Markedly altered colchicine kinetics in a fatal intoxication: examination of contributing factors

1. Colchicine poisoning, which is relatively rare, is associated with significant morbidity and mortality. Whilst a new treatment modality, in the form of colchicine-specific Fab fragments is on the horizon, currently available therapy is largely supportive. 2. The elimination of colchicine occurs primarily by hepatic metabolism, following a first-order process, with significant enterohepatic circulation. Renal extraction is responsible for approximately 20% of colchicine elimination. 3. We report a case of colchicine intoxication, complicated by the presence of co-ingestants, in which serum colchicine concentrations remained quasi-constant over the 3 days of the patient's survival, consistent with marked alterations both in metabolism and excretion. The initial presentation was relatively benign but the subsequent course was one of severe colchicine poisoning, resulting in death. 4. Severe colchicine toxicity appears to have resulted in a vicious cycle of progressive organ dysfunction and impaired elimination. 5. Josamycin, one of the co-ingestants and an inhibitor of P-glycoprotein, the membrane pump responsible for multidrug resistance, may have played a significant role in impeding the cellular and biliary elimination of colchicine. Co-ingested opioid and anticholinergic compounds may have altered colchicine absorption and gastrointestinal transit. 6. This case serves as a reminder of the need for attention to co-ingested drugs, to early aggressive therapy, and if available, to consideration of immunotherapy.     

Immature chemodifferentiation of Purkinje cell synapses revealed by 5''-nucleotidase ecto-enzyme activity in the cerebellum of the reeler mouse

Data from child and adolescent emergency mental health screening episodes prior and subsequent to privatized Medicaid managed care in Massachusetts are used to investigate the relationship between payer source and disposition and to compare the match between clinical need and disposition level of care. Having Medicaid as the payer in the post-Medicaid managed care period decreased the odds of hospitalization by nearly 60%. None of the clinical need variables that contributed to hospitalization for Medicaid episodes in the pre-Medicaid managed care period were significant in the post-Medicaid managed care period. Multiple forces shaping professional standards, decision making, and quality of care are described. Public sector agencies must lay the groundwork for comprehensive evaluation prior to the implementation of privatized Medicaid managed care initiatives.     

Play, creativity, and adaptive functioning: implications for play interventions

This study focuses on the potential role for nitric oxide on the actions of the parasympathetic innervation to the heart. Earlier, we showed that the nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) reduced the bradycardia induced by stimulation of vagal efferent motor fibres and that these effects are reversible through administration of the NOS substrate L-arginine. In the present study, we show that D-arginine does not reverse the effects of the inhibitors and confirm that they are reversed by L-arginine. Another NOS inhibitor, NG-nitro-L-arginine (L-NOARG), produced similar effects which were not reversed by L-arginine. In an examination of the effect of increasing NO availability with the NO donor sodium nitroprusside the vagally induced bradycardia was enhanced at all frequencies tested. In a separate series, the effects of NOS inhibitors and NO donors on the dromotropic actions of the vagus were examined. The NOS inhibitor L-NAME, reduced the increase in atrio-ventricular conduction delay normally induced by efferent vagal stimulation at all frequencies tested both in the 'paced' and 'unpaced' heart. Further, sodium nitroprusside enhanced this delay. Overall the study indicates that NO has an important facilitatory role on both the chronotropic and dromotropic actions of the vagus nerve on the heart and that NO may be a rate-limiting factor in the cardiac responses to vagal stimulation.     

Asterlingulatosides C and D, cytotoxic triterpenoid saponins from Aster lingulatus

Over the last few decades, European courses in which 'classical' tropical medicine (i.e. parasitology, entomology, and clinical aspects of tropical diseases) is taught have largely become anachronisms. Most countries in the tropics have their own medical schools and few have much need of expatriate doctors. There do, however, appear to be other ways in which Europeans may still help improve health in the tropics. One is to control the quality of the expatriate nurses who are still in demand in the tropics (often as cheaper, generally less demanding substitutes for doctors). This may be achieved by only training the best, insisting they spend some time after graduation gaining maturity before they leave for the tropics, ensuring they realise that their clinical skills will probably be inferior to their local counterparts in the tropics, and encouraging them to continue studying once abroad. The second way Europeans may help is to change the bias of their courses from teaching to training. There seems little doubt that the intellectual personalities of the brightest young men and women in the tropics often develop far better when they spend a period in a foreign environment, especially when they are allowed to function within a team, with trainees and trainers from other countries. Some 'international' courses may offer such benefits, especially if closely tailored to the needs of the trainees and their home countries.     

