The utility of the MELD score in predicting mortality following liver resection for metastasis.

BACKGROUND: The MELD score has been demonstrated to be predictive of hepatectomy outcomes in mixed patient samples of primary and secondary liver cancers. Because MELD is a measure of hepatic dysfunction, prior conclusions may rely on the high prevalence of cirrhosis observed with primary lesions. This study aims to evaluate MELD score as a predictor of mortality and develop a risk prediction model for patients specifically undergoing hepatic metastasectomy. METHODS: ACS-NSQIP 2005-2013 was analyzed to select patients who had undergone liver resections for metastases. A receiver operating characteristic (ROC) analysis determined the MELD score most associated with 30-day mortality. A literature review identified variables that impact hepatectomy outcomes. Significant factors were included in a multivariable analysis (MVA). A risk calculator was derived from the final multivariable model. RESULTS: Among the 14,919 patients assessed, the mortality rate was 2.7%, and the median MELD was 7.3 (range = 34.4). A MELD of 7.24 was identified by ROC (sensitivity = 81%, specificity = 51%, c-statistic = 0.71). Of all patients above this threshold, 4.4% died at 30 days vs. 1.1% in the group ≤7.24. This faction represented 50.1% of the population but accounted for 80.3% of all deaths (p < 0.001). The MVA revealed mortality to be increased 2.6-times (OR = 2.55, 95%CI 1.69-3.84, p < 0.001). A risk calculator was successfully developed and validated. CONCLUSIONS: MELD>7.24 is an important predictor of death following hepatectomy for metastasis and may prompt a detailed assessment with the provided risk calculator. Attention to MELD in the preoperative setting will improve treatment planning and patient education prior to oncologic liver resection.

Diagnostic accuracy of diffusion tensor imaging for pediatric cervical spinal cord injury.

STUDY DESIGN: Cross-sectional non-experimental study. OBJECTIVES: To examine diagnostic accuracy of diffusion tensor imaging (DTI) for pediatric spinal cord injury (SCI). SETTING: Pediatric Orthopedic Hospital. METHODS: Thirty-five subjects, 10 SCI and 25 controls, mean age 13.38 years underwent two scans with 3.0 T MR scanner. Fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) values were calculated. Subjects with SCI underwent examination of muscle strength, sensation and sacral sparing. Mean and s.d. values for FA, AD and RD were compared by group (controls, SCI with sacral sparing, SCI without sacral sparing) using analysis of variance for repeated measures. Comparisons were also made of DTI values at the injury site to values from cervical regions outside of the injury site. Specificity, sensitivity, receiver operating characteristics area under the curve (ROC AUC) and corresponding 95% confidence intervals were calculated. Resampling methods were used to validate the estimates from the final models. RESULTS: FA values differed among SCI subjects with intact sacral sparing, absent sacral sparing and controls, P<0.003 (adjusted). DTI values in combination showed the strongest diagnostic accuracy for predicting the presence of anal contraction (AD, RD; ROC AUC=0.90), deep anal pressure (FA; ROC AUC=0.88), S4-5 sensation (FA, RD; ROC AUC=0.93), motor level (FA, AD, RD; ROC AUC=0.92) and MRI level (FA, AD, RD; ROC AUC=0.92). Bootstrap and Jackknife median values indicated consistency of the parameter estimates. CONCLUSION: The predictive accuracy of DTI for sacral sparing end points and motor and MRI level of injury was good to strong.

Randomized controlled trial assessing participation and quality of life in a supported speed treadmill training exercise program vs. a strengthening program for children with cerebral palsy.

OBJECTIVE: A multi-site Randomized-Controlled Trial compared a home-based Supported Speed Treadmill Training Exercise Program (SSTTEP) with a strengthening exercise program in children with cerebral palsy (CP) on the following categories; Participation, quality of life (QOL), self-concept, goal attainment, and satisfaction. DESIGN: Twenty-six children with spastic cerebral palsy were assigned by site-based block randomization to the SSTTEP (n=14) or strengthening exercise (n=12) group. Both groups participated in a two week clinic-based induction period and continued the intervention at home for ten weeks. Data were collected at baseline, post-intervention (12 weeks), and follow-up (16 weeks). Assessments included the Canadian Occupational Performance Measure, Children's Assessment of Participation and Enjoyment Scale, Pediatric Quality of Life Cerebral Palsy Module, and Piers-Harris Children's Self-Concept Scale. Evaluators were blinded to group assignment at two sites. RESULTS: Satisfaction and performance on individual goals, participation, and parent-reported QOL improved in both groups with improvement maintained for four weeks post intervention. CONCLUSION: The hypothesis that the SSTTEP group would have better outcomes than the exercise group was not supported. However, both groups showed that children with CP can make gains in participation, individual goals, and satisfaction following a 12-week intensive exercise intervention, and these findings persisted for four weeks post intervention.

