Pharmacological evaluation of natural product analogues. I. Preliminary pharmacological evaluation of O-methylgortschakoine and O-methylpetaline

The synthesis of O-methylgortschakoine and O-methylpetaline was achieved through an unambiguous route. Pharmacological testing of O-methylgortschakoine in comparison to papaverine and 7,8-dimethoxy-N-methyltetrahydroisoquinoline, indicated that it possesses hypotensive, neuromuscular blocking and smooth muscle relaxant activities. 7,8-Dimethoxy-N-methyltetrahydroisoquinoline showed only nonspecific smooth muscle relaxation in our testing system. The 1-(p-methoxybenzyl)-substituent of O-methylgortschakoine appears to be required for this hypotensive and neuromuscular blocking effect. The quaternary analogue O-melthylpetaline was found to possess a more potent neuromuscular blocking activity.     

ACCESSORY SOLEUS MUSCLE: A PROBLEM OF AWARENESS

Reports of accessory soleus muscle are rare, perhaps as a result of it often remaining unrecognized. It presents as a swelling behind the ankle and may be mistaken for a tumour or inflammatory lesion, as occurred in the first of a series of three cases. The other two were incidental findings, one in a 30 year old man with an open tibial fracture and the other in a 9 month old child with a club foot. Patients present with either pain or a diagnostic problem. When large, it may make wearing of footwear difficult. Computerized tomography with electromyography enables confirmation of the diagnosis. Pain is relieved by epimysiotomy and when encountered incidentally during surgery, incision of the epimysium is all that is needed. Excision of the muscle may be considered only if wearing of footwear is difficult. The significance of its presence in a case of club foot is unknown. Disinsertion of its insertion was all that was required to obtain surgical correction of the deformity in the present case. Awareness of the condition will prevent unnecessary surgery in asymptomatic cases.     

Health‐related quality of life in multiple system atrophy

Although multiple system atrophy (MSA) is a neurodegenerative disorder leading to progressive disability and decreased life expectancy, little is known about patients' own evaluation of their illness and factors associated with poor health‐related quality of life (Hr‐QoL). We, therefore, assessed Hr‐QoL and its determinants in MSA. The following scales were applied to 115 patients in the European MSA‐Study Group (EMSA‐SG) Natural History Study: Medical Outcome Study Short Form (SF‐36), EQ‐5D, Beck Depression Inventory (BDI), Mini‐Mental state examination (MMSE), Unified MSA Rating Scale (UMSARS), Hoehn & Yahr (H&Y) Parkinson's disease staging scale, Composite Autonomic Symptom Scale (COMPASS), and Parkinson's Disease Sleep Scale (PDSS). Forty‐six percent of patients had moderate to severe depression (BDI ≥ 17); Hr‐QoL scores on the SF‐36 and EQ‐5D were significantly impaired. Pain, the only domain with similar scores in MSA and published PD patients, was reported more frequently in patients with MSA‐P (predominantly parkinsonian motor subtype) than MSA‐C (predominantly cerebellar motor subtype; 76% vs. 50%; P = 0.005). Hr‐QoL scores correlated most strongly with UMSARS motor, COMPASS, and BDI scores but not with MMSE scores, age at onset, or disease duration. The COMPASS and UMSARS activities of daily living scores were moderate‐to‐strong predictors for the SF‐36 physical summary score and the BDI and UMSARS motor scores for the SF‐36 mental summary score. This report is the first study to show that Hr‐QoL is significantly impaired in MSA. Although not all possible factors related to impaired Hr‐QoL in MSA could be assessed, autonomic dysfunction, motor impairment, and depression were most closely associated with poor Hr‐QoL, and therapeutic management, therefore, should concentrate upon these aspects of the disease. © 2006 Movement Disorder Society     

高血压病肠系膜动脉平滑肌细胞端粒酶活性表达的研究

目的 :探讨高血压病动脉平滑肌组织端粒酶活性与高血压的发病关系。方法 :采用PCR -ELISA法检测 30例高血压病患者和 2 0例血压正常者肠系膜动脉平滑肌细胞 (SMC)端粒酶活性。结果 :高血压患者端粒酶阳性表达 2 8例 (93.3% )。血压正常者端粒酶阳性表达 3例 (15 % )。差异非常显著 (P <0 .0 5 )。结论 :高血压病动脉平滑肌细胞端粒酶活性的表达升高 ,可能与高血压发病有关。     

老年认知功能障碍与脑结构CT测量的相关性研究

目的探讨脑萎缩与老年认知功能障碍之间的相关性。方法对开滦集团公司1063名离退休职工进行健康查体,用简易精神状态量表(MMSE)评定认知功能,按分界值将本次研究对象分为认知功能障碍组和认知功能正常组,同时用CT线性测量脑的相关部位以诊断脑萎缩情况,并对各型脑萎缩与认知功能的相关系数及提示老年认知功能障碍的敏感度、特异度、准确度进行分析。结果1063名观察对象中符合入选标准并资料完整者共计511名,其中108名有认知功能障碍,髓质脑萎缩55名、皮质萎缩5名、混合型萎缩30名;认知功能正常者403名,髓质脑萎缩214名、皮质萎缩13名、混合型萎缩62名。认知功能障碍组脑萎缩的发病率高于认知功能正常组,差异具有统计学意义(P<0.005);2组间颞叶海马钩回间距(26.86mm±3.73mmvs25.95mm±3.80mm)及海马钩回间距/大脑左右径的比值(0.21±0.02vs0.20±0.02)差异具有统计学意义(P<0.05);海马钩回间距、皮质脑萎缩、混合型脑萎缩与认知功能障碍呈负相关(分别为r=-0.094,P=0.034,r=-0.156,P≈0.000,r=-0.147,P≈0.000),以海马钩回间距20mm提示老年认知功能障碍的敏感度最高(98.14%),混合型脑萎缩的特异度(84.86%)、准确度最高(72.80%)。结论CT测量相关脑结构,判断脑萎缩类型可以为老年认知功能障碍的诊断提供有价值的信息。     

