Potential rebreathing after continuous positive airway pressure failure during sleep.

BACKGROUND: Continuous positive airway pressure (CPAP) is widely applied as a home treatment during sleep. Conventional CPAP devices are based on a blower to generate nasal pressure and to maintain air washout from the circuit. Because common CPAP systems do not incorporate alarms, failure in the device or in the electric supply could result in rebreathing. AIM: To assess the potential rebreathing to which a patient could be subjected after CPAP failure. METHODS: Four conventional CPAP devices, PV100 (Breas Medica; Molnlycke, Sweden), CP90 (Taema; Antony, France), and SoloPlus and BiPAP (Respironics, Murrysville, PA), and three common exhalation ports (Whisper Swivel [Respironics], Plateau [Respironics], and 4-mm orifice) were tested in a bench study. Rebreathing after failure was assessed by measuring the resistance of the exhalation port (REP) and the resistance of the tubing plus CPAP device (RTUB), and by measuring O(2) and CO(2) concentrations in the nasal mask in a subject breathing through a CPAP system. RESULTS: REP was much higher (approximately 30 cm H(2)O x s/L) than RTUB (approximately 1 cm H(2)O x s/L). Most (approximately 90%) of the breathing tidal volume would flow from/to the tubing plus CPAP device, which represents a dead space (> or = 0.5 L) similar to the patient's tidal volume. After CPAP failure, end-tidal O(2) in the mask changed from 16.8 to 9.2% and end-tidal CO(2) in the mask changed from 4.2 to 6.2%. By contrast, O(2) and CO(2) did not change when a nonrebreathing valve was placed in the mask. CONCLUSIONS: Common CPAP systems run a risk of inducing rebreathing in case of failure. This risk could be easily avoided by including a passive valve in the apparatus.     

Multiplexed variation scanning for 1,000 amplicons in hundreds of patients using mismatch repair detection (MRD) on tag arrays

Identification of the genetic basis of common disease may require comprehensive sequence analysis of coding regions and regulatory elements in patients and controls to find genetic effects caused by rare or heterogeneous mutations. In this study, we demonstrate how mismatch repair detection on tag arrays can be applied in a case-control study. Mismatch repair detection allows >1,000 amplicons to be screened for variations in a single laboratory reaction. Variation scanning in 939 amplicons, mostly in coding regions within a linkage peak, was done for 372 patients and 404 controls. In total, >180 Mb of DNA was scanned. Several variants more prevalent in patients than in controls were identified. This study demonstrates an approach to the discovery of susceptibility genes for common disease: large-scale direct sequence comparison between patients and controls. We believe this approach can be scaled up to allow sequence comparison in the whole-genome coding regions among large sets of cases and controls at a reasonable cost in the near future.     

Infectious mononucleosis in patients with inflammatory bowel disease under treatment with azathioprine

The use of immunomodulators for the treatment of inflammatory bowel disease is increasing. One of the most common adverse effects associated with this kind of drugs are infectious complications. In recent years, special attention has been paid to certain latent infections which, in patients under immunomodulatory therapy, can be reactivated and prove lethal. Consequently, preventive actions have been adopted, such as screening for hepatitis B virus and tuberculosis infection before starting these treatments. Primary infection with the Epstein-Barr herpesvirus is usually asymptomatic. However, this virus can have an aggressive course and even lead to the development of lymphoma. We report two cases of atypical infectious mononucleosis in patients with inflammatory bowel disease under azathioprine therapy and review the available evidence on the most appropriate therapeutic approach in this subset of patients.     

Static and dynamic upper airway obstruction in sleep apnea: role of the breathing gas properties

Increased upper airway collapsibility in the sleep apnea/hypopnea syndrome (SAHS) is usually interpreted by a collapsible resistor model characterized by a critical pressure (Pcrit) and an upstream resistance (Rup). To investigate the role played by the upstream segment of the upper airway, we tested the hypothesis that breathing different gases would modify Rup but not Pcrit. The study was performed on 10 patients with severe SAHS (apnea-hypopnea index: 59 +/- 14 events/hour) when breathing air and helium-oxygen (He-O2) during non-REM sleep. The continuous positive airway pressure that normalized flow (CPAPopt) was measured. Rup and Pcrit were determined from the linear relationship between maximal inspiratory flow VImax and nasal pressure (PN):VImax = (PN - Pcrit)/Rup. Changing the breathing gas selectively modified the severity of dynamic (CPAPopt, Rup) and static (Pcrit) obstructions. CPAPopt was significantly (p = 0.0013) lower when breathing He-O2 (8.44 +/- 1.66 cm H2O; mean +/- SD) than air (10.18 +/- 2.34 cm H2O). Rup was markedly lower (p = 0.0001) when breathing He-O2 (9.21 +/- 3.93 cm H2O x s/L) than air (15.92 +/- 6.27 cm H2O x s/L). Pcrit was similar (p = 0.039) when breathing He-O2 (4.89 +/- 2.37 cm H2O) and air (4.19 +/- 2.93 cm H2O). The data demonstrate the role played by the upstream segment of the upper airway and suggest that different mechanisms determine static (Pcrit) and dynamic (Rup) upper airway obstructions in SAHS.     

