Transcutaneous oxygen and carbon dioxide tensions compared to arterial blood gases in normals

BACKGROUND: Most hyperbaric medicine centers do not monitor arterial oxygen (P(aO(2))) and carbon dioxide (P(aCO(2))) tensions during hyperbaric oxygen, but many can transcutaneously monitor oxygen (P(tcO(2))) and carbon dioxide (P(tcCO(2))). METHODS: We compared P(tcO(2)) and P(tcCO(2)) measurements to simultaneous P(aO(2)) and P(aCO(2)) measurements in 10 healthy volunteers to determine if P(tcO(2)) and P(tcCO(2)) measurements are surrogates for P(aO(2)) and P(aCO(2)) in the hyperbaric environment. We took blood samples via arterial catheter and took P(tcO(2)) and P(tcCO(2)) chest measurements while the subjects were compressed in a monoplace hyperbaric chamber at pressures between 0.85 atmospheres absolute (atm abs) (our local atmospheric pressure, at altitude 1,300 m) and 3.0 atm abs, while the subjects breathed air, then oxygen. RESULTS: The P(tcO(2)) correlated with P(aO(2)) (r(2) = 0.99). Under all the conditions, the P(tcO(2)) values were lower than P(aO(2)) values by approximately 10%. The P(tcCO(2)) was 2-6 mm Hg higher than the P(aCO(2)), but the correlation was low (r(2) = 0.21). CONCLUSIONS: The P(tcO(2)) in normal humans may be used to estimate the P(aO(2)). The P(tcCO(2)) may not be an adequate reflection of the P(aCO(2)). It is unknown if P(tcO(2)) and P(tcCO(2)) measurements in critically ill patients can replace P(aO(2)) and P(aCO(2)) measurements.     

阵发性睡眠性血红蛋白尿症患者外周血T淋巴细胞亚群及活化分子表达的研究

目的　探讨阵发性睡眠性血红蛋白尿症 (PNH)患者T淋巴细胞的功能及活化状态与PNH临床的关系。方法　应用流式细胞术及免疫磁珠分选术 ,测定了 18例PNH患者外周血单个核细胞 (PBMNC)及CD59+ 和CD59-PBMNC中CD3 + 、CD4+ 及CD8+ 细胞表型 ,并测定了新诊断的未经治疗的 6例PNH患者外周血中NK细胞及CD4+ CD2 8+ /CD4+ 、CD8+ CD2 8+ /CD8+ 、CD4+ HLR DR+ /CD4+ 、CD8+HLR DR+ /CD8+ 及CD8+ CD3 8+ /CD8+ 淋巴细胞表面分子表达比值。结果　PNH患者PBMNC中CD3 +CD8+ /CD3 + CD4+ 细胞比值增加 ,为 1.2 2± 0 .5 1,对照组为 0 .86± 0 .2 7,两者比较 ,差异有显著性 (P <0 .0 5 )。分选后PNH患者CD59-PBMNC中CD3 + CD8+ /CD3 + CD4+ 细胞比值增加 ,为 2 .31± 1.5 6 ,CD59+PBMNC为 0 .6 2± 0 .2 7,两者比较 ,差异有统计学意义 (P <0 .0 1)。CD3 + CD8+ /CD3 + CD4+ 细胞比值与骨髓衰竭 (BMF)的级差相关分析呈正相关。PNH患者CD4+ CD2 8+ /CD4+ 细胞比值明显减少 ,为 0 .5 2±0 .11(对照为 1.0 0± 0 .0 6 ) ,而CD8+ HLR DR+ /CD8+ 增加 ,为 0 .4 5± 0 .2 6 (对照为 0 .10± 0 .0 6 )。结论　PNH患者CD3 + CD8+ /CD3 + CD4+ 细胞比值增加 ,病变表型细胞更易发生在CD8+ 细胞群中。CD4+ 细胞中CD2 8+ 辅助刺激因     

