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PubMed2001

Implications of the Human Genome Project for obstetrics and gynecology.

The initial sequencing of the human genome should be regarded as a milestone in a road that stretches years into the future; the full ramifications of the Human Genome Project are still only being theorized. Researchers will benefit from the catalog of human genes in studies of the genetics of disease susceptibility and the cell biology of gene interactions. Clinicians will increasingly offer genetic or biochemical testing to identify those at highest risk for a number of diseases. Drug discovery will eventually follow newly possible studies of gene expression and protein function. However the Human Genome Project eventually shapes medicine, it is certain that physicians, particularly obstetricians and gynecologists, will need to be well versed in the scientific and ethical issues involved, inasmuch as we will likely be at the center of the most heated debates.

Cell Communication↗
PubMed1992

Racial differences in childhood hospitalized pedestrian injuries.

This research provides an epidemiologic analysis of pedestrian-related injury discharges from The Children's Hospital of Alabama in Birmingham, utilizing a case-control design. Evidence is provided supporting the racial disproportionality of serious, nonfatal pedestrian injuries in children. These data indicate that pedestrian injuries resulting in hospitalization are more common among black children than among white children (odds ratio = 2.95) when compared with an age- and gender-matched control group of other hospitalized injuries. This racial association with pedestrian injury remained significant when the data were stratified by payment class, a proposed surrogate measure of socioeconomic status (adjusted odds ratio = 2.59). A catalog of harmful environmental factors that may be pervasive in black children's lives is provided as an aid in planning intervention programs and their evaluation.

Accidents, Traffic↗
PubMed1991

Postmortem preservation of ganglion cells in the human retina. A morphometric investigation with the carbocyanine dye DiI.

Postmortem morphometric investigation of autopsy material is helpful for understanding the alterations cells undergo during life. The present work was undertaken to determine the morphologic features of human retinal ganglion cells during the first 2 days after death. Ganglion cells of 16 retinas were obtained from eyes, the corneas of which had been retrieved for keratoplasties. The ganglion cells were stained with the fluorescent carbocyanine dye Dil and investigated 12 to 36 hours postmortem. All labeled cells identified as ganglion cells had well preserved, type-specific dendritic profiles that made it possible to catalog them according to the established classes of ganglion cells. The various types of cells have in common some typical morphologic changes that occur during the postmortem period of observation: swelling and varicosity in the cell bodies and along the dendritic branches and the axons. These swellings were consistent throughout the postmortem period and did not hinder the identification of particular types of ganglion cells. The two major types (parasol and midget) and various subtypes of ganglion cells were identified morphologically. There are two distinct morphologic types of midget cells which differ from each other in the pattern of dendritic branching. Particular emphasis was given to analyze the dendritic geometry of the large parasol cells. A new finding in the human retina is the frequent presence of large parasol ganglion cells, the axons of which course along aberrant intraretinal paths, especially in the extreme periphery of the retina.

Axons↗
PubMed1995

Postnatal development of the thoracic spine.

STUDY DESIGN: Forty-two thoracic spines ranging from neonate to 15 years of age were studied. OBJECTIVES: Postnatal development of the thoracic vertebrae and their component elements were cataloged. SUMMARY OF BACKGROUND DATA: This study was part of an ongoing series concerning the progressive morphologic development of the human postnatal skeleton. METHODS: The spines were studied morphologically and radiologically. RESULTS: Fusion of the thoracic spine neurocentral synchondroses occurs in a cranial to caudal direction in humans by 6 to 7 years of age. The transverse processes exhibit a progressive posterior and inferior angulation with age and moving down the thoracic spine. The facet joints angulate accordingly. The spinous processes elongate and increasingly angulate with age, especially in the mid-thoracic region. The relative contribution of the posterior elements, compared with the centrum, to the growth of the vertebral body progressively decreases moving down thoracic spine. CONCLUSION: This study demonstrated areas of anatomic change that undoubtedly play a role in normal and abnormal spine development.

Adolescent↗
PubMed2002

Pedicle screws with high electrical resistance: a potential source of error with stimulus-evoked EMG.

