Post-treatment States Research Articles

Clotrimazole-induced shifts in vaginal bacteriome and lipid metabolism: insights into recovery mechanisms in vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) is a prevalent condition affecting a significant proportion of women worldwide, with recurrent episodes leading to detrimental effects on quality of life. While treatment with clotrimazole is common, the specific alterations it evokes in the vaginal bacteriome and metabolome were previously underexplored. In this prospective study, we enrolled reproductive-age women diagnosed with single VVC and conducted comprehensive analyses of vaginal fungi, bacteriome, and metabolome before and after local clotrimazole treatment. We observed a significant reduction in Candida albicans and notable improvements in vaginal cleanliness. Advanced sequencing revealed substantial shifts in the vaginal bacteriome, with an increase in Lactobacillus-dominant communities post-treatment. Our findings identified 17 differentially abundant bacterial species, including notable decreases in pathogenic anaerobes such as Gardnerella vaginalis, Dialister micraerophilus, and Aerococcus christensenii, suggesting a restoration of a healthier microbial balance. Furthermore, metabolomic analysis revealed significant changes in 230 metabolites, particularly within lipid metabolism pathways, with marked downregulation of lipid-related compounds linked to inflammation. Correlation studies indicated a strong interplay between lipid metabolites and specific bacterial species, emphasizing the influence of clotrimazole treatment on microbial and metabolic interactions. Importantly, predictive models using microbiota and metabolite signatures demonstrated high accuracy in distinguishing pre- and post-treatment states. This research highlights clotrimazole's dual role in effectively clearing Candida infection and promoting a healthier vaginal microenvironment, paving the way for novel microbial and metabolomic-based diagnostic approaches to enhance VVC management and understand its underlying mechanisms.

Effectiveness of ultrasound-guided perineural hydro-dissection with 5% dextrose for pronator teres syndrome: a case series

Pronator teres syndrome (PTS) is s a proximal compressive neuropathy of the median nerve at the elbow level by the pronator teres muscle leading to pain and numbness in the area of the nerve distribution. Conservative treatment may be effective in 50-70% of cases with extremity rest and non-steroidal anti-inflammatory drugs, corticosteroids, and surgical decompression. Dextrose perineural hydro-dissection under ultrasound guidance is an interventional therapeutic option in cases of peripheral neuropathy due to nerve entrapment. This is a serial case study investigating the efficacy of dextrose perineural hydro-dissection for long-term pain relief in PTS. A numeric rating scale (NRS) and Quick-DASH (Quick-Disability of the Arm, Shoulder and Hand) were used to evaluate pre- and post-treatment states with ultrasound-guided 5% dextrose hydro-dissection therapy. All patients experienced satisfactory resolution on evaluation twelve months after treatment. In long-term evaluation, dextrose perineural hydro-dissection exhibits good clinical and functional outcomes for patients with PTS.
 Abbreviations: CTS - carpal tunnel syndrome; HD - hydro-dissection; NRS - numeric rating scale; PTS - Pronator teres syndrome; Quick-DASH - Quick-Disability of the Arm, Shoulder and Hand
 Key words: Pronator Syndrome; Pain; Perineural Hydro-Dissection; Median Neuropathy
 Citation: Tua Siahaan YM. Effectiveness of ultrasound-guided perineural hydro-dissection with 5% dextrose for pronator teres syndrome: a case series. Anaesth. pain intensive care 2023;27(5):607−613; DOI:
 10.35975/apic.v27i5.2318
 Received: July 11, 2023; Reviewed: August 27, 2023; Accepted: August 27, 2023

Abstract 2061: Deep immune profiling by mass cytometry revealed an association between the state of immune system before treatment and response to checkpoint inhibitor therapy in clear cell renal cell carcinoma

