Sex differences in quality of life after stroke were explained by patient factors, not clinical care: evidence from the Australian Stroke Clinical Registry.

BACKGROUND AND PURPOSE: Women may receive stroke care less often than men. We examined the contribution of clinical care on sex differences and health-related quality of life (HRQoL) after stroke. METHODS: We included first-ever strokes registered in the Australian Stroke Clinical Registry (2010-2014) with HRQoL assessed between 90 and 180 days after onset (EQ-5D-3L instrument) that were linked to hospital administrative data (up to 2013). Study factors included sociodemographics, comorbidities, walking ability on admission (stroke severity proxy) and clinical care (e.g. stroke unit care). Responses to the EQ-5D-3L were transformed into a total utility value (-0.516 'worse than death' to 1 'best' health). Quantile regression models, adjusted for confounding factors, were used to determine median differences (MD) in utility scores by sex. RESULTS: Approximately 60% (6852/11 418) of stroke survivors had an EQ-5D-3L assessment (median 139 days; 44% female). Compared with men, women were older (median age 77.1 years vs. men 71.2 years) and fewer could walk on admission (37.9% vs. men 46.1%, P < 0.001). Women had lower utility values than men, and the difference was explained by age and stroke severity, but not clinical care [MDadjusted = -0.039, 95% confidence interval: -0.056, -0.021]. Poorer HRQoL was observed in younger men (aged <65 years), particularly those with more comorbidities, and in older women (aged ≥75 years). CONCLUSIONS: Stroke severity and comorbidities contribute to the poorer HRQoL in young men and older women. Further studies are needed to understand age-sex interaction to better inform treatments for different subgroups and ensure evidence-based treatments to reduce the severity of stroke are prioritized.

The dispersion-brightness relation for fast radio bursts from a wide-field survey.

Despite considerable efforts over the past decade, only 34 fast radio bursts-intense bursts of radio emission from beyond our Galaxy-have been reported1,2. Attempts to understand the population as a whole have been hindered by the highly heterogeneous nature of the searches, which have been conducted with telescopes of different sensitivities, at a range of radio frequencies, and in environments corrupted by different levels of radio-frequency interference from human activity. Searches have been further complicated by uncertain burst positions and brightnesses-a consequence of the transient nature of the sources and the poor angular resolution of the detecting instruments. The discovery of repeating bursts from one source3, and its subsequent localization4 to a dwarf galaxy at a distance of 3.7 billion light years, confirmed that the population of fast radio bursts is located at cosmological distances. However, the nature of the emission remains elusive. Here we report a well controlled, wide-field radio survey for these bursts. We found 20, none of which repeated during follow-up observations between 185-1,097 hours after the initial detections. The sample includes both the nearest and the most energetic bursts detected so far. The survey demonstrates that there is a relationship between burst dispersion and brightness and that the high-fluence bursts are the nearby analogues of the more distant events found in higher-sensitivity, narrower-field surveys5.

Aspectos clínicos e histológicos da demodicose canina localizada e generalizada / Clinical and histological aspects of localized and generalized canine demodicosis

Demodicose é uma afecção cutânea causada pelo ácaro Demodex sp. diagnosticada com frequência na rotina clínica veterinária. Objetivou-se descrever as manifestações clínicas e histológicas de cães com demodicose nas formas localizada e generalizada, relacionando a quantidade de ácaros e os achados microscópicos ao quadro clínico. Foram estudados 46 cães, sendo 28 com demodicose generalizada e 18 com a forma localizada da doença, dos quais todos possuíam raspados de pele positivo. Destes caninos foram anotados dados de lesões macroscópicas em ficha dermatológica e coletaram-se amostras de pele para estudo microscópico. A análise histológica foi realizada por três avaliadores e os dados registrados sem comunicação entre os mesmos, sendo considerado o resultado que mais ocorreu. Alopecia, descamação, eritema e crostas foram lesões clínicas comuns às duas formas de apresentação da doença que mais ocorreram. Inflamação histológica dermal grave ocorreu especialmente nos cães com doença localizada e generalizada que possuíam piodermite concomitante e ácaros Demodex sp. foram visualizados com intensidade entre moderada e acentuada na maioria dos cães com ambas as formas da enfermidade. Perifoliculite foi a alteração folicular microscópica mais evidenciada nos caninos deste estudo, seguida por foliculite mural e furunculose que tiveram maior ocorrência relativa nos cães com demodicose localizada. De acordo com os resultados obtidos verificou-se que a gravidade das lesões histológicas não corresponde necessariamente à forma de apresentação clínica da enfermidade, além disso, a quantidade de ácaros não demonstrou ser indicativa de lesões clínicas localizadas ou generalizadas, bem como não é possível diferenciar a doença clínica através do exame histopatológico.(AU)

