Influence of transcutaneous spinal stimulation on human LTP-like pain amplification. A randomized, double-blind study in volunteers.

OBJECTIVE: Transcutaneous spinal direct current stimulation (tsDCS) has been proven to affect nociceptive signal processing. We designed a randomized, double-blind, cross-over study to investigate whether tsDCS applied before or after inducing long-term potentiation-(LTP)-like hyperalgesia may decrease nociceptive sensitivity. METHODS: In healthy volunteers, tsDCS (2.5mA, 15min) was applied to the thoracic spine prior (n=14) or immediately following (n=12) electrical high-frequency stimulation (HFS) to the thigh, inducing hyperalgesia. Mechanical and electrical perception were assessed before HFS stimulation and at three time points following HFS stimulation (all within 90min of HFS). Subjects took part in three separate sessions to test effects of anodal, cathodal, or sham tsDCS. RESULTS: Within 60minHFS led to unilateral changes on the conditioned side: mechanical pain thresholds tended to decrease and electrical detection thresholds significantly decreased (p<0.001); pain ratings measured using the numerical rating scale (NRS) increased for electrical stimuli (p<0.01) and two categories of mechanical stimuli ("Light(8-64mN)": p=ns; "Heavy(128-512mN)": p<0.01). Irrespective of stimulation order or polarity, tsDCS could not influence nociceptive sensitivity. CONCLUSION: Hyperalgesia was adequately induced, but tsDCS had no effect on HFS-induced sensitization. SIGNIFICANCE: While tsDCS has been shown to affect pain measures, our results suggest irrespective of time of stimulation or polarity that tsDCS may be less effective in modulating pain in a sensitized state in healthy subjects.

Transarterial Alcohol-Lipiodol Therapy in Patients with Hepatocellular Carcinoma Using Low Alcohol Concentrations.

PURPOSE: To evaluate transarterial alcohol-lipiodol therapy (TAL) with low concentrations of alcohol for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: 17 patients (69.3 ±â€Š10.7a, 13 male, 4 female) with previously untreated HCC (tumor diameter: 7.7 ±â€Š5.8 cm), who underwent 20 transarterial alcohol-lipiodol injections, were evaluated retrospectively. 14 patients had HCC with coexistent cirrhosis (Child-A n = 9, Child-B n = 4, Child-C n = 1). 9 patients presented an Okuda stage I, 7 patients an Okuda stage II and 1 patient an Okuda stage III. Infiltration of the portal vein was seen in 3 patients. RESULTS: 15 patients underwent TAL with an alcohol:lipiodol ratio of 1:2, another one with a ratio of 1:3 and yet another one with a ratio of 1:5. The median survival was 23 months, and the 1-year and 2-year survival rates were 62.7 % and 31.4 %, respectively. The median survival of patients with HCC < 7.5 cm (n = 10) was 25 months and significantly (p = 0.009) higher than for patients with HCC ≥ 7.5 cm (n = 7; 3 months). Tumor diameters ≥ 7.5 cm were associated with worse lipiodol-contrasting of HCC. Intrainterventional side effects were only feelings of slight abdominal pressure in 2 of 20 interventions. Postinterventional, mild side effects were observed after 3 interventions (abdominal pain n = 1, thoracic pain n = 1, fever n = 1). Serious complications were not observed, in particular there was no decompensation of liver cirrhosis. CONCLUSION: TAL with low concentrations of alcohol was a safe and effective treatment in our cohort in spite of extensive tumors and impaired liver function. TAL could be a treatment option for patients who cannot receive other therapies (e. g. TACE, RFA) because of their advanced tumor disease, liver cirrhosis or other contraindications. KEY POINTS: • TAL can be performed safely in advanced tumor disease and liver cirrhosis Citation Format: • Mohné F, Meyer C, Kuhl CK et al. Transarterial Alcohol-Lipiodol Therapy in Patients with Hepatocellular Carcinoma Using Low Alcohol Concentrations. Fortschr Röntgenstr 2016; 188: 676 - 683.

