Development of health diagnostics based on personalized medical models.

Due to rapid evolution of new technologies the concept of personalized medicine has evolved. Components include molecular biology, proteomics, metabolomic analysis, genetic testing, and molecular medicine for diagnostics. In addition to diagnostics these methods can be used to determine individual susceptibility to diseases and conditions. In conjunction with new diagnostic methods, new therapies can be tailored to the individual. These new technologies present a challenge in terms of the expansion of the medical record as well as the development of new methods for creating disease profiles. This article focuses on a computer-aided support for personalized medicine. Specific approaches are explored that permit automated data analysis for prognosis and treatment based on analysis methods for numeric and pictorial data. Although personalized medicine based on the genome of the patient are occasionally performed, because of the large amount of data new methods are needed to form general disease models as well as specific profiles of the individual patient.

Efficiency of oral fluid collection devices in extracting antibodies.

INTRODUCTION: To facilitate diagnoses, this study determined the efficacy of commercial oral fluid collection devices for their ability to recover three human immunoglobulin isotypes; immunoglobulin A (IgA), IgG, and IgM. METHODS: The sandwich enzyme-linked immunosorbent assay was used to determine antibody recovery from the following devices: (i) OraSure oral specimen collection device, (ii) saliva*sampler, (iii) ORALscreen collector, (iv) Dri-Angle, (v) no. 2 cotton roll, (vi) all-gauze sponges device, and (vii) DentaSwabs. For each isotype tested, the recovered eluate was compared with the concentration applied to the device. The performance of each device was determined at various antibody concentrations. RESULTS: Recovery of IgA from the saliva*sampler, ORALscreen collector, Dri-Angle and cotton roll was comparable to that seeded onto the device. When compared with the seeded IgG concentration, the mean concentration of antibody recovered by each product differed by approximately +/- 9 ng/ml. The average amount of IgM recovered by the cotton roll and all-gauze sponges device was approximately 29 and 39 ng/ml, respectively, less (P < 0.0001) than that seeded on the device. For all isotypes tested, the amount of antibody recovered from the device was dependent on the initial seeding concentration. CONCLUSION: Collectively, these data suggest that the product used for specimen collection can affect retrieval of antibodies and potentially confound patient diagnosis.

Intelligent agent model for remote support of rural healthcare for the elderly.

With the aging population, the number of individuals requiring long-term care is expected to dramatically increase in the next twenty years, placing an increasing burden on healthcare. Many patients are admitted to assisted living facilities at a fairly early stage due to their inability to perform normal daily living activities. The purpose of this study is to determine if the use of technology for both monitoring and intervention can permit elderly patients to remain in their homes for longer periods of time with the benefit of the comfort of familiar surroundings while at the same time reducing the burden on caregivers. In addition, remote access to healthcare can improve monitoring of the patient's physical and mental condition and involve the patient in his or her own care. The home monitoring and intervention system is based on intelligent agent methodology developed by the authors.

Non-linear analysis using continuous chaotic modeling.

Recent research in nanotechnology is opening exciting new avenues not only for understanding the human body but also for creating devices that can effectively interact with it to alleviate the effects of disease. These new developments present both challenges and opportunities for adaptation of existing methodologies to create new approaches for analysis and modeling of nanotechnology-based systems. The concept of continuous chaotic modeling presents an avenue for a paradigm shift away from traditional digital computing to take advantage of analog models that are more compatible with biological systems. The theoretical basis of continuous chaotic modeling is summarized, followed by illustrations of applications of this methodology.

The role of networks and artificial intelligence in nanotechnology design and analysis.

Techniques with their origins in artificial intelligence have had a great impact on many areas of biomedicine. Expert-based systems have been used to develop computer-assisted decision aids. Neural networks have been used extensively in disease classification and more recently in many bioinformatics applications including genomics and drug design. Network theory in general has proved useful in modeling all aspects of biomedicine from healthcare organizational structure to biochemical pathways. These methods show promise in applications involving nanotechnology both in the design phase and in interpretation of system functioning.

Inclusion of signal analysis in a hybrid medical decision support system.

