The impact of Tai Chi and Qigong mind-body exercises on motor and non-motor function and quality of life in Parkinson's disease: A systematic review and meta-analysis.

PURPOSE: To systematically evaluate and quantify the effects of Tai Chi/Qigong (TCQ) on motor (UPDRS III, balance, falls, Timed-Up-and-Go, and 6-Minute Walk) and non-motor (depression and cognition) function, and quality of life (QOL) in patients with Parkinson's disease (PD). METHODS: A systematic search in 7 electronic databases targeted clinical studies evaluating TCQ for individuals with PD published through August 2016. Meta-analysis was used to estimate effect sizes (Hedges's g) and publication bias for randomized controlled trials (RCTs). Methodological bias in RCTs was assessed by two raters. RESULTS: Our search identified 21 studies, 15 of which were RCTs with a total of 735 subjects. For RCTs, comparison groups included no treatment (n = 7, 47%) and active interventions (n = 8, 53%). Duration of TCQ ranged from 2 to 6 months. Methodological bias was low in 6 studies, moderate in 7, and high in 2. Fixed-effect models showed that TCQ was associated with significant improvement on most motor outcomes (UPDRS III [ES = -0.444, p < 0.001], balance [ES = 0.544, p < 0.001], Timed-Up-and-Go [ES = -0.341, p = 0.005], 6 MW [ES = -0.293, p = 0.06], falls [ES = -0.403, p = 0.004], as well as depression [ES = -0.457, p = 0.008] and QOL [ES = -0.393, p < 0.001], but not cognition [ES = -0.225, p = 0.477]). I2 indicated limited heterogeneity. Funnel plots suggested some degree of publication bias. CONCLUSION: Evidence to date supports a potential benefit of TCQ for improving motor function, depression and QOL for individuals with PD, and validates the need for additional large-scale trials.

Rumination variations: aetiology and classification of abnormal behavioural responses to digestive symptoms based on high-resolution manometry studies.

BACKGROUND: Rumination is the voluntary, albeit subconscious return of gastric contents to the mouth. Currently, rumination syndrome and repetitive belching disorders are considered separate diagnoses, as defined by Rome III criteria and high-resolution oesophageal manometry (HRM). AIM: To test the hypothesis that these conditions represent a common behavioural response to aversive digestive stimuli and that successful treatment can be directed at both the stimulus and the response. METHODS: Case-note review of consecutive patients with a final diagnosis of behavioural digestive disorders between August 2009 and October 2011. RESULTS: Thirty-five of 46 (76%) patients exhibited 'classical' rumination with abdomino-gastric strain (R-waves) driving gastric contents across the lower oesophageal sphincter; 5 (11%) had 'reflux-related' rumination with R-waves seen during gastro-oesophageal common cavity (reflux) events and 6 had (13%) supra-gastric belching. All received at least one biofeedback session at the time of diagnosis with a good response reported by 20/46 (43%) of the patients, which included 3 with supra-gastric belching. Additionally, rumination ceased in cases in which definitive treatment relieved the symptoms that triggered abnormal behaviour (e.g. fundoplication in 'reflux-rumination'). CONCLUSIONS: Rumination and many of its variations, excluding only some cases of supra-gastric belching, are associated with abdomino-gastric strain, a generic abnormal behavioural response to a variety of aversive digestive stimuli. All types of rumination can respond to biofeedback. High-resolution oesophageal manometry identifies subgroups with distinct mechanisms of disease that respond to specific management targeted at the symptoms that trigger the abnormal behaviour.

Tuberculosis in HIV programmes in lower-income countries: practices and risk factors.

BACKGROUND: Tuberculosis (TB) is a common diagnosis in human immunodeficiency virus (HIV) infected patients on antiretroviral treatment (ART). OBJECTIVE: To describe TB-related practices in ART programmes in lower-income countries and identify risk factors for TB in the first year of ART. METHODS: Programme characteristics were assessed using standardised electronic questionnaire. Patient data from 2003 to 2008 were analysed and incidence rate ratios (IRRs) calculated using Poisson regression models. RESULTS: Fifteen ART programmes in 12 countries in Africa, South America and Asia were included. Chest X-ray, sputum microscopy and culture were available free of charge in respectively 13 (86.7%), 14 (93.3%) and eight (53.3%) programmes. Eight sites (53.3%) used directly observed treatment and five (33.3%) routinely administered isoniazid preventive treatment (IPT). A total of 19 413 patients aged ≥ 16 years contributed 13,227 person-years of follow-up; 1081 new TB events were diagnosed. Risk factors included CD4 cell count (>350 cells/µl vs. <25 cells/µl, adjusted IRR 0.46, 95%CI 0.33-0.64, P < 0.0001), sex (women vs. men, adjusted IRR 0.77, 95%CI 0.68-0.88, P = 0.0001) and use of IPT (IRR 0.24, 95%CI 0.19-0.31, P < 0.0001). CONCLUSIONS: Diagnostic capacity and practices vary widely across ART programmes. IPT prevented TB, but was used in few programmes. More efforts are needed to reduce the burden of TB in HIV co-infected patients in lower income countries.