[Management of Idiopathic Frozen Shoulder - Prospective Evaluation of Mobilisation under Anaesthesia and an Additional Subacromial Cortisone Injection]. / Management der idiopathischen Schultersteife - prospektive Evaluation der reinen Narkosemobilisation und einer additiven subakromialen Kortikosteroidinjektion.

BACKGROUND: Management of primary frozen shoulder is still controversial. Many authors tend to treat patients with an arthroscopic release, if conservative therapy fails. We aimed to demonstrate the efficiency of manipulation under anaesthesia (MUA) in patients with primary frozen shoulder and to contrast the outcome of single MUA with the results of MUA with an additional subacromial injection of cortisone. MATERIAL AND METHODS: A prospective trial with a 1-year follow-up was performed. Between 2008 and 2011 30 patients with idiopathic frozen shoulder underwent MUA, 15 of them received an additional injection of triamcinolone and bupivacain. Thereafter all patients underwent a standardised physiotherapy treatment regime for three months. The patients were assessed for pain, function, range of motion and the Constant-Murley score (CMS) before MUA as well as 1, 6 and 12 months after the intervention. RESULTS: Range of motion increased significantly (p < 0.05) in all planes at every point of follow-up. Preinterventional abduction improved from 65.80° ± 13.25 to 145.40° ± 18.50, preinterventional forward flexion from 90.20° ± 18.98 to 155.60° ± 13.51 at 1 month after MUA. At this point 80 % of patients had returned to work, 66.7 % were free of pain. One year after MUA abduction was improved to 173.07° ± 6.03, forward flexion to 175.47° ± 4.03. The CMS rose significantly (p < 0.05) from 24.53 ± 9.28/100 to 73.97 ± 10.77/100 after 1 month and up to 86.30 ± 5.62/100 after 1 year. Range of motion and function as described for a healthy shoulder were recognised in every patient during 1 year. However additional subacromial injections of triamcinolone and bupivacain did not lead to a significant improvement. There were no complications reported. CONCLUSION: This study demonstrates that MUA is a safe and effective tool in the management of idiopathic frozen shoulder, if conservative therapy fails. An additional subacromial injection of cortisone however does not generate a significant improvement.

Preclinical aspects of anti-VEGF agents for the treatment of wet AMD: ranibizumab and bevacizumab.

Three anti-vascular endothelial growth factor (VEGF) therapies are currently used for the treatment of patients with wet age-related macular degeneration (AMD): pegaptanib, ranibizumab, and bevacizumab. Ranibizumab is an antibody fragment approved for the treatment of wet AMD. Bevacizumab is a full-length antibody registered for use in oncology but unlicensed for wet AMD. However, it is used off-label worldwide not only for wet AMD but also for various other ocular diseases associated with macular edema and abnormal vessel growth. We consider aspects of ranibizumab and bevacizumab in relation to their molecular characteristics, in vitro and in vivo properties, and preclinical safety data. Before 2009, most studies described the short-term toxicity of bevacizumab in multiple cell types of the eye. Since 2009, an increasing number of studies have compared the properties of ranibizumab and bevacizumab and investigated their impact on retinal cell functioning. Compared with bevacizumab, ranibizumab neutralizes VEGF better at low concentrations, maintains efficacy for longer, and has a higher retinal penetration and potency. Studies in animals demonstrate ranibizumab to be better localized to the injected eye, whereas bevacizumab appears to have a greater effect in the fellow eye. In humans, a localized and systemic effect has been reported for both molecules. In conclusion, overlapping yet distinct pharmacological properties of ranibizumab and bevacizumab indicate that safety or efficacy data from one cannot be extrapolated to the other.

Alcohol screening in general practices using the AUDIT: how many response categories are necessary?

