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Biomedical subjects

L Francis

Publications and source records attributed to L Francis.

At least 19 recordsLinked to original sources
PubMed1992

The validity of estimating heart disease reduction from a Framingham logistic equation.

We compared two ways in which a logistic equation could be used to estimate the number of heart disease events prevented after lowering blood cholesterol levels. Men were selected from an Australian population survey who met the entry criteria of the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT). The numbers of heart disease events expected over 7.4 years were calculated from the logistic equation after reducing the men's blood cholesterol by the amounts achieved in the LRC-CPPT placebo and treatment groups (our simulated placebo and treatment groups). The number of events prevented was calculated as the absolute difference between the simulated groups (9.48 per 1000 men per 7.4 years) and the percentage difference of the simulated groups multiplied by the observed incidence rate in the LRC-CPPT placebo group (13.66 per 1000 men per 7.4 years). The second estimate was closer to that observed in the LRC-CPPT (17.10 per 1000 men per 7.4 years), and we recommend this approach in cost-effectiveness studies.

Australia↗
PubMed1989

The use of non-prescription salbutamol inhalers by asthmatic patients in the Hunter Valley, New South Wales. Newcastle Retail Pharmacy Research Group.

Because of concern over the unsupervised use of bronchodilator aerosols, we studied the characteristics of a group of asthmatic subjects who purchased their salbutamol inhalers and a group of asthmatic subjects who obtained their inhalers by prescription. Community pharmacists distributed 360 questionnaires to consecutive patients who requested salbutamol inhalers; 320 questionnaires were returned (response rate, 89%). Of these, 240 respondents described themselves as asthmatic and stated that they obtained their inhalers exclusively or predominantly by either purchase (120 subjects) or prescription (120 subjects). Purchasers were younger than were users of prescribed inhalers and were more likely to be in current employment. The "purchase" group perceived less disability from chest disease than did the "prescription" group but were not different from the prescription group with respect to more-objective measures of disease severity, such as the occurrence of wheeze every day, nocturnal wakening with wheezing, and admissions to hospital with asthma. The purchasers had a low rate of consultation with family practitioners and specialists and reported a low use of prescription-only medications, particularly of inhaled corticosteroid agents. This study highlights the possible disadvantages of providing bronchodilator aerosols without prescription, and emphasizes an important counselling role for community pharmacists in the management of bronchial asthma.

Administration, Inhalation↗
PubMed1988

How much day surgery? Delphic predictions.

A list was compiled of 83 of the commonest operations, which according to published reports may be performed on day patients but which in our district were usually performed on inpatients. The results of a national Delphi study among anaesthetists and general surgeons who were known to be in favour of day surgery produced estimates of the probable rates of day surgery for each of those operations under ideal conditions. Comparison of these figures with those from a Delphi study carried out in one district and with figures for day surgery carried out in that district and with waiting list figures enabled two health districts to focus their efforts to increase day surgery. The figures from the national Delphi study could be applied in other districts if the following are taken into account: Hospital Activity Analysis data must be validated; though there was consensus among the national Delphi consultants, personal clinical opinions varied; the case load may grow as waiting lists decrease.

Age Factors↗
PubMed1988

DNA ploidy in thin melanoma.

DNA ploidy in benign nevi (BN), thin non-metastasizing melanomas (TNM) and thin metastasizing melanomas (TMM) was investigated using an image analyser to determine whether characteristics such as nuclear area (NA) and nuclear integrated optical density (IOD) could be used to distinguish between these lesions. NA measurements showed significant differences between samples of nevus cells and melanoma cells and nuclear IOD differences were significant between TNM and TMM samples. Differences in NA and nuclear IOD were detected across the three groups (BN, TNM and TMM) but the large variability within samples and within groups indicate further studies would be necessary to determine the usefulness of these results in terms of the rate of correct group classification of a single sample for diagnostic purposes.

Adolescent↗
PubMed1985

Suppression of Ag-induced release of EP (IL 1) by spleen cells of specifically desensitized donors: evidence for the role of a suppressor cell.

