A hydrochemically guided landscape classification system for modelling spatial variation in multiple water quality indices: Process-attribute mapping.

Spatial variation in landscape attributes can account for much of the variability in water quality relative to land use on its own. Such variation results from the coupling between the dominant processes governing water quality, namely hydrological, redox, and weathering and gradients in key landscape attributes, such as topography, geology, and soil drainage. Despite the importance of 'process-attribute' gradients (PAG), few water quality models explicitly account for their influence. Here a processes-based water quality modelling framework is presented that more completely accounts for the role of landscape variability over water quality - Process-Attribute Mapping (PoAM). Critically, hydrochemical measures form the basis for the identification and mapping of effective landscape attributes, producing PAG maps that attempt to replicate the natural landscape gradients governing each dominant process. Application to the province of Southland (31,824 km2), New Zealand, utilised 12 existing geospatial datasets and a total of 28,626 surface water, groundwater, spring, soil water, and precipitation analyses to guide the identification and mapping of 11 individual PAG. The ability of PAGs to replicate regional hydrological, redox, and weathering gradients was assessed on the accuracy with which the hydrochemical indicators of each dominant process (e.g. hydrological tracers, redox indicators) were estimated across 93 long-term surface water monitoring sites (cross-validated R2 values of 0.75-0.95). Given hydrochemical evidence that PAGs replicate actual landscape gradients governing the dominant processes, they were combined with a land use intensity layer and used to estimate steady-state surface water quality. Cross-validated R2 values ranged between 0.81 and 0.92 for median total nitrogen, total oxidised nitrogen, total phosphorus and dissolved reactive phosphorus. Models of particulate species E. coli and total suspended sediment, although reasonable (R2 0.72-0.73), were less accurate, suggesting finer-grained land use, landscape attribute, and/or flow normalised measures are required to improve estimation.

Assessing aluminium toxicity in streams affected by acid mine drainage.

Acid mine drainage (AMD) has degraded water quality and ecology in streams on the Stockton Plateau, the site of New Zealand's largest open-cast coal mining operation. This has previously been attributed largely to the effects of acidity and elevated aluminium (Al) concentrations. However, the toxicity of dissolved Al is dependent on speciation, which is influenced by pH which affects Al hydrolysis, as well as the concentrations of organic carbon and sulphate which complex Al. Methods for the assessment of the toxic fraction of Al, by chemical analysis and geochemical modelling, have been investigated in selected streams on the Stockton Plateau, where dissolved Al concentrations ranged from 0.034 to 27 mg L(-1). Modelling using PHREEQC indicated that between 0.2 and 85% of the dissolved Al was present as the free ion Al(3+), the most toxic Al species, which dominated in waters of pH = 3.8-4.8. Al-sulphate complexation reduced the Al(3+) concentration at lower pH, while Al-organic and -hydroxide complexes dominated at higher pH. Macroinvertebrate richness in the streams identified an Al(3+) 'threshold' of approximately 0.42 mg/L, above which taxa declined rapidly. Colorimetric 'Aluminon' analysis on unpreserved, unfiltered waters provided a better estimation of Al(3+) concentrations than inductively couple plasma-mass spectrometry (ICP-MS) on filtered, acidified waters. The Aluminon method does not react with particulate Al or strong Al complexes, often registering as little as 53% of the dissolved Al concentration determined by ICP-MS.

Metal removal via particulate material in a lowland river system.

Twelve month surveys of acid-soluble and dissolved trace metal concentrations in the lower Waikato River (in 1998/9 and 2005/6) showed abnormally low particulate Fe, Mn, Cu, Pb and Zn concentrations and mass flux in autumn, when the suspended particulate material (SPM) had a relatively high diatom and organic carbon content, and low Fe and Al content. Dissolved Mn, Cu and Zn concentrations also decreased in autumn, while dissolved Fe and Pb concentrations were unaffected. While SPM settlement under the low river flow conditions present in autumn can explain the removal of particulate metals, it does not explain dissolved metal removal. SPM-metal interaction was therefore investigated using seasonal monitoring data, experimental adsorption studies, sequential extraction and geochemical modelling. Pb binding to SPM occurred predominantly via Fe-oxide surfaces, and could be reliably predicted using surface complexation adsorption modelling. Dissolved Mn concentrations were controlled by the solubility of Mn oxide, but enhanced removal during autumn could be attributed to uptake by diatoms. Zn and Cu were also adsorbed on Fe-oxide in the SPM, but removal from the water column in autumn appeared augmented by Zn adsorption onto Mn-oxide, and Cu adsorption onto the organic extracellular surfaces of the diatoms.

