Robert H. Drachman

Phagocytosis: The Normal Process and Its Clinically Significant Abnormalities

Phagocytosis, one of the many mechanisms available to the host in its struggle against invading microorganisms, plays an important role in the critical early stages of bacterial infections and is thus a significant determinant of the eventual outcome of these infections.

Acute Infectious Gastroenteritis

Gastroenteritis caused by infectious agents still poses an annoying and sometimes serious problem even in well sanitated populations. Infectious non bacterial gastroenteritis, after many years of neglect, is now again receiving the investigative attention it deserves.

Physician productivity and medical care

Summary Both the shortage of health services and the rapidly escalating costs of medical care are likely to be improved by increases in physician productivity. The most promising efforts to improve productivity appear to be in the use of various types of assistants at all levels in the health care system. Some progress has been made in defining tasks and training. It is unclear how best to structure the administrative setting in which these personnel would function. However, current expectations about health care, particularly among the urban poor, are unlikely to be met unless new organizations for ambulatory care are developed and implemented. Physicians will need training in how best to use assistants and also in ways of improving productivity in general. Making house staff familiar with, or perhaps even dependent upon, assistants in ambulatory care would seem to be an important addition to training programs. For planning and evaluation in the area of productivity and costs, considerable expertise is required in several disciplines. It seems very clear that training for health services research must be stimulated and sufficient funds made available to train adequate numbers of investigators. There is no reason to accept less well-prepared professionals here than for biologic research. Good principles of financial management require that some small percentage of the vast federal expenditures for health care be devoted to expanded support for both research and training of investigators to maintain adequate study programs of health services effectiveness, quality, and acceptability, as well as productivity.

INCREASED RESISTANCE TO PNEUMOCOCCAL INFECTION IN FEMALE RATS AND DIETHYLSTILBESTEROL TREATED MALES

Female rats and males treated with diethylstilbesterol (DES) were more resistant to i.v. pneumococcal challenge than were untreated males. These observations may parallel the clinical findings.The i.v. LD50 in male rats for Pneumococcus Type 25 (Pn25) is 5×105 viable organisms. Challenge of female rats with this LD50 dose of the Pn25 resulted in a significantly lower mortality. Splenectomized male and female rats were challenged i.v. with the same numbers of viable pneumococci. All males died, while about one-half of the females survived. DES was given s.c., 0.5 to 1 mg per day for 5 days to male rats weighing about 200 gm, while similar control rats received cotton seed oil only, the vehicle for the DES. Body weight decreased about 35 gm by day 6. On day 8 DES treated males and controls were challenged i.v. with the LD50 dose of Pn25. Mortality in the DES treated males was comparable to that in females and was significantly different from mortality in cotton seed oil treated control males. In vitro phagocytic studies using the Pn25 as the test particle and two-way combinations of DES treated and normal cells and serum failed to reveal differences in cellular phagocytic activity or levels of serum opsonizing activity. In vivo DES was capable of producing changes in male rats which caused them to resemble females in their resistance to i.v. pneumococcal challenge.

Splenectomy and Impaired Resistance to Pneumococcal Infection

Efforts to devise an animal model in which splenectomy decreases the effectiveness ofhost defences against acute bacterial infection have been infrequently successful. It has been difficult to provide a challenge which sharply differentiates controls from the operated animals. A model is described in which all splenectomized rats died after intravenous (i.v.) challenge with an LD50 dose of pneumococcus Type 25. Normal rats immunized with pneumococcus Type 25 formalized bacteria and then challenged i.v. 3 to 6 days afterwards, all survived, while previously splenectomized rats, similarly immunized, all died. As the interval between immunizations and subsequent splenectomy was lenghtened in a stepwise fashion, the mortality following i.v. challenge fell from 80% to zero. Clearance of pneumococci from the blood stream reflected these results, more prompt disappearance of bacteria becoming evident at 1 to 3 hours after i.v. challenge in those most likely to survive. During this period of increasing antibacterial resistance both early antibody and the unique ability of the spleen to clear minimally opsonized bacteria were critical for effectiv antibacterial host defence. Early but delayed antibody could be detected in the immunized splenectomized rat, but was not adequate for protection in the absence of the spleen.