Aberrant prostaglandin synthase 2 expression defines an antigen-presenting cell defect for insulin-dependent diabetes mellitus.

Prostaglandins (PGs) are lipid molecules that profoundly affect cellular processes including inflammation and immune response. Pathways contributing to PG output are highly regulated in antigen-presenting cells such as macrophages and monocytes, which produce large quantities of these molecules upon activation. In this report, we demonstrate aberrant constitutive expression of the normally inducible cyclooxygenase PG synthase 2 (PGS(2)/ COX-2) in nonactivated monocytes of humans with insulin-dependent diabetes mellitus (IDDM) and those with islet autoantibodies at increased risk of developing this disease. Constitutive PGS(2) appears to characterize a high risk for diabetes as it correlates with and predicts a low first-phase insulin response in autoantibody-positive subjects. Abnormal PGS(2) expression in at-risk subjects affected immune response in vitro, as the presence of a specific PGS(2) inhibitor, NS398, significantly increased IL-2 receptor alpha-chain (CD25) expression on phytohemagglutinin-stimulated T cells. The effect of PGS(2) on CD25 expression was most profound in subjects expressing both DR04 and DQbeta0302 high-risk alleles, suggesting that this cyclooxygenase interacts with diabetes-associated MHC class II antigens to limit T-cell activation. These results indicate that constitutive PGS(2) expression in monocytes defines an antigen-presenting cell defect affecting immune response, and that this expression is a novel cell-associated risk marker for IDDM.

QUICKI does not accurately reflect changes in insulin sensitivity with exercise training.

A novel index of insulin sensitivity, the quick insulin sensitivity check index, termed QUICKI (1/[log (insulin) + log (glucose)]), was recently developed. We examined whether QUICKI accurately reflects changes in insulin sensitivity after exercise training, a perturbation known to improve insulin sensitivity. Sedentary, nondiabetic adults underwent a frequently sampled iv glucose tolerance test before and after 6 months of training. Insulin sensitivity was estimated from the glucose tolerance test using Bergman's minimal model (insulin sensitivity-minimal model), and QUICKI was calculated from basal insulin and glucose. Exercise increased (P = 0.003) insulin sensitivity-minimal model but did not change (P = 0.12) QUICKI. Before and after training, the rank-correlation between QUICKI and insulin sensitivity-minimal model was significant (r = 0.79, P = 0.0005; r = 0.56, P = 0.03, respectively). However, the rank-correlation between fasting insulin alone with insulin sensitivity-minimal model was as good (before training r = -0.77, P = 0.0009; after training r = -0.55, P = 0.03) as that between QUICKI and insulin sensitivity-minimal model. Fasting glucose was not related to insulin sensitivity-minimal model at either time. When difference scores (i.e. after pretraining values) were examined, neither QUICKI nor fasting insulin correlated with insulin sensitivity-minimal model (QUICKI vs. insulin sensitivity-minimal model r = 0.24, P = 0.39; fasting insulin vs. insulin sensitivity-minimal model r = -0.40, P = 0.14). We conclude that fasting insulin is equivalent to fasting insulin plus glucose (i.e. QUICKI) at estimating basal insulin sensitivity in nondiabetic adults. However, QUICKI does not accurately reflect exercise-induced changes in insulin sensitivity within individual subjects.

Genomic DNA methylation decreases in response to moderate folate depletion in elderly women.

BACKGROUND: Methylation of genomic DNA is dependent on an adequate supply of folate coenzymes. Previous data support the hypothesis that abnormal DNA methylation plays an integral role in carcinogenesis. To date, no studies assessing the effect of inadequate folate status on DNA methylation in older women (aged >63 y) have been reported. OBJECTIVE: The effect of moderate folate depletion followed by folate repletion on leukocyte genomic DNA methylation was investigated in elderly women (aged 60-85 y) to evaluate whether DNA methylation could be used as a functional indicator of folate status. DESIGN: Healthy, postmenopausal women (n = 33) consumed a moderately folate-depleted diet (118 microg folate/d) for 7 wk, followed by 7 wk of folate repletion with 200 or 415 microg/d, each provided as 2 different dietary treatments for a total of 4 treatment groups (n = 30). Leukocyte DNA methylation was determined on the basis of the ability of DNA to incorporate [(3)H]methyl groups from labeled S:-adenosylmethionine in an in vitro assay. RESULTS: Incorporation of [(3)H]methyl groups increased significantly (P: = 0.0025) in response to folate depletion, suggesting undermethylation of DNA. No significant changes were detected in [(3)H]methyl incorporation in any group over the 7-wk repletion period compared with postdepletion values. CONCLUSIONS: DNA methylation status may be used as a functional indicator of moderately depleted folate status. The slow response to the repletion diets observed suggests that normalization of DNA methylation after moderate folate depletion may be delayed in older women.