OBJECTIVES: Signal analysis has played an important role in cardiac diagnosis, both as a separate entity and in conjunction with clinical parameters. Hybrid systems are an effective method for developing higher-order decision models in which biomedical signal data can be incorporated. METHODS: The hybrid system components include a knowledge-based system that utilizes approximate reasoning techniques, a neural network model based on a potential function approach to supervised learning that uses the general class of Cohen orthogonal functions as potential functions, and a signal analysis component that relies on continuous chaotic modeling to produce a degree of variability in the time series. The hybrid system is illustrated in an application for differentiation among different types of dementia. RESULTS: Application of this method to cardiac diagnosis shows that chaotic parameters alone contribute significantly to correct classification while the addition of clinical parameters increases the sensitivity, specificity, and accuracy. Applications to electroencephalogram analysis indicate that the second-order difference plots display significant differences for the different types of EEG waves identifiable by frequency, both in shape and degree of dispersion. Hence the identification of these waves, and the duration of their occurrence, may provide suitable variables for chaotic analysis. CONCLUSIONS: Results from studies in cardiology demonstrate that using chaotic measures for ECG analysis provide useful information for classification. Sensitivity, specificity, and accuracy are increased if these methods are combined with other clinical parameters in a hybrid system. This approach has been extended to new applications based on EEG analysis combined with other relevant information.

Residual mercury content and leaching of mercury and silver from used amalgam capsules.

OBJECTIVE: The objective of this investigation was to carry out residual mercury (Hg) determinations and toxicity characteristic leaching procedure (TCLP) analysis of used amalgam capsules. METHODS: For residual Hg analysis, 25 capsules (20 capsules for one brand) from each of 10 different brands of amalgam were analyzed. Total residual Hg levels per capsule were determined using United States Environmental Protection Agency (USEPA) Method 7471. For TCLP analysis, 25 amalgam capsules for each of 10 brands were extracted using a modification of USEPA Method 1311. Hg analysis of the TCLP extracts was done with USEPA Method 7470A. Analysis of silver (Ag) concentrations in the TCLP extract was done with USEPA Method 6010B. RESULTS: Analysis of the residual Hg data resulted in the segregation of brands into three groups: Dispersalloy capsules, Group A, retained the most Hg (1.225 mg/capsule). These capsules were the only ones to include a pestle. Group B capsules, Valliant PhD, Optaloy II, Megalloy and Valliant Snap Set, retained the next highest amount of Hg (0.534-0.770 mg/capsule), and were characterized by a groove in the inside of the capsule. Group C, Tytin regular set double-spill, Tytin FC, Contour, Sybraloy regular set, and Tytin regular set single-spill retained the least amount of Hg (0.125-0.266 mg/capsule). TCLP analysis of the triturated capsules showed Sybraloy and Contour leached Hg at greater than the 0.2 mg/l Resource Conservation and Recovery Act (RCRA) limit. SIGNIFICANCE: This study demonstrated that residual mercury may be related to capsule design features and that TCLP extracts from these capsules could, in some brands, exceed RCRA Hg limits, making their disposal problematic. At current RCRA limits, the leaching of Ag is not a problem.

Muromonab-CD3-induced neurotoxicity: report of two siblings, one of whom had subsequent cyclosporin-induced neurotoxicity.

Muromonab-CD3 is widely used for immunosuppression in patients undergoing solid organ transplant. We report two siblings with oligomeganephronia and end-stage renal disease who developed encephalopathy and seizures from muromonab-CD3 following renal transplant. The first case is a 13-year-old girl who developed encephalopathy, seizure, and triparesis following renal transplant while muromonab-CD3 was used for immunosuppression. The second case was the 6-year-old sister of the first case, who also developed recurrent focal seizures while she was on muromonab-CD3 for renal transplant immunosuppression. In both cases, a sequential brain magnetic resonance image (MRI) showed progression of abnormalities from the cerebral cortex to the white matter. In the first case, the MRI normalized after muromonab-CD3 was discontinued. In the second case, the patient developed a leukoencephalopathy following cyclosporin administration. The pathophysiology of muromonab-CD3 encephalopathy is believed to be a disturbance to the blood-brain barrier mediated by cytokine release from lymphocyte stimulation by muromonab-CD3. Because the major histocompatibility complex genes are known to regulate cytokine responses, it is possible that the excessive production of cytokines that causes encephalopathy may occur in patients who share close major histocompatibility complex genes. Muromonab-CD3 in a patient whose sibling has developed cerebral complications from its use should be administered with caution. The second case suggests that muromonab-CD3 encephalopathy predisposes patients to develop cyclosporin neurotoxicity. Because the pathogenesis of muromonab-CD3 encephalopathy and cyclosporin-related cerebral complications are both potentially mediated through a disturbance of the blood-brain barrier, it is possible that one agent may predispose a patient to the complication of the other.

