David C. Dale

WEGENER'S GRANULOMATOSIS

SummaryThe clinical entity now known as Wegeners granulomatosis was first reported in 1936. Since then the diseases histopathology has been clarified, although its etiology remains unknown. Treatment requires immunosuppressant therapy and careful following of affected patients. The present report reviews the historical background for the discovering of Wegeners granulomatosis and current clinical considerations.

Colchicine therapy for familial mediterranean fever. A double-blind trial.

Abstract Eleven patients with long standing familial Mediterranean fever were studied in a double-blind trial using daily colchicine or placebo. During 60 courses of placebo, 38 attacks of familial...

Comparison of agents producing a neutrophilic leukocytosis in man. Hydrocortisone, prednisone, endotoxin, and etiocholanolone.

To study the potential application of glucocorticosteroid administration for the measurement of the bone marrow neutrophil reserve response, blood neutrophil count changes were measured in normal subjects after the administration of intravenous hydrocortisone (25, 50, 100, 200, and 400 mg) and oral prednisone (5, 10, 20, 40, and 80 mg). The upper three doses of both steroids increased the blood neutrophil count by approximately 4,000 cells/mm3. The neutrophilia occurring after hydrocortisone (200 mg) and/or prednisone (40 mg) was compared with that observed after endotoxin (0.8 ng/kg) and etiocholanolone (0.1 mg/kg) in 14 normal subjects, 7 patients with Wegeners granulomatosis on cyclophosphamide therapy and 10 patients with chronic idiopathic neutropenia. The normal responses (mean increase of blood neutrophils/mm3 above base line +/- 1 SEM) were: hydrocortisone 4,220 +/- 320, prednisone 4,610 +/- 360, endotoxin 6,060 +/- 880, and etiocholanolone 3,780 +/- 440. In the patient studies, etiocholanolone gave the smallest mean responses, but, in general, the results were similar for all agents. These data indicate that these glucocorticosteroids can be used as equivalent agents to endotoxin and etiocholanolone for measuring the neutrophil reserve response.

Alternate day prednisone. Leukocyte kinetics and susceptibility to infections

Abstract The effects of alternate-day and daily prednisone on leukocyte kinetics were studied in 20 patients with inflammatory diseases to investigate the mechanisms of corticosteroid-induced susceptibility to infections. With daily prednisone, both neutrophil and monocyte inflammatory responses were significantly decreased. In patients on alternate-day prednisone, who were studied during the day on which prednisone was administered, neutrophilia and monocytopenia occurred, and cutaneous inflammatory responses of monocytes, but not of neutrophils, were significantly reduced. On the day of therapy of alternate-day prednisone and with daily therapy the half-life of labeled blood neutrophils was significantly prolonged, and the prolongation was proportional to the dose of the drug given. In contrast, in patients maintained on alternate-day prednisone therapy and studied on the day off drug, leukocyte counts, inflammatory responses and neutrophil half-life were normal. (N Engl J Med 291:1154–1158, 1974)

Factitious fever and self-induced infection: a report of 32 cases and review of the literature.

We review in detail the syndromes of factitious fever and self-induced infection, with discussion of 32 cases studied at the National Institutes of Health and the extensive English language literature. In addition, we describe the nature of the underlying psychiatric illnesses and present guidelines for the diagnosis and management of these patients.

Periodic Hematopoiesis in Human Cyclic Neutropenia

Human cyclic neutropenia is characterized by severe depression of blood neutrophil levels approximately every 21 days. To investigate the mechanism of cyclic neutropenia four patients were studied with daily complete blood counts, serial bone marrow examinations, marrow reserve testing, serum muramidase determinations, DF(22)P granulocytokinetic studies, and, in one patient, in vivo [(3)H]TdR labeling. Periodogram analysis of the serial blood counts in the latter patient and visual inspection of multiple cycles in the others revealed periodic fluctuations in the levels of blood neutrophils, monocytes, lymphocytes, reticulocytes, and platelets. Rhythmic changes in the morphologic and radioisotopic studies as well as the marrow reserve tests and muramidase measurements were consonant with a mechanism of periodic failure of marrow production rather than peripheral destruction. Human cyclic neutropenia is analogous to cyclic neutropenia in the grey collie dog and may be viewed as the consequence of cyclic hematopoiesis.

Granulocyte transfusion therapy of experimental Pseudomonas pneumonia

Pseudomonas pneumonia was produced in dogs with radiation-induced leukopenia. Treatment of this infection with either gentamicin alone or gentamicin plus daily granulocyte transfusion was compared in a randomized controlled trail. The dogs receiving granulocytes plus gentamicin survived significantly longer than those treated with gentamicin alone (P < 0.05). The Pseudomonas immunotype which was inoculated into the dogs were recovered at autopsy from none of the granulocyte-transfused dogs, whereas seven or eight of the dogs treated with gentamicin alone had the inoculated Pseudomonas immunotype in the area of induced pneumonia at autopsy. As measured by the limulus test, the granulocyte-transfused dogs also did not have endotoxemia as frequently as the dogs given only gentamicin (P < 0.05). This controlled study establishes that transfused granulocytes can favorably alter the course of experimental Pseudomonas pneumonia and suggests that granulocyte transfusion may be a useful therapy in serious bacterial infections of leukopenic subjects.

Colon ulceration and perforation in Cyclic Neutropenia

Abstract Cyclic Neutropenia is a rare hematologic disease in which regular episodes of severe neutropenia, usually accompanied by fever, mucous membrane ulceration, and abdominal pain and tenderness, recur at approximately 3-wk intervals. 1,2 A patient with this disease, who developed localized colon necrosis, peritonitis, and clostridial septicemia during a neutropenic period, was treated recently. Exteriorization of the colon prior to perforation allowed for staged elective resection subsequently and provided a unique opportunity to observe the cyclic formation of mucosal ulcerations in the large bowel. Although cyclic neutropenia is rarely accompanied by life-threatening infection, this case serves to emphasize the potential severity of such a complication. Furthermore, abdominal pain, should it occur, merits careful observation since unrecognized colon necrosis has been the cause of death in previously reported cases of this disease. 4,5

Correction of human cyclic neutropenia with prednisolone.

A 70-year-old woman with cyclic neutropenia was treated with 16 mg of etiocholanolone and 25 mg of prednisolone intramuscularly every other day. During 14 weeks treatment amplitude of cyclic fluctuations in neutrophil counts gradually decreased, but pretreatment cycles returned promptly after treatment was stopped. Prednisolone alone every other day (25 mg) reproduced this result, and by 23 weeks, neutrophil counts became stable at about 1500 per cubic millimeter. tcycling of monocytes, platelets and reticulocytes was also eliminated, as were symptoms that had accompanied neutropenic periods. In addition, bone-marrow neutrophil precursors and neutrophil marrow reserves were stabilized. The patient was subsequently maintained satisfactorily with oral prednisolone, 20 mg every other day. These studies demonstrate that the discontinuous myeloid maturation that occurs in cyclic neutropenia can be corrected with prednisolone every other day.

Lactoferrin—Specific Localization in the Nuclei of Human Polymorphonuclear Neutrophilic Leukocytes

Summary Lactoferrin, a pink iron binding protein first isolated from bovine milk has been found in the nuclei and/or nuclear membrane of mature polymorphonuclear neutrophilic leukocytes. It is absent from all other cells of the hematopoietic system. Grossly normal amounts of lactoferrin were found to be present in the neutrophiles from patients with a variety of hematological abnormalities.