Disentangling the impact of Atlantic Niño on sea-air CO2 flux.

Atlantic Niño is a major tropical interannual climate variability mode of the sea surface temperature (SST) that occurs during boreal summer and shares many similarities with the tropical Pacific El Niño. Although the tropical Atlantic is an important source of CO2 to the atmosphere, the impact of Atlantic Niño on the sea-air CO2 exchange is not well understood. Here we show that the Atlantic Niño enhances (weakens) CO2 outgassing in the central (western) tropical Atlantic. In the western basin, freshwater-induced changes in surface salinity, which considerably modulate the surface ocean CO2 partial pressure (pCO2), are the primary driver for the observed CO2 flux variations. In contrast, pCO2 anomalies in the central basin are dominated by the SST-driven solubility change. This multi-variable mechanism for pCO2 anomaly differs remarkably from the Pacific where the response is predominantly controlled by upwelling-induced dissolved inorganic carbon anomalies. The contrasting behavior is characterized by the high CO2 buffering capacity in the Atlantic, where the subsurface water mass contains higher alkalinity than in the Pacific.

Anaemia Status in young Children / Эрүүл мэндийн лаборатори

Introduction@#The high rate of malnutrition in young children remains a serious public health issue. Intervention strategies aimed to rectify this situation have succeeded in reducing anaemia, with levels falling to 28.5%. Even so, anaemia levels are still unacceptably high, especially among infants aged 6 to 24 months. @*Goal@#The aim of this survey was to investigate the prevalence of anaemia and iron and folate deficiencies that may contribute to the relatively high rates of anaemia among children aged 6 to 36 months. @*Subjects and methods@#This study involved 243 apparently healthy children (122 boys, 121 girls) from Ulaanbaatar city and Bulgan, Bayankhongor, Dornod and Khovd aimags aged 6 to 36 months with no evidence of infection within the previous 7 days. Ethical approval of the study was obtained from the Medical Ethics Committee of the Mongolian Ministry of Health. Written informed consents were obtained from the guardians of each child. </br> Morning, non-fasting venipuncture blood samples were used for the determination of the levels of hemoglobin by the hemoglobinometer, of ferritin by the microparticle enzyme immunoassays technology and of folate by the microtiter technique. </br> The statistical analysis of test results was carried out using SPSS program, with a p-value <0.05 indicating statistical significance. @*Results@#The mean hemoglobin and ferritin concentrations were the highest in the oldest children (i.e., 24 to 36 months). The mean values for hemoglobin were higher in the participants from Ulaanbaatar, whereas the ferritin levels were higher in their counterparts from the rural settings. </br> Overall, 24% of the children were anaemic. Anaemia prevalence was greater among the children in the rural area than in Ulaanbaatar. The prevalence of iron deficiency anaemia was 15%, and unlike anaemia, was independent of setting. The oldest children aged 24 to 36 months had the lowest prevalence of iron deficiency anaemia in both Ulaanbaatar and the rural area. </br> The mean serum folate concentration was 19.9 nmol/L. The concentrations decreased with age in both settings, although the mean values in Ulaanbaatar were significantly higher for each age group than those for the rural settings. Only 4% of the children had folate deficiency. None of the participants in Ulaanbaatar had low serum folate concentrations. In the rural settings, the oldest children had the highest prevalence of folate deficiency. @*Conclusion@#The prevalence of anaemia and iron deficiency anaemia is high among children aged 6 to 36 months. This finding emphasizes the necessity for programs that supply young children and their mothers with micronutrients such as iron and folate.

BioBits™ Bright: A fluorescent synthetic biology education kit.

