Significant Changes In Severity Research Articles

Influence of lactoferrin and enzymatiс hydrolysates of cow's and mare's milk proteins on anaphylactic sensitivity and cytokine profile of rats

The development of innovative ingredients of specialized formula for children with intolerance to cow's milk proteins requires accounting the influence of the protein component on the allergic sensitivity. The aim of the research was to study the effect of lactoferrin (LF) from cow colostrum, cow's milk protein hydrolysate (CMPH) and mare's milk protein hydrolysate (MMPH) on the severity of the systemic anaphylaxis reaction, the levels of specific IgG antibodies and cytokines in rats parenterally sensitized with ovalbumin (OVA). Material and methods. The experiment was carried out on 4 groups of 26 male Wistar rats, which were sensitized intraperitoneally with chicken egg OVA and a systemic anaphylaxis reaction was induced on the day 29 by intravenous administration of a challenge dose of the antigen (6 mg per kg body weight). LF, CMPH and MMPH were introduced into the diet in doses of 1.4-2 g/kg body weight per day (on an average 1.59±0.04, 1.53±0.05 and 1.48±0.05 g per kg body weight respectively). The content of IgG antibodies in the blood serum was determined by an indirect ELISA; the levels of cytokines IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12(p70), IL-13, GM-CSF, IFN-γ and TNF-α were detected by multiplex immunoassay. Results. Dietary LF did not have a significant effect on the severity of active anaphylactic shock (AAS), concentrations of antibodies and cytokines in the blood of animals. As a result of CMPH consumption, there were no significant changes in AAS severity and IgG antibodies to OVA but significant increase in TNF-α level was observed as well as a significant decrease in IL-1α (p<0.05). In animals receiving MMPH, there were also no significant changes in the severity of AAS, but a 1.9-fold decrease in the level of IgG antibodies to OVA (p<0.001) was noticed along with a significant increase in IL-12(p70) (p<0.05) and IL-10 (p<0.10) level. Conclusion. Cosumption of LF by sensitized rats didn't significantly affect their anaphylactic sensitivity and cytokine profile, while CMPH intake induced some signs of pro-inflammatory processes. Consumption of MMPH was accompanied by the formation of an anti-inflammatory cytokine profile, which corresponds to a decrease in the intensity of the humoral immune response to the model allergen. Differences in the effects of two hydrolisates, which have similar degrees of hydrolysis, may be associated with the specific composition of glycopeptides formed during the enzymatic cleavage of milk protein produced by these two species of dairy animals.

Relationship of Hoarding and Depression Symptoms in Older Adults

Hoarding disorder (HD) is a debilitating neuropsychiatric condition that affects 2%–6% of the population and increases in incidence with age. Major depressive disorder (MDD) co-occurs with HD in approximately 50% of cases and leads to increased functional impairment and disability. However, only one study to date has examined the rate and trajectory of hoarding symptoms in older individuals with a lifetime history of MDD, including those with current active depression (late-life depression; LLD). We therefore sought to characterize this potentially distinct phenotype. We determined the incidence of HD in two separate cohorts of participants with LLD (n = 73) or lifetime history of MDD (n = 580) and examined the reliability and stability of hoarding symptoms using the Saving Inventory-Revised (SI-R) and Hoarding Rating Scale-Self Report (HRS), as well as the co-variance of hoarding and depression scores over time. HD was present in 12% to 33% of participants with MDD, with higher rates found in those with active depressive symptoms. Hoarding severity was stable across timepoints in both samples (all correlations >0.75), and fewer than 30% of participants in each sample experienced significant changes in severity between any two timepoints. Change in depression symptoms over time did not co-vary with change in hoarding symptoms. These findings indicate that hoarding is a more common comorbidity in LLD than previously suggested, and should be considered in screening and management of LLD. Future studies should further characterize the interaction of these conditions and their impact on outcomes, particularly functional impairment in this vulnerable population.

A Prospective Study Examining the Effect of Selected Topical and Systemic Drugs on Pruritus Grading System Score and STAT 6 Expression in Patients of Prurigo Nodularis.

