The potential effects of polyunsaturated ω-3 fatty acids on spinal cord injury: A systematic review & meta-analysis of preclinical evidence.

Polyunsaturated fatty acids (PUFAs) have received attention for their anti-inflammatory and antioxidant properties. Preclinical studies have investigated the efficacy of PUFAs in animal models of spinal cord injury (SCI) to determine if these properties can translate to neuroprotection and locomotor recovery. Findings from such studies have been promising, suggesting PUFAs as potential treatments against the neurological dysfunction induced by SCI. This systematic review and meta-analysis sought to investigate the efficacy of PUFAs for promoting locomotor recovery in animal models of SCI. PubMed, Web of Science and Embase (Ovid) were searched for relevant papers and those that examined the restorative effects of PUFAs on locomotor recovery in preclinical SCI models were included in our analysis. A random effects meta-analysis (restricted maximum likelihood estimator) was employed. A total of 28 studies were included and the results showed the claim that PUFAs have a beneficial therapeutic effect for promoting locomotor recovery (SMD = 1.037, 95% CI = 0.809-1.2644, p = <0.001) and cell survival (SMD = 1.101, 95% CI = 0.889-1.313, p = <0.001) in animal models of SCI. No significant differences for the secondary outcomes of neuropathic pain and lesion volume. Moderate asymmetry was observed in the funnel plots for locomotor recovery, cell survival and neuropathic pain measures, suggesting publication bias. Trim-and-fill analysis estimated 13, 3, 0 and 4 missing studies for locomotor recovery, cell survival, neuropathic pain, and lesion volume, respectively. A modified CAMARADES checklist was also used to assess risk of bias, showing that the median score for all included papers was 4 out of a possible 7.

Sacral neuromodulation for persistent faecal incontinence after laparoscopic ventral rectopexy for high-grade internal rectal prolapse.

AIM: Internal rectal prolapse is recognized as an aetiological factor in faecal incontinence. Patients found to have a high-grade internal rectal prolapse on routine proctography are offered a laparoscopic ventral rectopexy after failed maximum medical therapy. Despite adequate anatomical repair, faecal incontinence persists in a number of patients. The aim of this study was to evaluate the outcome of sacral neuromodulation in this group of patients. METHOD: Between August 2009 and January 2012, 52 patients who underwent a laparoscopic ventral rectopexy for faecal incontinence associated with high-grade internal rectal prolapse had persistent symptoms of faecal incontinence and were offered sacral neuromodulation. Symptoms were evaluated before and after the procedure using the Fecal Incontinence Severity Index (FISI) and the Gastrointestinal Quality of Life Index (GIQLI). RESULTS: Temporary test stimulation was successful in 47 (94%) of the patients who then underwent implantation of a permanent pulse generator. The median FISI score 1 year after sacral neuromodulation was lower than the median score before [34 (28-59) vs. 19 (0-49); P < 0.01], indicating a significant improvement in faecal continence. Quality of life (GIQLI) was significantly better after starting sacral neuromodulation [78 (31-107) vs. 96 (55-129); P < 0.01]. CONCLUSION: Patients may benefit from sacral neuromodulation for persisting faecal incontinence after laparoscopic ventral rectopexy.

Temporary sacral neuromodulation under local anaesthesia using new anatomical reference points.

BACKGROUND: Prior to implantation of an expensive sacral nerve stimulator, a 'screening phase' is undertaken. This report examines the feasibility of temporary sacral neuromodulation under local anaesthesia in an outpatient setting. We report on our technique, results and patient satisfaction. METHODS: Percutaneous nerve evaluation was performed in 184 patients using a new set of reference points and local anaesthesia to guide insertion of a test wire without the need for fluoroscopy in an outpatient setting. Three bony landmarks were used: tip of the coccyx, sacro-coccygeal joint and posterior superior iliac spine. The technical success was defined as stimulation in the perineal/anal area at amperages <6 mAmp. A consecutive cohort of 24 patients was asked to grade their pain and satisfaction regarding the procedure. RESULTS: Successful placement of the test wire was accomplished in 171 patients (93 %). Twelve patients required placement under fluoroscopy due to lack of sensation during stimulation (N = 7) procedural pain (N = 4) or failure to identify S3 or S4 (N = 2). There were two lead infections, one lead dislocation and one lead fracture. 22 of 24 patients (92 %) would recommend the procedure under local anaesthesia to other patients. CONCLUSIONS: Temporary sacral neuromodulation can be reliably performed in a more practical, less expensive outpatient setting under local anaesthesia without adversely influencing test outcome.

MCP-1 and murine prion disease: separation of early behavioural dysfunction from overt clinical disease.

