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Biomedical subjects

C Meier

Publications and source records attributed to C Meier.

At least 145 records · Page 8Linked to original sources

[Polyneuropathy, organomegaly, endocrinopathy and skin changes in a case of solitary myeloma].

The case is reported of a 32-year-old woman with polyneuropathy, organomegaly, edema, endocrinopathy, dark skin and solitary myeloma with monoclonal gammopathy of IgG/lambda type. More than 100 cases of this rare disorder have been observed up to now, mainly in Japan. In recent reviews the terms POEMS-syndrome or Crow-Fukase-syndrome have been used. Local radiotherapy of the myeloma led to lasting regression of symptoms. Studies with immunocytochemistry and immunoelectroblotting revealed specific antibody activity against hypophysis, suggesting that the pathologic monoclonal myeloma antibodies may damage the neuroendocrinic centers in hypothalamus and hypophysis as the primary target. Most of the multisystemic symptoms would thus be explained as secondary alterations.

Adult↗

Neuropathy of vasculitic origin in a case of Garin-Boujadoux-Bannwarth syndrome with positive borrelia antibody response.

A 42-year-old man suffered from erythema chronicum migrans on different parts of the body after repeated tick bites. A few months after the last tick bite he developed a painful neuropathy in both legs with patchy disturbance of sensibility, mild weakness of the feet and loss of the right ankle jerk. Repeated determinations of antibodies against borrelia spirochetes revealed increasing IgG titres. Biopsy of the left sural nerve, which was clinically and electrophysiologically affected, showed a vasculitis of epineurial vasa nervorum and severe angiopathic lesions of the perineurium and the neural parenchyma. Parenteral high-dose penicillin treatment resolved the clinical symptoms.

Adult↗

Perhexiline-induced lipidosis in the dark Agouti (DA) rat. An animal model of genetically determined neurotoxicity.

Perhexiline maleate, an antianginal compound, may cause severe adverse effects such as weight loss, hepatic dysfunction and peripheral neuropathy in a small proportion of patients. Since present evidence suggests that poor debrisoquine hydroxylators are at risk, we designed an experimental study comparing its neurotoxic effects in dark Agouti (DA) rats, with poor hydroxylation of debrisoquine with that in Sprague Dawley (SD) rats, which are vigorous hydroxylators. Light and electron microscopic investigations revealed neurotoxic changes in DA rats after cumulative doses which did not cause any changes in SD rats. Although there was no evidence of hepatic disturbance, morphological examination disclosed a heavy lipid deposition in neurons of dorsal root and sympathetic ganglia in DA rats. This was correlated with increased plasma and tissue concentrations of the drug. The lipid accumulation was similar to that observed in man with perhexilene-induced neuropathy. Our results suggest that perhexilene neurotoxicity in the DA rat is related to a genetically determined impairment of hydroxylation. The DA rat may serve as an animal model for investigating the potential neurotoxicity of drugs which are metabolized by hydroxylation of the debrisoquine type.

Animals↗

[Polyneuropathy after cisplatin treatment].

Polyneuropathy developed in 7 of 87 women who had been treated with cis-platinum for ovarian carcinoma. Distal disturbances of sensitivity were clinically prominent, the emphasis being on disturbed vibratory perception and acrognosis. No relevant signs of motor dysfunction were noticed, neither clinically nor neurophysiologically. Sural biopsies taken from two women revealed a primary axonal degeneration, mostly affecting the myelinic fibres of large diameter. In 3 cases mild reversion was seen, and in 4 cases no definite reversion, of the disturbed functions - uncertain gait and clumsiness of the hands - during the follow-up period of 6 to 30 months.

Aged↗

Polyneuropathy in paraproteinaemia.

Paraproteinaemias are frequently associated with peripheral neuropathies. "Benign" paraproteinaemia, myeloma and Waldenströms macroglobulinaemia may present clinically as polyneuropathy. Therefore immunoelectrophoresis is strongly recommended in the routine diagnosis of polyneuropathies of unknown origin. Peripheral neuropathies associated with paraproteinaemia are clinically, electrophysiologically, pathologically and probably also pathogenetically heterogeneous. There are subgroups such as demyelinating neuropathy associated with IgM paraproteinaemia, which show quite distinctive features. This survey describes the different types of paraproteinaemia and their associated peripheral neuropathies. The incidence, pathogenesis and therapy of peripheral neuropathy associated with monoclonal gammopathies are discussed.

Aged↗

A monoclonal antibody that binds to both astrocytes and myelin sheaths.

A monoclonal antibody designated III 5H8 was shown to bind both to astrocytes and to myelin sheaths as studied with immunocytochemical techniques on brain sections and cell cultures. Binding to astrocytes was confirmed by double immunofluorescent labelling of frozen sections and cell cultures with anti-GFAP, and appeared to be sensitive to formalin treatment. Binding to myelin sheaths was confirmed by comparing sections labelled with III 5H8 with sections labelled with antibodies against axons and myelin basic protein as well as by staining of sections of hypomyelinated spinal cord with III 5H8. On immunoblots of separated white matter III 5H8 revealed two bands, while on immunoblots of purified myelin only one band was seen. The findings are discussed with respect to the function of astrocytes in white matter and shared antigenic determinants between astrocytes and oligodendrocytes.

Animals↗

Heterogeneity of congenital motor and sensory neuropathies.