Bone remodeling markers in the detection of bone metastases in prostate cancer

BACKGROUND: Early detection of bone metastases in prostatic carcinoma is very useful in treatment and prognosis of the disease. The aim of this work was to evaluate the sensitivity and specificity of a group of bone markers in order to discriminate between prostate carcinoma patients without (M(0)) and with (M(1)) bone metastases. METHODS: Sixty-seven non-treated patients with: benign prostate hyperplasia (n=21), prostatic carcinoma in several stages without bone metastases (T(X)M(0)) (n=31) and with bone metastases (T(X)M(1)) (n=15) were studied. The following markers were studied: (A) bone formation: (1) serum bone alkaline phosphatase, IRMA (Tandem Ostase, Beckman); (2) serum procollagen I amino-terminal propeptide (PINP), RIA (Orion Diagnostica); (B) bone resorption: (1) urinary collagen I amino-terminal telopeptide (NTX), ELISA (Ostex); (2) collagen I carboxy terminal telopeptide (CTX): (2A) urinary alpha-CTX, RIA (Osteometer), (2B) serum beta-CTX, Elecsys (Roche); (3) collagen I cross-linked carboxy terminal telopeptide (ICTP), RIA (Orion Diagnostica). RESULTS: Levels of all bone markers were significantly higher in group M(1) than in group M(0). A complete separation of groups M(0) and M(1) was achieved with PINP and beta-CTX (100% sensitivity and specificity). CONCLUSIONS: These results support the use of PINP or beta-CTX as a tool to confirm the presence or absence of bone metastases in the first staging of prostatic carcinoma patients.     

S18616, a highly potent, spiroimidazoline agonist at alpha(2)-adrenoceptors: I. Receptor profile, antinociceptive and hypothermic actions in comparison with dexmedetomidine and clonidine

S18616 ((S)-spiro[(1-oxa-2-amino-3-azacyclopent-2-ene)-4, 2'-(8'-chloro-1',2',3',4'-tetrahydronaphthalene)]) displayed high affinity at native rat alpha(2)-adrenoceptors (AR)s (pK(i), 9.8), native human (h)alpha(2A)-ARs (9.6), and cloned halpha(2A)- (9.5), halpha(2B)- (9.2), and halpha(2C)- (9.0) ARs. It showed 40-fold lower affinity for halpha(1A)-ARs (8.4) and >/=100-fold lower affinity for rat alpha(1)-ARs (7.1), halpha(1B)-ARs (7.7), halpha(1D)-ARs (7.6), imidazoline(1) (7.4), and imidazoline(2) (7.4) sites and >100-fold lower affinity for all other (>50) sites. At halpha(2A)-ARs, in guanosine-5'-O-(3-[(35)S]thio)triphosphate binding studies, S18616 was a potent (partial) agonist: log effective concentration (pEC(50)), 9.3/maximal effect, 51%. This observation was corroborated employing a halpha(2A)-Gi1alpha fusion protein/GTPase assay (9.0/40%) in which the actions of S18616 were blocked by pertussis toxin. Employing guanosine-5'-O-(3-[(35)S]thio)triphosphate binding assays, S18616 was also a partial agonist at halpha(2C)-ARs (8.2/63%) but a full agonist (8.4/124%) at halpha(2B)-ARs. At halpha(2A)-, halpha(2B)-, and halpha(2C)-ARs, the selective alpha(2)-AR antagonist, atipamezole, abolished the actions of S18616: pK(b) values of 9.1, 9. 1, and 9.4, respectively. As determined by depletion of membrane-bound [(3)H]phosphatidyl inositols, S18616 behaved as a (less potent) agonist (7.8/79%) at halpha(1A)-ARs, an action abolished by prazosin (pK(b), 8.9). Reflecting alpha(2)-AR agonist properties, S18616 potently (>/=1 microg/kg, s.c.) and dose dependently elicited hypothermia and antinociception (nine diverse models) in rodents. These actions were dose dependently inhibited by chemically diverse alpha(2)- versus alpha(1)-AR antagonists, atipamezole, idazoxan, RX821,002, and BRL44418 (a preferential alpha(2A)-AR ligand). In contrast, the actions of S18616 were unaffected by the alpha(1)-AR antagonists, ARC239 and prazosin (which preferentially block alpha(2B/2C)- versus alpha(2A)-ARs). Although the affinity of dexmedetomidine at alpha(2)-ARs was lower than S18616; it displayed a similar receptor and functional profile. Clonidine displayed lower efficacy than S18616, was substantially less potent, and had marked affinity for imidazoline(1) sites and alpha(1)-ARs. In conclusion, S18616 is a novel, selective, and highly potent agonist at alpha(2)-ARs.     

