Long noncoding RNA GAS5: a novel marker involved in glucocorticoid response.

Glucocorticoids (GCs) exert their effects through regulation of gene expression after activation in the cytoplasm of the glucocorticoid receptor (GR) encoded by NR3C1 gene. A negative feedback mechanism resulting in GR autoregulation has been demonstrated through the binding of the activated receptor to intragenic sequences called GRE-like elements, contained in GR gene. The long noncoding RNA growth arrest-specific transcript 5 (GAS5) interacts with the activated GR suppressing its transcriptional activity. The aim of this study was to evaluate the possible role of GAS5 and NR3C1 gene expression in the antiproliferative effect of methylprednisolone in peripheral blood mononuclear cells and to correlate the expression with individual sensitivity to GCs. Subjects being poor responders to GCs presented higher levels of GAS5 and NR3C1 in comparison with good responders. We suggest that abnormal levels of GAS5 may alter GC effectiveness, probably interfering with the mechanism of GR autoregulation.

Systemic capillary leak syndrome. Case report.

We here report the case of a patient with systemic capillary leak syndrome (SCLS). This syndrome is a rare condition characterized by recurrent episodes of hypotension with hemoconcentration and hypoproteinemia. It is due to unexplained episodic capillary hyperpermeabilty that results in fluid and protein shift from the intravascular to the interstitial space: generalized edema, shock and renal failure follow. A 59 yo man was admitted to our intensive care unit because of unexplained shock with hemoconcentration, renal failure, and metabolic acidosis. Previous attemps to reverse shock in a medical ward with crystalloids and dopamine failed. An abdominal CT scan, a TEE, and chest X ray study were inconclusive. No sign or history of major infections or anaphylaxis were present. The patient was resuscitated with massive fluid infusions and norepinephrine on the guide of a Swan Ganz catheter. The diagnosis was made on the basis of a previous episode of severe shock complicated with renal failure and a compartment syndrome, the hemoconcentration, and the negative cardiopulmonary findings. A small amount of monoclonal immunoglobulin G, kappa chain, found in the serum confirmed the diagnosis. The SCLS should be considered in the differential diagnosis of idiopathic and anaphylactic shock. Patients may benefit from a prophylactic treatment with theophilline and terbutaline.

Reduction in gram-positive pneumonia and antibiotic consumption following the use of a SDD protocol including nasal and oral mupirocin.

The objective of this prospective, randomized, double-blind study was to evaluate the effect of the addition of mupirocin to the 'classical' topical SDD regimen (tobramycin 80 mg, polymyxin E 100 mg, amphotericin B 500 mg) on the development of ICU-acquired infections due to gram-positive bacteria. The study was carried out in an intensive care unit (ICU) of a 1400-bed community hospital. All patients admitted to the ICU during a 16-month period, who were expected to require mechanical ventilation for more than 24 hours, were randomized to receive either the 'classical' SDD regimen (Group A) or a modified regimen with mupirocin (Group B). Data from 223 patients requiring mechanical ventilation for at least 48 hours, who were neither infected nor receiving antibiotics on ICU admission, was analysed. A 2% paste containing tobramycin, polymyxin E and amphotericin B was applied every 6 hours in the oropharynx to the patients in Group A, while in Group B this formula was modified with the addition of 2% mupirocin. In Group B 0.2 ml of a 2% mupirocin ointment was also applied four times daily in both nostrils. Patients in Group A received a soft paraffin ointment as a placebo indistinguishable from mupirocin. Patients in both groups received the classic SDD regimen through the nasogastric tube. Systemic antibiotic prophylaxis was not used. Data on lower airway infection, and blood infection, infections of intravascular catheters, antibiotic consumption and expenditures for antibiotics were analysed. The diagnosis of ventilator-associated pneumonia (VAP) was based on quantitative cultures of protected specimen brush samples (PSB) or on the results of distal broncho-alveolar lavage (BAL). One hundred and four patients received the 'classical' SDD and 119 the modified regimen. Overall 29 patients, 20 in Group A and nine in Group B (p < 0.02) had a total of 33 cases of pneumonia. There were 23 episodes of pneumonia in Group A and 10 in Group B (p < 0.02). Gram-positive bacteria were isolated from samples in 17 episodes in Group A and six in Group B (p < 0.02). Staphylococcus aureus was isolated in nine cases of pneumonia in Group A and once in the 'mupirocin' group (p < 0.05). MRSA were isolated in seven out of nine cases in Group A and in the only case in Group B. There were no differences in the isolation of gram-negative bacilli. Antibiotic consumption and cost were lower in Group B. In conclusion, our data show that the topical use of a modified formula of SDD, with the addition of mupirocin to the oral paste and in the anterior nares, is associated with a reduction in lung infections caused by gram-positives and in a reduction in antibiotic consumption and in the overall expenditure for antibiotics.

