Arsenic accumulation by edible aquatic macrophytes.

Edible aquatic macrophytes grown in arsenic (As)-contaminated soil and sediment were investigated to determine the extent of As accumulation and potential risk to humans when consumed. Nasturtium officinale (watercress) and Diplazium esculentum (warabi) are two aquatic macrophytes grown and consumed in Hawaii. Neither has been assessed for potential to accumulate As when grown in As-contaminated soil. Some former sugarcane plantation soils in eastern Hawaii have been shown to have concentrations of total As over 500 mg kg(-1). It was hypothesized that both species will accumulate more As in contaminated soils than in non-contaminated soils. N. officinale and D. esculentum were collected in areas with and without As-contaminated soil and sediment. High soil As concentrations averaged 356 mg kg(-1), while low soil As concentrations were 0.75 mg kg(-1). Average N. officinale and D. esculentum total As concentrations were 0.572 mg kg(-1) and 0.075 mg kg(-1), respectively, corresponding to hazard indices of 0.12 and 0.03 for adults. Unlike previous studies where watercress was grown in As-contaminated water, N. officinale did not show properties of a hyperaccumulator, yet plant concentrations in high As areas were more than double those in low As areas. There was a slight correlation between high total As in sediment and soil and total As concentrations in watercress leaves and stems, resulting in a plant uptake factor of 0.010, an order of magnitude higher than previous studies. D. esculentum did not show signs of accumulating As in the edible fiddleheads. Hawaii is unique in having volcanic ash soils with extremely high sorption characteristics of As and P that limit release into groundwater. This study presents a case where soils and sediments were significantly enriched in total As concentration, but the water As concentration was below detection limits.

Stimulation of the methylation pathway for phosphatidylcholine synthesis in rat lungs by choline deficiency.

The methylation of phosphatidylethanolamine (PE) to form phosphatidylcholine (PC) was investigated using the isolated rat lung perfused with radiolabeled ethanolamine. Lungs from choline-deficient rats showed increased incorporation of radiolabel into PC at 2 h of perfusion. Increased PC synthesis from PE was also observed with lungs from rats fed a lipotrophic (choline plus methionine deficient) diet when methionine was added to the lung perfusate. These results indicate increased activity of the methylation pathway for lung PC synthesis during choline deficiency.

Glycerol 3-phosphate acylation in microsomes of type II cells isolated from adult rat lung.

Glycerol 3-phosphate acylation was studied in type II cells isolated from adult rat lung. The process was found to be largely microsomal. In the microsomes phosphatidic acid is the main product of glycerol 3-phosphate acylation. Glycerol-3-phosphate acyltransferase is rate limiting in the phosphatidic acid formation by the microsomes. Type II cell microsomes incorporate palmitoyl and oleoyl residues into phosphatidic acid at an equal rate if palmitoyl-CoA and oleoyl-CoA are added separately. However, if palmitoyl-CoA and oleoyl-CoA are added as an equimolar mixture the unsaturated fatty acyl moiety is incorporated much faster. Under the latter conditions monoenoic species constitute the most abundant products of glycerol 3-phosphate acylation. The microsomes incorporate both palmitoyl and oleoyl residues readily into both the 1- and 2-position of phosphatidic acid, even when palmitoyl-CoA and oleoyl-CoA are added together. Assuming that both phosphatidic acid phosphatase and cholinephosphotransferase do not discriminate against substrates with an unsaturated acyl moiety at the 1-position and a saturated acyl moiety at the 2-position, the last two observations indicate that a considerable percentage of phosphatidylcholine molecules synthesized de novo may have a saturated fatty acid at the 2-position and an unsaturated fatty acid at the 1-position, and that remodeling at the 1-position may be important for the formation of surfactant dipalmitoylphosphatidylcholine. They also indicate that type II cell microsomes are capable of synthesizing the dipalmitoyl species of phosphatidic acid. However, since there is a preference for the acylation of glycerol 3-phosphate with unsaturated fatty acyl residues, the percentage of dipalmitoyl species in the synthesized phosphatidic acid, and thereby the percentage of dipalmitoyl species in the phosphatidylcholine synthesized de novo, will probably depend on the relative availability of the various acyl-CoA species.