Background:Prurigo nodularis (PN) is a chronic dermatologic condition presenting as multiple papulonodular lesions occurring with intense pruritus. Though numerous agents (topical, systemic, phototherapy and biological drugs) have been tried, the outcomes are variable.Objectives:The aim of this study was to assess the role of topical and systemic therapies in primary PN by comparing the Pruritus Grading System (PGS) score at baseline and 1 month post-therapy.Materials and Methods:Of 86 diagnosed cases of PN, 49 cases of primary PN were clinically graded by Pruritus Grading System Score (PGSS), and assessed histopathologically by IHC staining (STAT-1, 3, and 6). Apart from topical agents, oral nortriptyline (mild grade), methotrexate (moderate grade) and thalidomide (severe grade) were administered, whereas doxepin was administered for itching. The PGSS was assessed after 1 month of therapy.Results:Among 49 patients of PN, the majority of patients showed a significant decrease in PGSS (P = <0.001) in 1 mont, which correlated with STAT-6 expression. The combination of different topical and oral agents resulted in a statistically significant change in severity, though individual drugs did not achieve statistically significant results.Conclusion:A combination of selected oral and topical agents can effectively control the severity of PN within one month, and this was found to correlate with STAT 6 expression.

Measurement Properties of the Psoriasis Symptom Inventory Electronic Daily Diary in Patients with Moderate to Severe Plaque Psoriasis.

The Psoriasis Symptom Inventory (PSI) is a patient-reported outcome instrument that measures the severity of psoriasis signs and symptoms. This study evaluated measurement properties of the PSI in patients with moderate to severe plaque psoriasis. This secondary analysis used pooled data from a phase 3 brodalumab clinical trial (AMAGINE-1). Outcome measures included the PSI, Psoriasis Area and Severity Index (PASI), static Physician's Global Assessment (sPGA), psoriasis-affected body surface area, 36-item Short-Form Health Survey version 2, and the Dermatology Life Quality Index (DLQI). The PSI was evaluated for dimensionality, item performance, reliability (internal consistency and test-retest), construct validity, ability to detect change, and agreement between PSI response and response measures based on the PASI, sPGA, and DLQI. Results supported unidimensionality, good item fit, ordered responses, and PSI scoring. The PSI demonstrated reliability: baseline Cronbach's alpha ≥ 0.92 and intraclass correlation coefficients ≥ 0.95. Correlations between PSI total score and DLQI item 1 (r = 0.86), DLQI symptoms and feelings (r = 0.87), and 36-item Short-Form Health Survey version 2 bodily pain (r = -0.61) supported convergent validity. PSI scores differed significantly (P < 0.001) among severity groups based on the PASI (< 12/≥ 12), sPGA (0-1/2-3/4-5), body surface area (< 5%/5%-10%/> 10%), and DLQI (≤ 5/> 5) at weeks 8 and 12. At week 12, the PSI detected significant changes in severity based on PASI responses (< 50/50- < 75/≥ 75) and sPGA (0-1/≥ 2), and showed good agreement (k ≥ 0.66) between PSI response and PASI, sPGA, and DLQI responses. The PSI demonstrated excellent validity, reliability, and ability to detect change in the severity of psoriasis signs and symptoms.

SU93. Targeted Treatment of a Genetic Mutation in Glycine Decarboxylase With d-Cycloserine in Psychotic Disorders

