Benzodiazepines inhibit the rate of neutrophil apoptosis

Background Benzodiazepines, which are commonly administered perioperatively, can depress immune function. Neutrophil apoptosis plays a central role in the regulation of inflammation. This is particularly important during and after surgery. Aim To examine the effects of benzodiazepines (midazolam and diazepam) on neutrophil apoptosis. Methods Venous blood samples were withdrawn from patients scheduled to undergo elective surgery, (a) immediately prior to, and 10 minutes after administration of midazolam 0.2mg/kg intravenously (n=11) and (b) immediately prior to, and 60 minutes after administration of diazepam 10mg po (n=10). Neutrophil apoptosis was measured by Annexin VFITC after 1 and 12 hours in culture. Results The percentage of apoptotic cells was significantly less after midazolam at 12% (11.9) hours in culture compared to pre-midazolam 29.7% (13.3) (p<0.05). After diazepam, the rates of neutrophil apoptosis were also significantly less after 12 hours in culture (p<0.05). Conclusion Administration of benzodiazepines in clinically relevant doses inhibits neutrophil apoptosis. In the perioperative period, this may influence the inflammatory response to surgery.     

Relapse cell population differs from acute onset clone as shown by absence of the initially activated N-ras oncogene in a patient with acute myelomonocytic leukemia

We have conducted a follow-up study of a patient with myelomonocytic leukemia exhibiting an N-ras mutation (Gln61----Lys61) using the polymerase chain reaction method and synthetic oligonucleotide hybridization probes. This method allowed us to detect as little as 3% of N-ras-mutated cells within a population. When the patient went into clinical remission, the mutation became undetectable. When a relapse occurred, the blasts did not carry the N-ras mutation. Analysis of M13 cloned amplified N-ras sequences from relapse DNA revealed exclusively the wild type allele of the N-ras gene. These findings suggest that the relapse cell population is derived from a different clone than the acute phase population. Furthermore, the data argue that N-ras mutation is not an initiating lesion in this case of acute myelomonocytic leukemia (AMML).     

Single breath-hold assessment of cardiac function using an accelerated 3D single breath-hold acquisition technique - comparison of an intravascular and extravascular contrast agent

Background

Cardiovascular magnetic resonance (CMR) is the current gold standard for the assessment of left ventricular (LV) function. Repeated breath-holds are needed for standard multi-slice 2D cine steady-state free precession sequences (M2D-SSFP). Accelerated single breath-hold techniques suffer from low contrast between blood pool and myocardium. In this study an intravascular contrast agent was prospectively compared to an extravascular contrast agent for the assessment of LV function using a single-breath-hold 3D-whole-heart cine SSFP sequence (3D-SSFP).

Methods

LV function was assessed in fourteen patients on a 1.5 T MR-scanner (Philips Healthcare) using 32-channel coil technology. Patients were investigated twice using a 3D-SSFP sequence (acquisition time 18–25 s) after Gadopentetate dimeglumine (GdD, day 1) and Gadofosveset trisodium (GdT, day 2) administration. Image acquisition was accelerated using sensitivity encoding in both phase encoding directions (4xSENSE). CNR and BMC were both measured between blood and myocardium. The CNR incorporated noise measurements, while the BMC represented the coeffiancy between the signal from blood and myocardium [1]. Contrast to noise ratio (CNR), blood to myocardium contrast (BMC), image quality, LV functional parameters and intra-/interobserver variability were compared. A M2D-SSFP sequence was used as a reference standard on both days.

Results

All 3D-SSFP sequences were successfully acquired within one breath-hold after GdD and GdT administration. CNR and BMC were significantly (p < 0.05) higher using GdT compared to GdD, resulting in an improved endocardial definition. Using 3D-SSFP with GdT, Bland–Altman plots showed a smaller bias (95% confidence interval LVEF: 9.0 vs. 23.7) and regression analysis showed a stronger correlation to the reference standard (R² = 0.92 vs. R² = 0.71), compared to 3D-SSFP with GdD.

Conclusions

A single-breath-hold 3D-whole-heart cine SSFP sequence in combination with 32-channel technology and an intravascular contrast agent allows for the accurate and fast assessment of LV function.

Trial registration

The study was approved by the local research ethics committee (Study No. 07/Q0704/2) and was registered with the Medicines and Healthcare Products Regulatory Agency (MHRA Study No. 28482/0002/001–0001, EudraCTnumber 2006–007042).     

Breath odor evaluation by detection of volatile sulfur compounds – correlation with organoleptic odor ratings

Background:  Detection of oral volatile sulfur compounds (VSC) by gas chromatography (GC) is a widely used method for evaluating breath odor. Air aspirated from the mouth is injected into the GC column for analysis. To eliminate discrepancies caused by variations in operator sampling or injection techniques, a new GC system designed to aspirate breath samples directly into the GC was developed.
Objective:  A clinical study was performed to compare this new automated breath-sampling GC system to organoleptic evaluation by two trained odor judges.
Methods:  A randomized, two-cell, double-blind, parallel design was used in which subjects were tested before and 3 h after using either a mouthrinse containing zinc or a matching placebo rinse. Thirteen subjects used the zinc mouthrinse, and 12 used the placebo. Subjects with a wide range of VSC levels were studied. The average organoleptic ratings for each subject at each time-point were compared with the average VSC measurements made with the GC, and Pearson product–moment correlation coefficients between the corresponding GC and organoleptic measurements were determined.
Results:  The correlation between the GC and organoleptic assessment methods were highly significant ( P  ≤ 0.001) for: total VSC, 0.65; H₂S, 0.63; CH₃SH, 0.61; and (CH₃)₂S, 0.46. The correlation between the two judges was also highly significant (0.823, P  < 0.001).
Conclusion:  These results demonstrate the utility of the automated GC method for evaluating breath odor.