载瘤动脉痉挛状态下栓塞脑动脉瘤18例

1 临床资料唐都医院神经外科在2004-02/2004-05间用电解弹簧圈栓塞治疗了颅内动脉瘤患者共46例,其中存在载瘤动脉痉挛18 (男 6,女12)例,年龄17～65岁,平均42岁,均以自发性蛛网膜下腔出血为首发症状,临床表现为头痛、呕吐、颈强.伴有意识障碍者8例;肢体功能障碍者3例;1例后交通动脉瘤伴有动眼神经麻痹.术前Hess-Hunt分级Ⅰ级1例,Ⅱ级9例,Ⅲ级7例,Ⅳ级1例. 全部病例均DSA造影检查确诊存在颅内动脉瘤及载瘤动脉痉挛.其中前交通动脉瘤11例,后交通动脉瘤4例,大脑中动脉分叉部动脉瘤2例,眼动脉瘤1例.全部病例均用电解弹簧圈栓塞.术后常规腰穿放出血性脑脊液,应用钙拮抗剂,静脉应用罂粟碱2 wk,同时高脑灌注压,高血容量,低血黏度等综合治疗.     

Clinical care and technical recommendations for 90yttrium microsphere treatment of liver cancer

Selective internal radiation therapy (SIRT) with ⁹⁰yttrium microspheres is a relatively new clinical modality for treating non-resectable malignant liver tumours. This interventional radiology technique employs percutaneous microcatheterisation of the hepatic arterial vasculature to selectively deliver radioembolic microspheres into neoplastic tissue. SIRT results in measurable tumour responses or delayed disease progression in the majority of eligible patients with hepatocellular carcinoma or hepatic metastases arising from colorectal cancer. It has also been successfully used as palliative therapy for non-colorectal malignancies metastatic to the liver. Although most adverse events are mild and transient, SIRT also carries some risks for serious and – rarely – fatal outcomes. In particular, entry of microspheres into non-target vessels may result in radiation-induced tissue damage, such as severe gastric ulceration or radiation cholecystitis. Radiation-induced liver disease poses another significant risk. By careful case selection, considered dose calculation and meticulous angiographic technique, it is possible to minimise the incidence of such complications to less than 10% of all treatments. As the number of physicians employing SIRT expands, there is an increasing need to consolidate clinical experience and expertise to optimise patient outcomes. Authored by a panel of clinicians experienced in treating liver tumours via SIRT, this paper collates experience in vessel mapping, embolisation, dosimetry, microsphere delivery and minimisation of non-target delivery. In addition to these clinical recommendations, the authors propose institutional criteria for introducing SIRT at new centres and for incorporating the technique into multidisciplinary care plans for patients with hepatic neoplasms.     

ORIGINAL ARTICLE: Enlarged hilar and mediastinal lymph nodes in chronic obstructive pulmonary disease

Introduction: To evaluate the frequency of enlarged hilar or mediastinal lymph nodes in patients suffering from chronic obstructive pulmonary disease (COPD). Methods: In a retrospective study, 89 patients with proven COPD were analysed. Exclusion criteria were history of malignant disease or clinical evidence of pneumonia. Prevalence, size, and localisation of enlarged lymph nodes were assessed by multi-slice computed tomography (MSCT) and correlated with the clinical stages following the GOLD classification as well as the MSCT findings of bronchitis and emphysema. Results: 44/89 (49%) of our patients showed enlarged lymph nodes. Lymph node enlargement was more often seen in the mediastinum (48%) than the hilar region (20%). The most common localisation of enlarged mediastinal lymph nodes was the regional station 7 following the ATS mapping (infracarinal). Patients with a stage I following the GOLD classification showed enlarged lymph nodes in 49% (18/37), stage II in 46% (12/26), stage III in 58% (7/12) and stage IV in 50% (7/14). These findings did not differ significantly (P > 0.05). Severe airway wall thickening (42/89) was significantly more often associated with an increase of nodal enlargement (64%) (P < 0.05). Conclusion: The present study demonstrates that enlarged hilar and mediastinal lymph nodes may occur in a rather high percentage of patients suffering from COPD, especially in those with the MSCT finding of severe bronchitis.     

