Heterogeneity of cerebral vasoreactivity in preterm infants supported by mechanical ventilation

The reaction of cerebral blood flow to acute changes in arterial carbon dioxide pressure (PaCO2) and mean arterial blood pressure was determined in 57 preterm infants supported by mechanical ventilation (mean gestational age 30.1 weeks) during the first 48 hours of life. All infants had normal brain sonograms at the time of the investigation. In each infant, global cerebral blood flow was determined by xenon-133 clearance two to five times within a few hours at different levels of PaCO2. Changes in PaCO2 followed adjustments of the ventilator settings. Arterial oxygen pressure was intended to be kept constant, and mean arterial blood pressure fluctuated spontaneously between measurements. The data were analyzed by stepwise multiple regression, with changes in global cerebral blood flow, PaCO2, mean arterial blood pressure, and postnatal age or intracranial hemorrhage used as variables. In infants with persistently normal brain sonograms, the global cerebral blood flow-carbon dioxide reactivity was markedly lower during the first day of life (mean 11.2% to 11.8%/kPa PaCO2) compared with the second day of life (mean 32.6/kPa PaCO2), and pressure-flow autoregulation was preserved. Similarly, global cerebral blood flow-carbon dioxide reactivity and pressure-flow autoregulation were present in infants in whom mild intracranial hemorrhage developed after the study. In contrast, global cerebral blood flow reactivity to changes in PaCO2 and mean arterial blood pressure was absent in infants in whom ultrasonographic signs of severe intracranial hemorrhage subsequently developed. These infants also had about 20% lower global cerebral blood flow before hemorrhage, in comparison with infants whose sonograms were normal, a finding that suggests functional disturbances of cerebral blood flow regulation. Several perinatal factors were tested, but only birth after abruptio placentae was related to subsequent periventricular hemorrhage (p = 0.037).     

Levodopa improves physical fatigue in Parkinson's disease: a double-blind, placebo-controlled, crossover study.

We quantitatively investigated the effect of carbidopa/levodopa (25/100) on physical fatigue during finger tapping and force generation in a double-blind, placebo-controlled crossover study. Parkinson's disease (PD) subjects were randomly assigned to carbidopa/levodopa or placebo for Visit 1 or 2 and participated in the following two studies: (1) Finger tapping. Twenty-five PD patients used their index fingers to strike two keys 20 cm apart on a musical instrument digital interface (MIDI) keyboard. The slopes of the regression line of dwell time and movement time were used to assess the rate of fatigue development. (2) Force generation. Twelve PD patients contracted the wrist extensors maximally to obtain a baseline maximum voluntary contraction (BMVC) force. Then they repetitively contracted the wrist extensors at 50% of the BMVC for 7 seconds and rested for 3 seconds. An interval maximum voluntary contraction (IMVC) was measured every three repetitions. Fatigue was defined as an IMVC of less than 60% of the BMVC. The slope of the regression line of IMVC was used to assess the rate of force decline. These two studies were repeated 1 hour after carbidopa/levodopa (25/100) or placebo. Subjects filled out the Multidimensional Fatigue Inventory (MFI) at the beginning of the first visit. Results showed that the slope of dwell time decreased with levodopa but not with placebo (P = 0.004). The rate of force decline also decreased with levodopa but not with placebo (P = 0.01). The subscores in the dimension of physical fatigue in the MFI did not correlate with the rate changes in dwell time or the rate changes in force decline. We concluded that (1) levodopa improves physical fatigue in finger tapping and force generation, (2) physical fatigue in Parkinson's disease is at least partially related to dopamine deficiency, and (3) the MFI measures different aspects of physical fatigue compared with those measured by finger tapping and force generation.     

