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Biomedical subjects

Jason Fine

Publications and source records attributed to Jason Fine.

15 recordsLinked to original sources

Circadian changes in granulocyte-macrophage colony-stimulating factor message in circulating eosinophils.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF), which stimulates eosinophil recruitment, activation, and survival, is expressed by activated eosinophils. Although eosinophil recruitment and enhanced survival have been associated with nocturnal asthma (NA), the contribution of GM-CSF to NA is unknown. OBJECTIVE: To determine whether circulating eosinophil GM-CSF expression correlates with the symptoms of NA. METHODS: The GM-CSF messenger RNA (mRNA) expression at 4 PM and 4 AM was determined by reverse-transcriptase polymerase chain reaction with Southern blot analysis in subjects with and without NA and in controls. RESULTS: A total of 142 asthma subjects were screened for nocturnal asthma with 1-week home peak expiratory flow rate (PEFR) monitoring. Eleven subjects had NA (>20% diurnal variation in PEFR on 4 of 7 days), and 6 met the criteria for non-NA (<10% diurnal variation in PEFR on 7 of 7 days); 8 controls were studied. In subjects with NA, GM-CSF mRNA expression in circulating eosinophils increased 3-fold at 4 AM compared with 4 PM. Diurnal changes in GM-CSF mRNA expression were not detected in the non-NA and control groups. CONCLUSIONS: Day-night variation in eosinophil GM-CSF expression is associated with circadian variation in airway function in asthma, a key manifestation of asthma severity.

Adolescent↗

Correlation between radiographic findings of osteoarthritis and arthroscopic findings of articular cartilage degeneration within the patellofemoral joint.

OBJECTIVES: To correlate radiographic findings of osteoarthritis on axial knee radiographs with arthroscopic findings of articular cartilage degeneration within the patellofemoral joint in patients with chronic knee pain. SUBJECTS AND METHODS: The study group consisted of 104 patients with osteoarthritis of the patellofemoral joint and 30 patients of similar age with no osteoarthritis of the patellofemoral joint. All patients in the study group had an axial radiograph of the knee performed prior to arthroscopic knee surgery. At the time of arthroscopy, each articular surface of the patellofemoral joint was graded using the Noyes classification system. Two radiologists retrospectively reviewed the knee radiographs to determine the presence of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts. The sensitivity and specificity of the various radiographic features of osteoarthritis for the detection of articular cartilage degeneration within the patellofemoral joint were determined. RESULTS: The sensitivity of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration within the patellofemoral joint was 73%, 37%, 4%, and 0% respectively. The specificity of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration within the patellofemoral joint was 67%, 90%, 100%, and 100% respectively. CONCLUSION: Marginal osteophytes were the most sensitive radiographic feature for the detection of articular cartilage degeneration within the patellofemoral joint. Joint-space narrowing, subchondral sclerosis, and subchondral cysts were insensitive radiographic features of osteoarthritis, and rarely occurred in the absence of associated osteophyte formation.

Adult↗

Subchondral bone marrow edema in patients with degeneration of the articular cartilage of the knee joint.

PURPOSE: To retrospectively determine at magnetic resonance (MR) imaging the prevalence of subchondral bone marrow edema beneath arthroscopically proved articular cartilage defects. MATERIALS AND METHODS: The study was performed in compliance with HIPAA regulations, and a waiver of informed consent was obtained from the institutional review board before the study was performed. The study consisted of 132 patients (70 men, 62 women; average age, 53 years) with articular cartilage defects of the knee joint who underwent MR imaging of the knee and subsequent arthroscopic knee surgery. At the time of arthroscopy, each articular cartilage lesion was graded by using the Noyes classification system. MR examinations were retrospectively reviewed to determine the size, depth, and location of subchondral bone marrow edema without knowledge of the arthroscopic findings. Pairwise Fisher exact tests and two-sample t tests were used to correlate MR imaging findings of subchondral bone marrow edema with the arthroscopic grade of articular cartilage degeneration. RESULTS: Subchondral bone marrow edema was seen beneath 105 (19%) of 554 articular cartilage defects identified at arthroscopy. It was not observed beneath any of the six grade 1 cartilage defects but was observed beneath eight (4.9%) of 163 grade 2A defects, 40 (14.4%) of 278 grade 2B defects, 54 (55.1%) of 98 grade 3A defects, and three (33.3%) of nine grade 3B defects. Subchondral bone marrow edema was also seen beneath four (1.4%) of 238 articular surfaces that appeared normal at arthroscopy. The mean depth and cross-sectional area of subchondral bone marrow edema increased with increasing grade of the articular cartilage lesion. CONCLUSION: Higher grades of articular cartilage defects are associated with higher prevalence and greater depth and cross-sectional area of subchondral bone marrow edema.

