Urine thebaine determination by liquid chromatography tandem mass spectrometry after poppy seed consumption.

Laboratories are challenged to distinguish whether a positive urine morphine result is due to heroin use or possible poppy seed consumption. Thebaine is an opium alkaloid that has been shown to be present in the urine of individuals who have consumed poppy seeds, as well as those who have used opium. It is not present in heroin. We present a sensitive, specific liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for thebaine. We show that thebaine is detectable after consumption of two different poppy seed-containing products for up to 72 h in urine. We discuss limitations of the assay and suggest how the test might best be used.

Clarithromycin vs ciprofloxacin as adjuncts to rifampicin and ethambutol in treating opportunist mycobacterial lung diseases and an assessment of Mycobacterium vaccae immunotherapy.

BACKGROUND: The mainstays of treatment for pulmonary disease caused by opportunist mycobacteria are rifampicin (R) and ethambutol (E). The role of macrolides, quinolones and immunotherapy with Mycobacterium vaccae is not clear. A trial was undertaken to compare clarithromycin (Clari) and ciprofloxacin (Cipro) as third drugs added to [corrected] 2 years of treatment with R and E for pulmonary disease caused by M avium-intracellulare (MAC), M malmoense and M xenopi (REClari and RECipro). An optional comparison of immunotherapy with M vaccae vs no immunotherapy was also performed. METHODS: Progress was monitored annually during the 2 years of treatment and for 3 years thereafter. If the patient was not improving at 1 year the regimen was supplemented by the addition of the drug not received in the original allocation of treatment. RESULTS: 371 patients (186 REClari, 185 RECipro) entered the study (170 MAC, 167 M malmoense, 34 M xenopi). All-cause mortality was high for both groups (44% REClari, 43% RECipro); for MAC it was higher with REClari than with RECipro (48% vs 29%) but for M malmoense (42% vs 56%) and M xenopi (29% vs 47%) it was higher with RECipro (p = 0.006). 3% died from their mycobacterial disease (REClari = RECipro). At the end of treatment, 4% of REClari and 10% of RECipro patients still had positive cultures. Among those with negative cultures at the end of treatment, 6% of the REClari group and 4% of the RECipro group had relapsed. At 5 years 30% of the REClari group were known to have completed treatment as allocated and to be alive and cured compared with 21% of the RECipro group (p = 0.04), but this difference was principally due to those with M malmoense (REClari 38%, RECipro 20%). Patients with MAC or M xenopi were more likely to have a poor outcome than those with M malmoense (p = 0.004), with no difference between REClari and RECipro. Overall, 20% in each group were unable to tolerate the regimen allocated, Cipro being associated with more unwanted effects than Clari (16% vs 9%, p = 0.05). No significant differences in outcomes were found between M vaccae-treated patients and those not treated with M vaccae immunotherapy. CONCLUSION: Considering all three species together, there were no differences in outcome between the REClari and RECipro groups. Immunotherapy did not improve outcome. New therapies, optimised management of co-morbid conditions and a more holistic approach must be explored in the hope of improving outcome.

A saccular origin of frequency tuning in myogenic vestibular evoked potentials?: implications for human responses to loud sounds.

Previous research has indicated that an early component of click-evoked myogenic potentials in the sternocleidomastoid muscle is vestibularly mediated, since it can be obtained in subjects with loss of cochlear function, but is absent in subjects with loss of vestibular function (Colebatch et al., 1994). We report here the results of an experiment to investigate whether this response shows any tuning properties. In a sample of 11 subjects, we obtained acoustically evoked EMG from the sternocleidomastoid muscle in response to 110 dB SPL 10 ms tone pips with frequencies of 100 Hz, 200 Hz, 400 Hz, 800 Hz, 1600 Hz and 3200 Hz. The results of this experiment indicate that this response does indeed have a well-defined frequency tuning which may be modelled as a resonance with a maximum response at frequencies between 300-350 Hz. The possible saccular origin of the tuning response and the consequences that this may have in human responses to loud sounds is discussed. Also discussed are the consequences of particular electrode arrangements in relation to the innervation and anatomy of sternocleidomastoid.