Effect of presumptive co-trimoxazole prophylaxis on pneumococcal colonization rates, seroepidemiology and antibiotic resistance in Zambian infants: a longitudinal cohort study.

OBJECTIVE: To ascertain the microbiological consequences of WHO's recommendation for presumptive co-trimoxazole prophylaxis for infants with perinatal HIV exposure. METHODS: Using a longitudinal cohort design, we followed HIV-exposed and HIV-unexposed infants trimonthly for up to 18 months per infant. HIV-exposed infants received daily co-trimoxazole prophylaxis from 6 weeks to > or = 12 months of age. Using Streptococcus pneumoniae as our sentinel pathogen, we measured how co-trimoxazole altered nasopharyngeal colonization, pneumococcal resistance to antibiotics and serotype distribution as a function of co-trimoxazole exposure. FINDINGS: From 260 infants followed for 3096 patient-months, we detected pneumococci in 360/1394 (25.8%) samples. HIV-exposed infants were colonized more frequently than HIV-unexposed infants (risk ratio, RR: 1.4; 95% confidence interval, CI: 1.0-1.9, P = 0.04). Co-trimoxazole prophylaxis reduced colonization by ca 7% but increased the risk of colonization with co-trimoxazole-resistant pneumococci within 6 weeks of starting prophylaxis (RR: 3.2; 95% CI: 1.3-7.8, P = 0.04). Prophylaxis with co-trimoxazole led to a small but statistically significant increase of nasopharyngeal colonization with pneumococci not susceptible to clindamycin (RR: 1.6; 95% CI: 1.0-2.6, P = 0.04) but did not increase the risk of non-susceptibility to penicillin (RR: 1.1; 95% CI: 0.7-1.7), erythromycin (RR: 1.0; 95% CI: 0.6-1.7), tetracycline (RR: 0.9; 95% CI: 0.6-1.5) or chloramphenicol (RR: 0.8; 95% CI: 0.3-2.3). Co-trimoxazole prophylaxis did not cause the prevailing pneumococcal serotypes to differ from those that are targeted by the 7-valent conjugate pneumococcal vaccine (RR: 1.0; 95% CI: 0.7-1.6). CONCLUSION: Co-trimoxazole prophylaxis modestly suppresses pneumococcal colonization but accelerates infant acquisition of co-trimoxazole- and clindamycin-resistant pneumococci. Co-trimoxazole prophylaxis appears unlikely to compromise the future efficacy of conjugate vaccines.

Clinical trial: the effects of adding ranitidine at night to twice daily omeprazole therapy on nocturnal acid breakthrough and acid reflux in patients with systemic sclerosis--a randomized controlled, cross-over trial.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is an important problem in systemic sclerosis due to impaired salivation and oesophageal function. AIM: To determine the efficacy of adding ranitidine at bedtime to control nocturnal acid breakthrough (NAB) and GERD in patients with systemic sclerosis already prescribed high-dose omeprazole. METHODS: Patients with systemic sclerosis and GERD symptoms (n = 14) were treated with omeprazole 20 mg b.d. and either placebo or ranitidine 300 mg at bedtime for 6 weeks in a randomized, cross-over, placebo controlled study. At the end of each period a 24 h pH-study with intragastric and oesophageal pH measurement was performed. RESULTS: Pathological acid reflux occurred in eight patients with omeprazole/placebo and in seven with omeprazole/ranitidine (P = ns) with technically adequate oesophageal pH-studies (n = 13). NAB was present in eight patients with omeprazole/placebo and six with omeprazole/ranitidine (P = ns) in whom technically adequate gastric pH-studies were obtained (n = 10). The addition of ranitidine had no consistent effect on patient symptoms or quality of life. CONCLUSION: Many patients with systemic sclerosis experienced NAB and pathological oesophageal acid exposure despite high-dose acid suppression with omeprazole b.d. Adding ranitidine at bedtime did not improve NAB, GERD or quality of life in this population.

