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Biomedical subjects

D J Fisher

Publications and source records attributed to D J Fisher.

At least 37 records · Page 2Linked to original sources

Influence of age on the effect of bidirectional cavopulmonary anastomosis on left ventricular volume, mass and ejection fraction.

OBJECTIVES: We sought to identify age-related differences in the ventricular response of patients after bidirectional cavopulmonary anastomosis (CPA) and to compare changes in the ventricular response among children < 3 years of age who underwent CPA with that of age-matched control subjects who had a systemic to pulmonary artery shunt alone. BACKGROUND: Pre-Fontan CPA has been advocated over a systemic to pulmonary artery shunt alone in patients with a single ventricle to facilitate ventricular volume unloading and minimize risk of the Fontan operation. METHODS: Our study evaluated 23 patients who initially received a systemic to pulmonary artery shunt as an initial procedure before subsequent Fontan palliation. In eight of these patients (group I), bidirectional CPA was performed before age 3 years, and in four (group II), it was performed after age 10 years. The remaining 11 patients (group III, age and weight control group for group I) were maintained with their initial shunt until they underwent Fontan palliation. Serial echocardiographic analysis was used retrospectively to evaluate left ventricular volume and mass and systolic pump function (ejection fraction) before and after bidirectional CPA. RESULTS: Through 10 months of follow-up, group I patients showed significant decreases in indexed end-diastolic volume both after CPA (120 ml/m1.5 body surface area vs. 78 ml/m1.5, p = 0.001) and in comparison with values in patients in group II and III, who showed no changes in end-diastolic volume (p < 0.001). Indexed ventricular mass decreased moderately after bidirectional CPA in group I (from 228 g/m1.5 body surface area to 148 g/m1.5) but remained unchanged in groups II and III. The differences in trends between groups I and III were significant (p = 0.03). Ejection fraction decreased significantly in group II versus group I patients (0.48 to 0.27 vs. 0.51 to 0.52, p < 0.05) after CPA. Oxygen saturation measurements before and after bidirectional CPA revealed a significant increase in group I (73% to 86%, p < 0.001) and a decrease in group II (82% to 73%, p < 0.01). CONCLUSIONS: Bidirectional CPA facilitates ventricular volume unloading and promotes regression of left ventricular mass in younger children (< 3 years) in preparation for a Fontan operation. In contrast, bidirectional CPA is of questionable value in older children as a staging procedure for Fontan palliation.

Aging↗

Echo-planar FLAIR imaging in evaluation of intracranial lesions.

Fluid-attenuated inversion-recovery (FLAIR) imaging is a magnetic resonance imaging technique that improves lesion detection in the brain. This technique suppresses signal from free water in cerebrospinal fluid and maintains the hyperintense lesion contrast of T2-weighted spin-echo imaging. Unfortunately, conventional FLAIR imaging requires a long acquisition time and provides a limited number of sections. A combination of echo-planar imaging and FLAIR imaging offers the image contrast effects of FLAIR imaging and the speed of echo-planar imaging. Clinically, the echo-planar FLAIR technique is most helpful in detecting subtle, early lesions that do not enhance, such as early infarct, demyelinating disease, early infection, and trauma. The increased magnetic susceptibility effect associated with the echo-planar technique can be clinically useful in detecting subtle hemorrhage and cavernous angioma. Echo-planar FLAIR imaging is a practical and efficient means of screening the entire brain in a short time.

Brain Diseases↗

Regulation of SERCA 2 expression by thyroid hormone in cultured chick embryo cardiomyocytes.

We investigated the role of thyroid hormone in the physiological perinatal increase in cardiac sarcoplasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (ATPase) expression. We isolated and cultured the cardiomyocytes in 10(-8) M triiodothyronine (T3) for 48 h and then measured SR Ca(2+)-ATPase mRNA and immunodetectable protein contents as well as SR-dependent 45Ca2+ uptake rate. We also examined the effect of T3 on expression of the same gene in monkey kidney CV-1 cells, which do not express thyroid hormone receptors. T3 increased cardiomyocyte SR Ca2+ pump mRNA content by 289 +/- 35%, and immunodetectable SR Ca2+ pump protein content by 255 +/- 44%, and SR-specific 45Ca2+ uptake rate by 189 +/- 22% (P < 0.01 for each). In contrast, T3 had no significant effect on the total cellular RNA or protein contents in the cardiomyocyte, and there was no effect of T3 on Ca(2+)-ATPase mRNA content in the thyroid hormone receptor-negative CV-1 cells. These data demonstrate that T3 increases expression of the cardiac SR Ca2+ pump, that the effect can be localized to the cardiomyocyte, and that the effect is dependent on thyroid hormone receptors. These data are consistent with pretranslational and possibly transcriptional level effect of thyroid hormone on the cardiac SR Ca2+ pump gene (SERCA 2). The gestation-associated increase in thyroid hormone may be at least partially responsible for the previously demonstrated perinatal increase in cardiac SR Ca2+ pump expression.