Systematic and random errors in compression testing of trabecular bone

We sought to quantify the systematic and random errors associated with-artifacts in the platens compression test for trabecular bone. Our hypothesis was that while errors may depend on anatomic site, they do not depend on apparent density and therefore have substantial random components. Trabecular bone specimens were first tested nondestructively using newly developed accurate protocols and then were tested again using the platens compression test. Percentage differences in modulus between the techniques (bovine) proximal tibia [n = 18] and humerus [n = 17] and human lumbar spine, [n = 9] were in the range of 4-86%. These differences did not depend on anatomic site (p = 0.21) and were only weakly dependent on apparent density and specimen aspect ratio (r² < 0.10). The mean percentage difference in modulus was 32.6% representing the systematic component of the end-artifact error. Neglecting the minor variations explained by density and specimen size (approximately 10%), an upper bound on the random error from end-artifacts in this experiment was taken as the SD of the modulus difference (±18.2%). Based on a synthesis of data taken from this study and from the literature, we concluded that the systematic underestimation error in the platens compression test can be only approximated and is in the range of 20-40%; the substantial random error (±12.5%) confounds correction, particularly when the sample size is small. These errors should be considered when interpreting results from the platens test, and more accurate testing techniques should be used when such errors are not acceptable.     

原发性阴道癌的放射治疗

原发性阴道癌的治疗方法有单纯放射治疗、手术或手术加放疗、放疗加化疗综合治疗等。治疗方法的选择主要取决于病变部位，病灶大小、期别、各单位医疗条件、医生的经验。原位癌可局部切除或单纯腔内放疗，Ⅰ期和少数Ⅱ期早期可行手术治疗或单纯放疗，Ⅱ期至Ⅳ期行单纯放射治疗或同时性进行放射治疗和化疗。     

Activation of guinea pig eosinophil respiratory burst by leukotriene B4: role of protein kinase C

Leukotriene B4 (LTB4) and the protein kinase C activator, 4-beta-phorbol dibutyrate (PDBu), both induced a pronounced and concentration-dependent stimulation of hydrogen peroxide (H2O2) generation by purified guinea pig peritoneal eosinophils in the concentration range 1 nM-1 microM. The LTB4 response was inhibited competitively by the specific LTB4 receptor antagonist, U-75302, with a KB of 25 nM, while the concentration-response curves for both stimuli were shifted rightwards (3.8-fold and 2.8-fold for LTB4 and PDBu, respectively) by the competitive protein kinase C inhibitor, 1-O-hexadecyl-2-O-methylglycerol at a concentration of 300 microM. LTB4 appears, therefore, to induce respiratory burst in eosinophils via a receptor-mediated mechanism involving protein kinase C.     

Distinct autophosphorylation sites sequentially produce autonomy and inhibition of the multifunctional Ca2+/calmodulin-dependent protein kinase

The multifunctional Ca2+/calmodulin-dependent protein kinase (multifunctional CaM kinase) may be an important mediator for neurotransmitters and hormones that utilize Ca2+ as a "second messenger." We examined the ability of autophosphorylation to convert the multifunctional CaM kinase to a Ca2+/calmodulin-independent (autonomous) form to determine whether autophosphorylation is a mechanism for short- or long-term enhancement of Ca2+ action. As the kinase incorporates phosphate during continuous stimulation by Ca2+/calmodulin, its ability to phosphorylate exogenous substrates becomes increasingly autonomous. Withdrawal of Ca2+ after a critical level of phosphate incorporation is reached leads to a "burst" or rapid increase in Ca2+-independent autophosphorylation. The "burst" of autophosphorylation is distinct from the initial Ca2+-dependent autophosphorylation, however, since it inhibits substrate phosphorylation. Both Ca2+-dependent and Ca2+-independent substrate phosphorylation are inhibited by this autonomous autophosphorylation. Thus, autophosphorylation has a dual role in modulating the activity of multifunctional CaM kinase. It initially enables the kinase to continue phosphorylating substrates after Ca2+ levels decline, but it eventually suppresses this autonomous activity. Tryptic phosphopeptide mapping demonstrates that appearance of phosphothreonine-containing peptides is common to several conditions used to generate an autonomous enzyme. Sequencing reveals the critical "autonomy" site to be threonine286. The inhibitory mode of autophosphorylation involves 3 additional phosphopeptides containing a serine and a threonine residue.