Immunological assessment is important to characterize the host defence response of trauma patients as infection is the most common cause of severe morbidity and late death. Sixty trauma patients were followed serially and divided into three groups: those with an uneventful recovery (n = 17), those with recovery after major sepsis (n = 27) and those who died (n = 16). The ability of peripheral blood monocytes to express the antigen HLA-DR was measured and compared to the results from 77 asymptomatic volunteers. After initial injury, there was a significant reduction from normal in the three trauma groups. It took one week for HLA-DR antigen expression to return to the normal range in the first group, three weeks in the second group, and in the third group it never returned to normal. Monocyte HLA-DR antigen expression, after incubation with lipopolysaccharide, distinguished those patients who survived from those who died. There was no difference in HLA-DR antigen expression between a high transfusion group of 31 patients who received 10 or more units of blood and a low transfusion group of 29 patients who received less than 10 units. The ability of monocytes to express HLA-DR antigen correlated directly with the clinical course in these patients and its measurement identified a group of patients at high risk of infection and death following trauma.
Intestinal epithelial cells migrate from the base of the crypt to the villi where they are shed. However, little is known about the cell shedding process. We have studied the role of apoptosis and wound healing mechanisms in cell shedding from human small intestinal epithelium. A method preparing paraffin sections of human small intestine that preserves cell shedding was developed. A total of 14 417 villus sections were studied. The relationship of cell shedding to leukocytes (CD45), macrophages (CD68) and blood vessels (CD34) were studied by immunohistochemistry. Apoptotic cells were identified using the M30 antibody against cleaved cytokeratin 18 and an antibody against cleaved caspase-3. Potential wound healing mechanisms were studied using antibodies against Zona Occludens-1 (ZO-1) and phosphorylated myosin light chains (MLCs). We found that 5.3% of villus sections contained a shedding cell. An eosin-positive gap was often seen within the epithelial monolayer beneath shedding cells. Shedding was not associated with leukocytes, macrophages or blood vessels. Cells always underwent apoptosis during ejection from the monolayer. Apoptotic bodies were never seen in the monolayer but morphologically normal cells that were positive for M30 or cleaved caspase-3 were often seen. ZO-1 protein was usually (41/42) localized to the apical pole of cells neighboring a shedding event. Phosphorylated MLCs could be identified in 50% of shedding events. In conclusion, cell shedding is associated with apoptosis though it remains unclear whether apoptosis initiates shedding. It is also associated with phosphorylation of MLCs; a process associated previously with wound healing.
Pneumatosis coli is a rare condition characterised by multiple gas-filled cysts within the bowel wall. We present 25 cases treated over the past 30 years. The patients' mean age was 59 years: 15 were female. Presenting symptoms included diarrhoea (n = 17), mucus discharge (n = 17), rectal bleeding (n = 15) and constipation (n = 12). Pneumatosis usually affected the left colon (96%), and diagnosis was by sigmoidoscopy and biopsy in 18 cases (72%). Pneumatosis coli was associated with psychiatric disorders (36%), chronic lung disease (20%) and colitis (12%). A redundant sigmoid colon was observed in 80% of cases on contrast radiology. Five patients had mucosal pseudolipomatosis on histological examination. Histological and immunohistochemical review indicated that the cysts were lined by cells of macrophage/monocyte phenotype and that many similar mononuclear cells were present in the adjacent submucosa and overlying mucosa. Treatment with antidiarrhoeals and anti-inflammatory drugs in 14 patients resulted in improvement in 9 cases (64%). Oxygen therapy (n = 9) always alleviated symptoms. There was a high recurrence rate (50-78%), but with further courses of therapy lasting remission was achieved in five patients. Two patients underwent colectomy. The associations of pneumatosis coli with psychiatric disorders and mucosal pseudolipomatosis are new and of possible pathogenetic significance. A novel pathogenetic mechanism is suggested to explain the association of pneumatosis coli and chronic respiratory disorders. A model of pneumatosis coli linking some of the apparently disparate pathogenetic theories is proposed.
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