scholarly journals Mitotane Treatment Combined With Unilateral Adrenalectomy in a Patient With Primary Pigmented Nodular Adrenocortical Disease Caused by a Start Codon Mutation of PRKAR1A Gene

2021 ◽  
Author(s):  
Xuemeng Liu ◽  
Minghao Guo ◽  
Bing Han ◽  
Yue Xu ◽  
Shuangxia Zhao ◽  
...  
Keyword(s):  
Low Dose ◽  
Adrenal Adenoma ◽  
The Body ◽  
Start Codon ◽  
Regulatory Subunit ◽  
Type I ◽  
Unilateral Adrenalectomy ◽  
Whole Exome ◽  
Alpha Gene ◽  
One Year

Abstract Background: Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing’s syndrome (CS). This study aimed to explore molecular basis and treatment strategy in a patient with PPNAD.Methods: Whole-exome sequencing (WES) was used to reveal the mutation of PRKAR1A gene, with immunohistochemistry (IHC) to observe the expression of mutant PRKAR1A. Low-dose Mitotane followed by unilateral adrenalectomy were performed to control hypercortisolism. Results: A case of 45-year-old female present with classical hypercortisolism as excessive weight gain, central obesity, and intractable hypertension. She experienced adrenal adenoma surgery 10 years ago with no improvement. Low dosage of Mitotane was used for 7 months to control the severe hypercortisolism. Then laparoscopic unilateral adrenalectomy was performed and pathological features supporting PPNAD. The germline mutation (c.1A>G) in the start codon of PRKAR1A (Protein Kinase cAMP-Dependent Type I Regulatory Subunit Alpha) gene was identified. Notably, the body weight and hypertension were improved obviously one year later even if she discontinued with the Mitotane treatment.Conclusion: Low-dose Mitotane followed by unilateral adrenalectomy showed satisfied treatment effect in this patient, which may be an alternative treatment for PPNAD patient instead of bilateral adrenalectomy.

A Randomized Trial of Lenalidomide Plus High-Dose Dexamethasone (RD) Versus Lenalidomide Plus Low-Dose Dexamethasone (Rd) in Newly Diagnosed Multiple Myeloma (E4A03): A Trial Coordinated by the Eastern Cooperative Oncology Group.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 74-74 ◽  
Author(s):  
S. Vincent Rajkumar ◽  
Susanna Jacobus ◽  
Natalie Callander ◽  
Rafael Fonseca ◽  
David Vesole ◽  
...  
Keyword(s):  
Disease Progression ◽  
Low Dose ◽  
Response Rate ◽  
Phase Iii ◽  
High Dose ◽  
Type I ◽  
Newly Diagnosed ◽  
High Dose Dexamethasone ◽  
Grade 3 ◽  
One Year

Abstract Aim: A phase III trial of lenalidomide plus high (standard) dose dex (RD) versus lenalidomide plus low dose dex (Rd) in newly diagnosed myeloma (MM). Methods: Pts with untreated, symptomatic MM were eligible. Pts in the RD arm (Arm A) received lenalidomide 25 mg/day PO days 1–21 every 28 days plus dex 40 mg days 1–4, 9–12, and 17–20 PO every 28 days; pts in the Rd arm (Arm B) received lenalidomide at the same dose plus dex 40 mg days 1, 8, 15, and 22 PO every 28 days. The primary endpoint was response rate at 4 months, with the null hypothesis being that the response rates in the two 2 arms are equivalent. Planned sample size was 196 eligible pts per arm with one-sided 0.10 Type I and 0.05 Type II error rate. All analysis were performed on an intent to treat basis. An independent DMC recommended release of study results. Results: 445 pts (median age, 65 yrs) were accrued; 223 randomized to RD, 222 to Rd. Median follow-up time is 17 months. Arms were well balanced for age, gender, stage, bone lesions, hemoglobin, beta-2 microglobulin, performance status, bone marrow plasma cells, and M protein levels at baseline. Major grade 3 or higher toxicities, including DVT/PE and infections, were significantly higher in the high dose dex arm (see Table). Overall survival (OS) at the second pre-planned interim analysis was significantly superior with lenalidomide plus low dose dex, P<0.001; one year survival 96% (Rd) versus 87% (RD). The 18 month survival rate is 91% versus 80%, respectively. OS differences in favor of the low dose dex arm were seen in pts <65 (P=0.022; one year rate 97% vs 92%) as well as pts 65 and older (P=0.002; one year rate 94% vs 83%), respectively. Sixty-one patients have died; 42 in the RD arm and 16 in Rd arm. The cause of death has been verified by detailed chart review in 38 patients. Of 29 verified deaths in the RD arm, 13 were due to disease progression, 6 thrombosis/embolism, 3 infection, 3 cardiac ischemia, 1 stroke, and 1 respiratory failure. Of 9 verified deaths in the Rd arm, 5 were due to disease progression, 2 infection, 1 thrombosis/embolism, and 1 cardiac arrest. Response rate data are expected to be available at the time of the meeting. Conclusions: Lenalidomide plus low-dose dexamethasone (Rd) is associated with superior OS compared to lenalidomide plus high-dose dexamethasone (RD) in newly diagnosed MM. The increased mortality in Arm A is due to disease progression (myeloma deaths) as well as increased toxicity. This study has major implications for the use of high-dose dexamethasone in the treatment of newly diagnosed MM. Major Grade 3 or Higher Adverse Events Toxicity Arm A % Arm B % P value Neutropenia 10 19 0.01 DVT/PE 25 9 <0.001 Infections 16 6 <0.001 Any grade 3 or higher non-hematologic 49 32 <0.001 Any grade 4 or higher non-hematologic 20 9 <0.001 Deaths in first 4 months 5 0.5 0.006

Phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): A trial coordinated by the Eastern Cooperative Oncology Group

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA8025-LBA8025 ◽  
Author(s):  
S. V. Rajkumar ◽  
S. Jacobus ◽  
N. Callander ◽  
R. Fonseca ◽  
D. Vesole ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Low Dose ◽  
Phase Iii ◽  
Bone Lesions ◽  
High Dose ◽  
Type I ◽  
Newly Diagnosed ◽  
High Dose Dexamethasone ◽  
Grade 3 ◽  
One Year

LBA8025 Background: We compared lenalidomide plus high (standard) dose Dex (R+HighD) versus lenalidomide plus low dose Dex (R+LowD) in newly diagnosed MM. Methods: Pts with untreated, symptomatic MM were eligible. Pts in both arms received lenalidomide 25 mg/day PO days 1–21 every 28 days. In addition, pts in the R+HighD arm received Dex 40 mg days 1–4, 9–12, and 17–20 PO every 28 days; pts in the R+LowD arm received Dex 40 mg days 1, 8, 15, and 22 PO every 28 days. The primary null hypothesis was that response rates at 4 months on the 2 arms are equivalent. Planned sample size was 196 eligible pts per arm with one-sided 0.10 Type I and 0.05 Type II error rate. Pre-planned interim analysis is performed by an independent DMC when full information is available on 25%, 50% and 75% of accrual. All analysis were intent to treat. Results: 445 pts (median age, 65 yrs) were accrued; 223 randomized to R+HighD, 222 to R+LowD. Arms were well balanced for age, gender, stage, bone lesions, hemoglobin, beta-2 microglobulin, performance status, bone marrow plasma cells, and M protein levels at baseline. Major grade 3 or higher toxicities included thromboembolism (22.1% with R+HighD vs 6.1% in R+LowD), infection/pneumonia (15.7% vs 7.5%) and hyperglycemia (9.7% vs 6.6%). Grade 3 or higher non-hematologic toxicities occurred in 65.9% (R+HighD) versus 54.9% (R+LowD) respectively; corresponding grade 4 or higher rates were 20.3% vs 13.1% respectively. Overall survival (OS) at first interim analysis was significantly superior with R+LowD, P<0.001; one year survival 96.5% (R+LowD) versus 86% (Rev+HighD). OS differences in favor of R+LowD were seen in pts <65 (P=0.015; one year rate 98% vs 90%) and pts 65 and older (P=0.004; one year rate 95% vs 83%), respectively. DMC recommended release of survival results, and recommended switching all pts to R+LowD. DMC also recommended closure of an expansion phase trial of R+HighD investigating optimal thromboprophylaxis. Conclusions: Lenalidomide plus low-dose dexamethasone is associated with superior OS compared to lenalidomide plus high-dose dexamethasone. This study has major implications for future use of high-dose dexamethasone in the treatment of MM. No significant financial relationships to disclose.

Sustained normoglycemia in newly diagnosed type I diabetic subjects. Short-term effects and one-year follow-up

Diabetes ◽  
1984 ◽  
Vol 33 (10) ◽  
pp. 995-1001 ◽  
Author(s):  
K. Perlman ◽  
R. M. Ehrlich ◽  
R. M. Filler ◽  
A. M. Albisser
Keyword(s):  
Type I ◽  
Newly Diagnosed ◽  
Short Term ◽  
One Year ◽  
Short Term Effects

Health-related quality of life one year after surgical treatment of the type I chronic aortic dissection

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Oksana Kamenskaya ◽  
Asya Klinkova ◽  
Irina Loginova ◽  
Alexander Chernyavskiy ◽  
Dmitry Sirota ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Surgical Treatment ◽  
Aortic Dissection ◽  
Type I ◽  
Health Related Quality ◽  
Chronic Aortic Dissection ◽  
Related Quality ◽  
Health Related ◽  
One Year

