Gating of cutaneous input to cerebellar climbing fibres during a reaching task in the cat.

1. Task-dependent modulation of cutaneous input to climbing fibres projecting to the C1, C2 and C3 zones in the cerebellar paravermal lobule V was investigated in awake cats during performance of a reaching task. 2. Climbing fibre responses resulting from low intensity (non-noxious) electrical stimulation of the ipsilateral superficial radial nerve were recorded as extracellular field potentials in the cerebellar cortex using chronically implanted microwires. 3. Response size, measured as the time-voltage integral of the evoked field potential, was assessed during three phases of the reaching movement, reaction, reach and grasp, and compared with the response size at rest. 4. At C1 and C3 zone recording sites response size was usually reduced during the task (7/10 sites). The reduction was most pronounced in the grasp phase, occasionally accompanied by a smaller reduction in the reach and reaction phases. In one case an enhancement was found in the reach phase. 5. Response size was also modulated during the task at four of six C2 zone recording sites. However, the results were mixed. In three cases the modulation resembled the pattern at C1/C3 sites with the responses being reduced in the grasp phase accompanied on occasion by a lesser reduction in the reach phase. In the remaining case there was an enhancement during grasp. In this case and one other there was also an enhancement during the reaction phase. 6. The findings indicate significant gating of cutaneous input to climbing fibres projecting to the C1, C2 and C3 zones during reaching movements, while the variability between recording sites suggests functional differences, both between and within zones.

Somatotopical organisation within the climbing fibre projection to the paramedian lobule and copula pyramidis of the rat cerebellum.

The climbing fibre projection to the paramedian lobule (lobule VII) and the copula pyramidis (lobule VIII) in the posterior lobe of the rat cerebellum was investigated in pentobarbitone-anaesthetised animals. Percutaneous electrical stimulation generated climbing fibre field potentials on the cerebellar surface that indicated a somatotopical organisation into five distinct cortical areas. Each area was identified by the site(s) of peripheral stimulation that evoked the largest response within that area, and from medial to lateral the cortex was subdivided as follows [principal site(s) of stimulation in parentheses with corresponding range of onset latencies]: in the paramedian lobule, area 1 (contralateral face, 17-18 ms), area 2 (ipsilateral forelimb, 10-15 ms) and area 3 (ipsi- and contralateral forelimbs, 16-26 ms and 15-30 ms, respectively); and in the copula pyramidis, area 4 (tail, 17-21 ms) and area 5 (ipsilateral hindlimb, 13-19 ms). In additional retrograde tracer experiments, small volumes of fluorescent-tagged beads were injected into each of the different areas and the location of retrogradely labelled olive cells was mapped. By comparison with other species, the results indicate that in the paramedian lobule area 1 corresponds to zone A2; area 2 corresponds, at least in part, to medial C1; and area 3 corresponds to C2; in addition, farther laterally, a C3 zone may be present. In the copula pyramidis, areas 4 and 5 correspond to subzones of medial C1. Overall, the results support the view that a general principle of cerebellar cortical organisation is a division into parasagittal zones, each characterised by its somatotopically organised climbing fibre input that arises from a specific, rostrocaudally oriented column of cells within the inferior olivary nucleus.

A comparison of pivmecillinam/pivampicillin and amoxycillin in acute exacerbations of chronic bronchitis.

Courses of 7 days on either 200 mg pivmecillinam/250 mg pivampicillin given twice daily or 250 mg amoxycillin given three times daily were compared in 3783 general practice patients with acute exacerbations of chronic bronchitis in a single-blind parallel group study. Patients on pivmecillinam/pivampicillin had significantly more 'excellent' responses, although there was no difference in overall response between treatments. Post-treatment sputum colour and consistency and peak expiratory flow rates were significantly better with pivmecillinam/pivampicillin. The incidence of side-effects was the same for both groups (approximately 10%), although significantly more patients reported lower gastro-intestinal problems with amoxycillin. Treatment was withdrawn due to side-effects in 47 (2.5%) patients on pivmecillinam/pivampicillin and 51 (2.7%) patients on amoxycillin. Amoxycillin is a standard therapy in the treatment of patients with acute exacerbations of chronic bronchitis. In this study, however, it was shown that pivmecillinam/pivampicillin offers benefits over amoxycillin in these patients.

A post-marketing acceptability study in 11,685 patients of the efficacy of timolol/bendrofluazide in the management of hypertension in general practice.

A post-marketing acceptability study was performed in 11,685 patients to assess the efficacy and acceptability of 10 mg timolol/2.5 mg bendrofluazide in patients with mild to moderate hypertension in general practice. The initial dose was 1 tablet/day. This was adjusted at weekly intervals up to a maximum of 4 tablets/day or until blood pressures of less than or equal to 95 mmHg diastolic or, in patients of greater than or equal to 60 years, less than or equal to 100 mmHg plus the patient's age (in years) systolic, were achieved. Stabilized patients were followed-up after 12, 24 and 48 weeks. Of the patients enrolled, 69% (8039) were successfully treated for at least 8 weeks, 26% (3033) were withdrawn and 5% (613) defaulted. One tablet/day was required by 61% of patients and 29% required 2 tablets/day to achieve stabilization. The mean reductions in systolic and diastolic blood pressures and pulse rate were 31 and 19 mmHg, and 11 beats/min, respectively. Over 60% of the patients enrolled were still taking timolol/bendrofluazide after 12 months' continuous therapy. The most frequently reported reason for withdrawal was an 'adverse event' which occurred in 15.4% (1805) of patients. Only 1.9% (217) failed to achieve target blood pressure on 4 tablets/day. This large study has shown timolol/bendrofluazide to be a highly effective and acceptable once daily therapy for mild to moderate hypertension in general practice.