Site specific bone adaptation response to mechanical loading.

Over 25 million Americans suffer from osteoporosis. Bone size and strength depends both upon the level of adaptation due to physical activity (applied load), and genetics. We hypothesized that bone adaptation to loads differs among mice breeds and bone sites. Forty-five adult female mice from three inbred strains (C57BL/6 [B6], C3H/HeJ [C3], and DBA/2J [D2]) were loaded at the right tibia and ulna in vivo with non-invasive loading devices. Each loading session consisted of 99 cycles at a force range that induced approximately 2000 microstrain (microepsilon) at the mid-shaft of the tibia (2.5 to 3.5 N force) and ulna (1.5 to 2 N force). The right and left ulnae and tibiae were collected and processed using protocols for histological undecalcified cortical bone slides. Standard histomorphometry techniques were used to quantify new bone formation. The histomorphometric variables include percentage mineralizing surface (%MS), mineral apposition rate (MAR), and bone formation rate (BFR). Net loading response [right-left limb] was compared between different breeds at tibial and ulnar sites using two-way ANOVA with repeated measures (p<0.05). Significant site differences in bone adaptation response were present within each breed (p<0.005). In all the three breeds, the tibiae showed greater percentage MS, MAR and BFR than the ulna at similar in vivo load or mechanical stimulus (strain). These data suggest that the bone formation due to loading is greater in the tibiae than the ulnae. Although, no significant breed-related differences were found in response to loading, the data show greater trends in tibial bone response in B6 mice as compared to D2 and C3 mice. Our data indicate that there are site-specific skeletal differences in bone adaptation response to similar mechanical stimulus.

A comparison of microLC/electrospray ionization-MS and GC/MS for the measurement of stable isotope enrichment from a [2H2]-glucose metabolic probe in T-cell genomic DNA.

Measurement of the proliferation of lymphocytes and other high-turnover cell populations in vivo can be accomplished through the incorporation of an isotopically labeled DNA precursor into actively dividing cells and the subsequent determination of the isotope enrichment in the isolated genomic DNA from selected cell populations. Two published gas chromatography/mass spectrometry (GC/MS) methods were successfully modified by our laboratory whereby a postinjection methylation reaction, rather than silylation or acetylation, was used to form a volatile derivative of deoxyadenosine (dA). We also developed a second robust microcapillary liquid chromatography-electrospray ionization (microLC-ESI)/MS method that is faster and more sensitive than the GC/MS method and does not require sample derivatization. Following administration of [6,6-(2)H(2)]-glucose to human immunodeficiency virus-infected patients, peripheral blood was drawn; cells were obtained by lymphapheresis and fractionated. DNA was isolated from the desired cell subtypes and enzymatically hydrolyzed to the free deoxyribonucleosides. The digest was analyzed using both capillary GC/MS and microLC/ESI-MS to measure the levels of the dA and [(2)H(2)]-dA or their reaction products. Sample enrichments were calculated by comparison to standard curves prepared from dA and [(2)H(2)]-dA. The microLC/ESI-MS method required fewer cells, less sample preparation, shorter analysis times, and a single calibration curve. Overall, the microLC/ESI-MS method is superior to the GC/MS method in terms of precision and accuracy, while providing a 4-fold increase in sensitivity (from 20 pmol at 0.2% [(2)H(2)]-dA enrichment to 5 pmol at 0.1% [(2)H(2)]-dA enrichment).

Vault prolapse and rectocele: assessment of repair using sacrocolpopexy with mesh interposition.

