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Biomedical subjects

C E Davis

Publications and source records attributed to C E Davis.

At least 127 records · Page 7Linked to original sources

Regulation of activated macrophage antimicrobial activities. Cooperation of lymphokines for induction of resistance to infection.

Macrophages treated with the soluble products of Ag-stimulated spleen cells from bacillus Calmette-Guérin-infected C3H/HeN mice (lymphokines) (LK] before infection developed the capacity to resist infection with obligately intracellular amastigotes of the protozoan parasite, Leishmania major: 40 to 60% fewer cells in LK-treated cultures were infected 2 h after exposure to parasites than cells in medium-treated controls. Macrophages treated with LK depleted of IFN-gamma failed to acquire this activated macrophage effector activity. Paradoxically, IFN-gamma by itself was also not effective. Activity of the ineffective, IFN-gamma-depleted LK was restored, however, by addition of 10 to 100 U/ml IFN-gamma, itself inactive. The induction of this antimicrobial activity was the result of the interaction of macrophages and several molecularly distinct LK, and IFN-gamma was a necessary but insufficient activation signal. The activation of macrophage resistance to infection by LK was 1) not signal sequence dependent, 2) absent in cells treated with the second signal at lower (4 degrees C) temperatures and in the presence of protein synthesis inhibitors, and 3) induced by the cooperation of IFN-gamma and LK of m.w. 45,000 and 33,000. These factors in LK constituted more than 85% total LK activity for induction of resistance to infection. A minor activity in LK, of m.w. 20,000, could apparently induce this effector activity in the absence of IFN-gamma: this activity was less than 15% of total LK activity.

Animals↗

Lymphokine-induced macrophage resistance to infection with Leishmania major.

Resistance to infection is an effector activity of macrophages that is induced by the cooperation of several molecularly distinct factors in LK: IFN and another nonIFN macrophage activation factor. Unlike many other effector activities of activated macrophages, signal sequence is not critical for induction of resistance to infection. Nor is the activation of macrophages for resistance to infection dependent upon the presence of T lymphocytes in the culture vessel: T cell-depleted peritoneal cell cultures and bone marrow-derived macrophages both develop resistance to infection with L. major in the presence of LK that contains IFN. Further characterization of this activity of activated macrophages will include the identification of LK that cooperate with IFN for induction of resistance to infection, and characterization of the LK-induced changes in macrophage function that mediate this resistant state.

Animals↗

Staphylococcus haemolyticus urinary tract infection in a male patient.

Urinary tract infections caused by staphylococci are usually attributed to Staphylococcus epidermidis or S. saprophyticus. The case study reported here describes a persistent urinary tract infection caused by S. haemolyticus in a 38-year-old male whose infection was ultimately resolved through the use of the antibiotic trimethoprim-sulfamethoxazole.

Adult↗

Race and sex differences in the correlates of blood pressure change.

Potential predictors of systolic and diastolic blood pressure change between 1960 and 1967 in the biracial population of Evans County, Georgia, were investigated. An all possible regressions multiple linear regression analysis was used. For systolic blood pressure change, the level of systolic blood pressure, age, and change in Quetelet index were significant (p less than 0.05) correlates in white men. The level of systolic blood pressure, the level and change of socioeconomic status, change in Quetelet index, and change in cholesterol were significant correlates for white women. The level of Quetelet index was of borderline significance (p less than 0.055) when the other significant variables were included in the model for white women. The change in Quetelet index was the only significant correlate of systolic blood pressure change in blacks. For diastolic blood pressure change, age, change in hematocrit, and change in Quetelet index were significant correlates for white men. Age, level and change of socioeconomic status, level and change of Quetelet index, and change in hematocrit were the significant correlates in white women. In black men, change in Quetelet index and age were significant. In black women, only age was a significant correlate of diastolic blood pressure change. These results indicate that there may be important differences in these correlates between race-sex groups and thus in the mechanism of blood pressure change for different race-sex groups. groups.

Adult↗

Optimal restricted two-stage designs.

