Biomedical subjects
A Feldman
Publications and source records attributed to A Feldman.
Role of data aggregation in biosurveillance detection strategies with applications from ESSENCE.
INTRODUCTION: Syndromic surveillance systems are used to monitor daily electronic data streams for anomalous counts of features of varying specificity. The monitored quantities might be counts of clinical diagnoses, sales of over-the-counter influenza remedies, school absenteeism among a given age group, and so forth. Basic data-aggregation decisions for these systems include determining which records to count and how to group them in space and time. OBJECTIVES: This paper discusses the application of spatial and temporal data-aggregation strategies for multiple data streams to alerting algorithms appropriate to the surveillance region and public health threat of interest. Such a strategy was applied and evaluated for a complex, authentic, multisource, multiregion environment, including >2 years of data records from a system-evaluation exercise for the Defense Advanced Research Project Agency (DARPA). METHODS: Multivariate and multiple univariate statistical process control methods were adapted and applied to the DARPA data collection. Comparative parametric analyses based on temporal aggregation were used to optimize the performance of these algorithms for timely detection of a set of outbreaks identified in the data by a team of epidemiologists. RESULTS: The sensitivity and timeliness of the most promising detection methods were tested at empirically calculated thresholds corresponding to multiple practical false-alert rates. Even at the strictest false-alert rate, all but one of the outbreaks were detected by the best method, and the best methods achieved a 1-day median time before alert over the set of test outbreaks. CONCLUSIONS: These results indicate that a biosurveillance system can provide a substantial alerting-timeliness advantage over traditional public health monitoring for certain outbreaks. Comparative analyses of individual algorithm results indicate further achievable improvement in sensitivity and specificity.
Coronary artery calcification in older adults to age 99: prevalence and risk factors.
BACKGROUND: Coronary artery calcification has been proposed as a noninvasive method to assess cardiovascular disease (CVD) risk. However, the prevalence and risk factors for coronary artery calcification in populations >65 years have not been well studied. METHODS AND RESULTS: Electron beam tomography was performed to assess coronary artery calcium (CAC) in 614 older adults aged, on average, 80 years (range, 67 to 99 years); 367 (60%) were women, and 143 (23%) were black. Calcium scores ranged from 0 to 5459. Median scores were 622 for men and 205 for women. Scores increased by age and were lower in blacks than in whites. Nine percent of subjects (n=57) had no CAC, and 31% (n=190) had a score lower than 100. A history of CVD was associated with calcium score. Age, male sex, white race, CVD, triglyceride level, pack-years of smoking, and asthma, emphysema, or bronchitis (chronic obstructive pulmonary disease) were independently associated with CAC score in the fourth quartile. CONCLUSIONS: A wide range of CAC scores was observed, suggesting adaptation with aging. CAC may have potential to predict CVD in older adults, but this remains to be determined.
Usefulness of electron beam tomography to detect progression of coronary and aortic calcium in middle-aged women.
Electron beam tomography (EBT) permits the noninvasive quantification of coronary and aortic calcium as a marker of atherosclerosis. Coronary and aortic calcium are strongly related to premenopausal cardiovascular risk factors in middle-aged women. This report evaluates changes in coronary and aortic calcium over an average of 18 months in 80 women. Measurement variation over time and between readings is also evaluated in these women who were followed through the menopausal transition. Eight years after menopause, 80 women (average age 63 years) underwent serial EBT of the coronary arteries and aorta separated by 18 months. Calcium scores were based on the number and density of calcific deposits. Duplicate readings were obtained to evaluate the effect of reading variation on calcium scores. At baseline, the median calcium score was 0 in the coronary arteries and 58 in the aorta. Average change in coronary (+11) and aortic (+112) calcium were significantly different from zero (p < 0.001). Reading variability did not contribute significantly to the variation in calcium scores. Extent of calcium in the coronary arteries was associated with progression of calcium in the aorta (p = 0.013). Both coronary and aortic calcium were significantly associated with premenopausal cardiovascular risk factors. Thus, progression of coronary and aortic calcium using EBT can be observed over a short time in healthy middle- aged women.
