Sonographically Measured Improvement in Diaphragmatic Mobility and Outcomes Among Patients Requiring Prolonged Weaning from the Ventilator.

BACKGROUND: The need of prolonged weaning from the ventilator is a well-known predictor of an unfavorable patients` outcome. Diaphragmatic dysfunction is a serious problem for these patients. We wanted to determine the survival in patients who were already intubated for more than 4 weeks before they were admitted to our weaning unit. In this prospective study, we wanted to investigate if the diaphragmatic function could improve or was related to survival over an 18 months follow up period. METHODS: 84 patients were included when they were able to breathe at least 10 minutes over a t-piece and sit upright for at least 5 minutes. The diaphragmatic function was estimated sonographically using the up and downward movement of the lung silhouette. Sonographic follow-ups were performed for over 18 months. The survival rate, outcome and changes in diaphragm mobility were investigated. RESULTS: a) Survival: 49 patients (58%) survived the 18 months follow up period - 30 had a good outcome; 19 needed assistance. b) Survival in relation to diaphragm mobility: If diaphragmatic mobility improved ≥ 15.5 mm on the left side, the probability of survival was 94% with a probability of 76% to have a satisfying outcome. CONCLUSION: Survival and outcome of prolonged weaning were significantly better when sonographically measured the mobility of left hemidiaphragm improved.

Diagnosis of late-onset congenital adrenal hyperplasia in clinical practice: current evaluation.

AIM: Aim of the study was to investigate the need to perform the adrenocorticotropic hormone (ACTH) stimulation test by recognizing the importance of a second look at basal serum 17-alpha hydroxyprogesterone (17-OHP) levels and calculating new serum 17-OHP cut-off level. METHODS: A total of 142 patients who had hyperandrogenism symptoms and had basal serum 17-OHP levels of higher than 1.3 ng/mL were scheduled to have an ACTH stimulation test performed. Prior to ACTH stimulation, 17-OHP levels were recorded and as second-look levels. RESULTS: Patients were divided to two groups, late-onset congenital adrenal hyperplasia (LOCAH) (25/142), non-LOCAH (117/142). There were statistically significant results related to cycle length and menstrual irregularity between two groups (P=0.042, P=0.041, respectively). In the LOCAH group, basal serum 17 OHP levels were higher than non-LOCAH (P=0.001). When basal serum 17-OHP levels were measured a second time, the need for performing the ACTH stimulation test was decreased. According to cut-off levels of 1.3 ng/mL, 100% of patients needing to take the second serum 17-OHP decreased to 83.1%, a cut-off level of 2 ng/mL decreased numbers from 74.65% to 35.92% and for 2.25 ng/mL 58.42% of patients was decreased to 26.77%. In this study we established 2.25 ng/ml is a superior cut-off level for 17-OHP, its sensitivity is 84% and specifity is 50.4%. CONCLUSION: The incidence of LOCAH is 1.35% among the patients with hyperandrogenism symptoms. We found a single measurement of serum 17-OHP level can be unreliable. Second 17-OHP test reduces the need of performing the ACTH stimulation test by approximately 30%.

Irradiation leads to apoptosis of Kupffer cells by a Hsp27-dependant pathway followed by release of TNF-alpha.

In a previous publication, we were able to show that irradiation of Kupffer cells, the liver resident macrophages, leads to an increased TNF-alpha concentration in the culture medium. The pathomechanisms underlying this phenomenon, however, remained to be elucidated. Here, we show that following irradiation of Kupffer cells, the apoptosis rate increased drastically within 48 h. At the same time, the total TNF-alpha concentration in cell lysates of Kupffer cells attached to the culture plate decreased. However, normalization of the TNF-alpha concentration with respect to cell number revealed that TNF-alpha concentration per attached cell remained constant during the observation period. Western blot analysis showed that heat shock protein 27 (Hsp27) is strongly downregulated and bax is upregulated in irradiated Kupffer cells as compared to sham-irradiated cells. Overexpression of Hsp27 in Kupffer cells was shown to prevent the effect of irradiation on bax expression, apoptosis and, at the same time, on increase of TNF-alpha concentration in the Kupffer cell medium. We conclude that irradiation of Kupffer cells leads to apoptosis because of downregulation of Hsp27 and consecutive upregulation of bax expression. Furthermore, we suggest that apoptosis of Kupffer cells leads to an increase of TNF-alpha concentration in the culture medium which may be due to cell death rather than active release or synthesis.