Pharmacological Treatment of Central Nervous System Trauma

Abstract: Traumatic injuries to the brain or spinal cord cause tissue damage, in part by initiating reactive biochemical changes. Pharmacological approaches aim to modify this delayed injury response by blocking one or more components of the reactive biochemical/metabolic cascade. This minireview summarizes both historical and recent developments in experimental and clinical treatment of CNS trauma. Potential treatments include: corticosteroids; antioxidants or free radical scavengers; drugs that modify arachidonic acid metabolism, platelet-activating factor antagonists; gangliosides; modulators of monoamine actions; opioid receptor antagonists; thyrotropin-releasing hormone and thyrotropin-releasing hormone analogues; glutamate receptor antagonists; calcium channel blockers; agents that modify the inflammatory/ immune response; and trophic factors. Understanding the mechanisms of action for these compounds can permit rational drug development/application, delineation of the therapeutic window, and laying of the ground-work for evaluating potential synergistic effects of combination treatment strategies.     

Normothermic renal artery perfusion: A comparison of perfusates

Hypothermia and preservative perfusates have been used to decrease ischemic renal injury. This study was performed to identify the preservative function of perfusates independent of the effects of hypothermia. Rats underwent 45 minutes of renal ischemia. Rectal and renal parenchyma temperatures were monitored and maintained within 1° C of normal. Perfusates were University of Wisconsin solution (UW), Euro-Collins solution, normal saline solution, and Ringer's lactate solution. A nonperfused ischemic control and a nonischemic control group were also evaluated. Parameters evaluated included serum creatinine and blood urea nitrogen levels, renal ischemic injury grade, renal weight, and gross appearance of the injured kidney. Rats treated with UW solution were found to have a significantly lower creatinine, blood urea nitrogen, and injury grade than the other three perfused groups. The external gross appearance of the UW-treated kidneys was normal, whereas that of the other groups demonstrated moderate to severe injury. Although the mean right/left renal weight difference of the UW-treated group was lower than that of the other three groups, this was not statistically significant. Under normothermic conditions in rats, UW solution affords significant renal protection from ischemia. Euro-Collins, normal saline, and Ringer's lactate solutions display no significant protective effect.Presented at the Twentieth Annual Meeting of the Peripheral Vascular Surgery Society, New Orleans, La., June 10, 1995.     

In vitro stability of a novel compliant poly(carbonate-urea)urethane to oxidative and hydrolytic stress.

Poly(ester)urethane and poly(ether)urethane vascular grafts fail in vivo because of hydrolytic and oxidative degradative mechanisms. Studies have shown that poly(carbonate)urethanes have enhanced resistance. There is still a need for a viable, nonrigid, small-diameter, synthetic vascular graft. In this study, we sought to confirm this by exposing a novel formulation of compliant poly(carbonate-urea)urethane (CPU) manufactured by an innovative process, resulting in a stress-free. Small-diameter prosthesis, and a conventional poly(ether)urethane Pulse-Tec graft known to readily undergo oxidation in a variety of degradative solutions, and we assessed them for the development of oxidative and hydrolytic degradation, changes in elastic properties, and chemical stability. To simulate the in vivo environment, we used buffered solutions of phospholipase A(2) and cholesterol esterase; solutions of H(2)O(2)/CoCl(2), t-butyl peroxide/CoCl(2) (t-but/CoCl(2)), and glutathione/t-butyl peroxide/CoCl(2) (Glut/t-but/CoCl(2)); and plasma fractions I-IV, which were derived from fresh human plasma centrifuged in poly(ethylene glycol). To act as a negative control, both graft types were incubated in distilled water. Samples of both graft types (100 mm with a 5.0-mm inner diameter) were incubated in these solutions at 37 degrees C for 70 days before environmental scanning electron microscopy, radial tensile strength and quality control, gel permeation chromatography, and in vitro compliance assessments were performed. Oxidative degradation was ascertained from significant changes in molecular weight with respect to a control on all Pulse-Tec grafts treated with t-but/CoCl(2), Glut/t-but/CoCl(2), and plasma fractions I-III. Pulse-Tec grafts exposed to the H(2)O(2)/CoCl(2) mixture had significantly greater compliance than controls incubated in distilled water (p < 0.001 at 50 mmHg). No changes in molecular weight with respect to the control were observed for the CPU samples; only those immersed in t-but/CoCl(2) and Glut/t-but/CoCl(2) showed an 11% increase in molecular weight to 108,000. Only CPU grafts treated with the Glut/t-but/CoCl(2) mixture exhibited significantly greater compliance (p < 0.05 at 50 mmHg). Overall, results from this study indicate that CPU presents a far greater chemical stability than poly(ether)-urethane grafts do.     

Protection against hyperglycemia in female nonobese diabetic mice treated with 15-deoxyspergualin.

