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Recurrent Pseudomonas infection associated with neutrophil dysfunction.

A 72-year-old male is described with a history of 4 episodes of Pseudomonas aeruginosa sepsis and chronic otitis media caused by pseudomonas species. In vitro testing of the patient's polymorphonuclear leukocytes (PMNs) revealed profoundly abnormal chemotactic responses and defective intracellular killing of Ps. aeruginosa, Staphylococcus aureus and Escherichia coli. Chemiluminescence production by the patient's PMNs in response to opsonized zymosan as well as endotoxin stimulated nitroblue tetrazolium dye reduction were markedly depressed. These data indicate the presence of a profound, apparently acquired, defect in PMN function in an elderly male. Detailed evaluation of adult patients with recurrent infections may reveal similar, apparently acquired defects in PMN function.

Aged

An appraisal of the nitroblue tetrazolium reduction test.

The available literature on the nitroblue tetrazolium reduction test is reviewed. The mechanism of this test is poorly understood. There are two basic methods of performing the test, namely, the stimulated and the spontaneous methods. However, the test procedure has not been standardized, and numerous modifications have ensued resulting in a number of technics. The stimulated test has proved to be valuable for screening patients or carriers with chronic granulomatous disease of childhood. It is one of the useful tests in studying neutrophil dysfunction. On the other hand, extensive accumulated data indicate that this test, be it stimulted or spontaneous, cannot be relied upon as an absolute test to differentiate bacterial from nonbacterial infectious disease as there have been numerous false-positive and false-negative results. When this test is used, the result should be interpreted in the context of other laboratory test results and the clinical picture of the patient. Preliminary data indicate that in certain diseases, if the initial test is positive in a particular patient, it may be useful as one of the follow-up tests to ascertain the activity of the disease process.

Bacterial Infections

Impaired neutrophil bactericidal activity correlates with the infection occurring after surgery for esophageal cancer.

We examined whether or not preoperative impaired bactericidal activities of polymorphonuclear neutrophils (PMN) are associated with infections following surgery for esophageal cancer. Intracellular killing (KI), superoxide anion-producing capacity (SOP), and myeloperoxidase (MPO) activity were measured in 22 patients with esophageal cancer, 27 with gastric cancer, and 13 age-matched controls. The average level of KI was significantly depressed in patients with esophageal cancer or with gastric cancer, to a similar extent, compared to findings in controls, but SOP was not. In esophageal cancer patients, the SOP level was significantly higher in those with postoperative septic complications than in those without such problems, whereas the KI level was depressed to a similar extent in both. Therefore, a depression of KI with elevation of SOP of PMN may serve to predict complications of infection following surgery in patients with esophageal cancer.

Adult

[Defective polymorphonuclear leukocyte function in chronic granulomatous muco-cutaneous candidiasis (author's transl)].

Chronic granulomatous muco-cutaneous candidiasis is reported in a 12-year-old boy who died of pulmonal cryptococcosis. Chemotactic and phagocytic functions of the neutrophilic polymorphonuclear leukocytes were deficient while the cell mediated immunity was not disturbed and no decrease of immunoglobulins and complement factors--especially C3 and C5--was found in the serum. The possibility is considered that the disturbance of lymphocyte mediated immune response is the normal, but not only fundamental aetiological factor of chronic muco-cutaneous candidiasis.

Animals

Fate of the retained rectum after subtotal colectomy for inflammatory disease of the colon.

Of forty-nine consecutive patients who underwent subtotal colectomy for inflammatory disease of the colon, 73.5 per cent required subsequent combined abdominoperineal resection of the retained rectum and only two patients had successful ileoproctostomy. For the patient whose rectum is substantially diseased along with the rest of the colon, one-stage total proctocolectomy is the preferred operation.

Adolescent

Lack of cytochalasin E-induced superoxide release by polymorphonuclear leucocytes of patients with chronic granulomatous disease: a new diagnostic test.

Reduction of exogenous cytochrome c was induced by the treatment of human polymorphonuclear leucocytes with cytochalasin E. The reduction was completely inhibited by superoxide, dismutase, indicating that superoxide anions were released from the cells. The leucocytes from two patients with chronic granulomatous disease did not show the release reaction that should have been brought on by the treatment. The cytochalasin-induced reduction of exogenous cytochrome c by polymorphonuclear leucocytes is so specific and sensitive that it seems to be useful for diagnosis of chronic granulomatous disease.

Adult

Cyanide-insensitive respiration of phagocytes in oxygen-treated whole blood.

Cyanide-insensitive respiration of phagocytes has been assayed polarographically in less than 0.5 ml of oxygenated venous blood. Cell separation procedures are avoided by use of whole blood as assay sample. The method is simple and gives quantitative results. The values obtained faithfully reflect in vivo capacity of phagocytes. Blood from boys with chronic granulomatous disease showed no burst of oxygen consumption during phagocytosis. Blood from their mothers showed about one-third activity of normal blood, indicating their carrier status.

Cyanides

Antigens of the Kell blood group system on neutrophils and monocytes: their relation to chronic granulomatous disease.

KX, an antigen related to the Kell blood group system, is present in trace amounts on normal red cells and is strongly active on the neutrophils of all of 50 persons thus far tested. Normal circulating monocytes are now shown to also bear KX determinants. Absence of neutrophil KX has been associated with all of three previously tested patients with chronic granulomatous disease. In this study two male siblings with CGD also have been shown to have KX negative leukocytes, and white blood cells from their heterozygous mother were found to have a reduced competency to absorb anti-KX. Five CGD boys are known to lack KX; the probability of this occurring by chance is greater 10(-6).

Absorption

Spectrum of function of neutrophils from carriers of sex-linked chronic granulomatous disease.

Bactericidal and metabolic activities were compared for polymorphonuclear leukocytes from normal controls, patients with sex-linked chronic granulomatous disease, five obligate carriers, and six potential carriers of CGD. Bacteria surviving at one hour were quantitated in a standardized assay which employed 1.25 Staphylococcus aureus per neutrophil. Heat-killed bacteria or a chemical agent, phorbol myristate acetate, were used to stimulate increases in utilization of oxygen, oxidation of [1--14C] glucose, and reduction of neotetrazolium chloride by PMN. The results demonstrate that PMN from the individual obligate carriers of CGD have a broad spectrum of functional capabilities. Neutrophils from one obligate carrier performed in the above in vitro tests and others on a par with normal control cells, whereas the PMN of others displayed deficiencies nearly as profound as those of the affected CGD patients. The observations parallel the broad range of phenotypic expression observed in heterozygotic carriers of other sex-linked recessive disorders as a result of random inactivation of the X chromosome. Although predictable from the current concept of random X inactivation, the spectrum has not been previously demonstrated for carriers of sex-linked recessive CGD and thus has important implications for the detection and counseling of carriers of CGD.

Blood Bactericidal Activity