Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET.

The aim of this study was to assess synovitis by (18)F-FDG PET in an individual joint analysis and in a global analysis of rheumatoid arthritis (RA) disease activity and to compare (18)F-FDG PET parameters with clinical, biologic, and sonographic (US) rheumatoid parameters. METHODS: Three hundred fifty-six joints were assessed in 21 patients with active RA: the knees in all subjects and either wrists as well as metacarpophalangeal and proximal interphalangeal joints in 13 patients, or ankles and the first metatarsophalangeal joints in the remaining 8 patients. PET analysis consisted of a visual identification of (18)F-FDG uptake in the synovium and measurements of standardized uptake values (SUVs). Independent assessors performed the clinical and US examinations. RESULTS: PET positivity was found in 63% of joints, whereas 75%, 79%, and 56% were positive for swelling, tenderness, and US analysis, respectively. Both the rate of PET-positive joints and the SUV increased with the number of positive parameters present (swelling, tenderness, US positivity) and with the synovial thickness. The mean SUV was significantly higher in joints where a power Doppler signal was found. In a global PET analysis, the number of PET-positive joints and the cumulative SUV were significantly correlated with the swollen and tender joint counts, the patient and physician global assessments, the erythrocyte sedimentation rate and C-reactive protein serum levels, the disease activity score and the simplified disease activity index, the number of US-positive joints, and the cumulative synovial thickness. CONCLUSION: (18)F-FDG PET is a unique imaging technique that can assess the metabolic activity of synovitis and measure the disease activity in RA.     

A randomized controlled trial of electromagnetic therapy in the primary care management of venous leg ulceration

OBJECTIVE: The aim was to establish the potential efficacy, tolerabilityand side-effect profile of electromagnetic therapy as an adjunctto conventional dressings in the treatment of venous leg ulcers. METHOD: A prospective, randomized, double blind controlled clinicaltrial was carried out in a dedicated leg ulcer clinic basedin one urban general practice. Nineteen patients with leg ulcersof confirmed venous aetiology were assessed. The main outcomemeasures were rate and scale of venous leg ulcer healing, changesin patient-reported pain levels, quality of life, degree ofmobility, side effect profile and acceptability to patientsand staff. RESULTS: Sixty-eight per cent of patients attending this dedicated clinicachieved improvements in the size of their ulcer (4, 21%, healedfully) and in reduced pain levels (P < 0.05) during the trial,despite the chronicity of ulcer histories. Patients treatedwith electromagnetic therapy at 800 Hz were found at day 50to have significantly greater healing (P < 0.05) and paincontrol (P < 0.05) than placebo therapy or treatment with600 Hz. All patients reported improved mobility at the end ofthe study. The electromagnetic therapy was well tolerated bypatients, with no differences between groups in reporting adverseevents, and proved acceptable to staff. CONCLUSION: Despite the small numbers in this pilot study, electromagnetictherapy provided significant gains in the healing of venousleg ulcers and reduction in pain. Keywords. Electromagnetic therapy, RCT, leg ulcers, primary care.     

Polyamines and cardiovascular hypertrophy in experimental hypertension

Biochemical mechanisms which control cardiac and vascular response to hypertension are still unclear. Modifications of polyamines (putrescine, spermine, spermidine) may play a role in this phenomenon, since these molecules have been shown of importance in the control of tissue growth. Ornithine Decarboxylase (ODC) catalyses the first and probably the rate limiting step in the biosynthesis of the polyamines. We thus attempted to detect modification of ODC activity in renovascular hypertension in the rat (G1K-1C) and tried to correlate hypertrophic response and ODC activity in the aorta (Ao), the left (LV) and the right (RV) ventricles. In this experimental model, the aortic ODC activity increased at day 1 and 2, after clipping the renal artery, whereas in the LV the ODC activity increased after day 3 but stay high at least until day 7. The peak of ODC activity comes before the increase in DNA synthesis which occurs at day 4 in Ao, and the increase in protein turnover observed at day 7 in LV. No significant variation of ODC activity neither changes in DNA or protein biosynthesis rate are observed in the RV. In parallel with changes in ODC activity, an increase in spermidine and spermine content and mainly in the spermidine/spermine ratio is observed in the Ao and the LV confirming stimulation in polyamine biosynthesis in hypertensive tissues. In conclusion: increase in ODC activity is observed only in these tissues that will develop hypertrophy or hyperplasia and this modification is observed before any increase in nucleic acids or protein tissues content or turnover rate.     

