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Biomedical subjects

Robert H Allen

Publications and source records attributed to Robert H Allen.

At least 19 recordsLinked to original sources

Risk factors for brachial plexus injury with and without shoulder dystocia.

OBJECTIVE: To ascertain whether brachial plexus palsy (BPP) that occurs without shoulder dystocia (SD) represents a traction injury during unrecognized SD or a natural phenomenon with a different mechanism of injury, we compared risk factors and outcomes between SD-associated and non-SD-associated BPP. STUDY DESIGN: Neonates with BPP after cephalic vaginal delivery were pooled from all deliveries at Johns Hopkins (June, 1993-December, 2004) and a dataset of litigated permanent BPP from multiple institutions (1986-2003), grouped by SD association based on clinician documentation and compared by using Fisher exact and t tests. RESULTS: Thirty percent of 49 non-SD-BPP and 11% of 280 SD-BPP lacked all risk factors for SD (P = .002). Compared with SD-BPP infants, non-SD-BPP infants were average weight (P < .001) and had cord pH less than 7.10 (P = .01) more commonly and exhibited a trend toward posterior shoulder involvement (P = .06). Nearly all non-SD-BPP were temporary, whereas more than 90% of permanent BPP were associated with SD (odds ratio 17, 7.3-39.6). CONCLUSION: Non-SD-BPP is uncommon and likely mechanistically distinct from SD-BPP. Risk factors, birth weight, fetal acidosis, posterior arm involvement, and injury severity distinguish between shoulder dystocia-related brachial plexus injuries and those not recorded as such.

Brachial Plexus↗

Activation of a novel isoform of methionine adenosyl transferase 2A and increased S-adenosylmethionine turnover in lung epithelial cells exposed to hyperoxia.

S-Adenosylmethionine (SAM, AdoMet) is the most important methyl donor used for synthesis of nucleic acids, phospholipids, creatine, and polyamines and for methylation of many bioactive molecules. The metabolic response of the lung to oxidative stress of hyperoxia requires increased RNA and protein synthesis for energy metabolism, growth arrest, and antioxidant defense. We studied the production of SAM and other aspects of methionine metabolism in lung epithelial cells exposed to hyperoxia. Human lung epithelial-like (A549) and primary small airway epithelial (SAE) cells were exposed to normoxia (21% O(2)) or hyperoxia (95% O(2)). Cell methionine and S-adenosylmethionine content increased in response to hyperoxia in SAE and A549 cells. Because methionine adenosyl transferase (MAT) is the rate-limiting enzyme of the pathway, we examined the expression of a lung epithelial isoform of MAT 2A in hyperoxia. Western blots revealed a novel MAT 2A isoform expressed in both cell types, with a lower molecular mass than that described in Jurkat cells. Cloning and sequencing of the MAT 2A cDNA revealed one silent nucleotide substitution compared to that expressed in Jurkat. The lower mass of MAT 2A in both lung epithelial cells indicated that the absence of the major posttranslational modification of MAT 2A found in Jurkat. MAT 2A protein progressively increased during hyperoxic exposure in both transformed and primary lung epithelium. Increased flux of (13)C-labeled methionine to S-adenosylhomocysteine (SAH) in A549 demonstrated that SAM's methyl group was utilized, and increased formation of cystathionine indicated that at least part of SAM generated was directed toward cysteine/GSH in the transsulfuration pathway. These results indicate activation of MAT 2A and the transmethylation pathway in the metabolic response to hyperoxia in lung epithelium.

Cell Line, Tumor↗

Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products.

BACKGROUND: Carotid plaque area is a strong predictor of cardiovascular events. High homocysteine levels, which are associated with plaque formation, can result from inadequate intake of folate and vitamin B12. Now that folic acid fortification is widespread in North America, vitamin B12 has become an important determinant of homocysteine levels. We sought to determine the prevalence of low serum levels of vitamin B12, and their relation to homocysteine levels and carotid plaque area among patients referred for treatment of vascular disease since folic acid fortification of enriched grain products. METHODS: We evaluated 421 consecutive new patients with complete data whom we saw in our vascular disease prevention clinics between January 1998 and January 2002. We measured total carotid plaque area by ultrasound and determined homocysteine and serum vitamin B12 levels in all patients. RESULTS: The patients, 215 men and 206 women, ranged in age from 37 to 90 years (mean 66 years). Most were taking medications for hypertension (67%) and dyslipidemia (62%). Seventy-three patients (17%) had vitamin B12 deficiency (vitamin B12 level < 258 pmol/L with homocysteine level > 14 mumol/L or methylmalonic acid level > 271 nmol/L). The mean area of carotid plaque was significantly larger among the group of patients whose vitamin B12 level was below the median of 253 pmol/L than among those whose vitamin B12 level was above the median: 1.36 (standard deviation [SD] 1.27) cm2 v. 1.09 (SD 1.0) cm2; p = 0.016. CONCLUSIONS: Vitamin B12 deficiency is surprisingly common among patients with vascular disease, and, in the setting of folic acid fortification, low serum vitamin B12 levels are a major determinant of elevated homocysteine levels and increased carotid plaque area.

