Autologous umbilical cord blood infusion followed by oral docosahexaenoic acid and vitamin D supplementation for C-peptide preservation in children with Type 1 diabetes.

We sought to determine if autologous umbilical cord blood (UCB) infusion followed by 1 year of supplementation with vitamin D and docosahexaenoic acid (DHA) can preserve C-peptide in children with type 1 diabetes. We conducted an open-label, 2:1 randomized study in which 15 type 1 diabetes subjects with stimulated C-peptide > .2 pmol/mL received either (1) autologous UCB infusion, 1 year of daily oral vitamin D (2000 IU), and DHA (38 mg/kg) and intensive diabetes management or (2) intensive diabetes management alone. Primary analyses were performed 1 year after UCB infusion. Treated (N = 10) and control (N = 5) subjects had median ages of 7.2 and 6.6 years, respectively. No severe adverse events were observed. Although the absolute rate of C-peptide decline was slower in treated versus control subjects, intergroup comparisons failed to reach significance (P = .29). Area under the curve C-peptide declined and insulin use increased in both groups (P < .01). Vitamin D levels remained stable in treated subjects but declined in control subjects (P = .01). DHA levels rose in treated subjects versus control subjects (P = .003). CD4/CD8 ratio remained stable in treated subjects but declined in control subjects (P = .03). No changes were seen in regulatory T cell frequency, total CD4 counts, or autoantibody titers. Autologous UCB infusion followed by daily supplementation with vitamin D and DHA was safe but failed to preserve C-peptide. Lack of significance may reflect small sample size. Future efforts will require expansion of specific immunoregulatory cell subsets, optimization of combined immunoregulatory and anti-inflammatory agents, and larger study cohorts.

Validation of anamnestic diagnostic criteria for recurrent aphthous stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is characterized by painful recurrent oral ulcers and is typically diagnosed via history and clinical examination. Our aim was to validate a set of anamnestic diagnostic criteria (RASDX) to increase the accuracy of RAS diagnosis, particularly when a clinical examination is not feasible. METHODS: Participants were enrolled during an unmatched case-control study. RASDX consisted of an initial phone screening using standardized questionnaires and recognition of RAS photographs in the clinic. The proportion of agreement with an examination by an oral medicine expert was calculated. RESULTS: A total of 115 participants were scheduled for a clinical diagnostic visit and 11 were withdrawn. The remaining 104 participants were aged 18-50 years, 54% women, 64% White and 20% Hispanic. Of these, all 49 controls with negative RASDX had no clinical ulcers. Of the 54 cases diagnosed with RAS by RASDX, 53 were clinically confirmed to have RAS lesions (99% agreement; exact one-sided 95% CI = 95-100%). CONCLUSIONS: RASDX, based on a combination of history and photograph recognition, was highly accurate compared with a diagnosis that employed an oral examination.

Immune biomarker panel monitoring utilizing IDO enzyme activity and CD4 ATP levels: prediction of acute rejection vs. viral replication events.

Infections have become as important an event as acute rejection posttransplant for long-term allograft survival. Less invasive biomarkers tested so far predict risk for one event or the other, not both. We prospectively tested blood and urine monthly for 12 months posttransplant from children receiving a kidney transplant. The IDO enzyme pathway was assessed by MS assays using the ratio of product l-kyn to substrate trp. Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with acute rejection or major infection events or stable group (no events) in the next 30 days. The 25 subjects experienced six discrete episodes of acute rejection in five subjects and 16 discrete events of major infection in 14 subjects (seven BK viruria, six cytomegaloviremia, one EB and cytomegaloviremia, and two transplant pyelonephritis). Mean serum kyn/trp ratios were significantly elevated in the group that experienced acute rejection (p = 0.02). Within-subject analyses revealed that over time, urine kyn/trp ratios showed an increase (p = 0.01) and blood CD4-ATP levels showed a decrease (p = 0.007) prior to a major infection event. These pilot results suggest that a panel of biomarkers together can predict over- or under-immunosuppression, but need independent validation.