AIMS: The Alcohol Use Disorders Identification Test (AUDIT) is a common screening instrument. This study analyses if response categories of the AUDIT might be dichotomized without affecting the psychometric properties of the questionnaire. METHODS: Participants between 18 and 65 years were recruited from general practices in two northern German cities. In total, 10,803 screenings were conducted (refusal rate: 5.9%). For those who were screened positive, the Munich-Composite International Diagnostic Interview (M-CIDI) was used for identification of 12-month Alcohol Use Disorders and at-risk consumption (exceeding 20/30 g per day). Abstinent subjects and screening positives without diagnostic interview were excluded from the analysis, leaving a sample of 7,112 subjects. ROC-Curves were calculated separately for each item in order to identify an optimal cut-off value. Finally, a version of the AUDIT based on dichotomized items was compared to the original version and its short-form, the AUDIT version based on three questions dealing with consumption AUDIT-C. RESULTS: As an optimal cut-off value for items on consumption, drinking at least once a week, having more than 1-2 drinks per occasion, and drinking 6 or more drinks in one sitting at least once a month were identified. For all questions on alcohol-related problems or dependence symptoms, having 'ever occurred' differed best between subjects with and without Alcohol Use Disorders or at-risk consumption. Sensitivity and specificity of the dichotomized version of the AUDIT did not differ from the original version, and both full versions performed superior compared to the AUDIT-C. CONCLUSION: Data indicate that the AUDIT response categories may be dichotomized without affecting its validity.

Adult bacterial meningitis: aetiology, penicillin susceptibility, risk factors, prognostic factors and guidelines for empirical antibiotic treatment.

Episodes of adult bacterial meningitis (ABM) at a Danish hospital in 1991-2000 were identified from the databases of the Department of Clinical Microbiology, and compared with data from the Danish National Patient Register and the Danish National Notification System. Reduced penicillin susceptibility occurred in 21 (23%) of 92 cases of known aetiology, compared to an estimated 6% in nationally notified cases (p < 0.001). Ceftriaxone plus penicillin as empirical treatment was appropriate in 97% of ABM cases in the study population, and in 99.6% of nationally notified cases. The notification rate was 75% for penicillin-susceptible episodes, and 24% for penicillin-non-susceptible episodes (p < 0.001). Cases involving staphylococci, Pseudomonas spp. and Enterobacteriaceae were under-reported. Among 51 ABM cases with no identified risk factors, nine of 11 cases with penicillin-non-susceptible bacteria were community-acquired. Severe sequelae correlated independently with age, penicillin non-susceptibility, mechanical ventilation and non-transferral to a tertiary hospital (p < 0.05; logistic regression). Other factors that correlated with severe sequelae by univariate analysis only were inappropriate clinical handling, abnormal consciousness, convulsions and nosocomial infection. Overall, the data indicated that neither age alone, community-acquired infection nor absence of identified risk factors can predict susceptibility to penicillin accurately. Recommendations for empirical antibiotic treatment for ABM should not be based exclusively on clinical notification systems with possible unbalanced under-reporting.

Regional mu opioid receptor regulation of sensory and affective dimensions of pain.

The endogenous opioid system is involved in stress responses, in the regulation of the experience of pain, and in the action of analgesic opiate drugs. We examined the function of the opioid system and mu-opioid receptors in the brains of healthy human subjects undergoing sustained pain. Sustained pain induced the regional release of endogenous opioids interacting with mu-opioid receptors in a number of cortical and subcortical brain regions. The activation of the mu-opioid receptor system was associated with reductions in the sensory and affective ratings of the pain experience, with distinct neuroanatomical involvements. These data demonstrate the central role of the mu-opioid receptors and their endogenous ligands in the regulation of sensory and affective components of the pain experience.

Anticonvulsant properties of the methanolic extract of Cyperus articulatus (Cyperaceae).

The methanolic extract of rhizomes of Cyperus articulatus, a plant used in traditional medicine in Africa and Latin America for many diseases, possesses anticonvulsant activity in mice. This extract protected mice against maximal electroshock (MES)- and pentylenetetrazol (PTZ)-induced seizures. It also delayed the onset of seizures induced by isonicotinic acid hydrazide and strongly antagonized N-methyl-D-aspartate-induced turning behavior. The ED(50) for protection against seizures was 306 (154-541) mg/kg intraperitoneally (i.p.) for the PTZ test and 1005 (797-1200) mg/kg i.p. for the MES test. The ED(50) of methanolic extract against N-methyl-D-aspartate-induced turning behavior was 875 (623-1123) mg/kg i.p. C. articulatus L. methanolic extract protected 54% of mice from seizures induced by strychnine at the dose of 1000 mg/kg i.p. but had no or a moderate effect only against picrotoxin- or bicuculline-induced seizures. With these effects, the rhizome of C. articulatus L. possesses anticonvulsant properties in animals that might explain its use as a traditional medicine for epilepsy in Africa.

