Usefulness of laser-evoked potentials and quantitative sensory testing in the diagnosis of neuropathic spinal cord injury pain: a multiple case study.

STUDY DESIGN: A retrospective study. OBJECTIVES: The aim of this study was to investigate the contribution of laser-evoked potentials (LEPs) and quantitative sensory testing (QST) to the diagnosis of neuropathic pain in patients with spinal cord injury (SCI) and inconclusive magnetic resonance imaging (MRI) findings. SETTING: A multidisciplinary pain center. METHODS: QST (DFNS protocol) and Tm-YAG-laser stimulation of the skin were applied within the pain site corresponding with dermatomes of altered sensation. Available MRI scans were reviewed. RESULTS: Thirteen individuals (50±16 years) with SCI were examined. In four cases with no detectable neural lesion on MRI, all QST but three LEP were abnormal. In four patients with poorly defined spinal lesion on MRI, all QST but three LEP only were abnormal. In four cases where pain was not matching adequately with MRI lesions, all patients had abnormal LEP and QST. In one patient showing a spinal cord atrophy, LEP was normal but QST was abnormal. Findings supported the diagnoses at-level (n=5) and below-level (n=8) SCI pain. Spinothalamic tract function assessed by LEP was normal in three cases, but QST was abnormal in all cases. CONCLUSIONS: As QST is a psychophysical examination depending on patient cooperation, we suggest that the combination of QST and LEP might be a valuable diagnostic tool to detect lesions of the somatosensory system in a subgroup of patients with neuropathic spinal cord injury pain and inconclusive MRI findings.

Short lasting transient effects of a capsaicin 8% patch on nociceptor activation in humans.

BACKGROUND: At high concentration, the TRPV-1 agonist capsaicin de-sensitizes nociceptors and reduces the intra-epidermal nerve density. METHODS: We investigated the effects of a 5 × 10 cm capsaicin 8% patch on C- and A-delta-nociceptor activation in ten healthy subjects before and at days 1-3-7-21 after patch application. Thermal thresholds, infrared thulium-YAG laser-evoked potentials (LEP) and heat pain (numeric rating scale, NRS, 0-10), electrically induced pain (10 pulses, 1.5-fold pain threshold intensity, five randomized series of 5-10-20-50-100 Hz), and axon-reflex flare (laser Doppler imaging) were recorded. RESULTS: Thermal hypoesthesia developed upon capsaicin 8% treatment. Warmth detection thresholds increased at day 1-3, heat pain thresholds were increased by about 2.6 °C after day 3, and laser-evoked heat pain remained significantly reduced for 7 days. Axon-reflex flare responses (days 1-3), but not supra-threshold electrically induced pain were significantly reduced by the capsaicin patch. CONCLUSIONS: Axonal nociceptor function assessed by electrical excitability tests supplements threshold tests of nociceptive endings. The differential analgesic effects of 8% capsaicin patches may be attributed to the kinetics of capsaicin and the different depth of nociceptive nerve fibres, yet, the time course does not match the long-lasting analgesia observed in neuropathic pain patients treated with the same patch. WHAT DOES THIS STUDY ADD?: Axonal nociceptor function assessed by supra-threshold electrical excitability tests did not coincide with capsaicin-induced transduction changes supplementing threshold measures of terminal nociceptor endings. Threshold measurements do not reflect the sustained effect of pain relief seen in neuropathic pain patients. Capsaicin-sensitive nociceptors responsible for spontaneous pain are either not specifically tested with currently available sensory stimulation protocols or have higher capsaicin sensitivity or slower recovery under neuropathic conditions.

Pain assessment according to the International Spinal Cord Injury Pain classification in patients with spinal cord injury referred to a multidisciplinary pain center.

STUDY DESIGN: This is a retrospective study. OBJECTIVES: The aim of this study was to investigate the epidemiology of pain types in patients with spinal cord injury (SCI) according to the International Spinal Cord Injury Pain (ISCIP) classification. SETTING: This study was conducted in a multidisciplinary pain center. METHODS: Socio-demographic and clinical data were examined and ISCIP classification was applied. RESULTS: Sixty-six individuals (51±13 years) with SCI had pain, a lesion older than 5 years in 67% and a pain history older than 5 years in 54% of patients. According to the ISCIP classification, nociceptive pain was present in 58% (musculoskeletal pain) and 3% (visceral pain) of the patients. At-level, below-level neuropathic pain and other neuropathic pain were observed, respectively in 53, 42 and 5% of patients. Unknown pain type was found in 8% of patients. Patients with complete lesions showed significantly more frequent neuropathic pain (P=0.021) and more frequent at-level SCI pain (P=0.00) compared with those with incomplete lesions. Patients with paraplegia had more often at-level pain (P=0.00), whereas patients with tetraplegia reported more often below-level pain (P=0.00). Patients had severe pain (mean intensity: 8.2 (±1.6) on a 0 to 10 numerical scale) and showed high grades of pain chronicity. Mild to severe depression and anxiety were present, respectively in 53 and 56% of patients. The health-related quality of life was low. CONCLUSION: The use of the ISCIP classification in a clinical setting is mirroring the very complex pain situation in patients with SCI referred to a multidisciplinary pain center, and it might be an important step for adequate pain therapy.