Alterations in Distribution of Blood Flow to the Lung''s Diffusion Surfaces During Exercise

We measured simultaneously, by single breath methods, pulmonary capillary blood flow (Q(c)), carbon monoxide diffusing capacity (DL(CO)), and isotopic oxygen ((18)O(18)O) diffusing capacity (DL(18) (O2)) in five normal males during conditions of rest and moderate exercise at mixed venous O(2) tensions (PO(2) 33-44 mm Hg). During moderate exercise at a work load of 100 W. pulmonary capillary blood flow increased from 6.9+/-1.5 to 12.9+/-3.4 min(-1) and DL(18) (O2) increased from 25+/-4 to 43+/-3 ml.min(-1).mm Hg(-1), whereas DL(CO) showed no significant change (45+/-5 to 49+/-10 ml.min(-1).mm Hg(-1)). DL(18) (O2) increased proportionally to Q(c) (r = 0.74), where DL(CO) did not (r = 0.08). The greater increase in DL(18) (O2) during exercise can be explained by a more homogeneous diffusion/perfusion (DL(O2)/Q(c)) distribution in the individual respiratory exchange units during exercise. This improved distribution of DL(O2)/Q(c) acts to help prevent an increase in alveolar-arterial O(2) tension difference from developing despite the decrease in pulmonary erythrocyte transit times that occur during exercise. The insignificant rise in DL(CO) with exercise under these hypoxic breathholding conditions may result from pulmonary vasomotor responses to short-term hypoxia or from relative insensitivity of DL(CO) to moderate levels of exercise.     

Characterization of Ileal Vitamin B12 Binding Using Homogeneous Human and Hog Intrinsic Factors

Elucidation of the mechanism of intrinsic factor (IF)-mediated vitamin B(12) (B(12)) binding to ileal binding sites has been hampered by the use of crude or only partially purified preparations of IF in previous studies. We have used homogeneous human IF and hog IF isolated by affinity chromatography to study [(57)Co]B(12) binding to ileal mucosal homogenates. The following observations were made: (a) Human IF-B(12) and hog IF-B(12) were bound to human, monkey, hog, dog, rabbit, mouse, hamster, and guinea pig ileal, but not jejunal, homogenates in amounts significantly greater than free B(12) or B(12) bound to five other homogeneous B(12)-binding proteins; (b) only IF-mediated B(12) binding was localized to ileal homogenates and was inhibited by EDTA; (c) values for the association constant (K(a)) for the various ileal homogenates mentioned above and human IF-B(12) and hog IF-B(12) ranged from 0.3 x 10(9) M(-1) to 13.0 x 10(9) M(-1). Apparent differences in the K(a) for human IF-B(12) and hog IF-B(12) existed in most species; (d) the number of ileal IF-B(12) binding sites per gram (wet weight) of ileal mucosa ranged from 0.3 x 10(12) to 4.9 x 10(12). The same value was always obtained with human IF-B(12) and hog IF-B(12) for any given homogenate preparation; (c) 100-fold excesses of free B(12) or human IF and hog IF devoid of B(12) did not significantly inhibit human IF-B(12) and hog IF-B(12) binding to human and hog ileal homogenates.THESE EXPERIMENTS PERFORMED WITH HOMOGENEOUS IF INDICATE THAT: (a) gastric factors other than IF are not required for B(12) binding to ileal IF-B(12)-binding sites: (b) the mechanism of ileal IF-B(12) binding is different from that of free B(12) or of B(12) bound to non-IF-B(12)-binding proteins; (c) human IF and hog IF have different structures; (d) human IF-B(12) and hog IF-B(12) bind to the same ileal binding sites; and (c) human and hog ileal IF-B(12) binding sites bind free B(12) and human and hog IF devoid of B(12) poorly, if at all.     

Alpha(4)beta(7)/alpha(4)beta(1) dual integrin antagonists block alpha(4)beta(7)-dependent adhesion under shear flow

