Gonadal and Adrenal Disorders

2016 ◽  
pp. 165-178
Author(s):  
Pankaj Shah
Keyword(s):  
Adrenal Hormones ◽  
Adrenocortical Hormones ◽  
Secondary Failure ◽  
Adrenocortical Failure

Adrenocortical failure most commonly is due to a decrease in production of 1 or more adrenal hormones. Clinically relevant deficiencies may involve cortisol or aldosterone or a combination of both. Decreased production of adrenocortical hormones may be a consequence of adrenocortical disease (primary failure) or tropic hormone loss (secondary failure).

Effect of adrenalectomy on the regulation of the secretion of gonadotrophins and prolactin in the lactating rat

1983 ◽  
Vol 98 (2) ◽  
pp. 227-232 ◽  
Author(s):  
P. van der Schoot ◽  
W. J. de Greef
Keyword(s):  
Plasma Levels ◽  
Inhibitory Action ◽  
Adrenal Glands ◽  
Marked Effect ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Blood Levels ◽  
Adrenal Hormones ◽  
Adrenocortical Hormones ◽  
Adrenalectomized Rats

The suckling stimulus exerts an inhibitory action on the release of gonadotrophins during lactation. The possible involvement of the adrenal glands in this process was examined by studying the plasma levels of gonadotrophins in lactating rats ovariectomized on the day after parturition. It appeared that the suppression, throughout suckling, of the rise in levels of gonadotrophins in blood after ovariectomy occurred to the same extent in adrenalectomized and in sham-operated animals. It thus seems unlikely that adrenocortical hormones, albeit secreted in larger quantities during lactation, exert an inhibitory effect on the release of gonadotrophins. Adrenalectomy had a marked effect on the plasma concentrations of prolactin during the second half of lactation. Whereas plasma concentrations of prolactin in the first half of lactation were similar in adrenalectomized and sham-operated rats, the concentrations in adrenalectomized rats did not undergo the reduction found in sham-operated rats. Adrenal hormones may thus be involved in the reduction of blood levels of prolactin observed in rats and in other mammals as lactation progresses.

Influence of Metabolic Control on Thromboxane Biosynthesis and Plasma Plasminogen Activator Inhibitor Type-1 in Non-insulin-dependent Diabetes mellitus

1996 ◽  
Vol 76 (01) ◽  
pp. 034-037 ◽  
Author(s):  
Giovanni Davì ◽  
Mario Belvedere ◽  
Sergio Vingneri ◽  
Isabella Catalano ◽  
Carlo Giammarresi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Control ◽  
Platelet Activation ◽  
Macrovascular Disease ◽  
Dependent Diabetes Mellitus ◽  
Secondary Failure ◽  
Diet And Exercise ◽  
Strict Diet ◽  
Niddm Patients ◽  
Pai 1

SummaryWe have previously shown that tight metabolic control by insulin therapy reduced thromboxane-dependent platelet activation in noninsulin-dependent diabetes mellitus (NIDDM) patients. The present study was undertaken to determine whether a similar effect could be obtained without switching diabetics in secondary failure to insulin treatment. For this purpose, we gave strict diet and exercise advise program and adjusted on a weekly basis the oral antidiabetic therapy (glipizide) that 26 patients with NIDDM had been given over the previous months.Basal measurements of urinary ll-dehydro-TXB2 and PAI-1 confirmed previous findings of enhanced levels of these parameters in NIDDM patients with macrovascular disease in comparison to age-and sex-matched controls. After 2-6 weeks, 16 patients achieved tight metabolic control associated with significant reduction of both thromboxane biosynthesis and PAI-1 levels; 10 patients remained in poor control and no significant decrease of both parameters was observed.We conclude that reduction of in-vivo platelet activation and PAI-1 antigen levels after metabolic improvement obtained by frequent reassessment of sulphonylurea therapy together with strict diet and exercise programs may have beneficial effects on the progression of diabetic micro- and macrovascular disease.