Intracellular axonemes within ciliated cells in the tracheal epithelium of domestic pigs.

Extended aggregates of intracellular axonemal derivatives can be seen within the apical cytoplasm of ciliated cells of apparently healthy domestic pigs. Such alterations were observed in 15 out of 20 animals. Complete (9 + 2) or incomplete (8 + 2 - 5 + 2) intracellular axonemes were found which sometimes arose from mature, irregularly arranged kinetosomes. In addition, bundles of single microtubules and microtubular pairs were found. In previous investigations on the ciliated epithelium of different mammals, intracellular axonemes were investigated only under pathological or experimental conditions. Our findings indicate that these alterations also occur in healthy animals. The extended aggregates of intracellular axonemal derivatives are more likely to be due to a failure of ciliary maturation than to a degradation of incorporated mature cilia.

The technique of taking brush biopsies of the nasal mucosa for electron microscopy.

Patients suffering from symptoms suggestive of a disorder of mucociliary clearance should be subjected to electron microscopic examination of the ciliated respiratory epithelium. Provided that all crucial points regarding technique and storage are adhered to, brush biopsy of the nasal mucosa is a reliable method facilitating the electron microscopical diagnosis of primary disorders of the ciliated epithelium.

Ultrastructural localization of microtubule-associated proteins (MAP) 1 in cilia of the respiratory tract.

The presence and localization of high molecular weight microtubule-associated proteins of the MAP 1 class in ciliated cells of porcine and rat respiratory tract was studied by immunoblotting and immunoelectron microscopy. Ciliary shafts of the porcine tracheal epithelium were isolated using a method that minimizes contamination of the preparation by other cellular fragments and fat. Immunoblotting with rabbit antibodies to bulk MAP 1 from hog brain clearly revealed the presence of anti-MAP 1-immunoreactive high molecular weight proteins of the MAP 1 size in these preparations. To localize MAP 1 proteins at the ultrastructural level, rat and porcine tracheal epithelia were embedded in LR White and subjected to immunogold electron microscopy. Anti-MAP 1-immunoreactive material was found at ciliary shafts and basal bodies, but not at basal feet or ciliary rootlets. Interestingly, the necklace region between the shaft and the basal body of the cilium was hardly reactive with anti-MAP 1 antibodies. This may indicate a reduced stability of ciliary microtubules in this region and could be an explanation why ciliary shafts in general break more easily there than elsewhere.

Pathophysiology of the ciliated epithelium of the respiratory mucosa in humans. Disorders of ciliogenesis.

If we want to interpret morphological alterations of the ciliated epithelium of the respiratory tract, we have to consider the physiological differentiation of ciliated cells and cilia. For this, we suggest a system in which disorders are distinguished at three distinct arrest levels of the ciliary development: (1) Disorders in the production of procentrioles (secondary centrioles) lead to partial or total aplasia of the ciliary apparatus. (2) Disorders in the development of kinetosomes from secondary centrioles result in a reduced number of cilia and malformations of ciliary components. (3) Disorders in the outgrowth of cilia result in morphological abnormalities of the peripheral ciliary shaft (i.e., immotile cilia syndrome). We suppose that at all three arrest levels hereditary factors may be important, whereas at levels 2 and 3 exogenous influences may cause these alterations too. Correlation between morphology and clinical status is made difficult by conditions of auxiliary mechanisms, like cough, which compensate the mucociliary dysfunctions. For the purpose of morphometric evaluation of the biopsies we established a method of light microscopical semiquantitative analysis of brush biopsies. The regenerative power of the ciliary apparatus with respect to these frequently observed abnormalities is discussed.

[Chronic dysplasia of the respiratory ciliary epithelium]. / Chronische Dysplasie des respiratorischen Flimmerepithels.

We report on a 14-year-old Turkish boy who suffered for more than seven years from recurrent pneumonia and bronchiectases. This led to the surgical removal of the left lower lobe. Brush biopsies taken from the bronchus and nose revealed severe dysmorphy of the ciliary epithelium with an altered cell-distribution of the normal surface pattern.

Amianthoid (asbestoid) transformation: electron microscopical studies on aging human costal cartilage.

