Regulation of mdr1b gene expression in Fischer, Wistar and Sprague-Dawley rats in vivo and in vitro.

Administration of 2-acetylaminofluorene (2-AAF) to rats increased mdr1b expression in Fischer, Wistar and Sprague-Dawley rat livers; however, the response was much smaller in Sprague-Dawley livers. To investigate the basis of this difference we further examined the regulation of the mdr1b gene in hepatocytes isolated from Fischer, Sprague-Dawley and Wistar rats. A time-dependent increase in basal expression of mdr1b but not mdr2 was observed in hepatocytes isolated from all three strains of rats. After 4 days in culture, a larger increase in mdr1b mRNA levels was observed in Fischer and Wistar rat hepatocytes (3.5- and 4.6-fold respectively) than Sprague-Dawley hepatocytes (2-fold). Treatment of primary hepatocytes with 2-AAF caused an induction of mdr1b expression that varied among the three strains. Notably, Sprague-Dawley hepatocytes were not responsive to 2-AAF. In contrast to the parent compound, the electrophilic metabolites N-hydroxy-2-acetylaminofluorene and N-acetoxy-2-acetylaminofluorene caused a dose-dependent induction of mdr1b expression in both Fischer and Sprague-Dawley hepatocytes, indicating that differences in the metabolic activation of 2-AAF between the strains may account for the differences in mdr1b by 2-AAF. Hepatocytes isolated from all three strains of rats showed an equivalent induction of mdr1b after treatment with cycloheximide. Nuclear run-on assays demonstrated that the increases in mdr1b expression with time in culture and after xenobiotic treatment were due to increased transcription.

Characterization of the basal and carcinogen regulatory elements of the rat mdr1b promoter.

In this report we characterized the transcriptional regulation of the rat mdr1b gene by xenobiotics. The expression of this gene was increased in primary rat hepatocytes and in the H4-II-E hepatoma cell line by exposure to carcinogens such as aflatoxin B1, N-acetoxy-2-acetylaminofluorene, and methyl methanesulfonate. Nuclear run-on experiments indicated that the higher steady-state levels of mdr1b mRNA were due to an increase in transcription. The 5'-flanking region of the mdr1b gene was isolated, sequenced, and functionally characterized in transient and stable transfection assays. A single transcription start site was identified for this gene; no alternate start sites were used after induction with aflatoxin B1. Deletion analysis of this promoter demonstrated that the sequence between nt -214 and -178 was critical for basal promoter activity. This region did not contain any consensus-binding sites for previously identified transcription factors. A negative regulatory region was also identified between nt -940 and -250. No specific carcinogen-responsive element was identified; the xenobiotic response required a large part of the promoter. These data suggest that the carcinogen induction of mdr1b expression is mediated through sequences that overlap or that are identical to the basal promoter element.

Metabolism of 2-(glutathion-S-yl)hydroquinone and 2,3,5- (triglutathion-S-yl)hydroquinone in the in situ perfused rat kidney: relationship to nephrotoxicity.

