Patients with ALS show highly correlated progression rates in left and right limb muscles.

ObjectiveAmyotrophic lateral sclerosis (ALS) progresses at different rates between patients, making clinical trial design difficult and dependent on large cohorts of patients. Currently, there are few data showing whether the left and right limbs progress at the same or different rates. This study addresses rates of decline in specific muscle groups of patients with ALS and assesses whether there is a relationship between left and right muscles in the same patient, regardless of overall progression.MethodsA large cohort of patients was used to assess decline in muscle strength in right and left limbs over time using 2 different methods: The Tufts Quantitative Neuromuscular Exam and Accurate Test of Limb Isometric Strength protocol. Then advanced linear regression statistical methods were applied to assess progression rates in each limb.ResultsThis report shows that linearized progression models can predict general slopes of decline with good accuracy. Critically, the data demonstrate that while overall decline is variable, there is a high degree of correlation between left and right muscle decline in ALS. This implies that irrespective of which muscle starts declining soonest or latest, their rates of decline following onset are more consistent.ConclusionsFirst, this study demonstrates a high degree of power when using unilateral treatment approaches to detect a slowing in disease progression in smaller groups of patients, thus allowing for paired statistical tests. These findings will be useful in transplantation trials that use muscle decline to track disease progression in ALS. Second, these findings discuss methods, such as tactical selection of muscle groups, which can improve the power efficiency of all ALS clinical trials

Lateral one-third gland resection in Cushing patients with failed adenoma identification leads to low remission rates: long-term observations from a small, single-center cohort.

BACKGROUND Currently, there are no guidelines for neurosurgeons treating patients with Cushing's disease (CD) when intraoperative adenoma identification is negative. Under these circumstances, a total hypophysectomy or hemi-hypophysectomy on the side indicated by inferior petrosal sinus sampling (IPSS) is the approach being used, although there is a subsequent risk of hypopituitarism. Data on whether one-third lateral pituitary gland resection results in cure of hypercortisolism and low rates of hypopituitarism remain inconclusive. METHODS Retrospective single-center study of CD patients with failed intraoperative adenoma identification and subsequent resection of the lateral one-third of the pituitary gland as predicted by IPSS. We assessed (i) histopathological findings, (ii) early and long-term remission rates, and (iii) rates of additional pituitary hormone insufficiency. RESULTS Ten women and three men met the inclusion criteria. At 3 months, remission was noted in six (46%) patients: three (23%) had histologically confirmed adenomas, two (15%) had ACTH hyperplasia, and one patient (8%) was positive for Crooke's hyaline degeneration. New pituitary hormone deficits were noted in two patients (15%). After a median (±SD) follow-up of 14±4 years, recurrence was noted in two (15%) patients. Long-term control of hypercortisolism was attained by 10 patients (77%), with additional therapies required in nine (69%) of them. CONCLUSIONS In CD patients with failed intraoperative adenoma visualization, lateral one-third gland resection resulted in low morbidity and long-term remission in 31% of patients without the need for additional therapies. Bearing in mind the sample size of this audit, the indication for lateral one-third-gland resection has to be critically appraised and discussed with the patients before surgery

Epidemiologic Differences Between Cyclosporiasis and Cryptosporidiosis in Peruvian Children

We compared the epidemiologic characteristics of cyclosporiasis and cryptosporidiosis in data from a cohort study of diarrhea in a periurban community near Lima, Peru. Children had an average of 0.20 episodes of cyclosporiasis/year and 0.22 episodes of cryptosporidiosis/year of follow-up. The incidence of cryptosporidiosis peaked at 0.42 for 1-year-old children and declined to 0.06 episodes/child-year for 5- to 9-year-old children. In contrast, the incidence of cyclosporiasis was fairly constant among 1- to 9-year-old children (0.21 to 0.28 episodes/child-year). Likelihood of diarrhea decreased significantly with each episode of cyclosporiasis; for cryptosporidiosis, this trend was not statistically significant. Both infections were more frequent during the warm season (December to May) than the cooler season (June to November). Cryptosporidiosis was more frequent in children from houses without a latrine or toilet. Cyclosporiasis was associated with ownership of domestic animals, especially birds, guinea pigs, and rabbits

Persistent bone impairment despite long-term control of hyperprolactinemia and hypogonadism in men and women with prolactinomas.

While prolactinoma patients have high bone turnover, current data are inconclusive when it comes to determining whether correction of hyperprolactinemia and associated hypogandism improves osteodensitometric data in men and women over the long term. In a large cohort of including 40 men and 60 women, we studied the long-term impact of prolactinoma treatment on bone mineral density (BMD) in men versus women, assessed adverse effects of a primary surgical or medical approach, and evaluated data for risk factors for impaired BMD at last follow-up using multivariate regression analyses. Median duration of follow-up was 79 months (range 13-408 months). Our data indicate that the prevalence of impaired BMD remained significantly higher in men (37%) than in women (7%, p < 0.001), despite the fact that hyperprolactinemia and hypogonadism are under control in the majority of men. We found that persistent hyperprolactinemia and male sex were independent risk factors for long-term bone impairment. Currently, osteoporosis prevention and treatment focus primarily on women, yet special attention to bone loss in men with prolactinomas is advised. Bone impairment as "end organ" reflects the full range of the disease and could become a surrogate marker for the severity of long-lasting hyperprolactinemia and associated hypogonadism