OBJECTIVE: To assess the sacrocolpopexy with mesh interposition in women with pelvic organ prolapse. DESIGN: A prospective study. SETTING: Tertiary referral urogynaecology and pelvic floor reconstruction unit. POPULATION: Twenty-nine consecutive women with symptomatic vault prolapse and rectocele. MAIN OUTCOME MEASURES: Subjective and objective success rates and complications. RESULTS: The mean age was 57 years. The mean number of past prolapse operations was 2.6 which included two past sacrospinous ligament fixations and 17 past posterior repairs. The mean follow up was 14 months. There was an increase in constipation from 41% to 50%, a decrease in faecal soiling from 21% to 10%, and an increase in incomplete defecation from 24% to 36% . Dyspareunia decreased from 38% to 17%, and there was some improvement in the stress and urge incontinence. There was a significant reduction of vault prolapse and rectocele (P < 0.001). All women with Stage II and Stage III vault prolapse were corrected, with an increase in Stage I prolapse from 20% to 27%. All women with Stage II and Stage III rectocele were corrected with a decrease in Stage I prolapse from 36% to 7% . The only significant interoperative complication was a cystotomy. One mesh became infected post-operatively which required removal. CONCLUSIONS: Sacrocolpopexy and mesh interposition is a safe and reliable operation for the correction of vault prolapse and rectocele. A long term follow up is necessary to detect any late complications.

Metabolic conversion of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) in the male F344/NCr Rat.

1,1-Dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) and 1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene (DDE) levels were measured by capillary gas chromatography with electron capture detection in liver and blood serum of male F344/NCr rats exposed for 2 weeks to DDD at dietary concentrations ranging from 8.51 ppm to 2,000 ppm. DDD burdens in serum ranged from <0.006 microM (limit of detection) in control rats to 1.1 microM in the rats fed DDD at 2,000 ppm. The corresponding liver burdens in these animals ranged from <0.006 micromol/kg liver (controls) to 11 micromol/kg liver in rats fed DDD at 2,000 ppm. Levels of DDE in serum or liver were undetectable (<0. 006 microM in serum; <0.006 micromol/kg liver) in rats fed control diet or diet containing 8.51 or 25.5 ppm DDD. The liver and serum burdens of DDE increased with dietary DDD concentration, reaching a maximum of 0.53 microM in serum and 4.7 micromol/kg liver in rats fed 2,000 ppm DDD. As a percentage of total DDD equivalents detected in liver or serum, the DDE burdens increased to a maximum of 36% and 31% in the serum and liver, respectively, of rats fed 689 ppm DDD. The possibility that the DDE might have been generated artifactually in the diet prior to administration to the rats was ruled out by analysis with capillary gas chromatography of the diet containing 2, 000 ppm DDD. The identification of DDE as a metabolite in liver extracts of rats fed 2,000 ppm DDD was confirmed with GC-MS. The results confirmed the presence of DDE as a metabolite of DDD.

Comparative pharmacodynamics of CYP2B induction by DDT, DDE, and DDD in male rat liver and cultured rat hepatocytes.

In this study the pharmacodynamics were characterized of rat hepatic cytochrome P-450 2B (CYP2B) induction by the pesticide DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] and its metabolites DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], which is bioretained, and DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], which is metabolized further and therefore less prone to bioaccumulate. DDT, DDE, and DDD were each found to be pure phenobarbital-type cytochrome P-450 inducers in the male F344/NCr rat, causing induction of hepatic CYP2B and CYP3A, but not CYP1A. The ED50 values for CYP2B induction (benzyloxyresorufin O-dealkylation) by DDT, DDE, and DDD were, respectively, 103, 88, and > or = 620 ppm in diet (14 d of exposure). The efficacies (Emax values) for induction of benzyloxyresorufin O-dealkylation by DDT, DDE, and DDD were 24-, 22-, and > or = 1-fold, respectively, compared to control values. The potencies of the three congeners for CYP2B induction appeared also to be similar, with EC50 values (based on total serum DDT equivalents) of 1.5, 1.8, and > or = 0.51 microM, respectively. The EC50 values based on DDT equivalents in hepatic tissue were 15, 16, and > or = 5.9 micromol/kg liver tissue, respectively. In primary cultures of adult rat hepatocytes, DDT, DDE, and DDD each displayed ability to induce total cellular RNA coding for CYP2B (ED50 values of 0.98, 0.83, and > or = 2.7 microM, respectively). These results suggest that DDT, DDE, and DDD each possess a high degree of intrinsic CYP2B-inducing ability for rat liver, despite marked differences in bioretention among the congeners.