Synthetic biology offers opportunities for experiential educational activities at the intersection of the life sciences, engineering, and design. However, implementation of hands-on biology activities in classrooms is challenging because of the need for specialized equipment and expertise to grow living cells. We present BioBits™ Bright, a shelf-stable, just-add-water synthetic biology education kit with easy visual outputs enabled by expression of fluorescent proteins in freeze-dried, cell-free reactions. We introduce activities and supporting curricula for teaching the central dogma, tunable protein expression, and design-build-test cycles and report data generated by K-12 teachers and students. We also develop inexpensive incubators and imagers, resulting in a comprehensive kit costing

Vitamin D Defciency in Mongolian Children / Эрүүл мэндийн лаборатори

Background: The prevalence of rickets is high among Mongolian children. The disease can be prevented by sufficient intake of vitamin D. Vitamin D is a fat-soluble vitamin that is naturally present in very few foods, and is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis. Serum concentration of 25(OH)D is the best indicator of vitamin D status. The aim of this study was to determine the concentrations of 25(OH)D in serum samples of small children and evaluate their vitamin D status. Materials and Methods: The concentrations of 25(OH)D were determined in serum samples of 98 children (54 male and 44 female) 6-36 months of age using a 2-step radioimmuno assay procedure. Vitamin D defciency was defned as 25(OH)D < 25nmol/L. Results: The mean serum 25(OH)D concentration was 29.00 nmol/L with no statistically signifcant differences between boys and girls, age groups and children from rural and urban areas. The vitamin D defciency among the surveyed children was 61.2%. The defciency was higher among children from Ulaanbaatar city (65.7% vs 51.9% in rural areas) and in boys (66.7% vs 55.8% in girls). Conclusion: The high level of vitamin D deficiency indicates that there is a need to promote the expansion of the coverage of vitamin D supplements among young children.

Vitamin D Defciency in Mongolian Children / Эрүүл мэндийн лаборатори

Background:The prevalence of rickets is high among Mongolian children. The disease can be prevented by sufficient intake of vitamin D. Vitamin D is a fat-soluble vitamin that is naturally present in very few foods, and is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis. Serum concentration of 25(OH)D is the best indicator of vitamin D status. The aim of this study was to determine the concentrations of 25(OH)D in serum samples of small children and evaluate their vitamin D status.Materials and Methods:The concentrations of 25(OH)D were determined in serum samples of 98 children (54 male and 44 female) 6-36 months of age using a 2-step radioimmuno assay procedure. Vitamin D defciency was defned as 25(OH)D < 25nmol/L.Results:The mean serum 25(OH)D concentration was 29.00 nmol/L with no statistically signifcant differences between boys and girls, age groups and children from rural and urban areas. The vitamin D defciency among the surveyed children was 61.2%. The defciency was higher among children from Ulaanbaatar city (65.7% vs 51.9% in rural areas) and in boys (66.7% vs 55.8% in girls).Conclusion:The high level of vitamin D deficiency indicates that there is a need to promote the expansion of the coverage of vitamin D supplements among young children.

Serum Levels of Selenium in Mongolian Children / Эрүүл мэндийн лаборатори

Background: Selenium (Se) is a trace element important for health. Its defciency has adverse effects on reproduction, immunocompetence and cardiovascular status. There is growing evidence that higher Se intakes are associated with reduced cancer risk. To date, there have been no studies conducted on the Se status of Mongolian children. Materials and Methods Non-fasting morning blood samples were collected from 240 children (122 male and 118 female) 6-36 months of age from the capital city of Mongolia and four provinces located in the south, north, east and west of the country. Inclusion criteria were apparently healthy children with no evidence of infection within the previous 7 days. The serum concentrations of Se were determined using graphite furnace atomic absorption spectrometry. Results: The mean serum Se concentration was 0.79 µmol/L. The indicator was higher for children in the rural provinces compared to those who lived in the capital city (0.81 µmol/L vs. 0.76 µmol/L, p=0.029). There was no statistically signifcant difference in the levels of Se detected between boys and girls (0.79 µmol/Lvs. 0.78 µmol/L, p=0.551). The serum concentration of Se increased with age (0.73µmol/L in the 6-11.9 months age group, 0.79 µmol/L in children aged 12-23.9 months and 0.82 µmol/L in 24-36-month-old participants). The prevalence of low serum Se in the surveyed population (<0.82 μmol/L) was 55.8%. The Se defciency tends to decrease with age (63.8% in the 6-11.9 months age group, 57.6% in participants 12-23.9 months of age and 48.2% in the oldest group). The prevalence of Se defciency is lower among children living in the western regions (38.3%) than among those from other areas of the country (60.4%). Conclusion: The high prevalence of Se defciency among Mongolian children shows that a wider survey that looks at the relationship between the blood Se and its concentrations in food and soil is needed.