Reduction of functional N-methyl-D-aspartate receptors in neurons by RNase P-mediated cleavage of the NR1 mRNA.
One approach to studying the functional role of individual NMDA receptor subunits involves the reduction in the abundance of the protein subunit in neurons. We have pursued a strategy to achieve this goal that involves the use of a small guide RNA which can lead to the destruction of the mRNA for a specific receptor subunit. We designed a small RNA molecule, termed 'external guide sequence' (EGS), which binds to the NR1 mRNA and directs the endonuclease RNase P to cleave the target message. This EGS has exquisite specificity and directed the RNase P-dependent cleavage at the targeted location within the NR1 mRNA. To improve the efficiency of this EGS, an in vitro evolution strategy was employed which led to a second generation EGS that was 10 times more potent than the parent molecule. We constructed an expression cassette by flanking the EGS with self-cleaving ribozymes and this permitted generation of the specified EGS RNA sequence from any promoter. Using a recombinant Herpes simplex virus (HSV), we expressed the EGS in neurons and showed the potency of the EGS to reduce NR1 protein within neurons. In an excitotoxicity assay, we showed that expression of the EGS in cortical neurons is neuroprotective. Our results demonstrate the utility of EGSs to reduce the expression of any gene (and potentially any splice variant) in neurons.
The routine use of personal patient dosimeters is of little value in detecting therapeutic misadministrations.
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Impact of atrial fibrillation on clinical status, atrial size and hemodynamics in patients after mitral valve replacement.
BACKGROUND AND AIM OF THE STUDY: The association between mitral valve disease and atrial fibrillation (AF) is well known, but few data exist regarding the impact of AF after mitral valve replacement (MVR) on NYHA functional class, atrial size and hemodynamic parameters. The present study was conducted to evaluate these issues. METHODS: Eighty-six patients (26 men, 60 women) who underwent MVR were evaluated by transthoracic echocardiography. Fifty-nine patients had chronic AF (AF group), and 27 were in sinus rhythm (sinus group). Variables analyzed included end-systolic left atrial and right atrial areas, tricuspid regurgitation, and presence and duration of AF. Peak and mean transprosthetic mitral valve gradients and pulmonary pressure were estimated by Doppler echocardiography. RESULTS: Groups were matched for age, sex and time from MVR (mean 6.6 years). Sixty-four patients (77%) had rheumatic heart disease, 18 (21%) had mitral valve disease, and two (2%) had mitral valve prolapse. Mean duration of AF was 11+/-12 years (range: 8-50 years). Preoperatively, AF patients had a worse NYHA class than sinus patients (2.8+/-0.8 versus 1.1+/-0.7, p = 0.001), but both had similar fractional shortening of the left ventricle and preserved prosthetic mitral valve function. Multivariate analysis identified AF as a single predictor of NYHA class after MVR. Although left and right atrial areas were larger in AF patients (47+/-25 versus 27+/-7 cm2, p = 0.0001 and 30+/-12 versus 17+/-5 cm2, p = 0.0001, respectively), the left:right atrial size ratio was not significantly different between groups. Multivariate analysis identified mean transmitral gradient and duration of AF as independent predictors of left atrial size after MVR (p = 0.01 and p = 0.0001, respectively). Tricuspid regurgitation and duration of AF were independent predictors of right atrial size (p = 0.003 and p = 0.0001, respectively). CONCLUSION: The presence of AF after MVR is associated with a worse NYHA functional class, increased transmitral gradients, and larger areas of both atria, when compared with sinus rhythm. Hence, a special effort should be made to correct arrhythmia during surgery, and in case of paroxysmal arrhythmia, earlier surgery should be considered before the condition becomes chronic.
NMDA but not non-NMDA excitotoxicity is mediated by Poly(ADP-ribose) polymerase.