STUDY DESIGN: Clinically relevant aspects of pedicle screws were subjected to electrical resistance testing. OBJECTIVES: To catalog commonly used pedicle screws in terms of electrical resistance, and to determine whether polyaxial-type pedicle screws have the potential to create a high-resistance circuit during stimulus-evoked electromyographic testing. SUMMARY OF BACKGROUND DATA: Although stimulus-evoked electromyography is commonly used to confirm the accuracy of pedicle screw placement, no studies have documented the electrical resistance of commonly used pedicle screws. METHODS: Resistance measurements were obtained from eight pedicle screw varieties (5 screws of each type) across the screw shank and between the shank and regions of the screw that would be clinically accessible to stimulus-evoked electromyographic testing with a screw implanted in a pedicle. To determine measurement variability, resistance was measured three times at each site and with the crown of the polyaxial-type screw in three random positions. RESULTS: Resistance across the screw shank ranged from 0 to 36.4 ohms, whereas resistance across the length of the monoaxial-type screws ranged from 0.1 to 31.8 ohms. Resistance between the hexagonal port and shank of polyaxial-type screws ranged from 0 to 25 ohms. In contrast, resistance between the mobile crown and shank of polyaxial-type screws varied widely, ranging from 0.1 ohms to an open circuit (no electrical conduction). Polyaxial-type screws demonstrated an open circuit in 28 of 75 measurements (37%) and a high-resistance circuit (exceeding 1000 ohms) in 5 of 75 measurements (7%). CONCLUSIONS: Polyaxial-type pedicle screws have the potential for high electrical resistance between the mobile crown and shank, and therefore may fail to demonstrate an electromyographic response during stimulus-evoked electromyographic testing in the setting of a pedicle breech. To avoid false-negative stimulus-evoked electromyographic testing, the cathode stimulator probe should be applied to the hexagonal port or directly to the screw shank, and not to the mobile crown.

Alloys↗
PubMed1990

Comparison of ultrafiltration devices for assessing theophylline protein binding.

The ability of two commercially available ultrafiltration devices to assess the protein binding of theophylline was compared using human serum albumin in pH 7.4 buffer at 37 degrees C. The devices compared were the Millipore-MC filter units (Catalog number UFC3LGC00) and the Amicon Centrifree Micropartition System; both rely on centrifugal force to separate the unbound and bound molecules. The results from each device were essentially identical provided that the Millipore units were centrifuged using conditions that would not allow heat buildup to occur and thereby cause a decrease in the binding. This problem could be minimized if the Millipore units were available in a low-binding 30,000 dalton cutoff membrane instead of the 10,000 dalton membrane currently available. The use of the Millipore 30,000 dalton cutoff polysulfone membrane (UFC3TTK00) reduced the centrifugation time necessary to obtain a sufficient volume of ultrafiltrate for assay, thereby minimizing the possibility of heat generation. Furthermore, the binding of theophylline to this device was low and comparable to the binding to the Centrifree devices. Because this low degree of membrane binding may not hold for other drugs, we would suggest that a Millipore unit supplied with a low-binding, 30,000 dalton cutoff membrane could provide binding data with an efficacy comparable to that achieved with the Centrifree devices.

Humans↗
PubMed2002

A catalogue of polymorphisms related to xenobiotic metabolism and cancer susceptibility.

High-throughput genotyping technology of multiple genes based on large samples of cases and controls are likely to be important in identifying common genes which have a moderate effect on the development of specific diseases. We present here a comprehensive list of 313 known experimentally confirmed polymorphisms in 54 genes which are particularly relevant for metabolism of drugs, alcohol, tobacco, and other potential carcinogens. We have compiled a catalog with a standardized format that summarizes the genetic and biochemical properties of the selected polymorphisms. We have also confirmed or redesigned experimental conditions for simplex or multiplex PCR amplification of a subset of 168 SNPs of particular interest, which will provide the basis for the design of assays compatible with high-throughput genotyping.

Cytochrome P-450 Enzyme System↗
PubMed2004

Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants.

OBJECTIVES: Completion of both the mouse and human genome sequences in the private and public sectors has prompted comparison between the two species at multiple levels. This review summarizes the cytochrome P450 (CYP) gene superfamily. For the first time, we have the ability to compare complete sets of CYP genes from two mammals. Use of the mouse as a model mammal, and as a surrogate for human biology, assumes reasonable similarity between the two. It is therefore of interest to catalog the genetic similarities and differences, and to clarify the limits of extrapolation from mouse to human. METHODS: Data-mining methods have been used to find all the mouse and human CYP sequences; this includes 102 putatively functional genes and 88 pseudogenes in the mouse, and 57 putatively functional genes and 58 pseudogenes in the human. Comparison is made between all these genes, especially the seven main CYP gene clusters. RESULTS AND CONCLUSIONS: The seven CYP clusters are greatly expanded in the mouse with 72 functional genes versus only 27 in the human, while many pseudogenes are present; presumably this phenomenon will be seen in many other gene superfamily clusters. Complete identification of all pseudogene sequences is likely to be clinically important, because some of these highly similar exons can interfere with PCR-based genotyping assays. A naming procedure for each of four categories of CYP pseudogenes is proposed, and we encourage various gene nomenclature committees to consider seriously the adoption and application of this pseudogene nomenclature system.

