A modular microfluidic architecture for integrated biochemical analysis

Microfluidic laboratory-on-a-chip (LOC) systems based on a modular architecture are presented. The architecture is conceptualized on two levels: a single-chip level and a multiple-chip module (MCM) system level. At the individual chip level, a multilayer approach segregates components belonging to two fundamental categories: passive fluidic components (channels and reaction chambers) and active electromechanical control structures (sensors and actuators). This distinction is explicitly made to simplify the development process and minimize cost. Components belonging to these two categories are built separately on different physical layers and can communicate fluidically via cross-layer interconnects. The chip that hosts the electromechanical control structures is called the microfluidic breadboard (FBB). A single LOC module is constructed by attaching a chip comprised of a custom arrangement of fluid routing channels and reactors (passive chip) to the FBB. Many different LOC functions can be achieved by using different passive chips on an FBB with a standard resource configuration. Multiple modules can be interconnected to form a larger LOC system (MCM level). We demonstrated the utility of this architecture by developing systems for two separate biochemical applications: one for detection of protein markers of cancer and another for detection of metal ions. In the first case, free prostate-specific antigen was detected at 500 aM concentration by using a nanoparticle-based bio-bar-code protocol on a parallel MCM system. In the second case, we used a DNAzyme-based biosensor to identify the presence of Pb(2+) (lead) at a sensitivity of 500 nM in <1 nl of solution.     

Maturity status of youth football players: a noninvasive estimate

PURPOSE: To estimate the biological maturity status of youth football players 9-14 yr old using a noninvasive method and to compare the body size of players of contrasting status. METHODS: Subjects were members of youth football teams in two central Michigan communities. Height and weight were measured on 653 boys 8.7-14.6 yr. Heights of biological parents of 582 boys were reported and subsequently adjusted for overestimation. Decimal age, height, and weight of the player and midparent height were used to predict mature (adult) height for the boy. Current height of each player was expressed as a percentage of his predicted mature height to provide an estimate of biological maturity status. Percentage of predicted mature height of each boy was expressed as a z-score to classify players into maturity groups. ANCOVA, controlling for age, was used to compare body size in contrasting maturity groups. RESULTS: Mean percentages of predicted mature height of the players matched those of longitudinal reference samples, but there was a trend for higher percentages among older players, suggesting advanced maturation. Overall, 405 boys were classified as on time/average in maturity status (69.6% [95%CI 65.7-73.3]), 154 were classified as early/advanced (25.5% [95%CI 23.0-30.3]), and only 23 were classified as late/delayed (3.9% [95%CI 2.6-6.0]). The gradient for height, weight, and BMI was as follows: early > on time > late, and differences were greater for weight and the BMI than for height. CONCLUSION: Percentage of predicted mature height attained at a given age appears to be a reasonable indicator of maturity status. The method needs to be validated with other more direct indicators (skeletal age, sexual maturation) and applied to other samples.     

Mercury in our environment

Mercury is a very useful metallic element that, while not particularly abundant in nature, can play an important role in the overall health of humans and animals. This article discusses the benefits and toxicological consequences of society's use of mercury. It also will focus upon the mining, processing, and uses of mercury in the United States, and then highlight the amounts of mercury that are released as wastes. Along the way, three important questions are addressed: How much mercury is released by human activities and by natural events? Do these releases pose a risk either to humans or to the environment in general? How does this information apply to dentistry?     

Limited, protected postsurgical motion does not affect the results of digital nerve repair

PURPOSE: Casting for 3 to 4 weeks has been the accepted protocol after primary repair of digital nerve lacerations. In contrast, combined digital nerve and flexor tendon repairs are rehabilitated with immediate postsurgical range of motion. The purpose of this study was to compare the results of primary nerve repair in isolated digital nerve lacerations immobilized after surgery with nerve repairs combined with flexor tendon repairs that are mobilized in a limited, protected fashion immediately after surgery. METHODS: We reviewed retrospectively patients who had had surgical repair of isolated digital nerve lacerations or combined digital nerve and flexor tendon lacerations. Demographics recorded included age, hand dominance, injured digit, and time to mobilization. Follow-up data included range of motion at the metacarpophalangeal, proximal interphalangeal, distal interphalangeal, and wrist joints; static 2-point discrimination; and Semmes-Weinstein monofilament testing. Between-group comparisons were based on t-tests for continuous measures and chi-square tests for categoric measures. Paired t-tests were used for within-group comparisons. All comparisons were based on 2-tailed.05-level tests. RESULTS: Fourteen patients (16 digits) with isolated nerve repairs (group 1) and 12 patients (14 digits) with combined nerve and tendon repairs (group 2) were evaluated. The average age and duration at follow-up evaluation were similar in the 2 groups. The average time to mobilization, however, was 21 days in group 1 and 4 days in group 2. Injuries occurred equally in dominant and nondominant hands. Good range of motion returned in all digits. In addition there was no significant difference in final 2-point discrimination and Semmes-Weinstein testing between groups 1 and 2. CONCLUSIONS: Our data showed a decrease in sensibility between the injured and uninjured digits in each of the 2 groups studied, as has been shown previously. The difference in sensibility between the 2 groups, however, was not statistically significant. These data challenge the long-held belief that digital nerve repairs should be completely immobilized after surgery.     

