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Biomedical subjects

A Garner

Publications and source records attributed to A Garner.

At least 55 records · Page 3Linked to original sources

Lacrimal gland hemangiopericytoma.

PURPOSE/METHODS: A 49-year-old woman with a left orbital mass was referred to an orbital clinic. Clinical investigation suggested a lacrimal gland lesion and the patient underwent lateral orbitotomy and excisional biopsy for a suspected pleomorphic adenoma in the lacrimal gland. RESULTS/CONCLUSION: Histopathologic evaluation disclosed a hemangiopericytoma originating within the lacrimal gland. Although hemangiopericytoma does not usually occur in this location, it may be added to the differential diagnosis of lacrimal gland enlargement.

Female↗

Topical heparin in the treatment of ligneous conjunctivitis.

BACKGROUND: Ligneous conjunctivitis is a rare acute or subacute membranous conjunctivitis of unknown etiology for which no generally accepted form of treatment is available. METHODS: Between 1972 and 1993, 17 patients with ligneous conjunctivitis were treated with excision biopsy, meticulous hemostasis, and immediate, intensive topical treatment with heparin, steroids, and, in 12 patients, alpha-chymotrypsin until all signs of conjunctival inflammation had subsided. RESULTS: On histologic examination, the lesions consisted of subepithelial deposits of fibrin in all patients. Eight patients had no recurrence (mean follow-up, 33.1 months) and in four patients the conjunctivitis was controlled after one repeat excision and topical treatment (mean follow-up, 40.3 months). One patient had three recurrences before responding to treatment (follow-up, 24 months). In four patients, treatment was unsuccessful, although lesion-free intervals were longer than usually seen in this condition (mean, 7.8 months). CONCLUSION: These results suggest that intensive and early use of topical heparin may improve therapy results in ligneous conjunctivitis.

Acute Disease↗

Effects of anaesthetic agents on basal and histamine-stimulated acid secretion in the fistula rat.

OBJECTIVES: Anaesthetized rats or surgically modified preparations such as the Shay rat are widely used to study upper gastrointestinal function in the laboratory. Despite the existence of reports demonstrating that agents such as barbiturates can influence acid output, a systematic study of the effects of anaesthetics on gastric secretion has not been undertaken. METHODS: Basal and histamine-stimulated acid output were measured in chronic fistula rats after administration of injectable and volatile anaesthetics frequently used in studies of gastric secretion in anaesthetized animals. With the exception of ether, for which recovery is very rapid, sedating rather than full anaesthetic doses were used. RESULTS: Chloralose (40 mg/kg) had no significant effect on gastric secretion. Pentobarbitone (25 mg/kg) inhibited basal and histamine-stimulated acid output, but the effect was relatively short-lived and secretion returned to control levels after 2 h. Urethane (750 mg/kg) markedly inhibited basal acid output and abolished the secretory response to histamine given 15 to 60 min later. The effects of urethane on acid secretion persisted for the entire 3 h duration of experiments, during which time basal acid output declined to levels observed in fully anaesthetized rats given 1.5 g/kg. Full anaesthesia with ether for 60 min also caused profound inhibition of basal secretion and, like urethane, abolished the effect of histamine despite the fact that the animals recovered consciousness within 5 min. CONCLUSIONS: The differential activity of anaesthetics and profound antisecretory activity of ether and urethane should be taken into account when studying gastrointestinal function and mucosal ulceration in anaesthetized animals.

Anesthetics, Intravenous↗

Review article: drug development in gastroenterology--the changing view of industry.

Rationalization within the pharmaceutical industry to combat escalating costs has included the close examination of research portfolios. Gastroenterology has been one of the casualties of this exercise and few companies currently retain a specific gastrointestinal research programme. Acid-peptic disease has been the victim of its own success, since the availability of a range of extremely effective drugs largely satisfies current medical needs. A safe, convenient and effective monotherapy able to eradicate Helicobacter pylori would be a commercially viable alternative to antisecretory drugs, leading to further expansion of the anti-ulcer market. The irritable bowel syndrome is probably too diverse a target for logical research: inflammatory bowel disease is probably too small a market to be attractive. Potentially effective drugs to treat these and other gastrointestinal diseases could emerge from broader research programmes, provided that companies retain the expertise and desire to develop such agents for gastrointestinal indications. Cancer of the gastrointestinal tract and associated organs undoubtedly represents a commercially attractive target, but new anti-tumour drugs are more likely to arise from generic research rather than programmes specifically directed at tumours of the gastrointestinal tract. The changing view of the pharmaceutical industry towards the development of gastrointestinal drugs is likely to have a negative impact on both fundamental and clinical research in gastroenterology.

