MiR-324-5p inhibition after intrahippocampal kainic acid-induced status epilepticus does not prevent epileptogenesis in mice.

Background: Acquired epilepsies are caused by an initial brain insult that is followed by epileptogenesis and finally the development of spontaneous recurrent seizures. The mechanisms underlying epileptogenesis are not fully understood. MicroRNAs regulate mRNA translation and stability and are frequently implicated in epilepsy. For example, antagonism of a specific microRNA, miR-324-5p, before brain insult and in a model of chronic epilepsy decreases seizure susceptibility and frequency, respectively. Here, we tested whether antagonism of miR-324-5p during epileptogenesis inhibits the development of epilepsy. Methods: We used the intrahippocampal kainic acid (IHpKa) model to initiate epileptogenesis in male wild type C57BL/6 J mice aged 6-8 weeks. Twenty-four hours after IHpKa, we administered a miR-324-5p or scrambled control antagomir intracerebroventricularly and implanted cortical surface electrodes for EEG monitoring. EEG data was collected for 28 days and analyzed for seizure frequency and duration, interictal spike activity, and EEG power. Brains were collected for histological analysis. Results: Histological analysis of brain tissue showed that IHpKa caused characteristic hippocampal damage in most mice regardless of treatment. Antagomir treatment did not affect latency to, frequency, or duration of spontaneous recurrent seizures or interictal spike activity but did alter the temporal development of frequency band-specific EEG power. Conclusion: These results suggest that miR-324-5p inhibition during epileptogenesis induced by status epilepticus does not convey anti-epileptogenic effects despite having subtle effects on EEG frequency bands. Our results highlight the importance of timing of intervention across epilepsy development and suggest that miR-324-5p may act primarily as a proconvulsant rather than a pro-epileptogenic regulator.

Immature murine hippocampal neurones do not develop long-term structural changes after a single isoflurane exposure.

BACKGROUND: Studies in developing animals show that a clinically relevant anaesthesia exposure increases neuronal death and alters brain structure. In the hippocampal dentate gyrus, the anaesthetic isoflurane induces selective apoptosis among roughly 10% of 2-week-old hippocampal granule cells in 21-day-old mice. In this work, we queried whether the 90% of granule cells surviving the exposure might be 'injured' and integrate abnormally into the brain. METHODS: The long-term impact of isoflurane exposure on granule cell structure was studied using a transgenic mouse model fate-mapping approach to identify and label immature granule cells. Male and female mice were exposed to isoflurane for 6 h when the fate-mapped granule cells were 2 weeks old. The morphology of the fate-mapped granule cells was quantified 2 months later. RESULTS: The gross structure of the dentate gyrus was not affected by isoflurane treatment, with granule cells present in the correct subregions. Individual isoflurane-exposed granule cells were structurally normal, exhibiting no changes in spine density, spine type, dendrite length, or presynaptic axon terminal structure (P>0.05). Granule cell axon terminals were 13% larger in female mice relative to males; however, this difference was evident regardless of treatment (difference of means=0.955; 95% confidence interval, 0.37-1.5; P=0.010). CONCLUSIONS: A single, prolonged isoflurane exposure did not impair integration of this age-specific cohort of granule cells, regardless of the animal's sex. Nonetheless, although 2-week-old cells were not affected, the results should not be extrapolated to other age cohorts, which may respond differently.

Semiquantitative determination of off-notes in mint oils by solid-phase microextraction.

Mint essential oils are produced by the steam distillation of dried or partially dried harvested plant material. In the United States, harvesting is done mechanically so that any weeds found in the field are concomitantly harvested. Steam distillation of contaminated plant material leads to off-notes in the oil, which are currently determined by a sensory panel. Furthermore, nonoptimized distillation conditions can lead to the thermal degradation of carbohydrates and proteins resulting also in the formation of very volatile off top-notes. As a result, the use of a nonequilibrated solid-phase microextraction (SPME) procedure to determine the off-notes is evaluated. The results of this evaluation include a combination of semiquantitative data, odor threshold data, and mathematical data manipulation to ascertain the capabilities of a SPME approach. The results are correlated with sensory panel data to yield a relatively rapid analytical methodology that can be used either in place of or in support of sensory analyses. The main advantage of the technique described is to provide some semiquantitative data in support of the odor-panel screening of mint oils for off-notes. Based on the data presented in this report, it is believed that this has been successfully demonstrated.

Obstetric complications and schizophrenia: a case control study based on standardised obstetric records.