[Chronic pelvic pain. Another diagnostic and therapeutic approach]. / Douleur pelvienne chronique. Une autre approche diagnostique et thérapeutique.

Chronic pelvic pain (CPP) is a frequent and difficult problem because despite the quality and diversity of diagnostic procedures no relevant etiology will be found in 30 to 40% of all cases. Psychologic and psychotherapeutic counselling is than usually proposed and usually not well accepted. A different approach can now be proposed according to a new semeiologic overall. In many cases the pain dominant is not visceral but parietal. The pelvic envelope is actually more painfull than the pelvic content. In these cases one can evoke the diagnosis of pelvic fibromyalgia and this is quite similar to classic fibromyalgia. This pelvifibromyalgia can be quantified with an algometric index. This form of pain actually is the somatisation of a past and difficult issue which will be very slowly and progressively revealed in the realm of a multidisciplinary and simultaneous physical and psychological approach. In the majority of cases these women have occurred physical, moral or sexual trauma inflicted by family members or a third party. Taking in account the physical dimension of body pain at the same time as psychotherapy will considerably enhance the efficiency of treatment. In our experience 70% of all women will be cured using this new approach.

An international comparison of cancer survival: metropolitan Toronto, Ontario, and Honolulu, Hawaii.

OBJECTIVES: Comparisons of cancer survival in Canadian and US metropolitan areas have shown consistent Canadian advantages. This study tests a health insurance hypothesis by comparing cancer survival in Toronto, Ontario, and Honolulu, Hawaii. METHODS: Ontario and Hawaii registries provided a total of 9190 and 2895 cancer cases (breast and prostate, 1986-1990, followed until 1996). Socioeconomic data for each person's residence at the time of diagnosis were taken from population censuses. RESULTS: Socioeconomic status and cancer survival were directly associated in the US cohort, but not in the Canadian cohort. Compared with similar patients in Honolulu, residents of low-income areas in Toronto experienced 5-year survival advantages for breast and prostate cancer. In support of the health insurance hypothesis, between-country differences were smaller than those observed with other state samples and the Canadian advantage was larger among younger women. CONCLUSIONS: Hawaii seems to provide better cancer care than many other states, but patients in Toronto still enjoy a significant survival advantage. Although Hawaii's employer-mandated health insurance coverage seems an effective step toward providing equitable health care, even better care could be expected with a universally accessible, single-payer system.

[Wound healing and hyperbaric oxygen. Experimental study of the angiogenesis phase in the rat]. / La cicatrisation sous oxygénothérapie hyperbare. Etude expérimentale de sa phase angiogénique chez le rat.

Hyperbaric oxygen therapy (HBO) is widely reported as highly favourable to wound healing. The experimental models generally used to investigate its effects are difficult to set up and reliable quantification of the results obtained is rarely achieved. The underlying pathophysiological mechanisms occurring during HBO remain poorly understood and its mode of application for clinical practice is difficult to standardise. Our study was carried out to assess the contributions of oxygen and hyperbaric pressure on the initial steps of wound healing. It was based on qualitative and quantitative analysis of the development of the angiogenic process in a granulation tissue bud, using animals implanted with fibrin chambers, an in vivo model initially described by Dvorak in guinea pigs. In our study, rats were further submitted to HBO (OHB group) or hyperbaric air (Air-HB group) treatments. The control group (Control group) consisted of rats maintained in the treatment tank under normal atmospheric conditions. Nine specific parameters were determined and analysed during the course of the angiogenic process by classical histological techniques. The vascular density and the height of the bud were particularly examined at day 7, 14 and 21 following chamber implantation. At D7 the neovessel density and bud height were significantly higher in OHB group than in Air-HB or Control groups, thus confirming the beneficial effects of this treatment on the initial steps of wound healing. Nevertheless, the results reported herein also suggest a possible inhibitory effect of hyperbaric therapy alone on this very early process, although the pathophysiological significance of this effect on wound healing remains to be determined.

