The atmosphere during the younger dryas.

One of the most dramatic climate change events observed in marine and ice core records is the Younger Dryas, a return to near-glacial conditions that punctuated the last deglaciation. High-resolution, continuous glaciochemical records, newly retrieved from central Greenland, record the chemical composition of the arctic atmosphere at this time. This record shows that both the onset and the termination of the Younger Dryas occurred within 10 to 20 years and that massive, frequent, and short-term (decadal or less) changes in atmospheric composition occurred throughout this event. Changes in atmospheric composition are attributable to changes in the size of the polar atmospheric cell and resultant changes in source regions and to the growth and decay of continental biogenic source regions.

Record of Volcanism Since 7000 B.C. from the GISP2 Greenland Ice Core and Implications for the Volcano-Climate System.

Sulfate concentrations from continuous biyearly sampling of the GISP2 Greenland ice core provide a record of potential climate-forcing volcanism since 7000 B.C. Although 85 percent of the events recorded over the last 2000 years were matched to documented volcanic eruptions, only about 30 percent of the events from 1 to 7000 B.C. were matched to such events. Several historic eruptions may have been greater sulfur producers than previously thought. There are three times as many events from 5000 to 7000 B.C. as over the last two millennia with sulfate deposition equal to or up to five times that of the largest known historical eruptions. This increased volcanism in the early Holocene may have contributed to climatic cooling.

Changes in Atmospheric Circulation and Ocean Ice Cover over the North Atlantic During the Last 41,000 Years.

High-resolution, continuous multivariate chemical records from a central Greenland ice core provide a sensitive measure of climate change and chemical composition of the atmosphere over the last 41,000 years. These chemical series reveal a record of change in the relative size and intensity of the circulation system that transported air masses to Greenland [defined here as the polar circulation index (PCI)] and in the extent of ocean ice cover. Massive iceberg discharge events previously defined from the marine record are correlated with notable expansions of ocean ice cover and increases in PCI. During stadials without discharge events, ocean ice cover appears to reach some common maximum level. The massive aerosol loadings and dramatic variations in ocean ice cover documented in ice cores should be included in climate modeling.

Induction of mammary gland carcinomas by the subcutaneous injection of 1-methyl-1-nitrosourea.

The efficacy of s.c. administration of 1-methyl-1-nitrosourea (MNU) for the induction of mammary carcinomas was compared with the i.v. method of carcinogen injection in female Sprague-Dawley rats. Group-housed animals fed a laboratory chow diet and distilled water ad libitum throughout the study were injected at 50 days of age with 50 mg MNU per kg body weight. The carcinogen was given either s.c. or i.v., via the jugular vein, to one of the two groups of 20 rats each. Animals were palpated for tumor detection weekly and necropsied 180 days after injection with the carcinogen. At the termination of the study, 180 days postcarcinogen, cancer incidences were similar, 95 versus 90% in animals given MNU either s.c. or i.v. with an average of 3.9 and 3.9 cancers per rat, respectively. Time of tumor appearances were essentially identical under both treatment conditions. Using either method of carcinogen administration resulted in the induction of approximately 2.4 times more carcinomas in the cervical-thoracic mammary glands than in the abdominal-inguinal glands with no differences observed in cancer occurrence in the left versus the right mammary gland chains. The data indicate that s.c. administration of MNU is as effective and specific in the induction of mammary carcinomas as is i.v. administration. The s.c. method has the advantage of being easier and faster to perform and permits reproducible treatment of large numbers of rats by a small technical staff.

Effect of combined selenium and retinyl acetate treatment on mammary carcinogenesis.

The influence of feeding a pharmacological level of either selenium (SE), retinyl acetate (RA), or selenium and retinyl acetate (SE + RA) on N-methyl-N-nitrosourea-induced mammary carcinogenesis was studied in female Sprague Dawley rats. Rats received 50 mg N-methyl-N-nitrosourea per kg body weight at 50 days of age. Seven days after carcinogen treatment, groups of 25 rats each were placed on laboratory chow diet supplemented with either a placebo or 300 mg RA, 4 mg SE, or 300 mg RA plus 4 mg SE per kg diet. Animals were palpated for detection of mammary tumors twice each week, and the study was terminated 130 days after N-methyl-N-nitrosourea was given. In comparison to the placebo group, treatment with RA or RA + SE reduced tumor incidence, lessened the average number of tumors per rat, and prolonged tumor latency. RA + SE had the greatest inhibitory effect on the carcinogenic process. The effect of combined treatment with RA and SE was additive in nature. The length of the estrous cycle was increased by treatment with RA + SE, and some pathological changes of the ovary and uterus were noted. This investigation provides the first evidence of an additive inhibitory effect resulting from combined treatment with RA and SE.