Cognitive impairment in Parkinson's disease: impact on quality of life of carers

Background

The quality of life (QoL) of informal caregivers of people with Parkinson's disease (PD) (PwP) can be affected by the caring role. Because of cognitive symptoms and diminished activities of daily living, in addition to the management of motor symptoms, carers of PwP and cognitive impairment may experience increased levels of burden and poorer QoL compared with carers of PwP without cognitive impairment. This study aimed to investigate the impact of cognitive impairment in PD upon QoL of carers.

Methods

Approximately 36 months after diagnosis, 66 dyadic couples of PwP and carers completed assessments. PwP completed a schedule of neuropsychological assessments and QoL measures; carers of PwP completed demographic questionnaires and assessments of QoL. Factor scores of attention, memory/executive function and global cognition, as derived by principal component analysis, were used to evaluate cognitive domains.

Results

Hierarchical regression analysis found lower Montreal Cognitive Assessment was a significant independent predictor of poorer carer QoL, in addition to number of hours spent caregiving, carer depression and PD motor severity. Attentional deficits accounted for the largest proportion of variance of carer QoL. Carers of PwP and dementia (n = 9) had significantly poorer QoL scores compared with PwP and mild cognitive impairment (n = 18) or normal cognition (n = 39) carers (p < 0.01).

Conclusions

Attentional deficits were the strongest predictor of carer QoL compared with other cognitive predictors. Carers for those with PD dementia reported the poorest QoL. Interventions such as respite or cognitive behavioural therapy to improve mood and self‐efficacy in carers may improve carer QoL. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd.     

Array‐CGH analysis indicates a high prevalence of genomic rearrangements in holoprosencephaly: An updated map of candidate loci

Holoprosencephaly (HPE) is the most frequent malformation of the brain. To date, 12 different HPE loci and 8 HPE genes have been identified from recurrent chromosomal rearrangements or from the sequencing of genes from Nodal and SHH pathways. Our cohort of HPE patients presents a high genetic heterogeneity. Point mutations were found in SHH, ZIC2, SIX3, and TGIF genes in about 20% of cases (with 10% in SHH). Deletions in these same genes were found in 7.5% of the patients and 4.4% presented with other subtelomeric gain or losses. Consequently, the molecular basis of HPE remains unknown in 70% of our cohorts. To detect new HPE candidate genes, we used array‐CGH to refine the previous karyotype based HPE loci map. We analyzed 111 HPE patients with high‐performance Agilent oligonucleotidic arrays and found that 28 presented anomalies involving known or new potential HPE loci located on different chromosomes but with poor redundancy. This study showed an impressive rate of 19 patients among 111 with de novo chromosomal anomalies giving evidence that microrearrangements could be a major molecular mechanism in HPE. Additionally, this study opens new insights on HPE candidate genes identification giving an updated HPE candidate loci map. Hum Mutat 30:1–8, 2009. © 2009 Wiley‐Liss, Inc.     

Small CGG repeat expansion alleles of FMR1 gene are associated with parkinsonism

Fragile X-associated tremor/ataxia syndrome (FXTAS) affects older males carrying premutation, that is, expansions of the CGG repeat (in the 55–200 range), in the FMR1 gene. The neurological changes are linked to the excessive FMR1 messenger RNA (mRNA), becoming toxic through a 'gain-of-function'. Because elevated levels of this mRNA are also found in carriers of the smaller expansion (grey zone) alleles, ranging from 40 to 54 CGGs, we tested for a possible role of these alleles in the origin of movement disorders associated with tremor.
We screened 228 Australian males affected with idiopathic Parkinson's disease and other causes of parkinsonism recruited from Victoria and Tasmania for premutation and grey zone alleles. The frequencies of either of these alleles were compared with the frequencies in a population-based sample of 578 Guthrie spots from consecutive Tasmanian male newborns (controls). There was a significant excess of premutation carriers (Fisher's exact test p = 0.006). There was also a more than twofold increase in grey zone carriers in the combined sample of the Victorian and Tasmanian cases, with odds ratio (OR ) = 2.36, and 95% confidence intervals (CI): 1.20–4.63, as well as in Tasmanian cases only (OR = 2.33, 95% CI: 1.06–5.13), compared with controls. The results suggest that the FMR1 grey zone alleles, as well as premutation alleles, might contribute to the aetiology of disorders associated with parkinsonism.     

