Hypercoagulability in Cushing’s syndrome: the role of specific haemostatic and fibrinolytic markers

Objective Hypercoagulability is a commonly described complication in patients with Cushing’s syndrome. Recent clinical studies have indicated various abnormalities of coagulation and fibrinolysis parameters which may be related to that phenomenon. The aim of this study was to investigate the mechanisms underlying the hypercoagulable state in patients with Cushing’s syndrome. Research methods and procedures A wide range of serum markers involved in the processes of blood coagulation and fibrinolysis was measured in a group of 33 patients with Cushing’s syndrome and 31 healthy controls. No participant was taking medication which could influence the result or had known diseases, except hypertension and diabetes, which could affect blood coagulation or fibrinolysis parameters. Results Patients with Cushing’s syndrome had higher levels of clotting factors II (P = 0.003), V (P < 0.001), VIII (P < 0.001), IX (P < 0.001), XI (P < 0.001) and XII (P = 0.019), protein C (P < 0.001), protein S (P < 0.001), C1-inhibitor (P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) (P = 0.004). The activity of fibrinolytic markers, plasminogen (P < 0.001), antithrombin (P < 0.001) and antithrombin antigen (P = 0.001) was also increased in the patient group. Conclusion The study has demonstrated hypercoagulability in patients with Cushing’s syndrome manifest as increased prothrombotic activity and compensatory activation of the fibrinolytic system. We propose the introduction of thromboprophylaxis in the preoperative and early postoperative periods, combined with a close follow-up in order to prevent possible thromboembolic events in patients with Cushing’s syndrome.     

The PDLIM5 gene and lithium prophylaxis: An association and gene expression analysis in Sardinian patients with bipolar disorder

A number of studies support the notion that lithium interacts with the protein kinase C (PKC) pathway, an important mediator of several intracellular responses to neurotransmitter signaling. PDLIM5 (PDZ and LIM domain 5; LIM) is an adaptor protein that selectively binds the isozyme PKC(epsilon) to N-type Ca(2+) channels in neurons. We tested for an association between three single nucleotide polymorphisms (SNPs) at the PDLIM5 gene and lithium prophylaxis in a Sardinian sample comprised of 155 bipolar patients treated with lithium. In order to evaluate whether PDLIM5 expression interacts with lithium response, we carried out gene expression analysis in lymphoblastoid cells of 30 bipolar patients. No association was shown between PDLIM5 polymorphisms and lithium response. When PDLIM5 expression was evaluated, no significant differences were detected between Full Responders to lithium (total score>or=7) and other patients (total score相似文献   

Is withdrawal-induced anxiety in alcoholism based on β-endorphin deficiency?

RATIONALE: Associations between several psychopathological alterations and lowered beta-endorphin(beta E) plasma levels have already been stated in former studies. However, whereas single measures during static conditions generally failed in linking beta E levels with psychopathology, dynamic changes of beta E in particular have been shown to be associated with spells of anxiety and depression. During alcohol withdrawal, a decreased secretion of beta E with a delayed normalization has been reported, but up to now only few data became available regarding the interaction of plasma beta E and psychopathological parameters. OBJECTIVES: The aim of our study was to test the hypothesis whether beta E during acute alcohol withdrawal is associated with anxiety, depression, and craving. METHODS: We observed self-rated anxiety, depression, and craving during alcohol withdrawal and assessed beta E levels (RIA) in a consecutive sample of 60 alcoholics on day 1 and day 14 after onset of withdrawal, and in 30 healthy volunteers. To control for mutual interactions of beta E and the pituitary-adrenocortical hormone secretion, plasma corticotropin (ACTH) and cortisol were also determined. RESULTS: In accordance with prior studies, beta E was significantly lowered on day 1 and day 14 of alcohol withdrawal relative to controls. Plasma levels of ACTH correlated significantly with beta E in alcoholics at both time points and in controls, without differing significantly between the groups. Self-rated anxiety, depression, and alcohol craving decreased significantly between day 1 and day 14. Levels of beta E were inversely correlated with anxiety day 1 (r=-0.58) and day 14 (r=-0.71). Partial correlation coefficients controlling for ACTH plasma levels revealed that this correlation was largely independent from ACTH. In addition, a significant inverse relationship was found between beta E and craving on day 14 (r=-0.28). No association appeared between beta E and depression. CONCLUSIONS: Our results give first evidence that lowered beta E during alcohol withdrawal may contribute to anxiety as a common disturbance during this state.     