Adult↗

Total homocysteine is associated with white matter hyperintensity volume: the Northern Manhattan Study.

BACKGROUND: Total homocysteine (tHcy) has been implicated as a risk factor for stroke and dementia, but the mechanism is unclear. White matter hyperintensities may be a risk factor for both, but studies of the relationship between tHcy and quantitative measures of white matter hyperintensity volume (WMHV) are lacking, especially in minority populations. METHODS: A community-based sample of 259 subjects with baseline tHcy levels underwent pixel-based quantitative measurement of WMHV. We examined the relationship between tHcy and WMHV adjusting for age, sociodemographics, vascular risk factors, and B12 deficiency. RESULTS: Higher levels of tHcy were associated with WMHV adjusting for sociodemographics and vascular risk factors. CONCLUSIONS: These cross-sectional data provide evidence that tHcy is a risk factor for white matter damage.

Aged↗

Comparing McRoberts' and Rubin's maneuvers for initial management of shoulder dystocia: an objective evaluation.

OBJECTIVE: This study was undertaken to objectively compare delivery traction force, fetal neck rotation, and brachial plexus elongation after 3 different initial shoulder dystocia maneuvers: McRoberts', anterior Rubin's, and posterior Rubin's. STUDY DESIGN: We developed a laboratory birthing simulator comprised of a maternal model with a 3-dimensional bony pelvis, an instrumented fetal model, a force-sensing glove, and a computer-based data acquisition system. A single operator performed 30 simulated shoulder dystocia deliveries using standard downward traction after 1 maneuver was performed. Ten deliveries simulated McRoberts' maneuver with fetal shoulders in the anteroposterior diameter. Ten deliveries involved approximately 30-degree oblique rotation of the anterior shoulder with the spine oriented anteriorly (anterior Rubin's maneuver). Ten deliveries involved approximately 30-degree rotation of the posterior shoulder to the opposite oblique pelvic diameter, with the spine oriented posteriorly (posterior Rubin's maneuver). Peak traction force, brachial plexus elongation, and neck rotation were compared between groups using analysis of variance, with P < .05 considered significant. RESULTS: Rubin's maneuvers were found to require less traction force than McRoberts': 16.2 +/- 2.1 lbs for McRoberts' compared with 8.8 +/- 2.2 lbs and 6.5 +/- 1.8 lbs for posterior and anterior Rubin's respectively (P < .0001). Brachial plexus extension was significantly lower after anterior Rubin's maneuver compared with McRoberts' or posterior Rubin's maneuvers. CONCLUSION In a laboratory model of initial maneuvers for shoulder dystocia, anterior Rubin's maneuver requires the least traction for delivery and produces the least amount of brachial plexus tension. Further study is needed to validate these results clinically.

Brachial Plexus↗

Temporary Erb-Duchenne palsy without shoulder dystocia or traction to the fetal head.

BACKGROUND: Although many retrospective studies report that brachial plexus palsies occur after vaginal delivery in the absence of recorded shoulder dystocia, there are no known prospective reports by a treating clinician (PubMed, English language only, 1952-June 2004, search terms: shoulder dystocia, nonshoulder dystocia, obstetric brachial plexus injury, Erb's palsy, Erb-Duchenne palsy, spontaneous vaginal delivery). CASE: A multiparous patient presented with a birth plan requesting that the baby be allowed to deliver on its own, without traction on the head and without suctioning. Although induced at term for elevated blood pressure, the otherwise healthy patient experienced a normal labor with a 30-minute second stage. At delivery, which was videotaped by the father, the fetal head presented over an intact perineum in a right-occiput-anterior position. Without traction, the anterior shoulder delivered spontaneously with the next contraction and Valsalva, followed by the posterior shoulder. The trunk followed routinely. The average-weight for gestational age neonate exhibited an Erb-Duchenne palsy of the right (posterior) arm that resolved on the fourth day of life. CONCLUSION: Temporary Erb-Duchenne palsy can occur in the posterior arm after normal labor and spontaneous delivery without shoulder dystocia or traction on the fetal head.

