Microvascular disturbances in the colonic mucosa in antibiotic-associated haemorrhagic colitis: Involvement of platelet aggregation

An ultrastructural study of the colonic mucosa was performed in four patients with antibiotic-associated haemorrhagic colitis and new findings are reported. Colonoscopy was performed and biopsy specimens were obtained within 24 h of the onset of bloody diarrhoea. Colonoscopy demonstrated diffuse oedematous and haemorrhagic mucosa with erosions and white coat. Light microscopy revealed mucosal haemorrhage and inflammatory cell infiltration. Ultrastructurally, platelet aggregation was frequently present in the lumina of colonic mucosal capillaries, causing engorgement of red blood cells in adjacent microvessels. Mild to severe damage was observed in capillary endothelial cells, including discontinuity of basement membranes, gaps between endothelial cells and the destruction of capillaries. There was no evidence of microvascular spasm. In conclusion, our findings suggest that antibiotics directly or indirectly cause microcirculatory disturbances, which result in tissue damage and haemorrhage, in the colonic mucosa.     

Clinical Trial with Authentic Recombinant Somatropin in Japan

Recombinant somatropin, produced by recombinant DNA technology, was administered by injection in daily doses of 8 IU to six healthy young volunteers. Daily injection for 4 days did not cause any significant change in the results of physical examination, blood count or urinalysis. Non-esterified fatty acid levels increased significantly from 0.45 ± 0.16 to 1.08 ± 0.12 mEq/litre (mean SEM) at 4 hours after the first injection (p<0.001). Plasma IGF-1 levels increased from 0.80 ± 0.14 units/ml to 1.72 ± 0.50, 3.22 ± 1.02, 3.17 ± 1.20 and 3.63 ± 0.78 units/ml at 24 hours after each daily injection for 4 days (p<0.001). Plasma hGH reached peak levels at 3 hours after intramuscular injection of recombinant somatropin, 4 IU, and this peak value was 57.3 ± 2.8 ng/ml. A total of 21 patients with pituitary dwarfism were also treated with recombinant somatropin for 6 months at a dose of 0.5 IU/kg/week. Their heights increased by 2.2–5.0 cm during the 6 months of treatment, which was calculated to be equivalent to 4.4–10.0 cm/year with a mean growth rate of 7.4 ± 0.4 cm/year. Anti-hGH antibody with a titre of 10 was observed in two patients at the end of 6 months of treatment.     

Urinary prolactin excretion in children with renal disease

The contribution of the kidney to the metabolism of prolactin has not yet been established. In the present study, urinary prolactin concentrations in 30 children with renal disease were measured by a newly devised, highly sensitive, time-resolved immunofluorometric assay. Median prolactin concentrations in the urine of children with renal disease, were 1.86 pmol/L⁻¹ of urine (range: 0.17–546.31 pmol/L⁻¹. By stepwise regression analysis, change in urinary prolactin levels as a function of the urinary β 2-microglobulin concentrations was detected. These results indicate that prolactin urinary excretion in children with renal disease is dependent on the renal proximal tubular function.     

An Attempt to Assess the Replacement Dose of Human Growth Hormone in the Treatment of Growth Hormone Deficient Children

Hibi, I., Tanaka, T., Yano, H., Umezawa, S., Kagawa, J., Tanae, A. and Ishikawa, E. (National Children's Medical Research Center, Tokyo, the National Children's Hospital, Tokyo and the Department of Biochemistry, Miyazaki Medical College, Miyazaki, Japan). Acta Paediatr Scand [Suppl] 337:87, 1987.
In 25 patients with hGH deficiency, who had been treated long-term with hGH, the mode of hGH administration was switched from the conventional method (0.3–0.5 IU/kg/week, in two or three divided doses, intramuscularly) to daily subcutaneous injection at 1900–2100 hours with a dose of 0.46 ± 0.07 IU/kg/week (equivalent to 14.7 ± 2.0 IU/m²/week). After 1–3 months of this new mode of hGH administration, blood and urine were sampled at 0900 hours after overnight fasting. Blood glucose, plasma insulin, plasma IGF-1 and plasma total IGF (after extraction) were analysed in blood samples. IGF-1 and hGH were measured in urine samples. These measurements indicated that the dose studied was close to a replacement one, but might be slightly higher than the exact replacement dose.     

