Spinal Wada test

Various doses of pentobarbital (1.25-20 mg) and lidocaine (2.5-20 mg) were injected selectively into the artery of Adamkiewicz and anterior spinal artery of 11 monkeys. Pentobarbital produced an acute paraplegia; lidocaine caused a transient paraplegia followed by hyper-reflexia and muscular fasciculation. Duration of effect varied from 5 to 60 minutes with both drugs and was dose related. Effects were totally reversible. The use of intraarterially administered barbiturates and lidocaine may be more sensitive than angiography for predicting cord blood supply during arteriography for spinal arteriovenous malformations or embolization of critical vessels, such as the right bronchial artery.     

Choroidal melanoma: I-125 plaque therapy

An iodine-125 eye plaque was used to treat 58 patients with choroidal melanoma. Patients were followed up for a mean of 48.7 months. Fifty patients had medium-sized lesions (height between 3.1 and 8.0 mm and base diameter less than 16.0 mm), and six patients had large lesions. There were 24 lesions less than 3.0 mm from the optic nerve. The average radiation dose to the apex of the tumor was 8,468 cGy (dose rate, 71 cGy per hour). Initial local disease control was achieved in 50 patients (86.2%). One patient with local treatment failure received another plaque treatment, which controlled disease, so the total disease control rate was 87.9%. Only eight patients died of their disease. Complications were similar to those with other treatment methods, but none of the patients in this study developed optic nerve atrophy.     

The ultrastructural localization of immunoglobulin in chronic lymphocytic lymphoma cells: changes in light and heavy chain distribution induced by mitogen stimulation

The distribution of light and heavy immunoglobulin chains in chronic lymphocytic leukemia (CLL) cells has been investigated at the ultrastructural level using an immunoperoxidase technique. Light chains were localized in the lumens of the perinuclear space and rough endoplasmic reticulum, while staining for heavy chains was weak or negative and generally confined to the membranes of the rough endoplasmic reticulum. This pattern is consistent with immunoglobulin biosynthetic studies on CLL cells in which light chains are synthesized in excess over heavy chains and secreted as the exclusive immunoglobulin product. The pokeweed mitogen stimulation of two populations of CLL cells for 6 days resulted in a balanced synthesis and secretion of light and heavy chains that was reflected in concomitant change in light and heavy chain distribution and intensity of staining using the immunoperoxidase technique.     

Therapeutic and pharmacokinetic relationships of flavone acetic acid: an agent with activity against solid tumors

Flavone acetic acid is a novel structure which exhibits an interesting spectrum of antitumor activity in preclinical studies. It has little antitumor activity in the leukemias and pronounced antitumor activity in solid tumors. Preclinical therapeutic, toxicologic, and pharmacokinetic studies are summarized and considered together to introduce the concept of a therapeutic window of effective plasma concentrations and effective exposure times in attempts to maximize therapeutic effects and minimize toxic effects. Plasma concentrations, predicted to fall from 600 to 100 micrograms/ml over 10 hours resulting from 267 mg/kg ip bolus injections in mice are curative to sc implanted colon 38. Doses of 356 mg/kg and higher cause acute lethality in many mice. Iv doses cause acute lethality in mice more frequently than ip doses, which suggests a peak toxic effect. However, iv infusions in mice, which also can be curative to colon 38, can also result in a lethal effect, although more delayed, even though the predicted plasma concentrations are much below the peak plasma concentrations that appear to be necessary for acute lethality. Plasma concentrations, 100 to 600 micrograms/ml predicted to result from single doses that are therapeutic and not acutely lethal in mice, if maintained by infusion in dogs for 28 hours or longer result in delayed lethality. We conclude that relatively high plasma concentrations (greater than 100 micrograms/ml) are needed for therapeutic activity with this antitumor agent and that lethality can result from two distinctly different causes. An acute lethality can result from an excessively high peak plasma concentration (greater than 600 micrograms/ml). A delayed lethality can result from a too-long exposure (greater than 24 hrs) at therapeutically effective plasma concentrations (100-600 micrograms/ml). We also note that unexpected kinetic differences exist among the mouse, dog, and man. Whereas usually with antitumor agents plasma clearances are proportional to body surface area, and hence faster in small species, quite the opposite is true with flavone acetic acid. Mice exhibit a slower plasma clearance relative to dogs and man.     