Vascular dysfunction in glycogen storage disease type I.

OBJECTIVE: To determine cardiovascular disease risk in a larger cohort of patients with glycogen storage disease (GSD) I through the use of noninvasive measures of arterial function and anatomy. STUDY DESIGN: Carotid intima media thickness (IMT), radial artery tonometry, and brachial artery reactivity were performed in 28 patients with GSD I (13F/15M, mean age 23 years) and 23 control subjects (19F/4M, mean age 23 years). RESULTS: The primary outcome measure, mean left distal IMT was greater in the GSD cohort (0.500+/-0.055 mm) than in the control group (0.457+/-0.039 mm) (P= .002, adjusted for age, sex, and body mass index). Mean augmentation index measured by radial artery tonometry was higher in the GSD cohort (16.4%+/-14.0%) than in the control group (2.4%+/-8.7%) (P< .001). No significant difference was observed between mean brachial artery reactivity in the GSD cohort (6.3%+/-4.9% change) versus control subjects (6.6%+/-5.1% change) (P= .46). CONCLUSIONS: GSD I is associated with arterial dysfunction evident by increased IMT and augmentation index. Patients with GSD I may be at increased risk for cardiovascular disease.

Production of 1-carbon units from glycine is extensive in healthy men and women.

Glycine undergoes decarboxylation in the glycine cleavage system (GCS) to yield CO(2), NH(3), and a 1-carbon unit. CO(2) also can be generated from the 2-carbon of glycine by 10-formyltetrahydrofolate-dehydrogenase and, after glycine-to-serine conversion by serine hydroxymethyltransferase, from the tricarboxylic acid cycle. To evaluate the relative fates of glycine carbons in CO(2) generation in healthy volunteers (3 male, 3 female, aged 21-26 y), primed, constant infusions were conducted using 9.26 micromol x h(-1) x kg(-1) of [1,2-(13)C]glycine and 1.87 micromol x h(-1) x kg(-1) of [5,5,5-(2)H(3)]leucine, followed by an infusion protocol using [1-(13)C]glycine as the glycine tracer. The time period between the infusion protocols was >6 mo. In vivo rates of whole-body glycine and leucine flux were nearly identical in protocols with [1,2-(13)C]glycine and [5,5,5-(2)H(3)]leucine and with [1-(13)C]glycine and [5,5,5-(2)H(3)]leucine tracers, which showed high reproducibility between the tracer protocols. Using the [1-(13)C]glycine tracer, breath CO(2) data showed a total rate of glycine decarboxylation of 96 +/- 8 micromol x h(-1) x kg(-1), which was 22 +/- 3% of whole-body glycine flux. In contrast, infusion of [1,2-(13)C]glycine yielded a glycine-to-CO(2) flux of 146 +/- 37 micromol x h(-1) x kg(-1) (P = 0.026). By difference, this implies a rate of CO(2) formation from the glycine 2-carbon of 51 +/- 40 micromol x h(-1) x kg(-1), which accounts for approximately 35% of the total CO(2) generated in glycine catabolism. These findings also indicate that approximately 65% of the CO(2) generation from glycine occurs by decarboxylation, primarily from the GCS. Further, these results suggest that the GCS is responsible for the entry of 5,10-methylenetetrahydrofolate into 1-carbon metabolism at a very high rate ( approximately 96 micromol x h(-1) x kg(-1)), which is approximately 20 times the demand for methyl groups for homocysteine remethylation.

The effects of local anesthetic concentration and dose on continuous infraclavicular nerve blocks: a multicenter, randomized, observer-masked, controlled study.