Contributions of a Formal Analysis Metaprocess to Breakthrough Failure Analysis Results

2003 ◽  
Author(s):  
Steve Ferrier ◽  
Kevin D. Martin ◽  
Donald Schulte
Keyword(s):  
Failure Analysis ◽  
Formal Analysis ◽  
Photon Emission ◽  
Flow Analysis ◽  
Formal Structure ◽  
Ic Design ◽  
Analysis Process ◽  
Secondary Failure ◽  
Leakage Failure ◽  
Wafer Manufacturing

Abstract Application of a formal Failure Analysis metaprocess to a stubborn yield loss problem provided a framework that ultimately facilitated a solution. Absence of results from conventional failure analysis techniques such as PEM (Photon Emission Microscopy) and liquid crystal microthermography frustrated early attempts to analyze this low-level supply leakage failure mode. Subsequently, a reorganized analysis team attacked the problem using a specific toplevel metaprocess.(1,a) Using the metaprocess, analysts generated a specific unique step-by-step analysis process in real time. Along the way, this approach encouraged the creative identification of secondary failure effects that provided repeated breakthroughs in the analysis flow. Analysis proceeded steadily toward the failure cause in spite of its character as a three-way interaction among factors in the IC design, mask generation, and wafer manufacturing processes. The metaprocess also provided the formal structure that, at the conclusion of the analysis, permitted a one-sheet summary of the failure's cause-effect relationships and the analysis flow leading to discovery of the anomaly. As with every application of this metaprocess, the resulting analysis flow simply represented an effective version of good failure analysis. The formal and flexible codification of the analysis decision-making process, however, provided several specific benefits, not least of which was the ability to proceed with high confidence that the problem could and would be solved. This paper describes the application of the metaprocess, and also the key measurements and causeeffect relationships in the analysis.

scholarly journals AB0213 SAVING GLUCOCORTICOIDS AFTER RITUXIMAB TREATMENT IN PATIENTS WITH REUMATOID ARTHRITIS. ANALYSIS OF A COMMON CLINICAL PRACTICE COHORT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1132.3-1133
Author(s):  
G. Jurado Quijano ◽  
L. Fernández de la Fuente Bursón ◽  
B. Hernández-Cruz ◽  
P. Muñoz Reinoso ◽  
V. Merino Bohóquez ◽  
...  
Keyword(s):  
Survival Rates ◽  
Categorical Variables ◽  
Rank Test ◽  
Published Data ◽  
Disease Modifying Drugs ◽  
Secondary Failure ◽  
Daily Dose ◽  
Student’S T ◽  
Common Clinical Practice

