Ongoing impairments following transient ischaemic attack: retrospective cohort study.

BACKGROUND AND PURPOSE: Clinical management after transient ischaemic attack (TIA) is focused on stroke prevention; however, a number of small studies suggest that patients may experience ongoing residual impairments. METHODS: This was a retrospective matched-cohort study using anonymized electronic primary care records from The Health Improvement Network database, which covers approximately 6% of the UK population. Adults (≥ 18 years old) who experienced a first TIA between 2009 and 2013 were matched in a ratio of 1:5 to controls by age, sex and general practice. The time to first consultation for fatigue, psychological impairment or cognitive impairment was estimated by Kaplan-Meier survivor functions and adjusted hazard ratios. RESULTS: A total of 9419 TIA patients and 46 511 controls were included. The Kaplan-Meier curves showed that TIA patients were more likely than controls to consult for all three impairments (P < 0.0001). Within 7.1 months (95% confidence interval (CI), 6.2-8.2), 25% of TIA patients consulted for psychological impairment compared with 23.5 months (95% CI, 22.5-24.6) for controls. Hazard ratios for TIA patients were 1.43 (95% CI, 1.33-1.54) for consulting for fatigue, 1.26 (95% CI, 1.20-1.31) for psychological impairment and 1.45 (95% CI, 1.28-1.65) for cognitive impairment. CONCLUSIONS: Transient ischaemic attack is associated with significantly increased subsequent consultation for fatigue, psychological impairment and cognitive impairment. These findings suggest that impairments exist after initial symptoms of TIA have resolved, which should be considered by clinicians when treating TIA patients.

Environmental applications of magnetic measurements.

A wide range of examples of the application of magnetic measurements to environmental studies illustrate the advantages of magnetic techniques over conventional methods. Magnetic measurements, in both the field and the laboratory, are particularly useful for reconnaissance work because of their spee and flexibility, Quantification as well as simple diagnosis of the transformation and movement of magnetic minerals within and between the atmosphere, lithosphere, and hydrosphere is practical. Techniques of investigating intrinsic and mineral magnetic properties, in addition to paleomagnetic remanence, are described in subjects as diverse as meteorology, hydrology, sedimentology, geophysics, and ecology.

Haploinsufficiency of the mSds3 chromatin regulator promotes chromosomal instability and cancer only upon complete neutralization of p53.

The mSin3 corepressor complex has been linked to diverse cancer signaling pathways through its capacity to regulate target gene expression via chromatin modification. mSds3, a cell essential gene, is a key component of the mSin3 complex serving to maintain its inherent histone deacetylase activity. mSds3 also serves an essential role in the establishment of pericentric heterochromatin, and genetic ablation of mSds3 results in chromosome missegregation. In contrast, mSin3A nullizygous cells show normal chromosome dynamics and cytogenetic profiles. The integral role of mSds3 in controlling chromosome segregation and mSin3-regulated transcriptional networks prompted efforts to determine the neoplastic impact of loss of one copy of mSds3 or mSin3A. In particular, we assessed whether loss of one copy of mSds3, alone or in combination with p53 mutation, results in aneuploidy and promotes a cancer-prone condition in the mouse. We observe that, in a p53 null background, loss of one mSds3 allele results in accelerated tumor onset and increased tumor burden. Notably, these mSds3(+/-) p53(-/-) tumors exhibit a more complex cytogenetic profile characterized by marked aneuploidy and centromeric associations. The presence of even one copy of p53 is sufficient to suppress the accelerated tumorigenesis in mSds3(+/-) mice, consistent with a key role for p53 in monitoring mitotic fidelity. These observations with Sds3 mutant mice contrast with mSin3A(+/-) p53(-/-) mice, which do not show an accelerated or increased tumor incidence relative to mSin3A(+/+)p53(-/-) controls, correlating with the absence of aneuploidy detected upon mSin3A genetic inactivation. This genetic study establishes that the capacity of mSds3 to cooperate with p53 deficiency in cancer predisposition relates to its specific role in chromosome segregation, rather than its central role in maintaining a functional mSin3A complex.

Confirmation of early menopause in fragile X carriers.

Fragile X carriers have a median age of menopause 6 to 8 years earlier than women in the general population, with 28% experiencing premature ovarian failure defined as menopause before the age of 40 years. This information was obtained from 203 returned questionnaires from women in the UK Fragile X Society.

Plasma lactoferrin levels in pregnancy and cystic fibrosis.

Plasma lactoferrin levels were determined by radioimmunoassay for the different weeks of normal pregnancy, in normal healthy adults and in children with and without cystic fibrosis. The lactoferrin levels were higher in pregnancy than in both male and female normal adults and showed a slight progressive increase up to week 29 and thereafter remained high. Five our of seven children with cystic fibrosis had markedly raised plasma lactoferrin levels from six to 16 times higher than the mean of a control group of children.

Anticonvulsant effects of the experimental induction of hippocampal theta activity.