Abstract Background: The identification of mutations in specific genes could enable personalized, “medically actionable” treatment interventions. We identified a potentially informative mutation, a rare structural rearrangement that includes a triplication of the glycine decarboxylase gene (GLDC). GLDC is the enzyme that catabolizes glycine, a precursor of d-serine, both of which are coagonists at the NMDA receptor (NMDAR). Four copies of GLDC would be expected to increase the degradation of glycine, resulting in low levels of brain glycine and NMDAR-mediated hypofunction, which has been strongly implicated in the pathophysiology of psychotic disorders. Carriers of this mutation may especially benefit from augmentation of psychotropic drug treatment with NMDAR coagonists. Methods: We carried out a double-blind placebo-controlled clinical trial (6 weeks per arm) of d-cycloserine (DCS), a partial agonist at the NMDAR glycine site, followed by 24 weeks of open-label DCS, in 2 related individuals who are carriers of the GLDC mutation, one with a diagnosis of bipolar disorder with psychotic features and the other with a diagnosis of schizo-affective disorder. Clinical assessments were carried out every 2 weeks using the PANSS, BPRS, YMRS, HAM-D, and CGI. The same individuals previously completed trials of acute and chronic glycine augmentation, which produced significant symptom improvement but caused problematic GI side effects. Results: Full trial results are still pending as the blind has not yet been broken. However, blinded analyses show significant changes in severity of clinical symptoms, indicating that DCS either produced dramatic clinical improvements or worsened symptom severity. Complete, unblinded results will be available and presented at the meeting. Conclusion: DCS may be an effective augmentation in psychotic individuals selected for being carriers of duplications or triplications of GLDC, or who are carriers of other genetic variants resulting in NMDAR hypofunction. If DCS reduced symptom severity, it is a preferable alternative to glycine as a targeted treatment in light of its clinical efficacy, ease of administration, and favorable side effect profile.

Perceived criticism predicts outcome of psychotherapy for panic disorder: Replication and extension.

We tested the relation of perceived criticism (PC) from a parent or spouse/romantic partner to outcome of psychotherapy for panic disorder (PD). Participants were 130 patients with PD (79% with agoraphobia) who received 24 twice-weekly sessions of panic-focused psychodynamic psychotherapy, cognitive-behavioral therapy, or applied relaxation therapy. Patients were predominantly White (75%), female (64%), and non-Hispanic (85%). At baseline, Week 5 of treatment, termination, and at 6- and 12-month follow-up, patients rated PC from the relative with whom they lived. Independent evaluators assessed the severity of PD at baseline, Weeks 1, 5, and 9 of treatment, termination, and the 2 follow-up points. Data were analyzed with piecewise (treatment phase, follow-up phase) latent growth curve modeling. The latent intercept for PC at baseline predicted the latent slope for panic severity in the follow-up (p = .04) but not the active treatment phase (p = .50). In contrast, the latent intercept for PD severity at baseline did not predict the latent slope on PC in either phase (ps ≥ .29). Nor did the slopes of PC and PD severity covary across treatment (p = .31) or follow-up (p = .13). Indeed, PC did not change significantly across treatment (p = .45), showing the stability of this perception regardless of significant change in severity of patients' PD (p < .001). Because PC predicts worse long-term treatment outcome for PD, study findings argue for interventions to address perceived criticism in treatment. (PsycINFO Database Record

SIgA response and incidence of upper respiratory tract infections during intensified training in youth basketball players.

The aim of the present study was to examine the effect of an intensified training phase followed by a tapering phase on the salivary immunoglobulin A concentration and on the upper respiratory tract infection (URTI) symptoms in young male basketball players. The session rating of perceived exertion method was used to quantify the internal training load, and the Wisconsin Upper Respiratory Symptom Survey-21 questionnaire was used to assess URTI symptoms. The Yo-Yo IR1 test and saliva collection were carried out at the beginning of the study (T1), after the intensified phase (T2), and after tapering (T3). A higher internal training load was observed for the intensified phase compared with the tapering phase (t=19.10; p<0.001), and a significant decrease in salivary immunoglobulin A concentration was detected (F=7.48; p=0.004) at T3 compared to T1 (p=0.02) and T2 (p=0.05). However, there was no significant difference between phases for severity of URTI (χ2= 2.83; p=0.242). The Yo-Yo IR1 test performance increased from T2 and T3 compared to T1 (F=58.24; p<0.001). There was no significant effect of aerobic fitness level on salivary immunoglobulin A response (F=1.095; p=0.344). In summary, the present findings suggest that an intensified training load followed by a tapering period negatively affects the mucosal immune function with no significant change in severity of URTI in young basketball players.

European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation.

European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation.