Poly(ADP-ribose) polymerase (PARP-1), a nuclear enzyme that facilitates DNA repair, may be instrumental in acute neuronal cell death in a variety of insults including, cerebral ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, and CNS trauma. Excitotoxicity is thought to underlie these and other toxic models of neuronal death. Different glutamate agonists may trigger different downstream pathways toward neurotoxicity. We examine the role of PARP-1 in NMDA- and non-NMDA-mediated excitotoxicity. NMDA and non-NMDA agonists were stereotactically delivered into the striatum of mice lacking PARP-1 and control mice in acute (48 hr) and chronic (3 week) toxicity paradigms. Mice lacking PARP-1 are highly resistant to the excitoxicity induced by NMDA but are as equally susceptible to AMPA excitotoxicity as wild-type mice. Restoring PARP-1 protein in mice lacking PARP-1 by viral transfection restored susceptibility to NMDA, supporting the requirement of PARP-1 in NMDA neurotoxicity. Furthermore, Western blot analyses demonstrate that PARP-1 is activated after NMDA delivery but not after AMPA administration. Consistent with the theory that nitric oxide (NO) and peroxynitrite are prominent in NMDA-induced neurotoxicity, PARP-1 was not activated in mice lacking the gene for neuronal NO synthase after NMDA administration. These results suggest a selective role of PARP-1 in glutamate excitoxicity, and strategies of inhibiting PARP-1 in NMDA-mediated neurotoxicity may offer substantial acute and chronic neuroprotection.
Anomalies of lateralization in man: a case of total situs inversus.
Total or complete visceral situs inversus is the complete inversion of position of the thoracic and abdominal viscera. The aim of this study is to report a case of complete situs inversus and to review our knowledge of the anomalies of lateralization. A case of complete sinus inversus was discovered incidentally during anatomic dissection in a female subject aged 87 years. The thoracic and abdominal organs had a position symmetric with the normal. This was associated with a common mesentery and incomplete rotation of the colon, placing the cecum under the left lobe of the liver. These alimentary anomalies were discovered in adult life during a surgical operation for small intestinal occlusion, as evidenced by the abdominal scar and peritoneal adhesions. No cardiac, pulmonary, splenic or facial sinus anomalies were encountered. The incidence of complete situs inversus is estimated as 1/8000 in the general population. It may be isolated or associated with malformations, especially cardiac or alimentary. It may be discovered in infancy because of associated anomalies but often remains asymptomatic and discovered by chance in adult life. Complete situs inversus may form part of the multiple malformational syndromes such as that of Kartagener, with recessive autosomal transmission (complete situs inversus, bronchiectasis, chronic sinusitis, male infertility), which represents 20-25% of cases of complete situs inversus. In view of the frequency of this type of anomaly, a knowledge of anomalies of lateralization is essential in clinical practice.
Utilization and outcome in an overnight psychiatric observation program at a Veterans Affairs Medical Center.
OBJECTIVE: The effectiveness of an overnight psychiatric observation program was evaluated. The program was designed to avoid unnecessary hospitalization of patients experiencing acute psychiatric crises. METHODS: Of 110 patients admitted to the observation unit at a Veterans Affairs medical center over a six-month period in 1996, the charts of 92 patients were retrospectively reviewed. Characteristics of patients referred to the program were documented, inpatient hospitalization rates and suicide rates in the six-month periods before and after admission to the observation unit were examined, and variables related to the need for hospitalization immediately after observation were explored. RESULTS: Most of the 92 patients (98 percent) were referred from the medical center's emergency room. At the time of observation, 80 percent of the patients were unemployed, 55 percent expressed suicidal or homicidal ideation, 49 percent were intoxicated or at risk for alcohol withdrawal, and 41 percent were homeless. The most frequent psychiatric diagnosis was substance abuse or dependence (77 percent). The large majority of patients (88 percent) were referred the next day to other outpatient programs for follow-up and treatment, which avoided costly inpatient treatment. In the six months before admission to the observation program, the mean number of inpatient psychiatric bed days was 9.8, compared with 2.7 days in the six-month period after discharge from the observation program. No increase in suicide gestures or attempts was noted among the patients. No variables significantly predicted admission to inpatient care after the observation period. CONCLUSIONS: Overnight observation programs may provide a cost-effective alternative to traditional inpatient treatment for some individuals with psychiatric disorders.
Chemically Modified Glucose Oxidase with Enhanced Hydrophobicity: Adsorption at Polystyrene, Silica, and Silica Coated by Lipid Monolayers.
