Intravenous ketorolac for pain management in a ventilator-dependent patient with thermal injury.

A patient with a long-standing history of chronic obstructive pulmonary disease suffered a thermal injury over 20% of his total body surface area. He required opiates for pain management and benzodiazepines for anxiety associated with dressing changes. The narcotics compromised his pulmonary function and level of consciousness, and interfered with several attempts to wean him from ventilator support.

Toxicodynamics of low level toxicant interactions of biological significance: inhibition of tissue repair.

Because of the complexity of studying the toxicological effects of mixtures of chemicals, much of the mechanistic information has become available through work with binary mixtures of toxic chemicals. Mechanisms derived from studies employing chemicals at individually nontoxic doses are more useful than the mechanisms of interactive toxicity at high doses from the perspective of environmental and public health. Several examples of chemical combinations and interactive toxicity at low doses are now available.

Effect of velocity on judgments of relative mass.

Research indicates that people can accurately judge the relative mass of colliding objects, i.e., which is heavier, if the collisions viewed involve actual physical objects.

Effects of a walking program on attributional style, depression, and self-esteem in women.

Few controlled studies describe the psychological effects of a walking program on nonclinical, premenopausal women. This experiment measured the effects of an 8-wk. walking program on female volunteers (N = 27) age 29 to 50 years (M = 37.

Injury and repair as opposing forces in risk assessment.

Recent advances in our understanding of the toxicodynamic events that follow infliction of injury have helped us to bridge the link between the tissue injury and the final outcome of that injury. In addition to infliction of tissue injury, toxic chemicals induce a biological compensatory response of tissue repair intended to overcome tissue injury through healing. Since stimulation of tissue repair is a simultaneous response accompanying injury, measuring this response in addition to quantifying injury might be helpful in tomorrow's risk assessment.

Topical exposure to chlordane reduces the contact hypersensitivity response to oxazolone in BALB/c mice.

Previous studies have shown that prenatal exposure to the organochlorine pesticide chlordane significantly decreases the ear swelling response to the contact allergen oxazolone in BALB/c mice. Alterations of macrophage function in the efferent arm of the contact hypersensitivity response have also been reported. In the current study, chlordane was applied topically and the effects of oxazolone-induced contact hypersensitivity were determined.

Age-related differences in TGF-alpha and proto-oncogenes expression in rat liver after a low dose of carbon tetrachloride.

The resiliency of rats during early post-natal development to CCl4 or to an interactive hepatotoxicity of chlordecone (CD) + CCl4 has been shown to be due to an efficient stimulation of tissue repair. The objective of the current study was to investigate if this is due to efficient expression of transforming growth factor-alpha (TGF-alpha) and proto-oncogenes. Postnatally developing (20 day old) and adult (60 day old) male Sprague-Dawley rats were challenged with a single low dose of CCl4 (100 microL/kg, ip) or corn oil.

Hepatocellular regeneration: key to thioacetamide autoprotection.

Low doses of thioacetamide stimulate cell division and tissue repair in the liver. The objective of this study was to develop an autoprotection model for thioacetamide and investigate if a low dose of thioacetamide (50 mg/kg orally) protects against lethality of a subsequently administered lethal dose (400 mg/kg orally) of the same compound. The extent of cell division was investigated to test if autoprotection results from augmented tissue repair and recovery from injury rather than decreased injury itself.

Combination therapy with 5-fluorouracil and L-canavanine: in vitro and in vivo studies.

L-Canavanine (CAV) is a potent L-arginine antagonist, produced by legumes such as the jack bean, Canavalia ensiformis. CAV is cytotoxic to MIA PaCa-2 human pancreatic cancer cells. We sought to determine whether CAV's efficacy as an anticancer agent might be increased in combination with 5-fluorouracil (5-FU), a pyrimidine antimetabolite with activity against solid tumors.

Age-related susceptibility to chlordecone-potentiated carbon tetrachloride hepatotoxicity and lethality is due to hepatic quiescence.

Previous studies revealed that postnatally developing rats are resilient to the lethal effects of chlordecone (CD) + carbon tetrachloride (CCl4) combination. The objective of this study was to investigate the underlying mechanism. We hypothesized that ongoing cell division and cell cycle progression as well as additional toxicant-induced stimulation of tissue repair help in restraining the progression of injury on the one hand, and in recovery through speedy healing on the other.

Childhood abuse as a factor in attrition from drug rehabilitation.

The following factors were examined as possible influences of clients' attrition from inpatient and outpatient drug-rehabilitation programs: depression (Center of Epidemiological Studies-Depression test), attributional style (Attributional Style Questionnaire), primary drug of choice, family incidence of substance abuse, and history of childhood physical abuse. A step-wise regression analysis indicated that a history of childhood abuse was a statistically reliable predictor of program noncompletion for 92 substance abusers who entered a drug-rehabilitation program.

Effects of type of exercise on depression in recovering substance abusers.

This experiment investigated the effects of three types of structured exercise (aerobics, bodybuilding, and circuit training) on depressive symptoms of 45 clients undergoing a 4-wk., inpatient rehabilitation program for substance abuse. Pre- and posttest measures included the Center of Epidemiological Studies--Depression, resting pulse rate, blood pressure, maximum strength on incline bench press, and estimates of aerobic fitness and body fat.

Research on hospital administrators' ethics: an agenda.

This discussion argues that whereas ethically questionable practices have been identified in many industries, the moral consequences of many hospital management decisions make this industry particularly worthy of ethics studies. Because health care, the hospital's product, typically represents more immediate, intimate, and possibly irreversible benefit or harm to its customer, the patient, than does the typical product of general industry, hospital executives should be held to higher ethical standards in their decision making. Yet little is known about the ethical thinking of hospital managers.