The alpha(4) integrin, alpha(4)beta(7), plays an important role in recruiting circulating lymphocytes to the gastrointestinal tract, where its ligand mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is preferentially expressed on high endothelial venules (HEVs). Dual antagonists of alpha(4)beta(1) and alpha(4)beta(7), N-(2,6-dichlorobenzoyl)-(L)-4-(2',6'-bis-methoxyphenyl)phenylalanine (TR14035) and N-(N-[(3,5-dichlorobenzene)sulfonyl]-2-(R)-methylpropyl)-(D)-phenylalanine (compound 1), were tested for their ability to block the binding of alpha(4)beta(7)-expressing cells to soluble ligand in suspension and under in vitro and in vivo shear flow. Compound 1 and TR14035 blocked the binding of human alpha(4)beta(7) to an (125)I-MAdCAM-Ig fusion protein with IC(50) values of 2.93 and 0.75 nM, respectively. Both compounds inhibited binding of soluble ligands to alpha(4)beta(1) or alpha(4)beta(7) on cells of human or rodent origin with similar potency. Under shear flow in vitro, TR14035 and compound 1 blocked binding of human alpha(4)beta(7)-expressing RPMI-8866 cells or murine mesenteric lymph node lymphocytes to MAdCAM-Ig with IC(50) values of 0.1 and 1 microM, respectively. Intravital microscopy was used to quantitate alpha(4)-dependent adhesion of fluorescent murine lymphocytes in Peyer's patch HEVs. When cells were prestimulated with 2 mM Mn(2+) to activate alpha(4)beta(7) binding to ligand, anti-alpha(4) monoclonal antibody (mAb) [10 mg/kg (mpk) i.v.] blocked adhesion by 95%, and anti-beta(1) mAb did not block adhesion, demonstrating that this interaction was dependent on alpha(4)beta(7). TR14035 blocked adhesion to HEVs [ED(50) of 0.01-0.1 mpk i.v.], and compound 1 blocked adhesion by 47% at 10 mpk i.v. Thus, alpha(4)beta(7)/alpha(4)beta(1) antagonists blocked alpha(4)beta(7)-dependent adhesion of lymphocytes to HEVs under both in vitro and in vivo shear flow.     

Vertical Distributions of Pulmonary Diffusing Capacity and Capillary Blood Flow in Man

In six normal upright subjects, a 100 mol bolus-composed of equal parts of neon, carbon monoxide, and acetylene (Ne, CO, and C(2)H(2))-was inspired from either residual volume (RV) or functional residual capacity (FRC) during a slow inspiration from RV to total lung capacity (TLC). After breath holding and subsequent collection of the exhalate, diffusing capacity and pulmonary capillary blood flow per liter of lung volume (D(L)/V(A) and Q(C)/V(A)) were calculated from the rates of CO and C(2)H(2) disappearances relative to Ne. The means: D(L)/V(A) = 5.26 ml/min x mm Hg per liter (bolus at RV), 6.54 ml/min x mm Hg per liter (at FRC); Q(C)/V(A) 0.537 liters/minute per liter (bolus at RV), 0.992 liters/minute per liter (at FRC). Similar maneuvers using Xenon-133 confirmed that, during inspiration, more of the bolus goes to the upper zone if introduced at RV and more to the lower, if at FRC. A lung model has been constructed which describes how D(L)/V(A) and Q(C)/V(A) must be distributed to satisfy the experimental data. According to this model, there is a steep gradient of Q(C)/V(A), increasing from apex to base, similar to that previously determined by other techniques-and also a gradient in the same direction, although not as steep, for D(L)/V(A). This more uniform distribution of D(L)/V(A) compared with Q(C)/V(A) indicates a vertical unevenness of diffusing capacity with respect to blood flow (D(L)/Q(C)). However, the relative degree of vertical unevenness of D(L)/V(A) compared with Q(C)/V(A) can account only in part for previous observations attributed to the inhomogeneity of D(L)/V(A) and Q(C)/V(A). Thus, a more generalized unevennes of these ratios must exist throughout the lung, independent of gravitation.     

Elucidation of the vasoactive intestinal peptide pharmacophore for VPAC(2) receptors in human and rat and comparison to the pharmacophore for VPAC(1) receptors

Vasoactive intestinal peptide (VIP) functions as a neurotransmitter involved in a number of physiological and pathological conditions. The actions of VIP are mediated through VPAC(1) and VPAC(2). In contrast to VPAC(1), which has been extensively studied, little is known about the pharmacology of VPAC(2). In this study we investigated the VIP pharmacophore for VPAC(2) by using alanine and D-amino acid scanning. We found significant species differences, and the human VPAC(2) (hVPAC(2)) expressed in Chinese hamster ovary (CHO) cells, which have been used in previous studies, differed significantly from the native hVPAC(2) in Sup T(1) cells and hVPAC(2) expressed in PANC1 cells. There was a close agreement between binding affinities and potencies for VPAC(2) activation. The amino acids whose backbone or side chain orientations were most important for high affinity potency are Asp(3), Phe(6), Thr(7), Tyr(10), Arg(12), Tyr(22), and Leu(23), whereas the side chains of Ser(2), Asp(8), Asn(9), Gln(16), Val(19), Lys(20), Lys(21), Asn(24), and Ser(25) are not essential. Comparison of the VIP pharmacophore between hVPAC(1) and hVPAC(2) demonstrated that the side chains of Thr(7), Tyr(10), Thr(11), and Tyr(22) were much more critical for high affinity for the hVPAC(2) than the hVPAC(1). In contrast, the orientation of the side chain of Asn(24) was more important for high affinity for the hVPAC(1). This study shows that in assessing the pharmacophore of VIP analogs for the VPAC(2), important species differences need to be considered as well as the expression system used. These results of our study should be useful for designing VPAC subtype-selective analogs, simplified analogs, and possibly metabolically stable analogs.     

