Activation of Classical Complement Pathway by Naturally Occurring Heteroantibodies in Normal Rabbit Serum. Effect on Subpopulations of Human Lymphoid Cells

Heteroantibodies present in normal rabbit serum (NRS) are toxic to human B lymphocytes, T lymphocytes, and monocytes. Even NRS, which exhibits little back ground cytotoxicity for human lymphoid cells in conventional HLA or B-cell lymphocytotoxic assays, can be shown to contain considerable activity by making two modifications in usual procedures: by washing cells in saline or balanced salt solutions devoid of protein or sugar substances, and by increasing incubation time for 1 h to 3--4 h. Using such modifications, the cytotoxic activity of NRS towards human lymphoid cells was investigated and was found to involve activation of the classical complement pathway rather than activation of the alternate complement pathway. Residual unwanted background cytotoxicity of NRS toward human lymphoid cells can be decreased without loss of desired complement activity either by heating NRS for 15 min at 50 degrees C or by mixing NRS with small amounts of normal human serum.     

Thymus involution in the acquired immunodeficiency syndrome

Acquired immunodeficiency syndrome (AIDS) is a severe disorder of unknown etiology and pathogenesis, predominantly affecting homosexual males and other high-risk groups and characterized by profound alterations in T-lymphocyte function. The authors have examined thymus tissue from 14 patients who died of AIDS and compared the results with findings in five control groups: healthy age-matched controls, elderly individuals, patients with chronic or debilitating illnesses other than AIDS, infants with conditions causing "stress atrophy," and patients with myasthenia gravis. The AIDS group included 11 homosexual males, 1 Haitian, 1 homosexual who was also a drug abuser, and a 10-month-old infant believed to have contracted AIDS following blood transfusion. All the AIDS cases showed marked thymus involution with severe depletion of both lymphocytes and epithelial elements. The latter component consisted primarily of thin cords and nests of primitive-appearing epithelial cells that could be defined by positive immunohistochemical staining for keratin. Many cases showed a variable plasma cell infiltration, and the majority exhibited distinct vascular changes in the form of hyalinization and/or onion-skin patterns, primarily in the adventitia. Most striking of all was the marked paucity of Hassall's corpuscles; four patients had none at all, while in the other ten patients all the Hassall's corpuscles were calcified. These changes were far more extensive than those seen in any of the control groups, which retained most of their complement of Hassall's corpuscles even in the face of marked overall involution. The physiologic function of Hassall's corpuscles is not known, but recent immunohistochemical studies have implicated them in the synthesis of "facteur thymique serique" (FTS, thymulin) and other thymic hormones known to play a role in regulating T-helper and suppressor cell activity. It is conceivable that the extensive destruction of Hassall's corpuscles observed in AIDS may be a crucial element in the pathogenesis of this syndrome.     

Catalytic degradation of Orange II in aqueous solution using diatomite-supported bimetallic Fe/Ni nanoparticles

A functional diatomite-supported Fe/Ni nanocomposite successfully remediated Orange II contaminant in aqueous solution. The hypothesis was that diatomite-supported Fe/Ni would not only be more effective than Fe/Ni but also require less metallic loading to effect the catalytic reaction. Batch experiments indicate that 99.00% of Orange II was removed using diatomite-supported Fe/Ni, while only 86.64 and 3.59% of Orange II were removed using bimetallic Fe/Ni nanoparticles and diatomite, after 6 h of reaction, respectively. Characterisation by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM) indicates that the use of diatomite as a support material reduced the aggregation of bimetallic Fe/Ni nanoparticles, thereby resulting in an enhancement in the reactivity. A synergistic mechanism for the removal of Orange II by diatomite-supported Fe/Ni was proposed which involves adsorption, followed by catalytic reduction. This study has demonstrated that diatomite may be a suitable support material for stabilizing and dispersing bimetallic Fe/Ni nanoparticles and the resulting diatomite-supported Fe/Ni composite could be a promising catalyst for the remediation of dye-contaminated wastewater.

A functional diatomite-supported Fe/Ni nanocomposite successfully remediated Orange II contaminant in aqueous solution.     

Membrane receptors and their redistribution in lymphoproliferative disorders.

