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Biomedical subjects

E A Knopp

Publications and source records attributed to E A Knopp.

At least 19 recordsLinked to original sources

Dynamic susceptibility contrast MR imaging: correlation of signal intensity changes with cerebral blood volume measurements.

Cerebral blood volume (CBV) maps derived from dynamic susceptibility contrast (DSC) magnetic resonance (MR) imaging provide valuable information regarding intracranial micro-hemodynamics and have been helpful in characterizing primary brain tumors and guiding stereotactic biopsy. Another parameter, the maximum signal drop (MSD) during the first pass of intravascular contrast bolus due to T2* effect, can also be measured directly without extensive post-processing and data manipulation. The purpose of our study is to determine whether MSD maps provide information similar to CBV maps in patients presenting with intracranial mass lesions. Twenty-nine patients with various intracranial mass lesions were studied with DSC MR imaging prior to stereotactic biopsy or volumetric resection. Maps of both CBV and MSD are calculated on a pixel-by-pixel basis and displayed as color overlays over the raw images. Relative CBV (rCBV) and MSD (rMSD) values were measured in regions of interest (ROIs) within areas of abnormality and compared. In addition, computer-generated noise was added to the data to estimate the sensitivity of each measurement to noise. The rMSD values were strongly correlated with rCBV values (r = 0.87, P = 0.0001). CBV values were much more sensitive to added noise than MSD values (P < 0.01). MSD maps derived from DSC MR imaging provide information similar to CBV maps in patients with intracranial mass lesions. MSD maps are a simple and reliable indicator of vascularity that can easily be incorporated into routine MR imaging.

Brain Neoplasms↗

Dynamic contrast-enhanced T2-weighted MR imaging of recurrent malignant gliomas treated with thalidomide and carboplatin.

BACKGROUND AND PURPOSE: Dynamic, contrast-enhanced MR imaging has allowed quantitative assessment of cerebral blood volume (CBV) in brain tumors. The purpose of our study was to compare postcontrast T1-weighted imaging with dynamic, contrast-enhanced T2*-weighted echo-planar imaging in the evaluation of the response of recurrent malignant gliomas to thalidomide and carboplatin. METHODS: Serial MR imaging was performed in 18 consecutive patients with recurrent malignant gliomas receiving both thalidomide and carboplatin for 12-month periods. Six patients undergoing carboplatin therapy alone were chosen as control subjects. Conventional postcontrast T1-weighted images were compared with relative CBV (rCBV) maps calculated on a pixel-by-pixel basis from dynamic echo-planar imaging data. Tumor progression was evaluated clinically using established criteria for malignant gliomas. Studies were performed at 2- to 3-month intervals, and imaging and clinical findings were compared. RESULTS: Tumor response to treatment, based on clinical findings, did not correlate well with conventional imaging findings. The rCBV values decreased significantly in all patients between the start of therapy and the first follow-up in the study group, but not in the control group. The difference in rCBV values between the clinically stable and the progressive group at 12-month follow-up was statistically significant, with the progressive group having higher values. CONCLUSION: Dynamic, contrast-enhanced MR imaging is a valuable adjunct to conventional imaging in assessing tumor activity during antiangiogenic therapy, and correlates better than conventional studies with clinical status and response to therapy.

Adult↗

Murine phospholipid hydroperoxide glutathione peroxidase: cDNA sequence, tissue expression, and mapping.