Assisted closure of fasciotomy wounds: A descriptive series and caution in patients with vascular injury.

INTRODUCTION: Negative pressure wound therapy (NPWT) and vessel loop assisted closure are two common methods used to assist with the closure of fasciotomy wounds. This retrospective review compares these two methods using a primary outcome measurement of skin graft requirement. METHODS: A retrospective search was performed to identify patients who underwent fasciotomy at our institution. Patient demographics, location of the fasciotomy, type of assisted closure, injury characteristics, need for skin graft, length of stay and evidence of infection within 90 days were recorded. RESULTS: A total of 56 patients met the inclusion criteria. Of these, 49 underwent vessel loop closure and seven underwent NPWT assisted closure. Patients who underwent NPWT assisted closure were at higher risk for requiring skin grafting than patients who underwent vessel loop closure, with an odds ratio of 5.9 (95% confidence interval 1.11 to 31.24). There was no difference in the rate of infection or length of stay between the two groups. Demographic factors such as age, gender, fracture mechanism, location of fasciotomy and presence of open fracture were not predictive of the need for skin grafting. CONCLUSION: This retrospective descriptive case series demonstrates an increased risk of skin grafting in patients who underwent fasciotomy and were treated with NPWT assisted wound closure. In our series, vessel loop closure was protective against the need for skin grafting. Due to the small sample size in the NPWT group, caution should be taken when generalising these results. Further research is needed to determine if NPWT assisted closure of fasciotomy wounds truly leads to an increased requirement for skin grafting, or if the vascular injury is the main risk factor.

SLC11A1 and VDR gene variants and susceptibility to tuberculosis and disease progression in East India.

SETTING: Despite efforts at disease control, the incidence of tuberculosis (TB) remains high in India. OBJECTIVE: To assess the role of VDR and SLC11A1 gene polymorphisms in the development of pulmonary TB (PTB) in an ethnically matched population of India. DESIGN: In this case-control study, five variants (INT4/ rs3731865, 823C/T/rs17221959, D543N/rs17235409, 577G/A/rs1059823 and TGTG deletion-3UTR/rs172 35416) of SLC11A1 and three (BsmI/rs1544410, FokI/ rs10735810 and TaqI/rs731236) of the VDR gene were studied in 101 TB patients and 225 controls from Kolkata, India. RESULTS: Statistically significant associations were ob- served for INT4: GC (OR 4.54 95%CI 2.38-8.68), CC (OR 35.20, 95%CI 9.15-135.38), 3 UTR (TGTG+ /-, OR 2.96, 95%CI 1.52-5.78), TGTG- /- (OR 3.52, 95%CI 1.62-7.61) and 823C/T (CT, OR 0.31, 95%CI 0.17-0.58) variants of the SLC11A1 gene. Significantly different genotype frequencies between different groups of patients elucidated the role of the INT4 (P = 0.031), 577G/A (P = 0.033) and FokI (P = 0.02) variants in disease progression and the development of cavitary disease. Five haplotypes were also identified as having a significant association with PTB. CONCLUSION: This study, the first to include evidence on 577G/A and INT4, reports a significant association between SLC11A1 gene variants and PTB with respect to susceptibility and subsequent disease progression in East India.

The International Standards for Neurological Classification of Spinal Cord Injury: relationship between S4-5 dermatome testing and anorectal testing.

