitis in humans.

Acetylmuramyl-Alanyl-Isoglutamine↗

Urinary phenethylamine response to d-amphetamine in 12 boys with attention deficit disorder.

Urinary phenethylamine (PEA), an endogenous amine similar to amphetamine in both molecular structure and pharmacological properties, was studied in 12 boys with attention deficit disorder with hyperactivity. d-Amphetamine and placebo were given for 14 days each in a counterbalanced crossover design; double-blind teacher behavior ratings and motor activity measurements were also obtained. Excretion of PEA, phenylacetic acid, creatinine, and d-amphetamine were measured. PEA was significantly increased and phenylacetic acid was unchanged after d-amphetamine administration, and change in PEA excretion correlated significantly with d-amphetamine excretion. There was no significant relationship between either clinical response to drug and change in PEA or phenylacetic acid excretion.

Attention Deficit Disorder with Hyperactivity↗

Mood-altering effects of disulfiram in alcoholics.

The effects of disulfiram on depression and anxiety were examined. In a 3-week double-blind study, 40 inpatients in al alcohol rehabilitation unit (ARU) were randomly assigned to receive placebo, 250 mg/day of disulfiram or 500 mg/day of disulfiram. During their first week in the ARU and prior to beginning medications, all subjects were administered the Zung self-rating depression scale, the Hamilton observer rating scale for depression, the Zung self-rating scale for anxiety and the Hamilton observer rating scale for anxiety. All subjects were rescored on these instruments at the end of their third week in the ARU. Three psychiatrists, blind to the medication condition, sequentially scored the Hamilton items. To evaluate intergroup differences at baseline as well as changes in scale scores during the 3 weeks, scale scores were subjected to analyses of variance. No statistically significant effect attributable to disulfiram was found but significant changes due to a time effect were noted.

Adult↗

Blood flow distribution in infant pigs subjected to surface cooling, deep hypothermia, and circulatory arrest. Deleterious effects in pigs with left-to-right shunts.

Surface cooling, deep hypothermia and circulatory arrest have been used effectively for correction of congenital heart defects in infancy. Which patients are best suited for this technique has not been addressed. The addition of surface cooling to deep hypothermia and circulatory arrest provides homogeneous cooling and avoids swelling due to reperfusion injury after circulatory arrest. However, surface cooling in patients with large left-to-right shunts causes increased peripheral resistance and increased shunting which can result in decreased perfusion of vital organs. The purpose of this study is to measure the effect of a large left-to-right shunt on total organ blood flow distribution in infant piglets during surface cooling, deep hypothermia, and circulatory arrest. Eleven 2-week-old piglets had surface cooling, deep hypothermia, and circulatory arrest for 45 minutes, followed by rewarming and weaning from cardiopulmonary bypass. Microspheres (15 mu) were injected before surface cooling, at 28 degrees C, at 15 degrees C, and after weaning from cardiopulmonary bypass. Group I (five piglets) was the control. Group II (six piglets) had a large (6 mm) left-to-right aortopulmonary shunt established before microsphere injection. Cardiac outputs in both Groups I and II decreased with surface cooling. The distribution of cardiac output in Group I did not change with surface cooling; however, Group II pigs showed marked change in distribution of cardiac output, resulting in decreased renal, visceral, and pulmonary flow (p less than 0.05). Amylase determinations before and after surface cooling, deep hypothermia, and circulatory arrest were unchanged in Group I but elevated in Group II (p less than 0.05). These observations suggest altered cellular metabolism in visceral organs during the period of surface cooling which may be compounded by circulatory arrest and rewarming.

Amylases↗