Phospholipid hydroperoxide glutathione peroxidase (PHGPx), also known as glutathione peroxidase 4 (GPX4), is a 19-kDa, monomeric enzyme that protects cells from lipid peroxide-mediated damage by catalyzing the reduction of lipid peroxides. PHGPx is synthesized in two forms, as a 194-amino acid peptide that predominates in gonadal tissue and localizes to mitochondria, and as a 170-amino acid protein that predominates in most somatic tissues and localizes to the cytoplasm. With the rapid amplification of cDNA ends (RACE) procedure, an 876-bp PHGPx cDNA was amplified from mouse testis, and a 767-bp PHGPx cDNA was amplified from mouse heart. The cDNA sequences were identical except that the testis cDNA contained an additional 109 bp at its 5' end. With a partial cDNA with complete homology to both the testis and myocardial PHGPx cDNAs, the murine tissue distribution of PHGPx mRNA expression was determined by Northern blotting. Highest level of PHGPx expression was found in the testis, followed by the kidney, heart and skeletal muscle, liver, brain, lung, and spleen. Northern blotting performed with a cDNA specific for the longer PHGPx transcript demonstrated that this longer PHGPx transcript was present only in the testis. A 1.4-kb PHGPx genomic fragment was amplified from murine kidney DNA and used to map the PHGPx gene by linkage analysis of restriction fragment length variants (RFLVs). The murine PHGPx gene (Gpx4) was mapped to a region of murine Chromosome (Chr) 10, located 43 cM from the centromere, that is syntenic with the human locus, which is located at the terminus of the short arm of human Chr 19. This information may be valuable in characterizing the role of PHGPx in modulating susceptibility to lipid peroxide-mediated injury in inbred murine strains and for targeted disruption of the gene.

Amino Acid Sequence↗

Glial neoplasms: dynamic contrast-enhanced T2*-weighted MR imaging.

PURPOSE: To evaluate the role of T2*-weighted echo-planar perfusion imaging by using a first-pass gadopentetate dimeglumine technique to determine the association of magnetic resonance (MR) imaging-derived cerebral blood volume (CBV) maps with histopathologic grading of astrocytomas and to improve the accuracy of targeting of stereotactic biopsy. MATERIALS AND METHODS: MR imaging was performed in 29 patients by using a first-pass gadopentetate dimeglumine T2*-weighted echo-planar perfusion sequence followed by conventional imaging. The perfusion data were processed to obtain a color map of relative regional CBV. This information formed the basis for targeting the stereotactic biopsy. Relative CBV values were computed with a nondiffusible tracer model. The relative CBV of lesions was expressed as a percentage of the relative CBV of normal white matter. The maximum relative CBV of each lesion was correlated with the histopathologic grading of astrocytomas obtained from samples from stereotactic biopsy or volumetric resection. RESULTS: The maximum relative CBV in high-grade astrocytomas (n = 26) varied from 1.73 to 13.7, with a mean of 5.07 +/- 2.79 (+/- SD), and in the low-grade cohort (n = 3) varied from 0.92 to 2.19, with a mean of 1.44 +/- 0.68. This difference in relative CBV was statistically significant (P < .001; Student t test). CONCLUSION: Echo-planar perfusion imaging is useful in the preoperative assessment of tumor grade and in providing diagnostic information not available with conventional MR imaging. The areas of perfusion abnormality are invaluable in the precise targeting of the stereotactic biopsy.

Adolescent↗

Mycosis fungoides metastasizing to the brain parenchyma: case report.

OBJECTIVE AND IMPORTANCE: Mycosis fungoides is a rare T-cell lymphoma of the skin that can, in one-half to three-quarters of patients suffering from this disease, involve the viscera in late stages of the disease. Although autopsy series performed more than 2 decades ago showed that the incidence of metastatic mycosis fungoides to the central nervous system is approximately one of seven, a total of only several dozen cases have been reported to date. As compared to meningeal involvement, intraparenchymal metastases are even rarer. We describe a biopsy-proven case of intraparenchymal central nervous system mycosis fungoides in a patient with nonprogressive skin involvement and no detectable visceral involvement, and we present a review of the relevant literature. CLINICAL PRESENTATION: A 68-year-old man, 3 years after the diagnosis of his skin disease, developed fatigue, confusion, and frontal lobe signs without the presence of cerebriform cells in the peripheral blood or any other clinical evidence of visceral involvement. Magnetic resonance imaging revealed a diffuse area of increased T2-weighted signal involving the white matter of both cerebral hemispheres as well as a focal area of T2 abnormality along the body of the corpus callosum. The radiological differential diagnosis was either leukodystrophy caused by chemotherapy, progressive multifocal leukoencephalopathy, or glioma with associated white matter changes. INTERVENTION: A stereotactic serial brain biopsy revealed diffuse perivascular infiltrates of atypical lymphocytes, as well as several large cells with cerebriform nuclei consistent with mycosis fungoides. The cells were immunoreactive for LCA, MT1, UCHL1, and CD3. CONCLUSION: We stress the importance of including mycosis fungoides as part of the differential diagnosis for a brain lesion in patients with cutaneous T-cell lymphoma, because treatments do exist, and we conclude that a serial stereotactic biopsy may be necessary to provide a definitive diagnosis.