Serum Levels of Selenium in Mongolian Children / Эрүүл мэндийн лаборатори

Background:Selenium (Se) is a trace element important for health. Its defciency has adverse effects on reproduction, immunocompetence and cardiovascular status. There is growing evidence that higher Se intakes are associated with reduced cancer risk. To date, there have been no studies conducted on the Se status of Mongolian children. Materials and Methods Non-fasting morning blood samples were collected from 240 children (122 male and 118 female) 6-36 months of age from the capital city of Mongolia and four provinces located in the south, north, east and west of the country. Inclusion criteria were apparently healthy children with no evidence of infection within the previous 7 days. The serum concentrations of Se were determined using graphite furnace atomic absorption spectrometry.Results:The mean serum Se concentration was 0.79 µmol/L. The indicator was higher for children in the rural provinces compared to those who lived in the capital city (0.81 µmol/L vs. 0.76 µmol/L, p=0.029). There was no statistically signifcant difference in the levels of Se detected between boys and girls (0.79 µmol/Lvs. 0.78 µmol/L, p=0.551). The serum concentration of Se increased with age (0.73µmol/L in the 6-11.9 months age group, 0.79 µmol/L in children aged 12-23.9 months and 0.82 µmol/L in 24-36-month-old participants). The prevalence of low serum Se in the surveyed population (<0.82 μmol/L) was 55.8%. The Se defciency tends to decrease with age (63.8% in the 6-11.9 months age group, 57.6% in participants 12-23.9 months of age and 48.2% in the oldest group). The prevalence of Se defciency is lower among children living in the western regions (38.3%) than among those from other areas of the country (60.4%).Conclusion:The high prevalence of Se defciency among Mongolian children shows that a wider survey that looks at the relationship between the blood Se and its concentrations in food and soil is needed.

Tissue iron deficiency and adiposity-related inflammation in disadvantaged preschoolers from NE Brazil.

BACKGROUND/OBJECTIVES: Earlier we reported an association between iron deficiency and overweight in Brazilian preschoolers. Here, we investigate whether this is the result of adipose-related inflammation. SUBJECTS/METHODS: Fasting serum C-reactive protein, α-1-acid glycoprotein (AGP), hepcidin, interleukin-6 (IL-6) and leptin, together with two iron biomarkers (serum ferritin and transferrin receptor (sTfR)), were measured in 364 disadvantaged preschoolers with a mean BMIZ (standardised Z-score for BMI) of 0.015, aged 3-6 years and attending day care in Salvador, Brazil. The role of genetic haemoglobin (Hb) disorders, intestinal parasites and dietary iron supply (calculated from serving sizes of 20 weekday menus) were also examined. RESULTS: Forty-eight children (13%) were overweight (BMIZ >1). Prevalence of tissue iron deficiency (sTfR >113.3 nmol/l; 30.6 vs 12.5%; P=0.002) and chronic inflammation (AGP >25 µmol/l; 19 vs 10%; P=0.025) were higher in overweight than in normal-weight children. From multiple regression, BMIZ was a positive predictor of log serum sTfR, ferritin and leptin, but not of log hepcidin or IL-6. Instead, major positive predictors of log hepcidin were log IL-6, followed by an elevated AGP and sex (male), whereas for log IL-6 elevated AGP was the only significant predictor. Besides BMIZ, sex (female) was also a major positive predictor of leptin. Heterozygous variant of sickle cell Hb (n=20), but not helminths, was also a positive predictor of log sTfR. Median dietary iron supply (mg/day) was above the WHO Recommended Nutrient Intake assuming moderate bioavailability and appeared adequate. CONCLUSIONS: The role of adiposity-related inflammation in tissue iron deficiency should be considered even when the prevalence of overweight is relatively low.

