Using explicit criteria, delirium was diagnosed in 15% of a cohort of 133 hospitalized patients. Following each patient's discharge or death, the length of stay was compared with the diagnosis related group-predicted length of hospitalization. An analysis of stay variations disclosed that delirious patients exceeded their predicted stay by an average of 13 days, while nondelirious patients exceeded theirs by 3.3 days. The mean (+/- SD) length of hospitalization for patients with delirium was significantly longer than for their nondelirious counterparts (21.6 +/- 23.7 days vs 10.6 +/- 10.1 days, respectively). Hospitals treating high proportions of patients with delirium as a comorbidity to a principal somatic diagnosis should institute measures for the early detection of and appropriate intervention in patients with this condition. These steps may help reduce prolonged hospitalizations and minimize financial risk under the current diagnosis related group reimbursement system.

Aged↗

PubMed1988

Inhibition of macrophage- and neutrophil-mediated cytotoxicity by verapamil.

Peripheral blood monocyte-derived macrophages and polymorphonuclear leukocytes (PMNs) obtained from normal donors kill tumor cells in vitro. However, if verapamil is added to the macrophages or neutrophil tumor cell suspensions in microgram concentrations (0.1 microgram to 0.1 mg), there is marked inhibition of tumor cell killing. The inhibitory effect for the macrophages resulted from an effect of verapamil on both the effector and target cells. When either the effector cells or target cells were preincubated with verapamil, they became resistant to the effects of the cytotoxic macrophages. Cytotoxicity was also inhibited when 0.1 mg of verapamil was added to the macrophages monolayers either at the time of addition of the tumor cells or 15-30 min after addition of the tumor cells, whereas no inhibition of cytotoxicity occurred when verapamil was added more than 30 min after the initiation of the cytotoxic reaction. For the neutrophils it was observed that the inhibitory activity resulted from an effect of verapamil on the effector cells rather than the target cells. When the effector cells were preincubated with verapamil they became incapable of killing the tumor cells, whereas preincubation of the target cells with verapamil had no effect on their ability to be killed by the neutrophils. Cytotoxicity was also inhibited when 0.1 mg of verapamil was added to the neutrophil monolayers either at the time of addition of the tumor cells or 15-60 min after addition of the tumor cells, whereas no inhibition of cytotoxicity occurred when verapamil was added more than 60 min after the initiation of the cytotoxic reaction.

Cytotoxicity, Immunologic↗

PubMed1987

Suppressor T cell activity in lymphoid interstitial pneumonia.

A case of lymphoid interstitial pneumonia was investigated for immunological abnormalities. Suppressor T cells were found. The abnormality in the lymphoid system could be corrected in vitro with levamisole. The patient thereafter developed histiocytic lymphoma and soon died without any response to chemotherapy.

Female↗

PubMed1987

Delirium: a test of the Diagnostic and Statistical Manual III criteria on medical inpatients.

Although 10% to 15% of patients admitted to acute care hospitals are in a state of delirium, few patients are given this diagnosis by their clinician. We field-tested the Diagnostic and Statistical Manual III (DSM-III) criteria for diagnosing delirium on 133 consecutively admitted patients to an acute medical ward. Twenty patients were delirious using DSM-III criteria, 19 more patients than were reported by the primary clinician. Seven delirious patients were less than 65 years of age (range, 32 to 64 years). Sixty-five percent of patients with delirium died, whereas significantly fewer (3.3%) of patients without delirium died (P less than .0001). We found that delirium could be readily and reliably detected (kappa coefficient of agreement = 0.62 for interrater reliability) using the DSM-III criteria. Clinicians should routinely screen hospitalized patients of all ages using DSM-III criteria to identify delirious patients for an immediate evaluation and treatment.

Adult↗

PubMed1987

Effect of neuropeptides on macrophage mediated cytotoxicity in normal donors and cancer patients.

The role of enkephalins, endorphins and other neuropeptides produced by the nervous system in the alteration of immune responsiveness is generally unknown. The present studies were undertaken to investigate the role of these neuropeptides in the modulation of cytotoxicity induced by LPS activated macrophages obtained from normal donors as well as breast cancer and Hodgkins disease patients. When the macrophages from normal donors were pretreated with these neuropeptides for 1 hr prior to co-culturing with target cells, macrophage mediated cytotoxicity was enhanced with 10(-6) M and 10(-8) M of [met]-enkephalin, 10(-6) M of [leu]-enkephalin and 10(-6) M and 10(-12) M of alpha-endorphin. However, when the macrophages were co-cultured with target cells in the presence of the neuropeptides, it was observed that 10(-6) M and 10(-12) M of alpha-endorphin enhanced cytotoxicity whereas no enhancement in cytotoxicity was observed when [met]-enkephalin or [leu]-enkephalin were added to the cultures. In fact, it appears that 10(-10) M of [met]-enkephalin and 10(-12) M of [leu]-enkephalin actually suppressed macrophage mediated cytotoxicity. When the opioid antagonist Naloxone was incubated with the neuropeptides in the presence of the macrophages the enhancement of macrophage killing produced by [met]-enkephalin, [leu]-enkephalin or alpha-endorphin was suppressed. When the breast cancer patients' macrophages were pretreated with these neuropeptides, enhancement in cytotoxicity was observed at 10(-10) M of [met]-enkephalin, and [leu]-enkephalin and at 10(-8) M and 10(-12) M of alpha-endorphin.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

PubMed1986

Do-not-resuscitate orders.

