Traumatic Cerebral Microbleeds in the Subacute Phase Are Practical and Early Predictors of Abnormality of the Normal-Appearing White Matter in the Chronic Phase

BACKGROUND AND PURPOSE:In the chronic phase after traumatic brain injury, DTI findings reflect WM integrity. DTI interpretation in the subacute phase is less straightforward. Microbleed evaluation with SWI is straightforward in both phases. We evaluated whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase.MATERIALS AND METHODS:Sixty of 211 consecutive patients 18 years of age or older admitted to our emergency department ≤24 hours after moderate to severe traumatic brain injury matched the selection criteria. Standardized 3T SWI, DTI, and T1WI were obtained 3 and 26 weeks after traumatic brain injury in 31 patients and 24 healthy volunteers. At baseline, microbleed concentrations were calculated. At follow-up, mean diffusivity (MD) was calculated in the normal-appearing WM in reference to the healthy volunteers (MD_z). Through linear regression, we evaluated the relation between microbleed concentration and MD_z in predefined structures.RESULTS:In the cerebral hemispheres, MD_z at follow-up was independently associated with the microbleed concentration at baseline (left: B = 38.4 [95% CI 7.5–69.3], P = .017; right: B = 26.3 [95% CI 5.7–47.0], P = .014). No such relation was demonstrated in the central brain. MD_z in the corpus callosum was independently associated with the microbleed concentration in the structures connected by WM tracts running through the corpus callosum (B = 20.0 [95% CI 24.8–75.2], P < .000). MD_z in the central brain was independently associated with the microbleed concentration in the cerebral hemispheres (B = 25.7 [95% CI 3.9–47.5], P = .023).CONCLUSIONS:SWI-assessed microbleeds in the subacute phase are associated with DTI-based WM integrity in the chronic phase. These associations are found both within regions and between functionally connected regions.

The yearly incidence of traumatic brain injury (TBI) is around 300 per 100,000 persons.^1,2 Almost three-quarters of patients with moderate to severe TBI have traumatic axonal injury (TAI).³ TAI is a major predictor of functional outcome,^4,5 but it is mostly invisible on CT and conventional MR imaging.^6,7DTI provides direct information on WM integrity and axonal injury.^5,8 However, DTI abnormalities are neither specific for TAI nor stable over time. Possibly because of the release of mass effect and edema and resorption of blood products, the effects of concomitant (non-TAI) injury on DTI are larger in the subacute than in the chronic phase (>3 months).^4,9,10 Therefore, DTI findings are expected to reflect TAI more specifically in the chronic than in the subacute phase (1 week–3 months).⁴ Even in regions without concomitant injury, the effects of TAI on DTI are dynamic, possibly caused by degeneration and neuroplastic changes.^6,11,12 These ongoing pathophysiological processes possibly contribute to the emerging evidence that DTI findings in the chronic phase are most closely associated with the eventual functional outcome.^12,13Although DTI provides valuable information, its acquisition, postprocessing, and interpretation in individual patients are demanding. SWI, with which microbleeds can be assessed with high sensitivity, is easier to interpret and implement in clinical practice. In contrast to DTI, SWI-detected traumatic microbleeds are more stable¹ except in the hyperacute^14,15 and the late chronic phases.¹⁶ Traumatic cerebral microbleeds are commonly interpreted as signs of TAI. However, the relation is not straightforward. On the one hand, nontraumatic microbleeds may be pre-existing. On the other hand, even if traumatic in origin, microbleeds represent traumatic vascular rather than axonal injury.¹⁷ Indeed, TAI is not invariably hemorrhagic.¹⁸ Additionally, microbleeds may secondarily develop after trauma through mechanisms unrelated to axonal injury, such as secondary ischemia.¹⁸DTI is not only affected by pathophysiological changes but also by susceptibility.¹⁹ The important susceptibility-effect generated by microbleeds renders the interpretation of DTI findings at the location of microbleeds complex. In the chronic phase, mean diffusivity (MD) is the most robust marker of WM integrity.^4,6 For these reasons, we evaluated MD in the normal-appearing WM.Much TAI research focuses on the corpus callosum because it is commonly involved in TAI^5,18,20 and it can reliably be evaluated with DTI,^5,21 and TAI in the corpus callosum is related to clinical prognosis.^6,20 The corpus callosum consists of densely packed WM tracts that structurally and functionally connect left- and right-sided brain structures.²² The integrity of the corpus callosum is associated with the integrity of the brain structures it connects.²³ Therefore, microbleeds in brain structures that are connected through the corpus callosum may affect callosal DTI findings. Analogous to this, microbleeds in the cerebral hemispheres, which exert their function through WM tracts traveling through the deep brain structures and brain stem,^24,25 may affect DTI findings in the WM of the latter.Our purpose was to evaluate whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase. We investigated this relation within the cerebral hemispheres and the central brain and between regions that are functionally connected by WM tracts.     

DEVELOPMENT OF INDICATORS TO MEASURE

This paper describes a study to capture the key roles and activities of nephrology nurses across different countries in Europe. The concept of the study and the need to clarify the activities of the nephrology nurse arose as part of a larger study to develop the European Practice Database (EPD) (1). The Research Board (EDTNA/ERCA) needed to identify key questions that would detect significant differences in the role and responsibilities of nephrology nurses in different countries and monitor the evolution over time of nephrology nursing practice in Europe. It was therefore appropriate to devise a separate small study to generate evidence based questions for the EPD and confirm the reliability and usefulness of the information captured.     