Prevalence and patterns of self-initiated nutritional supplementation in men at high risk of prostate cancer.

OBJECTIVE: To define the prevalence and patterns of self-initiated herbal and vitamin supplementation among men at high risk of developing prostate cancer, as there is increasing public awareness of prostate cancer screening, risk-factor assessment and prevention, leading to increasing interest in the use and systematic study of nutritional therapies for prostate cancer prevention. SUBJECTS AND METHODS: Since 1996 our institution has prospectively maintained a prostate cancer-risk registry through its Prostate Cancer Risk Assessment Program (PRAP). Eligibility includes African-American men, any man with at least one first-degree relative or two or more second-degree relatives with prostate cancer, or men who tested positively for the BRCA1 gene mutation. A 420-item self-administered questionnaire was completed and included the use of nutritional supplements and complementary therapies. We divided men into groups who used supplements to lessen their cancer risk and those who did not. The prevalence and patterns of use were evaluated and the two groups then compared for differences in demographic, socio-economic and risk-perception variables. RESULTS: In all, 345 high-risk men were enrolled in the PRAP over a 5-year period. Data on the use of dietary or herbal supplements were available on 333 men (97%), of whom over half (170) reported taking one or more supplements to prevent prostate cancer. Supplement use was divided into eight categories, including vitamins, minerals, extracts from fruits/seeds, organic compounds, flowers/bulbs, leaves/bark, roots, or animal products. Most commonly used for self-initiated chemoprevention were vitamins (95%), minerals (28%), and fruit/seed extracts (18%). More than a quarter of men (27%) took three or more agents. Men taking proactive preventative measures were statistically more likely to be Caucasian and aged > 60 years (P < 0.05). African-Americans were less likely to self-initiate preventative steps. Men taking supplements tended to return more often for follow-up and participate in PRAP longer, while those not taking supplements tended to earn less and report less self-perceived risk. CONCLUSIONS: A significant proportion of men at risk of developing prostate cancer initiate measures they perceive to reduce their risk. Although the chemopreventative efficacy of many of these supplements remains unsubstantiated, they are widely perceived by the public to reduce the risk of developing prostate cancer. These data provide an insight into patient perceptions and misconceptions of chemopreventative strategies, and may help to refine recruitment efforts in multi-institutional prostate cancer prevention trials.

Periprosthetic femoral fractures in Northern Ireland.

Twenty-five patients with periprosthetic femoral fractures were admitted to the Ulster Hospital between August 1998 and May 2000. Average age was 77 years (range, 42-96 years) with a female to male ratio of 2:1. Twenty-four of the fractures occurred following primary joint arthroplasty on average 7.6 years from insertion of the primary prosthesis. One patient sustained an intraoperative fracture during revision surgery. In the majority (80%), the periprosthetic femoral fracture was associated with a traumatic event. On average, two days elapsed from the time of injury until admission to our unit. Time from admission to surgery was on average 4 days. All patients were treated by open fracture fixation. Duration of stay in the fracture unit was on average 20 days. Prior to their fracture 92% of patients were living at home and 84% were mobile either unaided or with the use of a stick. At most recent review, 72% are back living at home and 60% are mobile either unaided or with the use of a stick. We emphasise that there is the likelihood of an increase in periprosthetic femoral fractures due to the increasing number of primary arthroplasties being performed on a more active, ageing population. Preventative measures and cost implications are also discussed.

AhR, ARNT, and CYP1A1 mRNA quantitation in cultured human embryonic palates exposed to TCDD and comparison with mouse palate in vivo and in culture.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is developmentally toxic in many species and induces cleft palate in the C57BL/6N mouse embryo. Palatogenesis in mouse and human embryos involves homologous processes at the morphological, cellular, and molecular levels. In organ culture, mouse and human palates respond similarly to TCDD. The present study quantitates the expression of AhR, ARNT, and CYP1A1 mRNA in human embryonic palates in organ culture. Palatal tissues were exposed to 1 x 10(-10), 1 x 10(-9), or 1 x 10(-8) M TCDD or control medium and sampled at 0, 2, 4, and 6 hours for quantitative RT-PCR using a synthetic RNA internal standard. Similar measurements of CYP1A1 gene expression were collected for mouse palates cultured in this model. In human palates, AhR expression correlated with ARNT and CYP1A1 mRNA expression. TCDD induction of CYP1A1 was time- and concentration-dependent. The expression of these genes presented a uniform and continuous distribution across the group of embryos, with no subset of either high or low expressors/responders. The ratio of AhR to ARNT was approximately 4:1. AhR mRNA increased during the culture period in both treated and control subjects; however, ARNT expression was relatively constant. TCDD did not alter either AhR or ARNT expression in a consistent dose- or time-related manner. Comparison of human and mouse data showed a high correlation across species for the induction of CYP1A1. Human embryos expressed approximately 350 times less AhR mRNA than the mouse, and in earlier studies it was shown that human palates required 200 times more TCDD to produce the same effects. When the morphological, cellular, and molecular responses to TCDD between mouse and human are compared, it seems highly unlikely that human embryos could be exposed to sufficient TCDD to achieve changes in palatal differentiation that would lead to cleft palate.

