Renal resistance to mercuric chloride toxicity during prolonged exposure in rats

An attempt was made to develop a model of chronic renal disease in the rat through repeated administration of a nephrotoxin specific for proximal tubular epithelium. Mercuric chloride was administered by subcutaneous injection in gradually increasing amounts over a period of 21 weeks. The dose ranged from 1.125 mg/kg once a week to 2.0 mg/kg twice a week. Measured parameters of renal function include plasma urea nitrogen, plasma creatinine, 24-hour urine output volume, and 24-hour urinary protein excretion. When compared to their own pretreatment values and those of the age/weight-matched control animals, the mercuric chloride-treated rats exhibited no significant abnormalities in these parameters of kidney function with the exception of a mild proteinuria at 21 weeks. Light microscopic examination of the kidneys of the mercury-treated rats revealed mild tubular, interstitial, and glomerular lesions which were significantly worse than those in the kidneys of the controls. This study demonstrates the ability of the kidney to sustain a considerable degree of resistance to inorganic mercury toxicity when exposure is continuous over a prolonged period of time. It also demonstrates the inability of commonly measured clinical laboratory parameters of kidney function to identify the effects of chronic mercuric chloride toxicity in the rat.     

Synthesis and antiviral activity of phosphonoacetic and phosphonoformic acid esters of 5-bromo-2'-deoxyuridine and related pyrimidine nucleosides and acyclonucleosides

Phosphonoacetic acid (PAA, 1) was coupled with various acyclonucleosides, 2'-deoxyuridines, cytidines, and arabinosyluracils, with 2,4,6-triisopropylbenzenesulfonyl chloride (TPS) or dicyclohexylcarbodiimide (DCCI) as condensing agents, to give a range of phosphonate esters. The carboxylic ester linkage of PAA to the 5'-position of 5-bromo-2'-deoxyuridine (BUdR, 3) was achieved via the mixed anhydride formed from (diethylphosphono)acetic acid and trifluoroacetic anhydride. Phosphonoformic acid (PFA, 2) was coupled with BUdR by using the DCCI method to give the phosphonate ester. Of these compounds only phosphonate esters in the 2'-deoxyuridine series showed significant activity against herpes simplex virus types 1 and 2. The BUdR-PAA derivative and the BUdR-PFA derivative were highly active, especially the latter, which was more active than the parent nucleoside BUdR against the type 2 virus. The active compounds may exert their effects by extracellular or intracellular hydrolysis to the corresponding antiviral agents, but an intrinsic component of antiviral activity may also be involved.     

Analog language teaching versus natural language teaching: Generalization and retention of language learning for adults with autism and mental retardation

Examined the effects of two instructional methods on language generalization and longterm retention in 23 adults with autism and severe to profound mental retardation. Analog language teaching employed discrete trials in a controlled setting concentrating on discrimination and identification of materials. Natural language teaching emphasized instruction through interactions that occurred incidentally to training students in the use of materials to perform functional tasks. Assessments were conducted under conditions favoring analog teaching to assure against partiality toward natural language teaching. Under such disadvantageous conditions, the methods of natural language teaching would be supported by results showing either no difference or an advantage in their favor. Both techniques increased initial and long-term generalization though the results suggest no relative superiority for either method under these assessment conditions. A significant interaction was found between prior functioning level and sequence of instruction. Because natural language teaching has many strengths, few drawbacks, and produces equal generalization and retention under disadvantageous conditions, it is strongly supported as preferable for people with autism and mental retardation.The authors acknowledge the important assistance provided by the following people: the staff and management of the Behavior Development and Learning Center at CSH/DC directed by Israel Perel, Lisa Kramer, Steve Hafferkamp, James Lowdermilk, and, finally, and especially, to the participants themselves.     

Recovery from coma that results as a complication of cardiac arrest followed by cardiopulmonary bypass

Many possible complications are associated with cardiopulmonary bypass. They are similar to the risks accompanying most surgical procedures and include stroke, renal failure, and death. This potential for complication increases when bypass exceeds 2 hours and rises sharply when pump time is prolonged more than 3 to 4 hours. One group of serious complications is major neurologic disorders. The risk of significant cerebral dysfunction, that is, severe focal stroke or coma, is about 1%, and this risk increases with age and coexistent cardiovascular disease. This article focuses on the complication of coma and the possible role cardiopulmonary bypass plays in improving survival rates. A case study is presented illustrating the potential role of cardiopulmonary bypass in the unexpected neurologic recovery from coma.     

Cytokines in anaesthesia

The scope of cytokine biology is fascinating with widespread applications anticipated in many areas of medical science. We have emphasized the fundamental roles that cytokines play in the control of normal immunological functions, defence mechanisms and normal cell growth, and how major surgery and trauma can affect these processes. It remains to be determined if morbidity and mortality may be improved after major illness and surgery by altering cytokine production and function.