Epileptic seizures occur less during wakefulness or paradoxical sleep, conditions during which hippocampal theta rhythm is seen. This leads to the hypothesis that this rhythm indicates a physiological state of the hippocampal formation which opposes its recruitment into seizures. This was tested by determining the effects of experimental induction or suppression of hippocampal theta activity on seizures. Hippocampal theta activity can be induced by chemical or electrical stimulation of the medial septal nucleus and adjacent nucleus of the diagonal band of Broca. Microinjections of the muscarinic agonist carbachol in the medial septum during pentylenetetrazol (PTZ) induced facial-forelimb seizures stopped behavioral seizures and EEG spiking within five seconds, and caused hippocampal theta activity. Medial septal electrical stimulation at 4-8 Hz had similar effects. Electrolytic medial septal lesions abolished hippocampal theta activity and lowered myoclonic and facial-forelimb PTZ seizure thresholds. Medial septal carbachol injections were also made during electrically kindled limbic status epilepticus. Within ten seconds, ictal behavior stopped and the EEG spike rate decreased by half with a gradual return to the baseline rate over three minutes. These results demonstrate that the hippocampal theta rhythm corresponds to a seizure-resistant condition, providing a possible explanation for the seizure promoting properties of slow wave sleep.

Fulminant ulcerative colitis in late pregnancy and the puerperium.

Four patients underwent emergency colectomy during pregnancy or the puerperium for complications of ulcerative proctocolitis. Three had inactive colitis at conception, while in the fourth the disease started during pregnancy. Three patients required subtotal colectomy and ileostomy for toxic dilatation during the third trimester or within 5 days of delivery, and the fourth underwent proctocolectomy postpartum for intractable colitis. There were no maternal deaths but 2 of 4 infants died. One child weighing 1.4 kg survived vaginal delivery during the 33rd week of pregnancy, 2 weeks after his mother had undergone emergency colectomy.

The facial profile in the diagnosis of fetal abnormalities.

In order to assess the significance of fetal facial anomalies detected by ultrasound, a 4 year review was made of all detailed antenatal scans performed in our department. Anomalies were detected in 24 fetuses. All findings were subsequently confirmed. Micrognathia was the most common finding, 38% of these had an abnormal karyotype, and 45% had a recognized skeletal dysplasia. Facial clefting was also commonly seen, both in isolation and associated with other abnormalities. When associated with other abnormalities, 40% of cases with facial clefting had a chromosomal abnormality indicating a need for karyotype analysis in these patients. Other anomalies detected included cebocephaly, hypotelorism, frontal bossing, exophthalmos and hypertelorism. We feel that visualization of the fetal face is an essential part of the assessment of intracranial abnormalities and is valuable in any situation where a chromosomal abnormality or a skeletal dysplasia is suspected.

Role of the fastigial nucleus in generalized seizures as demonstrated by GABA agonist microinjections.

The cerebellum is electrically and metabolically active during seizures. Numerous studies have also shown that cerebellar electrical stimulation and lesions of the cerebellar cortex or nuclei influence seizure threshold, but there are significant contradictions, with different effects observed even in investigations using the same species and similar seizure types and experimental manipulations. Discrete intracerebral microinjection of neuroactive agents has been used to characterize the way in which other brain regions control seizures, but has not been applied to the cerebellar systems. This approach has advantages because effects are restricted to specific receptors and spare passing axons; experimental variables also can be simply specified and reproduced. We used this method to characterize the role of the cerebellar nuclei in seizures and to determine if observed effects could be reproduced with different agents at different doses. Effects of bilateral control microinjections in the fastigial (medial) cerebellar nucleus were compared with different doses of the GABAA agonist piperidine-4-sulfonic acid and the GABAB agonist (-)baclofen (Bf). Soon after injection, the animals were ataxic. After 4 min, seizures were induced by timed continuous intravenous (i.v.) bicuculline (BIC) infusion. Both GABA agonists produced significant reductions in myoclonic, clonic, and tonic seizure thresholds. Injections just dorsal or anterior to this nucleus and bilateral dentate (lateral) nucleus injections had little effect on seizures. These results demonstrate that the cerebellar system does control seizures, but does not provide support for the early concept that cerebellar stimulation and systemic phenytoin block seizures through inhibition of cerebellar nuclei secondary to Purkinje cell activation.

Management of pregnancy complicated by hypertrophic obstructive cardiomyopathy.

We report our experiences with nine women suffering from hypertrophic obstructive cardiomyopathy who between them had 13 pregnancies, 10 of which were directly managed by us. Though at first we felt that the theoretical hazards of vaginal delivery indicated elective caesarean section, experience has convinced us that in the absence of an obstetrical contraindication these patients may be delivered vaginally provided a betaadrenergic blocking drug is administered during pregnancy and especially during labour, ergometrine is given at the end of the second stage, adequate supplies of cross-matched blood are available, and prophylaxis against infective endocarditis is administered. We have found no evidence of any adverse effects of either propranolol or pronethalol on the foetus.

The efficacy of graduated compression stockings in the prevention of deep vein thrombosis after major gynaecological surgery.

