Comparison of six cannabinoid metabolite assays

Numerous methods for the detection of urinary metabolites of marijuana constituents are available. Documentation of the sensitivity and specificity of these tests is needed before the determination of a pair of screening-confirmation tests can be made. This study used 88 clinical specimens to evaluate five commercially available marijuana metabolite methods and one new gas chromatography/mass spectrometry (GC/MS) method. The EMIT-d.a.u. test was found to have 2 to 3% unconfirmed positives when compared to the other methods evaluated. The new thin layer procedure, TOXI-LAB, was not as sensitive as the EMIT-d.a.u. procedure for some specimens, but proved to be a good confirmation for the EMIT-d.a.u. with elimination of all "unconfirmed positives." The Abuscreen (Roche) and the EMIT-st assays were positive for samples that contained larger amounts of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (11-nor-delta 9-THC-9-COOH). The Immunalysis-radioimmunoassay (RIA) was positive for all samples found positive by the GC/MS method, but the concentrations found by the two assays did not correlate. The GC/MS method was developed to use the same extraction as the thin layer procedure and provides confirmation for all procedures except 2 to 3% of the positive EMIT-d.a.u. results.     

Raising the ambient potassium ion concentration enhances carbachol stimulated phosphoinositide hydrolysis in rat brain hippocampal and cerebral cortical miniprisms

Summary The influence of the ambient potassium ion concentration ([K⁺]_ upon agonist stimulated hydrolysis of phosphoinositides (PI) has been studied in isolated miniprisms of rat hippocampus and cerebral cortex. When the external [K⁺] was raised from 6 to 18 mmol/l, there was little or no increase in the hydrolysis of PI in the absence of agonist, however, carbachol (100 mol/l) stimulated hydrolysis was greatly enhanced in both brain regions studied. Thus, carbachol stimulated the hydrolysis of PI to 146% and 386% of control levels at potassium concentrations of 5.8 and 18.2 mmol/l, respectively, in the rat hippocampus. A similar enhancement of muscarine (100 mol/l) stimulation was observed in cortical miniprisms with 18 mmol/l [K⁺]. A further enhancement was seen at higher ambient [K⁺], although basal hydrolysis of PI was then also increased. The carbachol-stimulated hydrolysis of PI found at both 6 and raised [K⁺] was prevented by atropine (1 and 10 mol/l) and tetraethylammonium (20 mmol/l), but not by 10 mmol/l Mg²⁺. Pirenzepine (50 nmol/l) also reduced this response. The ions Cs⁺ and Rb⁺ (but not Li⁺ or Tris⁺) produced a similar enhancement of the carbachol stimulation to that found with K⁺. At a buffer [K⁺] of 6 mmol/l, noradrenaline (100 mol/l) produced a 2-fold increase in the hydrolysis of PI whereas 5-hydroxytryptamine (100 mol/l) and histamine (500 mol/l) had little or no effect. However, histamine and 5-hydroxytryptamine did stimulate the hydrolysis of PI when [K⁺] was increased. Miniprism ATP content was not changed by a rise in [K⁺] to 18 mmol/l. The significance of these results is discussed in terms of the postsynaptic cellular events following cholinergic stimulation.     

Stereoselective inhibition of monoamine oxidase and semicarbazide-sensitive amine oxidase by 4-dimethylamino-2,α-dimethylphenethylamine (FLA 336)

Summary The in vitro inhibition by amiflamine [FLA 336(+)] and related compounds of the activity of rat monoamine oxidase (MAO)-A and-B, rat semicarbazide sensitive amine oxidase (SSAO) and human platelet poor plasma benzylamine oxidase was studied. Amiflamine was an MAO-A selective inhibitor, but also inhibits SSAO with both a reversible (competitive, K _i=200 mol/l) and a small time-dependent component which was irreversible in nature. The optical isomer FLA 336(–) was ten times less potent towards MAO-A. However, this compound was much more potent an inhibitor of SSAO (competitive, K _i=4.6 mol/l). The amiflamine metabolites FLA 788(+) and FLA 668(+) inhibited SSAO, but only at concentrations considerably higher than required for MAO-A inhibition. Ex vivo experiments indicated that there was no significant irreversible inhibition of rat heart and lung SSAO after both single and repeated administration of amiflamine at doses up to 20 times higher than required for inhibition of MAO-A within central serotoninergic neurones.     

Highly Pathogenic Avian Influenza A(H5N8) Virus Spread by Short- and Long-Range Transmission,France, 2016–17

We detected 3 genotypes of highly pathogenic avian influenza A(H5N8) virus in France during winter 2016–17. Genotype A viruses caused dramatic economic losses in the domestic duck farm industry in southwestern France. Our phylogenetic analysis suggests that genotype A viruses formed 5 distinct geographic clusters in southwestern France. In some clusters, local secondary transmission might have been started by a single introduction. The intensity of the viral spread seems to correspond to the density of duck holdings in each production area. To avoid the introduction of disease into an unaffected area, it is crucial that authorities limit the movements of potentially infected birds.     

