Spatial Analysis and Lead-Risk Assessment of Philadelphia, USA.

Childhood lead poisoning is an issue that continues to plague major U.S. cities. Despite efforts by the Philadelphia Department of Public Health to curtail systemic childhood lead poisoning, children continue to be identified with elevated blood lead levels. The persistence of elevated blood lead levels in children is concerning because lead poisoning has been linked to decreases in academic achievement and IQ, with associated repercussions for entire communities. This paper reports the results of an analysis of the spatial distribution of houses with lead paint (i.e., pre-1978), demolitions, and occurrence of historic smelters, in West and North Philadelphia, relative to elevated blood lead level data, to determine which lead sources act as primary lead-risk factors. The presence of lead paint in homes and the number of demolitions of older properties were found to have the highest correlations to elevated blood lead levels for children in Philadelphia. Using lead-risk factors including lead paint, housing code violations, demolitions, and owner-occupied housing units, a lead-risk assessment was performed at the census tract level to identify future soil sampling sites and high-risk neighborhoods in Philadelphia. These sites of high risk for lead exposure, and in particular the census tracts 175 and 172, should be prioritized for lead poisoning prevention initiatives.

Allometry of sexual size dimorphism in dioecious plants: do plants obey Rensch's rule?

Rensch's rule refers to a pattern in sexual size dimorphism (SSD) in which SSD decreases with body size when females are the larger sex and increases with body size when males are the larger sex. Many animal taxa conform to Rensch's rule, but it has yet to be investigated in plants. Using herbarium collections from New Zealand, we characterized the size of leaves and stems of 297 individuals from 38 dioecious plant species belonging to three distantly related phylogenetic lineages. Statistical comparisons of leaf sizes between males and females showed evidence for Rensch's rule in two of the three lineages, indicating SSD decreases with leaf size when females produce larger leaves and increases with leaf size when males produce larger leaves. A similar pattern in SSD was observed for stem sizes. However, in this instance, females of small-stemmed species produced much larger stems than did males, but as stem sizes increased, SSD often disappeared. We hypothesize that sexual dimorphism in stem sizes results from selection for larger stems in females, which must provide mechanical support for seeds, fruits, and dispersal vectors, and that scaling relationships in leaf sizes result from correlated evolution with stem sizes. The overall results suggest that selection for larger female stem sizes to support the weight of offspring can give rise to Rensch's rule in dioecious plants.

Implications of increased left ventricular mass index on in-hospital outcomes in patients undergoing aortic valve surgery.

BACKGROUND: Increased left ventricular mass index has been shown to be associated with higher mortality in epidemiologic studies. However, the effect of increased left ventricular mass index on outcomes in patients undergoing aortic valve replacement is unknown. METHODS: We studied 473 consecutive patients undergoing elective aortic valve replacement to assess the influence of left ventricular mass index on outcomes in patients having this procedure. Echocardiographic left ventricular dimensions were used to calculate left ventricular mass index (considered increased if >134 g/m(2) in male patients and >110 g/m(2) in female patients). RESULTS: Left ventricular mass index was increased in 24% of patients undergoing aortic valve replacement. Postprocedural complications (respiratory failure, renal insufficiency, congestive heart failure, and atrial and ventricular arrhythmias), length of stay in the intensive care unit, and in-hospital mortality were increased in patients with increased left ventricular mass index. Multivariable analysis identified prior valve surgery (odds ratio, 4.3; 95% confidence interval, 1.2-15.7; P =.030), left ventricular ejection fraction (odds ratio, 1.07; 95% confidence interval, 1.01-1.14; P =.020), history of hypertension (odds ratio, 8.2; 95% confidence interval, 2.2-30.4; P =.002), history of liver disease (odds ratio, 50.4; 95% confidence interval, 4.2-609.0; P =.002), and increased left ventricular mass index (odds ratio, 38; 95% confidence interval, 9.3-154.1; P <.001) as independent predictors of in-hospital mortality. Furthermore, low output syndrome was identified as the most common mode of death (36%) after aortic valve replacement in patients with increased left ventricular mass index. CONCLUSIONS: Increased left ventricular mass index is associated with increased adverse in-hospital clinical outcomes in patients undergoing aortic valve replacement. Although this finding warrants special modification in perioperative management, further studies are needed to address whether outcomes in asymptomatic patients with aortic valve disease could be improved by earlier aortic valve replacement before a significant increase in left ventricular mass index.

