The combination of inhaled corticosteroids and long-acting beta2-adrenoceptor agonists is increasingly used as maintenance therapy in patients with moderate to severe asthma or chronic obstructive pulmonary disease (COPD). The main effect of inhaled corticosteroids is thought to be mediated through suppression of airway inflammation, while long-acting beta2-adrenoceptor agonists are thought to work by inducing bronchodilation. However, there is emerging data to indicate that these two classes of drugs interact positively with each other, leading to added or perhaps synergistic benefits for patients. Corticosteroids enhance the expression of beta2-adrenoceptor, thus providing protection against desensitization and development of tolerance to beta2-adrenoceptor agonists, which may occur with prolonged use of these medications. Long-acting beta2-adrenoceptor agonists, on the other hand, may amplify the anti-inflammatory effects of corticosteroids by accelerating nuclear translocation of the glucocorticoid receptor complex, and enhancing transcription and expression of steroid-inducible genes in pro-inflammatory cells. In clinical trials, corticosteroids in combination with long-acting beta2-adrenoceptor agonists reduce exacerbation rates, and improve lung function and health status of patients with moderate to severe asthma or COPD beyond that achieved by individual component therapy. Their effects on mortality are unknown. There is a large clinical trial currently underway, which will provide mortality data by the year 2006. On balance, clinical evidence supports the use of combination therapy in moderate to severe asthma and COPD.

Medicinal plants have become extremely popular in the United States as botanical supplements, herbal medicines and sources of lead compounds for pharmaceutical development. It is estimated that in 1997 Americans used or consumed 5.1 billion US dollars worth of herbal medicines. For the protection of consumers, authentication of medicinal plants is a critical issue. Ideally, authentication should occur from the harvesting of the plant material to the final product. Unfortunately there is no single or superior method to assure 100 percent authentication during the entire process, but the goal can be achieved through the application of a variety of different methodologies. The whole process starts with good voucher specimens that act as reference material and to prove chain of custody. Macroscopic and microscopic examinations can be used as rapid and inexpensive identification techniques. Chemical analysis is by far the best method for the detection of contaminants and can be an excellent method for plant identification. Each of these methodologies has limitations and more analytical methods are needed to assist in the authentication process. Molecular biology offers an assortment of techniques that can be very useful for authentication of medicinal plants. This review covers various aspects of authentication methods, with special emphasis on molecular biology techniques.

A double-blind, placebo-controlled trial of gamma-vinyl gamma-aminobutyric acid (GVG) and 4,5,6,7-tetrahydroisoxazolo-(5,4-c) pyridine-3-ol (THIP) was carried out in drug-free schizophrenic patients with tardive dyskinesia. A significant decrease in dyskinetic symptoms occurred with the administration of GVG, associated with a twofold increase in cerebrospinal fluid levels of GABA; THIP produced a more moderate, yet consistent decrease in the involuntary movements. A pathophysiologic role for gamma-aminobutyric acid (GABA)-mediated neuronal transmission in tardive dyskinesia was explored by analyzing cerebrospinal fluid GABA concentrations in drug-free schizophrenic patients with and without tardive dyskinesia. A significant reduction in cerebrospinal fluid levels of GABA was observed in the dyskinetic schizophrenics compared with the nondyskinetic controls. These data compliment a growing body of experimental evidence suggesting a critical role for GABA-ergic neurons in the pathophysiology of tardive dyskinesia.

This study focuses on changes in adrenergic sensitivity in untransected sensory axons that innervate an area of skin made neuropathic by transection of neighboring nerves. The segmental nerve injury model is favorable for this since all axons in the L5 and L6 nerves are transected whereas the L4 axons are intact. Earlier findings are that pain behaviors develop after this injury and that these behaviors are ameliorated by sympathectomy. The present study shows that behavior indicating mechanical allodynia can be rekindled after sympathectomy by intradermal norepinephrine and alpha-2 but not alpha-1 adrenergic ligands and the rekindling can be blocked by alpha-2 but not alpha-1 adrenergic antagonists. By contrast neither intradermal norepinephrine nor other adrenergic agonists or antagonists have any demonstrable effects in the normal or after either neuropathic surgery or sympathectomy alone. These data suggest that the combination of neuropathic surgery and sympathectomy results in an upregulation of active alpha-2 adrenergic receptors on the undamaged sensory axons that provide the remaining sensory innervation to a neuropathic area partially denervated by segmental nerve lesions. These changes on undamaged axons presumably compliment similar changes on the transected axons and, thus play a role in the development of neuropathic pain.