Prevention of ventilator-induced lung injury with partial liquid ventilation

BACKGROUND/PURPOSE: Pulmonary injury from mechanical ventilation has been attributed to application of excess alveolar pressure (barotrauma) or volume (volutrauma). The authors questioned whether partial liquid ventilation (gas ventilation of the perfluorocarbon filled lung, PLV) would reduce ventilator-induced lung injury. METHODS: A tracheostomy tube and carotid artery catheter were placed in anesthetized Sprague-Dawley rats (500 +/- 50 g). Bovine serum albumin (BSA) labeled with Iodine (I) 125 was administered intraarterially. Ventilation with tidal volume (TV) of 5 mL/kg was initiated. The rats were then selected randomly to a 30-minute experimental period of one of the following ventilation protocols: continued atraumatic gas ventilation (GV, TV, 5 mL/kg; n = 10); atraumatic gas ventilation combined with intratracheal administration of 10 mL/kg perfluorocarbon (GV-PLV, TV, 5 mL/kg, n = 10); barotrauma (BT, peak inspiratory pressure [PIP], 45 cm H(2)O; n = 10); barotrauma with PLV (BT-PLV, PIP, 45 cm H(2)O; n = 8); volutrauma (VT, TV, 30 mL/kg; n = 8); or volutrauma with PLV (VT-PLV, TV, 30 mL/kg; n = 10). Animals were killed and the amount of radiolabeled BSA in both lungs was measured and normalized to the counts in 1 mL of blood from that animal (injury index). Data were analyzed by analysis of variance (ANOVA) with post-hoc t test comparison between groups. RESULTS: There was a significant difference in the (125)I-BSA injury index when all groups were compared (P <.001 by ANOVA). Post-hoc analysis showed a significant decrease in the injury index when comparing BT versus BT-PLV (P =.024) and VT versus VT-PLV (P =.014). CONCLUSION: (125)I-BSA leak produced during high-pressure or high-volume mechanical ventilation is reduced by partial liquid ventilation.     

Successful management of a chylothorax in infancy using a pleurectomy

The management of chylothorax is described in three infants. Because none of them had had a direct injury to the thoracic duct, it was suspected that the chylothoraces had a significant chance of recurrence after simple ligation of the duct. To avoid recurrence, formal stripping of the parietal pleura was performed using a technique not previously reported in the literature. The operation was simple to perform and resulted in resolution of the chylothorax in all infants. The three cases and details of the surgical procedure are described.     

Update: current management issues in malignant melanoma

The incidence of melanoma has increased continuously during the last decade. Surgery is the mainstay of therapy but, for patients with thick lesions or regional metastatic lymph nodes, there is a high risk of relapse. For this group of patients, there is no standard therapy or general agreement amongst oncologists. In this article, we review the current management of melanoma with regard to past completed adjuvant trials and open trials. Moreover, we discuss the role of chemotherapy in metastatic melanoma, in particular with attention to the use of fotemustine.     

Neuropharmacological evaluation of diethylether extract and xanthones of Gentiana kochiana

Diethylether extract of aerial parts of Gentiana kochiana mostly consists of two tetraoxygenated xanthones: gentiacaulein (1,7-dihidroxy-3,8-dimethoxyxanthone; 76.1%) and gentiakochianin (1,7,8-trihidroxy-3-methoxyxanthone; 14.2%). The extract and these xanthones were evaluated for the CNS pharmacological activity in rodents. In vitro assays on rat brain preparations revealed insignificant interaction of the compounds with the specific dopamine and serotonin receptors or synaptosomal uptake of serotonin. However, the extract and gentiacaulein strongly inhibited rat microsomal MAO A (IC50=0.22 microg/ml and 0.49 microM, respectively). Their effects on MAO B and a gentiakochianin blocking potential on both MAO enzymes were moderate. Behavioral examinations on mice showed that 10 day s.c. administration of the extract (20 mg/kg) significantly decreased immobility score in a forced swimming test and strongly inhibited ambulation and stereotypy in an open-field test. These effects resembled those induced by 10 mg/kg imipramine. The ex vivo MAO A activity in crude brain mitochondrial fraction of mice treated with 20 mg/kg of the extract was significantly elevated, whilst that outside brain nerve terminals was declined. This study suggests some antidepressant therapeutic potential of G. kochiana, particularly of gentiacaulein, with an ambiguity whether pharmacological mechanism could be related only to the central inhibition of MAO A.