Group Versus Individual Cognitive Treatment for Obsessive-Compulsive Disorder: Changes in Severity at Post-Treatment and One-Year Follow-up

Very few studies have compared the efficacy of individual and group cognitive behaviour therapy (CBT) for the treatment of Obsessive-Compulsive Disorder (OCD) by taking into consideration the change in OCD severity in both the short and long term. To conduct an open trial of individual versus group CBT for OCD, comparing the clinical and statistically significant changes in severity both at post-treatment and one year later. Forty-two OCD subjects were assigned to individual (n = 18) or group CBT (n = 24, in four groups). Sixteen and 22 subjects completed the treatment in the individual and group conditions, respectively. The Yale-Brown Obsessive Compulsive Scale was recorded at pre-treatment, post-treatment and at the one-year follow-up. At the end of treatment, the clinically significant change was comparable for the two treatment conditions and remained stable at the one-year follow-up. Of the 16 participants who completed the individual CBT treatment, 68.75% were classified as recovered at post-treatment, compared to 40.9% of those receiving group CBT. At follow-up the rate of recovery decreased to 62.5% in individual CBT and to 31.8% in group CBT. Group CBT is effective in decreasing OCD severity. The post-treatment changes were maintained one year later. Nevertheless, these changes were higher in the individual delivery of CBT.

Quadricuspid aortic valve associated with aortic stenosis and regurgitation: report of a case and a review of the literature.

Quadricuspid aortic valve (QAV) is a rare congenital heart valve disease, and more than half of QAV patients have severe aortic regurgitation (AR). We describe the case of a 66-year-old woman with QAV detected by transthoracic echocardiography during a medical checkup. Doppler echocardiographic examination showed mild aortic stenosis and mild AR. The patient has been under routine medical review without medication therapy. At follow-up echocardiographic examinations over a 4-year period, no significant changes in severity of aortic stenosis or AR were found. The clinical and functional characteristics of 192 cases of QAV were reviewed. The functional status of the QAV was known in 144 cases; of these, only 13 (9%) had both aortic stenosis and AR.

Effect of Helicobacter pylori Infection on Ghrelin Expression in Human Gastric Mucosa

One of the counter-effects of Helicobacter pylori eradication therapy is subsequent obesity. Ghrelin is a recently discovered growth hormone releasing peptide. This endogenous secretagogue increases appetite and facilitates fat storage. The majority of circulating ghrelin is produced in the gastric mucosa. Therefore, we aimed at investigating changes in ghrelin immunoreactivity in gastric mucosa tissues of patients infected with H. pylori. Sixty-one patients with H. pylori infection (25 cases each of duodenal and gastric ulcer, and 11 cases of gastritis) and 22 healthy controls without H. pylori infection were included in the study. H. pylori-infected patients received standard proton pump-based triple therapy followed by histological examination and (13)C-urea breath test to confirm H. pylori eradication. H. pylori was eradicated in 50 out of 61 patients. Biopsy specimens were obtained from antrum and corpus before and 3 months following eradication. Ghrelin expression was evaluated immunohistochemically with an anti-ghrelin antibody, and the number of ghrelin-positive cells determined per 1 mm(2) of the lamina propria mucosa. There was no relationship between ghrelin immunoreactivity and body weight or body mass index for healthy controls. The number of ghrelin-positive cells was significantly lower for H. pylori-infected patients than for healthy controls. However, the ghrelin-positive cell number increased significantly following H. pylori eradication without significant change in severity of atrophy. These data indicated that H. pylori infection affected ghrelin expression. After H. pylori eradication, gastric tissue ghrelin concentration increased significantly. This could lead to the increased appetite and weight gain seen following H. pylori eradication.

