The objectives of this study were to compare the survival of sarcoid patients with pulmonary fibrosis with that of the general population and to determine the causes of death and the incidence of evolutive complications. This retrospective cohort included 142 sarcoid patients in radiographic stage IV (74 males; mean ± SD age 48.1 ± 12 yrs). Their survival was compared with that of the general French population, matched for the year and age at diagnosis of stage IV disease, sex and length of follow-up. Expected survival probabilities were calculated year-by-year on the basis of probabilities provided by official demographic data for France. Survival curves were based on the Kaplan-Meier method and compared using the log-rank test. During the follow-up period (7.1 ± 4.8 yrs), pulmonary hypertension (PH) was observed in 29.7% of cases and aspergilloma in 11.3%. Long-term oxygen therapy was required in 12%. Survival was 84.1% at 10 yrs, which was worse than for the general population (p = 0.013). 16 (11.3%) patients died from the following causes: refractory PH (n = 5), chronic respiratory insufficiency (n = 4), acute respiratory insufficiency (n = 2), haemoptysis due to aspergilloma (n = 1), heart sarcoidosis (n = 1), nocardiosis (n = 1) and unknown causes (n = 2). Survival is significantly decreased in stage IV patients. 75% of fatalities are directly attributable to respiratory causes.
The increases in the level of plasma lipotropin (LPH) and in the LPH/ACTH ratio are considered diagnostic tools in ectopic ACTH syndrome. However, plasma ACTH is also elevated in this syndrome. We report a case of a small carcinoid tumor with an increase in both ACTH and LPH in plasma before surgery. Eight months after the tumoral resection, plasma LPH alone was increased again, whereas plasma ACTH and plasma and urinary cortisol remained normal in this apparently cured patient. This repeated abnormality was the only available feature that allowed successful removal of the occult tumoral residue.
The variations in plasma cortisol, testosterone and 17-hydroxyprogesterone (17-OHP) induced by an im injection of 0.25 mg cosyntrophin were studied in three groups of subjects: 16 healthy women, 16 hirsute women (HW) and 10 mild cases of congenital adrenal hyperplasia (CAH). The basal values of cortisol and testosterone were comparable between the three groups. In the patients with mild CAH, the mean 17-OHP concentration was increased: 483.9 ng/100 ml (113-1200 ng), but it should be noted that the individual values could overlap with the normal concentrations found in the controls and the HW during the luteal phase of the cycle. One hour after the injection of cosyntropin, a massive response of 17-OHP was observed in the mild cases of CAH, the mean basal concentration was multiplied by ten: 4843 ng/100 ml. The minimum concentration reached was 1740 ng/100 ml which is still 3-fold the highest level seen either in normal women (400 ng/ml) or in hirsute women (550 ng/100 ml). Determination of 17-OHP following a short-term ACTH stimulation, therefore provides evidence of partial 21-hydroxylase deficiency.
Introduction A defining aspect of the Intergovernmental Panel on Climate Change (IPCC) assessment reports (AR) is a formal uncertainty language framework that emphasizes higher certainty issues across the reports, especially in the executive summaries and short summaries for policymakers. As a result, potentially significant risks involving understudied components of the climate system are shielded from view. Methods Here we seek to address this in the latest, sixth assessment report (AR6) for one such component—the deep ocean—by summarizing major uncertainties (based on discussions of low confidence issues or gaps) regarding its role in our changing climate system. The goal is to identify key research priorities to improve IPCC confidence levels in deep ocean systems and facilitate the dissemination of IPCC results regarding potentially high impact deep ocean processes to decision-makers. This will accelerate improvement of global climate projections and aid in informing efforts to mitigate climate change impacts. An analysis of 3,000 pages across the six selected AR6 reports revealed 219 major science gaps related to the deep ocean. These were categorized by climate stressor and nature of impacts. Results Half of these are biological science gaps, primarily surrounding our understanding of changes in ocean ecosystems, fisheries, and primary productivity. The remaining science gaps are related to uncertainties in the physical (32%) and biogeochemical (15%) ocean states and processes. Model deficiencies are the leading cited cause of low certainty in the physical ocean and ice states, whereas causes of biological uncertainties are most often attributed to limited studies and observations or conflicting results. Discussion Key areas for coordinated effort within the deep ocean observing and modeling community have emerged, which will improve confidence in the deep ocean state and its ongoing changes for the next assessment report. This list of key “known unknowns” includes meridional overturning circulation, ocean deoxygenation and acidification, primary production, food supply and the ocean carbon cycle, climate change impacts on ocean ecosystems and fisheries, and ocean-based climate interventions. From these findings, we offer recommendations for AR7 to avoid omitting low confidence-high risk changes in the climate system.
Cibenzoline is a class Ic antiarrhythmic agent that can be used to treat supraventricular arrhythmias. A case is reported of cibenzoline overdose in a patient with impaired renal function, leading not only to the usual cardiac and metabolic symptoms (bradycardia and hypoglycaemia), but also to a myastheniform syndrome with acute respiratory failure. Neuromuscular blockade was demonstrated by repetitive supramaximal stimulation of the median nerve, and diaphragmatic involvement was evidenced by applying the same protocol to the phrenic nerve. Muscle strength recovered as serum cibenzoline levels decreased, allowing the patient to be weaned from the ventilator. This observation suggests that cibenzoline, like other antiarrhythmic agents, can be responsible for neuromuscular blockade, and should therefore be used with caution in patients with neuromuscular and respiratory diseases or with impaired renal function.
To assess the corticotrophic response to ovine corticotrophin releasing hormone (CRH) with the lowest dose of lysine vasopressin able to induce both the greatest stimulation and the lowest degree of side-effects.Fourteen healthy young adult males.Increasing intravenous doses (either 0, 0.03, 0.1, 0.3, or 1 IU) of lysine vasopressin, infused over 20 minutes, combined with a bolus of 100 micrograms ovine CRH.Radioimmunoassay of plasma ACTH, lipotrophin hormones and cortisol levels.(1) Responses to stimulation tests were evaluated as the area under the curves of plasma levels versus sample times, from 0 to 120 minutes after injection or start of perfusion (six subjects). The lowest dose of lysine vasopressin that induced an additional stimulation in the CRH-stimulated ACTH response was 0.3 IU. The combination of 1 IU lysine vasopressin with CRH doubled values of the area under the curve for the ACTH. Lysine vasopressin alone (0.3 and 1 IU) failed to stimulate ACTH responses. (2) The combined test (100 micrograms CRH and 1 IU lysine vasopressin) was carried out on eight additional control subjects. From a mean basal level of 23 +/- 5.6 (SEM), plasma ACTH peaked to 104.5 +/- 8 ng/l (23.0 +/- 1.8 pmol/l) as early as 20-30 minutes after the start of injection. When repeated after a two-week interval, the combined test induced identical stimulation in a given subject. Results of lipotrophin hormone determinations roughly paralleled those of ACTH. However the effects on cortisol levels were less clear. Subjects injected with CRH experienced slight facial flush. Following the 1 IU lysine vasopressin dosage, side-effects were reduced to skin pallor. No changes in heart-rate or blood-pressure were observed.Under these conditions, the combination of 100 micrograms CRH with 1 IU lysine vasopressin constitutes a powerful test for direct assessment of the pituitary reserve and therefore can be employed as a routine investigational tool.
