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Biomedical subjects

D Fisher

Publications and source records attributed to D Fisher.

At least 127 records · Page 7Linked to original sources
PubMed1994

Smoke inhalation with a concurrent systemic stress results in lung alveolar injury.

Smoke inhalation causes injuries to lung airways, and, at times, alveolar inflammation also develops over approximately 24 h. The pathophysiology of parenchymal lung injuries is unknown, and it is often fatal. We hypothesized that an inflammatory stress remote from the smoke-related lung insult was required for development of alveolar injuries. Spontaneously breathing rats were exposed, head only, to smoke generated by nonflaming pyrolysis (smoldering) of Douglas fir wood (DF), polyvinylchloride (PVC), or the combination of DF+PVC. Intraperitoneal injection of sterile oyster shell glycogen 4 h before smoke inhalation was used as an extra inflammatory stimulus. Histologic examinations revealed extensive airway inflammation in all smoke-exposed groups. Glycogen peritonitis alone caused no lung injuries, and in the absence of glycogen, smoke inhalation caused neither parenchymal lung injuries, assessed by [125I]bovine serum albumin (BSA) leakage, nor neutrophil infiltration, quantified by myeloperoxidase (MPO) activity. However, in rats pretreated with glycogen and studied 24 h after exposure to smoke from burning DF+PVC, [125I]BSA permeability was increased by 232 +/- 41% (SE; n = 13), MPO activity was increased 5-fold, from 2.6 +/- 0.4 (n = 7) to 13.9 +/- 1.4 (n = 19) A460/min/g lung, and histopathologic findings included extensive pulmonary inflammation. We conclude that inhalation of certain types of smoke will trigger pulmonary injury when an inflammatory process remote from the lungs is present.

Analysis of Variance↗
PubMed1994

Role of neutrophils and nitric oxide in lung alveolar injury from smoke inhalation.

We examined potential mechanisms responsible for the parenchymal lung injury seen in an animal model of smoke inhalation with concurrent inflammation. Rats injected with sterile glycogen and exposed to smoke generated by the nonflaming pyrolysis of combined Douglas fir wood and polyvinylchloride showed a 74% increase in 125I-albumin lung permeability and a fivefold increase in lung myeloperoxidase (MPO) compared with control rats. There was also a significant increase in plasma indices of oxidative injury in these animals. Compared with control animals, plasma concentrations of thiobarbituric acid reactive substances (TBARS) were elevated by 62%, the concentrations of reduced sulfhydryl groups declined by 37%, and the levels of dinitrophenylhydrazine-reactive proteins (DNPH-RP) were doubled. In addition, the plasma concentrations of nitrate (NO3-) in rats exposed to glycogen plus smoke were increased three times that of control animals. Injection of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), immediately after smoke exposure or induction of neutropenia using either nitrogen mustard or antineutrophil antiserum, abolished the increase in concentrations of circulating NO3-, and prevented changes in plasma concentrations of TBARS, DNPH-RP, lung MPO activity, and tissue permeability index. These data suggest that neutrophil activation and the production of nitric oxide-derived oxidants contribute to the lung and plasma indices of oxidative injury in this smoke inhalation model.

2,4-Dinitrophenol↗
PubMed1994

Cryptococcal meningitis (C. neoformans var. gattii) leading to blindness in previously healthy Melanesian adults in Papua New Guinea.

Cryptococcal meningitis is a common cause of chronic meningitis in Papua New Guinea, affecting apparently immunocompetent people. The majority of infections are believed to be due to Cryptococcus neoformans var. gattii. We have reviewed the records of 49 Melanesian adults who presented with proven cryptococcal meningitis to the University teaching hospital in Port Moresby, and compare our findings with other published studies of cryptococcal meningitis in the tropics and sub-tropics. None of the patients had an obvious cause of immunosuppression. Visual disturbances and fundoscopic changes of papilloedema or papillitis were particularly common. The in-hospital case fatality rate for patients treated with amphotericin B and flucytosine was 22.4%. Of the fully treated patients, 31% became completely blind before being discharged from hospital. Therapy directly aimed at reducing intracranial pressure may improve outcome.