Adult↗

Elevated methylmalonic acid is related to cognitive impairement in older adults enrolled in an elderly nutrition program.

Vitamin B12 status has been linked to cognitive impairment among older adults. Deficit in methylmalonic acid (MMA) may be reflective of cognitive impairment because it is a biochemically sensitive marker of B12 deficiency. In a cross-sectional study the contributions of different indices of B12 status, including serum B12, MMA and total homocysteine (tHcy), were measured in relation to cognitive functioning. B12 deficiency as measured by elevated MMA concentrations appeared to be most reflective of cognitive impairment and appeared to contribute unique variance to cognitive measures after controlling for other biochemical variables. Demographic variables, particularly education and age, were more strongly associated with cognitive measures than was MMA. Monitoring and reducing serum MMA concentrations by increasing the intake of vitamin B12 may provide protection against cognitive decline in this and other older populations.

Aged↗

S-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism.

We report studies of a Croatian boy, a proven case of human S-adenosylhomocysteine (AdoHcy) hydrolase deficiency. Psychomotor development was slow until his fifth month; thereafter, virtually absent until treatment was started. He had marked hypotonia with elevated serum creatine kinase and transaminases, prolonged prothrombin time and low albumin. Electron microscopy of muscle showed numerous abnormal myelin figures; liver biopsy showed mild hepatitis with sparse rough endoplasmic reticulum. Brain MRI at 12.7 months revealed white matter atrophy and abnormally slow myelination. Hypermethioninemia was present in the initial metabolic study at age 8 months, and persisted (up to 784 microM) without tyrosine elevation. Plasma total homocysteine was very slightly elevated for an infant to 14.5-15.9 microM. In plasma, S-adenosylmethionine was 30-fold and AdoHcy 150-fold elevated. Activity of AdoHcy hydrolase was approximately equal to 3% of control in liver and was 5-10% of the control values in red blood cells and cultured fibroblasts. We found no evidence of a soluble inhibitor of the enzyme in extracts of the patient's cultured fibroblasts. Additional pretreatment abnormalities in plasma included low concentrations of phosphatidylcholine and choline, with elevations of guanidinoacetate, betaine, dimethylglycine, and cystathionine. Leukocyte DNA was hypermethylated. Gene analysis revealed two mutations in exon 4: a maternally derived stop codon, and a paternally derived missense mutation. We discuss reasons for biochemical abnormalities and pathophysiological aspects of AdoHcy hydrolase deficiency.

Adenosylhomocysteinase↗

Cigarette smoke extract increases S-adenosylmethionine and cystathionine in human lung epithelial-like (A549) cells.

The effect of cigarette smoke extract (CSE) on S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and sulfur amino acid metabolism was examined in human lung epithelial-like (A549) cells exposed to various CSE concentrations (2.5-100%) for 24 or 48 h. Intracellular SAM and SAM/SAH ratio were elevated after exposure to CSE for 48 h. Cell SAH content decreased, but the effect was not consistent. Cellular cystathionine, cysteine, and methionine levels were increased after CSE exposure for 48h. Sub-acute exposure to CSE induced increases in cellular SAM and SAM/SAH ratio. The transsulfuration pathway was likely activated by CSE since cystathionine increased, potentially contributing to the increased total intracellular GSH content.

Amino Acids, Sulfur↗

Episiotomy versus fetal manipulation in managing severe shoulder dystocia: a comparison of outcomes.

OBJECTIVE: In severe shoulder dystocia, when initial maneuvers fail, either episiotomy or fetal manipulation (Rubin, Woods' screw, or posterior arm release) is recommended. We sought to compare maternal and neonatal outcomes between severe shoulder dystocia deliveries managed with episiotomy versus fetal manipulation. STUDY DESIGN: We identified severe shoulder dystocia deliveries from three databases: all shoulder dystocia deliveries (1993-2003 and 1994-1997) from two teaching institutions and litigated cases of shoulder dystocia-associated permanent brachial plexus palsy from multiple U.S. institutions. Pair-wise comparisons were made among three groups of deliveries: those managed by fetal manipulation without episiotomy (fetal manipulation-only), those managed by episiotomy without fetal manipulation (episiotomy-only), and those managed with both (episiotomy + fetal manipulation). Rates of brachial plexus palsy, neonatal depression, and anal sphincter trauma were compared among groups using chi 2 , with significance at P < .05. RESULTS: Among episiotomy-only, 13 of 22 (59.1%) sustained brachial plexus palsy, compared with 20 of 57 (35.1%) among fetal manipulation-only (P = .05). Twenty-eight of 48 (58.3%) in episiotomy + fetal manipulation had brachial plexus palsy, which did not differ from episiotomy-only (P = .95) but was higher than fetal manipulation-only (P = .02), suggesting that the addition of episiotomy conferred no benefit in averting neonatal injury. Anal sphincter trauma was significantly more common among episiotomy-only and episiotomy + fetal manipulation, compared with fetal manipulation-only. CONCLUSION: In severe shoulder dystocia, if fetal manipulation can be performed without episiotomy, severe perineal trauma can be averted without incurring greater risk of brachial plexus palsy.

