Effect of isoelectric point on biodistribution and inflammation imaging with indium-111-labelled IgG

Electrostatic effects play an important role in protein interactions and may alter the biodistribution of antibodies. To study the effect of molecular charge on the biodistribution and infection imaging properties of human polyclonal immunoglobulin G (IgG), its iso electric point was varied by changing the level of diethylene triamine penta-acetic acid (DTPA) substitution: 0.8, 0.9, 3.7, 5.1 and 5.9 DTPA/IgG. Biodistributions of the different IgG preparations were determined at 10 min, 1, 6, 24, and 48 h post injection in normal rats, and infection imaging properties were determined in rats withEscherichia coli thigh infections. The biodistribution was significantly affected by pl. The immunoglobulin preparations with 0.9 and 3.7 DTPA/IgG showed faster clearance from the circulation and generally lower accumulation in most organs. The images had a target-to-background ratio of approximately 1.3–2.3:1. These results suggest that even though targeting is not affected by the level of DTPA substitutions, preparations with 0.9 and 3.7 DTPA/IgG may be superior imaging agents because of reduced accumulation by background organs.     

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.     

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.     

Expression of human mu or alpha class glutathione S-transferases in stably transfected human MCF-7 breast cancer cells: effect on cellular sensitivity to cytotoxic agents.

Increased expression of certain glutathione S-transferase (GST) isoenzymes has frequently been associated with the development of resistance to alkylating agents and other classes of antineoplastic drugs in drug-selected cell lines. The question arises whether this phenomenon is causal or is a stress-induced response associated with drug resistance in these cell lines. We have constructed mammalian expression vectors containing the human GST mu and GST alpha 2 (Ha2) cDNAs and stably transfected them into the human breast cancer cell line MCF-7. Whereas the parental and pSV2neo-transfected cell lines display low GST activity, three individual transfected clones were identified in each group that expressed either GST mu or GST alpha 2. The range of GST activities was similar to those observed in cells selected for anticancer drug resistance. The GST mu specific activities were 56, 150, and 340 mlU/mg, compared with 10 mlU/mg of endogenous GST mu in control lines. Specific activities in GST alpha 2-transfected clones were 17, 28, and 52 mlU/mg, compared with no detectable alpha class GST in control lines. These clonal lines and the parental and pSV2neo-transfected control lines were tested for sensitivity to antineoplastic agents and other cytotoxic compounds. The clones with the highest activity in each group were 1.7-fold (GST alpha 2) to 2.1-fold (GST mu) resistant to the toxic effects of ethacrynic acid, a known substrate for GSTs. However, the GST-transfected cell lines were not resistant to doxorubicin, L-phenylalanine mustard, bis(2-chloroethyl)-1-nitrosourea, cisplatin, chlorambucil, or the GST substrates 1-chloro-2,4-dinitrobenzene or tert-butyl hydroperoxide. Thus, although L-phenylalanine mustard, bis(2-chloroethyl)-1-nitrosourea, chlorambucil, tert-butyl hydroperoxide, and 1-chloro-2,4-dinitrobenzene are known to be metabolized by glutathione-dependent GST-catalyzed reactions, there was no protection against any of these agents in MCF-7 cell lines overexpressing GST mu or GST alpha 2. We conclude that, at the levels of GST obtained in this transfection model system, overexpression of GST mu or GST alpha 2 is not by itself sufficient to confer resistance to these anticancer agents. These studies do not exclude the possibility that GST may be a marker of drug resistance or that other gene products not expressed in MCF-7 cells might cooperate with GST to confer drug resistance.     

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.     

Gonadotropin-releasing hormone agonist (leuprolide acetate) induced ovarian hyperstimulation syndrome in a woman undergoing intermittent hemodialysis

Moderate ovarian hyperstimulation syndrome occurred after LA was administered to control menorrhagia in an anephric woman who required hemodialysis. We postulate that women who require dialysis may be at special risk for the development of this syndrome.