Measurement of in situ hybridization.

Hybridization of labeled specific molecular probes to nucleic acids in tissues allows geometric and functional location of gene expression or of foreign genome sequences. Estimates of amounts and location of target nucleic acid sequence can be made with phosphor storage imaging and molecular controls.

The long-term cost-effectiveness of improving alcohol abstinence with adjuvant acamprosate.

A computer model was developed with decision analysis software to explore the long-term clinical and economic outcomes of alcohol abstinence maintenance with either standard counselling therapy or standard therapy plus 48 weeks of adjuvant acamprosate in detoxified alcoholic patients. Important complications of alcoholism were modelled using Markov processes, and included relapse (return to drinking), alcohol-related hepatic disease, acute and chronic pancreatitis, acute and chronic gastritis, oropharyngeal carcinoma, oesophageal carcinoma, alcoholic cardiomyopathy, alcohol-related peripheral neuropathy, alcoholic psychosis, accidental death, and suicide. Probabilities of developing complications were dependent on whether the patients within the cohort remained abstinent or had relapsed. Relapse rates, probabilities, and costs for acamprosate therapy and treatment of complications were taken from published literature. The analysis was performed from the German health insurance perspective. Life expectancy and total lifetime costs (costs of initial abstinence maintenance therapy plus costs of complications) were calculated for a typical male cohort with average age of 41 years, 80% with fatty liver, 15% with cirrhosis, 22% with chronic pancreatitis, and 1% with alcoholic cardiomyopathy at baseline. Life expectancy with and without acamprosate therapy was 15.90 and 14.70 years respectively, and discounted (5% per annum) average total lifetime costs per patient were DEM 46 448 and DEM 49 549 respectively. We conclude that, despite the acquisition costs of DEM 2177, adjuvant acamprosate therapy was both clinically and economically attractive under conservative assumptions.

Tumour cell kinetics as predictors of response in canine lymphoma treated with chemotherapy alone or combined with whole body hyperthermia.

Kinetic parameters including potential doubling time (Tpot), duration of S phase (Ts), labelling index (LI), and DNA index (DI) were obtained from 42 dogs with previously untreated lymphoma. Standard flow cytometric techniques using BrdUrd were employed. All dogs were treated with L-asparaginase and remission was induced in 26 dogs, which were then randomized to receive chemotherapy only (doxorubicin [DOX] alone or with lonidamine) or chemotherapy plus whole body hyperthermia (WBH). Dogs were treated every 3 weeks for up to five treatments and evaluated every 3 weeks for evidence of tumour recurrence. Within this subset of animals there was no difference in outcome based on treatment group. Median values for Tpot, Ts and LI were 3.4 days, 7.23 h and 12.49%, respectively. Dogs that had tumours with LI > or = 20% had a shorter time until recurrence than dogs with tumours characterized by LI < 20%. In dogs treated only with chemotherapy, dogs bearing tumours with longer than median Tpot and Ts values and lower than median LI had significantly longer remission duration than dogs with more rapidly proliferating tumours. Dogs treated only with chemotherapy, which had longer than median Tpot and Ts values and lower than median LI, had significantly longer remission duration than all other dogs in the study. The mechanisms in which kinetics are associated with response to chemotherapy are not clear and vary depending on tumour type and treatment regimen. More work is needed to understand factors involved in cell killing during in vivo hyperthermia.

Accumulation of fibrinogen-coated microparticles at a fibrin(ogen)-rich inflammatory site.

We have developed methods for coating with fibrinogen both liposomes and microscopic droplets of olive oil. Because the fibrinogen bound to them is functional in the classic sense of fibrin gelation, the coated microparticles may have potential as vehicles for the targeted delivery of various molecules to sites of fibrin(ogen) deposition in vivo. So that we could assess directly this potential, we first established a method for eliciting reproducibly a focal, fibrin(ogen)-rich, inflammatory lesion in a hind footpad of mice. We then monitored the tissue distribution of fibrinogen-coated microparticles following their injection into the tail vein of mice bearing this well-defined lesion. As happens with most microparticles following their intravenous administration, liposomes and oil droplets, whether coated with fibrinogen or not, accumulate rapidly in the liver and spleen of treated animals. Indeed, in the case of oil droplets, accumulation of fibrinogen-coated microparticles in those organs and in the lungs is even greater than that of fibrinogen-free microparticles. However, as distinct from fibrinogen-free liposomes and oil droplets, fibrinogen-coated microparticles also accumulate in the inflamed hind footpad. We conclude that fibrinogen-coated liposomes and oil droplets do have potential as vehicles for delivering molecules to sites of fibrin(ogen) deposition in vivo.