Abstract Checkpoint immunotherapy (CPI) and its combination with tyrosine kinase inhibitor (TKI) therapy are widely used in the treatment of many cancers, including clear cell renal cell carcinoma (ccRCC). Although recent advances in these therapies demonstrate effectiveness, a subset of patients are unresponsive. In this study, using deep immune profiling by mass cytometry (CyTOF), we analyzed peripheral blood mononuclear cell (PBMC) samples from 86 ccRCC patients pre- and post-treatment. The cohort included patients treated with first-line CPI (n = 43), TKI (n = 15) and combinatorial CPI+TKI (n = 28), with PBMC samples collected pre- (n = 41) and post- (n = 69) therapy (n = 24 patients total with paired samples). Samples were characterized by CyTOF analysis of 30 different cell surface markers. Using t-distributed stochastic neighbor embedding (tSNE) and Phenograph clustering, the presence of immune populations and subpopulations were characterized and associated with therapeutic response as well as longitudinally tracked. While most cell types did not differ between pre- and post-treatment states, a decrease in CD8 and CD4 PD1+ T cell subsets was observed in patients treated with CPI and CPI+TKI (p < 0.001). Also, increased CD8 effector memory T cells were observed in post-treatment samples in those treated with CPI or CPI+TKI (p < 0.001).Subsequent analysis of pre-treatment samples in the context of clinical outcome revealed specific features associated with favorable response to immunotherapy. Responders (R) in comparison with non-responders (NR) were characterized by an increased number of naive CD4 T cells (p = 0.03), CD8 T cells (p = 0.038), immature NK cells (p = 0.005) and lower percentage of granulocytes (p = 0.012). Using unsupervised hierarchical clustering, 8 patient groups were identified with a unique immune profile enriched by a certain PBMC population. Three groups (G1-G3), which included a high ratio of R, were enriched by naive T cells, immature NK cells and non-classical monocytes, respectively. The G4 group, enriched with B cells, consisted of R and NR in equal numbers. The G5-G8 groups, enriched with granulocytes, classical monocytes, mature NK-cells and effector CD8 T cells, respectively, were primarily comprised of NR. Patients with favorable pre-treatment immune profiles also belonged to favorable groups post-treatment, with a similar trend observed with unfavorable profiles. In conclusion, this analysis revealed a remarkable association between the initial immune status or “portrait” of the patient before therapy and subsequent therapeutic outcome as well as the development of therapeutic resistance. Citation Format: Svetlana Shishkova, Dmitry Tabakov, Evgeny Egorov, Akshaya Ramachandran, Yang Lyu, Krystle Nomie, Jessica Brown, Vladimir Zyrin, Alexander Zaytcev, Natalia Miheecheva, Ekaterina Postovalova, Alexander Bagaev, Ravshan Ataullakhanov, James Hsieh. Deep immune profiling by mass cytometry revealed an association between the state of immune system before treatment and response to checkpoint inhibitor therapy in clear cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2061.

Prospective study on resting state functional connectivity in adolescents with major depressive disorder after antidepressant treatment

Recent advances in functional magnetic resonance imaging (fMRI) have resulted in many studies on resting-state functional connectivity (rsFC) in depressed patients. Previous studies have shown alterations between multiple brain areas, such as the prefrontal cortex, anterior cingulate cortex, and basal ganglia, but there are very few prospective studies with a longitudinal design on adolescent depression patients. We therefore investigated the change in positive rsFC in a homogeneous drug-naïve adolescent group after 12 weeks of antidepressant treatment. Functional neuroimaging data were collected and analyzed from 32 patients and 27 healthy controls. Based on previous literature, the amygdala, anterior cingulate cortex (ACC), insula, hippocampus, and dorsolateral prefrontal cortex (DLPFC) were selected as seed regions. Seed-to-voxel analyses were performed between pre- and post-treatment states as well as between the patients and controls at baseline. The positive rsFC between the right DLPFC and the left putamen/right frontal operculum were shown to be higher in patients than in the controls. The positive rsFC between the left DLPFC and left putamen/left lingual gyrus was also higher in the patients than in the controls. The positive rsFC between the right dorsal ACC and the left precentral gyrus had reduced after the 12-week antidepressant treatment. Regions involved in the frontolimbic circuit showed changes in the positive rsFC in the depressed adolescents as compared to in the healthy controls. There were also significant changes in the positive rsFC after 12-weeks of antidepressant treatment. The involved regions were associated with emotional regulation, cognitive functioning, impulse control, and visual processing.

Temporal and spatial topography of cell proliferation in cancer.

