Studies on the contact system of coagulation during therapy with high doses of recombinant IL-2: implications for septic shock

Patients treated with high doses of interleukin-2 (IL-2) because of cancer, develop hemodynamic and vasopermeability changes, that resemble those observed in sepsis. These patients thus provide a unique opportunity to study the early events in the development of septic shock. We analysed the changes that occurred in the contact system of coagulation in plasma from 4 patients, who together received seven 12-day cycles of high doses of IL-2. Levels of factor XII and prekallikrein during the cycles progressively fell to 50 and 30% of their initial levels, respectively, whereas significant increases in plasma factor XIIa- and kallikrein-C1-inhibitor complexes were not observed (in 3 out of 211 samples slightly increased levels of both complexes were found). The reductions in factor XII and prekallikrein were only in part due to protein leakage, since levels were still significantly lower, i.e., 80 and 50%, respectively, when corrected for albumin decreases. Levels of high molecular weight kininogen (HMWK) also decreased during IL-2 therapy, however, this decrease paralleled that of albumin. SDS-PAGE analysis of plasma HMWK did not reveal increased cleavage of this protein. The reduction of factor XII and prekallikrein, corrected for protein leakage, significantly correlated with albumin levels and inversely with daily cumulative weight gain in the patients. Thus, we demonstrate that factor XII and prekallikrein decrease during IL-2 therapy. As these decreases, already observed after 1 day treatment, were disproportional to that of albumin, a negative acute phase reactant, and correlated with signs of the vascular leak syndrome, we favor the explanation that they reflected activation rather than a decreased synthesis of the contact system proteins.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of 2,3,5-triphenyltetrazolium chloride staining to delineate rat brain infarcts.

BACKGROUND AND PURPOSE: Accurate and reproducible determination of the size and location of cerebral infarcts is critical for the evaluation of experimental focal cerebral ischemia. The purpose of this study was to compare intracardiac perfusion of 2,3,5-triphenyltetrazolium chloride with immersion of brain tissue in 2,3,5-triphenyltetrazolium chloride to delineate brain infarcts in rats. METHODS: After 6, 24, or 48 hours of ischemia induced by permanent middle cerebral artery occlusion, some rats were perfused with 2,3,5-triphenyltetrazolium chloride; other rats were given an overdose of barbiturates, after which brain sections were immersed in 2,3,5-triphenyltetrazolium chloride. Coronal sections were taken 4, 6, and 8 mm from the frontal pole, and infarct areas in perfused and immersed sections were compared; subsequently, the same sections were stained with hematoxylin and eosin. RESULTS: In rats subjected to 24 or 48 hours of occlusion, areas of infarction were clearly defined with both 2,3,5-triphenyltetrazolium chloride staining techniques, and the infarct sizes correlated well with the results of hematoxylin and eosin staining (r = 0.85-0.94). CONCLUSIONS: These results demonstrate that intracardiac perfusion of 2,3,5-triphenyltetrazolium chloride is an accurate, inexpensive, and efficient staining method to detect infarcted tissue 24 and 48 hours after the onset of ischemia in rats.     

Experience with a metered-dose inhaler with a spacer in the pediatric emergency department

Studies of adults suggest that metered-dose inhalers with spacers are as effective as hand-held nebulizers for bronchodilator delivery. We studied 13 children with acute asthma. They received two puffs every 2 minutes from metered-dose inhalers with spacers (range, 4 to 14 puffs) titrated until improvement stopped. Peak expiratory flow increased 34% for metered-dose inhalers with spacers after the first 2 puffs and increased 87% for metered-dose inhalers with spacers after dose titration. After titration, respiratory rate decreased by 12%, heart rate increased by 2%, and breath sounds improved in 92% of the patients. We concluded that the metered-dose inhalers with spacers are an effective device for the treatment of asthma in the pediatric emergency department and that the use of metered-dose inhalers with spacers with titration can achieve significant bronchodilation in the treatment of patients with acute asthma.     

Intratemporal vascular tumors: detection with CT and MR imaging

The diagnostic contributions of computed tomography (CT) and magnetic resonance (MR) imaging were compared in 12 patients with benign intratemporal vascular tumors (hemangioma or vascular malformation). The tumors included six in the internal acoustic canal and six in the geniculate ganglion region. Clinical and histologic correlations were made. Two of the six patients with tumors in the internal acoustic canal underwent CT, and both required gas cisternography to show the tumor. Five patients in that group underwent MR imaging, and all five studies showed the tumor. All six patients with geniculate ganglion tumors underwent CT. Results in one study were questionable, and five showed the tumor. Five patients in this group underwent MR imaging, but the MR findings were positive in only two cases. MR imaging should therefore be performed before CT in the evaluation of facial nerve dysfunction, as it demonstrated all tumors in the internal acoustic canal and some in the geniculate ganglion region. If MR findings are negative, CT should then be performed to rule out a possible geniculate ganglion lesion.     

PharmaTrend as a management tool: capturing workload data

Several methods of collecting workload data for use in PharmaTrend, a computerized pharmacy management information system, are described. Although the number of indicators produced by PharmaTrend is limited by the input of the user, the integrity of the indicators that are produced is not compromised; this allows the user to implement PharmaTrend on a limited scale, such as for workload only. Workload data that can be used in PharmaTrend are collected routinely by most pharmacies. Many activities are already recorded in logs and other noncomputerized sources. The aid of members of the pharmacy department and other departments may be enlisted in collecting these data. Self-reporting through time sheets and cards can also be used to obtain data on the distribution of work hours. Recording is simplified if employees are told to record only exceptions to their usual job responsibilities. The PharmaTrend manual contains detailed definitions of the workload categories, but simpler and more practical definitions may have to be used. A computer spreadsheet program should probably be used for compiling data if they are collected from several sources; this will facilitate entry into PharmaTrend. Simple methods are available for capturing workload data for input into the PharmaTrend program.     

Platelet antibodies in systemic lupus erythematosus

In systemic lupus erythematosus (SLE), the precise cause of the thrombocytopenia is unknown. Since platelet associated IgG is increased in many patients, it has been suggested that the destruction of platelets might be dependent on specific antibodies. In nine patients with SLE, platelet associated immunoglobulins were found together with free serum antibody which bound to platelets from all normal subjects. Using an immunoblotting technique with membrane proteins from normal platelets incubated with patient sera, target antigens were localized on a band of mol wt 108,000 in two cases (B. and N.) and on a band of mol wt 66,000 in a third (M.). When the same technique was applied to autologous platelets of patient N., autoantibody binding to the protein of mol wt 108,000 was demonstrated. The antigenic determinants were not removed from the platelets by enzyme treatment or by disulphide bond reduction, and were localized in the cytoplasmic fraction of the platelets.