In vivo and in vitro metabolism of 2,4-dinitrotoluene in strain A mice.

The elimination and metabolism of a single dose (100 mg/kg) of 2,4-dinitrotoluene (2,4-DNT) in A/J mice were examined. After intraperitoneal administration, elimination was rapid, with 70% of the dose appearing in the urine within 4 hr. Four hours after oral administration, only 28.5% of the dose was excreted in the urine, which increased to 66% after 8 hr. Elimination via the feces was minimal (less than 2.1% of the dose) in both cases. From 0.5 to 4 hr after intraperitoneal administration, 3.6 to 8.8% of the urinary metabolites was unconjugated while 2.4 to 8.8% was present in the glucuronide fraction. After oral administration these amounts were 5.5 to 6.8% and 20.5 to 28.2% respectively. After both intraperitoneal and oral administration, no unchanged 2,4-DNT could be detected in the urine, and 2,4-dinitrobenzyl alcohol (2,4-DNBAlc) represented the most abundant identifiable neutral metabolite. Small amounts of 2,4-diaminotoluene, 2-amino-4-nitrobenzyl alcohol, 2-(N-acetyl)amino-4-nitrotoluene, 4-amino-2-nitrotoluene (4A2NT), and 2-amino-4-nitrotoluene (2A4NT) were also present. In almost all cases the largest proportion of metabolites represented unknowns, some of which exhibited the chromatographic properties of carboxylic acid metabolites. Metabolism of 2,4-DNT by liver and lung microsomes yielded mainly 2,4-DNBAlc with lower amounts of 4A2NT and 2A4NT, and their formation was dependent on the presence of oxygen and NADPH. Pretreatment of the animals with 2,3,7,8-tetrachlorodibenzo-p-dioxin resulted in increased yields of all three metabolites. Aerobic metabolism of 2,4-DNT by explants of the small intestine, large intestine, or by cecal contents yielded 2,4-DNBAlc, 2A4NT, 4A2NT and 4-(N-acetyl)amino-2-nitrotoluene (4Ac2NT). The proportion of reduced metabolites (2A4NT, 4A2NT, and 4Ac2NT) was much higher in these systems than with liver or lung microsomes and their formation by small intestine and cecal contents was enhanced several-fold under anaerobic conditions, while that of 2,4-DNBAlc was abolished. It is concluded that 2,4-DNT metabolism in the A/J mouse is rapid and complete and that the major neutral urinary metabolite is 2,4-DNBAlc. Minor amounts of reduced or partially reduced products appear to be formed mainly in the intestine, with a major role by its microflora.

Melanoma of the head and neck. Update and perspective.

The diagnosis and appropriate treatment of melanoma remains a controversial subject. A review of the literature as well as evaluation of our experience allows for a better understanding of this challenging problem and the development of some up-to-date guidelines in the treatment of this disease.

The prevalence and circumstances of child sexual abuse: changes across a decade.

OBJECTIVE: This study reports the prevalence of child sexual abuse of African American and European American women and compares the circumstances of these incidents to data collected a decade ago. METHOD: Stratified probability sampling was used to recruit comparable samples of African American and European American women in Los Angeles County for a larger study of women's sexual decision making. Incidents of contact abuse were obtained from women 18 to 36 years old in 1994 and compared to women with those demographic characteristics from a comparable 1984 dataset. The prevalence of abuse, characteristics of the victim, assault, alleged perpetrator, disclosure, and long-term effects by ethnic group affiliation were assessed. RESULTS: Of the total sample, 34% reported at least one incident prior to age 18. Ethnic differences were found with respect to prevalence, location of abuse, and number of incidents of rape. While comparisons made with the 1984 dataset revealed no significant difference in prevalence rates over the 10 year period, changes in circumstances were noted. CONCLUSIONS: Although the prevalence of child sexual abuse in Los Angeles County remained fairly stable, several circumstances of abuse underwent change. These characteristics are discussed in relation to how sexual abuse among ethnically diverse samples in Los Angeles County has changed over a decade and how these differences can help better tailor prevention messages to different communities.

[Coronary bypass surgery on the beating heart and surgery of an abdominal aortic aneurysm. Immediately sequential surgical treatments]. / Pontages coronaires à coeur battant et anévrisme de l'aorte abdominale. Traitement chirurgical en un temps.

