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Biomedical subjects

J H Kramer

Publications and source records attributed to J H Kramer.

At least 73 records · Page 4Linked to original sources
PubMed1993

Detection of alkoxyl and carbon-centered free radicals in coronary sinus blood from patients undergoing elective cardioplegia.

Confirmation of the involvement of free radicals in postischemic injury in human heart has been elusive. The present study was performed to determine the presence of free radicals in coronary sinus blood from patients undergoing elective open heart surgery and cardioplegia. Six patients who were scheduled for nonurgent elective open heart surgery were used in this study. Coronary sinus blood samples were withdrawn at 1, 3, 5, 10, 15, 20, and 25 min in post-cross-clamp and immediately mixed with isosmotic alpha-phenyl-tert-butylnitrone (PBN) and then centrifuged to obtain plasma. Plasma samples were extracted with toluene and analyzed using electron spin resonance (ESR) spectroscopy. We observed ESR spectra consistent with the formation of alkoxyl and carbon-centered radical adducts of PBN (aN = 13.6 G, a beta H = 1.9 G, and aN = 14.1 G, a beta H = 4.2 G) in six of six patients. We obtained complete free radical production time courses during reperfusion from five patients, and all demonstrated a biphasic profile with an initial burst from 5 to 10 min followed by a second maxima at 25 min. Total PBN-adduct production during reperfusion increased in patients subjected to longer aortic cross-clamp times (global ischemia). These data demonstrate that postcardioplegia free radical production is detectable in coronary sinus blood using an ex vivo spin-trapping technique and that the extent of formation may be related to the severity of ischemia.

Aged↗
PubMed1992

Prophylactic cranial irradiation dose effects on late cognitive function in children treated for acute lymphoblastic leukemia.

Prophylactic central nervous system treatment has dramatically improved the disease-free survival of children with acute lymphoblastic leukemia (ALL). Long-term neuropsychological sequelae are documented in children who received 2400 cGy prophylactic cranial irradiation. The dose was reduced to 1800 cGy. Available reports on developmental consequences, with short follow-up, have yielded inconsistent results. This study assesses radiation dose effects on cognitive function in children with leukemia who received central nervous system prophylaxis with 2400 cGy versus 1800 cGy whole brain radiotherapy. All leukemic children also received intrathecal methotrexate. A control group of children (treated for Wilms' tumor) received no central nervous system therapy. Nineteen children were treated with 2400 cGy, 16 children with 1800 cGy. The 12 control children received no irradiation. All patients were off therapy for at least 70 months. The 1800 cGy and 2400 cGy patient groups were off therapy for equivalent periods of time (range 70-123 mo) at follow-up testing. Mean age at diagnosis was 49 months, at testing: 142 months. The male to female ratio was 1/1. Standardized psychological tests were administered. Full-Scale, Verbal, and Performance IQ were measured with the Wechsler Intelligence Scale for Children-Revised. Wide Range Achievement Testing evaluated reading, spelling, and arithmetic abilities. Children treated with 1800 cGy performed significantly better than those who received 2400 cGy, and at the same level as controls. There were statistically significant differences between the 1800 cGy and 2400 cGy subjects in all measures. 2400 cGy patients had deficiencies in IQ and academic performance. 1800 cGy patients scored approximately 12 points higher than 2400 cGy children. Eleven children, two in the control group, two in the 1800 cGy, and seven in the 2400 cGy group had IQ scores of less than 90. Eight of the nine irradiated children with deficits had radiotherapy before age 5. These results indicate a mild, but diffuse information processing deficit in children who received 2400 cGy, but not in children who received 1800 cGy. These findings with a minimum of 6 years of follow-up provide new information on late effects of CNS prophylaxis in ALL. Reducing the cranial RT dose from 2400 cGy to 1800 cGy reduced neurotoxicity to acceptable levels.

Brain↗
PubMed1992

Brain SPECT imaging in progressive aphasia.