The use of consequential reasoning in cancer chemotherapy.

Knowledge-based decision support systems traditionally rely on condition-action rule structures, an adequate representation for simple decisions. In complex domains an important part of decision-making includes analysis of the consequences of a decision. Consequential reasoning is particularly important in medicine as potential risk and/or benefit can be included. In this paper, a knowledge structure and inference engine is described that permits the representation and analysis of consequential reasoning in a computer-assisted decision support system. The use of consequential reasoning is then illustrated in an application designed to assist in cancer chemotherapy decisions. The result is a method that is sensitive to individual patient reactions to chemotherapy agents, permitting an individualized approach to therapy. Individualized drug therapy is becoming increasingly feasible due to advances made in the field of genomics. The system is structured so that new information can be incorporated easily. Although the application shown here is to chemotherapy, the general methodology can be used in any area in which the consequences should significantly influence the decision.

Prevalence of dehiscences and fenestrations in modern American skulls.

BACKGROUND: The purpose of this study was to examine the prevalence, distribution, and features of alveolar dehiscences and fenestrations in modern American skulls and correlate their presence with occlusal attrition, root prominence, and alveolar bone thickness. METHODS: A representative sample of 146 dentate modern American skulls from a collection at the National Museum of Natural History were examined. RESULTS: The skulls were from subjects ranging in age from 17 to 87 years old (mean 49.1 years). The mean number of teeth per skull was 22.7 and the mean number of either dehiscence or fenestration defects per skull was 3.0. Of the 3,315 individual teeth examined, 4.1% (135) had dehiscences and 9.0% (298) had fenestrations. A dehiscence was present in 40.4% of the skulls, and a fenestration was present in 61.6% of skulls. Mandibular canines were most often affected by dehiscences (12.9%), while maxillary first molars were most often affected by fenestrations (37.0%). Sixty-seven percent of dehiscences were found in the mandible, and 58% of fenestrations were found in the maxilla. CONCLUSIONS: The presence of dehiscences and fenestrations were positively correlated with thin alveolar bone and negatively correlated with occlusal attrition. African-American males and Caucasian females were significantly more likely to have dehiscences, while African-American females were significantly more likely to have fenestrations.

Internal levator advancement by Müller's muscle-conjunctival resection: technique and review.

BACKGROUND: Müller's muscle-conjunctival resection surgery presumably works by advancing the levator aponeurosis of the upper eyelid. The amount of blepharoptosis and the lid's response to the instillation of phenylephrine hydrochloride onto the superior ocular fornix are used to determine the extent of surgery needed. OBJECTIVES: To demonstrate the procedure developed and popularized by Allen M. Putterman, MD, performed by Michael Mercandetti, MD, MBA, and to describe the relationship between the amount of Müller's muscle-conjunctival resection performed and the amount of elevation achieved. METHODS: Data were retrospectively analyzed based on surgical cases done over a 5-year period by one surgeon (A.M.P.). RESULTS: A linear regression model was developed. From this regression a simple table correlating the amount of resection with the amount of elevation desired was derived. CONCLUSION: The surgeon will need to modify the table based on his or her clinical experience and postoperative results.

Analysis of ordinal dental data: evaluation of conflicting recommendations.

Although recommendations for the appropriate analysis of non-normal and ordinal-scaled data have appeared in the dental research literature for many years, there is no consensus. When one is conducting statistical tests for differences between groups, the central concern is whether it is safe to use parametric tests (e.g., analysis of variance), or if only non-parametric ranking tests should be considered. Relevant statistical and scientific issues associated with non-normality and measurement scale are reviewed, and three conclusions are reached regarding the analysis of dental data: (1) Parametric tests are sufficiently robust relative to typical violations of normality; (2) presumed statistical prohibitions against the application of parametric methods to ordinal data do not actually exist; and (3) 'ordinal' dental indices have sufficient quantitative meaning to be considered quasi-interval. For these reasons, parametric tests should not be avoided; they will be valid and usually more powerful and more easily applied to complex designs than non-parametric alternatives.