Animals↗

Usefulness of turbo spin-echo MR imaging in the evaluation of meniscal tears: comparison with a conventional spin-echo sequence.

OBJECTIVE: Fast (turbo) spin-echo imaging techniques have replaced conventional spin-echo protocols in a large proportion of MR applications, with the principle advantage of decreased imaging time. The choice of echo train length is a key determinant of time savings realized, but the echo train length can also adversely affect image quality if too many echoes are incorporated into an image. Several recent studies have shown conflicting results regarding the usefulness of turbo spin-echo imaging in the evaluation of meniscal tears. We compare a turbo spin-echo sequence that has an echo train length of five with a conventional spin-echo sequence for evaluating meniscal tears. SUBJECTS AND METHODS: Forty knees in 39 consecutive patients referred for MR study of the knee were imaged using both conventional spin-echo and turbo spin-echo sequences. The turbo spin-echo sequence provided both proton density-weighted and T2-weighted images (dual echo technique) with an effective echo-train length of five. Nineteen knees (38 menisci) were studied arthroscopically. The arthroscopic findings were considered the reference standard. Spin-echo and turbo spin-echo images were reviewed retrospectively, and results were compared statistically. RESULTS: Of the 80 menisci evaluated with MR imaging, spin-echo and turbo spin-echo images provided concordant results in 95% of cases, with no statistically significant difference found between the two techniques (p < .05). Seventeen tears were found at arthroscopy in 38 menisci studied. Spin-echo and turbo spin-echo imaging had identical specificities (90%) and similar sensitivities (88% and 82%, respectively). CONCLUSION: This study shows that proton density-weighted sequences with an echo train length of five preserve sufficient high-spatial-frequency information to provide performance similar to that of conventional spin-echo sequences. Our data support the conclusion that fast spin-echo imaging with short echo train length is a reasonable substitute for conventional spin-echo imaging in the evaluation of the knee.

Adult↗

Resurgence of rabies. A historical perspective on rabies in children.

Wildlife rabies in certain parts of the United States has been increasing. With greater urbanization, many areas have seen an influx of wild animals such as raccoons and foxes that are known wildlife reservoirs of rabies. Rabies encephalitis has been a fatal illness recognized by humans throughout history. The purpose of this review is to examine the history of rabies throughout the world to elucidate the evolution of popular and scientific knowledge of the disease in animals and humans. By examining this development from a pediatric perspective, we gain insight into the prevention and treatment protocols recommended for children today. Pediatricians need to include education about prevention and treatment of rabies exposures in their anticipatory guidance sessions with families.

Animals↗

Recent insights into the regulation of cardiac Ca2+ flux during perinatal development and in cardiac failure.

Systolic and diastolic cardiac function improve during the transition from fetus to newborn to adult. This perinatal maturation is temporally correlated with and at least partially dependent on subcellular changes in the expression of several gene products that regulate cytosolic Ca2+ concentration. Expression of the Na(+)-Ca2+ exchanger of the sarcolemma is highest in the fetus, whereas expression of the sarcoplasmic reticulum Ca2+ pump and the voltage-dependent Ca2+ channel of the sarcolemma increase in conjunction with the perinatal maturation of cardiac function. Whereas cardiac relaxation in the normal mature heart depends primarily on the sarcoplasmic reticulum Ca2+ pump, relaxation in the fetal heart appears to be more dependent on transsarcolemmal Ca2+ flux. Like the fetal heart during prolonged relaxation, the failing human heart exhibits impaired relaxation and abnormal Ca2+ flux regulation. Although altered expression of several gene products has been demonstrated in the failing heart, the responsible factor(s) remains unknown.

Adult↗

The effect of contrast dose, imaging time, and lesion size in the MR detection of intracerebral metastasis.

