DNA probe technology: implications for service planning in Britain

For certain genetic conditions DNA testing identifies carriers and determines the risk status of foetuses, thus helping parents to make more informed prenatal decisions. Data, collected from three genetic centres in England and Wales from August 1986 to July 1990, are used to describe trends in demand for DNA testing, the impact of DNA tests on carrier risk assessment, and the use of DNA tests in relation to pregnancy outcome. Altogether the data include 23,388 subjects and 681 pregnancies in 8738 families divided into five cohorts by year of entry and referral. The most frequent gene disorders referred to the genetic centres are currently being tested or will soon be tested. For these disorders the initial high level of activity has declined and may have reached steady state. Demand for DNA services is high for cystic fibrosis and Duchenne muscular dystrophy, intermediate for Huntington's disease, and low for adult polycystic kidney disease, phenylketonuria and tuberous sclerosis. Based on these findings we suggest that demand for DNA tests will be high in serious, untreatable and slow progressing conditions with early onset; intermediate for conditions affecting intellect and neurological integrity with later onset; and low for treatable, late-onset conditions, or those for which there is evidence of heterogeneity, and variable penetrance. It would be helpful to assess the extent to which this view of demand is confirmed when the new disorders being DNA tested are considered and for the pattern of activity of DNA testing for some types of cancer. Since no DNA centre could offer a fully comprehensive testing service, it is recommended that a structure is created to audit overall activity, assist in policy formulation, and influence supraregional service organisation, in order that the spread of DNA services be planned as effectively as possible. This structure would facilitate monitoring of the evolution of contract specifications agreed by commissioners and providers on a regional basis.     

Knowledge of epilepsy among relatives of the epilepsy sufferer.

A 23-item questionnaire was constructed to assess awareness of basic facts about epilepsy. Close family members of the epilepsy sufferer achieved significantly higher scores on the questionnaire than individuals from families without experience of the condition. The questionnaire may be useful in the identification of family members of the epilepsy sufferer whose knowledge of the condition is low and who may require appropriate counselling.     

Intracellular Ca2+ buffers disrupt muscarinic suppression of Ca2+ current and M current in rat sympathetic neurons.

The role of intracellular Ca2+ concentration ([Ca2+]i) in the muscarinic suppression of Ca2+ current and M-type K+ current has been investigated in isolated rat sympathetic neurons using the whole-cell patch-clamp technique and fura-2 fluorescence measurements. Muscarinic stimulation suppressed currents without raising [Ca2+]i. Nonetheless, intracellular bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA) (11-12 mM), a Ca2+ chelator, reduced Ca2(+)-current suppression from 82 to 15%. For the latter, we explain the BAPTA action by a requirement for a certain minimum [Ca2+]i for continued operation of the pathway coupling muscarinic receptors to M-type K+ channels. The pathway coupling muscarinic receptors to Ca channels also showed some dependence on [Ca2+]i, but there may also be a blocking action of BAPTA that is independent of Ca2+ chelation.     

The uptake and costs of guidelines for stroke in a district of southern England.

STUDY OBJECTIVE: To assess the impact of guidelines for stroke management on the utilisation of services by patients and the cost consequences of implementation. DESIGN: Prospective audit. SETTING: District health authority in southern England. PATIENTS: A total of 468 live non-comatose stroke patients registered between November 1991 and May 1993. MAIN OUTCOME MEASURES: A comparison between the three, six month periods for investigations performed and rehabilitation received and their associated costs. RESULTS: The appropriateness of the use of investigations improved over time to between 88 and 92% except for computed tomography (CT) (24%). Younger, more severely impaired patients in a medical bed were more likely to have CT. Overall levels of rehabilitation were low. There was no change in use of physiotherapy (61% to 63%), a significant increase in occupational therapy (26% to 39%) and a non significant change in speech therapy (34% to 25%) over time. Guideline introduction caused a modest 23 Pounds increase in costs per patient in the 2nd six months and 41 Pounds in the 3rd six months but this sum could rise to 430 Pounds per patient if full implementation of the guidelines occurred which is still only around 13% of the costs of nursing care while in hospital. CONCLUSIONS: This 18 month aduit shows only modest changes in practice compared with guidelines, and overall levels of rehabilitation were low. The costs of full implementation seem considerable, but in fact constitute only a small proportion of nursing care costs.     

