Urinary excretion profiles of 11-nor-9-carboxy-delta9-tetrahydrocannabinol: a delta9-THCCOOH to creatinine ratio study.

Monitoring the major cannabinoid metabolite (delta9-THCCOOH) to creatinine ratio (M/C) has been used to predict new drug use. According to Huestis and Cone, the best accuracy (85.4%) for predicting new marijuana use was a ratio > or = 0.5 from two urine specimens collected at least 24 h apart. Manno et al. recommended an M/C ratio of > or = 1.5. Subjects with a history of chronic marijuana use were screened for cannabinoid use by immunoassay (50-ng/mL cutoff), and presumptive positives were confirmed by gas chromatography-mass spectrometry for delta9-THCCOOH (15-ng/mL cutoff). Creatinine was analyzed with a cutoff concentration of 25 mg/dL. The study objective was to apply the criteria from both groups of workers to determine if consecutive urine specimens (collected at least 24 h apart) positive for cannabinoids could be used to differentiate new marijuana use from the excretion of residual cannabinoid metabolite (delta9-THCCOOH) in an uncontrolled setting. Serial urine specimens (826) were collected from 26 individuals. Huestis and Cone and Manno et al. ratios indicated new drug use in 83% and 33% of serial urine specimens collected at least 24 h apart, respectively. Clinically, the Huestis and Cone ratio is recommended because of a lower false-negative rate (7.4%) than the Manno et al. false-negative rate (24%). In legal situations, we recommend using the Manno et al. ratio because of its lower false-positive rate (0.1%) as stated by Huestis and Cone.     

Experience with a urine opiate screening and confirmation cutoff of 2000 ng/mL.

Until recently, most laboratories used an opiate immunoassay screening and confirmation cutoff value of 300 ng/mL for codeine and morphine detection by gas chromatography-mass spectrometry (GC-MS). The cutoff value for opiates was increased to 2000 ng/mL or higher in various laboratories because of concerns that small doses of codeine and foods containing poppy seeds would give a positive opiate-screening result. Workplace drug-testing programs in the U.S. raised the opiate cutoff value to 2000 ng/mL on 30 November 1998. The objective of this study is to describe the results of opiate testing of 8600 urine specimens collected over 24 months with a 2000-ng/mL screening and confirmation (codeine and morphine) cutoff value. Specimens were screened by the EMITdau opiate assay using an in-house 2000-ng/mL morphine calibrator. Presumptive positive findings (N = 621) were analyzed quantitatively by GC-MS for codeine and morphine. One hundred and eighty six urine specimens were positive for codeine and morphine (> 2000 ng/mL), 298 specimens were positive for codeine only (> 2000 ng/mL) and 26 specimens were positive for morphine only (> 2000 ng/mL). All remaining specimens had codeine and morphine values < 2000 ng/mL. The codeine and morphine confirmation rate in this program reduced from 7.1% in 1994-1996 (300-ng/mL cutoff) to 2.1% in 1997-1998 with a 2000-ng/mL cutoff value. The codeine-only confirmation rate lowered from 6.6% (300-ng/mL cutoff) to 3.4% (2000-ng/mL cutoff). It was concluded that increasing opiate screening and codeine and morphine confirmation cutoff values led to > 300% reduction in the confirmed-positive rate for codeine and morphine and a 47% reduction in codeine-only confirmations in a urine drug-testing program where codeine was the major opiate used.     

Metabolic base production and mucosal vulnerability during acid inhibition in a mammalian stomachin vitro

Acid inhibition increases gastric mucosal susceptibility to damage by luminal acid. This might be due to reduced metabolic CO₂ and bicarbonate whereas, during normal acid, secretion cytoprotective CO₂/HCO₃- production parallels acid production. Metabolic activity and mucosal damage caused by luminal acid perfusion was determined in anin vitro mouse stomach, with and without acid inhibition, and at 0%, 1%, or 5% serosal CO₂ supply. Without acid inhibition there was no mucosal damage at any level of serosal CO₂/HCO₃- supply. Acid inhibition reduced metabolic CO₂ production by 29% (P<0.004) and resulted in microscopic damage to 55% of the mucosal area and perforation in four of five stomachs (P<0.05). Although, 1% CO₂ supply completely replaced the reduction in metabolic CO₂, it did not protect against mucosal damage. Overreplacement by 5% serosal CO₂/HCO₃- was required to prevent damage. There was no correlation between luminal CO₂/HCO₃- output and mucosal damage. The protection by endogenous or exogenous CO₂/HCO₃- appears to act intracellularly rather than by intragastric or intercellular neutralization.This study was supported by Swiss National Foundation grants 32-26369.89 and 32-33626.92. The morphometry equipment was supported by a grant from the Osterreichische Nationalbank.     

