Radiofrequency facet joint denervation in the treatment of low back pain: a placebo-controlled clinical trial to assess efficacy.

STUDY DESIGN: A prospective double-blind randomized controlled trial was performed. OBJECTIVE: To assess the efficacy of percutaneous radiofrequency articular facet denervation for low back pain. SUMMARY OF BACKGROUND DATA: Uncontrolled observational studies in patients with low back pain have reported some benefits from the use of facet joint radiofrequency denervation. Because the efficacy of percutaneous radiofrequency had not been clearly shown in previous studies, a randomized controlled trial was conducted to assess the efficacy of the technique for improving functional disabilities and reduce pain. METHODS: For this study, 70 patients with low back pain lasting of more than 3 months duration and a good response after intraarticular facet injections under fluoroscopy were assigned randomly to receive percutaneous radiofrequency articular facet denervation under fluoroscopic guidance or the same procedure without effective denervation (sham therapy). The primary outcomes were functional disabilities, as assessed by the Oswestry and Roland-Morris scales, and pain indicated on a visual analog scale. Secondary outcomes included spinal mobility and strength. RESULTS: At 4 weeks, the Roland-Morris score had improved by a mean of 8.4% in the neurotomy group and 2.2% in the placebo group, showing a treatment effect of 6.2% (P = 0.05). At 4 weeks, no significant treatment effect was reflected in the Oswestry score (0.6% change) or the visual analog pain score (4.2% change). At 12 weeks, neither functional disability, as assessed by the Roland-Morris scale (2.6% change) and Oswestry scale (1.9% change), nor the pain level, as assessed by the visual analog scale (-7.6% change), showed any treatment effect. CONCLUSIONS: Although radiofrequency facet joint denervation may provide some short-term improvement in functional disability among patients with chronic low back pain, the efficacy of this treatment has not been established.

Human antibodies to bacterial superantigens and their ability to inhibit T-cell activation and lethality.

Bacterial superantigens (BSAgs) cause massive stimulation of the immune system and are associated with various pathologies and diseases. To address the role of antibodies in protection against BSAgs, we screened the sera of 29 human volunteers for antibodies to the SAgs staphylococcal enterotoxin A (SEA), SEB, SEC1, and toxic shock syndrome toxin 1 (TSST-1). Although all volunteers had detectable levels of antibodies against SEB and SEC1, many (9 out of 29 volunteers) lacked detectable antibody to SEA or had minimal titers. Antibody titers to TSST-1 were well below those to SEB and SEC1, and three volunteers lacked detectable antibody to this BSAg. In addition, pooled immunoglobulin preparations obtained from different companies had antibody titers against SEs and TSST-1. There was a good correlation between antibody titers and inhibition of superantigenic effects of these toxins. Transfer of SEB-specific antibodies, obtained from pooled sera, suppressed in vitro T-cell proliferation and totally protected mice against SEB. These data suggest that the inhibitory activity of human sera was specific to antibodies directed against the toxins. Thus, it may be possible to counteract with specific antibodies BSAg-associated pathologies caused by stimulation of the immune system.

First lifetime back pain and psychiatry treatment: psychological factors and recovery in compensated workers.

The role of psychological factors in recovery from first lifetime low back pain (LBP) was explored in this study. Consecutive clients from one physiatry clinic in Montreal who had LBP of less than 3 months' duration, were on sick leave and receiving workers' compensation benefits, and reported the current event as first lifetime LBP were enrolled. Psychological factors that fluctuate with current events (Psychiatric Symptom Index) and remain stable over time (General Well Being Scale) were assessed. Outcomes were late return to work (> 31 days) and 1 year incidence of compensated recurrence. Results from two multivariate models indicated lower psychological distress predicted late return to work, and higher well being, higher aggressiveness, and lower anxiety predicted compensated recurrence. Researchers concluded psychological factors do not impact clients with all types of LBP in the same way. For individuals lacking prior LBP experience, better psychological functioning increased lengthy work absence. Thus, awareness of the clients' psychological profiles and previous LBP experiences may benefit recovery.

Cross-reactive antibodies prevent the lethal effects of Staphylococcus aureus superantigens.

