Myeloperoxidase and eosinophil peroxidase catalyzed the oxidation of bromide ion by hydrogen peroxide (H2O2) and produced a brominating agent that reacted with amine compounds to form bromamines, which are long-lived oxidants containing covalent nitrogen-bromine bonds. Results were consistent with oxidation of bromide to an equilibrium mixture of hypobromous acid (HOBr) and hypobromite ion (OBr-). Up to 1 mol of bromamine was produced per mole of H2O2, indicating that bromamine formation prevented the reduction of HOBr/OBr- by H2O2 and the loss of oxidizing and brominating activity. Bromamines differed from HOBr/OBr- in that bromamines reacted slowly with H2O2, were not reduced by dimethyl sulfoxide, and had absorption spectra similar to those of chloramines, but shifted 36 nm toward higher wavelengths. Mono- and di-bromo derivatives (RNHBr and RNHBr2) of the beta-amino acid taurine were relatively stable with half-lives of 70 and 16 h at pH 7, 37 degrees C. The mono-bromamine was obtained with a 200-fold excess of amine over the amount of HOBr/OBr- and the di-bromamine at a 2:1 ratio of HOBr/OBr- to the amine. In the presence of physiologic levels of both bromide (0.1 mM) and chloride (0.1 M), myeloperoxidase and eosinophil peroxidase produced mixtures of bromamines and chloramines containing 6 +/- 4% and 88 +/- 4% bromamine. In contrast, only the mono-chloramine derivative (RNHCl) was formed when a mixture of hypochlorous acid (HOCl) and hypochlorite ion (OCl-) was added to solutions containing bromide and excess amine. The rapid formation of the chloramine prevented the oxidation of bromide by HOCl/OCl-, and the chloramine did not react with bromide within 1 h at 37 degrees C. The results indicate that when enzyme-catalyzed bromide or chloride oxidation took place in the presence of an amine compound at 10 mM or higher, bromamines were not produced in secondary reactions such as the oxidation of bromide by HOCl/OCl- and the exchange of bromide with chlorine atoms of chloramines. Therefore, the amount of bromamine produced by myeloperoxidase or eosinophil peroxidase was equal to the amount of bromide oxidized by the enzyme. Bromide was preferred over chloride as the substrate for both enzymes.
Infections caused by Cunninghamella bertholletiae are being identified with increasing frequency in immunocompromised patients. We have treated two children with cancer for pulmonary infections caused by this rare fungus. Cunninghamella infection is found in a variety of populations of patients, including both children and adults undergoing chemotherapy. Clinical signs and symptoms are indistinguishable from those of other forms of zygomycosis. Outcome is poor: only three of 17 patients with such infection (including one of the two children described herein) have survived. Treatment involves aggressive surgical excision and administration of amphotericin B.
Background. The pulmonary toxicity of bleomycin‐containing chemotherapy combined with mantle radiotherapy in children treated for Hodgkin's disease was longitudinally assessed.
Methods. The results of serial pulmonary function studies in 37 children, newly diagnosed and treated at St. Jude Children's Research Hospital between September 23, 1983, and June 30, 1988, with cyclophosphamide, vincristine, and procarbazine (COP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus low dose mantle radiotherapy are analyzed. All patients had pulmonary function studies at least before the first bleomycin dose, after completion of radiotherapy, and serially upon discontinuation of therapy. Bleomycin therapy was withheld whenever measured carbon monoxide diffusing capacity was less than 50% of the dieted value.
Results. Vital capacity, diffusing capacity, diffusing capacity per unit of alveolar volume declined the first 6 months of therapy but improved there‐after. At 2 years postdiagnosis, diffusing capacity per unit of alveolar volume remained significantly reduced. Only one patient was symptomatic at the 2‐year point. The survival rate of these patients was 95% at a median follow‐up of 93 months.
Conclusion. If bleomycin is withheld when diffusing capacity is diminished to 50% predicted, clinical compromise of pulmonary function appears to be minimal in pediatric patients receiving alternating cycles of COP/ABVD in combination with low‐dose mantle radiotherapy. Survival was excellent, even with reduction of the total bleomycin dose.
Thirty patients (ages 5 to 13) hospitalized in a pediatric oncology intensive care unit (ICU) rated the presence and severity of their pain on the Faces Pain Scale (FPS) and the Poker Chip Tool (PCT). Parents independently rated the child's pain on these scales and each patient's nurse completed the Objective Pain Scale (OPS). Patients' ratings on the FPS correlated significantly with parents' ratings on this scale (tau = .48, P = .002) but not on the PCT (tau = .23, P = .16). Nurses' ratings on the OPS were moderately correlated with patients' FPS ratings (tau = .37, P = .02) but were only weakly associated with PCT ratings (tau = .27, P = .09). The majority of patients, parents, and nurses expressed a preference for the FPS over the PCT. The FPS appears to be a clinically useful and accurate approach for measuring the pain of pediatric oncology patients in an ICU but is limited to those who can participate in a self-report measurement.
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