Macrophages in host defense mechanisms.
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Biomedical subjects
Publications and source records attributed to A Sanders.
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Macrophages such as Kupffer cells in the liver are multifunctional cells. They are involved in host defense mechanisms and have a regulatory role in many biomedical processes. Their selective depletion, using liposome-encapsulated drugs, forms a widely accepted approach to studying their functional aspects in vivo. We have compared the Kupffer cell-depleting activities of liposome-encapsulated clodronate, propamidine, and ethylenediaminetetraacetic acid (EDTA) for this purpose. These molecules represent the drug families of bisphosphonates, diamidines (or aromatic polyamidines), and polyaminopolycarboxylic acid-chelating agents, respectively. The Kupffer cell-depleting activity of the liposome-encapsulated antimicrobial drug propamidine exceeded that of clodronate by about a factor of 10. EDTA appeared to be inefficacious for depletion of Kupffer cells in the rat.
Cardiovascular nurses are active participants in implementing emergency cardiac care (ECC) guidelines as advanced cardiac life support (ACLS) providers and instructors. Cardiovascular nurses should play a key role in the ECC guidelines revision process. The article discusses the process of the most recent ECC guideline developments and revisions and describes subsequent changes to ACLs protocols.
Macrophages and T lymphocytes play an important role in recovery from viral infections. During mouse hepatitis virus (MHV-A59) infection, a clear virus-specific class II-restricted cytotoxic T-cell response is generated. Transfer of these CD4+ cytotoxic T cells (CTL) into naive mice protects against a lethal challenge with MHV. However, their in vivo antiviral effector mechanism is not yet clear. To further investigate a possible effector mechanism, we studied the effect of adoptive transfer of CD4+ CTL on virus localization in spleen and liver. We showed that adoptive transfer of virus-specific T cells does not affect localization of MHV-A59 in different macrophage subsets. Interestingly, a rapid and large infiltrate of CD4+ T cells in and around MHV-A59-infected foci in the liver was observed early in infection, whereas no CD8+ T cells were detectable. Moreover, transfer of virus-specific T cells resulted in significantly decreased viral titres in the liver and spleen and a marginally increased anti-MHV-A59 IgM production. These results imply an important role for virus-specific CD4+ CTL in elimination of infectious MHV-A59 and induction of an effective immune response in the absence of CD8+ CTL.
Liposomes are used as carriers of drugs intended to manipulate macrophage functions. The normal in vivo fate of liposomes is phagocytosis, followed by phospholipase-mediated disruption of their phospholipid bilayers and intracellular release of their contents. Using this method for intracellular delivery of drugs, we have developed an approach for in vivo depletion of macrophages. Phagocytosis also forms a major feature of parasitic amoebae. In the present experiments, we investigated whether amoebae could be killed using the same approach (liposome-mediated "suicide" of amoebae). The results confirm that liposomes are ingested by Ent-amoeba invadens cultured under routine laboratory conditions. From various chelator molecules and their metalion complexes that were active in the liposome-mediated elimination of macrophages, Cu-ethylenediaminetetraacetic acid (EDTA) complexes appeared to be the most efficacious compounds in the elimination of E. invadens.
Acute postobstructive pulmonary edema may occur after airway obstruction. A decrease in intrathoracic and intraalveolar pressures causes an increased blood flow into the pulmonary vasculature and favors the development of pulmonary edema. Two mechanisms for the development of acute postobstructive pulmonary edema are proposed: type 1 follows acute airway obstruction, and type 2 follows relief of chronic airway obstruction.
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Selective depletion of macrophages from tissues in vivo can be used to investigate whether these cells are playing a role in defined biological processes. This question is particularly relevant to various host defense mechanisms. We have developed a macrophage 'suicide' technique, using the liposome mediated intracellular delivery of dichloromethylene-bisphosphonate (Cl2MBP or clodronate). The method is specific with respect to phagocytic cells of the mononuclear phagocyte system (MPS) for the following reasons: (1) The natural fate of liposomes is phagocytosis. (2) Once ingested by macrophages, the phospholipid bilayers of the liposomes are disrupted under the influence of lysosomal phospholipases. (3) Cl2MBP intracellularly released in this way does not easily escape from the cell by crossing the cell membranes. (4) Cl2MBP released in the circulation from dead macrophages or by leakage from liposomes, will not easily enter non-phagocytic cells and has an extremely short half life in the circulation and body fluids. In the present review, the preparation of Cl2MBP-liposomes has been described in detail. Furthermore, the mechanism of action of the new approach and its applicabilities are discussed.