Demodicosis is a skin condition caused by Demodex mite, frequently diagnosed in clinical routine. The purpose of this study was to compare the clinical and histological manifestations of localized and generalized demodicosis in dogs, relating the amount of mites and microscopic lesions. The study group was formed by 46 dogs, 28 with generalized demodicosis, and 18 with the localized form of the disease, all of them with positive skin scrapings. Macroscopic lesions data in dermatological form were noted, and skin samples were collected for microscopic study. The histopathological analysis was individually performed by three reviewers without intercommunication, being considered the result that more occurred. Alopecia, scaling, erythema, and crusting were the most common clinical lesions in both forms of the disease. Histological severe dermatitis occurred especially in dogs with localized and generalized disease that had concomitant pyoderma and Demodex sp. mites were visualized with intensity moderate and severe in the most dogs with both forms of the diseases. Perifolliculitis was the most evident microscopic follicular change in this study, followed by folliculitis and furunculosis wall, which had higher relative occurrence in dogs with localized demodicosis. According to the results obtained, the severity of histologic lesions does not necessarily correspond to the clinical presentation of the disease, in addition to the amount of mites that apparently is not indicative of localized or generalized clinical lesions, and cannot differentiate clinical disease by histopathology.(AU)

Encapsulation of nor-ß-lapachone into poly(d,l)-lactide-co-glycolide (PLGA) microcapsules: full characterization, computational details and cytotoxic activity against human cancer cell lines.

In this work, we characterize nor-ß-lapachone-loaded (NßL-loaded) microcapsules prepared using an emulsification/solvent extraction technique. Features such as surface morphology, particle size distribution, zeta potential, optical absorption, Raman and Fourier transform infrared spectra, thermal analysis data, drug encapsulation efficiency, drug release kinetics and in vitro cytotoxicity were studied. Spherical microcapsules with a size of 1.03 ± 0.46 µm were produced with an encapsulation efficiency of approximately 19%. Quantum DFT calculations were also performed to estimate typical interaction energies between a single nor-ß-lapachone molecule and the surface of the microparticles. The NßL-loaded PLGA microcapsules exhibited a pronounced initial burst release. After the in vitro treatment with NßL-loaded microcapsules, a clear phagocytosis of the spheres was observed in a few minutes. The cytotoxic activity against a set of cancer cell lines was investigated.

Controlled Release of Nor-ß-lapachone by PLGA Microparticles: A Strategy for Improving Cytotoxicity against Prostate Cancer Cells.

Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-ß-lapachone (NßL) in poly(d,l-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03 ± 0.46 µm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NßL on PLGA. Finally, the cytotoxic activity of NßL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug.

Advances in x-ray framing cameras at the National Ignition Facility to improve quantitative precision in x-ray imaging.

We describe an experimental method to measure the gate profile of an x-ray framing camera and to determine several important functional parameters: relative gain (between strips), relative gain droop (within each strip), gate propagation velocity, gate width, and actual inter-strip timing. Several of these parameters cannot be measured accurately by any other technique. This method is then used to document cross talk-induced gain variations and artifacts created by radiation that arrives before the framing camera is actively amplifying x-rays. Electromagnetic cross talk can cause relative gains to vary significantly as inter-strip timing is varied. This imposes a stringent requirement for gain calibration. If radiation arrives before a framing camera is triggered, it can cause an artifact that manifests as a high-intensity, spatially varying background signal. We have developed a device that can be added to the framing camera head to prevent these artifacts.

Higher mortality in patients with right hemispheric intracerebral haemorrhage: INTERACT1 and 2.

