Sodium channels accumulate at the tips of injured axons

The axolemmal distribution of voltage-gated sodium channels largely determines the regions of axonal electrical excitability. Using a wellcharacterized anti–sodium channel antibody, we examined peripheral nerve fibers focally injured by exposure to the neurotoxic agent, potassium tellurite (K₂TeO₃). Immunocytochemical and radioimmunoassay data showed a focal accumulation of sodium channels within the tips of injured axons. The major increase in sodium channel concentration occurred between 7 and 11 days after toxin exposure; however, immunocytochemically, excess sodium channels persisted in several axonal endings for a much longer time. The accumulation of sodium channels at injured axonal tips may be responsible, in part, for ectopic axonal excitability and the resulting abnormal sensory phenomena (especially pain and paresthesias) which frequently complicate peripheral nerve injury in humans. © 1994 John Wiley & Sons, Inc.     

The bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954)--II. A comparison of an Escherichia coli nitroreductase and Walker DT diaphorase.

A nitroreductase enzyme that has been isolated from Escherichia coli B is capable of bioactivating CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] to a cytotoxic agent, a property shared with the mammalian enzyme Walker DT diaphorase [NAD(P)H dehydrogenase (quinone), EC 1.6.99.2] as isolated from Walker cells. In contrast to Walker DT diaphorase, which can only reduce the 4-nitro group of CB1954, the E. coli nitroreductase can reduce either (but not both) nitro groups of CB1954 to the corresponding hydroxylamino species. The two hydroxylamino species are formed in equal proportions and at the same rates. CB1954 is reduced much more rapidly by the E. coli nitroreductase than by Walker DT diaphorase. If the reduction of CB1954 was carried out in the presence of V79 cells (which are insensitive to CB1954) a large cytotoxic effect was evident. This cytotoxicity was only observed under conditions in which the E. coli nitroreductase or Walker DT diaphorase reduced the drug. It is proposed that E. coli B nitroreductase would be a suitable enzyme for antibody-directed enzyme prodrug therapy (ADEPT) in combination with CB1954.     

Gangliosides of cultured astroglia

Cultured astrocytes prepared from newborn rat brain and 13-day-old chick embryonic brain were analyzed qualitatively and quantitatively for ganglioside content. All preparations contained approximately the same total level: 2.4-3.4 micrograms N-acetylneuraminic acid (NeuAc)/mg protein. In contrast, the value for primary cultures of neurons from chick embryonic brain was 5.9. The non-hexosamine-containing species, GM3 and GD3, comprised 75-85% of the total in astroglial cultures, the remainder consisting mainly of structural types other than the gangliotetraose series; choleragenoid assay revealed the latter to be virtually absent or to comprise at most a few percent. Deficiency of gangliotetraose synthesizing ability was indicated by the very low level of UDP-GalNac:GM3 N-acetylgalactosaminyltransferase detected in the cells. Treatment of cultured astrocytes with astroglial growth factor 2 or dibutyryl cyclic AMP caused little if any change in quantity or pattern of gangliosides. The large majority of cells stained in a manner characteristic of astrocytes: positive for glial fibrillary acidic protein, negative for galactosyl ceramides. Staining with cholera toxin and anti-GM1 antibody was essentially negative, as was that with tetanus toxin, A2B5 monoclonal antibody, and antibody to GD3. All evidence thus points to cultured astrocytes of rat and chick brain containing appreciable gangliosides, most of which are GM3 and GD3 with the majority of the remainder comprising structures other than the gangliotetraose type.     

Early and mid–term results of the Shelhigh stentless bioprosthesis in patients with active infective endocarditis

Summary Aims This study investigated the early and mid–term results following valve replacement with the new Shelhigh^? stentless bioprosthesis made entirely of biological material in patients with active infective endocarditis (AIE). Material and methods Between 02/2000 and 12/2004, 164 patients (n = 122 men, mean age 59, 18–85 years) received implantation of an AIE Shelhigh^? stentless bioprosthesis in the aortic, mitral, tricuspid or pulmonary position. A total of 119 patients (72.6%) had native AIE and 45 (27.4%) prosthetic AIE. A large proportion of the patients reached the operating room in a condition of cardiac decompensation: 37 (22.6%) patients were intubated, 40 (24.4%) had protracted septic shock and 41 (25.0%) required intensive catecholamine treatment. Surgery was regarded as urgent in 94 patients (57.4%) and was performed as an emergency procedure in 70 (42.6%). The mean follow–up time is 1.5 ± 0.11 years (range, 5 months to 5.2 years). Echocardiographic follow–up examinations were performed early postoperatively and after 12 months. Results In terms of the operative indication, we found a highly significant difference in the survival rate between patients who were operated on urgently vs in an emergency. In patients who died within 30 days, the main cause of death was septic multiorgan failure (67.6%). Only three patients required reoperation due to reinfection of the Shelhigh^? bioprostheses; this represents a reinfection rate of 1.8% in relation to the whole cohort. The postoperative echocardiographic examinations showed the Shelhigh^? valves to have very good hemodynamics without relevant pressure gradients. Conclusion Our experience in the use of Shelhigh^? bioprostheses in patients with native and prosthetic endocarditis show the early and mid–term results, in particular the low reinfection rate and the good hemodynamics, to be comparable with the results achieved using homografts. Since these prostheses are readily available and their implantation straightforward, they are increasingly being used in patients with endocarditis. These promising results need to verified in the long term. This paper was presented at a lecture held at the 71^st annual meeting of the German Society for Cardiology, Mannheim, 31. March—2. April 2005. Disclosure Form: The following study discloses my relationship with any corporate sponsor that might relate in some way to the subject presented.     