The exotoxins produced by Staphylococcus aureus, staphylococcal enterotoxins (SE) A-E and toxic shock syndrome toxin (TSST)-1, which are associated with serious diseases, including food poisoning and toxic shock syndrome, are termed superantigens (SAgs). To examine whether common antigenic epitopes were present and whether vaccination with 1 bacterial SAg could protect against challenge with a different SE or TSST-1, mice were vaccinated with SEA, SEB, SEC1, or TSST-1 individually or in combination. Mice injected with a single toxin developed high antibody titers against other SAgs. Marked improvement in survival was observed when immunized mice were challenged with a heterologous toxin. Mice vaccinated with a mixture of toxins were fully protected against 1 or multiple toxin challenges, indicating no interference effects of multivalent vaccinations. More importantly, higher titers were found against each SAg with the multivalent vaccination than with injection with a single SAg. Thus, immunizations with 1 SAg can induce cross-protective antibodies to heterologous SAgs, and multicomponent vaccination can enhance antibody responses against each bacterial SAg.

Epidural corticosteroid injections for sciatica due to herniated nucleus pulposus.

BACKGROUND: Although epidural corticosteroid injections are commonly used for sciatica, their efficacy has not been established. METHODS: In a randomized, double-blind trial, we administered up to three epidural injections of methylprednisolone acetate (80 mg in 8 ml of isotonic saline) or isotonic saline (1 ml) to 158 patients with sciatica due to a herniated nucleus pulposus. All patients had Oswestry disability scores higher than 20 (on a scale of 1 to 100, with scores of 20 or less indicating minimal disability, and higher scores greater disability). RESULTS: At three weeks, the Oswestry score had improved by a mean of -8.0 in the methylprednisolone group and -5.5 in the placebo group (95 percent confidence interval for the difference, -7.1 to 2.2). Differences in improvements between the groups were not significant, except for improvements in the finger-to-floor distance (P=0.006) and sensory deficits (P=0.03), which were greater in the methylprednisolone group. After six weeks, the only significant difference was the improvement in leg pain, which was greater in the methylprednisolone group (P=0.03). After three months, there were no significant differences between the groups. The Oswestry score had improved by a mean of -17.3 in the methylprednisolone group and -15.4 in the placebo group (95 percent confidence interval for the difference, -9.3 to 5.4). At 12 months, the cumulative probability of back surgery was 25.8 percent in the methylprednisolone group and 24.8 percent in the placebo group (P=0.90). CONCLUSIONS: Although epidural injections of methylprednisolone may afford short-term improvement in leg pain and sensory deficits in patients with sciatica due to a herniated nucleus pulposus, this treatment offers no significant functional benefit, nor does it reduce the need for surgery.

A cross-sectional study comparing the Oswestry and Roland-Morris Functional Disability scales in two populations of patients with low back pain of different levels of severity.

STUDY DESIGN: This cross-sectional study compares the Oswestry and Roland-Morris disability scales in two groups of patients with low back pain of different clinical and electromyographic severity. OBJECTIVES: To evaluate the correlation between functional disability and diagnoses. SUMMARY OF BACKGROUND DATA: There is an increasing need for functional disability measurements to be applied to the evaluation of therapy and outcome in patients experiencing low back pain. METHODS: Two very different groups of patients with low back pain completed the Oswestry and Roland-Morris self-administrated functional disability questionnaires. One group included patients presenting with an episode of mechanical low back pain with no clinical radiculopathy. The other group consisted of patients with low back pain and clinical and electromyographic evidence of radiculopathy. RESULTS: Patients diagnosed with low back pain who exhibited signs of radiculopathy on electromyography had a mean score of 49.1 +/- 17.1 on the Oswestry disability questionnaire; a mean score of 33.0 +/- 14.7 was found for patients who experienced "simple" low back sprain (with no radiculopathy). This difference was statistically significant (P < 0.0001). On the Roland-Morris questionnaire, the mean score obtained by the group of patients with radiculopathy was 59.1 +/- 21.8 compared with 45.4 +/- 19.4 for those with no radiculopathy. This difference was also statistically significant (P < 0.0001). Moreover, there exists a moderate correlation between both functional scales within each group of patients: 0.72 (P < 0.0001) in the group with radiculopathy and 0.66 (P < 0.0001) among those without radiculopathy. CONCLUSIONS: The authors conclude that both functional disability scales accurately discriminated between these two groups of patients with low back pain of very different clinical and electromyographic severity.

Potentiation of inhaled staphylococcal enterotoxin B-induced toxicity by lipopolysaccharide in mice.