Methylenetetrahydrofolate reductase mutation (677C-->T) negatively influences plasma homocysteine response to marginal folate intake in elderly women.

Individuals who are homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C --> T mutation have depressed serum folate (SF) and elevated plasma total homocysteine (tHcy) concentrations, which may affect folate requirements and increase the risk for coronary artery disease. A controlled metabolic study (14 weeks) using a depletion/repletion protocol was performed in women (aged 60 to 85 years, N = 33) to provide age-specific data on the effects of the MTHFR mutation on SF and tHcy status. Subjects consumed a moderately folate-deplete diet (118 microg/d) for 7 weeks, followed by 7 weeks of folate repletion with 200 or 415 microg/d provided as two different treatments. Following folate depletion, the mean SF concentration was lower for homozygous (P = .017) versus heterozygous subjects. Homozygotes for the 677C --> T mutation showed a higher (P = .015) percent increase in plasma tHcy (44%) than heterozygous (20%) or normal (15%) subjects. At week 7, the mean plasma tHcy concentration was higher in homozygous subjects (12.5 +/- 5.3 micromol/L, mean +/- SD) versus the heterozygous (10.8 +/- 3.8 micromol/L, P = .008) or normal (11.3 +/- 2.7 micromol/L, P = .001) genotype groups. Following folate repletion, plasma tHcy concentrations were not different between genotype groups, despite a higher (P < .016) SF concentration in subjects with the homozygous genotype. These data suggest that older women who are homozygous for the MTHFR 677C --> T mutation may be at risk for greater elevations in plasma tHcy in response to moderately low folate intake as compared with individuals with the normal or heterozygous genotypes.

Plasma homocyst(e)ine concentrations in pregnant and nonpregnant women with controlled folate intake.

OBJECTIVE: To assess the effects of folate intake and pregnancy on plasma total homocyst(e)ine concentrations in women during the second trimester of pregnancy compared with young, healthy nonpregnant women. METHODS: The diet provided either 450 or 850 microg of folate per day. These levels are approximately the current (400 microg/day) and previous (800 microg/day) Recommended Dietary Allowances for folate in pregnant women. Folate was provided as both food folate (120 microg/day) and supplemental folic acid (either 330 or 730 microg/day) for a period of 12 weeks. Plasma homocyst(e)ine (sum of free and protein-bound homocysteine), serum folate, and erythrocyte folate concentrations were determined weekly. RESULTS: Homocyst(e)ine concentrations were lower in pregnant women during the second trimester of normal pregnancy than in nonpregnant controls, independent of dietary folate intake. The overall mean (+/- standard deviation) homocyst(e)ine concentration of the pregnant subjects (5.4 +/- 1.4 micromol/L) was significantly lower than that observed in the nonpregnant control group (8.7 +/- 1.7 micromol/L) (P < .0001). This difference in homocyst(e)ine concentrations remained constant throughout the 12 weeks of the investigation. CONCLUSION: The folate intakes in this investigation were adequate to maintain constant homocyst(e)ine concentrations in pregnant and nonpregnant women. The lower homocyst(e)ine concentrations observed in pregnant subjects compared with nonpregnant controls may be a physiologic response to pregnancy.

Autonomous epicardial and endocardial boundary detection in echocardiographic short-axis images.

An autonomous endocardial and epicardial boundary detection (ABD) method is reported. One hundred ten cycles from 55 clinical studies were selected retrospectively. Image sequences were digitized at 512 x 480 pixel resolution. The point-by-point boundary positions of the ABD and the areas enclosed were compared with positions and enclosed areas drawn by three independent observers. Correlation coefficients for epicardial end-diastolic (ED) and end-systolic (ES) areas, endocardial ED and ES areas, muscle area, and fractional area change were 0.970, 0.976, 0.951, 0.985, 0.887, and 0.878, respectively. Bland-Altman analysis showed negligible biases with standard deviations comparable to those of the observers. The mean difference between the ABD border and the consensus observer border positions in 64 directions falls within the mean range of interobserver border positions, suggesting that shape is also well defined by the ABD.

