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Abnormalities of neutrophil function do not cause the migration defect in Crohn's disease.

Skin window tests were performed on 60 patients with Crohn's disease, 20 with ulcerative colitis, 16 with peptic ulceration, and 40 healthy controls. The numbers of neutrophils that migrated into the skin window chambers were significantly lower in patients with Crohn's disease. This abnormality was unrelated to the activity of the disease, site of involvement, or treatment. No significant abnormalities were found in the patients with other diseases of the gastrointestinal tract. The abnormality of neutrophil migration in the Crohn's patients does not seem to be due to a cellular defect, as neutrophils from patients with Crohn's disease migrate and phagocytose normally in vitro. Sera from patients with Crohn's disease did not inhibit cell migration or contain inhibitors of chemotaxis. The addition of serum that had been activated with zymosan to the chamber enhanced the emigration of neutrophils from the skin of patients with Crohn's disease. These results suggest that the depression of neutrophil migration into skin windows that is normally observed in Crohn's disease is due to a deficient local inflammatory response. This defective inflammatory response in Crohn's disease and the consequent delay in the accumulation of neutrophils could explain granuloma formation, the high recurrence rate after surgery, and the clinical course of exacerbations and remissions.

Adult↗

Leucocyte function in ulcerative colitis. Quantitative leucocyte mobilisation to skin windows and in vitro function of blood leucocytes.

Leucocyte function was evaluated by the in vivo mobilisation to skin windows with chambers and by the chemotactic, phagocytic, and nitro blue tetrazolium reducing capacity of blood leucocytes from 20 patients with ulcerative colitis. The total number of leucocytes mobilised to the chambers after 12 hours did not differ from those in 21 healthy volunteers. After 24 and 48 hours reduced number of leucocytes were mobilised by patients with ulcerative colitis (p less than 0.01). Correspondingly, the leucocyte migration rates were normal initially but were reduced after 18 hours Mobilisation in vivo was positively correlated to the blood neutrophil count (Rho:0.5549 po less than 0.02) but unrelated to clinical activity. Blood leucocytes showed reduced random migration in vitro as well as chemotactic response to casein (p less than 0.01). Serum independent and dependent phagocytosis did not differ from healthy volunteers. Nitro blue tetrazolium reduction by resting leucocytes was increased (p less than 0.01) in ulcerative colitis compared with controls. Our findings suggest altered in vivo mobilisation and in vitro migration of leucocytes in ulcerative colitis with increased spontaneous nitro blue tetrazolium reduction reflecting increased generation of potentially tissue damaging agents. The findings probably reflect changes secondary to the disease but which may be important in maintaining the inflammatory process.

Adult↗

Reaction of the human granulocyte system in successfully treated bacterial bronchopneumonia.

The behaviour of peripheral blood granulocyte pools, nitroblue tetrazolium reduction by granulocytes, migration of granulocytes out of skin windows, serum muramidase activity and bone marrow reserve of granulocytes during uncomplicated bronchopneumonia were studied. The time course of changes in these parameters during infection was established, and suggests maximal changes on day 2 of infection with gradual regression until 30 days after the disease onset, when they disappear.

Adult↗

Fetal breathing and behavior measured through a double-wall Plexiglas window in sheep.

The inability to see the fetus makes the assessment of fetal behavior difficult. To circumvent this problem we implanted a Plexiglas window in the left flank of the ewe. Fetuses were instrumented for measurements of sleep, breathing, and swallowing. Ten fetal sheep were studied on 32 occasions. Six fetuses were delivered through the window at term, and postnatal behavior was compared with intrauterine behavior. Fetuses observed during resting conditions alternated between periods of quiet sleep [high-voltage electrocortical activity (ECoG)] and active or rapid-eye-movement sleep (low-voltage ECoG). In quiet sleep, movements were absent except for periodic generalized electromyographic discharges. Eye and breathing movements were rare or absent. Swallowing was also absent. In active sleep, movements were increased with powerful breathing and swallowing activity. Fetal wakefulness defined by open eyes and purposeful movements of the head was never seen in utero but was clearly observed after delivery. We conclude that fetal wakefulness as defined postnatally was not able to be demonstrated in utero.

Animals↗

Influence of recombinant human erythropoietin therapy on in vivo chemotaxis and in vitro phagocytosis of polymorphonuclear cells of hemodialysis patients.

Recombinant human erythropoietin (rhu-EPO) mainly stimulates erythropoiesis, but also influences the production and function of polymorphonuclear granulocytes (PAN). We evaluated the influence of rhu-EPO therapy in patients on maintenance hemodialysis without iron overload on both phagocytic and chemotactic activity of polymorphonuclear leukocytes (PMN) obtained from blood and a skin chamber. The study comprised 28 dialysis patients (15 females, 13 males, age 22-78 years, dialysis sessions three times weekly 4-5 h, mean duration of dialysis treatment 4-99 months) and 20 healthy subjects (9 females, 11 males, age 18-56 years). The absolute number of leukocytes in the peripheral blood, the leukocyte mobilization (chemotactic activity) and the phagocytic activity of PMNs were tested in patients before (n = 28), and after (n = 18) reaching the target hematocrit of 30% and during the follow-up period. No alteration in the total leukocyte number (PMN, monocytes, lymphocytes) in the peripheral blood during rhu-EPO therapy could be seen. The phagocytic activity of PMNs slightly improved during the follow-up period whereas the decreased chemotactic activity remained unchanged.

Adolescent↗

Ultrastructure of skin window cells in malignant lymphoma.

The ultrastructure of cells in skin window preparations was analysed in 38 patients with malignant lymphoma and in 22 normal subjects. In the series as a whole, there were significant morphological changes in the macrophages between day 1 and day 2 consistent with cell maturation during the inflammatory response. At both intervals, lymphoma patients showed strikingly larger cell and nuclear profile areas as compared with normal subjects; there was a greater number of nucleoli per profile and proportionately more sections showed a Golgi complex. At day 1, a greater percentage of the patients' macrophages showed large numbers of phagocytic inclusions, but at day 2, significantly fewer profiles demonstrated this feature. These morphological findings could be a reflection of the known mononuclear phagocyte dysfunction in malignant lymphoma.

Adolescent↗

Skin window cellularity and macrophage changes in Hodgkin's and non-Hodgkin's lymphomas.

The cutaneous inflammatory response in patients with Hodgkin's and non-Hodgkin's lymphomas was investigated by light and scanning electron microscopy and compared with that of healthy subjects at 24 and 48 h. Both groups of patients showed a reduction in overall cellularity and statistically significant differences in macrophage surface morphology. In macrophages from healthy subjects, microvilli predominated but in lymphoma patients, cells with ruffles and/or ridges (resembling blood monocytes) were more frequent. In healthy subjects, the percentage of macrophages with predominant microvilli increased between day 1 and day 2. It is suggested that both the cellular response and the maturation (or activation) of macrophages are impaired in lymphomas.

Adolescent↗