Calcifying pseudoneoplasms of the neuraxis (CAPNON): clinical features and therapeutic options.

INTRODUCTION: Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, slow-growing lesions occurring anywhere in the central nervous system (CNS). Since their first description in 1978, only 39 cases have been reported in the literature. METHODS: The cases of two patients with histopathologically verified diagnoses of CAPNON are presented. Thereafter, we review all reports published so far with respect to study type, number of patients, anatomical area (intracranial, spinal, or both), clinical presentation, radiological presentation, therapy, duration of follow-up, incidence and type of complication, and outcome. Furthermore, current recommendations for the management of spinal and cerebral CAPNON are discussed. RESULTS: A total of 19 retrospective articles were identified and selected for review: 6 case series (31.6 %) and 13 reports of single cases (68.4 %). The 19 articles and our two additional cases added up to a total of 19 patients with spinal CAPNON and 22 patients with intracranial CAPNON. All patients were treated surgically. A follow-up was provided in 13 patients with spinal (68.4 %) and in 16 patients with intracranial CAPNON (72.7 %), respectively. The follow-up showed no signs of recurrence in 12 of 13 patients with spinal CAPNON (92.3 %) and in 15 of 16 patients with intracranial CAPNON (93.7 %). One-tailed Fisher's exact test revealed no significant difference between complete and incomplete resection in terms of disease recurrence (spinal: p = 0.6842; intracranial: p = 0.3749). Analysis of the literature did not reveal any deaths directly associated with CAPNON. CONCLUSIONS: Calcifying pseudoneoplasms are rare benign lesions of the CNS of yet unknown origin. Because of the increasing number of reports, this clinical entity should be taken into consideration in the differential diagnosis of intracranial and intraspinal calcified lesions.

Chronic denervation of rat hemidiaphragm: maintenance of fiber heterogeneity with associated increasing uniformity of myosin isoforms.

During several months of denervation, rat mixed muscles lose slow myosin, though with variability among animals. Immunocytochemical studies showed that all the denervated fibers of the hemidiaphragm reacted with anti-fast myosin, while many reacted with anti-slow myosin as well. This has left open the question as to whether multiple forms of myosin co-exist within individual fibers or a unique, possibly embryonic, myosin is present, which shares epitopes with fast and slow myosins. Furthermore, one can ask if the reappearance of embryonic myosin in chronically denervated muscle is related both to its re-expression in the pre-existing fibers and to cell regeneration. To answer these questions we studied the myosin heavy chains from individual fibers of the denervated hemidiaphragm by SDS PAGE and morphologically searched for regenerative events in the long term denervated muscle. 3 mo after denervation the severely atrophic fibers of the hemidiaphragm showed either fast or a mixture of fast and slow myosin heavy chains. Structural analysis of proteins sequentially extracted from muscle cryostat sections showed that slow myosin was still present 16 mo after denervation, in spite of the loss of the selective distribution of fast and slow features. Therefore muscle fibers can express adult fast myosin not only when denervated during their differentiation but also after the slow program has been expressed for a long time. Light and electron microscopy showed that the long-term denervated muscle maintained a steady-state atrophy for the rat's life span. Some of the morphological features indicate that aneural regeneration events continuously occur and significantly contribute to the increasing uniformity of the myosin gene expression in long-term denervated diaphragm.

Carnitine deficiency of skeletal muscle: report of a treated case.

We studied a 10-year-old girl with an insidious muscle disease beginning at age 7. Muscle biopsy showed that the majority of type I fibers were vacuolated and contained lipid excess. Carnitine deficiency was found in skeletal muscle. The patient was treated with 3.0 gm L-carnitine per day and with a medium-chain triglyceride diet. She showed a rapid improvement and recovery of strength. A muscle biopsy 8 months later showed a decreased lipid content. Oral carnitine replacement represents an effective treatment for the disease.

Toxic effects of cyclosporine on the endocrine pancreas of Wistar rats.