Background:Rituximab (RTX) is a monoclonal antibody against the CD20 B cell antigen that has been used successfully in recent years for the treatment of rheumatoid arthritis (RA). It is an effective drug that reaches survival rates of 60% at 5 years of treatment as reflected in the British experience. However, survival in Spanish patients is unknown.Objectives:To study the survival of RTX treatment and the characteristics of patients with RA treated with the drug since its commercialization in Spain.Methods:Observational, retrospective and analytical study of a cohort of patients with RA treated with at least one dose of RTX. We reviewed the medical records of all patients with RA from January 2007 to June 2017. A total of 178 previous defined variables were collected, highlighting data about treatment (use of RTX, associated conventional synthetic disease modifying drugs [FAMEsc], doses of corticosteroids [GC] used) and activity indices. Descriptive statistics were performed (median and the 25th and 75th percentiles are shown). The comparative analysis was done with χ2 and U of Mann Whitney for categorical variables and paired sign rank test or Student’s t for continuous. Survival Kaplan Mayer curves were constructed. The study was carried out in accordance with the standards of our Clinical Research Ethics Committee.Results:A total of 54 patients were analyzed. 74% (n = 40) of them were women, the age was 61.2 years (51.0 - 67.4). 74% (n = 40) presented some type of relevant comorbidity. Its RA was FR + in 96% (n = 52) and ACCP + in 78% (n = 42) of the cases, with an evolution time of 9.3 years (3.5-19, 2), and with radiographic erosions in up to 63% (n = 34). At the time of the start of the RTX, 100% of the patients (n = 54) received some FAMEsc, and 33 (61%) were treated with prednisone; the daily dose of prednisone was 9 (6-12) mg. The baseline DAS28-VSG was 5 (4.1 - 6.0). The duration of the follow-up was 56.6 (29.3-92.1) months. Patients received a mean of 5 (1-6) cycles of RTX at a dose of 1000 mg on days 0 and 15 in most cases. The final DAS28-VSG was 2.6 (2.1 - 4.0), p = 0.00001 compared to baseline. The delta between baseline and final DAS was -2.36 (-0.55 - -3.1). At the end of the RTX treatment, the EULAR response rate was good in 64% (n = 25), reaching remission in 17 (31%) of the patients, and moderate response in 21% (n = 8) of them (Figure 1). Only 2 (4%) patients were treated with GCC at the end of the follow-up, p<0,00001 compared to baseline. The daily dose of PDN at the end of follow-up was 6 mg in a case and 12 mg in the other, p=00001 compared to baseline. At the end of the follow-up 24%of the patients (n = 13) changed or discontinued the drug: 9 changed due to secondary failure, 2 suspended due to adverse events, 1 due to death due to prior neoplastic process and 1 due to complete disease remission. Survival at 1, 2, 3, 4, 5, 6 and 7 years was 92%, 92%, 82% 78%, 75%, 75% and 65% respectively; with a mean survival rate of 90 months (Figure 1).Conclusion:The results of our analysis show that patients with RA undergoing RTX treatment have adequate control of disease activity and drug survival rates, like published data. RTX treatment allowed stopped GCC treatment in 31 cases (90%).References:[1]Oldroyd AGS, et al. Rheumatology (Oxford). 2018 Jun 1;57(6):1089-1096.Disclosure of Interests:Gonzalo Jurado Quijano: None declared, Lola Fernández de la Fuente Bursón: None declared, Blanca Hernández-Cruz Speakers bureau: Sociedad Española de Reumatología, Abbvie, Roche, Bristol, MSD, Lilly, Pfizer, Amgen, Sanofi, Consultant of: Abbvie, Lilly, Sanofi, STADA, UCB, Amgen, Grant/research support from: Fundación para la Investigación Sevilla, Junta de Andalucía, Fundación Andaluza de Reumatología, Paloma Muñoz Reinoso: None declared, Vicente Merino Bohóquez: None declared, José Javier Pérez Venegas: None declared

scholarly journals Dynamic Repair and Robust Optimization of Complex Networks

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Pengtao Zhang ◽  
Peng Bai ◽  
Chaoqi Fu ◽  
Shanshan Li
Keyword(s):  
Energy Transfer ◽  
Repair Process ◽  
Recovery Efficiency ◽  
Repair Strategy ◽  
Coupling Structure ◽  
Secondary Failure ◽  
Fundamental Reason ◽  
Network Functions ◽  
The Impact ◽  
Failure Node

Network repair is indispensable for maintaining network security. Conventional static repair is relatively inefficient. In this study, by considering the energy transfer between nodes, a dynamic repair model was established. The fundamental reason for the secondary failure of repaired nodes during the dynamic repair process is the coupling structure of failure networks. A dynamic repair strategy was proposed that can effectively prevent the secondary failure of repair nodes influenced by energy during repair and can cause the redundant capacity of repair nodes to be used reasonably. By turning off the energy transfer function of the link to control the excessive flow of energy into the repair node to avoid the occurrence of secondary failure; on the other hand, by sharing part of the load of the failure node, realize the rational use of the redundant capacity of the repair node to reduce the impact of the failure node on the overall function of the network. The proposed strategy mitigated the effect of failure nodes on network functions and substantially improved the recovery efficiency of network functions. Furthermore, redundant edges, behaving as energy redundant links in a network structure, can considerably improve the robustness of the network by optimizing the removal of redundant edges. Dynamic repair is not only an efficient repair method but also a highly flexible choice for network repair.

scholarly journals FRI0493 THE INTERLEUKIN-1B INHIBITOR CANAKINUMAB FOR REFRACTORY STILL’S DISEASE: LONG-TERM EXPERIENCE IN 50 CONSECUTIVE PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 845.1-845
Author(s):  
K. Laskari ◽  
P. Athanassiou ◽  
A. Georgiadis ◽  
C. Gerodimos ◽  
G. Gkoni ◽  
...  
Keyword(s):  
Complete Remission ◽  
Median Time ◽  
Disease Onset ◽  
Adult Patients ◽  
Sustained Remission ◽  
Concomitant Treatment ◽  
Still’S Disease ◽  
Research Support ◽  
Still's Disease ◽  
Secondary Failure

