Lyso-lecithin fragility in blackwater fever and haemolytic jaundice

Red cells transfused into a case of haemolysing blackwater fever are destroyed just as readily as the patient's own cells, making it appear that it is not the red cells that are at fault in this condition, but that there is some circulating haemolysin.By an improved spectrophotometric technique it has now been shown that, like those of haemolytic jaundice, the red cells from blackwater fever have an increased fragility to lyso-lecithin, although their fragility to saline is normal, unlike that of the cells of haemolytic jaundice.These two facts taken together make it seem that in blackwater fever the cells may possess some abnormal feature, but that this is probably secondary to more fundamental changes that take place in the cells' environment. By using van Boros' formula it is possible to demonstrate that spherocytosis occurs in blackwater fever and is accompanied by decreases in diameter-thickness ratio, volumes and areas; that these changes in blackwater fever are intermediate between those taking place in haemolytic jaundice and normal controls, and are not related in blackwater fever to changes in hypotonic saline fragility. It is probable that the initial stage in the destruction of the cells is a change in the permeability of the cell membrane, which allows haemoglobin to escape. The cells have later been seen to swell, become “transparent,” and then to disappear. That they have not been broken up can be shown by resuspending them in saline when the “ghosts” reappear. This phenomenon takes place in both lyso-lecithin and snake venom haemolysis. If the process is allowed to continue the cells are finally disrupted, and will not reappear on saline resuspension.In haemolytic jaundice it seems that there may be some defect in the red cell as well as some “splenic factor,” shown by the fact that splenectomy fails to alter the abnormal fragility of the cells to saline, but does stop the periodic haemolysis. A combination of both abnormal cells and splenic factors would seem to be necessary for the destruction of the red cells in this condition. The same cannot be determined for blackwater fever.The enlargement of the spleen in so many of these haemolytic conditions is regarded by many as of considerable significance. The production of lyso-lecithin as a result of the separation of the cells and plasma in this organ has led to the suggestion that this powerfully haemolytic substance may play a part in the haemolyses of certain of these conditions.It is possible that lyso-lecithin fragility is in some way related to the action of this substance on the lipoids or lipo-protein complex in the red cell membrane. It has been shown that the amount of lipoid present in the cell envelope is closely related to the dimensions of the cell, and that the ability of the cell to increase its volume without being disrupted is related to the lipo-protein ratio in its membrane.The kinetics of lyso-lecithin haemolysis have not been worked out, but there is some ground for regarding the process as one of enzyme action where the enzyme lecithinase acting on a substrate of red cells or plasma lecithin results in the production of lyso-lecithin or some allied phosphatide. Lecithinase has been shown to be present in many conditions where haemolytic reactions take place, such as in favism, snake poisoning, Cl. welchii filtrates as well as in the spleen and peripheral blood. The degradation products of the action of lecithinase on lecithin are not always the same, nor are the various lecithinases alike.Although the end product of the action of snake venom lecithinase on lecithin is lyso-lecithin, yet this substance when injected into baboons in relatively huge amounts produces no haemolysis, and only a slight shift of the Price-Jones curve to the right. This is in sharp contrast to the haemolysis that follows the injection of snake venom freed of its neurotoxic factor. It is suggested that this difference may be due to the fact that in the former case the lecithin in the cells and/or plasma is not disturbed, whilst in the case of snake venom injection of the lecithinase present in the venom will split the lecithin of the cells and/or plasma and so disturb the intracellular lipo-protein complex.The part played by the reticulo-endothelial system in the haemolytic process is briefly discussed—the resulting decision being that no precise data are available to enable any conclusions to be reached either upon the part that this system plays in actually destroying red cells, or elaborating haemolysins that later lyse the cells.Proteolytic enzymes may be produced in the macrophages of the reticulo-endothelial system and these have been shown to be capable of destroying red and white cells.     

