Pathophysiologie und Differentialdiagnose der Dyspnoe

Dyspnea is the sensation of breathlessness, which is one of a few symptoms described as frightening and alarming. There are different hypotheses of pathophysiological mechanisms explaining a multitude of symptoms described by patients. Objective criteria for this commonly reported symptom do not exist. In general, one differentiates between dyspnea at rest and dyspnea on exertion. This article attempts to summarize the current understanding of dyspnea, explain the essential underlying pathophysiological mechanisms, discuss the broad differential diagnosis, and suggest diagnostic algorithms.     

Cognitive and motor development of children with and without congenital adrenal hyperplasia after early-prenatal dexamethasone

Dexamethasone (DEX) administration to the pregnant woman has become the treatment of choice for the prevention of genital masculinization in female fetuses affected with congenital adrenal hyperplasia (CAH). Although no somatic teratological side effects have been found to date, recent animal research has shown adverse effects of glucocorticoids on brain structures such as the hippocampus, raising concerns about possible functional side effects of DEX on human development. The current survey of 487 children, 1 month to 12 yr of age, focused on cognitive and motor development. The mothers of 174 prenatally DEX-exposed children (including 48 with CAH) and 313 unexposed children (including 195 with CAH) completed four standardized developmental questionnaires about their children. None of the comparisons of prenatally DEX-exposed children and unexposed controls was significant. Among the DEX-exposed children, increased duration of DEX exposure was correlated with significantly fewer developmental delays on three variables of one of the questionnaires, but none of the correlations reached significance, when Bonferroni corrections for multiple correlations were used. With the methods used, we were unable to document any adverse effects of early-prenatal DEX treatment in the doses recommended for the treatment of pregnancies at risk for CAH on motor and cognitive development.     

Posterolateral rotatory instability of the elbow secondary to sprain

We present a case of a 23 year-old man who presented to the emergency department after sustaining indirect trauma to the left elbow with unremarkable physical examination and normal radiographs. He presented again three weeks after with repeated episodes of locking and snapping of the left elbow occurring every time he attempted to rise from a chair while pushing the armrests, and when manoeuvring the steering wheel of his vehicle. On physical examination, the patient was apprehensive to the "lateral pivot shift" test as described by O'Driscoll et al. (1991) [1]. MRI of the left elbow demonstrated avulsion of the proximal epicondylar insertion of the lateral collateral ligament complex (LCLC). The "lateral pivot shift test" was positive under general anaesthesia. Lateral elbow radiograph taken during the test showed widening of the ulno-humeral joint space with posterior subluxation of the radial head. The patient underwent surgical treatment for posterolateral rotatory instability (PLRI) of the elbow. This case report aims to highlight the clinical aspects of the PLRI which may occur after a simple elbow sprain and be easily missed if not suspected; it also aims to draw attention to the importance of the "lateral pivot shift test" and the value of the stress lateral elbow radiograph in establishing the diagnosis of this rare and subtle entity.     

Progressive multifocal leukoencephalopathy secondary to JC virus infection after liver transplantation and treatment of recurrent hepatitis C

Progressive multifocal leucoencephalopathy due to JC virus is a rare complication of liver transplantation. Only four cases have already been described in the literature. This disease is difficult to differentiate from leucoencephalopathy associated with immunosuppressive drugs such as cyclosporin or tacrolimus. Positive diagnosis of progressive multifocal leucoencephalopathy no longer requires cerebral biopsy. It must be confirmed by positive JC virus RNA amplification in the cerebrospinal fluid. We report a case of progressive multifocal leucoencephalopathy occurring 18 months after liver transplantation for hepatitis C-related cirrhosis.     

Variations in postprandial ghrelin status following ingestion of high-carbohydrate, high-fat, and high-protein meals in males

AIM: The purpose of this study was to investigate the response of postprandial acylated ghrelin to changes in macronutrient composition of meals in healthy adult males. METHODS: A randomized crossover study was performed. Ten healthy adult males were recruited. All subjects received, on separate occasions, a high-carbohydrate (HC), a high-fat (HF), and a high-protein (HP) meal. Blood samples were collected before and 15, 30, 60, 120, and 180 min following the ingestion of each meal. Plasma acylated ghrelin as well as serum insulin, glucose, and triglycerides were measured. RESULTS: The levels of acylated ghrelin fell significantly following the three meals. The HC meal induced the most significant decrease in postprandial ghrelin secretion (-15.5 +/- 2.53 pg/ml) as compared with HF (-8.4 +/- 2.17 pg/ml) and HP (-10.0 +/- 1.79 pg/ml) meals (p < 0.05). However, at 180 min, the HP meal maintained significantly lower mean ghrelin levels (29.7 +/- 3.56 pg/ml) than both HC (58.4 +/- 5.75 pg/ml) and HF (45.7 +/- 5.89 pg/ml) meals and lower levels than baseline (43.4 +/- 5.34 pg/ml) (p <0.01). The postprandial insulin levels increased to significantly higher levels following the HC meal (+80.6 +/- 11.14 microU/ml) than following both HF (37.3 +/- 4.82 microU/ml) and HP (51.4 +/- 6.00 microU/ml) meals (p < 0.001). However, at 180 min, the mean insulin levels were found to be significantly higher following the HP meal (56.4 +/- 10.80 microU/ml) as compared with both HC (30.9 +/- 4.31 microU/ml) and HF (33.7 +/- 4.42 microU/ml) meals (p < 0.05). Acylated ghrelin was also found to be negatively correlated with circulating insulin levels, across all meals. CONCLUSIONS: These results indicate that the nutrient composition of meals affects the extent of suppression of postprandial ghrelin levels and that partial substitution of dietary protein for carbohydrate or fat may promote longer-term postprandial ghrelin suppression and satiety. Our results also support the possible role of insulin in meal-induced ghrelin suppression.     