The efficacy of graduated compression stockings in the prevention of deep vein thrombosis (DVT) after major gynaecological surgery was investigated in a controlled randomized prospective trial in 196 patients who were greater than 35 years of age. The stockings were worn by 104 of the 196 patients throughout their stay in hospital, the other 92 patients did not wear the stockings (control group). All the patients were scanned for DVT postoperatively with the 125I-labelled fibrinogen test. None of the 104 patients who wore the stockings developed a thromboembolism, but four of the 92 control patients who did not wear the stockings had DVT. This difference between the two groups was statistically significant.

Neurological normality after extreme birth asphyxia. Case report.

A case of extremely severe birth asphyxia is reported. In spite of successful resuscitation the arterial pH was still only 6.6 at the age of 1 h. Assessment at 3 years 10 months revealed that the child was not only completely normal, but was of superior intelligence. This case demonstrates the advisability of maintaining an optimistic approach even when very severe fetal acidosis is detected around the time of birth.

Tremor, ataxia and dementia in older men may indicate a carrier of the fragile X syndrome.

Recently it has been reported that late-onset tremor, gait unsteadiness and dementia can be associated with brain atrophy in males of normal intelligence and the pre-mutation carrier state of the fragile X syndrome. We have shown, by means of a telephone survey, that this association is probably causal rather than coincidental. These findings have uncovered another testable cause of late-onset neurological symptoms in males, which also has serious genetic implications for their daughters who are at risk of having sons with full mutations causing mental handicap - the fragile X syndrome.

Use of fructosamine and glycated haemoglobin to verify self blood glucose monitoring data in diabetic pregnancy.

Relationships between fructosamine and HbA1, and mean blood glucose over the previous 1-8 weeks, determined from self blood glucose monitoring with memory meters, were studied prospectively throughout 16 pregnancies in Type 1 diabetic women. Fructosamine correlated best (Spearman rank) with mean blood glucose over the previous 2 weeks in the first and second trimesters (0.5) and over the previous 1 week in the third trimester (0.39). HbA1 correlated best with mean blood glucose over the previous 8 weeks in the first and second trimesters (0.56), but over the previous 2 weeks in the third trimester (0.524) probably because of increased erythropoiesis in late pregnancy. From Deming regression models, 95% prediction intervals for mean blood glucose for fructosamine and HbA1 values were calculated, showing that fructosamine predicted levels of mean blood glucose more precisely than HbA1. These intervals can be used to estimate an individual pregnant diabetic woman's mean blood glucose from her fructosamine or HbA1 results and to verify self blood glucose monitoring data. In well-controlled diabetic pregnancy, both fructosamine and HbA1 reliably indicated trends in blood glucose but fructosamine estimated blood glucose levels more precisely.

An ascending seizure-controlling pathway in the medial brainstem and thalamus.

This study demonstrated that an ascending pathway from the laterodorsal tegmental nucleus (LDTg) of the pontomesencephalic tegmentum to the thalamic central medial intralaminar nucleus (CeM) controls the thresholds of experimental seizures. Electrolytic and excitotoxic lesions of the CeM and adjacent thalamus facilitated myoclonic, facial-forelimb clonic, and tonic pentylenetetrazol seizures. Microinjections of the GABAB agonist (-)baclofen in the LDTg facilitated myoclonic and facial-forelimb clonic but not tonic seizures. When LDTg injections of (-)baclofen were performed in animals with prior electrolytic lesions of the midline thalamus, the thresholds of myoclonic and facial-forelimb clonic seizures were unchanged compared to similarly lesioned rats with control vehicle LDTg injections. In addition, the lowering of tonic seizure threshold observed with thalamic lesions was reversed by these (-)baclofen injections. Taken together with past studies, these results imply that the LDTg controls myoclonic and facial-forelimb clonic seizures via ascending projections to the CeM and possibly other medial thalamic nuclei. We also postulate that the LDTg affects tonic seizures by two different, opposing pathways. Although the LDTg-CeM pathway is part of the "ascending reticular activating system," lesions of the midline thalamus did not affect spontaneous sleep, implying that the CeM does not have an essential role in sleep regulation.

Maternal postprandial blood glucose levels influence infant birth weight in diabetic pregnancy.

Relationships between maternal glycaemia and neonatal birth weight were studied prospectively in 14 tightly controlled pregnant women with pre-existing type 1 diabetes mellitus. Maternal glycaemia throughout pregnancy was determined from daily self blood glucose (BG) monitoring with memory meters and fortnightly fructosamine (Fr) and glycated haemoglobin (HbA1) measurements. Mean non-fasting BG and mean HbA1 throughout pregnancy correlated strongly (Spearman rank) with birth weight (0.64 and 0.73 respectively), as did mean second trimester non fasting BG (0.54), HbA1 (0.7) and Fr (0.64) and mean third trimester HbA1 (0.65), whereas mean fasting BG showed no significant correlations with birth weight at any age of pregnancy. The disparity between the strong correlation of non fasting BG with birth weight and the poor correlation of fasting BG suggests that postprandial as opposed to basal glycaemia significantly influences foetal growth and neonatal size.