The role of the Cell Saver autologous transfusion method in preventing the pulmonary distress syndrome during open-heart operations on children

Complex estimation of the state of the lungs at the postperfusion and early postoperative periods based on roentgenological, clinical data, investigations of the parameters of oxygenation and mechanics of respiration was carried out in 32 children with septal defects of the heart, operated upon under conditions of artificial blood circulation with different kinds of the transfusion maintenance including the apparatus "Cell Saver 5" (CS) for the reinfusion of autoerythrocytes. The dynamics of endotoxicosis, hematological parameters during and after operation and requirements in transfusion media were studied. Differences in these indicators were established between the patients operated upon with the use of donor hemocomponents and those who were operated upon with CS. It allowed a conclusion about the role of the method of intraoperative reinfusion of erythrocytes in substantially less frequency and severity of the postperfusional pulmonary complications in this category of patients.     

Distinct immunological states in murine cutaneous leishmaniasis by immunising with different amounts of antigen: the generation of beneficial, potentially harmful, harmful and potentially extremely harmful states

Infection of BALB/c mice with a standard and substantial number of Leishmania major parasites results in progressive disease, following the induction of a parasite-specific Th2 response. These mice have been designated as "susceptible" on this basis. We show that distinct types of immune response can be generated in "susceptible" BALB/c mice depending upon the number of parasites employed for infection, and that the pathophysiological consequences of such distinct responses are dramatically different. Infection with very low numbers of parasites results in the exclusive induction of a cell-mediated, Th1 response, and the generation of resistance to the standard and substantial challenge. Spleen cells from such resistant mice can confer resistance upon normal mice when transferred to them, but these spleen cells do not contain T cells expressing DTH or Th1 effector cells that produce IFN gamma on short term culture (48 hrs) with parasite antigen. The immune response in this case appears to result in the virtual elimination of parasites from the lymph node draining the site of infection and, by implication, from the infected mouse. We suggest that such elimination results in the absence of antigen stimulation and hence of effector T cells, and that "memory Th1 cells" are responsible for the capacity of spleen cells to confer resistance on normal mice. We predict such mice will not suffer parasitemia upon immune suppression, i.e. are not susceptible to reactivation disease. This is the "beneficial state". In contrast to this infection with a very low number of parasites infection with a low number usually results in one of two states: (i) The generation of a response with a very small Th2 component, production of a small amount of antibody, chronic parasitemia and hence chronic generation of parasite-specific effector Th1/Th2 cells, or (ii) The generation of a response with a greater Th2 component, the production of more antibody, the formation of a frank lesion, and the long term generation of a stable, mixed Th1/Th2 response. We refer to the latter state as borderline leishmaniasis in analogy with borderline leprosy. Parasites can be recovered from the draining lymph node in both these cases many months after infection. We therefore believe that mice infected with a low number of parasites, that harbour a chronic subclinical infection, will suffer reactivation disease upon immune suppression, and we consequently designate the state generated as potentially harmful. We consider mice with borderline disease to be in a harmful state. Mice immunised with high doses of parasite antigen produce in the long term Th2 responses, whereas those immunised with lower doses produce Th1 responses. Mice immunised to produce a Th2 response were subsequently infected with a very low number of parasites that is normally contained. The generation of a Th2 response results in the generation of a Th2 imprint, such that the response to the low dose infection is modulated from a Th1 to a Th2 mode, resulting in progressive disease. We argue that immunisation/vaccination, resulting in a state that deviates the protective response to a non-protective mode, may result in epidemics. Such a state has the potential for being extremely harmful.     

In support of the telomere concept

The frequency of recovered X-ray-induced (4000R) rearrangements that, in all probability mimic terminal deletions of the X chromosome was only one of, roughly, 10-5 X chromosomes screened for tip deficiencies. Although the single exception looks terminally deleted, it is probably capped by a very short or nonpolytene telomeric segment. It is apparent from these data that the probability of "healing" or stabilization of a terminally deleted X in the zygotic nucleus or developing embryo of Drosophila melanogaster is vanishingly small. The telomeric caps in two obviously interstitial deficiencies that were recovered represent, roughly, 1/500 of the length of a mitotic chromosome. These findings give some indication of the extreme difficulty of detecting short telomeric segments capping either deleted polytene chromosomes or deleted metaphase chromosomes of, for example, humans.     