The widely used immunosuppressive drug cyclosporine exerts toxic effects on various parenchymal organs including the liver and kidney. This study was performed with the aim of testing whether cyclosporine also affects the endocrine pancreas. Daily cyclosporine doses of 50 mg/kg body weight over 3 weeks in rats enhanced the serum bilirubin and creatinine concentrations, led to light-microscopic destruction in the liver and kidneys, and resulted in the development of an impaired glucose tolerance--and, later on, of hyperglycemia. The pancreatic insulin content decreased to 33% of values observed in vehicle-treated controls, which can be ascribed to a 50% decrease of beta-cell volume and a slightly smaller reduction of islet insulin content. The reduction of the cyclosporine dose to 15 mg/kg body weight daily, which also reduced the popliteal lymph node weight gain after allogeneic stimulation, was not accompanied by serochemical or morphological alterations of livers or kidneys in the rats when treated for 3 weeks. However, the animals had already developed an impaired glucose tolerance, accompanied by a decrease in pancreatic insulin content (to 50% that of controls), a decrease of islet insulin content (to 70%) and a reduced pancreatic beta cell volume (to 72%). The findings let us conclude that pancreatic beta cells are sensitive to toxic effects of cyclosporine in vivo. We suggest that the measurement of glucose tolerance, as a sensitive parameter of a toxic cyclosporine action, should be included in the monitoring of grafted patients under cyclosporine treatment.

[Relation between the labeling index and thymidine incorporation in cultured islands of Langerhans of the rat: stimulation of DNA synthesis by EGF-S3]. / Beziehung zwischen Markierungsindex und Thymidineinbau in kultivierten Langerhansschen Inseln der Ratte: Stimulation der DNS-Synthese durch FGF-S3.

DNA synthesis and labelling index of isolated neonatal rat islets were investigated during a 4 to 5 culture period in TCM 199 (10 mmol/l glucose) under selected conditions, as change of serum concentration in the medium or addition of a proliferation stimulating fraction. Additionally it should be proved whether the DNA-synthesis of pancreatic islets, measured as [3H]-thymidine incorporation, is representative for the amount of cells during the S-phase (= "growth fraction"). There is a correlation between the incorporation of [3H]-thymidine into the TCA-precipitate and the labelling index of islets determined on HE-stained radioautographs. For this reason and because of being less time-consuming, the measurement of DNA synthesis is a suitable screening method for selection of factors increasing the growth fraction of pancreatic beta-cells. Only the addition of FGF-S3 (growth stimulating raw prepared isolated from bovine brain) during culture caused a significant increase of DNA synthesis and labelling index of the islets. The labelling index of radioautographs stained by immunofluorescence method for insulin did not differ significantly from that determined at HE-stained radioautographs. Insulin secretion and content of the islets were not influenced by the addition of FGF-S3.

Differential expression of genes involved in the calcium homeostasis in masticatory muscles of MDX mice.

Duchenne Muscular Dystrophy (DMD) and its murine model, mdx, are characterized by Ca(2+) induced muscle damage and muscle weakness followed by distorted dentofacial morphology. In both, DMD patients and in mdx mice, could be proven so far that only the extraocular muscles (EOM) are not affected by muscular dystrophy. The EOMs are protected against calcium overload by enhanced expression of genes involved in the Ca(2+) homeostasis. We could recently demonstrate that masticatory muscles of mdx mice are differentially affected by muscle dystrophy. The dystrophic masseter and temporalis shows muscle histology comparable to all other skeletal muscles in this animal model, whereas dystrophic tongue muscles seem to develop a milder phenotype. Due to this fact it is to hypothesize that an altered Ca(2+) homeostasis seems to underlie the mdx masticatory muscle pathology. Aim of this study was to examine the mRNA and protein levels of the sarcoplasmic reticulum Ca(2+) ATPases SERCA1 and SERCA2, the plasma membrane Ca(2+) ATPases Atp2b1 and Atp2b4, the sodium/calcium exchanger NCX1, the ryanodine receptor 1, parvalbumin, sarcolipin, phospholamban and the L-type Ca(2+) channel alpha-1 subunit (Cacna1s) in Musculus masseter, temporalis, and tongue of 100 day old control and mdx mice. In mdx masseter muscle significant increased mRNA levels of NCX1 and Cacna1s were found compared to control mice. In contrast, the mRNA amount of RYR1 was significant reduced in mdx temporalis muscle, whereas ATP2b4 was significant increased. In mdx tongue a down-regulation of the ATP2b1, sarcolipin and parvalbumin mRNA expression was found, whereas the phospholamban mRNA level was significantly increased compared to controls. These data were verified by western blot analyses. Our findings revealed that mdx masticatory muscles showed an unequally altered expression of genes involved in the Ca(2+) homeostasis that can support the differences in masticatory muscles response to dystrophin deficiency.