BACKGROUND: It remains unclear whether local anesthetic concentration or total drug dose is the primary determinant of continuous peripheral nerve block effects. The only previous investigation, involving continuous popliteal-sciatic nerve blocks, specifically addressing this issue reported that insensate limbs were far more common with higher volumes of relatively dilute ropivacaine compared with lower volumes of relatively concentrated ropivacaine. However, it remains unknown if this relationship is specific to the sciatic nerve in the popliteal fossa or whether it varies depending on anatomic location. We therefore tested the null hypothesis that providing ropivacaine at different concentrations and rates, but at an equal total basal dose, produces comparable effects when used in a continuous infraclavicular brachial plexus block. METHODS: Preoperatively, an infraclavicular catheter was inserted using the coracoid approach in patients undergoing moderately painful orthopedic surgery distal to the elbow. Patients were randomly assigned to receive a postoperative perineural ropivacaine infusion of either 0.2% (basal 8 mL/h, bolus 4 mL) or 0.4% (basal 4 mL/h, bolus 2 mL) through the second postoperative day. Both groups, therefore, received 16 mg of ropivacaine each hour with a possible addition of 8 mg every 30 min via a patient-controlled bolus dose. Our primary end point was the incidence of an insensate limb during the 24-h period beginning the morning after surgery. Secondary end points included analgesia and patient satisfaction. RESULTS: Patients given 0.4% ropivacaine (n = 27) experienced an insensate limb, a mean (sd) of 1.8 (1.6) times, compared with 0.6 (0.9) times for subjects receiving 0.2% ropivacaine (n = 23; estimated difference = 1.2 episodes, 95% confidence interval, 0.5-1.9 episodes; P = 0.001). Satisfaction with postoperative analgesia (scale 0-10, 10 = highest) was scored a median (25th-75th percentiles) of 10.0 (8.0-10.0) in Group 0.2% and 7.0 (5.3-8.9) in Group 0.4% (P = 0.018). Analgesia was similar in each group. CONCLUSIONS: For continuous infraclavicular nerve blocks, local anesthetic concentration and volume influence perineural infusion effects in addition to the total mass of local anesthetic administered. Insensate limbs were far more common with smaller volumes of relatively concentrated ropivacaine. This is the opposite of the relationship previously reported for continuous popliteal-sciatic nerve blocks. The interaction between local anesthetic concentration and volume is thus complex and varies among catheter locations.

Effect of alternative chest compression techniques in infant and child on rescuer performance.

OBJECTIVE: Current chest compression (CC) guidelines for an infant recommend a two-finger (TF) technique with lone rescuer and a two- thumb (TT) technique with two rescuers, and for a child either an one hand (OH) or a two hand (TH) technique with one or two rescuers. The effect of a 30:2 compression:ventilation ratio using these techniques on CC quality and rescuer fatigue is unknown. We hypothesized that during lone rescuer CC, TT technique, in infant and TH in child achieve better compression depth (CD) without additional rescuer fatigue compared with TF and OH, respectively. DESIGN: Randomized observational study. SETTING: University-affiliated pediatric hospital. SUBJECTS: Adult healthcare providers certified in basic life support or pediatric advanced life support. INTERVENTIONS: Laerdal baby advanced life support trainer and Resusci junior manikin were modified to digitally record CD, compression pressure (CP) and compression rate. Sixteen subjects were randomized to each of the four techniques to perform 5 minutes of lone rescuer 30:2 compression:ventilation cardiopulmonary resuscitation. Rescuer heart rate (HR) and respiratory rate were recorded continuously and the recovery time interval for HR/respiratory rate to return to baseline was determined. Subjects were blinded to data recording. Groups were compared using two-sample, two-sided Student's t tests. MEASUREMENTS AND MAIN RESULTS: Two-thumb technique generated significantly higher CD and peak CP compared with TF (p < 0.001); there was no significant difference between OH vs. TH. TF showed decay of CD and CP over time compared with TT. Compression rate (per minute) and actual compressions delivered were not significantly different between groups. No significant differences in fatigue and recovery time were observed, except the TT group had greater increase in the rescuer's HR (bpm) from baseline compared with TF group (p = 0.04). CONCLUSIONS: Two-thumb compression provides higher CD and CP compared with TF without any evidence of decay in quality and additional rescuer fatigue over 5 minutes. There was no significant difference in child CC quality or rescuer fatigue between OH and TH. Two-thumb technique is preferred for infant CC and our data support the current guidelines for child CC.

