Leukokinetic Studies. VII. Morphology of the Bone Marrow and Blood of Dogs Given Vinblastine Sulfate

The effect of a single injection of vinblastine sulfate was studied in 50mongrel dogs. Nine of 34 dogs given 0.2 mg./Kg. of VLB died with gastrointestinal toxicity and the mortality rate increased as the dosage of VLB wasincreased. The morphologic pattern of leukocyte suppression and recovery inthe bone marrow and blood was studied in detail in surviving animals.

The cells of the bone marrow were markedly affected by VLB. Within 4hours there was an increase in the number of cells in metaphase and, by day1, virtually all proliferating leukocytes and erythrocytes had disappeared. Anorderly repopulation of the bone marrow followed.

The neutrophils, eosinophils, lymphocytes and monocytes of the blood wereall markedly altered in concentration after VLB. Each type of cell first decreased to abnormally small numbers and then increased to abnormally largenumbers in the blood. The curve of disappearance from and reappearance inthe blood differed for each cell type.

The changes in blood neutrophil number and morphology were correlatedwith changes in the blood neutrophil precursor cells of the marrow. The following conclusions were reached concerning the neutrophils and the assumptions implicit to these conclusions were detailed.

1. In the dog, the marrow contains enough post-mitotic granulocytes toreplace those lost from the blood for at least 3 to 4 days.

2. The release of mature neutrophils from the bone marrow is a functionof the rate at which blood neutrophils are lost and proceeds normally evenwhen the marrow granulocyte reserve is partially depleted.

Submitted on March 27, 1963 Accepted on August 20, 1963     

Growth in Infancy and Childhood in Girls with Turner's Syndrome

ABSTRACT. We describe spontaneous longitudinal growth in girls with Turner's syndrome (TS), using the infancy-childhood-puberty (ICP) growth model. Lenght/height during the first 12 years of life was studied in 58 Swedish girls with TS. Their mean length at birth was 47.8 cm (SDS –1.4) and mean height at 12.0 years of age 127.3 cm (SDS –3.0). A clear age-dependent subnormality was observed in the change in length-height SDS (ΔSDS). Mean ΔSDS values at ages 0.0 to 0.5 and 3.0 to 6.0 years were normal. In contrast, the mean ΔSDS at ages 0.5 to 3.0 and 6.0 to 12.0 years were subnormal. The onset of the childhood growth component (normally located between 0.5 and 1.0 year of age) was, on the average, delayed by 0.28 year. This accounts for the subnormality of ΔSDS at 0.5 to 3.0 years of age. About 50% of the variation in height at 12.0 years of age, as determined by a multiple linear regression analysis, was significantly explained by length at 0.5 year of age, age at the onset of the childhood component, and ΔSDS at 6.0 to 12.0 years of age.     

The staphylococcal scalded skin syndrome

Histochemical and electron microscopic studies were carried out on the newborn mouse model of the staphylococcal scalded skin syndrome to investigate the mechanism of action of the staphylococcal epidermolytic toxin that causes it. Histochemical studies showed that an intra-epidermal split develops below the subcorneal zone which is rich in catabolic enzymes (the so-called esterase-acid phosphatase-rich band). However, histochemical alterations in the enzyme pattern could not be demonstrated. The earliest change revealed by electron microscopy was a widening of the intercellular space, with the formation of microvilli at the level between the stratum spinosum and stratum granulosum where the split later occurs. A clearing of the peripheral cytoplasm along the cell membranes was also revealed. In pre-split areas, adhesion between cell membranes of adjacent cells seems to be lost; desmosomes continue to hold the cells together but the split develops when these are broken by mechanical pressure. Later, damaged cell membranes may be seen. Extracellular keratinosomes remain unchanged. Although these findings do not agree with the already divergent results of other studies, they help support the findings of all groups that cases of the Lyell syndrome produced by staphylococci do not occur through necrolysis; it is therefore inappropriate to continue applying the term ‘toxic epidermal necrolysis’ to such cases.     

Urinary Excretion of Kallikrein before and after Operation for Aldosterone-producing Adenoma

ABSTRACT. Hesse B, Rasmussen S, Lund JO, Christensen P, Damkjær Nielsen M. (Department of Clinical Physiology, Glostrup Hospital, and Institute for Experimental Medicine, Copenhagen, Denmark.) Urinary excretion of kallikrein before and after operation for aldosterone-producing adenoma. Urinary kallikrein excretion (UKal), determined by the esterase method, was measured in 10 normotensive volunteers, 10 patients with essential hypertension and in 7 patients with primary aldosteronism before and after operative removal of the adenoma. UKal values were low in 5 of the patients with essential hypertension. Preoperative UKal values in the patients with aldosteronism did not differ significantly from those of the normal subjects, but decreased in all after operation in parallel with changes in urinary excretion of tetrahydroaldosterone and plasma aldosterone concentration. The study supports the assumption of an association between the renal kallikrein-kinin system and the mineralo-corticoid state in man.