Monocytes or macrophages may be induced to produce IL 1 by activators (e.g., lipopolysaccharide endotoxin) that act directly or by antigens/mitogens (e.g., Con A) that stimulate inducer lymphocytes to release a lymphokine that stimulates macrophages. Using guinea pigs (GP) rendered delayed hypersensitive to ovalbumin (OVA), we investigated the role of spleen cells from normal, sensitized, and specifically desensitized GP in suppressing release of IL 1, measured as endogenous pyrogen (EP), from peritoneal exudates of sensitized GP when incubated with OVA in vitro. Co-cultivation of all three sources of spleen cells with GP peritoneal exudate cells and OVA suppressed EP release as measured in the rabbit fever assay, the effect being most marked with cells from desensitized GP, intermediate with cells from sensitized GP, and least with normal cells. This suppressor activity of spleen cells on in vitro EP release was not explained by nonspecific absorption of EP by the added cells and did not affect EP release by a stimulus that activates macrophages directly (heat-killed staphylococci). It required both lymphocytes and macrophages for its effect, but unlike some other suppressor factors, it was not modified by indomethacin, an inhibitor of prostaglandin release. This appears to be the first reported evidence for cell-mediated suppression of lymphokine-mediated release of IL 1, an important modulator of the immune system through its combined role as a lymphocyte-activating factor and an inducer of fever (EP).

Animals↗
PubMed1980

Release of endogenous pyrogen-activating factor from concanavalin A-stimulated human lymphocytes.

Evidence is presented that the mitogen concanavalin A stimulates human lymphocytes to produce a nonpyrogenic lymphokine (LK) that is capable of activating human monocytes but not granulocytes to produce endogenous pyrogen (EP) in vitro. The potency of this preparation should facilitate further studies to purify and characterize this agent and determine its relation to other know LK. It seems likely that this factor, which we have called EP-activating factor (EPAF), plays a significant role in the development of fever in states of delayed hypersensitivity in man.

Concanavalin A↗
PubMed1980

Release of an endogenous pyrogen from guinea pig leukocytes: the role of T lymphocytes and correlation with suppression (desensitization) of delayed hypersensitivity.

The pathogenesis of fever in delayed hypersensitivity (DH) was studied in guinea pigs immunized with either ovalbumin or bovine gamma-globulin in complete Freund's adjuvant. In vitro incubation of sensitized lymphocytes with the specific antigen used for immunization resulted in the elaboration of a lymphokine-like factor that activated either monocytes or neutrophils to release endogenous pyrogen (EP), the protein that causes fever. Specifically sensitized T cells appeared to be responsible for release of this EP-inducing factor. Desensitization of the dermal DH response to antigen was produced by several large injections of antigen and was associated with a reduced capacity of lymphocytes from such animals to activate phagocytic cells to release EP. This may explain the reduced fever (pyrogenic tolerance) that occurs when repeated injections of antigen are given to sensitized animals. Fever and the dermal response to DH seem to be closely linked reactions that have evolved to defend the host against invading pathogens. In both reactions, phagocytic cells appear to be activated by lymphokines derived from T lymphocytes specifically responding to microbial antigens.

Animals↗
PubMed1978

Pathogenesis of fever in delayed hypersensitivity: factors influencing release of pyrogen-inducing lymphokines.

In continuing studies on the pathogenesis of fever in states of delayed hypersensitivity, we have investigated the conditions for the release of an endogenous pyrogen (EP)-inducing lymphokine from draining-lymph-node lymphocytes of rabbits with delayed hypersensitivity to bovine gamma globulin. Using doses of 4 X 10(7) to 5 X 10(7) blood leukocytes (BL) as a source of EP, we found that ratios of about 5:1 of viable lymphocytes to BL were required to stimulate the BL to produce detectable amounts of EP in vitro. Both irradiated lymphocytes (1,700 R) as well as those from steroid-treated donors retained their ability to activate BL when incubated with antigen, properties consistent with activated "T" lymphocytes. In experiments to determine effects of temperature and duration of incubation on lymphokine release, the maximum EP-releasing activity was found to be present in supernatants of sensitized lymphocytes incubated with antigen for 18 h at 37 degrees C. These studies have confirmed that sensitized lymphocytes release a soluble, pyrogen-inducing lymphokine when incubated with antigen and further demonstrate that tissue macrophages (Kupffer cells) as well as BL can be activated to produce EP in vitro by this agent.

Animals↗
PubMed1978

Pathogenesis of fever in delayed hypersensitivity: role of monocytes.