Carboplatin, etoposide, and radiotherapy, followed by surgery, for the treatment of marginally resectable non-small cell lung cancer.

The present study was undertaken in order to determine the feasibility and efficacy of induction chemotherapy with carboplatin and etoposide, followed by weekly carboplatin and full-course radiotherapy as pre-operative therapy for marginally resectable non-small cell lung cancer (NSCLC). Twenty-eight patients with good Eastern Cooperative Oncology Group (ECOG) performance status ratings and stage IIIA NSCLC received induction chemotherapy with carboplatin (dose computed with the Egorin formula, days 1 and 29) and etoposide (100 mg/m2/day, days 1 through 3 and 29 through 31). This was followed by 100 mg/m2 weekly carboplatin given over 6 weeks, concurrently with 60 Gy radiotherapy. Patients with either responsive or stable disease underwent thoracotomy 4 weeks after the completion of combined-modality therapy. All 28 patients received the first chemotherapy cycle (average carboplatin dose, 407 mg/m2; range, 195 to 586 mg/m2). World Health Organization (WHO) grade 3/4 neutropenia and thrombocytopenia were observed in 53 and 34% of patients, respectively. There were three febrile neutropenic episodes, but no septic deaths. Five patients (18%) required dose reductions prior to the second chemotherapy cycle, but the dose intensity of carboplatin was maintained (average dose, 390 mg/m2; range, 195 to 586 mg/m2). In all, 82% of patients received full-dose radiotherapy, and 73% received at least five of six planned concurrent weekly carboplatin doses. Carboplatin doses were most frequently delayed for thrombocytopenia and/or leukopenia. Carboplatin did not increase the incidence of radiation-induced esophagitis. Only three patients required interruption of radiotherapy, for esophagitis (two patients) and persistent thrombocytopenia (one patient). The response rate to pre-operative therapy was 64%. In this study, we demonstrated the ability to deliver escalated doses of carboplatin with standard-dose etoposide as induction chemotherapy with reasonable myelotoxicity. The combined-modality therapy was well tolerated, and the addition of weekly carboplatin did not result in increased radiation-related toxicity. This neoadjuvant regimen is active in the treatment of locally advanced NSCLC, and compares favorably to other cisplatin-based regimens.

Flavanone absorption after naringin, hesperidin, and citrus administration.

Disposition of citrus flavonoids was evaluated after single oral doses of pure compounds (500 mg naringin and 500 mg hesperidin) and after multiple doses of combined grapefruit juice and orange juice and of once-daily grapefruit. Cumulative urinary recovery indicated low bioavailability ( < 25%) of naringin and hesperidin. The aglycones naringenin and hesperitin were detected in urine and plasma by positive chemical ionization-collisionally activated dissociation tandem mass spectrometry (PCI-CAD MS/MS). After juice administration, PCI-CAD MS/MS detected naringenin, hesperitin, and four related flavanones, tentatively identified as monomethoxy and dimethoxy derivatives. These methoxyflavanones appear to be absorbed from juice. Absorbed citrus flavanones may undergo glucuronidation before urinary excretion.

Practicality of a lithium dosing guide.

A method of dosing lithium based on a 24-hour serum lithium level obtained after a single 600-mg oral dose of lithium carbonate has been reported to provide a steady-state lithium concentration of 0.6--1.2 mEq/liter. Since this regimen is widely used in clinical practice, the authors designed a study to determine the practicality of the dosing guide. Of 13 patients who followed this dosing protocol, 4 (30.7%) failed to achieve the defined steady-state range. The authors discuss factors that may affect the reliability of the dosing guide.

Differences in the low-energy collision-activated dissociation of carboxylate anions from structurally similar prostaglandins: E2, F 2α, D 2, and DHKF 2α.

Some intriguing discoveries were made concerning the collision-activated dissociation behavior of the derivatized carboxylate anions of PGE2 and PGF2α. The carboxylate anion [MPFB](-) formed from electron-capture negative chemical ionization of the pentafluorobenzyl ester-trimethylsilyl derivative of PGF2α showed little fragmentation under typical collision gas pressures and energies (<2.0 mtorr N2 and <20 eV). In contrast, the daughter spectra of the carboxylate anion of the methoxime-pentafluorobenzyl ester-trimethylsilyl derivative of PGE2 produced many intense fragments under the same conditions.

