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.

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.

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.

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.

Cystic fibrosis carrier screening in two New South Wales country towns.

OBJECTIVE: To assess the feasibility of offering community testing for carrier status of delta F508, a gene mutation associated with cystic fibrosis (CF). DESIGN: Prospective pilot survey. SETTING: General practice, the two main high schools and workplaces in the country towns of Young and Harden (combined population, 14,940; with 7707 people aged 16-55 years) in New South Wales (NSW). PARTICIPANTS: Individuals aged 16 years and over. MAIN OUTCOME MEASURES: Number of delta F508 carriers, test uptake rates, mode of learning about the testing, motivation for testing, retention of knowledge about CF, and test results and emotional effects of knowledge about carrier status. RESULTS: We tested 610 people (8% of the population aged 16-55 years) and identified 47 carriers (20% of the expected number in the 7707 people aged 16-55 years). Testing in schools had the highest uptake. Retention of knowledge was high; all delta F508-positive individuals recalled their carrier status accurately. Anxiety was transient among carriers; over 90% of all respondents felt they had made the right decision to be tested. CONCLUSIONS: We recommend community testing for carrier detection and suggest targeting those with a family history of CF and girls aged over 16 in high schools.

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.

Ultrasound assessment of the efficacy of wound drains.

We report the use of ultrasound in the assessment of the efficacy of wound drains in preventing wound haematoma. 171 patients with proximal femoral fractures who underwent AO dynamic hip screw or hemiarthroplasty were randomized as to whether or not they should receive wound drainage. Patients then underwent ultrasound examination on the 5th postoperative day to localize and quantify any wound haematomas. Results show that drains are effective in preventing wound collections, but only while in situ; following the removal of drains the size of resulting wound collections is the same whether the wound has been drained or not (Student's t-test; t = 0.19, NS). This study questions current theories on the mechanisms by which wound drainage is thought to influence wound healing.

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.

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.

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.

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.

Memory loss during pregnancy.

OBJECTIVE: To investigate possible impairment of memory during pregnancy. DESIGN: The performance of pregnant women in a variety of tests of memory was compared to that of controls. SETTING: The Bristol Maternity Hospital. SUBJECTS: Forty-eight volunteer pregnant women attending for routine antenatal checks were compared to 19 nonpregnant controls. MAIN OUTCOME MEASURES: Subjectively perceived rating of memory impairment, objective measures of recall, recognition and priming memory. RESULTS: Pregnant and control groups were given a series of tests of memory at the end of which they were asked to rate their own memory at present compared to some weeks ago (when they were not pregnant). Of the pregnant women 39 out of 48 (81%) rated their current memory as being impaired; only three out of 19 (16%) of the control subjects did so. Objective tests revealed that the pregnant group was significantly impaired in the recall of lists of words, particularly when learning was incidental rather than explicit. The pregnant group was also significantly impaired in two measures of priming memory. No significant deficit was found in recognition. The deficits were found for both primigravid and multigravid women, and were present in all trimesters of pregnancy. CONCLUSIONS: The majority of women believe their memory to be impaired during pregnancy. Objectively, during pregnancy there is significant impairment of memory as tested by recall or by priming, but not by recognition. The pattern of memory loss differs from that of other amnesic conditions. Information imparted to pregnant patients may not be retained as well as might be expected.

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.

Objective and subjective memory impairment in pregnancy.

Pregnant subjects rated their memories as worse than normal and their ratings differed significantly from controls. Explicit memory tested by both recognition and recall was unimpaired. In contrast, implicit memory was significantly impaired in primigravidae. Impairment in implicit memory correlated with the subjective memory ratings. The dissociation of explicit and implicit memory is discussed.

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 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.