Teaching hypothesis-oriented thinking to medical students: the University of Florida's clinical investigation program.

Recent studies show alarming decreases in the proportions of physicians applying for federal resources and of graduating medical students who declare strong interest in pursuing careers as physician-scientists. To expose medical students in their formative years to hypothesis-driven experimental investigations in a clinical setting, the first-year curriculum at the University of Florida has involved students as both investigators and study subjects in patient-oriented research conducted in the General Clinical Research Center (GCRC). Each year a hypothesis-driven experiment is conceived by first-year medical students in the university's MD-PhD program. Later in the year, the protocol is implemented in the GCRC by the entire freshman class, whose members serve as volunteer study subjects or as investigators. The experimental data are analyzed by the MD-PhD students, who report their findings at national biomedical research meetings and submit a manuscript on their project to a peer-reviewed journal. The authors describe students' research projects over the first six years of this GCRC-based program. They also describe the responses of former students to a questionnaire about their perceptions of the value of the research program. Most respondents considered the GCRC research exercise to have been useful and relevant to their overall education, and many more declared a current interest in pursuing research careers compared with the number who had declared such interest as freshmen. The authors conclude that early integration of hands-on, patient-oriented research into the medical school curriculum is a positive educational experience for students, and may contribute to their ultimate pursuit of academic research careers.

Epidemiologic and outcome studies of patients who received platelet transfusions in the neonatal intensive care unit.

STUDY DESIGN: We conducted a historic cohort study of neonates who received platelet transfusions at the National Institute of Perinatology, Mexico City, from January 1997 to May 2000. We obtained descriptive and outcome data, and assessed demographic and laboratory means of predicting "good candidates" for a future recombinant thrombopoietin (rTpo) trial. RESULTS: A minority of the transfused patients (11.4%) received only one transfusion; the majority (88.6%) received multiple transfusions. Neonates who received one or more platelet transfusions were more likely to die (24.5% mortality) than neonates who received no platelet transfusions (3.7% mortality). Regression analyses indicated that the presence of liver disease was the best predictor of a "good candidate" for rTpo administration. CONCLUSION: The majority of neonates in our institution who receive platelet transfusions receive multiple, not single, transfusions. Receiving any platelet transfusion is a marker for high risk of death. Neonates with liver disease who receive platelet transfusions might be a reasonable group for a phase I rTpo trial.

The relationship between hematocrit and bleeding time in very low birth weight infants during the first week of life.

OBJECTIVES: The bleeding time is a measurement of platelet and capillary interaction following a small standardized cutaneous incision. In adults, anemia causes a prolongation of the bleeding time, and we hypothesized that the same would be true in very low birth weight (VLBW) infants during their first week of life. STUDY DESIGN: Template bleeding times, using the Surgicutt Newborn device, were performed on 20 VLBW weight infants 0.28 l/l had no significant reduction in bleeding time following transfusion. CONCLUSIONS: In VLBW infants, during their first week of life (the time when their risk of intraventricular hemorrhage is greatest), a low hematocrit is associated with a significant prolongation in the bleeding time.

Nurse-physician collaboration and satisfaction with the decision-making process in three critical care units.

OBJECTIVE: To assess and compare levels of nurse-physician collaboration and satisfaction with the decision-making process as reported by critical care nurses, resident physicians (residents), and attending physicians (attendings) in making decisions to transfer individual patients out of the critical care unit, and to assess if satisfaction predicts nurse retention. DESIGN: Longitudinal descriptive correlational study using self-reporting instruments. SETTINGS: A university hospital's surgical ICU, a community teaching hospital's medical ICU, and a community hospital's mixed ICU. SUBJECTS: Eighty-one nurses, 23 residents, and 37 attendings from the surgical ICU; 44 nurses and 51 residents from the medical ICU; 25 nurses and 45 attendings from the community hospital's ICU, reporting on the transfers of 473, 465, and 494 patients, respectively. MAIN OUTCOME MEASURES: Healthcare providers' reported levels of collaboration and satisfaction with the decision-making process, the correlations between collaboration and satisfaction, and nurse retention. RESULTS: Nurses and physicians within sites (except attendings from the surgical ICU) reported similarly moderate amounts of collaboration, but nurses reported less satisfaction with decision making than did physicians in all sites. Collaboration was related to satisfaction with decision making for all providers, but more strongly for nurses. The strength of the relationship for nurses was similar in all sites. Nurses' satisfaction with decision making did not predict their retention. CONCLUSIONS: Collaboration between nurses and physicians is a more important component of satisfaction with decision making for nurses than for physicians. Any interventions to change the amount of collaboration in practice must take account of this difference.

