Treatment of bone and soft tissue sarcomas of the hand and wrist

We studied 13 consecutive patients with bone and soft tissue sarcomas of the hand and wrist. Chondrosarcoma, Ewing's sarcoma, synovial sarcoma and epithelioid sarcoma were the most frequent histological diagnoses. Limb-sparing surgery was performed in ten patients but eventually three patients required an amputation. Surgical margins were wide in nine patients and marginal in four. Adjuvant therapy for nine patients consisted of chemotherapy in five and chemotherapy with radiation in four. Local recurrence occurred in two patients with epithelioid sarcoma. There was no significant relationship between surgical margin and local recurrence. Distant metastasis occurred in four patients. The 5-year survival rate was 66%. The mean functional score was 87%. Our study indicates that treatment consisting of resection of these tumours with either a wide margin or a marginal margin followed by adjuvant radiation appeared to be safe and resulted in an acceptable degree of limb function except in the patients with epithelioid sarcoma.     

Remifentanil is useful for cardiovascular stability during cesarean delivery in a parturient with Marfan's syndrome

A 25-year-old parturient with Marfan's syndrome was scheduled for cesarean delivery. She suffered with severe scoliosis and asymptomatic aortic root dilatation. To establish a cardiovascular stability and prevent aortic dissection perioperatively, we selected the use of remifentanil, an ultra-short acting opioid analgesic with general anesthesia. General anesthesia was induced with remifentanil (0.2 microg x kg(-1) x min(-1)), propofol (100 mg), and vecuronium bromide (10 mg). Anesthesia was maintained with 100% O2, sevoflurane (1-1.5%), and remifentanil (0.2-0.25 microg x kg(-1) x min(-1)). She remained hemodynamically stable during surgery. A lively infant was delivered and Apgar scores were 8 and 9 at 1 and 5 min, respectively. Their post-delivery courses were uneventful. Remifentanil was useful for anesthetic management in a pregnant patient with Marfan's syndrome undergoing cesarean delivery, although attention to infant's respiratory condition should be paid because remifentanil can cross the placenta.     

Campylobacter coli enteritis and Guillain-Barré syndrome: no evidence of molecular mimicry and serological relationship

Campylobacter coli was isolated from two Guillain-Barré syndrome (GBS) patients who had anti-GM1 and anti-GD1 IgG antibodies. Although both this bacteria and Campylobacter jejuni are common causes of diarrheal illness, previous studies have focused only on C. jejuni as the causal agent of GBS. To determine whether C. coli also is a causative agent, we examined the hypothesis that production of anti-ganglioside antibodies is induced by ganglioside-mimics on that bacterial lipo-oligosaccharide (LOS), as in C. jejuni-associated GBS. LOSs of both C. coli isolates had very weak reactivities with anti-GM1 and anti-GD1a IgG monoclonal antibodies, whereas those of some GBS-related C. jejuni isolates had strong reactivities. Anti-GM1 and anti-GD1a IgG antibodies from the two patients were not absorbed as much by the LOSs of their isolates as were those of GBS-related C. jejuni strains. These findings do not support the hypothesis of ganglioside mimicry on C. coli isolates' LOSs. We next made a serological assay of recent C. coli infection in 74 patients with GBS, 26 with Fisher syndrome (FS), 49 with other neurological diseases (OND), and 37 normal controls (NC) using the bacterial outer membrane protein as antigen. Eight (11%) GBS and two (8%) FS patients had two or three classes of IgG, IgM, and IgA anti-C. coli antibodies. Anti-C. jejuni IgG and IgA antibody titers were significantly higher than those of anti-C. coli (respectively, p = 0.03 and 0.01). This suggests that anti-C. coli antibodies cross-react with C. jejuni protein. We concluded that a C. coli infection was not the cause of GBS in our patients. Both isolation of a microorganism from, and the positive infectious serology of, GBS patients do not always indicate the causal agent.     

Ganglioside mimicry as a cause of Guillain-Barré syndrome

Guillain-Barré syndrome (GBS), characterized by acute progressive limb weakness and areflexia, is the prototype of postinfectious autoimmune diseases. Campylobacter jejuni is the most frequently identified agent of infection in GBS patients, often preceding acute motor axonal neuropathy (AMAN), a variant of GBS. Anti-GM1, anti-GM1b, anti-GD1a, and anti-GalNAc-GD1a IgG antibodies are associated with AMAN. Carbohydrate mimicry [Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-] was seen between the lipo-oligosaccharide of C. jejuni isolated from an AMAN patient and human GM1 ganglioside. Sensitization with the lipo-oligosaccharide of C. jejuni induces AMAN in rabbits as does sensitization with GM1 ganglioside. Paralyzed rabbits have pathological changes in their peripheral nerves identical to changes seen in human GBS. C. jejuni infection may induce anti-ganglioside antibodies by molecular mimicry, eliciting AMAN. This is the first verification of the causative mechanism of molecular mimicry in an autoimmune disease. To express ganglioside mimics, C. jejuni requires specific gene combinations that function in sialic acid biosynthesis or transfer. The knockout mutants of these landmark genes of GBS show reduced reactivity with GBS patients' sera, and fail to induce an anti-ganglioside antibody response in mice. These genes are crucial for the induction of neuropathogenic cross-reactive antibodies. An approach for evaluating intravenous immune globulin, a treatment for GBS, based on our animal model of AMAN is also discussed in this review, and recent advances made in this field are described.     

