A prospective study of urinary retention and risk of death after proximal femoral fracture.

Older age, dementia syndrome and impaired mobility are well recognized risk factors for fatality after fracture of the proximal femur. Urinary retention is recognized as a common complication of elective total hip replacement. In this investigation, we estimated the incidence of urinary retention associated with hip fracture in older women and assessed its relationship to 2-year post-operative fatality. Over a 7-month period, 309 women aged 65 and over were admitted to one trauma unit with hip fracture. Readings of post-voiding residual volume were taken on admission (pre-operative), within 24 hours of operation (post-operative) and 5-7 days post-operatively (recovery). Of the 309 patients, 244 (79%) had readings of post-voiding residual volume taken on admission; 90/244 (37%) had retention pre-operatively, 122/216 (56%) post-operatively and 40/183 (22%) in the recovery phase. One year after operation 305 patients were traced and median follow-up was 2 years. Older age, cognitive impairment, polypharmacy, impaired mobility and urinary retention on admission and during recovery were associated with a higher fatality in the first post-operative year. Pre-operative urinary retention is common among older women with proximal femoral fracture and affects over half post-operatively. Retention is one of several factors associated with higher fatality.

Inflammatory markers of lower respiratory tract infection in elderly people.

Bacterial infections of the respiratory tract are a major cause of morbidity and mortality in elderly people. The inflammatory response to such infection is an important protective process and has been suggested to be less effective in elderly patients. To investigate the inflammatory response in respiratory infections acquired in the community by elderly people we studied 52 consecutive patients who met the criteria for either a non-pneumonic chest infection or pneumonia. After exclusion, 41 patients were available for evaluation, with 25 fulfilling the criteria of pneumonia and 16 the criteria of chest infection. Pyrexia was a feature of the patients with pneumonia. Circulating levels of neutrophil elastase-alpha-1-antitrypsin complex and C-reactive protein were greater in the patients with pneumonia than in those with a chest infection and were reduced following antibiotic treatment. No changes occurred in the chest infection group for these markers of inflammation. In both groups, a further neutrophil granule protein, lactoferrin, was unaffected by antibiotic treatment. This study indicates that elderly patients with pneumonia can initiate an appropriate inflammatory response as demonstrated by clinical indicators and circulating mediators of the inflammatory response.

Dose duration of nebulized nedocromil sodium in exercise-induced asthma.

The dose-duration effect of nebulized nedocromil sodium was studied in ten patients with exercise-induced asthma (7 males mean (SEM) age 30.1 (3.5) yrs and predicted forced expiratory volume in one second (FEV1) 102%). All of these patients showed > 40% protection of their exercise asthma with 4 mg of nedocromil sodium delivered via metered dose inhaler. Three concentrations of nedocromil sodium (0.5, 2.5 and 10 mg.ml-1) and placebo were administered in double-blind, randomized manner. One ml of each solution was nebulized via a Wright nebulizer. Effects were assessed from the mean maximal percentage fall in FEV1 after 6-8 min treadmill exercise at 15, 135 and 255 min following each treatment and expressed as percentage protection. The mean baseline FEV1 values before and after treatments were comparable on four days of testing. Nedocromil sodium inhibited exercise-induced fall in FEV1 at all concentrations (p < 0.001) and the inhibitory effect was still present at 255 min. No differences were observed between active treatments.

Dose-response study of nebulised nedocromil sodium in exercise induced asthma.

Ten patients with exercise induced asthma, in whom inhaled nedocromil sodium 4 mg by metered dose inhaler attenuated the exercise fall in forced expiratory volume in one second (FEV1) by at least 40%, participated in a double blind dose response study to compare the protective effect of nedocromil sodium given 15 minutes before exercise challenge via a nebuliser (Wright) in concentrations of 0.5, 5, 10, and 20 mg/ml with that of placebo (saline). Response was assessed as the maximum fall in FEV1 after the patient had run on a treadmill for six to eight minutes. Plasma concentrations of nedocromil sodium were measured at the time of challenge. After exercise challenge the mean (SEM) maximum percentage falls in FEV1 were 30.3 (1.6) for the control run and 28.0 (4.1) after placebo. The percentage fall was attenuated by pretreatment with all concentrations of nedocromil sodium to 12.8 (2.8), 11.2 (2.1), 12.8 (2.1), and 14.1 (3.5) for the 0.5, 5, 10, and 20 mg/ml concentrations respectively (p less than 0.001). There were no significant differences between the different nedocromil concentrations. Mean plasma concentrations of nedocromil were proportional to dose. Thus concentrations of nebulised nedocromil sodium that ranged from 0.5 to 20 mg/ml gave a similar degree of protection (50-60%) against exercise induced asthma. This appears to be the maximum protection that can be achieved with nedocromil sodium and is similar to the protection obtained with 4 mg nedocromil administered by metered dose aerosol.

Effect of inhaled leukotriene C4 on cardiopulmonary function.