The present study reports on the fine structure of human costal cartilage at different ages in order to obtain information on the morphogenesis of amianthoid fibers. Our results reveal an overall increase of collagen fibril diameter with increasing age, even in areas with no signs of amianthoid transformation. Ultrastructural evidence is presented that this increase in diameter is due to a gathering of the preexisting collagen fibrils. The age-related change in collagen fibril diameter is paralleled by changes in the composition and ultrastructural appearance of cartilage proteoglycans (as revealed by acridine orange staining). Acridine-orange-positive filaments indicative for proteoglycans are markedly reduced in size with advancing age in centrally located regions of costal cartilage. Treatment with testicular hyaluronidase previous to acridine-orange staining leaves these small proteoglycan filaments unaffected. By contrast, the filaments visible after acridine-orange staining in the extracellular matrix near to the perichondrium are susceptible to hyaluronidase treatment. Infrequently, a sharp increase in collagen fibril diameter can be observed in territorial matrix areas of degenerating chondrocytes. This observation is conspicuous at ages of 10 and 20 years. Amianthoid transformation is characterized by the appearance of collagen fibrils strictly arranged in parallel. These amianthoid fibers are embedded in a matrix rich in small acridine-orange-positive filaments similar to the proteoglycan filaments observed in centrally located matrix regions. It can be concluded that extensive remodelling not only of the collagen fibrils but also of the cartilage proteoglycans is involved in the development of amianthoid transformation.

Glycocalyceal bodies--a marker for different epithelial cell types in human airways.

The surface epithelium of the mucosa of the nose, sinus maxillaris, trachea and bronchi of the human respiratory tract has been investigated with respect to surface differentiations, glycocalyx and glycocalyceal bodies. The luminal surface mainly is formed by ciliated, undifferentiated, and secretory cells; occasionally metaplastic epithelial regions, composed of flattened squamous cells are found. Ciliated cells as well as differentiating progenitor cells, recognizable by branched, microvillus-like surface differentiations - 'cytofila' which on mature ciliated cells are interposed between the cilia, exhibit a delicate glycocalyx. On the contrary, secretory, undifferentiated, and metaplastic squamous cells possess unbranched microvilli of different length and diameter, and exhibit a prominent glycocalyx of varying, individual expression. These latter cell types, in healthy control persons as well as in patients suffering from different diseases, showed glycocalyceal bodies. By means of the high number of investigated samples, more than 350, the occurrence and distribution of glycocalyceal bodies could be defined more exactly: in all investigated regions of the human respiratory tract--nose, sinus maxillaris, trachea, and bronchi--glycocalyceal bodies were found at the apical surface of undifferentiated cells, secretory cells, and metaplastic squamous cells; ciliated cells and their differentiating progenitor cells never showed glycocalyceal bodies; glycocalyceal bodies were found likewise in healthy control persons as well as in patients suffering from different diseases of the airways.

Histochemistry of the extracellular matrix of aging hyaline cartilage.

Cartilage proteoglycans (PGs) exhibit marked structural changes with increasing age. There is an increase in small PGs rich in KS as compared to larger PGs rich in chondroitin sulfate (CS) with increasing age. In the present study investigations have been performed to obtain more detailed information about the distribution of different glycosaminoglycans (GAGs). Changes were observed in the interterritorial matrix by means of ultrastructural visualization of PGs with acridin orange. The changes in the ultrastructural organization of the interterritorial matrix of costal cartilage are followed by significant changes in its mechanical properties.

Lectin-binding affinities of the epithelium in the respiratory tract. A light microscopical study of ciliated epithelium in rat, guinea pig, and hamster.

Complex carbohydrate components of surface coat and secretory granules were investigated in the laryngo-tracheo-bronchial epithelium of 3 laboratory animals (rat, guinea pig, and Syrian hamster). 2 groups of epithelial cells were distinguished in the light microscope: ciliated cells and non-ciliated cells. The latter mainly represent secretory cells and are subdivided into serous and mucous secretory cells. Apical glycocalix: In the rat, ciliated cells possess a significant number of Con A, RCA I, and WGA receptors, and a smaller number of UEA I binding sites. In hamsters and in guinea pigs additional binding sites for HPA could be demonstrated. The apical glycocalix of the non-ciliated cells in the rat evince marked staining with RCA I, WGA, and HPA, and less intensive binding of UEA I. In guinea pigs and in hamsters, the presence of additional Con A receptors was noted. Basolateral glycocalix: The basolateral surface coat of ciliated and non-ciliated cells shows identical lectin binding affinities. In the rat, the basolateral glycocalix binds RCA I; in the guinea pig, in addition, positive staining with UEA I and HPA is observed; in the hamster, the basolateral surface coat is outlined by RCA I and HPA receptors. Secretory products: Secretory granules of mucous cells in the rat react with Con A, UEA I and HPA lectins. In guinea pigs, these substances also bind RCA I and WGA lectins. Mucous granules in the secretory cells of the hamster are positive for Con A, RCA I, and HPA lectins. Granules of non-ciliated serous cells of rats bind Con A, UEA I, and HPA lectins. In the guinea pig, this reaction is weaker for UEA I lectin but comparable for Con A and HPA binding. A positive reaction with RCA I lectin only is found in the serous secretory granules of the hamster.

