Preparation of white cell-depleted red cells for 42-day storage using an integral in-line filter

A new blood pack system for the preparation of white cell-depleted red cells was studied. The system is a modified additive-solution quadruple-unit blood pack that incorporates a cellulose-acetate fiber depth filter in-line between the AS-3 additive bag and the CP2D collection bag. Mean +/- SD white cell removal from 156 units processed under standard production conditions was 97.7 +/- 2.7 percent; residual white cells were 1.1 +/- 1.0 x 10(8) per unit. Red cell loss was 10.0 +/- 1.0 percent (n = 43). Mean platelet removal was 80.9 percent from units from which platelet concentrates were not prepared (n = 47). Microaggregates did not form during storage, and hemolysis of filtered red cells was lower than that of unfiltered controls. Filtered AS-3 red cells stored for 42 days had a 51Cr survival of 80.1 +/- 5.7 percent (mean +/- SD) as compared with 78.9 +/- 6.2 percent for unfiltered controls (n = 17). This in-line filter system provides white cell-depleted, microaggregate-free red cells that can be stored for 42 days.     

Do not be alarmed,the patient is monitored

Many patients are believed to be at risk of dysrhythmias and are felt to require cardiac monitoring. These patients may not be deemed ill enough to occupy a high dependency or critical care bed and are monitored on general wards. Monitoring policies vary widely not only between institutions, but also between individual medical staff. These variations occur due to differing availability of resources and due to the lack of consensus regarding the risk for an individual patient. There is no clear evidence that monitoring patients outside high dependency areas is of benefit; inappropriate use of monitoring may actually increase patient risk.     

The Morbidity of Multiple Sclerosis

Although the clinical course of multiple sclerosis is benignin up to one-third of patients, it is important to recognizethe high rate of morbidity in others. Most individuals passthrough a remitting phase but in a significant proportion theclinical manifestations subsequently recur, persist or slowlyprogress, and disability accumulates with time. Here we describethe frequency and spectrum of morbidity in a population basedcohort of patients with multiple sclerosis. These statisticswill guide those providing health care resources and planningservices for patients with multiple sclerosis.     

Angiotensin-converting-enzyme inhibitors in the management of cardiac failure: are we ignoring the evidence?

The benefits of angiotensin-converting enzyme (ACE) inhibition in the management of cardiac failure have been extensively documented. However, little is known about its impact upon the investigation and management of this condition. We assessed how patients diagnosed as having cardiac failure were investigated, which patients were treated with ACE inhibitors and with what dosages. We reviewed the case notes of all 343 patients discharged from Aberdeen Royal Infirmary 1 July-31 December 1992 with a diagnosis of cardiac failure. In addition, a questionnaire was sent to the general practitioners of the 166 patients still alive in October 1994. Only 40% of patients were discharged from hospital on ACE inhibitors. In 58.8%, the diagnosis of cardiac failure was based purely on clinical or radiological grounds. At discharge, 76.1% of patients were on lower doses of ACE inhibitors than those used in the major survival studies; with 68.9% receiving similar doses two years later. The majority of patients with heart failure are under- investigated and under-treated.      

Clinical review: Treatment of new-onset atrial fibrillation in medical intensive care patients: a clinical framework

Atrial fibrillation occurs frequently in medical intensive care unit patients. Most intensivists tend to treat this rhythm disorder because they believe it is detrimental. Whether atrial fibrillation contributes to morbidity and/or mortality and whether atrial fibrillation is an epiphenomenon of severe disease, however, are not clear. As a consequence, it is unknown whether treatment of the arrhythmia affects the outcome. Furthermore, if treatment is deemed necessary, it is not known what the best treatment is. We developed a treatment protocol by searching for the best evidence. Because studies in medical intensive care unit patients are scarce, the evidence comes mainly from extrapolation of data derived from other patient groups. We propose a treatment strategy with magnesium infusion followed by amiodarone in case of failure. Although this strategy seems to be effective in both rhythm control and rate control, the mortality remained high. A randomised controlled trial in medical intensive care unit patients with placebo treatment in the control arm is therefore still defendable.     

