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Bromodichloromethane (BDCM) is a common municipal drinking water disinfection by-product, resulting in widespread trace human exposure via ingestion and inhalation. The present studies were designed to define organ-specific, BDCM-induced toxicity in wild type (p53(+/+)) and heterozygous (p53(+/-)) mice on both the FVB/N and C57BL/6 genetic backgrounds. Mice were exposed to BDCM vapor daily for 6 h/day and 7 days/week at concentrations of 0, 1, 10, 30, 100, or 150 ppm for 1 week and at 0, 0.3, 1, 3, 10, or 30 ppm for 3 weeks. In the 1-week exposure study, dose-dependent mortality and morbidity were observed at concentrations of 30 ppm and above and were as high as 100% at 150 ppm. In the 3-week exposure study, mortality and morbidity were found only in the 30-ppm exposure groups and were 0, 17, 67, and 33% for the wild-type C57BL/6, p53(+/-) C57BL/6, wild-type FVB/N, and p53(+/-) FVB/N mice, respectively. BDCM was a particularly potent kidney cytotoxicant. Dose-dependent tubular degeneration, necrosis, and associated regenerative cell proliferation greater than 10-fold over controls were seen at concentrations as low as 10 ppm in the kidneys of all strains at 1 week. Similar dose-dependent increases in hepatic necrosis, degeneration, and regenerative cell proliferation were observed but were induced only at concentrations of 30 ppm and higher. Pathological changes were more severe in the FVB/N compared to the C57BL/6 mice and were more severe in the heterozygotes compared to the wild-type mice. However, recovery and return of the percentage of kidney cells in S-phase to control levels was seen at 3 weeks. The estimated maximum tolerated dose for longer-term exposures was 15 ppm, based on mortality, induced kidney pathology, and regenerative cell proliferation. A one-year cancer bioassay was initiated with doses of 0, 0.5, 3, 10, and 15 ppm, based on this information. No pathological changes in the livers were found at the 13-week time point of that study. At 13 weeks, the kidney lesions and regenerative cell proliferation seen at the 1-week time point at doses of 10 ppm and above had resolved, and the cell proliferation rates had returned to baseline. Differences in toxicity indicate that caution be used in substituting wild-type mice for transgenic mice for range-finding studies to select doses for p53(+/-) cancer studies. Resolution of the kidney lesions indicates that periods of very high regenerative cell proliferation, potentially important in the carcinogenic process, may not be observed if measurements are taken only at 3 weeks of exposure or later.

Purpose: To determine if the lyse and wait (L&W) technique with a 4-mg dose of alteplase (tissue plasminogen activator; tPA) is a safe and effective method of declotting dialysis grafts as compared to use of the Arrow-Trerotola Percutaneous Thrombectomy Device (PTD) or the L&W technique with use of urokinase (UK)., Materials and Methods: Forty patients were randomized prospectively to undergo L&W declotting with use of 4 mg of tPA or mechanical thrombolysis with the PTD. The time interval to restored graft flow, total procedure time, hemostasis time, and anatomic success, clinical success, complications, and patency rates were analyzed. These were compared with historic results in 20 patients treated with the L&W technique with use of 250,000 U UK., Results: The immediate anatomic success rate was 95% in the tPA L&W and PTD groups. The mean in-room lysis time with restored flow was 10 minutes for L&W with tPA and 19 minutes for PTD (P = .002). The mean in-room procedure time was 39 minutes for L&W and 45 minutes for PTD (P = NS). Mean hemostasis time with use of manual compression was 44 minutes for L&W with tPA and 23 minutes for PTD (P = .057). The historic group of 20 patients who underwent L&W with UK had a 95% anatomic success rate, a mean of 14 minutes of lysis time, a mean of 34 minutes of procedure time, and a mean of 26 minutes of time to hemostasis. No bleeding complications occurred in the PTD group. Seven episodes of bleeding occurred in six patients given tPA; four were delayed 60-90 minutes after the procedure, one necessitated hospitalization, and two required additional therapies. Four of the 20 patients undergoing L&W with UK had minor puncture site bleeding during the procedure. The 3-month primary patency rates were 65%, 65%, and 60% for L&W with tPA, PTD, and L&W with UK, respectively (P = NS)., Conclusion: The 4-mg dose of tPA is effective but results in more bleeding complications and longer hemostasis times than mechanical thrombolysis with use of the PTD. Unlike in our experience with UK, bleeding complications with tPA were both major and delayed.