First results from the LUX dark matter experiment at the Sanford underground research facility.

The Large Underground Xenon (LUX) experiment is a dual-phase xenon time-projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota). The LUX cryostat was filled for the first time in the underground laboratory in February 2013. We report results of the first WIMP search data set, taken during the period from April to August 2013, presenting the analysis of 85.3 live days of data with a fiducial volume of 118 kg. A profile-likelihood analysis technique shows our data to be consistent with the background-only hypothesis, allowing 90% confidence limits to be set on spin-independent WIMP-nucleon elastic scattering with a minimum upper limit on the cross section of 7.6 × 10(-46) cm(2) at a WIMP mass of 33 GeV/c(2). We find that the LUX data are in disagreement with low-mass WIMP signal interpretations of the results from several recent direct detection experiments.

Poor dietary quality of complementary foods is associated with multiple micronutrient deficiencies during early childhood in Mongolia.

OBJECTIVE: To assess whether persistent micronutrient deficiencies in Mongolian children identified in our earlier biochemical study are associated with inadequacies in quantity and/or quality in their complementary diets. DESIGN: A cross-sectional study of breast-fed children aged 6-23 months, randomly selected from four districts in Ulaanbaatar and four provincial capitals. SUBJECTS: Weight and length were measured, and sociodemographic status, feeding practices and nutrient adequacy of complementary foods for children aged 6-8 months (n 26), 9-11 months (n 29) and 12-23 months (n 73) were assessed via questionnaire and in-home interactive 24 h recalls. RESULTS: No geographic differences existed so data were combined. Adherence to WHO infant and young child feeding practices was poor: few children were exclusively breast-fed up to 6 months of age or received the recommended number of feedings containing the recommended number of food groups. Nevertheless, energy intakes from complementary diets, primarily from cereals and non-nutritious snacks, were above WHO-estimated needs; <1 % of energy was from meat and eggs or fruits and vegetables. Median intakes and densities of most nutrients (except protein, thiamin and riboflavin) failed to meet WHO recommendations for at least two age groups, assuming average breast milk intake; greatest density deficits were for Fe > vitamin C > vitamin A > Zn > Ca. CONCLUSIONS: Complementary feeding in Mongolia is compromised by deficits in several micronutrients but not energy, in part because of frequent consumption of non-nutritious snacks. The latter may interfere with breast-feeding and should be avoided. Instead, wheat-based complementary foods should be enriched with affordable cellular animal foods and fruits rich in vitamin C to combat existing micronutrient deficits.

Multiple Micronutrient Defficiencies During Early Childhood / Монголын Анагаах Ухаан