STUDY DESIGN: Prospective cross-sectional multicenter study. OBJECTIVE: To evaluate the correlation, sensitivity, specificity and predictive values of S4-5 dermatome and the anorectal examination for determination of sacral sparing in the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination. SETTING: Two tertiary hospitals that specialize in pediatric spinal cord injuries. METHODS: In all, 189 patients who were at minimum 3 month after spinal cord injury participated in complete ISNCSCI examinations. All examiners completed training for the proper completion of the ISNCSCI examination. Correlations and sensitivity/specificity analyses were conducted between S4-5 dermatome testing and the anorectal examination. Results were analyzed by age of patient, examiner, tetraplegia/paraplegia classification and injury level (T10-S3, L1-S3 and S3). RESULTS: The correlation between S4-5 dermatome and anorectal sensation was moderate (0.62, P<0.001). Using the anorectal examination as the gold standard, the sensitivity of S4-5 testing was 0.60 (0.49, 70) and specificity was 0.96 (0.90, 0.99). No single age group, tester, level, or type of injury differed from the overall result. CONCLUSION: In the pediatric population, the correlation between S4-5 and anorectal sensation was lower than anticipated. The sensitivity of 0.62 for S4-5 testing and diminished sensation between T10 and S3 suggests that anorectal testing may either be a more sensitive representation of S4-5 function or activate an alternative neuronal pathway that is perceived by the patient. Further investigation into the validity of the sacral sparing components of the ISNCSCI examination is warranted.

Right ventricular beneficial effects of intracoronary SERCA2a gene transfer in an experimental model of heart failure.

SERCA2a gene transfer ameliorates heart failure pathologic processes in left ventricular myocardium. We sought to assess the simultaneous molecular changes that occur in the right ventricle. Sprague-Dawley rats underwent aortic banding and were followed by echocardiography for development of heart failure. After a decrease in fractional shortening of 25 % from baseline, intracoronary injection of adenoviral-SERCA2a or adenoviral-beta-galactosidase was performed. Successful gene transfer was confirmed by immunoblotting. Rats were randomly euthanized on post-operative day 7 or 21. Protein analysis including right ventricular levels of SERCA2a, betaARK1, inflammatory mediators (IL-1, IL-6 and TNF-alpha), apoptotic markers (Bax, Bak and Bcl-2) and MAPK (Jnk, p38 and Erk) was performed. Adenoviral-SERCA2a-treated animals showed increased right ventricular expression of SERCA2a compared with controls. Decreased levels of inflammatory markers were also demonstrated in this group. Expression of pro-apoptotic markers was similarly improved. Levels of MAPK were increased compared with the control group. These differences were most significant 7 days after gene transfer, but the majority of these changes persisted at 21 days. These results suggest that attenuation of pathologic mechanisms of calcium cycling, inflammation and apoptosis also occur in the right ventricular myocardium after SERCA2a gene transfer during heart failure. These findings support a therapeutic role for genetic manipulation of this pathway in patients with right ventricular or biventricular failure.

Noninvasive fetal RhCE genotyping from maternal blood.

BACKGROUND: The successful prevention of RhD disease has brought attention to other red blood cells' antigens causing alloimmunisation including RhC/c and RhE/e. Prenatal diagnosis of fetal Rh genotype from maternal blood is in clinical use in Europe but not in the USA. OBJECTIVE: To estimate the collective reported diagnostic accuracy of fetal RhCE genotyping from peripheral maternal blood and compare the results of genotyping when fetal cells and free fetal DNA (FfDNA) are used. SEARCH STRATEGY: English-written literature describing fetal RhCE determination from maternal blood using fetal cells or FfDNA was performed using medical subject headings and text words. The sources included Pubmed (1966-2007), Ovid (1966-2007), CINAHL, The Cochrane Library, ACP Journal Club and OCLC. Key words were prenatal diagnosis, fetal RhCE, fetal DNA in maternal blood and alloimmunisation. SELECTION CRITERIA: A study was considered eligible if it described fetal RhCE type determination using maternal peripheral blood reported in the English literature. Abstracts were excluded. DATA COLLECTION AND ANALYSIS: From each study, we determined the number of samples tested, fetal RhCE genotype, the source of the fetal DNA, gestational age, presence of alloimmunisation and confirmation of fetal RhCE type. Exclusions and inclusions were noted. We calculated composite estimates of accuracy using a weighted random effects model. We assessed the papers against an international quality, STARD checklist which is standards for reporting studies of diagnostic accuracy. MAIN RESULTS: We identified 20 protocols in six English-written publications reporting fetal RhC/c (seven protocols) and/or E/e (13 protocols) genotyping using DNA obtained from maternal blood for a total of 369 samples. For RhC/c, 176 samples were tested and for RhE/e, 193 samples were tested. Accuracy was determined for each study and for all studies. The combined accuracy of fetal genotype was 96.3% for RhC/c and 98.2% for RhE/e. Only a few samples of the sorted cells were found to be a source for accurate diagnosis, but plasma was consistently the best source of fetal RhCE genotyping in 147/147 (100%) for RhC/c and 168/168 (100%) for RhE/e. CONCLUSIONS: The combined accuracy of noninvasive fetal RhC/c or RhE/e determination using maternal peripheral blood is 96.3% and 98.2%, respectively. FfDNA in maternal plasma is a better source for genotyping reported to be 100% correct for both RHCE genotypes. Further studies and reports of accuracy from laboratories performing the tests are required before prenatal determination of fetal RhC/c or RhE/e genotypes from maternal blood can safely replace the current methods used in the management of the RhC/c or RhE alloimmunised pregnancies.