Alternative Splicing↗
PubMedDate not supplied

Expert clinical rules automate steps in delivering evidence-based care in the electronic health record.

A working framework is presented for interdisciplinary professionals for designing, building, and evaluating clinical decision support rules (expert rules) within the electronic health record. The working framework outlines the key workflow processes for eight health system organizations for selecting, designing, building, activating, and evaluating rules. In preparation, an interdisciplinary team selected expert rules for their organizations. A physician, a nurse, and/or pharmacy informatics specialists led the team for each organization. The team chose from a catalog of expert rules that were supported by regulatory or clinical evidence. The design process ensured that each expert rule followed evidence-based guidelines and was programmed to automate steps in planning and delivering patient care. Expert rules were prioritized when improving the safety and quality of care. Finally, clinical decision support rules were evaluated for abilities to improve the consistency and currency of assessments and follow-through on patient findings from these assessments. The informatics specialists from each of the health system organizations also participated in a health system oversight group to construct the key processes for this beginning framework. The group refined the processes for the selection, design, construction, activation, and evaluation of expert rules over the past 3 years. These steps offered direction to subsequent clinic and hospital organizations in a similar situation. This case study identified four key considerations when implementing and evaluating the clinical decision support expert rules within care delivery. In summary, the processes for decision support expert rules required rigorous development and change control processes to support operation.

Decision Making, Organizational↗
PubMed1995

Race and socioeconomic status in hypertension and renal disease.

Publications within the past year have added to our understanding of the relationships between race, socioeconomic status, hypertension, and renal disease. The catalog of racial differences in hypertension and renal disease has been enriched on several accounts. Some of these differences can be explained by specific intervening variables, but others remain attributed to race itself. Unfortunately, what 'race' actually represents is still subject to debate. This debate should be encouraged, because the lack of a clear concept of race hinders research in this area. The main new finding of the year may be a confirmation by several studies that low socioeconomic status is an independent risk factor for end-stage renal disease, regardless of race. Research explaining the mechanisms by which poverty affects the risk of kidney failure is urgently needed, as some of these mechanisms may lend themselves to preventive intervention. Interventions aimed at improving the serious socioeconomic consequences of treated end-stage renal disease are also receiving increasing attention, and have been shown to improve patient outcomes.

Humans↗
PubMed2003

Novel aspects of renal organic anion transporters.

PURPOSE OF REVIEW: Organic anion transporters, transmembrane proteins present in the renal proximal tubule, are a critical component of the human drug excretion machinery. Recent advances have clarified the function of these transporters, with broad clinical implications for pharmacogenetics, drug interactions and adverse reactions. Here, we discuss these issues in the context of the basic biology of the transporters. RECENT FINDINGS: Understanding of organic anion transporter function has proceeded on several fronts. The continued cataloging of organic anion transporter substrates has revealed that the transporters' activity likely underlies many common drug interactions and nephrotoxic adverse reactions. Meanwhile, immunohistochemical and physiological studies suggest their potential involvement in the apical as well as basolateral steps of renal organic anion secretion. In addition, studies of the genomic organization of these transporters reveal that they are found in pairs of similar and similarly expressed genes, suggesting that pair members are coordinately regulated. Finally, we hypothesize here that organic anion transporters might impact renal susceptibility to ischemia and toxic injury, because their uptake of substrates can result in the efflux of Krebs cycle intermediates, an important nutrient source for the proximal tubule. SUMMARY: The study of these transporters will likely have a significant impact on renal pharmacology and pharmacogenetics. In this regard, the generation of organic anion transporter gene knockout mice could provide invaluable models for defects in renal drug-handling. Ultimately, detailed knowledge of organic anion transporter function will assist in the choice of optimum pharmacological therapies.

Animals↗
PubMed2003

The etiology of childhood immune thrombocytopenic purpura: how complex is it?

Recent developments in genomics and basic immunology have provided a new set of tools for investigation into the etiology and treatment of childhood immune thrombocytopenia purpura (ITP). The genomic revolution is generating a catalog of germ-line common genetic variants, some of which could influence the susceptibility or outcome of ITP. Similarly, in vitro analyses and animal models have been employed to probe the basic alterations underlying ITP. The emergence of a more refined understanding of complex diseases such as ITP has important implications for prevention, therapy, and follow-up. The relative contribution of the genetic component and its interaction with the strong environmental stimulus, such as an acute, antecedent viral infection, remains to be determined.