Prion diseases are chronic, fatal neurodegenerative conditions of the CNS. We have investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the ME7 model of murine prion disease. MCP-1 expression increased in the CNS throughout disease progression and was positively correlated with microglial activation. We subsequently compared the inflammatory response, pathology and behavioural changes in wild-type (wt) mice and MCP-1 knockout mice (MCP-1-/-) inoculated with ME7. Late-stage clinical signs were delayed by 4 weeks in MCP-1-/- mice, and survival time increased by 2-3 weeks. By contrast, early changes in affective behaviours and locomotor activity were not delayed in onset. There was also no difference in microglial activation or neuronal death in the hippocampus and thalamus of wt mice and MCP-1-/- mice. These results highlight an important dissociation between prolonged survival, early behavioural dysfunction and hippocampal/thalamic pathology when considering therapeutic intervention for human prion diseases and other chronic neurodegenerative conditions.

Neuropathologically distinct prion strains give rise to similar temporal profiles of behavioral deficits.

Mouse-adapted scrapie strains have been characterized by vacuolation profiles and incubation times, but the behavioral consequences have not been well studied. Here, we compared behavioral impairments produced by ME7, 79A, 22L, and 22A strains in C57BL/6J mice. We show that early impairments on burrowing, glucose consumption, nesting and open field activity, and late stage motor impairments show a very similar temporal sequence in ME7, 79A, and 22L. The long incubation time of the 22A strain produces much later impairments. However, the strains show clear late stage neuropathological differences. All strains showed clear microglial activation and synaptic loss in the hippocampus, but only ME7 and 79A showed significant CA1 neuronal death. Conversely, 22L and 22A showed significant cerebellar Purkinje neuron loss. All strains showed marked thalamic neuronal loss. These behavioral similarities coupled with clear pathological differences could serve to identify key circuits whose early dysfunction underlies the neurological effects of different prion strains.

Preoperative chemoradiotherapy and total mesorectal excision surgery for locally advanced rectal cancer: correlation with rectal cancer regression grade.

PURPOSE: Preoperative long-course chemoradiotherapy is recommended for rectal carcinoma when there is concern that surgery alone may not be curative. Downstaging of the tumor can be measured as rectal cancer regression grade (1-3) and may be of importance when estimating the prognosis. The aim of this study was to look at the long-term results of tumor regression in patients receiving long-course chemotherapy before surgical resection of rectal cancer. METHODS: We reviewed those patients who received preoperative chemoradiotherapy followed by surgical resection for carcinoma of the mid rectum or distal rectum found to be stage T3/4 between January 1995 and November 1999. Patients received 45 to 50 Gy irradiation in 2-Gy fractions and an infusion of 5-fluorouracil. Surgical specimens were assessed for rectal cancer regression grade. Patients were followed up routinely with clinical examination, computed tomography, and colonoscopy. RESULTS: Sixty-five patients with a mean age 65 (range, 32-83) years underwent chemoradiotherapy before surgical resection. Thirty patients (46 percent) were classified as rectal cancer regression Grade 1, with 9 patients (14 percent) having complete sterilization of the tumor. Fifty-three patients (82 percent) underwent a curative resection. Overall survival, with a median follow-up of 39 (range, 24-83) months, was 67 percent and was associated with tumor downstaging. The local recurrence rate was 5.8 percent in those patients who underwent a curative resection and was significantly lower with rectal cancer regression Grade 1 tumors (P = 0.03). Eight of nine patients (89 percent) whose tumor had been sterilized were alive and well with no recurrence of tumor at a median follow-up of 41 (range, 24-70) months. CONCLUSIONS: Preoperative chemoradiotherapy resulted in significant regression of tumor. Overall survival was high and was associated with downstaging of tumor. The local recurrence rate was significantly lower with rectal cancer regression Grade 1 tumors and was not seen in patients with sterilized tumors.

A comparative study of asymmetric migration events across a marine biogeographic boundary.

In many nonclonal, benthic marine species, geographic distribution is mediated by the dispersal of their larvae. The dispersal and recruitment of marine larvae may be limited by temperature gradients that can affect mortality or by ocean currents that can directly affect the movements of pelagic larvae. We focus on Point Conception, a well-known biogeographic boundary between the Californian and Oregonian biogeographic provinces, to investigate whether ocean currents affect patterns of gene flow in intertidal marine invertebrates. The predominance of pelagically dispersing species with northern range limits at Point Conception suggests that ocean currents can affect species distributions by erecting barriers to the dispersal of planktonic larvae. In this paper, we investigate whether the predominantly southward currents have left a recognizable genetic signature in species with pelagically dispersing larvae whose ranges span Point Conception. We use patterns of genetic diversity and a new method for inferring cladistic migration events to test the hypothesis that southward currents increase southward gene flow for species with pelagically dispersing larvae. We collected mitochondrial DNA (mtDNA) sequence data for the barnacles Balanus glandula and Chthamalus fissus and also reanalyzed a previously published mtDNA dataset (Strongylocentrotus purpuratus, Edmands et al. 1996). For all three species, our cladistic approach identified an excess of southward migration events across Point Conception. In data from a fourth species with nondispersing larvae (Nucella emarginata, Marko 1998), our method suggests that ocean currents have not played a role in generating genetic structure.