3122 Background: Tumors are complex ecosystems where exogenous and endogenous cues are integrated to either stimulate or inhibit cancer cell proliferation. However, the nature of these complex cell cycle states, their spatial organization, response to perturbation, and implications for clinical outcomes, are poorly characterized in tumor tissues. Methods: We used multiplexed tissue imaging to develop a robust classifier of proliferation, the multivariate proliferation index (MPI), using 513 unique tumors across five cancer types. Next, we used dimensionality reduction analysis to assess how the patterns of cell cycle protein expression in tumors were altered in response to perturbation. Results: The MPI outperforms single markers, like Ki67, when classifying proliferative index across diverse tumor types and reveals the proliferative architecture of tumors in situ. We find that proliferative and non-proliferative cancer cells are organized across microscopic (cell-to-cell) and macroscopic (tissue-level) scales. Both domains are reshaped by therapy, and local clusters of proliferative and non-proliferative tumor cells preferentially neighbor distinct tumor-infiltrating immune cells. We further phenotyped non-proliferating cancer cells using markers of quiescent cancer cells, cancer stem cells, and dormant cancer cells. We found that these types of non-proliferating cancer cells can occupy distinct regions within the same primary tumor. In high-dimensional marker space, populations of proliferative cancer cells express canonical patterns of cell cycle protein markers, a property we refer to as “cell cycle coherence”. Untreated tumors exist in a continuum of coherence states, ranging from optimal coherence, akin to freely cycling cells in culture, to reduced coherence characterized by either cell cycle polarization or non-canonical marker expression. Coherence can be stereotypically altered by induction and abrogation of mitogen signaling in a HER2-driven model of breast cancer. Cell cycle coherence is modulated by neoadjuvant therapy in patients with localized breast cancer, and coherence is associated with disease-free survival after adjuvant therapy in patients with colorectal cancer, mesothelioma and glioblastoma. Conclusions: The MPI robustly defines proliferating and non-proliferating cells in tissues, with immediate implications for clinical practice and research. The coherence metrics capture the diversity of post-treatment cell cycle states directly in clinical samples, a fundamental step in advancing precision medicine. More broadly, replacing binary metrics with multivariate traits provides a quantitative framework to study temporal processes from fixed static images and to investigate the rich spatial biology of human cancers.

Progress in the basic and clinical research on the Schlemm's canal.

Glaucoma is a leading cause of irreversible blindness in the world. Intraocular pressure (IOP) plays a key role in glaucoma development and progression. Schlemm's canal (SC), an important structure of the anterior chamber angle, regulates the flow of aqueous humor and maintains IOP. Because of its special function of aqueous outflow, the SC has been intensive investigated recently. Several characteristics of SC in anatomy, physiology and pathophysiology have been revealed. Compare to normal, glaucomatous SC cells are more sensitive to substrate stiffness, have higher stiffness and and lower porosity leading to higher outflow resistance. And SC collapse caused by acute IOP increase is partially or totally reversal. With advanced inspection techniques, high-quality images of the SC can be obtained in vivo, which facilitates SC quantitative measurements clinically and allows us to investigate a new therapy paradigm for glaucoma. In this review, we summarize the basic and clinical research that focused on mechanisms of aqueous outflow resistance and SC changes in physiological, pathological, and post-treatment states.

Immune and Neuroendocrine Trait and State Markers in Psychotic Illness: Decreased Kynurenines Marking Psychotic Exacerbations.

Objective: Different patterns of immune system upregulation are present in the acute vs. post-treatment states of psychotic illness. We explored the existence of state and trait markers in the peripheral immune system and two immune-associated neuroendocrine pathways (IDO and GTP-CH1 pathway) in a longitudinal sample of psychosis patients. We also evaluated the association of these markers with neuropsychiatric symptomatology.Method: Plasma concentrations of peripheral blood markers were measured in a transdiagnostic group of 49 inpatients with acute psychosis and 52 matched healthy control subjects. Samples were obtained in patients within 48 h after hospital admission for an acute psychotic episode (before initiation of antipsychotics), after 1–2 weeks and again after 8 weeks of treatment. Kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), phenylalanine, tyrosine, nitrite, and neopterin were measured using HPLC and LC-MS/MS analysis. Concentrations of CRP, CCL2 (MCP1) and cytokines were determined with multiplex immunoassay. PANSS interviews and cognitive tests were performed at baseline and follow-up. Mixed model analyses were used to identify trait and state markers.Results: Patients had significantly higher plasma concentrations of CRP, CCL2, IL1RA, and lower concentrations of KA and KA/Kyn at all time points (F7.5–17.5, all p < 0.001). Increased concentrations of IL6, IL8, IL1RA, TNFα, and CCL2 and decreased QA and 3-HK (F8.7–21.0, all p < 0.005) were found in the acute psychotic state and normalized after treatment. Low nitrite concentrations at admission rose sharply after initiation of antipsychotic medication (F42.4, p < 0.001). PANSS positive scale scores during the acute episode correlated with pro-inflammatory immune markers (r ≥ |0.5|), while negative scale scores correlated inversely with IDO pathway markers (r ≥ |0.4|). Normalization of KA and 3-HK levels between admission and follow-up corresponded to a larger improvement of negative symptoms (r = 0.5, p < 0.030) A reverse association was found between relative improvement of SDST scores and decreasing KA levels (r = 0.5, p < 0.010).Conclusion: The acute psychotic state is marked by state-specific increases of immune markers and decreases in peripheral IDO pathway markers. Increased CRP, CCL2, and IL1RA, and decreased KA and KA/Kyn are trait markers of psychotic illness.