RT-PCR quantification of AHR, ARNT, GR, and CYP1A1 mRNA in craniofacial tissues of embryonic mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and hydrocortisone.

C57BL/6N mouse embryos exposed to hydrocortisone (HC) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) develop cleft palate. An interaction between these agents produces clefts at doses which alone are not teratogenic. The glucocorticoid receptor (GR) and dioxin receptor (AhR) mediated these responses and their gene expression was altered by TCDD and/or HC in palates examined on gestation day (GD) 14 by Northern blot analysis and in situ hybridization. The present study quantifies AhR, AhR nuclear translocator (ARNT), and GR mRNA at 4, 12, 24, and 48 h after exposure (time 0 = dose administration at 8 A.M. on gestation day 12) on GD12 to TCDD (24 micrograms/kg), HC (100 mg/kg) or HC (25 mg/kg) + TCDD (3 micrograms/kg). The induction of CYP1A1 mRNA was also quantified at 2, 4, 6, 12, 24, and 48 h for control and TCDD-exposed samples. Total RNA was prepared from midfacial tissue of 4-6 embryos/litter at each time and dose. An RNA internal standard (IS) for each gene was synthesized, which included the gene's primer sequences separated by a pUC19 plasmid sequence. Reverse transcription-polymerase chain reaction (RT-PCR) was performed on total RNA + IS using a range of 5-7 IS concentrations across a constant level of total RNA. PCR products were separated in gels (mRNA and IS-amplified sequences differed by 30-50 bases), ethidium bromide-stained, imaged (Hamamatsu Photonics Systems, Bridgewater, NJ), and quantified with NIH Image. CYP1A1 mRNA was significantly induced in the TCDD-exposed samples at all time points examined (p = 0.005 at 2 h and 0.001 after 2 h). During palatal shelf outgrowth on GD12, AhR mRNA levels increased significantly and this was not affected by treatment with TCDD or HC + TCDD. A significant increase in GR was detected at 24 h (p < 0.05) and this was unaffected by any of the exposures. Expression of ARNT increased at 12 h (p < 0.001); however, treatment with HC or HC + TCDD blocked this increase (p < 0.05). At 24 h, the TCDD-treated embryos had significantly lower ARNT mRNA compared with controls (p < 0.001). The relative overall expression level of the genes was AhR > ARNT > GR. Within individuals, expression of AhR and/or ARNT was highly correlated with GR level. In conclusion, CYP1A1 mRNA was expressed in developing craniofacial tissue and was highly induced by TCDD exposure. AhR, ARNT, and GR mRNA are upregulated in early palatogenesis, although not on the same schedule. The TCDD-induced decrease in ARNT at 24 h after dosing and the HC and HC + TCDD-induced delay in upregulation of ARNT may affect the dynamics of heterodimer formation between AhR and ARNT. The changes in ARNT mRNA level could also affect availability of this transcriptional regulator to interact with other potential partners, and these effects, separately or in combination, may be involved in disruption of normal embryonic development.

Application of cloth-based enzyme immunoassay for the characterization of monoclonal antibodies to Salmonella lipopolysaccharide antigens.

The specificity, detection limit, and stability of twelve anti-Salmonella monoclonal antibodies (Mabs) were evaluated by cloth-based enzyme immunoassay (CEIA) and polymyxin-cloth based enzyme immunoassay (p-CEIA). Using the p-CEIA, five Mabs were found to react with cholate extracted lipopolysaccharide (LPS) antigens of all 44 Salmonella strains representing 19 different serogroups examined, with the exception of the one strain of serogroup-O tested. These five Mabs did not react with cholate extracts of any of 16 Gram-positive or Gram-negative non-Salmonella bacteria tested. The detection limit of purified S. typhimurium LPS antigen in the p-CEIA was approximately 40 ng for four of the Mabs and approximately 20 ng for the other Mab. Four of the five Mabs were stable during storage at 22 degrees C-23 degrees C for 24 h. These four Mabs are potentially useful for the immunodetection of Salmonella in foods and other samples.