BACKGROUND AND PURPOSE: Controversy exists over the prognostic significance of the affected hemisphere in stroke. We aimed to determine the relationship between laterality of acute intracerebral haemorrhage (ICH) and poor clinical outcomes. METHODS: A subsidiary analysis of the INTERACT Pilot and INTERACT2 studies--randomised controlled trials of patients with spontaneous acute ICH with elevated systolic blood pressure (BP), randomly assigned to intensive (target systolic BP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Outcomes were the combined and separate end points of death and major disability (modified Rankin scale (mRS) scores of 3-6, 6 and 3-5, respectively) at 90 days. RESULTS: A total of 2708 patients had supratentorial/hemispheric ICH and information on mRS at 90 days. Patients with right hemispheric ICH (1327, 49%) had a higher risk of death at 90 days compared to those with left hemispheric ICH after adjustment for potential confounding variables (OR, 1.77 (95% CI 1.33 to 2.37)). There were no differences between patients with right and left hemispheric ICH regarding the combined end point of death or major disability or major disability in the multivariable-adjusted models (1.07 (0.89 to 1.29) and 0.85 (0.72 to 1.01), respectively). CONCLUSIONS: Right hemispheric lesion was associated with increased risk of death in patients with acute ICH. The laterality of the ICH does not appear to affect the level of disability in survivors. TRIAL REGISTRATION NUMBER: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079.

Stroke service: how can we improve and measure outcomes? Consensus summary from a global stroke forum.

The success of acute stroke treatment is first and foremost time-dependent, and the need for improvement in acute stroke management is demonstrated by the fact that only a minority of patients gain access to treatment - in particular, intravenous recombinant tissue plasminogen activator (IV tPA) - within the necessary time window. Standards of acute stroke care vary widely both regionally and nationally; consequently, various healthcare organizations have undertaken initiatives to measure and improve quality of care. To date, most quality measures have been process-based, focusing primarily on metrics of patient care in the acute hospital-based setting (e.g., time to recombinant tPA administration). Therefore, there remains a need for metrics designed to assess how improvements in process translate into patient outcomes. A global forum was convened to share best practice and provide consensus recommendations on core metrics for measuring improvements in access to care and patient outcomes. Recommendations for core metrics of patient outcomes include hospital-based outcomes (e.g., neurological status at 24 h, ambulatory status at discharge) and post-discharge outcomes (e.g., modified Rankin Scale score at 30 and/or 90 days). Recommendations for best practice relating to aspects of people, process, and technology involved in the stroke treatment pathway that may help provide improvements in these core outcome measures are also outlined.

Prevalence and risk factors for Equine Infectious Anemia in Poconé municipality, northern Brazilian Pantanal.

Serum samples collected from 547 equids in the Pantanal region of Brazil were evaluated for antibodies to Equine Infectious Anemia Virus (EIAV) by the agar gel immunodiffusion test. Risk factors associated with EIAV seropositivity were evaluated and spatial dependence investigated using a Spatial Lag Model. EIAV prevalence on farms in the Pantanal was 52.0% (13/25) with adjusted prevalence between equids of 31.5% (17.4-48.8% 95% CI). Intra-herd prevalence ranged from 5.0 to 77.0%. Statistical analysis demonstrated that farms and animals in regularly flooded areas had respectively 60 and 146 fold higher chance to be sero-positive than farms and animals located in non-flooded areas. Spatial Lag Model results were generally consistent with this conclusion although there was a negative spatial correlation between farms located within in regularly inundated regions, suggesting that other factors, such as management practices, probably play a significant role in transmission of EIAV. Equids with clinical signs were 3.74-fold more likely to be sero-positive than those without clinical signs. The results of this work reveal a high prevalence of EIAV in the Pantanal area of Brazil demonstrating that equids reared in this region are at great risk of infection.

Carotid endarterectomy for symptomatic, but "haemodynamically insignificant" carotid stenosis.

