The prevention and treatment of cerebral ischemia

Canadian Journal of Anesthesia/Journal canadien d'anesthésie - Although the major focus of recent cerebral protection research has been aimed at developing receptorspecific drugs, this...     

Myocardial tagging in polar coordinates with use of striped tags

Regional deformation abnormalities in the heart wall provide a good indicator of ischemia. Myocardial tagging with magnetic resonance imaging is a new method of assessing heart wall motion during contraction. Current methods of myocardial tagging either do not provide two-dimensional information or lack a coordinate system well adapted to the morphology of the heart. In this article, the authors describe a new tagging method that provides a true polar coordinate system, with both radial and angular dimensions. This is accomplished with use of a section-selective version of spatially modulated magnetization resulting in striped tags (STAGs). These STAG planes are placed in the myocardium in a star pattern so that they intersect on the long axis of the heart and stripes appear through the width of the heart wall. In the short-axis view during contraction, rotation around the long axis yields angular information such as shear and twist, while separation of the stripes within the myocardium permits measurement of radial thickening. Therefore, this method provides a coordinate system for calculating two-dimensional strain that is adapted to the morphology of the left ventricle.     

The effects of dizocilpine maleate (MK-801), an antagonist of the N-methyl-D-aspartate receptor, on neurologic recovery and histopathology following complete cerebral ischemia in primates

The present study was designed to determine if the noncompetitive excitatory amino acid antagonist, dizocilpine maleate, when administered after a 17 min period of complete cerebral ischemia in primates, would improve postischemic neurologic function and hippocampal histopathologic outcome when compared to placebo-treated animals. Ten pigtail monkeys were anesthetized and subjected to complete cerebral ischemia using an established neck tourniquet model. Five minutes postischemia, five monkeys received dizocilpine 300 micrograms/kg i.v. over 5 min, followed by an infusion of 150 micrograms/kg/h for 10 h. This produced plasma levels of the drug in excess of 30 ng/ml for the duration of the infusion. An additional five monkeys were treated with an identical volume of saline placebo. All monkeys received intensive care for the initial 24 to 48 h postischemia. At 96 h postischemia, there was no significant difference in neurologic function between the two groups (p = 0.53, with the placebo group having the numerically better outcome). There also was no significant difference between hippocampal histopathology scores between dizocilpine and placebo-treated monkeys. The authors conclude that dizocilpine is not an efficacious therapy in the treatment of neurologic injury that occurs following complete cerebral ischemia in this primate model.     

The effects of transient hyperglycemia on brain glucose in rats anesthetized with halothane

The effects of transient hyperglycemia on brain glucose and the relationship between blood and brain glucose were studied in 76 Sprague-Dawley rats anesthetized with halothane 1% inspired. In a common control group, blood and brain glucose were determined prior to any intervention (n = 10). A second group of 30 rats was given an iv infusion of 3.9 ml of saline over a 30-min period, and blood and brain glucose were subsequently determined at several time points: 30 min (immediately after the saline infusion), 45, 60, 90, or 120 min (n = 6 for each time point). A third group of 36 rats was administered 3 g/kg of glucose in 3.9 ml of iv saline over a similar 30-min period, and blood and brain glucose were measured at the same time periods as in saline-treated rats and also when half of the glucose infusion was given (time = 15 min; n = 6 for each time point). In the common control group, blood glucose was 114 +/- 14 mg/dl (6.4 +/- 0.8 mumol/ml; mean +/- SD) and brain glucose was 2.41 +/- 0.59 mumol/g. Saline infusion had no effect on brain or blood glucose. In contrast, glucose infusion in the study group produced significant increases in both blood and brain glucose, achieving maximal values of 488 +/- 60 mg/dl (27.4 +/- 3.4 mumol/ml) and 7.62 +/- 0.52 mumol/g, respectively, at the 30-min measurement period. The ratio of brain to blood glucose, normalized so that the common control group data achieved a value of 1, was less than unity during the period of glucose infusion. This ratio reached a nadir of 0.75 +/- 0.07 at the 30-min measurement period (P less than 0.05 versus saline infusion). Thereafter, with the cessation of glucose infusion, the ratio returned to 1 and eventually exceeded unity: the peak ratios were 1.23 +/- 0.13 and 1.16 +/- 0.21 at the 60- and 90-min period, respectively (P less than 0.05 versus saline treatment). The authors concluded that during periods of rapidly fluctuating blood glucose, there is a hysteresis between blood and brain glucose values; hence, it may not be possible to accurately estimate brain glucose by measuring blood glucose.     