[Will telemonitoring be adopted by patients with chronic heart failure?]. / Wird Telemonitoring von Patienten mit chronischer Herzinsuffizienz angenommen?

BACKGROUND: Remote Patient Management for chronic heart failure (CHF) is gaining increasing importance in health care. Telemonitoring is defined as daily measuring of health parameters by the patient and their transmission to a telemedical centre. The adherence of this action by the patient can be considered as a measure for RPM adoption. METHODS: The randomized controlled clinical trial TIM-HF (NCT 00543881) was conducted between 2008 and 2010 with 710 CHF patients with the primary endpoint total mortality for a mean follow-up of 21.5 ± 7.2 months. The non-prespecified analysis of adherence to daily measuring of ECG, blood pressure, weight and self-assessment was focused on sociodemographic and disease-related factors of the 354 RPM patients. RESULTS: The mean adherence to telemonitoring was more than 80% (absolute adherence: 81.8 ± 22.8%, relative adherence: 88.9 ± 21.5%). From the beginning of treatment 6.5% of the patients (23/354) have shown an adherence below average. The high adherence of the majority of the patients was stable for the entire study duration and irrespective of age, sex, severity of the disease and the presence of mild to moderate depression. CONCLUSION: A high adherence can be achieved by individual training of the patient regarding the handling of his disease, the use of telemedical devices and an easy-to-use telemonitoring system. The majority of the informed self-determined CHF patients NYHA class II/III are adopting telemonitoring and are adherent in the long term.

[The intracranial meningioma - therapeutic possibilities and limitations]. / Das intrakranielle Meningeom - Therapeutische Möglichkeiten und Grenzen.

Meningiomas are common intracranial tumours that arise from arachnoidal cells. Clinically they often manifest by headache, focal or generalized seizures, or neurologic deficits as a result of brain compression. More than 90 percent of these mostly slow growing meningiomas are benign. In symptomatic patients a resection should be performed with the intention to cure or at least alleviate symptoms. In cases of subtotal resection an adjuvant radiotherapy should be deliberated. Stereotactic radiotherapy as initial treatment is an effective alternative for meningiomas, especially in patients not suitable for surgery due to various reasons. In patients that are refractory to treatment or with unresectable disease a hormonal- or chemotherapy can be considered.

In vivo investigation of the inflammatory response against allylamine plasma polymer coated titanium implants in a rat model.

Titanium (Ti) is an established biomaterial for bone replacement. However, facilitation of osteoblast attachment by surface modification with chemical groups could improve the implant performance. Therefore, this study aimed to evaluate the effect of a plasma polymerized allylamine (PPAAm) layer on the local inflammation in a rat model. Three series (RM76AB, RM78AB, RM77AB) of PPAAm-treated Ti plates were prepared using different plasma conditions. Twelve male LEW.1A rats received one plate of each series and one uncoated control plate implanted into the back musculature. After 7, 14 and 56 days, four rats were euthanized to remove the implants with surrounding tissue. Total monocytes/macrophages, tissue macrophages, T-cells and MHC-class-II-positive cells were morphometrically counted. On day 14, the macrophage/monocyte number was significantly higher for the controls than for the PPAAm samples. On day 56, the RM76AB and RM78AB samples had significantly lower numbers than RM77AB and the controls. The same was found for the tissue macrophages. No change over time and no differences between the implants were found for the T-cells. For the number of MHC-class-II-positive cells, a significant decrease was found only for the RM78AB implants between day 14 and day 56. Physico-chemical analysis of the PPAAm implants revealed that the RM77AB implants had the lowest water absorption, the highest nitrogen loss and the lowest oxygen uptake after sonication. These results demonstrate that the PPAAm samples and the controls were comparable regarding local inflammation, and that different plasma conditions lead to variations in the material properties which influence the tissue reaction.

