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A Tomkinson

Publications and source records attributed to A Tomkinson.

44 records · Page 3Linked to original sources
PubMed1995

Hospital epistaxis admission rate and ambient temperature.

The incidence of epistaxis admissions to hospital and their relationship to ambient temperature is examined. A retrospective analysis of 1211 patients with epistaxis sufficiently severe to warrant hospital admission was performed over a period of 1836 consecutive days. Daily average temperature data for this time-period were examined and compared with admission rates. A marked increase in hospital attendance was apparent during colder days. Patients were admitted at a rate of 0.829 patients per day for temperatures less than 5 degrees C, (95% Confidence Interval: 0.737-0.928), compared with 0.645 patients per day for temperatures between 5.1 and 10 degrees C, (95% 0.586-0.708). On average the population of epistaxis patients attended on days that were 0.6 degree C colder (95% Confidence Interval: 0.2 degree C-0.9 degree C) than the average temperature for the time examined (P < 0.005, student's t-test).

Environment↗
PubMed1995

Errors arising in cross-sectional area estimation by acoustic rhinometry produced by breathing during measurement.

Standardization of acoustic rhinometry is becoming increasingly important as the use of this technique becomes more widespread. The effects of breathing through the nose during acoustic rhinometry were investigated to determine if this affected the measurements of minimal cross-sectional area. During inspiration, and inspiration with the contralateral nasal airway obstructed, the minimal cross-sectional area decreased by 12.48% (p < 0.05) and 56.68% (p < 0.01), respectively, from the measurement made during a breathing pause. During expiration the reverse was observed, with increases in the minimal cross-sectional area of 13.95% (p > 0.05) and 40.20% (p < 0.05), respectively. In all but quiet expiration, the minimum cross-sectional area recorded during respiratory manoevres, differed significantly from those measured during a breathing pause. We recommend that in order to avoid changes in nasal measurements during breathing, acoustic rhinometry should be performed during a brief breathing pause.

Acoustics↗
PubMed1995

Hutchinson's sign and its importance in rhinology.

Herpes zoster ophthalmicus usually has a typical appearance. However, if the disease is limited to the nasociliary branch of the trigeminal nerve, the ocular appearance may be confusing. Hutchinson in 1865 first noted that involvement of the external nasal branch of the fifth cranial nerve was associated with an increased incidence of ocular zoster. A case of herpes zoster ophthalmicus is presented that clinically resembled an ocular complication of sinus disease. The presence of a localized vesicular rash at the nasal tip assisted in an early diagnosis. Although this sign is known amongst ophthalmologists, its importance in rhinology is stressed. An anatomical explanation of Hutchinson's sign is given and the treatment of herpes zoster ophthalmicus is briefly discussed.

Acyclovir↗
PubMed1994

Possible role of cyclic AMP phosphodiesterases in the actions of ibudilast on eosinophil thromboxane generation and airways smooth muscle tone.