The development of syntheses providing enantiomerically pure alpha-amino acids has intrigued generations of chemists and been the subject of intense research. This report describes a general approach to functionalized alpha-amino acids based on catalytic asymmetric synthesis. Proline catalyzed Mannich-type reactions of N-PMP-protected alpha-imino ethyl glyoxylate with a variety of unmodified ketones to provide functionalized alpha-amino acids in high yields with excellent regio-, diastereo-, and enantioselectivities. Study of seven examples yielded six with product ee values of>> or = 99%. In reactions involving ketone donors where diastereoisomeric products could be formed, two adjacent stereogenic centers were created simultaneously upon carbon-carbon bond formation with complete syn-stereocontrol. Significantly, this methodology utilizes readily available and rather inexpensive starting materials, does not require any preactivation of substrates or metal ion assistance, and can be carried out on a gram scale under operationally simple reaction conditions. The keto-functionality present in the products provides a particularly attractive site for versatile modifications. This study compliments and extends our bioorganic approach to asymmetric synthesis to a versatile synthon class. Given that we have shown that a variety of optically active amino acids can be synthesized with proline catalysis, where an L-amino acid begets other L-amino acids, our results may stimulate thoughts concerning prebiotic syntheses of optically active amino acids based on this route.

The microbial mat community in the saltmarsh/evaporate flat interface at Laguna Figueroa involved in the deposition of laminated sediments was investigated. Pigment analysis, light microscopy and transmission electron microscopy were used to determine the relative abundance and distribution of phototrophic species. The community is vertically stratified into four distinct phototrophic populations. The layering could be distinguished by pigment and species composition. The two layers closest to the surface contained mostly oxygenic phototrophs and chlorophyll a as the primary photosynthetic pigment. Anoxic phototrophs predominated in the bottom two layers with bacteriochlorophylls a and c in the third layer and bacteriochlorophyll a and b in the bottom layer. The surface yellow layer was composed primarily of Navicula, Rhopalodia and other diatom species as well as the cyanobacteria Aphanothece sp. and Phormidium sp. Microcoleus chthonoplasces and Chroococcidiopsis sp. were the major cyanobacteria in the green colored second layer. In the third layer, pinkish-purple in color, purple photographs (Chromatium sp., Thiocapsa roseoparsicina) and filamentous green phototrophs (Chloroflexus sp., Oscillochloris sp.) were abundant. The fourth and deepest photosynthetic layer was salmon colored and composed primarily of Thiocapsa pfennigii, and other purple sulfur phototrophs. The pattern of alternating light (oxygenic community) and dark (anoxygenic community) layering preserved in older laminae is a consequence of this community structure. Study of the flat laminated mat over the 10-year period (1978-1988) including and after its destruction by catastrophic flooding events in 1978 and 1980, showed a succession of stratified communities culminating in the return of Microcoleus and the full compliment of layers by the fall of 1984.