The present studies were designed to investigate the role of monocytes in the pathogenesis of fever in delayed hypersensitivity. Adherent rabbit blood monocytes (from both normal and sensitized donors) were separated on Ficoll-Hypaque gradients and incubated with antigen (Ag; ovalbumin) and sensitized draining-lymph-node lymphocytes (or their supernatants) from rabbits with delayed hypersensitivity, and release of endogenous pyrogen was assayed. Results indicated that monocytes are activated to produce endogenous pyrogen by Ag and suspensions of draining-lymph-node cells or by an agent (lymphokine) in the supernatants of sensitized lymphocytes preincubated with Ag. The release of lymphokine was Ag specific and was correlated with the skin test reactivity of the donor rabbits to the sensitizing Ag. No evidence was found that Ag-antibody complexes or (in the case of sensitized monocytes) cytophilic antibodies play a role in the activity of this lymphokine which appears to act selectively on monocytes rather than on granulocytes.

Animals↗
PubMed1977

The release of an endogenous pyrogen from guinea pig leukocytes in vitro: a new model for investigating the role of lymphocytes in fevers induced by antigen in hosts with delayed hypersensitivity.

Guinea pig periotoneal exudate (PE) cells incubated overnight in vitro with heat-killed Staphylococci released an endogenous pyrogen (EP) that could be assayed by intravenous injection in rabbits. The febrile responses were linearly related to the dosage of EP over an eightfold range. PE cells derived from guinea pigs with delayed hypersensitivity (DH) to bovine gamma globulin (BGG), also released EP when incubated with antigen in vitro. This reaction was specific and did not occur withe PE cells from normal or complete Freund's adjuvant-sensitized guinea pigs. Studies indicated that monos and/or polymorphonuclear leukocytes rather than lymphocytes were the source of EP. However, when incubated with BGG and sufficient dosages of BGG-sensitized lymphocytes, normal PE cells released EP over a 42 h period. These results suggest that antigen stimulates specifically sensitized lymphocytes to release an agent (perhaps a lymphokine) that activates phagocytic cells to release EP. This model offers unique advantages for investigating in vitro the role of the lymphocyte in antigen-induced fever in DH as well as the relationship of this lymphocyte-induced activity to other known biologic activities mediated by antigen stimulated lymphocytes.

Animals↗
PubMed1972

Studies on the mechanism of fever accompanying delayed hypersensitivity. The role of the sensitized lymphocyte.

Experiments have been carried out to investigate the possible role of the sensitized lymphocyte in mediating the fevers of delayed hypersensitivity. Rabbits were made delayed hypersensitive to one of several heterologous proteins (bovine gamma globulin, bovine serum albumin, or human serum albumin) by footpad injection of antigen or antigen conjugated with dinitrophenol and incorporated in complete Freund's adjuvant. At intervals after sensitization, various tissues were removed, and single cell suspensions were incubated overnight with either carrier protein or conjugate in vitro. Release of an endogenous pyrogen (EP) was assayed by intravenous injection of the supernatant fluid into unsensitized rabbits. Of the tissues tested only those containing both lymphocytes and pyrogen-producing cells, blood, spleen, and draining lymph nodes, released detectable amounts of EP when incubated with antigen in vitro. Incubation of normal blood cells with specifically sensitized lymphocytes and antigen also resulted in significant release of pyrogen. Similarly, blood leukocytes released EP in vitro after mixture with supernates derived from incubation of sensitized lymphocytes and antigen. Cells and supernatant fluids from draining lymph nodes were usually effective in activating normal blood leukocytes earlier after sensitization than were those from mesenteric lymph nodes, suggesting that such cells, or antigen, had migrated from the original site of sensitization. The activator was soluble, nonpyrogenic in the dosages tested, and required incubation of viable cells with specific antigen for its production. These properties suggest that it may belong to the class of "lymphokines," biologically active agents released from lymphocytes that have been activated by immunologic or certain nonimmunologic stimuli.

Animals↗
PubMed1971

Plasma prolactin activity in inappropriate lactation.

Using a bioassay dependent on the development of a lactogenic response in rabbit mammary tissue cultured in vitro, prolactin distinct from immunoreactive growth hormone has been found in the plasma of patients of both sexes with inappropriate lactation with and without evidence of pituitary tumours. It has also been found in one patient with primary hypothyroidism and galactorrhoea, and in another during chlorpromazine therapy, but not in nine patients with gynaecomastia without galactorrhoea. Plasma prolactin levels were examined in seven patients during oral glucose tolerance tests: no change occurred in the four patients with pituitary tumours, but the levels were suppressed in the three patients with normal pituitary fossae. Prolactin appears to be a distinct pituitary hormone in man, as in animals, and also to be aetiologically related to states of inappropriate lactation.

Acromegaly↗