Adult↗

Randomized trial of McRoberts versus lithotomy positioning to decrease the force that is applied to the fetus during delivery.

OBJECTIVE: In an effort to reduce shoulder dystocia incidence and morbidity, some obstetricians use prophylactic maternal hip hyperflexion (McRoberts maneuver), with the hope of facilitating delivery and decreasing the traction needed for delivery. The objective of this study was to evaluate whether the delivery force is reduced with the prophylactic McRoberts maneuver in a prospective, objective manner. STUDY DESIGN: Between April 2002 and July 2003, we randomly assigned multiparous women with term, cephalic singleton gestations to delivery in the lithotomy or McRoberts position. A single physician used a force-measuring system that consisted of a custom glove with force sensors to record the amount of force that was exerted on the fetal head. The primary outcomes of the study were peak force (pounds; highest force needed to accomplish entire delivery), peak force for delivery of anterior shoulder (pounds), and peak force rate (pounds per second; the duration required to reach the peak force). RESULTS: The peak force was not different between the patients in the lithotomy position (n=13) versus the McRoberts position (n=14; 7.2 +/- 0.8 lbs vs 8.0 +/- 0.7 lbs; P = .5). The peak force for delivery of the anterior shoulder (6.7 +/- 0.8 lbs vs 7.1 +/- 0.7 lbs; P = .7) and peak force rate (32.3 +/- 7.0 lbs/sec vs 29.1 +/- 3.5 lbs/sec; P = .7) were not different between the patients in the lithotomy position versus the McRoberts position, respectively. There was no difference between the groups for gestational age, birth weight, incidence of diabetes mellitus, or operative vaginal delivery. The subjective degree of difficulty of the delivery correlated with the peak force (R2 = 0.53; P = .001). CONCLUSION: The use of the McRoberts maneuver before clinical diagnosis of shoulder dystocia provides no reduction in the force that is used in traction on the fetal head during vaginal delivery in multiparous patients. The acceptance of this maneuver to be used prophylactically requires re-evaluation.

Adult↗

Effect of epidural anaesthesia on clinician-applied force during vaginal delivery.

OBJECTIVE: Epidural anesthesia (EA) is used in 80% of vaginal deliveries and is linked to neonatal and maternal trauma. Our objectives were to determine (1) whether EA affected clinician-applied force on the fetus and (2) whether this force influenced perineal trauma. STUDY DESIGN: After informed consent, multiparas with term, cephalic, singletons were delivered by 1 physician wearing a sensor-equipped glove to record force exerted on the fetal head. Those with EA were compared with those without for delivery force parameters. Regression analysis was used to identify predictors of vaginal laceration. RESULTS: The force required for delivery was greater in patients with EA (n = 27) than without (n = 5) (P < .01). Clinical parameters, including birth weight (P = .31) were similar between the groups. Clinician force was similar in those with no versus first- versus second-degree laceration (P = .5). Only birth weight was predictive of laceration (P = .02). CONCLUSION: Epidural use resulted in greater clinician force required for vaginal delivery of the fetus in multiparas, but this force was not associated with perineal trauma.

Anesthesia, Epidural↗

Outcome assessment of hand function after radial artery harvesting for coronary artery bypass.

The radial artery has gained widespread acceptance as a conduit for coronary artery bypass. Advantages include minimal donor site discomfort, ease of handling, excellent early patency rates, and the possibility of freedom from late conduit atherosclerosis. Although most series describe minimal morbidity, a significant incidence of radial sensory neuropathy and isolated instances of hand claudication and ischemia have been reported. We performed an outcome study utilizing the Short Form-36, the Upper Limb-Disabilities of Arm, Shoulder and Hand, and a modified self-administered hand diagram to compare 288 patients undergoing coronary artery bypass utilizing the radial artery with a control group of 174 patients undergoing coronary artery bypass without the radial artery. The data were analyzed by the t test for continuous variables and the chi-square test for categorical variables, and subsequently a multivariate regression model was constructed. No patients developed hand claudication or ischemia. Although there was an incidence of radial sensory neuropathy of 9.9% associated with radial artery harvest, it was not significantly higher than the incidence in the control group (5.2%, p =.16). Intrinsic patient factors such as obesity, age, diabetes, and peripheral vascular disease were the principal determinants of overall health and quality of life issues.