Cross validation of the 1-mile walking test for men with mental retardation.

The purpose of this study was to cross validate the equation developed by Rintala et al. (1992) to estimate the cardiorespiratory efficiency of men with mental retardation (MR). Subjects were 19 healthy men (27 +/- 8 yr) with MR (IQ = 58 +/- 12). Following familiarization, a graded maximal treadmill test and two 1-mile walk tests (Rockport Fitness Walking Test, RFWT) were administered. The peak VO2 value was the criterion measure used to cross validate the equation. The equation was: Peak VO2 (ml.kg-1.min-1) = 101.92 - 2.356 (MILE)-0.420 (WEIGHT). The mean differences were 2.04 (MILE1)(P = 0.02) and 2.43 (MILE2)(P = 0.004) ml.kg-1.min-1. A significant positive correlation was found between measured peak VO2 and predicted peak VO2 on both 1-mile walks (r = 0.91 and 0.93). For both predicted peak VO2 values, the Total Error (TE) was greater than standard error of estimate (SEE), indicating a systematic difference between the measured and predicted peak VO2 values. Moreover, only 58% of the measured peak VO2 values fell within the prespecified range. Test-retest reliability of RFWT was R = 0.96. However, the prediction equation underestimated the actual cardiorespiratory levels in 74% and 79% of the subjects, depending on the trial. Because the equation developed in this research underestimates the measured VO2 values for the majority of these subjects, the test is probably not statistically valid, even if reliable, and the prediction formula needs to be revised for this population.

Baccalaureate student gerontological nursing experiences: raising consciousness levels and affecting attitudes.

The purpose of this study was to evaluate perceived learning and attitude changes of nursing students (n = 144) toward care of the elderly population as a result of a senior capstone course in gerontological nursing. Theory content emphasized maximizing individual capabilities of the elderly and quality of life. Clinical placements occurred in a variety of community and institutional settings, with a wide spectrum of elderly. Student attitudes were assessed using researcher-designed tools for quantitative and qualitative outcome measurements. Significant improvements in student attitudes were found (p < 001). Community-based settings provided significantly more positive experiences (p < .05) compared with institutional care. Qualitative findings revealed students gained positive awareness plus growth in professional abilities. We conclude that a senior capstone course with multi-site, independent, innovative projects can produce positive attitudes and heightened consciousness regarding gerontological nursing. Other nurse educators can benefit from these findings.

Elevated liver function tests in a case of moderate ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome is a recognized complication of ovulation induction. Abnormalities in liver function have been considered to be a rare manifestation of the severe form of ovarian hyperstimulation syndrome (OHSS). A 28 year old woman with primary infertility underwent ovulation induction and intrauterine insemination. She was diagnosed with moderate OHSS and was followed as an outpatient. Early in her course of treatment she complained of upper right quadrant pain. Her work-up included an upper right quadrant ultrasound which showed only moderate ascites. Liver function tests at that time were elevated in a hepatocellular damage pattern. Liver function test elevations, as well as the ovarian hyperstimulation, resolved spontaneously in 10 days. Transient abnormalities in liver function do not appear to be limited to the most sever forms of OHSS.

Nitrite, N-nitroso compounds, and other analytes in physiological fluids in relation to precancerous gastric lesions.

