The monoclonal antibody Alz-50, used to reveal cytoskeletal changes in Alzheimer's disease, also reacts with a large subpopulation of somatostatin neurons in the normal human hypothalamus and adjoining areas

The monoclonal antibody Alz-50 is directed against Alzheimer's disease-related modified tau proteins and reveals cytoskeletal changes, i.e. neurofibrillary tangles and dystrophic neurites. The present study shows that, in the hypothalamus of non-demented control subjects, this same antibody gives a distinctive staining pattern of a subpopulation of somatostatin neurons and beaded fibers. Furthermore, Alz-50 occasionally recognizes somatostatin-containing cell bodies and dystrophic neurite-like fibers in the (neuritic) senile plaques of AD patients. These observations have direct consequences for the interpretation of Alz-50 staining in diagnostic usage and for the assessment of Alzheimer's disease-like changes induced by β-amyloid in experimental animal brains. On dot spotting, Alz-50 was found to bind to a number of fragments from the somatostatin precursor, of which somatostatin_15–28 stained best. Preadsorption of Alz-50 by somatostatin_15–28, as well as other specificity tests, failed, however, to provide any clue to the nature of the unknown compound(s) stained in the control hypothalamus.     

Binswanger's disease in the absence of chronic arterial hypertension

Summary The cerebral changes are described in a woman of 54 who suffered from Binswanger's encephalopathy: there were no signs or symptoms of chronic arterial hypertension. The disease presented as dementia of about 3 years duration. Computed tomography of the brain 2. 5 years before her death showed bilateral widespread hypodense lesions in the cerebral white matter. She died of an asthmatic attack. Autopsy disclosed extensive bilateral degeneration of the central white matter, lacunes and gliosis. Severe obliterative arteriolosclerosis occurred in the meningeal vessels and those supplying the affected parts of the brain. Light microscopy showed that the most severe lesions occurred in the arterioles. Immunohistochemistry demonstrated profound extravasation of plasma proteins chiefly albumin, indicating dysfunction of the blood-brain barrier. Thus, the lesions characteristic of Binswanger's encephalopathy may develop in the absence of chronic arterial hypertension. Additional pathogenic factors, possibly genetic predisposition to vascular injury may play a role in the development of this condition.Supported by grants from the Swedish Medical Research Council, Project No 12X-03020 and 1987 Års Stiftelse för Strokeforskning     

Death certification and coding for ischaemic heart disease in Tasmania

Official records show that the rates of mortality from ischaemic heart disease (IHD) in Tasmania have been the highest of all the Australian states for most of the past decade. This study assesses the accuracy of the official Tasmanian mortality data for IHD in 1987 and 1988 for males aged 25 to 74 years using routinely available clinical and pathological data supplemented by information from the attending doctor. Our findings show that a death officially coded to ICD 9 rubrics 410–414 (IHD) in Tasmania has 94% sensitivity and a positive predictive value of 90% for fatal definite acute myocardial infarction or possible coronary death as defined by the WHO. Comparison of our results with those of two earlier studies undertaken in Australian mainland centres indicates that differences in the official statistics for coronary mortality between Tasmania and the mainland states reflect true differences in the risk of coronary death. While the results from three Australian studies suggest that the routine system of death certification is reasonably accurate, careful monitoring of death certification and coding practices need to be undertaken regularly in all states of Australia if secular changes in regional patterns of coronary mortality are to be regarded as credible. (Aust NZ J Med 1992; 22: 114–118.)     

高血糖导致肾脏高灌注的机制研究

探讨了高血糖对整体大鼠和离体灌注鼠肾（ＩＰＲＫ）血流动力学的影响及其机制。结果显示：高血糖在整体大鼠和ＩＰＲＫ均可引起肾血浆流量（ＲＰＦ）、肾小球滤过率（ＧＦＲ）的增加；在ＩＲＰＫ阻断管－球反馈后，高血糖不再能诱发上述改变；结构和葡萄糖相似的Ｄ－α－甲基－葡萄糖苷在ＩＰＲＫ可引起与相同渗透浓度的葡萄糖相似的ＲＰＦ，ＧＦＲ增加；血红蛋白不改变高血糖对肾血流动力学的影响。提示：高血糖可支接引起肾脏高灌注、高滤过，其机制主要是对管一球反馈的抑制，此抑制效应可能与葡萄糖的结构相关。内皮由来性舒张因子（ＥＤＲＦ）在高血糖导致的ＩＰＲＫ高灌注中不起主要作用。     