Vagal regulation during bottle feeding in low-birthweight neonates: support for the gustatory-vagal hypothesis

BACKGROUND AND PURPOSE: Linear accelerators equipped with multileaf collimators (MLCs) are becoming more common and are widely available from most commercial manufacturers. There is a need to ensure they retain their commissioning specification using a preventative maintenance and quality control (QC) programme. This paper considers the design criteria of the Philips MLC which are important to the production of a comprehensive quality control programme. MATERIALS AND METHODS: The specific QC problems related to MLCs are identified as the positional accuracy of the leaves and their relationship to the back-up collimators, leakage considerations, the relationship of X-ray to light field and the influence of gravity on the positioning and leakage characteristics of the leaves. These problems are considered in relation to the general design considerations of the MLC, and methods of performing routine quality control checks are discussed. RESULTS AND CONCLUSIONS: The introduction of MLCs into clinical use results in new QC procedures being developed but it can be concluded that for the Philips MLC only an extra 30 min of QC time is needed per month and that its use has added little to the general down-time of this department.     

Assessment of nutritional status in CAPD patients: serum albumin is not a useful measure

INTRODUCTION: In CAPD patients serum albumin is frequently used as an index of nutritional status, although it is recognized that hypoalbuminaemia may be caused by many factors. We have further examined the relationship between serum albumin and nutrition. METHODS: Nutritional status was assessed by biochemistry, anthropometry, mid-arm muscle circumference, muscle strength (hand grip and back), and lean body mass (from anthropometry, creatinine kinetics and bioimpedance) in a group of 76 stable CAPD patients. Correlations between biochemical and nutritional parameters were sought and data were compared between patient groups defined by serum albumin (> or = 37 vs < 37 g/l on two occasions 2 months apart) and separately according to subjective global assessment score (normal nutrition, A vs mild to moderate, B, and severe, C, malnutrition). RESULTS: In patients with a low SGA score, actual body weight, body mass index, mid-arm muscle circumference, lean body mass, subscapular skinfold thickness, hand grip strength (males and females) and iliac and triceps skinfold thicknesses and back strength (females only) were all significantly less than in patients with a normal SGA score. In contrast, none of these variables differed in either gender when patients were compared according to serum albumin. Serum albumin was correlated with serum creatinine (r = 0.45, P = 0.01), daily urine protein excretion (r = -0.42, P = 0.02) and uncorrected weekly creatinine clearance (r = -0.39) in females, but not with any index of body composition in either gender. CONCLUSION: Whilst SGA identified a patient group with significantly abnormal body mass, muscle mass and muscle strength, serum albumin did not. Serum albumin is not a useful marker of malnutrition in stable patients on CAPD.     

A dilemma in analysis: issues in the serial measurement of quality of life in patients with advanced lung cancer

Despite the availability of several instruments to evaluate quality of life (QL) over time in patients with lung cancer, barriers in measurement remain. This methodological study used LCSS data (Lung Cancer Symptom Scale, a disease- and site-specific QL measure) to examine analysis methods to quantify QL where data needed for serial evaluation may be missing. Data from two large randomized trials, conducted at 30 centers, of a new combination chemotherapy regimen incorporating a new agent for patients (n = 673) with Stage III and IV non-small cell lung cancer were obtained for this study. QL had been prospectively measured at baseline, day 29, and every six weeks thereafter using the LCSS. For the slope analysis (SA) and area under the curve (AUC) analyses, an adjustment score of zero was used to indicate QL on the day of death (mortality adjustment) and each subsequent day until the end of the assessment period. Significant differences in QL, symptom scores and known prognostic factors at baseline were found in the attrition group. SA and AUC analysis allowed inclusion of 581 patients, giving an adequacy rate of 86%. By using a mortality adjustment, an additional 45 patients were included, increasing the inclusion rate to 93%. With the use of the mortality adjustment, QL was shown to decline over the interval, as opposed to rise if the adjustment had not been performed. The conclusions of the study were: (1) analysis for serial data using SA and AUC provides useful, but differing information; (2) when attrition (caused by death) is a factor, a mortality adjustment presented a more accurate assessment of QL as an endpoint; (3) more frequent evaluations of QL will capture rapid changes in patient status and reduce the attrition bias; (4) all patients should be followed until they die; and (5) QL should be given full consideration as a primary endpoint separate from survival.