Olefin metatheses in metal coordination spheres: versatile new strategies for the construction of novel monohapto or polyhapto cyclic, macrocyclic, polymacrocyclic, and bridging ligands.

The broad applicability of the title reaction is established through studies of neutral and charged, coordinatively saturated and unsaturated, octahedral and square planar rhenium, platinum, rhodium, and tungsten complexes with cyclopentadienyl, phosphine, and thioether ligands which contain terminal olefins. Grubbs' catalyst, [Ru(=CHPh)(PCy3)2(Cl)2], is used at 2-9 mol% levels (0.0095-0.00042 M, CH2-Cl2). Key data are as follows: [(eta5-C5H4(CH2)6CH=CH2)Re(NO)(PPh3)-(CH3)], intermolecular metathesis (95 %); [(eta5-C5H5)Re(NO)(PPh3)(E(CH2CH=CH2)2)]+ TfO (E=S, PMe, PPh), formation of five-membered heterocycles (96-64%; crystal structure E = PMe); [(eta5-C5Me5)Re(NO)(PPh((CH2)6CH=CH2)2)(L)]n+ nBF4-(L/n = CO/1, Cl/0), intramolecular macrocyclization (94-89%; crystal structure L= Cl); fac-[(CO)3Re(Br)(PPh2(CH2)6CH=CH2)2] and cis-[(Cl)2Pt(PPh2(CH2)6CH=CH2)2], intramolecular macrocyclizations (80-71%; crystal structures of each and a hydrogenation product); cis-[(Cl)2Pt(S(R)(CH2)6CH= CH2)2], intra-/intermolecular macrocyclization (R=Et, 55%/24%; tBu, 72%/ <4%); trans-[(Cl)(L)M(PPh2(CH2)6CH=CH2)2] (M/L = Rh/CO, Pt/C6F5) intramolecular macrocyclization (90-83%; crystal structure of hydrogenation product, M=Pt); fac-[W(CO)3(PPh((CH2)6CH=CH2)2)3], intramolecular trimacrocyclization (83 %) to a complex mixture of triphosphine, diphosphine/ monophosphine, and tris(monophosphine) complexes, from which two isomers of the first type are crystallized. The macrocycle conformations, and basis for the high yields, are analyzed.

Can the morbidity of asthma be reduced by high dose inhaled therapy? A prospective study.

A community based, prospective study of the value of high dose inhaled therapy for the reduction of the morbidity of asthma has been undertaken. One hundred and sixty adults with airflow obstruction were treated for up to 9 months with increasing doses of salbutamol. Two thirds of the patients also received increasing doses of beclomethasone dipropionate in a 'partially double-blind' manner. The FEV1 rose by at least 10 per cent of that predicted in one third of the total patients and the overall mean domiciliary peak expiratory flow rates rose by approximately 50 l/min-1. All chronic symptoms were abolished in half of the patients and acute attacks of asthma in the majority. Asthma was controlled in a greater proportion of patients more effectively and rapidly by a combination of inhaled steroids and beta agonist than by salbutamol alone, particularly when inhaled steroids were started in relatively high dosage.

Compliance with inhaled therapy and morbidity from asthma.

Patient compliance with a standardized incremental regimen of inhaled anti-asthma therapy has been assessed in a large, prospective study in general practice. Urine salbutamol estimations were made in 30 patients who had the largest improvement with therapy (mean increase in FEV1 0.45 l above baseline: Responsive) and in 30 patients whose airflow obstruction failed to improve (FEV1-0.14 l: Nonresponsive). The urine salbutamol concentrations rose over the 9 month period in the responsive patients as expected with the incremental doses prescribed, and were significantly higher than urine levels in nonresponsive patients at two dose levels. Poor compliance with prescribed inhaled therapy is an important cause of persistent morbidity from asthma.

Does urinary salbutamol reflect compliance with the aerosol regimen in patients with asthma?

Compliance with inhaled beta agonist therapy in a group of asthmatic patients in general practice has been monitored using a high performance thin layer chromatographic assay of salbutamol in urine. Urine salbutamol levels were lower than expected in five of 51 patients and much higher than expected in a further 11 patients. These results suggest the assay may be clinically useful for monitoring compliance of asthmatic patients with inhaled salbutamol.

An audit of morbidity associated with chronic asthma in general practice.

A survey of 312 adult asthmatic subjects has been undertaken. Only 3.5% of the total adult list were known to have asthma and this may represent underdiagnosis. Spirometry was normal in under half the patients and below 50% predicted in one fifth. Forced expired volume in 1s had declined more rapidly than expected with increasing age, particularly amongst smokers. Morbidity from asthma was extensive, patients reporting substantial breathlessness and restrictions of their life style; nearly half had lost time from work in the preceding twelve months. Morbidity was correlated with spirometry.