The effect of pravastatin and atorvastatin on coenzyme Q10.

BACKGROUND: Coenzyme Q10 (CoQ10) is an antioxidant and plays an important role in the synthesis of adenosine triphosphate. Studies suggest that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce CoQ10 levels; however, no studies have directly compared HMG-CoA reductase inhibitors in a randomized crossover fashion. METHODS: Twelve healthy volunteers received either 20 mg pravastatin (P) or 10 mg atorvastatin (A) for 4 weeks in a randomized crossover fashion. There was a 4- to 8-week washout period between the 2 phases. CoQ10 levels and a lipid profile were obtained. RESULTS: There was no difference in CoQ10 levels from baseline to post-drug therapy for either P or A (0.61 +/- 0.14 vs 0.62 +/- 0.2 microg/mL and 0.65 +/- 0.22 vs 0.6 +/- 0.12 microg/mL, respectively; P >.05). There was a significant difference in low-density lipoprotein (LDL) levels from baseline to post-drug therapy for both P and A (97 +/- 21 vs 66 +/- 19 mg/dL and 102 +/- 21 vs 52 +/- 14 mg/dL, respectively; P <.01). There was no significant correlation between LDL and CoQ10. CONCLUSIONS: P and A did not decrease CoQ10 despite a significant decrease in LDL levels. These findings suggest that HMG-CoA reductase inhibitors do not significantly decrease the synthesis of circulating CoQ10 in healthy subjects. Routine supplementation of CoQ10 may not be necessary when HMG-CoA reductase inhibitor therapy is administered.

Case study: how to apply data mining techniques in a healthcare data warehouse.

Healthcare provider organizations are faced with a rising number of financial pressures. Both administrators and physicians need help analyzing large numbers of clinical and financial data when making decisions. To assist them, Rush-Presbyterian-St. Luke's Medical Center and Hitachi America, Ltd. (HAL), Inc., have partnered to build an enterprise data warehouse and perform a series of case study analyses. This article focuses on one analysis, which was performed by a team of physicians and computer science researchers, using a commercially available on-line analytical processing (OLAP) tool in conjunction with proprietary data mining techniques developed by HAL researchers. The initial objective of the analysis was to discover how to use data mining techniques to make business decisions that can influence cost, revenue, and operational efficiency while maintaining a high level of care. Another objective was to understand how to apply these techniques appropriately and to find a repeatable method for analyzing data and finding business insights. The process used to identify opportunities and effect changes is described.

Case of the month.

Each month, we will present a challenging Case of the Month for Green Journal readers, who must use their clinical acumen to arrive at the correct answer. We will also post the case each month on the Journal's web site (http://www.elsevier.com/ajmselect). Several possible answers may be consistent with the case presentation; use your best judgment. Please send your answer (one per respondent) to The Green Journal at editors@amjmed.org or via FAX to (415) 447-2799. Indicate the case to which you are responding and include your complete address. The correct answer will appear in the next issue of the Journal. The first five persons who submit correct answers will receive a free one-year subscription to the Journal. Because of the volume of answers we receive, neither correct nor incorrect answers can be individually acknowledged. Colleagues of Drs. Green, Nallamothu, and Shea are not eligible for this month's case. If you would like to contribute a case, please submit a brief synopsis (<250 words) to the editorial office.

Insertion of a telomere repeat sequence into a mammalian gene causes chromosome instability.

