Orally administered N-acetylcysteine may improve general well-being in patients with mild chronic bronchitis.

Oral N-acetylcysteine (NAC) exerts a beneficial action in chronic bronchitis by reducing the number of exacerbations. There have been few studies of the effect of NAC (or of any other drug) on general well-being in chronic bronchitis. We used an established psychiatric instrument (General Health Questionnaire; GHQ) and a visual analogue scale (VAS) to measure well-being in a 22-week, placebo-controlled, double-blind, parallel-group study of NAC administered as sustained release tablets 600 mg b.i.d., including during the winter months, to patients with mild chronic bronchitis. One hundred and fifty-three patients were accepted for randomized treatment, 129 finished the study (59 NAC, 70 placebo), and well-being was measured in 105 (46 NAC, 59 placebo). The number of observed exacerbations was unexpectedly low in both groups. The number was lowest in the NAC group, however, the difference did not reach statistical significance in the present study (P = 0.08). There were no statistically significant differences between NAC and placebo in subjective symptom scores, FEV1 or FVC. The distribution of GHQ score at baseline was uneven, but NAC was significantly superior to placebo in terms of a favourable effect on GHQ score. GHQ score correlated with the number of exacerbations, and VAS correlated with GHQ score. This study therefore demonstrates the validity of measuring general well-being in patients with mild chronic bronchitis. Future studies of the treatment of chronic bronchitis should use a battery of more specifically adapted instruments which are now becoming available to measure well-being.

Influence of oral magnesium supplementation on cardiac events among survivors of an acute myocardial infarction.

OBJECTIVE: To investigate the effect of long term oral magnesium treatment on incidence of cardiac events among survivors of an acute myocardial infarction. DESIGN: Double blind, placebo controlled parallel study in which patients were randomised to treatment or placebo. SETTING: Two coronary care units and corresponding outpatient clinics. SUBJECTS: 468 survivors of an acute myocardial infarction (289 men and 178 women) aged 31-92. INTERVENTIONS: One tablet of 15 mmol magnesium hydroxide or placebo daily for one year. MAIN OUTCOME MEASURES: Incidences of reinfarction, sudden death, and coronary artery bypass grafting in one year. RESULTS: There was no significant difference between treatment and placebo groups in the incidence of each of the three cardiac events, but when the events were combined and drop outs were excluded from calculations there was a significantly higher incidence of events in the treatment group (56/167 v 33/153; relative risk 1.55 (95% confidence interval 1.07 to 2.25); p = 0.02). When the timing of events was incorporated by means of a Kaplan-Meier plot the treatment group showed a significantly higher incidence of events whether drop outs were included or excluded (p < 0.025). CONCLUSION: Long term oral treatment with 15 mmol magnesium daily doses not reduce the incidence of cardiac events in survivors of an acute myocardial infarction and, indeed, seems to increase the risk of developing a cardiac event. Consequently, this treatment cannot be recommended as secondary prophylaxis for such patients.

[Steroid response after long-term treatment with oral N-acetylcysteine in patients with chronic obstructive bronchitis]. / Steroidrespons efter langtidsbehandling med oral N-acetylcystein hos patienter med kronisk obstruktiv bronchitis.

The significance of long-term treatment with N-acetylcystein (NAC) for the steroid response on pulmonary function and general symptoms was investigated in patients with chronic bronchitis and moderate respiratory obstruction. All of the patients had received preliminary treatment with oral NAC in a dosage of 1,200 mg daily (Mucomyst Retard) or a placebo for 22 weeks in a double-blind design. After the conclusion of the long-term treatment but before the code was revealed, 37 non-allergic patients with irreversible respiratory obstruction participated in a follow-up investigation with 30 mg prednisone daily for 14 days. The peak flow was measured twice daily and the symptoms of bronchitis were registered by completion of 13 visual analogue scales. Pulmonary function was measured by means of spirometry on days 0, 7 and 14, respectively. In both of the treated groups, slight increase in the daily registered peak flow was found but no changes in the results of spirometry or the symptoms. Comparison between the groups revealed a significantly greater increase in the evening peak flow in the group which had received preliminary treatment with NAC. It is concluded that, in this investigation, no clinically relevant effect of long-term preliminary treatment with NAC on the results of a steroid test was observed in patients with chronic bronchitis and moderate respiratory obstruction.

One-year death rate in 270 patients with suspected acute myocardial infarction, initially treated with intravenous magnesium or placebo.