Morphological evaluation of bone defect regeneration after treatment with two different forms of bone substitution materials on the basis of BONITmatrix.

In the design of biomaterials for therapeutic application the evaluation of cellular/tissue responses play a key role. In this study, the in vivo bone-regenerative capacity and resorption of granular BONITmatrix and a paste-like bone substitution material on the basis of BONITmatrix were investigated in a rat cranial defect model. The results obtained with both biomaterials were compared to each other. For these, the paste-like composite and the granular BONITmatrix were implanted in adult male WOK-W rats, the skulls were harvested after eight weeks, and histopathological examinated. The comparison of the both tested biomaterials showed that the paste-like composite is much better to handle, the resorption of the material and the ossification process is much faster than those of granular BONITmatrix. The amount of newly formed bone was also measured and more bone formation was found in bone defects filled with the paste-like composite compared to those with granular BONITmatrix. The present study showed that both biomaterials could stimulate bone regeneration, but the paste-like composite leads in comparison to granular BONITmatrix to an accelerated more comprehensive bone regeneration.

[Pain reduction after cervical spine surgery. Outcome after implantation of a cervical wing cage in degenerative diseases of the cervical spine--a prospective study]. / Schmerzreduktion nach Operation an der Halswirbelsäule. Ergebnisse nach Implantation eines zervikalen Wing-Cages bei degenerativen Halswirbelsäulenerkrankungen -- eine prospektive Untersuchung.

AIM: Surgery in cervical spine disease using titanium cages is a common procedure to reduce the pain and neurological deficits. This study was aimed to evaluate the results in pain reduction using the wing cage intraoperatively. METHOD: In this prospective study demographic data were noted, whereas special emphasis was placed on pain, which was noted using a visual pain scale and the prolo score, neurological deficits and the causing pathology. Furthermore, questions about the use of analgesics and the duration of pain were asked. After operation with insertion of a wing cage instead of the disk, a neurological investigation 6, 12 and 24 months later was done to evaluate the postoperative status. RESULTS: 54 patients underwent a cervical discectomy in 64 segments as therapy for neck pain or a radiculopathy caused by osteochondrosis or disc disorder. Patients with brachialgia profited most from the operation. Less improvement was seen in cases of osteochondrosis or combined pathology. CONCLUSION: Patients with pain caused by discs in the cervical spine, have better improvement than patients with other pathologies. This should be taken into account when choosing the mode of therapy.

Abnormal myomuscular junctions and AChE in a congenital neuromuscular disease.

We studied a patient with a congenital neuromuscular disease clinically characterized by ophthalmoplegia, slight limb muscle weakness, and normal electromyography. In the muscle biopsy, there were frequent examples of interdigitation of areas of muscle and extracellular spaces giving a fragmented appearance to muscle fibers. These structures resemble myomuscular junctions; acetylcholinesterase activity was present in the vicinity of these structures and on the muscle cell surface.

Prospective investigations of long-term normoglycaemic BB/OK-rats: serial determination of glucose tolerance, insulitis, B-cell volume density and pancreatic insulin content.

Pancreatic tissue was obtained by repeated surgical biopsies from BB/OK rats (n = 62), which maintained normoglycaemia up to 250 days. The tissue was used to determine pancreatic insulin content, islet volume density, pancreatic B-cell volume density and the presence of mononuclear cell infiltrations within and around pancreatic islets (insulitis). The BB/OK rats were also characterized by determination of glucose tolerance. In 50 d old BB/OK rats lymphatic infiltration of pancreatic islets are rare. The mean value of relative B-cell volume density amounted to 0.71 +/- 0.05% and the pancreatic insulin content was 21.31 +/- 1.29 pmol/mg wet weight. 70 d old BB/OK rats are characterized by an identical relative B-cell volume density and pancreatic insulin content, although in 70% of the animals an invasion of immunocytes could be observed. At an age of 90 and 120 d the BB/OK rats were characterized by an increased number of islets having insulitis accompanied by a decrease of pancreatic insulin content and B-cell volume density. The individual evaluation of the investigated BB/OK rats revealed in each animal the presence of insulitis accompanied by a decreased B-cell volume density and a diminished pancreatic insulin content. Animals older than 120 d do reenhance the pancreatic insulin content and B-cell volume density attended by an impairment of glucose tolerance. The results suggest that all BB/OK rats are characterized by a spontaneous pancreatic B-cell destruction, which was arrested and/or interrupted in the animals maintaining normoglycaemia up to 250 d.