Progressive aphasia without dementia is a relatively uncommon neurobehavioral syndrome. The initial presentation of progressive aphasia without cognitive impairment may pose a diagnostic dilemma. The authors report a patient with progressive aphasia. The initial neuro-imaging studies (MRI, CT) were not diagnostically helpful. However, brain SPECT imaging with Tc-99m HMPAO clearly demonstrated a left temporal lobe abnormality. This report discusses the potential clinical usefulness of brain SPECT imaging in the evaluation of neurobehavioral disorders.

Aphasia↗
PubMed1992

Beta-blockers, calcium channel blockers and the sulfhydryl-ACE inhibitors demonstrate protection against free-radical-mediated injury of cardiovascular cells and membranes.

During reperfusion of previously ischemic cardiac tissue, oxygen-centered free radicals are generated and may result in peroxidative injury of cardiovascular cells and membranes. Since the occurrence of reperfusion injury in patients is unpredictable, particularly in those patients with chronic ischemic coronary artery disease, silent ischemia and those predisposed to significant coronary spasm, it would be advantageous to provide continuing therapy with antioxidant agents.

Adrenergic beta-Antagonists↗
PubMed1992

A prospective study of cognitive functioning following low-dose cranial radiation for bone marrow transplantation.

This study prospectively examined the effects of low doses of cranial irradiation on psychological development in children. The subjects were 22 children receiving bone marrow transplantation. Fifteen children receiving cranial doses ranging from 350 to 1200 cGy as part of their conditioning regimen were contrasted to seven children who were not irradiated. Measures of intellectual and psychosocial development were administered to all subjects prior to transplant and again at one-year posttransplant. There were no decrements in psychological functioning at the one-year follow-up, regardless of the dose of cranial radiation received or the age at which radiation was administered. In addition, there were no significant differences in test scores relative to baseline in a smaller cohort of children followed up for 3 years. Although no significant between-group findings were found, examination of individual cases revealed a high degree of variability, with decrements in IQ of 10 points or more found in 7 children at the one-year follow-up. Findings suggest that doses less than 1500 cGy may prove to be relatively well tolerated with respect to long-term cognitive and psychosocial development, even in young children, although caution is urged in light of the limited length of follow-up.

Adolescent↗
PubMed1991

Cognitive function in children with leukemia. Effect of radiation dose and time since irradiation.

The effect of two cranial radiation (CRTX) doses and the time since radiation therapy on cognitive functioning were studied in 35 children who completed therapy for acute lymphoblastic leukemia (ALL). The patients were grouped according to CRTX dose (2400 or 1800 cGy) and evaluated for general intelligence, academic achievement, and visual motor integration. Those who received 2400 cGy (n = 20) scored ten points below those treated with 1800 cGy (n = 15) on verbal intelligence quotient and achievement tests of reading, spelling, and arithmetic. The effect of time since radiation therapy on these measures of cognitive function was significant (P = 0.001 to 0.03); the effect of CRTX dose was not. Visual motor integration scores in both groups fell below the 33rd percentile. The effect of CRTX dose and time since radiation therapy on visual motor integration and performance intelligence quotient were not significant. Thus, the interval between treatment and the emergence of cognitive impairments may be longer after lower CRTX doses, and deficits in nonverbal areas such as visual motor integration may appear first. A larger study is needed to confirm these findings from a limited sample of long-term survivors of ALL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Propranolol reduces anoxia/reoxygenation-mediated injury of adult myocytes through an anti-radical mechanism.

