Impact of a toxicology service on a metropolitan teaching hospital.

OBJECTIVE: To evaluate the impact of a toxicology service on a major metropolitan teaching hospital. METHOD: A descriptive comparative study of all patients presenting with poisoning or suspected poisoning 12 months before and after the commencement of a toxicology service. Data on length of stay in the emergency department, disposition, length of stay of admitted patients and substance(s) involved were examined. RESULTS: A total of 1,316 poisoned patients were studied. There was a statistically significant increase in self-poisonings from 612 to 704 (P = 0.002) and in the number of admissions from 113 to 192 (P < 0.05). There was no significant change in emergency department length of stay. The average length of stay for patients admitted under the care of the toxicology service decreased, especially for complicated patients. CONCLUSION: In the first 12 months of operation the toxicology service treated more patients than the 12-month period prior to commencement, achieving a decrease in average length of stay for those patients admitted to the service. The emergency department length of stay was not altered. We surmise that by decreasing average length of stay for the patients under the care of the toxicology service, the net increase in the general pool of unoccupied beds improves bed access for all emergency department patients.

Neglected opportunities in apoptosis research.

Interest in apoptosis is currently growing rapidly, and previous articles in this series in TCB have described a number of recent advances in the field. Certain aspects of the process, however, have been relatively neglected. In this article, John Kerr draws attention to some of them, with the hope that he may indicate potentially productive areas for future research.

Apoptosis. Its significance in cancer and cancer therapy.

Apoptosis is a distinct mode of cell death that is responsible for deletion of cells in normal tissues; it also occurs in specific pathologic contexts. Morphologically, it involves rapid condensation and budding of the cell, with the formation of membrane-enclosed apoptotic bodies containing well-preserved organelles, which are phagocytosed and digested by nearby resident cells. There is no associated inflammation. A characteristic biochemical feature of the process is double-strand cleavage of nuclear DNA at the linker regions between nucleosomes leading to the production of oligonucleosomal fragments. In many, although not all of the circumstances in which apoptosis occurs, it is suppressed by inhibitors of messenger RNA and protein synthesis. Apoptosis occurs spontaneously in malignant tumors, often markedly retarding their growth, and it is increased in tumors responding to irradiation, cytotoxic chemotherapy, heating and hormone ablation. However, much of the current interest in the process stems from the discovery that it can be regulated by certain proto-oncogenes and the p53 tumor suppressor gene. Thus, c-myc expression has been shown to be involved in the initiation of apoptosis in some situations, and bcl-2 has emerged as a new type of proto-oncogene that inhibits apoptosis, rather than stimulating mitosis. In p53-negative tumor-derived cell lines transfected with wild-type p53, induction of the gene has, in rare cases, been found to cause extensive apoptosis, instead of growth arrest. Finally, the demonstration that antibodies against a cell-surface protein designated APO-1 or Fas can enhance apoptosis in some human lymphoid cell lines may have therapeutic implications.

Ethionine-induced atrophy of rat pancreas involves apoptosis of acinar cells.

The mechanism of acinar cell loss occurring during ethionine-induced atrophy of the pancreas was investigated. Rats were given a standard diet, a protein-depletion diet (PDD), or a PDD with low- (0.04 g/kg body wt; LDE) or high- (0.4 g/kg; HDE) dose ethionine administered intraperitoneally daily for 10 days. Changes were most extensive in the animals given a PDD and HDE: After 10 days, pancreatic weight was reduced by 72%, and most of the acinar cells had disappeared. Prior to their deletion, these cells showed cytoplasmic vacuolation and enhanced autophagy. The main mechanism involved in their deletion was apoptosis, the apoptotic bodies being phagocytosed and degraded by adjacent acinar cells and intraepithelial macrophages. In contrast, necrosis of acinar cells was rare. Interstitial inflammation and apoptosis of capillary endothelial cells were also observed. In animals given a PDD and LDE, enhanced apoptosis occurred later and was more limited in extent, and additional manifestations of cell injury were not evident. As in other circumstances where glandular atrophy is effected by apoptosis, the basic tissue architecture was preserved, thus explaining the known capacity for the pancreas to regenerate after ethionine is discontinued.

Spontaneous apoptosis in NS-1 myeloma cultures: effects of cell density, conditioned medium and acid pH.

Apoptosis is a form of cell death which plays an important role in many biological processes including the regulation of B and T lymphocyte functions. We report here the spontaneous development of extensive apoptosis in cultures of the NS-1 mouse myeloma cell line following overgrowth. The apoptosis was identified by both its ultrastructural features and its DNA fragmentation pattern. High cell density and conditioned medium, but not acid pH, were found to be major inducers of apoptosis in this experimental system.

Ultrastructure of the rat pancreas after experimental duct ligation. II. Duct and stromal cell proliferation, differentiation, and deletion.

Ligation of the pancreas in rats was followed by rapid atrophy of the distal part of the gland, where deletion of the acinar cells by apoptosis and simultaneous extensive proliferation of duct cells resulted in the lobules being converted into groups of closely packed small ducts within 5 days. We found no ultrastructural evidence that cells lining these small ducts arose from acinar cells by a process of dedifferentiation, as has been suggested by some investigators. During the succeeding weeks, some of the ductal lining cells developed islet cell or partial acinar cell differentiation. The latter soon died by apoptosis, and some ductlike and islet cells were also deleted by this means. Most of the apoptotic bodies formed in the ducts were phagocytosed by intraepithelial macrophages. In the longer term, continuing apoptosis eventually resulted in the disappearance of many ducts, only their thickened basal laminae remaining. Differentiation of stromal fibroblasts into contractile myofibroblasts may have contributed to shrinkage of the duct-obstructed glandular tissue, and apoptosis of endothelial cells probably accounted for the associated reduction of the capillary bed.