Audit of surgical delay in relationship to outcome after proximal femoral fracture.

To ascertain the influence of surgical delay on outcome after proximal femoral fracture in elderly females, a cohort study of patients presenting in 1987 was compared to 1989/90. Organisational changes in the intervening period were introduced to reduce delay to surgical intervention. Two hundred and eighty females aged 65 years and over presenting from the local catchment area of an acute inner-city teaching hospital were enrolled in the study. Seventy-nine patients received surgery in 1987 and 186 in 1989/90. The one year mortality was 34% and 26% respectively. The proportion receiving surgery within 24 hours rose from 34% in 1987 to 57% in 1989/90. The relative hazard of the group receiving surgery on day 2 in comparison to day 1 was 1.7 (95% CI 1.0 to 2.9) when adjusted for co-variance of age and mental score. Medically fit elderly patients presenting with proximal femoral fracture have improved survival with early surgery within 24 hours of admission. Improvements in the organisation of hospital care will result in important benefits for the increasing number of elderly females presenting with proximal femoral fracture.

Bisubstrate inhibitors of farnesyltransferase: a novel class of specific inhibitors of ras transformed cells.

We describe the biological properties of a new class of potent farnesyltransferase (FT) inhibitors designed as bisubstrate analog inhibitors. These inhibitors incorporate the structural motifs of both farnesyl pyrophosphate and the CAAX tetrapeptide, the two substrates of the reaction catalyzed by FT. Both the phosphinate inhibitor, BMS-185878, and the phosphonate inhibitor, BMS-184467, exhibited higher in vitro FT selectivity than some of the previously reported CVFM peptidomimentics and benzodiazepine analogs. Xenopus oocyte maturation induced by microinjected oncogenic Ras proteins was blocked by coinjected BMS-184467 and BMS-185878. However, both inhibitors showed poor cell activity presumably because of the doubly charged nature of the compounds. Thus, masking the charge on the carboxylate ion markedly improved the cell permeability of BMS-185878, leading to BMS-186511, the methyl carboxyl ester prodrug. BMS-186511 inhibited FT activity in whole cells as determined by inhibition of p21 Ras protein processing, inhibition of farnesylation of proteins including Ras and the accumulation of unfarnesylated Ras proteins in the cytosolic fraction. While the cellular effects of these bisubstrate analog inhibitors had no significant effect on growth of untransformed NIH3T3 cells, they produced pronounced inhibition of Ras transformed cell growth. Both the anchorage dependent and independent growth of ras transformed cells were severely curtailed by micromolar concentrations of BMS-186511. We also found that both H-ras and K-ras transformed cells are affected by this bisubstrate inhibitor. However, K-ras transformed cells appear to be less sensitive. The inhibition of FT activity in cells and the ensuing inhibition of ras transformed cell growth is further manifested in distinct morphological changes in cells. Cells flattened, became less refractile and grew in contact inhibited monolayer. Moreover, the highly diffused character of the actin cytoskeleton in the ras transformed cells was dramatically reverted to an organized network of stress cables crisscrossing the entire cells upon treatment with BMS-186511. All of these effects of BMS-186511 are limited to ras transformed cells that utilize farnesylated Ras, but are not seen in transformed cells that use geranylgeranyl Ras or myristoyl Ras. Significantly, these FT inhibitors did not produce any signs of gross cytotoxicity in untransformed, ras transformed cells or other oncogene transformed cells.

Hypersensitivity to diphtheria toxin by mouse cells expressing both diphtheria toxin receptor and CD9 antigen.

