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Biomedical subjects

J Gillen

Publications and source records attributed to J Gillen.

At least 19 recordsLinked to original sources

Noninvasive quantification of total sodium concentrations in acute reperfused myocardial infarction using 23Na MRI.

The transport of sodium and potassium between the intra- and extracellular pools and the maintenance of the transmembrane concentration gradients are important to cell function and integrity. The early disruption of the sodium pump in myocardial infarction in response to the exhaustion of energy reserves following ischemia and reperfusion results in increased intracellular (and thus total) sodium levels. In this study a method for noninvasively quantifying myocardial sodium levels directly from sodium (23Na) MRI is presented. It was used to measure total myocardial sodium on a clinical 1.5T system in six normal dogs and five dogs with experimentally-induced myocardial infarction (MI). The technique was validated by comparing total sodium content measured by 23Na MRI with that measured by atomic absorption spectrophotometry (AAS) in biopsied tissue. Total sodium measured by 23Na MRI was significantly elevated in regions of infarction (81.3 +/- 14.3 mmol/kg wet wt, mean +/- SD) compared to noninfarcted myocardial tissue from both infarcted dogs (36.2 +/- 1.1, P < 0.001) and from normal controls (34.4 +/- 2.8, P < 0.0001). Myocardial tissue sodium content as measured by 23Na MRI did not vary regionally in the lateral, anterior, or inferior regions in normal hearts (ANOVA, P = NS). Sodium content measured by 23Na MRI agreed with the mean AAS estimates of 31.3 +/- 5.6 mmol/kg wet wt (P = NS) in normal hearts, and did not differ significantly from AAS measurements in MI (P = NS). Thus, local tissue sodium levels can be accurately quantified noninvasively using 23Na MRI in normal and acutely reperfused MI. The detection of regional myocardial sodium elevations may help differentiate viable from nonviable, infarcted tissue.

Animals↗

Superparamagnetic iron oxide MION as a contrast agent for sodium MRI in myocardial infarction.

An intravascular iron-based contrast agent was used as a sodium (23Na) MRI T2 relaxant in an effort to suppress the blood signal from the ventricular cavities in normal and infarcted canine myocardium in vivo. 23Na MRI signal decreases in blood were attributed to decreases in the fast (T2f) and slow (T2s) transverse relaxation components, which were quantified as a function of dose and MRI echo time (TE). In vivo 23Na MRI signal decreases up to 65% were noted in ventricular blood when imaging under dose and TE conditions of 10 mg/kg body weight and 5 ms, respectively. Contrast injection followed by subsequent 23Na MRI in canine myocardial infarction led to a clear delineation of the location of the injured tissue, as identified by postmortem triphenyltetrazolium chloride staining, and to an improvement in the contrast-to-noise ratio between the blood in the ventricular chamber and the infarcted tissue that was as high as 3.3-fold in the postcontrast images in comparison to the precontrast images.

Animals↗

Venous blood effects in spin-echo fMRI of human brain.

The spin-echo response to visual activation was studied as a function of spatial resolution at a field of 1.5 T. The results showed that the increase in absolute T(2) upon activation was as large as 22.8 +/- 3.1% (P < 0.05) at the highest resolution (5.3 mm(3)), while it was as small as 3.5 +/- 0.2% (P < 0.05) at the lowest resolution (42.2 mm(3)). In addition, upon increasing resolution, the spin-echo signal decay as a function of echo time changed from monoexponential to nonexponential. These data indicate that, when using the standard resolution for fMRI studies at 1.5 T, the effects of spin-echo changes in the draining veins are of major contribution to the total blood oxygenation level-dependent (BOLD) signal changes measured in voxels encompassing the activated brain areas. The data can be quantitatively accounted for using a model based on the intravascular origin of the spin-echo effect including both macrovascular and microvascular effects. Existing theories for the spin-echo BOLD effect based on diffusion through field gradients predict negligible spin-echo effects inside the large vessels and are therefore incompatible with the data. Magn Reson Med 42:617-626, 1999.