Hic-5 promotes endothelial cell migration to lysophosphatidic acid.

Endothelial cell migration is critical for proper blood vessel development. Signals from growth factors and matrix proteins are integrated through focal adhesion proteins to alter cell migration. Hydrogen peroxide-inducible clone 5 (Hic-5), a paxillin family member, is enriched in the focal adhesions in bovine pulmonary artery endothelial (BPAE) cells, which migrate to lysophosphatidic acid (LPA) on denatured collagen. In this study, we investigate the role of Hic-5 in LPA-stimulated endothelial cell migration. LPA recruits Hic-5 to the focal adhesions and to the pseudopodia in BPAE cells plated on collagen, suggesting that recruitment of Hic-5 to focal adhesions is associated with endothelial cell migration. Knockdown of endogenous Hic-5 significantly decreases migration toward LPA, confirming involvement of Hic-5 in migration. To address the role of Hic-5 in endothelial cell migration, we exogenously expressed wild-type (WT) Hic-5 and green fluorescent protein Hic-5 C369A/C372A (LIM3 mutant) constructs in BPAE cells. WT Hic-5 expression increases chemotaxis of BPAE cells to LPA, whereas migration toward LPA of the green fluorescent protein Hic-5 C369A/C372A-expressing cells is similar to that shown in vector control cells. Additionally, ERK phosphorylation is enhanced in the presence of LPA in WT Hic-5 cells. A pharmacological inhibitor of MEK activity inhibits LPA-stimulated WT Hic-5 cell migration and ERK phosphorylation, suggesting Hic-5 enhances migration via MEK activation of ERK. Together, these studies indicate that Hic-5, a focal adhesion protein in endothelial cells, is recruited to the pseudopodia in the presence of LPA and enhances migration.

Patterns of lower extremity innervation in pediatric spinal cord injury.

STUDY DESIGN: Retrospective review. OBJECTIVES: To identify relationships between lower extremity innervation and level of injury, mechanism of injury, and age at injury in a pediatric population with spinal cord injury (SCI). Secondarily, relationships between innervation and completeness of injury, time since injury, race, and sex were evaluated. SETTING: Pediatric orthopedic referral hospital, Philadelphia, Pennsylvania. METHODS: Records of 190 subjects, ages 1-21 years, were reviewed. Data collected from the medical record included lower extremity muscle innervation, American Spinal Injury Association (ASIA) level and class, mechanism of injury, age at injury, time since injury, race, and sex. To determine innervation, lower extremity muscles had been tested using surface electrical stimulation and identified as being innervated or denervated. If a muscle responded weakly, strength duration testing was performed. For analysis via logistic regression, subjects were grouped based upon level and mechanism of injury. RESULTS: A relationship (P<0.0001) was found between ASIA level and lower extremity innervation of all muscles and between length of time since injury and lower extremity innervation for some muscles. Following multiple logistic regression, only ASIA level remained as an independent predictor of lower extremity innervation status. CONCLUSION: Our results show that lower extremity innervation does differ based on the level of the injury. Denervation began to be seen with injuries in the lower thoracic region and more predominantly with injuries in the lumbar region. This supports our hypothesis that the incidence of lower motor neuron injuries would increase as injuries became more caudal. Our hypotheses of a relationship between innervation status and mechanism of injury and age at injury were not supported. This information is important in determining treatment strategies, eligibility for electrical stimulation techniques, and potential regenerative strategies. SPONSORSHIP: This study was funded by Shriners Hospitals for Children, Grant #8530.

