SPiQE: An automated analytical tool for detecting and characterising fasciculations in amyotrophic lateral sclerosis

ObjectivesFasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). Compared to concentric needle EMG, high-density surface EMG (HDSEMG) is non-invasive and records fasciculation potentials (FPs) from greater muscle volumes over longer durations. To detect and characterise FPs from vast data sets generated by serial HDSEMG, we developed an automated analytical tool.MethodsSix ALS patients and two control patients (one with benign fasciculation syndrome and one with multifocal motor neuropathy) underwent 30-minute HDSEMG from biceps and gastrocnemius monthly. In MATLAB we developed a novel, innovative method to identify FPs amidst fluctuating noise levels. One hundred repeats of 5-fold cross validation estimated the model’s predictive ability.ResultsBy applying this method, we identified 5,318 FPs from 80 minutes of recordings with a sensitivity of 83.6% (+/? 0.2 SEM), specificity of 91.6% (+/? 0.1 SEM) and classification accuracy of 87.9% (+/? 0.1 SEM). An amplitude exclusion threshold (100 μV) removed excessively noisy data without compromising sensitivity. The resulting automated FP counts were not significantly different to the manual counts (p = 0.394).ConclusionWe have devised and internally validated an automated method to accurately identify FPs from HDSEMG, a technique we have named Surface Potential Quantification Engine (SPiQE).SignificanceLongitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.     

Time to think outside the box? Prothrombin time,international normalised ratio,international sensitivity index,mean normal prothrombin time and measurement of uncertainty a novel approach to standardisation

BACKGROUND: The prothrombin time (PT) assay is the most clinically ordered coagulation test, and most often used for monitoring of vitamin K antagonist therapy (e.g., warfarin), where results are expressed as an international normalised ratio (INR). The INR is in essence the patient's PT 'mathematically adjusted' to a standardised value taking into account the peculiarities of the test system as defined by an ISI (international sensitivity index) and MNPT (mean normal prothrombin time). Although some manufacturers provide assigned ISI values for specific PT reagents and instrumentation, it is still recommended practice that laboratories check or validate these ISIs, as well as estimate the MNPT. Where an ISI is not provided by a manufacturer, the laboratory needs to estimate its own value. Current recommendations suggest the use of commercial reference-plasma calibration sets, but there is limited information on the performance of these in the field. RESULTS: We report a comparative study that assessed the utility of three such commercial calibration plasma sets, used as recommended, as well as alternate or supplementary procedures for estimation of ISI and MNPT. The latter included one novel approach using comparative data of 'existing' versus 'replacement' reagent, as well as assessment of external quality assurance data. Although MNPT value estimates were not grossly disparate, a wide variety of ISI values (e.g., 1.12-1.30 for our primary instrument) was obtained with the different plasma sets. CONCLUSION: Because of the above, further verification checks are required prior to acceptance of ISI and MNPT estimates generated from commercial plasma calibration sets. We also provide some recommendations regarding the process of standardisation of INR testing.     

Verapamil decreases glucuronidase activity in the gut

The present investigation addressed the role of verapamil for oral pharmacokinetics of morphine-6-beta-glucuronide (M6G). Male Sprague-Dawley rats received 62.5 mg kg(-1) M6G-dihydrate orally w/wo pre-treatment with 70 mg kg(-1) verapamil. Intravenous M6G (3.9 mg kg(-1) ) and oral morphine (52.7 mg kg(-1) morphine-hydrochloride) were also employed. Oral bioavailability of M6G and the fraction of M6G deglucuronidated to morphine were estimated from areas under the plasma-concentration vs. time curves (AUC) of morphine and its glucuronides. As initial results pointed towards inhibition of glucuronidases by verapamil, its capability to specifically inhibit E. coli and/or rat intestinal beta-glucuronidase was assessed using altered cleavage of the model substrate 4-methylumbelliferyl-beta-D-glucuronide (MUG). Oral bioavailability of M6G was 2.1%; 13% of oral M6G was deglucuronidated to morphine. Co-administration of verapamil did not increase the AUC of M6G. AUCs of morphine and morphine-3-glucuronide were smaller in the verapamil group than in controls. Verapamil co-administration decreased the fraction of M6G deglucuronidated to morphine to 4.6%. In vitro experiments provided evidence that verapamil inhibits beta-glucuronidase from E. coli with an IC(50) of 30 microM, whereas no inhibition of the rat beta-glucuronidase from small intestine was seen. In conclusion, verapamil decreased intestinal deglucuronidation of M6G by inhibiting E. coli beta-glucuronidase. This indicates that verapamil is not suited as P-gp inhibitor in experiments involving glucuronides. An increase in the intestinal absorption of M6G due to P-gp-inhibition was not observed at the verapamil dose studied.     