Brain↗

Computer-assisted anthropometry for outcome assessment of cleft lip.

Anthropometry and clinical examination best evaluate the morphology of repaired cleft lip and nose. An original, accurate, and practical image analysis of the lip and nose, which takes advantage of the mathematic, geometric, and organizational capabilities of public domain NIH-Image software (http://rsb.info.nih.gov/nih-image/), has been developed and tested over the past 6 years. A modified structured physical examination form that complements this analysis is under study. Accuracy of NIH-Image-based anthropometry was compared with direct measurements of 22 linear distances on the lip and nose. Twenty-five sets of direct measurements were taken, prospectively, on 15 children with repaired cleft lip over a 6-year period. The results were submitted to regression analysis. Then, relevant lip and nasal tip aesthetics were evaluated by the measuring capabilities of NIH-Image to create a quantitative assessment tool. For each episode, 15 possible faults were weighted, according to aesthetics and deformity, to provide an adverse score. The sum of the 5 lip scores, 10 nose scores, and combination gave respective grades. The analysis was modified to stratify congenital deformity to relate severity of disease to outcome. This analysis was applied to digitized images of 19 consecutive children, immediately prior to repair of complete unilateral cleft lip and nose, at the time of palate repair, and annually from the age of 3 to 6 years. There were 19 NIH-Image-based measurements of the congenital deformity and 35 measurements of surgical results; four children had three sets of records, eight had two sets, and seven had one set Descriptive statistics were applied. Following 556 paired direct and computer-assisted measurements, exceptional linear correlation was shown with a Pearson R coefficient of 0.96. The best correlation was lines within the plane of the camera lens, with the average difference ranging between 0.025 and 0.997 mm. Visual inspection of frontal and submental photographs of excellent, good, and poor results substantiates the ability of this analysis to quantify and grade a spectrum of relevant cleft lip and nasal anatomy. For these 19 patients, there was a broad range of performance scores, approximating a normal distribution. The mean of the NIH-Image-based analysis scores, 16.91, was a (very) good grade. A single standard deviation of 6.88 extended up into excellent and down to fair. The congenital analysis indicated a range of deformity. Comparing deformity with outcome, simple regression analysis had a coefficient of determination (R2) of 0.223, indicative of a weak positive relationship. An accurate and practical morphologic computer-assisted outcome assessment of repaired cleft lip and nasal deformity has been developed. There is a weak direct correlation between severity of deformity and outcome. Testing in multiple clinics is warranted.

Anthropometry↗

Functional brain MR imaging based on bolus tracking with a fast T2*-sensitized gradient-echo method.

Dynamic physiological scanning, based on temporary changes in local field homogeneity during the passage of a contrast agent bolus, has been performed hitherto with echo-planar imaging (EPI) or conventional gradient-recalled techniques (FLASH). Here, it is shown that the T2* sensitivity of conventional FLASH techniques can be improved drastically on a conventional whole body instrument by delaying the gradient-echo until the subsequent TR-period without increasing total imaging time. Examples are given for a full k-space matrix (128 x 256) obtained within 2 s with a TE of 25 ms, resulting in images free of artifacts. The method is applied to bolus tracking through the brain of healthy volunteers during visual stimulation and in the dark. An average increase of regional cerebral blood volume (rCBV) in the visual cortex of 10.9% (n = 9, p = .001) was found.

Blood Volume↗

Factors associated with recurrence and voice quality following radiation therapy for T1 and T2 glottic carcinomas.

