Inherited mutations in the erythropoietin receptor (EPOR) causing premature termination of the receptor cytoplasmic region are associated with dominant familial erythrocytosis (FE), a benign clinical ...condition characterized by hypersensitivity of erythroid progenitor cells to EPO and low serum EPO (S-EPO) levels. We describe a Swedish family with dominant FE in which erythrocytosis segregates with a new truncation in the negative control domain of the EPOR. We show that cells engineered to concomitantly express the wild-type (WT) EPOR and mutant EPORs associated with FE (FE EPORs) are hypersensitive to EPO-stimulated proliferation and activation of Jak2 and Stat5. These results demonstrate that FE is caused by hyperresponsiveness of receptor-mediated signaling pathways and that this is dominant with respect to WT EPOR signaling.
Context:
Familial and sporadic GH-secreting pituitary adenomas are associated with mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. Patients with an AIP mutation (AIPmut) ...tend to have more aggressive tumors occurring at a younger age.
Objective:
The objective of the study was to investigate the frequency of AIPmut in patients diagnosed at 30 years of age or younger.
Design:
The German Acromegaly Registry database (1795 patients in 58 centers) was screened for patients diagnosed with acromegaly at 30 years of age or younger (329 patients). Sixteen centers participated and 91 patients consented to AIPmut analysis.
Intervention:
DNA was analyzed by direct sequencing and multiplex ligation dependent probe amplification
Main outcome Measures:
The number of patients with AIPmut was measured.
Results:
Five patients had either a mutation (c.490C>T, c.844C>T, and c.911G>A, three males) or gross deletions of exons 1 and 2 of the AIP gene (n = 2, one female). The overall frequency of an AIPmut was 5.5%, and 2.3% or 2.4% in patients with an apparently sporadic adenoma or macroadenoma, respectively. By contrast, three of four patients (75%) with a positive family history were tested positive for an AIPmut. Except for a positive family history, there were no significant differences between patients with and without an AIPmut.
Conclusions:
The frequency of AIPmut in this registry-based cohort of young patients with acromegaly is lower than previously reported. Patients with a positive family history should be tested for an AIPmut, whereas young patients without an apparent family history should be screened, depending on the individual cost to benefit ratio.
Aims: Anxiety disorders have been shown to be correlated with an activation of coagulation and impairment of fibrinolysis. The aim of the study was to assess whether medication with a serotonergic ...antidepressant, which has been associated with abnormal bleeding, may modify this effect.
Methods: Thirty‐one anxiety patients, mostly with comorbid depression, and 31 healthy controls were included in the study. Group differences between anxiety patients medicated with a serotonergic antidepressant, patients without serotonergic antidepressant and controls were assessed for activated partial thromboplastin time, fibrinogen, factor VII, factor VIII, von Willebrand factor, von Willebrand ristocetin cofactor activity, prothrombin fragment 1 + 2, thrombin‐antithrombin complex, d‐dimer, α2‐antiplasmin, plasmin‐α2‐antiplasmin complex (PAP), tissue plasminogen activator and plasminogen activator inhibitor. Intervening variables, such as age, sex, body mass index and smoking, were accounted for.
Results: We found lower coagulation measures for fibrinogen (P = 0.03) and plasminogen activator inhibitor (P = 0.01), and higher levels of PAP (P = 0.046) in patients with serotonergic antidepressant than in patients without serotonergic antidepressant. When controlling for smoking and body mass index, differences between the two groups were significant for PAP (P = 0.02), von Willebrand ristocetin cofactor activity (P = 0.02) and activated partial thromboplastin time (P = 0.046). Coagulation scores were similar in patients with serotonergic antidepressant to those of healthy controls.
Conclusions: Serotonergic antidepressants may counteract a procoagulant effect of anxiety and/or depression in anxiety patients.
The aim of this work was to examine a possible association between a clinically relevant panic disorder and plasma total homocysteine concentration.
23 patients with panic disorder with or without ...agoraphobia confirmed by a standardized clinical interview (Structural Clinical Interview for DSM-IV-German version) and 23 healthy controls matched for gender and age completed questionnaires (SCL-K9, STAI, ADS, STAXI) and had blood drawn after a 15 min rest. Plasma total homocysteine concentrations were measured by competitive enzyme immunoassay. Interfering variables such as age, gender, smoking status, comorbid depression and medication were controlled for.
Patients with panic disorder had higher plasma homocysteine concentrations in comparison to the control group (mean value 11.00 vs. 9.14 mumol/l, p = 0.04 with age, gender, smoking status, comorbid depression and antidepressant medication being controlled for). Furthermore, homocysteine plasma concentration was positively correlated with Global Severity of Symptoms (SCL-K9, r(Pearson) = 0.41, p < 0.01).
The findings of this study suggest a link between elevated plasma homocysteine levels and panic disorder. This raises a new hypothesis of another pathway to an increased risk of cardiovascular events in anxious individuals.
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