SummaryBackgroundStudies evaluating titration of antihypertensive medication using self-monitoring give contradictory findings and the precise place of telemonitoring over self-monitoring alone is unclear. The TASMINH4 trial aimed to assess the efficacy of self-monitored blood pressure, with or without telemonitoring, for antihypertensive titration in primary care, compared with usual care.MethodsThis study was a parallel randomised controlled trial done in 142 general practices in the UK, and included hypertensive patients older than 35 years, with blood pressure higher than 140/90 mm Hg, who were willing to self-monitor their blood pressure. Patients were randomly assigned (1:1:1) to self-monitoring blood pressure (self-montoring group), to self-monitoring blood pressure with telemonitoring (telemonitoring group), or to usual care (clinic blood pressure; usual care group). Randomisation was by a secure web-based system. Neither participants nor investigators were masked to group assignment. The primary outcome was clinic measured systolic blood pressure at 12 months from randomisation. Primary analysis was of available cases. The trial is registered with ISRCTN, number ISRCTN 83571366.Findings1182 participants were randomly assigned to the self-monitoring group (n=395), the telemonitoring group (n=393), or the usual care group (n=394), of whom 1003 (85%) were included in the primary analysis. After 12 months, systolic blood pressure was lower in both intervention groups compared with usual care (self-monitoring, 137·0 [SD 16·7] mm Hg and telemonitoring, 136·0 [16·1] mm Hg vs usual care, 140·4 [16·5]; adjusted mean differences vs usual care: self-monitoring alone, −3·5 mm Hg [95% CI −5·8 to −1·2]; telemonitoring, −4·7 mm Hg [–7·0 to −2·4]). No difference between the self-monitoring and telemonitoring groups was recorded (adjusted mean difference −1·2 mm Hg [95% CI −3·5 to 1·2]). Results were similar in sensitivity analyses including multiple imputation. Adverse events were similar between all three groups.InterpretationSelf-monitoring, with or without telemonitoring, when used by general practitioners to titrate antihypertensive medication in individuals with poorly controlled blood pressure, leads to significantly lower blood pressure than titration guided by clinic readings. With most general practitioners and many patients using self-monitoring, it could become the cornerstone of hypertension management in primary care.FundingNational Institute for Health Research via Programme Grant for Applied Health Research (RP-PG-1209-10051), Professorship to RJM (NIHR-RP-R2-12-015), Oxford Collaboration for Leadership in Applied Health Research and Care, and Omron Healthcare UK.

The perirhinal cortex of the temporal lobe is essential for the familiarity discrimination component of recognition memory. In view of the importance of changes in calcium ion concentration for synaptic plasticity, the present study examined the effects of L-type voltagedependent calcium channel (VDCC) antagonism on rat perirhinal-based familiarity discrimination processes and plasticity including long-term depression (

A variety of stimuli cause sensory hair cell loss in the mammalian inner ear. This loss occurs by several differing processes, the significance of which remains undetermined. This study examines the relationship between the intensity of the damaging stimulus and the mode of hair cell loss found in the vestibular sensory epithelia of the rat. The ototoxin 3,3'-iminodipropionitrile (IDPN) was administered to rats at three different intoxication rates: acute exposure to high doses, repeated exposure to intermediate doses, and subchronic exposure to low doses. The morphology of the vestibular epithelia was examined by light microscopy and by scanning and transmission electron microscopy (SEM and TEM). In addition, DNA fragmentation in the epithelia was assessed by terminal deoxynucleotidyl transferase (tdt)-dUTP-nick-end-label (TUNEL). One day after acute IDPN, necrosis of hair cells was observed. However, at day 4 with this dose, and 1 and 4 days after repeated exposure, apoptotic figures and positive TUNEL labeling predominated. Subchronic IDPN resulted in a slowly evolving extrusion of basically intact hair cells in the crista and utricle. The data demonstrate that extrusion is a major mechanism of hair cell demise in mammals, that necrosis, apoptosis, and extrusion form a continuum of modes of hair cell loss, and that the intensity of the damaging stimulus determines the prevalence of each mode: Necrosis was most evident when the intensity was at its highest, whereas extrusion predominated when the intensity was at the lowest end of the scale.

The inferior olive climbing fibre projection is key to cerebellar contributions to motor control. Here we present evidence for a novel tool, trans-crotononitrile (TCN), to selectively inactivate the olive to study its functions. Anatomical, electrophysiological and behavioural techniques have been used in rats to assess the CNS effects of TCN, with a focus on the olivocerebellar projection. These findings were compared with those obtained with 3-acetylpyridine (plus nicotinamide administered 3.5 h later, 3AP + 3.5 h). Fluoro-Jade B cell labelling showed that TCN and 3AP + 3.5 h induce neurodegeneration primarily within the inferior olive, with no other targets in common. Recordings of evoked field potentials on the cerebellar cortical surface showed that both neurotoxins can reduce transmission in climbing fibre but not mossy fibre pathways. Both histological and electrophysiological differences suggest that TCN and 3AP have distinct mechanisms of action. Estimates of the numbers of surviving cells within individual subdivisions of the olive indicate that TCN and 3AP + 3.5 h cause different patterns of subtotal olivary lesion: most surviving neurons are present in the rostral (TCN) or caudal (3AP + 3.5 h) parts of the medial accessory olive, which are associated with two different cerebellar modules: the C2 and A modules, respectively. In behavioural studies, TCN and 3AP + 3.5 h produced differences in motor deficits consistent with the notion that these cerebellar modules have distinct functional responsibilities. Thus, studies using TCN as compared with 3AP + 3.5 h have the potential to shed light on the contributions of different cerebellar modules in motor control.