Evaluation of 63 patients undergoing primary radiation therapy for treatment of T1 and T2 glottic carcinomas was undertaken to evaluate the success of primary treatment and to identify factors which might influence recurrence or voice quality. Twelve patients (19%) recurred following radiation therapy, with ultimate salvage in 11, for a 3-year survival rate of 98%. Voice preservation was achieved in 83%. Continued smoking after radiation therapy was associated with significantly greater risk of recurrence. Stage of tumor and anterior commissure involvement were not associated with increased recurrences. Sixty-seven percent of patients who did not recur had good voice quality after treatment. Vocal fold stripping or excisional biopsy rather than limited biopsy for initial diagnosis, complications of treatment, and continued smoking after treatment were all significantly associated with an increased risk of poorer voice quality after treatment while bilateral vocal fold tumors were associated with risks that approached significance. Voice analysis of five patients revealed that objective changes in voice can be detected after radiation therapy in those with associated risk factors but may be normal in those without these risk factors.

Adult↗

Survey of reproductive health among female MR workers.

Epidemiologic data were obtained to evaluate potential risks from exposure to the static and time-varying magnetic fields used in magnetic resonance (MR) imaging. A questionnaire sent to women workers in more than 90% of clinical MR facilities in the United States addressed menstrual-reproductive experiences, work activities, and potential confounders (eg, age, smoking, alcohol use). In 1,915 completed questionnaires, 1,421 pregnancies were reported: 280 occurred in an MR worker (technologist or nurse), 894 in an employee in another job, 54 in a student, and 193 in homemakers. Comparing MR-worker pregnancies with those occurring in employees at other jobs, a relative risk ratio of 1.27 (95% confidence interval [CI], 0.92-1.77) was found for spontaneous abortions; for conception taking more than 12 months, 0.90 (CI, 0.54-1.51); for delivery before 39 weeks, 1.19 (CI, 0.76-1.88); for birth weight below 5.5 lb (2.5 kg), 1.01 (CI, 0.50-2.04); and for male gender of the offspring, 0.99 (CI, 0.80-1.22). Adjustment for maternal age, smoking, and alcohol use also failed to markedly change any of the associations. These results suggest that there is not a substantial increase in these common adverse reproductive outcomes.

Female↗

Multisection proton MR spectroscopic imaging of the brain.

The authors developed a hydrogen-1 proton magnetic resonance (MR) imaging method in which metabolic information is acquired by obtaining multiple sections through the brain. A spin-echo sequence is used for section selection, an octangular outer volume saturation pulse for lipid suppression, and a chemical-shift-selective saturation pulse for water suppression. High-quality maps of choline, creatine, and N-acetylaspartate were obtained in six studies performed in four volunteers. Water and lipid signal from the skull area was well suppressed by the pulse sequence used.

Adult↗

Comparison of the rates of adverse drug reactions. Ionic contrast agents, ionic agents combined with steroids, and nonionic agents.

The influence of ionic agents alone, of diatrizoate plus two oral doses of methylprednisolone premedication, and of a nonionic agent (iohexol) upon the frequency and severity of adverse drug reactions (ADRs) was compared in ten hospitals during three separate time periods from 1985 to 1989. Nonionic agents were found to reduce significantly total ADRs; 52 of 8857 patients receiving nonionic agents experienced reactions, versus 263 of 6006 patients for ionics (P less than .0001). The frequency of reactions classed as mild (2.9% for ionic agents versus 0.476 for nonionic agents: P less than .001), moderate (1.2% versus 0.1%; P less than .001), or severe (0.37% versus 0.01%; P less than .001), also favored nonionic agents. Steroid premedication provided some protection, but iohexol was significantly better with respect to mild reactions (2.9% versus 0.4%, P less than .001), moderate reactions (0.9% versus 0.1%, P less than .01), and severe reactions (0.25% versus 0.01%, P less than .01). The contrast medium was the greatest risk factor for adverse reaction (odds ratio 7.3), while prior contrast reaction (odds ratio 6.25), and hay fever (odds ratio 2.3) were found to be significant independent risks. We conclude that nonionic agents are safer for intravenous use than ionic agents given alone or with corticosteroid premedication.