Adolescent↗
PubMed1993

Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support.

BACKGROUND: Radiolabeled monoclonal antibodies recognizing B-lymphocyte surface antigens represent a potentially effective new therapy for lymphomas. We assessed the biodistribution, toxicity, and efficacy of anti-CD20 (B1 and 1F5) and anti-CD37 (MB-1) antibodies labeled with iodine-131 in 43 patients with B-cell lymphoma in relapse. METHODS: Sequential biodistribution studies were performed with escalating doses of antibody (0.5, 2.5, and 10 mg per kilogram of body weight) trace-labeled with 5 to 10 mCi of 131I. The doses of radiation absorbed by tumors and normal organs were estimated by serial gamma-camera imaging and tumor biopsies. Patients whose tumors were estimated to receive greater doses of radiation than the liver, lungs, or kidneys (i.e., patients with a favorable biodistribution) were eligible for therapeutic infusion of 131I-labeled antibodies according to a phase 1 dose-escalation protocol. RESULTS: Twenty-four patients had a favorable biodistribution, and 19 received therapeutic infusions of 234 to 777 mCi of 131I-labeled antibodies (58 to 1168 mg) followed by autologous marrow reinfusion, resulting in complete remission in 16, a partial response in 2, and a minor response (25 to 50 percent regression of tumor) in 1. Nine patients have remained in continuous complete remission for 3 to 53 months. Toxic effects included myelosuppression, nausea, infections, and two episodes of cardiopulmonary toxicity, and were moderate in patients treated with doses of 131I-labeled antibodies that delivered less than 27.25 Gy to normal organs. CONCLUSIONS: High-dose radioimmunotherapy with 131I-labeled antibodies is associated with a high response rate in patients with B-cell lymphoma in whom antibody biodistribution is favorable.

Antibodies, Monoclonal↗
PubMed1993

Strongyloidiasis in the Northern Territory. Under-recognised and under-treated?

OBJECTIVE: To describe the clinical and laboratory features and management of Strongyloides stercoralis infection in the Top End of the Northern Territory. DESIGN: A 12-month retrospective review of clinical records of patients confirmed on stool microscopy to be infected with S. stercoralis. SETTING: The Royal Darwin Hospital (RDH), a 300-bed referral hospital servicing the tropical areas of the Northern Territory, which have a population of 120,000, 21% of which is Aboriginal. RESULTS: Potentially pathogenic gastrointestinal parasites were identified in 205 patients over the 12 months. Of these, 68 patients had strongyloidiasis--64 were Aboriginal, three were Caucasian and one was of New Guinean origin. Thirty-seven (54%) were under five years of age. Patients came from all regions served by RDH, including urban Darwin. Seventy-five per cent of adults had chronic underlying disease and 80% of children under five years old were below 80% of standard weight for age. Gastrointestinal symptoms were absent in 28%; occasionally, severe disease occurred. Eosinophilia with greater than 0.7 x 10(9) cells/L was present in 57% of patients. Only 57% of cases were treated with thiabendazole. CONCLUSION: In the Top End of the Northern Territory, Strongyloides infection is endemic in Aboriginal communities, but also occasionally occurs in non-Aboriginal people. It is likely that the infection is frequently not recognised. Current community-based anthelmintic regimens have succeeded in reducing the prevalence of hookworm infection, but strongyloidiasis still appears to be a prevalent condition. The possibility of hyperinfection or disseminated strongyloidiasis in immunocompromised patients such as renal transplant recipients and people infected with the human immunodeficiency virus needs consideration in this endemic area. The interaction in northern Australia of S. stercoralis with human T-lymphotropic virus type I and with undernutrition warrants further study.

Adolescent↗
PubMed1993

Polymer-derivatized technetium 99mTc-labeled liposomal blood pool agents for nuclear medicine applications.

