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Biomedical subjects

G H Downie

Publications and source records attributed to G H Downie.

6 recordsLinked to original sources
PubMed2002

Pulmonary arteriovenous malformation.

Pulmonary arteriovenous malformations (PAVM) are rare pulmonary vascular anomalies. Although most patients are asymptomatic, PAVMs can cause dyspnoea from right-to-left shunt. Because of paradoxical emboli, various central nervous system complications have been described including stroke and brain abscess. There is a strong association between PAVM and hereditary haemorrhagic telangiectasia. Chest radiography and contrast enhanced computed tomography are essential initial diagnostic tools but pulmonary angiography is the gold standard. Contrast echocardiography is useful for diagnosis and monitoring after treatment. Most patients should be treated. Therapeutic options include angiographic embolisation with metal coil or balloon occlusion and surgical excision.

Arteriovenous Malformations↗
PubMed2001

Therapeutic efficacy of granulocyte-macrophage colony-stimulating factor in patients with idiopathic acquired alveolar proteinosis.

Alveolar proteinosis (AP) is characterized by excessive surfactant accumulation, and most cases are of unknown etiology. Standard therapy for AP is whole-lung lavage, which may not correct the underlying defect. Because the hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is required for normal surfactant homeostasis, we evaluated the therapeutic activity of GM-CSF in patients with idiopathic AP. Fourteen patients received 5 microg/kg/d GM-CSF for 6 to 12 wk with serial monitoring of the alveolar-arterial oxygen gradient ([A-a]DO2), diffusing capacity of carbon monoxide, computed tomographic scans, and exercise testing. Patients not responding to 5 microg/kg/d GM-CSF underwent stepwise dose escalation, and responding patients were retreated at disease recurrence. Stored pretreatment sera were assayed for GM-CSF-neutralizing autoantibodies. According to prospective criteria, five of 14 patients responded to 5 microg/kg/d GM- CSF, and one of four patients responded after dose escalation (20 microg/kg/d). The overall response rate was 43% (mean improvement in [A-a]DO2 = 23.2 mm Hg). Responses lasted a median of 39 wk, and were reproducible with retreatment. GM-CSF was well-tolerated, with no late toxicity seen. The only treatment-related factor predictive of response was GM-CSF-induced eosinophilia (p = 0.01). Each of 12 patients tested had GM-CSF-neutralizing autoantibodies present in pretreatment serum. We conclude that GM- CSF has therapeutic activity in idiopathic AP, providing a potential alternative to whole-lung lavage.

Adolescent↗
PubMed1993

Cholelithoptysis. A complication following laparoscopic cholecystectomy.

A 59-year-old woman who underwent laparoscopic cholecystectomy for symptomatic cholecystitis presented four months later with fever, malaise, anorexia, hemoptysis and lithoptysis. Chemical analysis of the expectorated lithes revealed them to be gallstones. Ultrasound studies of the right upper quadrant demonstrated both supradiaphragmatic and subdiaphragmatic fluid collections containing echogenic fragments. ERCP failed to demonstrate retained ductal stones or fistula formation. To our knowledge, this is the first reported case of cholelithoptysis and demonstrates an unusual complication of gallstone retention following laparoscopic cholecystectomy.

Bronchi↗
PubMed1992

Interleukin-2 directly increases albumin permeability of bovine and human vascular endothelium in vitro.

The direct effects of interleukin-2 (IL-2) on albumin permeability of cultured bovine pulmonary artery endothelial cell (BPAEC) and human arterial endothelial cell (HAEC) monolayers were studied. BPAEC were exposed to IL-2 (500 to 25,000 U/ml) for 4 h. The steady-state transfer rate of [125I]albumin across the BPAEC monolayer was 3.3 +/- 0.4%/h (n = 10) in control BPAEC (diluent alone), was significantly increased in BPAEC exposed to 500 U/ml of IL-2 (72 +/- 3% above control values, n = 6, P less than 0.02), and further increased in BPAEC exposed to 5,000 U/ml (60 +/- 2% increase above 500 U/ml values, n = 5, P less than 0.02). No further increase was noted after exposure to 25,000 U/ml of IL-2. Additionally, no further increase in [125I]albumin transfer rates was noted in BPAEC exposed to 5,000 U/ml of IL-2 for 24 versus 4 h. Similar changes were found using HAEC. Preincubation of HAEC with an anti-IL-2 low-affinity receptor antibody (anti-IL-2R alpha) inhibited the IL-2-induced permeability increase. Expression of IL-2R alpha receptors in HAEC incubated with 5,000 U/ml of IL-2 for 4 h was also found. Thus, IL-2 appears to have a direct effect on cultural arterial endothelial monolayers not requiring the presence of other cell types or serum proteins. IL-2-induced increases in endothelial macromolecular permeability may play an important role in the pathogenesis of the IL-2-induced vascular leak syndrome seen in vivo.

Albumins↗
PubMed1983

Lung injury mediated by antibodies to endothelium. I. In the rabbit a repeated interaction of heterologous anti-angiotensin-converting enzyme antibodies with alveolar endothelium results in resistance to immune injury through antigenic modulation.

To study the effects of relatively long-term interaction of antibodies with surface antigens of lung endothelium, rabbits were intravenously injected for a maximum of 4 d with goat anti-rabbit lung angiotensin-converting enzyme (Gt anti-RbACE) antibodies. On day 1 69%, on day 2 13%, and on days 3 and 4 of injection none of the rabbits developed lethal pulmonary edema. By immunofluorescence microscopy, deposits of GtIgG, frequently in association with RbC3, were found along the endothelium of alveolar capillary walls in all rabbits studied on day 1, in 57% on day 2, in 33% on day 3, and in none of them on day 4. While in vitro anti-ACE antibodies bound in a linear pattern to the lung endothelium, the binding pattern in vivo was distinctly granular. The in vivo interaction of antibodies with ACE also redistributed ACE in a granular pattern along capillary walls. In contrast to the granular deposition of injected anti-ACE IgG and F(ab')2 fragments of anti-ACE IgG, Fab fragments of anti-ACE IgG localized, without fixing C3, in a linear pattern along the endothelium of lung capillaries and did not modify the normal distribution of ACE. However, when the injection of Fab fragments of Gt anti-RbACE IgG was followed by an injection of Rb anti-GtIgG serum, granular deposits of Gt Fab fragments, RbIgG and RbC3 were seen along alveolar capillary walls. Biochemical measurement of ACE activity in lung homogenates provided data in agreement with those obtained by immunofluorescence microscopy, showing diminished activity to none on day 4, with some return of ACE activity on day 5, 24 h after the last injection of antibody, and normal values on day 21. The results obtained indicate that divalent antibodies to an antigen expressed on the plasma membrane of rabbit lung endothelial cells promotes a rapid redistribution of antigenic receptors, fixation of complement and, in surviving rabbits, disappearance of the antigen from the endothelial cells that are no longer susceptible to immune injury. In vivo "immunologic enzymectomy" induced by a ligand-surface antigen interaction is an example of antigenic modulation. These events may have an important role in the pathogenesis of inflammatory lesions induced by antibodies reacting with antigens expressed on the plasma membrane of cells in the lung and in other organs.

Animals↗