Mechanism-based pharmacodynamic modeling of S(-)-atenolol: estimation of in vivo affinity for the beta1-adrenoceptor with an agonist-antagonist interaction model

The aim of this study was the development of an agonist-antagonist interaction model to estimate the in vivo affinity of S(-)-atenolol for the beta(1)-adrenoreceptor. Male Wistar-Kyoto (WKY) rats were used to characterize the interaction between the model drugs isoprenaline (to induce tachycardia) and S(-)-atenolol. Blood samples were taken to determine plasma pharmacokinetics. Reduction of isoprenaline-induced tachycardia was used as a pharmacodynamic endpoint. The pharmacokinetic-pharmacodynamic relationship of isoprenaline was first characterized with the operational model of agonism using the literature value for the affinity (K(A)) of isoprenaline (3.2 x 10(-8) M; left atria WKY rats). Resulting estimates for baseline (E(0)), maximal effect (E(max)), and efficacy (tau) were 374 (1.9%), 130 (5.9%), and 247 (33%) beats per minute, respectively. In addition, the interaction between isoprenaline and S(-)-atenolol was characterized using a pharmacodynamic interaction model based on the operational model of agonism that describes the heart rate response based on the affinity of the agonist (K(A)), the affinity of the antagonist (K(B)), the efficacy (tau), the maximal effect (E(max)), the Hill coefficient (n(H)), the concentrations of isoprenaline and atenolol, and the displacement of the endogenous agonist adrenaline. The estimated in vivo affinity (K(B)) of S(-)-atenolol for the beta(1) -receptor was 4.6 x 10(-8) M. The obtained estimate for in vivo affinity of S(-)-atenolol (4.6 x 10(-8) M) is comparable to literature values for the in vitro affinity in functional assays. In conclusion, a meaningful estimate of in vivo affinity for S(-)-atenolol could be obtained using a mechanism-based pharmacodynamic modeling approach.     

In irradiation chimeras, K or D regions of the chimeric host, not of the donor lymphocytes, determine immune responsiveness of antiviral cytotoxic T cells

The H-2 haplotype of the chimeric host determines the responder phenotype of maturing T cells. Spleen cells of chimeric mice formed when (K(k) nonresponder to D(b) × K(b) responder to D(b) plus vaccinia)F(1) bone marrow cells were used to reconstitute K(b)D(b) (C57BL/6 D(b) responder) irradiated recipients generated high levels of D(b) plus vaccinia virus-specific cytotoxic T cells. The same stem cells used to reconstitute K(k)D(b) (B10.A (2R) D(b) nonresponder) irradiated recipients resulted in spleen cells that responded well to K plus vaccinia, but responsiveness to D(b) was low. A generally low response to D(k) plus vaccinia, which seems to be regulated by D(k), was confirmed in chimeras. Thus, K(d)D(d) (D(d) plus vaccinia responder) stem cells differentiating in a K(d)D(k) chimeric host failed to generate a measurable response to D(k) plus vaccinia. In contrast, stem cells from K(d)D(k) (D(k) plus vaccinia low responders) differentiating in a K(d)D(d) (K(d) and D(d) high responders to vaccinia) host do generate responsiveness to D(d) plus vaccinia. These results indicate that in chimeras, the Ir phenotype is independent of the donor T cell’s Ir genotype, and that thymic selection of a T cell’s restriction specificity for a particular H-2 allele of the chimeric host also defines that T cell’s/r phenotype.     

Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D(2)-like receptor and alpha(1)/alpha(2)-adrenoceptor

The accompanying multivariate analysis of the binding profiles of antiparkinson agents revealed contrasting patterns of affinities at diverse classes of monoaminergic receptor. Herein, we characterized efficacies at human (h)D(2SHORT(S)), hD(2LONG(L)), hD(3), and hD(4.4) receptors and at halpha(2A)-, halpha(2B)-, halpha(2C)-, and halpha(1A)-adrenoceptors (ARs). As determined by guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding, no ligand displayed "full" efficacy relative to dopamine (100%) at all "D(2)-like" sites. However, at hD(2S) receptors quinpirole, pramipexole, ropinirole, quinerolane, pergolide, and cabergoline were as efficacious as dopamine (E(max)100%); TL99, talipexole, and apomorphine were highly efficacious (79-92%); piribedil, lisuride, bromocriptine, and terguride showed intermediate efficacy (40-55%); and roxindole displayed low efficacy (11%). For all drugs, efficacies were lower at hD(2L) receptors, with terguride and roxindole acting as antagonists. At hD(3) receptors, efficacies ranged from 33% (roxindole) to 94% (TL99), whereas, for hD(4) receptors, highest efficacies (approximately 70%) were seen for quinerolane, quinpirole, and TL99, whereas piribedil and terguride behaved as antagonists and bromocriptine was inactive. Although efficacies at hD(2S) versus hD(2L) sites were highly correlated (r = 0.79), they correlated only modestly to hD(3)/hD(4) sites (r = 0.44-0.59). In [(35)S]GTPgammaS studies of halpha(2A)-ARs, TL99 (108%), pramipexole (52%), talipexole (51%), pergolide (31%), apomorphine (16%), and quinerolane (11%) were agonists and ropinirole and roxindole were inactive, whereas piribedil and other agents were antagonists. Similar findings were obtained at halpha(2B)- and halpha(2C)-ARs. Using [(3)H]phosphatidylinositol depletion, roxindole, bromocriptine, lisuride, and terguride displayed potent antagonist properties at halpha(1A)-ARs. In conclusion, antiparkinson agents display diverse agonist and antagonist properties at multiple subtypes of D(2)-like receptor and alpha(1)/alpha(2)-AR, actions, which likely contribute to their contrasting functional profiles.     

Radioiodination of human intrinsic factor

Human intrinsic factor (IF) saturated with (60)Co-labeled cyanocobalamin ((60)CoB(12)) was purified and then iodinated with (125)I to yield (125)I-labeled IF-(60)CoB(12) preparations of high specific activity. Sephadex G200 and DEAE-cellulose chromatography of the iodinated IF-(60)CoB(12) complex showed coincidence of the major (125)I and the (60)Co radioactivity peaks. During starch-gel electrophoresis (60)Co radioactivity from noniodinated and iodinated complexes migrated to the same extent while (125)I radioactivity from the iodinated complex migrated slightly further anodally than did the (60)Co radioactivity. After the iodinated complex was mixed with antibody to the IF-B(12) complex (antibody II) the (125)I and (60)Co radioactivity were: (a) precipitated in similar amounts by antiglobulin serum. (b) eluted coincidentally in the 19S region on Sephadex G200, and (c) excluded to the same extent from starch gel during electrophoresis. After equilibrium exchange of IF "blocking" antibody (antibody I) for (60)Co-vitamin B(12) on (125)I-labeled IF. (125)I radioactivity from the IF-antibody I complex: (a) was precipitated by antiglobulin serum, (b) was eluated in the 19S region on Sephadex G200 gel filtration, and (c) migrated slowly towards the anode on starch-gel electrophoresis. Urinary excretion of (60)Co radioactivity in pernicious anemia patients after oral administration of (60)Co-vitamin B(12) bound to freshly prepared (125)I-labeled IF was similar to that obtained with noniodinated intrinsic factor.These results show that iodination of IF-(60)CoB(12) complex does not markedly alter the chromatographic, electrophoretic, antigenic, or absorption-promoting properties of IF.     

多色荧光原位杂交技术检测急性淋巴细胞白血病复杂核型异常

本研究建立多色荧光原位杂交（M—FISH）技术平台，探讨其在检测急性淋巴细胞白血病（ALL）复杂核型异常中的应用。联合应用常规细胞遗传学方法和M—FISH技术分析了5例伴有复杂核型异常的ALL患者。结果表明：M—FISH证实了原有的异常t（9；22）、t（1；19）和t（y；1），同时还发现了新的异常der（1）（1：：3：：7）、der（6）t（6；9）（q？；p13）、der（1）t（1；11）、der（12）t（1；12）、der（3）t（3；5）、der（2）t（2；16）、der（9）（9：：18：：7）和der（7）（9：：18：：7），并且纠正了原有的错误分析，其中der（9）（9：：18：：7）及der（7）（9：：18：：7）为世界上首例报道。结论：M—FISH在检测ALL复杂核型中的应用前景广阔，是进行精确染色体核型分析所不可缺少的先进手段。     