OBJECTIVE: Carotid endarterectomy (CEA) guidelines in symptomatic carotid stenosis are based on NASCET and ECST criteria with 70% or greater carotid stenosis as estimated from a catheter angiogram the major indication. This has several problems: (1) lack of reliable correlation between non-invasive imaging and catheter angiography, which has been largely superseded by non-invasive imaging in investigating carotid stenosis; (2) errors inherent in estimating the degree of stenosis from catheter angiography; (3) disregard for the fact that stroke risk also depends on plaque stability, and number of ischaemic events. METHODS: A retrospective review of ischaemic events, imaging results, operative findings, surgical complications and stroke-free follow-up in 31 patients presenting over a 23 year period with TIA/stroke (symptoms lasting > 24 h and/or imaging evidence of infarction) who had 70% or less carotid stenosis (on non-invasive imaging), but nonetheless underwent CEA. RESULTS: Nineteen patients had small strokes, 7 had TIAs and 5 had ocular events; 28 patients had features of unstable plaque on imaging; 19 patients experienced multiple events before CEA. All had haemorrhagic, ruptured plaque at CEA. One patient suffered an intra-operative stroke, only 1 patient suffered a further stroke/TIA (mean follow-up 4.2 years). CONCLUSION: To predict the likelihood of major stroke in symptomatic carotid stenosis and the benefit of CEA, plaque stability and the number of ischaemic events might be as important as an estimate of the degree of stenosis.

Significance of perihematomal edema in acute intracerebral hemorrhage: the INTERACT trial.

BACKGROUND: Uncertainty surrounds the effects of cerebral edema on outcomes in intracerebral hemorrhage (ICH). METHODS: We used data from the INTERACT trial to determine the predictors and prognostic significance of "perihematomal" edema over 72 hours after ICH. INTERACT included 404 patients with CT-confirmed ICH and elevated systolic blood pressure (BP) (150-220 mm Hg) who had the capacity to commence BP lowering treatment within 6 hours of ICH. Baseline and repeat CT (24 and 72 hours) were performed using standardized techniques, with digital images analyzed centrally. Predictors of growth in edema were determined using generalized estimating equations, and its effects on clinical outcomes were estimated using a logistic regression model. RESULTS: Overall, 270 patients had 3 sequential CT scans available for analyses. At baseline, there was a highly significant correlation between hematoma and perihematomal edema volumes (r(2) = 0.45). Lower systolic BP and baseline hematoma volume were independently associated with absolute increase in perihematomal edema volume. History of hypertension, baseline hematoma volume, and earlier time from onset to CT were independently associated with relative increase in edema volume. Both absolute and relative increases in perihematomal edema growth were significantly associated with death or dependency at 90 days after adjustment for age, gender, and randomized treatment, but not when additionally adjusted for baseline hematoma volume. CONCLUSIONS: The degree of, and growth in, perihematomal edema are strongly related to the size of the underlying hematoma of acute intracerebral hemorrhage, and do not appear to have a major independent effect in determining the outcome from this condition.

Psychosocial impact of screening for intracranial aneurysms in relatives with familial subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: In families with > or =2 relatives with intracranial aneurysms (IAs), screening for IAs in asymptomatic first-degree relatives is often recommended. We assessed the long-term psychosocial impact of such screening. METHODS: We identified all persons with IA (screen-positives) and matched them for age and sex with 2 controls without IA (screen-negatives) from hospital-based registers of familial IA. Persons underwent telephone interviews using questionnaires that covered the areas of psychosocial impact of screening, health-related quality of life (HRQoL), and mood. Data were compared between screen-positives and screen-negatives, and with reference populations. RESULTS: Overall, 105 persons from 33 families with IA were included, of whom 35 were screen-positive and 70 were screen-negative. Of the screen-positives, 12 (44%) had reduced their work and 23 (66%) had experienced changes in > or =1 area of independence, self-esteem, future outlook, or personal relationships. In contrast, only 1 (2%) screen-negative person had stopped working and 12 (17%) others had experienced changes in their self-esteem, future outlook, or relationships. Screen-positives had lower HRQoL compared with screen-negatives and the reference population, whereas both screen groups had higher mean depression scores than the reference population. Despite these effects, only 3 persons regretted participating in screening. CONCLUSIONS: Although screening for IA is an important preventative strategy in high-risk individuals, it is associated with considerable psychosocial effects, both positive and negative. Greater awareness of such outcomes, and appropriate intervention where necessary, would appear to be a necessary component of IA screening programs.

Interventions for treating depression after stroke.

