Computer-based System for the Virtual-Endoscopic Guidance of Bronchoscopy.

The standard procedure for diagnosing lung cancer involves two stages: three-dimensional (3D) computed-tomography (CT) image assessment, followed by interventional bronchoscopy. In general, the physician has no link between the 3D CT image assessment results and the follow-on bronchoscopy. Thus, the physician essentially performs bronchoscopic biopsy of suspect cancer sites blindly. We have devised a computer-based system that greatly augments the physician's vision during bronchoscopy. The system uses techniques from computer graphics and computer vision to enable detailed 3D CT procedure planning and follow-on image-guided bronchoscopy. The procedure plan is directly linked to the bronchoscope procedure, through a live registration and fusion of the 3D CT data and bronchoscopic video. During a procedure, the system provides many visual tools, fused CT-video data, and quantitative distance measures; this gives the physician considerable visual feedback on how to maneuver the bronchoscope and where to insert the biopsy needle. Central to the system is a CT-video registration technique, based on normalized mutual information. Several sets of results verify the efficacy of the registration technique. In addition, we present a series of test results for the complete system for phantoms, animals, and human lung-cancer patients. The results indicate that not only is the variation in skill level between different physicians greatly reduced by the system over the standard procedure, but that biopsy effectiveness increases.

Automatic axis generation for virtual bronchoscopic assessment of major airway obstructions.

Virtual bronchoscopy (VB) has emerged as a paradigm for more effective 3D CT image evaluation. Systematic evaluation of a 3D CT chest image using VB techniques, however, requires precomputed guidance data. This guidance data takes the form of central axes, or centerlines, through the major airways. We propose an axes-generation algorithm for VB assessment of 3D CT chest images. For a typical high-resolution 3D CT chest image, the algorithm produces a series of airway-tree axes, corresponding airway cross-sectional area measurements, and a segmented airway tree in a few minutes on a standard PC. Results for phantom and human airway-obstruction cases demonstrate the efficacy of the algorithm. Also, the algorithm is demonstrated in the context of VB-based 3D CT assessment.

Pharmacogenetic screening for susceptibility to fetal malformations in women.

OBJECTIVE: To present a review of the literature and research on the pharmacogenetics of congenital defects, with a focus on the need for predictive maternal genotype assays. DATA SOURCE: MEDLINE searches (January 1985-January 1999), past reference reviews, and unpublished research. STUDY SELECTION: Review of relevant human, animal, and basic science studies. DATA EXTRACTION: Data on research on polymorphisms, genotyping, cytochrome P450 enzyme systems, epoxide hydrolase, folate metabolism, metabolism of anticonvulsant medications, molecular genetics of neural tube defects, variations in drug metabolism, and environmental exposures were evaluated. DATA SYNTHESIS: Data synthesis includes not only a review of the literature but suggests ways such data might be used to facilitate the development of maternal genotype assays, with the goal of preventing birth defects. CONCLUSIONS: Individuals vary in how they metabolize drugs and handle toxic environmental exposures. In an ideal pregnancy, there is no or limited exposure to medications and environmental agents. However, in women with chronic medical conditions such as heart disease and seizures, this is often not possible. Unfortunately, no techniques have been available to identify those at risk in this population. Gene polymorphisms for a specific enzyme may result in an absence or reduction in the level of enzyme activity or in no change at all, with little effect on the structure/function of the gene product(s); they are not associated with clinical phenotypes in either the mother or the fetus. Other polymorphisms may be only markers. Thus, developing genotyping assays for women that are predictive of phenotype expression in the fetus is the key to screening for polymorphisms. As more mutations are identified and clinical, pharmacologic, biologic, and pharmacokinetic relationships are established, using these polymorphisms to develop a genotyping assay for women may become a clinical reality, possibly leading to preventive prepregnancy or prenatal treatment that may play an increasingly effective role in maternal care.

Analysis of select folate pathway genes, PAX3, and human T in a Midwestern neural tube defect population.

