Functional and phenotypic characterization of human peripheral blood stem cell harvests: a comparative analysis of cells from consecutive collections

A considerable number of patients with malignancies who are treated with high-dose therapy and hematopoietic stem cell transplantation subsequently relapse. Analyses of peripheral blood stem cell (PBSC) harvests obtained from 49 cancer patients showed that the PBSC harvest contained precursors for antitumor effector cells. Ex vivo manipulation of these harvests to maximize the antitumor effector cell activity may provide a new therapeutic approach to decrease or eliminate any minimal residual disease that remains after high-dose therapy. Characterization of PBSC from consecutive collections determined the collections best suited for ex vivo augmentation of antitumor cytotoxic effector cells. We report the results of a functional and phenotypical characterization of PBSC obtained from six consecutive collections from 18 cancer patients receiving granulocyte-macrophage colony-stimulating factor (GM- CSF) for hematopoietic stem/progenitor cell mobilization. The PBSC were evaluated for their cytotoxicity using the 51Cr-release assay. The frequency and subsets of lymphocytes were determined using flow cytometry with appropriate specific marker antibodies and differential cell counts. The content of hematopoietic progenitor cells in each collection was determined using a colony-forming unit granulocyte- macrophage (CFU-GM) culture assay. The frequency of cytotoxic effector cells including lymphokine-activated killer (LAK) cell precursors and lymphocytes was significantly greater (P < .05) in the early collections, whereas the later collections contained significantly (P < .05) more CFU-GM progenitor cells and fewer cytotoxic effector cells. Thus, our results show that PBSC obtained from advanced cancer patients do contain considerable levels of precursor cells for the generation of LAK cell populations. These results suggest that cells from the earlier collections are best suited for ex vivo manipulation to augment the antitumor effects.     

A mechanism for the hypoprothrombinemia of the acquired hypoprothrombinemia-lupus anticoagulant syndrome

Antibodies that bind prothrombin without neutralizing its coagulant activity were demonstrated in the plasma of two patients with the acquired hypoprothrombinemia-lupus anticoagulant syndrome. The first patient's plasma contained less than 1% prothrombin activity and no detectable prothrombin antigen. The second patient's plasma contained about 6% of both prothrombin activity and antigen. Neither patient's plasma neutralized the prothrombin coagulant activity of normal plasma or of purified prothrombin added in vitro. Nevertheless, double immunodiffusion studies and binding experiments utilizing 125I- prothrombin demonstrated the presence of prothrombin antibodies in each patient's plasma. A Scatchard analysis of the binding data obtained with different concentrations of 125I-prothrombin and the first patient's plasma indicated the presence of a high affinity antibody, apparent Kd approximately 10(-10)M, and a lower affinity antibody, apparent Kd approximately 10(-9)M. Studies utilizing purified cleavage products of prothrombin suggested that the antibodies were directed against an epitope or epitopes located on the carboxyl-terminal, latent thrombin segment of the prothrombin molecule. We postulate that the acquired hypoprothrombinemia in these two patients and in other reported patients with the acquired hypoprothrombinemia-lupus anticoagulant syndrome stems from rapid clearance from the circulation of prothrombin antigen-antibody complexes.     

Oral health of Adelaide nursing home residents: longitudinal study

Objective: The Adelaide Dental Study of Nursing Homes aimed to quantify oral disease experience, incidence and increments in Adelaide nursing home residents. Methods: Questionnaires and dental inspections were completed at baseline and at 1‐year for residents from randomly selected Adelaide nursing homes. Results: The residents were very functionally dependent, cognitively impaired and behaviourally difficult older adults with complex oral problems and dental treatment needs. The prevalence of edentulism (total tooth loss) (63%) decreased and more residents were retaining natural teeth. Existing residents had a mean of 10.8 teeth present and new residents had a mean of 12.7 teeth present. Residents’ previous experiences of caries (decay) were high – existing residents had a mean of 1.2 decayed teeth and new residents had a mean of 0.8 decayed teeth. Residents’ caries increments (new decay) over the 1‐year period were high (coronal = 2.5 surfaces; root = 1.0 surfaces), especially in those who had lost weight and who could eat fewer food types. These levels of caries were many times greater than had been reported for community‐dwelling older adults. Large accumulations of plaque, calculus and debris (food) were evident on residents’ natural teeth and dentures, especially those with dementia. Up to 25% of residents owned dentures that were not worn. Residents with dementia gave their carers complex and challenging oral hygiene care problems. Existing and new residents had similar general health and oral health characteristics, with the exceptions that new residents had significantly more filled tooth surfaces, and fewer decayed retained roots. Conclusion: New residents were being admitted to the nursing homes with a compromised oral health status or developed severe oral diseases and conditions within several months of their admittance. Residents’ oral diseases, especially coronal and root caries, rapidly progressed during their stay in residential care.     