BACKGROUND: Depressive and anxiety disorders following stroke are often undiagnosed or inadequately treated. This may reflect difficulties with the diagnosis of abnormal mood among older people with stroke-related disability, but may also reflect uncertainty about the effectiveness of such therapies in this setting. OBJECTIVES: To determine whether pharmacological, psychological, or electroconvulsive treatment (ECT) of depression in patients with stroke can improve outcome. SEARCH STRATEGY: The Cochrane Stroke Group Trials Register (last searched June 2003). The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2002), MEDLINE (1966 to September 2002), EMBASE (1980 to September 2002), CINAHL (1982 to September 2002), PsychINFO (1967 to September 2002), Applied Science and Technology Plus (1986 to September 2002), Arts and Humanities Index (1991 to September 2002), Biological Abstracts (1969 to September 2002), General Science Plus (1994 to September 2002), Science Citation Index (1992 to September 2002), Social Sciences Citation Index (1991 to September 2002), and Sociofile (1974 to September 2002). Reference lists from relevant articles and textbooks were searched, and authors of known studies and pharmaceutical companies who manufacture psychotropic medications were contacted. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing different types of pharmaceutical agents with placebo, or various forms of psychotherapy with standard care (or attention control), in patients with recent, clinically diagnosed, acute stroke, where treatment was explicitly intended of treat depression. DATA COLLECTION AND ANALYSIS: Primary analyses focussed on the prevalence of diagnosable depressive disorder at the end of treatment. Secondary outcomes included depression or mood scores on standard scales, disability or physical function, death, recurrent stroke, and adverse effects. We did not pool the data for summary scores. We performed meta-analysis for only some binary endpoints and data on adverse events. MAIN RESULTS: Nine trials, with 780 participants, were included in the review. Data were available for seven trials of pharmaceutical agents, and two trials of psychotherapy. There were no trials of ECT. The analyses were complicated by the lack of standardised diagnostic and outcome criteria, and differing analytic methods. There was no strong evidence of benefit of either pharmacotherapy or psychotherapy in terms of a complete remission of depression following stroke. There was evidence of a reduction (improvement) in scores on depression rating scales, and an increase in the proportion of participants with anxiety at the end of follow up. REVIEWERS' CONCLUSIONS: This review found no evidence to support the routine use of pharmacotherapeutic or psychotherapeutic treatment for depression after stroke. More research is required before recommendations can be made about the most appropriate management of depression following stroke.

Interventions for preventing depression after stroke.

BACKGROUND: Abnormal mood is an important consequence of stroke and may affect recovery and outcome. However, depression and anxiety are often not detected or inadequately treated. This may in part be due to doubts about whether anti-depressant treatments commenced early after the onset of stroke will prevent depression and improve outcome. OBJECTIVES: To determine if pharmaceutical or psychological interventions can prevent the onset of depression, including depressive illness and abnormal mood, and improve physical and psychological outcomes, in patients with stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (June 2003). In addition we searched the following electronic databases: Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2002), MEDLINE (1966 to September 2002), EMBASE (1980 to September 2002), CINAHL (1982 to September 2002), PsychINFO (1967 to September 2002), Applied Science and Technology Plus (1986 to September 2002), Arts and Humanities Index (1991 to September 2002), Biological Abstracts (1969 to September 2002), General Science Plus (1994 to September 2002), Science Citation Index (1992 to September 2002), Social Sciences Citation Index (1991 to September 2002), and Sociofile (1974 to September 2002). Reference lists from relevant articles and textbooks were searched, and authors of known studies and pharmaceutical companies who manufacture psychotropic medications were contacted. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing different types of pharmaceutical agents (eg selective serotonin reuptake inhibitors) with placebo, or various forms of psychotherapy against standard care (or attention control), in patients with a recent clinical diagnosis of stroke, where the treatment was undertaken with the explicit intention of preventing depression. DATA COLLECTION AND ANALYSIS: The primary analyses focussed on the proportion of patients who met the standard diagnostic criteria for depression applied in the trials at the end of follow-up. Secondary outcomes included depression or mood scores on standard scales, disability or physical function, death, recurrent stroke, and adverse effects. MAIN RESULTS: Twelve trials involving 1245 participants were included in the review. Data were available for nine trials (11 comparisons) involving different pharmaceutical agents, and three trials of psychotherapy. The time from stroke onset to entry ranged from a few hours to six months, but most patients were recruited within one month of acute stroke. The duration of treatments ranged from two weeks to one year. There was no clear effect of pharmacological therapy on the prevention of depression or on other measures. A significant improvement in mood was evident for psychotherapy, but this treatment effect was small and from a single trial. There was no effect on diagnosed depression. REVIEWERS' CONCLUSIONS: This review identified a small but significant effect of psychotherapy on improving mood, but no effect of either pharmacotherapy or psychotherapy on the prevention of depressive illness, disability, or other outcomes. More evidence is therefore required before any recommendations can be made about the routine use of such treatments to improve recovery after stroke.

