Cytokine-secreting cells in relapsing multiple sclerosis patients treated with high-dose intravenous methylprednisolone]

Domon L, a heat-treated component of gram-negative bacterium Achromobacter stenohalis, is used for the treatment of infectious diseases of animals. Here, we investigated the immunopotentiating potential of Domon L. In vitro studies showed that Domon L enhanced nitric oxide (NO) formation from murine macrophage RAW264.7 cells in concert with interferon (IFN)-gamma. The effect of Domon L on NF-kappaB activation was investigated, in order to understand the molecular mechanisms of enhanced NO formation by Domon L. Domon L induced translocation of NF-kappaB to the nucleus in RAW264.7 cells. Induction of NF-kappaB dependent gene expression by Domon L was further confirmed using a transfectant containing an NF-kappaB-luciferase reporter gene. In vivo injection of Domon L elevated both serum IL-6 and mucoprotein, whose gene expression is partly under the control of NF-kappaB. The spleen cells of rats treated with Domon L produced much more NO when stimulated with LPS + IFN gamma than spleen cells of untreated rats. These results suggest that Domon L acts as an anti-infectious agent via NF-kappaB activation.     

Pure alexia and word-meaning deafness in a patient with multiple sclerosis

OBJECTIVE: To describe pure alexia and auditory comprehension problems in a young woman with multiple sclerosis (MS). PATIENT: A 33-year-old woman with MS who complained of difficulties in reading and comprehending spoken language was referred for a neuropsychological examination. Reading difficulties were confirmed and most of the reading errors were additions, omissions, and substitutions of single letters. While the patient reported that the letters seemed to disappear before her eyes, no general problems with visual attention, visual discrimination, or scanning were detected. No difficulties with spelling were reported. The auditory comprehension deficit is interpreted as a form of a semantic access disorder and is not due to generalized slowing in information processing or conceptual disintegration. CONCLUSIONS: Pure alexia is unusual in MS and to our knowledge only 1 other case has been reported (in Japanese). Memory impairments and slowed information processing are probably the most frequent cognitive sequelae of the disease and, consequently, the literature is biased toward the study of those cognitive domains. However, given the wide distribution of sclerotic plaques in MS, it could be argued that we should expect some variability of cognitive changes in MS. Striking deficits as seen in this patient should make us more sensitive to this possibility.     

Anesthetic managements of a patient with multiple sclerosis using propofol

We experienced anesthetic management of a 45-yr-old female patient with a 12-yr history of multiple sclerosis who underwent orthopedic surgeries three times under general anesthesia. We chose rapid induction with propofol and maintained the anesthesia with nitrous oxide, oxygen, and sevoflurane. We monitored both core and peripheral temperatures to avoid the rapid increase of core temperature, which might worsen the symptoms of the disease. There is no other report of anesthesia using propofol as induction agent for a patient with multiple sclerosis. We succeeded in the satisfactory perioperative management of the patient.     

Allogeneic bone marrow transplant for chronic myelogenous leukemia in a patient with multiple sclerosis

A novel Clostridium bifermentans strain toxic to mosquito larvae on ingestion was isolated from a soil sample collected from secondary forest floor. This strain was designated as serovar paraiba (C. b. paraiba) according to its specific H antigen. Clostridium bifermentans paraiba is most toxic to Anopheles maculatus Theobald larvae (LC50 = 0.038 mg/liter), whereas toxicity to Aedes aegypti (Linn.) (LC50 = 0.74 mg/liter) and Culex quinquefasciatus Say (LC50 = 0.11 mg/liter) larvae was 20 and 3 times lower, respectively. The toxicity to An. maculatus larvae is as high as that of Bacillus thuringiensis serovar israelensis. C. b. paraiba was also found to exhibit significant per os insecticidal activity toward adult Musca domestica (Linn.).     

Pre-and post-mortem MR imaging of unsuspected multiple sclerosis in a patient with Alzheimer's disease

A patient with the clinical diagnosis of Alzheimer's disease is presented in whom pre-mortem T2-weighted MRI revealed a periventricular white matter lesion. Postmortem T2 weighted MRIs of the formalin fixed brain revealed the same white matter lesion. Microscopically, classical Alzheimer changes were found and, unsuspectedly, the histopathological correlate of the white matter lesion proved to be an old, inactive, MS plaque. A similar lesion was discovered in the cervical myelum. These findings illustrate that T2-weighted post-mortem MRIs are highly comparable to pre-mortem images and that MRI is sensitive in detecting clinically silent white matter lesions. The histopathology of such lesions may also include MS plaques.     