Nonhuman primates are the established model for evaluating toxic responses to staphylococcal enterotoxins (SEs), as they react similarly to humans. Rodents are generally considered unresponsive to SEs. Binding affinities and T-cell reactivity suggest that SE binds more efficiently to primate major histocompatability complex class II receptors than to mouse receptors. We investigated the potentiation of staphylococcal enterotoxin B (SEB) inhalation toxicity by lipopolysaccharide (LPS) in BALB/c mice. Lethality occurred only when SEB was potentiated by LPS. Neither SEB nor LPS produced lethal effects alone. Temporal responses of interleukin 1 alpha, tumor necrosis factor alpha, interleukin 2, and interferon-gamma evoked by inhaled SEB were enhanced by LPS. By 24 hr after intoxication, serum cytokines decreased to baseline levels, and consistent pulmonary perivascular leukocytic infiltrates were evident histologically. Histologic lesions induced by inhalation exposure to SEB by mice, with or without potentiation by LPS, were similar to those in the rhesus monkey. Predominant pulmonary lesions included severe, diffuse interstitial and alveolar pulmonary edema, leukocytic infiltrates, mild perivascular edema, and alveolar fibrin deposition. Although the mechanism of aerosolized SEB-induced toxicity has not been completely resolved, similarities in histologic lesions, cytokine responses, and acute dose-response suggest the LPS-potentiated mouse model may be a credible alternative to the nonhuman primate model.

Back school in a first episode of compensated acute low back pain: a clinical trial to assess efficacy and prevent relapse.

OBJECTIVE: To assess the efficacy of a back school program for patients with a first episode of acute work-related low back pain requiring compensation. DESIGN: A randomized single-blind controlled trial. SETTING: A private physiatrics outpatient clinic. PATIENTS: The mean duration of low back pain was 15 days. INTERVENTION: Eligible patients were randomized to a standard treatment program that included daily physiotherapy (n = 86) or the same program with the addition of back school (n = 82). The back school program consisted of three 90-minute sessions given by a single trained instructor at 0, 1, and 8 weeks. MAIN OUTCOME MEASURES: The primary outcomes were the time off work for the presenting episode of back pain and the number and duration of recurrences in the year following the study onset. Secondary outcomes included the level of pain, spinal mobility, active straight-leg raising, and functional disability assessed by the Oswestry and Roland-Morris scales. RESULTS: Those randomized to the back school group gained significantly more knowledge, based on the multiple choice examination (p = .0001) and performed the exercise program significantly better (p = .0001) than the standard care group. There were no differences between the two treatment groups for either of the primary outcomes. The median time to return to work from randomization was 33 days for both the back school and the standard care groups (p = .48). The number of compensated recurrences of low back pain over 1 year was similar (back school = 14, standard care = 10, p = .16), as was the median duration of these episodes (back school = 25 days, standard care = 70 days, p = .21). There were no significant differences favoring the back school group for any of the secondary outcomes at the posttreatment, 6-month, or 12-month assessments. CONCLUSION: A back school intervention in addition to standard care resulted in no reduction in the time to return to work or the number or duration of recurrences of low back pain requiring compensation over a period of one year.

Diagnostic accuracy of technologies used in low back pain assessment. Thermography, triaxial dynamometry, spinoscopy, and clinical examination.

STUDY DESIGN: A prospective blind study compared three new technologies to assess back pain. OBJECTIVE: To assess the diagnostic accuracy and comparability of thermography, triaxial dynamometry, and spinoscopy in the assessment of recent onset work-related low back pain. SUMMARY OF BACKGROUND DATA: The role of these technologies in assessing patients with low back pain is unproved. METHODS: Forty-one patients with low back pain and 46 control subjects were assessed by each technology and by two clinical examiners blind to clinical status. Twenty patients were trained to simulate a healthy back without low back pain, and 50% of the control subjects were trained to simulate the presence of a low back pain disorder. Each technology was interpreted on two occasions by each of two readers. RESULTS: Thermography performed significantly worse than did triaxial dynamometry, spinoscopy, and clinical examination. The diagnostic accuracy of the last three was similar, and inter-rater comparability did not differ significantly. Among simulators, the diagnostic accuracy of triaxial dynamometry and spinoscopy was significantly higher than that of clinical examination, although considerable inaccuracy remained in assessing individual subjects. CONCLUSIONS: The diagnostic accuracy of thermography in recent onset low back pain does not support its use. Among those simulating normality or low back pain, triaxial dynamometry and spinoscopy have greater diagnostic accuracy than does a single clinical evaluation. However, for an individual, the inaccuracy that remains limits the use of triaxial dynamometry or spinoscopy for diagnosis in recent onset low back pain.

