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Objectives/hypothesis: The study investigates the effect of local injections of botulinum toxin type A (Botox) into the major salivary glands of the head in various states of hypersalivation. In particular, we studied pathological states with permanent as well as passing hypersalivation disorders and present new indications for local application of botulinum toxin to the salivary glands. Study Design: Retrospective clinical investigation. Methods: A total of 55 to 65 units of Botox were injected under sonographic control into the left and right parotid and submandibular glands of four patients with hypersalivation resulting from head and neck carcinoma, tracheostomy, and "idiopathic" hypersalivation disorder. At defined time intervals following injection, flow rate, total protein and immunoglobulin A content, and the enzymatic activities of amylase, acid phosphatase, and kallikrein were determined in the saliva. The patients were clinically examined to assess the severity of their symptoms, including sonographic control of the major salivary glands. Results: All four patients reported distinct improvement of their symptoms within 1 week after injection. Salivary flow rate had considerably dropped, whereas the concentrations of the salivary components were much increased. Sonography did not reveal any changes of the salivary gland parenchyma. Therapeutic side effects were absent. Conclusions: Treatment of hypersalivation by local injections of Botox into the salivary glands of the head is a reliable and efficient therapy without side effects for certain otolaryngological diseases, especially if injections are performed under sonographic control. Extension of this therapeutic concept to other indications is suggested. [ABSTRACT FROM AUTHOR]

Key words: intrathecal humoral immunity; JC virus; kidney transplantation; polymerase chain reaction; progressive multifocal leukoencephalopathy [ABSTRACT FROM PUBLISHER]

A computer-assisted method permits collection of large numbers of measurements of fibre profiles in electron micrographs of human sural nerve biopsies. The method is based on simultaneous demonstration of fibre calibre and of sheath thickness in terms of the g-ratio (quotient axon diameter/fibre diameter), and on the recalculation of all parameters for circular fibre profiles. The fibres of small and large diameters of human sural nerves were found to form separate populations with distinctly different trends for sheath thickness and also different patterns of maturation. Preliminary data in neuropathy show that this method gives a better distinction of the extent of damage to either of the two populations; it also permits assessment of the number of regenerating or remyelinating fibres. [ABSTRACT FROM AUTHOR]

Autoantibodies of the IgG isotype, specifically directed against intestinal alkaline phosphatase (IAP), occur transiently in the majority of sera from patients with acute bacterial infections. Sometimes they are observed in autoimmune diseases. Using a T cell proliferation assay, it was found that isolated peripheral blood mononuclear cells (PBMC) from IAP autoantibody (IAPA)-positive patients (n= 18) responded significantly to IAP, whereas proliferation could not be induced in PBMC from healthy donors (n = II). Significant stimulation of PBMC from patients (n = 11) was not obtained by use of transferring, a common autoantigen in humans, indicating the specificity of stimulation of IAP-reactive T cells. Furthermore, T cell proliferation was observed when a highly purified IAP fragment (CNBr 21) spanning amino acids 334-462 of the primary structure of IAP was used as antigen. Thus, it was shown that an immunodominant T cell epitope resides within the CNBr 21 fragment which also contains a discontinuous B cell epitope as evaluated previously. Double immunocytochemical staining of T cell depleted PBMC with IAP and an anti-human CD5 antibody allowed the detection of CD5+ B lymphocytes, which probably produce natural IAPA (nIAPA). These nIAPA-specific CD5+ B cells occurred with approximately the same frequency among T cell-depleted PBMC from healthy donors and those from patients. In contrast, IAPA-producing CD5- B cells were found in B cell-enriched preparations from patients, but not in those from healthy individuals. [ABSTRACT FROM AUTHOR]

Here, we present a case of a 64-year-old female suffering from a severe form of antibody-positive myasthenia gravis. Under an immunosuppressive regimen with cyclosporine A, she experienced an episode of thoracic herpes zoster followed by intense post-herpetic neuralgia. In order to avoid drug interactions as well as adverse effects of carbamazepine in myasthenia gravis, gabapentin was chosen for the treatment of neuropathic pain. Within a few days she noticed increasing weakness, but continued medication for 8 weeks as gabapentin was not identified as the hazardous agent by her physician. Acetylcholine receptor antibody levels remained unchanged, but increased decrement was observed clinically and in repetitive nerve stimulation. After withdrawal of gabapentin, she recovered quickly to her previous condition.

