C-reactive protein and seizures in focal epilepsy: a video-electroencephalographic study

Purpose: C‐reactive protein (CRP) has been studied extensively in many noninflammatory neurologic conditions, but there has been little study of CRP in the context of seizures or epilepsy. The purpose of this study was to examine CRP concentrations in patients with refractory focal epilepsy who were undergoing video‐electroencephalography (EEG) monitoring compared with healthy controls, and CRP change during 24 h after a seizure. Methods: CRP levels were measured in serum at the onset of video‐EEG recording (CRP‐0h) and at 3, 6, 12, and 24 h after index seizure (the first verified localized‐onset seizure) in 31 patients during inpatient video‐EEG monitoring by using high sensitivity measurement of CRP concentration. The patients were categorized into two groups: temporal lobe epilepsy (TLE; n = 15) and extratemporal lobe epilepsy (XLE; n = 16). Eighty healthy volunteers served as controls. Key Findings: CRP‐0h concentration was significantly higher in patients with refractory focal epilepsy than in controls (3.5 vs. 0.7 mg/ml, p < 0.001). All five patients with elevated CRP‐0h (>mean + 2 standard deviations in controls) had TLE (vs. none in XLE; p = 0.018). Index seizure type was associated with CRP increase from baseline to maximum level after index seizure (p = 0.005). The most important predictor of increase in CRP level was secondarily generalized tonic–clonic seizure (SGTCS; p = 0.030). Significance: The higher baseline levels in patients with epilepsy compared with healthy controls demonstrates that CRP concentrations are also affected in refractory epilepsy. Our data suggest that SGTCS stimulates CRP production. These results emphasize the association between inflammation and refractory epilepsy.     

Repair of maxillary alveolar cleft defects with two different bioabsorbable implants: an experimental study in growing rabbits

Two different bioabsorbable implants and their ability to promote bone formation in repair of experimental maxillary defects were investigated. A poly-L/D-lactide mesh and a two-layer composite membrane consisting of a film made of a copolymer of L-lactic acid and )-caprolactone combined with the polylactide mesh were used as implants. A standard alveolar defect was made bilaterally in the maxilla and filled with autogenous bone grafts in 30 growing rabbits. Follow-up was 10 weeks. Three experimental groups were formed: (1) defect covered with polylactide mesh versus control defect without implant, (2) defect covered with composite membrane versus control defect, and (3) defect covered with membrane on one side and with mesh on the other. Radiological, histological and histomorphometric evaluations were performed. In histomorphometric measurements, a significantly larger quantity of bone was observed in the composite membrane-covered defects compared with the polylactide mesh-covered and the control defects. Osteogenic activity was also highest in the membrane-covered defects. The bioabsorbable composite membrane appears to promote healing of experimental maxillary alveolar defects in accordance with the principle of guided tissue regeneration. The polylactide mesh alone was less potent in promoting healing of the defect, although an enhancing effect on osteogenic activity was observed.     

Prefabricating bone in muscle by using free tibial periosteal grafts and self-reinforced polyglycolide and poly-L-lactide pins

To investigate the possibility of prefabricating bone of predetermined form in muscle using free tibial periosteal grafts and biodegradable pins, operations were performed on 12 growing rabbits. In each animal, (1) a graft around a self-reinforced polyglycolide (SR-PGA) pin, (2) a graft around a self-reinforced poly-L-lactide (SR-PLLA) pin, (3) a SR-PGA pin, and (4) a SR-PLLA pin were implanted in the dorsal muscles for 6 weeks. Histological and histomorphometric evaluations were performed. Bone formation from periosteal grafts was observed in all 12 animals. The shape of the newly-formed bone was grossly cylindrical in all specimens except one. Bone formation was stronger around the SR-PGA pins than around the SR-PLLA pins. The pins without grafts did not induce any bone formation, but fibrous tissue encapsulation instead. A mild foreign body reaction was elicited by SR-PGA pins, while it was almost absent with SR-PLLA pins. It is thus possible to prefabricate bone in a cylindrical form in growing rabbits using free tibial periosteal grafts and SR-PGA or SR-PLLA pins implanted in muscle.     