The changes in transcutaneous oxygen saturation (SaO2%) and airway responses to inhaled histamine and leukotriene C4 (LTC4) were examined in 10 asthmatic patients, and the effect of inhaled LTC4 (16 nmol) on cardiopulmonary hemodynamics was examined in seven nonasthmatic patients undergoing diagnostic cardiac catheterization. In asthmatic patients, LTC4 produced oxygen desaturation on two occasions. At a lower dose (2.0 nmol) LTC4 produced a marked fall in SaO2% that lasted less than 15 min and occurred in the absence of significant bronchoconstriction as measured by changes in FEV1, FEF25-75, and SGaw. At a higher cumulative dose (7 nmol), LTC4 caused prolonged oxygen desaturation with slow recovery and this was associated with significant bronchoconstriction. In contrast, histamine inhalation produced a single response with a fall in both FEV1 and SaO2% of short duration. The dose-response characteristics of LTC4 and histamine on oxygen desaturation in asthmatic patients appear to differ significantly and probably are dependent on relative sensitivities of pulmonary vascular and bronchial smooth muscle to these agonists. A single inhaled dose of LTC4 in nonasthmatic subjects produced a marked drop in PaO2 with significant increase in AaPO2, and this was associated with a mean (SEM) decrease in FEV1 of 14% (2.5) from the baseline. The mean cardiac output fell by 15% (3.4) without significant changes in blood pressure and heart rate. There was no electrocardiographic evidence of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of cooling and drying in hyperventilation induced asthma.

Respiratory heat loss has been proposed as a mechanism of exercise induced asthma. Whether the predominant stimulus is airway drying or cooling remains unclear. We have measured changes in FEV1 after isocapnic cold air hyperventilation (CAH) (-23.4 degrees (SD 0.43 degrees) C) and dry ambient air hyperventilation (AAH) (18.7 degrees (0.52 degrees)C) in seven asthmatic patients (mean age 31 (SD 9) years and baseline FEV1 3.2(0.9)1) and in seven normal subjects (age 28(6) years and FEV1 3.6(0.7)1). The inspired water content in both cases was 0.3 mg/l air. The rate of respiratory heat exchange per breath was calculated in watts (W) with microcomputer based equipment. Cold air hyperventilation caused a fall in FEV1 almost twice that of ambient air hyperventilation at each level of ventilation: CAH v AAH (% fall) 8.0 (5.1) v 3.9 (4.0) at 15 l/min, 11.6 (7.8) v 7.0 (4.4) at 30 l/min, and 20.7 (10.9) v 12.4 (6.3) at 60 l/min. Identical latent heat loss (evaporative drying) was imposed on the airway during the two challenges. Sensible heat loss (convective cooling) in cold air hyperventilation was 41 W at 15 l/min, 63 W at 30 l/min, and 114 W at 60 l/min; whereas in ambient air hyperventilation the loss was 6, 13, and 23 W respectively. It is concluded that the rate of cooling of the upper airway is the predominant stimulus in hyperventilation induced asthma.

Effect of azelastine on bronchoconstriction induced by histamine and leukotriene C4 in patients with extrinsic asthma.

Azelastine, a new oral agent with antiallergic and antihistamine properties, has been shown to inhibit the effect of histamine and leukotriene (LT) in vitro, though not a specific leukotriene receptor antagonist. The effect of both a single dose (8.8 mg) and 14 days' treatment (8.8 mg twice daily) with azelastine on bronchoconstriction induced by LTC4 and histamine has been examined in 10 patients with mild asthma in a placebo controlled, double blind, crossover study. LTC4 and histamine were inhaled in doubling concentrations from a dosimeter and the results expressed as the cumulative dose (PD) producing a 20% fall in FEV1 (PD20FEV1) and 35% fall in specific airways conductance (PD35sGaw). The single dose of azelastine produced a significantly greater FEV1 and sGaw values than placebo at 3 hours, but this bronchodilator effect was not present after 14 days of treatment. Azelastine was an effective H1 antagonist; after a single dose and 14 days' treatment with placebo the geometric mean PD20FEV1 histamine values (mumol) were 0.52 (95% confidence interval 0.14-1.83) and 0.54 (0.12-2.38), compared with 22.9 (11.5-38.3) and 15.2 (6.47-35.6) after azelastine (p less than 0.01 for both). LTC4 was on average 1000 times more potent than histamine in inducing bronchoconstriction. Azelastine did not inhibit the effect of inhaled LTC4; the geometric mean PD20FEV1 LTC4 (nmol) after a single dose and 14 days' treatment was 0.60 and 0.59 with placebo compared with 0.65 and 0.75 with azelastine. The PD35sGaw LTC4 was also unchanged at 0.66 and 0.73 for placebo compared with 0.83 and 0.74 for azelastine. Thus prolonged blockade of H1 receptors did not attenuate the response to LTC4, suggesting that histamine and LTC4 act on bronchial smooth muscle through different receptors. Four patients complained of drowsiness while taking azelastine but only one who was taking placebo and three patients complained of a bitter, metallic taste while taking azelastine.