Argon plasma coagulation (APC) is a thermal coagulation technique that uses ionized argon to transmit high-frequency electrical current, contact free, to tissue. APC has been used in surgery for more than 20 years, particularly for the hemostasis of superficial bleeding. Although APC has become well established in gastrointestinal endoscopy since its introduction in 1991, very few reports of its use in bronchoscopy exist to date. From June 1994 to June 1998, 364 patients (80 women, 284 men), 88% with a confirmed malignant tumor, were treated prospectively in a total of 482 sessions. The single most common indication was recanalization of malignant airway stenoses (186 patients). The defined therapy objective was achieved with good results in 67% of patients. More than 90% of interventions were performed with rigid bronchoscopy. Despite less penetration compared with Nd:YAG laser, extensive bronchial tumors were treatable, in which coagulated tumor fractions were removed either with forceps or bronchoscope tip. The second indication was bleeding in the central airways (119 patients). Acute hemostasis was achieved in 118 patients, 20% in whom the flexible technique under local anesthesia was used. In 34 patients, APC was successfully used to recanalize occluded stents. Rare indications included benign endobronchial tumor, fistula conditioning before fibrin adhesion, and the treatment of scar tissue stenosis. Summarizing all complications, a rate of 3.7% "per treatment" was recorded. Two patients died within 24 hours; their deaths were not directly related to APC. APC is an effective and safe technique for the treatment of bronchologic tumor ablation and hemostasis and can be used with local anaesthetic with flexible bronchoscopy or rigid bronchoscopy with general anesthesia. Compared with Nd:YAG laser, APC is an economic alternative technique offering more effective hemostasis. Furthermore, APC is of particular value as a compliment to well-known techniques, increasing the options in interventional bronchoscopy.

The emission of trace metal pollutants by industry and transport takes place on a scale large enough to alter atmospheric chemistry and results in measurable differences between the urban background of inhalable particulate matter (PM) in different towns. This is particularly well demonstrated by the technogenic release into the atmosphere of V, Ni, and lanthanoid elements. We compare PM concentrations of these metals in large datasets from five industrial towns in Spain variously influenced by emissions from refinery, power station, shipping, stainless steel, ceramic tiles and brick-making. Increased La/Ce values in urban background inhalable PM, due to La-contamination from refineries and their residual products (fuel oils and petcoke), contrast with Ce-rich emissions from the ceramic related industry, and clearly demonstrate the value of this ratio as a sensitive and reliable tracer for many point source emissions. Similarly, anomalously high V/Ni values (>4) can detect the influence of nearby high-V petcoke and fuel oil combustion, although the use of this ratio in urban background PM is limited by overlapping values in natural and anthropogenic materials. Geochemical characterisation of urban background PM is a valuable compliment to the physical monitoring of aerosols widely employed in urban areas, especially given the relevance of trace metal inhalation to urban health issues.

The role of social support in weight management is not fully understood, as more support has been linked to both favorable and unfavorable outcomes. We examined social support in relation to weight loss maintenance, comparing between maintainers and regainers of weight loss. The MedWeight study is a Greek registry of people who have intentionally lost ≥10 % of their weight and are either maintaining this loss for over a year (maintainers), or have regained weight (regainers). Demographics and lifestyle habits questionnaires are completed online. Dietary assessment is carried out by two telephone 24 h recalls. Perceived social support was assessed by validated scales examining support from family and friends regarding healthy eating and exercise. 289 maintainers and 122 regainers participated. Regainers received more support compared to maintainers. However, maintainers reported receiving compliments and active participation, whereas regainers receiving verbal instructions and encouragements. Maintainers who received diet support displayed improved dietary intakes, such as lower energy intake; regainers' diet was unaffected by support. Positive, rather than instructive, support appears beneficial in weight loss maintenance.

The objectives of this study were to characterize the phenotype and genotype of 36 non-O157 Shiga toxin-producing Escherichia coli (STEC) strains isolated from humans, ovines, or bovines, including the top 6 (O26, O45, O103, O111, O121, and O145) and three other serogroups implicated in serious illness (O91, O113, and O128). Biofilms were formed by all strains with intermediate to strong biofilm producers (n = 24) more common at 22°C than at 37°C (p < 0.001) and 48 and 72 h (p < 0.001) than 24 h of incubation time. Biofilm-forming potential differed by serogroup and origin with O113 and human strains exhibiting the highest potential (p < 0.001). Biofilm-associated genes, csgA/csgD/crl/fimH (100%), flu (94%), rpoS (92%), ehaA(α) (89%), and cah (72%), were most prevalent, while mlrA (22%) and ehaA(β) (14%) were least prevalent, although there was no clear compliment of genes associated with strains exhibiting the greatest biofilm-forming capacity. Among 12 virulence genes screened, iha and ehxA were present in 92% of the strains. The occurrence of stx1 in the top 6 serogroups (8/12, 67%) did not differ (p = 0.8) from other serogroups (17/24, 71%), but stx2 was less likely (confidence interval [CI] = 0.14-1.12; p = 0.04) to be in the former (9/24, 38%) than the latter (9/12, 75%). Excluding serogroups, O91 and O121, at least one strain per serogroup was resistant to between three and six antimicrobials. Streptomycin (31%), sulfisoxazole (31%), and tetracycline (25%) resistance was most common and was 35-50% less likely (p < 0.05) in human than animal strains. All non-O157 STEC strains were able to form biofilms on an abiotic surface, with some exhibiting resistance to multiple antimicrobials. Potential as a reservoir of antimicrobial resistance genes may be another hazard of biofilms in food-processing plants. As a result, future strategies to control these pathogens may include measures to prevent biofilms.

Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative disorder. Although allogeneic stem cell transplantation can induce long-term remissions, relapse rates remain high and innovative approaches are needed. Since donor lymphocyte infusions have clinical activity in JMML, T-cell-mediated immunotherapy could provide a nonredundant treatment approach to compliment current therapies. Gamma-globin, an oncofetal protein overexpressed by clonogenic JMML cells, may serve as a target of an antitumor immune response. We predicted 5 gamma-globin-derived peptides as potential human leukocyte antigen (HLA)-A2 restricted cytotoxic T lymphocyte (CTL) epitopes and showed that 4 (g031, g071, g105, and g106) bind A2 molecules in vitro. Using an artificial antigen-presenting cell (aAPC) that can process both the N- and C-termini of endogenously expressed proteins, we biochemically confirmed that g105 is naturally processed and presented by cell surface A2. Furthermore, g105-specific CD8(+) CTLs generated from A2-positive healthy donors were able to specifically cytolyze gamma-globin(+), but not gamma-globin(-) JMML cells in an A2-restricted manner. These results suggest that this aAPC-based approach enables the biochemical identification of CD8(+) T-cell epitopes that are processed and presented by intact cells, and that CTL immunotherapy of JMML could be directed against the gamma-globin-derived epitope g105.

BACKGROUND

Several technologies have been proposed to support the reduction of insomnia complaints. A user-centered assessment of these technologies could provide insight into underlying factors related to treatment adherence.

OBJECTIVE

Gaining insight into adherence to technology-mediated insomnia treatment as a solid base for improving those adherence rates by applying adherence-enhancing strategies.

METHODS

Adherence to technology-mediated sleep products was studied in three ways. First, a meta-analysis was performed to investigate adherence rates in technology-mediated insomnia therapy. Several databases were queried for technology-mediated insomnia treatments. After inclusion and exclusion steps, data from 18 studies were retrieved and aggregated to find an average adherence rate. Next, 15 semistructured interviews about sleep-support technologies were conducted to investigate perceived adherence. Lastly, several scenarios were written about the usage of a virtual sleep coach that could support adherence rates. The scenarios were discussed in six different focus groups consisting of potential users (n=15), sleep experts (n=7), and coaches (n=9).

RESULTS

From the meta-analysis, average treatment adherence appeared to be approximately 52% (95% CI 43%-61%) for technology-mediated insomnia treatments. This means that, on average, half of the treatment exercises were not executed, suggesting there is a substantial need for adherence and room for improvement in this area. However, the users in the interviews believed they adhered quite well to their sleep products. Users mentioned relying on personal commitment (ie, willpower) for therapy adherence. Participants of the focus groups reconfirmed their belief in the effectiveness of personal commitment, which they regarded as more effective than adherence-enhancing strategies.

CONCLUSIONS

Although adherence rates for insomnia interventions indicate extensive room for improvement, users might not consider adherence to be a problem; they believe willpower to be an effective adherence strategy. A virtual coach should be able to cope with this "adherence bias" and persuade users to accept adherence-enhancing strategies, such as reminders, compliments, and community building.