The effects of propranolol (PRO) and atenolol (ATE) on adult canine myocytes exposed to 30 min anoxia (A:95% N2/5% CO2) and subsequent reoxygenation (R:95% O2/5% CO2) for up to 20 min was investigated. In some studies, comparison of effects were made with that of superoxide dismutase (SOD). Although anoxia alone produced only minimal injury, reoxygenation in the absence of the beta-blockers or SOD was associated with significant losses of cellular viability, elevated release of cellular lactate dehydrogenase, and increased formation of lipid peroxidation products. Myocytes exposed to A/R in the presence of d,1-PRO (20, 200 microM) were afforded substantial, concentration-dependent protection during 20 min reoxygenation. Significant protection was also observed in the presence of 2 microM d-PRO (non-active beta-blocker), but only after a longer preincubation period (2 h). SOD (10 micrograms/ml) provided equi-potent protection to that of 200 microM d,1-PRO. By contrast, the more water-soluble beta-blocker, ATE (200 microM), offered only minor protection. Electron Spin Resonance spin trapping studies using alpha-phenyl-tert-butylnitrone (PBN) were also performed with A/R myocytes in the presence or absence of drug treatment. Short-term (10 min) exposure to d,1-PRO (200 microM) prior to A/R, or to SOD, resulted in a 71-84% reduction in total PBN lipid radical adduct formation (alkoxyl; alpha H = 2.0-2.5 G, alpha N = 13.5-13.75 G); long-term exposure (2 h) to 2 microM d-PRO resulted in a 51% reduction. These data suggest that the superoxide anion was an initiator of events leading to subsequent lipid radical formation and that the anti-peroxidative properties of PRO appear to be independent of beta-receptor blockade.

Adrenergic beta-Antagonists↗
PubMed1991

Propranolol preserves ultrastructure in adult cardiocytes exposed to anoxia/reoxygenation: a morphometric analysis.

The protective effect of d,l-propranolol was studied using freshly isolated canine ventricular cardiocytes (1.5 x 10(6)/mL) exposed to 30 min anoxia (95% N2/5% CO2) and 0, 3, 20, and 45 min of reoxygenation (95% O2/5% CO2). In addition to preventing lipid peroxide formation, propranolol maintained cellular viability, and minimized ultrastructural alterations. In the absence of propranolol, the outer mitochondria become swollen and rounded up within the first few minutes of reoxygenation. The perinuclear mitochondrial area increased only slightly. We observed that the cellular injury process proceeded differentially from the exterior to the interior, with a mitochondrial area increase and outer membrane rupture. Sarcolemmal damage was also observed with prevalent blebbing and membrane loss. The Z-lines became wider and more diffuse with reoxygenation. Injury to the nuclear double membrane was observed. Incubation with propranolol showed significant protection during postanoxia reoxygenation. In contrast, the more water soluble beta-blocker atenolol only exhibited slight protection. In addition, d-propranolol (the non beta-blocking isomer) and the antioxidant enzymes, SOD and catalase, showed significant protection. These data support previous findings concerning the antioxidant properties of propranolol which appear to be independent of beta-receptor blockade.

Animals↗
PubMed1991

Visual hierarchical analysis of Block Design configural errors.

Patients have been frequently observed to violate the overall configuration on the WAIS-R Block Design subtest. The significance of these configural errors was investigated with hierarchical patterns consisting of large "global" shapes made from smaller "local" shapes. Subjects were administered two similarity judgment tasks in which they were asked to decide which of two hierarchically structured comparison figures most resembled a standard figure. Results indicated that subjects who made configural errors on Block Design were less likely than a matched sample who did not make configural errors to select the comparison figure that resembled the standard figure at the global level. Furthermore, the present findings were obtained from subjects without known right-hemisphere lesions, suggesting that the correlation between Block Design errors and global/local performance is applicable to a broad range of patient and non-patient populations. The data are consistent with the view that errors on Block Design may reflect differences in the perceptual encoding of global/local features.

Adult↗
PubMed1991

Factors affecting decisions to institutionalize demented elderly.

This study followed 321 community-based patients with documented dementias, 22% of whom were institutionalized after 1 year. Multivariate analyses indicated that none of the patient characteristics, such as level of cognitive, psychiatric, or neurological impairment, predicted institutionalization. Social psychological characteristics, type and number of caregivers, and subjective caregiver distress did predict which patients were ultimately institutionalized. Implications for treatment planning are discussed.