Epidemiological impact of prolonged systematic use of topical SDD on bacterial colonization of the tracheobronchial tree and antibiotic resistance. A three year study.

OBJECTIVE: to evaluate the effect of the prolonged systematic use of topical SDD (tobramycin 80 mg, polymyxin E 100 mg, amphotericin B 500 mg) on ICU ecology as expressed by changes in tracheal colonization and bacterial resistances. DESIGN: Prospective microbiological survey. SETTING: Polyvalent ICU of a 2000 beds general hospital. PATIENTS: Data concerning bacterial strains isolated from the tracheo-bronchial aspirates of all the patients admitted to a polyvalent ICU over 3 consecutive periods of 12 months ('88, '89, '90) were prospectively entered in a database and subsequently analyzed. During a 3-year period 502 patients required artificial ventilation for more than 72 h and 332 of them ('89 and '90) were treated with SDD. All samples collected within 72 h from ICU admission were excluded as well as duplicate samples from the same patients. INTERVENTION: All the patients admitted to the ICU in '89 and '90 and submitted to artificial ventilation for at least 24 h were routinely treated with topical SDD without i.v. antibiotic prophylaxis; in '88 SDD was not employed. MEASUREMENTS AND RESULTS: Criteria for collecting sputum samples and microbiological procedures remained unchanged throughout the study-time. Positive sputum were significantly less in '89 (80.8% versus 92.3% p < 0.001) and this was due to a very sharp decrease in the isolation of Gram-negative strains from 43-28% (-64% p < 0.0001) involving both: Enterobacteriaceae (-45%) and Pseudomonaceae (-77%). In 1990; however, a new increase in Gram negative was observed, although the overall amount of Gram-negative was still 49% lower in '90 if compared to '88 (p < 0.0001). A dramatic increase in Pseudomonas isolation was the only factor responsible for the "rebound" observed. An increasing percentage of Pseudomonas developed a resistance towards tobramycin and only 45% of Pseudomonas strains turned out to be sensible to tobramycin in '90 against 79% in '88. A similar trend was registered for all aminoglycosides with the exception of amikacin. Gram-positive colonizations tended to increase (+63%) (p < 0.0001) and this was mainly due to Coagulase negative Staphylococci (+290% p < 0.0001) and S. pneumoniae, whereas S. aureus isolations decreased (-18%) but not significantly. CONCLUSIONS: Our data suggest that the prolonged use of SDD is associated with dramatic changes in ICU ecology: the incidence of Gram negative colonization is significantly diminished by SDD whereas Gram positive tend to increase. Pseudomonas developed an increasing resistance towards tobramycin one of the components of the SDD formula we used.

[Paradoxical embolism: a case]. / Embolia paradossa: un caso.

We report a case of pulmonary embolism complicated by paradoxical embolism (which is rarely diagnosed in life). Foramen ovale patency is a relatively common condition and this, together with the presence of pulmonary embolism, increases the probability of paradoxical embolism.