2,3,5-(Triglutathion-S-yl)hydroquinone [2,3,5-(triGSyl)HQ] (20 mumol/kg) and 2-(glutathion-S-yl)hydroquinone [2-(GSyl)-HQ] (250 mumol/kg) both cause nephrotoxicity when administered to male rats, although the former is considerably more potent than the latter. To address the issue of the differential potency of these conjugates we investigated the metabolism and toxicity of 2,3,5-(triGSyl)HQ and 2-(GSyl)HQ in the in situ perfused rat kidney. Infusion of 5 and 10 mumol 2,3,5-(triGSyl)HQ into the right renal artery caused a time-dependent elevation in gamma-glutamyl transpeptidase (gamma-GT) excretion into urine produced by both the perfused and the contralateral kidneys. At the lower concentration, gamma-GT excretion was greater from the perfused kidney, whereas gamma-GT excretion from the perfused and contralateral kidneys was the same at the higher concentration. Using HPLC-EC to analyze urine and bile, metabolites of 2,3,5-(triGSyl)HQ (10 mumol) were observed only within the first 30 min of perfusion. At the lower dose (5 mumol) neither parent compound nor metabolites were found in urine or bile. Infusion of 40 mumol 2-(GSyl)HQ into the right renal artery also caused a time-dependent excretion of gamma-GT into urine: excretion being greater from the perfused kidney. HPLC-EC analysis of urine and bile from 2-(GSyl)HQ perfused kidneys demonstrated the formation of three known metabolites; 2-(N-acetyl-cystein-S-yl)HQ (9.2 +/- 0.5 mumol). 2-(cystein-S-ylglycine)HQ (0.8 +/- 0.3 mumol), and 2-(cystein-S-yl)HQ (1.3 +/- 0.3 mumol). Unchanged 2-(GSyl)HQ was detected in the urine and bile (0.8 +/- 0.1 mumol). A greater fraction of the dose (74%) was recovered in urine following infusion of 40 mumol 2-(GSyl)[14C]HQ than of 10 mumol 2,3,5-(triGSyl)[14C]HQ (29%). In contrast, a greater fraction of the dose was retained by the kidney following treatment with 10 mumol 2,3,5-(triGSyl)[14C]HQ than following treatment with 40 mumol 2-(GSyl)[14C]HQ (36 and 11%, respectively). This result suggests that metabolites derived from 2,3,5-(triGSyl)[14C]HQ are more reactive than those derived from 2-(GSyl)[14C]HQ, which is consistent with the finding that 2,3,5-(tricystein-S-yl)hydroquinone exhibits a lower oxidation potential than 2-(cystein-S-yl)hydroquinone. Differences in the reactivity of the metabolites derived from 2,3,5-(triGSyl)[14C]HQ and 2-(GSyl)[14C]HQ probably account for the more potent nephrotoxicity of 2,3,5-(triGSyl)HQ.

Metabolism and toxicity of 2-bromo-(diglutathion-S-yl)-hydroquinone and 2-bromo-3-(glutathion-S-yl)hydroquinone in the in situ perfused rat kidney.

2-Br-(diglutathion-S-yl)hydroquinone (2-Br-(diGSyl)HQ) is a potent nephrotoxicant, causing glucosuria, enzymuria, proteinuria, elevations in blood urea nitrogen, and severe histological alterations to renal proximal tubules at doses of 10-15 mumol/kg. In contrast, 2-Br-3-(glutathion-S-yl)hydroquinone (2-Br-3-(GSyl)HQ) is substantially less nephrotoxic than 2-Br-(diGSyl)HQ and requires a dose of at least 50 mumol/kg to cause modest elevations in blood urea nitrogen concentrations. The reason or reasons for this difference in potency is unclear, but since inhibition of renal gamma-glutamyl transpeptidase (gamma-GT) prevents 2-Br-(diGSyl)HQ-mediated nephrotoxicity, metabolism of these conjugates by the kidney must play an important role. To address this question we have compared the metabolism and toxicity of 2-Br-(diGSyl)HQ and 2-Br-3-(GSyl)HQ in the in situ perfused rat kidney (ISPRK). Following infusion of 20 mumol 2-Br-3-(GSyl)HQ into the right renal artery of male Sprague Dawley rats, a total of 23.5 +/- 1.9% (mean +/- SE) of the dose was accounted for in urine and bile over a period of 180 min. 2-Bromo-3-(cystein-S-yl)hydroquinone and 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone were identified in urine, and unchanged 2-Br-3-(GSyl)HQ was identified in urine and bile. The product arising from the oxidative cyclization of 2-bromo-3-(cystein-S-glycine)hydroquinone, 2H-(3-glycine)-7-hydroxy-8-bromo-1,4-benzothiazine, was also identified in urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Medial collateral ligament knee sprains in college football. Effectiveness of preventive braces.

This is the second of 2 articles on a 3-year investigation of medial collateral ligament sprains of the knee to assess the effectiveness of prophylactic knee braces in NCAA Division I college football players. Position, string, type of session, and daily brace wear were recorded. The injury rates for braced and unbraced knees were used to create an incidence density ratio. The data were stratified and simultaneously controlled for position, string, and session and evaluated for their statistical significance. The 987 Big Ten players generated 155,772 knee exposures over the study period (50% braced). Noticeable differences existed in the rates of injury for the braced and unbraced knees in almost every position during practices, depending on player or nonplayer status. When the influential factors of position, string, and session are considered, there is a consistent but not statistically significant tendency for the players wearing preventive knee braces to experience a lower injury rate than for their unbraced counterparts. For starters and substitutes in the line positions, as well as the linebackers and tight ends, there was a consistent trend toward a lower injury rate in both practices and games. The braced players in the skill positions (backs/kickers), at least during games, exhibited a higher injury rate.