Management of asthma in general practice.

An audit of the management of asthma in two large general practices has been undertaken. The overall level of therapy prescribed was, in general, related to both the objective severity of the patients' asthma and the extent of symptoms. However, many individual patients received sub-optimal therapy. Prophylactic inhaled beta agonists were used infrequently. Inhaled steroids were prescribed to only one third of the patients and to less than half of severely affected patients. The results suggest that this group of adult asthmatics were relatively under treated in general practice, but a prospective study with proven compliance is necessary to confirm this.

Is there a circadian variation in respiratory morbidity?

In a retrospective study of the time of presentation to an accident and emergency department patients with acute respiratory symptoms presented more commonly at night compared to a control group with abdominal pain. In a subsequent prospective study doctors from a GP deputizing service were called much more frequently at night by patients with asthma than by those with other symptoms. These findings refute the suggestion that the observed increased mortality from respiratory diseases at night results from reduced medical care as a consequence of a reluctance of patients to present during the night.

Bronchodilator effect of disodium cromoglycate administered as a dry powder in exercise induced asthma.

A double-blind, placebo controlled study of the effects of disodium cromoglycate (DSCG), administered as a dry powder via the spinhaler, in established exercise-induced asthma, was carried out. DSCG resulted in an increase in the rate of recovery compared with placebo. The findings confirm that DSCG has bronchodilator properties.

Late response in exercise-induced asthma.

Eight subjects induced bronchospasm by free-range running. Four of these demonstrated a late response at 5-6 hr after exercise. When compared to the other group of four subjects, who also developed an early response but no late response, the difference in FEV1 at 5-6 hr was highly statistically significant. Although the phenomenon is not universally manifest it should no longer be held that there is no late response in exercise-induced asthma.

Inhaled therapy reduces morning dips in asthma.

14 asthmatic patients with nocturnal symptoms and morning dips in peak expiratory flow rate (PEFR) were treated with regular inhaled salbutamol for 1 or 2 weeks, followed by regular inhaled beclomethasone dipropionate, in addition to salbutamol, for a further 2 weeks. Mean PEFR rose to normal values in all but 1 patient. Morning dips in PEFR were substantially reduced in 8 patients. There was an equivalent rise in mean PEFR in the other 6 patients, but their morning dips did not improve. Inhaled salbutamol reduced the dips in the responsive patients, but addition of inhaled steroid produced further improvement. Inhaled beta agonist alone improved mean PEFR in these patients, but inhaled steroids produced most of the improvement in the other subgroup. No patient experienced side-effects. Thus mean PEFR can be improved and morning dips in PEFR reduced in a high proportion of asthmatic patients by the use of regular inhaled therapy without resorting to less-well-tolerated oral agents.

Invasive aspergillosis following post-influenzal pneumonia.

We describe a diabetic patient in whom fatal invasive aspergillosis complicated influenzal pneumonia.

Bronchodilator effects of disodium cromoglycate in exercise-induced bronchoconstriction.

Twelve asthmatic subjects (mean age 23.3 years) exercised on three separate occasions, during which they all received combinations of disodium cromoglycate (DSCG) aerosol (10 mg) or placebo, both before and after exercise in a randomized double-blind study. There was a significant improvement in resting FEV1 in those subjects receiving DSCG before exercise compared with placebo (P less than 0.05). Following exercise there was a more rapid recovery of FEV1 in those receiving DSCG after exercise compared with placebo (P less than 0.005). The greatest differences in FEV1 between placebo and DSCG treated groups were seen in the first 20 minutes after receiving the drug in the post-exercise period. These findings suggest that DSCG has a significant bronchodilator effect.

Five year follow-up of effects of treatment of mild and moderate hypertension.

A five-year follow-up study of the effects of treating patients with both mild and moderate hypertension was performed. The patients were identified during a hospital-based community survey of hypertension. A total of 961 patients were divided into four groups. The first group, the controls, were age- and sex-matched normotensive subjects selected sequentially from the same survey. The second group were patients defined as well-controlled hypertensives; the third group were patients whose blood pressures were less well-controlled; and the fourth group consisted of patients who, for various reasons, were not treated and as such acted as an untreated control group. Both mortality and morbidity were considerably greater in the untreated patients than in the normal subjects. The well-controlled hypertensive patients showed no difference in either morbidity or mortality from normal subjects. The less well-controlled patients had a significantly greater cardiovascular morbidity but no excess mortality over groups 1 and 2. This was true for both mild and moderate hypertension and for women as well as men. These findings therefore confirm the conclusions of other recent studies that good control of hypertension at all levels and in both sexes is justified by the reduction in morbidity and that even less than excellent control is of considerable benefit.