Influence of dobutamine on the variables of systemic haemodynamics, metabolism, and intestinal perfusion after cardiopulmonary resuscitation in the rat

BACKGROUND: Global left ventricular dysfunction after successful resuscitation from cardiac arrest may be treated successfully with dobutamine but the effects on intestinal perfusion are unknown. METHODS: In 24 male Sprague-Dawley rats ventricular fibrillation was induced. After 4 min of untreated cardiac arrest, precordial chest compression was performed for 4 min; adrenaline (epinephrine) (90 microg kg(-1)) was injected, followed by defibrillation. Return of spontaneous circulation was achieved in 18 animals, which were allocated to receive saline 0.9% (control group, n = 6), dobutamine at 5 microg kg(-1) min(-1) (n = 6) or dobutamine at 10 microg kg(-1) min(-1) (n = 6). Measurements of haemodynamic variables and intestinal tonometer P(CO2) were made before induction of ventricular fibrillation and 15, 30, 60, and 120 min postresuscitation. RESULTS: At 120 min postresuscitation, mean aortic pressure was 82 +/- 20, 104 +/- 19, and 113 +/- 15 mmHg for the control group, the dobutamine (5 microg kg(-1) min(-1)) group and the dobutamine (10 microg kg(-1) min(-1)) group (P < 0.05 for comparison of the dobutamine (10 microg kg(-1) min(-1)) group versus the control group). Respective abdominal aortic blood flow was 107 +/- 16, 133 +/- 49, and 145 +/- 18 ml min(-1) kg(-1) (P < 0.05 for comparison of the dobutamine (10 microg kg(-1) min(-1)) group versus the control group), and superior mesenteric artery blood flow was 25 +/- 9, 28 +/- 8, and 33 +/- 8 ml min(-1) kg(-1). Arterial lactate was significantly higher (P < 0.05) in the control group (2.3 +/- 0.6 mmol l(-1)) than in the dobutamine (5 microg kg(-1) min(-1)) group (1.6 +/- 0.3 mmol l(-1)) and dobutamine (10 microg kg(-1) min(-1)) group (1.5 +/- 0.3 mmol l(-1)). Tonometrically derived P(CO2) gap was highly elevated at 15 min of postresuscitation and returned to prearrest level at 120 min postresuscitation in all groups. CONCLUSIONS: Dobutamine enhances the recovery of global haemodynamic and metabolic variables early after cardiac arrest.     

t(8;21)急性髓系白血病的免疫表型特点

目的研究用流式细胞术免疫表型分析t(8;21)(q22;q22)急性髓系白血病(AML)的免疫表型特点.方法采用常规细胞形态学/细胞化学、流式细胞术间接免疫荧光标记技术和R显带核型分析(MIC)进行分型,部分加用RT-PCR检测AML1/ETO融合基因.结果①294例初治AML患者中,64例t(8;21)AML,占21.8%,在M2中高达54.7%.64例t(8;21)AML中M2占81.3%;②与对照组比较,t(8;21)AML高表达CD19和CD34,低表达CD33(P＜0.001);③以20%阳性细胞作为阳性标准,CD19阳性率在AML为13.6%(294例中40例),t(8;21)AML为50%(64例中32例),显著高于无t(8;21)AML组的3.5%(230例中8例)(P＜0.001);④在t(8;21)AML患者中,CD19+和(或)CD34+58例(90.6%)、CD19-和(或)CD34-6例(9.4%).结论t(8;21)AML特别是M2/t(8;21)高表达CD19与CD34,CD19与t(8;21)密切相关,CD19是预测t(8;21)的指标之一.     