Levels of gastric juice nitrite, several urinary N-nitroso compounds, and other analytes were examined among nearly 600 residents in an area of Shandong, China, where precancerous gastric lesions are common and rates of stomach cancer are among the world's highest. Gastric juice nitrite levels were considerably higher among those with gastric juice pH values above 2.4 versus below 2.4. Nitrite was detected more often and at higher levels among persons with later stage gastric lesions, especially when gastric pH was high. Of those with intestinal metaplasia, 17.5% had detectable levels of gastric nitrite, while this analyte was detected in only 7.2% of those with less advanced lesions. Relative to those with undetectable nitrite, the odds of intestinal metaplasia increased from 1.5 (95% confidence interval = 0.6-4.1) to 4.1 (95% confidence interval = 1.8-9.3) among those with low and high nitrite concentrations, respectively. Urinary acetaldehyde and formaldehyde levels also tended to be higher among those with more advanced pathology, particularly dysplasia. However, urinary excretion levels of total N-nitroso compounds and several nitrosamino acids differed little among those with chronic atrophic gastritis and intestinal metaplasia and dysplasia, consistent with findings from recent studies in the United Kingdom, France, and Colombia. The data from this high-risk population suggest that elevated levels of gastric nitrite, especially in a high pH environment, are associated with advanced precancerous gastric lesions, although specific N-nitroso compounds were not implicated.

Relative potencies of induction of hepatic drug-metabolizing enzyme genes by individual PCB congeners.

The induction of a variety of drug-metabolizing enzymes by polychlorinated biphenyl (PCB) congeners that elicit a 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD)-type hepatic pleiotropic response, including 2,3,3',4,4'-pentachlorobiphenyl (BZ 105), 2,3',4,4',5-pentachlorobiphenyl (BZ 118), 2,3,3',4,4',5-hexachlorobiphenyl (BZ 156), and 3,3',4,4',5,5'-hexachlorobiphenyl (BZ 169) was examined. Following dietary exposure to the individual congeners for 5 days, livers were removed and catalytic assays for cytochrome P450 (CYP) isozymes 1A1 and 1A2 were performed. Additionally, total cellular RNA coding for hepatic drug-metabolizing genes (CYP 1A1, CYP 1A2, microsomal epoxide hydrolase, glutathione S-transferase [GST] Ya/Yc, and the TCDD-inducible isozyme of aldehyde dehydrogenase [ALDH] was quantified. 3-Methylcholanthrene (MC), TCDD, or BZ 156 (32 ppm) caused nearly maximal induction of the CYP 1A proteins but lower induction of the other genes. When the dose-response curves for induction of various drug-metabolizing genes (CYP 1A1 and 1A2, microsomal epoxide hydrolase, the GST Ya/Yc subfamily and ALDH) were examined, a spectrum of ED50s (half-maximal inductions) was observed. While CYP 1A2 exhibited an ED50 of 1.7 ppm, the induction of ALDH was shifted far to the right (ED50 > 11 ppm). Thus, different genes in a single tissue may display different dose-response characteristics. The potency (extent of induction of CYP 1A1 activity resulting from a given dietary dose) was BZ 169 >> BZ 156 > BZ 118 > BZ 105. In contrast, the potencies of the four congeners for CYP 1A1 induction were nearly equivalent when related to hepatic PCB burden, apparently due to the preferential accumulation in the liver of BZs 169 and 156 following low-level administration in the diet.

Metacognitive strategies in a college world literature course.

Students at most reading levels in the World Literature Survey at Gallaudet University benefitted from the inclusion of metacognitive exercises in the course. These exercises emphasized pre-reading, reading, and post-reading strategies designed to improve reading comprehension and retention, but they also proved valuable as prompts to group discussion and to teacher-student communication. Results of this class approach suggest the usefulness of such exercises in "content" courses in general to improve attendance, discussion, and grades.

Accumulation and persistence of individual polychlorinated biphenyl congeners in liver, blood, and adipose tissue of rats following dietary exposure to Aroclor 1254.