Effect of an inorganic and organic form of dietary selenium on the promotional stage of mammary carcinogenesis in the rat.

The relative effectiveness of either sodium selenite or selenomethionine in the inhibition of mammary carcinogenesis was studied in virgin female Sprague-Dawley rats. In one experiment, rats were given 50 mg of 1-methyl-1-nitrosourea per kg of body weight s.c. at 50 days of age. Beginning 7 days post-1-methyl-1-nitrosourea, they were assigned to a basal diet containing 0.1 ppm of selenium or basal diet supplemented to contain either 4, 5, or 6 ppm of selenium as sodium selenite or 5 or 6 ppm of selenium as selenomethionine. Selenium treatment was continued until termination of the study 135 days after 1-methyl-1-nitrosourea treatment. Sodium selenite, at the 5-ppm level, was the most effective chemopreventive agent. The highest level of selenomethionine (6 ppm) caused grossly apparent liver damage. No liver damage was noted in sodium selenite-treated rats. In a second experiment, rats were given 5 mg of 7,12-dimethylbenz(a)anthracene at 50 days of age. Beginning 7 days after 7,12-dimethylbenz(a)anthracene treatment, rats were assigned randomly to the control group or to one of two selenium treatment groups receiving either 3.4 ppm of selenium as sodium selenite or 3.4 ppm as selenomethionine in their drinking water. Selenium supplementation was continued throughout the study until its termination at 111 days postcarcinogen . Sodium selenite significantly reduced cancer incidence and the average number of cancers per rat. Treatment with selenomethionine was less effective and caused severe liver damage. Although both sodium selenite and selenomethionine can inhibit some aspect of the postinitiation stage(s) of mammary carcinogenesis, selenium provided as sodium selenite was the more effective and less toxic of the two chemicals. Increasing the dose of sodium selenite above 5 ppm did not enhance the inhibitory activity of selenium.

Effect of retinyl acetate on the occurrence of ovarian hormone-responsive and -nonresponsive mammary cancers in the rat.

The inhibitory activity of retinyl acetate against the induction of ovarian hormone-responsive and -nonresponsive mammary gland adenocarcinomas was studied in intact and castrated female Sprague-Dawley rats. Three experiments were conducted. Mammary cancer was induced by a single p.o. administration of 7,12-dimethylbenz(a)anthracene (DMBA) at 50 days of age. Animals in Experiments 1 and 2 each received 20 mg DMBA, whereas those in Experiment 3 received 15 mg. In all experiments, animals were fed a chow diet supplemented per kg with either a placebo or 328 mg retinyl acetate starting 7 days after carcinogen treatment. In Experiment 1, rats were castrated at either 7, 60, or 90 days postcarcinogen and were killed 120 days after DMBA was given. In Experiment 2, rats were castrated 30 days after DMBA and were killed 240 days after carcinogen treatment. In Experiment 3, rats were castrated when a detected tumor attained a measurable diameter, and the hormone responsiveness of their tumors was subsequently determined. The experiment was terminated 279 days after DMBA treatment. In both intact and castrated rats, mammary tumor occurrence was inhibited by treatment with retinyl acetate. However, there were no differences in the latency to appearance time of hormone-responsive and -nonresponsive cancers in intact animals receiving either placebo or retinyl acetate. The data indicate that retinyl acetate inhibits DMBA-induced mammary tumorigenesis in either the presence or the absence of the ovaries. It appears that retinyl acetate is effective in inhibiting both ovarian hormone-responsive and -nonresponsive mammary tumors.

Effect of short-term feeding of sodium selenite on 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in the rat.

