Quality of life in patients with endometriosis and the effect of pertubation with lidocaine - a randomized controlled trial.

OBJECTIVE: Pertubation with lidocaine has been shown to reduce pain (on a VAS-scale) in women with endometriosis. A clinical study was performed to evaluate the effect of lidocaine pertubations on quality of life. DESIGN: Double-blind, randomized and controlled trial. SETTING: Three outpatient units in Stockholm, Sweden. POPULATION: Eligible patients had endometriosis with dysmenorrhoic pain >VAS 50 mm. METHODS: The patients were randomized to pre-ovulatory pertubations with lidocaine (n = 24) or placebo (n = 18) during three consecutive menstrual cycles. The procedure comprised passing the solution through the uterus and the Fallopian tubes via an intracervical balloon catheter. The effect was evaluated with the validated Endometriosis Health Profile-30 questionnaire before and after treatments. MAIN OUTCOME MEASURES: Changes in scores at six and 12 months from baseline were compared between the groups with the Mann-Whitney U-test. RESULTS: After 6 months there was a significant difference between the lidocaine (n = 19) and the placebo (n = 16) groups for the dimension social support (median -18.8 vs. -6.3, p = 0.034), whereas there were no significant differences for the other dimensions after 6 or 12 months. The mean changes in the lidocaine group were above the minimal important difference levels in eight of 12 measurements of quality of life dimensions compared with two of 12 in the placebo group. CONCLUSIONS: This clinical trial indicates that pertubations with lidocaine might improve the social support dimension of quality of life in patients with endometriosis.

Minimal clinically important difference for pain on the VAS scale and the relation to quality of life in women with endometriosis.

OBJECTIVES: The minimal important difference can be helpful in interpreting data from clinical trials. The objective of the study was to calculate the minimal important difference for improvement on the VAS scale for women with endometriosis. STUDY DESIGN: A prospective study was conducted to evaluate the effect of pertubation with lignocaine on dysmenorrhea and quality of life in women with endometriosis. Data collected in the trial were used for additional analyses in the present descriptive study. Eligible women (n=37) had endometriosis with pain>VAS 50mm (visual analogue scale). MAIN OUTCOME MEASURES: In a questionnaire, women evaluated their maximum pain on the VAS- scale during every menstrual period before and after treatment. They also estimated the changes in overall pain level by answering the response categories "much better", "somewhat better", "about the same", "somewhat worse" or "much worse". The women were grouped according to their own estimation of change in pain intensity after four months. The minimal important differences for change on the VAS scale correlate to the mean change for women who felt "somewhat better" (n=18) excluding those who were pain free (n=2). RESULTS: The minimal important difference for improvement on the VAS scale was found to be -39mm and/or -49%. CONCLUSION: If the patients have a pain level of at least 50mm on VAS scale at inclusion, the cut off for success in clinical trials is suggested to be defined as an either >40mm or a >50% decrease on VAS scale. Trial registry ClinicalTrials.gov Identifier: NCT01329796.

Effect of Lignocaine on IL-6, IL-8, and MCP-1 in Peritoneal Macrophages and Endometriotic Stromal Cells.

OBJECTIVE: The objective was to evaluate the effect of lignocaine on cytokine expression and secretion in vitro in peritoneal fluid macrophages and endometriotic stromal cells. DESIGN: Experimental in vitro study on human cells. POPULATION AND SAMPLE: Peritoneal fluid (n = 10) and samples from endometriotic cysts (n = 7) were collected from 13 women (women with endometriosis n = 8, and healthy controls n = 5) during surgery for clinical reasons. METHODS: Macrophages from the peritoneal fluid and cells from the inside of the endometriotic cysts capsules were isolated and cultivated for 24 to 48 hours in medium with and without the supplement of lignocaine 0.1 or 1.0 mg/mL. Relative gene expression of monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), and IL-8 was evaluated with quantitative polymerase chain reaction and compared between treated and untreated cells with Wilcoxon matched pairs. The concentrations of MCP-1, IL-6, and IL-8 were measured using enzyme-linked immunosorbent assay and were compared between treated and untreated cells with Wilcoxon matched pairs. RESULTS: The gene expression and protein secretion of IL-8 in endometriotic stromal cells after incubation with lignocaine 0.1 mg/mL were significantly decreased after 24 hours compared to the controls ( P = .028 and P = .018). Macrophages from healthy controls had a significant lower gene expression of all tested cytokines ( P = .043) after treatment with lignocaine, but there were no significant differences in protein level. Macrophages from women with endometriosis showed diverging results since 3 of 5 samples showed increased gene expression of 1 (n = 2) or 2 cytokines (n = 1) after lignocaine treatment. CONCLUSION: Lignocaine can affect the gene expression and secretion of some proinflammatory cytokines in vitro.

A pilot study of facial, cranial and brain MRI morphometry in men with schizophrenia: part 2.

This pilot study applies a new 3D morphometric MR method to test the hypothesis that men with schizophrenia (vs. controls) have deviant facial shapes and landmark relations in cranio/facial/brain (CFB) regions. This constitutes Part 2 of paired articles in this issue of Psychiatry Research: Neuroimaging, in which Part 1 presents the new method in detail. MRI coordinates from CFB landmarks of 23 patients and 15 controls were identified and then aligned with the Procrustes model, leaving shape as the only unit-less geometrical information. Men with schizophrenia had significantly longer mid- and lower-facial heights, and greater lower (left) facial depth, with a tendency toward rotation along the facial midline. This supports findings from earlier anthropometric and 3D studies of the "exterior" (face). In contrast, none of the patient-control differences for the new "interior" (cranial-brain) distances reached statistical significance. These results need to be retested on a larger sample of both sexes.

Serum concentration of lignocaine after pertubation: an observational study.

OBJECTIVE: The objective of this study was to report the serum concentration of lignocaine after pertubation in patients with endometriosis. DESIGN: Prospective observational study. SETTING: The study was carried out at a gynaecological outpatient unit in Stockholm, Sweden. POPULATION: Eligible patients had endometriosis with a dysmenorrhoic pain score of >50 mm on a visual analogue scale, and patent fallopian tubes. METHODS: Patients with endometriosis (n = 25) were included in the study. The patients received pre-ovulatory pertubations with lignocaine hydrochloride 10 mg (n = 16) or ringer acetate (placebo, n = 9). The procedure comprised passing the study solution through the uterus and the fallopian tubes via an intra-cervical balloon catheter. Serum samples were collected at 0, 5, 15 and 30 min after pertubation. MAIN OUTCOME MEASURES: The serum samples were analysed for the concentration of lignocaine with an LCMS-SIM method. RESULTS: Low levels of lignocaine were detected in the serum samples following pertubation of 10 mg lignocaine hydrochloride. The highest observed concentration was seen after 30 min (mean 0.050 µg/ml), with an individual maximum of 0.124 µg/ml. Maximum concentration (C max) and time to C max (T max) could not be calculated, since the highest values were observed in the 30-min samples, which was the last sample obtained. Lignocaine was not detected after pertubation with placebo. CONCLUSIONS: The serum levels of lignocaine following pertubation of 10 mg lignocaine hydrochloride are detectable but low. Lignocaine pertubated through the fallopian tubes reaches the peritoneal cavity and diffuses through the peritoneum into the blood circulation. Pertubation with lignocaine is safe and has no lignocaine-related adverse events.