牛圈湖油田超前注水非线性渗流数值模拟研究

在渗流规律实验研究基础上,建立了牛圈湖特低渗透油藏流体渗流的非线性渗流模型,通过数值模拟在超前注水油水井间建立有效的驱动压力梯度,确定了牛圈湖西山窑低压油藏合理的井距为200m、注采井距为150m和裂缝穿透比为0.5,通过对注采参数的优化模拟,确定地层压力系数达到1.1时油井投产为最佳时期.     

Operative creation of left to right cardiac shunts: pulmonary functional sequelae

The tuberomammillary nucleus, a cluster of cells in the posterior hypothalamus, is the only known source of brain histamine. Although this nucleus is well described in terms of anatomy and neurochemistry, only little is known about its function. In the present study, the effect of a lesion in the region of this nucleus on intracranial self-stimulation was examined. Rats were implanted bilaterally with stimulating electrodes in the lateral hypothalamus and unilaterally with one lesion electrode in the region of this nucleus. After three days of baseline testing, half of the animals were given an electrolytic lesion. The animals were retested for six consecutive days, and thereafter weekly for another seven weeks. From the second day postlesion on, we unexpectedly found a gradual increase in response rate, which peaked on day 13 in the ipsilateral hemisphere only. Although there was no further increase over subsequent days, response rates remained elevated during the following seven weekly tests. The observed increase in lateral hypothalamic self-stimulation after an electrolytic lesion of the tuberomammillary nucleus is discussed in terms of an inhibitory system, possibly located in the region of this nucleus which, when removed by the lesion, increased reinforcing effects of the electrical brain stimulation. The fact that the effects on self-stimulation were lateralized to one hemisphere rules out an interpretation in terms of unspecific "performance" variables that could influence rate of lever pressing.     

pR plasmid replication provides evidence that single-stranded DNA induces the SOS system in vivo

The aim of this study was to quantitate factors affecting the initial "peak" of the pulmonary artery (PA) drug concentrations after i.v. bolus drug administration, which is a determinant of the subsequent drug uptake into both the lungs and other well-perfused organs. Indocyanine green (ICG) was used as a marker drug in anaesthetized (1.5% halothane) sheep prepared with an inferior vena cava injection catheter and a large-gauge pulmonary artery blood sampling catheter. For three ranges of cardiac output, 2.5-mg doses of ICG were injected in the following combinations: 10 ml injected over 1, 5 or 10 s; 5 or 25 ml injected over 1 s. On-line PA ICG concentrations were recorded for approximately 60 s using a densitometer. The mean maximum PA ICG concentrations (2-8 mg litre-1), the mean times at which they occurred (7-18 s after injection) and the time lags before ICG was detected in the PA (4-9 s), were inversely related to cardiac output, but linearly related to the time over which the injection was made. The area under the curve of the peak was related inversely to cardiac output only, while the aspect ratio of the peak was related inversely to the time over which the injection was made only. The injectate volume had no effect on any of the measured values. We conclude that, in some circumstances, the rate of injection of drugs with narrow margins of safety should be tailored to the cardiac output of an individual.     

Cloning of the human uroplakin 1B cDNA and analysis of its expression in urothelial-tumor cell lines and bladder-carcinoma tissue

The human uroplakin 1B (UPK1B) gene codes for a structural protein which is a terminal differentiation component of the asymmetric unit membrane on the apical surface of the mammalian bladder. UPK1B is a member of the tetraspan family of proteins, many of which have de-regulated patterns of expression in cancer. Using polymerase-chain-reaction techniques, we have cloned a partial human UPK1B cDNA which codes for the putative full open reading frame for the UPK1B protein. The deduced human UPK1B protein sequence has 92% and 93% amino-acid homology with bovine UPK1b and mink TI1 proteins respectively. Using Northern analysis, we show that the human UPK1B gene is highly expressed in normal human urothelium. However, expression of UPK1B mRNA was undetectable or markedly reduced in 11 out of 16 samples of transitional-cell-bladder-carcinoma tissue and in all 5 bladder-carcinoma cell lines when compared with normal urothelial tissue. The molecular mechanism of down-regulation of RNA expression does not appear to involve gross gene rearrangements or allelic loss.     