Menogaril: a new anthracycline agent entering clinical trials

Menogaril [menogarol, 7(R)-O-methylnogarol, 7-OMEN] is a new anthracycline agent which was chosen for clinical trials based on: broad spectrum activity against a panel of murine tumors, lower cardiotoxicity than doxorubicin in the chronic rabbit model, differences in biochemical effects from other anthracyclines suggesting a possible difference in mechanism of action, murine antitumor activity by oral as well as parenteral routes. Biochemical studies indicated that, in comparison to doxorubicin, menogaril is bound weakly to DNA, inhibits RNA synthesis less, and has different cell cycle phase-specific cytotoxicity. Pharmacology studies in the mouse and dog using HPLC analytical methodology have shown multiexponential clearance from plasma and metabolism of menogaril to a material which co-chromatographs with N-demethylmenogaril in addition to at least two other metabolites of unknown structure. Oral bioavailability studies in the mouse showed significant absorption of menogaril from the gastrointestinal tract followed by first-pass metabolism. In acute toxicity studies in the rat, the dog, and the monkey, dose-related myelosuppression and gastrointestinal toxicity predominated. Phase I clinical trails on menogaril are currently in progress on a variety of schedules.     

Efficacy and adverse effects of intravenous lignocaine therapy in fibromyalgia syndrome

Background

To investigate the effects of intravenous lignocaine infusions (IV lignocaine) in fibromyalgia.

Methods

Prospective study of the adverse effects of IV lignocaine in 106 patients with fibromyalgia; retrospective questionnaire study of the efficacy of IV lignocaine in 50 patients with fibromyalgia.

Results

Prospective study: Two major (pulmonary oedema and supraventricular tachycardia) and 42 minor side-effects were reported. None had long-term sequelae. The commonest was hypotension (17 cases). Retrospective study: Pain and a range of psychosocial measures (on single 11-point scales) improved significantly after treatment. There was no effect of the treatment on work status. The average duration of pain relief after the 6-day course of treatment was 11.5 ± 6.5 weeks.

Conclusions

Intravenous lignocaine appears to be both safe and of benefit in improving pain and quality of life for patients with fibromyalgia. This needs to be confirmed in prospective randomised controlled trials.

     

Global patterns of healthy life expectancy in the year 2002

Background  

Healthy life expectancy – sometimes called health-adjusted life expectancy (HALE) – is a form of health expectancy indicator that extends measures of life expectancy to account for the distribution of health states in the population. The World Health Organization reports on healthy life expectancy for 192 WHO Member States. This paper describes variation in average levels of population health across these countries and by sex for the year 2002.     

Is distortion correction necessary for digital subtraction angiography in the Gamma Knife treatment of intra-cranial arteriovenous malformations?

OBJECTIVE: The published literature maintains that distortion correction of digital subtraction angiography is essential for accurate definition of the arteriovenous malformation (AVM) nidus when performing Gamma Knife radiosurgery. However, as Gamma Knife treatments usually involve small volume targets, which are purposely positioned as close to the centre of the frame as possible, we postulated that the angiographic target images should be minimally distorted. Thus, the use of uncorrected images would not significantly compromise the accuracy of the treatment. We investigated this postulate. DESIGN: Patient and phantom images with and without distortion correction were assessed. The errors measured in the angiograms were compared to those of MR and CT images of the same subjects. Any errors less than 0.5 mm in any modality were accepted as intrinsic. RESULTS: All errors measured in the study were sub-millimetre. In the patient group, errors with distortion correction averaged 0.13 mm (range 0-0.3 mm). Without distortion correction, errors averaged 0.34 mm (range 0.1-0.6 mm). By comparison, the average error for intracranial MR imaging was 0.3 mm, with a maximum of 0.6 mm. CONCLUSION: For small, intracranial AVMs distortion correction did not significantly reduce the errors associated with the definition of the stereotactic co-ordinates. We suggest that prior to the purchase of this software, similar in-house testing should be performed.