T cell growth factor receptors. Quantitation, specificity, and biological relevance

To examine directly the hypothesis that T cell growth factor (TCGF) interacts with target cells in a fashion similar to polypeptide hormones, the binding of radiolabeled TCGF to various cell populations was investigated. The results indicate that TCGF interacts with activated T cells via a receptor through which it initiates the T cell proliferative response. Internally radiolabeled TCGF, prepared from a human T leukemia cell line and purified by gel filtration and isoelectric focusing, retained biological activity and was uniform with respect to size and charge. Binding of radiolabeled TCGF to TCGF-dependent cytolytic T cells occurred rapidly (within 15 rain at 37 degrees C) and was both saturable and largely reversible. In addition, at 37 degrees C, a receptor- and lysosome-dependent degradation of TCGF occurred. Radiolabeled TCGF binding was specific for activated, TCGF-responsive T cells. Whereas unstimulated lymphocytes of human or murine origin and lipopolysaccharide-activated B cell blasts expressed few if any detectable binding sites, lectin- or alloantigen-activated cells had easily detectable binding sites. Moreover, compared with lectin- or alloantigen-activated T cells, long-term TCGF-dependent cytolytic and helper T cell lines and TCGF-dependent neo-plastic T cell lines bound TCGF with a similar affinity (dissociation constant of 5-25 pM) and expressed a similar number of receptor sites per cell (5,000-15,000). In contrast, a number of TCGF-independent cell lines of T cell, B cell, or myeloid origin did not bind detectable quantities of radiolabeled TCGF. Binding of radiolabeled TCGF to TCGF-responsive cells was specific, in that among several growth factors and polypeptide hormones tested, only TCGF competed for binding. Finally, the relative magnitude of T cell proliferation induced by a given concentration of TCGF closely paralleled the fraction of occupied receptor sites. As the extent of T cell clonal expansion depends on TCGF and on the TCGF receptor, the dissection of the molecular events surrounding the interaction of TCGF and its receptor that these studies permit, should provide new insight into the hormonelike regulation of the immune response by this lymphokine.     

Characteristics of white cell-reduced red cells stored in tri-(2- ethylhexyl)trimellitate plastic

BACKGROUND: Standard blood storage containers contain extractable plasticizers that accumulate in blood during storage and are an unintended transfusion product. However, extractable plasticizers have a protective effect on the red cell membrane and improve red cell storage variables. Prestorage white cell reduction also improves selected red cell storage variables. STUDY DESIGN AND METHODS: The study evaluated whether the beneficial effect of prestorage white cell reduction would offset the negative effect of the absence of extractable plasticizer in red cells stored in AS-3 for 42 days at 4 degrees C. Filtered red cells stored in polyvinylchloride containers with the nonextracting plasticizer, tri-(2-ethylhexyl)trimellitate (TEHTM), were compared to unfiltered red cells stored in polyvinylchloride containers with the extractable plasticizer di-(2- ethylhexyl)phthalate (DEHP). RESULTS: Poststorage supernatant potassium and red cell osmotic fragility were significantly higher in white cell- reduced TEHTM units than in unfiltered DEHP units. The mean 24-hour recovery of the filtered TEHTM red cells was significantly lower than that of the unfiltered DEHP red cells (69.1 +/− 7.4% vs. 77.1 +/− 5.1%, p < 0.05, n = 8). CONCLUSION: These data demonstrate that white cell reduction before 42-day storage in TEHTM containers with currently approved preservatives does not yield an acceptable red cell component.     

Self recognition in allogeneic radiation bone marrow chimeras. A radiation- resistant host element dictates the self specificity and immune response gene phenotype of T-helper cells

The specificity of the self-recognition repertoire in fully allogeneic (A {arrow} B), semiallogeneic (A {arrow} A x B and A x B {arrow} A), and double donor (A + B {arrow} A) radiation bone marrow chimeras was assessed by the ability of their spleen cells to generate in vitro primary plaque-forming cell (PFC) responses to trinitrophenyl- keyhole limpet hemocyanin. In contrast to spleen cells from semiallogeneic and double donor chimeras, intact spleen cells from fully allogeneic BI0 {arrow} B10.A and B10.A {arrow} B10 chimeras were not capable of generating responses to trinitrophenyl (TNP)-keyhole limpet hemocyanin. However, cultures containing a mixture of both B10 {arrow} B10.A and B10.A {arrow} B10 spleen cells did respond, demonstrating that all the cell populations required for the in vitro generation of T-dependent PFC responses were able to differentiate into functional competence in a fully allogeneic major histocompatibility complex (MHC) environment. The self recognition repertoire of T-helper cells from fully allogeneic A {arrow} B chimeras was determined to be specific for the recognition of host, not donor, MHC determinants in that they were able to collaborate with cells expressing only host MHC determinants but not with cells expressing only donor MHC determinants, even though the functional lymphocytes in these chimeras were shown to be of donor origin. Experiments utilizing double donor A + B {arrow} A chimeras further demonstrated that the ability of chimeric T cells to recognize allogeneic MHC determinants as self structures was a function of a radiation-resistant host element and not simply a consequence of the tolerization of T cell precursors to allogeneic MHC determinants, because strain A lymphocytes isolated from A + B {arrow} A chimeras were tolerant to both A and B MHC determinants but were restricted to the self recognition of syngeneic host type A MHC determinants. Finally, the Ir gene phenotype expressed by B10 {arrow} B10.A and B10.A {arrow} B10 chimeric lymphocytes was determined by their ability to function in the Ir gene controlled response to TNP-poly-L-(Tyr,Glu)-poly-D,L-Ala-poly- L-Lys [(T,G)-A--L]. The ability of lymphocytes to function in TNP-(T,G)-A--L responses was not determined by their genotype but rather paralleled the specificity of their self recognition repertoire for high responder (H-2 (b)) determinants. The possible degeneracy of the MHC-specific self recognition repertoire is discussed, and a model is proposed for Ir gene regulation in which expression of Ir gene function by lymphocytes is an antigen-nonspecific consequence of the specificity and cross-reactivity of their self recognition repertoire.     