The fixed sample p value at the final stage of a group sequential design may be "significant" while the overall p value for the trial as designed may be "nonsignificant." This can lead to confusion in reporting and interpreting final stage results. Two-stage designs are presented that allow acceptance, rejection, or continuation at the first stage while retaining the fixed sample critical value at the second stage. The designs are optimized under this restriction to minimize the expected sample size under the null hypothesis, the expected sample size under a specific alternative hypothesis, or the maximum expected sample size. These restricted designs are almost fully efficient when compared to optimal unrestricted two-stage designs. Additionally, one can interpret the results of hypothesis tests at the final stage as though a fixed sample design had been used. Examples are given which illustrate the use of these restricted plans in the design and analysis of clinical trials.

Biometry↗

In vitro susceptibility of Mycobacterium avium complex to antibacterial agents.

In vitro agar dilution susceptibility studies were performed utilizing 20 isolates (24 against rifamycin) of Mycobacterium avium complex against several antimicrobial agents not routinely tested in the mycobacteriology laboratory. Thirteen strains were susceptible to gentamicin at 4 micrograms/ml, 20 to amikacin at 8 micrograms/ml, 18 to streptomycin at 8 micrograms/ml, 20 to kanamycin at 8 micrograms/ml, 20 to trimethoprim/sulfamethoxazole at 2 micrograms/ml, 12 to sulfisoxazole at 10 micrograms/ml, 14 to rifabutin at 1 microgram/ml. No activity was found with penicillin G, cephapirin, moxalactam, vancomycin, clindamycin, erythromycin, trimethoprim, or minocycline. This data suggests a potential use of trimethoprim/sulfamethoxazole, sulfisoxazole, amikacin, gentamicin, and kanamycin in the treatment of infections caused by this group of organisms.

Anti-Bacterial Agents↗

Improving house staff ordering of three common laboratory tests. Reductions in test ordering need not result in underutilization.

Most studies of modifying test ordering have focused on costs. Questions not addressed are whether programs to reduce testing lead to a higher proportion of clinically indicated tests and is underutilization an adverse outcome of such programs? To investigate this, we studied the house staff's ordering of three common laboratory tests at baseline and after educational and administrative interventions. Over a 2-year period, 3,603 urine cultures, sputum cultures, and admission urinalyses were reviewed. A lecture emphasizing the indications for these tests followed by chart audit and weekly feedback increased the proportion of clinically indicated tests. Subsequently, an administrative intervention requiring the intern to list the reason for ordering the test on the laboratory request form further improved test ordering. Underutilization, defined as a failure to order a potentially indicated test, was assessed during two representative periods. The "underutilization rate" (omitted tests per 100 patients) was no worse during maximal intervention than it was 9 months after the last intervention (7.7 vs. 11.1, NS). No immediate adverse consequences resulted from tests not ordered. Our findings indicate that it may be possible to selectively reduce the ordering of unnecessary tests without sacrificing quality of care.

Clinical Laboratory Techniques↗

Dietary and other correlates of changes in total and low density lipoprotein cholesterol in hypercholesterolemic men: the lipid research clinics coronary primary prevention trial.

Correlates of changes in total (TOTAL-C) and low density lipoprotein cholesterol (LDL-C) were examined in the 3806 hypercholesterolemic men of the Lipid Research Clinics Coronary Primary Prevention Trial. These correlates included changes in weight, dietary and alcohol intake, plasma glucose and thyroxine, cigarette smoking, packet count, lipid-lowering drugs other than cholestyramine, and antihypertensive drugs. In both placebo plus diet and cholestyramine plus diet treatment groups, decreases in Quetelet index and in saturated fat and cholesterol intake and increases in polyunsaturated fat intake were consistently associated with reductions in TOTAL-C and in LDL-C. In the cholestyramine group, plasma glucose and smoking were predictors of increased TOTAL-C and LDL-C; age and packet count were predictors of decreased TOTAL-C and LDL-C. Diuretic use was associated with increases in TOTAL-C in both groups and with increases in LDL-C in the cholestyramine group.

Adult↗

Differentiation of Cryptococcus neoformans serotypes by isoenzyme electrophoresis.

Cryptococcus neoformans has been divided into four serotypes by specific agglutination in immune rabbit sera. Based on mating characteristics of the perfect state and epidemiologic and biochemical differences, the serotypes have been divided into two major pairs. In an attempt to characterize the serotypes further, the authors studied 22 strains of C. neoformans by the technic of horizontal starch-gel isoenzyme electrophoresis. The glucose-phosphate isomerase and phosphoglucomutase of serotypes A, C, D, and a subset of the serotype B strains migrated to distinguishable locations in this system. The activities of the remainder of the serotype B strains co-migrated with the serotype C strains. Thus, this technic distinguishes all the serotypes of C. neoformans except for a subset of serotype B and should be a useful adjunct for further elucidation of the epidemiologic and biochemical differences among serotypes.