Different lymphocyte subset distribution within "insulitis" islets of normoglycaemic and prediabetic BB/OK rats of similar age.

The fact that insulitis occurs also in normoglycaemic BB rats led us to investigate the phenotypes of lymphocytes invading the pancreatic islets of prediabetic BB/OK rats in comparison to age- and sex-matched normoglycaemic animals in a retrospective analysis. By using a panel of monoclonal antibodies we investigated the number of pan T-cells, T-helper cells, cytotoxic T-cells and NK-cells and determined the number of activated cells by measurement of class I, class II and IL-2 receptor positive cells. The bound primary antibodies were visualized using the APAAP-technique. The prediabetic rats showed a significantly decreased pancreatic insulin content which was drastically reduced at diagnosis of diabetes. This was accompanied by reduction of the B-cell volume density. The prediabetic as well as the long-term normoglycaemic BB rats showed an accumulation of mononuclear cells (all phenotypes investigated) within the pancreatic islets. Concerning the phenotypes of infiltrating cells there was no qualitative difference between long-term normoglycaemic and prediabetic rats but quantitatively an enhanced amount of W3/25+, OX-8+, OX-6+ and ART-18+ cells could be observed in the prediabetic animals. From our results we conclude that an immunological B-cell destructive process occurs also in long-term normoglycaemic BB rats by participation of mononuclear cells qualitatively not different from those observed in prediabetic animals. Activated T-cells (OX-19+, OX-8+, W3/25+) expressing class II antigens (OX-6+) and the IL-2 receptor (ART-18+) seem to play a significant role in the amplified immunological pancreatic B-cell destruction.

Pregnancy-associated changes in the endocrine pancreas of normoglycaemic streptozotocin-treated Wistar rats.

The effect of pregnancy on pancreatic insulin content and relative B-cell volume has been studied in normoglycaemic Wistar rats treated with streptozotocin 14 days before mating. A single intravenous injection of streptozotocin (30 mg/kg body weight) caused a significant reduction of pancreatic insulin content and B-cell volume. The islet insulin content was 60% of control values. However, pregnancy-associated adaptation was preserved in these streptozotocin-treated animals. Plasma insulin levels, pancreatic insulin and B-cell volume were significantly enhanced compared with non-pregnant rats investigated on the same date. The incorporation of [3H]-thymidine into islets from pregnant rats (day 10.5) was higher than that in islets isolated from non-pregnant animals. After delivery insulin content and B-cell volume returned to pre-pregnant values. Also during a longer period after streptozotocin treatment (156 days), no measurable enhancement of B-cell volume and pancreatic insulin content was observed indicating the unresponsiveness of residual B cells to compensate spontaneously for the loss despite persisting normoglycaemia.

The long-term culture of encapsulated pancreatic islets.

A new encapsulation technique, the formation of a polyelectrolyte complex membrane from sodium cellulose sulphate and a polycationic solution (polydimethyldiallylammoniumchloride) can be used for culturing pancreatic islets. After 5 weeks of culture, such encapsulated islets were morphologically well preserved, and parameters of cell viability and functionality such as DNA content and DNA synthesis, insulin content and stimulated insulin release were not different between the encapsulated and non-encapsulated control islets. A lower insulin secretion into the medium of the encapsulated islets during the first 3 weeks of culture can probably be explained by the capsule diameter (4-5 mm) and should be improved using microcapsules with a diameter of less than 1 mm.