Thrombotic microangiopathies (TMAs) include several diseases, most prominently are thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). TMAs are characterized by profound thrombocytopenia, microangiopathic hemolytic anemia and organ ischemia. In most cases TTP results from deficiency of ADAMTS13, the von Willebrand factor-cleaving protease leading to increase of ultra-large von Willebrand factor (ULVWF) multimers. Congenital TTP is due to mutations in the gene of ADAMTS13 whereas acquired TTP is due to production of autoantibodies against ADAMTS13. In both cases severe deficiency of ADAMTS13 exists. However, the presence of ADAMTS13 activity does not rule out TTP. Diagnostic criteria of TTP are based on clinical features of neurologic and renal disfunction along with anemia and thrombocytopenia, low ADAMTS13 activity, and the presence of ULVWF. The standard treatment of TTP includes plasma exchange, protein A immunoabsobtion, immunosuppressive drugs, CD20 antibodies against B cells, and splenectomy. HUS is commonly caused by infection with Shiga-toxin produced by Escherichia coli. HUS is characterized by thrombocytopenia, anemia, renal impairment and diarrhea. Rarely, atypical HUS appears as a consequence of mutations related to the alternative pathway for the compliment system. Plasmapheresis in HUS is not efficient. Alternatively, plasma therapy and in some cases dialysis are used. TMA diseases may be associated with other infections, bone marrow transplantation, pregnancy, systemic vasculitis, and certain drugs.

Available data suggest a possible link between abnormal vitamin D level and abnormal glucose homeostasis, two of the most common chronic medical conditions. Both conditions are associated with inflammation, and the exact mechanism for role of either on the other is not well clear. Literature investigating the link between vitamin D and either pre-diabetic states or diabetes is reviewed. Vitamin D deficiency is detrimental to insulin synthesis and secretion in animal and human studies. In humans, it has been shown by majority of observational studies, that vitamin D is positively correlated with insulin sensitivity and its role is mediated both by direct mechanism through the availability of vitamin D receptors in several tissues and indirectly through the changes in calcium levels. Large number of, but not all, variable samples cross sectional human trials have demonstrated an inverse relation between vitamin D status and impaired glucose tolerance, insulin resistance or diabetes. To compliment this conclusively, evidence from intervention studies is critically warranted before we can frankly state that vitamin D plays a role in diabetes prevention or treatment. Absence of both sizable prospective observational trials utilizing 25(OH)D as the main variable and the non-availability of randomized studies specifically designed to assess the effects of vitamin D on pre-diabetes and diabetes states, are the main obstacles to draw solid and conclusive relationships.

Noninvasive in vivo molecular-genetic imaging has developed over the past decade and involves nuclear (PET, gamma camera), magnetic resonance, and in vivo optical imaging systems. Although three different imaging strategies - "direct," "indirect" and "surrogate" - are being used, most current in vivo molecular imaging strategies are "indirect" and involve the coupling of a "reporter gene" with a complimentary "reporter probe." Imaging the level of probe accumulation provides indirect information related to the level of reporter gene expression. Reporter gene constructs are driven by upstream promoter/enhancer elements; reporter gene expression can be "constitutive" leading to continuous transcription and used to identify the site of transduction and to monitor the level and duration of gene (vector) activity. Alternatively, reporter gene expression can be "inducible" leading to controlled gene expression. Controlled gene expression can be tissue-specific and/or responsive to the level of endogenous promoters and transcription factors. Several examples of imaging endogenous biological processes in animals using reporter constructs, radiolabeled probes and PET imaging are reviewed, including: 1) imaging transcriptional regulation (e.g., p53-dependent gene expression), 2) imaging weak promoters (cis- vs. trans-reporter configurations), 3) imaging post-transcriptional regulation of gene expression, 4) imaging protein-protein interactions. The development of versatile and sensitive assays that do not require tissue sampling will be of considerable value for monitoring molecular-genetic and cellular processes in animal models of human disease, as well as for studies in human subjects in the future. Non-invasive imaging of molecular-genetic and cellular processes will compliment established ex vivo molecular-biological assays that require tissue sampling, and will provide a spatial as well as a temporal dimension to our understanding of various diseases.

OBJECTIVE

To compare the clinical interview process, content of the medical dialog, and emotional tone of the veterinarian-client-patient interaction during wellness appointments and appointments related to a health problem in companion animal practice.

METHODS

Cross-sectional descriptive study.