Lymphoid cells from 20 patients with lymphoproliferative disorders, including chronic lymphocytic leukemia, hairy cell leukemia, Sezary syndrome, lymphoma, and lymphadenitis, were studied for redistribution of surface membrane immunoglobulins (SmIg) and concanavalin A (Con-A) receptors. Fluorescein-labeled polyvalent goat anti-human immunoglobulin and fluoresceinated concanavalin A were used as ligands. Results were similar with both ligands. The highest percentage of capping of ligand-membrane receptors was noted in mononuclear cells from patients with "hairy" cell leukemia: from 24% to 90%. These cells showed moderate to marked fluorescein activity and were able to cap within 15 min at 4 degrees C. Chronic lymphocytic leukemia cells showed a weak fluorescein stain with a very low percentage of cells (0%--16%) capping. Lymph node cells from patients with lymphoma demonstrated moderate to strong fluorescein activity with only an average of 3% of the cells capping; while lymphoid cells from patients with lymphaedenitis showed an average of 27.5% capping and moderate fluorescein activity. Capping of Con-A receptors in mononuclear cells from patients with Sezary syndrome was poor (0%--14%) with moderate fluorescein intensity. This report demonstrates difference in density and mobility of binding sites for SmIg and Con-A on the surface membrane of lymphoid cells from various subclasses of lymphoproliferative disorders. These differences may assist in the differential diagnosis and classification of these conditions.     

Discrete Choice Experiment to Estimate Breast Cancer Patients’ Preferences and Willingness to Pay for Prophylactic Granulocyte Colony-Stimulating Factors

ObjectivesRising out-of-pocket costs for cancer patients have increased shared decision making. Clinical guidelines recommend prophylactic granulocyte colony-stimulating factor (G-CSF) for patients receiving chemotherapy with a 20% or greater risk of febrile neutropenia. A discrete choice experiment was conducted to explore breast cancer patients’ preferences and willingness to pay (WTP) for prophylactic G-CSF to decrease the risk of chemotherapy-induced febrile neutropenia.MethodsAn online discrete choice experiment questionnaire survey of a national US convenience sample of self-reported breast cancer patients with prior chemotherapy treatment was conducted. Sixteen paired G-CSF treatment scenarios, each with four attributes (risk of disruption to chemotherapy schedule due to low white blood cell counts, risk of developing an infection requiring hospitalization, frequency of administration, and total out-of-pocket cost) were presented with a follow-up “no treatment” option. Participant preferences and WTP out of pocket were estimated by logistic regression.ResultsParticipants (n = 296) preferred G-CSF regimens with lower out-of-pocket costs, lower risk of chemotherapy disruption, lower risk of infection, and greater convenience (one G-CSF injection per chemotherapy cycle). Participants’ WTP was $1076 out of pocket per cycle to reduce the risk (high to low) of disrupting their chemotherapy schedule, $884 per cycle to reduce the risk (24% [high] to 7% [low]) of infection, and $851 per cycle to decrease the number of G-CSF injections (11 to 1) per cycle.ConclusionsParticipants highly valued specific features of prophylactic G-CSF treatment including maintaining their chemotherapy schedule, lowering their risk of infection, and reducing the number of injections. Physicians should consider patient preferences to inform the best treatment choices for individual patients.     