In a double-blind, placebo-controlled study, 273 patients with suspected acute myocardial infarction (AMI) were randomized to receive either 48-h magnesium (Mg) or placebo therapy intravenously, initiated immediately on admission to hospital. We describe the results from a 1-year survey in 270 of the patients, who were available for follow-up. Patients were equally divided: 135 received Mg and 135 received placebo. Mg treatment was associated with a marked reduction in 1-year death rate from 32% in the placebo group to 20% in the Mg group (p = 0.018). If only death from ischemic heart disease is considered, the figures were 28% in the placebo group as opposed to 15% in the Mg group (p = 0.006). This reduction was mainly due to a reduction in mortality during the initial 30 days after inclusion in the study (17% vs. 7%), after which the difference in mortality between the two groups did not reach statistical significance (18% vs. 15%, p = 0.56). The beneficial effect of Mg on mortality was partly linked to a reduced incidence of arrhythmias (27% vs. 16%), and partly to a reduced incidence of infarction (63% vs. 48%) during the initial hospitalization. However, factors unknown to us were also involved, as revealed by a remaining statistically significant partial regression coefficient, when sex, age, cardiovascular history, development of AMI, and development of arrhythmias were considered. It is concluded that intravenous Mg treatment is beneficial to patients with acute ischemic heart disease and should be adopted as part of the routine treatment of these patients.

Value of Tru-cut lung biopsy in focal and diffuse lung disease.

The results of 382 consecutive Tru-cut lung biopsies were reviewed to evaluate this investigation. The age of the patients ranged from 16 to 84 years (median 63 years); 284 patients suffered from focal and 98 from diffuse lung disease. Of the 206 patients with focal disease in whom the final diagnosis was a malignancy, 161 (78%) had a correct biopsy diagnosis. Of the 78 patients in whom the final diagnosis was non-malignant disease, 60 (77%) had a correct biopsy diagnosis. In diffuse pulmonary disease the histological diagnosis was correct in 75 of 98 patients (77%). In focal benign disease and in diffuse disease the reliability of the diagnosis increased with the specificity of the diagnosis. Where the biopsy diagnosis was not in accordance with the final diagnosis, histological examination usually showed normal lung tissue (with or without non-specific inflammation), necrotic tissue, or no tissue at all. Two patients died from the procedure. Minor complications occurred in 18%. It is concluded that the usefulness of Tru-cut biopsy is not confined to malignant focal disease; it is also reliable in benign focal disease and diffuse pulmonary disease when a specific diagnosis is obtained.

Magnesium deficiency in patients with ischemic heart disease with and without acute myocardial infarction uncovered by an intravenous loading test.

An intravenous magnesium-loading test with 30 mmol/L of magnesium was used to evaluate the magnesium status in 38 patients with ischemic heart disease (IHD) admitted to the coronary care unit with suspected acute myocardial infarction (AMI), in ten healthy volunteers (control group), and in nine patients with chronic IHD in a stable phase of their disease (chronic IHD group). Sixteen of the patients admitted with acute disease proved to have AMI (AMI group) and 22 did not (non-AMI group). Patients with IHD both with and without AMI retained significantly more magnesium (9.3 and 10.7 mmol/L [22.6 and 26 mg/dL], respectively) than did the control group (1.4 mmol/L [3.4 mg/dL]). This 34% magnesium retention points to a state of magnesium deficiency in patients with IHD. However, since the patients with and without AMI did not differ, the observations do not indicate that AMI is associated with a more severe magnesium deficiency than that found in other IHD patients without AMI. When the patients with IHD were subgrouped according to long-term diuretic treatment, the patients (n = 19) receiving long-term diuretic treatment had a 39% retention of magnesium (11.6 mmol/L [28.2 mg/dL]) compared with a 29% retention (8.7 mmol/L [21.1 mg/dL]) observed in 19 patients who were not receiving long-term diuretic treatment. This observation was not influenced by the presence or absence of AMI. An even higher level of magnesium retention (17.1 mmol/L [41.6 mg/dL] equals 57% retention) was found when investigating patients with chronic ischemic heart disease in a stable phase of their disease. This indicates that patients with IHD may be severely magnesium deficient; that long-term diuretic treatment contributes to this deficiency, but that diuretic treatment per se is not the only cause of this condition.

Kinetics of disopyramide in decreased hepatic function.

The elimination kinetics of disopyramide was studied in 9 patients with decreased hepatic function (DHF) due to histologically verified cirrhosis of the liver, and in 11 patients with ischaemic heart disease (IHD). Disopyramide 100 and 150 mg was given intravenously as a bolus to the patients with IHD and DHF, respectively, followed by a continuous infusion of disopyramide 0.3 (DHF group) and 0.4 mg X min-1 (IHD group) until steady-state was achieved. A significant (p less than 0.001) positive correlation between the percentage unbound and total serum concentration of disopyramide was demonstrated in both groups. The percentage of unbound disopyramide at a total serum concentration of 5.9 mumol X l-1 was 45.5% and 19.4% in the DHF and IHD groups, respectively. A negative correlation (r = -0,751, p less than 0.05, and r = -0.827, p less than 0.01 in the IHD and DHF patients, respectively) between the free fraction of disopyramide and alpha 1-acid glycoprotein was observed. The serum concentration of alpha 1-acid glycoprotein, the major binding protein of disopyramide, was significantly lower in the patients with DHF. The clearance of unbound disopyramide and its total volume of distribution and half-life were significantly lower in the DHF patients. No difference in total elimination clearance could be demonstrated. The clinical implication of the present findings appear to be that the dosage of disopyramide should be reduced by 25% when it is given intravenously to patients with decreased hepatic function.