Diatrizoate Meglumine↗

Clinico-pathological findings in non-immune hydrops fetalis.

Non-immune hydrops fetalis is becoming a relatively more important cause of hydrops as the incidence of rhesus-related hydrops falls. We describe a series of 33 cases, occurring over a 7 year period covering most of the 1980's. We found a very wide range of aetiological factors, but cardiac conditions, both structural and dysrhythmic, formed the largest subgroup (12 cases, 36%). Seven cases (22%) remained idiopathic. Prognosis was very poor, with only 4 infants surviving. Outcome was best in the cases due to intra-uterine supraventricular tachycardia. Nineteen cases were detected antenatally, but except in the cases of fetal tachyarrhythmias, this had little effect on outcome.

Female↗

Proton magnetic resonance spectroscopy of small regions (1 mL) localized inside superficial human tumors. A clinical feasibility study.

It is demonstrated that the stimulated echo technique for proton magnetic resonance spectroscopy (MRS) can be used to study metabolites in volumes of interest (VOIs) as small as 1 mL localized within superficial human tumors. Access to these small VOIs is important for characterization of tissue regions within a tumor, before, during and after treatment. Spectral appearance resembles that from studies on extracts, and cell suspensions and perfused cells of several tumor types. For the first time proton MRS was used to study cancer treatment in vivo in humans, for a case of radiation treatment of squamous cell carcinoma. No spectral evidence of changed metabolism prior to reduction in tumor size was found. However, after the first period of radiation (39 Gy, 4 weeks), complete disappearance of the metabolite resonances from the spectrum was observed, while a considerable mass still remained, suggesting effective cell destruction upon treatment. Needle aspiration cytology of this mass showed absence of malignant cells, supporting this result.

Carcinoma, Squamous Cell↗

Comparison of single-shot localization methods (STEAM and PRESS) for in vivo proton NMR spectroscopy.

Two single-shot localization techniques, STEAM and PRESS, are analyzed with regard to specifications for in vivo localized proton NMR. In particular, attention is paid to optimum signal intensity per unit volume, sensitivity to motion and diffusion, shortest attainable echo time, water suppression and editing possibilities. Experimental results are shown for cat brain at 4.7 T and human brain at 1.5 T. Both STEAM and PRESS are highly effective localization methods. For long echo times, PRESS is the method of choice, because it offers a factor of two gain in signal intensity. In addition, the method is less sensitive to motion and diffusion, and not susceptible to multiple-quantum effects. STEAM offers advantages for observation of (coupled) metabolites with short T2, because (a) shorter TEs can be attained and (b) effective water suppression sequences can be implemented without penalty in echo time. Differences relating to editing possibilities and B1 dependence, possibly important in choosing a method, are discussed.

Animals↗

Use of indomethacin suppositories in the prophylaxis of recurrent ureteral colic.

To determine the effects of indomethacin suppositories in the relief of acute colic and prevention of recurrent colic, we instituted a prospective double-blind, placebo-controlled protocol. Patients were randomized to receive either 50 mg. indomethacin or placebo suppositories every 8 hours and all patients received prescriptions for supplemental narcotics to be used on an as needed basis. Relief of colic was assessed by counting the total number of supplemental narcotics used by each patient per 24 hours during the study period, which was defined as until passage of the calculus or 5 days. There were 41 patients entered into the study protocol and complete followup was available for 26. Mean calculus size was 3.4 mm. in the indomethacin group versus 3.1 mm. in the placebo group. All 13 patients in the control group had recurrent episodes of colic and 8 of these 13 had more than 1 recurrent episode. Five patients in the placebo group required admission to the hospital for control of pain. In contrast, only 4 of the 13 patients in the treatment group had colic and only 1 had more than 1 episode of colic. No patient in the active drug group required admission to the hospital for control of pain. Over-all the ratio of supplemental narcotic used by the placebo group versus the indomethacin group was 7.6:1 (p less than 0.005). The mean interval time to passage of the calculus was slightly lower in the indomethacin group (89 versus 82 hours) but this difference was not statistically significant (p greater than 0.10). Our data strongly support the use of indomethacin suppositories in the prevention of recurrent colic secondary to ureteral calculi.

