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N J Simmonds

Publications and source records attributed to N J Simmonds.

11 recordsLinked to original sources
PubMed2006

Radiotherapy: a novel treatment for pneumothorax.

Pneumothorax is a relatively common condition that is usually managed either conservatively, by chest tube drainage or, if a refractory air leak persists, then with cardiothoracic intervention. However, there is a small group of patients with a persistent air leak in whom surgical intervention is felt to be inappropriate. This study looks at a novel management strategy in a patient presenting with this scenario. A male with underlying bullous lung disease presented with a right pneumothorax. Complete re-expansion was not achieved, despite chest tube drainage and suction. Cardiothoracic intervention was felt to be inappropriate and the air leak persisted despite prolonged conservative management. Ventilation scintigraphy was therefore used to localise the air leak prior to targeted radiotherapy in an attempt to seal the leak via radiation-induced fibrosis. Three weeks after the first fraction of radiotherapy, the air leak ceased. In complex cases of pneumothorax with persistent air leak where cardiothoracic intervention is deemed inappropriate, identification of the air leak site and localised radiotherapy could be considered.

Adult↗
PubMed1999

Antioxidant effects of aminosalicylates and potential new drugs for inflammatory bowel disease: assessment in cell-free systems and inflamed human colorectal biopsies.

BACKGROUND: The therapeutic efficacy of 5-aminosalicylic acid in inflammatory bowel disease may be related to its antioxidant properties. AIM: To compare in vitro the antioxidant effects of conventional drugs (5-aminosalicylic acid, corticosteroids, metronidazole), with new aminosalicylates (4-aminosalicylic acid, balsalazide) and other potential therapies (ascorbate, N-acetylcysteine, glutathione, verapamil). METHODS: Compounds were assessed for efficacy in reducing the in vitro production of reactive oxygen species by cell-free systems (using xanthine/xanthine oxidase, with or without myeloperoxidase) and by colorectal biopsies from patients with ulcerative colitis using luminol-amplified chemiluminescence. RESULTS: 5-aminosalicylic acid and balsalazide were more potent antioxidants than 4-aminosalicylic acid or N-acetyl-5-aminosalicylic acid in cell-free systems. 5-aminosalicylic acid (20 mM) and balsalazide (20 mM) inhibited rectal biopsy chemiluminescence by 93% and 100%, respectively, compared with only 59% inhibition by 4-aminosalicylic acid (20 mM). Hydrocortisone, metronidazole and verapamil had no significant effect on chemiluminescence in any system. Ascorbate (20 mM) inhibited chemiluminescence by 100% in cell-free systems and by 60% in rectal biopsies. N-acetyl cysteine (10 mM), and both oxidized and reduced glutathione (10 mM), completely inhibited chemiluminescence in cell-free systems, but not with rectal biopsies. CONCLUSIONS: The antioxidant effects of compounds varies between cell-free systems and inflamed colorectal biopsies. The effect of drugs on the chemiluminescence produced by these two assay systems is useful for screening potentially new antioxidant treatments for inflammatory bowel disease. Ascorbate seems worth further study as a novel therapy.

Adrenal Cortex Hormones↗
PubMed1994

Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite production in vivo.

To determine if reactive oxygen metabolites have a pathogenic role in Helicobacter pylori (H pylori) related gastroduodenal disease, this study measured their production in antral mucosal biopsy specimens. Two related chemiluminescence techniques were used comparing H pylori positive (n = 105) and negative patients (n = 64) with a similar spectrum of macroscopic disease. After chemiluminescence assays, biopsy specimens were graded histologically. Increased luminol dependent chemiluminescence (detecting reactive oxygen metabolites through peroxidase catalysed reactions) was found in H pylori positive patients (median photon emission = 6.4 x 10(3)/min/mg wet weight (95% confidence intervals 3.6 to 9.9)) but not H pylori negative cases (-0.9 (-1.3 to -0.6)) (p = 0.0001). Similar results were found using lucigenin (which reacts directly with oxygen metabolites, particularly superoxide): (H pylori positive 0.9 (0.1 to 3.2); H pylori negative -1.2 (-3.4 to -0.6)) (p = 0.0003). Chemiluminescence was greater in H pylori positive compared with negative tissue when samples were grouped by equivalent macroscopic or microscopic damage. This difference was in part accounted for by a greater neutrophil infiltration in the H pylori positive mucosa, but when biopsy specimens with equivalent neutrophil infiltration could be compared directly, positive specimens gave greater chemiluminescence than negative. Smoking, drugs, and alcohol consumption had no independent effect. It is concluded that excess mucosal reactive oxygen metabolite production is associated with H pylori gastric antral infection and may be an important pathogenic mechanism. There is no evidence for reactive oxygen metabolite participation in the pathogenesis of gastric mucosal injury in cases unrelated to H pylori infection.

