Practical value of a new serum digitoxin assay

The purpose of this study was to evaluate a new fluorescence polarization immunoassay, TDx, for digitoxin by comparing the results of this assay with those of a radioimmunoassay (RIA). Thirty-three serum samples were obtained from 15 patients during, and for 4 weeks after, a 4-week course of digitoxin therapy. Each sample was separated by centrifugation, coded, and frozen until analysis. At the time of analysis, each sample was divided and analyzed simultaneously by TDx and RIA. Nine samples yielded results less than 2 ng/ml (limit of assay sensitivity) by one or both methods and were excluded from further data analysis. Linear regression analysis of the results of the remaining 24 paired samples (x = TDx, y = RIA) revealed a strong correlation coefficient of r2 = 0.95, slope = 0.95, and a y intercept of -0.99 (y = -0.99 + 0.95x). Additionally, the TDx results were lower than the RIA values in only five of 33 paired samples; and these occurred in four patients who had a significantly lower mean estimated creatinine clearance than that of the other 11 patients (39.0 +/- 9.1 ml/min/1.73 m2 vs. 63.3 +/- 11.8 ml/min/1.73 m2, p less than 0.01). The TDx system is a comparable alternative to the RIA method, but differences in specificity and sensitivity may exist and should be evaluated more thoroughly.     

Neutropenic enterocolitis in adults with acute leukemia

Neutropenic enterocolitis has been previously described only by case reports and literature reviews. Of 499 adults with acute leukemia seen over a 23-year period (1962 to 1985), 13 cases (2.6%) of neutropenic enterocolitis have been reported. Eleven of these 13 patients were profoundly neutropenic (mean white blood cell count, 472/cu mm) and developed abdominal symptoms during either initial induction or relapse of acute leukemia. Histologic confirmation was available in ten cases, five cases after surgical resection and five cases at autopsy after nonoperative management. Three patients with isolated ileocecal inflammation without infarction at the time of surgery were successfully managed without resection. Five patients treated with surgery died four to 64 weeks postoperatively (mean survival, 21.6 weeks) of nonsurgical complications of leukemia. Three patients were still alive, one patient 42 months after right hemicolectomy and two patients five months after exploration only. All five patients managed medically died an average of 1.4 days (range, zero to four days) after the onset of abdominal pain. Survival in patients with acute leukemia who develop neutropenic enterocolitis is determined by early recognition and appropriate surgical exploration that can be expected to yield an acceptable operative mortality.     

Acute airway management. Role of cricothyroidotomy

Thirty-four cases of emergency cricothyroidotomy performed formed from September 1984 through January 1988 are reviewed. Thirty-one of the cases were required out of 2,200 acute-trauma patients. The indication for cricothyroidotomy was inability to establish an airway by intubation usually in a situation of possible neck injury or severe facial trauma. Fourteen of the patients died as a result of their injuries, 13 of these in the first several hours after injury. The 20 surviving patients are studied in two groups: eleven patients whose cricothyroidotomy remained in place until decannulation (group I) and nine patients who underwent tracheostomy subsequent to cricothyroidotomy (group II). Clinical follow-up included physical examination in all survivors and endoscopic evaluation in twelve patients. Three minor complications were discovered in each of the two groups and two major complications were noted in group II. The major complications included a case of tracheal stomal stenosis requiring tracheal resection and a case of partially obstructing tracheal granulation tissue requiring endoscopic resection. This study supports the use of emergency cricothyroidotomy in situations in which intubation is not successful or thought to be safe. Data is also presented that suggests that tracheostomy subsequent to emergency cricothyroidotomy does not necessarily reduce airway-related morbidity in these patients.     

