The platelet defect in leukemia. Platelet ultrastructure, adenine nucleotide metabolism, and the release reaction.

The ultrastructure and adenine nucleotide metabolism of platelets from patients with acute leukemia were studied to elucidate possible mechanisms for the platelet dysfunction observed in this clinical setting. Nonstimulated (resting) platelets from leukemic patients varied greatly in size; exhibited marked variation in the number of alpha granules present per cell; had poorly delineated circumferential bands of microtubules; and often grossly dilated open channel systems or cytoplasmic vacuolization. The intracellular concentrations of ATP and ADP were significantly below normal, and the specific radioactivity of ATP and ADP of nonstimulated platelets in leukemia was equivalent to or exceeded that seen in stimulated normal platelets. Addition of ADP or collagen to platelets from leukemic patients was followed by retarded and incomplete shape change, delayed and incomplete centripetal migration of subcellular organelles, impaired degranulation, and the formation of loose aggregates composed of relatively few platelets. Stimulation of "leukemic" platelets with collagen led to the release of significantly subnormal amounts of ATP and ADP and no significant change in the specific radioactivity of the intracellular nucleotides. In contrast to the results in normal platelets, the conversion of ATP to inosine monophosphate and hypoxanthine in platelets in leukemia failed to increase significantly with collagen stimulation. The results indicate that abnormalities exist in the storage pool of adenine nucleotides and the release mechanism of platelets in acute leukemia. These defects appear to contribute to an impairment in the release reaction in these platelets. Many of the ultrastructural and metabolic defects seen in acute leukemia occur in platelets in preleukemia.     

Sepsis: an arginine deficiency state?

OBJECTIVE: Sepsis is a major health problem considering its significant morbidity and mortality rate. The amino acid L-arginine has recently received substantial attention in relation to human sepsis. However, knowledge of arginine metabolism during sepsis is limited. Therefore, we reviewed the current knowledge about arginine metabolism in sepsis. DATA SOURCE: This review summarizes the literature on arginine metabolism both in general and in relation to sepsis. Moreover, arginine-related therapies are reviewed and discussed, which includes therapies of both nitric oxide (NO) and arginine administration and therapies directed toward inhibition of NO. DATA: In sepsis, protein breakdown is increased, which is a key process to maintain arginine delivery, because both endogenous de novo production from citrulline and food intake are reduced. Arginine catabolism, on the other hand, is markedly increased by enhanced use of arginine in the arginase and NO pathways. As a result, lowered plasma arginine levels are usually found. Clinical symptoms of sepsis that are related to changes in arginine metabolism are mainly related to hemodynamic alterations and diminished microcirculation. NO administration and arginine supplementation as a monotherapy demonstrated beneficial effects, whereas nonselective NO synthase inhibition seemed not to be beneficial, and selective NO synthase 2 inhibition was not beneficial overall. CONCLUSIONS: Because sepsis has all the characteristics of an arginine-deficiency state, we hypothesise that arginine supplementation is a logical option in the treatment of sepsis. This is supported by substantial experimental and clinical data on NO donors and NO inhibitors. However, further evidence is required to prove our hypothesis.     

Inhibition of human lymphocyte reactivity by plasma fibronectin in vitro

The effect of purified human plasma fibronectin (FN) on the reactivity of human lymphocyte-rich mononuclear cells to mitogens and allogeneic cell interactions was studied. Concentrations of FN from 25 to 100 micrograms per 250 microL of culture consistently depressed phytohemagglutinin (PHA) responses. To exert an inhibitory effect, FN must be present within 20 hours after the addition of PHA to cells, and, therefore, it appears to interfere with early events in the transformation process. Increasing the concentration of PHA failed to reduce the inhibitory effect of FN, which suggests that the depressed response was not the result of FN-PHA complex formation, which would reduce the amount of mitogen available for stimulation. This possibility was supported by the finding that FN also inhibited the mixed lymphocyte response (MLR), in a reaction that was not dependent on the activity of soluble antigen or mitogen. In contrast, the stimulation of lymphocytes to undergo transformation that is induced by the nonlectin mitogen, sodium periodate, was unaffected by FN. Periodate-treated cells are, however, already stimulated to undergo transformation, prior to their exposure to FN. FN did not interfere with the activity of interleukin-2, nor did it indirectly regulate lymphocyte responses by modifying the production and/or effect of humoral regulatory factors released from the adherent accessory cells (macrophages). These studies show that FN is a potent immunosuppressive agent in vitro.     

Adult patients' perceptions of pain management at triage: a small exploratory study

Research studies reveal that pain management in Accident and Emergency (A&E) is often sub-optimal. The administration of simple oral analgesics at triage in a large teaching hospital provided the rationale to explore pain management in A&E from the patient's perspective in a small-scale exploratory study using a broadly qualitative approach. Structured interviews using open-ended questions and lasting no longer than 20 minutes explored patients' experiences and opinions of pain assessment, and pain management at triage. A sample of convenience produced a group of 65 patients from which 18 patients; 9 males and 9 females participated. Analysis of the data revealed that 16 patients presented in pain. Triage nurses trained to administer analgesics were available for 7 patients; 2 patients received analgesia. Six patients did not receive a pain assessment and in 3 cases the triage nurse was trained to administer analgesia. Sixteen patients considered pain management at triage to be important. The study reinforces the subjective and complex nature of pain, raises pragmatic questions regarding triage, the need for sustained education and training with any advance in nursing practice and further research regarding patients' perceptions of pain management in A&E.     

The theory-practice gap: ECMO research example

AIM: The time taken for research findings to enter clinical practice can be very lengthy. A contributing factor is the time lag between the research literature identifying the issue, and medical and nursing texts discussing it. The example of ECMO (Extracorporeal Membrane Oxygenation) is used to examine this issue, specifically the extent to which relevant nursing journals and textbooks discuss the effects of ECMO on medication. METHOD: A systematic review of papers identifying the problem (pharmacokinetics in ECMO patients) and the dissemination of this to clinicians was undertaken. Publications used by those exploring the problem were most likely to be found in Medline, and those disseminating to nurses in CINAHL. Textbooks on neonatal nursing and paediatric intensive care with sections on ECMO were also explored. RESULTS: There are several studies that show drug delivery is altered in patients receiving ECMO, dating back to 1989. Only three papers likely to be accessed by clinicians were found to address the effect of ECMO on drug delivery. Two of the textbooks addressed these issues but it took eight years from the issue being first raised to any medical or nursing text discussing it. CONCLUSION: Nurses will most likely not be aware of the latest research in their area if they rely on textbooks. Advanced education that gives critical appraisal and literature-searching skills, such as found in master's courses, should help the clinical nurse employ evidence based practice.