PURPOSE: To evaluate the effect of MR contrast dose versus delayed imaging time on the detection of metastatic brain lesions based on lesion size. METHODS: Contrast MR examinations with gadoteridol were obtained in 45 patients with brain metastases. The patients were divided into two groups: 16 received cumulative standard dose (0.1 mmol/kg) and 29 received cumulative triple dose (0.3 mmol/kg). Both groups were evaluated at two dose levels (lower dose and higher dose) with two separate injections. Each patient received an initial bolus injection of either 0.05 (cumulative standard dose) or 0.1 (cumulative triple dose) mmol/kg of gadoteridol to reach the lower-dose level and underwent imaging immediately and 10 and 20 minutes later. Thirty minutes after injection, an additional bolus injection of 0.05 (cumulative standard dose) or 0.2 (cumulative triple dose) mmol/kg was administered to reach the cumulative higher-dose level (cumulative standard dose, 0.1 mmol/kg; cumulative triple dose, 0.3 mmol). Images were acquired immediately. RESULTS: There was no difference in the detection rate for lesions larger than 10 mm among T2-weighted, lower-dose immediate and delayed, or immediate higher-dose images in both study groups. Lesions smaller than 10 mm had improved detection with delayed imaging in both study groups; however, the immediate higher-dose studies still had the highest detection rate. CONCLUSION: In the evaluation of small central nervous system metastases, either delayed imaging after the injection of standard contrast dose or higher contrast dose may improve their detection, and therefore affect clinical management. Higher contrast dose (cumulative triple dose) studies appear to be more effective than delayed imaging with standard dose.

Brain↗

Lifelong management of patients with a single functional ventricle: a protocol.

Of the wide variety of congenital heart defects, the single functional ventricle continues to be one of the most enigmatic. Compared with patients who have complex congenital heart defects and 2 functional ventricles, patients with a single functional ventricle have greater surgical and long-term morbidity and mortality, and use more medical resources. Recent investigations have shown that patients with a single functional ventricle often have very satisfactory hemodynamics soon after a modified Fontan repair but then develop dilated cardiomyopathy during the subsequent decade. The cause and pathogenesis of the cardiomyopathy have not yet been determined. Many publications have examined individual aspects of the care of these patients based on retrospective reviews, but very few have provided comprehensive prospective methods for managing patients with a single functional ventricle. We hypothesized that a comprehensive management protocol with regular review of the results would provide a better understanding of the problems encountered in these patients and thus improve long-term outcome. Herein, we present our initial protocol for the lifelong management of patients with a single functional ventricle.

Clinical Protocols↗

Granulocytic ehrlichiosis and meningitis in a dog.

A 4-year-old male mixed-breed dog from the Sierra Nevada mountains in California was referred because of epistaxis and signs of cervical pain. Dermacentor variabilis ticks were found on the dog at the time of physical examination. Clinicopathologic abnormalities included nonregenerative anemia, thrombocytopenia, and rare intracytoplasmic morulae within circulating neutrophils. Abnormalities of the CSF included pleocytosis and intracytoplasmic morulae in approximately 9% of neutrophils. Serum antibody titers for Ehrlichia canis (40,960) and Rickettsia rickettsii (5,120) were high, and titer for E equi (40) was moderate. Treatment included administration of tetracycline, chloramphenicol, doxycycline, and prednisone. The dog had several relapses, but long-term remission was eventually achieved. Granulocytic ehrlichiosis has previously been associated with anemia, thrombocytopenia, and polyarthritis in dogs. This case suggests that granulocytic ehrlichiosis may be associated with meningitis and that the organisms that cause granulocytic ehrlichiosis may have the same vector as do the spotted fever-group rickettsiae.

Animals↗

The subcellular basis for the perinatal maturation of the cardiocyte.

In the experimental animal, the transition from tetus to newborn to adult has long been associated with an improvement in systolic and diastolic cardiac function. Recent studies using noninvasive methods have demonstrated a similar perinatal improvement in ventricular function in the human. These perinatal changes in cardiac function have been correlated with subcellular changes in expression of sarcoplasmic reticulum Ca2+ release channel and Ca2+ ATPase proteins (the primary regulators of phasic Ca2+ cycling in the mature heart), as well as with isoform switching among the myofibrillar proteins. The reduced sarcoplasmic reticulum-dependent regulation strongly supports the concept that during perinatal maturation, systolic and diastolic cardiac function are more dependent on transsarcolemmal Ca2+ flux.