The authors report sequential association during the same general anaesthetic of coronary bypass surgery on the beating heart and surgery of an abdominal aortic aneurysm. Two aorto-coronary bypass grafts were carried out without cardiopulmonary bypass using the two pediculated internal mammary arteries (without manipulation of the ascending aorta), followed, after closure of the chest and monitoring in the operating theatre for one hour, by reinstallation of the patient for treatment of an infra-renal abdominal aortic aneurysm by classical prosthetic implantation. The postoperative course was uncomplicated. Sequential management of coronary revascularisation without cardiopulmonary bypass and aortic aneurysmal lesions during the same anaesthetic provides an alternative to classical two-stage surgery in selected patients.

[A survey of the diffusion and impact of consensus development conference on infections caused by central venous catheters in an anesthesiologist team]. / Enquête sur la diffusion et l'impact d'une conférence de consensus sur les infections liées aux cathéters veineux centraux au sein d'une équipe d'anesthésistes-réanimateurs.

OBJECTIVES: To assess the diffusion and the impact on the professional practices of a consensus conference (CC) by the French speaking Society of Intensive Care on "Central venous catheter-related sepsis in intensive care". STUDY DESIGN: Before-after survey with two successive questionnaires. MATERIAL AND METHODS: Two questionnaires (Q1 and Q2) were circulated either to intensivists (group 1) or to anaesthetists (group 2) of a University Hospital, before (Q1) and after (Q2) distribution of the CC conclusions. They aimed to assess the diffusion of the conclusions by the CC; the professional practices before the CC and their modifications after consideration of the recommendations by the CC. RESULTS: Out of the 55 consulted, 85% answered Q1, and 71% Q2. Among them, 42% were aware of the conclusions of the CC before starting the survey-73.5% from group 1 and 28% from group 2. Therefore, conversely to anaesthetists, intensivists, did not significantly modify their professional practices after consideration of the CC conclusions. CONCLUSION: This study shows a satisfactory diffusion of the content of jury's recommendations among anesthetists whereas the impact was less satisfactory with intensivists. The impact of a CC could probably be improved by a better diffusion of the consensus statements and by the intervention of local linkmen.

[Iatrogenic gas embolism following surgical lavage of a wound with hydrogen peroxide]. / Embolie gazeuse iatrogène après lavage chirurgical d'une plaie à l'eau oxygénée.

The use of hydrogen peroxide (H2O2) in surgery for its antiseptic properties has been associated with life-threatening complications. We report a case of severe oxygen embolism after wound irrigation with H2O2 in a 17-year-old boy undergoing surgical dressing of a large thigh trauma under general anaesthesia. During muscle lavage with 400 mL of H2O2 3%, severe shock suddenly occurred. On the basis of clinical presentation, the diagnosis of pulmonary gas embolism was strongly suspected. Symptomatic treatment initiated immediately, restaured a normal haemodynamic state within a few minutes and the patient recovered without sequelae. The degradation of H2O2 results in considerable amounts of gaseous oxygen. One mL of H2O2 can produce in the tissues 10 mL of oxygen. This gas can enter the circulation and determine severe embolism. The treatment should be initiated without delay. The administration of H2O2 under pressure is contraindicated during surgery.

[Chylothorax complicating a subclavian puncture controlled by positive-pressure expiratory ventilation]. / Chylothorax compliquant une ponction sous-clavière contrôlé par la ventilation avec pression expiratoire positive.

We report a case of traumatic chylothorax which occurred after a right subclavian vein catheterisation. Chyle output exceeded 4 L.day-1 despite a continuous drainage of the pleural space, cessation of oral intake and mechanical ventilation. It was cured by addition of PEP to ventilation. The various causes and therapeutic approaches are reviewed.

[Paraplegia after aorto-bifemoral prosthesis: systematized dysautonomic symptoms should evoke spinal cord damage]. / Paraplégie après pontage aorto-bifémoral: des troubles neurovégétatifs systématisés doivent faire évoquer l'accident médullaire.

We report a case of paraplegia following aorto-bifemoral by-pass surgery for infrarenal aortic occlusive disease. The first symptoms of spinal cord damage were systematized dysautonomic symptoms including mottled skin and sudation. Such symptoms, occurring during recovery from anaesthesia are an indication for checking the status of the spinal cord.

[Superior mesenteric artery syndrome]. / Syndrome de l'artère mésentérique supérieure.

The superior mesenteric artery syndrome (SMAS) is a rare complication of spine surgery. A series of four patients who experienced a SMAS after surgery for either post-traumatic quadriplegia, paraplegia or scoliosis is reported. SMAS is a condition in which the third portion of the duodenum is squeezed between the superior mesenteric artery anteriorly, and the aorta and vertebral column posteriorly. Weight loss is the major factor of development of a SMAS. Other causes include either spine surgery or trauma or application of a body cast. Delay in diagnosis may result in death. Diagnosis is obtained with either a CT scan with injection and oral contrast medium or an upper gastro-intestinal X-ray study. The latter allows the insertion of a feeding tube beyond the obstruction. A conservative treatment is started for correction of dehydration and electrolyte imbalance, and followed by nasojejunal feeding. Surgery is indicated in case of failure of conservative treatment.