Bootstrap-type confidence intervals for quantiles of the survival distribution.

In this paper we outline and illustrate an easy to program method for analytically calculating both parametric and non-parametric bootstrap-type confidence intervals for quantiles of the survival distribution based on right censored data. This new approach allows for the incorporation of covariates within the framework of parametric models. The procedure is based upon the notion of fractional order statistics and is carried forth using a simple beta transformation of the estimated survival function (parametric or non-parametric). It is the only direct method currently available in the sense that all other methods are based on inverting test statistics or employing confidence intervals for other survival quantities. We illustrate that the new method has favourable coverage probabilities for median confidence intervals as compared to six other competing methods.

Dose-response relationship of megakaryocyte progenitors from the bone marrow of thrombocytopenic and non-thrombocytopenic neonates to recombinant thrombopoietin.

Megakaryocyte (MK) progenitors from the marrow of adults undergo dose-dependent clonogenic proliferation in response to recombinant thrombopoietin (rTpo). It is unknown whether progenitors from the marrow of thrombocytopenic neonates display rTpo dose-dependent proliferation and whether they are more or less sensitive to rTpo than progenitors from non-thrombocytopenic neonates or adults. To assess this, we cultured marrow from four thrombocytopenic and four non-thrombocytopenic neonates, and from six healthy adults, in a serum-free system in the presence of increasing concentrations of rTpo (0-100 ng/ml). Marrow from the thrombocytopenic and non-thrombocytopenic neonates generated three times more MK colonies/105 light density cells (129 +/- 39 and 167 +/- 30 respectively) than marrow from adults (54 +/- 30, P < 0.0001) at a rTpo concentration of 50 ng/ml. Neonatal and adult samples had a rTpo dose-dependent increase in MK colonies. However, neonates reached a maximal number of colonies at a rTpo concentration of 10 ng/ml, compared with 50 ng/ml in adults, resulting in a larger area under the rTpo dose-response curve for neonatal progenitors (P = 0. 0047). Neonates also generated more large MK colonies than the adults (24% vs. 2% at 100 ng/ml).

Pharmacokinetics, pharmacodynamics, and safety of administering pegylated recombinant megakaryocyte growth and development factor to newborn rhesus monkeys.

Thrombocytopenia is common among sick neonates. Certain groups of thrombocytopenic adults respond favorably to the administration of recombinant thrombopoietin or to pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a recombinant human polypeptide that contains the receptor-binding N-terminal domain of thrombopoietin. The effectiveness and safety of such treatment in neonates, however, have not been reported. The purpose of the present study was to determine the biologic activity and safety of PEG-rHuMGDF administration to newborn rhesus monkeys. Eight monkeys were divided into four groups and treated subcutaneously with 0.00, 0.25, 1.00, or 2.50 microg/kg once daily for 7 d. Complete blood counts, serum chemistries, clotting panels, and MGDF levels were followed serially, and hematopoietic progenitor cell assays were performed on bone marrow aspirates before the first dose and again on d 8. Pharmacokinetic evaluations were performed on the animals that received the highest dose of PEG-rHuMGDF. All monkeys had normal growth during the study period, and all chemistries, clotting studies, and blood pressure measurements were normal. The peak serum MGDF concentration occurred at 3 h, and the half-life was 8.4 to 13.0 h. As in adult rhesus monkeys, platelet counts in the treated neonates began to rise on d 6, peaked on d 11, and returned to baseline by d 23. The two highest doses generated an 8- to 12-fold increase in platelets, whereas those treated with 0.25 microg/kg had a 6-fold increase. Other hematologic parameters measured were unaffected. Thus, newborn monkeys responded to doses of PEG-rHuMGDF that were similar to or smaller than (per kilogram body weight) those that are effective in adult animals and did so without obvious short-term toxicity.

Folate catabolism in pregnant and nonpregnant women with controlled folate intakes.

