The conserved Trp114 residue of thioredoxin reductase 1 has a redox sensor-like function triggering oligomerization and crosslinking upon oxidative stress related to cell death.

The selenoprotein thioredoxin reductase 1 (TrxR1) has several key roles in cellular redox systems and reductive pathways. Here we discovered that an evolutionarily conserved and surface-exposed tryptophan residue of the enzyme (Trp114) is excessively reactive to oxidation and exerts regulatory functions. The results indicate that it serves as an electron relay communicating with the FAD moiety of the enzyme, and, when oxidized, it facilitates oligomerization of TrxR1 into tetramers and higher multimers of dimers. A covalent link can also be formed between two oxidized Trp114 residues of two subunits from two separate TrxR1 dimers, as found both in cell extracts and in a crystal structure of tetrameric TrxR1. Formation of covalently linked TrxR1 subunits became exaggerated in cells on treatment with the pro-oxidant p53-reactivating anticancer compound RITA, in direct correlation with triggering of a cell death that could be prevented by antioxidant treatment. These results collectively suggest that Trp114 of TrxR1 serves a function reminiscent of an irreversible sensor for excessive oxidation, thereby presenting a previously unrecognized level of regulation of TrxR1 function in relation to cellular redox state and cell death induction.

Survival and recurrent strokes in patients with different subtypes of stroke: a fourteen-year follow-up study.

In this study, 339 patients (154 men, 185 women) with a median age of 74 years (range 23-97) admitted to the Stroke Unit, Department of Neurology in 1986, have been followed up for 14 years. The diagnoses were intracerebral hemorrhage (ICH; 30, 8.8%), cardioembolic cerebral infarction (CE, 71, 20.9%), lacunar infarction (LI; 47, 13.9%) and atherosclerotic cerebral infarction (ACI; 191, 56.3%). The cumulative probabilities of recurrent stroke rates at 1-, 5- and 10-year follow-ups were 13.5% (95% confidence interval, CI, 9.6-17.4), 38.7% (95% CI 32.6-44.8) and 53.9% (95% CI 46.7-61.1). According to Cox proportional hazard regression analysis, age, severity of stroke, previous stroke and systolic blood pressure are each of importance in predicting recurrent stroke. During the observation period, 290 patients (85.5%) died. The mortality rate of 24.5% during the first year was 4.5 times higher compared to the normal population of the same age and gender. Patients with LI had lower mortality rates compared to ICH by the log rank test (p = 0.0275); to CE (p = 0.000) and to ACI (p = 0.049). Thirty-nine percent of all vascular deaths after the first year were caused by recurrent strokes. Fatal index/recurrent stroke occurred statistically more frequently in the CE group versus the non-CE one (p = 0.005). Cox proportional hazard regression analysis indicated that age, severity of stroke, previous stroke, heart failure and fasting blood glucose exceeding 6 mmol/l or history of diabetes were each predictors of mortality. In conclusion, this study has shown the worse outcomes for all subtypes of stroke compared to the normal population and also clearly pointed out independent predictors of recurrent stroke or death at the time of diagnosis.

[Binswanger disease. A blood pressure-related dementia]. / Binswangers sjukdom. En blodtrycks-relaterad demens.

Interest in Binswanger's disease has increased during the past decade, owing to the possibility of detecting white matter changes with computerised and magnetic resonance tomography. This paper consists in a summary of clinical symptoms and signs and possible diagnostic criteria, discussion of differential diagnosis, and the presentation of two own cases. Both patients manifested mild dementia and gait disturbance, and one had frequent drop attacks. Severe supra- and infra-tentorial white matter changes were present in both cases. It is important to consider a possible diagnosis of Binswanger's disease, as treatment of the appropriate risk factors may prevent or delay the development of dementia.

Comparison between a new computerized and an analogue videophotometric, cross-correlation technique for measuring skin capillary blood cell velocity in humans.

The capillary blood cell velocity (CBV) was measured using two different cross-correlation systems. Cross-correlation was performed by (1) a self-tracking, analogue cross-correlation technique and (2) by a new fully computerized system. The CBV was measured at rest and during venous occlusion and postocclusive reactive hyperemia (PRH) after 1-min arterial occlusion. The PRH response was described by determining the peak CBV. The correlations between the values obtained by the two systems were highly significant. CBV at rest: r = 0.97 (p < 0.001); CBV during venous occlusion: r = 0.97 (p < 0.001), peak CBV during PRH: r = 0.97 (p < 0.001). The stability of measurements with the computerized system was high. Only 0.08% of CBV variations was due to repeated measurements. This computerized system represents a reliable innovation which greatly facilitates CBV measurements, especially in clinical practice. The program includes automatic calculation of data (mean and maximum and minimum CBV, area under the curve, and integral, etc.).

Differences in the outcome of patients with TIA versus minor stroke.

In the Swedish aspirin low dose trial (SALT) 101 patients were enrolled from the Department of Medicine, Falun. 42 patients had experienced TIA/amaurosis fugax, whereas 59 patients had suffered a minor stroke/retinal infarction. History of hypertension treated or known untreated occurred statistically more frequently in the minor stroke group at randomisation (P less than 0.01) and the mean diastolic blood pressure (DBP) was higher in the minor stroke group during the observation time (P less than 0.05; ANOVA). The minor stroke group had less favourable outcomes according to survival curves (stroke or death) during a mean observation time of 34 months in each group (P less than 0.05 at 29 months). The findings of the present trial suggest that hypertension and the higher mean DBP during the observation time might explain the better outcome of end points of stroke or death in patients with TIA.