Negative chemical ionization in quadrupole ion trap mass spectrometry: Effects of applied voltages and reaction times.

The effects of applied voltages and reaction times on negative ion chemical ionization in the quadrupole ion trap are investigated. Mass-selected ejection of undesired reagent ions and selective mass storage of only negative ions are required for practical negative ion chemical ionization. This is achieved by application of rf and dc voltages to the ring electrode to control the mass-to-charge ratios one polarity) of ions stored, as well as by application of a supplemental rf voltage applied across the endcap electrodes to selectively eject ions of a particular mass-to-charge ratio. Even with careful control of these parameters, negative chemical ionization is not as sensitive as electron ionization and positive chemical ionization because of the lack of thermal electrons in the ion trap. Mass selection of the hydroxide anion as a reagent ion and exclusion of all positive ions provide [M - H](-) ions with little or no fragmentation for a wide variety of compounds.

Internal pulsed valve sample introduction on a quadrupole ion trap mass spectrometer.

A pulsed valve positioned just outside the ion trap electrodes (within the vacuum chamber) has been characterized. The observed gas pulse widths and the maximum ion intensities were found to decrease as the distance between the pulsed valve and the ion trap electrodes increased. An explanation is presented within. The pulsed valve was found to impart temporal separation in ion-molecule reactions by permitting the removal of interfering neutrals. Other factors that affect the degree of temporal separation also are presented.

Probing trapped ion energies via ion-molecule reaction kinetics: Quadrupole ion trap mass spectrometry.

We present a detailed study of the energies of the ions stored in a quadrupole ion trap mass spectrometer (QITMS). Previous studies have shown that the rate constant, k, for the charge exchange reaction Ar(+) N(+) 2 →, N(+) 2+Ar increases with increasing ion-molecule center-of-mass kinetic energy (K.E.cm). Thus, we have determined k for this chemical "thermometer" reaction at a variety of Ar and N2 pressures and have assigned K.E.cm values as a function of the q2 of the Ar(+) ion both with and without He buffer gas present in the trap. The K.E.cm energies are found to lie within the range 0.11-0.34 eV over the variety of experimental conditions investigated. Quantitative "cooling" effects due to the presence of He buffer gas are reported, as are increases in K.E.cm due to an increase in the q2 of the Ar(+) ion. "Effective" temperatures of the Ar(+) ions in He buffer are determined based on a Maxwell-Boltzmann distribution of ion energies. The resulting temperatures are found to lie within the range ≈ 1700-3300 K. We have also examined the K.E.cm, values arising from the chemical thermometer reaction of O(+) 2 with CH4, as previous assignments of effective ion temperatures based on this reaction have been called into question.

Nonlinear resonance effects during ion storage in a quadrupole ion trap.

Contributions of higher-order fields to the quadrupolar storage field produce nonlinear resonances in the quadrupole ion trap. Storing ions with secular frequencies corresponding to these nonlinear resonances allows absorption of power from the higher-order fields. This results in increased axial and radial amplitudes which can cause ion ejection and collision-induced dissociation (CID). Experiments employing long storage times and/or high ion populations, such as chemical ionization, ion-molecule reaction studies, and resonance excitation CID, can be particularly susceptible to nonlinear resonance effects. The effects of higher-order fields on stored ions are presented and the influence of instrumental parameters such as radiofrequency and direct current voltage (qZ and az values), ion population, and storage time are discussed.

Alternating RF/DC Isolations for Quantitation with Coeluting Internal Standards in Gas Chromatography/Ion Trap Mass Spectrometry.

A new ion trap scan function for gas chromatography/mass spectrometry (GC/MS) quantitation is described that employs alternating mass-selective storage (rf/dc isolation) of ions from an analyte and its coeluting isotopically labeled internal standard. This scan includes two separate ionization/isolation/mass analysis sequences within the same scan function, each optimized for either the analyte or the internal standard. This results in alternating between analyzing the analyte and the internal standard during their coelution. The method is conceptually similar to using two different scan functions to analyze either the analyte or the internal standard in alternating scans; however, it is much faster because it eliminates the slow procedure of continuously downloading alternating scan functions from disk. This allows more data points to be obtained over a GC peak, resulting in more reproducible GC peak profiles as well as better sensitivity and precision. Results of calibration curves spanning four orders of magnitude (0.5 pg to 5 pg injected on column) obtained by using this method give excellent linear correlations (r (2) > 0.9990) and precision (relative standard deviations of triplicate injections < 10%).