Quality of routine spirometry tests in Dutch general practices

Background

Spirometry is an indispensable tool for diagnosis and monitoring of chronic airways disease in primary care.

Aim

To establish the quality of routine spirometry tests in general practice, and explore associations between test quality and patient characteristics.

Design of study

Analysis of routine spirometry test records.

Setting

Fifteen general practices which had a working agreement with a local hospital pulmonary function laboratory for spirometry assessment regarding test quality and interpretation.

Method

Spirometry tests were judged by a pulmonary function technician and a chest physician. Proportions of test adequacy were analysed using markers for manoeuvre acceptability and test reproducibility derived from the 1994 American Thoracic Society spirometry guideline. Associations between quality markers and age, sex, and severity of obstruction were examined using logistic regression.

Results

Practices performed a mean of four (standard deviation = 2) spirometry tests per week; 1271 tests from 1091 adult patients were analysed; 96.4% (95% confidence interval [CI] = 95.6 to 97.2) of all tests consisted of ≥3 blows. With 60.6% of tests, forced expiratory time was the marker with the lowest acceptability rate. An overall 38.8% (95% CI = 36.0 to 41.6) of the tests met the acceptability as well as reproducibility criteria. Age, sex, and severity of obstruction were associated with test quality markers.

Conclusion

The quality of routine spirometry tests was better than in previous reports from primary care research settings, but there is still substantial room for improvement. Sufficient duration of forced expiratory time is the quality marker with the highest rate of inadequacy. Primary care professionals should be aware of patient characteristics that may diminish the quality of their spirometry tests. Further research is needed to establish to what extent spirometry tests that are inadequate, according to stringent international expert criteria, result in incorrect clinical interpretations in general practice.     

Distinct molecular requirements for activation or stabilization of soluble guanylyl cyclase upon haem oxidation-induced degradation

Background and purpose:

In endothelial dysfunction, signalling by nitric oxide (NO) is impaired because of the oxidation and subsequent loss of the soluble guanylyl cyclase (sGC) haem. The sGC activator 4-[((4-carboxybutyl){2-[(4-phenethylbenzyl)oxy]phenethyl}amino)methyl[benzoic]acid (BAY 58-2667) is a haem-mimetic able to bind with high affinity to sGC when the native haem (the NO binding site) is removed and it also protects sGC from ubiquitin-triggered degradation. Here we investigate whether this protection is a unique feature of BAY 58-2667 or a general characteristic of haem-site ligands such as the haem-independent sGC activator 5-chloro-2-(5-chloro-thiophene-2-sulphonylamino-N-(4-(morpholine-4-sulphonyl)-phenyl)-benzamide sodium salt (HMR 1766), the haem-mimetic Zn-protoporphyrin IX (Zn-PPIX) or the haem-dependent sGC stimulator 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-pyrimidin-4-ylamine (BAY 41-2272).

Experimental approach:

The sGC inhibitor 1H-(1,2,4)-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) was used to induce oxidation-induced degradation of sGC. Activity and protein levels of sGC were measured in a Chinese hamster ovary cell line as well as in primary porcine endothelial cells. Cells expressing mutant sGC were used to elucidate the molecular mechanism underlying the effects observed.

Key results:

Oxidation-induced sGC degradation was prevented by BAY 58-2667 and Zn-PPIX in both cell types. In contrast, the structurally unrelated sGC activator, HMR 1766, and the sGC stimulator, BAY 41-2272, did not protect. Similarly, the constitutively haem-free sGC mutant β₁H105F was stabilized by BAY 58-2667 and Zn-PPIX.

Conclusions:

The ability of BAY 58-2667 not only to activate but also to stabilize oxidized/haem-free sGC represents a unique example of bimodal target interaction and distinguishes this structural class from non-stabilizing sGC activators and sGC stimulators such as HMR 1766 and BAY 41-2272, respectively.