Medical Treatment in Cushing’s Syndrome : Dopamine Agonists and Cabergoline

Dopamine (DA) is a catecholamine with a wide range of functions and whose five subtype receptors are found in different organs where they exert a mainly inhibitory action. Since this action may also appear in a number of secretory tumors in various locations, DA agonists have elicited some interest as a medical treatment for hypercorticism. Non-iatrogenic Cushing’s syndromes are due in 70% of the cases to a pituitary adrenocorticotropic hormone (ACTH) producing adenoma, and, less frequently, to an adrenal adenoma or an ectopic ACTH secretion by a neuroendocrine tumor. First-line treatment in Cushing’s syndrome consists of the surgical removal of the secreting tumor. However, surgery may not achieve a complete cure in a number of cases, hence emphasizing the potential benefit of a medical complementary treatment, which could also benefit patients as an alternative approach, either when waiting for, or when the patient is not eligible for surgery. Studies of corticotropic adenomas have shown that 80% of these tumors express D2 receptors. Clinical trials of DA agonists in Cushing’s disease have shown an inhibitory effect of these drugs with an inhibition of ACTH secretion and/or a decrease of tumor size. There are only a few cases of documented use of DA agonists in ectopic ACTH secretion, but when the tumor expresses DA receptors, DA agonists may represent a useful complementary treatment. DA receptors are also expressed in normal and tumoral adrenals, suggesting a potential use of DA agonists in Cushing’s syndrome secondary to adrenal tumors. However, clinical data regarding this specific situation are very scarce, maybe due to the relatively high rate of surgical cure of adrenal adenomas. In conclusion, DA agonists represent a potential preparatory or complementary treatment for endogenous Cushing’s syndrome, especially in Cushing’s disease. These compounds may be underused as suggested by the scarce number of publication and case reports in the literature. In the future, association of these drugs with somatostatin analogs may also prove beneficial

Clinical case of the month. A patient with advanced non-small-cell lung cancer presenting with an exceptional response to targeted therapies

peer reviewedAdvanced non-small-cell lung cancers are diseases of late diagnosis with bad prognosis. Conventional chemotherapies are not very efficient. Over the last years, many research works have been performed in this way to improve prognosis. Targeted therapies seem promising. They were notably developed against epithelial growth factor receptors and tumoral angiogenesis. We report here the clinical history of a patient with an advanced non-small-cell lung cancer presenting an exceptional response to small-molecule tyrosine kinase inhibitors

Do novel gravitational environments alter the grip-force/load-force coupling at the fingertips?

In this experiment we examined the coupling between grip force and load force observed during cyclic vertical arm movements with a hand-held object, performed in different gravitational environments. Six subjects highly experienced in parabolic flight participated in this study. They had to continuously move a cylindrical object up and down in the different gravity fields (1g, 1.8 g and 0 g) induced by parabolic flights. The imposed movement frequency was 1 Hz, the object mass was either 200 or 400 g, the amplitude of movement was either 20 or 40 cm and an additional mass of 200 g could be wound around the forearm. Each subject performed the task during 15 consecutive parabolas. The coordination between the grip force normal to the surface and the tangential load force was examined in nine loading conditions. We observed that the same normal grip force was used for equivalent loads generated by changes of mass, gravity or acceleration despite the fact that these loads required different motor commands to move the arm. Moreover, our results suggest that the gravitational and inertial components of the load are treated adequately and independently by the internal models used to predictively control the required grip force. These results indicate that the forward internal models used to control precision grip take into account the dynamic characteristics of the upper limb, the object and the environment to predict the object's acceleration and, in turn, the load force acting at the fingertips

The effects of a change in gravity on the dynamics of prehension.

