New evidence for,and challenges in,linking small CGG repeat expansion FMR1 alleles with Parkinson's disease

We recently reported a significant increase in the frequency of carriers of grey zone (GZ) alleles of FMR1 gene in Australian males with Parkinson's disease (PD) from Victoria and Tasmania. Here, we report data comparing an independent sample of 817 PD patients from Queensland to 1078 consecutive Australian male newborns from Victoria. We confirmed the earlier finding by observing a significant excess of GZ alleles in PD (4.8%) compared to controls (1.5%). Although both studies provided evidence in support of an association between GZ‐carrier status and increased risk for parkinsonism, the existing evidence in the literature from screening studies remains equivocal and we discuss the need for alternative approaches to resolve the issue.     

Poly-L-lactic acid tack synovitis after arthroscopic stabilization of the shoulder

BACKGROUND: Progress has been made in the design of bioabsorbable implants, with reduced complication rates and slower degradation times. PURPOSE: To report on complications related to use of poly-L-lactic acid implants after arthroscopic shoulder stabilization procedures. STUDY DESIGN: Retrospective cohort study. METHODS: Between 1997 and 1999, 52 patients underwent arthroscopic stabilization at one institution with an average of 2.2 poly-L-lactic acid tacks. Ten patients (19%), with an average age of 30 years, developed delayed onset of symptoms at an average of 8 months after surgery, including pain in all 10 and progressive stiffness in 6. The patients underwent magnetic resonance imaging and arthroscopic evaluation and debridement. RESULTS: Nine patients had gross implant debris. Evidence of glenohumeral synovitis was seen arthroscopically in all 10 patients. Three patients had significant full-thickness chondral damage on the humeral head. All preexisting labral lesions were healed. One year after arthroscopic debridement, loose body removal, and synovectomy, seven patients reported no or minimal pain and full return of motion. Two patients continued to have persistent pain and stiffness, and one patient reported discomfort with overhand throwing; all three had chondral lesions. CONCLUSIONS: Patients with symptoms of delayed pain and progressive stiffness after arthroscopic stabilization with poly-L-lactic acid implants should be evaluated for synovitis and chondral injury. Arthroscopic treatment provides a significant decrease in symptoms and increased range of motion.     

Adolescent nutrition in a rural community in Bangladesh

The objective of this study was to assess the nutritional status of adolescent boys and girls in a rural community in Bangladesh. Between December 1996 and January 1997, a cross-sectional survey was carried out in 803 households, each containing at least one adolescent, sampled consecutively from four purposely-selected villages in Rupganj Thana, Narayanganj district. Initially, the guardians of 1483 healthy and unmarried 10–17 year old adolescents (51% boys and 49% giris) were interviewed about family structure and socio-economic status. Out of these children, 906 (47% boys and 53% girls) from 597 households were weighed, had their height and MUAC measured and were clinically examined. Blood was then collected from 861 adolescents for haemoglobin estimation. The median monthly income per person in these 597 families was approximately Taka 554 (US $12). Twenty seven per cent of the household heads were labourers, 21% were solvent farmers, 14% ran small scale businesses and 6% were unemployed. Sixty seven per cent of adolescents were thin (defined as BMI < 5th centile of WHO recommended reference) with 75% boys and 59% girls being affected. The percentage of thin adolescents fell from 95% at age 10 years to 12 % at age 17 years. The prevalence of stunting (height for age < 3rd centile NCHS/WHO) was 48% for both boys and girls and rose from 34% at age 10 to 65% at age 17. On clinical examination angular stomatitis was present in 46%, 27% nad glossitis, 38% had pallor, 11% ha’d dental caries, 3.2% had an conspicuously enlarged thyroid and 2.1% had eye changes of vitamin A deficiency. According to INACG (International Nutritional Anaemia Consultative Group, 1985) cut-off values, 94% of the boys and 98% of the girls were anaemic. We conclude that rural Bangladesh adolescents suffer from high rates of malnutrition and almost universal anaemia. Nutritional interventions to target this population are urgently required.     

Bepridil up-regulates cardiac Na+ channels as a long-term effect by blunting proteasome signals through inhibition of calmodulin activity

Background and purpose:

Bepridil is an anti-arrhythmic agent with anti-electrical remodelling effects that target many cardiac ion channels, including the voltage-gated Na⁺ channel. However, long-term effects of bepridil on the Na⁺ channel remain unclear. We explored the long-term effect of bepridil on the Na⁺ channel in isolated neonatal rat cardiomyocytes and in a heterologous expression system of human Na_v1.5 channel.

