Masaki Matsumi

Nonimmersive Virtual Reality Mirror Visual Feedback Therapy and Its Application for the Treatment of Complex Regional Pain Syndrome: An Open‐Label Pilot Study

OBJECTIVE Chronic pain conditions such as phantom limb pain and complex regional pain syndrome are difficult to treat, and traditional pharmacological treatment and invasive neural block are not always effective. Plasticity in the central nervous system occurs in these conditions and may be associated with pain. Mirror visual feedback therapy aims to restore normal cortical organization and is applied in the treatment of chronic pain conditions. However, not all patients benefit from this treatment. Virtual reality technology is increasingly attracting attention for medical application, including as an analgesic modality. An advanced mirror visual feedback system with virtual reality technology may have increased analgesic efficacy and benefit a wider patient population. In this preliminary work, we developed a virtual reality mirror visual feedback system and applied it to the treatment of complex regional pain syndrome. DESIGN A small open-label case series. Five patients with complex regional pain syndrome received virtual reality mirror visual feedback therapy once a week for five to eight sessions on an outpatient basis. Patients were monitored for continued medication use and pain intensity. RESULTS Four of the five patients showed >50% reduction in pain intensity. Two of these patients ended their visits to our pain clinic after five sessions. CONCLUSION Our results indicate that virtual reality mirror visual feedback therapy is a promising alternative treatment for complex regional pain syndrome. Further studies are necessary before concluding that analgesia provided from virtual reality mirror visual feedback therapy is the result of reversing maladaptive changes in pain perception.

Protective role of heme oxygenase-1 in the intestinal tissue injury in an experimental model of sepsis.

ObjectiveThe aim of this study was to examine the role of heme oxygenase-1 induction in the intestinal tissue injury in a rat model of sepsis. DesignRandomized, masked, controlled animal study. SettingUniversity-based animal research facility. SubjectsSprague-Dawley male rats, weighing 220–250 g (n = 126). InterventionsRats were injected with lipopolysaccharide (10 mg/kg) intraperitoneally. Another group of rats was injected with interleukin-6 (10 &mgr;g/kg) intravenously. In some rats, tin mesoporphyrin (1 &mgr;mol/kg) was administered intravenously 1 hr before lipopolysaccharide treatment. Measurements and Main ResultsFollowing lipopolysaccharide treatment, expression of heme oxygenase-1 and nonspecific &dgr;-aminolevulinate synthase (ALAS-N), the rate-limiting enzymes of heme catabolism and biosynthesis, respectively, was examined in various regions of the intestine. Lipopolysaccharide treatment markedly increased heme oxygenase-1 messenger RNA and protein concentrations in the mucosal epithelial cells in the duodenum and the jejunum, whereas its expression in the ileum and the colon was hardly detectable and was not influenced by the treatment. ALAS-N messenger RNA was also more markedly increased in the duodenum, the jejunum, and the ileum than in the colon following lipopolysaccharide treatment. Interleukin-6 administration also induced heme oxygenase-1 and ALAS-N gene expression in a pattern similar to that following lipopolysaccharide treatment. In contrast to the marked heme oxygenase-1 expression in the upper intestine, lipopolysaccharide-induced mucosal injury and inflammation in the upper intestine were far less than observed in the lower intestine as judged both by tumor necrosis factor-&agr; gene expression and by histologic analysis. Of note, inhibition of heme oxygenase activity by tin mesoporphyrin produced a significant tissue injury in the upper intestine of the lipopolysaccharide-treated animals. ConclusionsIntestinal heme oxygenase-1 and ALAS-N gene expression was regulated in a site-specific manner in a rat model of sepsis. Our findings also suggest that heme oxygenase-1 induction may play a fundamental role in protecting mucosal epithelial cells of the intestine from oxidative damages that occur in sepsis.