No lymphokines in T-cells around loosened hip prostheses

Research results have been contradictory about the role of lymphocytes and immune response in aseptic loosening of total hip replacement (THR). Conclusive evidence is still lacking in spite of extensive in vivo and in vitro studies. Our study was designed to check whether T-cells were activated and if they produced lymphokines in synovial membrane-like interface tissue around loosened THRs. Tissue sections were stabilized and permeabilized to allow the cytokine-specific antibodies to penetrate through the cell membrane and the membranes of intracellular organelles. This technique, combined with computer-assisted image analysis, permits the detection and quantitation of lymphokine-producing cells. We found that the number of T-cells was low, and none of the T-cells was activated, as shown by the absence of interleukin-2 receptor (IL-2R) immunoreactivity. There was no cell producing lymphokines, such as interleukin-2 (IL-2), interferon-gamma (IFN-γ), and tumor necrosis factor-beta (TNF-β). Our results suggest that T-cell-mediated immune response is not actively involved in aseptic loosening of THR.     

Multi-score estimation of catecholamine fluorescence for clinical purposes

Experience accumulated at multi-score semiquantitation of catecholamine fluorescence of glyoxylic acid-treated stretch preparations of human clinical specimens is presented. The methodology and criteria of quantitation are described in detail. For an example, comparison between 3 different methods for analyzing neural-bound noradrenaline in human myocardial tissue in various heart diseases (obtained during the course of cardiac surgery) is presented: Biochemical determination of tissue noradrenaline content multi-score estimation of catecholamine fluorescence of glyoxylic acid-treated stretch preparations microfluorimetric analysis of the same stretch preparations. The results show that the multi-score estimation method gives a reliable concept of the relative amounts of noradrenaline stored in the intrinsic adrenergic nerve net (corresponding closely to the individual and group differences observed at biochemical noradrenaline determination). In addition, possible regional differences, alterations in the structural integrity of the inbuilt intrinsic nerve net, and other structural changes (e.g. pathological catecholamine accumulations) are easily recognized, whereas biochemical estimation cannot give information on structural aspects, which may have important clinical repercussions. Microfluorimetry does not seem suitable for studies on human myocardial specimens for several reasons which are discussed. The method of multi-score estimation of catecholamine fluorescence described and discussed is recommended for other similar and related studies on human clinical materials.     

The role of polyglycolic acid rods in the regeneration of cartilage from perichondrium in rabbits.

The role of polyglycolic acid (PGA) rods in the regeneration of cartilage from perichondrium was investigated in 12 growing rabbits. The fifth rib cartilage was resected subperichondrially from both sides. A 10 X 1.5 mm self-reinforced polyglycolic acid (SR-PGA) rod was inserted on one side to replace the resected cartilage and the retained perichondrium was sutured around the implant. On the control side the perichondrium was shaped into a tube without an implant. Samples were taken 4, 12, and 20 weeks after operation. Pronounced neocartilage formation was seen on both sides, and had grown to form a tube around the implant. Also new bone formation was seen in 12 and 20 weeks. Foreign body reaction was seen inside the implants in every animal.     

Effect of the Choice of Primary Chemotherapy on the Cumulative Length of Stay in Hospital for Multiple Myeloma

The actual use of hospital beds for patients with multiple myeloma was calculated from a randomised trial of primary treatment with either melphalan and prednisone (MP, 66 patients) or intensive combination chemotherapy with vincristine, cyclophosphamide, lomustine, melphalan and methylprednisolone (MOCCA, 64 patients). The survival of the patients was similar in both arms, and the samples, 20 and 32 patients, respectively, were well representative for the whole arms. The average numbers of hospital days were similar fur both arms. For the first year MP 33.2 (SD 27.6) vs. MOCCA 32.1 (SD 19.0), and during the first to 4th years 78.5 (SD 45.9) vs. 67.8 (SD 34.1). For the year of death it was 50.4 (SD 33.1) vii. 36.3 (SD 27.0), respectivelly. Thus the choice of primary chemotherapy whether conventional or more aggressive had no influence on the actual number of in-patient hospital days concerned. When the combination chemotherapy schedule is well tolerated it can be administered just as well on an ambulatory basis or by using it with very short admissions. It seems that the need for inpatient care for patients with multiple myeloma is mostly related to the complications of the disease itself and to intercurrent disorders including infections.     