BACKGROUND: There have been many reports of a higher incidence of 'obstetric complications' in the histories of schizophrenics than of controls, but because of the methodological shortcomings of most of these comparisons the relationship remains controversial. METHOD: Comprehensive records covering all psychiatric hospital admissions and all hospital deliveries in Scotland since 1971 made it possible to identify the obstetric records of people born in 1971-74 who were subsequently admitted to hospital with a diagnosis of schizophrenia, and then to compare their standardised obstetric records with those of closely matched controls. RESULTS: One hundred and fifteen schizophrenic/control pairs were compared. The former showed a highly significant (P < 0.001) excess of complications of both pregnancy and delivery. In particular, there was a significant excess of pre-eclampsia (10 v. 2) and of infants detained in hospital for neonatal care (18 v. 6). CONCLUSION: The raised incidence of obstetric complications often reported in people with schizophrenia is genuine and probably contributes to the aetiology of the condition.

Safety and place of birth in Scotland.

BACKGROUND: The recent publication of policies suggesting women should have choice about where they give birth prompted a comparison of stillbirth and neonatal mortality rates for three types of maternity unit in relation to changes in booking and place of delivery. METHODS: Scottish Maternity Discharge records and data from stillbirth and neonatal death reports for Scotland were used to analyse stillbirth and neonatal mortality rates according to the level of care, birthweight and cause of death for the years 1986-1990. RESULTS: For those categories of stillbirths and neonatal deaths which are amenable to prevention by perinatal care, intrapartum stillbirth rates were higher in general practitioner (GP) units than in consultant units, but these accounted for only 11 stillbirths and the difference is compatible with chance variation. Neonatal mortality among babies weighting 2500 g or more was independent of type of hospital. Among babies weighing under 1500 g or 1500-2499 g, neonatal mortality was significantly higher in non-teaching hospitals than in teaching hospitals. CONCLUSIONS: Although the differences are compatible with chance variation, there is some suggestion that small GP hospitals might have higher rates of intrapartum stillbirths and such rates should be monitored. Provided that there are no barriers to transfer to hospitals with consultant units when appropriate, there is no evidence that these small GP hospitals are unsafe. The high neonatal mortality rates, especially among babies weighing 1500-2499 g in non-teaching consultant units, compared with teaching units, should be investigated further.

A case-control investigation of perinatal risk factors for childhood IDDM in Northern Ireland and Scotland.

OBJECTIVE: To identify perinatal risk factors for childhood insulin-dependent diabetes mellitus (IDDM) and determine if they differ between early-onset and late-onset disease. RESEARCH DESIGN AND METHODS: We selected 258 diabetic children in Northern Ireland and 271 diabetic children in Scotland from population-based registers. For each diabetic child, five matched control subjects were drawn from the same population. All perinatal data were recorded routinely at birth. Odds ratios (ORs) were estimated for parental age, social class, breast-feeding, deprivation measures, and other perinatal variables. RESULTS: Scottish data indicated an increased risk among children born to older mothers (OR = 2.43, 95% confidence interval [CI] 1.49-3.97 for mothers > or = 35 years of age relative to those < 25 years of age). Northern Ireland data showed no such effect. Only Northern Ireland data showed an excess risk in children of professional or managerial families (OR = 1.51, 95% CI 1.11-2.04). A small but nonsignificant reduction in risk among breast-fed children was observed only after adjustment for social class (OR = 0.76, 95% CI 0.54-1.07). Deprivation measures were associated with reductions in risk. Children delivered by cesarean section were at increased risk in both Northern Ireland (OR = 1.66, 95% CI 1.10-2.50) and Scottish (OR = 1.70, 95% CI 1.12-2.59) data. In Northern Ireland data only, children of first pregnancies were at increased risk (OR = 1.41, 95% CI 1.03-1.93). Both data sets indicated that a first pregnancy was a more important risk factor for early-onset disease than for late-onset disease. CONCLUSIONS: Many reported risk factors are weak and show inconsistencies between studies. They may be secondary to more direct, as-yet-undiscovered risk factors. Although irrelevant in the majority of cases, the increased risk associated with delivery by cesarean section deserves further study.

Clinical and angiographic recurrence following PTCA for nonacute total occlusions: comparison of one- versus five-minute inflations.