Molecular characterization of a neuronal low-voltage-activated T-type calcium channel.

The molecular diversity of voltage-activated calcium channels was established by studies showing that channels could be distinguished by their voltage-dependence, deactivation and single-channel conductance. Low-voltage-activated channels are called 'T' type because their currents are both transient (owing to fast inactivation) and tiny (owing to small conductance). T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing. Here we report the identification of a neuronal T-type channel. Our cloning strategy began with an analysis of Genbank sequences defined as sharing homology with calcium channels. We sequenced an expressed sequence tag (EST), then used it to clone a full-length complementary DNA from rat brain. Northern blot analysis indicated that this gene is expressed predominantly in brain, in particular the amygdala, cerebellum and thalamus. We mapped the human gene to chromosome 17q22, and the mouse gene to chromosome 11. Functional expression of the channel was measured in Xenopus oocytes. Based on the channel's distinctive voltage dependence, slow deactivation kinetics, and 7.5-pS single-channel conductance, we conclude that this channel is a low-voltage-activated T-type calcium channel.

Pathophysiology of infection with gastrointestinal nematodes in domestic ruminants: recent developments.

Infection with gastrointestinal nematodes, particularly Ostertagia species in domestic ruminants, continues to represent an important cause of impaired productivity in temperate parts of the world. The mechanisms responsible for such losses include changes in feed intake, gastrointestinal function, protein, energy and mineral metabolism, and body composition, and were described in detail at the last Ostertagia Workshop (Fox, M.T. 1993. Pathophysiology of infection with Ostertagia ostertagi in cattle. Vet. Parasitol. 46, 143-158). Since then, research into the pathophysiology of infection has focused on three main areas: mechanisms of appetite depression; changes in gastrointestinal function; and alterations in protein metabolism. Studies on the mechanisms responsible for appetite depression in Ostertagia-infected cattle have continued to support a close association between impaired feed intake and elevated blood gastrin concentrations. Alternative explanations will have to be sought, however, to account for the drop in feed intake associated with intestinal parasitism in which blood gastrin levels normally remain unaltered. Such work in sheep, and more recently in laboratory animals, has shown that central satiety signals are associated with inappetance accompanying intestinal infections, rather than changes in peripheral peptide levels. Changes in gastrointestinal function have also attracted attention, particularly the mechanisms responsible for increases in certain gut secretions, notably pepsinogen and gastrin. Elegant experimental studies have established that the gradient in pepsinogen concentration between abomasal mucosa and local capillaries could alone account for the increase in blood concentrations seen in Type 1 ostertagiosis. Additional factors, such as increases in capillary permeability and in surface area, probably contribute to such responses in cases of Type 2 disease. The increase in blood gastrin concentrations that accompanies Ostertagia infections in cattle is associated with the concurrent rise in abomasal pH. However, in sheep, additional factors appear to contribute to the hypergastrinaemia which may occur independent of parasite-induced changes in gastric pH. Alterations in protein metabolism have been well documented in ruminants harbouring monospecific infections with either abomasal or intestinal nematodes. More recently, however, the effects of dual abomasal and intestinal infections have been investigated and demonstrated that the host is able to compensate for impaired abomasal digestion provided that the intestinal parasite burden does not occupy the main site of digestion and absorption in the latter organ. An alternative method of improving the host's protein balance, dietary supplementation, has been shown not only to improve productivity, but also to enhance the innate resistance of susceptible breeds of sheep to Haemonchus and to accelerate the development of immunity to Ostertagia in lambs.

The taste of intravenous thiopentone.

Patients sometimes notice an onion or garlic taste before losing consciousness with thiopentone. An assessment of 113 patients revealed that 42% of patients noticed this taste. The effect was observed less in older patients. There was no statistically significant difference in the incidence between men and women. Premedicated patients had a lower incidence, but this was explained by the greater proportion of older patients receiving a premedication. If the taste effect of thiopentone is genetically determined then it is a different gene to thiocarbamate which has about 75% tasters.