We sought to determine the activity of inhibiting and facilitating cortical circuits in areas surrounding a hand muscle motor representation in focal dystonia and in controls. In 15 patients with hand dystonia, 16 patients with blepharospasm, and age-matched controls, we applied suprathreshold transcranial magnetic stimuli with a figure-eight coil over the optimal representation of the relaxed abductor digiti minimi muscle of the dominant hand. Additional conditioning stimuli were given through a second figure-eight coil that was held either above the test coil or 2 cm or 4 cm apart in the anterior, posterior, lateral, or medial direction. We measured intracortical excitability in each of the nine positions of the conditioning coil. Intracortical inhibition was reduced in both patient groups at all conditioning coil positions. With both coils centered, the intracortical facilitation did not differ between patients and controls. After shifting the conditioning coil, the intracortical facilitation tended to be less diminished in patients than in controls, this difference between patients and controls was significant for the anterior, posterior, and medial 4-cm conditioning coil shift. Our results demonstrate decreased intracortical inhibition in the cortical hand muscle representation not only in patients with hand dystonia, but also in patients with blepharospasm. In addition, our findings in both patient groups show a trend toward a relatively increased intracortical facilitation in surrounding motor areas., (Copyright 2002 Movement Disorder Society)

Background: Hypersecretion disorders of the exocrine glands of the head and neck area are a therapeutic problem in the field of otorhinolaryngology. In the present study, we demonstrate the effectiveness of local injections of botulinum toxin A to block secretions of exocrine glands of the head and neck area., Patients and Methods: Four patients suffering from hypersecretion disorders received local injections of botulinum toxin A. Two patients suffered from disorders of the salivary glands: one presented an idiopathic hypersialorrhea and another a salivary fistula after parotidectomy. A third patient suffered from epiphora and a further patient presented severe hyperhidrosis on the pilose head region. In a retrospective clinical study, the outcome of therapy was evaluated by clinical examination and chemical parameters., Results: Clear blocking of secretion in the treated glands could be demonstrated in all four cases. Possible side effects of the treatment could not be observed., Conclusions: The present study was able to demonstrate a clear blocking of secretion of the exocrine glands of the head and neck region through botulinum toxin A, offering an improvement in therapy especially for the innovative indication of blocking the salivary glands of the head.

Matrix metalloproteinase-9 (MMP-9) and its specific inhibitor, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), were analysed by enzyme-linked immunosorbent assay (ELISA) and by zymography in serum and cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS). In contrast to patients with inflammatory diseases, MMP-9 levels were not elevated in CSF of ALS patients. In serum, however, compared to healthy donors, MMP-9 was significantly (p = 0.0003) increased up to levels as high as those of viral meningoencephalitis (VM) or bacterial meningitis (BM) patients. MMP-9 levels remained elevated during long-term observation of ALS patients. In the absence of an inflammatory response, the results indicate that the increase of MMP-9 in serum of ALS patients might be caused by upregulation of MMP-9 in denervated muscles or in degenerating peripheral nerves following motor neurone loss.

The human spongiform encephalopathies are a group of neurodegenerative disorders of unknown origin. They comprise a group of horizontally transmissible and genetically determined diseases. We present here a case of Creutzfeldt-Jakob disease with an unusually long clinical course, in which the prion protein was localized immunohistochemically. The generally accepted hypothesis on the pathogenesis of these diseases is the so-called 'prion-hypothesis'. The implications of this hypothesis are discussed and a short review of the literature is given.

The reactivity and specificity of locally produced cerebrospinal fluid (CSF) antibodies against antigens of Treponema pallidum were assessed by Western blotting in patients with clinical signs of parenchymal or meningovascular neurosyphilis. All nine patients showed local production of treponeme-specific antibodies in the central nervous system (CNS). In most of the patients serum and CSF antibodies were bound to the same antigens: the common treponemal 48/45 kDa protein and the putative specific T. pallidum protein in the range of 12-14 kDa. In some patients the intensity of staining obtained by CSF antibodies was higher than that derived from serum, indicating locally produced antibodies. In contrast to other more acute inflammatory CNS diseases, no expanded or different antigen binding of the CSF antibodies compared with serum antibodies was found in neurosyphilic patients. The results presented are discussed with regard to the role of the blood-brain barrier in antibody concentrations of CSF and serum.

A recently developed immunocytochemical antigen-binding sandwich test for the identification of specific activated B lymphocytes was applied to cerebrospinal fluid cells and peripheral blood mononuclear cells in patients with acute neuroborreliosis. Discrimination of antigen-binding phagocytes was achieved by double staining with monoclonal antibodies. Specific activated B lymphocytes were much more numerous in cerebrospinal fluid than in blood, showing great interindividual differences. When intrathecal immunoglobulin production was present, the number of specific activated B lymphocytes was also high. The specificity of all activated B lymphocytes ranged from 10% to 60% and was higher in the acute stage than after treatment.

Highly purified (less than 95%) eosinophilic granulocytes and myelin phagocytosing macrophages were isolated from enzyme digested mouse peripheral nervous tissue undergoing Wallerian degeneration by sequential centrifugation on Ficoll-Hypaque together with uncoated and immunoglobulin-coated sheep red blood cells. Isolation of eosinophils is a first step for further investigation of the role of these cells during Wallerian degeneration. Myelin phagocytes were found in the Fc receptor positive cell population, while undigested myelin and Schwann cells remained in the interphase.

