Pain ratings and somatosensory evoked responses to repetitive intramuscular and intracutaneous stimulation in fibromyalgia syndrome.

To determine the presence of perceptual sensitization and related brain responses we examined 15 patients with fibromyalgia syndrome and 15 healthy controls comparable in age and sex. Multichannel EEG recordings and pain ratings were obtained during the presentation of 800 painful electrical intramuscular and intracutaneous stimuli to the left m. erector spinae and the left m. extensor digitorum. The stimulus intensity was adjusted to 50% between pain threshold and tolerance. Detection and pain thresholds were significantly lower in the fibromyalgia syndrome group. Sensitization occurred for both groups during intramuscular stimulation. In the EEG data the fibromyalgia syndrome patients showed higher N80 amplitudes compared with the healthy controls. Arm stimulation and intramuscular stimulation yielded higher N80 and N150 amplitudes compared with intracutaneous stimulation or stimulation of the back. These results indicate lower pain thresholds in the fibromyalgia syndrome patients after electrical stimulation and a higher N80 amplitude both indicative of enhanced sensory processing in this group.     

Evidenced-Based Guidelines on the Treatment of Fibromyalgia Patients: Are They Consistent and If Not,Why Not? Have Effective Psychological Treatments Been Overlooked?

We compared the recommendations and methodology of several recent evidence-based guidelines for the management of patients with fibromyalgia published by professional organizations: 1) American Pain Society (APS; 2005), 2) Association of the Scientific Medical Societies in Germany (AWMF; 2012), 3) Canadian Pain Society (CPS; 2013; also used in the United Kingdom), and 4) European League Against Rheumatism (EULAR; 2016). Each guideline used systematic reviews and meta-analyses as highest level of evidence; APS, CPS, and AWMF also included individual randomized clinical trials. The APS, CPS, and AWMF assigned the highest ranking of recommendation to aerobic exercise, cognitive-behavioral therapy, amitriptyline, and multicomponent treatment. In contrast, the most recent EULAR guidelines assign the highest level of recommendation to exercise, contrary to the 2008 EULAR guidelines, which recommended pharmacotherapy. Although there was some consistency for pharmacological treatment recommendations among the 4 guidelines, APS, CPS, and AWMF guidelines gave the higher ranking to cognitive-behavioral therapy and multicomponent treatments. The inconsistencies across guidelines can be attributed to the criteria used for study inclusion, outcome measures used, weighting systems, and composition of the review panels. A guideline consensus is needed to harmonize the discrepancies.

Novel alpha- and beta-amino acid inhibitors of influenza virus neuraminidase

In an effort to discover novel, noncarbohydrate inhibitors of influenza virus neuraminidase we hypothesized that compounds which contain positively charged amino groups in an appropriate position to interact with the Asp 152 or Tyr 406 side chains might be bound tightly by the enzyme. Testing of 300 alpha- and beta-amino acids led to the discovery of two novel neuraminidase inhibitors, a phenylglycine and a pyrrolidine, which exhibited K(i) values in the 50 microM range versus influenza virus A/N2/Tokyo/3/67 neuraminidase but which exhibited weaker activity against influenza virus B/Memphis/3/89 neuraminidase. Limited optimization of the pyrrolidine series resulted in a compound which was about 24-fold more potent than 2-deoxy-2,3-dehydro-N-acetylneuraminic acid in an anti-influenza cell culture assay using A/N2/Victoria/3/75 virus. X-ray structural studies of A/N9 neuraminidase-inhibitor complexes revealed that both classes of inhibitors induced the Glu 278 side chain to undergo a small conformational change, but these compounds did not show time-dependent inhibition. Crystallography also established that the alpha-amino group of the phenylglycine formed hydrogen bonds to the Asp 152 carboxylate as expected. Likewise, the beta-amino group of the pyrrolidine forms an interaction with the Tyr 406 hydroxyl group and represents the first compound known to make an interaction with this absolutely conserved residue. Phenylglycine and pyrrolidine analogs in which the alpha- or beta-amino groups were replaced with hydroxyl groups were 365- and 2,600-fold weaker inhibitors, respectively. These results underscore the importance of the amino group interactions with the Asp 152 and Tyr 406 side chains and have implications for anti-influenza drug design.     

What degree of work overload is likely to cause increased sickness absenteeism among nurses? Evidence from the RAFAELA patient classification system

AIM: This paper reports a study examining whether nurses' work overload is associated with increased sick leave and quantifying the loss of working days from work overload. BACKGROUND: The RAFAELA patient classification system indicates nursing care intensity in relation to an optimum and is one of the few validated monitoring instruments of patient-associated workload among nurses. However, it is not clear whether work overload is a risk factor for increased sickness absenteeism, an important occupational problem in health care. METHOD: An observational cohort study was carried out with 877 nurses, 31 wards and five Finnish hospitals. Patient-associated workload scores from the RAFAELA system were based on a 6-month monitoring period in 2004. Records of 12-month self certified (1-3 days) and medically certified (>3 days) periods of sick leave in the same year were obtained from employers' registers. FINDINGS: The mean workload was 9% (sd = 8%) above the optimum. There was a linear trend between increasing workload and increasing sick leave (P < or = 0.006). Among nurses with workload > or =30% above the optimum the rate of self certified periods of sick leave was 1.44 (95% CI 1.13-1.83) times higher than among those with an optimum workload. The corresponding rate ratio for medically certified sick leave was 1.49 (1.10-2.03). These excess rates of sickness absence resulted in 12 extra sick leave days per person-year. CONCLUSION: Measuring nurses' workload may be an important part of strategic human resource management of nurses to reduce sick leave among nurses.     

MALT lymphoma of the parotid salivary gland

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma was described for the first time in 1983 by Isaacson and Wright. It was classified into extranodal non-Hodkin's lymphomas of B-cell lymphocytes of the marginal zone of reactive lymphe follicles. It is characterized by both hyperplasia and colonization of plasmocytic, centrocytoid and monocytoid cells, by the infiltration of interfollicular and parafollicular parts of interstitium, as well as by the invasion of clusters of neoplastic lymphoid cells of the glandular epithelium, forming the pathognomic lymphoepithelial MALT limphoma lesions. CASE REPORT: In this paper we presented the two female patients, 59 and 75 years of age, with MALT lymphomas, associated with Miculicz's and Sj?gren's syndromes. The paper also underlined rather many-month-long, indolent clinical course, evalution of both tumors, massive in size, as well as two-sided localization in the case of the Miculicz's syndrome. After the subtotal parotidectomy, using conservation of nerve facialis, the tissue blocks were fixed in 10% formaldehyde. The paraffine sections were stained by routine histochemical and an immunohistochemical method by using monoclonal antibodies for both B-cell and T-cell lymphomas, due to the verification of lymphoepithelial lesions. The MALT lymphoma diagnosis was based on the histological criteria and confirmed by an immunohistochemical method. After the surgical therapy accompanied by chemotherapy, the patients were controlled at regular intervals, and residual MALT lymphoma did not appear. CONCLUSION: MALT lymphoma is a rare tumor of the salivary glands, with the most frequent localization in the parotide gland. It had a slow clinical course, without metastases in both patients. The diagnosis was made pathohistologically and confirmed immunohistochemically. The surgical therapy was accompained by adjuvant chemotherapy.