Experimental evaluation and tomographic characterization of polymer gel conformance treatment

Excessive water production from hydrocarbon reservoirs is considered as one of major problems, which has numerous economic and environmental consequences. Polymer-gel remediation has been widely used to reduce excessive water production during oil and gas recovery by plugging high permeability zones and improving conformance control. In this paper, we investigate the performance of a HPAM/PEI (water-soluble Hydrolyzed PolyAcrylaMide/PolyEthyleneImine) polymer-gel system for pore space blockage and permeability reduction for conformance control purpose. First, the gel optimum composition, resistance to salt and long life time are determined using bottle tests as a standard method to specify polymer-gel properties. Then the performance and stability of the optimized polymer-gel are tested experimentally using coreflood tests in sandpack core samples. The effects of different parameters such as gel concentration, initial permeability of the cores, and formation water salinity on the final permeability of the cores are examined. Finally, the gel flow-induced local porosity changes are studied in both a sandpack core and a real carbonate sample using grayscale intensity data provided from 3D Computed Tomography (CT) images in pre- and post-treatment states. The results show that the gel system has a good strength at the middle formation water salinity (in the range of typical sea water salinity). In addition, despite a higher performance in high permeability cores, the gel resistance to degradation in such porous media is reduced. The CT images reveal that the initial porosity distribution has a great influence on the performance of the gel to block the pore space.

Adhesive bonding of 3D-printed plastic components

ABSTRACTTensile strength of adhesive bonds with three different commercial epoxy resins and laser sintered polyamide 12 (PA 12) has been evaluated by means of Centrifugal Adhesion Testing Technology (CATT, LUMiFrac Adhesion Analyzer). Different post treatment states (as received and chemically smoothed) and pre-treatment states (as received and atmospheric plasma) of the PA 12 surface have been considered. It has been shown that the epoxy resins infiltrate the surface porosity of the laser sintered material, which leads to a special fracture pattern. Tensile strength of the adhesive bonds has been significantly improved after atmospheric plasma pretreatment. Chemical smoothing had a neglicable effect on the tensile strength of the tested specimens, but lead to a change in fracture pattern, especially without atmosphric plasma pretreatment.

Quantitative Dynamic Thoracic MRI: Application to Thoracic Insufficiency Syndrome in Pediatric Patients.

Background Available methods to quantify regional dynamic thoracic function in thoracic insufficiency syndrome (TIS) are limited. Purpose To evaluate the use of quantitative dynamic MRI to depict changes in regional dynamic thoracic function before and after surgical correction of TIS. Materials and Methods Images from free-breathing dynamic MRI in pediatric patients with TIS (July 2009-August 2015) were retrospectively evaluated before and after surgical correction by using vertical expandable prosthetic titanium rib (VEPTR). Eleven volumetric parameters were derived from lung, chest wall, and diaphragm segmentations, and parameter changes before versus after operation were correlated with changes in clinical parameters. Paired analysis from Student t test on MRI parameters and clinical parameters was performed to detect if changes (from preoperative to postoperative condition) were statistically significant. Results Left and right lung volumes at end inspiration and end expiration increased substantially after operation in pediatric patients with thoracic insufficiency syndrome, especially right lung volume with 22.9% and 26.3% volume increase at end expiration (P = .001) and end inspiration (P = .002), respectively. The average lung tidal volumes increased after operation for TIS; there was a 43.8% and 55.3% increase for left lung tidal volume and right lung tidal volume (P < .001 for both), respectively. However, clinical parameters did not show significant changes from pre- to posttreatment states. Thoracic and lumbar Cobb angle were poor predictors of MRI tidal volumes (chest wall, diaphragm, and left and right separately), but assisted ventilation rating and forced vital capacity showed moderate correlations with tidal volumes (chest wall, diaphragm, and left and right separately). Conclusion Vertical expandable prosthetic titanium rib operation was associated with postoperative increases in all components of tidal volume (left and right chest wall and diaphragm, and left and right lung tidal volumes) measured at MRI. Clinical parameters did not demonstrate improvements in postoperative tidal volumes. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Paltiel in this issue.