Possible Involvement of Tissue-Type Plasminogen Activator in Gastric Ulcer Formation —Biochemical Evaluation Using Biopsy Specimens From Gastric Mucosa—

Abstract: Microvascular endothelial changes are thought to be a crucial step in the development of hemorrhagic changes in various pathological states. Tissue-type plasminogen activator (t-PA) is an endothelium-derived fibrinolytic mediator which regulates microvascular permeability. In this study, we determined the activity and amount of t-PA in the biopsy specimens taken from gastric mucosa of patients with gastric ulcers to evaluate endothelial alterations and vascular permeable changes in situ. In addition, to elucidate the relationship between local fibrinolytic disturbance and systemic blood coagulation, several factors such as plasminogen activator inhibitor were also assayed. The results of this investigation revealed that the mucosal t-PA amount in the active ulcer proved to be 2–3 folds higher than that in healthy controls, however, t-PA levels in plasma samples showed no remarkable differences among the groups. Increased t-PA activity appeared to well correlate to the degree of inflammation of gastric mucosa in contrast to t-PA amount which was still increased in healed ulcer lesion. PAI-1 in plasma samples from gastric ulcer patients showed a significantly high level as compared with healthy subjects. The present study indicates that t-PA activation may play an important role in the pathogenesis of gastric ulcer formation and that t-PA determination in gastric biopsy specimens may be useful for the evaluation of clinical activity of gastric ulcers in terms of the mucosal microvascular endothelial changes.     

A Case of Crohn's Disease which Initially Presented with Diffuse Inflammation in the Rectum and Sigmoid Colon

Abstract: This case report describes a female patient with Crohn 's disease who had diffuse proctosigmoiditis without a longitudinal ulcer or cobblestone appearance at the initial attack. She was treated with sulfasalazine on the presumptive diagnosis of ulcerative colitis. Two and a half months later, painful ulcers in the oral cavity and a deep longitudinal ulcer in the sigmoid colon were found, and a non-caseous granuloma was revealed in the biopsy specimens taken from the sigmoid colon. A definitive diagnosis of Crohn's disease was established from these findings and treatment with a corticosteroid was effective.     

Immunoglobulin G subclass distribution of human anticolon antibodies in ulcerative colitis

Abstract Immunoglobulin G (IgG) subclasses of anticolon antibodies were studied in patients with ulcerative colitis (UC) using enzyme-linked immunosorbent assay (ELISA). The concentrations of total serum IgG subclasses were also measured by ELISA. The values for total serum IgG subclasses in patients with UC were not significantly different from those in normal controls, while the ratio of IgG₁ to IgG₂ in the patients was significantly higher than that in normal controls. All four IgG subclasses of autoantibodies were demonstrated in the sera of the patients. IgG₄ anticolon antibodies were detected most frequently (15 out of 18 patients, 83%). IgG₂ was the next most prevalent (9 of 18 patients, 50%). The activity of anticolon antibodies in each subclass did not correlate with the concentration of the corresponding serum IgG subclass. Seven cell lines producing anticolon antibodies were obtained from the colonic mucosa of the patients by Epstein-Barr virus (EBV) transformation. IgG subclasses of anticolon antibodies secreted by these cell lines were also varied. IgG₄ subclass was secreted by three EBV transformed cell lines, all of which produced IgG₄ anticolon antibodies. These results suggest that all four different IgG subclasses could respond to the colon antigens and that various antigens in colonic mucosa or lumen may contribute to the induction of those autoantibodies. In addition, the prominence of IgG₄ anticolon antibodies may support the pathogenic role of this subclass in UC as in other autoimmune diseases.