The Impact of COVID-19 on Routine Medical Care and Cancer Screening

BackgroundCOVID-19 restrictions and fear dramatically changed the use of medical care. Understanding the magnitude of cancelled and postponed appointments and associated factors can help identify approaches to mitigate unmet need.ObjectiveTo determine the proportion of medical visits cancelled or postponed and for whom. We hypothesized that adults with serious medical conditions and those with higher anxiety, depressive symptoms, and avoidance-oriented coping would have more cancellations/postponements.DesignFour nationally representative cross-sectional surveys conducted online in May, July, October, and December 2020.Participants59,747 US adults who completed 15-min online surveys. 69% cooperation rate.MeasuresPhysical and mental health visits and cancer screening cancelled or postponed over prior 2 months. Plan to cancel or postpone visits over the next 2 months. Relationship with demographics, medical conditions, local COVID-19 death rate, anxiety, depressive symptoms, coping, intolerance of uncertainty, and perceived COVID-19 risk.Key ResultsOf the 58% (N = 34,868) with a medical appointment during the 2 months before the survey, 64% had an appointment cancelled or postponed in May, decreasing to 37% in December. Of the 41% of respondents with scheduled cancer screening, 20% cancelled/postponed, which was stable May to December. People with more medical conditions were more likely to cancel or postpone medical visits (OR 1.19 per condition, 95% CI 1.16, 1.22) and cancer screening (OR 1.20, 95% CI 1.15, 1.24). Race, ethnicity, and income had weak associations with cancelled/postponed visits, local death rate was unrelated, but anxiety and depressive symptoms were strongly related to cancellations, and this grew between May and December.ConclusionsCancelled medical care and cancer screening were more common among persons with medical conditions, anxiety and depression, even after accounting for COVID-19 deaths. Outreach and support to ensure that patients are not avoiding needed care due to anxiety, depression and inaccurate perceptions of risk will be important.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-07254-x.KEY WORDS: COVID-19, missed medical appointments, cancer screening     

Quality Measures for Supportive Cancer Care: The Cancer Quality-ASSIST Project

Patients and physicians often cite symptom control as one of their most important goals in cancer care. Despite this, a previous systematic review found few tools for evaluating the quality of supportive cancer management. We developed a comprehensive set of quality indicators for evaluating pain and nonpain symptom management as well as care planning needs in cancer patients. Based on the prevalence and quality-of-life data, clinician-researchers prioritized pain, psychosocial distress, dyspnea, nausea and vomiting, fatigue and anorexia, treatment-associated toxicities, and information and care planning for quality-indicator development. Using search terms and selection criteria, we identified English-language documents from Medline (1997–2007) and Internet-based searches. Based on this evidence, clinician-reviewers proposed process quality indicators. We then used the VA Health Services Research and Development (VA HSR & D) appropriateness methods to compile the ratings of a multidisciplinary, international expert panel of the validity and feasibility of each indicator. The panel judged 92 out of 133 (69%) proposed quality indicators valid and feasible (15 out of 23 pain, 5 out of 6 depression, 8 out of 11 dyspnea, 15 out of 19 nausea and vomiting, 13 out of 26 fatigue and anorexia, 23 out of 32 other treatment-associated toxicities, and 13 out of 16 information and care planning). Of the final indicators, 67 are potentially useful for inpatient and 81 for outpatient evaluation, and 26 address screening, 12 diagnostic evaluation, 20 management, and 21 follow-up. These quality indicators provide evidence-explicit tools for measuring processes critical to ensuring high-quality supportive cancer care. Research is needed to characterize adherence to recommended practices and to evaluate the use of these measures in quality improvement efforts.     

Comparison of bone marrow aspirates and biopsies in pediatric patients with ALL at days 7 and 14 of induction therapy

The percentage of blasts in the bone marrow aspirates at day 7 or 14 of induction therapy in pediatric ALL patients is an indicator of rapid early response and an independent prognostic factor for long term outcome. Discrepancies between the percentages of blasts in bone marrow aspirates compared to biopsies have been reported. In a retrospective study on 44 consecutive patients diagnosed with ALL between 1998 and 2001, important differences were observed in the percentage of blasts between bone marrow aspirates and biopsies at days 7 and 14 of induction therapy.     

Hybrid leukemia and the 5q-abnormality

Most cases of acute leukemia with deletions of chromosome 5q (5q-) are acute myelogenous leukemia. 5q- in acute lymphoid leukemia is rare. We studied a case of acute leukemia with 5q- using morphologic, cytochemical, immune and molecular techniques. Morphologic and cytochemical techniques were consistent with ALL (FAB L-2, PAS+, MPO-, ASD-). TdT was present. Immune studies suggested a T-cell phenotype (CD5+, CD7+); however, there was no rearrangement of the T beta-cell receptor gene. Surprisingly, the leukemia cells also expressed the CD13 myeloid antigen. Dual staining analysis showed co-expression of lymphoid and myeloid antigens on most cells. Based on these data and a review of previous reports we suggest that acute leukemia associated with the 5q- abnormality can occur in an immature stem cell resulting in a hybrid leukemia.