Equivalent dynamic human brain NK1-receptor occupancy following single-dose i.v. fosaprepitant vs. oral aprepitant as assessed by PET imaging.

The type 1 neurokinin receptor (NK1R) antagonist aprepitant and its i.v. prodrug fosaprepitant have been approved for prevention of acute and delayed nausea and vomiting associated with chemotherapy. This study evaluated the magnitude and duration of brain NK1R occupancy over a period of 5 days after single-dose i.v. infusion of 150-mg fosaprepitant and single-dose oral administration of 165-mg aprepitant, using serial [(18)F]MK-0999 positron emission tomography (PET) in 16 healthy subjects. Each subject underwent three scans. Brain NK1R occupancy rates after i.v. fosaprepitant at time to peak concentration (T(max); ~30 min), 24, 48, and 120 h after the dose were 100, 100, ≥97, and 41-75%, respectively. After aprepitant, NK1R occupancy rates at these time points (T(max) ~4 h) were ≥99, ≥99, ≥97, and 37-76%, respectively. Aprepitant plasma concentration profiles were comparable for the two dosage forms. The study illustrates the utility of PET imaging in determining central bioequivalence in a limited number of subjects.

Inheritance and segregation of virus and herbicide resistance transgenes in sugarcane.

Transgenic sugarcane parents containing multiple copies of herbicide resistance ( bar) and Sorghum mosaic virus (SrMV) resistance ( hut) genes were crossed with non-transgenic sugarcane varieties. Segregation of the transgenes in the progeny was determined using Southern blot analysis; herbicide resistance and SrMV resistance were assessed using bioassays. The segregation data were used to infer linkage relationships between transgenes in the parent plants. In two of the parents, all transgene insertions were linked in one position in the genome, although some recombination between insertion events did occur. In the third parent, insertion had occurred in two independent, unlinked loci. Analysis of progeny of this parent indicated that rearrangement or mutation occurred in both loci, resulting in non-parental transgene DNA fragments in some progeny. Most transgenic progeny containing the bar gene showed resistance to herbicide. SrMV inoculation indicated that a fairly high proportion of the transgenic progeny showed susceptibility. As the post-transcriptional gene silencing mechanism responsible for the virus resistance phenotype may be reset during meiosis, phenotypic screening of older plants may be a more reliable indication of virus resistance than screening young seedlings. This is the first report of transgene segregation in sugarcane, and we have demonstrated that transgenic sugarcane parents showing stable inheritance of transgenes can be effectively used in breeding programs.

A study to investigate the ability of subjects with chronic lung diseases to activate the roadside Lion Alcolmeter SL-400.

The Lion Alcolmeter SL-2 is widely used for road-side breath-testing by police in the UK. However, some individuals with lung diseases have difficulty in activating the device. This study describes an investigation that we have carried out on a new device called the Lion Alcolmeter SL-400 which has recently been introduced into use by police forces in the UK. The manufacturers state that the machine requires a minimum continuous expiratory flow rate of 25 litres per minute and a minimum expired volume of 1.5 litres, after which a breath sample is automatically taken and analysed. Our study was designed to investigate the ability of subjects with a variety of lung diseases to activate this device. The 40 adult subjects investigated consisted of 10 normal controls, 10 with asthma, 10 with chronic obstructive pulmonary disease and 10 with restrictive lung disease. After baseline lung function tests were performed, the subjects were then given alcohol to drink, the amount of which was based upon their body weight. After a gap of at least 20 minutes, the subjects were then asked to attempt up to three blows into the Alcolmeter. Our results showed that three asthmatic subjects, four with chronic obstructive pulmonary disease and two with restrictive lung disease, failed to successfully activate the device even after three attempts. All of the subjects who failed to activate the device had an expired breath volume of more than 1.5 litres, but seven out of these nine subjects had a Forced Expiratory Volume (FEV1) of less than 1.1 litres. In conclusion, this study has shown that some subjects with lung diseases may have difficulty in activating the SL-400 roadside alcolmeter device.