A phase II study of i.v. methylprednisolone in secondary-progressive multiple sclerosis

We have used rats with streptozotocin-induced diabetes to investigate the effects of hyperglycaemia-mediated impaired nucleoside uptake on the actions of endogenous adenosine in hippocampal slices. In control tissue under conditions of anoxia and aglycaemia the rise in the extracellular adenosine concentration resulted in complete inhibition of synaptic activity in about 2 min. In slices from previously hyperglycaemic rats the inhibition of synaptically mediated responses occurred significantly faster, although this change could be prevented by insulin treatment. Application of the selective adenosine A1 receptor antagonist [8-cyclopentyl-1,3-dipropylxanthine (DPCPX)] prevented the anoxia/aglycaemia-mediated inhibition and, furthermore, abolished the differences in the electrophysiological responses between control and diabetic tissue. The effects of impaired nucleoside uptake could be mimicked in control slices by applying the nucleoside uptake blocker hydroxynitrobenzylthioinosine (HNBTI). This had the effect of speeding up the rate of anoxia/aglycaemia-induced synaptic inhibition in control tissue to that seen in diabetic tissue. However, such treatment had no effect on the responses in diabetic tissue as expected if the HNBTI-sensitive uptake process was already inhibited by the chronic hyperglycaemia. The impairment of nucleoside uptake by chronic hyperglycaemia results in the potentiation of the modulatory actions of endogenous adenosine in the central nervous system. Such an alteration in adenosine function may be important in explaining behavioural and pathological changes associated with diabetes mellitus.     

Favorable response to intravenous methylprednisolone and cyclophosphamide in children with severe neuropsychiatric lupus

OBJECTIVE: To evaluate the effect of intravenous methylprednisolone (IVMP) and cyclophosphamide (IVCy) in children with severe neuropsychiatric (NP) systemic lupus erythematosus (NPSLE). METHODS: We studied 7 consecutive pediatric patients with severe NPSLE. All patients were treated initially with IVMP and IVCy followed by monthly IVCy for at least 3 months, and then every 2 and/or 3 months according to clinical response. Prednisone was given at 1-2 mg/kg during the first month. Laboratory studies included routine laboratory tests, antinuclear antibodies, anti-dsDNA, antiphospholipid antibodies, and complement components C3 and C4. Neurodiagnostic studies included cerebrospinal fluid, magnetic resonance imaging, computed tomography scanning, single photon emission computed tomography and electroencephalography. RESULTS: Three patients had organic brain syndrome with psychosis, 3 had seizures, 1 stroke, 1 cerebral vasculitis, 1 optic neuritis, and 1 transverse myelitis. In 3 of these cases, nervous system involvement was the initial presentation of SLE. Five patients had 2 or more NP manifestations. Most of them were accompanied by general SLE activity. Anticardiolipin antibodies were positive in 3 patients and none was anticoagulated. All patients improved, 6 patients had a complete recovery and 1 patient recovered with minor neurological deficit. All but one improved significantly within the first week of combined IVMP and IVCy. The mean time of follow-up was 37 months (range 8-55). IVCy was well tolerated with minimal side effects. CONCLUSION: Early aggressive treatment with combined IVMP and IVCy followed by monthly IVCy may be an effective therapy for severe NPSLE in children.     

Failure of intravenous immunoglobulin to arrest progression of multiple sclerosis: a clinical and MRI based study

Due to the modest benefit, inconvenience and high cost of currently available therapies for MS, it is appropriate to seek alternative treatments. Based on anecdotal evidence suggestive of benefit for i.v.IG in MS, we conducted an open-label, unblinded protocol of i.v.IG in nine MS patients. The patients were given induction doses of i.v.IG followed by monthly boosters for 1 year and had clinical, MRI and CSF analyses performed. Patients included were both progressive and relapsing. There was no clinical benefit nor apparent MRI benefit utilizing this protocol. During treatment the majority of patients continued to progress or have attacks and MRI demonstrated continued accumulation of T2-weighted lesions. CSF was unaffected by treatment.     