THYROID DYSFUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE: THE STATE OF THE PROBLEM AND THE WAYS OF SOLVING

2018 ◽  
Vol 22 (4) ◽  
pp. 40-49 ◽  
Author(s):  
A. R. Volkova ◽  
O. D. Dygun ◽  
B. G. Lukichev ◽  
S. V. Dora ◽  
O. V. Galkina
Keyword(s):  
Chronic Kidney Disease ◽  
Thyroid Gland ◽  
Kidney Disease ◽  
Thyroid Hormones ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
The Body ◽  
Type I ◽  
Low T3 ◽  
Iodine Excretion

Disturbance of the thyroid function is often detected in patients with different profiles. A special feature of patients with chronic kidney  disease is the higher incidence of various thyroid function  disturbances, especially hypothyroidism. It is known that in patients  with chronic kidney disease (CKD) iodine excretion from the body is  violated, since normally 90% of iodine is excreted in urine.  Accumulation of high concentrations of inorganic iodine leads to the  formation of the Wolf-Chaikoff effect: suppression of iodine  organization in the thyroid gland and disruption of the thyroid  hormones synthesis. Peripheral metabolism of thyroid hormones is  also disturbed, namely, deiodinase type I activity is suppressed and  peripheral conversion of T4 into T3 is inhibited (so-called low T3  syndrome). Therefore, patients with CKD are often diagnosed with  hypothyroidism, and the origin of hypothyroidism is not always  associated with the outcome of autoimmune thyroiditis. The article  presents an overview of a large number of population studies of  thyroid gland dysfunction in patients with CKD, as well as  experimental data specifying the pathogenetic mechanisms of  thyroid dysfunction in patients with CKD. Therapeutic tactics are still  not regulated. However, in a number of studies, replacement therapy with thyroid hormones in patients with CKD had some advantages.

scholarly journals Collagen-Based Electrospun Materials for Tissue Engineering: A Systematic Review

2021 ◽  
Vol 8 (3) ◽  
pp. 39
Author(s):  
Britani N. Blackstone ◽  
Summer C. Gallentine ◽  
Heather M. Powell
Keyword(s):  
Systematic Review ◽  
Tissue Engineering ◽  
Collagen Type I ◽  
The Body ◽  
Pool Data ◽  
Type I ◽  
High Concentrations ◽  
Increased Strength

Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match that of the native ECM. This systematic review aims to pool data from available manuscripts on electrospun collagen and tissue engineering to provide insight into the connection between source material, solvent, crosslinking method and functional outcomes. D-banding was most often observed in electrospun collagen formed using collagen type I isolated from calfskin, often isolated within the laboratory, with short solution solubilization times. All physical and chemical methods of crosslinking utilized imparted resistance to degradation and increased strength. Cytotoxicity was observed at high concentrations of crosslinking agents and when abbreviated rinsing protocols were utilized. Collagen and collagen-based scaffolds were capable of forming engineered tissues in vitro and in vivo with high similarity to the native structures.

scholarly journals Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hieu Hoang Trung ◽  
Toru Yoshihara ◽  
Akito Nakao ◽  
Katsumi Hayashida ◽  
Yoshiki Hirata ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fear Conditioning ◽  
Open Field ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Regulatory Subunit ◽  
Type I ◽  
Schaffer Collateral ◽  
Normal Behavior ◽  
Collateral Pathway

AbstractThe RIβ subunit of cAMP-dependent protein kinase (PKA), encoded by Prkar1b, is a neuronal isoform of the type I regulatory subunit of PKA. Mice lacking the RIβ subunit exhibit normal long-term potentiation (LTP) in the Schaffer collateral pathway of the hippocampus and normal behavior in the open-field and fear conditioning tests. Here, we combined genetic, electrophysiological, and behavioral approaches to demonstrate that the RIβ subunit was involved in body tremor, LTP in the Schaffer collateral pathway, and fear conditioning memory in rats. Genetic analysis of WTC-furue, a mutant strain with spontaneous tremors, revealed a deletion in the Prkar1b gene of the WTC-furue genome. Prkar1b-deficient rats created by the CRISPR/Cas9 system exhibited body tremor. Hippocampal slices from mutant rats showed deficient LTP in the Schaffer collateral–CA1 synapse. Mutant rats also exhibited decreased freezing time following contextual and cued fear conditioning, as well as increased exploratory behavior in the open field. These findings indicate the roles of the RIβ subunit in tremor pathogenesis and contextual and cued fear memory, and suggest that the hippocampal and amygdala roles of this subunit differ between mice and rats and that rats are therefore beneficial for exploring RIβ function.

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