The effect of beta adrenergic blockade on bronchial sensitivity to acetyl-beta-methacholine in normal and allergic rhinitis subjects.

The effect of propranolol inhalation on sensitivity to methacholine inhalation was studied in normal and allergic rhinitis subjects to determine whether beta adrenergic blockade alters sensitivity to mediators in nonasthmatic atopic individuals. A partial beta adrenergic blockade is suggested as being instrumental in asthma. Hay fever patients studied showed similar effects and also developed asthma for the first time.     

Cytotoxicity of ionophore A23187 for basophils and other human blood cells.

The calcium ionophore A23187(A23) at concentrations exceeding 1 microgram/ml has been shown to be progressively cytotoxic for human blood basophils, neutrophils, lymphocytes, and erythrocytes. Toxicity to basophils was considered to be manifested by the increasing inability of 2-deoxyglucose (2DG) to inhibit histamine release (HR) at increasing concentrations of A23. The toxicity to neutrophils and lymphocytes was demonstrated by decreased lactate production (LP) after incubation with A23 of Ficoll-Hypaque fractions greatly enriched in each respective cell type. Red cells present in dextran-sedimented leukocytes were increasingly susceptible to lysis during washing subsequent to exposure to increasing concentrations of A23. A concentration of 4 microgram A23/ml, which is cytotoxic at 37 degrees C, produced optimal and noncytotoxic HR at 22 degrees C. It was possible to reduce A23 concentrations required for optimal HR by increasing Ca++ from 0.6 to 3 mM.     

Characteristic features of actinomycin D-induced paw inflammation of the rat.

Features of paw edema induced by subplantar injection of actinomycin D (act D) were investigated in rats. The paw edema was produced as early as the 1st day and reached a maximal level on the 3rd or the 4th day. Thereafter, it began to subside progressively and was considerably reduced by the 16th day following act D (20 μgm) injection. A direct dose response relationship between the amount of act D injected and the intensity of the paw edema was obtained. No difference in β-glucuronidase and acid phosphatase activity was found between saline and act D-injected paws on the 2nd day. This was followed by an increase in the activity of both enzymes on the 4th, 8th, and 16th days after injection. The histamine content of the saline and act D-injected paws remained unchanged during the early phase of inflammation. A marked increase in the histamine content was noted during the late phase in the drug-injected paw. The effects of act D treatment on capillary permeability to Evans blue dye (EBD) and the edema formation of the paw revealed that a maximal increase in vascular permeability to EBD occurred on the 1st day and was maintained until the 8th day. In contrast to permeability, the paw edema on the 1st day was minimal and increased progressively until the 3rd or 4th day. Thereafter, both the permeability and the paw edema began to diminish and were considerably reduced on the 16th day. Aspirin and hydrocortisone treatment were ineffective in suppressing the act D-induced paw inflammation. Indomethacin produced a somewhat dose-related anti-inflammatory effect against the inflammation caused by this drug.     

The synthesis and actions of mouse and human interferons in mouse-human hybrid cells.

Lines of mouse-human hybrid cells segregating either mouse or human chromosomes were used for the analysis of various aspects of the production and actions of mouse and human interferons. In one of the hybrid cell lines capable of producing both mouse and human interferons, the proportion of the two interferon activities produced varied greatly under different inducing conditions, suggesting that there are differences in the triggering mechanisms of the two interferons. Generally both mouse and human interferon production could be enhanced (“superinduced”) by sequential treatment with cycloheximide and actinomycin D; however, in one of the lines producing both mouse and human interferon, only the latter could be superinduced. There was no correlation between the capacity of the lines to produce mouse or human interferons and the sensitivity to their action. However, there was good correlation between the sensitivity to the antiviral action and the priming action (i.e., enhancement of subsequent interferon production) by the two interferons. Thus, line 55-91F2 produced both mouse and human interferons, but was sensitive to the antiviral and priming actions of human interferon only. Line GM52 × BalbVC15 produced only mouse interferon but was sensitive to the antiviral and priming actions of both interferons.     