Introduction. The high rate of malnutrition in young Mongolian children is a serious issue. Anemia, stunting and rickets have all been identified as significant problems. Low levels of serum folate have been reported among some young children in two previous surveys. Zinc is a growth-limiting micronutrient that may contribute to the persistent stunting in young Mongolian children. The traditional rice and wheat-based complementary foods used for young child feeding are likely to be inadequate in zinc. Certainly, the overall prevalence of stunting in Mongolia (i.e., 20%) is suggestive of substantial risk of zinc deficiency. It is possible that co-existing low selenium status may exacerbate zinc deficiency, because selenium compounds regulate the delivery of zinc from metallothioneine to zinc enzymes. To date, however, there have been no studies on the selenium and zinc status of the Mongolian population. Study objective. The objective of this study was to assess the biochemical indicators of micronutrient deficiency among 6-36 months old children. Subjects and methods. This cross-sectional study was conducted in four districts of Ulaanbaatar city and in centers of Bulgan, Bayanhongor, Dornod and Khovd aimags and included 243 (122 male and 121 female) apparently healthy children aged 6 to 36 months. Hemoglobin analysis was performed using a hemoglobinometer Hemocue AB, serum ferritin was analyzed by enzyme immunoassay technology, serum retinol by high-pressure liquid chromatography, serum zinc and selenium were analyzed by atomic absorption spectrophotometry and serum 25(OH)D analysis was performed using radioimmuno assay procedure. Results. Mean hemoglobin, serum ferritin, folate, 25(OH)D, retinol, zinc and selenium concentrations in children from Ulaanbaatar city and aimag centers were determined. Age-group differences for the means were significant for hemoglobin, serum ferritin, serum folate (p=0.001)and serum zinc(p=0.01). The differences between Ulaanbaatar and the aimag centers were also significant for hemoglobin, serum ferritin, serum zinc (p=0.05) and serum folate (p=0.001). 24.3% of the children were anemic. The prevalence of anemia was greater among the children in the aimag centers than in Ulaanbaatar city and in younger children than in the oldest age group. The prevalence of iron deficiency anemia was 15.3% and was independent of setting but was lowest in the oldest children aged 24 to 36 months. Of all the surveyed children, only 3.7% had low level of serum folate. The overall prevalence of low serum retinol levels indicative of vitamin A deficiency was 33.7%, with no differences by setting or age group. 74.7% of the children had low serum zinc concentrations. There was no significant difference in the prevalence between children living in Ulaanbaatar city and the aimag centers, or among the three age groups of children in either setting. The overall prevalence of low serum selenium concentrations was 57.7%, with no differences in the prevalence by setting or age-group. The prevalence of low serum levels of 25(OH)D was 61% and was highest among the children aged 6 to 12 months of Ulaanbaatar city. Conclusion: 1. Zinc deficiency had the highest prevalence (74.7%) among the surveyed children, followed by low serum selenium levels (57.7%). 2. 36% of the children were at risk of two and 64% of more than two coexisting micronutrient deficiencies. 3. There is a need for multi-micronutrient programs that take into account the potential interactions of micronutrients instead of the present single micronutrient based interventions on-going in Mongolia.

Understanding of informed consent and surgeon liability by the public and patients.

PURPOSE: To evaluate understanding of the fundamental concepts of informed consent by the public and patients. METHODS: Questionnaires were distributed to any persons (aged more than 16 years) attending the Palmerston North Hospital (excluding in-patients). The first 1000 completed questionnaires were analysed using the Chi squared test. RESULTS: The fundamental concepts of informed consent were not appreciated by most respondents; only 18%, 13%, and 5% of them agreed with its implications in terms of self-autonomy, confidentiality, and battery, respectively. 64% of respondents preferred to take sole responsibility to decide which procedure to undergo, 31% preferred to be guided by the surgeon, and 5% by a brief explanation only. 21% of the respondents considered the surgeon liable in the event of an unmentioned rare complication, 43% considered the surgeon not liable, and 34% were undecided. CONCLUSION: Understanding of medico-legal implications of informed consent (e.g. self-autonomy, confidentiality, and battery) by the public and patients is poor. Their expectations regarding self-autonomy seem unrealistic. It is time for surgeons, legal experts, and the public to confer and make informed consent a practical, user-friendly tool rather than the legal obstacle that it is today.

Impact of engineering flow conditions on plasmid DNA yield and purity in chemical cell lysis operations.