Protective effects of niacinamide in staphylococcal enterotoxin-B-induced toxicity.

Staphylococcal enterotoxins (SE) interact with major histocompatibility complex (MHC) class II cell-surface receptors, eliciting signal transduction in antigen-presenting cells (APC). Subsequent toxin-class II complex interaction with specific T-cell receptors induces T-cell activation. We investigated the effect of niacinamide and interleukin (IL)-10 on SEB-induced responses. In a macrophage cell line, niacinamide (ED50--2mM) and IL-10 (ED50--7U/ml) inhibited interferon (IFN)-gamma-induced MHC class II expression in a dose-dependent manner. Also, niacinamide was a potent inhibitor of T-cell proliferation induced by SEB (ED50-- 1 mM) while IL-10 has minimal effects. In mice, the temporal responses of IL-1alpha, tumor necrosis factor (TNF)-alpha, IL-2, and IFN-gamma evoked by SEB were synergistically potentiated by lipopolysaccharide (LPS). Lethality occurred only when SEB was potentiated by LPS. Niacinamide or IL-10 improved survival of mice after lethal SEB challenge. Niacinamide reduced cytokine serum levels, although the pattern differed from that of IL-10. Niacinamide primarily reduced IL-2 and IFN-gamma, while IL-10 predominantly reduced IL-1alpha and TNF-alpha. The immunomodulatory effects of niacinamide observed on SEB-induced activation of APC and T-cells in vitro and in the LPS potentiated murine model for SEB-induced toxicity suggest it may have therapeutic value.

Hemodynamic and calorimetric changes induced by microcystin-LR in the rat.

Microcystin-LR, a cyclic peptide from the cyanobacterium Microcystis aeruginosa, given at acutely toxic doses causes severe hepatic interstitial hemorrhage. Hemodynamic, calorimetric and acid-base balance changes after i.v. microcystin were measured. The effect of isoproterenol, dopamine, methylprednisolone and whole-blood volume expansion on the immediate hemodynamic effects after toxin administration were also evaluated. A dose of 100 micrograms kg-1 was invariably lethal for rats in all studies. Pathophysiological changes included: a sustained, rapid decline in cardiac output and stroke volume; an acute hypotension responsive to volume expansion with whole blood; a decreased heart rate, responsive to both isoproterenol and dopamine; an early decline in oxygen consumption, carbon dioxide production and metabolic rate accompanied by progressive hypothermia; and acid-base balance changes indicating partially compensated metabolic acidosis. The lethal effects of microcystin-LR were previously attributed to hypovolemic shock as a result of hepatic interstitial hemorrhage. These results indicate that, in addition, there may be a cardiogenic component that limits the physiological cardiac reserve, compromising a normal response to circulatory inadequacy.

Regulation of staphylococcal enterotoxin B-elicited nitric oxide production by endothelial cells.

The effect of staphylococcal enterotoxin B (SEB)-elicited inducible nitric oxide synthase (iNOS) in mouse endothelial cells was investigated. Results showed that SEB stimulated the same level of NO production in gamma interferon (IFN-gamma)-primed cells as did trichloroacetic acid-extracted lipopolysaccharide. The kinetics of induced NO production and expression of mRNA for iNOS differed markedly in endothelial and macrophage cells. Induced endothelial nitrite production was transient and was 15 to 20% of that generated by macrophage cells; mRNA levels peaked by 2 h and then steadily declined, whereas macrophage message levels continually increased. The ability of endothelial cells to produce SEB-induced NO depended on priming with IFN-gamma, although detectable mRNA could be elicited by SEB alone. Induction of endothelial iNOS mRNA was inhibited by cycloheximide, which indicated a requirement for de novo protein synthesis. Niacinamide and interleukin-10 significantly reduced SEB-induced endothelial NO production. Both are reported to affect IFN-gamma-induced class II major histocompatibility complex (MHC) expression on antigen-presenting cells. Niacinamide reduced iNOS mRNA levels and markedly reduced IFN-gamma induction of endothelial class II MHC surface antigen. Interleukin-10 did not consistently reduce iNOS mRNA expression and had no effect on IFN-gamma induction of endothelial class II MHC surface antigen. These results suggest that SEB interacts with IFN-gamma-primed endothelial cells to elicit induced NO and that this induction can be effectively modulated at the receptor or transcriptional level.