Antioxidants↗
PubMed1993

Comparison of nisoldipine and nifedipine as additional treatment in hypertension inadequately controlled by atenolol.

Twenty-eight patients (11 Caucasian, 17 black) whose blood pressure was more than 160/96 mmHg after 4 weeks on placebo added to atenolol 100 mg/day were randomly given, in addition, nisoldipine 10 mg or nifedipine 20 mg each twice a day for 8 weeks in a double-blind cross-over study. There was a statistically significant (P < 0.001) fall in blood pressure with no change in heart rate, both supine and erect, on both drugs. There were no significant differences between nisoldipine and nifedipine. Adverse effects were recorded in 15%, 17% and 35% of the patients available for safety comparison for placebo, nisoldipine and nifedipine, respectively. There were no significant differences between the black and Caucasian patients in blood pressure responses, although the study had only a low power to detect these. However, the fasting serum triglyceride levels at the end of both calcium antagonist treatment periods were highly significantly lower in the black patients compared with the Caucasian patients. Nisoldipine, which has a higher coronary vascular selectivity and less negative inotropism than nifedipine, is as effective and as well tolerated as nifedipine in patients whose hypertension is inadequately controlled on atenolol. It may have a special role in hypertensive patients with impaired left ventricular function.

Atenolol↗
PubMed1992

Controlled trial of endoscopic injection treatment for bleeding from peptic ulcers with visible vessels.

Controlled trials have shown that bleeding peptic ulcers can be successfully treated by endoscopy and injection of adrenaline, with or without sclerosant. However, these trials have been done in major research centres, and endoscopic treatment of upper gastrointestinal bleeding has not yet become routine in general hospitals. We have done a prospective, randomised, controlled trial of injection treatment for bleeding peptic ulcers in a district general hospital. Between April, 1989, and June, 1991, all patients with acute upper gastrointestinal bleeding (n = 555) underwent endoscopy by an experienced endoscopist within 24 h of admission. 98 patients were found to have an ulcer with a visible vessel, of whom 93 were randomised to injection (n = 48) or standard treatment alone (n = 45). Injection treatment consisted of 1-2 ml of 1 in 10,000 adrenaline injected at four to six sites around the ulcer. Adrenaline and 5% ethanolamine oleate (1-2 ml) were then injected directly into the vessel. The medical team managing the patient was unaware of the endoscopic treatment given. The two groups were similar for age, initial haemoglobin concentration, shock, and ulcer site. Rebleeding (injected 8 [16.7%] vs control 21 [46.7%], p = 0.011) was significantly reduced in treated patients. The treated group also had lower mortality (4 [8.3%] vs 9 [20%]), requirement for surgery (4 [8.3%] vs 8 [17.8%]), and mean blood-transfusion requirement (5 vs 7.5 units). Endoscopic injection treatment in our patients significantly reduced rebleeding rate and may have other benefits. This cheap and widely applicable treatment can be used routinely in the management of patients with bleeding peptic ulcers who are at high risk of rebleeding.

Adolescent↗
PubMed1992

Chemiluminescence assay of mucosal reactive oxygen metabolites in inflammatory bowel disease.

Previous studies suggesting increased reactive oxygen metabolite (ROM) production in inflammatory bowel disease have been restricted to peripheral blood and isolated intestinal phagocytes. In the current study, chemiluminescence and the effect of various scavengers, enzymes, and enzyme inhibitors were used to show that ROMs account for the increased production of oxidants by colorectal mucosal biopsy specimens in inflammatory bowel disease. Luminol-amplified chemiluminescence was increased in active ulcerative colitis [macroscopic grade 1: 25 photons.mg-1.min.10(-3) (median), 8-47 (95% confidence intervals), n = 40; grade 2: 89, 65-156, n = 30; grade 3: 247, 133-562, n = 13] and Crohn's disease [mild: 9, 3-84, n = 6; severe: 105, 25-789 (range), n = 5] compared with normal-looking mucosa (ulcerative colitis: 0.8, 0.4-1.4, n = 22, P less than 0.01; Crohn's disease: 0.8, 0.1-2, n = 6, P less than 0.05) and controls (0.6, 0.04-1.4, n = 52, P less than 0.01). In ulcerative colitis, luminol chemiluminescence correlated with microscopic inflammation (Spearman's p = 0.74, P = 0.0001) and was decreased by sodium azide (-89%, P less than 0.05), taurine (-31%, P less than 0.05), catalase (-23%, P less than 0.05), and dimethyl sulfoxide (-29%, P less than 0.05). Superoxide dismutase and oxypurinol decreased lucigenin chemiluminescence in ulcerative colitis by -63% (P less than 0.05) and -27% (P less than 0.05), respectively. Luminol chemiluminescence correlated with lucigenin chemiluminescence (Spearman's rho = 0.72, P = 0.003). These results suggest that neutrophil-derived oxidants (superoxide, hydrogen peroxide, hydroxyl radical, and hypochlorite) are generated in colorectal mucosa in active inflammatory bowel disease and support the hypothesis that production of such metabolites by neutrophils is of major pathogenetic importance.