Light and electron microscopic identification of elastic, elaunin and oxytalan fibers in human tracheal and bronchial mucosa.

The elastic fiber system in the human tracheal and bronchial mucosa was studied by light and electron microscopy. Elastic fibers, elaunin fibers, and oxytalan fibers were discerned. These fibers were identified by means of their staining characteristics (elastica stains, methods for disulfide-groups) and on account of their fine structural morphology. Elastic fibers consist of elastin and few "elastic-fiber microfibrils". The relative amount of elastin (compared to the amount of elastic-fiber microfibrils) is large in elastic fibers but small in elaunin fibers. Oxytalan fibers - by contrast - are pure bundles of microfibrils. In the light microscope a well-defined elastic lamina separates the lamina propria and the submucosa of the normal mucous membrane. The elastic lamina is formed by coarse strands of longitudinally running elastic fibers. A delicate network of elastica-positive fibers is attached to the basement membrane of the epithelial layer (subepithelial elastic layer). A few of these elastica-positive fibers branch out, traverse the region of the thickened basement membrane, and insert into the basal lamina of the epithelium. A loose network of elastica-positive fibers is present both in the lamina propria and in the submucosa. Plates of cartilage, glandular epithelium, and bundles of smooth muscle cells are enveloped by delicate elastica-positive fibers. Electron microscopy shows the lamina elastica to be predominantly composed of elastic fibers, whilst elaunin fibers form the subepithelial elastic layer. Fibers penetrating the thickened basement membrane of the epithelium are identified as oxytalan fibers. All three types of fibers are present throughout the lamina propria and in the submucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Conservation of veins with preservation of viable endothelium.

The influence of cryoprotective agents on the endothelium of jugular veins of dogs was examined after silver staining on en face preparations. Comparatively low concentrations of Glycerol or DMSO caused distinct morphological changes. Quick-freezing of air-filled vessels by liquid nitrogen permitted reservation of vessels with vital endothelium and comparatively mild morphological changes. Such vessels could be replanted after quick thawing. 2-4 days thereafter the endothelium of the grafts contained nuclei stainable with hematoxilin. The area covered by this endothelium remained devoid of parietal thrombi 2-4 days after replantation. However, lyophilized vessels grafted under the same conditions, were covered by large mural thrombi 2-4 days after the grafting procedure and no endothelial cells were found histologically.

[Activation and cell-aggregation of mononucleus cells after short-term stimulation with mitogen and tuberculin]. / Aktivierung und Zellaggregation mononukleärer Rundzellen nach einer Kurzzeitstimulation mit Mitogenen und Tuberkulin. Mit 8 Abbildungen.

The aim of the study was the description of morphological changes in mononukleated cells after short-term stimulation by mitogen and tuberculin visible by light- and electronmicroscopy and in differences between nucleus areas measured by planimetry. Already 1 hr. after p.h.a. stimulation lymphocytes forme clusters in which the mononucleated cells were present mostly as irritated and exhausted cells. In PPD-stimulated lymphocytes clusters were formed after 16 to 24 hrs. These cells were activated. Within clusters strong intercellular contacts were visible using the electron-microscopy. The results of planimetry in regard to nucleus areas of lymphocytes and monocytes were significantly dependent from the kind of mitogen or antigen and the duration of incubation time (analysis of variance).

[Myocardial involvement in a special form of Erb's muscular dystrophy (type Becker-Kiener) (author's transl)]. / Herzmuskelbeteiligung bei einer Sonderform der Erbschen Muskeldystrophie (Typ Becker-Kiener).

A 22-year-old man with cardiac symptoms had been treated for myocarditis for two years. But the clinical course and special tests, including isoenzyme measurements, electromyography, peripheral muscle and myocardial biopsy, established the diagnosis of X chromosome-linked muscular dystrophy (type Becker-Kiener) with an associated cardiomyopathy (raised left-ventricular end-diastolic pressure). Light- and electron-microscopic studies of the (right ventricular) myocardial biopsy revealed degenerative changes like those seen in peripheral muscle.

[Teratologic-neurotoxicologic studies on biglumide (K-2004) and thalidomide]. / Teratologisch-neurotoxische Prüfung von Biglumid (K-2004) und Thalidomid.

Comparison of the teratogenic and neurotoxic influence of thalidomide with the new hypnosedative preparation Biglumide (K-2004) revealed significant differences. Malformations could be seen only after treatment with thalidomide. Some results concerning the thalidomide-treated group of animals could be interpreted as a retardation of development in the posterior root ganglia.