Tissue repair response as a function of dose in thioacetamide hepatotoxicity.

The purpose of the present study was to establish a dose-response relationship for thioacetamide (TA), where tissue regeneration as well as liver injury were two simultaneous but opposing responses. Male Sprague-Dawley rats were injected intraperitioneally with a 12-fold dose range of TA, and both liver injury and tissue repair were measured. Liver injury was assessed by serum enzyme elevations.

Cadmium disposition in the earthworm Eisenia fetida.

The disposition of cadmium was examined in the earthworm Eisenia fetida using two exposure media, filter paper, and artificial soil. Uptake and elimination rates were estimated to be 0.03039 and 0.

Stimulated hepatic tissue repair underlies heteroprotection by thioacetamide against acetaminophen-induced lethality.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that causes massive centrilobular hepatic necrosis at high doses, leading to death. The objectives of this study were to test our working hypothesis that preplaced cell division and hepatic tissue repair by prior thioacetamide (TA) administration provides protection against APAP-induced lethality and to investigate the underlying mechanism. Male Sprague-Dawley rats were treated with a low dose of TA (50 mg/kg, intraperitoneally [i.

Nutritional impact on the final outcome of liver injury inflicted by model hepatotoxicants: effect of glucose loading.

Fifteen percent glucose in drinking water for 7 days increased lethality of four structurally and mechanistically different model centrilobular hepatotoxicants (acetaminophen, thioacetamide, chloroform, and carbon tetrachloride) in male Sprague-Dawley rats (n = 10/group). A nonlethal injection of thioacetamide was lethal in glucose loaded rats and therefore was chosen for further studies. Serum enzyme elevations and liver histopathology revealed that actual infliction of liver injury peaked between 36 to 48 h after thioacetamide injection; however, the liver injury progressed in rats receiving glucose, whereas it regressed in rats maintained on normal diet and drinking water without glucose supplement.

Comparative developmental and maternal neurotoxicity following acute gestational exposure to chlorpyrifos in rats.

Chlorpyrifos (CPF), an organophosphorus (OP) insecticide, exerts toxicity through inhibition of acetylcholinesterase (AChE). In the present study, pregnant Sprague-Dawley rats were given CPF (200 mg/kg, sc) as a single dose on gestation d 12 (GD12) and then sacrificed on either GD16, GD20, or postnatal d 3 (PND3) for measurement of maternal and developmental indicators of toxicity. While most CPF-treated rats exhibited no overt signs, a subset (4/28) showed moderate to severe signs of "cholinergic" toxicity at 2-3 d after treatment, and these rats were omitted from further studies.

2-Butoxyethanol autoprotection is due to resiliance of newly formed erythrocytes to hemolysis.

Pretreatment with a low dose of a toxic chemical protecting the animals from a subsequently administered lethal dose of the same chemical is called autoprotection. Autoprotection by model hepatotoxicants has been recently shown to be due to augmentation of cell division and tissue repair as well as an inherent resiliance of newly divided cells. The present studies were designed to investigate if an autoprotection model could be established in an extrahepatic tissue.

Possible involvement of a neurotrophic factor during the early stages of organophosphate-induced delayed neurotoxicity.

Little is known regarding early biochemical events in organophosphate-induced delayed neurotoxicity (OPIDN) except for the essential inhibition of neurotoxic esterase (NTE). We hypothesized that a trophic factor may be produced in situ shortly after exposure to the OP which participates in the progression of OPIDN. To bioassay for such a growth-modulating factor(s), we treated chickens with the neuropathic agents diisopropylfluorophosphate (DFP) or cyclic phenyl saligenin phosphate (PSP), with or without phenylmethylsulfonyl fluoride (PMSF, a chemical which markedly modifies OPIDN).

Effect of tamoxifen on mitoxantrone cytotoxicity in drug-sensitive and multidrug-resistant MCF-7 cells.

The influence of the antiestrogen tamoxifen (TAM) on the activity of mitoxantrone (MXN), was evaluated against wild-type MCF-7/WT and their multidrug-resistant variant MCF-7/ADR cells. Multidrug resistance (MDR) in this cell line which was selected for resistance to Adriamycin (ADR), is associated with increased expression of P-glycoprotein (P-gp). In a clonogenic assay it was observed that TAM (1-10 microM) significantly enhanced the activity of MXN in the MCF-7/ADR but not in the drug-sensitive cell line.

Novel mechanisms in chemically induced hepatotoxicity.

This review focuses on cellular events that modulate hepatotoxicity subsequent to initial liver insult. Cellular events that determine the nature and extent of hepatotoxic injury and the ultimate outcome of that injury are also discussed. The roles of cell types other than hepatocytes, hepatocyte organelle-specific processes, and regeneration in progression or recovery from liver injury are emphasized.

Inhibition of the growth of human pancreatic cancer cells by the arginine antimetabolite L-canavanine.

L-Canavanine (CAV), the L-2-amino-4-guanidinooxy structural analogue of L-arginine (ARG), is a potent ARG antagonist which occurs in the jack bean, Canavalia ensiformis. This ARG antimetabolite is active against L1210 murine leukemia and a solid colonic tumor in the rat. Our initial studies using a microtiter assay show that CAV exhibits a 50% inhibitory concentration of approximately 2 mM against the human pancreatic adenocarcinoma cell line, MIA PaCa-2, when these cells are grown in Dulbecco's modified Eagle's medium containing 0.