自体移植静脉内皮细胞的缺血安全时限

目的:观察离体后不同缺血时间自体移植静脉内皮细胞的损伤程度,分析移植静脉内皮细胞缺血的安全时限。方法:实验于2005-07/2005-12在中国人民解放军胸心外科研究所完成。选择健康成年家犬29只,购自解放军第二军医大学实验动物中心。①不同缺血时间移植静脉内皮细胞损伤实验:按随机数字表法选取5只家犬,取双侧股静脉,按离体后0min,30min,60min,90min4个时间点行扫描电镜及透射电镜检查,观察内皮细胞的损伤程度,Ⅰ级正常,Ⅱ级轻度,Ⅲ级中度,Ⅳ级重度,Ⅴ级坏死,将Ⅰ,Ⅱ,Ⅲ级损伤归类为可逆性损伤;将Ⅳ,Ⅴ级损伤归类为不可逆损伤。②自体移植静脉内皮细胞缺血安全时限实验:将剩余24只家犬建立犬股静脉离体不同时间(30min,60min,90min)的自体移植模型,在术后1d,3d,7d,14d再次手术取出静脉,行扫描电镜检查,比较不同时间点移植静脉内皮覆盖率。结果:①缺血0min,30min,60min,90min组(n=60)不可逆性损伤内皮细胞数分别为12,6,28,33,缺血60min、90min组内皮细胞的损伤程度明显重于缺血0min和30min组。各组的内皮细胞覆盖率比较差异无显著性意义(P>0.05)。②24只模型犬全部存活,切口愈合佳,无红肿、溢脓或裂开。③移植术后1d,14d,缺血30min,60min及90min组内皮细胞覆盖率差异无显著性意义(P>0.05),而术后3d,7d,缺血30min组的内皮细胞覆盖率显著高于缺血60min及90min组[(62.21±3.52)%,(40.09±2.56)%,(36.17±4.55)%(P<0.01);(82.31±3.76)%,(60.22±3.23)%,(59.39±4.27)%(P<0.01)]。结论:缺血60min后静脉内皮细胞的超微结构会发生明显的不可逆性损害,移植静脉内皮细胞缺血的安全时限是60min。     

Emergence of a fluoroquinolone-resistant strain of Streptococcus pneumoniae in England

OBJECTIVE: To determine the epidemiological relationship between pneumococci of serotype 9V, with reduced susceptibility to ciprofloxacin, penicillin and erythromycin, referred to the Reference Laboratory during 1997-2001. METHODS: Isolates were characterized by multilocus sequence typing (MLST), PFGE, and sequencing of parC and gyrA. Relevant clinical data were sought. RESULTS: Forty-eight isolates were received from nine laboratories in England, but 35 (73%) were from one laboratory in Birmingham, and were mostly from elderly patients receiving ofloxacin or ciprofloxacin for respiratory infections. There were two quinolone resistance phenotypes, with ciprofloxacin, moxifloxacin and gemifloxacin MICs of 8-32, 0.5-1 and 0.125-0.25 mg/L, and 64-256, 4-16 and 1-4 mg/L, respectively. Each of three isolates from the former group had mutations in parC, whereas each of nine isolates from the more resistant group had mutations in both parC and gyrA. Several also had increased quinolone efflux. Typing of 27 quinolone-resistant isolates showed that eight were indistinguishable from the epidemic Spain9V-3 (ST156) clone, while the remainder belonged to a novel but related type (ST609), that differed from Spain9V-3 at 2/7 alleles (2 bp changes in aroE and 1 bp change in gdh). Both MLST types were represented among isolates with high- and low-level quinolone resistance. Three of five serotype 9V isolates from Birmingham, with reduced susceptibility to penicillin and erythromycin, and ciprofloxacin MICs of 1-2 mg/L, belonged to MLST type ST609, while another was indistinguishable from the Spain9V-3 clone. Review of records of 32 patients from Birmingham indicated that some isolates were nosocomial, whereas others were acquired in the community. CONCLUSIONS: In the late 1990s, a quinolone-resistant strain, clonally related to Spain9V-3, emerged in England, principally in Birmingham.