Background:Interleukin-1 (IL-1) is a major mediator of the inflammatory cascade in Still’s disease and an established therapeutic target.Objectives:To assess the efficacy and safety of the IL-1b inhibitor canakinumab in adolescent and adult patients with refractory Still’s disease.Methods:We conducted a retrospective longitudinal outcome study of 50 consecutive patients aged 39 years (median, range 14-72), fulfilling the Yamaguchi disease classification criteria, with active disease despite treatment with corticosteroids (CS) (n=11) and/or methotrexate (n=9) and/or biologics (n=30) [tumor necrosis factor inhibitors (n=13), IL-6 blockade (n=7), abatacept (n=2), anakinra (n=24); ≥1 biologics (n=13)]. Canakinumab 150-300 mg was administered sc, starting every 4 (n=48) or 8 weeks (n=2), for a median of 24 months (range 3-84). Concomitant treatment included CS (n=41), methotrexate (n=12) and leflunomide (n=3).Results:Complete remission was initially achieved in 78% of patients within a median time of 3 months, irrespective of age at disease onset. Partial clinical and laboratory response was evident in 20%. Canakinumab was discontinued in one patient with resistant disease (primary failure) and in 6 out of 10 initial responders, who relapsed during treatment (secondary failure). Of 39 patients in complete remission, increase in drug administration interval and/or drug dose reduction was attempted in 7, of which only 1 relapsed, whereas drug discontinuation was attempted in 19 patients for a median time of 8 months (range 3-68), of which 8 relapsed. Overall, in half of all disease flares, canakinumab re-introduction or intensification was successful. Canakinumab had a significant CS sparing effect permitting weaning in 21 of 41 cases. Infections (20%, severe 4%) and leucopenia (6%) led to treatment cessation in one patient.Conclusion:In this largest so far real-life patient cohort with refractory Still’s disease, high rates of sustained remission were induced by canakinumab both in adolescent and adult patients.Disclosure of Interests:Katerina Laskari: None declared, Panagiotis Athanassiou Grant/research support from: MSD, Genesis pharma, Janssen, Consultant of: Roche, Genesis pharma, Janssen, Speakers bureau: MSD, Janssen, Roche, Genesis pharma, Athanasios Georgiadis: None declared, Charalampos Gerodimos: None declared, Georgia Gkoni: None declared, Dimitrios Daoussis: None declared, Theodoros Dimitroulas: None declared, Despoina Dimopoulou: None declared, Chrysoula Iliou: None declared, Ioannis Kallitsakis Grant/research support from: MSD, Speakers bureau: Genesis pharma, Bristol-Myers Squibb, Dimitrios Karamitsos: None declared, Christina Katsiari: None declared, Stamatis-Nick Liossis: None declared, Clio Mavragani: None declared, CHARALAMPOS PAPAGORAS: None declared, Dimitrios Pikazis: None declared, Ioannis Raftakis: None declared, Theodosios Sarikoudis: None declared, Loukas Settas: None declared, Prodromos Sidiropoulos: None declared, Despoina Soukera: None declared, Evangelos Theodorou: None declared, Panagiota Tsatsani: None declared, Eleni Tsiakou: None declared, Dimitrios Vassilopoulos: None declared, PANAYIOTIS VLACHOYIANNOPOULOS: None declared, Georgios Vosvotekas: None declared, Paraskevi V. Voulgari: None declared, Marina Zakalka: None declared, Maria Tektonidou Grant/research support from: AbbVie, MSD, Novartis and Pfizer, Consultant of: AbbVie, MSD, Novartis and Pfizer, Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB

scholarly journals POS0461 RESPONSE TO BIOLOGIC THERAPY IN RHEUMATOID ARTHRITIS: RETHINKING OUR CLASSIFICATION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 462.1-462
Author(s):  
E. Vallejo-Yagüe ◽  
S. Kandhasamy ◽  
E. Keystone ◽  
A. Finckh ◽  
R. Micheroli ◽  
...  
Keyword(s):  
Treatment Response ◽  
Real World ◽  
Observational Studies ◽  
Initial Response ◽  
Primary Response ◽  
Sustained Response ◽  
Secondary Response ◽  
Real World Data ◽  
World Data ◽  
Secondary Failure