DTS-II is a highly diphtheria toxin (DT)-sensitive cell line previously isolated by transfection of wild-type DT-resistant mouse L-M(TK-) cells with the cDNA encoding a monkey Vero cell DT receptor. DTS-II cells are as toxin-sensitive as Vero cells, have approximately 3-fold more receptors than Vero cells, and have approximately 10-fold lower affinity for DT than Vero cells. We now cotransfected DTS-II cells with a plasmid containing the Vero cell cDNA coding for CD9 antigen (pCD9) and with a plasmid containing the gene for hygromycin resistance (pHyg). The stably transfected hygromycin-resistant colonies were screened for DT hypersensitivity employing a replica plate system. A DT-hypersensitive colony was isolated and purified. The purified DT-hypersensitive cells, DTS-III, (i) are approximately 10-fold more toxin-sensitive than DTS-II and Vero cells and (ii) bear approximately 10(6) DT receptors per cell (i.e., approximately 20-fold and approximately 60-fold more receptors than DTS-II and Vero cells, respectively), but their receptor affinity is still approximately 10-fold lower than that of Vero cells. Cross-linking experiments employing 125I-labeled DT demonstrated that DTS-II and DTS-III cells have essentially the same profile of DT-binding cell-surface protein(s), suggesting that CD9 antigen, although expressed on the cell surface of DTS-III cells, may not be in close proximity to the DT-binding domain of the receptor. CD9 may affect DT receptor expression by increasing receptor density at the cell surface. By employing DTS-III cells it should be possible to purify and characterize the DT cell-surface receptor protein(s).

A computerised system of screening for deep venous thrombosis.

We have developed a computer controlled system of strain gauge plethysmography for use as a screening tool for proximal segment venous thrombi which is simple to use, well tolerated by patients and extremely accurate. The computerised test was evaluated in 171 limbs of 163 symptomatic patients by comparison with subsequent ascending venography. Each of twenty occlusive proximal segment thrombi were identified, one non occlusive thrombus screened normal giving an overall sensitivity of 95.2%. The specificity of the test was 80% with a negative predictive value of 99.0%. The computerised system allows accurate screening for proximal segment venous thrombosis, and may permit more selective use of venography in the symptomatic post-operative limb.

Child sexual abuse in Shelby County, Tennessee: a new epidemic?

Following the introduction of a comprehensive child sexual abuse program in 1985, there was a significant increase in the number of validated incidents of abuse involving minors. However, following the initial increase, the number of validated incidents of abuse remained relatively stable at about 30-35 per month. While the overall validation rate was 57%, it fluctuated widely from as low as 21% to as high 92%. The validation rate rose from 1984 through 1987, declining in the latter part of 1989. The validation rate appeared to reflect the number of validated cases and not be dependent upon the number of reported cases. The number of cases validated was not significantly correlated with time, but was moderately correlated with the number of cases reported (estimated Spearman correlation coefficient was .45 with p less than .05). However, after adjusting for time, the partial correlation between the number of validated and the number of reported cases was no longer significant. The percent of validated cases (the validation rate) was correlated with number of cases validated (estimated Spearmen correlation coefficient was .84 with p less than .0001), but not with the number of cases reported. Validation rates were higher for girls than for boys, 71.1% and 31.8% respectively. The majority of the perpetrators (78%) were known to the children and had access to the victims. In over half the incidents, family members were implicated as the perpetrators.

Impedance plethysmography. A noninvasive screening method to detect deep-vein thrombosis.

Impedance plethysmography (IPG) is a useful noninvasive detection of proximal segment thrombosis. Seven hundred patients treated with total hip arthroplasty were examined preoperatively and several times postoperatively using this technique. Twenty-one abnormal IPG results were obtained, and venography confirmed that 12 of these patients had proximal segment thrombi and five had evidence of calf thrombi. Four venograms were completely clear, demonstrating a false-positive rate of 1.3% (including calf thrombi). Six patients with normal IPG results had calf thrombi. All positive venograms indicating a thrombus in the proximal venous segment were indicated with a positive IPG result, giving a sensitivity of 100%. The standardization of the procedure involving constant leg elevation has assisted in the accuracy of this screening system.

Epinephrine-induced premature ventricular contractions and changes in arterial blood pressure and heart rate during I-653, isoflurane, and halothane anesthesia in swine.