Anti-Ulcer Agents↗

Histological study of oxalosis in the eye and adnexa of AIDS patients.

Review of a series of 98 eyes removed at autopsy from 86 AIDS patients identified 12 cases (14%) showing varying degrees of microscopic calcium oxalate deposition. The oxalate crystals were birefringent using polarisation microscopy and were stained histochemically by the silver nitrate-rubeanic acid method (Yasue), a stain considered to be specific for calcium oxalate. In two cases, the deposition was extensive and involved the surface of the ciliary processes, ciliary body and pars plana of the retina, the retinal and optic nerve blood vessel wall, a few retinal pigment cells, and the anterior inner sclera. A lesser degree of intraocular involvement was observed in the remaining 10 cases. In all but two eyes, where a peripheral active area of cytomegalovirus retinitis was present, no other significant microscopical abnormality was found. Clinically, these patients were asymptomatic. At autopsy, oxalate deposits were found in the kidney and/or thyroid in seven of the patients.

Acquired Immunodeficiency Syndrome↗

Orbital involvement in multifocal fibrosclerosis.

Multifocal fibrosclerosis is a condition of unknown aetiology, characterised by fibrous lesions occurring at a variety of sites. Clinical variants include retroperitoneal fibrosis, Riedel's thyroiditis, sclerosing cholangitis, and mediastinal fibrosis. Orbital pseudotumour has been reported as a manifestation of this condition. Three patients with multifocal fibrosclerosis in whom orbital involvement was the dominant feature are described.

Aged↗

The mechanism of action of gastrin releasing peptide (GRP) in stimulating avian gastric acid secretion.

The mechanisms of action of gastrin and gastrin releasing peptide (GRP) in stimulating gastric acid secretion were examined in the anaesthetized turkey. Gastrin and GRP produced dose-dependent increases in acid secretion that were inhibited by the gastrin/CCK-B antagonist CI988. The antagonist did not affect the acid secretory responses to histamine or carbachol. A GRP antagonist (M216140) inhibited the acid response to GRP, but not gastrin. The results suggest that in birds, GRP stimulates acid secretion by release of gastrin, which acts in turn on classical gastrin/CCK-B receptors in the proventriculus.

Analysis of Variance↗

Are most intraocular "leiomyomas" really melanocytic lesions?

BACKGROUND: Intraocular smooth muscle tumors have long been a subject of controversy. The advent of immunohistochemistry with antibodies against HMB-45, S-100, smooth muscle actin, desmin, and vimentin has helped greatly in the distinction between smooth muscle tumors and melanocytic lesions. METHODS: Twenty-seven archival tissue blocks from patients who had had intraocular leiomyomas or leiomyosarcomas diagnosed were located and fresh sections cut and stained for the above markers. The cases constituted 24 iris lesions and 3 ciliary body lesions. RESULTS: All 24 iris tumors were reclassified as iris melanocytic lesions. Two of the three ciliary body leiomyomas retained their classification, and the third was reclassified as a spindle B-cell melanoma. CONCLUSION: The authors suggest that intraocular leiomyomas are much rarer than previously suggested and that many of the cases previously reported in the literature are open to question.

Actins↗

Changes in c-myc expression and the kinetics of dexamethasone-induced programmed cell death (apoptosis) in human lymphoid leukaemia cells.