Prediction of bile duct stones and complications in gallstone pancreatitis using early laboratory trends.

OBJECTIVES: We aimed to determine whether early trends in the serum pancreatic enzymes and liver tests of patients with gallstone pancreatitis predict persistent common bile duct (CBD) stones and complications. METHODS: Medical records of patients with gallstone pancreatitis were reviewed retrospectively. Serial serum pancreatic enzymes and liver tests were recorded until the time of cholangiography. Laboratory trends were analyzed by comparing initial results obtained in the emergency department to subsequent results obtained 8-24 h, 24-48 h, and 48-72 h after presentation. RESULTS: Of 154 patients with gallstone pancreatitis, 28 (18%) had persistent CBD stones at cholangiography. Complications and death were more frequent in patients with persistent CBD stones than in those without CBD stones (29% and 11% vs 12% and 1%, respectively; p < 0.05). Laboratory trends predicted both persistent CBD stones and complications of pancreatitis. When any laboratory value rose between admission and 24-48 h of hospitalization, persistent CBD stones were present in 31% of cases, versus 8% of those in whom all laboratory values remained constant or fell (p = 0.001). Likewise, complications occurred in 21% of those with any rising laboratory value, versus 8% of those in whom all values remained constant or fell (p < 0.05). CONCLUSIONS: Patients with gallstone pancreatitis and rising serum chemistries had a 4-fold risk of persistent CBD stones and a nearly 3-fold risk of complications compared to patients in whom all chemistry values remained constant or fell. This simple prediction rule may identify patients with biliary pancreatitis who are most likely to benefit from early interventions to diagnose and remove persistent CBD stones.

The tools of disability outcomes research functional status measures.

OBJECTIVE: To review the major functional status measures currently used in rehabilitation research, including the domains and scope of functional status measures, as well as the psychometric properties of selected functional status measures and their use in adult rehabilitation populations. DATA SOURCES: Measures of physical functioning widely used in rehabilitation research. STUDY SELECTION: Major generic measures included the following activities of daily living and instrumental activities of daily living: the FIM instrument, the Katz Activities of Daily Living Scale, the Level of Rehabilitation Scale, the Barthel index, and the Patient Evaluation and Conference System. Measures were evaluated based on published evidence of validity, reliability, and sensitivity. DATA EXTRACTION: Measures were chosen on the basis of the amount and quality of published research on the functional measures widely used in rehabilitation medicine. Independent research of computer databases and reviews of functional measures were conducted to determine suitability for inclusion. The quality and validity of the measures were assessed using standard psychometric guidelines. DATA SYNTHESIS: Measures were evaluated based on published evidence of validity, reliability, sensitivity response and administrative burdens and instrument bias. Each criterion was graded on a 3-point scale reflecting the level of evidence. CONCLUSION: Researchers in the field of disabilities research need to consider carefully study objectives when measuring physical functioning in people with disabilities.

Measurement of proteases in human subgingival dental plaque by fluorescence polarization.

Fluorescence polarization (FP) was examined as a rapid quantitative method to assay the proteases in subgingival plaque. Protease activity was measured by a decrease in FP at 0.5-min intervals over 5 min, using BODIPY-alpha-casein, a protein substrate. To quantitate activity, the least absolute deviation (LAD) slope for each assay was determined. Protease activity increased with the quantity of plaque (r=0.416, P<0.001). Of the 208 subgingival plaque samples, 87 contained detectable protease activity, with a mean of about 4 microg trypsin equivalents above a general background of 1 microg per site. The mean plaque protease activity of 89 paired samples from 15 individuals had decreased by 1.1 microg trypsin equivalents per site when measured at 8 months after tooth scaling and root planing (P<0.01). Most isolates of Porphyromonas gingivalis, Treponema denticola, Prevotella nigrescens, and Prevotella intermedia implicated in the pathogenesis of adult periodontitis exhibited high activity in the FP assay. The assay is rapid, quantitative and requires only one-tenth of the plaque sampled using a single pass with a Gracey curette at a single tooth site.

Early-onset Moyamoya syndrome in a patient with Down syndrome: case report and review of the literature.