Algorithms to qualify respiratory data collected during the transport of trauma patients

We developed a quality indexing system to numerically qualify respiratory data collected by vital-sign monitors in order to support reliable post-hoc mining of respiratory data. Each monitor-provided (reference) respiratory rate (RR(R)) is evaluated, second-by-second, to quantify the reliability of the rate with a quality index (QI(R)). The quality index is calculated from: (1) a breath identification algorithm that identifies breaths of 'typical' sizes and recalculates the respiratory rate (RR(C)); (2) an evaluation of the respiratory waveform quality (QI(W)) by assessing waveform ambiguities as they impact the calculation of respiratory rates and (3) decision rules that assign a QI(R) based on RR(R), RR(C) and QI(W). RR(C), QI(W) and QI(R) were compared to rates and quality indices independently determined by human experts, with the human measures used as the 'gold standard', for 163 randomly chosen 15 s respiratory waveform samples from our database. The RR(C) more closely matches the rates determined by human evaluation of the waveforms than does the RR(R) (difference of 3.2 +/- 4.6 breaths min(-1) versus 14.3 +/- 19.3 breaths min(-1), mean +/- STD, p < 0.05). Higher QI(W) is found to be associated with smaller differences between calculated and human-evaluated rates (average differences of 1.7 and 8.1 breaths min(-1) for the best and worst QI(W), respectively). Establishment of QI(W) and QI(R), which ranges from 0 for the worst-quality data to 3 for the best, provides a succinct quantitative measure that allows for automatic and systematic selection of respiratory waveforms and rates based on their data quality.     

应用波强技术初步评价原发性高血压患者血流动力学变化

目的 探讨波强(WI)技术评价原发性高血压患者血流动力学变化的临床应用价值.方法 对36例原发性高血压患者和30名年龄匹配的健康成人的颈动脉进行超声扫查,应用WI软件获取WI曲线,测量收缩早期峰值(W1)、收缩晚期峰值(W2)、收缩中期负向区面积(NA)、心电图R波顶点至W1的时间间隔(R-1st)、W1至W2的时间间隔(1~(st)-2~(nd))及时间标化后的R-1_(HR)~(st)、1~(st)-2~(nd)HR等参数.结果 ①与正常对照组比较,原发性高血压组W1值升高,差异有统计学意义(P＜0.01),两组间W2值、NA值、R-1st、1~(st)-2~(nd)、R-1_(HR)~(st)、1~(st)-2(_(HR)~(nd))差异无统计学意义(P＞0.05).②W1值与脉压、收缩压呈显著正相关(r=0.66和r=0.55,P＜0.01),W2值与脉压、收缩压亦呈显著正相关(r=0.62和r=0.44,P＜0.01),W1值、W2值与年龄和DBP无相关性(P＞0.05).结论 WI技术提供的血流动力学参数为临床综合评价高血压患者的心脏、血管功能及其相互作用提供新方法.     

Concomitant Block of the Rapid (I(Kr)) and Slow (I(Ks)) Components of the Delayed Rectifier Potassium Current is Associated With Additional Drug Effects on Lengthening of Cardiac Repolarization

BACKGROUND: The delayed rectifier potassium current, which comprises both a rapid (I(Kr)) and as slow (I(Ks)) component, is a major outward current involved in repolarization of cardiac myocytes. I(Kr) is the target of most drugs that prolong repolarization, whereas electrophysiological effects resulting from combined block of I(Kr) and I(Ks) still need to be characterized. METHODS AND RESULTS: Studies in isolated, buffer-perfused guinea pig hearts were undertaken to compare lengthening of cardiac repolarization under conditions of I(Kr) block alone, I(Ks) Block alone, or combined block of I(Kr) and I(Ks). In protocol A, isolated perfusion with N-acetylprocainamide (NAPA) (I(Kr) block), indapamide (I(Ks) block), or combined NAPA/indapamide was performed at a pacing cycle length of 250 msec. Increases in monophasic action potential duration measured at 90% polarization (MAPD(90)) from baseline after perfusion with NAPA 100 μmol/L (IC(50) for block of I(Kr)) was 19 +/- 6 msed (P <.05), after indapamide 100 μmol/L (EC(50) for block of I(Ks)) 13 +/- 2 msec (P <.05), but 42 +/- 5 msec after combined NAPA 100 μmol/L and indapamide 100 μmol/L (P <.05 vs. baseline and isolated administrations), suggesting the possibility of excessive lengthening of cardiac repolarization by blocking both I(Kr) and I(Ks). As well, in protocol B where sequential perfusions with dofetilide (I(Kr) blocker), dofetilide/indapamide, and indapamide in the same hearts were used, combined dofetilide/indapamide infusion showed a greater increase in MAPD(90) during all pacing cycles studied (250 to 150 msec). CONCLUSIONS: Combined I(Kr) and I(Ks) block may lead to excessive lengthening of cardiac repolarization. This may predispose patients to proarrhythmia during coadministration of drugs.