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Biomedical subjects

A Damiano

Publications and source records attributed to A Damiano.

At least 19 recordsLinked to original sources

The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults.

The objective of this study was to refine the APACHE (Acute Physiology, Age, Chronic Health Evaluation) methodology in order to more accurately predict hospital mortality risk for critically ill hospitalized adults. We prospectively collected data on 17,440 unselected adult medical/surgical intensive care unit (ICU) admissions at 40 US hospitals (14 volunteer tertiary-care institutions and 26 hospitals randomly chosen to represent intensive care services nationwide). We analyzed the relationship between the patient's likelihood of surviving to hospital discharge and the following predictive variables: major medical and surgical disease categories, acute physiologic abnormalities, age, preexisting functional limitations, major comorbidities, and treatment location immediately prior to ICU admission. The APACHE III prognostic system consists of two options: (1) an APACHE III score, which can provide initial risk stratification for severely ill hospitalized patients within independently defined patient groups; and (2) an APACHE III predictive equation, which uses APACHE III score and reference data on major disease categories and treatment location immediately prior to ICU admission to provide risk estimates for hospital mortality for individual ICU patients. A five-point increase in APACHE III score (range, 0 to 299) is independently associated with a statistically significant increase in the relative risk of hospital death (odds ratio, 1.10 to 1.78) within each of 78 major medical and surgical disease categories. The overall predictive accuracy of the first-day APACHE III equation was such that, within 24 h of ICU admission, 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed (r2 = 0.41; receiver operating characteristic = 0.90). Recording changes in the APACHE III score on each subsequent day of ICU therapy provided daily updates in these risk estimates. When applied across the individual ICUs, the first-day APACHE III equation accounted for the majority of variation in observed death rates (r2 = 0.90, p less than 0.0001).

Age Factors

Lack of preferential transmission of diabetic HLA alleles by healthy parents to offspring in Spanish diabetic families.

HLA-DR3 or -DR4 segregation distortion to normal or insulin-dependent (ID) diabetic offspring of 108 Spanish families whose parents were healthy was not observed; however, DR3 or DR4 ID offspring is significantly increased in the present study, since parents were chosen after tracing ID children. These results are discrepant with those found by others in families with diabetic parents in other ethnic groups. These conflicting data could be due to sampling errors or segregation distortion. Thus, ethnic group differences in a genetic (T/t-like) or metabolic mechanism might confer advantages to DR3- or DR4-bearing gametes from ID diabetic parents, but segregation distortion might only affect certain HLA DR3 or DR4 extended haplotypes which are frequent and characteristic for certain ethnic groups (i.e. B8-DR3-BfS-C4AQOB1 and Bw62-DR3-BfS-C4A383 in most caucasians) but not for other haplotypes in other ethnic groups (Spaniards; B18-DR3-BfF1-C4A3BQO and BwX-DR4-BfX-C4AXBX).

Adolescent

Statistical methods for short-term projections of AIDS incidence.

Short-term projections of AIDS incidence are critical for assessing future health care needs. This paper focuses on the method of back-calculation for obtaining short-term projections. The approach consists of back-calculating from AIDS incidence data through use of the incubation period distribution to obtain estimates of the numbers previously infected. The numbers previously infected are then projected forward to obtain short-term projections. An approach is suggested for accounting for new infections in short-term projections of AIDS incidence. Back-calculation requires accurate AIDS incidence data. A method which is computationally easy to implement is proposed for estimating the distribution of the delays in reporting AIDS cases. It was found that the reporting delay distribution in the United States varies by geographic region of diagnosis. Back-calculation also requires a reliable estimate of the incubation period distribution. Statistical issues associated with estimating the incubation period distribution are considered. The methods are applied to obtain short-term projections of AIDS incidence in the United States. The projected cumulative AIDS incidence in the U.S. by the end of 1992 was 287,100 under the assumption that there are no new infections after 1 July 1987, and 330,600 under the assumption that the infection rate remains constant. These projections do not account for the new broadened AIDS surveillance definitions or the underreporting of AIDS cases to the Centers for Disease Control.

Acquired Immunodeficiency Syndrome

Dissociation of membrane binding and lytic activities of the lymphocyte pore-forming protein (perforin).