Cancer epigenetics comes of age

The discovery of numerous hypermethylated promoters of tumour-suppressor genes, along with a better understanding of gene-silencing mechanisms, has moved DNA methylation from obscurity to recognition as an alternative mechanism of tumour-suppressor inactivation in cancer. Epigenetic events can also facilitate genetic damage, as illustrated by the increased mutagenicity of 5-methylcytosine and the silencing of the MLH1 mismatch repair gene by DNA methylation in colorectal tumours. We review here current mechanistic understanding of the role of DNA methylation in malignant transformation, and suggest Knudson's two-hit hypothesis should now be expanded to include epigenetic mechanisms of gene inactivation.     

Maternal virus load and perinatal human immunodeficiency virus type 1 subtype E transmission, Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group

To determine the rate and risk factors for human immunodeficiency virus (HIV)-1 subtype E perinatal transmission, with focus on virus load, pregnant HIV-infected women and their formula-fed infants were followed prospectively in Bangkok. Of 281 infants with known outcome, 68 were infected (transmission rate, 24.2%; 95% confidence interval, 19.3%-29.6%). Transmitting mothers had a 4.3-fold higher median plasma HIV RNA level at delivery than did nontransmitters (P<.001). No transmission occurred at <2000 copies/mL. On multivariate analysis, prematurity (adjusted odds ratio [AOR], 4.5), vaginal delivery (AOR, 2.9), low NK cell percentage (AOR, 2.4), and maternal virus load were associated with transmission. As RNA quintiles increased, the AOR for transmission increased linearly from 4.5 to 24.8. Two-thirds of transmission was attributed to virus load>10,000 copies/mL. Although risk is multifactorial, high maternal virus load at delivery strongly predicts transmission. This may have important implications for interventions designed to reduce perinatal transmission.     

Analytical and biologic variability in measures of hemostasis, fibrinolysis, and inflammation: assessment and implications for epidemiology

CONTEXT: Central venous catheters impregnated with chlorhexidine and silver sulfadiazine have recently been introduced for the prevention of catheter-related infections. However, there remains some uncertainty regarding the efficacy of these catheters because of conflicting reports in the literature. OBJECTIVE: To evaluate the efficacy of chlorhexidine-silver sulfadiazine-impregnated central venous catheters in the prevention of catheter-related bloodstream infection. DATA SOURCES: Studies identified from a computerized search of the MEDLINE database from January 1966 to January 1998, reference lists of identified articles, and queries of principal investigators and the catheter manufacturer. STUDY SELECTION: Randomized trials comparing chlorhexidine-silver sulfadiazine-impregnated central venous catheters with nonimpregnated catheters were included. The outcomes assessed were catheter colonization and catheter-related bloodstream infection confirmed by catheter culture. DATA EXTRACTION: Twelve studies met the inclusion criteria for catheter colonization and included a total of 2611 catheters. Eleven studies with a total of 2603 catheters met the inclusion criteria for catheter-related bloodstream infection. Most patients in these studies were from groups considered to be at high risk for catheter-related infections. Summary statistics were calculated using Mantel-Haenszel methods under a fixed-effects model. DATA SYNTHESIS: The summary odds ratio for catheter colonization was 0.44 (95% confidence interval [CI], 0.36-0.54; P<.001), indicating a significant decrease in catheter colonization associated with impregnated catheters. The studies examining the outcome of primary interest, catheter-related bloodstream infection, had a summary odds ratio of 0.56 (95% CI, 0.37-0.84; P = .005). CONCLUSIONS: Central venous catheters impregnated with a combination of chlorhexidine and silver sulfadiazine appear to be effective in reducing the incidence of both catheter colonization and catheter-related bloodstream infection in patients at high risk for catheter-related infections.