Cryptococcus↗

In vitro susceptibility of fungi to killing by neutrophil granulocytes discriminates between primary pathogenicity and opportunism.

Pathogenic fungi, according to their propensity to cause infection of apparently normal individuals, can be grouped into either primary pathogens (e.g., Coccidioides, Histoplasma, Paracoccidioides, Blastomyces, and Sporothrix) or opportunists (e.g., Candida, Mucoraceae, Aspergillus spp., Petriellidium, and Trichosporon). There is, however, no unifying concept explaining the difference between the virulence of the two fungal categories. Previously we have speculated that neutrophils are the common denominator of the high natural resistance to opportunistic fungi. Accordingly, we then compared the susceptibility to killing by neutrophil granulocytes of Histoplasma, Blastomyces, Paracoccidioides, and Sporothrix with that of 14 opportunistic fungi. We found the four virulent dimorphic yeasts, in contrast to opportunistic fungi, to be resistant to killing by neutrophils. Virulent dimorphic yeasts were ingested by neutrophils, and triggered a respiratory burst comparably to opportunists but were less susceptible to hydrogen peroxide, suggesting that differences in the susceptibility to microbicidal products of leukocytes may explain the difference in virulence.

Blastomycosis↗

Detection of blood (hemoglobin) contamination in poultry muscle tissue.

Incidence of blood spots in fresh marketed poultry and batter or breaded frozen fried chicken may be related to certain processing parameters (i.e., stunning, bleed-out time). Spectrophotometric and cation exchange high performance liquid chromatography (HPLC) procedures were evaluated as potential methods to test for hemoglobin (Hb) contamination in poultry tissue. Muscle tissue was blended with TRIS-ethylenediaminetetraacetate buffer, pH 7.4, centrifuged and the extract scanned for absorbance at 540 and 580 nm. Tests with model systems gave a linear regression coefficient of r + .98 for detection of 0 to 1% blood in experimentally contaminated tissue. Analyses of extracts by cation exchange HPLC (545 nm) showed three separation peaks characteristic of hemoglobin. Isoelectrofocusing of the extracts on thin-layer polyacrylamide gels (pI 3 to 10) was also evaluated. These procedures could prove useful in subsequent studies to determine the cause of blood spotting in muscle tissue.

Animals↗

Growth and antigenic variation of Trypanosoma brucei, T. rhodesiense and T. gambiense in subcutaneous millipore chambers.

The inability to cultivate infective bloodstream forms of the African trypanosomes in cell-free media has complicated studies of the biology of trypanosomes and the pathogenesis of trypanosomiasis. We attempted to overcome this problem by subcutaneous implantation in mice of Millipore chambers that isolate trypanosomes from cells but permit diffusion of soluble substances across their membranes. Chambers were inoculated with 5 X 10(4) to 5 X 10(5) per ml Trypanosoma brucei, T. rhodesiense or T. gambiense; the trypanosomes multiplied rapidly, persisted for as long as five weeks, and remained infective, even when the original inocula were freed of donor cells by ion-exchange. The presence of anti-trypanosomal IgG and IgM in the sera and chambers of recipient mice proved that trypanosomal and mammalian products crossed the membranes. Chamber trypanosomes also expressed two important aspects of normal in vivo biological behaviour: (i) differentiation from long slender to short stumpy bloodstream forms and (ii) antigenic variation. Death of trypanosomes was associated with the presence of IgM antibody in the chambers. This model provides a system for study of an entire population of trypanosomes in an extravascular, cell-free environment.

Animals↗

Effect of theophylline on differentiation of Trypanosoma brucei.

Differentiation of Trypanosoma brucei in the mammal limits the degree of parasitemia and prepares the trypanosome for passage back into the tsetse fly. In an attempt to define the signals that control differentiation, we found that theophylline, in contrast to indomethacin, blocked differentiation, prolonged parasitemia, elevated prostaglandin and cyclic AMP concentrations of rat plasma, and depressed intratrypanosomal cyclic AMP. Relatively nontoxic drugs that alter differentiation are powerful tools for elucidating the events that control this important process.

Aminophylline↗