Concerns exist as to whether individuals with relative manganese deficiency or excess may be at increased risk for manganese toxicity following inhalation exposure. The objective of this study was to determine whether manganese body burden influences the pharmacokinetics of inhaled manganese sulfate (MnSO(4)). Postnatal day (PND) 10 rats were placed on either a low (2 ppm), sufficient (10 ppm), or high (100 ppm) manganese diet. The feeding of the 2 ppm manganese diet was associated with a number of effects, including reduced body weight gain, decreased liver manganese concentrations, and reduced whole-body manganese clearance rates. Beginning on PND 77 +/- 2, male littermates were exposed 6 h/day for 14 consecutive days to 0, 0.092, or 0.92 mg MnSO(4)/m(3). End-of-exposure tissue manganese concentrations and whole-body (54)Mn elimination rates were determined. Male rats exposed to 0.092 mg MnSO(4)/m(3) had elevated lung manganese concentrations when compared to air-exposed male rats. Male rats exposed to 0.92 mg MnSO(4)/m(3) developed increased striatal, lung, and bile manganese concentrations when compared to air-exposed male rats. There were no significant interactions between the concentration of inhaled MnSO(4) and dietary manganese level on tissue manganese concentrations. Rats exposed to 0.92 mg MnSO(4)/m(3) also had increased (54)Mn clearance rates and shorter initial phase elimination half-lives when compared with air-exposed control rats. These results suggest that, marginally manganese-deficient animals exposed to high levels of inhaled manganese compensate by increasing biliary manganese excretion. Therefore, they do not appear to be at increased risk for elevated brain manganese concentrations.

Dissolution rate can influence the pulmonary clearance of a metal and thus affect its delivery to the brain and other organs. The goal of this study was to determine the exposure-response relationship for the relatively soluble sulfate (MnSO(4)) and insoluble tetroxide (Mn(3)O(4)) forms of inhaled manganese in adult male CD rats. Rats were exposed 6 h/day for 7 days/week (14 exposures) to either MnSO(4) or Mn(3)O(4) at 0, 0.03, 0.3, or 3 mg Mn/m(3). End-of-exposure olfactory bulb, striatum, cerebellum, bile, lung, liver, femur, serum, and testes (n = 6 rats/concentration/chemical) manganese concentrations and whole-body (54)Mn elimination were then determined. Increased whole-body (54)Mn clearance rates were observed in animals from the high-dose (3 mg Mn/m(3)) MnSO(4) and Mn(3)O(4) exposure groups. Elevated manganese concentrations in the lung were observed following MnSO(4) and Mn(3)O(4) exposure to > or=0.3 mg Mn/m(3). Increased olfactory bulb and femur manganese concentrations were also observed following MnSO(4) exposure at > or=0.3 mg Mn/m(3). Elevated striatal, testes, liver, and bile manganese concentrations were observed following exposure to MnSO(4) at 3 mg Mn/m(3). Elevated olfactory bulb, striatal, femur, and bile manganese concentrations were observed following exposure to Mn(3)O(4) at 3 mg Mn/m(3). Animals exposed to MnSO(4) (3 mg Mn/m(3)) had lower lung and higher olfactory bulb and striatal manganese concentrations compared with levels achieved following similar Mn(3)O(4) exposures. Our results suggest that inhalation exposure to soluble forms of manganese results in higher brain manganese concentrations than those achieved following exposure to an insoluble form of manganese., (Copyright 2001 Academic Press.)