Child↗
PubMed1986

Use of SOHIO's health information system.

A computerized system using concepts of profiling and problem orientation will be described and examples of its use demonstrated. The system contains or accesses files on employee demography, job history, and current task lists, inventory of workplace risks categorized as physical, chemical, and functional, a master chemical inventory, and individual exposure records. By using Systemized Nomenclature of Medicine codes, a complete medical file catalogs all physiological and pathological variables, disease states, and functional responses. Profiling exposures and medical conditions enhances inquiry of the large data base that is accumulated.

Environmental Exposure↗
PubMed2000

Mining variations in genes of innate and phagocytic immunity: current status and future prospects.

The large number of sequence variations in human genes reflects the diversity of human populations and the response to prior environmental and pathogen challenges. Currently, major efforts are under way to identify and catalog single-nucleotide polymorphisms for use in genetic studies designed to explore the contribution of common variants to both disease susceptibility and interindividual differences in outcomes. So far, the most productive approach has been to search with candidate genes for which there is a scientific rationale (eg, prior data on the biologic implications of one or more variant alleles). Recently, there has been an explosion in the number of genetic association studies seeking to correlate one or more well-defined outcomes with variant alleles. These studies provide a foundation for identifying and applying genetic risk factors to clinical medicine. However, a number of challenges must be met before widespread use in clinical medicine can be undertaken. These include more efficient bioinformatics, basic insights into the significance of the variant alleles, ethical issues, and the availability of cost-effective, high-throughput platforms for genotype analysis.

Human Genome Project↗
PubMed2006

Antibiotic use in pregnancy and lactation: what is and is not known about teratogenic and toxic risks.

OBJECTIVE: Over ten million women are either pregnant or lactating in the United States at any time. The risks of medication use for these women are unique. In addition to normal physiologic changes that alter the pharmacokinetics of drugs, there is the concern of possible teratogenic and toxic effects on the developing fetus and newborn. This article reviews the risks and pharmacokinetic considerations for 11 broad-spectrum antibiotics that can be used to treat routine and life-threatening infections during pregnancy and lactation. DATA SOURCES: Information from the U.S. Food and Drug Administration (FDA) product labels, the Teratogen Information Service, REPROTOX, Shepard's Catalog of Teratogenic Agents, Clinical Pharmacology, and the peer-reviewed medical literature was reviewed concerning the use of 11 antibiotics in pregnant and lactating women. The PubMed search engine was used with the search terms "[antibiotic name] and pregnancy," "[antibiotic name] and lactation," and "[antibiotic name] and breastfeeding" from January 1940 to November 2005, as well as standard reference tracing. METHODS OF STUDY SELECTION: One hundred twenty-four references had sufficient information concerning numbers of subjects, methods, and findings to be included. TABULATION, INTEGRATION, AND RESULTS: The teratogenic potential in humans ranged from "none" (penicillin G and VK) to "unlikely" (amoxicillin, chloramphenicol, ciprofloxacin, doxycycline, levofloxacin, and rifampin) to "undetermined" (clindamycin, gentamicin, and vancomycin). Assessments were based on "good data" (penicillin G and VK), "fair data" (amoxicillin, chloramphenicol, ciprofloxacin, doxycycline, levofloxacin, and rifampin), "limited data" (clindamycin and gentamicin), and "very limited data" (vancomycin). Significant pharmacokinetic changes occurred during pregnancy for the penicillins, fluoroquinolones and gentamicin, indicating that dosage adjustments for these drugs may be necessary. With the exception of chloramphenicol, all of these antibiotics are considered compatible with breastfeeding. CONCLUSION: Health care professionals should consider the teratogenic and toxic risk profiles of antibiotics to assist in making prescribing decisions for pregnant and lactating women. These may become especially important if anti-infective countermeasures are required to protect the health, safety, and survival of individuals exposed to pathogenic bacteriologic agents that may occur from bioterrorist acts.

Anti-Bacterial Agents↗
PubMed2003

Audiologic manifestations of patients with post-treatment Lyme disease syndrome.