Production of platelet-derived growth factor in aseptic loosening of total hip replacement

Aseptic loosening is the predominant cause of total hip implant failure. It has been assumed that a layer or membrane, containing macrophages, fibroblasts and vascular endothelial cells, of synovial-like tissue develops at the implant-to-bone interface almost invariably and, with time, somehow leads to loosening of the components from the surrounding bone. These cells produce a variety of cytokines and proteolytic enzymes which stimulate bone resorption. Platelet derived growth factor (PDGF) may be one of the cytokines which stimulate bone resorption and contribute to aseptic loosening in total hip replacement (THR). Synovial-like membrane from the implant or cement-to-bone interface (n=10) and pseudocapsule (n=10) were obtained from ten patients operated on for aseptic loosening of THR. As a control, nine samples of connective tissues were obtained from patients who had mandibular or maxillary fractures fixed with bone implant. The avidin-biotin-peroxidase complex (ABC) method with polyclonal rabbit anti-human IgG against the A-chain and B-chain of PDGF was used for staining. ABC-alkaline phosphatase-anti-alkaline-phosphatase double staining with monoclonal mouse anti-human fibroblast IgG₁ and CD68 antibodies was used to ascertain the cellular origin of PDGF. Results of the PDGF staining were quantitated by a semi-automatic VIDAS image analysis system. The PDGF-A and PDGF-B chain containing cells were found in all periprosthetic tissues, in particular in macrophages with phagocytosed particulate debris, but to some extent also in fibroblasts and in endothelial cells. The numbers of PDGF-A and PDGF-B chain positive cells per mm² in synovial-like interface membrane (1881±486 and 1877±214) and pseudocapsule (1786±236 and 1676±152) were higher (P<0.01) around loose THR than in control tissue (821±112 and 467±150), respectively. The results of the present study suggest that PDGF is preferably expressed by macrophages, which to an increased extent produce it in the synovial-like interface membrane and pseudocapsular synovial-like membrane. Because of its role in bone resorption, it may well play a role in periprosthetic bone loss and aseptic loosening and deserves more detailed study as a mediator and potential target in the modulation or prevention of loosening of THR. Received: 11 March 1997 / Accepted: 9 January 1998     

Life-threatening complications of cardiac operations and occurrence of myocardial catecholamine bombs

Myocardial catecholamine bombs (huge local intra-axonal accumulations of catecholamine, mainly norepinephrine, within cardiac tissue) were observed in (right auricular) myocardial biopsy specimens in 16 of 65 adult patients selected randomly from a series of elective cardiac operations. The occurrence of catecholamine bombs was in highly significant correlation (p less than 0.001) with the occurrence of life-threatening complications of cardiac operations (life-threatening arrhythmias [ventricular tachycardias, ventricular fibrillation, asystole], clinically evident perioperative myocardial infarction/postoperative low-output syndrome, death). There was a very close correlation between the occurrence of catecholamine bombs and life-threatening arrhythmias. Life-threatening arrhythmias occurred in 13 patients. Eight of them belonged to the group of 16 patients with catecholamine bombs and five belonged to the group of 49 patients with no bombs; the difference (8/16 versus 5/49) is very clear (p less than 0.001). It was our experience that dangerous arrhythmias related to catecholamine bombs may occur as late as during the second postoperative week. We believe our observations are of considerable clinical importance, because catecholamine bombs are easily identified by fluorescence microscopic examination of right auricular myocardial specimens retrieved intraoperatively, and patients at high risk can then be selected (during the operation) for more extensive and prolonged surveillance and possibly prophylactic treatment.