Acridines↗
PubMed1992

Mucosal reactive oxygen metabolite production in duodenal ulcer disease.

To investigate the hypothesis that reactive oxygen metabolites are important in the pathophysiology of duodenal ulcer disease, their production by duodenal mucosal biopsy specimens was measured using luminol and lucigenin amplified chemiluminescence. Luminol chemiluminescence, expressed as background corrected median photon emission/mg/min x 10(3) (95% confidence intervals), was increased in duodenal inflammation as assessed macroscopically: ulcers 20.3 (4.8 to 51.3), n = 29; severe duodenitis 13.9 (6.6 to 75.3), n = 16; mild duodenitis 0.0 (-0.5 to 0.8), n = 56; controls -0.8 (-1.3 to -0.1), n = 41; p = 0.0001, Kruskal-Wallis) and microscopically: severe 17.0 (9.3 to 51.3), n = 12; moderate 0.3 (-2.8 to 5.8), n = 17; mild -0.1 (-1.8 to 1.0), n = 17; controls -0.8 (-1.6 to 0.0), n = 15; (p = 0.0001). Luminol chemiluminescence was directly related to both the macroscopic and microscopic severity of duodenal damage (Spearman's R = + 0.53, + 0.55 respectively, both p = 0.0001), to histochemical assessment (myeloperoxidase activity) of neutrophil infiltration (R = + 0.63; p = 0.04), and to lucigenin chemiluminescence (R = + 0.56, p = 0.0002). Luminol chemiluminescence was inhibited by sodium azide (-80%), catalase (-73%), and dimethyl sulphoxide (-24%). Superoxide dismutase inhibited lucigenin more than luminol dependent chemiluminescence (-61% and -7% respectively, p < 0.05). Within disease groups, Helicobacter pylori antral infection was associated with increased duodenal chemiluminescence, whereas smoking, alcohol, and use of NSAIDs or H2 blockers had no influence. Their disease related generation in duodenal mucosa supports a role for reactive oxygen metabolites in the pathogenesis of duodenitis and duodenal ulcer. These metabolites might include superoxide, hydrogen peroxide, hydroxyl, and products of myeloperoxidase activity.

Adult↗
PubMed1992

Circulating von Willebrand factor in inflammatory bowel disease.

Raised circulating von Willebrand factor is a recognised marker of vascular injury. To evaluate the role of vascular injury in the pathogenesis of inflammatory bowel disease, serum von Willebrand factor in Crohn's disease, ulcerative colitis, confirmed bacterial diarrhoea, and healthy subjects was measured. von Willebrand factor values were raised in 9/14 patients (p = 0.007) with active Crohn's disease, 15/28 (p = 0.0004) with inactive Crohn's disease, 16/23 (p = 0.0003) with active ulcerative colitis, 9/27 (p = 0.04) with inactive ulcerative colitis, and 15/17 (p = 0.0001) patients with bacterial diarrhoea. Serum von Willebrand factor was unrelated to disease activity in Crohn's disease but was significantly raised in active (p = 0.02) compared with inactive ulcerative colitis. In contrast to controls, the detection of von Willebrand factor from inflammatory bowel disease sera and that from fractured endothelial cells was significantly inhibited by the reducing agent, dithiothreitol, suggesting the presence of an additional dithiothreitol sensitive form of the molecule derived from injured endothelial cells in inflammatory bowel disease. That serum von Willebrand factor is raised in quiescent as well as active Crohn's disease is compatible with the proposal that vascular injury is a fundamental abnormality in this disorder. The raised von Willebrand factor values in active inflammatory bowel disease and bacterial diarrhoea could be caused by either vascular injury, occurring secondary to bowel inflammation, or to an acute phase response resulting from endothelial cell stimulation by mediators released during the inflammatory process. Raised circulating von Willebrand factor could contribute to the increased risk of thrombosis associated with active inflammatory bowel disease.

Bacterial Infections↗
PubMed1990

Contracturing granulomatous myositis: a separate entity.

Granulomatous muscle disease is most commonly seen in sarcoidosis, but may be seen in association with a wide variety of other disorders or in isolation. Patients with granulomatous myositis usually present with slowly progressive muscle pain and weakness affecting mainly proximal muscles. There are, however, a few reports of granulomatous muscle disease presenting with flexion contractures of the limbs. Two further patients with granulomatous muscle disease and flexion contractures of the limbs, but with no evidence of systemic granulomatous disease, is presented. It is suggested that such patients represent a separate clinical entity that is distinct from idiopathic granulomatous myositis presenting with muscle pain and weakness. The association of contracturing granulomatous myositis with a long-standing vasculitis in one patient suggests that the two conditions may be related.

Aged↗