Coronary Artery Bypass↗

Low ratio of S-adenosylmethionine to S-adenosylhomocysteine is associated with vitamin deficiency in Brazilian pregnant women and newborns.

BACKGROUND: Pregnant women with low cobalamin concentrations are unable to provide the necessary amount of cobalamin to their fetuses. The effect of low maternal cobalamin concentrations on transmethylation metabolism in pregnant women and their newborns is unknown. OBJECTIVE: We investigated the relation between maternal and neonatal cobalamin concentrations and changes in total homocysteine (tHcy), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH). DESIGN: Hematologic data and concentrations of cobalamin, red blood cell folate, serum folate, tHcy, methylmalonic acid, SAM, SAH, and other metabolites were measured in 119 serum specimens from pregnant Brazilian women (gestational age: 37-42 wk) and their newborns' placental veins at the time of delivery. RESULTS: The tHcy concentrations were higher in placental vein serum from newborns whose mothers had low cobalamin. Serum SAH concentrations were elevated and serum SAM and methionine concentrations were decreased in pregnant women with lower cobalamin concentrations. SAM:SAH was significantly decreased in both cobalamin-deficient pregnant women and their newborns. CONCLUSIONS: Lower maternal cobalamin concentrations are associated with higher tHcy and lower SAM:SAH in newborns. Because SAM:SAH is closely linked with the activity of numerous enzymatic methylation reactions, these results suggest that methylation could be impaired in cobalamin-deficient pregnant women and their newborns.

Adult↗

Vitamin B12 deficiency as a worldwide problem.

Pernicious anemia is a common cause of megaloblastic anemia throughout the world and especially in persons of European or African descent. Dietary deficiency of vitamin B12 due to vegetarianism is increasing and causes hyperhomocysteinemia. The breast-fed infant of a vitamin B12-deficient mother is at risk for severe developmental abnormalities, growth failure, and anemia. Elevated methylmalonic acid and/or total homocysteine are sensitive indicators of vitamin B12-deficient diets and correlate with clinical abnormalities. Dietary vitamin B12 deficiency is a severe problem in the Indian subcontinent, Mexico, Central and South America, and selected areas in Africa. Dietary vitamin B12 deficiency is not prevalent in Asia, except in vegetarians. Areas for research include intermittent vitamin B12 supplement dosing and better measurements of the bioavailability of B12 in fermented vegetarian foods and algae.

Anemia, Megaloblastic↗

Quantification of serum and urinary S-adenosylmethionine and S-adenosylhomocysteine by stable-isotope-dilution liquid chromatography-mass spectrometry.

BACKGROUND: We have developed an assay that uses stable-isotope-dilution liquid chromatography-mass spectrometry to assess S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in body fluids to investigate the relationship of these metabolites to hyperhomocysteinemia. METHODS: Commercially obtained SAM (D(3) methyl) and (13)C(5)-SAH uniformly labeled in the adenosyl moiety, which was synthesized using S-adenosylhomocysteine hydrolase, were added to samples followed by perchloric acid protein precipitation, C(18) chromatography, and analysis by liquid chromatography-mass spectrometry with quantification by comparison of the areas of internal standard and endogenous peaks. RESULTS: Estimates of intraassay imprecision (CV) were 5% and 17% for SAM and SAH, respectively (n = 10). SAM decreased and SAH increased in serum and plasma samples at both 4 degrees C and room temperature over 80 h. SAM and SAH were unstable in samples stored longer than 2 years at -20 degrees C. In 48 volunteers, the estimated reference intervals [from mean (2 SD) of log-transformed data] for serum SAM and SAH were 71-168 and 8-26 nmol/L, respectively. Fractional excretion of SAM was higher than that of SAH, and the urinary SAM:SAH ratio was much higher than the serum or erythrocyte SAM:SAH ratios. CONCLUSIONS: Stable-isotope-dilution liquid chromatography-mass spectrometry can be used to quantify SAM and SAH in biological fluids and tissues. Sample handling and storage must be stringently controlled for any epidemiologic or clinical use of such assays.

Adult↗