Animals↗

Brain parenchymal infection in bone marrow transplantation patients: CT and MR findings.

OBJECTIVE: The purpose of this study was to assess the MR and CT appearance of brain infection after bone marrow transplantation and to correlate the appearances with laboratory and pathologic findings. MATERIALS AND METHODS: We retrospectively reviewed the records of seven bone marrow transplant recipients with radiologic evidence of brain infection. RESULTS: Forty-one lesions were detected in seven patients with proved infectious foci outside the brain before brain infection was suspected clinically. Six patients had low total WBC or lymphocyte counts and one patient had normal total WBC and lymphocyte counts. Most lesions in patients with low total WBC or lymphocyte counts showed no appreciable edema or contrast enhancement. However, all lesions detected in the patient with normal total WBC and lymphocyte counts showed marked vasogenic edema and ring enhancement. CONCLUSION: Brain infection in bone marrow transplant recipients during immunosuppression exhibited MR characteristics different from those typically seen in immunocompetent patients. This appearance may be related to a diminished immunologic/inflammatory response.

Adult↗

Delineation of gliomas with various doses of MR contrast material.

PURPOSE: To examine the effects of different gadolinium doses on the delineation of gliomas, particularly the demonstration of abnormal enhancement on T1-weighted images extending beyond the zone of apparent signal abnormality on corresponding T2-weighted images. METHODS: During phase II clinical trials of gadoteridol, 23 patients with pathologically proved gliomas were studied by MR with various doses of gadoteridol, ranging from 0.05 to 0.3 mmol/kg. RESULTS: All of the gliomas were readily detected by T2-weighted images. Twelve of 23 patients demonstrated enhancement on T1-weighted images extending beyond the zone of apparent signal abnormality demonstrated on T2-weighted images. These findings were seen in none of the six patients (0%) studied at 0.05 mmol/kg, one of five patients (20%) studied at 0.1 mmol/kg, four of five patients (80%) studied at 0.2 mmol/kg, and seven of seven patients (100%) studied at 0.3 mmol/kg. CONCLUSIONS: The detection of symptomatic gliomas does not require a contrast agent because they are generally large and readily demonstrated on T2-weighted images. However, the area of postcontrast enhancement of gliomas seems to be greater with higher doses of contrast agent. The cause of the abnormal enhancement extending beyond the zone of apparent signal abnormality on T2-weighted images seen in this limited study is unknown and probably represents tumor infiltration. The frequency of detection of such findings appears to be proportional to the dose of contrast material used.

Brain↗

Febrile infants at low risk for serious bacterial infection--an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group.

OBJECTIVE: Prospective studies were conducted to test the hypothesis that infants unlikely to have serious bacterial infections (SBI) can be accurately identified by low risk criteria. METHODS: Febrile infants (rectal T > or = 38 degrees C) < or = 60 days of age were considered at low risk for SBI if they met the following criteria: 1) appear well; 2) were previously healthy; 3) have no focal infection; 4) have WBC count 5.0-15.0 x 10(9) cells/L (5000-15,000/mm3), band form count < or = 1.5 x 10(9) cells/L (< or = 1500/mm3), < or = 10 WBC per high power field on microscopic examination of spun urine sediment, and < or = 5 WBC per high power field on microscopic examination of a stool smear (if diarrhea). The recommended evaluation included the culture of specimens of blood, cerebrospinal fluid, and urine for bacteria. Outcomes were determined. The negative predictive values of the low risk criteria for SBI and bacteremia were calculated. RESULTS: Of 1057 eligible infants, 931 were well appearing, and, of these, 437 met the remaining low risk criteria. Five low risk infants had SBI including two infants with bacteremia. The negative predictive value of the low risk criteria was 98.9% (95% confidence interval, 97.2% to 99.6%) for SBI, and 99.5% (95% confidence interval, 98.2% to 99.9%) for bacteremia. CONCLUSIONS: These data confirm the ability of the low risk criteria to identify infants unlikely to have SBI. Infants who meet the low risk criteria can be carefully observed without administering antimicrobial agents.

Anti-Bacterial Agents↗

Phase III multicenter trial of high-dose gadoteridol in MR evaluation of brain metastases.