Pharmaceutical interventions for emotionalism after stroke.

BACKGROUND: Antidepressants may be useful in the treatment of abnormal crying associated with stroke. OBJECTIVES: To determine whether pharmaceutical treatment reduces the frequency of emotional displays in people who suffer from emotionalism after stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched June 2003). In addition we searched the following electronic databases: Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3 2002), MEDLINE (1966 to September 2002), EMBASE (1980 to September 2002), CINAHL (1982 to September 2002), PsychINFO (1967 to September 2002), Applied Science and Technology Plus (1986 to September 2002), Arts and Humanities Index (1991 to September 2002), Biological Abstracts (1969 to September 2002), General Science Plus (1994 to September 2002), Science Citation Index (1992 to September 2002), Social Sciences Citation Index (1991 to September 2002), and Sociofile (1974 to September 2002). We searched reference lists from relevant articles and textbooks, and contacted authors of known studies and pharmaceutical companies who manufacture psychotropic medications. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials, comparing psychotropic medication to placebo, in people with stroke and emotionalism (also known as emotional lability or pathological crying and laughing). DATA COLLECTION AND ANALYSIS: Data were obtained on people who no longer met criteria for emotionalism, as defined in studies, and on reduction in frequency of crying at the end of treatment. Data were not pooled because of the multiplicity of definitions and outcome measures. MAIN RESULTS: Five trials involving 103 participants were included. Four trials showed large effects of treatment: 50% reduction in emotionalism, improvements (reduction) in the frequency of compulsive laughter, and lower (better) scores on the Pathological Laughter and Crying scale. The confidence intervals were wide, however, indicating that treatment may have had only a small positive effect, or even a small negative effect (in one trial). Subgroup analysis was not performed due to the multiple methods of assessment of emotionalism within and between trials. Only one study systematically recorded and reported adverse events; no discernible difference was seen between groups. Participants allocated active treatment were more likely to leave early from trials. REVIEWERS' CONCLUSIONS: Antidepressants can reduce the frequency and severity of crying or laughing episodes. The effect do not seem specific to one drug or class of drugs. However, our conclusions must be qualified by several methodological deficiencies in the studies. More reliable data are required before recommendations can be made about the treatment of post-stroke emotionalism.

Thyrotoxicosis after complete or partial lithium withdrawal in two patients with bipolar affective disorder.

OBJECTIVES: To highlight and discuss thyrotoxicosis after lithium withdrawal as a potential complication of lithium therapy for bipolar disorder. CASE REPORTS: Both patients presented developed thyrotoxicosis, the first patient after stopping the lithium completely, and the second patient after a reduction in the lithium dose. CONCLUSIONS: Clinicians should be alert to the possibility of thyrotoxicosis emerging when lithium is being completely or partially withdrawn. Such withdrawal could unmask a latent hyperthyroidism.

Subarachnoid haemorrhage occurrence exhibits a temporal pattern - evidence from meta-analysis.

The aim of the present meta-analysis was to determine a temporal pattern of occurrence of subarachnoid haemorrhage (SAH). A MEDLINE 1966-2001 and EMBASE (1980-2001) literature search and hand search of relevant references were performed for population-based incidence studies that reported the time of SAH occurrence. Data from all identified relevant studies were combined into a pooled rate ratio (RR), with corresponding 95% confidence intervals (CI) using the Mantel-Haenszel method. Overall, eight population-based studies were included in the analysis. A total of 2533 first-ever cases of SAH were reported in the studies identified. Risk of SAH occurrence was the highest in the period between 6 am and 12 am (RR = 3.19; 95% CI 3.03-3.36; early morning as a reference variable) and between 12 p.m. and 6 p.m. (RR = 2.63; 95% CI 2.47-2.80), in winter and spring (RR = 1.10; 95% CI: 1.02-1.17; and RR = 1.07; 95% CI: 1.01-1.13, respectively; summer as a reference variable) and on Sunday (RR = 1.22; 95% CI 1.09-1.37; Monday as a reference variable). The evidence suggests that occurrence of SAH exhibits a seasonal (winter and spring) peak, diurnal (late morning peak) and daily (Sunday peak) pattern. It is suggested that the occurrence of some major acute vascular events (total ischaemic strokes, intracerebral haemorrhage and myocardial infarction) may be influenced by common triggering factors.