AC/A ratios in myopic and emmetropic Hong Kong children and the effect of timolol§

Purpose: Caucasian children with myopia have elevated response accommodative vergence to accommodation (AC/A) ratios. The purpose of this study was twofold: to determine if response AC/A ratios vary with refractive error and with myopic progression rate in Hong Kong Chinese children, and to determine the effect of beta‐adrenergic antagonism with topical timolol application on AC/A ratios. Methods: Thirty children aged eight to 12 years participated in the study. All refractive errors were corrected with spectacle lenses. Accommodative responses were measured using a Shin‐Nippon autorefractor and concurrent changes in vergence were assessed using a vertical prism and a Howell‐Dwyer card at three metres and 0.33 metre. Accommodative demand was altered using plus or minus two dioptre lenses and lens‐ and distance‐induced response AC/A ratios were calculated. Measurements were repeated 30 minutes after the instillation of topical timolol maleate (0.5 per cent). Results: AC/A ratios appeared higher in progressing myopic children but the difference was not statistically significant. Timolol application reduced accommodative convergence (AC) in the stable myopes (reduction = ‐3 ± 1.14^A) but not in the emmetropes (0.69 ± 0.9^P) or progressing myopes (0.16 ± 0.43^A) and this difference between refractive groups was statistically s ignificant (F^2,27= 3.766; P= 0.036). However, timolol did not produce a significant change in the accommodative response to positive or negative lenses or response AC/A ratios. Conclusions: We did not find that AC/A ratios in myopic Chinese children were elevated and therefore, it is unlikely that elevated AC/A ratios are responsible for the high levels of myopia that occur in Hong Kong. The finding that timolol reduced AC in the stable myopes suggests that the autonomic control of accommodative convergence in these children may be different from that in emmetropic children and those with progressing myopia.     

Lumbosacral glioblastoma and leptomeningeal gliomatosis complicating the course of a cervicothoracic astrocytoma WHO grade II

CASE REPORT: The reported female patient underwent sub-total resection of an intra-medullary cervicothoracic astrocytoma classified as WHO grade II in 1984 at the age of 18 months and received local irradiation. In 1989, a local recurrence was diagnosed and a partial resection was performed. Sixteen years later, a small recurrent cervicothoracic tumour was found and spinal seeding to the equine nerve roots and the left cerebellar cortex was apparent on MRI. The patient was implanted with a ventriculoperitoneal shunt for a pseudo-tumour cerebri producing papilloedema, which eventually lead to amaurosis. After an extended biopsy, the invasive lumbosacral tumour was classified as glioblastoma multiforme. Two months later, the patient died after rapid progression of the caudal cranial nerve dysfunction. DISCUSSION AND CONCLUSION: Anaplastic progression and dissemination of spinal astrocytomas even two decades after initial diagnosis and treatment are rare. Therapies and diagnostic follow-up strategies are discussed.     

甘露醇和低温对兔骨骼肌缺血再灌流损伤的保护作用

通过兔后肢缺血模型，观察了甘露醇和低温对骨骼肌缺血再灌流损伤的保护作用。结果：甘露醇和低温可以不同程度地降低再灌流后患肢静脉回流血中细胞内酶（ＣＰＫ、ＬＤＨ、ＡＳＴ）的活性和脂质过氧化反应终末代谢产物丙二醛（ＭＤＡ）的含量，减轻骨骼肌细胞超微结构的破坏。两者单独应用效果不明显（Ｐ＞０．０５），联合应用效果非常明显（Ｐ＜０．０１）。提示自由基介导的脂质过氧化反应参与骨骼肌缺血再灌流损伤，甘露醇和低温对其具有协同保护作用。     

The accommodative response,refractive error and mental effort: 1. The sympathetic nervous system

The accommodative response of 12 emmetropic subjects was measured for an array of numbers located at -1,-3 and -5 dioptres using an objective infra-red optometer. Responses were compared for passive (reading numbers) and active (adding numbers) conditions. The imposition of mental effort induced a significant increase in mean response for the -1 D stimulus, a response equivalent to the passive condition at -3 D and a reduction in response at -5 D. Mental effort induced similar responses for the -1 D and -3 D locations when sympathetic innervation to the ciliary muscle was blocked with the beta-receptor antagonist timolol maleate. Responses for the -5 D location were, however, significantly increased. It is proposed that sympathetic inhibition can modify the effect of mental effort on near accommodative responses.     

Proximal myotonic myopathy

Three Swedish patients with proximal muscle weakness, myotonia and lack of CTG expansion on genetical analysis are presented. Clinical neurological and neurophysiological examination and muscle biopsy were performed. There was an indication of autosomal dominant inheritance in 2 of the 3 patients. The main symptoms and clinical findings in the 3 patients were weakness of the proximal muscles, myotonia, muscle stiffness, muscle pain and muscle atrophy. Neurophysiological examination showed myotonic bursts and muscle biopsy snowed a variation of fibre sizes, an increased number of muscle fibres with centralized nuclei and scattered atrophic muscle fibres. Laboratory data showed elevated CK, GT and LD in 1 patient. Before genetical analysis was performed, all 3 patients had been diagnosed as atypical cases of myotonic dystrophy. However, the symptoms, clinical signs, laboratory data, electrophysiological and muscle biopsy findings were compatible with proximal myotonic myopathy (PROMM).