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Biomedical subjects

D W Johnson

Publications and source records attributed to D W Johnson.

At least 163 records · Page 9Linked to original sources

Effects of U74006F on multifocal cerebral blood flow and metabolism after cardiac arrest in dogs.

Lipid peroxidation reactions during reperfusion after cardiac arrest may contribute to postischemic cerebral hypoperfusion, which in turn can contribute to permanent neurological dysfunction. We designed this study to determine whether the aminosteroid U74006F, a putative inhibitor of lipid peroxidation, mitigates cerebral multifocal hypoperfusion after cardiac arrest. We used our established dog model of ventricular fibrillation cardiac arrest (no blood flow) of 12.5 minutes, reperfusion by cardiopulmonary bypass of less than or equal to 5 minutes, and control of extracerebral variables during 4 hours postarrest. Cerebral blood flow was monitored by the stable xenon computed tomography method. Changes in cerebral oxygen consumption were obtained from mean blood flow values of coronal slices and the cerebral arteriovenous (sagittal sinus) oxygen content difference. A treatment group (n = 5) received U74006F starting with reperfusion (1.5 mg/kg i.a. plus 1.5 mg/kg i.v.) and three additional (graded) doses over 4 hours (total dose 4.5, 7.5, or 14.5 mg/kg). The U74006F-treated group showed the same postarrest transient hyperemia and protracted hypoperfusion in terms of global (computed tomography slice), regional, and local (multifocal) cerebral blood flow values and the same global cerebral oxygen consumption pattern as a concurrent control group (n = 5). At 1-4 hours postarrest, in both groups there was mismatching of global cerebral oxygen consumption, which reached baseline values, in relation to global cerebral blood flow and oxygen delivery, which remained at 50% of baseline. We conclude that treatment with U74006F after prolonged cardiac arrest causes no deleterious side effects and does not seem to alter multifocal postarrest cerebral blood flow and oxygen consumption.

Animals↗

Exogenous opioids increase plasma prolactin in Holstein calves primarily via a dopaminergic mechanism.

A study was conducted to determine whether exogenous opioids increase prolactin (PRL) secretion in Holstein heifer calves via a dopaminergic mechanism. Twenty-four Holstein heifer calves ranging in age from 5 to 7 mo were assigned to one of four treatment groups (six/treatment): 1) injection of saline (SAL); 2) injection of a synthetic enkephalin (D-Ala2, N-Me-Phe4, Met(O)5-ol enkephalin; DAMME); 3) injection of DAMME after pretreatment with the long-acting dopamine agonist 2-bromo-alpha-ergocryptine; or 4) injection of thyrotropin-releasing hormone (TRH) after pretreatment with 2-bromo-alpha-ergocryptine. Calves were equipped with indwelling jugular cannulas on d 1, and baseline plasma PRL concentrations were established. Animals receiving 2-bromo-alpha-ergocryptine were injected s.c. 3 h after the last baseline sample was drawn on d 1. On d 2, calves assigned to receive SAL, DAMME, or TRH were injected 2 h after the start of sampling, and sampling was continued for an additional 4.5 h. Basal plasma PRL was lower (P less than .01) on d 2 in calves injected with 2-bromo-alpha-ergocryptine than baseline levels on d 1. Plasma PRL was higher (P less than .01) in calves not pretreated with 2-bromo-alpha-ergocryptine after DAMME injection on d 2 but was not different after DAMME injection in calves pretreated with 2-bromo-alpha-ergocryptine. In contrast, plasma PRL increased (P less than .01) after TRH injection on d 2 in calves pretreated with 2-bromo-alpha-ergocryptine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Non-small cell lung cancer: treatment results at a USAF referral center.

The treatment results of 197 consecutive patients with non-small cell carcinoma of the lung managed at David Grant USAF Medical Center between January 1978 and September 1985 were reviewed. Patients were staged according to 1983 AJCC criteria as follows: 52 stage I, 28 stage II, and 117 stage III. Five-year survival and freedom from relapse (FFR) were 24% and 32%, respectively, for the entire population. Survival and FFR by stage were: stage I, 68% and 77% (5-year); stage II, 32% and 43% (5-year); and stage III, 10% and 10% (3-year), respectively.

