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G Philip

Publications and source records attributed to G Philip.

At least 37 records · Page 2Linked to original sources

Nonallergic rhinitis. Pathophysiology and models for study.

Nonallergic rhinitis is a diagnosis of exclusion which is given to patients who suffer perennial nasal congestion, rhinorrhea, and/or sneezing with no identifiable allergic etiology. Because there is still no clear understanding of the pathophysiology, it is possible that a number of different disease processes may be included within this clinically defined entity. This report does not attempt to present an overall discussion of the clinical approaches to patients with nonallergic rhinitis. Instead, an outline is presented of various research approaches which may be used in its study. A number of nasal provocation models using nonallergic stimuli are available for application in the laboratory. These include intranasal methacholine challenges, intranasal histamine challenges, nasal inhalation of cold dry air, and intranasal capsaicin challenges. These models provide certain insights into mechanisms of nonallergic hyper-responsiveness. An additional approach to the study of nonallergic rhinitis is to examine available therapies, allowing the clinician to evaluate various pathways of importance in the disease process. These approaches provide a certain understanding of this common but perplexing entity, although further study is still required.

Capsaicin↗

The human nasal response to capsaicin.

Airway sensory nerves play a role in reactions to inhaled allergens, irritants, and physical stimuli. Capsaicin, the pungent principle of hot peppers, stimulates a subcategory of sensory nerves. To study the consequences of selective activation of airway sensory nerves in the human nose, we administered capsaicin nasal challenges to eight volunteers (four normal subjects and four subjects with perennial allergic rhinitis). Capsaicin (20 mumol/L), when sprayed into the nose, induced burning, rhinorrhea, and lacrimation. Capsaicin also induced a significant increase in total protein content of nasal lavage fluid after challenge compared with vehicle (increase from before challenge to 1 minute after challenge, 172 +/- 55 vs 46 +/- 29 micrograms/ml, p < 0.001). In contrast to many animal studies, capsaicin did not increase vascular permeability in the airway, because albumin content of nasal lavage fluid was not increased (p = 0.86). On the other hand, lactoferrin, a marker of glandular secretion, was increased (p < 0.005). Repetitive capsaicin challenge every 10 minutes led to tachyphylaxis of symptoms, total protein secretion, and lactoferrin secretion. Compared with vehicle, unilateral capsaicin (6 mmol/L) disk challenge induced significant secretion both ipsilateral (21.3 +/- 4.2 vs 4.9 +/- 2.1 mg, p < 0.01) and contralateral (18.2 +/- 4.4 vs 7.4 +/- 1.9 mg, p < 0.04) to challenge. Thus we have shown that capsaicin challenge to the human nose leads to airway sensory nerve activation. Further, we have demonstrated that capsaicin stimulates a predominantly central neuronal response and that the induced secretory response is of glandular rather than vascular origin.

Adult↗

Reflex activation of nasal secretion by unilateral inhalation of cold dry air.

Exposure to cold dry air induces rhinorrhea and other nasal symptoms in many persons. To evaluate whether this response involves a neurogenic component, we delivered a unilateral cold dry air (UniCDA) nasal challenge to volunteers with previously documented reactivity to cold dry air. We measured their nasal secretory responses bilaterally using small filter paper discs to absorb secretions from the nasal mucosa. UniCDA increased nasal secretion both ipsilateral (p < 0.001) and contralateral (p < 0.001) to the challenge when compared with control challenge. Topical atropine (0.225 mg), a muscarinic antagonist, inhibited ipsilateral secretion (p < 0.002) when given ipsilateral to UniCDA. When atropine was given contralateral to UniCDA, there was a trend toward reduction of contralateral secretion but no effect on ipsilateral secretion. Topical anesthesia with lidocaine given ipsilateral to UniCDA inhibited ipsilateral (p < 0.02) and contralateral (p < 0.05) secretion immediately after challenge. Topical anesthesia did not inhibit methacholine-induced nasal secretion. Thus, UniCDA stimulates reflex secretion both ipsilateral and contralateral to challenge which is inhibitable by interrupting either the efferent or the afferent arm of the reflex arc. This human in vivo model supports the importance of neural mechanisms in airway responsiveness to an environmental stimulus.

Adult↗

Demonstration of bilateral cholinergic secretory response after unilateral nasal cold, dry air challenge.

Cold, dry air (CDA) causes rhinorrhoea and nasal congestion in some individuals. This response can be mimicked in the laboratory by exposing susceptible individuals to cold, dry air nasal breathing. One of the characteristics of this response is that nasal secretions are produced by both nostrils after a unilateral challenge. This study evaluated the role of cholinergic innervation on the ipsi- and contralateral responses to unilateral CDA challenge. Twelve individuals participated in a randomized, double-blind, placebo-controlled, 3-way crossover study where local atropine and placebo were alternated ipsilateral and the contralateral to the CDA challenge. The reproducibility of the model, assessed by the response after pre-treating with placebo, was excellent; after placebo, the ipsilateral response was double the size of the contralateral. Regardless of the site of application, atropine significantly reduced the secretory response to CDA by 60-70%. However, significant secretions were still induced by CDA, even after atropine treatment. We conclude that cholinergically-mediated neuronal pathways play a major role in the nasal secretory response to CDA. Additional neuronal pathways may, however, be involved. This method is a tool to understand the different components of the mucosal response to a cold and dry environment.