PERSISTENCE OF SYMPTOMS REPORTED OVER TIME BY GULF WAR VETERANS

Although casualties were extremely low among nearly 697,000 American service personnel who served in Operations Desert Shield and Desert Storm in 1990–1991, after the war many returning veterans complained about persistent, yet unexplained health problems. The resulting controversy gave rise to the term ‘Gulf War Syndrome’ or ‘Gulf War-related illnesses’. The present research investigates whether changes in health status and symptom reporting by Gulf War veterans persist over a 5-year period. A sample of 398 randomly selected veterans completed mail questionnaires in 1995 (Time 1) and 2000 (Time 2). The participants were asked to report whether they experienced any of 48 symptoms and if so, whether the symptoms were ‘mild,’ ‘moderate,’ or ‘severe.’ The results suggest that both the average number of symptoms reported and average symptom severity have changed little over time. Respondents reported a mean of 21.96 mild, moderate, or severe symptoms at Time 1, and a mean of 22.73 symptoms at Time 2 t (397) = .1.695, p = .091). There was no significant change in mean symptom severity collapsed across the 48 symptoms measured at Time 1 and Time 2 (Time 1: M = .82, Time 2: M = .84; t (397) = .802, p = .423). While a multivariate repeated measures analysis of variance did suggest a significant overall difference in the severity of individual symptoms reported at Time 1 and Time 2 (F (48, 350) = 2.469, p < .05), tests of within-subjects contrasts indicated that after a bonferoni adjustment, there were no significant changes in the severity within any of the specific pairs of symptoms reported at Time 1 and Time 2. In fact, changes in the severity of only four symptoms approached significance–problems with eyes or vision (Time 1: M = .83; Time 2: M = .96), difficulty breathing (Time 1: M = .75; Time 2: M = .62), skin problems (Time 1: M = 1.09; Time 2: M = .94), and difficulty remembering (Time 1: M = 1.30; Time 2: M = 1.45) (p < .005, p < .004, p < .003, and p < .002, respectively). These findings are important in showing the persistent nature of the symptoms that these veterans report. Our findings suggest that symptoms related to Gulf War illness are not resolving over time.

Serial follow-up of adults with repaired tetralogy of Fallot

Objectives and Background. Sudden death has long been considered a major contributor to mortality in pediatric patients with corrected tetralogy of Fallot. However, this may not apply to the patient with repaired tetralogy of Fallot who has survived into adulthood. Consequently we followed up a cohort of such adults to establish the clinical outcome and risk factors affecting their survival.Methods. A baseline group of 151 adult patients with repaired tetralogy of Fallot were followed up for a mean of 3.2 years. The overall mortality rate was low (0.009 death/patient-year). Four patients died during follow-up, but only two deaths can be attributed to tetralogy of Fallot repair, and there were no sudden cardiac deaths. Clinically 94% of patients have remained in New York Heart Association functional class I.A subset of 36 patients were followed up for a mean of 6.7 years. This group had three sets of serial testing at 3-year intervals consisting of right heart catheterization at the initial study only, 24-h Holter ambulatory electrocardiographic (ECG) monitoring, exercise ECG and rest and exercise radionuclide angiography.Results. Exercise capacity assessed by serial exercise stress testing remained stable over the follow-up period, whereas the presence of exercise-induced arrhythmias steadily decreased. Most patients had no significant arrhythmias and had no significant change in severity of arrhythmia with time. Radionuclide angiography showed significant improvement in exercise right ventricular ejection fraction over time but a progressive decrease in left ventricular ejection fraction at both rest and exercise. However, the left ventricular ejection fraction is still within the normal limits for our laboratory.Conclusions. Adults with repaired tetralogy of Fallot have a very good prognosis and a low risk of sudden death. However, ventricular function may change over time and should be carefully monitored.

Incontinence in the Elderly: Objective Demonstration and Quantitative Assessment

Subjective and objective methods of demonstrating incontinence and assessing its severity have been compared in a group of elderly patients with a high incidence of severe urge incontinence. It was found that 24-h in-patient monitoring of urine leakage was the most sensitive method of demonstrating incontinence, with videourodynamic testing almost as good. In comparison, a 1-h pad test was poor. Visual inspection during physical examination seldom demonstrated leakage. For quantitative assessment of severity, 24-h monitoring gave the most reproducible results; it was also able to reveal significant changes in severity in response to pharmaceutical treatment. A 1-h pad test was less reproducible and suggested changes that were only poorly consistent with 24-h monitoring. The subjective responses of the patients were not useful in assessing changes in the severity of incontinence. Twenty-four hour monitoring thus stands out as a superior method of demonstrating and assessing incontinence.