The role of intracellular free calcium in the cellular response to hyperthermia.

The intracellular free calcium (Ca++i) concentration was measured in several cell lines after heating at 45.0 degrees C using flow cytometry with indo-1. Chinese hamster ovary 10B2 (CHO) cells do not stain well with indo-1, so a CHO mutant cell line (CHO IS1) isolated in our laboratory with much-improved stainability for indo-1 was used to study CA++i changes in heated CHO cells. BALB-3T3 (mouse) and EJ30 (human) cells were also studied. Cells were heated in the sample holder of the cell sorter in order to measure Ca++i within seconds after heating. Ca++i increased rapidly within the first 5 min of heating at 45.0 degrees C in all three lines, though the magnitude of the increase varied for each cell line. The Ca++i returned rapidly to baseline after heating in CHO IS1 cells and BALB-3T3 cells. After 5 min of heating, the Ca++i plateaued in the EJ30 and IS1 cells, but decreased in the 3T3 cells. There was an inverse relationship between the Ca++i after 10 min at 45 degrees C and survival for the different cell lines. Thermotolerant cells experienced a similar change in Ca++i during heating as non-thermotolerant cells, though the kinetics were somewhat different for the IS1 cells. A bimodal distribution of Ca++i developed in EJ30 cells by 2 min after heating. Cells sorted from the near-normal Ca++i region of the histogram had a 2-fold higher survival rate than the cells which had a high Ca++i concentration. These data support the view that Ca++i changes during heating are not the principal factor in heat-induced cell death.

Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation.

We report here on a preliminary human autologous transplantation study of retroviral gene transfer to bone marrow (BM) and peripheral blood (PB)-derived CD34-enriched cells. Eleven patients with multiple myeloma or breast cancer had cyclophosphamide and filgrastim-mobilized PB cells CD34-enriched and transduced with a retroviral marking vector containing the neomycin resistance gene, and CD34-enriched BM cells transduced with a second marking vector also containing a neomycin resistance gene. After high-dose conditioning therapy, both transduced cell populations were reinfused and patients were followed over time for the presence of the marker gene and any adverse effects related to the gene-transfer procedure. All 10 evaluable patients had the marker gene detected at the time of engraftment, and 3 of 9 patients had persistence of the marker gene for greater than 18 months posttransplantation. The marker gene was detected in multiple lineages, including granulocytes, T cells, and B cells. The source of the marking was both the transduced PB graft and the BM graft, with a suggestion of better long-term marking originating from the PB graft. The steady-state levels of marking were low, with only 1:1000 to 1:10,000 cells positive. There was no toxicity noted, and patients did not develop detectable replication-competent helper virus at any time posttransplantation. These results suggest that mobilized PB cells may be preferable to BM for gene therapy applications and that progeny of mobilized peripheral blood cells can contribute long-term to engraftment of multiple lineages.

Stathmin in mung bean leaves and rat brain.

Stathmin is a highly-conserved, cytosolic protein whose synthesis and phosphorylation is closely associated with growth and differentiation. Although conserved among vertebrates, stathmin has not been identified in plants. In the present study, anti-stathmin antibodies were generated against a synthetic peptide corresponding to amino-acid residues 32-44 of rat stathmin, and these antibodies were used to probe immunoblots of proteins from rat brain and mung bean. The antibodies recognized 12-kDa, 21-kDa and 22-kDa proteins in cytosolic fractions from mung bean leaves and a 12-kDa protein in cytosolic fractions from roots. The two larger proteins identified by the antibodies have apparent molecular weights and isoelectric points similar to those of rat brain stathmin. These results are the first to show that stathmin-like proteins are present in plants.

Filtration of shed mediastinal blood.

Re-infusion of shed blood carries the risk of re-infusing cellular debris. All re-infusion devices have some sort of integral filtration which is variably supplemented with a second intravenous filter. Using electron microscopy we have observed what debris is collected by secondary filtration. In 12 patients studied, nine out of 12 filters had significant amounts of cellular debris present, but not clearly related to increased rates of postoperative bleeding. Noncellular debris, silicon and strands of cellulose were also observed. Although we have not detected any clinically significant embolic phenomena from re-infusion of shed mediastinal blood, it seems prudent to include a second filter prior to re-infusion.