Presence of residual basal cell carcinoma in re-excised specimens is more probable when deep and lateral margins were positive

In order to quantify presence of residual BCC in patients with histologic positive margins after the first excison and to correlate the presence of residual tumor in re‐excised lesions with the location of the positive margin on the first excision, a retrospective evaluation of 2053 surgically treated BCC was performed. Only 38.3% of the re‐excised lesions showed residual tumor. In the group of re‐excised lesions where residual BCC was found, 13% had lateral positive margin in the first excision, 39% had deep positive margin and 48% had both lateral and deep positive margins. In the group of re‐excised lesions where no residual BCC was found, 49% of the primary excised lesions had lateral positive margin, 32% had deep positive margin and 19% had both deep and lateral positive margins. The association between residual tumor and positive margins was statistically significant (p = 0.01). Our findings confirm that presence of residual tumour is more likely when both lateral and deep margins are compromised.     

In vivo and in vitro activation of natural killer cells in advanced cancer patients undergoing combined recombinant interleukin-2 and LAK cell therapy

Patients with advanced metastatic cancer were given combined autologous lymphokine activated killer (LAK) cell and recombinant interleukin-2 (rIL-2) therapy on a National Cancer Institute extramural phase II trial. Systemic administration of rIL-2 resulted in pronounced lymphocytopenia. Within two days after completion of in vivo rIL-2 therapy, there was a dramatic increase in absolute numbers of circulating lymphocytes, and cytotoxic activity against tumor cell targets was mediated by peripheral blood lymphocytes, indicating in vivo generation of LAK activity. Patients were leukapheresed and cells cultured for three to four days in rIL-2. rIL-2 cultured cells from all patients demonstrated cytotoxic activity. In order to characterize the effector cell, T cells and natural killer (NK) cells were isolated to greater than 95% purity by flow cytometry. Cytotoxic activity was mediated by rIL-2--activated NK cells, whereas T cells demonstrated no substantial activity. The circulating in vivo cytotoxic effectors detected after in vivo rIL-2 therapy were also shown to be rIL-2--activated NK cells. Results from these studies demonstrate that all patients were capable of generating a cytotoxic response, and that the cytotoxic effector cells were rIL-2--activated NK cells, identified by the phenotype CD3--, Leu 19+.     

Effect of disease severity and pharmacotherapy of asthma on oral health in asthmatic children

Abstract – Oral health was studied in a group of asthmatic children (n = 61). The children were divided in two groups, 5–10 and 11–18 yr of age. The individuals with asthma were further sub grouped with respect to the disease severity. Severe asthma was defined as more than 10 asthmatic attacks per year. This patient group had daily medication compared to children with moderate asthma (<10 asthmatic attacks/yr) who medicated temporarily. 55 age matched children from the same area made up the control group. Ail children were examined clinically and two bitewing radiographs were taken. The results showed no statistically significant differences concerning caries prevalence and gingival condition in asthmatic children compared to a healthy control group. The study shows that neither the asthma per se nor the disease severity affected the caries prevalence and gingival condition in asthmatic children.     

NK cell function in a patient with IgM monoclonal antibody against myelin-associated glycoprotein

Anti-Leu 7 antibody reacts with determinants on a subset of natural killer (NK) cells and myelin-associated glycoprotein (MAG). In a patient patient with peripheral neuropathy and IgM autoantibodies against MAG, we found the distribution and functions of NK cells to be normal.     

Craniofacial growth in bone marrow transplant recipients treated with growth hormone after total body irradiation

Abstract— The effect of growth hormone (GH) treatment on craniofacial development was studied in five children exhibiting growth retardation following bone marrow transplantation. Linear and angular measurements were made on lateral radiographic cephalograms taken prior to the start of GH treatment and after an average treatment time of 1.2 yr. The results showed that the mean growth increments of mandibular length in the GH treated children, exceeded the corresponding values of the control group by 150% during the period of investigation. It is suggested that this dimensional increase in the patients was due to GH stimulation on the chondral growth process in the mandibular condyles.     

Influence of phenytoin on cytoplasmic free Ca2+ level in human gingival fibroblasts

Abstract— Influence of 5,5-diphenylhydantoin (phenytoin;PHT) on the cytoplasmic free Ca²⁺ concentration, [Ca²⁺]ⁱ, was studied in fura 2 loaded adherent monolayers of human gingival fibroblasts derived from three patients before and after 9 months of PHT therapy. In the patient where gingival overgrowth developed during PHT medication (responder), addition of PHT to gingival fibroblasts derived before PHT medication induced a transient extracellular Ca²⁺ dependent increase in [Ca²⁺]ⁱ. In a non-responder patient, where gingival overgrowth did not develop during the same period of PHT therapy, addition of PHT to gingival fibroblasts derived before the start of medication did not significantly affect [Ca²⁺]_i. Under extracellular Ca²⁺ deficient conditions, addition of PHT to serum-starved fibroblasts derived from the two categories of patients before the medication resulted in an increase in [Ca²⁺]_i. In fibroblasts derived from the responder patient during PHT medication, in contrast to those from the non-responders (n = 2), the basal level of [Ca²⁺]_i was significantly decreased. The results indicate that, in the cases studied, there is a relationship between PHT induced alterations in [Ca²⁺]_i in gingival fibroblasts and the clinical development of gingival overgrowth.