1. The possible role of cyclic AMP phosphodiesterase (PDE) in the inhibitory actions of ibudilast on tracheal smooth muscle contractility and eosinophil thromboxane generation was investigated. 2. Ibudilast was a non-selective inhibitor of partially purified cyclic nucleotide PDE isoenzymes from pig aorta and bovine tracheal smooth muscle, exhibiting only moderate potency against bovine tracheal PDE IV (IC50 = 12 +/- 4 microM, n = 3). Similar or slightly lower potencies were displayed against PDEs I, II, III and V. In contrast, rolipram exhibited selectivity for PDE IV (3 +/- 0.5 microM, n = 3). 3. Ibudilast (IC50 = 0.87 +/- 0.37 microM, n = 3), like rolipram (IC50 = 0.20 +/- 0.04 microM, n = 3), was a more potent inhibitor of membrane-bound PDE IV from guinea-pig eosinophils than of partially purified PDE IV from bovine tracheal smooth muscle. The potency of ibudilast increased when the eosinophil enzyme was solubilised with deoxycholate and NaCl (IC50 = 0.11 +/- 0.05 microM, n = 3) or exposed to vanadate/glutathione complex (V/GSH) (IC50 = 0.11 +/- 0.02 microM, n = 3). The potency of rolipram was also increased by solubilization (IC50 = 0.012 +/- 0.003, n = 3) or V/GSH (IC50 = 0.012 +/- 0.003, n = 3). 4. In intact eosinophils, ibudilast (0.032 microM-20 microM) potentiated isoprenaline-induced cyclic AMP accumulation in a concentration-dependent manner, being approximately 20 fold less potent than rolipram. Little or no effect on basal cyclic AMP levels was observed with either compound. The cyclicAMP-dependent protein kinase activity ratio was significantly increased following incubation of eosinophils with either ibudilast (20 MicroM) or rolipram (20 MicroM) in the absence or presence of isoprenaline.5. Leukotriene B4 (300 nM)-induced thromboxane generation from guinea-pig eosinophils was inhibited by ibudilast (IC50 = 11.3 +/- 3.7 MicroM, n = 5) and rolipram (IC50 = 0.280 +/- 0.067 MicroM, n = 5) in a concentration-dependent manner.6. Ibudilast (10 nM-1 MicroM), whilst generally less potent than rolipram (1 nM- 1 MicroM), produced concentration-dependent relaxation of spasmogen (methacholine, histamine, LTD4)-induced tone in the guinea pig isolated tracheal strip. Ibudilast was less potent in reversing the methacholine (IC50 = 1.95 +/- 0.40 JM,n =6)-induced contraction than those of histamine (IC50 = 0.18 +/- 0.70 MicroM, n =6) or leukotriene D4(LTD4, IC50 = 0.12 +/- 0.05 MicroM, n = 6). Rolipram also exhibited a similar pattern of activity, although the difference in potency against methacholine (IC50 = 0.1 +/- 0.01 MicroM, n = 6) compared with the other two spasmogens, histamine (IC50 = 0.034 +/- 0.017 MicroM, n = 7) and LTD4 (IC50 = 0.026 +/- 0.008 MicroM, n = 7), was not as great.7. These results demonstrate that ibudilast, like rolipram, has several biological actions on the eosinophil and airways smooth muscle which may be attributed to inhibition of cyclic AMP PDE. These actions may account, at least in part, for the recently reported anti-asthma effects of ibudilast.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Anti-inflammatory and bronchodilator properties of RP 73401, a novel and selective phosphodiesterase type IV inhibitor.