Moyamoya disease is a chronic occlusive cerebrovascular disorder. It can occur as a primary disease or as a syndrome associated with a variety of conditions. Usually it takes 1 to 2 years to develop a classic moyamoya pattern. We report a 20-month-old girl with Down syndrome and moyamoya syndrome who presented with seizure and hemiparesis. To our knowledge, this is the youngest case reported with moyamoya syndrome and Down syndrome. The prognosis and current treatment of moyamoya syndrome and its relation to Down syndrome are reviewed. There is some reason to speculate that the abnormalities associated with Down syndrome might create a vulnerability for the development of moyamoya syndrome.

Buccal alveolar exostoses: prevalence, characteristics, and evidence for buttressing bone formation.

BACKGROUND: Buttressing bone formation has been described as the development of thickened or exostotic buccal alveolar bone in response to heavy occlusal forces. Little supporting evidence for this model has been found in previous literature, however, and there is little seen on the prevalence or characteristics of buccal alveolar exostoses. METHODS: A sample of 416 selected teeth and investing bone in 52 modern skeletal specimens at the National Museum of Natural History were examined. Two measures of heavy occlusal function--periodontal ligament (PDL) width and occlusal attrition--were analyzed for their relationship to three parameters of buccal alveolar bone (exostoses, lipping, and overall thickness). RESULTS: Buccal alveolar bone enlargements were found in 25% of all teeth examined: 18% were expressed as marginal bony lippings and 7% as buccal exostoses. Exostoses were mainly seen around maxillary molars and bicuspids, especially in males, while lippings were seen in molars, bicuspids, and mandibular incisors, with even gender distribution. When findings were controlled for arch and tooth type, no significant correlations were found between wider PDL spaces or occlusal attrition and exostotic, lipped, or thicker alveolar bone. CONCLUSIONS: These results indicate a lack of anatomic evidence for the theory of buttressing bone formation and suggest that other factors may be of greater importance in the etiology of buccal bone enlargements. Incidentally, no correlation was found between widened PDL spaces or severe occlusal attrition and the presence of cervical loss of tooth structure, which casts doubt on the currently popular concept of abfraction.

Recovery of upper-extremity strength in complete and incomplete tetraplegia: a multicenter study.

OBJECTIVE: To examine upper-extremity motor recovery of subjects with tetraplegia with both complete and incomplete injuries, to predict which patients and at what time they would recover a motor level. DESIGN: Prospective, multicenter clinical study of upper-extremity motor recovery in subjects with acute traumatic spinal cord injury. SETTING: Three regional spinal cord injury centers. SUBJECTS: One hundred sixty-seven individuals with acute traumatic tetraplegia (144 males [86%], and 23 females [14%]) between the ages of 15 and 75 years (mean age, 35.5 yrs). METHODS: Subjects were examined and classified using sequential manual muscle tests performed on admission, 72 hours, 1, 2, and 3 weeks, and 1, 2, 3, 6, 12, 18, and 24 months postinjury. C5 biceps, C6 extensor carpi radialis, C7 triceps, and C8 flexor digitorum profundus were evaluated using a 0-5 scale. Analyses of the right motor levels used a series of logistic regression models, and for multiple measurements on each subject, models were estimated using generalized estimating equations. RESULTS: The analysis for recovery of the biceps for the C4 group showed 70% of complete compared with 90% of incomplete injuries recovered (p < .001); of the extensor carpi radialis in the C5 group, 75% complete and 90% incomplete recovered (p < .002); and of the triceps in the C6 group, 85% of complete and 90% of incomplete injuries recovered (p < .16). CONCLUSION: Predicting future potential for upper-extremity motor recovery and for independence in self-care in groups of patients at a specific motor level is possible within the first week of injury.

Stress fractures of the pelvis in female navy recruits: an analysis of possible mechanisms of injury.

The purpose of our study was to investigate possible risk factors and mechanisms for the development of pelvic stress fractures in female Navy recruits. We used a case-control retrospective study of female Navy recruits undergoing basic military training. We compared anthropometric and activity data between recruits with pelvic stress fractures (N = 25) and female recruits who completed training without injury (N = 61). Recruits developing pelvic stress fractures were significantly (p < 0.05) shorter and lighter and were more frequently Asian or Hispanic than recruits without stress fractures. In addition, recruits with pelvic stress fractures reported marching in the back of their training division, were road guards, and felt that their stride was too long during training activities more often than recruits without injury. Self-reported fitness, activities before recruit training, or a history of amenorrhea was not found to be associated with the development of a pelvic stress fracture in our population.