The effects of 15-deoxyspergualin (15-DS), a newly described immunosuppressive agent, have been studied on the development of diabetes in female NOD mice. 15-DS treatment was started two weeks after weaning i.e. at five weeks of age. The mice received either one daily intraperitoneal injection of 15-DS (2.5 mg/kg body weight) or saline for two weeks. The mice were then injected every third day up to eight months of age for evaluation of the diabetes incidence. In another set of experiments the mice were treated up to three months of age, whereafter islet insulin release, islet insulin content and DNA content was measured together with an evaluation of spleen cell proliferation rates. Different spleen cell subsets were studied directly after the two weeks of daily injections. In the saline group 8 out of 9 mice developed diabetes, whereas only 4 out of 11 of the 15-DS treated mice became diabetic (p < 0.05). There was no difference between the groups in islet insulin release in response to glucose, however, the islet insulin release increased after one week in culture. The 15-DS treatment did not affect the insulin or DNA content of the isolated islets or the insulin concentration in the pancreas. No detectable changes in the relative number of CD4+ and CD8+ T-cell subsets in the spleen were seen and there were no obvious differences in splenocyte proliferation rates. The histological examinations of the pancreatic glands showed gradual increasing signs of islet inflammation with age and 15-DS could apparently not prevent this.(ABSTRACT TRUNCATED AT 250 WORDS)     

Behavioral conditioning of endotoxin-induced plasma iron alterations

The cascade of physiologic mechanisms in response to infection, the acute-phase response, is recognized as playing a major role in host defence. One such response is the hypoferremia that is consistently reported to occur during bacterial infection. This study aimed to determine whether the alterations in plasma iron were conditionable using the conditioned taste aversion (CTA) paradigm. The regime involved the pairing of a novel-tasting saccharin solution with bacterial endotoxin. Seven days after the initial pairing of these stimuli (the test day), the saccharin solution was represented. Animals exposed to this condition displayed a significant reduction in the level of plasma iron. Animals treated with an intraperitoneal dose of 400 μg/Kg lipopolysaccharide (LPS) displayed lower conditioned iron levels than rats infused with 100 μg/Kg LPS; however, this difference was not significant. These results showed that in addition to other acute-phase responses (fever and anorexia), plasma iron alterations are able to be manipulated through behavioral manipulations.     

Bicycle Helmet Wearing in Children: A Seven-Year, Observational Study in Broward County, Florida

We evaluated the effectiveness of statewide bicycle legislation using direct observation of the number of elementary and middle school children riding bicycles with and without helmets to or from school over a 7-year period. The percentage of children wearing helmets increased dramatically over the past 7 years (to a high of 81%) due to the passage of state law that required helmet usage. Rates for elementary school children were consistently higher than rates of middle school children. Numerous children still do not wear helmets, particularly older children. Further interventions are needed to promote helmet wearing.     

Case report 720

A man presented with a mass in the left first metacarpal bone. Later, his chest radiograph showed extensive, bilateral, rounded opacities in both lungs with enlarged hilar lymph nodes, and he developed expanding lesions in the left radius, ulna, and metacarpal bones. The pulmonary lesions were treated with radiotherapy and cytotoxic agents, and the tumor mass in the first metacarpal was debulked. All biopsies showed similar features of a mixed tumor (pleomorphic adenoma) with metastatic or embolic pulmonary involvement; ultrastructural and immunocytochemical investigations supported this unique diagnosis. The patient remains well 15 years after the initial diagnosis. It is possible that the myoepithelial elements in this case had been displaced intraosseously during development. We are not aware of a similar case in the literature.     

An Approach to Emergency Department Photography

In the emergency department, photography requires an expedient, portable, adaptable, and relatively simple camera system to take advantage of fleeting opportunities for recording visually educational material. These prerequisites are different from those for traditional medical photography, for which relatively plentiful time and advanced equipment are routinely available. Medical photography departments provide an invaluable service, but are rarely convenient for immediate or spontaneous emergency. department photographs. Although no single system or technique is optimal in all these areas, the authors find certain components and approaches work well. They review photographic equipment, paying attention to speed, ease of use, and quality of output. They also review simple techniques such as film choice, lighting, close-up photography, standardization, copy work, and radiographs. Attention to these details can help the inexperienced photographer obtain a system and begin to enjoy the rewards of effective photography in the emergency department.     

Myocardial sestamibi single-photon emission tomography: Variations in reference values with gender, age and rest versus stress?

Reference data files support the evaluation of myocardial perfusion single-photon emission tomography (SPET). The aim of this study was to create a large reference data base for technetium-99m sestamibi SPET, age and gender matched to the general patient population. One hundred and twenty-eight healthy volunteers (76 males and 52 females) with a likelihood of coronary artery disease of less than 5% underwent rest and maximal exercise^99mTc-sestamibi SPET with a 2-day protocol and 180° elliptical rotation. The normalized activity values of^99mTc-sestamibi in the inferior wall differed significantly between men and women. Age variations were found for men in the anterior wall. Normalized activity values in all four walls were strikingly similar during rest and stress. Our results suggest that the use of reference files in^99mTc-sestamibi SPET requires a gender- and, for males, possibly an age-matched reference population. Different reference files at rest and during stress might not be necessary.     

Corticotropin-Releasing Factor Reduces Lipopolysaccharide-Induced Pulmonary Vascular Leak

Previous studies have suggested that corticotropin-releasing factor (CRF) has immunoregulatory effects in addition to its neuroendocrine role. We examined the ability of CRF to inhibit lipopolysaccharide (LPS)-induced pulmonary vascular leak in vivo. Female BALB/C mice were treated with either normal saline (NS) or CRF prior to injection with LPS. Pulmonary vascular leak was inhibited by CRF as assessed by measurement of lung wet-to-dry ratios. The stress-induced increase in serum corticosterone levels in mice injected with LPS alone was not further increased by treatment with CRF. This indicates that the effect of CRF was not mediated centrally by stimulation of endogenous steroid release. Histologic examination of the lungs revealed that leukocyte infiltration was significantly depressed in CRF-treated mice thus confirming the protective effect of CRF. In addition, a modest prolongation of survival was demonstrated in CRF-treated mice following challenge with LPS (p=.08). These data indicate the potential utility of CRF as a modulator of pulmonary vascular leak.