Surgical therapy in patients with active infective endocarditis: seven-year single centre experience in a subgroup of 255 patients treated with the Shelhigh stentless bioprosthesis

OBJECTIVE: We investigated outcomes after surgical therapy in patients with active infective endocarditis (AIE) with regard to survival in relation to surgical urgency, valve position, number of valves implanted and abscess formation. We aimed to identify independent risk factors for early mortality. METHODS AND RESULTS: Two hundred and fifty-five patients received Shelhigh bioprostheses between February 2000 and March 2007. A total of 74.1% had native and 25.9% prosthetic AIE. Surgery was regarded as urgent in 57.3% and as an emergency procedure in 38.4%. There was a highly significant difference in survival rate between patients who were operated on urgently versus in an emergency (p<0.0001), between single and double valve replacement (p=0.0206) and between patients with and without abscess formation (p=0.0245). There were two cases of early reinfection (0.78%) and six of late reinfection (2.35%) leading to re-operation. CONCLUSIONS: The survival of patients differs significantly in dependence on their surgical urgency. Better outcome could have been achieved if patients had been referred earlier for surgery and operated upon before heart failure or septic shock developed. Long-term survival was better in patients without abscess formation. The low reinfection rate of Shelhigh bioprostheses in AIE is promising and the early and mid-term results achieved need to be verified in the long-term course.     

Rhythmic movements in idiopathic REM sleep behavior disorder.

Reported are two cases of video-PSG captured head-rolling occurring, in the context of REM Sleep Behavior Disorder (RBD) episodes, in two patients affected with idiopathic RBD and without past personal or familiar history of Rhythmic Movement Disorder during sleep. It has been speculated that the activation of neuronal pathways which underlie REM-related loss of motor control in RBD, may involve the Central Pattern Generator neuronal networks leading to the induction of Rhythmic Movements during RBD episodes, thereby allowing the re-emergence, in pathological conditions in later life, of a motor behavior typically seen in the early stage of life.     

Preoperative pulmonary rehabilitation in patients undergoing lung resection for non-small cell lung cancer.

BACKGROUND: The impact of short-term preoperative pulmonary rehabilitation on exercise capacity of patients with chronic obstructive pulmonary disease undergoing lobectomy for non-small cell lung cancer is evaluated. METHODS: A prospective observational study was designed. Inclusion criteria consisted of an indication to lung resection because of a clinical stage I or II non-small cell lung cancer and a chronic obstructive disease on preoperative pulmonary function test. In such conditions, maximal oxygen consumption by a cardio-pulmonary exercise test was evaluated; when this resulted as being < or =15 ml/kg/min a pulmonary rehabilitation programme lasting 4 weeks was considered. Twelve patients fulfilled inclusion criteria, completed the preoperative rehabilitation programme and underwent a new functional evaluation prior to surgery. The postoperative record of these patients was collected. RESULTS: On completion of pulmonary rehabilitation, the resting pulmonary function test and diffuse lung capacity of patients was unchanged, whereas the exercise performance was found to have significantly improved; the mean increase in maximal oxygen consumption proved to be at 2.8 ml/kg/min (p<0.01). Eleven patients underwent lobectomy; no postoperative mortality was noted and mean hospital stay was 17 days. Postoperative pulmonary complication was recorded in 8 patients. CONCLUSIONS: Short-term preoperative pulmonary rehabilitation could improve the exercise capacity of patients with chronic obstructive pulmonary disease who are candidates for lung resection for non-small cell lung cancer.     

术中射频消融后病灶刮除治疗脊柱转移瘤

目的:探讨术中射频消融(RFA)后再行病灶刮除术治疗脊柱转移瘤的可行性及疗效.方法:2004年～2006年,对11例脊柱转移瘤患者术中实施RFA后再行病灶刮除术,将FRA前后病灶标本进行光镜和电镜病理检查,随访患者疼痛缓解情况及肿瘤复发情况.结果:术中未出现脊髓和神经根损伤,RFA后瘤组织固缩,刮除顺利,出血量350～3800ml,平均1024.5ml.全部病例得到6个月以上随访,平均9.8个月,全部患者生存期超过6个月,VAS评分术前平均5.8分,术后6个月时平均1.9分.1例出现局部肿瘤复发.RFA前的标本光、电镜检查均未见肿瘤组织坏死.RFA后光镜检查3例无明显坏死,9例肿瘤细胞完全坏死:电镜检查10例肿瘤细胞完全坏死,1例肿瘤细胞部分坏死,1例无明显坏死.结论:术中RFA后再行病灶刮除治疗脊柱转移瘤安全可行,有利于肿瘤的刮除,减少局部复发的风险.