Regulation by transforming growth factor-beta 1 of expression and function of the receptor for IFN-gamma on mouse macrophages.

Transforming growth factor-beta (TGF-beta) is known phenomenologically as a negative regulator of several functions of mouse bone marrow macrophages. The studies reported here extend this list by showing that TGF-beta can suppress cytolytic activity of mouse bone marrow culture-derived macrophages that already have become activated by IFN-gamma and LPS for tumor cell killing, as well as confirm that this cytokine can interfere with the induction of activation. Suppression was caused by a shift in the dose response curve for IFN-gamma rather than absolute inhibition; the 50% effective dose for IFN-gamma was increased approximately fourfold by treatment with TGF-beta. TGF-beta also decreased the absolute number of IFN-gamma R on the surfaces of pretreated macrophages by approximately 30 to 35%, without altering the affinity with which IFN-gamma bound. The increased concentration of IFN-gamma needed to produce the higher level of receptor occupancy explained the observed shift in the IFN-gamma dose response curve. These results suggest that TGF-beta mediates its negative regulatory effects on macrophage activation by interfering with coupling of the IFN-gamma R to the pathways that induce and maintain macrophage activation for tumor cell killing. Such effects are consistent with the view that TGF-beta is a negative regulator of macrophage activation for tumor cell killing. Because of this fact, neoplastic cells that secrete this cytokine may have a distinct survival advantage.

Characterization and use of monoclonal and polyclonal antibodies against the mouse interferon-gamma receptor.

To facilitate investigation of its physical and functional properties, 11 monoclonal antibodies (mAbs) and a goat polyclonal IgG specific for the mouse interferon- (IFN-gamma) receptor were characterized and their potential uses studied. Eight of the mAbs interacted with epitopes on the extracellular domain of the receptor, two interacted with epitopes on the intracellular domain, and one interacted with an epitope that could not be localized definitively to either region. Of the 11 mAbs, the majority (8) were IgGs, 2 were IgMs, and 1 was an IgA. Relative avidities of the seven that could be determined ranged from 333 to 0.002 microM-1. Both the polyclonal goat IgG and mAb GR-20 (the latter specific for an epitope in the binding site for IFN-gamma) blocked binding of the ligand and, as expected, prevented induction by IFN-gamma of priming of macrophages for tumor cell killing. None of the other mAbs had an effect despite the fact that GR-22 partially (greater than 50%) blocked binding of IFN-gamma. Neither the polyclonal IgG nor any of the mAbs had an agonist effect. The relative usefulness of the antibodies for immunoprecipitation, immunoblotting, immunoassay, and cell staining with and without prior fixation is described. The results of immunocytochemical staining directly confirmed that the majority of immunologically reactive receptor protein expressed by cells is intracellular. To facilitate use by other investigators, the hybridomas that produce these mAbs will be offered to the American Type Culture Collection.

Stable expression of a secreted form of the mouse IFN-gamma receptor by rat cells.

The biologic effects of IFN-gamma are mediated through a receptor that is expressed in relatively low abundance on normal mammalian cells. As a consequence, investigations of the physicochemical and ligand-binding properties of the purified receptor have been limited. The work reported here characterizes a secreted form of the receptor for mouse IFN-gamma, made by deletion of the nucleotides that code for the anchoring domain from a cDNA that encodes the receptor binding protein and its related signal peptide. When transfected into rat XC cells, this construct produced up to approximately 1 mg/liter of a secreted protein that had the characteristics of the native receptor. Both the secreted protein and its mRNA were of sizes that were consistent with loss of the transmembrane region. The protein was detectable by a mAb that is specific for an epitope that is found in the ligand binding site of the receptor for mouse IFN-gamma, as well as by a goat polyclonal IgG that is monospecific for the mouse IFN-gamma R. Supernates that contained the secreted protein blocked binding of IFN-gamma to mouse IFN-gamma R and inhibited in a dose-dependent manner the IFN-gamma-mediated priming of mouse bone marrow culture-derived macrophages for tumor cell killing. Availability of relatively large amounts of a secreted protein that retains ligand-binding activity should facilitate purification and basic studies of the receptor binding protein and could provide new approaches to the treatment/prevention of diseases that arise due to inappropriate response of cells to IFN-gamma. In addition, because this secreted receptor, unlike others, consists of both the extracellular and intracellular domains, it is likely that it will be useful in determining how the cytoplasmic portion of the receptor is involved in receptor function.