Chemical lysis of bacterial cells using an alkaline solution containing a detergent may provide an efficient scalable means for selectively removing covalently closed circular plasmid DNA from high-molecular-weight contaminating cellular components including chromosomal DNA. In this article we assess the chemical lysis of E. coli cells by SDS in a NaOH solution and determine the impact of pH environment and shear on the supercoiled plasmid and chromosomal DNA obtained. Experiments using a range of plasmids from 6 kb to 113 kb determined that in an unfavorable alkaline environment, where the NaOH concentration during lysis is greater than 0.15 +/- 0.03 M (pH 12.9 +/- 0.2), irreversible denaturation of the supercoiled plasmid DNA occurs. The extent of denaturation is shown to increase with time of exposure and NaOH concentration. Experiments using stirred vessels show that, depending on NaOH concentration, moderate to high mixing rates are necessary to maximize plasmid yield. While NaOH concentration does not significantly affect chromosomal DNA contamination, a high NaOH concentration is necessary to ensure complete conversion of chromosomal DNA to single-stranded form. In a mechanically agitated lysis reactor the correct mixing strategy must balance the need for sufficient mixing to eliminate potential regions of high NaOH concentrations and the need to avoid excessive breakage of the shear sensitive chromosomal DNA. The effect of shear on chromosomal DNA is examined over a wide range of shear rates (10(1)-10(5) s(-1)) demonstrating that, while increasing shear leads to fragmentation of chromosomal DNA to smaller sizes, it does not lead to significantly increased chromosomal DNA contamination except at very high shear rates (about 10(4)-10(5) s(-1)). The consequences of these effects on the choice of lysis reactor and scale-up are discussed.

Quantification of proteins and metabolites by mass spectrometry without isotopic labeling or spiked standards.

A new method is presented for quantifying proteomic and metabolomic profile data by liquid chromatography-mass spectrometry (LC-MS) with electrospray ionization. This biotechnology provides differential expression measurements and enables the discovery of biological markers (biomarkers). Work presented here uses human serum but is applicable to any fluid or tissue. The approach relies on linearity of signal versus molecular concentration and reproducibility of sample processing. There is no use of isotopic labeling or chemically similar standard materials. Linear standard curves are reported for a variety of compounds introduced into human serum. As a measure of analytical reproducibility for proteome and metabolome sampling, median coefficients of variation of 25.7 and 23.8%, respectively, were determined for approximately 3400 molecular ions (not counting their numerous isotopes) from 25 independently processed human serum samples, corresponding to a total of 85000 individual molecular ion measurements.

Gaulin homogenization: a mechanistic study.

Free radical-based oxidation has been detected in the normal operating regime of the Gaulin homogenizer, demonstrating that cavitation occurs in this important industrial bioprocessing equipment. Free radical generation is suppressed by imposition of back pressure, proving that such cavitation occurs in the impingement section. The calculated value of the cavitation number is consistent with submerged jet cavitation, wherein a high-speed jet exiting from the valve gap accelerates fluid in the impingement region, creating the vacuum conditions for cavitation. Using polysaccharides as a model shear-sensitive compound, their breakage pattern in the homogenizer was characterized by molecular size and polydispersity and compared to those of fluid shear flows in capillary tubes and cavitating flow from a sonic horn. The results indicate that breakage occurs primarily by fluid shear, although a contribution by cavitation is also apparent when back pressure is applied. Because biological molecules can readily react with free radicals and the alterations caused thereby are subtle in nature, a thorough evaluation of the impact of free radicals in upstream homogenization is warranted.

Stability of gentamicin sulfate and tobramycin sulfate in extemporaneously prepared ophthalmic solutions at 8 degrees C.