Medial collateral ligament knee sprains in college football. Brace wear preferences and injury risk.

In this prospective, multiinstitutional analysis of medial collateral ligament sprains in college football players, we categorized 987 previously uninjured study subjects according to frequency of wearing preventive knee braces, studied the patterns by which 47 of 100 injuries occurred to unbraced knees, and identified several extrinsic, sport-specific risk factors shared for both braced and unbraced knees. The attendance, brace wear choice, position, string, and session of each participant were recorded daily; medial collateral ligament sprains were reported whenever tissue damage was confirmed. Both the likelihood of wearing braces and risk of injury without them was highly dependent on session (games/practices), position group (line, linebacker/tight end, skill), and string group (players/nonplayers). Subjects wearing braces often faced a high injury risk to their unbraced knees, a finding compatible with the opinion that braces were a necessary evil, best worn when concern over danger of injury outweighed desire for speed and agility. It is concluded that to avoid misinterpretations due to the confounding influence of brace wear selection bias, accurate investigation of daily brace wear patterns is required. Then, before considing the impact of preventive knee braces, a repartitioning of the data base is essential to assure that only similar groups will be compared.

Identification of multi-S-substituted conjugates of hydroquinone by HPLC-coulometric electrode array analysis and mass spectroscopy.

Chemical reaction of 1,4-benzoquinone with GSH gives rise to several multisubstituted hydroquinone (HQ)-GSH conjugates, each of which causes renal proximal tubular necrosis when administered to male Sprague-Dawley rats. In addition, HQ has recently been reported to be nephrocarcinogenic following long-term exposure in male rats. Since neither the mechanism nor the extent of HQ oxidation and thioether formation in vivo is known, we have assessed both the qualitative and quantitative significance of HQ-thioether formation in vivo and in vitro. HQ (1.8 mmol/kg, ip) was administered to AT-125-pretreated male Sprague-Dawley rats, and bile and urine samples were analyzed with a HPLC-coulometric electrode array system (CEAS) and by liquid chromatography (LC)/continuous-flow fast atom bombardment (CF-FAB) mass spectroscopy. Five S-conjugates of hydroquinone were identified in bile, and one S-conjugate was identified in urine. The major biliary S-conjugate identified was 2-glutathion-S-ylhydroquinone [2-(GSyl)HQ] (18.9 +/- 2.7 mumol). Additional biliary metabolites were 2,5-diglutathion-S-ylhydroquinone [2,5-(diGSyl)HQ] (2.2 +/- 0.6 mumol), 2,6-diglutathion-S-ylhydroquinone [2,6-(diGSyl)HQ] (0.7 +/- 0.3 mumol),2,3,5-triglutathion-S-ylhydroquinone [2,3,5-(triGSyl)HQ] (1.2 +/- 0.1 mumol), and 2-(cystein-S-ylglycyl)hydroquinone. 2-(N-Acetylcystein-S-yl)HQ was the only urinary thioether metabolite (11.4 +/- 3.6 mumol) identified. The quantity of S-conjugates excreted in urine and bile within 4 h of HQ administration [34.3 +/- 4.5 mumol (4.3 +/- 1.1% of dose)] appears sufficient to propose a role for such metabolites in HQ-mediated nephrotoxicity and nephrocarcinogenicity. Rat liver microsomes catalyzed the NADPH-dependent oxidation of HQ (300 microM), in the presence of GSH, to form 2-(GSyl)HQ,2,5-(diGSyl)-HQ, and 2,6-(diGSyl)HQ. A fraction of the microsomal oxidation of HQ appears to be catalyzed by cytochrome(s) P450, although the exact amount remains unclear. 2-(GSyl)HQ,2,5-(diGSyl)-HQ, and 2,6-(diGSyl)HQ (300 microM) also underwent NADPH-dependent oxidation and GSH conjugation in liver microsomes. The extent of the nonenzymatic oxidation of HQ and its GSH conjugates correlated, approximately, with their half-wave oxidation potentials.

The effects of 2,3,5-(triglutathion-S-yl)hydroquinone on renal mitochondrial respiratory function in vivo and in vitro: possible role in cytotoxicity.