Explore the source record for details and available documents.

Brain Diseases↗

PubMed1986

Suppression or enhancement by superoxide dismutase of tumor cell killing by macrophages of normal donors and breast cancer patients.

This study was designed to examine the role superoxide production by macrophages plays in tumor killing. When superoxide dismutase was added to the normal macrophage-tumor cell (MA-160 cell line) suspensions macrophage mediated tumor cytotoxicity was suppressed. In contrast, superoxide dismutase often greatly enhances the cytotoxic ability of macrophages from breast cancer patients. To determine whether the inability of breast cancer patients' macrophages to kill tumor cells might be related to decreased levels of O2- production, we measured the amount of O2- generated by both normal and breast cancer patients' macrophages. The macrophages obtained from the normal donors produced 46.0 +/- 6.7 nanomoles O2-/10(6) macrophages per 10 minutes (mean +/- S.E. of 9 donors). In contrast, macrophages from the four breast cancer patients who possessed cytotoxic macrophages produced 56.4 +/- 5.2 nanomoles O2-/10(6) macrophages per 10 minutes whereas those from the 6 breast cancer patients who possessed non-cytotoxic macrophages produced 18.6 +/- 3.2 nanomoles O2-/10(6) macrophages per 10 minutes. Thus, it appears that there is a relationship between macrophage cytotoxicity and the level of O2- produced. Furthermore, it is possible that the inability to generate sufficient amounts of O2- might explain the inability of breast cancer patients' macrophages to kill tumor cells in some cases.

Breast Neoplasms↗

PubMed1986

Lidocaine inhibits macrophage mediated cytotoxicity and enhances neutrophil mediated cytotoxicity.

Peripheral blood monocyte derived macrophages and polymorphonuclear leukocytes (PMNs) obtained from normal donors kill tumor cells in vitro. However, if lidocaine is added to the macrophage tumor cell suspensions in microgram concentrations (0.1 micrograms-0.1 mg), there is marked inhibition of tumor cell killing. The inhibitory effect for the macrophages resulted from an effect of lidocaine on the effector cells. When the effector cells were preincubated with lidocaine, inhibition in macrophage mediated cytotoxicity was observed. Cytotoxicity was also inhibited when 0.01 mg of lidocaine was added to the macrophage monolayers either at the time of addition of the tumor cells or 15-60 min after addition of the tumor cells whereas no inhibition of cytotoxicity occurred when lidocaine was added more than 60 min after the initiation of the cytotoxic reaction. For the neutrophils it was observed that the lidocaine actually had an enhancing effect rather than inhibitory effect on their ability to kill tumor cells.

Antineoplastic Agents↗

PubMed1986

Effects of in vivo treatment with ibuprofen on macrophage function in breast and colon cancer patients.

In this study, the capacity of macrophages from breast and colon cancer patients to become cytotoxic for tumor cells after in vivo administration of the prostaglandin inhibitor, Ibuprofen, has been investigated. Prior to the administration of the drug, each patient's macrophages were tested for their ability to kill tumor cells in the presence and absence of 10(-7) M Ibuprofen. The patients were given 400 mg Ibuprofen 4 times daily for 28 days. At days 14 and 28 after commencing the study, blood samples were drawn and the macrophages were tested for their ability to kill tumor cells in vitro. The patients were divided into 3 groups: Category I, patients possessing non-cytotoxic macrophages in the presence and absence of Ibuprofen; Category II, patients possessing non-cytotoxic macrophages in the absence of the drug and cytotoxic macrophages in the presence of the drug; and Category III, patients possessing cytotoxic macrophages in the absence of the drug and non-cytotoxic macrophages in the presence of the drug. Category I cancer patients generally responded the most effectively to in vivo administration of Ibuprofen at day 28 whereas Category II patients responded the most effectively at day 14. Category II patients became non-responsive when tested again at day 28 and Category I patients became non-responsive when the study was extended to day 42. Category III patients were generally non-responsive at all time points studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

PubMed1986

Role of hydrocortisone, chloroquine and prednisolone in neutrophil mediated cytotoxicity.