Organization of dopamine D1 and D2 receptors in human striatum: receptor autoradiographic studies in Huntington's disease and schizophrenia

The technique of quantitative autoradiography was used to examine the effects of Huntington's disease (HD) and schizophrenia on the organization of striatal dopamine (DA) D1 and D2 receptors. Whereas the striatum of HD cases showed a reduction in the density of D1 ([3H]SCH 23390) and D2 ([3H]spiroperidol) receptors, the patterning of D2 receptor loss did not match that of the D1 receptor loss. The HD loss of D1 D1 receptors (65%) is far greater than the loss of D2 receptors (28%). Whereas there was a dorsal-ventral gradient of effect on both receptor subtypes, the effects of HD on D2 receptors in the ventral putamen (PUT) and nucleus accumben septi (NAS) were minimal. Similarly, muscarinic M1 and M2 receptors demonstrate different patterns of alteration in HD. The M2 subtype, labeled with [3H]N-methylscopolamine (in the presence of excess pirenzepine to occlude M1 sites), was depleted far more than the M1 receptor subtype, labeled with [3H]pirenzepine. Although the effects of HD on [3H]mazindol labeling of DA terminals were more heterogeneous, there appeared to be a relative preservation of this afferent input to the striatum of the HD cases. In the schizophrenic cases, our autoradiographic studies confirm previous reports of an elevation of D2 receptor density in the striata of many schizophrenics. This increase was evident even though two of the three cases were known to have not been treated with neuroleptics, and the third case may also have been drug naive. However, the increase was far greater in the NAS (164%) and ventral PUT (173%) than more dorsally in the striatum (68%). The density of D1 receptors and DA terminals labeled with [3H]mazindol in the striatum of schizophrenics was not significantly different from that of control cases. Thus in both HD and schizophrenia, the ratio of D2/D1 receptors is altered in favor of the D2 population, particularly in the NAS.     

Lack of correlation between coronary artery calcium and myocardial perfusion imaging

BACKGROUND: Coronary artery calcium (CAC) provides evidence of coronary atherosclerosis and has significant prognostic power. Although prior studies have documented a relationship between CAC and hemodynamically significant coronary artery stenosis, the results have not been conclusive. METHODS AND RESULTS: We evaluated 126 consecutive patients who underwent electron beam computed tomography CAC scoring by use of the Agatston method and stress myocardial perfusion imaging (MPI) within 3 months of each other. The analysis revealed no correlation between absolute CAC score and age- and gender-adjusted CAC scores with MPI. Overall, 18% of patients had abnormal MPI results irrespective of their CAC. CONCLUSION: CAC scoring and stress MPI should be thus considered complementary approaches rather than exclusionary in the evaluation of the patient at risk for coronary artery disease.     

A Comparison of Depressive Symptoms in Stroke and Primary Care: Applying Rasch Models to Evaluate the Center for Epidemiologic Studies-Depression Scale

OBJECTIVES: Clinical trials and community-based studies often include the Center for Epidemiologic Studies-Depression scale (CES-D) as a measure of depression outcome. We compared responses to symptom-related items on the CES-D by depressed stroke and primary-care patients for several purposes: 1) to illustrate the use of Item Response Theory (IRT)-based (Rasch) models for comparing scale functioning across different patient subgroups; and 2) to inform clinicians and outcome researchers about scale functioning and depressive symptomatology in stroke- compared with primary care-based depression. METHODS: Two data sources were analyzed, including 32 depressed patients who were 3 months poststroke, and 366 depressed primary-care patients. Presence of depression was based on a CES-D score 16 or higher. Rasch models were used to assess item fit and compare item hierarchies between depressed primary-care and stroke patients. RESULTS: Item hierarchies were similar for poststroke depression and primary care-based depression. Interpersonal disruption items were the most difficult to endorse for both groups. No items misfit the scale in primary-care depression. Items relating to restless sleep, unfriendliness, and crying slightly misfit the scale in stroke patients, that is, may measure a different trait. Differential item functioning (DIF) between the groups was identified for items relating to appetite, restless sleep, crying, and feeling disliked. CONCLUSIONS: Results generally supported the use of the CES-D as measure of depression outcome, particularly in primary care-based depression. DIF may imply that slightly different clusters of depressive symptoms are reported by depressed stroke patients compared with primary care, but this is conjectural given the small stroke sample size and the same items have been previously associated with bias in studies of large nonstroke samples. This study found Rasch models to be useful tools to investigate scale performance for different clinical applications.     