Indicators of free radical activity in patients developing radiation pneumonitis

PURPOSE: Radiation pneumonitis is thought to occur as the result of excess free radical generation following radiotherapy. Various in vitro studies have shown that large doses of irradiation can cause membrane lipid peroxidation and the oxidation of protein sulphuryl groups. We, therefore, studied two circulating markers of lipid peroxidation and an indicator of "catalytic iron" (potentially available iron to catalyze the generation of free radicals) in patients undergoing radiotherapy. METHODS AND MATERIALS: The 9,11 diene conjugate of 9,12 linoleic acid, expressed as their molar ratio (percentage molar ratio (MR)) and thiobarbituric acid reactive acid-substances (TBARS), as well as levels of circulating desferrioxamine-chelatable iron assay, were assayed. Serial blood samples were taken over a 3-month period in 25 patients with inoperable nonsmall cell lung cancer. RESULTS: Ten patients developed radiation pneumonitis. The patients who developed pneumonitis showed a tendency for the serum percentage molar ratio to increase after a week. The change in the percentage molar ratio between Time 0 and 1 week of radiotherapy was significantly higher in the group that subsequently developed pneumonitis compared to the group that did not (p = 0.002). The initial serum TBARS levels in patients were not significantly elevated compared to controls and there was no difference in the serum TBARS levels in the pneumonitis and nonpneumonitis groups throughout the study period. After 1 week of radiotherapy the group that subsequently developed pneumonitis had a significantly higher level of desferrioxamine-chelatable iron (DFx-iron) compared with the nonpneumonitis group (p = 0.05). CONCLUSION: These data suggest that both the percentage MR and DFx-iron appear to reflect an increased susceptibility to develop radiation pneumonitis and after 1 week of radiotherapy they indicate patients who are likely to subsequently develop pneumonitis. Hence, these indicators could indicate the group of patients that could benefit from intervention therapies with antioxidants.     

A short encounter with Anna Freud at Berggasse 19.

This article discusses a short encounter with Dr. Anna Freud in her former consulting office in Vienna at 19 Berggasse in May 1977. Dr. Freud had gone to Vienna for the laying of a marble plaque at the site of the former BelleVue Hotel where Sigmund Freud had first started his work on the 'interpretation of dreams'. In 1900 Dr. Sigmund Freud had written to Wilhelm Fliess "Do you suppose that some day a marble tablet will be placed on the house, inscribed with the words: 'in this house on July 24, 1895, The Secret of Dreams was revealed to Dr. Sigmund Freud' At this moment I see little prospect of it". This request was realized on 6 May 1977 and the author who was present at the ceremonies, describes some of the events.     

A survey of different approaches to management of menstrual disturbances in women using injectable contraceptives

This report summarises a survey of the management of menstrual disturbances occurring during injectable progestogen use (depot-medroxyprogesterone acetate, DMPA, and norethisterone enanthate, NET-EN) by 35 investigators from 20 countries with ongoing experience of these contraceptives. A wide range of approaches are described. The most frequently emphasised aspect of management is thorough pre-treatment counselling with further support and counselling at follow-up visits. Oestrogens in various forms are widely used for the treatment of prolonged, frequent or heavy episodes of bleeding, but nowadays are not usually used for the induction of withdrawal bleeding in women with amenorrhoea. Heavy or "severe" bleeding appears to be very uncommon and figures of 1-2% were frequently mentioned. Anecdotal information suggests that intramuscular doses or longer courses (14-21 days) of oral oestrogen, including the combined pill, are more likely to successfully stop an episode of bleeding than short courses. However, there are no hard data to show that a course of oestrogen treatment has any beneficial effect on long-term bleeding patterns. Nevertheless, temporary cessation of spotting or light bleeding may be sufficiently reassuring to the patient to ensure continued use of the method. There appears to be very little risk associated with the short-term oestrogen regimens currently used. Dilatation and curettage is almost never necessary to stop an episode of bleeding, but may occasionally be recommended for diagnostic reasons. It is clear that the bleeding disturbances associated with DMPA and NET-EN use are poorly understood and that urgent research is necessary to clarify pathophysiological mechanisms and improve management.     