The kinetics of dexamethasone-induced death of CCRF CEM clone C7A human lymphoblastic leukaemia cells was determined with respect to changes in the expression of the c-myc protein. Cell death was characterised as being by apoptosis: cells with an intact plasma membrane had condensed chromatin and were characterised as having approximately 300 kbp fragments when DNA integrity was analysed by pulsed-field electrophoresis. Onset of apoptosis required a minimum of 36 h exposure to 5 microM dexamethasone; before this time no apoptotic cells were observed. This 36 h incubation period appeared to be necessary to prime the cells for subsequent death by apoptosis. In the continued presence of dexamethasone the percentage of apoptotic cells increased to 60% apoptotic cells by 54 h. Investigation of changes in c-myc protein showed that it was undetectable after 12 h of incubation with dexamethasone, although cells were not committed to die at this time. Cells were treated with dexamethasone for 54 h and for various pulsed periods with a non-toxic concentration of cycloheximide (200 nM). When cycloheximide was present during the first 36 h priming period of dexamethasone treatment, there was an immediate loss of c-myc protein and apoptosis at 54 h was completely inhibited. In contrast, there was no inhibition of apoptosis when dexamethasone-treated cells were incubated with an 18 h pulse of cycloheximide added after 36 h. Cells exposed to dexamethasone for 36 h ('primed') were given various periods of dexamethasone-free incubation before readdition of dexamethasone for a further 18 h. The longer the cells were free of drug after priming, the less susceptible they became to apoptosis, suggesting a slow decay of their 'memory' of the initial 36 h period of exposure. Cycloheximide inhibited the decay of this memory. Removal of dexamethasone after a 36 h exposure was characterised by a subsequent 24 h suppression of c-myc protein expression. Despite this, 90% of cells became refractory to apoptosis before the reappearance of c-myc protein. The evidence does not support the hypothesis that changes in c-myc expression are required for the engagement of apoptosis of CEM cells.

Apoptosis↗

Cholecystokinin type B receptor antagonist PD-136,450 is a partial secretory agonist in the stomach and a full agonist in the pancreas of the rat.

Gastrin (cholecystokinin type B (CCK-B)) receptor antagonists may help to elucidate the physiological role of gastrin, have therapeutic potential as acid antisecretory drugs, and may be of use as adjuvant therapy for gastrin sensitive tumours. In binding studies, the gastrin receptor antagonist PD-136,450 had at least 1000 fold greater affinity for gastrin (CCK-B) than CCK-A receptors. In this study the biological activity of PD-136,450 was evaluated in conscious and anaesthetised rats. PD-136,450 antagonised gastrin stimulated acid secretion after subcutaneous (IC50: 0.28 mumol/kg; conscious rats) and intravenous (IC50: 0.17 mumol/kg; anaesthetised rats) administration. In basal secreting fistula animals, the compound stimulated acid output to 30 (5)% of the maximal response to gastrin. Stimulant activity was not caused by gastrin release. As an agonist PD-136,450 was about 350 times less potent than gastrin-17 on a molar basis. In addition, PD-136,450 was a powerful agonist of pancreatic secretion in anaesthetised rats. The specific gastrin antagonist L-365,260 inhibited the (partial) agonist activity of PD-136,450 in the stomach and the specific CCK-A receptor antagonist L-364,718 inhibited the agonist activity of PD-136,450 in the pancreas. It is concluded that the agonist effect of PD-136,450 is mediated via interaction with the gastrin (CCK-B) receptor in the stomach and the CCK-A receptor in the pancreas.

Animals↗

Emergence of cornea guttata in donor tissue: a cause of late graft failure.

Analysis of 321 failed full-thickness corneal transplant specimens submitted for histopathological examination over a 10-year period has identified 10 instances in which the defect appeared to have been caused by the development of cornea guttata in the donor tissue. The primary condition necessitating keratoplasty in 5 of the 10 patients was Fuchs' endothelial dystrophy but, given the limited capacity of corneal endothelium for regeneration, it is considered unlikely that the defect in the grafts represented a recurrence. In 7 of 8 cases for which the duration of graft survival was known the endothelial disorder presented as a long-term event and it is assumed that the condition was not present at the time of the keratoplasty. The rare emergence of Fuchs' dystrophy in donor transplant tissue should be added to the potential causes of late graft failure.

Adult↗

Histopathology of diabetic retinopathy in man.

The retinal changes associated with diabetes mellitus are a consequence of the systemic microangiopathy with modifications related to the intraocular environment. The vascular disorders underlying background retinopathy are arteriolar hyalinosis (which together with abnormalities in the circulating blood can give rise to focal capillary closure), venular dilatation, and capillaropathy in the form of pericyte degeneration, basement membrane thickening and microaneurysm formation. Retinal complications consist of plasma exudation and punctate haemorrhages. Maculopathy is due to cystoid oedema. Increasing closure of capillaries is linked with cotton-wool spots and intraretinal microvascular anomalies, the former reflecting a consequence and the latter a response to increased ischaemia. Vascular proliferation in front of the retina originates from venules close to areas of ischaemia; the endothelium may be fenestrated initially and fibrosis may accompany the new vessels.

Capillaries↗

Pathogenesis of acanthamoebic keratitis: hypothesis based on a histological analysis of 30 cases.