The anatomy of an OPTI: Part 2. The CORE system. Ohio Osteopathic Hospital Association. Ohio Association of Osteopathic Medical Directors. Ohio Osteopathic Association.

In July 1995, the American Osteopathic Association (AOA) Board of Trustees passed new regulations regarding the accreditation of osteopathic graduate medical education (GME) by establishing the Osteopathic Postdoctoral Training Institutions (OPTI) system. This system must be phased in by July 1999. The principal changes resulting from the OPTI system include establishing requirements for college cosponsorship of GME programs and for the number of residency programs, interns, and residents to be trained by the OPTI. In essence, OPTI is an osteopathic acronym for consortium. Each OPTI must include at least one college of osteopathic medicine (COM) and one AOA-accredited hospital. The OPTIs will be subject to interval AOA inspections and will be required to demonstrate a governing system, mission statement, organizational structure, and the presence of faculty development programs. The first article in this two-part series, published in the October JAOA, provided a general blueprint for OPTI building and presented both positive and negative issues germane to the formation of OPTIs. Part 2 reinforces the considerations outlined in Part 1 by describing the formation of a large OPTI--the Ohio University College of Osteopathic Medicine (OU-COM) Centers of Osteopathic Regional Education (CORE) system. Key features are described, including the mission statement, organizational structure, committee system, governance, GME programs, operations, and budget.

Anatomy of an OPTI: Part I. Form, function, and relationships.

In July 1995, the American Osteopathic Association (AOA) Board of Trustees passed new regulations for the accreditation of osteopathic graduate medical education (GME) programs by establishing the Osteopathic Postdoctoral Training Institutions (OPTI) system, to be implemented over 4 years. The resulting changes include requirements for college cosponsorship of GME programs and the establishment of standards for the minimum number of residency programs, interns, and residents. The OPTIs will be subject to AOA inspections at least every 5 years. Proponents of the OPTI system claim it will strengthen the profession by promoting educational collaboration, raising academic standards, and requiring appropriate resources to support osteopathic medical education. Opponents fear that it will be too resource intensive, create an additional layer of unnecessary bureaucracy, and have a negative impact on small colleges, hospitals, and states. Despite the controversy, a process for applying for OPTI status has been developed by the AOA, and a number of hospitals and colleges are already developing OPTIs. This article, the first in a two-part series, identifies issues and barriers to be considered in the formation of OPTIs and articulates principles underlying successful collaborations. In Part 2 these issues, principles, and barriers will be reinforced by describing the process used to form a large OPTI--the Ohio University College of Osteopathic Medicine (OU-COM) Centers for Osteopathic Regional Education (CORE) System.

Ambulatory care training standards for continuity of care in osteopathic family medicine.

The authors developed statewide standards of excellence for ambulatory care training in an osteopathic medical consortium of family medicine residency programs. A total of 16 osteopathic family medicine residency programs joined with the Michigan State University-College of Osteopathic Medicine to form the Consortium for Osteopathic Graduate Medical Education Training (COGMET) Family Medicine Division. Standards were developed and implemented on a statewide basis for all member residency programs. Initial qualitative evaluations discovered minor as well as more substantive noncompliance after a 6-month trial. Results from longitudinal quantitative evaluations will determine the effectiveness of these standards.

Identification by mutational analysis of four critical residues in the molybdenum cofactor domain of eukaryotic nitrate reductase.

The nucleotide sequence of the nitrate reductase (NR) molybdenum cofactor (MoCo) domain was determined in four Nicotiana plumbaginifolia mutants affected in the NR apoenzyme gene. In each case, missense mutations were found in the MoCo domain which affected amino acids that were conserved not only among eukaryotic NRs but also in animal sulfite oxidase sequences. Moreover an abnormal NR molecular mass was observed in three mutants, suggesting that the integrity of the MoCo domain is essential for a proper assembly of holo-NR. These data allowed to pinpoint critical residues in the NR MoCo domain necessary for the enzyme activity but also important for its quaternary structure.