The influence of pulmonary artery morphology on the results of operations for major aortopulmonary collateral arteries and complex congenital heart defects

OBJECTIVE: Congenital heart defects with major aortopulmonary collateral arteries show marked variability in the size and distribution of native pulmonary arteries. We sought to classify the size and distribution of native pulmonary arteries and to determine their influence on surgical outcome. METHODS: Between 1989 and 2002, 164 patients underwent surgical intervention for congenital heart defects with major aortopulmonary collateral arteries (median age, 10 months). Three patterns of native pulmonary arteries were identified: intrapericardial native pulmonary arteries present (group I); confluent intrapulmonary native pulmonary arteries without intrapericardial native pulmonary arteries (group II); and nonconfluent intrapulmonary native pulmonary arteries (group III). Thirty-seven (23%) patients had single-stage and 76 (47%) patients had multistage complete repair. Thirty (18%) patients await septation, and 8 (5.0%) patients are not septatable. Follow-up is 98% complete (median follow-up, 5.8 years). RESULTS: In the 164 patients there were 15 (9.1%) early and 12 (7.3%) late deaths. Early mortality after complete repair was 4.4% (n = 5). Actuarial survival was 90% +/- 3% and 85% +/- 4% at 1 and 10 years, respectively. Actuarial freedom from surgical or catheter reintervention in septated patients was 77% +/- 4% and 45% +/- 8% at 1 and 10 years, respectively. On multivariate analysis, the morphology of the native pulmonary arteries was the only factor that influenced actuarial survival after complete repair (P =.04). Group III had the highest risk of death after septation (P =.008). Group II fared better than group III after the initial operation (P <.05). CONCLUSIONS: Current classifications of congenital heart defects with major aortopulmonary collateral arteries are based on the presence or absence of intrapericardial pulmonary arteries. We have identified a subgroup without intrapericardial native pulmonary arteries but with confluent intrapulmonary native pulmonary arteries. This group has a better outcome than those with nonconfluent intrapulmonary native pulmonary arteries.     

Relationship between processes of care and coronary bypass operative mortality and morbidity

BACKGROUND: Information is limited regarding the effects of processes of care on cardiac surgical outcomes. Correspondingly, many recommended cardiac surgical processes of care are derived from animal experiments or clinical judgment. This report from the VA Cooperative Study in Health Services, "Processes, Structures, and Outcomes of Cardiac Surgery," focuses on the relationships between 3 process groups (preoperative evaluation, intraoperative care, and supervision by senior physicians) and a composite outcome, perioperative mortality and morbidity. METHODS: Data on 734 risk, process, and structure variables were collected prospectively on 3,988 patients who underwent coronary artery bypass grafting at 14 VA medical centers between 1992 and 1996. Data reduction was accomplished by examining data completeness and variation across sites and surgeon, using previously published data and clinical judgment. We then applied multivariable logistic regression to the 39 remaining processes of care to determine which were related to the composite outcome after adjusting for 17 patient-related risk factors and controlling for intraoperative complications. RESULTS: Our first analysis showed several measures of operative duration, the use of inotropic agents, transesophageal echo, lowest systemic temperature, and hemoconcentration/ultrafiltration, to be powerful predictors of the composite outcome. Because the use of inotropic agents and operative duration may be related to an intermediate outcome (eg, intraoperative complications), we performed a second analysis omitting these processes. The use of intraoperative transesophageal echo and hemoconcentration/ultrafiltration remained significantly associated with an increased risk of an event (odds ratios 1.60 and 1.36, respectively). CONCLUSIONS: Our results viewed in the context of past studies suggest the possibility that inotropic use, TEE, and hemoconcentration/ultrafiltration may have adverse effects on operative outcome. Further evaluation of these processes of care using observational data, as well as randomized trials when feasible, would be of interest.     

Immunochemotherapy with rituximab and temozolomide for central nervous system lymphomas

BACKGROUND: Methotrexate-based and alkylator-based chemotherapy regimens are associated with renal and bone marrow toxicities, which limit their use in patients with central nervous system (CNS) lymphomas. The authors report their experience with an immunochemotherapy regimen consisting of rituximab and temozolomide in patients with primary or metastatic CNS lymphoma. METHODS: Seven patients who had received rituximab and temozolomide were identified from the database of the brain tumor clinic at the authors' institution: three patients had developed recurrent primary CNS lymphoma (PCNSL), one patient had newly diagnosed PCNSL but had poor renal function, and three other patients with systemic non-Hodgkin lymphoma developed recurrent lymphoma in the brain only. Patients were scheduled to receive 4 cycles of induction rituximab on Day 1 and temozolomide on Days 1-5 of a 28-day cycle. Thereafter, their treatment included a total of up to 8 maintenance cycles of temozolomide alone on Days 1-5 of a 28-day cycle. A gadolinium-enhanced magnetic resonance image of the head was obtained after every two cycles of treatment. RESULTS: All patients received rituximab without toxicity. Of the 4 patients who received induction temozolomide at doses > 150 mg/m(2) daily on Days 1-5, 2 experienced Grade 2 leukopenia and thrombocytopenia. Five patients achieved a radiographic complete response, and two patients had partial responses after induction treatment. The median response duration was 6 months (range 3-12+ months), and the median survival was 8 months (range 3+-12+ months). CONCLUSIONS: Although median survival was short, immunochemotherapy with rituximab and temozolomide was well tolerated and exhibited efficacy in this elderly and heavily pretreated cohort. The data obtained in the current study suggest that the optimal induction dose combination consists of rituximab 375 mg/m(2) on Day 1 and temozolomide 150 mg/m(2) daily on Days 1-5.