METHODS

A random sample of 50 companion animal practitioners in southern Ontario and a convenience sample of 300 clients and their pets.

METHODS

For each practitioner, 6 clinical appointments (3 wellness appointments and 3 problem appointments) were videotaped. The Roter interaction analysis system was used to analyze the resulting 300 videotapes.

RESULTS

Wellness appointments were characterized by a broad discussion of topics, with 50% of data-gathering statements and 27% of client education statements related to the pet's lifestyle activities and social interactions. Wellness appointments included twice as much verbal interaction with the pet as did problem appointments, and the emotional atmosphere of wellness appointments was generally relaxed. There were more social talk, laughter, statements of reassurance, and compliments directed toward the client and pet. In contrast, during problem appointments, 90% of the data gathering and client education focused on biomedical topics. Coders rated veterinarians as hurried during 30 of the 150 (20%) problem appointments; they rated clients as anxious during 39 (26%) problem appointments and as emotionally distressed during 21 (14%).

CONCLUSIONS

Results suggested that veterinarian-client-patient communication differed between wellness and problem appointments. Owing to the emphasis on biomedical content during problem appointments, veterinarians may neglect lifestyle and social concerns that could impact patient management and outcomes, such as client satisfaction and adherence to veterinarian recommendations.

Continuous improvement in bioanalytical method development is desired in order to ensure the quality of the data and to better support pharmacokinetic (PK) and safety studies of biotherapeutics. One area that has been getting increasing attention recently is in the assessment of "free" and "total" analyte and the impact of the assay format on those assessments. To compliment these considerations, the authors provide a critical review of available literature and prospectively explore methods to mitigate the potential impact of anti-drug antibody on PK assay measurement. This challenge is of particular interest and importance since biotherapeutic drugs often elicit an immune response, and thus may have a direct impact on quantification of the drug for its PK and safety evaluations.

Preimplantation genetic diagnosis (PGD) is currently one of the practical options available for couples at-risk to avoid the birth of children with genetic and chromosomal disorders. Despite its novelty, PGD has already become an alternative to traditional prenatal diagnosis, allowing establishing only unaffected pregnancies avoiding the risk for pregnancy termination. Indications for PGD have currently expanded beyond those practices in prenatal diagnosis, such as late-onset diseases with genetic predisposition, and preimplantation HLA typing with the purpose of establishing potential donor progeny for stem cell treatment of siblings, which makes PGD also an important compliment to prenatal diagnosis. The fact that more than 1,000 apparently healthy unaffected children have been born after PGD suggests its accuracy, reliability, and safety. PGD is presently an excellent option for carriers of balanced translocations, and appears to be of special value for avoiding age-related aneuploidies in patients of advanced reproductive age. The accumulated experience of thousands of PGD cycles for poor prognosis in vitro fertilization (IVF) patients provides strong evidence of the improvement of clinical outcome, particularly obvious from the reproductive history of patients. This makes of practical relevance to inform couples at-risk about availability of PGD option, so they make their own choice in avoiding the birth of affected offspring and having healthy children of their own.

Peripheral nerve regeneration is a complex series of events, involving bi-directional interactions between regenerating axons and Schwann cells. These authors have demonstrated in their laboratory that nerves will regenerate through a 3-cm autogenous venous nerve conduit (AVNC) in an animal model and, with Dr. David Chiu, a similar distance in the human. They have shown that the upper limit of nerve regeneration in an empty AVNC was 3 cm, with no evidence of nerve growth at the 6-cm mark (no-growth model). Most recently, they have demonstrated rapid growth at 1 month in a 3-cm AVNC filled with Schwann cells, compared to poor-to-no-regrowth at 1 month in controls. While, in theory, Schwann-cell-derived growth factor should be sufficient to supplant the requirement for Schwann cells, in practice, therapies with growth factors have failed in clinical trials, with some resulting in severe morbidity and mortality for the subjects. The present study showed excellent nerve regeneration through a 6-cm AVNC with the addition of autologous Schwann cells, breaking the barrier in the previous no-growth model. In the first stage, autologous Schwann cells were harvested from the contralateral peroneal nerve of the rabbit and expanded in culture. The Schwann cells were purified to >99 percent homogeneity using differential adhesion and antibody-compliment-mediated cytolysis. In the second stage, 6 cm of gluteal vein were harvested and used as a conduit that was filled with either Matrigel or a slurry of Matrigel and 10(6)/ml autologous Schwann cells (n=6 control and 6 experimental animals). The non-donor side peroneal was exposed and transected, leaving a gap of 6 cm. The filled gluteal vein graft (AVNC) was then anastomosed to the proximal and distal peroneal nerve stumps, and the rabbits were allowed to recover. Four months postoperatively, the animals were subjected to transcardiac perfusion with EM grade fixative. The grafts were analyzed at the light and electronmicroscopic levels, and showed excellent growth of nerve at 6 cm, the distal end of the AVNC.