OBJECTIVE: The purpose of this study was to characterize auditory function in patients diagnosed with post-treatment Lyme disease syndrome (PTLDS). DESIGN: Eighteen patients with PTLDS were evaluated and compared to a normal population. Evaluations consisted of pure tone and speech thresholds, word recognition (WRS), acoustic immittance battery, auditory brain stem response (ABR), and loudness discomfort level (LDL). Both seropositive and seronegative patients were evaluated. Audiologists were blinded to patient status. RESULTS: Forty four percent of the patients had one or more abnormal pure tone thresholds compared to gender- and age-adjusted norms. Thirty-one percent showed abnormally reduced LDLs, and 17% had abnormal acoustic reflexes at one or more frequencies. CONCLUSIONS: This paper catalogs previously unstudied long-term auditory system sequelae resulting from PTLDS. Our most significant finding was the dramatically reduced loudness tolerance in the presence of either normal or minimally impaired hearing. The clinician is encouraged to consider PTLDS when confronted with these or similar findings in patients having history of Borrelia burgdorferi infection and continued complaints.

Adult↗
PubMed2003

Physical characteristics of polyaxial-headed pedicle screws and biomechanical comparison of load with their failure.

STUDY DESIGN: Pedicle screw strength or load to failure was biomechanically evaluated, and the geometric characteristics of pedicle screw instrumentation systems were compared. OBJECTIVES: To compare the features of pedicle screw systems, and to demonstrate the failure point of the polyaxial pedicle screw head. SUMMARY OF BACKGROUND DATA: Many pedicle screw instrumentation systems are currently available to the spine surgeon. Each system has its unique characteristics. It is important for the surgeon to understand the differences in these pedicle screw systems. Pedicle screw load to failure has not been subjected to a comparison study. METHODS: The physical characteristics of each pedicle screw instrumentation system were determined. Features of rods, instruments, and pedicle screws were cataloged. Biomechanical testing of the pedicle screw construct was performed to determine the site and force of the load to failure. Nine pedicle screw systems were evaluated. Testing was performed with a pneumatic testing system under load control. Three polyaxial screws were used for each test at a load rate of 100 N/second. The load failure value was the force at which the pedicle screw or polyaxial head-screw interface initially deflected. RESULTS: Biomechanical testing demonstrated in all instances that the polyaxial head coupling to the screw was the first failure point. Although there have been subtle design differences in the instruments over time, the features of the pedicle screw instrument sets have become remarkably similar. CONCLUSIONS: Biomechanical pedicle screw load-to-failure data demonstrated that the polyaxial head coupling to the screw is the first to fail and may be a protective feature of the pedicle screw, preventing pedicle screw breakage. Knowing the physical characteristics of the available pedicle screw instrumentation systems may allow the choice of pedicle screw best suited for a given clinical situation.

Biomechanical Phenomena↗
PubMed2005

A new classification of thoracolumbar injuries: the importance of injury morphology, the integrity of the posterior ligamentous complex, and neurologic status.

STUDY DESIGN: A new proposed classification system for thoracolumbar (TL) spine injuries, including injury severity assessment, designed to assist in clinical management. OBJECTIVE: To devise a practical, yet comprehensive, classification system for TL injuries that assists in clinical decision-making in terms of the need for operative versus nonoperative care and surgical treatment approach in unstable injury patterns. SUMMARY OF BACKGROUND DATA: The most appropriate classification of traumatic TL spine injuries remains controversial. Systems currently in use can be cumbersome and difficult to apply. None of the published classification schemata is constructed to aid with decisions in clinical management. METHODS: Clinical spine trauma specialists from a variety of institutions around the world were canvassed with respect to information they deemed pivotal in the communication of TL spine trauma and the clinical decision-making process. Traditional injury patterns were reviewed and reconsidered in light of these essential characteristics. An initial validation process to determine the reliability and validity of an earlier version of this system was also undertaken. RESULTS: A new classification system called the Thoracolumbar Injury Classification and Severity Score (TLICS) was devised based on three injury characteristics: 1) morphology of injury determined by radiographic appearance, 2) integrity of the posterior ligamentous complex, and 3) neurologic status of the patient. A composite injury severity score was calculated from these characteristics stratifying patients into surgical and nonsurgical treatment groups. Finally, a methodology was developed to determine the optimum operative approach for surgical injury patterns. CONCLUSIONS: Although there will always be limitations to any cataloging system, the TLICS reflects accepted features cited in the literature important in predicting spinal stability, future deformity, and progressive neurologic compromise. This classification system is intended to be easy to apply and to facilitate clinical decision-making as a practical alternative to cumbersome classification systems already in use. The TLICS may improve communication between spine trauma physicians and the education of residents and fellows. Further studies are underway to determine the reliability and validity of this tool.

Humans↗