Adult↗

Arthroscopic validation of radiographic grading scales of osteoarthritis of the tibiofemoral joint.

OBJECTIVE: The purpose of this study was to use the Kellgren-Lawrence, Ahlback, and Brandt grading scales to correlate radiographic grade of osteoarthritis with the actual degree of articular cartilage degeneration within the tibiofemoral joint in patients with chronic knee pain. SUBJECTS AND METHODS: The study group consisted of 125 patients with symptomatic osteoarthritis of the tibiofemoral joint. For all patients, standing anteroposterior radiographs of the knee were obtained before arthroscopic knee surgery. Each articular surface of the tibiofemoral joint was graded at arthroscopy. Two radiologists retrospectively reviewed the knee radiographs without knowledge of the arthroscopic findings to determine the presence and severity of osteoarthritis of the tibiofemoral joint using the Kellgren-Lawrence, Ahlback, and Brandt grading scales. Correlation coefficients describing the relation between grade of osteoarthritis and severity of articular cartilage degeneration were calculated for each grading scale. RESULTS: The correlation coefficients for the Kellgren-Lawrence, Ahlback, and Brandt grading scales were 0.49, 0.41, and 0.56, respectively. The differences between the correlation coefficients for the Kellgren-Lawrence and Ahlback grading scales and the correlation coefficients for the Brandt and Ahlback grading scales were statistically significant (p < 0.05). Many patients with no radiographic findings of osteoarthritis had significant articular cartilage degeneration within the tibiofemoral joint. CONCLUSION: The Kellgren-Lawrence and Brandt grading scales were equally effective in defining the presence of and estimating the severity of osteoarthritis of the tibiofemoral joint but had only a moderately strong correlation with the actual degree of articular cartilage degeneration.

Adult↗

Microcomputed tomography colonography for polyp detection in an in vivo mouse tumor model.

This study was initiated to evaluate the efficacy of negative contrast-enhanced microcomputed tomography (microCT) colonography for the noninvasive detection of colonic tumors in living mice. After colonic preparation, 20 anesthetized congenic mice were scanned with high-resolution microCT. Images were displayed by using commercial visualization software and interpreted by two gastrointestinal radiologists, who were unaware of tumor prevalence and findings at gross pathology. Two-dimensional multiplanar images were assessed by using a five-point scale to distinguish colonic tumors (polyps) from fecal pellets (5 = definitely a tumor, 4 = probably a tumor, 3 = indeterminate, 2 = probably not a tumor, 1 = definitely not a tumor). Gross pathologic evaluation of excised mouse colons served as the reference standard. Data analysis included dichotomizing results, with 1-2 indicating no tumor and 3-5 indicating tumor and also receiver operator characteristic curve analysis with area under the curve for threshold-independent assessment. A total of 41 colonic polyps in 18 of the 20 mice were identified at gross examination on necropsy, of which 30 measured 2-5 mm and 11 measured <2 mm in size. The pooled per-polyp sensitivity for lesions >2 mm was 93.3% (56/60). The pooled per-mouse sensitivity for polyps >2 mm was 97.1% (33/34). Pooled specificity for distinguishing fecal pellets from tumor was 98.5% (65/66). The combined area under the curve from receiver operator characteristic curve analysis was 0.810 +/- 0.038 (95% confidence interval, 0.730-0.890). These findings indicate that accurate noninvasive longitudinal monitoring of colon tumor progression or response to various therapies is now technically feasible in live mice by using this microCT colonography method.

Animals↗

Temporal lobe epilepsy and the selective reminding test: the conventional 30-minute delay suffices.