Changes in extracellular adenosine levels and population spike amplitude during graded hypoxia in the rat hippocampal slice

Summary Concentrations of adenosine and inosine in the incubation media of baths containing rat hippocampal slices were measured during graded hypoxia. Slices were exposed to atmospheres containing 95%, 71%, 48%, 24%, or 0% oxygen, with 5% CO₂ and a balance of N₂. Absorbance HPLC measurements were made with samples drawn from static tissue baths each containing four slices supported on a net at the interface between the medium and the atmosphere. Concentrations of adenosine and inosine were proportionate to the fractional oxygen content. They were significantly higher in atmospheres of 24% and 0% O₂. Introducing a 95% N₂/5% O₂ atmosphere in place of 95% O₂/5% CO₂ resulted in a roughly 4-fold increase in the adenosine concentration in the bath. The adenosine transport blocker dipyridamole (200 M), and the convulsant drug picrotoxinin (300 M), had little effect on basal levels of adenosine measured at 95% O₂ but significantly augmented the responses seen at 48%, 24% and 0% O₂. Picrotoxinin, while increasing the adenosine concentration did not change the ratio of adenosine to inosine. In contrast, dipyridamole significantly increased the ratio of adenosine to inosine. Evoked population spikes were recorded from the CA1 layer. The population spike amplitude was depressed as the fractional oxygen content was reduced. It is concluded that adenosine regulation in the slice preparation is similar to that seen in the intact animal. In particular, the amounts of adenosine released into the incubation medium are related to oxygen availability.     

Redo hepatic resection for metastatic colorectal carcinoma

Redo hepatic resection for recurrent colorectal metastasis was performed in eight patients. There was no operative mortality; major morbidity occurred in 25% and minor morbidity in 13% of patients. Four patients are alive and disease-free at 9, 23, 39, and 49 months, respectively, after their repeat hepatic resection. Four patients have died of recurrent disease, with a median time to recurrence of 6 months and median survival of 15 months. Patterns of failure include hepatic failure alone in two patients and pulmonary and hepatic failure in two. Repeat liver resection can be performed safely and may be beneficial in some patients with recurrent metastases confined to the liver after previous hepatic metastasectomy.

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Resumen El tratamiento quirúrgico de las metástasis hepáticas recurrentes luego de una resección inicial no ha sido considerado como opción terapeútica. Sin embargo, varios informes recientes han documentado el hecho de que la resección repetida es técnicamente factible y que puede resultar en prolongados intervalos libres de enfermedad en 38% a 50% de los pacientes. Con anterioridad al présente reporte, solo 62 pacientes sometidos a resección hepática repetida por cancer colorrectal metastásico han sido descritos en la literatura. Se requieren estudios adicionales, y nuestro grupo présenta su experiencia para complementar esta base de datos.Se describe la resección redo-hepática por metástasis colorrectales recurrentes en ocho pacientes. No hubo mortalidad operatoria, se registró morbilidad mayor en 25% y menor en 13%. Cuatro pacientes se encuentran vivos y libres de enfermedad a los 9, 23, 39 y 49 meses después de la nueva resección hepática. Cuatro pacientes han muerto por enfermedad récurrente con un tiempo medio de recurrencia de 6 meses, y un tiempo medio de sobrevida de 15 meses. Los lugares de falla incluyen sólo dos en el hígado y dos en el pulmón. La resección repetida del hígado puede ser realizada con seguridad y puede ser beneficiosa en algunos pacientes con metástasis récurrentes confinadas al hígado después de una metastasectomía previa.

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Résumé La résection itérative de métastases hépatiques d'un cancer colorectal a été pratiquée chez 8 patients. Il n'y a eu aucune mortalité opératoire. La morbidité majeure a été de 25% (2 patients), alors qu'elle a été mineure chez un patient (13%). Quatre patients sont en vie et apparement sans maladie à 9, 23, 39, et 49 mois après leur deuxième résection. Quatre patients sont morts de récidive avec une médiane d'intervalle libre avant la récidive de 6 mois, et une survie médiane de 15 mois. La récidive a été dans deux cas au niveau du foie seul et dans deux autres cas, simultanément au niveau du poumon et du foie. La résection itérative de métastases hépatiques est faisable avec sûreté et peut apporter un plus chez certains patients déjà opérés de leur métastase.