Diabetic retinopathy is the leading cause of blindness in working aged-adults in westernised countries. Diabetic macular oedema (DMO) is a manifestation of diabetic retinopathy and is the leading cause of the visual impairment that occurs with diabetic retinopathy. There are multiple ways of classifying DMO; however, none appear to be wholly satisfactory. DMO occurs more frequently in type 2 diabetes mellitus, and appears to be more prevalent as the duration of diabetes increases, and as the severity of diabetic retinopathy worsens. There are multiple risk factors in common with diabetic retinopathy, such as hyperglycaemia, hypertension and dyslipidaemia; however, specific factors such as the presence of renal disease appear to be more significantly associated with DMO. Whereas the gold standard for diagnosis of DMO is via clinical examination, there is considerable variability involved, and hence, this has led to the advent of more objective methods of quantifying the degree of retinal thickness, such as optical coherence tomography. Laser photocoagulation appears to be the only universally acceptable treatment of choice to date; however, this is a destructive therapy, and its side effects coupled with the suboptimal efficacy has led to the advent of potential new therapies which will undoubtedly compliment the existing approaches, in the future management of a patient with DMO.

Purpose: The oligometastatic state is a proposed entity between localized cancer and widely metastatic disease, comprising an intermediate subset of metastatic cancer patients. Most data to support locally-directed treatment, such as stereotactic ablative radiotherapy (SABR), for oligometastases are from retrospective institutional reports. Following the success of a recently completed and reported phase II trial demonstrating important clinical outcomes, herein we review the current landscape of ongoing clinical trials in this context. Materials and methods: A review of currently activated and registered clinical trials was performed using the clinicaltrials.gov database from inception to February 2019. A search of actively recruiting trials, using the key words oligometastases, SABR, and various related terms was performed. Search results were independently reviewed by two investigators, with discrepancies settled by a third. Data abstracted from identified studies included study type, primary disease site, oncologic endpoints, and inclusion/exclusion criteria. Results: Of the initial 216 entries identified, 64 met our review eligibility criteria after full-text review. The most common study type was a phase II clinical trial (n = 35, 55%) with other study designs ranging from observational registry trials to phase III randomized controlled trials (RCTs). A minority of trials were randomized in design (n = 17, 27%). While most studies allowed for metastases from multiple primary disease sites (n = 22, 34%), the most common was prostate (n = 13, 15%), followed by breast, gastrointestinal, non-small cell lung cancer (NSCLC), and renal (n = 6, 9% each). In studies with a solitary target site, the most common was liver (n = 6, 9%) followed by lung (n = 3, 5%). The most common primary endpoints were progression-free survival (PFS) (n = 20, 31%) and toxicity (n = 10, 16%). A combined strategy of systemic therapy and SABR was an emerging theme (n = 23, 36%), with more recent studies specifically evaluating SABR and immunotherapy (n = 9, 14%). Conclusion: The safety and efficacy of SABR as oligometastasis-directed treatment is increasingly being evaluated within prospective clinical trials. These data are awaited to compliment the abundance of existing observational studies and to guide clinical decision-making.

OBJECTIVE

To investigate acupuncture treatment during labour with regard to pain intensity, degree of relaxation and outcome of the delivery.

METHODS

Randomised controlled trial.