Granules isolated from CTL and NK cells contain a cytolytic pore-forming protein (PFP/perforin). At low temperatures (on ice), PFP binds to erythrocyte membranes without producing hemolysis. Hemolysis occurs when the PFP-bound erythrocytes are warmed up to 37 degrees C, which defines a temperature-dependent, lytic (pore-formation) step distinct from the membrane-binding event. Ca2+ and neutral pH are required for both membrane binding and pore formation by PFP. Serum, LDL, HDL, and heparin inhibit the hemolytic activity of PFP by blocking its binding to lipid membranes. Lysis by PFP that has bound to erythrocyte membranes is no longer susceptible to the effect of these inhibitors. The hemolytic activities associated with intact granules and solubilized PFP show different requirements for Ca2+ and pH, indicating that cytolysis produced by isolated granules may involve an additional step, possibly fusion of granules with membranes. It is suggested that three distinct Ca2+- and pH-dependent events may be involved during cell killing by CTL and NK cells: fusion of cytoplasmic granules of effector cells with their plasma membrane, releasing PFP from cells; binding of the released PFP to target membranes; and insertion of monomers and the subsequent formation of lytic pores in the target membrane. The serum-mediated inhibition of membrane binding by PFP could prevent the accidental injury of bystander cells by cell-released PFP, but would allow cytolysis to proceed to completion once PFP has bound to the target membrane.

Calcium

Isolation and characterization of a serine esterase from cytolytic T cell granules.

Cytotoxic T lymphocytes and lymphocytes with NK-like activity contain a serine esterase activity which has been localized to their cytoplasmic granules by cytochemistry and subcellular fractionation studies. The serine esterase-specific inhibitor 3H-DFP labels two protein species in the granules. The two proteins, referred to as serine esterases 1 and 2 (SE 1 and SE 2), migrate with Mr of 34-36 kd and 28-30 kd, respectively, under reducing conditions. SE 1 shows trypsin-like activity and has been purified to apparent homogeneity. Under nonreducing conditions, SE 1 has an Mr of 60-66 kd, suggesting that it may consist of two disulfide-linked subunits of 34-36 kd each. SE 1 cleaves fibrin and casein, has a pl greater than 10, and optimal activity at pH 8. The substrate specificity of SE 2 is not known. The serine esterase activity is secreted by lymphocytes that have been stimulated with the calcium ionophore A23187. The serine esterases described here could play an active role in cell-mediated killing.

Animals

Analysis of enzymatic activities of subcellular and chromatographic fractions by an automated colorimetric microassay system.

A simple, automated colorimetric microassay system has been designed to quantitate enzyme activities commonly used as markers for subcellular compartments. This system relies on the spectrophotometric reading of microtiter wells containing the chromophore products. The microassay allows rapid, economical, and quantitative analysis of enzyme activities associated with sucrose or Percoll gradient fractions used for subcellular fractionation studies as well as the screening of a large number of fractions derived from HPLC and other separation columns used for enzyme purification. We describe its use for the quantitation of activities associated with acid and alkaline phosphatases, alkaline phosphodiesterase, beta-glucuronidase, alpha-N-acetylglucosaminidase, alpha-mannosidase, alpha-L-fucosidase, glycosidases, serine esterases, and succinate dehydrogenase, and give the range of their sensitivities. This microassay system has been applied to the isolation of granules of cytolytic lymphocytes and to the identification and purification of a serine esterase from the isolated granules of these cells.

Chromatography

Extracellular release of lymphocyte cytolytic pore-forming protein (perforin) after ionophore stimulation.

The cytolytic pore-forming protein (PFP, perforin) of lymphocyte granules has recently been isolated and characterized. The lytic activities expressed by both the isolated granules and the purified PFP require the presence of Ca2+. Here, we report on the extracellular release of PFP after stimulation of lymphocytes with the Ca2+ ionophore A23187, which degranulates the cells. The secreted protein associates with lipid to form structural and functional channels and supramolecular complexes that partially resist dissociation by sodium dodecyl sulfate and reducing agents. Immunoblots of the released material reveal positive identification with antibodies specific for mouse PFP and human complement component C9, indicating cross-reactivity between these two molecules. By using these specific antibodies as immunoadsorbents, the lymphocyte PFP has been affinity purified from the supernatant of stimulated cells. The extracellular release of PFP is associated with simultaneous formation of functional ion-nonselective channels with conductances of 550-600 pS in 0.15 M NaCl, as measured in planar model bilayers. In the absence of extracellular Ca2+, 15% of the maximal release activity is observed. Ca2+ appears to be required to elicit both secretion by lymphocytes and the assembly of the released PFP into tubular polymers. Similar secretion of PFP may occur during cell killing by lymphocytes, resulting in its assembly on target membranes to form tubular transmembrane lesions.

Animals

[Acute brucellosis: our experience over a 3-year period].

Authors, based on objectives data of large incidence of acute Brucellosis in their job area in the last years, get in every patient coming in their Medicine Internal Department suffering from it through three years. They analyse mainly the epidemiological, clinic-biological and therapeutics aspects of this acute pathology. The epidemiological conclusions established on the objective analysis of the series issue make known great interest. The increase of this illness does not happen to be because of infection in animal farms, but for the existence of food channels that are not under sanitary control.

Adolescent