Estimation of mutagenic/carcinogenic potential of environmental contaminants by ion-molecule reactions and tandem mass spectrometry.

The ability to produce and detect products of model DNA/carcinogen ion-molecule reactions is demonstrated in the ion source and the collision cell of a triple quadrupole tandem mass spectrometer. Reaction between adenine and benzoyl chloride in the ion source is shown to produce the DNA adduct benzoyl adenine. The daughter ion mass spectrum of the reaction product is compared to that of the synthesized standard. Mass chromatograms of the reaction between mass-selected pyridine ions and various analytes eluting from a GC column into the collision cell are demonstrated and illustrate the ability to detect only the GC eluates that react with pyridine. This technique could provide a rapid and sensitive method for screening complex environmental samples for carcinogens, as well as for estimating the relative mutagenic/carcinogenic potential of environmental contaminants.

Infrared multiple photon dissociation in the quadrupole ion trap via a multipass optical arrangement.

The design of a novel multipass optical arrangement for use with infrared multiple photon dissociation (IRMPD) in the quadrupole ion trap is presented. This design circumvents previous problems of limited IR laser power, small IR absorption cross sections for many molecules, and the limited ion statistics of trapping and detection of ions for IRMPD in the quadrupole ion trap. In contrast to previous designs that utilized the quadrupole ion store, the quadrupole ion trap was operated in the mass selective instability mode with concurrent resonance ejection. The instrumental design consisted of a modified ring electrode with three spherical concave mirrors mounted on the inner surface of the ring. This modified design allowed for eight laser passes across the radial plane of the ring electrode. IRMPD of protonated bis(2-methoxyethyl)ether (diglyme) was used to characterize the performance of the multipass ring electrode. Two consecutive reactions for the IRMPD of protonated diglyme were observed with a lower energy channel predominant at less than 0.6 J (irradiation times from 1 to 30 ms) and a second channel predominant at energies greater than 0.6 J (irradiation times > 30 ms). Other studies presented include a discussion of the dissociation kinetics of protonated diglyme, the use of a pulsed valve for increased trapping efficiency of parent ion populations, and the effects of laser wavelength and of ion residence time in the radial plane of the ring electrode on photodissociation efficiency.

Epidemiology of hyperuricemia in an ambulatory elderly population.

The relationship of serum uric acid concentration to age and sex was assessed in 1,701 participants in a geriatric multiphasic screening clinic. Included were 1,067 women and 634 men. The mean uric acid level for men was 6.35 mg/100 ml compared to 5.44 mg/100 ml for women. No statistically significant increases in serum uric acid between age groups were apparent, except for women over 84 years of age. The mean serum urate concentrations found in this geriatric study are higher than those reported for other population groups, suggesting a higher normal value for the elderly.

Selected physiologic and drug effects on serum uric acid levels in an elderly population.

A total of 2,923 elderly subjects were studied to determine the relationship between obesity, hypertension, thyroid disease, renal function, alcohol consumption, selected drugs, and the serum uric acid level. Comparison of the serum uric acid levels with indices of obesity demonstrated a strong correlation in normotensive (p less than .0001) and hypertensive (p less than .001) subjects. The serum creatinine level, when used alone, was not a reliable indicator of renal function. Of the drugs evaluated, diuretics had the most pronounced effect upon the serum uric acid level.

Differential response of lung and liver of juvenile rats to choline deficiency.

