Cloxacillin chemoprophylaxis in the Chediak-Higashi syndrome.
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Biomedical subjects
Publications and source records attributed to D C Dale.
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12 grey collie dogs had cyclic neutropenia with the neutropenia recurring at 11.8+/-0.1-day intervals. The recovery from neutropenia was accompanied by a single wave of myeloid proliferation, an increase in marrow myeloid-labeling indices, and an increase in serum muramidase levels. After recovery from neutropenia during the period when blood neutrophils (PMN) were normal or increased, marrow myeloid precursors became scarce. The decline in marrow precursors and marrow PMN reserves heralded the recurrence of neutropenia. Neither diisopropyl fluorophosphate (DF(32)P) leukokinetic studies nor the rate of development of neutropenia suggested shortened PMN survival as a mechanism for the neutropenia. These studies indicate that the cyclic neutropenia is due to a regularly recurring failure in PMN production.
Two grey collie dogs had regular cyclic fluctuations in the number of all formed elements of the blood. The period lengths for all elements for an individual dog were the same, but the pattern of fluctuation for each element was distinctive. Normal dogs lacked periodic fluctuations.The patterns of day-to-day variation in the normal dogs counts were consistent with a first-order autoregressive process of serial dependence (i.e., each observation of the series depends on the last preceding observation and no others). The grey collie counts showed the same pattern of serial dependence after the component of the over-all variability due to cyclic oscillation was removed. These data suggest that a defect of hematopoietic regulation at the stem cell level leads to periodic interruptions of production of all hematopoietic elements and accounts for the cycles seen in the peripheral blood counts.
The urinary activities for bone marrow colony formation were measured on consecutive 24-hour urine samples from two gray collie dogs with cyclic neutropenia and from two normal collies. The activity varied cyclically in the gray collies with a peak activity developing during the neutropenic phase, which antecedes the return of blood neutrophils. The activity fell to undetectable levels after the blood neutrophil counts returned to the normal range. The urine of normal dogs showed no activity. Since the dogs with cyclic neutropenia have been shown to have periodic hematopoiesis, these data suggest a regulatory hormonal role for the substance measured by this assay.
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Patients with familial Mediterranean fever (FMF) who were part of a double-blind trial of daily colchicine as prophylaxis for their disease had leukocyte functions studied while receiving colchicine or placebo. Leukocytes taken from these patients while on prophylactic doses of colchicine produced normal quantities of leukocytic pyrogen, ingested bacteria normally, and migrated normally in chemotatic chambers. In addition these patients had normal numbers of circulating T and B lymphocytes as well as normal blastogenic reponses of their peripheral lymphocytes to mitogenic stimuli. The patients on colchicine, however, had significantly fewer neutrophils and monocytes accumulating at skin-window sites 24 hours after the initial abrasion. Because the early phase of the skin-window response was normal in these patients, the decreased late response may be related to a failure to amplify the initial inflammatory reaction. The reduced capacity to generate a normal inflammatory response may account for the failure of these patients to develop full attacks while taking colchicine.
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