1. We have investigated the effects of RP 73401, a novel, potent and highly selective cyclic nucleotide phosphodiesterase (PDE) type IV inhibitor, in guinea-pig and rat models of bronchoconstriction and allergic inflammation. In some models, the effects of RP 73401 have been compared with those of the standard PDE type IV inhibitor, rolipram. 2. RP 73401 (0.4-400 micrograms kg-1, intratracheally (i.t.) on lactose) inhibited antigen-induced bronchospasm in previously sensitized conscious guinea-pigs (ID50: 7 +/- 1 micrograms kg-1) and in anaesthetized rats (ID50: 100 +/- 25 micrograms kg-1). Rolipram inhibited the antigen-induced bronchospasm in guinea-pigs with an ID50 of 5 +/- 1 micrograms kg-1. In guinea-pig bronchoalveolar lavage (BAL) fluid, total inflammatory cell and eosinophil numbers were reduced by RP 73401 (ID50s: 3.9 +/- 0.8 micrograms kg-1 and 3.2 +/- 0.7 micrograms kg-1, respectively). In the rat, inflammatory cell numbers are less affected. Only the highest dose of RP 73401 (400 micrograms kg-1) significantly inhibited eosinophil influx (41 +/- 16% inhibition). 3. RP 73401 (0.02-100 micrograms kg-1, i.v.) inhibited PAF-induced bronchial hyperreactivity to bombesin in the anaesthetized guinea-pig (ID50: 0.09 +/- 0.03 micrograms kg-1) and inhibited (0.4-40 micrograms kg-1, i.t.) histamine-induced airway microvascular leakage in the anaesthetized guinea-pig by approximately 60% at all doses. 4. RP 73401 relaxed guinea-pig isolated trachea under basal tone (EC50: 9 nM) and when precontracted with histamine (IC50: 2 nM), methacholine (IC50: 29 nM) or leukotriene D4 (LTD4, IC50: 4 nM). 5. RP 73401 (0.4-100 microg kg-1, i.t.) inhibited bronchospasm induced by histamine (ID.%: 34 +/- 6 microg kg-1), methacholine (ID50: 66 +/- 12 pg kg-1) and LTD4 (ID50: <4 microg kg-1) in the anaesthetized guinea pig.Against these same bronchoconstrictors, rolipram (i.t.) had ID5o values of 44 +/- 4, 72 +/- 18 and<4 pg kg- respectively. RP 73401 (4 and 40 pg kg-, i.t.) increased the magnitude and duration of bronchodilatation produced by salbutamol in the anaesthetized guinea-pig. At doses producing significant bronchodilatation, RP 73401 was without effect on heart rate or blood pressure in the anaesthetized guinea-pig. RP 73401 (0.01 -0.25 mg kg-1, i.v.) did not affect heart rate and produced only a small fall in blood pressure in the anaesthetized rat.6. These data demonstrate that RP 73401 and rolipram inhibit antigen- and mediator-induced bronchospasmin guinea-pigs with the same potency. Furthermore, RP 73401 administered directly into the airways, protects against allergic airway inflammation. These results indicate the importance of PDE IV in regulating smooth muscle and inflammatory cell activity. At doses suppressing the inflammatory response in the lung, RP 73401 had little effect in the cardiovascular system. RP 73401 may have a role as a bronchodilator and, more importantly, as a prophylactic anti-inflammatory agent in the treatment of asthma.

Albuterol↗
PubMed1993

Comparison of the effects of selective inhibitors of phosphodiesterase types III and IV in airway smooth muscle with differing beta-adrenoceptor subtypes.

1. The relaxant properties of the type IV adenosine 3',5'-cyclic monophosphate phosphodiesterase (cyclic AMP PDE) inhibitor, rolipram and the beta 2-selective and non-selective beta-adrenoceptor agonists salbutamol and isoprenaline, were compared on the guinea-pig, bovine, and mouse trachea and porcine bronchus all precontracted with methacholine (EC30). 2. Rolipram and both beta-agonists produced concentration-dependent reversal of the methacholine-induced tone in the four airway preparations. 3. Isoprenaline and salbutamol were similar in potency on the guinea-pig (-log10IC50:8.43, 8.06) and bovine (-log10 IC50:8.52, 8.40) airways. In contrast, salbutamol was much less potent than isoprenaline on the mouse trachea (> 1000 fold) and the porcine bronchus (> 100,000 fold). 4. The potency of rolipram approached that of isoprenaline on the guinea-pig and bovine trachea (beta 2-adrenoceptors predominate). However, rolipram was significantly less active than isoprenaline on the porcine bronchus (1000 fold) and mouse trachea (> 2000 fold) where beta 2-adrenoceptors predominate. 5. Siguazodan, the type III cyclic AMP PDE inhibitor, produced concentration-dependent relaxations of the porcine bronchus and guinea-pig trachea contracted with methacholine. Siguazodan was 100 fold more active than rolipram in pig tissues indicating the type III isoenzyme may be of greater functional significance in this tissue. In contrast, siguazodan was 15 times less potent that rolipram in guinea-pig airways suggesting a greater role for the type IV PDE. 6. These findings may reflect a possible relationship between the beta 2-adrenoceptor subtype and the functional importance of the type IV PDE isoenzyme. A similar relationship may exist between beta 1-adrenoceptors and the PDE type III isoenzyme.

Albuterol↗
PubMedDate not supplied

Prostatic cancer presenting as dysphagia.

Neurological dysfunction from base of skull metastasis of prostate cancer is rare. In this case, dysphagia was the presenting symptom and relief occurred after orchidectomy. Improvement of neurological symptoms usually occurs only after local radiotherapy.

Aged↗