Human polymorphonuclear leukocytes (PMNs) obtained from normal donors kill tumor cells in vitro. This system was utilized to study the role of lysosomal enzyme release in the cytotoxicity of human neutrophils. When the neutrophils were incubated with hydrocortisone, chloroquine and prednisolone, which are drugs known to stabilize lysosomal membranes, hydrocortisone and chloroquine were unable to inhibit cytotoxicity whereas treatment with prednisolone inhibited cytotoxicity. Recovery in cytotoxicity was observed as the dose of prednisolone utilized was decreased. Cytotoxicity equivalent to that observed with no added drug was found 5 X 10(-7) M for prednisolone. Pretreatment of neutrophils with a dose of prednisolone known to inhibit cytotoxicity (5 X 10(-6) M) resulted in decreased release of the lysosomal enzyme, acid phosphatase, in comparison to untreated neutrophils.

Acid Phosphatase↗

PubMed1985

Isolation of tumoricidal human factors from lymphoid cells and enzymatic digestion of these factors into small fragments retaining tumoricidal effects.

Gel filtration and immunoadsorption techniques have been utilized to purify tumoricidal factors from sturgeon sera as well as human plasma. Two pure proteins with cytotoxic activity were isolated from the sturgeon serum (factors A2 and B2) and two additional cytotoxic factors were isolated from human plasma (Factors A and B). In another study, human factors A and B were quantitated in both normal donor and cancer patients' plasma. It was found that the cancer patients produced at least 50% less tumoricidal factors than did the normal donors. Furthermore, when the secretions from various lymphoid cell populations were purified utilizing immunoadsorbent techniques, it was found that the macrophages generally were producing the human tumoricidal factors. Both the sturgeon and the human factors were enzymatically cleaved into several small molecular weight fragments. Sephadex G-75 column chromatography was then utilized to isolate the enzymatic cleavage fragments. Three fragments with cytotoxic activity were isolated from both sturgeon factor A2 and B2. Similarly, human factor A was digested into two fragments with cytotoxic activity and factor B was digested into three fragments with cytotoxic activity. The molecular weights of the cytotoxic sturgeon and human fragments ranged from 14,000 to 23,000 whereas the intact sturgeon and human factors had a molecular weight slightly greater than 67,000. Ultimately, if these small molecular weight fragments can be sequenced, then it would be possible to prepare a synthetic analog which might have future potential as a mode of treatment for cancer patients.

Animals↗

PubMed1985

Inhibition of neutrophil-mediated cytotoxicity by exogenous adenosine 5'-triphosphate.

Human polymorphonuclear leukocytes (PMNs) obtained from normal donors kill human tumor cells in vitro. However, if adenosine 5'-triphosphate (ATP) is added to the neutrophil tumor cell suspensions in micromolar concentrations (10-100 microM), there is marked inhibition of neutrophil-mediated cytotoxicity. The inhibitory activity resulted from an effect of ATP on both the effector cells as well as the target cells. When either the effector cells or target cells were preincubated with ATP they became resistant to the effects of the cytotoxic neutrophils. In addition, inhibitory activity was specific to ATP; as it was not demonstrated with GTP, UTP, or CTP. However, when the other adenosine compounds (AMP and ADP) were tested, both AMP and ADP had some inhibitory activity. Cytotoxicity was also inhibited when 100 microM of ATP were added to the neutrophil monolayers either at the time of addition of the tumor cells or 15-60 min after addition of the tumor cells whereas no inhibition of cytotoxicity occurred when ATP was added more than 1 hr after the initiation of the cytotoxic reaction.

Adenosine Diphosphate↗

PubMed1985

Specificity of macrophage-mediated cytotoxicity: role of target and effector cell fucose.

In this study, we have examined the role cell surface carbohydrates play in the activation of macrophages to kill tumor cells as well as the effect removal of tumor cell surface fucose has on the susceptibility of the treated target cells to the cytotoxic macrophages. After incubation of human monocyte-derived macrophages with alpha-L-fucosidase, a glycosidase which splits terminal alpha-L-fucose from oligosaccharides, the macrophages were no longer able to respond to lipopolysaccharide (LPS). These experiments strongly suggest that alpha-L-fucose probably comprises an essential part of the macrophage membrane receptor for LPS. In another series of experiments tumor cells were treated with alpha-L-fucosidase prior to co-cultivation with macrophages to determine whether the presence of alpha-L-fucose on the tumor cell surface had any effect on macrophage mediated cytotoxicity. It was found that the MA-160 sensitive tumor target, after alpha-L-fucosidase treatment, became resistant to the effects of the cyto-toxic macrophages whereas the effect of the alpha-L-fucosidase treatment was blocked by addition of alpha-L-fucose to the incubation mixture.

Cell Line↗