Piriformis muscle syndrome: an underdiagnosed cause of sciatica

This is a retrospective review of 26 patients with sciatica due to the piriformis muscle syndrome. Most patients had pain in the buttock area and sciatica, and most experienced difficulty walking and sitting, even for short periods of time. Reproduction of the sciatica upon deep palpation, either by gluteal or rectal route, was diagnostic. Reproduction of sciatica occurred in 92% of the patients upon deep digital palpation and in 100% of the patients upon rectal or pelvic examination. Other signs were helpful but not consistent. After the appropriate diagnosis, the treatment was relatively easy and rewarding. This study emphasizes that the diagnosis of piriformis muscle syndrome is clinical; without the appropriate clinical examination, it can be easily misdiagnosed.     

alpha-Lipoic acid in dietary supplements: development and comparison of HPLC-CEAD and HPLC-ESI-MS methods

Alpha-lipoic acid is an antioxidant used both in the prevention and treatment of various oxidative stress related diseases. It is an important constituent of some dietary supplements and can also be found in plant and animal sources. A rapid method for the determination of alpha-lipoic acid in dietary supplements based on high performance liquid chromatography coupled with a coulometric electrode array detector (CEAD) and an electrospray ionization mass spectrometer (ESI-MS) was developed. First, alpha-lipoic acid was extracted with methanol by sonication, chromatographic separation was then achieved by isocratic elution [acetonitrile/methanol/50mM potassium dihydrogen phosphate (pH 3, adjusted with phosphoric acid): 350/65/585, v/v/v] using an ACE 3-C-18 column at a flow rate of 0.45 ml/min. alpha-Lipoic acid was detected by means of a CEAD at +300, +400, +450, +500, +550, +600, +650, and +700 mV against palladium reference electrodes. For ESI-MS detection (negative mode), the composition of the mobile phase was changed to 0.1% acetic acid in water/acetonitrile 55:45, v/v applying a flow rate of 0.2 ml/min. The presented methods were utilized to determine the alpha-lipoic acid content in six dietary supplements. The results of both detection modes were in good correlation.     

MeCP2 mutation causes distinguishable phases of acute and chronic defects in synaptogenesis and maintenance, respectively

Over 200 mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2) are known to cause Rett syndrome (RTT), a multiphasic neurodevelopmental disorder that results in motor and cognitive impairments; however, little is known about the neurobiology of RTT. Here, we employ the MeCP2^308/y mouse model of RTT to investigate the course of the neuronal defects imparted by MeCP2 mutation. Using the olfactory system as a neurodevelopmental model, we describe an acute but transient defect in olfactory sensory neuron maturation during synaptogenesis and elaboration of the glomerular neuropil. This defect is overcome through compensatory responses that restore homeostasis. However, a chronic problem in glomerular organization emerges, which eventually leads to increased neuronal apoptosis. This multiphasic course comprising acute developmental and chronic defects in synaptogenesis and maintenance may represent the neurobiological correlates of clinical RTT, and suggests that different therapeutic strategies may be appropriate at different clinical stages of this disease.     

Formulation and process considerations for beads containing Carbopol 974P, NF resin made by extrusion-spheronization

Preliminary studies revealed that Carbopol 974P, NF resin could be incorporated into beads manufactured by extrusion and spheronization, and can slow the release of a highly water soluble drug if calcium chloride was included in the granulating fluid to reduce the tack of the wetted polymer. In this study, the same approach was used to produce high quality chlorpheniramine maleate beads with a prolonged release duration. Because of the complex nature of the extrusion and spheronization process and the various components in the bead formulations, a statistically sound factorial experiment was considered for this study. A one-half fraction of a two level factorial design with three center points was employed to estimate the effects of simultaneously modifying multiple process and formulation variables, including the Carbopol concentration, calcium chloride concentration, water content, and the spheronization speed and time. Product yield, average bead roundness, and the drug release profile were selected as responses. Increasing the Carbopol content across the experimental range resulted in a significant (P<0.05) reduction in the percentage drug released at 25, 40, and 60 min. Results suggest that combining the conditions of high Carbopol, high water, and low calcium chloride levels with low spheronization speeds at long spheronization times produce the highest quality bead with the longest drug release duration.     

Irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer

Out of every 17-18 individuals in the US, one develops colorectal cancer (CRC) in their lifetime. Of individuals diagnosed with CRC, > 50% present or develop metastatic disease, which, if untreated, is associated with 6-9 months median survival. Although surgical resection is the primary treatment modality for CRC, chemotherapy is the mainstay of treatment for metastatic or unresectable disease. For nearly three decades, 5-fluorouracil (5-FU) has been the chemotherapy of choice for treatment of CRC. However, the response rates to single 5-FU therapy have been suboptimal with an objective tumour response of 10-20%. Attempts have been made to improve the efficacy of 5-FU by either schedule alteration (protracted infusion versus intravenous push) or biochemical modulation with leucovorin (LV). Continuous infusion induced more tumour regression and prolonged the time-to-disease progression with some significant impact on survival (11.3 versus 12.1 months; p < 0.04). 5-FU/LV resulted in a significant increase in overall response rates and in the prolongation of disease-free survival in the adjuvant setting, although severe toxicities represent a major clinical problem. The last 10 years have seen the addition of several new agents such as irinotecan, oxaliplatin, raltitrexed, bevacizumab and cetuximab. The prognosis has significantly improved with the addition of these agents, with median survivals now > 20 months. This review paper focuses on irinotecan, oxaliplatin and raltitrexed when used alone and in combination.     

Multiplex bead immunoassay analysis of aqueous humor reveals distinct cytokine profiles in uveitis

PURPOSE: To extensively characterize the complex network of cytokines present in uveitis aqueous humor (AqH), and the relationships between cytokines and the cellular infiltrate. METHODS: AqH from noninflammatory control subjects and patients with idiopathic, Fuchs' heterochromic cyclitis (FHC), and herpes-viral or Beh?et's uveitis were analyzed for IL-1beta, -2, -4, -5, -7, -8, -10, -12, -13, -15, TNFalpha, IFNgamma, CCL2 (MCP-1), CCL5 (RANTES), CCL11 (Eotaxin), TGFbeta2, and CXCL12 (SDF-1), using multiplex bead immunoassays. The cellular infiltrate was also determined for each sample. RESULTS: Idiopathic uveitis AqH, compared with noninflammatory controls, was characterized by high levels of IL-6, IL-8, CCL2 and IFNgamma, the levels of which correlated with each other. For IL-6 and IL-8 these levels were proportional to the number of neutrophils present. By contrast, the levels of both TGFbeta2 and CXCL12 decreased in idiopathic uveitis AqH with increasing inflammation. Cluster analysis showed a degree of segregation between noninflammatory and idiopathic uveitis AqH. Further examination using random forest analysis yielded a complete distinction between these two groups. The minimum cytokines required for this classification were IL-6, IL-8, CCL2, IL-13, TNFalpha, and IL-2. CONCLUSIONS: Application of multiplex bead immunoassays has allowed us to identify distinct patterns of cytokines that relate to both clinical disease and the cellular infiltrates present. Bioinformatics analysis allowed identification of cytokines that differentiate idiopathic uveitis from noninflammatory control AqH and are likely to be important for the pathogenesis of uveitis.