The inhibitory activity of short-term feeding of one of four concentrations of dietary selenium against the induction of mammary gland carcinomas by 7,12-dimethylbenz(a)anthracene (DMBA) was studied in female Sprague-Dawley rats. When 28 days old, the animals were placed on a Torula yeast diet formulation which contained, by analysis, either 0.05, 0.15, 1.05, or 2.06 microgram of selenium, as sodium selenite, per g of diet. Mammary cancer was induced by a single p.o. administration of either 7.5 or 15.0 mg DMBA at 50 days of age. The animals were maintained on the above diets until 14 days after carcinogen treatment at which time all animals were transferred to a chow diet containing 0.21 microgram of selenium per g of diet. The study was terminated 120 days after DMBA administration. The concentrations of selenium in the liver and mammary tissue measured at the time of DMBA treatment increased with increasing levels of dietary selenium (p less than 0.05). At the low dose of DMBA, there was a trend towards reduction in the number of cancers with increased amounts of selenium, but the only significant difference occurred between groups fed the next to lowest and the highest level of selenium. At the high dose of DMBA, the number of observed cancers showed a strong dose effect (p less than 0.05). In addition, tumor load was significantly reduced in selenium-supplemented rats (p less than 0.05), and there was a significant delay (p less than 0.05) in the time to appearance of the cancers of animals receiving the highest level of selenium when compared with those receiving the lowest level. The dietary concentrations of selenium shown to inhibit the early stage(s) of cancer induction in this system were both significantly lower and fed for a shorter time interval than that which was previously reported.

Effect of concentration of D,L-2-difluoromethylornithine on murine mammary carcinogenesis.

The appearance of chemically induced mammary gland carcinomas in virgin female Sprague-Dawley rats was blocked by the administration of D,L-2-difluoromethylornithine (DFMO) in drinking water during the stage of tumor promotion. Rats were given injections s.c. at 50 days of age with either 35 mg of 1-methyl-1-nitrosourea (MNU) per kg of body weight or the 0.9% NaCl solution in which the carcinogen was dissolved. At 57 days of age, the rats were each randomly allocated to one of 14 treatment groups. Ten groups (five solvent treated and five MNU treated) were assigned to treatments consisting of 0.00, 0.0625, 0.125, 0.25, or 0.50% (w/v) solution of DFMO in their drinking water; two MNU-treated groups were placed on or removed from DFMO treatment (0.5%; w/v) at 90 days post-carcinogen exposure; and two carcinogen-treated groups received either putrescine (0.5-g/kg diet) or putrescine and DFMO (0.5%; w/v) throughout the experiment. The study was terminated 183 days after carcinogen treatment. All doses of DFMO exerted a protective effect against the induction of mammary cancer; however, only the feeding of the 0.125% and the 0.5% solutions of DFMO resulted in a significant reduction in cancer incidence. The average number of cancers per rat was reduced, and cancer-free time was extended at all concentrations of DFMO. The protective effect of DFMO was sustained following withdrawal of treatment at 90 days post-MNU injection. Feeding putrescine in conjunction with DFMO treatment partially blocked the inhibitory activity of DFMO. DFMO treatment did not affect food or water intake; body weight gain; the weight of ovaries, uterus, adrenal glands, liver, kidney, or spleen; or the periodicity of the estrous cycle. These data provide evidence of an inhibitory effect of DFMO against mammary cancer induced by MNU which cannot be attributed to a systemic toxic effect of this compound.

Effect of exercise on the induction of mammary carcinogenesis.

Although data reported in several epidemiological investigations indicate that reduced consumption of dietary fat and increased levels of physical activity are associated with reduced risk for breast cancer, the results of some studies do not support these observations. Underlying this situation is the unanswered question about whether degree of body fatness, which is affected by dietary composition, total caloric intake, and energy expenditure, is the critical determinant affecting breast cancer risk. The objective of this work was to establish whether increasing energy expenditure by exercise would reduce the occurrence of mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene (DMBA) in animals consuming a high fat diet to the level of occurrence observed in sedentary animals consuming a low fat diet. Female Sprague-Dawley rats were obtained at 21 days of age and maintained on a 5% (w/w) corn oil diet (AIN-76A) until they were 64 days of age. At 50 days of age, rats received either 5 mg DMBA or the solvent in which the carcinogen was dissolved. Fourteen days after DMBA intubation they were randomized into one of three groups: 5% fat (w/w), sedentary; 24.6% fat (w/w), sedentary; or 24.6% fat (w/w), exercised. Animals were exercised on a motor-driven treadmill at a belt speed of 20 m/min and a 1-degree incline for 15 min/day, 5 days/week for 18 weeks. Feeding a high fat versus a low fat diet increased the number of breast cancers induced and the rate at which they appeared in agreement with previous investigations. However, rather than retarding the development of tumors as was hypothesized, moderate treadmill exercise increased the incidence and number of cancers induced and shortened cancer latency in comparison to animals that received either the high fat or low fat diet and were sedentary. Body composition was not altered by the exercise regime imposed, although these animals weighed more than either sedentary group. These data document a heretofore unreported effect of a moderate level of aerobic work on breast cancer induction.