Menstrual cycle and appetite control: implications for weight regulation

Hormonal fluctuations associated with the menstrual cycle influence appetite control and eating behaviour. Energy intake varies during the reproductive cycle in humans and animals, with a periovulatory nadir and a luteal phase peak. Patterns of macronutrient selection show less consistency but a number of studies report carbohydrate cravings in the premenstrual phase, particularly in women with premenstrual syndrome. The cyclical nature of food cravings are frequently, but not invariably, associated with depression. Fluctuations in appetite, cravings and energy intake during the menstrual cycle may occur in parallel with cyclical rhythms in serotonin, which can be accompanied by affective symptoms. The premenstrual phase can be considered as a time when women are especially vulnerable to overconsumption, food craving and depression; this is often associated with low serotonin activity.      

Expression of superoxide dismutase and xanthine oxidase in myometrium, fetal membranes and placenta during normal human pregnancy and parturition

Superoxide, an agent which attenuates the half-life of nitric oxide, is metabolized and synthesized by superoxide dismutase (SOD) and xanthine oxidase, respectively. Over the last few years much work has focused on the role of nitric oxide in human parturition. The aim of this study was to determine whether the onset of human parturition is associated with a change in the expression of copper/zinc superoxide dismutase (Cu/Zn SOD), manganese superoxide dismutase (Mn SOD) or xanthine oxidase within the uterus. Samples of myometrium, placenta, decidua and fetal membranes were obtained from women before and after the onset of labour at term. Immunocytochemistry was used to localize Cu/Zn SOD, Mn SOD and xanthine oxidase and measure SOD enzyme activity. Cu/Zn and Mn SOD-like immunoreactivity was detected in syncytiotrophoblast cells, villous stromal cells and endothelial cells of blood vessels in the placenta. In the myometrium Cu/Zn and Mn SOD were localized to myocytes and endothelial cells and to some vascular smooth muscle cells. In the fetal membranes we observed staining for Cu/Zn SOD and Mn SOD in the amnion, chorion, extravillous trophoblast and decidua. There was no difference in SOD enzyme activity or staining intensity for SOD between different cell types before and during labour. Xanthine oxidase immunoreactivity was identified in each of the tissues examined and again there was no difference in immunostaining in tissues obtained from women delivered before or after the onset of labour. These results show that the pregnant uterus is capable of both synthesizing and degrading superoxide and suggest that superoxide dismutase and xanthine oxidase may play a role in the maintenance of uterine quiescence during pregnancy, but not in the initiation of parturition.      

Hydrosalpinges adversely affect markers of endometrial receptivity

While in-vitro fertilization (IVF) was initially developed in women with tubal factor infertility, recent clinical studies have suggested that the presence of hydrosalpinges lowers implantation and pregnancy rates. We postulated that these hydrosalpinges cause impaired endometrial receptivity. A total of 103 women with hydrosalpinges were prospectively evaluated, and compared with 55 infertile and 44 fertile controls. All women had endometrial biopsies during the window of implantation, analysed by conventional histological criteria, and also stained for three integrin markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha vbeta3). Women with hydrosalpinges (cases) expressed significantly less of the alpha vbeta3 integrin compared with controls. There was no difference in expression of alpha1beta1 or alpha4beta1 among groups. A significantly greater number of cases had out of phase histology and missing alpha vbeta3 (type I defects) and absent integrin expression despite normal histological maturation (type II) defects, compared with controls. Of 20 women with impaired endometrial receptivity who were also biopsied after hydrosalpinx surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven percent of type I and 57% of type II defects were corrected postoperatively. Using markers of endometrial receptivity, this study demonstrates that inflammatory hydrosalpinges have an adverse effect on endometrial receptivity, which in some cases may be overcome by surgical treatment of the hydrosalpinx.