Effects of transcendental meditation on symptoms and electrocardiographic changes in patients with cardiac syndrome X.

Chest pain with normal coronary angiograms is often associated with chronic sympathetic activation, anxiety, and depression, and is resistant to conventional antianginal treatment. The practice of transcendental meditation, a standard relaxation method for 3 months twice daily, significantly improved exercise tolerance, angina episodes, and quality of life in 9 women; the positive findings in this study warrant further research.

Double-blind study of pulsing magnetic field effects on multiple sclerosis.

We performed a double-blind study to measure the clinical and subclinical effects of an alternative medicine magnetic device on disease activity in multiple sclerosis (MS). The MS patients were exposed to a magnetic pulsing device (Enermed) where the frequency of the magnetic pulse was in the 4-13 Hz range (50-100 milliGauss). A total of 30 MS patients wore the device on preselected sites between 10 and 24 hours a day for 2 months. Half of the patients (15) randomly received an Enermed device that was magnetically inactive and the other half received an active device. Each MS patient received a set of tests to evaluate MS disease status before and after wearing the Enermed device. The tests included (1) a clinical rating (Kurtzke, EDSS), (2) patient-reported performance scales, and (3) quantitative electroencephalography (QEEG) during a language task. Although there was no significant change between pretreatment and posttreatment in the EDSS scale, there was a significant improvement in the performance scale (PS) combined rating for bladder control, cognitive function, fatigue level, mobility, spasticity, and vision (active group -3.83 +/- 1.08, p < 0.005; placebo group -0.17 +/- 1.07, change in PS scale). There was also a significant change between pretreatment and posttreatment in alpha EEG magnitude during the language task recorded at various electrode sites on the left side. In this double-blind, placebo-controlled study, we have demonstrated a statistically significant effect of the Enermed magnetic pulsing device on patient performance scales and on alpha EEG magnitude during a language task.

Pavlovian conditioning of morphine hyperthermia: assessment of interstimulus interval and CS-US overlap.

The present study examined the effect of interstimulus interval on acquisition of conditioned thermal responses produced by trials in which a light/noise stimulus (CS) was repeatedly paired with infusion of morphine sulphate (US). Rats were implanted with a chronic intravenous catheter for drug delivery and a biotelemetry device for remote monitoring of core body temperature. In experiment 1, different groups received morphine either 0.5 (group P0.5) or 15 min (group P15) after onset of the 15-min CS. A third group was exposed to an identical number of CS and US presentations but in an explicitly unpaired manner (group UP). After repeated exposure to morphine, all groups showed a more rapid rise in body temperature in response to drug infusion. Test presentations of CS alone revealed conditioned hyperthermic responses to CS in groups P0.5 and P15. However, the response of the P15 group was smaller than that of the P0.5 group, suggesting weaker conditioning at the longer interstimulus interval. The contribution of CS-US overlap to the diminished associative strength observed in the P15 group was assessed in experiment 2. Groups P0.5/15 and P0.5/30 received infusions of morphine 0.5 min after onset of a 15- or 30-min CS, respectively. Group P15/30 received morphine 15 min after onset of a 30 min CS, whereas group UP/30 received explicitly unpaired presentations of the US and a 30-min CS. Enhancement of the hyperthermic effect of morphine was observed in all groups after ten conditioning trials. Test presentations of the CS without drug revealed that all paired groups had acquired conditioned hyperthermic responses. These results support the conclusion that drug-induced conditioning can occur at relatively long interstimulus intervals when there is sufficient temporal overlap between the CS and unconditioned response evoked by the drug US.

A comparison of tissue reactions to Ketac-Fil and amalgam.

The objective of this study was to compare the bone tissue reactions of Ketac-Fil to the most commonly used retrograde filling material, amalgam, in a rat model. Forty-eight Harlan rats were divided into three groups: amalgam, Ketac-Fil, and controls. Following anesthesia, the right lower incisor was extracted from each animal. A 3-mm long x 1-mm diameter polyethylene tube filled with amalgam or Ketac-Fil was implanted in the extraction site. The animals were killed at 14, 42, and 90 days; and the mandibles were dissected en block and processed histologically. The inflammatory reaction was assessed by the number of plasma cells, lymphocytes, polymorphonuclear neutrophils, giant cells, and osteoclasts within 100 microns of the implant. Bone formation was determined as either present or absent in the same area. There was no statistically significant bone apposition within 100 microns of the Ketac material, and there was a statistically significant increase in inflammation in the amalgam group. This study indicates that both Ketac-Fil and amalgam are relatively biocompatible, and provides support for clinical usage tests of Ketac-Fil as a retrograde filling material.