Elevated serum insulin-like growth factor 1 in recurrent aphthous stomatitis.

Over 100 million Americans experience recurrent aphthous stomatitis (RAS) at some point in life. To develop targeted drugs for RAS treatment, it is critical to identify its etiology. We determined if serum insulin-like growth factor 1 (IGF-1) and related factors are associated with RAS, because both RAS prevalence and IGF-1 are highest during puberty. We analyzed data from 1,480 Third National Health and Nutrition Examination Survey participants aged 20-40 years. Participants with a history of diabetes or lupus, cotinine levels 6 ng/ml or higher or glycemia 110 mg/dl or higher were excluded. We compared levels of IGF-1, IGFBP-3, leptin, and insulin in participants with a positive vs. negative RAS history in the prior 12 months. We used logistic regression in SAS/SUDAAN to account for the complex sampling design. The odds of a positive RAS history were 1.31 times higher for every 100 ng/ml increase in serum IGF-1. This association persisted after adjustment for age, race/ethnicity, medication intake, body mass index, insulin, leptin, glycemia, and income (adjusted OR = 1.30, 95% CI [1.06, 1.60]; p = 0.013). The odds of a positive RAS history were also higher among non-Hispanic white compared with non-Hispanic black participants (adjusted OR = 4.37, 95% CI [3.00, 6.38]). Leptin, IGFBP-3, and insulin levels did not differ by RAS status. The significantly higher IGF-1 levels in participants with a positive RAS history compared with controls suggest a possible role of the IGF-1 pathway in RAS etiology.

Ambulatory continuous femoral nerve blocks decrease time to discharge readiness after tricompartment total knee arthroplasty: a randomized, triple-masked, placebo-controlled study.

BACKGROUND: The authors tested the hypotheses that, compared with an overnight continuous femoral nerve block (cFNB), a 4-day ambulatory cFNB increases ambulation distance and decreases the time until three specific readiness-for-discharge criteria are met after tricompartment total knee arthroplasty. METHODS: Preoperatively, all patients received a cFNB (n = 50) and perineural ropivacaine 0.2% from surgery until the following morning, at which time they were randomly assigned to either continue perineural ropivacaine or switch to perineural normal saline. Primary endpoints included (1) time to attain three discharge criteria (adequate analgesia, independence from intravenous analgesics, and ambulation of at least 30 m) and (2) ambulatory distance in 6 min the afternoon after surgery. Patients were discharged with their cFNB and a portable infusion pump, and catheters were removed on postoperative day 4. RESULTS: Patients given 4 days of perineural ropivacaine attained all three discharge criteria in a median (25th-75th percentiles) of 25 (21-47) h, compared with 71 (46-89) h for those of the control group (estimated ratio, 0.47; 95% confidence interval, 0.32-0.67; P <0.001). Patients assigned to receive ropivacaine ambulated a median of 32 (17-47) m the afternoon after surgery, compared with 26 (13-35) m for those receiving normal saline (estimated ratio, 1.21; 95% confidence interval, 0.71-1.85; P = 0.42). CONCLUSIONS: Compared with an overnight cFNB, a 4-day ambulatory cFNB decreases the time to reach three important discharge criteria by an estimated 53% after tricompartment total knee arthroplasty. However, the extended infusion did not increase ambulation distance the afternoon after surgery. (ClinicalTrials.gov No. NCT00135889.).

Ambulatory continuous posterior lumbar plexus nerve blocks after hip arthroplasty: a dual-center, randomized, triple-masked, placebo-controlled trial.

