Higher Preimplantation Opioid Doses Associated With Long‐Term Spinal Cord Stimulation Failure in 211 Patients With Failed Back Surgery Syndrome

ObjectiveSpinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period.Materials and methodsThe study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries.ResultsHigher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001).ConclusionsHigher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation.     

Abdominalchirurgisch relevante Aspekte des Suizidversuchs

In this retrospective study of 24 patients who were treated at our clinic during the last 22 years after having attempted suicide, we evaluated aspects concerning abdominal-and transplantation surgery. There was a predominance of “hard” (70%) versus “soft” (30%) methods for suicide attempt. Intra-abdominal injuries resulting from attempted suicide by stabbing or shooting should lead to laparotomy— the prognosis is then good. Surgical treatment after intoxication, especially caustic ingestion, depends on endoscopic and clinical findings. The highly increased rates of suicide significantly by kidney transplantation. The risk of suicide after transplantation is further diminished with improved immunosuppressive treatment. Only in a few cases there is an indication for liver transplantation— in some cases of fulminant hepatic failure caused by self-administered paracetomol overdose. Auxiliary liver transplantation may then be considered.     

Reflex increases in heart-rate induced by perfusing the hind leg of the rat with solutions containing lactic acid

The hypothesis that metabolic receptors in skeletal muscle influence heart-rate during exercise was tested by means of a perfused preparation of the rat's hind legs. The isolated leg was connected to the body only by nerve and bone and was perfused with tyrode solution. The humoral changes of exercise were simulated by perfusing with modified tyrode solutions in which concentration of K⁺, osmolality, concentrations of lactic acid, and inorganic phosphate were changed to reflect to those occurring during heavy exercise. Only perfusion with a solution enriched with lactic acid elicited a significant increase in heart-rate. The response disappeared when the nerve supply to the leg was cooled or sectioned. 20–60 s after the start of perfusion with solution of high [lactic acid] heart-rate began to increase reaching a maximum ( ± SE = 20.2 ± 8.2,n = 7) after about 2 min. The effect on heart-rate increased when the venous concentration of lactic acid was increased the range from 3 to 10 mmol/l. In further experiments, we tried to separate the effects of pH and lactate. Heart-rate responses were induced only at low pH and at low pH the extent to which heart-rate changed increased with increases in lactate concentration.     

A549 lung epithelial cells grown as three-dimensional aggregates: alternative tissue culture model for Pseudomonas aeruginosa pathogenesis

A three-dimensional (3-D) lung aggregate model was developed from A549 human lung epithelial cells by using a rotating-wall vessel bioreactor to study the interactions between Pseudomonas aeruginosa and lung epithelial cells. The suitability of the 3-D aggregates as an infection model was examined by immunohistochemistry, adherence and invasion assays, scanning electron microscopy, and cytokine and mucoglycoprotein production. Immunohistochemical characterization of the 3-D A549 aggregates showed increased expression of epithelial cell-specific markers and decreased expression of cancer-specific markers compared to their monolayer counterparts. Immunohistochemistry of junctional markers on A549 3-D cells revealed that these cells formed tight junctions and polarity, in contrast to the cells grown as monolayers. Additionally, the 3-D aggregates stained positively for the production of mucoglycoprotein while the monolayers showed no indication of staining. Moreover, mucin-specific antibodies to MUC1 and MUC5A bound with greater affinity to 3-D aggregates than to the monolayers. P. aeruginosa attached to and penetrated A549 monolayers significantly more than the same cells grown as 3-D aggregates. Scanning electron microscopy of A549 cells grown as monolayers and 3-D aggregates infected with P. aeruginosa showed that monolayers detached from the surface of the culture plate postinfection, in contrast to the 3-D aggregates, which remained attached to the microcarrier beads. In response to infection, proinflammatory cytokine levels were elevated for the 3-D A549 aggregates compared to monolayer controls. These findings suggest that A549 lung cells grown as 3-D aggregates may represent a more physiologically relevant model to examine the interactions between P. aeruginosa and the lung epithelium during infection.     

Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid

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Guinea pig C3 specific rabbit single chain Fv antibodies from bone marrow, spleen and blood derived phage libraries

We constructed combinatorial immunoglobulin libraries from the whole rabbit antibody repertoire of bone marrow, spleen and peripheral blood of a rabbit immunized with guinea pig complement protein C3. By means of the phage display technology we selected guinea pig C3 specific single chain Fv (scFv) antibodies from each of the libraries. None of the scFv antibodies cross reacted with guinea pig C3a, human C3 or rat C3. The frequency of bone marrow derived C3 positive clones was much higher as compared to blood or spleen derived clones. Additionally bone marrow and spleen derived clones show higher diversity than clones, obtained from blood, as determined by fingerprint analysis with the restriction enzyme AluI. Dissociation rate constants for all scFvs were similar, indicating that the source of the scFvs had no influence on affinities. The antibody fragments were used to analyze complement activation during xenotransplantation. Several blood or bone marrow derived scFvs bound to C3 located on rat liver endothelium after hyperacute rejection of a heterotopically transplanted rat liver into guinea pig. These data demonstrate that monoclonal rabbit scFvs can be easily generated from recombinant phage display libraries, constructed from spleen, blood or bone marrow. The selected guinea pig C3 specific scFvs appear to be useful to detect complement activation during xenotransplantation in guinea pigs.     

增殖核抗原和p53蛋白在大肠癌组织中的表达

目的：探讨增殖核抗原（proliferation cell nuclear antigen,PCNA)和p53蛋白表达与大肠癌组织分化的关系。方法,用免疫组织化学方法观察58例大肠癌手术标本PCNA和p53蛋白的表达情况,结果：PCNA阳性着色分布于细胞核内,癌组织PNCA阳性细胞数量明显多于正常肠组织,且分化愈差PCNA阳性的癌细胞数量愈多。P53蛋白阳性占51＝7％（30／58）,但正常大肠组织均呈阴性反应,中,低分化大肠癌P53蛋白阳性率高于高分化的大肠癌,结论：PCNA阳性细胞数和P53蛋白表达与大肠癌的分化程度有关,PCNA阳性标志指数可作为判断大肠癌细胞增殖状态和估计预后的一个可靠参数。