Axonal dysfunction and disability in a relapse of multiple sclerosis: longitudinal study of a patient

In a 6-year longitudinal study of a patient with relapsing progressive multiple sclerosis (MS), we used proton magnetic resonance spectroscopy to assess N-acetylaspartate (NAA) from a large central brain volume to evaluate the relationship between this marker of neuronal integrity and clinical disability. During the follow-up period, there was one major relapse and its subsequent partial remission. Changes in the brain NAA to creatine ratio correlated strongly with clinical disability (Spearman rank coefficient = -0.73, p < 0.001). We interpret this as evidence that axonal dysfunction or loss contributes to functional impairment of patients with MS. Because the NAA signal in the large volume of interest originated predominantly from white matter that appeared normal on conventional MRI, these results also suggest that some degree of axonal dysfunction may be widespread in acute, severe relapses.     

Pressor response to isometric exercise in patients with multiple sclerosis

The purpose of this study was to determine whether patients with multiple sclerosis (MS) would show attenuated heart rate and/or pressor responses to isometric handgrip exercise. Patients with MS (30 males, 74 females, aged 23-61 yr) and control subjects (9 males, 16 females, aged 25-47 yr) performed isometric handgrip exercise at 30% of maximal voluntary contraction (MVC) to fatigue. Systolic, diastolic, and mean arterial pressure (MAP) increased linearly in both groups, but were significantly lower (P < 0.05) in patients with MS at 20%, 40%, 60%, 80%, and 100% of exercise duration. Mean change in MAP at fatigue was +47.9 mm Hg for controls and +28.2 mm Hg for patients with MS, with 18 patients with MS between -6 mm Hg and +15 mm Hg. Heart rate increased normally in patients with MS. To predict change in MAP at fatigue in patients with MS, stepwise regression analysis using six variables yielded an R2 of 0.26. These data suggest that in some patients MS lesions exist in areas of autonomic cardiovascular control that result in attenuated pressor responses to exercise. In 17% of patients tested, attenuation was profound. Data also suggest an abnormal dissociation between the heart rate and pressor response to static work in patients with MS.     

Coping with a diagnosis of multiple sclerosis.

Examined the relation between coping and depression in 38 women and 12 men (aged 21–58 yrs) recently diagnosed with multiple sclerosis (MS). A semistructured interview was used to assess how Ss coped with the onset of disabling illness, and to assess depressive symptomatology. According to Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) criteria, 18 Ss were diagnosed with major depression, 11 Ss were diagnosed with adjustment disorder with depressed mood, and 21 Ss did not satisfy the criteria for any affective disorder. Interview results indicate that nondepressed Ss were more likely to use present focus and avoidance/denial strategies to deal with illness onset than Ss with major depression or adjustment disorder. Discussion addresses why these strategies may be an adaptive means of dealing with the onset of MS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Life-threatening anaphylactoid reaction after intravenous gadoteridol administration in a patient who had previously received gadopentetate dimeglumine

We report a case of a life-threatening anaphylactoid reaction to gadoteridol. The reaction resulted in hospitalization but did respond to medical treatment. Resuscitation equipment and properly trained personnel should be available if these agents are being administered.     

Lipid peroxidation in patients with multiple sclerosis

Questions of lipid metabolism in patients with multiple sclerosis are considered in the light of biomembrane (myelin) pathology. The results of of the study of the lipids fatty acids spectrum in the blood plasma and the secondary product of their spontaneous and NADPhH-dependent peroxidation, malonic dialdehyde, are stated. The dependence of changes in saturation of fatty acids spectrum and dialdehyde concentrations on the stage and heaviness of the multiple sclerosis is shown. Certain dynamics of lipid metabolism indices as a result of treatment was found. The authors also give some recommendations as to the use of drugs at various stages of the disease.     

Influenza vaccination in patients with multiple sclerosis

Vaccination was well tolerated by 93 patients with multiple sclerosis who received a total of 209 doses of influenza vaccine. In one patient, evidence of a new lesion developed after vaccination; the relapse rate was less than would be expected in the natural course of the illness. Toxic and allergic reactions appeared with 7% and 0.5% of the vaccinations, respectively--a rate no higher than that observed in the general population.     

Heparin removal after cardiopulmonary bypass in a patient with adverse reaction to protamine

A 74-year-old man underwent elective coronary surgery under cardiopulmonary bypass. A few minutes after the protamine administration was started, he suddenly developed a severe hypotension necessitating cardiac massage and recannulation for pump assistance. A further test dose of protamine provoked an identical reaction. We installed a Heparin Removal Device, which allows for ex-vivo deheparinization. In 35 minutes ACT decreased from 480 sec to 180 sec and clots appeared in the operating field. This system provides an excellent alternative to protamine in patients with an adverse reaction to protamine.