Conventional memory assessment may fail to identify memory dysfunction characterized by intact recall for a relatively brief period but rapid forgetting thereafter. This study assessed learning and retention after 30-min and 24-hr delays on auditory and visual selective reminding tests (SRTs) in right (n=20) and left (n=22) temporal lobe epilepsy (TLE) patients and controls (n=49). The left TLE group performed significantly worse than controls on all 3 trials of both tests. The right TLE group differed from the controls on all 3 visual SRT trials and on learning for the auditory SRT. There were no between-groups differences in rate of information lost at the 30-min versus the 24-hr delay. At the individual level, there was no difference in the percentage of patients versus controls who demonstrated isolated memory impairment at the 24-hr delay. Accelerated forgetting over 24 hr is uncommon in TLE patients.

Adolescent↗

Sleep architecture in children with idiopathic generalized epilepsy.

PURPOSE: Children with epilepsy experience sleep disturbances, behavioral and attentional problems at higher rates than their peers. However, the relation between sleep disturbances and the observed behavioral and attentional abnormalities is poorly defined. METHODS: Children with primary generalized epilepsy who were seizure free and between the ages of 5 and 18 years were matched with age- and gender-matched healthy controls and underwent two consecutive nights of nocturnal polysomnography with extended electroencephalography. Connor's Continuous Performance Test (CPT) was administered to assess daytime attentional function. Parents completed the Child Behavior Checklist (CBCL) to assess their emotional-behavioral status. Two sample t tests were used to examine group differences. Spearman correlations were used to examine the relation between sleep variables and behavior and attention variables. Multiple regression analysis was used to identify independent predictors of abnormal behavior and attention among patients. RESULTS: Eleven children with primary generalized epilepsy and eight age- and sex-matched controls participated in the study. Children with epilepsy had longer stage 1 sleep percentage (7.19 +/- 3.2 vs. 4.8 +/- 3.5; p = 0.05) and latency to rapid-eye-movement (REM) sleep (123.5 +/- 40.1 vs. 101.75 +/- 24.3; p = 0.018) compared with controls. Children with epilepsy had worse attention (CPT index, 10.94 +/- 6.55 vs. 3.42 +/- 4.04; p = 0.004) and exhibited significantly higher CBCL Total Behavior and Internalizing Behavior Problem scales. Whereas regression analysis showed no independent predictors of abnormal behavior and attention, a tendency toward association between CBCL total behavior scale and REM percentage (r= 0.55; p = 0.07), and between CPT overall index and stage 1 sleep percentage (r= 0.40; p = 0.10) was noted. CONCLUSIONS: Sleep architecture is abnormal in children with primary generalized epilepsy. Further studies are needed to determine whether abnormalities in sleep architecture contribute to poor daytime behavior and attention.

Adolescent↗

Assessment of acute renal transplant rejection with blood oxygen level-dependent MR imaging: initial experience.

PURPOSE: To prospectively assess the oxygenation state of renal transplants and determine the feasibility of using blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging to differentiate between acute tubular necrosis (ATN), acute rejection, and normal function. MATERIALS AND METHODS: This HIPAA-compliant study had institutional human subjects review committee approval, and written informed consent was obtained from all patients. BOLD MR imaging was performed in 20 patients (age range, 21-70 years) who had recently received renal transplants. Six patients had clinically normal functioning transplants, eight had biopsy-proved rejection, and six had biopsy-proved ATN. R2* (1/sec) measurements were obtained in the medulla and cortex of transplanted kidneys. R2* is a measure of the rate of signal loss in a specific region and is related to the amount of deoxyhemoglobin present. Statistical analysis was performed by using a two-sample t test. Threshold R2* values were identified to discriminate between transplanted kidneys with ATN, those with acute rejection, and those with normal function. RESULTS: R2* values for the medulla were significantly lower in the acute rejection group (R2* = 15.8/sec +/- 1.5) than in normally functioning transplants (R2* = 23.9/sec +/- 3.2) and transplants with ATN (R2* = 21.3/sec +/- 1.9). The differences between the acute rejection and normal function groups (P = .001), as well as between the acute rejection and ATN groups (P < .001), were significant. Acute rejection could be differentiated from normal function and ATN in all cases by using a threshold R2* value of 18/sec. R2* values for the cortex were higher in ATN (R2* = 14.2/sec +/- 1.4) than for normally functioning transplants (R2* = 12.7/sec +/- 1.6) and transplants with rejection (R2* = 12.4/sec +/- 1.2). The difference in R2* values in the cortex between ATN and rejection was statistically significant (P = .034), although there was no threshold value that enabled differentiation of all cases of ATN from cases of normal function or acute rejection. CONCLUSION: R2* measurements in the medullary regions of transplanted kidneys with acute rejection were significantly lower than those in normally functioning transplants or transplants with ATN. These results suggest that marked changes in intrarenal oxygenation occur during acute transplant rejection.

