175 research outputs found
Effectiveness of Metyrapone in Treating Cushing's Syndrome: A Retrospective Multicenter Study in 195 Patients
Background:
Cushing's syndrome (CS) is a severe condition with excess mortality and significant morbidity necessitating control of hypercortisolemia. There are few data documenting use of the steroidogenesis inhibitor metyrapone for this purpose.
Objective:
The objective was to assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with CS.
Design:
This was designed as a retrospective, multicenter study.
Setting:
Thirteen University hospitals were studied.
Patients:
We studied a total of 195 patients with proven CS: 115 Cushing's disease, 37 ectopic ACTH syndrome, 43 ACTH-independent disease (adrenocortical carcinoma 10, adrenal adenoma 30, and ACTH-independent adrenal hyperplasia 3).
Measurements:
Measurements included biochemical parameters of activity of CS: mean serum cortisol âday-curveâ (CDC) (target 150â300 nmol/L); 9 am serum cortisol; 24-hour urinary free cortisol (UFC).
Results:
A total of 164/195 received metyrapone monotherapy. Mean age was 49.6 ± 15.7 years; mean duration of therapy 8 months (median 3 mo, range 3 d to 11.6 y). There were significant improvements on metyrapone, first evaluation to last review: CDC (91 patients, 722.9 nmol/L [26.2 Όg/dL] vs 348.6 nmol/L [12.6 Όg/dL]; P < .0001); 9 am cortisol (123 patients, 882.9 nmol/L [32.0 Όg/dL] vs 491.1 nmol/L [17.8 Όg/dL]; P < .0001); and UFC (37 patients, 1483 nmol/24 h [537 Όg/24 h] vs 452.6 nmol/24 h [164 Όg/24 h]; P = .003). Overall, control at last review: 55%, 43%, 46%, and 76% of patients who had CDCs, UFCs, 9 am cortisol less than 331 nmol/L (12.0 Όg/dL), and 9 am cortisol less than upper limit of normal/600 nmol/L (21.7 Όg/dL). Median final dose: Cushing's disease 1375 mg; ectopic ACTH syndrome 1500 mg; benign adrenal disease 750 mg; and adrenocortical carcinoma 1250 mg. Adverse events occurred in 25% of patients, mostly mild gastrointestinal upset and dizziness, usually within 2 weeks of initiation or dose increase, all reversible.
Conclusions:
Metyrapone is effective therapy for short- and long-term control of hypercortisolemia in CS
An overview of the cutaneous porphyrias
This is an overview of the cutaneous porphyrias. It is a narrative review based on the published literature and my personal experience; it is not based on a formal systematic search of the literature. The cutaneous porphyrias are a diverse group of conditions due to inherited or acquired enzyme defects in the porphyrinâhaem biosynthetic pathway. All the cutaneous porphyrias can have (either as a consequence of the porphyria or as part of the cause of the porphyria) involvement of other organs as well as the skin. The single commonest cutaneous porphyria in most parts of the world is acquired porphyria cutanea tarda, which is usually due to chronic liver disease and liver iron overload. The next most common cutaneous porphyria, erythropoietic protoporphyria, is an inherited disorder in which the accumulation of bile-excreted protoporphyrin can cause gallstones and, rarely, liver disease. Some of the porphyrias that cause blistering (usually bullae) and fragility (clinically and histologically identical to porphyria cutanea tarda) can also be associated with acute neurovisceral porphyria attacks, particularly variegate porphyria and hereditary coproporphyria. Management of porphyria cutanea tarda mainly consists of visible-light photoprotection measures while awaiting the effects of treating the underlying liver disease (if possible) and treatments to reduce serum iron and porphyrin levels. In erythropoietic protoporphyria, the underlying cause can be resolved only with a bone marrow transplant (which is rarely justifiable in this condition), so management consists particularly of visible-light photoprotection and, in some countries, narrowband ultraviolet B phototherapy. Afamelanotide is a promising and newly available treatment for erythropoietic protoporphyria and has been approved in Europe since 2014
The Swiss Black Swan Bad Scenario: Is Switzerland Another Casualty of the Eurozone Crisis?
Phytochemical characterization of turnip greens (Brassica rapa ssp. rapa): A systematic review
Objective The Turnip (Brassica rapa L. ssp. rapa) is a leaf and root vegetable grown and consumed worldwide. The consumption of Turnip has been associated with beneficial effects on human health due to their phytochemicals that may control a variety of physiological functions, including antioxidant activity, enzyme regulation, and apoptotic control and the cell cycle. The current systematic review of the literature aims to evaluate both the profile and quantity of phytochemicals commonly found in Turnip greens and to provide perspectives for further investigation. Methods This review was conducted following the PRISMA guidelines. Four bibliographic databases (PubMed, Embase, Web-of-Science and Cochrane Central Register of Controlled Trials) were searched to identify published studies until April 8th, 2020 (date last searched) without data and language restriction. Studies were included if they used samples of Turnip greens (the leaves), and evaluated its phytochemical content. Two reviewers independently evaluated the titles and abstracts according to the selection criteria. For each potentially eligible study, two reviewers assessed the full-texts and independently extracted the data using a predesigned data extraction form. Results Based on the search strategy 5,077 potentially relevant citations were identified and full texts of 37 studies were evaluated, among which 18 studies were eligible to be included in the current review. The majority of included studies were focused on identification of glucosinolates and isothiocyanates (n = 14, 82%), four studies focused on organic acids, and five studies reported phenolic component profile in Turnip greens. Among included studies nine studies (50%) provided information on phytochemi
EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks
BACKGROUND AND AIMS: Acute hepatic porphyria
comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can
experience acute neurovisceral attacks, debilitating chronic
symptoms, and long-term complications. There is a lack of
multinational, prospective data characterizing the disease and
current treatment practices in severely affected patients.