The Association Between Depressive Symptoms and Acute Exacerbations of COPD

Background  Depression is an important comorbidity for patients with chronic obstructive pulmonary disease (COPD). The association between depression and acute exacerbations of COPD is unknown. This study was designed to determine the frequency of COPD exacerbations in outpatients with and without depressive symptoms. Methods  In this retrospective cohort study, patients with a primary diagnosis of COPD were followed for 1 year after discharge from a pulmonary rehabilitation program and the frequency of exacerbations was recorded. Upon completion of the program, all patients were administered the Short-Form 36 Health Survey (SF-36), which contains a mental health domain. Patients were classified as having depressive symptoms based on their domain score, which was separately validated in a second population of patients. Results  Of the 194 patients with COPD who completed the pulmonary rehabilitation program, 32 (16.5%) had depressive symptoms. There were no differences in terms of age, race, pack-years, forced expiratory volume in 1 second (FEV₁), 6-minute walk distance, body mass index, use of supplemental oxygen, use of inhaled steroids, or the Charlson Comorbidity Index between patients with and without depressive symptoms. Patients with depressive symptoms had more exacerbations in the following year (1.91 vs. 1.36; p = 0.02), were 2.8 times more likely to have ever had an exacerbation (95% confidence interval (CI), 1.1–7.3; p = 0.03), and suffered a first exacerbation earlier (148 days compared with 266 days; p = 0.04) than nondepressed patients. Conclusions  COPD patients with depressive symptoms have a significantly higher risk for exacerbations. Early screening for depression in patients with COPD may help identify those patients at higher risk for subsequent exacerbations. J. H. Jennings has no conflict of interest to declare. B. DiGiovine has no conflict of interest to declare. D. Obeid has no conflict of interest to declare. C. Frank has received honoraria for speaking engagements from Pfizer.     

Potent antitumor activity of a novel cationic pyridinium-ceramide alone or in combination with gemcitabine against human head and neck squamous cell carcinomas in vitro and in vivo

In this study, a cationic water-soluble ceramide analog L-threo-C6-pyridinium-ceramide-bromide (L-t-C6-Pyr-Cer), which exhibits high solubility and bioavailability, inhibited the growth of various human head and neck squamous cell carcinoma (HNSCC) cell lines at low IC50 concentrations, independent of their p53 status. Consistent with its design to target negatively charged intracellular compartments, L-t-C6-Pyr-Cer accumulated mainly in mitochondria-, and nuclei-enriched fractions upon treatment of human UM-SCC-22A cells [human squamous cell carcinoma (SCC) of the hypopharynx] at 1 to 6 h. In addition to its growth-inhibitory function as a single agent, the supra-additive interaction of L-t-C6-Pyr-Cer with gemcitabine (GMZ), a chemotherapeutic agent used in HNSCC, was determined using isobologram studies. Then, the effects of this ceramide, alone or in combination with GMZ, on the growth of UM-SCC-22A xenografts in SCID mice was assessed following the determination of preclinical parameters, such as maximum tolerated dose, clearance from the blood, and bioaccumulation. Results demonstrated that treatment with L-t-C6-Pyr-Cer in combination with GMZ significantly prevented the growth of HNSCC tumors in vivo. The therapeutic efficacy of L-t-C6-Pyr-Cer/GMZ combination against HNSCC tumors was approximately 2.5-fold better than that of the combination of 5-fluorouracil/cis-platin. In addition, liquid chromatography/mass spectroscopy analysis showed that the levels of L-t-C6-Pyr-Cer in HNSCC tumors were significantly higher than its levels in the liver and intestines; interestingly, the combination with GMZ increased the sustained accumulation of this ceramide by approximately 40%. Moreover, treatment with L-t-C6-Pyr-Cer/GMZ combination resulted in a significant inhibition of telomerase activity and decrease in telomere length in vivo, which are among downstream targets of ceramide.