In this study, we examined whether perinatal exposure by inhalation to hydrogen sulfide (H2S) had an adverse impact on pregnancy outcomes, offspring prenatal and postnatal development, or offspring behavior. Virgin male and female Sprague-Dawley rats (12 rats/sex/concentration) were exposed (0, 10, 30, or 80 ppm H2S; 6 h/day, 7 days/week) for 2 weeks prior to breeding. Exposures continued during a 2-week mating period (evidence of copulation = gestation day 0 = GD 0) and then from GD 0 through GD 19. Exposure of dams and their pups (eight rats/litter after culling) resumed between postnatal day (PND) 5 and 18. Adult male rats were exposed for 70 consecutive days. Offspring were evaluated using motor activity (PND 13, 17, 21, and 60+/-2), passive avoidance (PND 22+/-1 and 62+/-3), functional observation battery (PND 60+/-2), acoustic startle response (PND 21 and 62+/-3), and neuropathology (PND 23+/-2 and 61+/-2). There were no deaths and no adverse physical signs observed in F0 male or female rats during the study. A statistically significant decrease in feed consumption was observed in F0 male rats from the 80-ppm H2S exposure group during the first week of exposure. There were no statistically significant effects on the reproductive performance of the F0 rats as assessed by the number of females with live pups, litter size, average length of gestation, and the average number of implants per pregnant female. Exposure to H2S did not affect pup growth, development, or performance on any of the behavioral tests. The results of our study suggest that H2S is neither a reproductive toxicant nor a behavioral developmental neurotoxicant in the rat at occupationally relevant exposure concentrations (< or =10 ppm).

Background: This study quantifies the changes in bone height of the posterior area of the edentulous mandible when the load of complete dentures is borne entirely by anteriorly placed osseointegrated implants., Methods: Thirty-three patients, of whom there were radiographs from the beginning of implant loading and from a follow-up visit at least three years later (a mean of 6.6 years later), were included in the study. Working with panoramic radiographs, the authors took height measurements in the premolar area (15 millimeters distal to the most distal implants). A valid correction factor was available because implants of known length were proximal to the area being evaluated., Results: The authors calculated descriptive statistics using means, standard deviations, medians and proportions as appropriate. A P-value of less than .05 was considered significant. Of the 33 subjects, most showed increases in bone height--29 (87.9 percent) on the right side and 28 (84.9 percent) on the left side. The mean change in all subjects was +1.0 mm (range -0.8 to +3.3 mm). A comparison of mandibular height at implant placement vs. follow-up showed a statistically significant increase bilaterally (P < .001)., Conclusions: This study demonstrates that dentures for edentulous mandibles that are borne totally by implants in the anterior area conserve or enhance the bone of the posterior portion of the mandible. An important future study should test the effect of implant-assisted restorations for the edentulous mandible that load the posterior ridge (a bar clasp, for example)., Clinical Implications: One of the considerations in planning treatment for the edentulous mandible should be the preserving effect of totally implant-borne restorations vs. the continued resorption of the body of the mandible with conventional dentures.

The pathology associated with obstructive sleep apnea is cumulative and progressive. When patients fail to improve with continuous nasal airway pressure or other, less-invasive treatments, surgery should be considered. The initial approach to the surgical patient is identification of all areas of potential obstruction. There are often several sites of obstruction, which can occur anywhere in the upper respiratory tract. One or more procedures may be needed to address these areas. The objective of surgery is to relieve these obstructing sites without interfering with the normal functionality of the upper airway.

1,3-Butadiene and styrene are oxidized, in part, by cytochrome P450 2E1 and have been shown to metabolically interact in rodents exposed by inhalation to mixtures of both compounds. Because the reactive metabolites of butadiene and styrene are thought to be responsible for the toxicity of each compound, metabolic interactions may alter the response in animals exposed to mixtures of butadiene and styrene compared with the response in animals exposed to butadiene alone or styrene alone. The purpose of this study was to quantitate alterations in genotoxicity and cytotoxicity in male B6C3F1 mice exposed to mixtures of butadiene and styrene. Male B6C3F1 mice were exposed to 6.25, 62.5, 200, or 625 ppm butadiene alone, 50 ppm styrene alone, or mixtures of 6.25, 62.5, 200, or 625 ppm butadiene and 50 ppm styrene. Genotoxicity was assessed by quantitating the frequency of micronucleated polychromatic erythrocytes in bone marrow. Cytotoxicity was assessed by counting total spleen and thymus cells and by quantitating the frequency of polychromatic erythrocytes in the peripheral blood. Butadiene and mixtures of butadiene and styrene were genotoxic in mice, as shown by a significant increase in the frequency of micronucleated polychromatic erythrocytes. The increased frequency following exposure to mixtures of butadiene and styrene was not significantly different compared with the frequency following exposure to butadiene alone. Styrene and mixtures of butadiene and styrene were cytotoxic in mice, as shown by significantly decreased number of spleen cells. Exposure to mixtures of butadiene and styrene with butadiene concentrations of 62.5 or 625 ppm significantly reduced the number of thymus cells. Exposure to 200 ppm or 625 ppm butadiene alone, or to mixtures of 200 ppm or 625 ppm butadiene and 50 ppm styrene, significantly reduced the frequency of polychromatic erythrocytes in the peripheral blood. The results of the study demonstrate that exposure to mixture of butadiene and styrene does not reduce the respective genotoxicity of butadiene or cytotoxicity of styrene.