Extracellular matrix molecules regulate endothelial cell migration stimulated by lysophosphatidic acid.

BACKGROUND: Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are lipids that bind G-protein coupled receptors and differentially promote transmigration of endothelial cells. OBJECTIVE: To determine if endothelial cell transmigration stimulated by LPA, not S1P, is dependent on the extracellular matrix. METHODS: Bovine pulmonary artery (BPAE) endothelial cell transmigration and locomotion were measured using a modified-Boyden chamber and video microscopy, respectively. Results were related to strength of adhesion and characteristics of cell adhesive contacts. RESULTS AND CONCLUSIONS: BPAEs responded to LPA by transmigration through gelatin- or collagen-coated filters, but not through fibronectin-, vitronectin-, or fibrinogen-coated filters. Fewer cells adhered to collagen or gelatin than to fibronectin in a static cell adhesion assay or after application of a g-force to detach cells. Video microscopy revealed that S1P stimulates large lamellipodia on two-dimensional fibronectin substrate. LPA stimulated lamellipodia on fibronectin, but the trailing edge remained attached, resulting in sting ray-shaped cells in video microscopy. LPA-treated cells on gelatin released the trailing edge. To understand how the extracellular matrix may regulate endothelial cell shape during movement, we surveyed changes in focal adhesion proteins. More Hic-5, a paxillin homolog, was detected in the detergent insoluble fraction of BPAEs attached to gelatin than fibronectin. No such difference was found in paxillin. In BPAEs, Hic-5 was localized to smaller punctate structures on fibronectin and longer, thinner focal adhesions on gelatin. These results indicated that localization of Hic-5 and strength of adhesion correlate with endothelial cell transmigration stimulated by LPA, but not with transmigration stimulated by S1P.

Role of diltiazem in pregnant women with chronic renal disease.

OBJECTIVE: To determine whether diltiazem therapy decreases proteinuria during pregnancy in women with chronic renal disease, resulting in decreased risk of pre-eclampsia, preterm delivery and intrauterine fetal growth restriction. METHODS: We undertook retrospective data collection by chart review of pregnant women with chronic renal disease. Women treated with and without diltiazem were compared by independent t test analysis. RESULTS: Seven women were eligible for inclusion in the study. Individual patient trends revealed decreased or attenuated increase in proteinuria across gestation with diltiazem therapy. Mean arterial pressure was also decreased in the therapy group compared to increased pressure in the third trimester in the group with no therapy. The incidence of fetal growth restriction and need for labor induction were lower in the diltiazem-treated group. CONCLUSIONS: Diltiazem, a non-dihydropyridine calcium channel antagonist, decreases proteinuria and preserves renal structure and function and should be considered an alternative to angiotensin converting enzyme inhibitors in pregnancy in women with chronic renal disease.

The effect of muscle hypoperfusion-hyperemia on repetitive vertical jump performance.

Alterations in skeletal muscle blood flow can greatly influence exercise performance. Brief periods of arterial hypoperfusion and subsequent hyperemia (hypoperfusion-hyperemia) have been shown to decrease the rate of skeletal muscle fatigue in a model of repeated, isometric wrist flexion exercise. However, the mechanism by which hypoperfusion-hyperemia influences dynamic motor skills remains unknown. The purpose of this study was to determine the effects of brief hypoperfusion-hyperemia (by femoral cuff occlusion) on repetitive vertical jump performance. Recreationally trained men and women (n = 10, mean +/- SD age, 25 +/- 2 years), performed 2 randomly assigned jumping trials, each consisting of 40 maximal effort vertical jumps. Jump height was videotaped on a Sony digital video recorder and analyzed with the Scion Images program. Trial 1 consisted of 40 vertical jumps without femoral artery occlusion. Trial 2 consisted of 40 vertical jumps preceded by femoral artery cuff occlusion for 90 seconds at 200 mm Hg, followed by 10 seconds of hyperemia before jumping. For both trials, the rate of decline in power output in men and women was approximately 20%. Hypoperfusion-hyperemia had no significant effect on vertical jumping power output, perhaps because additional muscle groups used to jump vertically (e.g., gluteals and arms) were not occluded. These results warrant further research on the effect of hypoperfusion-hyperemia on strength and power measures.