Measurement of the urinary folate catabolites, para-aminobenzoylglutamate (pABG) and the more predominant acetylated form, acetamidobenzoylglutamate (apABG), has been used to assess folate requirements in both pregnant and nonpregnant women. Folate catabolite excretion has been reported to be significantly higher in pregnant women (second trimester) compared with nonpregnant controls. The primary goals of this study were to determine if pregnant women in a controlled metabolic study excreted higher quantities of urinary folate catabolites than nonpregnant controls and if catabolite excretion was influenced by folate intake. We evaluated the effect of gestation and folate intake on the urinary excretion of apABG and pABG in pregnant women (n = 12; wk 14-26 gestation) and nonpregnant controls (n = 12) assigned to consume folate levels approximating the current (400 microg/d) and previous (800 microg/d) RDA. Subjects were fed a controlled diet containing 120 microg folate/d and either 330 or 730 microg synthetic folic acid/d. In contrast to previously reported data, no differences in mean folate catabolite excretion were detected between pregnant and nonpregnant subjects. Catabolite excretion (pABG + apABG) decreased significantly relative to initial values in pregnant women consuming 450 microg folate/d (-40 +/- 20%; mean +/- SD) and final mean excretion was significantly lower in the pregnant women consuming 450 microg folate/d (86 +/- 32 nmol/d) compared with 850 microg folate/d (148 +/- 20 nmol/d). Data from this study indicate that second trimester pregnant women do not excrete more folate catabolites than nonpregnant controls and that consumption of 450 vs. 850 microg folate/d results in a significant reduction in the quantity of folate catabolites excreted.

Plasma thrombopoietin concentrations in thrombocytopenic and non-thrombocytopenic patients in a neonatal intensive care unit.

Thrombocytopenia is a frequent occurrence in the neonatal intensive care unit (NICU), but the role of thrombopoietin (Tpo) in the pathophysiology is unknown. We obtained serial plasma Tpo concentrations in 20 thrombocytopenic neonates in our NICU, and performed bone marrow studies in 15. The initial Tpo levels ranged from undetectable (<41 pg/ml) to 1112 pg/ml and did not correlate with gestational age or platelet count. Neonates with decreased marrow megakaryocytes did not have plasma Tpo levels as high as those reported in adults, particularly in small for gestational age infants (Tpo < 300 pg/ml). In 14/15 neonates followed until resolution, the Tpo concentration decreased as the platelet count increased.

Folate status response to controlled folate intake in pregnant women.

A metabolic study (84-d) was conducted to investigate the folate status response of pregnant subjects (n = 12) during their second trimester and nonpregnant controls (n = 12) to folate intakes approximating the current (400 microg/d) and former (800 microg/d) recommended dietary allowance (RDA). The overall goal of the study was to provide metabolic data to assist in the interpretation of the current RDA for folate. Subjects were fed a controlled diet containing 120 +/- 15 microg/d (mean +/- SD) folate and either 330 or 730 microg/d synthetic folic acid. Outcome variables between and within supplementation groups were compared at steady state. Serum folate was higher (P 0.05) were detected in serum folate between pregnant and nonpregnant women within the same supplementation group. Urinary 5-methyl-tetrahydrofolate excretion was greater (P 0.05) in 5-methyl-tetrahydrofolate excretion were detected between pregnant and nonpregnant women within supplementation groups. Differences (P

Titration emulation: a computer-assisted technique that simplifies the quantification of anti-dsDNA antibodies using the Crithidia luciliae assay.

Titers of anti-double-stranded (ds) DNA antibodies in sera from patients with systemic lupus erythematosus (SLE) using the Crithidia luciliae assay method were compared by conventional titration vs the titration emulation method (ImageTiter) to evaluate whether the latter assay can replace manual titration. Titers by the two methods were identical or within one dilution in 98% (41/42) of samples. A single sample showed a two-dilution difference. Titration emulation showed a tendency to under-estimate the titer of high titer anti-dsDNA samples, although the difference was small. Titration emulation is a suitable alternative to the conventional titration method, offering an accurate and cost-effective approach to quantification of anti-dsDNA antibodies.

Origin and fate of erythropoietin in human milk.