I653 is a new inhalation anesthetic having especially desirable recovery characteristics because of its very low blood and tissue solubility. Investigations of its cardiovascular and electroencephalographic effects have revealed actions similar to those of isoflurane. However, these studies did not evaluate the potential of I653 to predispose the heart to epinephrine-induced arrhythmias. In this investigation, we studied eight domestic swine to compare the effects of I653 with those of other anesthetics on the cardiac arrhythmogenic actions of intravenously infused epinephrine. I653, isoflurane, and halothane each were given, on separate days, at 0.7-0.8 and at 1.1-1.2 MAC. The rate of infusion of epinephrine needed to produce premature ventricular contractions (PVCs) when the animals were anesthetized with I653 (6.9 +/- 0.7 and 6.6 +/- 0.9 micrograms.kg-1.min-1 at 0.8 and 1.2 MAC) did not differ from that during isoflurane anesthesia (5.7 +/- 1.1 and 6.0 +/- 1.0 micrograms.kg-1.min-1 at 0.7 and 1.1 MAC), but was greater than that required during halothane anesthesia (1.3 +/- 0.2 and 1.1 +/- 0.3 micrograms.kg-1.min-1 at 0.7 and 1.1 MAC). Similar mean arterial blood pressures and heart rates resulted from like infusions of epinephrine during I653 and isoflurane anesthesia. PVCs occurred at lesser infusion rates of epinephrine and at lower mean arterial blood pressures and heart rates with halothane than with I653 or isoflurane. Anesthetic concentration, over the range studied, did not alter the infusion rate of epinephrine required to produce arrhythmias with any anesthetic. The authors conclude that I-653 and isoflurane have similar properties with respect to epinephrine-induced arrhythmias and increases in heart rate and arterial blood pressure.

I653 and isoflurane produce similar dose-related changes in the electroencephalogram of pigs.

I653 is a new volatile anesthetic structurally similar to enflurane and isoflurane. Since enflurane can induce convulsions, whereas isoflurane progressively depresses cortical electrical activity, the authors believed it important to assess the effect of I653 on the EEG (in both the "time" and "frequency" domain). The EEG was assessed visually and quantitatively, and a new EEG parameter was introduced. The burst-suppression ratio (percentage of time the EEG was isoelectric) quantified the extent of burst suppression phenomena. Eight swine were anesthetized with I653 or isoflurane in oxygen and in random sequence, exposed to approximately 0.8, 1.2, or 1.6 MAC with normocapnea and to 1.2 MAC with hypocapnea (PETCO2 of 25 mmHg). Four animals were also anesthetized with 3.2% (1.2 MAC) enflurane in oxygen. Both I653 and isoflurane produced a dose-related depression of cortical electrical activity. At 0.8 and 1.2 MAC of either agent, occasional sharp waves occurred singly, were apparently not related to external (auditory) stimuli, and probably represented normal variation in the EEG. No electrographic or gross motor seizures occurred with either I653 or isoflurane. In contrast, all pigs given enflurane developed seizures during hypocapnea. At equipotent concentrations, I653 and isoflurane had the same effect on EEG parameters. Increasing doses of either I653 or isoflurane caused decreasing amplitude and frequency and increasing suppression. Hypocapnea during either agent slightly increased high-frequency activity, and slightly decreased burst suppression.

Cardiovascular effects of I653 in swine.

I653 (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether) is a new inhalation anesthetic with a low blood-gas partition coefficient and no demonstrable toxicity. The authors examined its cardiovascular effects at 0.8, 1.2, and 1.6 MAC in eight chronically instrumented domestic swine mechanically ventilated to maintain normocarbia. These data were compared with those obtained while the animals were conscious and while anesthetized with isoflurane at approximately equal MAC multiples. I653 caused dose-related decreases in mean arterial blood pressure (95 +/- 2 mmHg, mean +/- SE, conscious; 65 +/- 3 mmHg, 0.8 MAC; 55 +/- 3 mmHg, 1.2 MAC; and 48 +/- 2 mmHg, 1.6 MAC). At 0.8 MAC, systemic vascular resistance decreased 35% from the conscious condition value. Despite the decreases in blood pressure and systemic vascular resistance, and dose-dependent increases in right- and left-heart filling pressures, stroke volume fell in a dose-related fashion (2.11 +/- 0.10, 1.57 +/- 0.08, 1.37 +/- 0.06, and 1.10 +/- 0.06 ml/kg; conscious, 0.8, 1.2, and 1.6 MAC). At 0.8 MAC, cardiac output was unchanged (220 +/- 12 ml.min-1.kg-1) from the conscious condition (210 +/- 8 ml.min-1.kg-1), as heart rate increased (142 +/- 7 beats/min, at 0.8 MAC vs. 100 +/- 3 beats/min, conscious) and systemic vascular resistance decreased. At concentrations greater than 0.8 MAC, heart rate decreased towards but did not reach the conscious value (127 +/- 4 at 1.2 MAC, 120 +/- 4 at 1.6 MAC). Systemic vascular resistance increased slightly at 1.6 MAC compared to the values at 0.8 and 1.2 MAC, but was always less than in the conscious condition.(ABSTRACT TRUNCATED AT 250 WORDS)