Arthur R. Page

Defective Polymorphonuclear-Leukocyte Function and Chronic Granulomatous Disease in Two Female Children

Abstract In vitro studies of polymorphonuclear-leukocyte function in two female patients with clinical and pathological features of chronic granulomatous disease of childhood showed defective bacte...

The pattern of genetic transmission of the leukocyte defect in fatal granulomatous disease of childhood

The leukocyte-phagocytic function test which was found to be abnormal in boys with fatal granulomatous disease of childhood has been found to be abnormal to an intermediate extent in their mothers. Nine of nine mothers were shown to be abnormal, whereas none of eight fathers and none of five healthy brothers exhibited a defect. 10 of 16 female siblings were abnormal to the same degree as their mothers, as were all three maternal grandmothers available for study. Assuming that this intermediate functional defect represents the heterozygous state, the nine family pedigrees are entirely compatible with the concept that the trait is transmitted on the X-chromosome.A tetrazolium dye-phagocytosis histochemical test was also abnormal in the carrier females and provided independent confirmation of the selection of the female siblings suspected of being carriers for the trait. In addition, this procedure gives indirect evidence that the gene in question is subject to the random inactivation that appears to affect many X-linked genes in mammalian females. The family members were also studied with two of the metabolic assays that have been shown to be abnormal in the cells of affected boys. One assay, the oxidation of the first carbon of glucose-1-(14)C by the isolated leukocytes, was significantly abnormal in the cells of carrier females. The other assay, the oxidation of formate-(14)C by leukocytes of heterozygotes was not significantly different from control values. The practical problem of diagnosing patients would appear to be best solved with a tetrazolium dye procedure, whereas the more subtle abnormality in carrier females is best detected with the leukocyte function test. Improved methods for the function test are being developed.

Suppression of plasma cell hepatitis with 6-mercaptopurine

Abstract Four patients with plasma cell hepatitis were treated with 6-mercaptopurine (6-MP). In each case evidence of liver disease, as measured by liver function tests, was suppressed. Studies in human beings on the effect of 6-mercaptopurine on antibody production and on the expression of delayed hypersensitivity showed no effect with the dosages used. 6-Mercuptopurine in a dose of 1.5 mg. per kg. was effective in reducing the inflammatory response in half the patients studied. This antiinflammatory effect was not seen in the three patients with plasma cell hepatitis studied. Evidence from other laboratories indicates that 6-mercaptopurine prevents virus replication. We think that the best explanation of the effect of 6-mercaptopurine on plasma cell hepatitis is that it suppresses a chronic virus infection.

Wheal and erythema allergy in patients with agammaglobulinemia.

Abstract Atopic diseases have been reported in patients with low gamma globulin levels, associated with demonstrable skin-sensitizing antibodies in some cases. One patient is reported here who lost previous wheal and erythema sensitivity when she developed a severe hypogammaglobulinemia. Typical atopic dermatitis occurred in 4 of 23 boys with congenital, sex-linked, recessive agammaglobulinemia. No wheal and erythema allergy was demontrable in any of these patients. Attempts to induce the development of skin-sensitizing antibodies to an Ascaris extract in 6 congenital agammaglobulinemic patients were uniformly unsuccessful. These patients did, however, all develop delayed sensitivity to the Ascaris.

Long-term results of therapy in patients with chronic liver disease associated with hypergammaglobulinemia

Abstract Analysis of the long-term results of aggressive therapy in a group of twenty-one patients with chronic liver disease and marked hypergammaglobulinemia revealed improvement in survival when this group is compared by a life-table technic to previously published untreated series of patients. Most of the patients who responded favorably to therapy showed improvement in liver structure in serial biopsy specimens. An analysis of clinical and laboratory findings revealed a constellation of prognostic indicators that may prove helpful in predicting response to therapy.

Metabolic and Functional Studies of Monocytes in Congenital Neutropenia

Summary. Children with the severe form of congenital neutropenia usually die from infection by 2 yr of age. Metabolic and functional studies of monocytes from three patients with this disease were undertaken to understand further the role of monocytes in the hosts defences against bacterial infection. The bactericidal capacity of monocytes compared favourably to the bactericidal capacity of control neutrophils (PMN). Metabolic studies of monocytes and control leucocytes showed similar stimulation of oxygen consumption, hexose monophosphate pathway activity arid 125iodide fixation during phagocytosis. Further, myeloperoxidase (MPO) activity of patients’monocytes was comparable to the activity of control leucocytes. Using the Rebuck skin window, very few of the patients’mononuclcar cells were seen to migrate during the initial 2–4 hr of observation. During this time, the PMN migration of controls was maximal. Following the relatively acellular period observed in patients, a brisk mononuclear cell infiltration occurred apparently independent of the presence of neutrophils. Epinephrine injection into patients stimulated a marked increase of blood monocytes, suggesting the existence of a marginal monocyte pool. An injection of hydrocortisone caused an unexplained 3–8‐fold decrease in circulating monocytes. The delay of phagocytic cell migration to an inflammatory site, and the apparent sensitivity of monocytes to hydrocortisone may account in part for the increased susceptibility to infection in patients with severe congenital neutropenia.

A study of steroid-induced granulocytosis in a patient with chronic benign neutropenia of childhood.

An infant with chronic benign neutropenia of childhood was found to respond to a sudden, transient, stress‐induced rise in plasma corticoid level with a pronounced rise in peripheral neutrophil count. Neutrophil survival studies were performed following this stress‐induced neutrophilia and during and following hydrocortisone stimulation. Measurement of the decline in total neutrophil‐associated radioactivity showed that neurophils were removed from the circulation at a normal rate while measurement of neutrophil specific activity indicated that the observed steroid‐induced granulocytosis was a result of marrow released of neurtrophils.

Passive Transfer with Circulating Leukocytes of Delayed Hypersensitivity to Cat Scratch Antigen.

Summary Delayed type hypersensitivity to cat scratch disease can be passively transferred by blood leukocytes, but not by plasma from hypersensitive donors convalescent from the disease.

Immunodeficiency, xanthomas and obstructive liver disease

Chronic obstructive liver disease and secondary hyperlipidemia developed in an immunodeficient boy. Sequential addition of cholestyramine and phenobarbital to his medical regimen, following an initial response to bile drainage, resulted in the disappearance of xanthomas and pruritus, and the restoration of normal serum concentrations of lipids and bile acids. This improvement may result from shifting the bile acid pool from the peripheral blood compartment to the enterohepatic circulation.