Telomere repeat sequences cap the ends of eucaryotic chromosomes and help stabilize them. At interstitial sites, however, they may destabilize chromosomes, as suggested by cytogenetic studies in mammalian cells that correlate interstitial telomere sequence with sites of spontaneous and radiation-induced chromosome rearrangements. In no instance is the length, purity, or orientation of the telomere repeats at these potentially destabilizing interstitial sites known. To determine the effects of a defined interstitial telomere sequence on chromosome instability, as well as other aspects of DNA metabolism, we deposited 800 bp of the functional vertebrate telomere repeat, TTAGGG, in two orientations in the second intron of the adenosine phosphoribosyltransferase (APRT) gene in Chinese hamster ovary cells. In one orientation, the deposited telomere sequence did not interfere with expression of the APRT gene, whereas in the other it reduced mRNA levels slightly. The telomere sequence did not induce chromosome truncation and the seeding of a new telomere at a frequency above the limits of detection. Similarly, the telomere sequence did not alter the rate or distribution of homologous recombination events. The interstitial telomere repeat sequence in both orientations, however, dramatically increased gene rearrangements some 30-fold. Analysis of individual rearrangements confirmed the involvement of the telomere sequence. These studies define the telomere repeat sequence as a destabilizing element in the interior of chromosomes in mammalian cells.

Early spontaneous recovery of left ventricular function in patients with myocarditis.

The natural history of myocarditis is varied. We describe 6 out of a cohort of 15 consecutive patients with histopathologic evidence of myocarditis who showed a remarkable early symptomatic and spontaneous recovery of left ventricular systolic function. The left ventricular ejection fraction increased to > or = 50% at discharge, and this improvement was maintained at late follow-up. The other 9 patients, despite clinical improvement, were not thought to have spontaneous recovery. Neither clinical severity of the illness (NYHA functional class) nor left ventricular ejection fraction at presentation demonstrated any difference in the two groups. By contrast, a smaller left ventricular internal diameter at end-diastole and a smaller left atrial dimension as determined by transthoracic echocardiography were predictive of spontaneous recovery. Firstly, we confirm that the natural history of myocarditis is indeed varied with the possibility of early spontaneous recovery; secondly we suggest that left ventricular internal diameter at end-diastole and left atrial dimension may have prognostic implications in this disease.

Requirement for Wnt3 in vertebrate axis formation.

Several studies have implicated Wnt signalling in primary axis formation during vertebrate embryogenesis, yet no Wnt protein has been shown to be essential for this process. In the mouse, primitive streak formation is the first overt morphological sign of the anterior-posterior axis. Here we show that Wnt3 is expressed before gastrulation in the proximal epiblast of the egg cylinder, then is restricted to the posterior proximal epiblast and its associated visceral endoderm and subsequently to the primitive streak and mesoderm. Wnt3-/- mice develop a normal egg cylinder but do not form a primitive streak, mesoderm or node. The epiblast continues to proliferate in an undifferentiated state that lacks anterior-posterior neural patterning, but anterior visceral endoderm markers are expressed and correctly positioned. Our results suggest that regional patterning of the visceral endoderm is independent of primitive streak formation, but the subsequent establishment of anterior-posterior neural pattern in the ectoderm is dependent on derivatives of the primitive streak. These studies provide genetic proof for the requirement of Wnt3 in primary axis formation in the mouse.

Risk analysis for aortic surgery using hypothermic circulatory arrest with retrograde cerebral perfusion.

BACKGROUND: Retrospective analysis of 144 patients undergoing aortic arch reconstruction using hypothermic circulatory arrest (HCA) with retrograde cerebral perfusion (RCP) for cerebral protection was performed. METHODS: The diagnosis, procedure, and anatomic site of the arch anastomosis were analyzed to see if they were independent predictors of mortality or morbidity. In addition age, gender, HCA-RCP times, preoperative malperfusion (both treated and untreated), surgical status, and redo surgery status were also examined to determine their influence on the incidence of death and complications. Both multivariate and univariate analysis were performed using linear regression and cross-tabulation with either chi2 or Fisher's exact test where appropriate. RESULTS: Preoperative surgical status (emergent) and the presence of untreated preoperative malperfusion were the only variables that were significant independent predictors for mortality (p <0.05). No variable was significant for the prediction of stroke or other complications. The severity of surgery had no bearing on the patient outcome. CONCLUSIONS: Complex aortic surgery using HCA-RCP can be performed with acceptable risk to the patients.