Interactions of C12 surfactants with the skin: Changes in enzymes and visible and histological features of rat skin treated with sodium lauryl sulphate

Rat skin was treated with 35 mm-sodium lauryl sulphate (SLS) and samples were taken after one, three or five treatments, or 24 hr after the fifth treatment for measurement of enzyme release and epidermal enzyme levels. Release of acid phosphatase (AP) and lactate dehydrogenase (LDH) was significantly higher than in controls after five treatments with SLS, and epidermal levels of AP, LDH and N-acetylglucosaminidase were also higher than in controls in skin taken 24 hr after the fifth treatment. The relationship of these changes to the irritant response, assessed visually and histologically, was investigated in two out of three experiments. Although the timing of the irritant response was variable, enzyme release accompanied the development of erythema and oedema in each case, and extensive enzyme release was associated histologically with epidermal oedema and an increase in dermal leucocytes. The increase in epidermal enzyme activities also followed the development of the reaction to SLS, and it seemed to be related to epidermal thickening.     

消支护精散对雄性大鼠解脲支原体感染生殖器组织学变化的实验研究

目的:探讨消支护精散对雄性大鼠生殖器解脲支原体感染的防治作用。方法:采用膀胱注射法(逆行性感染)造模,以强力霉素作对照,观察模型大鼠生殖器的病理形态变化。结果:解脲支原体经膀胱感染后,能继发引起生殖系统多种组织器官的损伤,睾丸生精细胞脱落,胞浆空泡化,部分精子细胞核皱缩,细胞核染色质边移、凋亡,前列腺、精囊、附睾等组织上皮细胞结构紊乱。治疗后模型组实验大鼠精子畸形率明显增高,中药组与强力霉素组精子畸形率较低,中药组与正常组交配雌鼠受孕率明显高于强力霉素组与模型组。结论:消支护精散能消除解脲支原体,改善精子存活率和活动力,提高雌性大鼠受孕率。     

Seven Cases of Gastric Perforation in Roux-en-Y Gastric Bypass Patients: What Lessons Can We Learn?

Background Patients undergoing Roux-en-Y gastric bypass for the resolution of morbid obesity have significant medical sequelae related to their weight. One of the most common comorbid conditions is joint pain requiring the use of non-steroidal anti-inflammatory medications (NSAIDs). In addition to NSAIDs, patients may engage in behaviors such as smoking and alcohol misuse that increase the risk of long-term postoperative complications to include gastric perforation. Methods Data on 1,690 patients undergoing gastric bypass surgery were collected prospectively and reviewed retrospectively. Results We identified seven patients who presented to an emergency room and subsequently required emergent surgical intervention for repair of gastric perforation. Six of the seven cases involved use or abuse of NSAIDs. Conclusion Important characteristics were identified including the use of NSAIDs, alcohol use, and non-compliance with routine long-term postoperative follow-up. Identifying those patients at high risk may decrease the incidence of this potentially life-threatening complication.     

Quantitative studies of lower motor neuron degeneration in amyotrophic lateral sclerosis: Evidence for exponential decay of motor unit numbers and greatest rate of loss at the site of onset

Objective

To use our Bayesian method of motor unit number estimation (MUNE) to evaluate lower motor neuron degeneration in ALS.

Methods

In subjects with ALS we performed serial MUNE studies. We examined the repeatability of the test and then determined whether the loss of MUs was fitted by an exponential or Weibull distribution.

Results

The decline in motor unit (MU) numbers was well-fitted by an exponential decay curve. We calculated the half life of MUs in the abductor digiti minimi (ADM), abductor pollicis brevis (APB) and/or extensor digitorum brevis (EDB) muscles. The mean half life of the MUs of ADM muscle was greater than those of the APB or EDB muscles. The half-life of MUs was less in the ADM muscle of subjects with upper limb than in those with lower limb onset.

Conclusions

The rate of loss of lower motor neurons in ALS is exponential, the motor units of the APB decay more quickly than those of the ADM muscle and the rate of loss of motor units is greater at the site of onset of disease.

Significance

This shows that the Bayesian MUNE method is useful in following the course and exploring the clinical features of ALS.     

美国推广电子健康档案的新举措：MU标准

作为刺激经济复苏方案的一部分，美国拟在全国推广电子健康档案。 投入大量资金需要一个分配方案，为此新出台MU（Meaningful Use）标准。介绍MU评估标准中规定的医院应该达到的23个目标，阐明不同用户对MU标准的需求，指出重点内容、目前的问题、挑战和可能影响。