Aged↗
PubMed1991

Postischemic free radical production in the venous blood of the regionally ischemic swine heart. Effect of deferoxamine.

BACKGROUND: We tested the hypothesis that secondarily produced free radicals can be detected in venous coronary effluent without the need for direct exposure of postischemic tissue to the spin trapping agent alpha-phenyl-tert-butylnitrone (PBN). METHODS AND RESULTS: The left anterior descending coronary artery (LAD) of pigs was ligated for 15, 30, 40, or 60 minutes, and the tissue was subsequently reperfused for 60 minutes. Venous effluent (6.5 ml) from the risk area was withdrawn sequentially at 1.5-minute intervals during reperfusion. The effluent blood was immediately infused (4.5 ml/min) with an isotonic saline solution containing 120 mM PBN: Preischemic control effluent samples were collected in an identical fashion. Plasma from each sample was extracted in organic solvent and subsequently analyzed by electron spin resonance (ESR) spectroscopy. Another group of pigs received an infusion of the metal chelator deferoxamine mesylate (25 mg/kg/hr) into the right atrium starting 1 hour before the 40-minute ligation and continuing throughout ligation and reperfusion. We were able to demonstrate the postischemic production of ESR signals for PBN adduct(s) from untreated hearts having spectral characteristics similar to an alkoxyl adduct (PBN-RO.; hyperfine splitting constants for beta-hydrogen [alpha H] = 2.0-2.25 G; nitrogen [alpha N] = 13.5-13.75 G). The reperfusion time course of PBN adduct production had a unique pattern: 1) multiple low-level bursts during the initial 15 minutes of reperfusion, and 2) a prominent PBN adduct signal during a relatively late time (20-25 minutes) of reperfusion. Total postischemic PBN adduct production rose with increasing duration (15-60 minutes) of ischemia and was associated with a progressive elevation of total lactate dehydrogenase in the effluent. Infusion of deferoxamine markedly diminished PBN adduct production as well as total release of lactate dehydrogenase. CONCLUSIONS: These data suggest the potential feasibility of using an ex vivo ESR spin trapping technique in blood-perfused models of cardiovascular injury and that chelatable free iron contributes to the production of alkoxyl radicals.

Alcohols↗
PubMed1990

Oxygen radical-mediated injury of myocytes-protection by propranolol.

UIe effects of propranolol and atenolol on free radical mediated injury in myocytes were examined. Freshly isolated adult canine myocytes were incubated with a superoxide generating (from dihydroxyfumarate) and Fe-catalyzed free radical system. Exposure of the myocytes to free radicals for 20 min resulted in more than a 5-fold increase in thiobarbituric acid reactant (peroxide) formation and elevated levels of lactate dehydrogenase (LDH) activity released into the media compared to controls. Ultrastructurally, severe sarcolemmal damage, mitochondrial and myofibril derangements were evident. At 40 min, cellular viability (trypan blue exclusion) in the samples exposed to free radicals decreased to about one-third of controls; concomitantly, major losses in total cellular phospholipids occurred. When the cells were pretreated with 200 microM propranolol before the addition of free radicals, both peroxide formation and increased LDH release were inhibited; in agreement, complete ultrastructural preservation was observed. In addition, the subsequent losses in cellular viability and phospholipids were prevented. For comparison, the more water soluble beta-blocker, atenolol at 200 microM was shown ineffective in providing significant protection against the induced injury. The results suggest that propranolol may provide antiperoxidative protection to myocytes when elevated levels of free radicals are present.

Animals↗
PubMed1989

The premature aging hypothesis: old before its time?