Preemptive pain control in patients having laparoscopic hernia repair: a comparison of ketorolac and ibuprofen.

OBJECTIVES: To determine if nonsteroidal anti-inflammatory drugs provide adequate pain control for patients having laparoscopic hernia repair and to compare the effectiveness of ketorolac tromethamine with ibuprofen in reducing postoperative laparoscopic hernia pain. DESIGN AND SETTING: Prospective double-blind randomized study at a 100-bed community hospital. PATIENTS: Seventy patients ranging in age from 16 to 83 years scheduled for elective laparoscopic inguinal hernia repair. INTERVENTIONS: Patients undergoing laparoscopic hernia repair were enrolled in a double-blind randomized study to compare the 2 treatments. Group 1 received a placebo capsule 1 hour before surgery and ketorolac tromethamine, 60 mg intravenously, at the time of trocar insertion. Group 2 received ibuprofen, 800 mg an hour before surgery, and isotonic sodium chloride solution, 2 mL intravenously, at the time of trocar insertion. In addition, all patients received local infiltration of 30 mL of bupivacaine hydrochloride into their trocar sites. All patients were discharged within 5 hours of the operation and were instructed to take 400 mg of ibuprofen orally every 4 hours for 24 hours whether or not they were experiencing pain. A 24-hour supply of ibuprofen was provided to all study patients. Pain was assessed using the Visual Analog Pain Scale with a maximum pain rating of 100. Assessments were done at the time of and 18 hours after discharge. MAIN OUTCOME MEASURE: Postoperative pain 18 and 24 hours after discharge was assessed using a standardized questionnaire in a telephone interview by a registered nurse from the Outpatient Surgical Unit. RESULTS: There was no significant difference in the level of pain experienced by 35 patients who received ketorolac intravenously and 35 who received ibuprofen orally. There was no significant difference between the 2 treatment groups in the amount of pain experienced at discharge and 18 hours after discharge. CONCLUSIONS: Pain relief from ibuprofen, 800 mg, administered orally an hour before laparoscopic hernia repair was not statistically different from that obtained with intravenous ketorolac, 60 mg, administered intraoperatively when comparing the hospital discharge pain score and the mean and highest pain scores 18 hours after discharge. Ibuprofen offers equivalent pain control at a lower cost and reduced potential for adverse drug events compared with intravenous ketorolac in patients having laparoscopic hernia repair. No patient required narcotic supplementation, and pain control was judged satisfactory by all the patients.

Dietary vanadyl(IV) sulfate inhibits chemically-induced mammary carcinogenesis.

The induction of murine mammary carcinogenesis by 1-methyl-1-nitrosourea was blocked by the feeding of a purified diet formulation supplemented with 25 p.p.m. vanadium as vanadyl(IV) sulfate during the post initiation stages of the neoplastic process. Treatment with vanadyl(IV) sulfate reduced both cancer incidence and the average number of cancers per rat and prolonged the median cancer-free time without inhibiting the overall growth of the animals. Vanadyl(IV) sulfate appears to be an effective non-toxic agent for the chemoprevention of experimental breast cancer in the rat.

Increased lipolysis to beta-adrenergic stimulation after dehydroepiandrosterone treatment in rats.

Young adult male rats were treated with 4 mg dehydroepiandrosterone (DHEA)/100-g diet for 4 wk or were fed the same purified diet unadulterated (51 carbohydrate:20 fat: 23.5 protein; wt/wt). After 1 wk body weight and fat mass of the DHEA-fed rats were significantly less than the controls. By the end of week 3, fat-free mass of the DHEA rats was less than the controls. Neither food intake nor resting metabolism, measured by indirect calorimetry, was different between groups. Isolated epididymal adipocytes of DHEA rats were significantly smaller and isoproterenol (x 10(7) M) stimulation of glycerol release was 53% greater (P < 0.01) than the controls. Basal rate of glycerol release increased significantly for both groups in response to the adenosine inhibitor adenosine deaminase; there were no significant interaction effects. Inhibition of lipolysis by the adenosine analogue phenylisopropyladenosine was similar between groups. Findings support the hypothesis that DHEA reduces adiposity directly by increased lipolysis, but the mechanism of action does not involve a change in the antilipolytic function of adenosine.