Female F344/NCr rats were exposed continuously to Aroclor 1254 (1, 3.3, 10, 33, or 100 ppm in the diet) for 7, 28, or 84 days in order to assess the accumulation of polychlorinated biphenyls (PCBs) in liver, blood, and adipose tissue. The persistence of the individual PCB congeners which are detected in liver was examined in the three tissues of additional groups of rats exposed for 7 days followed by 21 days on control diet, or for 28 days followed by 56 days on control diet. Limited accumulation of PCB congeners with low chlorine substitution (tri- and tetrachlorobiphenyls) in the liver and blood, and preferential retention of highly substituted PCB congeners (penta- and hexachlorobiphenyls) were observed in rats continuously exposed to Aroclor. In these rats, time- and dose-dependent increases in the relative levels of two congeners which cause profound phenobarbital-type induction [2,2',3,4,4',5'-hexachlorobiphenyl (BZ# 138) and 2,2',4,4',5,5'-hexachlorobiphenyl (BZ# 153)] were detected in the liver and adipose tissue. Rats receiving control diet following Aroclor treatment displayed a time- and dose-dependent decrease in the relative levels in blood, adipose and hepatic tissue of 2,3,3',4,4'-pentachlorobiphenyl (BZ# 105) and 2,3',4,4',5-pentachlorobiphenyl (BZ# 118), two of the major congeners showing both TCDD- and phenobarbital-type induction. These rats also displayed increases in the relative adipose levels of another relatively potent mixed-type inducer, 2,3,3',4,4',5-hexachlorobiphenyl (BZ# 156), and increases in adipose and hepatic levels of the pure phenobarbital-type inducer, 2,2',4,4',5-pentachlorobiphenyl (BZ# 99).

Promotion by polychlorinated biphenyls of lung and liver tumors in mice.

Polychlorinated biphenyls (PCB), which are tumor promoters, have been found in human tissues for decades. Their contribution to cancer risk may only now start to appear, due to long human cancer latency and the nature of tumor promotion. Epidemiological associations have been seen between PCB exposure or tissue content and cancer at several sites. In rodents, tumor promotion by PCBs has been little studied in tissues other than liver. Previously, in an experiment modeling infant carcinogen exposure following PCBs received in milk, lung and liver tumors, initiated neonatally in mice by the environmental nitrosamine N-nitrosodimethylamine (NDMA), were promoted by later treatment with Aroclor 1254. The present study was undertaken to confirm and characterize the effects of Aroclor 1254 on tumor number, latency, size and malignancy. Male Swiss mice were given NDMA on postnatal day 4 and Aroclor 1254 (250 mg/kg) on day 8, and killed at intervals. Eight PCB congeners were quantified in the carcasses. Incidences of mice with NDMA-initiated lung tumors at 28 weeks of age were increased 2.5-fold by PCBs. Multiplicities of lung tumors were enhanced four-fold by PCBs at 28 and 52 weeks. By 72 weeks tumor numbers were similar in the NDMA-only and NDMA-PCB groups. Liver tumors first occurred in significant numbers at 52 weeks and only in mice receiving both NDMA and PCBs. As for the lung, at 72 weeks the incidence was high in both the NDMA-only and NDMA-PCB groups. Sizes of tumors and liver carcinoma incidence were not altered by PCB treatment. Carcass analysis revealed a significant positive association between lung tumor numbers at 28 weeks and relative percentage of 2,2',4,4',5-pentachlorobiphenyl, with no other correlations. The results confirm that PCBs promote lung as well as liver tumors, by triggering the early appearance of latent initiated tumors otherwise presenting in old age.

Subchronic dietary exposure to Aroclor 1254 in rats: accumulation of PCBs in liver, blood, and adipose tissue and its relationship to induction of various hepatic drug-metabolizing enzymes.