Administration of 2,3,5-(triglutathion-S-yl)hydroquinone [2,3,5-(triGSyl)HQ] to rats causes severe renal proximal tubular necrosis. Although the cellular target(s) for 2,3,5-(triGSyl)HQ is not known, substantial evidence implicates mitochondria as the primary cellular target for aliphatic S-conjugates. To determine whether mitochondria are targets for 2,3,5-(triGSyl)HQ, the in vivo and in vitro effects of this conjugate on rat renal mitochondria (RRM) were investigated. In vitro exposure of RRM to 2,3,5-(triGSyl)HQ inhibited site I-supported respiration to a much greater extent than site II-supported respiration. Inhibition of mitochondrial function, as manifested by decreases in the respiratory control ratios, were a consequence of significant elevations in state 4 respiration. Inhibition of constitutive gamma-GT activity with AT-125 had no effect on the ability of 2,3,5-(triGSyl)HQ to decrease mitochondrial function. The effects of 2,3,5-(triGSyl)HQ on mitochondrial function in vivo were subsequently assessed. Shortly (0.5-2.0 hr) following administration of 2,3,5-(triGSyl)HQ (20 mumol/kg, iv) to rats, a significant elevation of state 4 respiration was observed. Thereafter (4-16 hr) state 4 respiration returned to control values and state 3 respiration became significantly depressed. A total collapse in RRM function occurred by 24 hr. The effects of 2,3,5-(triGSyl)HQ on state 4 respiration preceded significant elevations in blood urea nitrogen, which occurred at 8 hr. However, pretreatment of animals with probenecid, an inhibitor of organic anion transport, caused a significant decrease in the 2,3,5-(triGSyl)HQ-mediated elevations in state 4 respiration at 1 hr, without preventing the subsequent development of renal necrosis. In contrast, AT-125, which protected animals from 2,3,5-(triGSyl)HQ-mediated nephrotoxicity, had no effect on the early (1 hr) elevations in state 4 respiration but did prevent the later (8 hr) decreases in state 3 respiration. The data suggest that the early elevation in state 4 respiration observed in vivo is unlikely to contribute to 2,3,5-(triGSyl)HQ-mediated nephrotoxicity. The relationship between the decrease in state 3 respiration seen at later time points and the subsequent development of toxicity require further study before a cause and effect relationship can be determined.

Nephrotoxicity of 2-bromo-(cystein-S-yl) hydroquinone and 2-bromo-(N-acetyl-L-cystein-S-yl) hydroquinone thioethers.

The in vivo toxicity of isomeric cystein-S-yl and N-acetylcystein-S-yl conjugates of 2-bromohydroquinone was determined in male Sprague-Dawley rats. 2-Bromo-(dicystein-S-yl)hydroquinone [2-Br-(diCYS)HQ] and 2-bromo-(di-N-acetyl-L-cystein-S-yl)hydroquinone [2-Br-(diNAC)HQ] were considerably more nephrotoxic than their corresponding monosubstituted thioethers and 2-Br-(diCYS)HQ was more nephrotoxic than 2-Br-(diNAC)HQ. 2-Br-(diCYS)HQ caused elevations in blood urea nitrogen (BUN) concentrations and increases in the urinary excretion of glucose, lactate dehydrogenase (LDH), and gamma-glutamyl transpeptidase (gamma-GT) at a dose of 25 mumol/kg (iv). In contrast, 2-Br-(diNAC)HQ caused significant elevations in BUN at 100 mumol/kg and glucosuria and enzymuria at 50 mumol/kg. 2-Br-3-(CYS)HQ and 2-Br-5&6-(CYS)HQ caused increases in the biochemical indices of nephrotoxicity at doses between 50 and 150 mumol/kg whereas 2-Br-5-(NAC)HQ and 2-Br-6-(NAC)HQ required doses of 150-200 mumol/kg to cause smaller, though significant increases in urinary glucose, gamma-GT, and LDH excretion. The histological alterations caused by each thioether were qualitatively similar; only differences in the extent of the renal proximal tubular damage were observed. The initial lesion appears to involve the cells of the medullary ray and the S3M within the outer stripe of the outer medulla. The in vivo nephrotoxicity of 2-Br-(DiCYS)HQ, 2-Br-(diNAC)HQ, and the most potent monosubstituted thioethers, 2-Br-5&6-(CYS)HQ and 2-Br-6-(NAC)HQ, was investigated further. Pretreatment of animals with aminooxyacetic acid, an inhibitor of cysteine conjugate beta-lyase (beta-lyase), had no effect on the toxicity of 2-Br-(diCYS)HQ, partially inhibited the toxicity of 2-Br-5&6-(CYS)HQ, and almost completely protected against the toxicity of both 2-Br-6-(NAC)HQ and 2-Br-(diNAC)HQ. Thus, the nephrotoxicity of 2-Br-5&6-(CYS)HQ, 2-Br-6-(NAC)HQ, and 2-Br-(diNAC)HQ may be mediated, in part, via their processing by beta-lyase. Pretreatment of animals with probenecid, an inhibitor of renal organic anion transport, completely protected against the toxicity of 2-Br-(diNAC)HQ but had no effect on the toxicity of the other thioethers.