Caring for a relative with dementia: family caregiver burden

AIM: This paper is a report of part of a study to investigate the burden experienced by families giving care to a relative with dementia, the consequences of care for the mental health of the primary caregiver and the strategies families use to cope with the care giving stressors. BACKGROUND: The cost of caring for people with dementia is enormous, both monetary and psychological. Partners, relatives and friends who take care of patients experience emotional, physical and financial stress, and care giving demands are central to decisions on patient institutionalization. METHOD: A volunteer sample of 172 caregiver/care recipient dyads participated in the study in Cyprus in 2004-2005. All patients were suffering from probable Alzheimer's type dementia and were recruited from neurology clinics. Data were collected using the Memory and Behaviour Problem Checklist, Burden Interview, Center for Epidemiological Studies-Depression scale and Ways of Coping Questionnaire. FINDINGS: The results showed that 68.02% of caregivers were highly burdened and 65% exhibited depressive symptoms. Burden was related to patient psychopathology and caregiver sex, income and level of education. There was no statistically significant difference in level of burden or depression when patients lived in the community or in institutions. High scores in the burden scale were associated with use of emotional-focused coping strategies, while less burdened relatives used more problem-solving approaches to care-giving demands. CONCLUSION: Caregivers, especially women, need individualized, specific training in how to understand and manage the behaviour of relatives with dementia and how to cope with their own feelings.     

Blood pressure variability and white matter hyperintensities in older adults with cardiovascular disease

The present study examined the relationship between multiple blood pressure (BP) indices and white matter hyperintensities (WMH) in a sample of 39 older adults with cardiovascular disease (CVD). Resting BP was measured using an automated monitor every 10 min for 2 h. WMH were quantified on FLAIR images and separate indices were generated for neocortical, periventricular and subcortical brain regions. Correlation analyses revealed systolic BP variability was related to neocortical and total WMH. A function of systolic BP variability and average diastolic pressure showed the strongest relationships, including significant correlation to neocortical, subcortical and total WMH. No BP index was related to WMH in periventricular regions. Exploratory analyses showed only the function of systolic BP variability and average diastolic pressure predicted total WMH, whereas as age, CVD conditions and psychosocial factors did not. These findings demonstrate BP variability is an important contributor to WMH in older adults with CVD and suggests it may have differential relationships to WMH in different brain regions. Additional studies are needed to examine the role of autoregulatory systems in the development of WMH, particularly those using beat-to-beat measures of BP.     

Short tandem repeat and human leukocyte antigen mutations or losses confound engraftment and typing analysis in hematopoietic stem cell transplants

Clonal chromosomal abnormalities are often found in the tumor cells of patients with malignancies. These abnormalities can cause downregulation of human leukocyte antigen (HLA) and instability of short tandem repeat (STR) DNA sequences, confounding HLA typing and/or engraftment analysis in hematopoietic stem cell transplants (HSCT). We describe here the abnormalities observed during testing of 600 HSCT patients. HLA molecular typing was performed by reference strand conformational analyses and/or sequence-based typing. STR testing was performed with 10 to 16 STR primer sets, following 1 to 4 informative loci in each patient. Eight patients exhibited either loss of heterozygosity (4 STR, 3 HLA) or STR length mutation (n = 1), and 5 of the 8 exhibited correlative cytogenetic abnormalities. Diagnoses were acute myelogenous leukemia (AML; n = 7) or myelofibrosis (MFIB: n = 1), yielding an 11% incidence of these chromosomal abnormalities among the subset of 72 AML/MFIB HSCT patients. These results highlight some of the problems encountered and the possibility for interpretive errors that can arise when analyzing molecular typing and engraftment data, particularly among AML/MFIB patients.     