To assess potential efficacy of longer inflations to reduce restenosis, 49 patients with nonacute total occlusions were randomized into two groups after successful guide wire passage across the occlusive stenosis. Twenty-one group I patients had all inflations less than 1 minute, while 28 group II patients received at least one inflation of 5 minutes' duration. There was no significant difference between group I and group II patients in mean age (56 +/- 3 versus 57 +/- 2 years), percent male sex (76% versus 68%), or frequency of left anterior descending (LAD) percutaneous transluminal coronary angioplasty (PTCA) (33% versus 32%), p = NS for all. All lesions post PTCA were less than or equal to 50% stenosed and no patient had coronary artery bypass surgery (CABG). Mean post PTCA stenosis was 29 +/- 2% for group I versus 33 +/- 2% for group II, p = NS. Clinical follow-up was available for all patients 8 +/- 0.6 months after PTCA. Recurrent symptoms were present in 8 of 21 (38%) group I patients compared with 12 of 28 (43%) patients in group II, p = NS. Angiographic follow-up was available in 32 patients (65%), with confirmation of restenosis in seven (33%) group I patients and in 11 (39%) group II patients, p = NS. In conclusion, this prospective study suggests that recurrence rates following successful PTCA of nonacute total occlusions is not modified by 5-minute versus 1-minute inflations.

Trends in infant mortality in Scotland, 1970-1987.

Infant mortality rates in Scotland have fallen by 56.6 per cent from 19.6 per 1000 live births in 1970 to 8.5 per 1000 in 1987. The reduction has been more marked in the early neonatal period than at later ages. The causes of death, based on generally high post-mortem rates, have been examined in functional groups and the changes over time are described. Ninety per cent of neonatal deaths throughout the period reviewed were due to congenital anomalies, asphyxia or immaturity-associated conditions. Eighty per cent of post-neonatal deaths are now due to congenital anomaly or sudden infant death syndrome (SIDS). The principal shifts in cause of death groups from infections and external causes in the 1970s to SIDS in the 1980s are described in detail and are probably related to improved recognition of the syndrome of sudden infant death, rather than to true changes.

Accuracy of death certificates in neonatal deaths.

Death certificates of neonates were compared with detailed clinical and pathological information provided for a national neonatal mortality survey. The systematic method of assigning the cause of death to one of seven broad categories in the survey found complete agreement with the underlying cause of death on the death certificate in 83 per cent of cases (274/330). There was only a minor disagreement involving clinical opinion in a further 6.7 per cent (22). The reasons for disagreement in the remaining 10.3 per cent (34) were examined. In the majority of instances, 6.0 per cent (20), the fault lay with the certifying doctor who provided inadequate or inaccurate information on the death certificate or who, in providing all the information, appeared to be ignorant of coding rules. In 1.2 per cent (4) the fault lay with coding inaccuracies or misapplication of coding rules in failing to select the underlying cause in a correct sequence of clinical events. In the remaining 3.0 per cent (10) of cases the rules governing the survey did not follow the WHO coding rules.

Outcome indicators: who benefits?

Most of the recent work on performance indicators has concentrated on the provision or activities of health services rather than on their impact on the patients and populations who use them. Although the precise relationship between treatment and outcome is often unclear, simple examination of routinely available data can show whether mortality and morbidity are changing in desired directions. This pinpoints topics for more detailed professional review. It is incumbent on doctors to match the concern over the efficient use of health services with information about their effects on people's health.

Classifying perinatal death: an obstetric approach.

Consultation between the clinicians and epidemiologists responsible for the Perinatal Mortality Surveys in Scotland and in the Northern Regional Health Authority in England showed that the classification of perinatal death introduced more than 30 years ago by Sir Dugald Baird still retained its utility, but that unintentional differences in the way cases were being classified had threatened the validity of temporal or geographical comparisons. To overcome this problem an effort has now been made to define the main terms used in this classification more precisely. To preserve continuity, the main structure of the original groupings has been retained; but the opportunity has been taken to adjust certain minor groups in conformity with recent ideas, and also to modify definitions to take into account the greatly improved prognosis for babies of very low birthweight. Otherwise, it is thought that subclassification of the main groups offers a better method of exploring new hypotheses than any radical alteration of the main groups themselves.

Cervical suture in Scotland: strengths and weaknesses in the use of routine clinical summaries.

National routinely collected hospital data for 12 months from June 1976 were used to provide information on patients with cervical suture during pregnancy. The past obstetric history and outcome of the pregnancy after suture was contrasted with the experience of all pregnant women during the same year. The nature of the data did not allow adequate examination of any change in the rate of fetal wastage, before and after suture; or in the secular change in fetal wastage in the pregnant population. After cervical suture the rates of both premature delivery and of perinatal mortality were higher than in the general pregnancy population. The perinatal mortality rate in the cervical suture group showed a greater improvement after suture than was seen to occur between previous and current pregnancies in the whole population, although the excess improvement in pregnancy outcome that occurred after cervical suture could not be definitely ascribed to the suture.