Covalent modification of glucose oxidase from Aspergillus niger by the palmitic acid ester of N-hydroxysuccinimide at a molar ratio ester:protein of 56:1 results in the formation of the enzyme derivative with 11 attached palmitic chains. Surface hydrophobicity measurements by a fluorescent probe, 8-anilino-1-naphthalenesulfonate, indicate a drastic increase in the hydrophobicity index of glucose oxidase after such a modification. The modified glucose oxidase displays a much higher adsorption affinity for hydrophilic (silica) as well as for hydrophobic (silica coated by phosphatidyl choline and cholesterol monolayers and polystyrene latex beads) surfaces, and forms more compact surface layers compared to the native glucose oxidase. Such a difference results from a spontaneous formation of micelle-like aggregates (clusters) of the hydrophobized enzyme molecules (average size 500 nm), which come into contact with a surface. A possible structure of the glucose oxidase surface layers and the nature of the forces determining the adsorption of the enzyme on various adsorbents are discussed. Copyright 1999 Academic Press.
Coexistence of malignant melanoma, Hodgkin's disease and follicular lymphoma with expression of the B-cell leukaemia/lymphoma (bcl-2) oncogene.
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Measurement of the effective size of the input phosphor of an x-ray image intensifier.
A technique is described, using a mobile radiographic x-ray unit, for determining the effective size of the input phosphor of an image intensifier (I.I.), in particular for a unit with over-table x-ray tube, under-table II, and with the I.I. physically inaccessible. The techniques described also enable (1) locating the central axis of the I.I.; (2) the ratio, R, of the dimensions of the radiological image incident upon the front of the I.I. to the dimensions of the image on the monitor screen; and (3) the distance between the input phosphor and the table top, which is needed to determine the distance from focal spot to input phosphor.
Anticonvulsant effect of felbamate in the pentylenetetrazole kindling model of epilepsy in the rat.
The present study was designed to examine the ability of felbamate, a novel antiepileptic agent, to antagonize the increase in seizure severity (i.e., chemical kindling) produced by chronic treatment with initially subconvulsant doses of pentylenetetrazol (PTZ). Rats were treated with PTZ (30 mg/kg, i.p., three times a week) for 8 consecutive weeks. Two other groups of rats received felbamate (300 or 400 mg/kg, i.p.), 90 min before each dose of PTZ. Pretreatment with felbamate at either dose prevented the progression of rank of seizures during chronic treatment with PTZ. Thus, the mean seizure score by the end of the chronic treatment (0-5 scale) was 0 in vehicle treated controls, 3.3 in rats treated with PTZ alone, 1.5 in rats treated with PTZ plus felbamate (300 mg/kg, i.p.) and 0.9 in the group treated with PTZ plus felbamate (400 mg/kg, i.p.). Felbamate also antagonized the long-term increase in the sensitivity to the convulsant effects of GABA function inhibitors observed in PTZ-kindled rats. Thus, the administration of a challenge dose of isoniazid (120 mg/kg, s.c.), picrotoxin (1.5 mg/kg, i.p.) or PTZ itself (15 mg/kg, i.p.), 15 to 45 days after the end of the chronic treatment regimen, induced convulsions in > 80% of PTZ-kindled rats and in < 20% of rats treated with PTZ + felbamate (400 mg/kg). The results are discussed in terms of the multiple mechanisms that can contribute to the anticonvulsant action of felbamate in the PTZ kindling model of epilepsy.
Bathing incompetent patients.
Bathing incompetent patients can be a difficult experience, both for the patient and the nurse. When incompetent patients express a wish not to be bathed, or actively resist being bathed, it is even more stressful.
Acute reversal of pheochromocytoma-induced catecholamine cardiomyopathy.
Pheochromocytoma is a rare neuroendocrine tumor. We report a case of pheochromocytoma-induced cardiomyopathy in an 18-year old white female. A review of the literature indicated that this is the most dramatic reversal of pheochromocytoma cardiomyopathy reported. With aggressive medical management, there was complete recovery of the hemodynamic, echocardiographic, and electrocardiographic abnormalities within 14 days. This case emphasizes the importance of aggressive and appropriate medical therapy in pheochromocytoma heart disease.