Contrasting effects of recombinant human granulocyte-macrophage colony- stimulating factor (CSF) and granulocyte CSF treatment on the cycling of blood elements in childhood-onset cyclic neutropenia

Recombinant human granulocyte colony-stimulating factor (G-CSF) treatment has been shown to increase average neutrophil counts substantially in patients with childhood-onset cyclic neutropenia (or "cyclic hematopoiesis"), but not to eliminate the cyclic oscillations of neutrophil counts or those of other blood elements (monocytes, platelets, eosinophils, and reticulocytes) that are characteristic of this hematopoietic disorder. Indeed, oscillations of neutrophil counts are amplified during G-CSF treatment. We have compared the effects of recombinant granulocyte-macrophage-CSF (GM-CSF) with those of G-CSF in three patients with this disease (2 men and 1 woman, 17, 30, and 32 years of age). These patients were treated with GM-CSF (2.1 micrograms/kg/day, subcutaneously) for 6 weeks, preceded and followed by 6 to 13 weeks of detailed observation to document changes in the cyclic oscillations of blood neutrophils and other blood elements; two of the patients were subsequently treated with G-CSF (5.0 micrograms/kg/d, subcutaneously) and observed for comparable periods of time. Unlike G-CSF treatment, which increased average neutrophil counts more than 20-fold, GM-CSF increased neutrophil counts only modestly, from 1.6- to 3.9-fold, although eosinophilia of varying prominence was induced in each patient. However, at the same time, GM-CSF treatment dampened or eliminated the multilineage oscillations of circulating blood elements (neutrophils, monocytes, platelets, and/or reticulocytes) in each of the patients. In contrast, G-CSF treatment of the same patients markedly amplified the oscillations of neutrophil counts and caused the cycling of other blood elements (monocytes in particular) to become more distinct. These findings support the conclusion that the distinctive cycling of blood cell production in childhood-onset cyclic neutropenia results from abnormalities in the coordinate regulation of both GM-CSF-responsive, multipotential progenitor cells and G-CSF-responsive, lineage-restricted, neutrophil progenitors.     

Critical Role of Trauma and Emergency Surgery Physicians in Patient Satisfaction: An Analysis of Consumer Assessment of Healthcare Providers and Systems,Hospital Version Data from 186,779 Patients and 168 Hospitals in a National Healthcare System

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A Critical Perspective on the Role of Catheter Ablation in Management of Atrial Fibrillation

Catheter ablation for atrial fibrillation (AF) is a procedural treatment option that has yet to find its final place in AF rhythm management. So far, other than pulmonary vein isolation, it does not have an indisputable mechanistic basis. It is empirical, not truly individualized on the basis of a diagnostic procedure. Success for the procedure is usually couched in terms of a measure of recurrence of AF. Existing data concerning recurrence have several confounders. Recurrence data are often subjective: They are based on surveys and symptoms rather than objective electrocardiogram (ECG) determination of recurrence, patients are highly selected, concurrent use of antiarrhythmic drugs is included or excluded, redo procedures may or may not be included, and follow-up is frequently a year or less. The nature of the AF (paroxysmal, persistent, long-standing persistent) greatly impacts success rates, which range from 20% to 85%. The procedure is probably infrequently a lifelong “cure” for AF. Best estimate of the risk of a complication from each procedure is about 4.5%, the commonest being tamponade (1.3%), vascular access complications (1.5%), and stroke or transient ischemic attach (1%). Risk of a fatal complication is estimated at 0.15%. There is no convincing evidence that the procedure decreases the risk of death, stroke, or hospitalization for heart failure, but the available randomized trials have enrolled patients inappropriate for assessment of impact on these clinical outcomes. Much remains to be done. Currently the procedure is indicated for relief of symptoms in selected patients, usually who have failed antiarrhythmic drug therapy.     

Percutaneous fluoroscopic removal of a knotted Swan–Ganz catheter in a patient with a persistent left‐sided superior vena cava

Knotting of intravascular catheters is an uncommon but a well‐recognized occurrence. The Swan–Ganz catheter (SGC) is the one that knots most commonly. A case of a knotted SGC is described in a patient with a persistent left‐sided superior vena cava, and we propose that the presence of a left‐sided superior vena cava is a risk factor for knot formation not previously reported. We review the published work on the risk factors for knot formation and on the techniques used to remove knotted SGC. We describe a technique using a gooseneck snare and Omni Flush catheter (Angiodynamics, Queensbury, NY, USA) to loosen and untie a knotted SGC.     