Treatment of pulmonary disease caused by opportunist mycobacteria.

Opportunist mycobacterial infections localised to the chest may be treated with combinations of standard antimycobacterial drugs. The combination of rifampicin and ethambutol seems to be particularly effective, both in vivo and in vitro. In vitro sensitivity testing with single drugs may have a role in the future when the levels of in vitro resistance compatible with the clinical response to treatment are eventually established. Sensitivity testing against drugs in combination may prove useful for modifying treatment regimens in those patients who either fail to respond to initial chemotherapy or relapse. Further evidence on this will, it is hoped, emerge from the prospective studies currently in progress.

A study of evening primrose seed oil in atopic asthma.

It has shown recently that Evening Primrose Oil (Efamol) produces a significant clinical improvement in atopic eczema. Efamol contains gamma-linolenic acid which is a precursor to PGE1 a more consistent bronchodilator than PGE2. We have conducted a double blind placebo controlled study in atopic asthmatics given Efamol for an eight week period looking at the control of asthma, including histamine challenge tests. We have found no effect on the asthma or challenge tests although Efamol produced an alteration in fatty acid profile. The patients showed an abnormal fatty acid profile. We speculate that such fatty acid abnormalities could be important in the aetiology of asthma.

Hypothalamic sites which control the surges of prolactin secretion induced by cervical stimulation.

Artificial stimulation of the uterine cervix (CS) of the rat institutes two daily surges of PRL. These surges in turn activate and maintain luteal progesterone secretion for a 13-day interval known as pseudopregnancy. Electrolytic lesions of the medial preoptic area (MPOA) or electrical stimulation of the dorsomedial-ventromedial areas (DMN-VMN) of the hypothalamus also induce pseudopregnancies. This study was designed to determine if these pseudopregnancies are also characterized by the biphasic pattern of PRL secretion. Bilateral electrolytic lesions were placed in the MPOA on the morning of either estrus or the 14th day after ovariectomy. Both experimental models had nocturnal (0500 h) but no diurnal (1900 h) surges of PRL on the second day after placement of the lesion. Sham-lesioned rats had neither surge. When both surges were initiated by CS on proestrus, placement of the lesion on estrus blocked the diurnal but not the nocturnal surge of PRL. These data suggest that the MPOA possesses neurons which are inhibitory to nocturnal surges and stimulatory to diurnal surges of PRL and that CS removes the inhibition over the former and stimulates the latter. Electrical stimulation of the DMN-VMN initiates both surges of PRL in intact or ovariectomized rats. Thus, CS may also act either directly or indirectly w;thin the DMN-VMN to induce both surges of PRL.

Chemical and biological properties of B16 murine melanoma cells grown in defined medium containing bovine serum albumin.

The addition of 1 percent (w/v) bovine serum albumin (BSA) to the F12 medium utilized for the growth of the B16 melanoma cells significantly stimulated the growth of this cell line. The synthesis of mucopolysaccharides and sialoglycopeptides in this medium is identical with that in Eagle's minimal essential medium with Earle's balanced salt solution supplemented with 2 mM L-glutamine, twice the recommended concentration of vitamins, nonessential amino acids, sodium pyruvate, and 10 percent (v/v) fetal calf serum. Cell volume and morphology did not change significantly, under the different growth conditions and tumorigenicity, as assayed by injection of cultured cells into syngeneic animals, was not decreased. Analysis of the BSA used indicated the presence of a sialoglycoprotein contaminant. This sialoglycoprotein contaminant was present in all lots examined and contains N-acetyl-and N-glycolylneuraminic acid, mannose, galactose, and glucosamine. The sialoglycoprotein can be removed by chromatography on acetate form anion-exchange resin at pH 4.3. F12 media containing the purified BSA plus selenite and the sodium salts of palmitic, oleic, and linoleic acids supported growth of the melanoma cells to the same extent as did the media containing unpurified BSA, indicating that the sialoglycoprotein has no role in sustaining the growth of the cells.