Cost Effectiveness of the Oncotype DX Genomic Prostate Score for Guiding Treatment Decisions in Patients With Early Stage Prostate Cancer

ObjectiveTo determine the cost-effectiveness of using the Oncotype DX Genomic Prostate Score (GPS), a 17-gene expression assay that can be used to inform decisions regarding active surveillance (AS) vs immediate treatment. MethodsWe developed a Markov model simulating 20-year outcomes for 65-year-old men with very low-, low-, or favorable intermediate-risk prostate cancer undergoing AS vs immediate treatment using GPS vs no testing. Utilities, costs, and probabilities were extracted from the literature and National Medicare Fee Schedules to determine incremental cost-effectiveness ratios (ICER) from a payer perspective. ResultsIn the overall cohort, the ICER of GPS-guided therapy was $31,394 per quality-adjusted life-year (QALY). When stratified by risk group, the ICER was $25,343 per QALY in very low-risk, $28,911 per QALY in low-risk, and $39,695 per QALY in favorable intermediate-risk patients. On sensitivity analysis, findings were robust against a willingness-to-pay of $100,000 per QALY to variations in key model parameters, including the cost of annual management of AS, probability of exiting AS to treatment, cost of treatment, and probability of biochemical failure post-treatment. However, the cost-effectiveness was sensitive to small differences in the utility of AS and the utility of no evidence of disease post-treatment states. ConclusionThe use of the GPS was cost-effective in guiding treatment decisions regarding AS vs immediate treatment. The cost-effectiveness was sensitive to small differences in the utilities of the AS and no evidence of disease post-treatment states, highlighting the importance of assessing patient preferences.

Interventions for preventing and treating cardiac complications in Duchenne and Becker muscular dystrophy and X-linked dilated cardiomyopathy.

Interventions for preventing and treating cardiac complications in Duchenne and Becker muscular dystrophy and X-linked dilated cardiomyopathy.

Decision analysis defining optimal management of clinical stage 1 high-risk nonseminomatous germ cell testicular cancer with lymphovascular invasion

BackgroundRisk of recurrent disease for men with clinical stage 1 high-risk nonseminomatous germ cell testicular cancer (CS1 NSGCT) with lymphovascular invasion (LVI) after orchiectomy is 50% and current treatment options (surveillance [S], retroperitoneal lymph node dissection [RPLND], or 1 cycle of BEP [BEP ×1]) are associated with a 99% disease specific survival, therefore practice patterns vary. We performed a decision analysis using updated data of long-term complications for men with CS1 NSGCT with LVI to quantify and assess relative treatment values. MethodsDecision analysis included previously defined utilities (via standard gamble) for posttreatment states of living from 0 (death from disease) to 1 (alive in perfect health) and updated morbidity probabilities. We quantified the values of S, RPLND, and BEP ×1 via the rollback method. Sensitivity analyses including a range of orchiectomy cure rates and utility values were performed. ResultsEstimated probabilities favoring treatment with RPLND (0.97) or BEP ×1 (0.97) were equivalent and superior to surveillance (0.88). Sensitivity analysis of orchiectomy cure rates (50%–100%) failed to find a cure rate that favored S over BEP ×1 or RPLND. Varying utility values for cure after S from 0.92 (previously defined utility) to 1 (perfect health), failed to find a viable utility state favoring S over BEP ×1 or RPLND. An orchiectomy cure rate of ≥82% would be required for S to equal treatment of either type. ConclusionsWe demonstrate that for surveillance to be superior to treatment with BEP ×1 or RPLND, the orchiectomy cure rate must be at least 82%, which is not expected in a patient population with high-risk CS1 NSGCT.