By using the lipophilic chelator, dipalmitoylphosphatidylethanolamine-diethylenetriaminetetraacetic acid (DPPE-DTTA), lipid vesicles may be prepared labeled on their surface with technetium 99m. When technetium-labeled vesicles were injected intravenously into rabbits, the half-life for clearance of the label from the circulation was less than 30 min. By further incorporating a synthetic phosphatidylethanolamine-monomethoxypoly(ethylene glycol) 5000 conjugate (PE-MPEG) the circulation half-life of the radiolabel was increased, liver uptake decreased and exchange of technetium from the vesicle surface suppressed, depending upon both the DPPE-DTTA and PE-MPEG content. For vesicles containing 20 mol% DPPE-DTTA, incorporation of PE-MPEG had no effect upon the circulation half-life of the radiolabel, however, for vesicles containing 2 mol% DPPE-DTTA, incorporation of more than 4 mol% PE-MPEG increased the circulation half-life of the label to more than 12 h. Less than 2 mol% PE-MPEG or 8 mol% ganglioside GM1 were, however, ineffective at increasing the circulation half-life of surface-bound technetium. It was shown that unilamellar lipid vesicles with DPPE-DTTA can be lyophilized in the presence of external sucrose, subsequently rehydrated with no change in vesicle size and labeled with technetium. It is suggested that polymer-derivatized, technetium-labeled vesicles may prove a useful substitute for technetium-labeled red blood cells as a vascular marker in various nuclear medicine procedures and that lyophilization/rehydration provides a possible route to realization of such vesicles in a pharmaceutically useful form.

Animals↗
PubMed1993

Phase partitioning detects differences between phospholipase-released forms of alkaline phosphatase--a GPI-linked protein.

A number of enzymes are known to release alkaline phosphatase and other glycan phosphatidylinositol-anchored proteins from membrane surfaces. We describe a novel approach to detect and measure these activities by partitioning in aqueous phase systems. The procedures avoid the complications of micelle-formation involving hydrophobic molecules that may arise with detergent-based partition systems and can clearly distinguish between inositol-specific phospholipase C and D activities.

Alkaline Phosphatase↗
PubMed1993

Two-phase partitioning applied to changes in phospholipid asymmetry.

In summary aqueous two-phase polymer partition is a useful addition to the range of techniques available for determining lipid asymmetry in model and in biological membrane systems. The methodology is straightforward, the experimental requirements simple and the materials used inexpensive. We have demonstrated its usefulness in several model membrane systems rendered asymmetric by the establishment of a membrane potential across the lipid bilayer and in monitoring Ca(2+)-induced asymmetry in human erythrocytes.

Electrophysiology↗
PubMed1993

Cryptococcus neoformans in tropical northern Australia: predominantly variant gattii with good outcomes.

BACKGROUND: Infection with Cryptococcus neoformans is common in the Northern Territory of Australia. Disease is life threatening and treatment is prolonged and often complicated by the need for surgery and difficulties with medical therapy. AIMS: To document incidence, demography, risk factors, clinical features and outcomes of infection and to determine differences between gattii and neoformans varieties. METHODS: Case records of all patients (n = 35) diagnosed with cryptococcal infection at the Royal Darwin Hospital between 1976 and 1992 were reviewed retrospectively. Current status of patients was ascertained. Variety identification of isolates was determined by growth in canavanine-glycine-bromthymol blue agar. RESULTS: Of the 35 patients, 23 had meningitis, ten had pneumonia, one had a dermal infection and one had fungaemia with no obvious focus. Twelve (52%) meningitis cases and two (20%) pneumonia cases had no predisposing disease. Thirteen (57%) meningitis cases had concomitant pulmonary cryptococcosis. Twenty-nine patients with Aboriginal and six were Caucasian, with a relative risk for Aboriginals compared with non-Aboriginals of 20.6 (95% CI 8.6-49.5). Arnhemland was the commonest location of infection, with an annual incidence in Aboriginals of 0.14/1000. Fourteen (78%) of 18 isolates tested were C. neoformans var. gattii. Management was characterised by the frequent need for adjunctive surgery and prolonged or repeat courses of systemic antifungal therapy. Despite this, long-term outcomes are encouraging with a mortality of 14% overall and 9% in meningitis patients. The river red gum (Eucalyptus camaldulensis) has a limited distribution in Arnhemland and ongoing studies are seeking alternative environmental sources of C. neoformans var. gattii.