Adult↗

Knowledge discovery from structured mammography reports using inductive logic programming.

The development of large mammography databases provides an opportunity for knowledge discovery and data mining techniques to recognize patterns not previously appreciated. Using a database from a breast imaging practice containing patient risk factors, imaging findings, and biopsy results, we tested whether inductive logic programming (ILP) could discover interesting hypotheses that could subsequently be tested and validated. The ILP algorithm discovered two hypotheses from the data that were 1) judged as interesting by a subspecialty trained mammographer and 2) validated by analysis of the data itself.

Algorithms↗

On sample size for sensitivity and specificity in prospective diagnostic accuracy studies.

The design of a study of disease screening tests may be based on hypothesis tests for the sensitivity and specificity of the tests. The case-control study requires knowledge of the disease status of patients at the time of enrollment. This may not be possible in a prospective setting, when the gold standard is obtained subsequent to the initial screening and the number of diseased individuals is random and can not be fixed by design. Several ad hoc procedures for determining the total sample size are commonly used by practitioners, for example, the prevalence inflation method. The properties of these methods are not well understood. We develop a formal method for sample size and power calculations based on the unconditional power properties of the test statistics. The approach provides novel insights into the behaviour of the commonly used methods. We find that the ad hoc prevalence inflation method may serve as a useful approximation to our rigorous framework for sample size determination in the prospective set-up. The design of a large population-based study of mammography for breast cancer screening illustrates the key issues.

Breast Neoplasms↗

Estimating equations for association structures.

This paper investigates generalized estimating equations for association parameters, which are frequently of interest in family studies, with emphasis on covariance estimation. Separate link functions are used to connect the mean, the scale, and the correlation to linear predictors involving possibly different sets of covariates, and separate estimating equations are proposed for the three sets of parameters. Simulations show that the robust 'sandwich' variance estimator and the jackknife variance estimator for the correlation parameters are generally close to the empirical variance for the sample size of 50 clusters. The results contradict Ziegler et al. and Kastner and Ziegler, where the 'sandwich' estimator obtained from the software MAREG was shown to be unsuitable for practical usage. The problem appears to arise because the MAREG variance estimator does not account for variability in estimation of the scale parameters, but may be valid with fixed scale. We also find that the formula for the approximate jackknife variance estimator in Ziegler et al. is deficient, resulting in systematic deviations from the fully iterated jackknife variance estimator. A general jackknife formula is provided and performs well in numerical studies. Data from a study on the genetics of alcoholism is used to illustrate the importance of reliable variance estimation in biomedical applications.

Alcoholism↗

Efficacy of epidural injections of Kenalog and Celestone in the treatment of lower back pain.