Enteric-coated acetylsalicylic acid plus dipyridamole compared with anticoagulants in the prevention of ischemic events in patients with transient ischemic attacks.

From December 1976 through March 1982, 188 patients entered an open non-random study carried out on hospitalized patients with a history of transient ischemic attacks or amaurosis fugax. Ninety-two patients received peroral anticoagulants usually combined with heparin treatment during the first days of treatment, and 96 patients enteric-coated acetylsalicylic acid 0,5 g twice daily plus dipyridamole 75 mg twice daily. The patients were followed up to March 1983, irrespective of whether treatment was changed or not. Recurrent transient ischemic attack or amaurosis fugax occurred more frequently (P less than 0.01) from 2 months of follow-up and throughout the observation period in the antiplatelet-treated group. There were no statistically significant differences between the 2 groups on the originally given treatment for endpoints such as stroke (6 patients on anticoagulants, 12 patients on antiplatelet therapy) or stroke or death (11 patients on anticoagulants, 17 patients on antiplatelet therapy). The findings from this trial suggest that anticoagulant treatment is superior to antiplatelet therapy given in the prevention of ischemic attacks and that this difference mainly exists during the first one to 2 months after onset of transient ischemic attacks or amaurosis fugax.

Evaluation of anticoagulants in patients with cerebral infarction with slight to moderate neurological deficit.

In a non-randomized controlled study carried out on 238 hospitalized patients with cerebral infarction, anticoagulant treatment (AC) was compared with the natural course in the prevention of transient ischemic attacks (TIA), cerebral infarction, stroke, stroke or death. 137 patients were allocated to AC, mean follow-up 30.5 months, and 101 patients were allocated to the controls (untreated group), mean follow-up 25.2 months. There were no statistically significant differences among the patients in the group who had suffered TIA (AC treated group 10.2%, untreated group 5.9%), cerebral infarction (AC treated group 10.2%, untreated group 11.9%), stroke (AC treated group 14.6%, untreated group 12.9%), stroke or death (AC treated group 22.6%, untreated group 19.8%). Minor bleedings occurred significantly more frequently (P less than 0.01) in the treated group. Severe bleedings occurred in 8 patients in the treated group (5.8%) compared to 1 of the controls (1%). It is concluded from the trial that AC can only seldom be recommended as prophylactic against new strokes in patients with cerebral infarction due to arterial thromboembolism.

Cimetidine, but not oxmetidine, penetrates into the cerebrospinal fluid after a single intravenous dose.

1 Thirty-six patients with various neurological diseases or symptoms received single intravenous doses of either cimetidine 400 mg (n = 19) or oxmetidine 200 mg (n = 17), 15 or 60 min before a diagnostic lumbar puncture. 2 In the 15 min CSF samples concentrations of cimetidine were detectable but not measurable in 5 and non-detectable in 3 patients. 3 In the 60 min CSF samples the concentrations of cimetidine were detectable in all 11 patients and were measurable in 8 of these patients with a mean +/- s.e. mean of 0.12 +/- 0.01 microgram/ml. These CSF concentrations were correlated to simultaneously measured plasma concentrations (P less than 0.01). The mean ratio CSF/plasma concentration was 0.03. 4 No detectable concentrations of oxmetidine were found either in the 15 min (n = 9) or in the 60 min (n = 8) liquor samples. 5 Cimetidine penetrates the blood-drain barrier slowly and not freely after a single dose. Our data suggest that the new histamine H2-receptor antagonist oxmetidine does not cross this barrier.

Results from 88 consecutive prophylactic carotid endarterectomies in cerebral infarction and transitory ischemic attacks.

Thirty-two patients with transitory ischemic attacks (TIA), 55 with cerebral infarction (minor stroke) and one with a disturbing bruise underwent carotid endarterectomy during a 4 year period. Within the first 2 weeks postoperatively, 10 patients (11%) had developed new neurological symptoms from the operated side. Two patients died postoperatively due to major stroke and 2 patients developed persistent neurological deficits, yielding a total operative mortality and permanent morbidity rate of 4.5%. In the other 6 patients, the neurological signs and symptoms disappeared completely within one month. During a follow-up for an average of 21 months, the only symptoms from the operated side were TIA in 2 patients, while 3 patients developed TIA and 5 infarctions from other vascular territories.

Comparison between directional Doppler and angiography in the diagnosis of internal carotid artery disease.

Directional Doppler examination (DD) with flow registration over the supraorbital and supratrochlear arteries and over the carotid artery in the neck was adopted to 99 carotid arteries in 56 patients without previous knowledge of angiography results, and thereafter DD and angiography findings were compared. On subgrouping of the angiography results into internal carotid artery (ICA) stenosis less than 50%, greater than 50%, and occlusion, a correct diagnosis was obtained by DD on 90 vessels (91%). All 11 ICA occlusions were correctly diagnosed by DD. The incorrect results obtained with DD were as follows: Four ICA stenosis less than 50% were classified as stenosis greater than 50%; four stenosis greater than 50% were classified as less than 50%; one stenosis greater than 50% was classified as occlusion. DD is a useful noninvasive screening method for the detection of occlusion and greater than 50% stenosis of ICA.