Aged↗

Contrast-enhancing progressive multifocal leukoencephalopathy: radiological and pathological correlations: case report.

OBJECTIVE AND IMPORTANCE: Progressive multifocal leukoencephalopathy (PML), a demyelinating disease caused by the JC papovavirus, is an opportunistic infection afflicting patients with impaired cellular immunity. Although initially described in patients with hematological malignancies, PML has become associated with several other immunocompromised states, particularly human immunodeficiency virus (HIV) infection. There are numerous central nervous system manifestations in patients with acquired immunodeficiency syndrome. A major characteristic that distinguishes PML from other more common lesions, such as toxoplasmosis or non-Hodgkin's lymphoma, is the lack of contrast enhancement. We describe a case of PML that exhibits contrast enhancement, and we conclude that the diagnosis of PML must be considered in patients with HIV who have contrast-enhancing lesions. CLINICAL PRESENTATION: A 40-year-old woman presented with progressive hemiparesis, blurred vision, and ataxia. Magnetic resonance imaging revealed a contrast-enhancing lesion involving the left middle cerebellar peduncle, causing mild compression of the fourth ventricle. INTERVENTION: The patient underwent a stereotactic serial biopsy with the presumptive diagnosis of moderate- to high-grade glioma. Histological examination of the biopsy specimen revealed early PML. Subsequently, a test for HIV was obtained and the results were positive. CONCLUSION: We have reported another atypical radiographic characteristic of PML associated with HIV. We conclude that PML lesions can enhance after the administration of gadolinium. Therefore, the diagnosis of PML must be entertained in patients whose test results were positive for HIV with contrast-enhancing lesions and that a stereotactic serial biopsy may be necessary to provide a definitive diagnosis.

Adult↗

The role of magnetic resonance angiography in the assessment of intracranial vascular disease.

Magnetic resonance techniques have a significant role in the evaluation of intracranial vascular diseases; however, to achieve an appropriate diagnosis, a combination of both magnetic resonance imaging and angiography are needed. It is extremely important for the interpreting physician to be aware of the potential limitations of the techniques being used. With this knowledge, magnetic resonance techniques can eliminate the need for more invasive procedures. An overview of the current methods and their applications and limitations is provided.

Brain↗

Venous disease and tumors.

MR imaging of the venous system of the brain plays an important role in the diagnosis and follow up of intracranial venous vascular diseases. This article serves to acquaint the reader with the currently available methods to study the venous vascular system in addition to covering specific instances in which these methods should be used.

Brain↗

Primary lymphoma of the cauda equina: myelographic, CT myelographic, and MR appearance.

This case demonstrates the myelographic, CT myelographic, and MR appearance of primary lymphoma of the cauda equina. It also illustrates the utility of high-resolution CT myelography in certain lesions of the cauda equina. The authors feel that CT myelography, with its inherent ability to depict individual nerve roots and therefore any pathologic involvement as well, should be considered an adjunct to MR in imaging the cauda equina.

Aged↗

'Pulsatile' left atrial-femoral artery bypass. A new method of preventing extension of myocardial infarction.

A left atrial-femoral artery (LA-FA) bypass system was designed to deliver synchronous pulsatile blood flow. We compared it with nonpulsatile LA-FA bypass in its effectiveness to limit infarct extension after ligation of the left anterior descending coronary artery at its origin in 35 dogs. Nonpulsatile LA-FA bypass resulted in a 70% reduction in the size of infarct. The addition of synchronous diastolic counterpulsation (P-LA-FA) further reduced the size of infarct, when compared with that in controls (95%) or animals that underwent LA-FA bypass (83%). Both LA-FA and P-LA-FA bypasses limited infarct extension and reduced mortality after acute coronary occlusion through effective unloading of the left ventricle. The addition of diastolic counterpulsation to LA-FA bypass led to further significant infarct reduction, when compared with LA-FA bypass alone. These effects were most likely secondary to improvements in myocardial blood flow distribution.