BACKGROUND: The authors tested the hypotheses that after hip arthroplasty, ambulation distance is increased and the time required to reach three specific readiness-for-discharge criteria is shorter with a 4-day ambulatory continuous lumbar plexus block (cLPB) than with an overnight cLPB. METHODS: A cLPB consisting of 0.2% ropivacaine was provided from surgery until the following morning. Patients were then randomly assigned either to continue ropivacaine or to be switched to normal saline. Primary endpoints included (1) time to attain three discharge criteria (adequate analgesia, independence from intravenous analgesics, and ambulation > or = 30 m) and (2) ambulatory distance in 6 min the afternoon after surgery. Patients were discharged with their cLPB and a portable infusion pump, and catheters were removed on the fourth postoperative day. RESULTS: Patients given 4 days of perineural ropivacaine (n = 24) attained all three discharge criteria in a median (25th-75th percentiles) of 29 (24-45) h, compared with 51 (42-73) h for those of the control group (n = 23; estimated ratio = 0.62; 95% confidence interval, 0.45-0.92; P = 0.011). Patients assigned to receive ropivacaine ambulated a median of 34 (9-55) m the afternoon after surgery, compared with 20 (6-46) m for those receiving normal saline (estimated ratio = 1.3; 95% confidence interval, 0.6-3.0; P = 0.42). Three falls occurred in subjects receiving ropivacaine (13%), versus none in subjects receiving normal saline. CONCLUSIONS: Compared with an overnight cLPB, a 4-day ambulatory cLPB decreases the time to reach three predefined discharge criteria by an estimated 38% after hip arthroplasty. However, the extended infusion did not increase ambulation distance to a statistically significant degree.

Chest compression quality and rescuer fatigue with increased compression to ventilation ratio during single rescuer pediatric CPR.

OBJECTIVE: The effects of the recommended 30:2 compression:ventilation (C:V) ratio on chest compression rate (CR), compression depth (CD), compression pressure (CP) and rescuer fatigue is unknown during pediatric CPR. We hypothesized that a 30:2 C:V ratio will decrease compression depth and compression pressure and increase rescuer fatigue compared with a 15:2 ratio. DESIGN: Randomized crossover observational study. METHODS: Adolescent, child and infant manikins were modified to digitally record compression rate, compression depth, compression pressure and total compression cycles (CC). BLS or PALS certified volunteers were randomized to five CPR groups: adolescent (AD), child 1-hand (OH), child 2-hand (TH), infant two-finger (TF) and infant two-thumb (TT). Each rescuer performed each ratio for 5 min with the order randomized. Rescuer heart rate (HR) and respiratory rate (RR) were recorded continuously during CPR and used to determine the recovery time (RT) for HR/RR to return to baseline. Data (mean+/-S.D.) were contrasted by paired differences for quantitative data and the sign rank test for ordinal data. RESULTS: Eighty subjects (16 per group) were randomized. The peak compression pressure and compression rate were not different within any group, but total compression cycle were higher in all 30:2 groups. Compression depth (mm) was not significantly different within any group. The rescuer's HR (bpm) increased significantly during 30:2 CPR in AD and OH group with no significant differences in RR and recovery time. Subjects reported that 15:2 CPR was easier to perform (P<0.001). CONCLUSION: During single rescuer pediatric BLS, more compression cycles were achieved with 30:2 C:V ratio without effect on compression depth, pressure and rate. Increased HR with 30:2 C:V ratio was noted during larger manikin CPR without subjective difference of reported fatigue. Most rescuers in AD and TF group did not achieve recommended compression depth regardless of C:V ratio.

The effects of varying local anesthetic concentration and volume on continuous popliteal sciatic nerve blocks: a dual-center, randomized, controlled study.