The impact of new technology on a clinical practice.

The use of xenograft stentless tissue valves has increased because of excellent hemodynamics and availability. This article describes the impact of the incorporation of this new technology into a single institutional practice over time. A time span for continual usage of the new stentless Freestyle valve was divided into four distinct chronological groups and evaluated. Data on 266 consecutive patients receiving the Freestyle prosthesis were analyzed with regard to demographics, degree of illness, complexity of surgery, and outcomes to discover any distinct changes over time with respect to experience and acquired confidence and surgical expertise. Findings among the four groups were compared using Student's t-test. The only change in patient demographics was younger age (mean age decreased from 70 to 62 years). The number of procedures rose steadily, and the degree of illness increased as noted in the increase between groups in the percentage of patients with comorbidities (from 45% to 92%). The complexity of surgery score steadily increased (from 1.9 to 2.5); however, the mean cross-clamp time did not change. The surgical mortality rate for the entire study was 3.4%. In group 1, the mortality was 7.5% but decreased rapidly and remained steady throughout the rest of the study. The use of the Freestyle stentless conduit in a single practice over time shows a distinct learning curve. With experience, valves are placed in younger, sicker patients who require more complex surgery. Surgical outcomes and efficiency improve with acquired surgical expertise.

Endoluminal stenting for unprotected left main stenosis in Takayasu's arteritis.

We describe 2 patients with Takayasu's arteritis and left main coronary stenosis who were considered poor candidates for surgical revascularization. Elective left main coronary artery balloon angioplasty followed by endoluminal stenting was performed with excellent results. At 3-mo follow-up, one patient had evidence of in-stent restenosis, but the other remained asymptomatic. In selected patients with Takayasu's arteritis and left main coronary stenosis, elective endoluminal stenting can be used as a definitive procedure or as a bridge to surgical revascularization.

Evaluation of thoracic aortic disease with the use of helical CT and multiplanar reconstructions: comparison with surgical findings.

PURPOSE: To assess the accuracy of helical computed tomography (CT) in differentiating different types of thoracic aortic disease, to determine the incremental value of multiplanar reconstructions, and to determine if helical CT could help to reliably predict the need for intraoperative hypothermic circulatory arrest. MATERIALS AND METHODS: Forty-nine patients underwent pre-operative helical CT with multiplanar reconstructions. Images were reviewed for type and location of pathologic lesions and for features that indicated the need for hypothermic circulatory arrest. The incremental yield of multiplanar reconstructions compared with that of axial images was assessed. Imaging findings were compared with surgical findings. RESULTS: The types of lesions present in the patients included 36 aneurysms (three were ruptured), six penetrating ulcers, five dissections, and two pseudoaneurysms. The accuracy of diagnosis was 92% (45 of 49 patients) with the use of CT (both with and without multiplanar reconstruction). The necessity of hypothermic circulatory arrest was successfully predicted in 94% (45 of 48 patients) of cases. CONCLUSION: Helical CT, both with and without the use of multiplanar reconstruction, enabled highly accurate differentiation among diseases of the thoracic aorta and prediction of the need for hypothermic circulatory arrest.

Analysis of regulatory elements of the developmentally controlled chorion s15 promoter in transgenic Drosophila.

The Drosophila s15 chorion gene is expressed only in the follicular epithelium surrounding the developing oocyte, with tight quantitative control and a very narrow temporal specificity. We have used germ-line transformation analysis to conduct an extensive mutational dissection of its promoter between -189 and -39 bp relative to the transcriptional start site. Quantitative control and temporal specificity are disrupted by several of these mutations. The results suggest that this 150-bp DNA region encompasses many positive and negative, at least partially degenerate, cis-regulatory elements, which are involved in specifying the highly precise expression pattern of the s15 gene during development.