Understanding cognitive development: automaticity and the early years child

In recent years a growing body of evidence has implicated deficits in the automaticity of fundamental facts such as word and number recognition in a range of disorders: including attention deficit hyperactivity disorder, dyslexia, apraxia and autism. Variously described as habits, fluency, chunking and over learning, automatic processes are best understood in terms of their distinctive properties. While typically identified as fast, parallel, attention-free processes, a commonly agreed definition of automaticity continues to elude theorists investigating this concept. Most theorists would, however, agree that since attentional resources are finite, automaticity of basic facts serves to free sufficient mental resources for a learner to focus their attention on the novel or more complex aspects of a task. Yet despite the importance of automaticity to the learner, the term remains largely unfamiliar to most educationalists and early years practitioners. In order to address this issue, the present paper seeks to review several influential theories of automaticity, to describe the problems associated with defining a process as automatic and to draw from relevant research to demonstrate how the early years environment can be organised to promote automaticity in the young learner.     

SI12Lymphocyte Subsets Following Autologous Transfer of CD25 Depleted Leukapheresis Products

The CXCL12/CXCR4 chemokine axis is a well characterized and important chemotactic stimulus/receptor unit that orchestrates the homing and migration of cells to the bone marrow and to ischemic tissues following tissue damage. Here, we demonstrate that the sialomucin, CD164, a regulator of haemopoietic precursor cell adhesion to stroma and entry of primitive CD34⁺CD38^lo/‐ precursor cells into cycle, modulates the migration of CD133⁺ cord blood cells to CXCL12 by associating with the CXCR4 receptor. This was demonstrated by a reduction in CD133⁺ cell migration on fibronectin to CXCL12 (i) by engaging the functional class II glycosylation‐dependent epitope on CD164 with the 103B2/9E10 class II but not the N6B6 class III antibody; and (ii) by RNAi knockdown of CD164 protein levels in CD133⁺ cells. The inhibition of migration was more pronounced in the more primitive CD34⁺CD38^lo/‐ cell subset. Similar studies using the Jurkat cell line confirmed these findings and led to further analyses using alternative chemokines. A direct association between CXCR4 and CD164 was demonstrated by the co‐localisation of CD164 with CXCR4 and VLA‐4 and VLA‐5 at the leading edge of CD133⁺ cells when CXCL12 was presented on fibronectin. This was further supported by immunoprecipitation studies that demonstrate in the absence of CXCL12, CXCR4 is associated only with VLA‐4 and VLA‐5 but on exposure to CXCL12, CD164 is rapidly recruited to the CXCR4 complex. Knock‐down of CD164 using siRNA revealed that signalling through CXCR4 via PKC‐ζ was significantly dampened. Our findings therefore support a novel association between three distinct families of cell surface receptors that regulate both cell migratory and proliferative responses and identify a CD164 as a key regulator of the CXCL12/CXCR4 axis.     

Esmolol for treatment of intraoperative tachycardia and/or hypertension in patients having cardiac operations. Bolus loading technique

Esmolol, administered as a bolus followed by continuous infusion, was used to treat the occurrence of transient tachycardia and hypertension or tachycardia alone before cardiopulmonary bypass in 45 patients. The study was conducted in two phases. Phase I (15 patients) was a dose-finding study and phase II (30 patients) was a randomized, double-blind, placebo-controlled efficacy study. All patients received the last dose of their usual beta-adrenergic blocker the night before the operation and were anesthetized with midazolam, vecuronium, and enflurane in oxygen. Treatment criteria were either a systolic blood pressure greater than 140 mm Hg and a heart rate greater than 70 or a heart rate greater than 80 beats/min. In phase I, graduated doses of esmolol were given to successive patients. A dose of 80 mg followed by a 12 mg/min infusion was declared effective. Phase II patients were randomized to receive esmolol (n = 16) or placebo (n = 14). Hemodynamic data were collected at baseline and 1, 3, 5, and 10 minutes after the administration of esmolol. Plasma norepinephrine was measured at baseline, 1, and 10 minutes. Esmolol significantly (p less than 0.05) reduced heart rate at 1, 3, 5, and 10 minutes but did not change blood pressure, pulmonary artery diastolic pressure, right atrial pressure, cardiac output, or systemic vascular resistance. Our results show that a bolus loading dose of esmolol is safe and effective in the treatment of tachycardia in patients with ischemic heart disease and that esmolol rapidly blocks the beta-adrenergic effects of norepinephrine associated with surgical stress.