Correlation between the Distribution of Contrast Medium and the Extent of Blockade during Epidural Anesthesia

Background: If the epidural spread of contrast medium can be well correlated with the spread of local anesthetics, epidurography can predict the dermatomal distribution of the anesthetic block. The authors evaluated the relation between radiographic and analgesic spread. Methods: An epidural catheter was inserted in 90 patients, and predicted catheter tip position was recorded. The analgesic area was determined by pinprick after a 5-ml injection of 1.5% lidocaine, and epidurography was performed after a 5-ml injection of 240 mg I/ml iotrolan. Patients were assigned to three groups according to catheter tip position (group C: C–T4; group T: T5–T10; group L: T11–L), and patterns of spread were compared. In 16 of 90 subjects, radiographic and analgesic spread was further investigated after an additional 5-ml injection of iotrolan and lidocaine. Results: The total radiographic spread correlated well with analgesic spread (right side: Y = 0.84 X + 0.16, r = 0.92, P < 0.01; left side: Y = 0.78 X + 0.45, r = 0.91, P < 0.01). The mean radiographic spread in the cephalad and caudal directions from the catheter tip also correlated well with mean analgesic spread (r = 0.97, P < 0.01, each direction). The mean distance between the predicted catheter tip and radiographically determined positions was 1.0 ± 0.8 segments: the value in group T was significantly larger than that in groups C (P < 0.05) and L (P < 0.01). Although the correlation of radiographic spread with age was statistically significantly (r = 0.39, P < 0.01), great individual variation in spreading pattern was seen. In 16 subjects, mean radiographic spread correlated well with analgesic spread after 5- and 10-ml injections of iotrolan and lidocaine. Conclusions: Epidurography is useful to indicate epidural catheter position and can help to predict the exact dermatomal distribution of analgesic block.

Heme Oxygenase-1 is an Essential Cytoprotective Component in Oxidative Tissue Injury Induced by Hemorrhagic Shock

Hemorrhagic shock causes oxidative stress that leads to tissue injuries in various organs including the lung, liver, kidney and intestine. Excess amounts of free heme released from destabilized hemoproteins under oxidative conditions might constitute a major threat because it can catalyze the formation of reactive oxygen species. Cells counteract this by rapidly inducing the rate-limiting enzyme in heme breakdown, heme oxygenase-1 (HO-1), which is a low-molecular-weight stress protein. The enzymatic HO-1 reaction removes heme. As such, endogenous HO-1 induction by hemorrhagic shock protects tissues from further degeneration by oxidant stimuli. In addition, prior pharmacological induction of HO-1 ameliorates oxidative tissue injuries induced by hemorrhagic shock. In contrast, the deletion of HO-1 expression, or the chemical inhibition of increased HO activity ablated the beneficial effect of HO-1 induction, and exacerbates tissue damage. Thus, HO-1 constitutes an essential cytoprotective component in hemorrhagic shock-induced oxidative tissue injures. This article reviews recent advances in understanding of the essential role of HO-1 in experimental models of hemorrhagic shock-induced oxidative tissue injuries with emphasis on the role of its induction in tissue defense.

Increased Carbon Monoxide Concentration in Exhaled Air After Surgery and Anesthesia

Heme oxygenase-1 (HO-1) is induced by oxidative stress and is thought to confer protection against oxidative tissue injuries. HO-1 catalyzes the conversion of the heme moiety of hemeproteins, such as hemoglobin, myoglobin, and cytochrome P450, to biliverdin, liberating carbon monoxide (CO) in the process. CO reacts with hemoglobin to form carboxyhemoglobin. In this study, to examine the effect of anesthesia and/or surgery on endogenous CO production, we measured the amount of exhaled CO and the arterial carboxyhemoglobin concentration of patients who underwent surgery under general or spinal anesthesia. Both CO and carboxyhemoglobin concentrations were significantly larger on the day after surgery than during the preoperative period (P <0.05) and in the recovery room (P < 0.05), regardless of anesthesia. However, neither index differed between general and spinal anesthesia. These results suggest that oxidative stress caused by anesthesia and/or surgery may induce HO-1, which catalyzes heme to produce CO, leading to increased exhaled CO concentration.