     

Rapid assessment of dietary intake of fat, fiber, and saturated fat: validity of an instrument suitable for community intervention research and nutritional surveillance

Abstract Traditional methods to assess changes in dietary intake, for example food frequency questionnaires or 24-hour dietary recalls, are often not practical: they are lengthy, expensive, and unsuitable for telephone administration. This article describes the development and evaluation of an approach to the rapid assessment of the dietary intake of nutrients of most interest in health promotion research; total fat, saturated fat, dietary fiber, and percent of calories from fat. In this validation study on 97 women, short dietary questionnaires were compared to two criterion measures of usual dietary intake, a food frequency questionnaire and the mean of two four-day diet records. Correlations between self-administered short questionnaires and four-day diet records were 0.52, 0.53, 0.61, and 0.40 for total fat, percent of calories from fat, saturated fat, and dietary fiber, respectively. These correlations are similar to those observed between food frequency questionnaires and four-day diet records, which suggests that this approach to developing and administering short dietary questionnaires may be useful in situations where more expensive and time-consuming methods of dietary assessment are not practical.     

Intimate combination of low- and high-resolution image data: I. Real-space PET and (1)H(2)O MRI, PETAMRI.

Two different types of (co-registered) images of the same slice of tissue will generally have different spatial resolutions. The judicious pixel-by-pixel combination of their data can be accomplished to yield a single image exhibiting properties of both. Here, axial (18)FDG PET and (1)H(2)O MR images of the human brain are used as the low- and high-resolution members of the pair. A color scale is necessary in order to provide for separate intensity parameters from the two image types. However, not all color scales can accommodate this separability. The HSV color model allows one to choose a color scale in which the intensity of the low-resolution image type is coded as hue, while that of the high-resolution type is coded as value, a reasonably independent parameter. Furthermore, the high-resolution image must have high contrast and be quantitative in the same sense as the low-resolution image almost always is. Here, relaxographic MR images (naturally segmented quantitative (1)H(2)O spin-density components) are used. Their essentially complete contrast serves to effect an apparent editing function when encoded as the value of the color scale. Thus, the combination of (18)FDG PET images with gray-matter (GM) relaxographic (1)H(2)O images produces visually "GM-edited" (18)FDG PETAMR (positron emission tomography and magnetic resonance) images. These exhibit the high sensitivity to tracer amounts characteristic of PET along with the high spatial resolution of (1)H(2)O MRI. At the same time, however, they retain the complete quantitative measures of each of their basis images. Magn Reson Med 42:345-360, 1999. Published 1999 Wiley-Liss, Inc.     

Respiratory symptoms in older people and use of domestic gas appliances

BACKGROUND: Studies in children and young women have indicated an increased risk of respiratory illness in association with the use of domestic gas appliances, possibly caused by oxides of nitrogen generated when gas is burned. It is not known whether risks are similarly increased in older subjects. METHODS: A questionnaire about respiratory symptoms in the past year and potential risk factors for respiratory disease was mailed to 6000 men and women aged 65 years and older who were selected at random from the lists of general practices in North Bristol, UK. Associations between symptoms and the use of gas appliances were examined by logistic regression with adjustment for age, sex, social class, and smoking habits. RESULTS: Questionnaires were completed by 4792 (80%) of those mailed. The most common symptoms were exercise induced breathlessness, wheeze, or chest tightness (51%); wheeze (27%); morning phlegm (20%); and daytime breathlessness at rest (19%). In an analysis that included all subjects only weak associations were found with use of gas appliances, odds ratios all being 1.2 or less. The risks associated with use of a gas hob tended to be higher in women, with odds ratios of 1.36 (95% CI 1.01 to 1.83) for wheeze and 1.33 (95% CI 0.56 to 3.17) for morning chest tightness, but were lower than had been reported previously in younger women. CONCLUSION: The absence of stronger associations cannot readily be explained by bias or confounding. Gas cookers and fires are unlikely to be an important cause of respiratory illness in the elderly. If they do cause such illness, the largest risks are likely to be in women who use gas hobs.     

Contrasts in gait mechanics of individuals with proximal femoral focal deficiency: Syme amputation versus Van Nes rotational osteotomy

Lower-limb kinematics and kinetics during preferred and fast speeds of walking were measured in persons with proximal femoral focal deficiency to compare outcomes after Syme amputation (nine subjects) with those after Van Nes rotational osteotomy (10 subjects). Subjects with a Van Nes rotational osteotomy and full tibial rotation (seven subjects) demonstrated prosthetic knee function during stance as they were able to support a flexed-knee posture at both speeds and produced greater knee-extensor moments at preferred speeds as compared with the Syme group (p < 0.05). Nonprosthetic limb compensatory mechanics were significantly exacerbated in subjects with a Syme amputation compared with the Van Nes group: (a) stance-phase vaulting, resulting in greater inappropriate ankle-power generation at both walking speeds, (b) excessive hip-extensor moments at fast speeds, (c) excessive hip-power absorption and generation at both speeds, and (d) excessive knee-joint power generation at both speeds (p < 0.05). The improved gait after Van Nes rotational osteotomy is one factor that should be considered when making clinical decisions for children with proximal femoral focal deficiency.