Unequal crossing-over: a common basis of single alpha-globin genes in Asians and American blacks with hemoglobin-H disease

The alpha-globin genes of five black Americans, two Chinese, and five Filipinos with HbH disease (an alpha-thalassemia state in which there is a single functional alpha gene) were analyzed by restriction endonuclease techniques. All subjects were found to have one chromosome 16, lacking both alpha genes, and another containing a single alpha gene (--/-alpha). Restriction endonuclease patterns of the DNA obtained from all 12 subjects were identical and compatible with unequal crossing-over as the mechanism of origin of the single alpha gene in these individuals.     

Effect of LVAD outflow conduit insertion angle on flow through the native aorta

Background and aim: The goal of this study was to evaluate the effect of surgical anastomosis configuration of the aortic outflow conduit (AOC) from a continuous flow left ventricular assist device (LVAD) on the flow fields in the aorta using CFD simulations. The geometry of the surgical integration of the LVAD is an important factor in the flow pattern that develops both in series (aortic valve closed, all flow through LVAD) and in parallel (heart pumping in addition to LVAD).

Methods: CFD models of the AOC junctions simulate geometry as cylindrical tubes that intersect at angles ranging from 30° to 90°. Velocity fields are computed over a range of cardiac output for both series and parallel flow.

Results: Our results demonstrate that the flow patterns are significantly affected by the angle of insertion of the AOC into the native aorta, both during series and parallel flow conditions. Zones of flow recirculation and high shear stress on the aortic wall can be observed at the highest angle, gradually decreasing in size until disappearing at the lowest angle of 30°. The highest velocity and shear stress values were associated with series flow.

Conclusions: The results suggest that connecting the LVAD outflow conduit to the proximal aorta at a shallower angle produces fewer secondary flow patterns in the native cardiovascular system.     

儿科哮喘临床治疗的研究进展

儿童过敏性疾病包括很多种,过去几年其发病率在发达国家有所上升.这类疾病是一些有遗传倾向的儿童受环境因素而诱发,而现在对于这些环境因素仍不完全清楚.异位三合症（atopic triad）通常是指异位性皮炎、过敏性鼻炎和哮喘,患者常同时出现三种疾病的症状,并且一般由最初的异位性皮炎和食物过敏发展到过敏性鼻炎、环境过敏症和哮喘,我们将此过程称之为“遗传性过敏症进行曲”（atopic march）.     

Percutaneous injury, blood exposure, and adherence to standard precautions: are hospital-based health care providers still at risk?

To examine factors associated with blood exposure and percutaneous injury among health care workers, we assessed occupational risk factors, compliance with standard precautions, frequency of exposure, and reporting in a stratified random sample of 5123 physicians, nurses, and medical technologists working in Iowa community hospitals. Of these, 3223 (63%) participated. Mean rates of hand washing (32%-54%), avoiding needle recapping (29%-70%), and underreporting sharps injuries (22%-62%; overall, 32%) varied by occupation (P<.01). Logistic regression was used to estimate the adjusted odds of percutaneous injury (aOR(injury)), which increased 2%-3% for each sharp handled in a typical week. The overall aOR(injury) for never recapping needles was 0.74 (95% CI, 0.60-0.91). Any recent blood contact, a measure of consistent use of barrier precautions, had an overall aOR(injury) of 1.57 (95% CI, 1.32-1.86); among physicians, the aOR(injury) was 2.18 (95% CI, 1.34-3.54). Adherence to standard precautions was found to be suboptimal. Underreporting was found to be common. Percutaneous injury and mucocutaneous blood exposure are related to frequency of sharps handling and inversely related to routine standard-precaution compliance. New strategies for preventing exposures, training, and monitoring adherence are needed.