Female F344/NCr rats were exposed continuously (7-84 days) or discontinuously (7 days exposure/21 days control diet or 28 days exposure/56 days control diet) to various dietary concentrations (1-100 ppm) of Aroclor 1254. There were dose- and time-dependent increases in PCB levels in liver, blood, and adipose tissue. Following removal of the rats from diet containing Aroclor 1254, there was a relatively rapid decrease in PCB levels, particularly in rats exposed to higher concentrations of Aroclor 1254. In parallel with the alterations in PCB levels observed, the rats showed striking dose- and time-dependent increases in hepatic levels of CYP1A1 and CYP1A2, as determined by various methods [RNA analysis, immunochemical detection, or measurement of the O-dealkylation of methoxyresorufin (CYP1A2) or ethoxyresorufin (CYP1A1)]. In rats removed from the Aroclor 1254 diet, catalytic activity for CYP1A1 as well as RNA levels for both CYP1A1 and CYP1A2 rapidly diminished. In contrast to the high levels of induction of CYP1A1 and CYP1A2 observed, limited induction (< 5-fold) of epoxide hydrolase, quinone oxidoreductase, and aldehyde dehydrogenase was detected, even in rats exposed to the highest concentration of Aroclor (100 ppm) for up to 84 days. Furthermore, induction of these non-CYP hepatic drug-metabolizing genes exhibited distinctly different concentration-response curves. The ratios of hepatic CYP1A1 activity to hepatic PCB burden were similar for rats exposed continuously to Aroclor in the diet for 7, 28, or 84 days, and for rats exposed discontinuously (7 days Aroclor/21 days control diet or 28 days Aroclor/56 days control diet). Thus, hepatic PCB levels alone appeared to be reasonably predictive of CYP1A1 levels under a variety of modes of exposure. When the ratio of CYP1A1 activity to adipose or blood PCB concentration was determined, similar ratios were observed for rats exposed continuously for 7, 28, or 84 days. However, lower ratios were observed for rats discontinuously exposed to Aroclor in the diet. These results have important implications with respect to: (a) employing PCB levels in various tissues to predict biological effects, and (b) determining different concentration-response curves for the various biological effects induced by PCBs.

Induction of cytochrome P-450 in Sigmodon hispidus (cotton rats) exposed to dietary Aroclor 1254.

The induction of immunoreactive cytochrome P-450 protein and associated catalytic activities in 10-wk-old male and female Sigmodon hispidus (cotton rats) exposed for 2 wk to low dietary levels of Aroclor 1254 (0.33, 1.0, 3.3, 10, and 33 ppm), or the prototype P-450 inducers phenobarbital, DDT, clotrimazole, and beta-naphthoflavone was examined. Ethoxy-(ETR), methoxy- (MTR), pentoxy- (PTR), and benzyloxyresorufin (BZR) O-dealkylation activities were significantly increased at 0.33 ppm Aroclor for males and 1.0 ppm for females, when compared to control levels. O-Dealkylation activities peaked at 3.3 ppm for males and 10 ppm for females. ETR and MTR O-dealkylation activities were increased four- to eightfold while PTR and BZR O-dealkylation activities increased only two- to threefold. Liver/body weight ratios also increased, with the maximum ratios observed at the highest Aroclor dose, and were associated with histopathologic hepatocyte lesions. While increases in liver/body weight ratio, immunoreactive CYP2B protein, and BZR O-dealkylation were detected following phenobarbital treatment, no increase in PTR O-dealkylation activity was observed. These results demonstrate that S. hispidus (both males and females) are extremely sensitive to low dietary levels of Aroclor 1254, responding with increases in liver/body weight ratio, immunoreactive P-450 protein, and O-dealkylation activities. The cotton rat would appear to be a sensitive feral target species for detecting exposure to certain environmental contaminants.

Enhanced response to ozone exposure during the follicular phase of the menstrual cycle.