Effect of tamoxifen and D,L-2-difluoromethylornithine on the growth, ornithine decarboxylase activity and polyamine content of mammary carcinomas induced by 1-methyl-1-nitrosourea.

The effect of combined treatment with D,L-2-difluoromethylornithine (DFMO) and tamoxifen on the growth status, ornithine decarboxylase (ODC) activity and polyamine content of established 1-methyl-1-nitrosourea (MNU)-induced mammary tumors was investigated. DFMO treatment, a 0.125% solution provided as drinking water, inhibited the rate of tumor occurrence and reduced the number of mammary tumors induced by a high dose of MNU (50 mg/kg body weight) during the first 120 days post-carcinogen treatment. Tamoxifen was administered daily via s.c. injection (25 micrograms/100 g body weight) to tumor-bearing rats in both treatment groups, i.e. control and DFMO-treated, for a 30-day period beginning 120 days after carcinogen. Tamoxifen treatment induced tumor regression but the percentage of regressing, static or growing tumors was no different in the presence or absence of DFMO. Whereas the mammary tumors of DFMO-treated rats had reduced ODC activity and lower polyamine concentrations in comparison to the tumors of untreated animals, tamoxifen had no effect on these parameters independent of its effect on tumor growth status. DFMO did not increase the efficacy of tamoxifen in inducing tumor regression.

Effect of energy intake on the promotion of mammary carcinogenesis by dietary fat.

The effect of low-fat and high-fat diets on the induction of mammary carcinomas by 1-methyl-1-nitrosourea (MNU) was studied in female Sprague-Dawley rats. All rats were given MNU (25 mg/kg body wt) at 50 days of age. For the first 17 weeks after carcinogen administration, they were fed a purified diet containing either 5 or 20% fat incorporated into agar gel. Food intake was restricted, so that the amounts fed provided the same amount of net utilizable energy each day for both groups, regardless of the fat content of the diets. From 17 to 32 weeks, the diets were fed ad libitum. During the restricted feeding period, there was no significant difference in tumor incidence or in the number of tumors detected between the groups. During the weeks in which animals were fed ad libitum, significantly more tumors appeared in the high-fat group than in the low-fat group. The data provide support for the hypothesis that consumption of a high-fat diet can lead to an enhancement of mammary carcinogenesis. It appears, however, that diets must be consumed ad libitum for the stimulatory effect on tumor occurrence to be exhibited.

Size-selective predation on groundwater bacteria by nanoflagellates in an organic-contaminated aquifer.

Time series incubations were conducted to provide estimates for the size selectivities and rates of protistan grazing that may be occurring in a sandy, contaminated aquifer. The experiments involved four size classes of fluorescently labeled groundwater bacteria (FLB) and 2- to 3-microns-long nanoflagellates, primarily Spumella guttula (Ehrenberg) Kent, that were isolated from contaminated aquifer sediments (Cape Cod, Mass.). The greatest uptake and clearance rates (0.77 bacteria.flagellate-1.h-1 and 1.4 nl.flagellate-1.h-1, respectively) were observed for 0.8- to 1.5-microns-long FLB (0.21-microns3 average cell volume), which represent the fastest growing bacteria within the pore fluids of the contaminated aquifer sediments. The 19:1 to 67:1 volume ratios of nanoflagellate predators to preferred bacterial prey were in the lower end of the range commonly reported for other aquatic habitats. The grazing data suggest that the aquifer nanoflagellates can consume as much as 12 to 74% of the unattached bacterial community in 1 day and are likely to have a substantive effect upon bacterial degradation of organic groundwater contaminants.

Isolation of rat mammary epithelial cells for polyamine analysis.

Mammary epithelial cells were isolated from either abdominal-inguinal glands or mammary tumours of rats, after enzymic digestion of the tissues, and were analysed for polyamine content. Optimum conditions were developed for the isolation of cells in sufficient yield for the analysis of polyamines from 1 g of mammary gland or 0.5 g of tumour tissue. Complete recoveries of the polyamines in the tissues were achieved in the isolated epithelial cells.