Comparison of conservative and surgical treatment methods in patients with meniscopathy

Objective: Arthroscopic surgery is currently a well-known treatment method for meniscal pathologies. This study aims to compare conservative and surgical methods in patients with meniscopathy. Materials and Methods: The retrospective analyses of 68 patients with meniscal tear were included in this study. Patients were divided into two groups: a medical treatment group (MTG) and a surgical treatment group (STG). Diagnosis was perfomed by physical examination and magnetic resonance imaging (MRI). All patients were evaluated before and after treatment with main pain score (MPS), International Knee Documentation Committee (IKDC) score, body mass index (BMI), and Ultrasensitive C-reactive protein (US-CRP). In the MTG group, 31 patients underwent medical treatment with naproxen sodium for three days, ice application, activity modification, and muscle exercises. In the STG group, 37 patients underwent arthroscopic partial menisectomy and naproxen sodium for three days. Parameters characterizing pretreatment and posttreatment states were compared statistically. The MPS, IKDC, BMI, and US-CRP values of both groups were recorded at baseline and three months after treatment. Results: Surgical treatment group (STG): In this group, after three months of treatment, MPS decreased and IKDC scores increased significantly when compared with baseline (P 0.1799, respectively). Medical treatment group (MTG): In this group, MPS decreased and BMI increased significantly after three months compared with preoperative scores (P 0.05, respectively). Conclusion: IKDC and pain scores of patients with meniscal tear improved by arthroscopic knee surgery.

Morphological adaptation of muscle collagen and receptor of advanced glycation end product (RAGE) in osteoarthritis patients with 12 weeks of resistance training: influence of anti-inflammatory or glucosamine treatment

The aim of this study was to investigate the effect of 12-week resistance training on morphological presence of collagen and RAGE (receptor for advanced glycation end products) in skeletal muscle of patients with knee osteoarthritis (OA). Little is known about the influence of exercise on the skeletal muscle matrix that supports joints affected by OA mainly when it is associated with medication taken by OA patients (non-steroid anti-inflammatory drugs (NSAID) and glucosamine). A biopsy was collected from the vastus lateralis muscle in all patients before and after 12-week period of training. The patients (age 55-69 years) were divided into three groups, treated with NSAID, glucosamine or placebo. In addition, the muscle samples were analysed by immunohistochemistry for collagen types, RAGE and capillaries ratio. An increment in immunoreactivity for type IV collagen after the training period was observed in 72 % of all biopsies when compared with their respective baseline samples. Reduced immunoreactivity of collagen type I was observed in all patients treated with glucosamine. A significant increase with training in the amount of RAGE was detected in the placebo group only (p < 0.05). Comparison of post-treatment states indicated significant differences between the placebo and glucosamine group data, demonstrating increased levels in the placebo group (p < 0.05). These findings suggest a basement membrane remodelling in favour of a strengthened extracellular matrix surrounding individual muscle fibres after 12 weeks of resistance training. Glucosamine with training appeared to attenuate RAGE accumulation more than was seen with NSAID or placebo in skeletal muscle of OA patients.

Can transcranial magnetic stimulation be used to evaluate patients with narcolepsy?

Narcolepsy is a rare, chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy and other manifestations of dissociated rapid eye movement in sleep. We assessed the utility of transcranial magnetic stimulation (TMS) as an objective tool to elucidate the cortical excitability changes and also to analyze its role in assessing the treatment efficacy in narcolepsy. Eight patients with narcolepsy under our regular follow-up from 2000 to 2009 at our Sleep disorder clinic were chosen. All of them underwent polysomnography, multiple sleep latency tests and TMS. Resting motor threshold (RMT), cortical silent period (CSP) and central motor conduction time (CMCT) were assessed using TMS in both drug-naïve and post-treatment states. Eight controls were also subjected to all the three investigations. Appropriate statistical methods were used. The mean RMT (%) pre-treatment was higher in narcolepsy patients than that in controls, and it normalized following treatment. CSP and CMCT were unaffected in narcolepsy patients as compared to controls. This study shows that the cortical excitability is significantly low in narcolepsy patients. This motor cortex hypoexcitability becomes normal with the institution of treatment, pari passu with the control of symptoms. In future, TMS may be considered as an effective tool for documenting the treatment efficacy in patients with narcolepsy.