The spalt-related gene of Drosophila melanogaster is a member of an ancient gene family, defined by the adjacent, region-specific homeotic gene spalt.

We report the full coding sequence of a new Drosophila gene, spalt-related, which is homologous and adjacent to the region-specific homeotic gene, spalt. Both genes have three widely spaced sets of C2H2 zinc finger motifs, but spalt-related encodes a fourth pair of C-terminal fingers resembling the Xenopus homologue, Xsal-1. The degrees of sequence divergence among all three members of this family are comparable, suggesting that the Drosophila genes originated from an ancient gene duplication. The spalt-related gene is expressed with quantitative variations from mid-embryogenesis (8-12 h) to the adult stage, but not in ovaries or early embryos. Expression is localized to limited parts of the body, including specific cell populations in the nervous system. In the wing disc, spalt and spalt-related are expressed in indistinguishable domains; in the nervous system and some other organs the expression patterns extensively overlap but are not identical, indicating that the genes have partially diverged in terms of developmental regulation. A characteristic central set of zinc fingers specifically binds to an A/T-rich consensus sequence, defining some DNA binding properties of this ancient family of nuclear factors.

Variations in prothrombin time and international normalized ratio over 24 hours in warfarin-treated patients.

STUDY OBJECTIVE: To determine the variation of prothrombin times and international normalized ratio (INR) over 24 hours in humans. DESIGN: Prospective, parallel study. SETTING: University-affiliated general clinical research center. PATIENTS: Six patients receiving long-term warfarin therapy and six sex-matched controls. INTERVENTIONS: Warfarin was administered to the patients at 6:00 P.M. MEASUREMENTS AND MAIN RESULTS: Prothrombin times and INR were determined every 2 hours over 24 hours. Time of study entry, meals, and sleep cycles were controlled. A significant cosinor rhythm for prothrombin times and INR (p < or = 0.03) occurred in warfarin-treated patients, suggesting that diurnal variation occurs. The mean difference between the peak and trough prothrombin times was 1.8 +/- 0.9 seconds (range 0.8-3 sec) with a mean change of 9.3% +/- 3.7%. The peak prothrombin time and INR values occurred between 4:00 A.M. and 8:00 A.M. in five patients, and trough values between 6:00 P.M. and midnight in five. No significant cosinor rhythm was noted for controls (p > 0.5). CONCLUSION: Significant variations in prothrombin time and INR occurred in patients receiving warfarin therapy, with the highest values occurring in the morning and the lowest in the evening. These results may have clinical implications for patients receiving either high- or low-intensity warfarin therapy.

The effect of dosage release formulations on the pharmacokinetics of propranolol stereoisomers in humans.

Recent studies in dogs have suggested that the disposition of S- and R-propranolol may depend on the input rate of drug delivered to the liver. Therefore, this study was designed to determine whether differences in the disposition of S- and R-propranolol occur in humans when altering the input rate of propranolol by giving different dosage forms of the drug. Twelve healthy subjects were enrolled in a single-dose, 4-way crossover pharmacokinetic study in which racemic propranolol was given according to 1 of 4 treatments: one 80-mg immediate-release (IR) tablet, phase A; two 80-mg IR tablets, phase B; a 160-mg controlled-release capsule, phase C; or a 10-mg IV bolus, phase D. The results showed no significant differences in the ratios of S/R-propranolol for AUC, clearance, or overall mean concentration among the oral dosage groups. Significant differences in these parameters including Cmax S/R ratio were seen between the oral phases and the IV phase. These differences appear to be related more to the route of administration than to the low input rate. However, at high concentrations there may be input-rate alteration in S/R ratios. Specifically, for phase B, which had the highest Cmax concentrations, the Cmax S/R ratio was significantly lower than the other oral dosage groups A and C (Cmax S/R ratios: 1.44 versus 1.54 and 1.54, respectively; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative evaluation of the hemodynamic effects of oral cimetidine, ranitidine, and famotidine as determined by echocardiography.