[Quality of blood salvaged in orthopedic surgery by washing swabs]. / Qualité du sang récupéré en chirurgie orthopédique par le lavage des compresses.

OBJECTIVE: To establish the feasibility and safety of recuperating blood absorbed by swabs used during orthopaedic surgery. STUDY DESIGN: Open, prospective study. PATIENTS: Included were children undergoing potentially haemorrhagic orthopaedic surgery for whom intraoperative blood salvage seemed possible. Excluded were those with contraindications for this procedure such as septic surgery and cancer surgery. METHOD: Intraoperative swabs used within the surgical field were collected by a surgical assistant, also in charge of weighing and washing them. The liquid was collected by the aspiration system of a recuperation-washing machine (RWM). The salvaged red blood cells were collected and retransfused at the end of surgery. Several samples of the washing liquid of the swabs and salvaged blood were taken during the procedure. The correlation between the quantity of blood shed and salvaged was calculated. The biological and clinical tolerance of the transfusion was assessed. RESULTS: Twelve patients undergoing surgery for scoliosis have been included. An average of 278 mL of blood were salvaged. In the washed cell concentrates the haematocrit was 54% and the free haemoglobin concentration was 3.84 g.L-1. All the bacteriological tests were negative over the first 24 hours. CONCLUSION: Provided that a strict operatory protocol is followed, this study demonstrates the possibility of recuperating blood from swabs used during major orthopaedic surgery.

Fear of fat, disregulated-restrained eating, and body-esteem: prevalence and gender differences among eight- to ten-year-old children.

Examined whether: (a) societal directives to be thin are perceived among children, (b) discontent with body and attitudes and behaviors associated with eating disorders begin before adolescence, and (c) these differ by sex. These issues were assessed in 239 Grade 3 students. Scales of eating and weight attitudes and behaviors for this under-studied population were either created or modified from existing instruments. These 8- to 10-year-old children expressed weight, dieting, and physique concerns that reflect Western sociocultural values and preoccupation with body weight and dieting. Sex differences were examined and revealed several but not very reliable distinctions at this young age. These findings appear to be consistent with research on adolescents. The components that may lead to the development of an eating disorder or disregulated-restrained eating in a vulnerable adolescent may be both internalized and expressed at a very early age.

Distribution, elimination, and test for carcinogenicity of 2,6-dinitrotoluene after intraperitoneal and oral administration to strain a mice.

After intraperitoneal (ip) and oral (po) administration of 2,6-dinitrotoluene (2,6-DNT), the distribution, elimination, and lung tumor response were determined in strain A mice. In a 30-wk bioassay and at total ip doses of 600, 1500, or 3000 mg/kg, or total po doses of 1200, 3000, or 6000 mg/kg, 2,6-DNT did not produce an increase in lung adenomas when compared to vehicle-treated controls. The urine was the major route of elimination of both ip and po administered 3H-labeled 2,6-DNT, with 87.6, 55.2, and 49.1% of ip doses of 1, 10, and 100 mg/kg, respectively, excreted within 4 h. The corresponding amounts excreted after po administration were 33.6, 25.2, and 24.3%, which increased to 53.7, 53.5, and 48.6% after 8 h. The distribution of 2,6-DNT in various tissues (blood, liver, kidneys, lungs, small and large intestine) showed no evidence for preferential uptake or retention at any of the ip or po doses. Terminal half-lives of radioactive material in the liver were 1.11, 0.95, and 1.16 h after ip doses of 1, 10, and 100 mg/kg, respectively. At all ip doses (1, 10, and 100 mg/kg), rapid and extensive metabolism of 3H-labeled 2,6-DNT was observed, as judged by the low amounts (less than 2% of the total 3H/tissue) of unchanged 3H-labeled 2,6-DNT that could be reisolated from blood, liver, small intestine, or lungs at 2 h after administration. The extent of 3H-labeled 2,6-DNT metabolism by these tissues after po administration was similar, except for the relatively high amounts of unchanged 3H-labeled 2,6-DNT (approximately 50% of the total 3H/tissue between 1 and 8 h after 100 mg/kg) present in the small intestine. At these times, negligible (less than 2%) unchanged 3H-labeled 2,6-DNT was present in the large intestine. It is concluded that ip or po administered 2,6-DNT is not carcinogenic in the strain A mouse lung-tumor bioassay. Excretion in the urine is the major mode of elimination after either ip or po administration, but is slower after po than after ip dosing. It is likely that the liver and small intestine are major sites of 2,6-DNT metabolism, and it is possible that po administered 2,6-DNT is also metabolized by the microflora of the large intestine.