Electrophysiological alterations after mechanical circulatory support in patients with advanced cardiac failure.

BACKGROUND: Recognizing that mechanical circulatory support with a left ventricular assist device (LVAD) induces changes in myocardial structure and contractile function, we examined whether there are changes in ventricular conduction and/or repolarization among failing human hearts after LVAD implantation. METHODS AND RESULTS: We examined 12-lead electrocardiograms before surgery, immediately after LVAD placement, and at a delayed (>1 week) postoperative time point in 23 patients who were receiving LVAD support for refractory heart failure. The immediate effects of hemodynamic unloading via LVAD placement included a decrease in QRS duration from 117+/-6 to 103+/-6 ms (P<0.01), an increase in absolute QT duration from 359+/-6 to 378+/-8 ms (P<0.05), and an increase in the heart rate-corrected QT interval (QTc) from 379+/-10 to 504+/-11 ms (P<0.01). None of these immediate changes were observed among 22 patients undergoing routine coronary artery bypass grafting. With sustained cardiac unloading via LVAD support, there was a marked decrease in the QTc from 504+/-11 to 445+/-9 ms (P<0.001). Studies in isolated cardiac myocytes, obtained at the time of transplantation, confirmed that delayed decreases in heart rate-adjusted QTc were the result of decreases in action potential duration after LVAD support. CONCLUSIONS: Acute electrocardiogram responses to LVAD placement demonstrate the dependence of QRS and QT duration on load in the failing human heart. Delayed decreases in QTc and action potential duration reflect reversal of electrophysiologic remodeling in the failing heart. Shortening of the action potential duration likely contributes to the improved cellular contractile performance observed after sustained LVAD support.

Patients with end-stage congestive heart failure treated with beta-adrenergic receptor antagonists have improved ventricular myocyte calcium regulatory protein abundance.

BACKGROUND: Alterations in Ca(2+)-handling proteins are thought to underlie the deranged Ca(2+) transients that contribute to deterioration of cardiac function in congestive heart failure (CHF). Clinical trials in CHF patients have shown that treatment with beta-adrenergic receptor antagonists (betaB) improves cardiac performance. The present study determined whether the abundance of Ca(2+)-handling proteins is different in failing hearts from patients treated or untreated with beta B. METHODS AND RESULTS: Ca(2+) regulatory protein abundance was compared in LV myocardium of 10 nonfailing hearts (NF group) and 44 failing hearts (CHF group) removed at transplantation. Analysis was performed in betaB-treated (betaB-CHF) and non-betaB treated (non-betaB-CHF) patients and in 4 subgroups: ischemic cardiomyopathy (ICM, n=10), nonischemic dilated cardiomyopathy (DCM, n=10), ICM with betaB therapy (betaB-ICM, n=12), and DCM with betaB therapy (betaB-DCM, n=12). Sarcoplasmic reticulum Ca(2+) ATPase, phospholamban, and Na(+)-Ca(2+) exchanger protein abundance were determined by use of Western blot analysis. Ca(2+) transients were measured with fluo-3. Sarcoplasmic reticulum Ca(2+) ATPase was significantly less abundant whereas phospholamban and Na(+)-Ca(2+) exchanger were not significantly altered in non-betaB-CHF versus NF. Sarcoplasmic reticulum Ca(2+) ATPase in the betaB-ICM and betaB-DCM was greater than in non-betaB-CHF and were not different than in NF. Ca(2+) transients in non-betaB-CHF myocytes had significantly smaller peaks and were prolonged versus NF myocytes. Ca(2+) transients from betaB-CHF myocytes had shorter durations than in betaB-CHF myocytes. CONCLUSIONS: betaB treatment in CHF patients can normalize the abundance of myocyte Ca(2+) regulatory proteins and improve Ca(2+)-handling.

Differential effects of acetaminophen pretreatment on hepatic aflatoxin B(1)-DNA binding, cellular proliferation, and aflatoxin B1-induced hepatic foci in rats and hamsters.