Background:In rheumatoid arthritis (RA), primary failure with biologic treatment may be understood as lack of initial clinical response, while secondary failure would be loss of effectiveness after an initial response. Despite these clinical concepts, there is no unifying operational definition of primary and secondary non-response to RA treatment in observational studies using real-world data. On top of data-driven challenges, when conceptualizing secondary non-responders, it is unclear if the mechanism behind loss of effectiveness after a brief initial response is similar to loss of effectiveness after previous benefit sustained over time.Objectives:This viewpoint aims to motivate discussion on how to define primary and secondary non-response in observational studies. Ultimately, we aim to trigger expert committees to develop standard terminology for these concepts.Methods:We discuss different methodologies for defining primary and secondary non-response in observational studies. To do so, we shortly overview challenges characteristic of performing observational studies in real-world data, and subsequently, we conceptualize whether treatment response should be a dichotomous classification (Primary response/non-response; Secondary response/non-response), or whether one should consider three response categories (Primary response/non-response; Primary sustained/non-sustained response; Secondary response/non-response).Results:RA or biologic registries are a common data source for studying treatment response in real-world data. While registries include disease-specific variables to assess disease progression, missing data, loss of follow-up, and visits restricted to the year or mid-year visit may present a challenge. We believe there is a general agreement to assess primary response within the first 6 month of treatment. However, conceptualizing secondary non-response, one could wonder if a patient with brief initial response and immediate loss of it should belong to the same response category as a patient who relapses after a period of prior benefit that was sustained over time. Until this concern is clarified, we recommend considering a period of sustained response as a pre-requisite for secondary failure. This would result in the following three categories: a) Primary non-response: Lack of response within the first 6 months of treatment; b) Primary sustained response: Maintenance of a positive effectiveness outcome for at least the first 12 months since treatment start; c) Secondary non-response: Loss of effectiveness after achieved primary sustained response. Figure 1 illustrates this classification through a decision tree. Since the underlying mechanisms for treatment failure may differ among the above-mentioned categories, we recommend to use the three-category classification. However, since this may pose additional methodological challenges in real-world data, optionally, a dichotomous 12-month time-point may be used to assess secondary non-response (unfavourable outcome after 12-months) in comparison to primary non-response or non-sustained response (unfavourable outcome within the first 12-months). Similarly, to study primary response, the solely 6-month timepoint may be used.Conclusion:A unified operational definition of treatment response will minimize heterogeneity among observational studies and help improve the ability to draw cross-study comparisons, which we believe would be of particular interest when identifying predictors of treatment failure. Thus, we hope to open the room for discussion and encourage expert committees to work towards a common approach to assess treatment primary and secondary non-response in RA in observational studies.Disclosure of Interests:Enriqueta Vallejo-Yagüe: None declared, Sreemanjari Kandhasamy: None declared, Edward Keystone Speakers bureau: Amgen, AbbVie, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Novartis, Pfizer Pharmaceuticals, Sanofi Genzyme, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis, Grant/research support from: Amgen, Merck, Pfizer Pharmaceuticals, PuraPharm, Axel Finckh Speakers bureau: Pfizer, Eli-Lilly, Paid instructor for: Pfizer, Eli-Lilly, Consultant of: AbbVie, AB2Bio, BMS, Gilead, Pfizer, Viatris, Grant/research support from: Pfizer, BMS, Novartis, Raphael Micheroli Consultant of: Gilead, Eli-Lilly, Pfizer and Abbvie, Andrea Michelle Burden: None declared

scholarly journals THE CHARACTERIZATION OF FOUR NEW METABOLITES OF ADRENOCORTICAL HORMONES

1955 ◽  
Vol 212 (1) ◽  
pp. 449-460 ◽  
Author(s):  
David K. Fukushima ◽  
Norma S. Leeds ◽  
H. Leon Bradlow ◽  
Theodore H. Kritchevsky ◽  
Madeleine B. Stokem ◽  
...  
Keyword(s):  
Adrenocortical Hormones ◽  
New Metabolites
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