High-flow-rate haemodiafiltration as a brain-support therapy proceeding to liver transplantation for hyperacute fulminant hepatic failure

In fulminant hepatic failure (FHF), rapidly progressive cerebral oedema remains the main fatal complication and an obstacle in liver transplantation. A 29-year-old Japanese woman presented with sudden-onset hepatic encephalopathy and jaundice. Hepatic encephalopathy deteriorated within 2 days of the onset of jaundice. She manifested extensory sustained clonus and was responsive only to pain. Diffuse cerebral oedema was noted on brain computerized tomography (CT) scan. Urgent living-donor liver transplantation (LDLT) at the time of admission was abandoned because of deterioration of neurological status and radiologically evident diffuse cerebral oedema. Instead, a high-flow-rate (7.2-9.0 l/h) haemodiafiltration with a high-performance membrane was commenced, combined with plasma exchange. This treatment regimen resulted in a gradual improvement of hepatic encephalopathy and complete disappearance of cerebral oedema within 7 days. Liver regeneration did not occur during this period, as evident by CT scan volumetry and serological tests. LDLT was subsequently performed using the right liver lobe of the patients brother. Our case suggests that high-flow-rate haemodiafiltration with a high-performance membrane, combined with plasma exchange, could potentially be brain-support therapy for patients with FHF, and may contribute, when combined with liver transplantation, to the improvement of prognosis in hyperacute FHF.

A 27-year-old man who died of acute liver failure probably due to trichloroethylene abuse

Acute liver failure from abuse of volatile substances is not usual. We encountered a case involving a 27-year-old man with acute liver and kidney failure followed by severe brain edema, probably caused by abuse of glue containing trichloroethylene. The clinical course was observed from the first day, when serum transaminases were normal, until death on day 12. The trichloroethylene metabolite trichloroacetate was detected in his urine.

Metallothionein and zinc metabolism in endotoxin shock rats.

Zinc metabolism in endotoxicosis was investigated in rats. The zinc concentration in the serum decreased, while zinc contents increased in the lung, kidney and liver. Marked increase in zinc level was observed in the liver. In the liver cells, zinc concentrations of mitochondria and cytosol increased, but not in microsome. Metallothioneins (MTs), which probably participate in zinc metabolism, were induced by endotoxin administration. Although the same level of MT-2 as that of MT-1 was induced by zinc, the level of MT-2 was 3 to 4 fold higher than that of MT-1 by administrations of endotoxin or glucocorticoid hormone. Since no metallothionein was induced directly by addition of endotoxin to the media of cultured cells, the endotoxin was found not to induce MTs directly. The effect of zinc on superoxide generation of polymorphonuclear leukocytes was also studied. Zinc was found to inhibit superoxide generation dose-dependently.

A case of methotrexate-induced acute renal failure successfully treated with plasma perfusion and sequential hemodialysis.

A Case of Methotrexate-lnduced Acute Renal Failure Successfully Treated with Plasma Perfusion and Sequential Hemodialysis K. Kenji Kawabata H. Hirofumi Makino Y. Yoshio Nagake H. Hiroaki Tokioka M. Masaki Matsumi Y. Yoshitaka Morita K. Kosuke Ota K. Kenichi Shikata Z. Zensuke Ota 3rd Department of Internal Medicine and Department of Anesthesiology and Resuscitation, Okayama University Medical School, Okayama, Japan

An increase in exhaled CO concentration in systemic inflammation/sepsis

Despite recent progress in Critical Care Medicine, sepsis is still a major medical problem with a high rate of mortality and morbidity especially in intensive care units. Oxidative stress induced by inflammation associated with sepsis causes degradation of heme protein, increases microsomal free heme content, promotes further oxidative stress and results in cellular and organ damage. Heme-oxygenase-1 (HO-1) is a rate-limiting enzyme for heme breakdown. HO-1 breaks down heme to yield CO, iron and biliverdin. Measurement of CO in exhaled air may potentially be useful in monitoring changes in HO enzyme activity in vivo, which might reflect the degree of inflammation or oxidative stress in patients with systemic inflammation. The increased exhaled CO concentrations were observed after anesthesia/surgery, in critically ill patients and also in systemic inflammation/sepsis. Some reports also showed that exhaled CO concentration is related to mortality. Further studies are needed to elucidate whether increased endogenous CO production may predict a patients morbidity and mortality. Techniques for monitoring CO are continuously being refined and this technique may find its way into the office of clinicians.