Colic↗

Loss of low-affinity serotonin receptors upon storage of human platelets.

Platelets actively accumulate virtually all plasma serotonin within their dense granules. As a readily isolated, homogeneous cell type, platelets have served as a model for serotonin uptake into neurological tissue, in addition to defining the role of serotonin in hemostasis. The number of serotonin receptor types on the platelet membrane and the function of these receptors has not been conclusively demonstrated. The presence of different receptor types that may be altered or lost in disease or upon aging (in vitro storage or in vivo) could have significant physiological effects on platelet function. This report demonstrates that at least two receptor types are present on freshly prepared human platelets. However, after 3 to 4 days of storage in autologous plasma, the low-affinity, high-capacity serotonin receptor appears to be lost. This phenomenon probably accounts for some of the discrepancies reported in the literature. The high-affinity receptor present in both freshly isolated and stored platelets binds about 9 x 10(3) serotonin molecules per platelet. Binding can be completely blocked by imipramine; however, some passive diffusion appears to occur even at the low level of extracellular serotonin concentrations employed in these studies (nanomolar range). The influx of serotonin into platelets appears to be poorly reversible, even in reserpine-treated cells, where the extravesicular cytoplasmic concentration would be high. The loss of the low-affinity serotonin receptor type reported in these studies may be directly or indirectly associated with the reduced responsiveness observed in stored platelets.

Biological Transport↗

Description and validation of an ECG removal procedure for EMGdi power spectrum analysis.

We describe a cross-correlation procedure for removing contaminating electrocardiogram (ECG) complexes from the diaphragmatic electromyogram (EMGdi). First, the operator selects ECG templates from the EMGdi signal during expiratory intervals. Second, these templates are used to locate ECG complexes occurring during inspiratory EMGdi activity. Third, at the point of maximum correlation between the template and these ECG complexes, the template is adjusted in size and offset to "match" the ECG complex, and adjustments are determined by the linear regression coefficients. Finally, the modified template is subtracted from the EMGdi signal. To evaluate our method, we compared the power spectral density (PSD) obtained from processing EMGdi signals by our method with those obtained from the EMGdi signal in which ECG complexes had been removed by gating. Our results indicate that PSD obtained by these two different methods shows no statistically significant differences with respect to the following features: centroid frequency, median frequency, total power, standard deviation, skewness, and kurtosis.

Analysis of Variance↗

Evaluation of a ventilatory muscle endurance training program in the rehabilitation of patients with chronic obstructive pulmonary disease.

To evaluate the role of ventilatory muscle endurance training (VMET) in the rehabilitation of outpatients with chronic obstructive pulmonary disease, we carried out a prospective random allocation trial of VMET versus IPPB. Data were obtained from 15 men allocated to VMET and from 17 men assigned to IPPB. The mean age of our experimental cohort was 61 +/- SEM 1 yr, and the FEV1 was 1.2 +/- 0.1 L. Prior to and after 6 wk of daily therapy, the following data were obtained on each subject: (1) vital statistics, (2) standard pulmonary function tests, (3) activities of daily living (ADL), (4) maximal sustainable ventilatory capacity (MSVC), (5) psychologic status (PS), and (6) exercise tolerance (ET). Prior to therapy, the VMET and IPPB groups showed no significant differences with respect to these parameters. After therapy, VMET subjects exhibited a greater increase (p less than 0.05) in MSVC than did IPPB subjects. However, VMET and IPPB groups did not differ with respect to improvements noted in ADL, PS, and ET. These results from our controlled study raise the possibility that some aspect of the experimental protocol, other than VMET, accounted for the improvements noted in ADL, PS, and ET.

Adult↗