Osseointegrated implants placed prior to maxillary downgrafting were utilized to stabilize the repositioned maxilla and interpositional bone graft. Eleven-month follow-up revealed complete healing of the 1.5-cm osteotomy gap and no maxillary relapse. Implant stabilization may be one solution to the relapse associated with inferior repositioning of the maxilla.

This study evaluates the first 51 consecutive cases treated for limitation of mandibular movement due to closed lock. Eighty joints (22 unilateral, 29 bilateral) were treated with arthroscopic surgery. The mean follow-up was 29.4 weeks, with a range of 6 to 77 weeks. These results showed an immediate improvement after arthroscopy followed by a more gradual improvement during the next 6 months, with a plateau in improvement thereafter. All cases, unilateral and bilateral, generally reached the same level of opening.

Interactions between test chemicals and pollutants can confound toxicology studies. To test the sensitivity of the regenerating olfactory epithelium to additional challenge with the olfactory epithelial toxicant methyl bromide (MeBr), Fischer 344 (F344) rats received 2 6-hr inhalation exposures (separated by a 28-day recovery period) to either 0 or 175 ppm MeBr. The regenerating epithelium was resistant to the second MeBr exposure. In addition, histopathologic examination revealed squamous epithelial hyperplasia in the vestibule; inflammation, epithelial necrosis, mucosal erosions, and squamous metaplasia of the respiratory epithelium in the anterior nose; and olfactory sensory cell loss in the dorsal medial meatus. These changes could not be attributed to MeBr, but they were correlated with housing in filter-capped cages between MeBr exposures and were presumably caused by volatile pollutants from soiled bedding. Moreover, olfactory sensory cell loss in the dorsal medial meatus was associated with local resistance to MeBr-induced damage in rats with pollutant-induced changes. Analysis of cage air revealed a progressive increase in ammonia levels between bedding changes (up to 50 ppm), but exposure to 300 ppm ammonia in an additional experiment reproduced only the anterior nasal lesions and not olfactory sensory cell loss. This study demonstrates that 1) regenerating olfactory epithelium is refractory to further MeBr toxicity; 2) pollutants from soiled bedding (in addition to ammonia) produce nasal lesions; and 3) pollutant-induced changes modify the nasal response to inhaled MeBr.

The protein dystrophin is absent from patients with Duchenne muscular dystrophy and from the muscles of mdx mice. Recent studies have shown that dystrophin is located at the surface membrane and at the triadic junction, where it is associated with the transverse tubular membrane. Since the triadic junction is the site of excitation-contraction (EC) coupling, we have investigated whether intramembrane charge movement, a step in EC coupling, is modified by the absence of dystrophin. Charge movements are thought to arise from the transverse tubular membrane and to underlie the dependence of sarcoplasmic reticulum Ca2+ release on transverse tubular membrane potential. We find no differences between intramembrane charge movements or passive membrane electrical properties measured in muscles from mdx mice compared with normal mice. If dystrophin does play a role in EC coupling, that role is likely to be subsequent to the charge movement step.

A statistically significant inverse association was generally found between plasma total lipid, cholesterol, or phospholipid and biotin status of 300-day-old male inbred BHE (IN-BHE) rats. Plasma, liver, and carcass lipid of both sexes generally had a significant direct association with liver lactate dehydrogenase activity; an inverse association in males resulted with improved biotin status. Elevated plasma lactate indicative of anaerobic glycolysis was found. It is proposed that an increased reductive environment - a consequence of accumulated NADH - could account for enhanced triglyceride synthesis and that this effect could explain the obesity in the IN-BHE rats. After the injection of 300 mug of biotin, plasma levels of lactate and pyruvate fell in male rats, indicating a stimulatory effect of biotin upon the oxidative pathways in these animals.