BACKGROUND: It remains unknown whether local anesthetic concentration, or simply total drug dose, is the primary determinant of continuous peripheral nerve block effects. We therefore tested the null hypothesis that providing different concentrations and rates of ropivacaine, but at equal total doses, produces comparable effects when used in a continuous sciatic nerve block in the popliteal fossa. METHODS: Preoperatively, a perineural catheter was inserted adjacent to the sciatic nerve using a posterior popliteal approach in patients undergoing moderately painful orthopedic surgery at or distal to the ankle. Postoperatively, patients were randomly assigned to receive a perineural ropivacaine infusion of either 0.2% (basal 8 mL/h, bolus 4 mL) or 0.4% (basal 4 mL/h, bolus 2 mL) through the second postoperative day. Therefore, both groups received 16 mg of ropivacaine each hour with a possible addition of 8 mg every 30 min via a patient-controlled bolus dose. The primary end point was the incidence of an insensate limb, considered undesirable, during the 24-h period beginning the morning after surgery. Secondary end points included analgesia and patient satisfaction. RESULTS: Patients given 0.2% ropivacaine (n = 25) experienced an insensate limb with a mean (sd) of 1.8 (1.8) times, compared with 0.6 (1.1) times for subjects receiving 0.4% ropivacaine (n = 25; estimated difference = 1.2 episodes, 95% confidence interval, 0.3-2.0 episodes; P = 0.009). In contrast, analgesia and satisfaction were similar in each group. CONCLUSIONS: For continuous popliteal-sciatic nerve blocks, local anesthetic concentration and volume influence block characteristics. Insensate limbs were far more common with larger volumes of relatively dilute ropivacaine. During continuous sciatic nerve block in the popliteal fossa, a relatively concentrated solution in smaller volume thus appears preferable.

Neonatal heart rate variability and intraventricular hemorrhage: a case study.

PURPOSE: The purpose of this study was to compare heart rate variability (HRV) in low-risk, pre-term infants to one infant diagnosed with intraventricular hemorrhage (IVH). METHOD: A case study design was used to compare HRV of one subject diagnosed with IVH to a convenience sample of 38 low-risk, pre-term infants at 30 and 31 post-menstrual weeks of age. Heart periods were recorded for 300-s with the infant in an active sleep state. Heart rate variability was quantified by spectral analysis. A confidence interval comparison of the total spectral components (0.02-2.0 Hz), high-frequency components (0.20-2.0 Hz), and the low-frequency components (0.02-0.20 Hz) was conducted. FINDINGS: At 30 weeks' post-menstrual age, 10 days following diagnosis, with a grade-III IVH, the low frequency components were above the 90th percentile. One week later, at 31 weeks, the low frequency components had decreased to the 27th percentile range, and the total and high frequency components were at or below the 25th percentile range of the confidence intervals for the low-risk, pre-term infants. DISCUSSION: The neurobehavioral organization of pre-term infants is limited due to prematurity and the cumulative effect of medical complications (such as IVH). This study has implications for the use of HRV in the identification of infants diagnosed with IVH.

Cystic fibrosis transmembrane conductance regulator deficiency exacerbates islet cell dysfunction after beta-cell injury.

The cause of cystic fibrosis-related diabetes (CFRD) remains unknown, but cystic fibrosis transmembrane conductance regulator (CFTR) mutations contribute directly to multiple aspects of the cystic fibrosis phenotype. We hypothesized that susceptibility to islet dysfunction in cystic fibrosis is determined by the lack of functional CFTR. To address this, glycemia was assessed in CFTR null (CFTR(-/-)), C57BL/6J, and FVB/NJ mice after streptozotocin (STZ)-induced beta-cell injury. Fasting blood glucose levels were similar among age-matched non-STZ-administered animals, but they were significantly higher in CFTR(-/-) mice 4 weeks after STZ administration (288.4 +/- 97.4, 168.4 +/- 35.9, and 188.0 +/- 42.3 mg/dl for CFTR(-/-), C57BL/6J, and FVB/NJ, respectively; P < 0.05). After intraperitoneal glucose administration, elevated blood glucose levels were also observed in STZ-administered CFTR(-/-) mice. STZ reduced islets among all strains; however, only CFTR(-/-) mice demonstrated a negative correlation between islet number and fasting blood glucose (P = 0.02). To determine whether a second alteration associated with cystic fibrosis (i.e., airway inflammation) could impact glucose control, animals were challenged with Aspergillus fumigatus. The A. fumigatus-sensitized CFTR(-/-) mice demonstrated similar fasting and stimulated glucose responses in comparison to nonsensitized animals. These studies suggest metabolic derangements in CFRD originate from an islet dysfunction inherent to the CFTR(-/-) state.