OBJECTIVE: Epidural corticosteroid injections have been used extensively to treat lower back pain, but the relative effectiveness of one corticosteroid versus another has never been reported in a large patient series. We retrospectively reviewed 597 patients who had epidural corticosteroid injections to determine any difference in Kenalog or Celestone efficacy. MATERIALS AND METHODS: We reviewed charts and self-reported pain score evaluations of 597 patients who received either Kenalog or Celestone Soluspan as an epidural injection for the treatment of lower back pain from 1997 to 2002 at our university hospital and affiliated Veterans Affairs hospital. Kenalog was used for the initial 2 years and Celestone was used for the next 3 years. Fluoroscopic guidance was used to confirm epidural location, and each patient was injected with a mixture of 5 mL of 0.5% preservative-free lidocaine and 2 mL of either Kenalog 40 mg/mL (triamcinolone acetonide injectable suspension) or Celestone Soluspan 6 mg/mL (betamethasone sodium phosphate and betamethasone acetate injectable suspension). Each patient was given a standardized pain evaluation sheet that used an 11-point scale for initial pain severity. Scoring of pain compared with baseline during the following 14 days was based on a 5-point scale of pain improvement or worsening. RESULTS: On days 0-3 after the procedure, no statistical significance in improvement of lower back and buttock pain was seen between groups. On day 7, 59% of Celestone recipients and 73% of Kenalog recipients showed improvement in lower back pain (p = 0.002, Pearson's chi-square test), and 58% of Celestone recipients and 75% of Kenalog recipients had improvement in leg or buttock pain (p < 0.001). On day 14, 54% of Celestone recipients and 71% of Kenalog recipients showed improvement in lower back pain (p < 0.001), and 54% of Celestone recipients and 71% of Kenalog recipients had improvement in leg or buttock pain (p < 0.001). CONCLUSION: The epidural injection of Celestone Soluspan and Kenalog reduced lower back and radicular pain in more than half the patients, although Kenalog reduced pain in a significantly larger number of patients than Celestone Soluspan at 1 and 2 weeks after injection.

Anti-Inflammatory Agents↗

Supplementary motor area activation in patients with frontal lobe tumors and arteriovenous malformations.

BACKGROUND AND PURPOSE: Some patients who undergo surgical resection of portions of the supplementary motor area (SMA) have severe postoperative motor and language deficits, whereas others have no deficits. We tested the hypothesis that in some patients with lesions affecting the SMA, the contralateral SMA exhibits some of the activation normally associated with the ipsilateral SMA. METHODS: Functional MR imaging studies in seven healthy volunteers and 19 patients with frontal lobe tumors or arteriovenous malformations were reviewed retrospectively. The hemisphere in which the SMA activation predominated was tabulated for right and left motor tasks. The relative hemispheric dominance in the SMA for the right and left motor tasks was compared in the healthy and patient groups and with the location of the lesion in the patient group. RESULTS: None of the control subjects performing a right hand motor task activated predominantly the right SMA. Fifty percent of the patients with lesions overlapping the left SMA performing the right motor task activated predominantly the right SMA. Fifty-seven percent of control subjects performing the left hand motor task activated the left SMA predominantly. One hundred percent of patients with lesions overlapping the right frontal SMA performing the left motor task activated the left SMA predominantly. Differences between patients and controls were statistically significant. CONCLUSION: A lesion that contacts or overlaps the SMA is associated with an increased functional MR imaging response within the contralateral SMA.

Adolescent↗

Desmin characteristics of CD11b-positive fibers after eccentric contractions.

PURPOSE: The purpose of this study was to determine the desmin characteristics of fibers infiltrated by CD11b-leukocytes in fast- and slow-twitch murine muscles after eccentric contractions. METHODS: We developed a computer image analysis procedure to quantify the percentage of intramyofiber CD11b-leukocyte infiltration. Only CD11b-positive fibers that exhibited identifiable borders were examined. Patterns of leukocyte infiltration of these fibers were distinguished and confirmed quantitatively by determining the mean percentage of leukocyte infiltration. We examined the desmin characteristics of these fibers with the same image analysis system and quantified the percentage of the fiber that demonstrated antidesmin staining. The influence of sex and muscle type on desmin characteristics and percentage of CD11b-leukocyte infiltration also was analyzed. RESULTS: The percentage of CD11b-leukocyte infiltration was less than 50% for the majority of fibers. Three intramyofiber leukocyte infiltration patterns were identified that had significantly different mean percentages of leukocyte infiltration: 14%, 27%, and 47% (P < 0.001). Of the three desmin characteristics (normal, increased, and decreased) that were observed, almost three fourths of the fibers exhibited increased desmin. A significant difference in the percentage of increased desmin was found among the CD11b-leukocyte infiltration patterns (P = 0.01). Fibers with the least amount of CD11b-leukocyte infiltration showed the greatest amount of increased desmin. Sex and muscle type did not influence any of these findings. CONCLUSION: Increased desmin appears to be associated with an early stage of intramyofiber leukocyte infiltration after eccentric contractions.

Animals↗