Maternal hemoglobin F levels may have an adverse effect on neonatal birth weight in pregnancies with sickle cell disease

A total of 26 patients with sickle cell disease were followed up through 32 pregnancies. There was no correlation between days in hospital or number of painful crises and either birth weight or birth weight percentile. The number of dense irreversibly sickled and least deformable cells was negatively correlated with birth weight percentile (r = -0.63, p less than 0.01). Patients' initial hemoglobin levels were positively correlated with birth weight percentile (r = 0.52, p less than 0.004). Hemoglobin F, on the other hand, was significantly inversely correlated with birth weight percentile. Nine pregnancies with small-for-gestational-age infants had an average hemoglobin level of 9.1% +/- 4.5%. In contrast, patients who were delivered of appropriate-for-gestational-age infants (23 pregnancies) had an average hemoglobin F level of 3.6% +/- 2.9% (p less than 0.01). We conclude that total hemoglobin levels and dense cells are correlated with birth weight percentile; moreover, the higher the maternal hemoglobin F levels the higher the risk of small-for-gestational-age infants. We speculate that although high hemoglobin levels may be beneficial to the fetus, high maternal hemoglobin F levels could increase the desaturation of non-F cells and induce placental obstruction.     

The metabolic load of stored blood. Implications for major transfusions in infants.

Plasma electrolyte, intermediary metabolite, and hormone concentrations were measured in samples of 110 units of citrate phosphate dextrose blood being used for clinical transfusions. The most important changes from the physiological range were in sodium, potassium, glucose, and lactate concentrations. Mean sodium concentrations fell from 170 mmol/l at the beginning of storage to 156 mmol/l at the end and mean potassium concentrations rose from 7 mmol/l to 25 mmol/l. Glucose had a mean concentration of 20 mmol/l at the beginning of storage and had only fallen to 15 mmol/l at the end. Mean lactate concentrations increased from 7 mmol/l at the beginning of storage to 25 mmol/l at the end. Many samples had cortisol, insulin, and growth hormone concentrations within the physiological range. Citrate phosphate dextrose blood contains a large substrate load that changes during storage and that should be taken into account when infants are transfused large volumes of blood. The strong correlation coefficients with duration of storage for sodium, potassium, and lactate (-0.71, 0.91, and 0.90, respectively) indicate that concentrations of these substrates can be predicted within a narrow range if the duration of blood storage is known.     

Ascorbic acid prevents cognitive deficits caused by chronic administration of propionic acid to rats in the water maze

Propionic acidemia is an inherited neurometabolic disorder characterized by progressive neurological deterioration with psychomotor delay/mental retardation, convulsions and coma, and whose pathophysiology is poorly unknown. In the present study, we investigated the effect of chronic administration (from the 5th to the 28th days of life) of propionic acid (PA), the major metabolite accumulating in tissues of patients affected by propionic acidemia, on the cognitive performance of adult rats in the Morris water maze task. PA doses ranged from 1.44 to 1.92 micromol/g body weight as a function of animal age. Control rats were treated with saline in the same volumes. Chronic postnatal days (5-28) PA treatment had no effect on body weight. However, it impaired spatial performance in the water maze. We also determined the effect of ascorbic acid (AA) administered, alone or combined with PA, on the same behavioral parameters in order to test whether free radicals could be responsible for the behavioral alterations observed in PA-treated animals. AA was able to prevent the behavioral alterations provoked by PA, implying that oxidative stress may be involved in these effects. Furthermore, we also investigated the total radical-trapping antioxidant potential (TRAP) in the hippocampus of the animals. We observed that TRAP was significantly reduced in the brain of propionic acidemic rats and that co-administration of AA prevented this effect. The results provide evidence that early PA treatment induces long-lasting behavioral deficits, which are possibly caused by oxygen reactive species generation, and suggest that oxidative stress may be involved in the neuropathology of propionic acidemia.     

Life threatening ventricular arrhythmias with transient or correctable causes

Traditionally, myocardial ischemia, electrolyte disorders, and proarrhythmic drug reactions have been considered transient and correctable causes of life threatening ventricular tachyarrhythmias. Recent evidence suggests that patients whose ventricular tachyarrhythmias are attributed to these "causes" have a poor outcome. This overview reviews the available literature examining ischemia, electrolyte disorders and pro-arrhythmic drug reactions as potentially reversible causes of ventricular tachycardia (VT) and ventricular fibrillation (VF). While all 3 are undoubtedly involved in the genesis of these tachyarrhythmias, and all 3 deserve particular clinical attention (outlined in the text), difficulties in the identification and/or reversal of their influences exist. Proarrhythmic drug reaction may be a reversible cause of VT/VF, hypokalemia and hypomagnesemia should be considered risk factors for VT/VF, and the role of ischemia is complex. Accordingly, physicians should use extreme caution in attributing life-threatening ventricular tachyarrhythmias to these 3 conditions. Further research is required to identify "truly reversible" causes of VT/VF.