慢性阻塞性肺疾病呼吸驱动影响因素分析

目的:探讨慢性阻塞性肺疾病(COPD)病人呼吸驱动与肺功能、血气及静息能量代谢之间的关系.方法:26例COPD和21例正常对照者分别测定口腔阻断压P0.1、呼吸肌功能[最大吸气压(PIMAX)、最大呼气压(P EMAX)]、肺通气功能[努力肺活量(FVC)、一秒率(FEV,%)]、残气(RV/TLC)、弥散功能(DLCO)、静息能量代谢(REE)、呼吸商(RQ)、血气分析及Borg分级等.结果:COPD组P0.1和P0.1/PIMAX高于对照组(P＜0.01).相关分析COPD组P0.1与PaO2、SaO2负相关(r分别为-0.62,-0.53,P均＜0.05),而与PaCO2相关性不明显.Borg分级与P0.1正相关(r=0.63,P＜0.05),P0.1与FVC、FEV1%、RV/TLC、DLCO以及RQ无相关性,P0.1/PIMAX与REE有正相关关系(r=0.41,P＜0.05).结论:COPD呼吸驱动增高,不仅与PaO2,SaO2相关,还与静息能量代谢及Borg分级等相关.     

Clinical and immunological effects of azithromycin in Behçet''s disease

Background: The aim of this study was to evaluate the effects of azithromycin on mucocutaneous manifestations, oral health and immune response in Behçet's disease (BD). Methods: Eight BD patients with active mucocutaneous symptoms were treated with azithromycin for 4 weeks. Oral health, clinical manifestations and in vitro interleukin (IL)‐12, interferon (IFN)‐γ, IL‐10 and monocyte chemotactic protein (MCP)‐1 responses were evaluated before and after treatment. Results: The number of folliculitic lesions, healing time of oral ulcers and scores of plaque indexes (PLIs) were lower after azithromycin treatment (P < 0.05). Scores of PLIs correlated positively with the healing time of oral ulcers (P = 0.02). Although a trend towards increased stimulated IL‐10 responses with azithromycin was observed, no statistically significant difference was found. Stimulated and unstimulated MCP‐1, IFN‐γ and IL‐12 responses were similar before and after treatment (P > 0.05). Conclusion: Azithromycin was observed to be effective in decreasing folliculitic lesions and fastening the healing time of oral ulcers in BD.     

Haemoglobin at time of referral prior to dialysis predicts survival: an association of haemoglobin with long-term outcomes

Haemoglobin (Hgb) levels are known to be associated with numerousadverse outcomes in both chronic kidney disease (CKD) and non-CKDpatients. This analysis evaluates the association of baseline haemoglobinlevels on survival in CKD patients, who are followed by nephrologists,irrespective of glomerular filtration rate (GFR), prior to initiationof renal replacement therapy (RRT) and erythropoietin hormonereplacement therapy. Analysis of data from the provincial database (PROMIS, PatientRegistration and Outcome Management Information System) in BritishColumbia, Canada, was undertaken. Records used for the analysisincluded all CKD patients at first registration: GFR <60ml/min/1.73 m², not yet on dialysis, starting from May 1998to October 2002, and who had complete data (defined as age andgender, diabetic status, eGFR and Hgb levels). The primary objective of this study was to determine the associationof Hgb and survival controlling for eGFR at first registrationvalue, age, gender and diabetic status. Multivariate Cox proportionalhazards analysis with time to death as outcome variable wasperformed. The cohort included 3028 patients: the mean age was 65 years,28% were diabetic, and the mean eGFR in the cohort was 21 ml/min/1.73m². The cohort is representative of the BC CKD and dialysispopulation regarding ethnicity: 64% Caucasian, 32% Asian. Medianfollow-up was 27 months, 1 year survival was 0.92, 2 year survivalwas 0.85. Hgb at initial registration is a statistically independentpredictor of survival (RR = 0.875 for every 10 g/l, 95% CI:0.835–0.917, P = 0.0001), after adjusting for age, gender,diabetic status and baseline eGFR. Further analysis, controllingfor RRT, demonstrated a similar association between Hgb andsurvival (RR = 0.853 for every 10 g/l, 95% CI: 0.799–0.910,P = 0.0001), after adjusting for above variables. Substantialvariation in Hgb values exists at all GFR levels. These findings underscore the importance of evaluating Hgb atall GFR levels, and the need to study the impact of modificationof Hgb at different GFR levels on survival.