IT training. A classroom at your fingertips

Computer-based training is still in its infancy in the NHS. Yet it could offer a cost-effective solution to the challenges posed by new technology, argues Andrew Fraser.     

Factors predicting the acute effect of pamidronate on serum calcium in hypercalcemia of malignancy

Summary In this study we retrospectively reviewed results of the first 9 days of treatment with pamidronate at doses of 30 mg (n=13), 45 mg (n=9), and 90 mg (n=13) in an attempt to see what factors influenced the response of serum calcium to pamidronate.The nadir of serum calcium obtained post treatment was correlated with pretreatment levels of nephrogenous cyclic adenosine monophosphate (NcAMP), the renal tubular threshold for phosphate reabsorption (TmPO4), and the renal tubular threshold for calcium reabsorption (TmCa). Using the post treatment serum calcium levels, patients were divided into good and poor responders depending on whether a normal serum calcium was obtained.Pretreatment NcAMP was significantly correlated with the magnitude of the response of serum calcium (r=0.45, P=0.0001). Pretreatment NcAMP was significantly higher in the poor responders (mean±SEM): 65.0±9.4 nmol/liter GF (poor responders) versus 29.6±6.3 (good responders), P=0.004. NcAMP as a predictor of the acute response of serum calcium showed a sensitivity of 93% and a specificity of 72%. Pretreatment TmPO4 was negatively correlated with the serum calcium response post treatment (r=-0.41, P=0.003). However, though TmPO4 tended to be lower in the poor responders, this was not statistically significant [0.65 mmol/liter GF±0.09 (poor responders) versus 0.76 mmol/liter GF±0.06 (good responders)]. As a predictor of the acute response of serum calcium, TmPO4 was less good with a sensitivity of 70% and specificity of 58%. No significant correlation was present between TmCa and the serum calcium response. A significant negative correlation was evident between NcAMP and TmPO4 (r=-0.35, P=0.003), however, no significant correlation was evident between NcAMP and TmCa or TmPO4 and TmCa.These results suggest that in a hypercalcemic patient where evidence exists for the presence in circulation of a factor with PTH-like activity (i.e., NcAMP is elevated or TmPO4 is low) the response of serum calcium to pamidronate is less good. NcAMP would appear to be a useful predictor of the response of serum calcium, whereas TmPO4 is less discriminating.     

Photoinactivation of the crayfish segmental giant neuron reveals a direct giant-fiber to fast-flexor connection with a chemical component

The escape tail flip of the crayfish is "commanded" by 2 sets of giant-fiber (GF) interneurons. In each hemisegment, these drive the motor giant (MoG) abdominal flexor motor-neuron through a monosynaptic electrical connection, but the remaining 8 or 9 fast-flexor (FF) motorneurons receive most of their input via a disynaptic electrical pathway through the segmental giant (SG) neuron. We have investigated a monosynaptic GF-FF pathway, which operates in parallel to the disynaptic GF-SG-FF pathway, by using dye-mediated photoinactivation to remove the SGs from the tail-flip circuit. SG photoinactivation involves an initial broadening of the spike, leading to a long-duration, massively depolarized plateau. This is followed by loss of spike capability, a gradual reduction in the resting potential, and eventual total loss of electrical responsiveness. After bilateral photoinactivation of the SGs, a spike in one set of GFs, the medial giants (MGs), produces little if any effect in FFs in any ganglion. A spike in the other set, the lateral giants (LGs), produces an EPSP in FFs with a declining anterior-to-posterior segmental gradient in amplitude. These differences in LG and MG outputs, which are obscured in the intact circuit by the common MG/LG-SG-FF pathway, give clues to a probable early evolutionary form of the circuit. The LG-FF connection in anterior ganglia has a significant electrical component. However, it also has an apparent monosynaptic chemical component, as revealed by the response to saline containing cadmium ions, and to cooling the preparation. This is the first physiological evidence for chemical output from a crayfish GF.