Erythropoietin (Epo) is a normal constituent of human milk, but the origin and fate of this cytokine in milk are not known. Regarding its origin, we hypothesized that cells of the mammary gland secrete Epo into milk actively and, therefore, that concentrations in milk do not correlate with concentrations in serum. Regarding its fate, we hypothesized that Epo concentrations in milk change with time postpartum and that Epo in milk is protected from digestion in the neonatal gastrointestinal tract. To address these issues, we measured Epo concentrations in 103 milk samples (ELISA), 55 of which were paired with serum. Mammary duct epithelial cells were evaluated as a source of Epo by breast tissue immunohistochemistry and by cell culture. Circulating and milk Epo were compared by Western analysis to detect size differences, possibly reflecting differences in processing. Epo stability in simulated conditions of digestion was evaluated. We observed that milk Epo concentrations increase as a function of duration of breast-feeding and have a negative correlation with serum Epo or milk protein concentration. Mammary duct epithelial cells from breast biopsies of lactating women had marked immunoreactivity to Epo, but such activity was minimal to absent in nonlactating breast tissue. Further evidence that mammary duct epithelia produce Epo was obtained by observing Epo mRNA and protein expression in cultured human mammary epithelial cells. The molecular size of Epo in milk and serum is identical. Recombinant Epo added to human milk or commercial infant formulas was relatively stable in conditions that simulate gastric and small intestinal conditions of newborn infants; however, recombinant Epo added to D(5)W was not protected from digestion. We conclude that Epo concentrations in milk increase as a function of the duration of breast feeding, that Epo is actively secreted into human milk by mammary duct epithelia, and that the Epo within milk is largely protected from digestion.

Granulocyte colony-stimulating factor serum and urine concentrations in neutropenic neonates before and after intravenous administration of recombinant granulocyte colony-stimulating factor.

BACKGROUND: Recombinant granulocyte colony-stimulating factor (rG-CSF) has been suggested as a treatment for certain varieties of neonatal neutropenia, but little is known about the pharmacologic disposition of rG-CSF in that population. METHODS: Ten neutropenic neonates were treated with rG-CSF, 10 micrograms/kg intravenously once daily for 3 to 5 days. Serum and urine samples were obtained before rG-CSF dosing and at intervals thereafter for G-CSF quantification by enzyme-linked immunosorbent assay. RESULTS: Five of the neutropenic neonates (termed group 1) were not infected but likely had hyporegenerative neutropenia (4 were born after pregnancy-induced hypertension/intrauterine growth restriction, and 1 had Rh hemolytic disease). Five other infants (group 2) had neutropenia accompanying bacterial sepsis and shock. Before receiving the first dose of rG-CSF, endogenous G-CSF serum and urine concentrations were relatively low in group 1, averaging 130 pg/mL (range: 48-209) in serum and 53 pg/mL (range: 15-141) in urine. Serum concentrations immediately before the final dose were much higher (range: 81-24 835 pg/mL), whereas urine concentrations were unchanged (range: <7 pg/mL-126 pg/mL). In group 2 patients, before receiving the first-dose of rG-CSF, endogenous concentrations were very high, averaging 59 575 pg/mL (range: 20 028-98 280) in serum and 3189 pg/mL (range: 23-4770) in urine. Predose serum concentrations before the final dose (range: 427-14 460 pg/mL) were lower than before the first dose. The area under the concentration curve after the first dose of rG-CSF administration in group 1 was significantly lower than after the first dose in group 2, but no difference in area under the concentration curve was observed between groups 1 and 2 after the last dose of rG-CSF. SPECULATION: The principal means of clearing G-CSF from the serum is by saturable binding to specific G-CSF receptors (G-CSF-Rs). Therefore, the very high G-CSF serum and urine concentrations of group 2 patients before the first rG-CSF dose implies that their G-CSF-Rs were saturated before the dose was given. We speculate that if G-CSF-Rs are saturated with endogenous G-CSF, treatment with rG-CSF will add little or nothing to the granulocytopoietic effort. On this basis, we judge that neonates with septic shock and neutropenia are unlikely to derive benefit from rG-CSF administration.

The importance of cerebrospinal fluid lactate in the evaluation of congenital lactic acidosis.

In 27 of 28 children with congenital lactic acidosis, cerebrospinal fluid lactate was higher than venous blood lactate. The mean +/- SEM difference between these variables was 2.4 +/- 0.3 mmol/L (P =.0001). Girls or patients with pyruvate dehydrogenase deficiency had higher cerebrospinal fluid lactate concentrations than boys or patients with respiratory chain defects or mitochondrial DNA mutations.