Exposure to ozone (O3), a toxic component of photochemical smog, results in significant airway inflammation, respiratory discomfort, and pulmonary function impairment. These effects can be reduced via pretreatment with anti-inflammatory agents. Progesterone, a gonadal steroid, is known to reduce general inflammation in the uterine endometrium. However, it is not known whether fluctuations in blood levels of progesterone, which are experienced during the normal female menstrual cycle, could alter O3 inflammatory-induced pulmonary responses. In this study, we tested the hypothesis that young, adult females are more responsive to O3 inhalation with respect to pulmonary function impairment during their follicular (F) menstrual phase when progesterone levels are lowest than during their mid-luteal (ML) phase when progesterone levels are highest. Nine subjects with normal ovarian function were exposed in random order for 1 hr each to filtered air and to 0.30 ppm O3 in their F and ML menstrual phases. Ozone responsiveness was measured by percent change in pulmonary function from pre- to postexposure. Significant gas concentration effects (filtered air versus O3) were observed for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), and forced expiratory flow between 25 and 75% of FVC (FEF25-75; p < .05). More importantly, the pulmonary function flow rates, FEV1 and FEF25-75, showed a significant menstrual phase and gas concentration interaction effect, with larger decrements observed in the F menstrual phase when progesterone concentrations were significantly lower. We conclude that young, adult females appear to be more responsive to acute O3 exposure during the F phase than during the ML phase of their menstrual cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Achieving smoke-free hospitals. Tips for administrators.

Almost thirty years have passed since the surgeon general of the United States released the first report on the effects of smoking (U.S. Department of Health, Education, and Welfare 1964). Over the ensuing years, further reports have expanded our knowledge of the widespread physiological effects of tobacco smoke and those at greatest risk (U.S. Department of Health, Education, and Welfare 1979; U.S. DHHS 1987, 1991, 1992; American Medical Association 1989). Subsequently, there has been a dramatic decrease in the number of smokers; more than thirty-six million Americans have quit smoking since the surgeon general's report (U.S. DHHS 1987, 7). Supporting this trend are the surgeon general's national health objectives for the year 2000 to achieve smoke-free work environments (Koop 1985). All of these trends contribute to current efforts to make hospitals smoke-free environments.

Selective retention of polychlorinated biphenyl congeners in lung and liver after single-dose exposure of infant mice to Aroclor 1254.

Infant male Swiss mice (8 days old) were given a single i.p. injection of 500 mg/kg of the polychlorinated biphenyl (PCB) mixture, Aroclor 1254, a treatment found in previous studies to result in promotion of nitrosamine-initiated lung and liver tumors. The amounts of the nine congeners that account for > 90% of the PCBs still present 1 day after treatment were quantified in liver, lung, and remainder of carcass 1, 7, 56, 84, and 112 days after treatment. Rates of decrease (half-times, dt1/2s) for total PCB concentration and for individual congeners were compared within and between compartments and with body weight doubling time. In carcass (adipose compartment) there was net loss beyond that expected from dilution due to growth, with the predicted lower dt1/2s for the more metabolizable congeners. By contrast, in lung, after a rapid loss during the 1st week, all congeners except for #153 (2,2'4,4'5,5'-hexachlorobiphenyl [HCB]) were retained and decreased in amount only as a function of dilution due to growth. One result was that congeners #105 (2,3,3',4,4'-pentachlorobiphenyl [PeCB]) and #138 (2,2',3,4,4',5'-HCB) constituted a higher proportion in lung than in carcass. A complex pattern was observed in liver: relative to carcass, there was retention of all congeners during the prepubertal growth phase, again with specific enrichment of #105, followed by more rapid depletion of certain congeners later. PCB-binding proteins and changes in lipid composition may contribute to these phenomena, which are of human relevance in that these congeners are commonly found in human serum and adipose samples.

Cardiovascular response during hemodialysis and hemofiltration: thermal, membrane, and catecholamine influences.