Adolescent↗
PubMed1993

Pseudomyxoma peritonei.

Pseudomyxoma peritonei results from implantation of malignant tumors or irritation from ruptured benign cysts. This disease is traditionally characterized by accumulation of mucinous ascites, relatively long survival period and absence of extraperitoneal metastases. Disease progression is difficult to predict because of the spectrum of underlying pathologic entities. Four unusual instances of pseudomyxoma peritonei are presented. An instance of the neoplasm confined to the splenic parenchyma suggests potential for hematogenous dissemination. The tumor can be limited to and extend along the retroperitoneum. Retained rectal tissue after proctocolectomy may be a possible origin of disease. Enterobronchial fistula formation is a serious long term complication. Aggressive surgical approach with resection of the bulk of disease offers the optimal palliation and prognosis.

Female↗
PubMed1992

Nuclear magnetic relaxation dispersion and 31P-NMR studies of the effect of covalent modification of membrane surfaces with poly(ethylene glycol).

Covalent attachment of methoxypoly(ethylene glycol) (MPEG) 5000 to the surface of unilamellar liposomes composed of egg phosphatidylcholine and dioleoylphosphatidylethanolamine (DOPE) (8:2) containing paramagnetic chelates, either entrapped within the interior volume of the liposomes, or associated with the membrane surface, had no effect upon the measured spin-lattice relaxation rates (1/T1) for water in these systems. 31P-NMR studies indicate no destabilization of dioleoylphosphatidylcholine (DOPC)/(DOPE) (1:1) vesicles following attachment of MPEG. However, in DOPC/DOPE (1:3) mixtures, covalent modification with MPEG results in a destabilization of multilamellar vesicles into smaller vesicular structures. These results indicate that covalent attachment of poly(ethylene glycol) to liposomal magnetic resonance agents may prove a useful method for increasing their utility as vascular MR agents by extending their lifetime in the circulation, without decreasing the relaxivity of paramagnetic species associated with the liposome, but that the presence of PEG covalently attached to the membrane surface may modify the polymorphic phase behavior of the lipid system to which it is covalently linked.

Lipid Bilayers↗
PubMed1992

Erythrocyte partitioning in dextran-poly(ethylene glycol) aqueous phase systems. Events in phase and cell separation.

Early events in the partitioning process which involve characteristic kinetics of cell- and phase-specific interactions and phase separation have been described previously. This paper reports on red cell-phase droplet interactions pertaining at the time of usual phase sampling (i.e., the time at which a clear bulk interface is first apparent) and beyond in cell partitioning and countercurrent distribution experiments. In non-charge-sensitive phase systems close to the critical point, cells can be free or attached to phase droplets. Cells that are free are virtually completely in the top phase, whereas different cell populations that show essentially complete binding to droplets can nevertheless have different partition ratios and be separated, thus reflecting the effects of the difference in the cells' avidity for the phase droplets during the early, elapsed events in partitioning. At higher polymer concentrations (i.e., higher interfacial tensions), the cell populations, completely bound to phase droplets, partition completely to the interface, and consequently cannot be separated. When such systems are made charge-sensitive by the generation of a Donnan potential between the phases or made into affinity systems by the incorporation of PEG ligands (e.g., PEG-palmitate), there is a decrease in the avidity of the cells for phase droplets. The resulting increase in the ratio of free to droplet-bound red cells in the top phase at the time of sampling correlates with an increase in the partition ratio, P, observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