Species differences in renal gamma-glutamyl transpeptidase activity do not correlate with susceptibility to 2-bromo-(diglutathion-S-yl)-hydroquinone nephrotoxicity.

Administration of 2-bromo-(diglutathion-S-yl)hydroquinone (2-Br-[diGSyl]HQ) (10-30 mumol/kg; i.v.) to rats causes severe renal proximal tubular necrosis. gamma-Glutamyl transpeptidase (gamma-GT) catalyses the first step in the metabolism of glutathione (GSH) and its S-conjugates and the toxicity of 2-Br-(diGSyl)HQ can be emeliorated by inhibition of renal gamma-GT. Species differences in the specific activity of renal gamma-GT have been reported and we now describe the relationship between renal gamma-GT and species differences in susceptibility to 2-Br-(diGSyl)HQ nephrotoxicity. Although rats exhibited the highest specific activity of renal gamma-GT, and were the most sensitive species toward 2-Br-(diGSyl)HQ-mediated nephrotoxicity, renal gamma-GT activity did not correlate with susceptibility in the other species examined. Indeed, the guinea pig, which expressed the lowest activity of renal gamma-GT between the species (8% of the rat) was the only other rodent found to be responsive toward 2-Br-(diGSyl)HQ at the highest dose tested (200 mumol/kg; intracardiac). Thus, factors other than gamma-GT activity probably play an important role in modulating species susceptibility to 2-Br-(diGSyl)HQ nephrotoxicity. Although the reason(s) for the interspecies variation in response to 2-Br-(diGSyl)HQ are unclear at present, it seems possible that differences in both renal biochemistry, such as differences in the relative activities of cysteine conjugate N-acetyl transferase and deacetylase, and renal physiology, contribute to the observed results.

Differences in the localization and extent of the renal proximal tubular necrosis caused by mercapturic acid and glutathione conjugates of 1,4-naphthoquinone and menadione.

We have previously demonstrated that administration of various benzoquinol-glutathione (GSH) conjugates to rats causes renal proximal tubular necrosis and the initial lesion appears to lie within that portion of the S3 segment within the outer stripe of the outer medulla (OSOM). The toxicity may be a consequence of oxidation of the quinol conjugate to the quinone followed by covalent binding to tissue macromolecules. We have therefore synthesized the GSH and N-acetylcysteine conjugates of 2-methyl-1,4-naphthoquinone (menadione) and 1,4-naphthoquinone. The resulting conjugates have certain similarities to the benzoquinol-GSH conjugates, but the main difference is that reaction with the thiol yields a conjugate which remains in the quinone form. 2-Methyl-3-(N-acetylcystein-S-yl)-1,4-naphthoquinone caused a dose-dependent (50-200 mumol/kg) necrosis of the proximal tubular epithelium. The lesion involved the terminal portion of the S2 segment and the S3 segment within the medullary ray. At the lower doses, that portion of the S3 segment in the outer stripe of the outer medulla displayed no evidence of necrosis. In contrast, 2-methyl-3-(glutathion-S-yl)-1,4-naphthoquinone (200 mumol/kg) caused no apparent histological alterations to the kidney. 2-(Glutathion-S-yl)-1,4-naphthoquinone and 2,3-(diglutathion-S-yl)-1,4-naphthoquinone (200 mumol/kg) were relatively weak proximal tubular toxicants and the lesion involved the S3 segment at the junction of the medullary ray and the OSOM. A possible reason(s) for the striking difference in the toxicity of the N-acetylcysteine conjugate of menadione, as opposed to the lack of toxicity of the GSH conjugate of menadione, is discussed. The basis for the localization of the lesion caused by 2-methyl-3-(N-acetylcystein-S-yl)-1,4-naphthoquinone requires further study.

The development of a master's degree program based on perceived future practice needs.