909 Association of Serum Cytokines &amp; Albumin in Visceral Leishmaniasis

Background and aims: Investigating the cause of hypoalbuminemia in the Visceral leishmaniasis (kala azar), this study was designed to measure the levels of these cytokines in kala azar patients and to assess any correlation between their levels with serum albumin. Methods: From March 2007 to May 2008, thirty kala azar patients, were enrolled in the study. The diagnosis was documented by the presence of related clinical signs and symptoms plus at least one positive laboratory test (one or more of these three: Indirect fluorescent antibody(IFA) equal to or more than 1/128, k39 strip test, and bone marrow aspiration). We measured the serum levels of albumin, and cytokines at the pre-treatment state and also one week after treatment and in a control group consisting of 38 healthy children. Results: Albumin was decreased and IL-6 and TNF were increased significantly in the pre-treatment state.IL-1 was not statistically decreased in the pretreatment. There was a negative association between serum albumin and IL-6 levels in both the pre- and post-treatment states. (r =-0.43 and r = -0.35 respectively). In the post-treatment state serum albumin increased and IL-6 levels decreased. This increment wasn't statistically significant, that could be explained by the low number of patients. Conclusion: Serum levels of IL-6 and TNF are increased significantly in the active phase of kaka azar. Also, there is a negative association between serum levels of IL-6 and albumin in the active and convalescent states of the visceral leishmaniasis.

F-18 FDG PET/CT Findings in Two Patients With Pyothorax-Associated Lymphoma

We report 2 cases of pyothorax-associated lymphoma that underwent F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) examinations during pre- and post-treatment states. The FDG PET/CT examinations were able to define the massive lesions as areas of intensive FDG uptake. After radiotherapy, follow-up PET/CT examinations showed the disappearance of the abnormal FDG uptake, although the residual masses remained in the original regions. Finally, we concluded that these lesions had entered remission based on the PET/CT findings. These cases indicate that PET/CT is a useful modality for detecting pyothorax-associated lymphoma and for evaluating the efficacy of treatments.

The precision of health state valuation by members of the general public using the standard gamble

Precision is a recognised requirement of patient-reported outcome measures but no previous studies of the precision of methods for obtaining health state values from the general public, based on specific health state descriptions or vignettes, have been carried out. The methodological requirements of policy makers internationally is driving growth in the use of methods to obtain utilities from the general public to inform cost per quality-adjusted life-year (QALY) analyses of health technologies being considered for adoption by health systems. The precision of five comparisons of the outcomes of treatments, based on health state descriptions, was assessed against the results of clinical trials which showed a statistically and clinically significant improvement using an internet panel of members of the UK general public. Health states were developed to depict the baseline and post-treatment states from these exemplar clinical trials. Preferences for health states were obtained using bottom-up titrated standard gamble over the internet, and differences between summary health state values corresponding to the treatment and comparator groups within each exemplar study were compared. Results are considered in the context of various estimates for the minimally important difference in utility values. Participation among members of the internet panel in the five exemplars ranged from 27 to 59. In four of the five exemplars, the utility-based estimates of treatment benefit showed significant differences between groups and were greater than an assumed minimally important difference of 0.1. Mean utility differences between groups were: 0.23 (computerised cognitive behavioural therapy for depression, P < 0.001), 0.11 (hip resurfacing for hip osteoarthritis, P < 0.001), 0.0005 (cognitive behavioural therapy for insomnia, P = 0.98), 0.15 (pulmonary rehabilitation for COPD, P < 0.001) and 0.11 (infliximab for Crohn's disease, P < 0.001). The confidence intervals around the estimates of utility-based treatment effect in three of the five examples did not exclude the possibility of a difference smaller than a minimally important difference of 0.1. Recent empirical evidence suggests a lower minimally important difference (0.03) may be more appropriate, in which case our results provide further reassurance of preservation of precision in health state description and valuation. The precision of estimates of treatment effects based on preference data obtained from disease-specific measurements in clinically significant studies of health technologies was acceptable using an internet-based panel of members of the general public and the standard gamble. Definition of the minimally important difference in utility estimates is required to adequately assess precision and should be the subject of further research.

Strengthening of threaded connections of titanium and high-temperature nickel-chromium alloys by thermovibration treatment

The article presents results of a study of the strengthening of threaded connections M6 and M8 of alloys EI698, VT16, and VTZ-1 by thermovibration treatment to raise their creep resistance. Treatment regimes and empirical formulas for determining the index of strengthening (for the EI698 alloy) are discussed. Data on long-term strength of threaded connections in initial and post-treatment states, and on the effect of aging on retention of the strengthening effect, are presented along with some mechanical and fatigue characteristics.