PURPOSE: To assess the efficacy and safety profile of high-dose (0.3 mmol/kg cumulative dose) gadoteridol in patients with suspected central nervous system metastatic disease. METHODS: We studied 67 patients using an incremental-dose technique. Patient monitoring included a medical history, physical examination, vital signs, and extensive laboratory tests within 24 hours before and after the MR examination. Precontrast T1- and T2-weighted spin-echo studies were performed, followed by intravenous injection of 0.1 mmol/kg of gadoteridol. T1-weighted images were acquired immediately after and at 10 and 20 minutes after injection. At 30 minutes an additional 0.2 mmol/kg of gadoteridol was administered (0.3-mmol/kg cumulative dose), and T1-weighted images were acquired. Cases demonstrating abnormal MR findings were assessed for efficacy by unblinded and blinded reviewers and were analyzed quantitatively. RESULTS: Three adverse effects in two patients were considered to be related to gadoteridol administration. No adverse effects were serious; all self-resolved. Forty-nine cases showed abnormal MR findings and were included in the efficacy analysis. A significantly greater number of lesions was seen on the high-dose as opposed to the standard-dose images. Blinded and unblinded readers identified 5 and 8 patients, respectively, with solitary lesions on standard-dose examination and multiple lesions on high-dose examination. Two patients who had normal standard-dose findings had lesions identified on high-dose studies. Quantitative analysis of 133 lesions in 45 patients demonstrated significant increases in lesion signal intensity on high-dose studies when compared with standard-dose studies. CONCLUSION: Gadoteridol can be safely administered up to a cumulative dose of 0.3 mmol/kg. High-dose contrast studies provide improved lesion detectability and additional diagnostic information over studies performed in the same patients with a 0.1-mmol/kg dose and aid in patient diagnosis and treatment. High-dose gadoteridol study may facilitate the care of patients with suspected central nervous system metastasis.

Adolescent↗

Cost-effectiveness of high-dose MR contrast studies in the evaluation of brain metastases.

PURPOSE: To investigate the cost-effectiveness of high-dose MR contrast studies in the management of brain metastases. METHODS: During the phase III clinical trial of high-dose contrast studies (0.3 mmol/kg), 11 of 27 patients were judged by the reviewers to have potential treatment changes based on the additional information provided by the high-dose studies. We retrospectively evaluated how many of these 27 patients had actual treatment changes because of the results of the high-dose study. Using the fee schedule at our institution, the cost-effectiveness was analyzed based on the cost savings from treatment changes and the additional expense of implementing the high-dose studies. RESULTS: A total of 3 craniotomies ($22,800 each) and 2 aggressive courses of radiation therapy ($1122 each) were avoided in 4 patients because of the additional lesions detected by the high-dose studies. This resulted in a treatment cost savings of $70,644. The extra expense for implementing the high-dose study is $9126 for a single injection in all 27 patients, $9295 for 2 separate injections completed in 1 visit in the 11 patients, and $11,154 for 2 separate injections completed in 2 separate visits. The cost savings in management (diagnosis and treatment) therefore ranged from $59,490 to $61,518 for all patients and from $2203 to $2278 per patient. CONCLUSION: Based on our limited data, the high-dose study seems to impact positively on the cost-effectiveness in the management of brain metastases. However, because our study had limitations, our results need to be confirmed with a larger patient population and a more standardized treatment approach and fee schedule.

Adult↗

Sequential MR enhancement pattern in normal pituitary gland and in pituitary adenoma.

PURPOSE: To measure and evaluate the temporal enhancement characteristics of the normal pituitary gland and pituitary adenoma. METHODS: Thirty healthy subjects and 10 patients with sellar pituitary adenomas were studied prospectively using dynamic MR imaging with a 5- or 10-sec temporal resolution during a bolus injection of gadolinium. RESULTS: Qualitative visual analysis demonstrated a consistent sequential pattern of pituitary enhancement in which the posterior lobe enhanced earlier than the anterior lobe by approximately 35 sec. Quantitative analysis revealed that posterior lobe enhancement occurred 9.8 +/- 1.5 sec (mean +/- SEM) before the anterior lobe in healthy subjects, whereas tumor enhancement occurred significantly before the anterior lobe but only slightly before the posterior lobe in patients with adenomas. CONCLUSION: The sequential enhancement pattern of the normal pituitary gland was found to be consistent with its vascular anatomy. In contrast to previous reports, pituitary adenomas were found to enhance earlier than the anterior lobe. These results suggest that pituitary adenomas have a direct arterial blood supply, similar to that of the posterior pituitary lobe.

Adenoma↗