The stability of gentamicin sulfate and tobramycin sulfate in fortified ophthalmic solutions stored under refrigeration was studied. Fortified gentamicin ophthalmic solution and fortified tobramycin ophthalmic solution were prepared to a final theoretical concentration of 13.6 mg/mL by using commercially available ophthalmic and injectable solutions. Volumes of each solution were packaged in plastic bottles and refrigerated at 4-8 degrees C. Samples of each solution were analyzed by fluorescence polarization immunoassay on days 0 (before refrigeration), 1, 2, 3, 4, 7, 14, 28, 63, and 91. To validate the method, identical solutions were prepared, stored under refrigeration at 4-8 degrees C, and analyzed by a stability-indicating high-performance liquid chromatographic assay on days 0 (before refrigeration), 9, 28, 56, and 91. Fluorescence polarization immunoassay showed the mean concentrations of gentamicin and tobramycin on day 91 to be 104.4% and 97.4%, respectively, of the time 0 concentrations; the difference was not significant in either case. HPLC validated these results; the mean concentration of gentamicin and tobramycin on day 91 was 103.3% and 101.2%, respectively, of the mean day 0 concentrations. Gentamicin and tobramycin in ophthalmic solutions prepared by mixing ophthalmic and injectable products and stored in plastic bottles at 4-8 degrees C were stable for three months.

Pharmacokinetic comparison of 5 g of azlocillin every 8 h and 4 g every 6 h in healthy volunteers.

To compare the multiple-dose pharmacokinetics of two dosage regimens of azlocillin, we studied 12 healthy volunteers via a randomized, crossover design with a 2-week washout phase between regimens. Serum and urine samples were collected for 8 h following the fifth dose of a regimen of 4 g every 6 h and the fourth dose of a regimen of 5 g every 8 h. Data for concentrations in serum were fitted to a two-compartment open model by nonlinear regression. Statistically significant differences (P less than 0.05) were observed in the following parameters (mean +/- standard deviation) for the 4- and 5-g regimens, respectively: area under the serum concentration-time curve during the dosing interval, 592 +/- 140 versus 772 +/- 151 micrograms.h/ml; terminal elimination rate constant, 0.5364 +/- 0.0912 versus 0.4758 +/- 0.0486 h-1; renal clearance, 87.6 +/- 16.1 versus 76.1 +/- 13.5 ml/min; maximum drug concentration in serum, 381 +/- 89 versus 473 +/- 90 micrograms/ml; and minimum drug concentration in serum, 19 +/- 10 versus 8 +/- 4 micrograms/ml. No significant differences were seen in the following parameters: V1, V beta, k10, k12, k21, total systemic clearance, and nonrenal clearance. These data support the presence of saturable renal elimination of azlocillin, as well as the feasibility of an 8-h dosing interval.

Phenytoin-induced hypersensitivity reactions.

A case of phenytoin-induced hepatitis with mononucleosis is reported, and syndromes associated with phenytoin hypersensitivity reactions are discussed. A 23-year-old black woman with a two-month history of seizure disorder was admitted to a hospital with nausea, vomiting, fever, lymphadenopathy, diffuse maculopapular rash, left-upper-quadrant tenderness, and hepatomegaly. She was receiving phenytoin sodium 300 mg/day; carbamazepine 200 mg four times daily had been discontinued four days before admission because of leukopenia. Phenytoin was discontinued after admission; however, phenytoin 1 g i.v. was given for a tonic-clonic seizure two days after admission, after which swelling of the face and legs and pruritus developed. Over the next few days, signs and symptoms of hepatotoxicity progressed, and she became comatose. Seizures were treated with diazepam. She began to recover after 10 days of supportive therapy and was discharged several weeks later on primidone therapy. Serious phenytoin hypersensitivity reactions may appear as dermatologic, lymphoid, or hepatic syndromes. Fever, rash, and lymphadenopathy often accompany hepatic injury. Encephalopathy and death may occur. Proposed mechanisms for phenytoin hypersensitivity include antigen-antibody reactions, alteration of lymphocyte function, and an enzyme abnormality causing the production of toxic metabolites. Treatment is supportive; phenobarbital and carbamazepine may be used with caution as alternate anticonvulsant therapy. The possibility of phenytoin hypersensitivity reactions should be considered when patients receiving phenytoin have unusual symptoms, particularly fever, rash, and lymphadenopathy.