Four diets, varying in kind and amount of fat, were calculated to meet the needs of adult men. Commonly available U.S.A. food were used. Fourteen days of menus, each with five caloric levels varying from 2,400 to 4,000 kcal, were calculated. Chemical analyses of composites were carried out to determine proximate composition, food energy, selected vitamins and minerals, sugars, fatty acids, and sterols. The diets were used in a controlled study of the effects of fat level and P:S on blood pressure, blood lipids, platelet aggregation, and other variables. In general, good agreement was found between calculated and analyzed nutrient contents. However, analyzed values for fiber, iron, cholesterol, and vitamin C showed larger than desirable differences from calculated values.

In a dietary study conducted to evaluate the effects of low-fat, low-cholesterol diets on the reduction of blood lipids in man, meals were analyzed for proximate composition, ten vitamins, fourteen minerals and trace minerals, fatty acids, tocopherols, and cholesterol; Validity of the calculated nutrient composition of the diets was assessed by comparing calculated with determined values. Comparisons were also made of the determined values with 1974 Recommended Dietary Allowances. Analyzed values and those calculated from Agriculture Handbood No. 8 were exceptionally close, except for calcium; By analysis, on a per-kilogram basis, the 35-per-cent-fat-calorie diet more nearly met the Recommended Dietary Allowances for most of the nutrients than did the 25-per-cent-fat-calorie diet. However, on a per-1,000-kcal basis, there were few differences between nutrients in diets with the two levels of fat calories.

The central giant-cell granuloma is a benign, fairly uncommon lesion that can appear clinically and radiographically similar to many other lesions. When histopathological examination discloses a giant-cell lesion of bone, clinical, radiographic, and laboratory data must be obtained and carefully analyzed to rule out such conditions as hyperparathyroidism, Paget's disease, and cherubism, and to confirm the diagnosis of central giant-cell granuloma. Once the diagnosis is established, thorough curettage or surgical excision of the tumor is recommended to assure complete removal. Although recurrence is rare, periodic postoperative examination is also suggested.

A study was conducted to evaluate the effects on blood lipids and lipoproteins of feeding 21 healthy volunteers, 40-60 yr old, foods commonly eaten in the United States for two 40-day periods. Activities of lactate dehydrogenase (LDH) and LDH isoenzymes, lactate, and pyruvate were monitored. Results showed that LDH activity was significantly lower in all subjects at the end of the 25% fat-calorie period (period I) than at the beginning of the study, but rose above initial levels at the end of the 35% fat-calorie period (period II). While total LDH fell during period I, relative activity of M type subunits of LDH rose significantly in relation to H type in both sexes. This rise is probably indicative of an increase in glycolytic activity as a consequence of the increased intake of dietary carbohydrate. In period I, lactate and pyruvate decreased significantly in males (pyruvate greater than lactate) but not in females. Values for males returned to near initial levels in period II. The ratio of lactate/pyruvate was elevated in both sexes after period I. The greater change in pyruvate relative to lactate with increased dietary carbohydrate suggests increased Krebs Cycle activity. There was a statistically significant positive correlation between lactate, pyruvate, and serum triglyceride for males after they ate the 25% and 35% fat-calorie diets and for females after they ate the 35% fat-calorie diet, but not between lactate, pyruvate, and serum cholesterol for either sex.

The effects of biotin deprivation on various plasma constituents were studied in male Sprague-Dawley rats, some of which were also treated with sodium nitrate (NaNO2), extra niacin or linoleate. A basal diet containing 15% pork fat (lard), 30% egg white and sucrose, was fed for 7 weeks, with or without a weekly supplement of 150 microgram biotin and the other substances mentioned. Biotin-deprived rats ate significantly less food, gained less weight and had lower food efficiency ratios than biotin-supplemented rats. Rats given NaNO2 in the drinking water had significantly higher levels of methemoglobin than those without it; values were highest when extra niacin or linoleate was added to the diet. Lactate was highest in deprived rats and was lowest in rats supplemented with biotin alone. Blood lipids were higher with than without biotin, regardless of NaNO2. Levels of phospholipids and triglycerides were highest when extra niacin was added to the diet. Further studies are needed to define the role of biotin in oxidation-reduction reactions and in regulation of lipid metabolism.