Phase I study of heat-deployed liposomal doxorubicin during radiofrequency ablation for hepatic malignancies

PurposeA phase I dose escalation study was performed with systemically delivered lyso-thermosensitive liposomal doxorubicin (LTLD). The primary objectives were to determine the safe maximum tolerated dose (MTD), pharmacokinetic properties, and dose-limiting toxicity (DLT) of LTLD during this combination therapy.Materials and MethodsSubjects eligible for percutaneous or surgical radiofrequency (RF) ablation with primary (n = 9) or metastatic (n = 15) tumors of the liver, with four or fewer lesions as large as 7 cm in diameter, were included. RF ablation was initiated 15 minutes after starting a 30-minute intravenous LTLD infusion. Dose levels between 20 mg/m² and 60 mg/m² were evaluated. Magnetic resonance imaging, positron emission tomography, and computed tomography were performed at predetermined intervals before and after treatment until evidence of recurrence was seen, administration of additional antitumor treatment was performed, or a total of 3 years had elapsed.ResultsDLT criteria were met at 60 mg/m², and the MTD was defined as 50 mg/m². RF ablation was performed during the peak of the plasma concentration–time curve in an effort to yield maximal drug deposition. LTLD produced reversible, dose-dependent neutropenia and leukopenia.ConclusionsLTLD can be safely administered systemically at the MTD (50 mg/m²) in combination with RF ablation, with limited and manageable toxicity. Further evaluation of this agent combined with RF ablation is warranted to determine its role in the management of liver tumors.     

Glucocorticoid‐induced hyperglycemia (糖皮质激素诱导的高血糖)

Corticosteroid‐induced hyperglycemia is a common medical problem that can lead to frequent emergency room visits, hospital admissions and prolonged hospital stay, in addition to the well known morbidity associated with hyperglycemia. However, the diagnosis and treatment of corticosteroid‐induced hyperglycemia is surprisingly undervalued by most professionals, probably because of the lack of quality studies to determine specific strategies of action. In the present review, we discuss the pathophysiology of corticosteroid‐induced hyperglycemia, focusing on diverse patterns of hyperglycemia induced by the different formulations, and provide clues for diagnosis based on the duration of treatment and the administration schedule of corticosteroids. We propose a treatment strategy based on both the pathophysiology of the process and the mechanism of action of different corticosteroids, and take into account dosing and administration timing to predict the duration of therapy. Finally, we propose treatment goals that differ slightly between the transient and continuous use of corticosteroids based on evidence from clinical practice guidelines of diabetes care both in ambulatory and hospital settings.     

Changes in Insulin Requirements From the Onset of Continuous Subcutaneous Insulin Infusion (CSII) Until Optimization of Glycemic Control

The aim was to evaluate changes in insulin requirements from onset of continuous subcutaneous insulin infusion (CSII) until glucose optimization in type 1 diabetes and to determine patient characteristics to be considered when CSII is implemented. We retrospectively analyzed 74 type 1 diabetic patients over a follow-up of 5 months after starting CSII. Patients without a decrease in HbA1c levels at the end of follow-up were excluded. We compared total daily doses (TDD), basal/bolus distribution, basal diurnal/nocturnal proportion, number of basal segments, and HbA1c levels in relation to sex, age, body mass index (BMI), diabetes duration, and indication for CSII. At follow-up, HbA1c decreased by 0.75%, TDD decreased by 18%, basal rate was 60% of TDD, and diurnal basal rate was 60% of total basal rate. Insulin requirements were higher in males and in obese patients. Female patients and patients with longer diabetes duration showed a higher percentage of basal insulin. The number of basal segments was 4.9 ± 2.9. Basal requirements were higher in the second half of the nocturnal period. The dawn phenomenon was more relevant in men. Improvements in glycemic control were more marked in younger patients, in patients with higher HbA1c, in patients using more basal segments, and in patients initiating CSII for glucose control before pregnancy. Sex, diabetes duration, and BMI should be considered when initiating CSII. Our findings may help clinicians in clinical decision making regarding CSII therapy.