Evaluating the clinical nurse specialist. A review

This paper reviews evaluative studies on the role of clinical nurse specialists and aims to describe and categorise research according to the methods used. By using the structure, process and outcome framework a clear pattern of research development and evidence emerges. It appears that significant benefits accrue for patients from the contribution of nurse specialists, but more experimental studies with combined methods should now be applied to this area.     

Action of nifedipine of BAY K8644 is dependent on calcium channel state in single smooth muscle cells from rabbit ear artery

The actions of nifedipine or BAY K 8644 were studied on barium currents recorded from single, collagenase- and elastase-dispersed, smooth muscle cells from the rabbit ear artery using the whole-cell configuration of the patch-clamp technique. Nifedipine (3M) caused a reduction in the barium current (I_Ba) evoked by steps to potentials positive of-10mV. This was characterized by a pronounced initial block, an increase in the rate of current decay during the voltage-clamp step, but by no increase in block if pulses were repeated every 600ms. Rapid extracellular application of nifedipine (1M) during the sustained current component (using a new concentration-jump technique) was found to have no effect on I_Ba over 4s at +20mV, but after returning to the holding potential (-60mV) for 10s, sustained I_Ba was subsequently abolished. BAY K 8644 (1M) increased I_Ba at all potentials, and on rapid application during the sustained current component markedly potentiated I_Ba. The results suggest that nifedipine binds with high affinity to the closed, available state of the Ca⁺⁺ channels but they do not suggest binding to the open or inactivated states. The effect of BAY K 8644 is consistent with high affinity binding to the open or inactivated and to the closed, available states.     

Structure and properties of methacrylate based dental restorative materials

The chemistry and structure of the dimethacrylate resins and the nature of the filler systems in dental composite resins are reviewed in relation to their influence on the setting behaviour, dimensional stability, aesthetics, fracture behaviour and adhesive potential. It is clear that a deeper understanding of the structure of the polymeric matrix and the mechanism of clinical wear is required. As a result of ongoing research in this area and with the development of dentine adhesives, the future prospects of composite resins are encouraging.     

Cation-osmotic haemolysis in stroke patients

Erythrocyte microrheology changes were measured by cation-osmotic haemolysis (COH) in healthy donors, patients with ischameic stroke, and patients who died within four days after a stroke. COH in patients with stroke was significantly decreased in comparison with that from healthy donors. In patients who died, COH was significantly decreased compared to patients who survived. The relationship between cationosmotic haemolysis and erythrocyte deformability is discussed.     

Molecular identification and localization of Trp homologues,putative calcium channels,in pregnant human uterus

The mechanisms underlying the switch from uterine quiescence to contractile activity in labour are not clearly understood. Increasing evidence suggests that pathways of myometrial calcium homeostasis, including store-operated calcium entry (SOCE), may play an important role. The molecular basis of the membrane-associated calcium channels contributing to SOCE in pregnant human myometrium is not known, but they are likely to be hetero- or homo-oligomeric assemblies of transient receptor potential channel (TrpC) proteins, encoded by the mammalian homologues of Drosophila Trp genes. This study has therefore determined Trp gene expression and also TrpC protein expression and localization in term pregnant human myometrial tissue and primary cultured human myometrial smooth muscle (HMSM) cells. RT-PCR amplified fragments of Trp1, Trp3, Trp4, Trp6 and Trp7. PCR products were 100% homologous to published human sequences. Western blot analysis detected TrpC1, TrpC3, TrpC4 and TrpC6 proteins, which were of expected size. Immunolocalization revealed TrpC1, TrpC3, TrpC4 and TrpC6 protein expression in myometrial tissue and HMSM cells. TrpC protein immunostaining in HMSM cells was distributed in a distinct reticular fashion. TrpC proteins may be candidate proteins forming SOCE channels in term pregnant human myometrium.