Therapeutic potential of dichloroacetate for pyruvate dehydrogenase complex deficiency.

We reviewed the use of oral dichloroacetate (DCA) in the treatment of children with congenital lactic acidosis caused by mutations in the pyruvate dehydrogenase complex (PDC). The case histories of 46 subjects were analyzed with regard to diagnosis, clinical presentation and response to DCA. DCA decreased blood and cerebrospinal fluid lactate concentrations, and was generally well tolerated. DCA may be particularly effective in children with PDC deficiency by stimulating residual enzyme activity and, consequently, cellular energy metabolism. A controlled trial is needed to determine the definitive role of DCA in the management of this devastating disease.

Peripheral neuropathy in genetic mitochondrial diseases.

Peripheral neuropathy is an underrecognized but common occurrence in genetic mitochondrial disorders. To gain insight into the frequency and clinical presentation of this complication, nerve conduction studies were performed on 43 subjects with congenital lactic acidosis enrolled in a controlled clinical trial of oral dichloroacetate. Median and peroneal motor conduction studies and median and sural sensory conduction studies were performed on each patient. The mean amplitude of the peroneal motor nerve (P < 0.001) and the conduction velocities of the median (P < 0.001) and peroneal (P < 0.001) motor nerves were uniformly lower in our subjects than in healthy literature control subjects. There were no significant differences in sensory nerve conduction studies. A generalized reduction in motor nerve conduction velocity was the dominant electrophysiological abnormality in the patients in this study and was independent of age, sex, or congenital mitochondrial disorder. We postulate that cellular energy failure is the most likely common cause of peripheral neuropathy in patients with genetic mitochondrial diseases, owing to the high demand for adenosine triphosphate via aerobic carbohydrate metabolism by nerve tissue.

Assessing the relationship between preterm delivery and various microorganisms recovered from the lower genital tract.

OBJECTIVE: To determine if the likelihood of preterm delivery is more dependent on the specific organisms present in the vagina than on the presence of bacterial vaginosis. METHODS: We evaluated the vaginal fluid of a prospective cohort of women at 23-32 weeks of gestation with signs and symptoms of preterm labor and intact membranes. Forward stepwise logistic regression models were used to evaluate the relationship between preterm delivery and the presence of anaerobic bacteria, Gardnerella, ureaplasmas and mycoplasmas, and sialidase. RESULTS: The cohort included 137 women, and complete delivery information was available for 134 of them. The rate of preterm delivery was 28% (37 of 134). Mycoplasma genitalium independently was associated with spontaneous preterm delivery (OR 3.48; 95% CI 1.41, 8.57). After controlling for this factor, none of the other variables were significantly prognostic for spontaneous preterm delivery (residual overall p = 0.19). CONCLUSION: The presence of Mycoplasma genitalium in the vagina of pregnant women is an independent risk factor for spontaneous preterm delivery.

Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism.

BACKGROUND: A common genetic polymorphism [transcobalamin (TC) 776C-->G] may affect the function of transcobalamin, the protein required for vitamin B-12 cellular uptake and metabolism. Remethylation of homocysteine is dependent on the production of 5-methyltetrahydrofolate and adequate vitamin B-12 for the methionine synthase reaction. OBJECTIVES: The objectives were to assess the influence of the TC 776C--> G polymorphism on concentrations of the transcobalamin-vitamin B-12 complex (holo-TC) and to determine the combined effects of the TC 776C-->G and methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphisms and vitamin B-12 status on homocysteine concentrations. DESIGN: Healthy, nonpregnant women (n = 359; aged 20-30 y) were screened to determine plasma vitamin B-12, serum holo-TC, and plasma homocysteine concentrations and TC 776C-->G and MTHFR 677C-->T genotypes. RESULTS: The serum holo-TC concentration for women with the variant TC 776 GG genotype was significantly different (P = 0.0213) from that for subjects with the CC genotype (74 +/- 37 and 87 +/- 33 pmol/L, respectively). An inverse relation was observed between plasma homocysteine concentrations and both serum holo-TC (P G polymorphism negatively affects the serum holo-TC concentration and provide additional evidence that vitamin B-12 status modulates the homocysteine concentration in this population.