Linear tomography's clinical accuracy and validity for presurgical dental implant analysis.

Accurate assessment of alveolar ridge morphology and inferior alveolar canal location is critical in the presurgical planning phase for dental implant therapy. This study examined the accuracy and validity of linear tomography in the presurgical assessment of potential mandibular implant sites. Seven subjects (six oral and maxillofacial surgeons and one oral radiologist) traced the mandibular cortical bone and inferior alveolar canal on linear tomographic images taken from five mandibles on five separate occasions over 5 weeks. Tracings and the sectioned mandibles were scanned into a computer and assessed for eight measurement criteria. Statistically significant findings were present for intraobserver variability, interobserver variability, and differences between the perceived and actual anatomic structures within the assessed plane of section. These findings demonstrate that the inherent dimensional instability of linear tomography severely limits its diagnostic and clinical role in preoperative implant site assessment.

Long-range alpha detector.

Historically, alpha-particle detectors have been limited by the very short range of alpha particles in air. This results in a number of problems inherent to alpha contamination detectors, such as relatively poor sensitivity, geometry limitations, and inefficient monitoring techniques. In this paper, we document tests of a new long-range alpha detector. The charges generated by the interaction of alpha particles with air can be transported over significant distances (several meters) in a moving current of air generated by a small fan. An ion chamber located in front of the fan measures the current carried by the moving ions and, hence, detects the alpha decays.

Analysis of biological samples using prompt gamma radiations induced by 14.7-MeV neutrons.

We investigate a method for determining the elemental composition of biological samples that uses prompt gamma rays induced by 14.7-MeV neutrons. Alpha particles are produced simultaneously with the neutrons, which exit opposite the alpha detector through the vacuum chamber wall. The sample under investigation is irradiated and emits gamma radiations in a spectral energy distribution characteristic of the material. Barium-fluoride (BaF2) and high-purity germanium (HPGe) gamma detectors view the sample and record the spectrum of gamma radiation.

The effects of chronic obstructive airways disease on the ability to drive and to use a roadside alcolmeter.

Subjects with chronic obstructive airways disease may have difficulty with the roadside alcolmeter. Twenty-six subjects with a FEV1/FVC less than 60% were asked to use an alcolmeter simulator. Only ten were able to produce the necessary flow rate of 28 l min-1 for a minimum of 2.7 s, two could produce the same total volume (1.25 l) at 10 l min-1 for 7.5 s, five could only expel 10 l min-1 for 4.5 s, and nine were unable to trigger the alcolmeter at even these very low flow rates. Subjects with an FEV1 of less than 1.51 or FEV1% predicted less than 50% were very unlikely to be able to activate the alcolmeter. Ten healthy subjects were investigated to assess the accuracy of the roadside alcolmeter at a flow rate of 10 l min-1 compared to 40 l min-1. No significant difference was found in breath alcohol levels between the two flow rates. It is proposed that some modification could be made to the roadside alcolmeter, without affecting its accuracy, to allow some subjects with chronic obstructive lung disease to activate the device. A postal survey of 284 subjects with a FEV1/FVC less than 60% was carried out. Of those who were drivers or exdrivers, 24.7% had had to stop or reduce their driving because of their respiratory disease. This group had a significantly lower FEV1% predicted (P = 0.035) than those whose driving was unaffected.

A subset of memory CD4+ helper T lymphocytes identified by expression of Pgp-1.

The Pgp-1 glycoprotein (Ly-24 antigen) is acquired by mature murine T lymphocytes at the time of primary antigen stimulation Pgp-1 was previously shown to be a useful cell surface marker for distinguishing antigen-specific memory CD8+ T lymphocytes after immunization. Here we demonstrate that this observation extends to CD4+ T lymphocytes. Antigen-specific CD4+ T cells in mice immunized with sperm whale myoglobin or keyhole limpet hemocyanin were contained nearly exclusively in the minor Pgp-1+ subset.