Cefpodoxime 10 μg disc screening test for detection of Neisseria gonorrhoeae with mosaic PBP2 and decreased susceptibility to extended-spectrum cephalosporins for public health purposes

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae remains a global public health problem. Susceptibility to first-line treatment extended-spectrum cephalosporins (ESCs) is decreasing worldwide resulting in therapeutic failures with oral ESCs. This study describes a cefpodoxime 10 μg disc test for screening for gonococci containing a penA mosaic allele encoding a mosaic penicillin-binding protein 2 (PBP2) and decreased ESC susceptibility. Selected clinical gonococcal isolates (n = 315), containing a high proportion of gonococci with decreased ESC susceptibility and high geographical, temporal and genetic diversity, were examined using agar dilution (n = 149; cefpodoxime and ceftriaxone) and Etest (n = 315; cefixime), and disc diffusion using a commercially available cefpodoxime 10 μg disc (n = 315). penA sequencing was performed on all isolates. The 2008 WHO gonococcal reference strains (n = 8) were included as quality controls. Using a ≤11 mm annular radius of growth inhibition as the breakpoint for the cefpodoxime 10 μg disc, all 78, with exception of one isolate (13 mm), mosaic PBP2-containing isolates, which also displayed decreased susceptibility to oral ESCs, were identified. In addition, 85 non-mosaic PBP2-containing isolates (44% of which contained a PBP2 A501 alteration) had annular radii ≤11 mm and raised minimal inhibitory concentrations to the ESCs. Screening for detection of mosaic PBP2-containing gonococci and decreased ESC susceptibility, most pronounced to oral ESCs, using a commercially available cefpodoxime 10 μg disc was rapid, inexpensive and sensitive. This test can be used in AMR surveillance programmes for public health purposes especially in less-resourced settings. Further studies to refine this disc testing-based approach are in progress.     

Evaluation of six commercial nucleic acid amplification tests for detection of Neisseria gonorrhoeae and other Neisseria species

Molecular detection of Neisseria gonorrhoeae in extragenital samples may result in false-positive results due to cross-reaction with commensal Neisseria species or Neisseria meningitidis. This study examined 450 characterized clinical culture isolates, comprising 216 N. gonorrhoeae isolates and 234 isolates of nongonococcal Neisseria species (n = 218) and 16 isolates of other closely related bacteria, with six commercial nucleic acid amplification tests (NAATs). The six NAATs tested were Gen-Probe APTIMA COMBO 2 and APTIMA GC, Roche COBAS Amplicor CT/NG and COBAS 4800 CT/NG tests, BD ProbeTec GC Qx amplified DNA assay, and Abbott RealTime CT/NG test. All assays except COBAS Amplicor CT/NG test where four (1.9%) isolates were not detected showed a positive result with all N. gonorrhoeae isolates (n = 216). Among the 234 nongonococcal isolates examined, initial results from all assays displayed some false-positive results due to cross-reactions. Specifically, the COBAS Amplicor and ProbeTec tests showed the highest number of false-positive results, detecting 33 (14.1%) and 26 (11%) nongonococcal Neisseria isolates, respectively. On the first testing, APTIMA COMBO 2, APTIMA GC, Abbott RealTime, and Roche COBAS 4800 showed lower level of cross-reactions with five (2.1%), four (1.7%), two (1%), and two (1%) of the isolates showing low-level positivity, respectively. Upon retesting of these nine nongonococcal isolates using freshly cultured colonies, none were positive by the APTIMA COMBO 2, Abbott RealTime, or COBAS 4800 test. In conclusion, the COBAS Amplicor and ProbeTec tests displayed high number of false-positive results, while the remaining NAATs showed only sporadic low-level false-positive results. Supplementary testing for confirmation of N. gonorrhoeae NAATs remains recommended with all samples tested, in particular those from extragenital sites.     

Intersecting Guidelines: Administering Erythropoiesis-Stimulating Agents to Chronic Kidney Disease Patients with Cancer

There has been a dramatic sea change in the use of erythropoiesis-stimulating agents (ESAs) for anemic persons with chronic kidney disease (CKD) or cancer patients undergoing chemotherapy. An important area that has not been addressed previously is a CKD patient who also has a malignancy. Clinical guidelines exist that outline recommended treatments for each disease, but the intersection of the two disease processes presents difficult decisions for patients and physicians. Herein, we review the background underlying recent revisions in clinical alerts and guidelines for ESAs, and provide guidance for treating anemia among CKD patients who are receiving no therapy, chemotherapy with curative intent, or chemotherapy with palliative intent. The guiding principle is that comprehensive assessment of risks and benefits in the relevant clinical setting is imperative.