Nine patients on regular dialysis were studied, in a cross-over format comparing hemodialysis (HD) and hemofiltration (HF), to identify potential mechanisms of the disparate hemodynamic responses. Dialysis and substitution fluid composition (high sodium, acetate), treatment time, fluid loss rate, and membrane type (AN 69) were matched. Cardiac output was determined by changes in thoracic electrical bioimpedance. Cardiac output remained stable during HF but increased during HD (p < 0.001, HD vs. HF), despite a parallel reduction in stroke volume. The heart rate response was significantly greater during HD relative to HF (p < 0.01). Systemic vascular resistance remained stable during HF but decreased significantly during HD (p < 0.05). Although there was a modest fall during HD, the difference in blood pressure at the end of treatment between HD and HF was not significant. Comparable increases in body temperature were observed during both treatments. Plasma catecholamines increased in parallel during HD and HF and following orthostatic stimulation at the end of treatment, and extracorporeal catecholamine clearances were similar. The values for serum sodium, total CO2, anion gap, potassium, and hematocrit at the end of treatment were similar, whereas total serum calcium was significantly greater following HD. There were no significant differences in indices of myocardial contractility or central blood volume. These results suggest that the disparate hemodynamic responses to fluid and solute removal during HD and HF can be dissociated from changes in osmolality or venous tone, membrane bioincompatibility, thermal stress, or differences in acetate delivery or catecholamine release. The explanation for the disparate hemodynamic responses between these two treatment modalities remains unclear. A role for an as yet unidentified vasodilatory substance generated during dialysate exposure, or convectively removed during hemofiltration, remain intriguing possibilities.

Induction of hepatic CYP1A in male F344/NCr rats by dietary exposure to Aroclor 1254: examination of immunochemical, RNA, catalytic, and pharmacokinetic endpoints.

Male F344/NCr rats were exposed to low dietary concentrations of Aroclor 1254 (0-33 ppm) for 7 days, following which the induction of selected hepatic drug metabolizing enzymes was monitored. CYP1A1, measured indirectly by assaying the O-dealkylation of ethoxyresorufin in 9000 g supernatants, was increased 1.5-, 3-, 8-, and 37-fold following 7 days of exposure to 1.0, 3.3, 10, and 33 ppm Aroclor, respectively. In contrast, the O-dealkylation of benzyloxyresorufin, an indirect measure of CYP2B1 activity, was increased approximately 4-fold following exposure to 33 ppm dietary Aroclor. Measurement of the non-P450-mediated activities epoxide hydrolase, DT-diaphorase, and aldehyde dehydrogenase (NADP+, benzaldehyde) revealed < 4-fold inductions following feeding of 33 ppm Aroclor. In view of the relatively high sensitivity of the CYP1A-specific catalytic endpoint as a biomarker for Aroclor exposure, alternative endpoints for detecting induction of this subfamily of P450 were also examined. The extent of in vivo CYP1A induction was assessed by measuring serum concentrations of zoxazolamine 150 min following an intraperitoneal dose of 100 mg/kg body wt. Slight decreases in serum zoxazolamine concentration were observed in rats exposed to as little as 1.0 ppm dietary Aroclor 1254, while profound decreases were seen in rats exposed to > or = to 10 ppm Aroclor. Immunodetection of CYP1A1 protein, with a monoclonal antibody directed against this cytochrome, revealed a 2.9-fold increase in rats exposed to as little as 1.0 ppm Aroclor, and approximately 10- and 44-fold increases following exposure to 3.3 and 10 ppm dietary Aroclor, respectively. Increases in total hepatocellular RNA coding for CYP1A1 and CYP1A2, quantified by hybridization to specific oligonucleotide probes, corresponded well to the increases in hepatic O-dealkylase activity for ethoxyresorufin (CYP1A1) and methoxyresorufin (CYP1A2), respectively. Thus, CYP1A induction, directly or indirectly measured with a variety of endpoints, represents a highly sensitive biomarker for exposure to relatively low doses of Aroclor 1254 in the rat.