Effects of acetaminophen (AAP) pretreatment on hepatic aflatoxin B1 (AFB(1))-DNA binding, cellular proliferation, and AFB(1)-induced glutathione S-transferase placental form (GST-P) positive hepatocytes and foci have been examined in young male rats and hamsters. Intraperitoneal (i.p.) dosing of 600mg AAP 3h before AFB(1) i.p. injection showed three-fold more AFB(1)-DNA binding in hamsters and 40% less binding in rats. Cell proliferation analyzed by bromodeoxyuridine incorporation was not significant (0.4-0.6%) 24-96h after AAP (600mg) treatment of rats; however, proliferation was stimulated and was maximum (11%) in hamsters at 72h after AAP treatment. Dosing of rats with AFB(1) alone at 0.5 or 2.5mg level gave an appreciable number of GST-P positive minifoci (two to nine cells) with a few foci larger than 100 microm; pretreatment with AAP (300 or 600mg) 48h before 0.5 or 2.5mg AFB(1) had no effect on the number and focal area of foci. In hamsters, 1 or 2mg AFB(1) alone yielded GST-P positive hepatocytes without any minifoci. Pretreatment with AAP (600mg) 48 or 72h before 1 or 2mg AFB(1) produced increases in both GST-P positive hepatocytes and minifoci. Thus, marked changes are observed after AAP pretreatment in hamsters compared to rats.

Predicting outcome in pediatric coin ingestion.

OBJECTIVE: To determine the relationship between coin size, coin location, patient age, and patient weight and likelihood of coin passage through the esophagus following pediatric coin ingestion. A secondary objective is to test the hypothesis that coin denomination can be determined based on radiographic appearance. METHODS: A retrospective review was performed of all children seen and evaluated for coin ingestion at a single institution over a 25-month period. Outcome measures included the number of coins that were retained in the esophagus, and the number that passed. Various factors were assessed for their predictive value in judging outcome in coin ingestion cases. RESULTS: Nineteen percent of patients (15/79) in the study passed their ingested coins. Coin denomination could be accurately determined on every patient that had a standard AP or lateral X-ray film. These findings were marked when compared with the lack of reliability of history in determining coin denomination. Patients who passed coins were as a group older (4.6 vs. 3.2 year, P=0.04), but did not differ significantly by weight (19.5 vs. 15.4 kg, P=0.07) from those that retained the coins. Coins located at the gastroesophageal junction had a significantly higher passage rate than coins located elsewhere in the esophagus (89 vs. 8.2%, P<0.01). Coin size was not predictive of coin passage (P=0.7 by chi(2)). CONCLUSIONS: Radiographic assessment of coin denomination is reliable, but in this study could not be used to predict coin passage. Patient age and coin location at the gastroesophageal junction, however, do correlate with this event.

Role of polymorphisms in codons 143 and 160 of the O6-alkylguanine DNA alkyltransferase gene in lung cancer risk.

O6-Alkylguanine DNA alkyltransferase (AGT) plays an important role in the repair of alkylating agent-induced DNA damage and protection from the carcinogenic effects of environmental agents. To examine the importance of the AGT codon 143 and codon 160 polymorphisms in risk for lung cancer and to assess the prevalence of these polymorphisms in different racial groups, we performed genotype analysis of lung cancer patients and matched controls. The prevalence of the AGT143Val allele in controls was 0.07 in Caucasians and 0.03 in African Americans. The AGT143Val allele was not detected in an unmatched Asian control cohort. The prevalence of the AGT160Arg variant allele was 0.01 in Caucasians, 0.02 in African Americans, and 0.03 in Asians. A marginally significant association was observed between the AGT codon 143 (isoleucine/valine) genotype and risk for lung cancer (odds ratio = 2.1; 95% confidence interval = 1.01-4.7). The prevalence of the AGT160Arg variant allele was similar in lung cancer cases versus matched controls. These results suggest that the AGT codon 143 polymorphism may play an important role in risk for lung cancer.

Urinary tract infections in women with bacterial vaginosis.

OBJECTIVE: To evaluate the risk of urinary tract infections in women with bacterial vaginosis. METHODS: One hundred twenty-nine women who presented for routine gynecologic examinations were evaluated for bacterial vaginosis and urinary tract infections between June 1998 and March 1999. RESULTS: Sixty-seven women had bacterial vaginosis and 62 women did not. Fifteen women with bacterial vaginosis (22.4%) had urinary tract infections, compared with six (9.7%) of those without it. Bacterial vaginosis was associated with an increased risk of urinary tract infections (odds ratio 2.79; 95% confidence interval 1.05, 8.33). CONCLUSION: Women with bacterial vaginosis are at increased risk for urinary tract infections.