Evidence for prenatal competition among the central arbors of trigeminal primary afferent neurons.

Previous studies have shown that damage to vibrissa follicles in newborn rats and mice does not alter the brainstem representations of the remaining vibrissa as demonstrated by staining for mitochondrial enzymes such as cytochrome oxidase (CO) succinic dehydrogenase. This study asked whether this lack of effect might be due to the fact that the trigeminal primary afferents in rodents are already quite well developed at birth. We assessed this possibility by using CO staining the evaluate patterns in the brainstems of pre- and postnatal rats. A vibrissa-related pattern began to emerge in trigeminal nucleus principalis and subnucleus interpolaris (Spl) by embryonic day (E-) 19 and appeared fully developed by the day of birth (P-0). We also made partial lesions of the vibrissa pad on E-15-20 and on P-0, killed pups on P-5-7, and measured the size of the CO-stained patches in Spl on both sides of the brainstem. The correspondence between CO patches and clusters of primary afferent terminal arbors was verified in some animals by combining transganglionic horseradish peroxidase tracing and CO staining. Vibrissa pad damage on E-15-18 resulted in significant (20.1-36.9%) increases in the average area of the remaining CO patches in Spl ipsilateral to the lesion. Vibrissa pad damage on E-19, E-20, and P-0 produced small (6.2-8.9%), but insignificant, increases in patch size in Spl ipsilateral to the lesion. We used anatomical and electrophysiological methods to determine whether our lesions altered the trigeminal innervation of surviving vibrissa follicles. We recorded single trigeminal ganglion cells from 12 rats that sustained vibrissa pad lesion on E-17. As in normal rats, all of the 49 vibrissa-sensitive ganglion cells isolated in the lesioned animals were responsive to deflection of one and only one vibrissa. We also dissected 11 deep vibrissal nerves from intact follicles in adult rats that sustained fetal vibrissa pad damage on E-17, and counted numbers of myelinated axons in 1 microns plastic sections. These data were compared with counts from corresponding follicles on the intact side of the face. The average number of myelinated axons innervating follicles in the damaged vibrissa pads was 196.8 +/- 27.9, and that for the corresponding contralateral nerves was 194.6 +/- 25.7. These data suggest that competitive interactions among the central arbors of trigeminal primary afferents in fetal life may influence the development of central vibrissa representations and, further, that lesion-induced central changes need not be correlated with alterations in the peripheral innervation of undamaged follicles.     

Benzazepinone calcium channel blockers. 2. Structure-activity and drug metabolism studies leading to potent antihypertensive agents. Comparison with benzothiazepinones.

As part of a program to discover potent antihypertensive analogues of diltiazem (3a), we prepared 1-benzazepin-2-ones (4). Benzazepinones competitively displace radiolabeled diltiazem, and show the same absolute stereochemical preferences at the calcium channel receptor protein. Derivatives of 4 containing a trifluoromethyl substituent in the fused aromatic ring show potent and long-acting antihypertensive activity. Studies of the metabolism of 4 lead to the metabolically stable antihypertensive calcium channel blockers 5a and 5c. Benzazepinone 5a is a longer acting and more potent antihypertensive agent than the second generation diltiazem analogue TA-3090 (3e).     

A latent class model for repeated measurements experiments.

Standard models for the analysis of repeated measurements assume a common response profile for all experimental units within a treatment group. However, in many applications this under-represents the nature of the response. There may be several distinct modes of response within a group (for example, responders versus non-responders to a given treatment), or there may be a set of distinct response profiles which are common to all the treatment groups. In these situations the effect of treatment can be characterized both by the shape of the fitted profiles and by estimating the proportion of cases who exhibit each particular response profile. This paper describes how such experiments may be analysed through the introduction of a latent variable into the standard model. Maximum likelihood estimation is straight-forward using the EM algorithm. Model choice requires some care, but good-fitting models can be identified via inspection of residuals and the use of empirical semi-variogram plots. Once the number of distinct profiles has been determined, treatment effects can be investigated using likelihood-ratio statistics. The approach is illustrated with a re-analysis of a dataset first described by Grizzle and Allen.     

NHS Direct usage in a GP population of children under 5 years: is NHS Direct used by people with the greatest health need?

This study compares health status, demographic and socioeconomic characteristics of users and non-users of NHS Direct in order to establish whether the service is being used by people with the greatest need for healthcare services. It suggests that use of NHS Direct is widespread among carers of children under 5 years old, but there is evidence that it may not be accessed equitably by those from ethnic minorities, lower socioeconomic groups and those with established ill health.     

Usefulness of the minute ventilation test in predicting successful extubation in newborn infants: a randomized controlled trial.

OBJECTIVE: We performed a prospective, randomized clinical trial to compare the usefulness of the minute ventilation test (MVT) with clinical judgement in predicting readiness for extubation in preterm newborns with respiratory distress syndrome requiring surfactant therapy and mechanical ventilation. STUDY DESIGN: A total of 42 preterm infants with respiratory distress syndrome were randomized when they reached preselected ventilator settings. The primary outcome measure was the time from study entry to extubation, provided the infant remained extubated for at least 24 hours. RESULTS: Infants evaluated by the MVT were extubated in a significantly shorter period of time (mean of 8 hours) than those evaluated clinically (mean of 36 hours). The extubation failure rate was similar in the two groups. CONCLUSION: The MVT is an easily performed objective measure that can be used to predict readiness for extubation in preterm infants. In this study, it significantly shortened the time for extubation and was not associated with a higher rate of reintubation.     

Legal issues in contact lens practice with special reference to the practice of orthokeratology

This report aims to encourage optometrists to reflect on the legal implications of clinical contact lens practice, with particular reference to the practice of orthokeratology (ortho-k), which has seen a recent revival of interest. A patient may claim compensation if an optometrist is negligent by breaching his duty to exercise reasonable care and skill in diagnosis, advice or treatment. However, the optometrist will only be liable for reasonably foreseeable harm to the patient, so practitioners need to be fully aware of the foreseeable risks. Failure to adequately inform the patient may lead to a claim for negligence, if disclosure of the risks would have influenced the patient's decision to undergo or forego the procedure. It is important that the professional bodies establish guidelines on acceptable practice, with particular emphasis on the provision of information to patients. Reasonable disclosure, use of appropriate information/consent forms, and proper documentation of cases, should all focus on the needs of, and benefits to, patients.