Confidentiality is a promise rooted in tradition, law, and medical ethics. Emergency physicians treat a variety of patients to whom confidentiality is of vital importance: employees, celebrities, victims of violence or disaster, minors, students, criminals, drug abusers, and patients with STDs. EDs should develop methods of ensuring confidentiality for all patients. Although confidentiality is an important principle that should be respected and guarded, it is not absolute. Various laws mandate disclosure of certain patient information; in addition, an overriding moral duty may occasionally require a breach of confidentiality. As Beauchamp and Childress noted, "the therapeutic role may sometimes have to yield to one's role as citizen and as protector of the interests of others." In general, however, circumstances requiring a breach of confidentiality are rare.
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Classical insulin-dependent diabetes mellitus (IDDM) is relatively uncommon in Indian-Asians whether in India or in the UK and this may be related to immunogenetic factors. We have studied the presence or absence of islet cell antibodies and other auto-antibodies in 36 subjects with IDDM and 41 controls, all of Indian origin. Islet cell antibodies (ICA-IgG) were found in 8 subjects with IDDM but in none of the controls. Four of the 8 patients with ICA-IgG also possessed the complement fixing variety (CF-ICA). There was no definite association between possession of ICA and HLA-DR antigens. Thyroid antibodies were commoner in patients (22%) compared with controls (7%) as were parietal cell antibodies (8.3% vs 4.8%). None of the patients or controls had adrenal antibodies. The frequency of organ-specific antibodies in Indian-Asians with IDDM is similar to that of white Caucasians. The overall frequency of ICA is, however, lower than that reported for white Caucasians although the temporal distribution is similar. We conclude that even though the prevalence of IDDM in Indian-Asians is lower than in white Caucasians there is no evidence that different immunological mechanisms are involved in the pathogenesis of IDDM in the two groups.
Pulmonary aspiration syndromes--aspiration of gastric contents and aspiration-associated plueropulmonary infections--are discussed.
A study was done comparing resuscitability and 24-hour neurologic outcome in fibrillating dogs that were treated with either phenylephrine (a primary alpha agonist) or epinephrine. Ventricular fibrillation was induced electrically in 18 dogs. After three minutes, standard CPR was instituted using a mechanical resuscitator. Dogs were given phenylephrine or epinephrine at nine minutes and defibrillation was attempted at 12 minutes. Dogs underwent hemodynamic monitoring and pharmacologic support, if necessary, for an additional 90 minutes. At four, eight, 12, and 24 hours, a standard neurologic examination was performed and deficit scores were assigned by an observer blinded to the drug given. Fourteen of the 18 dogs were resuscitated. There were no statistically significant differences in the epinephrine- or phenylephrine-treated groups with regard to number of animals resuscitated, time and interventions required for resuscitation, initial cardiac rhythm post resuscitation, or occurrence of ventricular fibrillation during resuscitation. No differences were found in arterial, central venous, or myocardial perfusion pressures during CPR. Phenylephrine-treated dogs tended to have higher mean pressures in the critical care period (15 to 30 minutes), although this was not significant. Total neurologic deficit scores were 127.8 +/- 83.8 for the phenylephrine-treated group and 129.4 +/- 87.4 for the epinephrine group. No significant differences were found in the level of consciousness, cranial nerve function, motor skills, or general behavior scores. We conclude that there is no difference in neurologic or cardiovascular outcome when phenylephrine is compared to epinephrine in a canine model of cardiac arrest and cardiopulmonary resuscitation.
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The concentration achieved in the infected tissue is of fundamental importance in the use of antibiotics. Erythromycin labelled with the positron-emitting nuclide carbon-11 and positron tomography were used to compare local concentrations of this antibiotic in the pneumonic and unaffected lungs of five patients with lobar pneumonia. The time course of uptake of erythromycin into the extravascular compartment (i.e., the intracellular, interstitial, and alveolar compartments) of the pneumonic lung was measured. The mean extravascular concentrations obtained during the first hour after an intravenous injection of 270 mg erythromycin lactobionate were similar in the pneumonic lung and the unaffected lung (5.5 +/- 2.2 and 6.6 +/- 2.2 micrograms/g, respectively). An effective concentration of erythromycin was reached in the pneumonic lung within 10 min of the injection and was maintained throughout the period of measurement (60 min).