Oral ciprofloxacin therapy for infections in cancer patients.

Forty six episodes of infection in 43 cancer patients were treated with oral ciprofloxacin at a dose of 750 mg every 8 h. The overall clinical response was 85%. Patients with microbiologically proven infections had a higher response rate (90%) than patients with infections from whom no causative organism(s) could be isolated (69%). Two of three neutropenic patients responded favourably. Favourable responses were seen in a variety of infections including bacteraemia, urinary tract infection, respiratory tract infection and skin and soft-tissue infection. Resistance to ciprofloxacin developed in one isolate of Pseudomonas aeruginosa. Side effects were mild and were predominantly gastrointestinal in nature. Orally administered ciprofloxacin is safe and effective for the therapy of many serious infections in cancer patients. However, more data are required in patients who are neutropenic.

Use of nuclear magnetic resonance spectroscopy to study the effects of ethanol consumption on liver metabolism and pathology.

The application of NMR spectroscopy to studies of intact organs represents a powerful technology applicable for investigations of alcohol-induced liver disease in animal models. NMR-assisted studies of ethanol metabolism and its related pathology are now possible utilizing the 13C and 31P nuclei primarily. The major advantage of the technology includes the capacity to investigate biochemical processes at the level of the intact organ which is analyzed as a perfused preparation or in situ in an anesthetized animal model. Quantitative measurements of compounds containing either 31P or 13C nuclei are possible, and the kinetics of precursor incorporation into compounds associated with carbohydrate, lipid, and amino acid metabolism are readily followed. The concentrations of free Mg2+ and the pH of the intact liver can be monitored as a function of external perturbation and/or metabolic disturbances.

Training and education approaches for parents of children with special needs.

This is a review of attempts made to involve and to train parents in the endeavour of helping their children with special needs. The reasons for parent involvement are discussed, before describing and contrasting the variety of theoretical orientations and parenting skills that have been considered in this work, and the influences of parent and child characteristics. Detailed consideration is given to the methods used in training and their effectiveness. Although parent involvement can be said to be of value, more effort is required in terms of careful conceptualization and more elaborate multivariate research before definite answers may be provided for many of the issues raised.

Experimental analysis of EMG feedback in treating cerebral palsy.

Three subjects diagnosed as having severe choreoathetoid cerebral palsy were trained in the use of EMG feedback procedures. Both between- and within-session controls, including reversals of baseline, attempted muscle control with feedback, and muscle control without feedback, were employed to analyze the contribution of feedback procedures to improvements in muscle control. The data (1) indicate that feedback enhanced muscle control and (2) provide evidence of generalization of feedback effects to no-feedback conditions and untrained muscles.

Reactivation of the lipid-depleted pyruvate oxidase system from Escherichia coli with cell envelope neutral lipids.

The pyruvate oxidase system of Escherichia coli is composed of a soluble flavoprotein, pyruvate oxidase (EC 1.2.2.2, pyruvate:ferricytochrome b1 oxidoreductase), and an electron transport system associated with the cell envelope-membrane fraction. The membrane particles contain 15% lipid by weight. Fractionation of the lipids revealed that abut one-third are neutral lipids and two-thirds are phospholipids. The relative ratio of ubiquinone to menaquinone within the neutral lipid fraction is 15:1 on a molar basis. Removal of the lipids from the membrane particles by extraction with aqueous acetone or hydrolysis of the phospholipids by treatment with Bacillus cereus phospholipase C results in a complete loss of electron transport activity. Analysis of the particles extracted with aqueous acetone revealed that practically all the neutral lipids and 65% of the phospholipids are removed by this treatment. Phospholipase treatment results in a loss of 75% of the membrane phospholipid phosphorus; however, the diglycerides and the neutral lipids produced by phospholipase hydrolysis remain associated with the particles. Addition of neutral lipid and a detergent, hepta-DL-alanyl dodecylamide to the acetone-extracted material results in a restoration of 37% of the original particle activity. Addition of neutral lipid and hepta-DL-alanyl dodecylamide to phospholipase-treated particles completely restores the original electron transport activity. Furthermore, addition of ubiquinone from either yeast (UQ6) or E. coli (UQ8) will restore pyruvate oxidase activity when the quinones are supplemented with photoinactivated neutral lipid. No restoration of activity to phospholipase-treated particles is noted upon the addition of either menaquinone 6 or menaquinone 8 to the reconstitution system. In fact, these compounds appear to suppress restoration of activity when they are added to reaction mixtures containing neutral lipid and phospholipase-treated particles.