Animals↗

Experimental and clinical assessment of the adequacy of partial bypass in maintenance of spinal cord blood flow during operations on the thoracic aorta.

We studied both experimentally and clinically the efficacy of partial bypass techniques in maintaining spinal cord blood flow and physiological function during surgical procedures on the thoracoabdominal aorta. We attempted to define the level of distal aortic pressure required to safely ensure normal neurological function in the absence of critical intercostal occlusion. Six dogs underwent left thoracotomy with baseline measurements of spinal cord blood flow and spinal cord impulse conduction (somatosensory evoked potentials). Following exclusion of the entire descending thoracic aorta from the left subclavian artery to the T-13 level, partial left atrium-femoral artery bypass was instituted, and baseline levels of proximal and distal aortic pressure were maintained during a 30-minute stabilization period. Mean distal aortic pressure then was progressively altered at 30-minute intervals to 100, 70, and 40 mm Hg. Measurements of spinal cord blood flow and somatosensory evoked potential were repeated at the end of each interval for comparison with baseline. No significant changes in spinal cord blood flow or somatosensory evoked potential were observed in any animal with a distal aortic pressure greater than or equal to 70 mm Hg. With a pressure of 40 mm Hg, normal flow and somatosensory evoked potentials were maintained in 5 of the 6 dogs. Loss of somatosensory evoked potential, with simultaneous loss of spinal cord blood flow at the T-6 level, occurred in 1 dog. Restoration of distal aortic pressure to 70 mm Hg in all animals resulted in immediate return of somatosensory evoked potential. Loss of somatosensory evoked potential routinely occurred in animals with a distal aortic pressure less than 40 mm Hg. Clinically, 9 patients have undergone operation for lesions of the thoracoabdominal aorta using shunt or bypass techniques. Normal somatosensory evoked potentials were preserved in 7 patients with maintenance of adequate distal aortic pressure (greater than or equal to 60 mm Hg) without evidence of postoperative neurological deficit. Two patients showed hypotensive somatosensory evoked potential loss (distal aortic pressure less than 40 mm Hg). Prolonged distal hypotension (85 minutes of aortic cross-clamping) in the latter resulted in paraplegia. We conclude that maintenance of a distal aortic pressure greater than 60 to 70 mm Hg will uniformly preserve spinal cord blood flow in the absence of critical intercostal exclusion. Should distal aortic pressure be inadequate, early reversible changes in the somatosensory evoked potential will alert the surgeon. Failure to institute measures to reverse these changes may result in paraplegia.

Animals↗

Preservation of myocardial ATP. Comparison of blood vs crystalloid cardioplegia.

Preservation of myocardial high-energy phosphates correlates with the heart's ability to resume normal function following aortic crossclamping (AXC). The ability of the canine myocardium to synthesize and maintain ATP during 180 minutes of AXC was evaluated in 12 hearts subjected to either blood or crystalloid cardioplegic arrest. Group 1 hearts were arrested by infusion of 750 ml of blood potassium cardioplegia (BKC) solution into the aortic root initially and every 30 minutes, as were group 2 (six) hearts but with a crystalloid cardioplegia (CC) solution. Transmural left ventricular biopsy specimens were obtained for ATP analysis prior to AXC (control), before and after cardioplegia injections 2, 4, and 6, prior to unclamping (180 minutes of AXC), and 30 minutes following reperfusion. ATP levels increased significantly above control (p less than 0.005) during the 180 minutes of AXC immediately following infusion of BKC. At the end of 180 minutes of AXC and following 30 minutes of reperfusion, ATP was noted to be normal in this group (p = NS). In contrast, ATP levels fell significantly (p less than 0.005) during the period of aortic cross-clamping in the crystalloid cardioplegia group and did not return to normal even after 30 minutes of reperfusion (p less than 0.005). We concluded that BKC, by presenting the arrested myocyte with adequate oxygen and substrate, allows for synthesis and preservation of myocardial ATP during periods of AXC as long as three hours. In this respect, it should be regarded as superior to CC, which permits a statistically significant depletion of ATP (p less than 0.005) uncorrected, even after 30 minutes of reperfusion in the beating, nonworking state.