Adult↗

Metabolism of hexacosatetraenoic acid (C26:4,n-6) in immature rat brain.

Rat brain was recently found to contain polyenoic very-long-chain fatty acids (VLCFA) belonging to the n-3 and n-6 series with four, five and six double bonds and even-carbon chain lengths from 24 to 38 [Robinson, Johnson & Poulos (1990) Biochem. J. 265, 763-767]. In the present paper, the metabolism in vivo of hexacosatetraenoic acid (C26:4,n-6) was studied in neonatal rat brain. Rats were injected intracerebrally with [1-14C]C26:4,n-6 and the labelled metabolites were examined after 4 h. Radioactivity was detected mainly in non-esterified fatty acids, with smaller amounts in other neutral lipids and phospholipids. Radiolabelled fatty acid products included C28-36 tetraenoic and C26-28 pentaenoic VLCFA formed by elongation and desaturation of the substrate, and C14-24 saturated, C16-24 monoenoic, C18-24 dienoic, C18-22 trienoic and C20-24 tetraenoic fatty acids formed from released [1-14C]acetate either by synthesis de novo or by elongation of endogenous fatty acids. The data suggest that polyenoic VLCFA are synthesized in brain from shorter-chain precursor fatty acids and undergo beta-oxidation.

Animals↗

Unique molecular species of phosphatidylcholine containing very-long-chain (C24-C38) polyenoic fatty acids in rat brain.

Rat brain has been shown to contain polyenoic very-long-chain fatty acids (VLCFA) belonging to the n-3 and n-6 series with four, five and six double bonds and even-carbon chain lengths from 24 to 38. These fatty acids are almost exclusively located in unusual molecular species of phosphatidylcholine at the sn-1 position of the glycerol backbone, whereas saturated, monoenoic and polyenoic fatty acids with less than 24 carbon atoms are present at the sn-2 position. Polyenoic VLCFA phosphatidylcholine in neonatal rat brain is enriched with n-6 pentaenoic and n-3 hexaenoic VLCFA with up to 36 carbon atoms, whereas the corresponding phospholipid in adult rat brain mainly contains n-6 tetraenoic and n-3 pentaenoic VLCFA with up to 38 carbon atoms. The total amount of polyenoic VLCFA associated with phosphatidylcholine is highest in the brain of immature animals. Polyenoic VLCFA phosphatidylcholine appears to be predominantly confined to nervous tissue in rats, and it is envisaged that this phospholipid is of physiological significance.

Animals↗

Use of acetazolamide-challenge xenon CT in the assessment of cerebral blood flow dynamics in patients with arteriovenous malformations.

Arteriovenous malformations (AVMs) may cause symptoms related to a reduction of cerebral blood flow (CBF) to surrounding brain parenchyma. To evaluate this compromise of hemodynamic reserve (commonly referred to as steal phenomenon), we used acetazolamide challenge and stable-xenon CT (Xe/CT). Baseline Xe/CT studies in 13 patients with AVMs were followed by an acetazolamide challenge to the vascular reserve. Blood flow maps were quantitated by using region-of-interest (ROI) software. ROI findings were categorized into four groups on the basis of the presence or absence of normal baseline CBF and presence or absence of normal augmentation of CBF. ROIs were designated as near site (within the vascular territory supplying the AVM) or far site (outside the vascular territory supplying the AVM). One patient had a normal baseline and normal augmentation of CBF (group 1). The other patients had a combination of one or more of the other three categories. Ten patients had parenchymal areas that exhibited either a normal or low baseline CBF with decreased augmentation; both conditions were interpreted as decreased vascular reserve (groups 2 and 3). Eleven patients had parenchymal areas that showed a low baseline CBF and normal augmentation with acetazolamide (group 4), interpreted as having a decreased demand for CBF but having a normal vascular reserve. Decreased vascular reserve was found in 27% of the nearsite areas and 17% of the far-site areas. No patients had only far-site abnormal vascular reserve. We believe that compromised vascular reserve can best be evaluated with a challenge study, such as this acetazolamide-challenge Xe/CT study.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗

The evaluation of selenium status of sheep from the major production areas of Morocco.