Activation of sickle red blood cell adhesion via integrin-associated protein/CD47-induced signal transduction.

Peripheral human red blood cells (RBCs) are not generally known to become activated and adhesive in response to cell signaling. We show, however, that soluble thrombospondin via integrin-associated protein (IAP; CD47) increases the adhesiveness of sickle RBCs (SS RBCs) by activating signal transduction in the SS RBC. This stimulated adhesion requires occupancy of IAP and shear stress and is mediated by the activation of large G proteins and tyrosine kinases. Reticulocyte-enriched RBCs derived from sickle-cell disease (SCD) patients are most responsive to IAP-induced activation. These studies therefore establish peripheral SS RBCs as signaling cells that respond to a novel synergy between IAP-induced signal transduction and shear stress, suggesting new therapeutic targets in SCD.

Integrin-associated protein is an adhesion receptor on sickle red blood cells for immobilized thrombospondin.

The adhesive protein thrombospondin (TSP) potentially mediates sickle (SS) red blood cell (RBC) adhesion to the blood vessel wall, thereby contributing to vaso-occlusive crises in sickle cell disease. We previously reported that SS RBCs bind to immobilized TSP under flow conditions, whereas normal (AA) red cells do not. However, the SS RBC receptors that mediate this interaction are largely unknown. Here it is reported that integrin-associated protein (IAP), or CD47, mediates the adhesion of these cells to immobilized TSP under both flow and static conditions. A peptide derived from the C-terminal IAP binding site of TSP also supports sickle cell adhesion; adhesion to this peptide or to TSP is inhibited specifically by the anti-IAP monoclonal antibody, 1F7. Furthermore, these data suggest that IAP on SS RBCs is structurally different from that expressed on AA RBCs but that IAP expression levels do not vary between AA and SS RBCs. This structural difference may contribute to the enhanced adhesion of SS RBCs to immobilized TSP. These results identify IAP as a TSP receptor on SS RBCs and suggest that this receptor and its binding site within TSP represent potential therapeutic targets to decrease vaso-occlusion. (Blood. 2001;97:2159-2164)

Is there a temporal pattern in the occurrence of subarachnoid hemorrhage in the southern hemisphere? Pooled data from 3 large, population-based incidence studies in Australasia, 1981 to 1997.

BACKGROUND AND PURPOSE: Publications on the temporal pattern of the occurrence of subarachnoid hemorrhage (SAH) have produced conflicting results. Variations between studies may relate to the relatively small numbers of SAH cases analyzed, including those in meta-analyses. METHODS: We identified all cases of SAH from 3 well-designed population-based studies in Australia (Adelaide, Hobart, and Perth) and New Zealand (Auckland) during 3 periods between 1981 and 1997. The diagnosis of SAH was confirmed with CT, cerebral angiography, cerebrospinal fluid analysis, or autopsy in all cases. Information on the time of occurrence of each event was obtained. Risk ratios (RRs) and 95% CIs were calculated using Poisson regression, with age, sex, smoking status, and history of hypertension entered in the model as covariates. RESULTS: A total of 783 cases of SAH were registered. Age- and sex-adjusted RRs of SAH occurrence were highest in the period between 6 AM and 12 MIDNIGHT (RR 3.2, 95% CI 2.4-4.3) and in winter and spring (RR 1.3, 95% CI 1.1-1.5; RR 1.3, 95% CI 1.1-1.5; respectively). No particular pattern of SAH occurrence was observed according to the day of the week. Restriction of the analyses to proved aneurysmal SAH did not substantially change the point estimates. CONCLUSIONS: Circadian and circaseptan (weekly) fluctuations of SAH occurrence in the southern hemisphere are similar to those in the northern hemisphere, but the occurrence of SAH in Australasia exhibits clear seasonal (winter and spring) peaks.