Adenosine Triphosphate↗

The factors influencing early patency of coronary artery bypass vein grafts: correlation of angiographic and ultrastructural findings.

To test the hypothesis that suboptimal preparation of saphenous veins may adversely affect early patency of aorta-coronary artery bypass grafts, a nonrandomized prospective study was undertaken comparing two methods of saphenous vein preparation prior to grafting. Forty recatheterizations were performed during the postoperative hospital stay (approximately 10 days) in two groups of asymptomatic patients who had undergone isolated coronary artery bypass grafting. Veins from patients in Group I were bathed in autologous, heparinized blood at 20 degrees C and distended to 80 mm Hg, prior to grafting. The veins from Group II patients were prepared in an identical manner, except that the bathing solution consisted of heparinized electrolyte solution with added papaverine (0.6 mg/lg). Segments of vein from each group were obtained prior to grafting and preserved in 3% glutaraldehyde for subsequent electron microscopic studies. Operative technique in both groups of patients was identical and all procedures were performed by the same surgeons. Comparison of patients in Group I and II revealed no significant difference in the number of diseased vessels per patient (3.1 versus 3.4), number of grafts per patient (2.9 versus 2.9), native vessel diameter (1.9 versus 1.7 mm), and postoperative graft flows (65 versus 68 cc/min). However, early postoperative graft patency in Group II patients was 93% versus 80% in patients in Group I (p less thn 0.01). Electron microscopic analysis revealed severe spasm of venous smooth muscle in the blood-stored veins causing intraluminal smooth muscle cell cytoplasmic protrusions with resultant endothelial separation and desquamation. Formation of fibrin-platelet microaggregates was common. These findings were not present in the solution-treated veins. In view of these ultrastructural findings, and the highly significant difference in patency rates, we have abandoned all blood storage techniques and now prepare saphenous veins by soaking them in a clear bathing medium with added heparin and papaverine. Long-term follow-up of these patients is currently in progress and may reveal even more dramatic results than we have heretofore observed.

Coronary Angiography↗

Blood potassium cardioplegia administration. Comparison of myocardial protection offered by three techniques.

To investigate the best method of administration of blood potassium cardioplegia, 19 dogs were studied while undergoing 120 minutes each of aortic crossclamping (myocardial temperature, less than 15 degrees C). Group 1 (six dogs) underwent a single 120-minute period of aortic crossclamping with the heart protected by multiple reinjections (1,000 mL every 30 minutes) of blood potassium cardioplegia solution (potassium chloride, 30 mEq/L; pH, 8; temperature, less than 15 degrees C). Group 2 (six dogs) underwent four separate 30-minute periods of aortic crossclamping, but allowing hearts to beat in a nonworking state for 20 minutes at 35 degrees C between each arrest interval. Hearts in group 3 (seven dogs) were initially arrested as described above, following which a continuous infusion (75 mL/min; KCl, 10 mEq/L) of blood potassium cardioplegia solution was maintained throughout the arrest period. Measurements of myocardial metabolism, ventricular function, regional blood flow, and ultrastructure were carried out before arrest and 30 minutes after final unclamping. Analysis of the data revealed no significant benefit of one method over another, with the exception that adenosine triphosphate level was least preserved with intermittent unclamping and reperfusion. Because continuous perfusion techniques are more cumbersome than multidose reinjection, and intermittent aortic crossclamping lengthens total cardiopulmonary bypass time, we favor the simplest approach, multidose reinjection during a single uninterrupted period of aortic crossclamping.

Adenosine Triphosphate↗