In order to evaluate the selenium status of sheep in the major raising areas of Morocco, blood selenium concentration, erythrocyte glutathione peroxidase activity and feed selenium levels were determined. A total of 843 blood samples from sheep and 118 feed samples were analyzed. Results showed that 73% of sheep sampled had blood selenium concentrations below 100 ng/ml, and were deficient or marginal. Erythrocyte glutathione peroxidase activity was below 19 IU/g hemoglobin and feed selenium levels below 0.1 mg/kg on a dry matter basis. The erythrocyte glutathione peroxidase activity was highly correlated with blood selenium concentration over a wide range of selenium levels (r = 0.88, P less than 0.001, N = 622), indicating that the enzyme can be used as an indicator of the selenium status of grazing sheep.

Animal Feed↗

Evaluation of biochemical evidence of congenital nutritional myopathy in two-week prepartum fetuses from selenium-deficient ewes.

Muscle damage attributable to selenium (Se)/vitamin E deficiencies is known to develop at birth or later in lambs. The purpose of this study was to determine whether and when muscle damage develops in utero. Thirty pregnant ewes maintained on Se-deficient forages from birth were allotted to 3 equal groups. Half of each group was given a single IM injection of 0.056 mg of Se/kg of body weight, 1 month before parturition. At 3 weeks before parturition, cesarean section-derived fetuses from Se-deficient ewes did not have evidence of muscle damage. At 2 weeks before parturition, fetuses from Se-deficient ewes had biochemical evidence of congenital nutritional myopathy, as evidenced by low blood Se concentration (P less than 0.05) and by increased plasma creatinine kinase (P less than 0.001) and lactate dehydrogenase (P less than 0.01) activities, compared with fetuses from Se-treated ewes. Thus, for optimal protection of fetuses and newborn lambs in Se-deficient areas, Se should be administered to ewes at least 1 month before parturition.

Animals↗

Incidental white matter hyperintensities on magnetic resonance imaging in HIV-1 infection. Multicenter AIDS Cohort Study.

Magnetic resonance (MR) scans were performed as part of a prospective neuropsychological study within the Multicenter AIDS Cohort Study. Fifty HIV-1-seronegative men, 85 HIV-1-seropositive men without constitutional symptoms, and 14 with symptomatic HIV disease underwent MR imaging using a uniform protocol. Scans were rated by neuroradiologists blinded to all clinical details except age. The majority of MR scans were normal in all of the clinical groups and no covert mass lesions or diffuse white matter abnormalities were identified. Focal hyperintensities in the white matter were observed in 24% of the HIV-1 seronegatives, 26% of HIV-1 asymptomatic seropositives (CDC II/III), and 17% of those with ARC/AIDS. No significant associations were noted between the white matter hyperintensities and HIV-1 serostatus, neurological abnormalities, CD4 count, alcohol or drug use, hypertension, or smoking. In one individual classified with early HIV-1 dementia, MR demonstrated several hyperintensities in the deep parietal white matter, but at autopsy no microscopic abnormalities corresponding to the MR findings were identified. Our studies imply that focal white matter hyperintensities identified on MR are not specific for HIV-1 infection and are probably incidental and of no clinical significance.

AIDS-Related Complex↗

Metabolism of saturated and polyunsaturated fatty acids by normal and Zellweger syndrome skin fibroblasts.

The metabolism of 1-11C-labelled derivatives of palmitic (C16:0), arachidonic (C20:4,n-6) lignoceric (C21:0) and tetracosatetraenoic (C24:4,n-6) acids was studied in normal skin fibroblast cultures and in cultures of fibroblasts from peroxisome-deficient (Zellweger's syndrome) patients. Radiolabelled products of the fatty acids included carbon dioxide. C14-24 saturated and mono-unsaturated fatty acids formed from released acetate either by synthesis de novo or by elongation of endogenous fatty acids, fatty acids formed by 2-6-carbon elongation of added substrates, and a number of water-soluble compounds, some of which were tentatively identified as the amino acids glutamine, glutamic acid and asparagine. The labelled amino acids were found predominantly in the culture medium. Zellweger's syndrome fibroblasts showed a marked decrease in radiolabelled carbon dioxide and water-soluble-product formation from (I-14C)-labelled arachidonic, tetracosatetraenoic and lignoceric acids but not from [I-14C]palmitic acid, and the production of radiolabelled C14-18 fatty acids was also diminished. However, the elongation of individual fatty acids was either normal or above normal. Our data support the view that the oxidation of 20:4, 24:4 and 24:0 fatty acids in cultured skin fibroblasts takes place largely in peroxisomes, and further that the acetyl-CoA released by the beta-oxidation process is available for the synthesis of fatty acids and amino acids. We speculate that the generation of C2 units used for synthesis is a major peroxisomal function and that this function is absent or greatly impaired in Zellweger's syndrome cells.