Investigating cyclic vertical arm movements with an instrumented hand-held load in an airplane undergoing parabolic flight profiles allowed us to determine how humans modulate their grip force when the gravitational and the inertial components of the load force are varied independently. Eight subjects participated in this study; four had already experienced parabolic flights and four had not. The subjects were asked to move the load up and down continuously at three different gravitational conditions (1 g, 1.8 g, and 0 g). At 1 g, the grip force precisely anticipated the fluctuations in the load force, which was maximum at the bottom of the object trajectory and minimum at the top. When gravity changed, the temporal coupling between grip force and load force persisted for all subjects from the first parabola. At 0 g, the grip force was accurately adjusted to the two load force peaks occurring at the two opposite extremes of the trajectory due to the absence of weight. While the experienced subjects exerted a grip force appropriate to a new combination of weight and inertia since their first trial, the inexperienced subjects dramatically increased their grip when faced with either high or low force levels for the first time. Then they progressively released their grip until a continuous grip-load force relationship with regard to 1 g was established after the fifth parabola. We suggest that a central representation of the new gravitational field was rapidly acquired through the incoming vestibular and somatic sensory information

Importance of cutaneous feedback in maintaining a secure grip during manipulation of hand-held objects

Previous research has shown that grip and load forces are modulated simultaneously during manipulation of a hand-held object. This close temporal coupling suggested that both forces are controlled by an internal model within the CNS that predicts the changes in tangential force on the fingers. The objective of the present study was to examine how the internal model would compensate for the loss of cutaneous sensation through local anesthesia of the index and thumb. Ten healthy adult subjects (5 men and 5 women aged 20-57 yr) were asked to grasp, lift, and hold stationary, a 250 g object for 20 s. Next, the subjects were asked to perform vertical oscillatory movements over a distance of 20 cm at a rate of 1.0 Hz for 30 s. Eleven trials were performed with intact sensation, and 11 trials after a local ring-block anesthesia of the index and thumb with bupivacain (5 mg/ml). During static holding, loss of cutaneous sensation produced a significant increase in the safety margin. However, the grip force declined significantly over the 20-s static hold period. During oscillatory arm movements, grip and load forces were continuously modulated together in a predictive manner as suggested by Flanagan and Wing. Again, the grip force declined over the 30-s movement, and 7/10 subjects dropped the object at least once. With intact sensation, the object was never dropped; but with the fingers anesthetized, it was dropped on 36% of the trials, and a significant slip occurred on a further 12%. The mean correlation between the grip and load forces for all subjects deteriorated from 0.71 with intact sensation to 0.48 after digital anesthesia. However, a cross-correlation calculated between the grip and load forces indicated that the phase lag was approximately zero both with and without digital anesthesia. Taken together, the data from the present study suggest that cutaneous afferents are required for setting and maintaining the background level of the grip force in addition to their phasic slip-detection function and their role in adapting the grip force/load force ratio to the friction on initial contact with an object. Finally, at a more theoretical level, they correct and maintain an internal model of the physical properties of hand-held objects

Long-term oxygen therapy: mortality rate, short-term predictive mortality factors

OBJECTIVES: The aims of this study were to assess the survival rate at one year of patients receiving long-term oxygen therapy (LTOT) as prescribed by the National Institute for Health and Disability Insurance's imposed criteria based on international recommendations, to search for short-term predictive factors for mortality and to measure the impact of LTOT on the frequency of hospitalization due to COPD exacerbations. METHODS: We conducted a retrospective analysis of 416 patients suffering from chronic respiratory insufficiency and started on long-term oxygen therapy between 2012 and 2014. The survival curves were estimated by the Kaplan-Meier method. Cox regression models were used to estimate the impact of the variables on survival. The evolution of patients hospitalized for COPD exacerbation was analysed by the McNemar test. RESULTS: The average age of our cohort was 70+/-10 years. It included 57% women and 78% patients with COPD. The one-year survival rate (n=416) under LTOT was 75%. Identified predictive mortality factors were coronary insufficiency [HR (95% CI): 1.8 (1.2-2.8); P=0.0083], reduction of the left ventricular ejection fraction [HR (95% CI): 2.5 (1.3-4.9); P=0.0080], the presence of osteoporosis [HR (95% CI): 1.7 (1.0-2.9); P=0.040]. There was a 28% reduction in the frequency of hospitalization for exacerbations of COPD during the year after starting LTOT. CONCLUSIONS: Mortality at one year with LTOT was about 25%. Factors predictive of mortality at one year included coronary insufficiency, reduction of the left ventricular ejection fraction and osteoporosis. LTOT seems to reduce hospitalizations due to exacerbations of COPD

Pericarditis revealing an anti-Jo-1 anti-synthetase syndrome in an elderly patient

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