Adult↗

Histopathological and microanalytical study of zirconium dioxide and barium sulphate in bone cement.

AIMS: To report the appearances of zirconium dioxide and barium sulphate in interface membranes, synovium, and other tissues around joint prostheses. METHODS: Histological sections from 23 specimens were reviewed by light microscopy and polarisation. Scanning electron microscopy and x ray microanalysis were performed on routinely processed paraffin wax sections. RESULTS: Polyethylene, metals, and polymethylmethacrylate cement debris were easily recognisable. Almost all the cement remnants contained either zirconium dioxide or barium sulphate, confirmed by microanalysis. The contrast media had characteristic light microscopic appearances. Zirconium was identified in macrophages away from cement remnants. CONCLUSION: The presence of radiographic contrast media in tissues around prosthetic joints is common but not widely recognised.

Adult↗

Comparative studies on the properties of glycogen phosphorylases from the foot muscles of two benthic bivalves, Sunetta scripta and Villorita cyprenoides, having different habitats.

Glycogen phosphorylase (1,4-alpha-D-glucan:orthophosphate-alpha-D-glucosyl transferase, EC 2.4.1.1) was partially purified from two bivalves found in different habitats, viz. Villorita cyprenoides, an estuarine bivalve, and Sunetta scripta, a marine bivalve, and their properties compared with other animal phosphorylases. While the kinetic mechanism was same as that of phosphorylases from other animal sources, it differed in the control mechanism from other phosphorylases. The observed differences support the earlier finding that the control mechanism adopted by different animals is dependent on the evolutionary status and energy needs.

Animals↗

Unusual bony lesions of histiocytosis X in a patient previously treated for Hodgkin's disease.

We present an unusual case of multifocal Histiocytosis X in a 78-year-old man treated for Hodgkin's Disease 33 and 24 years previously. The Hodgkin's Disease at first involved cervical nodes and 9 years later axillary and inguinal nodes and was treated by radiotherapy. Chronic destructive lesions developed in the femora and pelvis and bone biopsies showed a curious mixture of fibroblastic tissue and foamy macrophages. These lesions eventually resulted in pathological fractures of the femoral necks, and bilateral hip replacements were required seven years after initial detection of the bony lesions. There was a focal infiltrate of S-100 protein positive histiocytic cells containing Birbeck granules in the femoral heads. There was radioisotopic and radiological evidence of other skeletal lesions. The association between Histiocytosis X and Hodgkin's Disease is recognised but rare and its significance is discussed.

Adult↗

Diversity of antigens expressed on the surface of erythrocytes infected with mature Plasmodium falciparum parasites in Papua New Guinea.

Antigens were detected on the surface of erythrocytes from children with acute falciparum malaria in Madang, Papua New Guinea. These parasite-induced erythrocyte surface antigens (PIESA) were serotyped with convalescent sera from children and hyperimmune sera from adults in parasite infected cell agglutination assays (PICAs) and by inhibition of binding of infected cells to melanoma cells. Extensive serological diversity of PIESA was demonstrated. A significant correlation between serotypes defined by reactivity of immune sera in PICA and inhibition of melanoma cell binding (MCB) was observed. This suggests that both assays measure antibody responses to the same antigen(s). Increased recognition of different PIESA specificities with age is consistent with the hypothesis that repeated exposure to malaria confers immunity against a range of PIESA serotypes and parallels the development of clinical immunity to malaria in this area of Papua New Guinea.

Adult↗

Rabbit muscle phosphorylase derivatives with oligosaccharides covalently bound to the glycogen storage site.

Linear maltooligosaccharides, e.g., maltoheptaose or terminal 4-O-methylmaltoheptaose, activated by cyanogen bromide, react covalently with rabbit muscle phosphorylases b and a (EC 2.4.1.1). Site-specific modification prevents further binding to glycogen and shifts the phosphorylase a tetramer-dimer equilibrium in favor of the dimer. Use was made of these properties to separate by affinity chromatography and gel filtration phosphorylase a dimers with specifically bound oligosaccharide from unspecifically modified products. The phosphorylase a-maltoheptaose derivative carries one oligosaccharide residue per monomer and can be distinguished from the native enzyme by its electrophoretic mobility in polyacrylamide gels or by affinity electrophoresis. Phosphorylase a preparations with covalently bound maltooligosaccharides are enzymatically active in the presence of a primer and alpha-D-glucopyranose 1-phosphate (glucose-1-P). Methylation of the nonreducing chain terminus of the bound oligosaccharide has no effect on glycogen synthesis. These findings exclude the participation of bound oligosaccharides in chain elongation. Purified covalent phosphorylase a-maltoheptaose complexes are stable dimers. They are no longer activated by glycogen. The properties of covalently modified phosphorylase-oligosaccharides are consistent with and provide direct evidence for the existence of a glycogen storage site in rabbit muscle phosphorylases. Covalent occupation of the storage site renders the affinity of glucose-1-P to phosphorylase a independent of modulation by glycogen, supporting the assumption that the glycogen storage site is involved in interactions with the catalytic site.

Animals↗