Carbon Dioxide↗

Low dose combined chemotherapy/radiotherapy in the management of locally advanced urethral squamous cell carcinoma.

The successful treatment of a patient with bulky squamous cell carcinoma of the urethra using low dose preoperative radiation therapy and concurrent chemotherapy is described. Dramatic rapid tumor response facilitated surgical resection of the remaining microscopic disease. This clinical behavior is remarkably similar to that seen with squamous cell carcinoma of the anal canal and esophagus when a similar regimen is used. At the latter tumor sites the successful use of combination radiotherapy and chemotherapy has reduced the morbidity of subsequent surgery, and in selected cases has obviated the need for a radical operation. Further investigation of such combination treatment is warranted for urethral carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Serial noninvasive studies do not herald postoperative failure of femoropopliteal or femorotibial bypass grafts.

We performed a 5-year retrospective case-control study of 232 patients undergoing femoropopliteal (n = 188) or femorotibial (n = 44) bypass to determine if serial noninvasive studies herald postoperative graft failure. We correlated serial ankle/arm pressure indices (API) with graft patency. An interval drop in API of greater than or equal to 0.20 was considered hemodynamically significant, but interventional therapy was carried out only for clinically symptomatic graft failure and an API less than 0.20 above the preoperative value. The cumulative 5-year limb salvage rate was 82% and the patient survival was 63%. A significant drop in API did not correlate with cumulative 5-year graft patency. The 5-year cumulative primary graft patency rates were 60% and 62% in patients with stable and interval drops in API, respectively (Z = 0.15, p = N.S.) These results suggest that a significant drop in postoperative API does not predict patients with impending femoropopliteal or femorotibial graft failure. We believe that routine noninvasive surveillance and prophylactic intervention on detected asymptomatic lesions in leg bypass grafts may not be justified.

Adult↗

Collaborative skill instruction for promoting positive interactions between mentally handicapped and nonhandicapped children.

Structuring cooperative learning activities has been shown to be an effective technique for integrating handicapped and nonhandicapped students. Previous research in this area has focused on the relative effects of cooperative versus competitive and individualistic learning situations upon peer relations and academic achievement. Few investigations have examined the various elements within the cooperative learning model that appear to promote positive peer interactions among handicapped and nonhandicapped students. The present study evaluated the influence of collaborative skill instruction versus no collaborative skill instruction on the social interaction behaviors of moderately/severely handicapped and nonhandicapped students participating in group science activities. These data reveal that students receiving collaborative skill instruction interacted more positively with one another than those who did not receive the instruction.

Adolescent↗

Determination of irreversible ischemia by xenon-enhanced computed tomographic monitoring of cerebral blood flow in patients with symptomatic vasospasm.