Taenia solium Cysticercosis Hotspots Surrounding Tapeworm Carriers: Clustering on Human Seroprevalence but Not on Seizures

Cysticercosis is a parasitic disease caused by the tapeworm Taenia solium, common in areas with limited sanitation or with migration from these populations. The adult parasite is hosted in the human intestine and releases large numbers of eggs with the feces. Human beings sometimes ingest eggs due to poor hygiene, and then eggs sometimes lodge on the brain and after a few years can cause intense headaches and seizures. During a study in seven rural communities in Peru, individuals exposed to T. solium eggs were often tightly clustered at the homes or immediate surrounding of the carriers of the adult parasite. However, no aggregation of cases of seizures was found near carriers. It appears that seizures do not cluster around carriers because several years pass between exposure to T. solium eggs and the onset of seizures. During these years the adult parasite has probably died or people had moved within or even outside their communities. Therefore, only a partial understanding of the epidemiology of cysticercosis is gained by studying seizures cases

Prediction of Long-Term Restenosis After Carotid Endarterectomy Using Quantitative Magnetic Resonance Angiography.

Background To detect restenosis after carotid endarterectomy (CEA), long-term monitoring is required. However, non-selective follow-up is controversial and can be limited by costs and logistical considerations. Objective To examine the value of immediate perioperative vessel flow measurements after CEA using quantitative magnetic resonance angiography (QMRA) to detect patients at risk of long-term restenosis. Methods A prospective cohort study with long-term sonographic follow-up after CEA for symptomatic internal carotid artery stenosis (ICAs) > 50%. In all patients, vessel flow has been assessed both pre- and postoperatively using QMRA within ±3 days of surgery. Data on QMRA assessment were analyzed to identify patients at risk of restenosis for up to 10 years. Results Restenosis was recorded in 4 of 24 patients (17%) at a median follow-up of 6.8 ± 2.6 years. None of them experienced an ischemic event. Perioperative flow differences were significantly greater in patients without long-term restenosis, both for the ipsilateral ICA (p < 0.001) and MCA (p = 0.03), compared to those with restenosis (p = 0.22 and p = 0.3, respectively). The ICA mean flow ratio (p = 0.05) tended to be more effective than the MCA ratio in predicting restenosis over the long term (p = 0.35). Conclusion Our preliminary findings suggest that QMRA-based mean flow increases after CEA may be predictive of restenosis over the long term. Perioperative QMRA assessment could become an operator-independent screening tool to identify a subgroup of patients at risk for restenosis, in whom long-term monitoring is advised

A new evaluation of the uncertainty associated with CDIAC estimates of fossil fuel carbon dioxide emission

Three uncertainty assessments associated with the global total of carbon dioxide emitted from fossil fuel use and cement production are presented. Each assessment has its own strengths and weaknesses and none give a full uncertainty assessment of the emission estimates. This approach grew out of the lack of independent measurements at the spatial and temporal scales of interest. Issues of dependent and independent data are considered as well as the temporal and spatial relationships of the data. The result is a multifaceted examination of the uncertainty associated with fossil fuel carbon dioxide emission estimates. The three assessments collectively give a range that spans from 1.0 to 13% (2 σ). Greatly simplifying the assessments give a global fossil fuel carbon dioxide uncertainty value of 8.4% (2 σ). In the largest context presented, the determination of fossil fuel emission uncertainty is important for a better understanding of the global carbon cycle and its implications for the physical, economic and political world

Restenosis after microsurgical non-patch carotid endarterectomy in 586 patients

Carotid endarterectomy (CEA) reduces the risk of stroke in patients with symptomatic (>50%) and asymptomatic (>60%) carotid artery stenosis. Here we report the midterm results of a microsurgical non-patch technique and compare these findings to those in the literature

Human neural stem cells enhance structural plasticity and axonal transport in the ischaemic brain

Stem cell transplantation promises new hope for the treatment of stroke although significant questions remain about how the grafted cells elicit their effects. One hypothesis is that transplanted stem cells enhance endogenous repair mechanisms activated after cerebral ischaemia. Recognizing that bilateral reorganization of surviving circuits is associated with recovery after stroke, we investigated the ability of transplanted human neural progenitor cells to enhance this structural plasticity. Our results show the first evidence that human neural progenitor cell treatment can significantly increase dendritic plasticity in both the ipsi- and contralesional cortex and this coincides with stem cell-induced functional recovery. Moreover, stem cell-grafted rats demonstrated increased corticocortical, corticostriatal, corticothalamic and corticospinal axonal rewiring from the contralesional side; with the transcallosal and corticospinal axonal sprouting correlating with functional recovery. Furthermore, we demonstrate that axonal transport, which is critical for both proper axonal function and axonal sprouting, is inhibited by stroke and that this is rescued by the stem cell treatment, thus identifying another novel potential mechanism of action of transplanted cells. Finally, we established in vitro co-culture assays in which these stem cells mimicked the effects observed in vivo. Through immunodepletion studies, we identified vascular endothelial growth factor, thrombospondins 1 and 2, and slit as mediators partially responsible for stem cell-induced effects on dendritic sprouting, axonal plasticity and axonal transport in vitro. Thus, we postulate that human neural progenitor cells aid recovery after stroke through secretion of factors that enhance brain repair and plasticity