The need for an accessible master's degree program was determined through informal communication between practicing nurses and nursing educators. The purpose of the descriptive study was to project a master's degree program based on perceived future nursing practice needs. Forty-seven nurse administrators and staff nurses responded to a mailed survey (61.8%). The respondents were asked to make predictions regarding the probability of occurrence of 18 previously Delphi-generated events by the year 2000. Respondents also provided judgments regarding the degree of agreement/disagreement that various content items would be critical to survival in practice and best learned in a master's degree program. Most respondents agreed that general education content items were both critical to survival and best learned by master's education. Less strong agreement that nursing content items were critical to survival and best learned in a master's degree program was an unexpected finding. A multidisciplinary master's program for all health-care professionals was proposed.

Sequential oxidation and glutathione addition to 1,4-benzoquinone: correlation of toxicity with increased glutathione substitution.

The chemical reaction of 1,4-benzoquinone with glutathione results in the formation of adducts that exhibit increasing degrees of glutathione substitution. Purification of these adducts and analysis by 1H and 13C nuclear magnetic resonance spectroscopy revealed the products of the reaction to be 2-(glutathion-S-yl)hydroquinone; 2,3-(diglutathion-S-yl)hydroquinone; 2,5-(diglutathion-S-yl)hydroquinone; 2,6(diglutathion-S-yl)hydroquinone; 2,3,5-(triglutathion-S-yl)hydroquinone; and 2,3,5,6-(tetraglutatathion-S-yl)hydroquinone. The initial conjugation of 1,4-benzoquinone with glutathione did not significantly affect the oxidation potential of the compound. However, subsequent oxidation and glutathione addition resulted in the formation of conjugates that, dependent upon the position of addition, become increasingly more difficult to oxidize. Increased glutathione substitutions, which resulted in an increase in oxidation potentials, paradoxically resulted in enhanced nephrotoxicity. The triglutathion-S-yl conjugate was the most potent nephrotoxicant; the diglutathion-S-yl conjugates exhibited similar degrees of nephrotoxicity; the mono- and tetraglutathion-S-yl conjugates were not toxic. Thus, with the exception of the fully substituted isomer, the severity of renal necrosis correlated with the extent of glutathione substitution. The lack of toxicity of the fully substituted isomer is probably a consequence of its inability to alkylate tissue components. Thus, the conjugation of glutathione with quinones does not necessarily result in detoxification, even when the resulting conjugates are more stable to oxidation. The inhibition of gamma-glutamyl transpeptidase by AT-125 protected against 2,3,5-(triglutathion-S-yl)hydroquinone-mediated nephrotoxicity. It is suggested that other extra-renal sites expressing relatively high levels of gamma-glutamyl transpeptidase might therefore also be susceptible to hydroquinone-linked glutathione conjugate toxicity. This pathway might also contribute to the carcinogenicity and mutagenicity of certain quinones.

Reducing the incidence of falls in high risk patients.

The incidence of patient falls in any acute and chronic care facility is a continuing challenge for nursing administrators. A computerized program was designed to identify common characteristics of 180 patients who had experienced a fall during 1986 at a midwest hospital. Based on analysis of the data, an integrated process of assessment, diagnosis, and intervention was developed and implemented. Early indications of success have been identified.

Metastatic adenocarcinoma of the temporal bone.

Metastatic carcinoma involving the temporal bone is an unusual occurrence. A review of the world literature reveals a total of 102 reported cases. Secondary cancers of the temporal bone arise most frequently from mammary, renal, and bronchogenic carcinomas, all of which show a tendency to metastasize to bone. The pathogenesis of spread to the temporal bone is most commonly by the hematogenous route, but extension from intracranial involvement has also been noted. The symptoms of facial nerve paralysis, otalgia, and aural discharge are consistently associated with patients found to have aural cancers. These symptoms are, however, most frequently indicative of mastoid infection; it is therefore, imperative to consider the possibility of a malignant neoplasm in patients with these symptoms.

Diagnostic sonography in general surgery.

Eighty-seven patients who had sonographic examinations at the Orange County Medical Center were studied retrospectively to evaluate the usefulness and reliability of this noninvasive technique, and sonographic results were compared with findings at operation or findings made using other diagnostic methods. With a variety of lesions, the overall accuracy of diagnosis by sonography was 85%. In the remaining 15% of studies, false-positive or false-negative results were observed. The accuracy varied with the organ involved, the greatest being renal and hepatic masses. Ultrasound, when used in addition to careful surgical assessment of the patient, was found to be most useful in the diagnosis and follow-up of abdominal problems in surgical patients.