The results of a histopathological study of 30 cases of Acanthamoeba keratitis are construed as indicating a four stage pathogenetic sequence: (1) initial infection, involving breaching of the surface epithelium; (2) keratocyte depletion by the invading trophozoites; (3) inflammatory response mediated by neutrophil polymorphonuclear leucocytes; (4) stromal necrosis attributable to leucocytic activity.

Acanthamoeba↗

Gastroduodenal mucosal protection.

The barrier that protects the undamaged gastroduodenal mucosa from autodigestion by gastric juice is a dynamic multicomponent system. The major elements of this barrier are the adherent mucus gel layer, which is percolated by the HCO3- secretion from the underlying epithelial cells; the epithelial layer itself, which provides a permeability barrier and can rapidly repair superficial damage by a process of cell migration referred to as reepithelization or restitution; and a specially adapted vasculature, which provides a supply of HCO3- for transcellular transport and/or diffusion into the mucus layer. Passive diffusion of intestinal HCO3- into the lumen is particularly important when there is superficial damage resulting in increased leakiness of the mucosal epithelium. The process of reepithelization occurs by the migration of performed cells from gastric pits or duodenal crypts. This process is quite distinct from the wound healing and associated inflammatory response that accompany more severe injury or chronic damage. The adherent mucus gel acts as a physical barrier against luminal pepsin and provides a stable unstirred layer that supports surface neutralization of acid by mucosal HCO3-. Surface neutralization by mucosal HCO3- provides a major mechanism of protection against acid in the proximal duodenum. In the stomach, where luminal acidity can fall to around pH 1, other mechanisms of protection must exist, since the surface pH gradient is reported to collapse when luminal H+ exceeds approximately 10 mM. This collapse of the surface pH gradients may reflect, at least in part, that such studies have been mostly performed on non-acid-secreting mucosa where the supply of HCO3- to the interstitium from the parietal cells will be reduced. However, because the gastric mucosa can withstand prolonged exposure to acid without apparent damage, this implies an intrinsic resistance of the epithelial apical surface. This is amply illustrated within the gastric glands that do not secrete mucus and HCO3- yet are exposed to undiluted pepsin and an isotonic solution of HCl. Bicarbonate and mucus secretions together with mucosal blood flow are under paracrine, endocrine, and neural control. The rate of reepithelialization will depend on local chemotactic factors, adhesion mechanisms, and the creation of an acid/pepsin/irritant-free environment under a protective gelatinous or mucoid cap. If optimal conditions are met, then the rate of reepithelialization appears to depend primarily on the intrinsic properties of the migrating cells themselves rather than control by exogenous mediators.(ABSTRACT TRUNCATED AT 400 WORDS)

Acids↗

The pathology of abortive neovascular outgrowths from the retina.

Seven abortive neovascular outgrowths (ANVOs) from diabetic retinas were obtained for examination either by biopsy during pars plana vitrectomy (2) or after discovery within enucleated globes (5). Scanning and electron microscopical, histochemical, immunohistochemical and retinal digest techniques were used. The ANVOs consisted of nodules of vessels without an extravascular fibrous component. Two of them contained aneurysm-like dilatations of constituent vessels, and all the specimens showed gross hyaline thickening of the vessel walls. The vascular sclerosis was probably due to accumulation of plasma proteins in the walls of the damaged vessels, which contributes to their involution seen clinically after retinal photocoagulation.

Adult↗

Haemangiopericytoma of the orbit.

Orbital haemangiopericytomas are ideally managed by complete surgical excision in the first instance. This is frequently not achieved, because difficulty in making the diagnosis preoperatively results in incisional biopsy and the highly vascular nature of the tumour makes complete excision difficult. A series of 12 patients with orbital haemangiopericytoma seen over a 23-year period is presented. The following combination of clinical and radiological features is suggestive of haemangiopericytoma. 1. Painless non-axial proptosis with downward displacement of the globe. 2. Intermittent upper lid swelling. 3. A soft, superiorly located mass with poorly defined borders, especially with a blue hue. 4. A superiorly located, rounded or elongated extraconal mass on CT, isodense with brain, with smooth, well-defined borders and moderate to marked enhancement with the injection of intravenous contrast medium. 5. Significant blush in all three phases of carotid angiography, without prominent arteriovenous shunting. Once haemangiopericytoma is suspected, complete surgical excision is recommended.

Adult↗