Estimated causes of death in Thailand, 2005: implications for health policy

Background  

Almost 400,000 deaths are registered each year in Thailand. Their value for public health policy and planning is greatly diminished by incomplete registration of deaths and by concerns about the quality of cause-of-death information. This arises from misclassification of specified causes of death, particularly in hospitals, as well as from extensive use of ill-defined and vague codes to attribute the underlying cause of death. Detailed investigations of a sample of deaths in and out of hospital were carried out to identify misclassification of causes and thus derive a best estimate of national mortality patterns by age, sex, and cause of death.     

神经生长因子对小鼠突触体内Ca^2＋水平的调节作用

观察了多次海马内微注射ＮＧＦ对小鼠突触体内游离钙水平的影响，并在离体情况下观察ＮＧＦ对ＥＧＴＡ和ＣａＣｌ２分别造成突触体内低钙和高钙状态的调节作用。结果如下：（１）在体实验表明，一定剂量的ＮＧＦ可显著降低老年小鼠海马突触体内游离钙水平（Ｐ＜００５）；（２）离体实验表明，当突触体游离钙水平降低时，适当剂量的ＮＧＦ具有升高游离钙水平的作用；而突触体内游离钙水平升高时，则ＮＧＦ有降低游离钙水平的作用。提示ＮＧＦ对游离钙水平的双向调节作用可能是ＮＧＦ改善老年性记忆衰退的作用机制。     

Total anorectal reconstruction with a double dynamic graciloplasty after abdominoperineal reconstruction for low rectal cancer

PURPOSE: Total anorectal reconstruction with a double dynamic graciloplasty was performed after abdominoperineal reconstruction (APR) for low rectal cancer. In four patients an additional pouch was constructed to improve neorectal motility and capacity. The aim of this study was to evaluate the results in the first 20 patients and to report on the preliminary results of patients with an additional pouch. METHODS: Twenty patients with a mean age of 52 (range, 25–71) years and a rectal tumor at a mean of 3 (range, 0–5) cm from the anal verge were treated. In 14 patients the Miles resection, colon pull-through, and construction of a neosphincter were performed in one session. Six patients had the double graciloplasty at an average of 4.1 (range, 1.1–8.8) years after APR. In four patients a pouch was constructed with an isolated segment of distal ileum. RESULTS: After a mean follow-up of 24 (range, 1–60) months after APR, none of the patients developed local recurrence, whereas four patients developed distant metastasis. Fifteen of 20 patients were available for evaluation, and 5 patients were still in training. Of these 15 patients, 8 patients were continent (53 percent), 2 patients were incontinent, and in 5 patients the perineal stoma was converted to an abdominal stoma. Failures were attributable to necrosis of the colon stump (n=2) and incontinence (n=3). At 26 weeks mean resting pressure was 44 (standard deviation (SD), 28) mmHg, and mean pressure during stimulation was 90 (SD, 46) mmHg at a mean of 35 (SD, 1.2) volts at 52 weeks. Mean defecation frequency was three times per day (range, 1–5). Of the eight patients who were continent, six used daily enemas. Mean time to postpone defecation was 11 (range, 0–30) minutes. CONCLUSION: In experienced hands, the double dynamic graciloplasty is an oncologically safe procedure that can have an acceptable functional outcome in a well-selected group of patients. However, to improve the outcome, further modifications will be necessary. So far, the addition of a pouch has not resulted in improved outcome. Supported by the Profileringsfonds of the Maastricht University Hospital, The Netherlands, and by the Stichting Fondsenwervingsactie Volksgezondheid, Amsterdam, The Netherlands. Read in part at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1995.     

Characterization of an immunologic polymorphism (D79H) in the heavy chain of factor V.

BACKGROUND: During the study of a family with hereditary factor (F)V deficiency (FV Amersfoort, 1102 A > T in exon 7) we identified an individual with 5% FV heavy chain antigen (FV(HC)) and 50% FV light chain antigen (FV(LC)). Further testing revealed that apart from the FV Amersfoort allele a second variant FV allele was segregating in this family, which encodes for a FV molecule with a reduced affinity for mAb V-23 used in the FV heavy chain ELISA (ELISA(HC)). OBJECTIVE: Identification and characterization of the molecular basis responsible for the reduced affinity of the variant FV for mAb V-23. METHODS: Family members of the proband were screened for mutations in the exons coding for the heavy chain of FV, after which the recombinant variant FV could be generated and characterized. Next, the cases and controls of the Leiden Thrombophilia Study (LETS) were genotyped for carriership of the variant FV. RESULTS: In the variant FV allele a polymorphism in exon 3 (409G > C) was identified, which predicts the replacement of aspartic acid 79 by histidin (D79H). Introduction of this mutation in recombinant FV confirmed that it reduces the affinity for binding to mAb V-23. The substitution has no effect on FV(a) stability and Xa-cofactor activity. In Caucasians the frequency of the FV-79H allele is approximately 5%. Analysis of the LETS revealed that the FV-79H allele is not associated with FV levels (FV(LC)), activated protein C sensitivity (using an activated partial thromboplastin time-based test) or risk of venous thrombosis (OR 1.07, CI 95: 0.7-1.7). CONCLUSION: The D79H substitution in FV should be considered as a neutral polymorphism. The monoclonal antibody V-23, which has a strongly reduced affinity for FV-79H, is not suitable for application in diagnostic tests.