Recovery from rocuronium by sugammadex does not affect motor evoked potentials

Motor evoked potential (MEP) monitoring has been employed to detect the spinal cord injury during spinal, neurosurgical and cardiovascular operations. Muscle relaxants diminish the amplitude of MEP because MEP is the picture of electromyogram. In 5 cases undergoing MEP monitoring, we examined the effect of rocuronium followed by the administration of sugammadex on MEP Anesthesia was induced with propofol (target controlled infusion 3.0-3.5 microg x ml(-1)) and remifentanil 0.15-0.3 microg x kg(-1) x min(-1), and the trachea was intubated with the use of rocuronium 0.6 mg x kg(-1) without any muscle rigidity, bucking and laryngospasm. General anesthesia was maintained by total intravenous anesthesia using propofol and remifentanil with no muscle relaxants. Immediately after the tracheal intubation, sugammadex 4 mg x kg(-1) was intravenously given. The amplitude of MEP was measured just before the administration of rocuronium, immediately after the tracheal intubation, and 1, 2, 3, 5 min following the administration of sugammadex. Sugammadex restored the MEP amplitude, deteriorated by rocuronium, in 3 to 5 min to the level of non-paralytic muscles. In one case, it took 8 min to restore the MEP of hemiparetic leg. Taking these findings into consideration, it is likely that rocuronium might not affect the MEP when reversed by sugammadex, and should be safe for smooth tracheal intubation in patients who need MEP monitoring.     

Nilotinib attenuates renal injury and prolongs survival in chronic kidney disease

The tyrosine kinase inhibitor imatinib is beneficial in experimental renal diseases, but the effect of the new tyrosine kinase inhibitor nilotinib on the progression of renal failure is unknown. We administered either nilotinib or vehicle to Sprague-Dawley rats beginning 2 weeks after 5/6 nephrectomy (Nx) or laparotomy and continuing for 8 weeks. Serum creatinine levels were significantly lower in the nilotinib group after 6 and 8 weeks of treatment. Furthermore, nilotinib-treated rats had less proteinuria, attenuated glomerulosclerosis and tubulointerstitial damage, and reduced macrophage infiltration into the tubulointerstitium. Treatment with nilotinib also significantly decreased renal cortical expression of profibrogenic genes, such as IL-1β and monocyte chemotactic protein-1, which correlated closely with the tubulointerstitial damage score and ED1-positive macrophages score. In addition, nilotinib treatment significantly prolonged survival. Taken together, these results suggest that nilotinib may limit the progression of chronic kidney disease.     

Effect of divided supplementation of remifentanil on seizure duration and hemodynamic responses during electroconvulsive therapy under propofol anesthesia

Purpose

Although a reduced dose of propofol combined with remifentanil is often used in anesthesia for electroconvulsive therapy (ECT), there have been few studies in which the optimal technique for injection of remifentanil was examined in detail. The aim of this study was to evaluate the effects of single and divided injection of remifentanil combined with propofol on seizure duration and hemodynamic responses during ECT.

Methods

Twenty-six ASA I?CII patients were enrolled in this study and received a total of 78 ECTs. Each patient received propofol 1.2?mg/kg (group P), remifentanil 1???g/kg followed by propofol 0.5?mg/kg (group R1), and remifentanil 1???g/kg followed by propofol 0.5?mg/kg and thereafter remifentanil 2???g/kg (group R2). Succinylcholine 1?mg/kg was used for muscle paralysis after loss of consciousness.

Results

Although mean motor seizure durations were significantly longer in groups R1 and R2 than in group P (P?P?P?Conclusions Divided use of remifentanil at 1 and 2???g/kg combined with propofol 0.5?mg/kg produces an acceptable outcome in both seizure duration and hemodynamic stability during ECT compared with the standard hypnotic doses of propofol alone or remifentanil 1???g/kg followed by propofol 0.5?mg/kg.     

Climbing exercise enhances osteoblast differentiation and inhibits adipogenic differentiation with high expression of PTH/PTHrP receptor in bone marrow cells

We developed previously a mouse voluntary climbing exercise model as a physiological mechanical loading model and reported that climbing exercise increased bone formation, but its effect on adipogenesis is unknown. We assessed the effects of loading and PTH/PTHrP receptor (PTHR1) on bone marrow adipocyte differentiation in relation with osteoblast differentiation. 8-week-old C57BL/6J male mice were divided into ground control (GC) and climbing exercise (EX) group. Mice were housed in 100-cm towers and climbed up toward a bottle placed at the top of the cage to drink water. The values of bone volume and osteoblast number were significantly higher while those of marrow adipocyte volume and number were significantly lower in the 28dayEX group than 28dayGC group. The mRNA expression levels of adipocyte differentiation genes CCAAT/enhancer-binding proteins (C/EBP) beta and delta were lower in 4dayEX mice, while the adipocyte specific genes fatty acid binding protein (aP2) and phosphoenolpyruvate carboxykinase (PEPCK) expressions were lower in 7dayEX mice. In primary bone marrow cell cultures, the number of alkaline phosphatase-positive colony forming units-fibroblastic (ALP+ CFU-f) and Oil-red-O-positive cells were both increased in the 4dayEX group. Climbing exercise transiently increases both osteogenic and adipogenic potential in bone marrow stromal cells, and inhibits terminal adipocyte differentiation and promotes osteoblast differentiation. Immunoreactivity for the PTHR1 was intense on osteoblastic cell lineage in the endosteal tibial metaphysis. PTHR1 mRNA expression was increased in 4dayEX mice and PTHR1-positive cells were increased after 7 days in the experimental group. Ex vivo addition of PTHR1 antibody decreased and that of PTHrP(1-34) increased the number of ALP+ CFU-f in bone marrow cell cultures obtained at 4 days after the exercise, while the addition of PTHR1 antibody increased and PTHrP(1-34) decreased the number of Oil-red-O-positive cells. Our results indicate that climbing exercise enhanced osteoblast differentiation and inhibited terminal differentiation of adipocyte progenitors with high expression of PTHR1 in bone marrow cells.