The effect of choline deficiency on the lung lipids of actively growing male Sprague-Dawley rats was investigated using a washed soy protein diet deficient in choline and methionine (lipotrophic). The livers from deficient animals had a significantly increased total lipid content and decreased phosphatidylcholine (PC) content and PC-to-phosphatidylethanolamine ratio (P less than 0.01). Although lung free choline levels were decreased 40% compared with controls (P less than 0.05), the PC content of the whole lung homogenate was unchanged. However, disaturated phosphatidylcholine from animals receiving the lipotrophic diet was significantly increased in the lavage and proportionally decreased in the lavaged lung tissue compared with controls (P less than 0.01). This study indicates that, despite decreased lung choline levels as a result of ingesting a lipotrophic diet, and unlike the liver, lung PC content is maintained at normal values. Although the lung total PC levels are maintained, there is a change in the partition of this lipid pool between the tissue and the alveolar space.

Synthesis of phosphatidylcholine by rat lung during choline deficiency.

The effect of choline deficiency on the de novo pathway for phosphatidylcholine (PC) synthesis in the lung was investigated in rats fed a washed soy protein (lipotrophic) diet deficient in choline and methionine for 2-3 wk. Lungs from lipotrophic rats showed a decreased content of choline and choline-phosphate (P less than 0.05) compared with control but no change in content of cytidine 5'-diphosphocholine or PC. Isolated perfused lungs from lipotrophic rats were evaluated for choline and fatty acid utilization for PC synthesis. Lipotrophic lungs perfused with 5 microM [14C-methyl]-choline chloride showed increased incorporation into PC while there was no significant effect at saturating levels of choline (100 microM). There was increased incorporation of [1-14C]-palmitic acid into PC and diglyceride and increased incorporation of D-[U-14C]glucose into fatty acids of PC. Increased choline and glucose incorporation was not due to alteration of intracellular specific activity of these substrates. This study indicates the utilization of choline and fatty acid for PC synthesis is stimulated as a result of choline deficiency while lung CDP-choline concentration is maintained, possibly through regulation of choline phosphate cytidyl transferase activity. These mechanisms compensate for decreased choline availability to maintain the PC content of lungs.

Doxycycline in the prevention of hepatic dysfunction: an evaluation of its use following jejunoileal bypass in humans.

A prospective randomized study was carried out to evaluate doxycycline hyclate in the prevention of hepatic dysfunction following jejunoileal bypass for morbid obesity. Forty-five patients were entered into the study and were observed for a year or more. Patients received either 100 mg of doxycycline hyclate twice daily on postoperative days 5 through 10 and then 100 mg daily for six weeks, or no drug. At six weeks, 12 weeks, and 12 months after the operation, biochemical levels were measured. After one year all patients had a liver biopsy. Doxycycline, in the regimen, was not demonstrated to be of value in the prevention of hepatic dysfunction in these patients. A lack of correlation was demonstrated between the biochemical definition of hepatic dysfunction and liver histopathology.

A comparative study of netilmicin-cefoxitin and gentamicin-cefoxitin in surgical patients with serious systemic infection.

A double-blind, randomized study of gentamicin and netilmicin, each in combination with cefoxitin, was done to compare their respective efficacy and toxicity in patients with serious systemic infection. Thirty-seven surgical patients were evaluated for efficacy and 46 patients were evaluated for toxicity. The most frequently cultured organisms were Escherichia coli (15), Klebsiella sp (9), Proteus sp (6), and Bacteroides sp (4). For 23 patients treated with gentamicin-cefoxitin (G-C), the clinical response was favorable in 20/21 (95.2%) evaluable cases, and elimination or marked reduction of 33/34 (97.1%) organisms was achieved. For 14 patients treated with netilmicin-cefoxitin (N-C), the clinical response was favorable in 13/13 (100%) evaluable cases, and 19/20 (95%) organisms were eliminated or markedly reduced. Nephrotoxicity was defined as an increase in serum creatinine to greater than 25% over baseline with an absolute rise of at least 0.5 mg/100 ml to a value greater than or equal to 1.3 mg/100 ml. Based on these criteria, nephrotoxicity was seen in 2/27 (7.4%) patients treated with G-C and in 3/19 (15.8%) patients treated with N-C. Ototoxicity was defined as a greater than 20 dB loss at any frequency. Based on these criteria, ototoxicity was seen in 5/27 (18.5%) patients treated with G-C and 2/19 (10.5%) patients treated with N-C. The data show no significant difference in toxicity and suggest that netilmicin and gentamicin are both highly effective in combination with cefoxitin in patients who have serious infections after surgery.