Sciatic nerves undergoing Wallerian degeneration are subject to massive invasion by monocytes bearing Fc receptors. The present experiments were done to explore the potential role of the Fc receptors. The effect of suppressed immunoglobulin levels on the rate of Wallerian degeneration was studied in the n. medioulnaris of the chick and in murine sciatic nerve. In the avian model, total immunoglobulin production was eliminated by bursectomy. The mice were injected after birth with antibodies against IgM, causing a selective reduction of immunoglobulin M levels. Myelin degeneration was measured in both groups by computer-assisted line sampling and corrected for intrafascicular edema. In both models, there were only minor differences with the controls. Immunoglobulins, accordingly, do not seem to play a significant role in the efficiency of myelin phagocytosis by monocytes during Wallerian degeneration. The study also includes data on the degree and the distribution of edema in nerves undergoing Wallerian degeneration.

Milk-borne lactose levels were measured by means of a continuous automatic analyser on the basis of the o-toluidine method. The results obtained and the high accuracy thus established were verified by statistical calculation. The technique enables one single person to test 400 milk samples for lactose in one working day.

The neuropathy caused by a single dose of isoniazid in rats was studied with a computer-assisted morphometric method. Scatter diagrams of the g ratio (quotient fibre diameter/axon diameter) define regenerating fibres as a distinct population, distinguishable from the surviving fibres by reduced sheath thickness and reduced axon calibre. There was also evidence of a subtle direct toxic effect on the entire fibre population, causing axon shrinkage masked by readjustment of the myelin sheath.

The new approach used in this study is based on the concept that axon caliber is not the only factor affecting the thickness of the myelin sheath. It is necessary to consider the entire geometric proportions of the internode, since sheath thickness corresponds to the relationship between axon caliber and the length of the internode. This type of analysis was applied to the regenerated internodes in rat sciatic nerves. Survival periods of 4, 9, 18 and 36 weeks were studied after lesions had been placed in young adult rats. The data show significantly thinner sheaths for regenerated fibers as compared with normal nerves, consistent with previous observations. This reduction in sheath thickness, however, corresponded quantitatively to the degree of foreshortening of internodes in the regenerated nerves. An average reduction of 10 in the quotient internode length/fiber caliber corresponded to a reduction of about 0.015 in the relative thickness of the sheath (quotient axon diameter/fiber diameter). This means that regenerated myelin sheaths are not truly hypoplastic; rather, they are adapted to the reduced internode length, and have the same relationship found for normal fibers. In partially damaged nerves there was a clear distinction in terms of sheath thickness between regenerated fibers and undamaged fibers. Demonstration of this phenomenon by scatter diagrams opens new possibilities for the quantitative assessment of neuropathies.

Allogenic graft rejection leads to rapid tissue destruction of nerves transplanted directly into a muscle lodge. If the nerves are enclosed in 5.0 micron pore chambers and transplanted into the peritoneal cavity, there is no allogenic graft rejection. The phagocytosis of myelin by invading cells is, however, not disturbed, showing that these cells can distinguish the degenerating myelin from the Schwann cell without being responsive to the Schwann cell's allotype. If the allografts are allowed to predegenerate for 4 wk in 0.22 micron pore chambers which do not admit any cells, there is a striking mitigation of the allogenic graft rejection if the nerves are subsequently released from the chamber. Myelin phagocytosis in such nerves is also reduced. These observations indicate the existence of a hierarchy of cellular recognition mechanisms involved in nerve tissue degradation. Phagocytosis of the myelin sheath by macrophages involves recognition mechanisms which differ from those of the allogenic rejection of the Schwann cell, presumably mediated by T lymphocytes.

The thickness of the myelin sheath is known to increase with axon caliber, but there is also a superimposed, slight variation in sheath thickness depending on whether a fiber of a given caliber has very long or very short internodes. This relationship between myelin sheath thickness and the geometric proportion of the internode has been shown in subserial sections of isolated nerve fibers. It allows a prediction of sheath thickness from the quotient internode length/axon caliber, or conversely, a prediction of internode foreshortening from sheath thickness. We applied this new approach to the analysis of sciatic fiber populations of frogs, mice, rats and cats. The geometric proportions of these fibers were defined by the quotient internode length/fiber caliber. This quotient was compared with minor variation in sheath thickness as determined with a computer-assisted technique measuring large numbers of fibers in low-power electron micrographs. The method also calculated fiber shrinkage and recalculated all data for circular fiber profiles. The data obtained confirmed previous electron microscopic measurements showing that there is a slight reduction in sheath thickness when a fiber of a given caliber has relatively short internodes, and vice versa. A population of very thin, thinly myelinated fibers was also revealed. Sheath thickness and the geometric proportions of internodes in frogs differed markedly from those in mammals.

Described in this paper is an experimental milking kit by which to collect first quarter milking samples directly from the milk pipeline system during full operation of the milking parlor. Measurement of electric conductivity of milk samples thus collected during the milking process may provide information on the occurrence of subclinical mastitis in the herd concerned. Discussed are results obtained from comparative measurement of milk conductivity, indirect determination of milk cell counts, as well as from clinical udder checks and bacteriological milk tests in seven large herds.