Experimental approach:

Na⁺ currents were recorded by whole-cell voltage-clamp technique. Na⁺ channel message and protein were evaluated by real-time RT-PCR and Western blot analysis.

Key results:

Treatment of cardiomyocytes with 10 µmol·L⁻¹ bepridil for 24 h augmented Na⁺ channel current (I_Na) in a dose- and time-dependent manner. This long-term effect of bepridil was mimicked or masked by application of W-7, a calmodulin inhibitor, but not KN93 [2-[N-(2-hydroxyethyl)-N-(4-methoxy benzenesulphonyl)]-amino-N-(4-chlorocinnamyl)-N-methylbenzylamine], a Ca²⁺/calmodulin-dependent kinase inhibitor. During inhibition of protein synthesis by cycloheximide, the I_Na increase due to bepridil was larger than the increase without cycloheximide. Bepridil and W-7 significantly slowed the time course of Na_v1.5 protein degradation in neonatal cardiomyocytes, although the mRNA levels of Na_v1.5 were not modified. Bepridil and W-7 did not increase I_Na any further in the presence of the proteasome inhibitor MG132 [N-[(phenylmethoxy)carbonyl]-L-leucyl-N-[(1S)-1-formyl-3-methylbutyl]-L-leucinamide]. Bepridil, W-7 and MG132 but not KN93 significantly decreased 20S proteasome activity in a concentration-dependent manner.

Conclusions and implications:

We conclude that long-term exposure of cardiomyocytes to bepridil at therapeutic concentrations inhibits calmodulin action, which decreased degradation of the Na_v1.5 α-subunit, which in turn increased Na⁺ current.     

Evaluation and treatment of failed rotator cuff repairs

Factors associated with failed rotator cuff repair generally fall into two categories: (1) factors associated with misdiagnosis or incomplete diagnosis or (2) factors associated with surgical technique. Causes of failure associated with misdiagnosis include cervical disc disease, thoracic outlet syndrome, AC joint arthrosis, suprascapular nerve entrapment, instability, os acromiale, and biceps tendon pathology. Factors associated with surgical technique include inadequate decompression, excessive acromial bone resection, deltoid dehiscence, deltoid reattachment failure, and nerve injury. Appropriate postoperative rehabilitation is also critical to avoid early failure or postoperative stiff shoulder.Careful examination of the patient preoperatively to determine the initial cause of failure will lead to good decision making and aid in avoiding unnecessary surgery that may not provide any significant improvement in the patient’s overall status. Short-term follow-up indicates that patients with a combined massive rotator cuff defect can achieve a favorable outcome with salvage procedures, such as a latissimus dorsi tendon transfer.     

前列痛栓治疗前列腺痛的药效学研究

目的：探讨和验证前列痛栓治疗前列腺痛的药效。方法：采用小鼠肛门给药，以空白，消炎痛栓为对照组。测定前列痛栓对小鼠扭体次数，网状内皮系统吞噬指数，耳廓肿胀，肉芽增生及大鼠小肠肌电的影响。结果：前列痛栓能明显减少小鼠扭体次数，优于消炎痛栓；对网状内皮系统吞噬功能，二甲苯所致小鼠耳廓肿胀和滤纸片埋入形成的肉芽增生及大鼠小肠肌电的影响。与消炎痛栓相近。结论：前列痛栓治疗前列腺痛有显著的镇痛作用。     

N-(1-乙氧羰基-3-苯氨甲酰基丙基)甘氨酰甘氨酸衍生物的合成

报道4个N-(1-[1-乙氧羰基-3-(对甲)苯氨甲酰基]丙基甘氨酰｝-N-取代甘氨酸(XI_1～4)和5个1-[1-乙(或甲)氧羰基-3-(对甲)苯氨甲酰基]丙基-4-取代-1,4-哌嗪-2,5-二酮(XII_1～5)共9个估计有血管紧张素转化酶抑制活性化合物的合成和鉴定。所有这些化合物及9个相应的酯(X_1～9)均未见文献报道。药理初试结果,化合物XII₂,XII₅,XI₄和XII₁均有较强降压活性。     

Coracoid impingement: diagnosis and treatment

Coracoid impingement is a controversial, well-known diagnosis that results in anterior shoulder pain. Idiopathic, traumatic, and iatrogenic etiologies have been identified. Proper diagnosis requires a focused clinical examination of the anterior shoulder and adjacent structures. MRI and CT are helpful in evaluating coracoid morphology as well as the integrity of the rotator cuff and long head of the biceps. Imaging is an essential diagnostic tool. Initial management consists of physical therapy and injection therapies. Surgery may be required when nonsurgical methods are unsuccessful. Successful functional and subjective outcomes have been reported with both open and arthroscopic techniques.