METHODS

Delivery ward at a tertiary care centre hospital in Sweden.

METHODS

Ninety parturients who delivered during the period April 12, 1999 and June 4, 2000.

METHODS

Forty-six parturients were randomised to receive acupuncture treatment during labour as a compliment, or an alternative, to conventional analgesia.

METHODS

Assessments of pain intensity and degree of relaxation during labour, together with evaluation of delivery outcome.

RESULTS

Acupuncture treatment during labour significantly reduced the need of epidural analgesia (12% vs 22%, relative risk [RR] 0.52, 95% confidence interval [CI] 0.30 to 0.92). Parturients who received acupuncture assessed a significantly better degree of relaxation compared with the control group (mean difference -0.93, 95% CI -1.66 to -0.20). No negative effects of acupuncture given during labour were found in relation to delivery outcome.

CONCLUSIONS

The results suggest that acupuncture could be a good alternative or complement to those parturients who seek an alternative to pharmacological analgesia in childbirth. Further trials with a larger number of patients are required to clarify if the main effect of acupuncture during labour is analgesic or relaxing.

In a prospective randomised controlled trial, 48 students were randomly assigned to stress reduction training before exams with self-hypnosis, Johrei or a mock neurofeedback relaxation control. Peripheral blood lymphocyte subpopulations and self-reported stress (Perceived Stress Scale) were measured before training and 1-2 months later as exams approached. Absolute number and percentages of CD3(+)CD4(+) and CD3(+)CD8(+) T lymphocytes, CD3(-)CD56(+) Natural Killer cells (NK cells) and NK cell cytotoxic activity was measured from venous blood. Stressed participants showed small but significant declines in both CD3(-)CD56(+) NK cell percentages and NK cell cytotoxic activity levels while CD3(+)CD4(+) T cell percentages increased, changes supported by correlations with perceived stress. The effects of stress were moderated in those who learned Johrei at exam time; 11/12 showed increases in CD3(-)CD56(+) NK cell percentages with decreased percentages of CD3(+)CD4(+) T cells, effects not seen in the relaxation control group. Stress was also buffered in those who learned and practised self-hypnosis in whom CD3(-)CD56(+) NK cell and CD3(+)CD4(+) T cell levels were maintained, and whose CD3(+)CD8(+) T cell percentages, shown previously to decline with exams, increased. The results compliment beneficial effects on mood of self-hypnosis and Johrei. The results are in keeping with beneficial influences of self-hypnosis and provide the first evidence of the suggestive value of the Japanese Johrei procedure for stress reduction, which clearly warrants further investigation.

Few studies have directly compared the visuo-motor transformation of grasp pre-shaping or transport-grasp coordination of reach-to-grasp movements between the two hands. Our objective was to determine if there are manual asymmetries in right-handed adults as a foundation to investigate hemispheric specialization in individuals post-stroke. Twelve non-disabled right-handed adults performed rapid reach-to-grasp movements to cylinders of three sizes as vision of the arm and hand was partially occluded. We reasoned that the hand system (left or right) that is superior in anticipatory planning of aperture scaling and movement preparation would be more likely to exhibit early grasp pre-shaping under this experimental manipulation. Movement time, hand path, transport velocity, and aperture were derived from 3D electromagnetic sensor data. The visuo-motor transformation of object sizes into an action of aperture pre-shaping was quantified using the correlations between initial aperture velocity and object diameter, and peak aperture and object diameter. Coordination between hand transport and aperture grasping was quantified using the cross-correlation between transport velocity and aperture size. Peak aperture and object diameter were strongly correlated for both hands. However, early aperture velocity and object diameter were correlated only for left-hand movements. Cross-correlation analyses revealed a strong association between transport velocity and aperture only for right-hand movements. Together, these results suggest earlier anticipatory control for the left hand in the visuo-motor transformation of grasp pre-shaping and a stronger transport-grasp linkage for the right hand. Further, initial aperture velocity was a more sensitive measure of these manual asymmetries than peak aperture. Our findings compliment the specialization previously observed for pointing movements of the dominant and non-dominant hemispheric/limb system and the coordinated control of complex movements and visuo-spatial components, respectively.