APPROACH AND RESULTS: EXPLORE is a prospective,
multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic
porphyria who experience recurrent attacks. Eligible patients
had a confirmed acute hepatic porphyria diagnosis and had
experienced â„3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months
before the study, patients reported a median (range) of 6
(0-52) acute attacks, with 52 (46%) patients receiving hemin
prophylaxis. Chronic symptoms were reported by 73 (65%)
patients, with 52 (46%) patients experiencing these daily.
During the study, 98 (88%) patients experienced a total of
483 attacks, 77% of which required treatment at a health
care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic
ÎŽ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, ÎŽ-aminolevulinic acid, and porphobilinogen compared with
the upper limit of normal in healthy individuals were observed
at baseline and increased further during attacks. Patients had
impaired quality of life and increased health care utilization.
CONCLUSIONS: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as
well as chronic symptoms that adversely influenced day-to-day
functioning. In this patient group, the high disease burden
and diminished quality of life highlight the need for novel
therapies. (Hepatology 2020;71:1546-1558)
EXPLORE: A prospective, multinational natural history study of patients with acute hepatic porphyria with recurrent attacks
BACKGROUND AND AIMS: Acute hepatic porphyria
comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can
experience acute neurovisceral attacks, debilitating chronic
symptoms, and long-term complications. There is a lack of
multinational, prospective data characterizing the disease and
current treatment practices in severely affected patients.
APPROACH AND RESULTS: EXPLORE is a prospective,
multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic
porphyria who experience recurrent attacks. Eligible patients
had a confirmed acute hepatic porphyria diagnosis and had
experienced â„3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months
before the study, patients reported a median (range) of 6
(0-52) acute attacks, with 52 (46%) patients receiving hemin
prophylaxis. Chronic symptoms were reported by 73 (65%)
patients, with 52 (46%) patients experiencing these daily.
During the study, 98 (88%) patients experienced a total of
483 attacks, 77% of which required treatment at a health
care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic
ÎŽ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, ÎŽ-aminolevulinic acid, and porphobilinogen compared with
the upper limit of normal in healthy individuals were observed
at baseline and increased further during attacks. Patients had
impaired quality of life and increased health care utilization.
CONCLUSIONS: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as
well as chronic symptoms that adversely influenced day-to-day
functioning. In this patient group, the high disease burden
and diminished quality of life highlight the need for novel
therapies. (Hepatology 2020;71:1546-1558)
Absence of Membrane Phosphatidylcholine Does Not Affect Virulence and Stress Tolerance Phenotypes in the Opportunistic Pathogen Pseudomonas aeruginosa
During growth in presence of choline, both laboratory and clinical Pseudomonas aeruginosa strains synthesize phosphatidylcholine (PC), and PC makes up âŒ4% of the total membrane phospholipid content. In all the strains tested, PC synthesis occurred only when choline is provided exogenously. Mutants defective in synthesis of PC were generated in the strain backgrounds PAO1 and PA14. Minimum inhibitory concentration studies testing sensitivity of PC-deficient strains towards various antibiotics and cationic antimicrobial peptides revealed no differences as compared to wild-type strains. Mutants incapable of synthesizing PC were also found to be unaffected in motility and biofilm formation on abiotic surfaces, colonization of biotic surfaces and virulence in a mouse infection model. A global phenotypic microarray was further used to identify conditions wherein membrane PC may play a role of in P. aeruginosa. No culture conditions were identified wherein wild-type and PC-deficient mutants showed phenotypic differences. Membrane PC may serve a highly specific role during P. aeruginosa interactions with its eukaryotic hosts based on all the clinical strains tested retaining the ability to synthesize it during availability of choline
The changing role of china in the global illegal cigarette trade
This study explores the history of the illegal production, distribution, and smuggling of cigarettes in mainland China. Data were obtained from a content analysis of 931 media reports retrieved from LexisNexis for the time period 1975 until 2010, and from other open sources. The illegal cigarette trade first emerged in the form of violations of state tobacco monopoly regulations. In the course of the restructuring of the legal tobacco sector, which occurred under external political pressure to open the Chinese market to foreign competition, an illegal cigarette industry emerged which at first primarily produced fake Chinese brand cigarettes for the domestic black market. At the same time, China became a destination country for smuggled genuine Western brand cigarettes. It was only after effective crackdowns against cigarette smuggling and domestic distribution channels in the late 1990s that the Chinese illegal cigarette industry shifted to exporting large numbers of counterfeit Western brand cigarettes to black markets abroad. Chinaâs current role as a leading supplier of counterfeit cigarettes is a result of the contradictions of the economic reform process and of external licit and illicit forces that worked toward opening up the Chinese tobacco sector to the outside world
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