Metabolism and DNA adduct formation of 2-acetylaminofluorene by bladder explants from human, dog, monkey, hamster and rat.

Cultured bladder explants from human, dog, monkey, hamster and rat were used to study the metabolism, and DNA-adduct formation of [3H]2-acetylaminofluorene (AAF). After 24 h of incubation with 1 microM [3H]AAF, the organic-soluble and glucuronide fractions represented 29.0-58.4% and 0.7-10.8%, respectively, of the total amount of radioactive material in the medium. In the organic-soluble fraction of all species, the presence of both ring-hydroxylated (at the 7-, 9-, 5-, 3- and 1-carbons) metabolites and N-hydroxy-AAF could be demonstrated, with 7-hydroxy-AAF and 9-hydroxy-AAF being the most ubiquitous metabolic products. In addition, 2-aminofluorene could be detected in all cases with the highest amounts formed by dog bladder explants. Species susceptible to aromatic amine-induced bladder carcinogenesis (human and dog) showed widely varying DNA binding (0.23 +/- 0.20 and 1.95 +/- 1.2 mumol AAF/mol deoxyribonucleotide, respectively), and in explants of the less susceptible species (monkey, hamster and rat) DNA binding was comparable (0.46 +/- 0.21, 0.37 +/- 0.07 and 0.34 +/- 0.27, respectively). Enzymatic hydrolysis of the [3H]AAF--DNA to the nucleoside level revealed that N-(deoxyguanosine-8-yl)-2-aminofluorene, together with small amounts (5.9-15.4% of the total) of its imidazole ring-opened derivative, was the most ubiquitous adduct formed (17.8-47.2% of the total) in all species, except the dog. In dog bladder DNA, N-(deoxyguanosine-8-yl)-2-acetylaminofluorene was the principal DNA adduct (39.0-46.5% of the total) with smaller amounts (15.5-22.2% of the total) in the other species. In addition, small amounts (3.5-8.6% of the total) of another adduct, 3-(deoxygaunosin-N2-yl)-2-acetylaminofluorene, could be detected in all cases. It is concluded that bladder explants of the human, dog, monkey, hamster and rat metabolize AAF mainly to ring-hydroxylated products, but also form small amounts of the proximate carcinogenic metabolite N-hydroxy-AAF. Neither the overall binding of AAF to bladder DNA, nor the formation of specific AAF--DNA adducts is correlated with the relative susceptibilities of these five species to aromatic amine-induced urinary bladder carcinogenesis.

A comparison of the lung adenoma response in strain A/J mice after intraperitoneal and oral administration of carcinogens.

This study was undertaken to compare the ability of a series of compounds from different chemical classes to induce lung tumors in strain A/J mice after either ip or po administration. 3-Methylcholanthrene, benzo(a)pyrene, urethan, diethylnitrosamine, ethylnitrosourea, and dimethylhydrazine induced a significant (p less than 0.05; t test) increase in the lung tumor response when given both ip and po. 2,4-Dinitrotoluene, 2,6-dinitrotoluene, and a 2:1 mixture of 2,4-dinitrotoluene and 2,6-dinitrotoluene were inactive by both routes of administration and at all dose levels. The lung tumor response to all doses of 3-methylcholanthrene and benzo(a)pyrene, the highest dose of diethylnitrosamine, and the middle doses of both ethylnitrosourea and dimethylhydrazine varied as a function of the route of administration. This finding was most evident for the polycyclic hydrocarbons, e.g., the average number of lung tumors per mouse in animals that received the middle dose of 3-methylcholanthrene or the highest dose of benzo(a)pyrene by the ip route exceeded that by the po route by factors of 12 and 13, respectively. Tissue distribution and elimination studies were conducted in an effort to determine the basis for the observed difference in lung tumor response to 3-methylcholanthrene after ip or po administration. The data indicated that 3-methylcholanthrene persists for longer periods in the animals when given ip, thus potentially providing an extended carcinogenic stimulus. Extrapulmonary lesions observed at a higher than normal frequency at necropsy included peritoneal sarcomas (in 3-methylcholanthrene-treated mice), and both squamous cell carcinomas of the forestomach and abnormal lesions of the liver (in diethylnitrosamine-treated mice).