STUDY OBJECTIVE: To evaluate the influence of cimetidine, ranitidine, famotidine, and placebo on cardiac performance as determined by echocardiography. DESIGN: Randomized, four-way crossover trial. SETTING: Echocardiography laboratory at a university hospital. PARTICIPANTS: Twelve healthy volunteers. INTERVENTIONS: Volunteers received oral treatment with placebo, cimetidine 800 mg, ranitidine 300 mg, or famotidine 40 mg once/day for 7 days. MEASUREMENTS AND MAIN RESULTS: On the seventh day of each study phase, 2 hours after administration of the final dose, each subject underwent cardiac echocardiography and Doppler flow studies. No significant differences were detected in ejection fraction, peak flow velocity, or percentage fractional shortening among the treatment phases. A large degree of variability in ejection fraction was observed, with some subjects experiencing marked decreases. CONCLUSION: The histamine-2 (H2)-receptor antagonists had no effect on the hemodynamic variables as determined by echocardiography. The variability in the hemodynamic response may in part explain the conflicting results reported in the literature. It also raises the question as to whether certain individuals are more sensitive to the potential cardiac effects of H2-receptor antagonists.

Evaluation of dosage-release formulations on inhibition of drug clearance: effect of sustained- and immediate-release verapamil on propranolol pharmacokinetic parameters.

Limited information exists regarding the influence of dosage-release formulation on inhibition of drug metabolism. Therefore, the purpose of this study was to evaluate the effect of immediate-release (IR) and sustained-release (SR) verapamil on the pharmacokinetic parameters of propranolol in 12 healthy men. IR propranolol, 160 mg, was administered alone (Phase A) and following either IR verapamil, 80 mg t.i.d., (Phase B) or SR verapamil, 240 mg q.d., (Phase C) in a randomized crossover fashion. Of the 12 subjects enrolled, only seven were able to be analyzed secondary to assay interference. Oral clearances for L-propranolol for Phases A, B, and C were 198 +/- 70, 156 +/- 76, and 143 +/- 85 L/h, respectively. Oral clearances for D-propranolol for Phases A, B, and C were 203 +/- 96, 172 +/- 96, and 152 +/- 102 L/h, respectively. No significant differences were observed. However, when the verapamil groups (Phase B and C) were combined and compared to Phase A, a significant decrease in clearance for propranolol isomers was observed. In conclusion, due to the unexpected low numbers of patients evaluated, no significant differences in oral clearance were observed among the three treatment phases. However, there is a trend suggesting that SR verapamil had the greatest effect on propranolol clearance, which may warrant caution when changing from one formulation to another.

Wnt-3a regulates somite and tailbud formation in the mouse embryo.

Amphibian studies have implicated Wnt signaling in the regulation of mesoderm formation, although direct evidence is lacking. We have characterized the expression of 12 mammalian Wnt-genes, identifying three that are expressed during gastrulation. Only one of these, Wnt-3a, is expressed extensively in cells fated to give rise to embryonic mesoderm, at egg cylinder stages. A likely null allele of Wnt-3a was generated by gene targeting. All Wnt-3a-/Wnt-3a- embryos lack caudal somites, have a disrupted notochord, and fail to form a tailbud. Thus, Wnt-3a may regulate dorsal (somitic) mesoderm fate and is required, by late primitive steak stages, for generation of all new embryonic mesoderm. Wnt-3a is also expressed in the dorsal CNS. Mutant embryos show CNS dysmorphology and ectopic expression of a dorsal CNS marker. We suggest that dysmorphology is secondary to the mesodermal and axial defects and that dorsal patterning of the CNS may be regulated by inductive signals arising from surface ectoderm.