Neurotologic findings of a patient with acquired immune deficiency syndrome.

A Caucasian male contracted acquired immune deficiency syndrome (AIDS) following a blood transfusion during heart surgery. Four years later he developed dizziness, dysequilibrium, and emotional disturbances. Neurotologic evaluation implicated central vestibular and auditory dysfunction. Electronystagmographic findings showed ataxic pursuit and optokinetic nystagmus, with a total loss of caloric excitability. The auditory brain stem response indicated delayed absolute and interpeak latencies, and the synthetic sentence identification test yielded abnormally reduced scores bilaterally. Psychological tests suggested organic brain disease with severe anxiety and depression. At autopsy, the AIDS retrovirus was found in mononuclear and multinucleated giant cells in the cortical and subcortical gray matter, cerebral and cerebellar white matter, and throughout the brain stem. Pathologic changes were consistent with the patient's neurotologic profile.

The prevention of carcinoma of the cervix.

Annual exfoliative cytologic examination is recommended by many physicians and by the American Cancer Society. A method to appraise the costs and the value of this service in comparison with competing health care measures has been developed. Further research is needed to develop the most cost-effective method.

Antibody against the antigen receptor of a plasmacytoma prolongs survival of mice bearing the tumor.

A transplantable plasmacytoma, TEPC-15 in BALB/c mice, induces a transient antibody response directed against the combining region of the myeloma protein produced by the tumor. Mice immunized with mitomycin-treated tumor cells produce similar antibody but do not develop tumor; mice so immunized survive longer than untreated mice when inoculated with viable TEPC-15 cells. This protection afforded by immunization can be transferred by serum alone; the protective effect of passively given serum is eliminated by absorbing out antibody directed against the myeloma protein.

Diabetic emergencies: hypoglycemia and ketoacidosis.

Because hypoglycemia may be rapidly fatal it must be diagnosed and treated early. Ketoacidosis may be difficult to differentiate from hypoglycemia. The diagnosis, treatment and causes of both diabetic emergencies are described. Once rehydration is instituted, further management can be directed using appropriate laboratory and bedside studies that allow stabilization with a high degree of control.

Survival with mammary cancer related to the interaction of germinal center hyperplasia and sinus histiocytosis in axillary and internal mammary lymph nodes.

In a review of the histologic sections of axillary and internal mammary lymph nodes removed during surgery for invasive ductal carcinoma of the breast, we found that 16 of 17 patients in whom sinus histiocytosis was the dominant lymphoid proliferative reaction are alive with no evidence of cancer 5 or more years after operation. In contrast, 5 of 6 patients in whom germinal center hyperplasia was the only significant reaction found died of cancer in less than 5 years. Patients with both sinus histiocytosis and germinal center hyperplasia in significant amounts had survival that was intermediate; 17 of 25 of these patients are currently alive and apparently free of cancer. In addition, 5 of 6 patients in whom no evidence was found of any lymphoid proliferative reaction and 3 of 3 patients with diffuse cortical hyperplasia in their axillary lymph nodes died of cancer in less than 5 years. Germinal center hyperplasia was associated with nodal metastases anatomically in individual lymph nodes and statistically in the series of cases. The internal mammary lymph nodes of most cases showed less proliferative reaction to tumor than the axillary lymph nodes. The pattern of proliferative reactions in lymph nodes and its correlation with survival after surgery suggest that different immune reactions may either suppress or enhance the growth of carcinoma of the breast.

Mesocolic lymph node histology is an important prognostic indicator for patients with carcinoma of the sigmoid colon: an immunomorphologic study.

Histologic parameters which are thought to reflect either cell-mediated (T cell) or humoral (B cell) immune responses in lymph nodes have been studied in regional lymph nodes draining carcinoma of the sigmoid colon. Patients whose lymph nodes show morphological evidence of cell-mediated immunity, manifested either by an increased number of paracortical immunoblasts or sinus histiocytosis, survive significantly longer than those whose lymph nodes show no such changes. Patients whose lymph nodes show simultaneous paracortical activity and sinus histiocytosis have the best survival of all. Of this latter group, 11/13 (83 percent) are living without signs of recurrent tumor 5 or more years after surgery. Histologic parameters which suggest an antibody-mediated immune response (germinal center activity) were not an important prognostic indicator. The occurrence of favorable lymph node histology does not appear to significantly correlate with the modified Duke's classification. Rather, the favorable changes allow selection of a large proportion of those patients within the various Duke's categories who are destined to become long-term survivors.

Observations on a model of the biology of carcinoma of the cervix: a poor fit between observation and theory.

The role of the mathematical model is to express the biological theory in the form of a set of numerical predictions which can be reconciled with data. We have fitted the model implicit in current theory, and the predictions from that do not fit the observed facts. Either the theory or the observed facts (or both) are wrong. If the facts are right, then our final model (Model II) points to the changes in the theoretical concept which are necessary. Increasing conversion from carcinoma in situ to invasive carcinoma with age must be accepted and explained. The fall in prevalence of dysplasia and carcinoma in situ before the major onset of invasive cancer must be fully appreciated and explained. The regression of carcinoma in situ to dysplasia or normal in large numbers must be accepted and explained either biologically or by error in categorization, or both.

The rate of division of antibody-forming cells during the early primary immune response.

Mitotic blocking agents, colchicine or Velban, were used to estimate cycle times of spleen cells which release hemolysin for sheep erythrocytes (plaque-forming cells). The cells were obtained either from rats immunized with sheep erythrocytes or from cultures of mouse spleen cells immunized in vitro with the same antigen. 2, 3, or 4 days after immunization, animals or cell cultures were treated with mitotic blocking agents for periods of time ranging from 2.5 to 7 hr; plaque-forming cells were then enumerated. Decreased numbers of plaque-forming cells were found after such treatment. The extent of reduction was a function of duration of the drug treatment and the method of immunization, but was independent of the time after immunization. The evidence presented is consistent with premises that: (a) plaque-forming cells in mitosis do not release sufficient antibody to be detected, (b) mitotic blocking agents, by arresting plaque-forming cells in metaphase, prevent not only detection of these cells but also the increase in number of plaque-forming cells which would have resulted from cell division, (c) mitotic blocking agents do not affect release of antibody by cells in interphase. Cell cycle times, based on the extent of reduction of plaque-forming cells per unit time of drug treatment, were estimated using a mathematical model appropriate for an exponentially increasing population of cells. Cell cycle times estimated using the mitotic blocking agents agreed well with cell doubling times calculated from the increase in plaque-forming cells occurring 1-4 days after immunization. Increased responses produced by higher antigen doses or treatment of immunized animals with an adjuvant resulted from an increased rate of division of responding cells and their progeny. The results are consistent with a cell selection theory of antibody formation. Antigenic stimulation causes relatively few cells to proliferate and to synthesize antibody; apparently the magnitude of the response is dependent primarily on the rate of division of responding cells. It is suggested on the basis of observations of in vitro-immunized cell cultures that the rate of division of responding cells may be dependent on the rate of interaction between two cell types, both of which are essential for the in vitro plaque-forming cell response.