Neural tube defects (NTDs) are a common birth defect, seen in approximately 1/1,000 births in the United States. NTDs are considered a complex trait where several genes, interacting with environmental factors, create the phenotype. Using a Midwestern NTD population consisting of probands, parents, and siblings from Iowa, Minnesota, and Nebraska, we analyzed a range of candidate genes, including 5,10-methylenetetrahydrofolate reductase (MTHFR), folate receptors-alpha (FOLR1; hereafter abbreviated "FR-alpha") and -beta (FOLR2; hereafter, "FR-beta"), methionine synthase (hereinafter, "MS"), T, the human homolog of the murine Brachyury gene, and the paired-box homeotic gene 3 (PAX3), for association with NTDs. We were unable to demonstrate an association using a previously described Ala-->Val mutation in MTHFR and the majority of our NTD populations. However, we discovered a silent polymorphism in exon 6 of MTHFR which conserved a serine residue and which showed significant association with NTDs in our Iowa population. Analysis of exon 7 of MTHFR then demonstrated an Ala-->Glu mutation which was significantly associated with our Iowa NTD population; however, we could not replicate this result either in a combined Minnesota/ Nebraska or in a California NTD population. Using polymorphic markers for MS, FR-beta, T, and PAX3, we were unable to demonstrate linkage disequilibrium with our NTD populations. A mutation search of FR-alpha revealed one proband with a de novo silent mutation of the stop codon. This work provides a new panel of genetic variants for studies of folate metabolism and supports, in some NTD populations, an association between MTHFR and NTDs.

Abnormalities in control of ventilation in newborn infants with myelomeningocele.

OBJECTIVE: The objective of this study was to assess respiratory responses of newborn infants with myelomeningocele through pneumograms and carbon dioxide challenge, and to evaluate the possibility of predicting which patients with myelomeningocele acquired respiratory symptoms related to the Arnold-Chiari deformity and brain-stem dysfunction. METHODS: All surviving infants with spina bifida who were born at the University of Iowa Hospitals and Clinics (UIHC) or were transferred there on the first day of life between January 1987 and January 1991 were assessed with a pneumogram and CO2 challenge once they were medically stable, and were followed for a mean of 30 months (10 to 53 months). RESULTS: Thirty patients met the inclusion criteria for this study; four died before being studied. Of the 26 remaining patients, 12 were born at the UIHC and 14 were transferred to the UIHC on the first day of life. Of the 26 infants studied, 12 (46%) had abnormalities on the pneumogram, including 2 with significant periodic breathing and 10 with episodes of desaturation below 87%. Of the 26 infants studied, 4 had no detectable response to an increasing fraction of CO2 in inspired air on the CO2 challenge and 12 had an increase in exhaled minute ventilation per increase in the alveolar fraction of CO2 in exhaled air more than 2 SD below the mean. Only 10 patients (38.5%) had normal ventilatory responses to the increasing fraction of CO2 in inspired air. On follow-up, only one study patient had symptoms related to Arnold-Chiari deformity and brain-stem dysfunction (bilateral vocal cord paralysis). His neonatal CO2 challenge results and his pneumogram were normal. CONCLUSION: We conclude that these two tests are not useful in predicting which patients will have symptoms related to Arnold-Chiari deformity. Specificity for the pneumogram and the CO2 challenge was 0.52 and 0.36, respectively. Sensitivity was zero for both tests, although this result is limited by the low incidence of symptomatic Arnold-Chiari deformity in this sample. As previous investigators have found, a significant number of patients with meningomyelocele had abnormal ventilatory patterns. These ventilatory abnormalities indicate that even in the absence of severe symptoms, the control of the ventilatory response is somewhat impaired in many patients with meningomyelocele. This alteration in ventilatory control is probably related to abnormalities in the development of the brain stem.

Early identification and treatment necessary to prevent malnutrition in children and adolescents with severe disabilities.

Children with severe developmental disabilities frequently have nutrition and growth problems that range from moderate to severe. Because of notable continuing medical concerns and lowered growth expectations, parents and physicians may fail to recognize gradual deterioration in nutritional status before severe medical complications occur. The two cases reported in this article illustrate the need for early identification and treatment to prevent the development of notable morbidity secondary to malnutrition. Children and adolescents who have growth parameters consistently below age norms require assessment and monitoring by a registered dietitian to detect feeding problems and intake changes and to provide early intervention to help prevent negative consequences (eg, dehydration, protein-energy malnutrition, decubitus ulcers, increased rate and duration of infections, and altered bowel motility). An initial assessment should consist of measurement of length or height, weight, triceps, and subcapsular skinfolds; dietary and feeding history and a review of medical history; and biochemical testing as indicated by the medical and dietary histories. Monitoring frequency, which is determined by age, severity of condition, and response to treatment, may vary from weekly to bimonthly.