In patients with subarachnoid hemorrhage, delayed neurological deficits, often followed by infarction, are believed to result from ischemia caused by vasospasm. Cerebral blood flow (CBF) data have been useful in predicting the risk of vasospasm in these patients and in distinguishing those deficits caused by vasospasm. Although CBF thresholds for infarction have been established in animals, few clinical studies have correlated CBF values with neurological symptoms and infarction. To assess the sensitivity to ischemia provided by xenon-enhanced computed tomography (Xe/CT) of CBF and to define the clinical significance of specific values that it measures, we compared the clinical, CT, and Xe/CT findings on CBF in 51 patients with subarachnoid hemorrhage caused by ruptured aneurysms. Each patient had 1 to 6 Xe/CT studies. Fourteen patients had symptomatic vasospasm. In all 14, the first post deficit Xe/CT study found abruptly reduced CBF, either regionally or globally. In 9 of these 14 patients, flow values fell below 15 ml/100 g/min in 2 or more adjacent 2-cm cortical regions of interest, and in all 9, concurrent follow-up CT scans showed infarction in these regions. Eight of the 9 had paralysis and a severe sensory deficit. No patient whose CBF remained above 18 ml/100 g/min developed infarction. The blood flow studies caused neither significant complications nor neurological deterioration. The Xe/CT CBF method appears very sensitive to the early detection of symptomatic vasospasm. In most patients with subarachnoid hemorrhage, this noninvasive technique can replace angiography to delineate the location and severity of vasospasm, and may be useful in predicting the development of infarction.

Blood Flow Velocity↗

MR imaging of the pars interarticularis.

MR imaging of the lumbar spine has become a useful method for the noninvasive evaluation of low back pain. However, bone abnormalities are more difficult to detect than soft-tissue lesions, such as herniated disk. We reviewed 14 MR images of the lumbar spine in adults with spondylolisthesis. These were correlated with CT scans and plain films in all cases. From the CT scans and plain films we found that seven patients had spondylolysis and that seven had other causes for their spondylolisthesis. It was our opinion that the MR images suggested an abnormality of the pars interarticularis in all seven of the cases confirmed to have spondylolysis and in six of the seven patients that did not have spondylolysis. We also studied four cadaver lumbar spine, obtained as blocks of tissue, and scanned in the coronal, sagittal, and axial planes with MR and in the sagittal and axial planes with CT. The tissue blocks were then sectioned in the sagittal plane. Spondylolysis is suggested on sagittal MR images when there is an inability to resolve the marrow signal in the pars as uninterrupted from the superior to the inferior facet. This is caused by a dark signal on all pulsing sequences in the pars resulting from marginal sclerosis at the site of the break. If there is also a gap at the site of the break then there will also be an increased signal in the gap resulting from the presence of soft tissue. We found four situations in which the pars can simulate spondylolysis on sagittal MR images: (1) sclerosis of the neck of the pars: (2) partial volume imaging of the degenerative spur of the superior facet slightly lateral to the pars; (3) partial facetectomy; and (4) osteoblastic metastatic replacement of the marrow of the pars.

Adult↗

The acetazolamide challenge: imaging techniques designed to evaluate cerebral blood flow reserve.

Cerebral blood flow was analyzed by the stable xenon (Xe)/CT scanning technique in 29 patients with significant vascular lesions before and after administration of an acetazolamide (Diamox) vasodilatory challenge. Three response types were identified: I, normal flow before Diamox with flow augmentation after Diamox; II, low flow before Diamox with flow augmentation after Diamox; and III, low or normal flow before Diamox with no augmentation or decreased flow after Diamox. Twenty-four percent of the patients studied qualified for category III. We believe that patients in this category represent a group of individuals without blood flow reserve whose clinical management should include careful consideration of their hemodynamic status. The Xe/CT scanning technique with the addition of Diamox flow challenge is a clinically accessible and effective method for assessing cerebral blood flow and blood flow reserve.

Acetazolamide↗

Efficacy of oral cyclosporine given prior to liver transplantation.

The bioavailability of oral cyclosporine (CYS) dissolved in a large quantity of milk given just before liver transplantation (LTX) was evaluated in 30 patients, given randomly timed oral CYS before LTX, by measurements of CYS blood levels at induction, 2 h later, and at the time of graft reperfusion. Adequate blood CYS levels, defined as greater than or equal to 500 ng/mL (FPIA), could reliably be achieved only when the drug was administered 4 to 7 h preoperatively. Patients receiving the drug less than 4 h preoperatively generally had low levels thereafter (two of seven patients had greater than or equal to 500 ng/mL in any sample, compared with 13 of 14 patients in the 4-7-h group, P less than 0.011); an interval of greater than 7 h yielded unpredictable results. Fluids and blood products transfused, and preoperative ascites or ICU care, were not related to blood CYS levels. Oral CYS should be given 4 to 7 h before LTX to achieve adequate levels.

Anesthesia↗