This study tested the hypothesis that alcoholism results in premature aging of memory functioning. It was proposed that support for the premature aging hypothesis must come from qualitative as well as quantitative similarities between younger alcoholics and older controls. The California Verbal Learning Test (CVLT) was administered to young and old alcoholics and to young and old controls. The CVLT provides measures of recall, recognition, learning strategies, and error types. Alcoholism and aging produced similar levels of immediate and delayed free recall. However, poor recognition memory and more frequent intrusion and false positive errors were associated with alcoholism but not with aging. Qualitative differences in error types between alcoholism and aging were also found. Results indicated that alcoholism and aging produce independent verbal learning decrements.

Adult↗
PubMed1989

Effects of chronic alcoholism on perception of hierarchical visual stimuli.

Visuospatial processing in chronic alcoholism was investigated by asking subjects to make similarity judgements of hierarchically constructed visual stimuli. Comparison figures were similar to a standard figure at the global or local level. Alcoholics were less influenced by the global patterns in their similarity judgements than were controls. On the WAIS-R Block Design subtest, alcoholics were also more likely than controls to distort the outer configuration of the design. Results indicate that alcoholism affects global processing on both experimental visuoperception tasks and on clinical measures of visuospatial ability. Implications for models of alcoholic dysfunction are discussed.

Adult↗
PubMed1989

Clinical-physiologic correlates of Alzheimer's disease and frontal lobe dementia.

Thirty patients with degenerative dementia underwent clinical evaluation, neuropsychological testing, and single photon emission computed tomography (SPECT) with the blood flow tracer [123I]-N-isopropyl-p-iodoamphetamine. Five of these patients were clinically and psychologically different from the others, demonstrating predominant behavioral disturbances with relative preservation of memory function. These five patients, who were felt to have a frontal lobe dementia (FLD), showed SPECT perfusion patterns which differed from the remaining 25 patients, who were diagnosed as having Alzheimer's disease (AD), and from 16 healthy control subjects. The FLD patients showed diminished perfusion in orbitofrontal, dorsolateral frontal, and temporal cortex relative to controls, while the AD patients showed lower perfusion in temporal and parietal cortex than controls. The FLD patients also showed hypoperfusion in both frontal cortical regions relative to AD patients. The pattern of performance on neuropsychological testing paralleled these differences in regional perfusion. These results suggest that clinical evaluation and physiological imaging may enable the differentiation of groups of degenerative dementia patients during life.

Aged↗
PubMed1988

Absence of white matter changes on magnetic resonance imaging in children treated with CNS prophylaxis therapy for leukemia.

Previous studies have shown that magnetic resonance imaging (MRI) is sensitive to white matter changes in children receiving cranial radiation of 3000 cGy or greater. The current study used MRI to investigate the integrity of white matter in children receiving 1800 to 2400 cGy of cranial radiation. Ten survivors of acute lymphoblastic leukemia (ALL) who received intrathecal methotrexate (MTX) and either 1800 or 2400 cGy of cranial radiation were studied with MRI and neuropsychologic testing. Magnetic resonance (MR) scans were normal in nine of ten patients. One patient had prominent and asymmetrical lateral ventricles and mildly enlarged cortical sulci. White matter tracts were normal in appearance. However, seven of nine children had below average intellectual functioning. Results indicate that children receiving less than 2500 cGy of cranial radiation fail to show white matter changes on MRI, despite evidence of cognitive impairment.

Brain↗
PubMed1988

Visuospatial functioning before and after commissurotomy. Disconnection in hierarchical processing.

A patient who underwent complete cerebral commissurotomy was tested before and after surgery on tasks involving drawing and recognition memory for visual hierarchical stimuli. These stimuli consisted of a large, higher-level form constructed from smaller, lower-level forms. Postoperatively, the patient was more accurate in drawing and recognizing higher-level forms relative to lower-level forms when responding with his left hand and primarily right hemisphere, whereas he showed the opposite pattern when responding with his right hand and primarily left hemisphere. Implications of these findings for theories of the cerebral organization of visuospatial processing are discussed.

Adult↗