Exercise training, without weight loss, increases insulin sensitivity and postheparin plasma lipase activity in previously sedentary adults.

OBJECTIVE: To determine the effects of exercise, without weight loss, on insulin sensitivity (S(I)), postheparin plasma lipase activity (PHPL), intravenous fat clearance rate (K(2)), and fasting lipids in sedentary adults. RESEARCH DESIGN AND METHODS: At baseline and after 6 months of walk training (intensity 45-55 or 65-75% heart rate reserve, frequency 3-4 or 5-7 days/week, duration 30 min/session), anthropometric indexes, S(I), PHPL, K(2), and fasting lipids were measured in 18 sedentary adults (12 women, 6 men; 51.9 +/- 5.8 years of age, BMI 28.9 +/- 4.6 kg/m(2)). RESULTS: Exercise increased S(I) (2.54 +/- 2.74 vs. 4.41 +/- 3.30 microU ml(-1) x min(-1), P < 0.005) and both lipoprotein lipase (LPL) (1890 +/- 1380 vs. 4926 +/- 1858 nEq free fatty acid [FFA]. ml(-1). h(-1)) and hepatic lipase (HL) activities (3326 +/- 1605 vs. 4636 +/- 1636 nEq FFA. ml(-1) x h(-1)) (both P < 0.001), without altering BMI, waist circumference, K(2), or fasting lipids. Correlations between changes in LPL and the total:HDL cholesterol ratio (r = -0.54) and changes in the LPL:HL ratio and waist circumference (r = -0.50) were significant (P < 0.05). CONCLUSIONS: Exercise, without weight loss, increases S(I) and PHPL activity in previously sedentary adults, without changing K(2) or fasting lipid levels. Furthermore, increased LPL is associated with a decreased total:HDL ratio, and an increased LPL:HL ratio is associated with a decreased waist circumference. Therefore, even modest amounts of exercise in the absence of weight loss positively affect markers of glucose and fat metabolism in previously sedentary, middle-aged adults.

Differential metabolic effects of saturated versus polyunsaturated fats in ketogenic diets.

Ketogenic diets (KDs) are used for treatment of refractory epilepsy and metabolic disorders. The classic saturated fatty acid-enriched (SAT) KD has a fat:carbohydrate plus protein ratio of 4:1, in which the predominant fats are saturated. We hypothesized that a polyunsaturated fat-enriched (POLY) KD would induce a similar degree of ketosis with less detrimental effects on carbohydrate and lipid metabolism. Twenty healthy adults were randomized to two different weight-maintaining KDs for 5 d. Diets were 70% fat, 15% carbohydrate, and 15% protein. The fat contents were 60 or 15% saturated, 15 or 60% polyunsaturated, and 25% monounsaturated for SAT and POLY, respectively. Changes in serum beta-hydroxybutyrate, insulin sensitivity (S(I)), and lipid profiles were measured. Mean circulating beta-hydroxybutyrate levels increased 8.4 mg/dl in the POLY group (P = 0.0004), compared with 3.1 mg/dl in the SAT group (P = 0.07). S(I) increased significantly in the POLY group (P = 0.02), whereas total and low-density lipoprotein cholesterol increased significantly in the SAT group (both P = 0.002). These data demonstrate that a short-term POLY KD induces a greater level of ketosis and improves S(I), without adversely affecting total and low-density lipoprotein cholesterol, compared with a traditional SAT KD. Thus, a POLY KD may be superior to a classical SAT KD for chronic administration.