Histologic studies of human skin test responses to ragweed and compound 48/80: III. Effects of alternate-day steroid therapy

Our previous studies have shown depressed eosinophil responses in skin test reactions to pollen antigens and compound 48/80 in those just completing a 1-wk course of daily steroids. Wheal reactions were unaffected. In this study, 6 ragweed-sensitive atopic subjects were studied before and on the seventh day (“day on”) and day 8 (“day off”) of a course of alternate-day steroids. Blood neutrophil levels rose on day 7 and were similar to baseline on day 8, whereas blood eosinophil levels were significantly reduced on both days 7 and 8. Neutrophil responses in skin test reactions were depressed on day 7 and normal on day 8. In contrast, the tissue eosinophil responses were depressed significantly, and to similar degree, on both days 7 and 8. These findings are of potential significance in evaluating the clinical effects of steroids in allergic diseases.     

Different specificities of an HLA-DRw6 haplotype detected by alloreactive T lymphocytes

DRw6 has been difficult to define serologically. In the present experiments we have developed T cell lines in order to characterize the components of a DRw6 haplotype. This was accomplished by priming T cells with allogeneic mononuclear cells mismatched for DRw6, Dw6, and MT2. Subsequently, three sublines with distinct reactivity patterns were derived by limiting dilution. The specificities detected by these sublines included: (a) a specificity found on a subset of cells positive for DRw6 which was inhibited by monoclonal antibodies against DS(DC), the human homologue of the murine IA-encoded molecules, (b) another DRw6-associated specificity blocked by an MT2-like antibody, and (c) an MT2-like specificity blocked by monoclonal antibodies reactive with a different MT2-associated determinant. These results show that more than one IE-like, as well as the DS/DC (IA-like) molecules, carry distinctive antigenic epitopes that can be recognized by allogeneic T cells. Primed T cell lines may be useful for a better definition of certain haplotypes which are at present difficult to characterize with serological reagents alone.     

Effects of female sterilization: one year follow-up in a prospective controlled study of psychological and psychiatric outcome

A prospective controlled study of the psychological effects of elective interval and postpartum tubal sterilization was carried out on a selected sample of women. Subjects were interviewed pre-operatively (n = 138) and one year post-operatively (n = 116; 83%), using standardized instruments and procedures, including the Present State Examination. No differences within or between sterilization and control groups were found over the follow-up year in the prevalence of psychiatric morbidity, which was no higher than would be expected in a general population sample. Beneficial effects of sterilization were reported on a number of psychosexual variables. Adverse effects such as regret or deterioration in marital relationship were rare, but were more likely to occur in postpartum subjects, among whom abdominal pain was also reported more commonly at one year follow-up than pre-operatively. The relevance of "normal" postnatal events and of the role of pre-operative counselling are considered in relation to these findings. Less favourable outcome at one year follow-up was commonly associated with higher PSE scores pre-operatively.     

The effect of cost containment on the practice of cardiology: predictions

When health care cost containment is tied to unit pricing, the system may become price-driven rather than care-driven. Although the incentives engendered by unit pricing may not necessarily result in practices detrimental to the young or the patient with relatively pure disease, the potential for adverse effects on the elderly, the poor and the chronically ill is real. Hospitals will soon emphasize quick turnover, efficiency and intensive care. Diagnostic evaluations and chronic disease care will be moved out of hospitals into physician owned-and-operated facilities and out-of-hospital settings, respectively. The health care system will fractionate, and quality control will require restructuring to achieve the present level of quality assurance. Cardiologists, as well as other physicians, will need to alter their teaching style and teaching locations. Better methods for predicting outcomes will need to be developed; we will no longer have the safety net of following a patient closely and altering management plans according to the patient's response. Cost containment may occur under diagnosis related groups, preferred provider organizations, health maintenance organizations and other prepaid or "capped" systems. There are, however, many issues relative to cost versus quality that need to be resolved if severe detrimental effects on care are to be avoided.     

ER "capture" of the skid-row alcoholic

In response to the spiraling anger and frustration voiced by the emergency room (ER) medical staff and the observed negative interactions between the alcohol-dependent patient and the ER staff, the author completed a 6-month retrospective review of all patients evaluated by the ER service with a complaint of alcohol abuse, chronic alcoholism, or requesting detoxification. As a result of that study, an ER-based comprehensive approach to the management of this population was proposed. Utilizing an existing Connecticut state statute, a specific approach to manage the skid-row alcoholic arriving repeatedly in the ER was developed. I report on this ER-based model and an approach to "capturing" the skid-row alcoholic.