Electromagnetic treatment of shoulder periarthritis: a randomized controlled trial of the efficiency and tolerance of magnetotherapy.

The potential benefit of magnetotherapy was investigated in 47 consecutive outpatients with periarthritis of the shoulder. Using a controlled triple-blind study design, one group of patients received hot pack applications and passive manual stretching and pulley exercises; the other group received the same therapy plus magnetotherapy. Treatment was administered three times a week. For a maximum of three months, a standardized treatment protocol was used. There was no significant improvement in pain reduction or in range of motion with electromagnetic field therapy. After 12 weeks of therapy, the patients who received magnetotherapy showed mean pain scores of 1.5 (+/- .61 SD) at rest, 2.2 (+/- .76 SD) on movement, and 1.9 (+/- .94 SD), on lying, compared to scores for the control group of 1.4 (+/- .65 SD), 2.2 (+/- .7 SD), and 1.9 (+/- .95 SD), respectively. Linear pain scale scores improved from 71 to 21 for both groups. At 12 weeks the gain in range of motion was mean 109 degrees +/- 46.8 in patients receiving electromagnetic field therapy, compared to 122 degrees +/- 33.4 for the controls (not significant). At entry, the functional handicap score was 53.5 for both groups. At 12 weeks, it was 24 for the magnetotherapy group and 17 for the control group (difference not significant). In conclusion, this study showed no benefit from magnetotherapy in the pain score, range of motion, or improvement of functional status in patients with periarthritis of the shoulder.

Respiratory effects of brevetoxin and saxitoxin in awake guinea pigs.

Ptychodiscus brevis toxin (brevetoxin) is associated with 'Florida red tide' and cause neurotoxic shellfish poisoning. Saxitoxin is the agent of paralytic shellfish poisoning. Clinical reports of human intoxication suggest that both toxins affect the respiratory system. The toxins were administered by slow intravenous infusion. The effects of the toxins on respiratory function of awake guinea pigs in a pressure plethysmograph were studied. Both toxins caused lactic acidosis of unknown etiology, which was compensated for by increased minute volume with brevetoxin (PbTx-3)- but not with saxitoxin-intoxicated animals. In general, brevetoxin increased ventilation, before respiratory failure, while saxitoxin had a depressive effect on ventilation. Airways resistance was not increased, nor was dynamic compliance decreased during intoxication, although the data suggest that respiratory system failure was the primary cause of death. The responses seen in these experiments are consistent with the dissimilar molecular actions of these toxins.

Cardiorespiratory effects of brevetoxin (PbTx-2) in conscious, tethered rats.

The cardiorespiratory effects of various doses of brevetoxin (0-100 micrograms PbTx-2/kg) were studied in conscious, tethered rats, After surgical preparation and a 24 hr recovery, toxin or vehicle was infused into the tethered, awake rats for 1 hr. They were then monitored for 6 hr or until death. Toxin-infused rats had decreased core and peripheral temperatures and decreased respiratory rates; these values were all low in the 100 micrograms/kg group at the time of death. Blood gas values remained within normal limits, except terminally. Electrocardiographic (ECG) disturbances, noted in all groups given greater than or equal to 25 micrograms/kg, included heart block, premature ventricular contractions and idioventricular rhythms. It was concluded that brevetoxin causes changes in cardiac conduction and multiple changes in nervous system function.

No effect of modulators of reactive oxygen-induced pathology on microcystin-LR intoxication.

Because reactive oxygen species are formed during the metabolism of several toxins that cause similar pathologic changes, we hypothesized that compounds that alter the concentration of reactive oxygen species would alter the toxic effects of the peptide-hepatotoxin produced principally by Microcystis aeruginosa. Pretreatment with alloxan, butylated hydroxyanisole or desferrioxamine did not alter the severity of microcystin-LR intoxication in fed mice. Furthermore, fasting mice for 24 hr before testing, which unmasks lipid peroxidation in paracetamol intoxication, did not alter the effect of butylated hydroxyanisole pretreatment.