Dietary linoleate was effective to increase LDL fluidity in adult men but did not significantly influence VLDL or HDL fluidities. Lipoproteins were isolated ultracentrifugally from plasma of sixteen healthy, free living male volunteers consuming controlled diets formulated from typical U.S.A. foods to have 35 energy % fat with 10 g (diet L) or 30 g (diet H) linoleate per day, 30-50 g saturated fatty acids/day and the balance mainly monounsaturated fatty acids. Calculated cholesterol intakes were 500 mg/day at each calorie level. Changes in LDL fluidity were detected as differences in diphenylhexatriene (DPH) fluorescence polarization upon crossover between the two controlled diets. Thermotropic measurement of DPH fluorescence anisotropy and compositional analyses indicated that LDL and HDL fluidities were dependent upon phospholipid and triacylglycerol concentrations, respectively, and were modulated by the presence of cholesteryl esters. Fatty acid analyses of the major lipid classes of the isolated lipoproteins indicated that changes, upon diet crossover, in DPH fluorescence anisotropy, were a linear function of the incremental change in LDL phospholipid linoleate. The fluorescent probe described an environment corresponding to the fatty acyl moieties of the phospholipids on the LDL periphery, which composition is apparently under dietary control. It is suggested that the diet induced fluidity changes may affect the conformation of the apoprotein moiety on the LDL surface and thus the potential for LDL interaction with cellular LDL receptors.

An ultrastructural comparison was made between the transverse tubular systems of the extensor digitorum longus (fast twitch) and the soleus (slow twitch) muscles in the rat. Quantitative measurements were made of the volume fraction, surface to volume ratio, surface density and foot density of the T system membrane. The values for the volume fraction and surface density were approximately 50% higher in the fast twitch (extensor digitorum longus) than the slow twitch (soleus) muscle. The dimensions of the tubules and hence the surface to volume ratio was the same in the two muscles. There was no difference in the spacing of the feet, so the reported three to fivefold difference in charge movement cannot be associated with a difference in foot density. Material lying within the lumen of the T tubules was observed in the majority of tubule profiles. This material, not hitherto described, was particulate or, more commonly, laminar in form.

A double-blind study of the effect of biotin supplementation (0.9 mg/day) of self-selected diets on plasma lipids and other plasma constituents was carried out in 40 men and women, age 30 to 60 years, for 71 days. Comparison of percent change from control levels showed significant treatment effects on more plasma constitutents than did comparison of the means of the actual levels. In an analysis of period of period changes, the largest differences were observed generally during the first two weeks after supplementation when small but statistically significant positive changes for biotin-treated men and women differed significantly from changes for the placebo-treated in total lipid, total phospholipid, and alpha + beta lipoprotein cholesterol. At the end of the study, these levels were at or below initial levels. Plasma biotin levels were elevated by biotin supplementation. There was a negative correlation between biotin levels and total plasma lipids. Responses os some lipid constituents of plasma were greater in volunteers who initially had elevated levels of lipids than in those who initially had normal levels of lipids. It is concluded that human requirements for biotin should be studied by new approaches and with modern techniques. Questions raised regarding the role bo biotin in the lipid metabolism of normal men and women should be investigated further.

A pilot study was undertaken to determine if moderate changes in linoleate (18:2 omega 6) intake would modulate the prostaglandin E turnover concurrently with, or independently of, changes in the plasma prostaglandin (PG) precursor levels. Four adult male volunteers in good health were fed two controlled diets containing 35% of energy from fat, with either 10 (diet L) or 30 g (diet H) linoleate/day, 30 to 50 g saturated fatty acids/day, and the balance mainly monounsaturated fatty acids. All four subjects were consuming sufficient amounts of polyunsaturates before the study. Protein (13-14%) and carbohydrate (51-53%) contribution to total caloric intake was kept constant. The menu cycle was 7 days, and all diets were calculated to provide adequate amounts of nutrients known to be required by man when data were available. Plasma fatty acids were determined by gas-liquid chromatography, and the turnover of E prostaglandins was assessed by measuring the urinary output of the major metabolite of PGE1 + PGE2 (PGE-M). Whereas we found a clear correlation between 18:2 omega 6 intake and 18:2 omega 6 concentrations in the neutral lipid (P = 0.007) and phosphoglyceride (P = 0.012) fractions of plasma, arachidonate (20:4 omega 6) concentrations in those same plasma fractions did not respond significantly to changes in linoleate intake. Moreover, we could not detect an influence of moderate changes in dietary levels of 18:2 omega 6 on the systemic production of PGE as measured by the daily urinary output of PGE-M.