Six children suffering from a congenital motor and sensory neuropathy (CMSN) are described. Severe muscle hypotonia, areflexia and a delay of motor development are detectable in all of them. Sural nerve biopsies exhibited an almost complete absence of myelinated fibres and a correspondingly slow nerve conduction velocity (NCV) of less than 10 m/s was detectable in four patients. A few segments with hypermyelination adjacent to gross hypomyelination were seen in the fifth patient, and the NCV was 15 m/s. The sural nerve of the sixth patient showed a loss of thick myelinated nerve fibres, and his NCV was 25 m/s. These results demonstrate the histological heterogeneity of CMSN which was already detected by the NCV. The relation of our findings to the classification of HMSN by Dyck and Lambert (1968) is discussed.

Child↗

Passive transfer studies in demyelinating neuropathy with IgM monoclonal antibodies to myelin-associated glycoprotein.

Serum or IgM fraction from two patients with a demyelinating neuropathy and IgM monoclonal antibodies to myelin-associated glycoprotein were injected in three different animal species. There were no clinical, electrophysiological or morphological signs of demyelination in either chronic or acute passive transfer experiments. These results suggest that the pathogenesis of this human demyelinating neuropathy may be more complex than has been assumed.

Animals↗

Refsum's disease: management by diet and plasmapheresis.

A case of Refsum's disease treated by serial plasma exchanges together with a moderate low phytanate diet is reported. Serial plasma exchanges determined a rapid significant clinical improvement (neuropathy and cerebellar ataxia) that allowed immediate return to full-time employment. The initial improvement could be maintained by intermittent serial plasmapheresis despite partial failure of the initially introduced low phytanate diet bringing 20 mg phytanic acid daily. A new dietary regimen bringing 10 mg phytanic acid was later introduced that was well tolerated. No liquid formula was used. The clinical improvement was clearly correlated to a fall in serum phytanic acid from 45.3 to 16.2 mg/100 ml.

Adult↗

Coronary artery bypass grafts. Influence of preoperative risk factors on the late postoperative course.

In order to assess the influence of preoperative risk factors on the late postoperative course, 186 consecutive patients in whom coronary artery bypass graft (CABG) was performed for chronic stable angina (169 men, 17 women, mean age +/- SD 54 +/- 8 years) were followed for an average of 54 (6 to 113) months. The overall five-year survival rate by life-table analysis was 90 +/- 2 percent. The postoperative course was considered favorable in 112 patients (60 percent) in whom angina was absent or improved by at least 2 NYHA classes throughout the entire follow-up, and was unsatisfactory in 74 patients. It was concluded that the late postoperative course of patients with CABG was unfavorably influenced by the presence of two or three risk factors, and a high preoperative cholesterol level was the only single risk factor associated with unsatisfactory outcome.

Adult↗

[Immunopathogenesis of polyneuropathies in paraproteinemia].

Polyneuropathies are the most common neurological complications of paraproteinemias . In many cases pathogenesis remains unclear. In two patients with chronic demyelinating neuropathy in IgM-paraproteinaemia subtle methods were applied ( immunoelectroblot and immunocytochemistry). It could be demonstrated that the pathologic antibodies in the patients' serum reacted specifically with an antigen in the sheath, the myelin-associated glycoprotein. These observations suggest an antibody-mediated immunopathogenesis of the patients' polyneuropathy and invite prospects for a rational treatment with immunosuppressive approaches.

Aged↗

Nemaline myopathy appearing in adults as cardiomyopathy. A clinicopathologic study.

We examined a 29-year-old woman with nemaline myopathy that appeared as cardiomyopathy. Clinical examination showed dilated cardiomyopathy, but no neuromuscular abnormalities of the skeletal muscles. Electromyography showed neither neurogenic nor myopathic abnormalities. A biopsy specimen from the quadripecs muscle showed typical nemaline bodies in about 50% of the muscle fibers. The patient died six months later of biventricular heart insufficiency. Autopsy revealed nemaline bodies in the working and conducting tissues of the myocardium. Earlier, the patient's mother and one of her sisters died unexplained, sudden deaths at the ages of 47 and 37 years, respectively. Sections of the myocardium taken from the sister at autopsy were available, and also disclosed nemaline bodies after restaining with trichrome.

Adult↗

Polyneuropathy in Waldenström's macroglobulinaemia: reduction of endoneurial IgM-deposits after treatment with chlorambucil and plasmapheresis.

A case of progressive polyneuropathy associated with Waldenström's macroglobulinaemia is reported. A monoclonal IgM-lambda gradient was detected in the serum and cerebro-spinal fluid. By electro-immunoblot analysis antibodies against myelin-associated glycoprotein were found in the serum and cerebro-spinal fluid. The motor and sensory conduction velocities of several peripheral nerves were markedly decreased, and examination of visual evoked potentials (VEPs) revealed pathological latencies. Sural nerve biopsies before and after treatment with chlorambucil and plasmapheresis showed nerve fibre loss and demyelination. In the pre-treatment biopsy, heavy accumulations of filamentous material were found which stained positively for IgM by immuno-cytochemistry. Such accumulations had disappeared in a biopsy performed after treatment. The morphological findings were correlated with an improvement of clinical and electro-physiological findings.

Chlorambucil↗

Demyelinating polyneuropathy associated with monoclonal IgM-paraproteinaemia. Histological, ultrastructural and immunocytochemical studies.

Histological, ultrastructural and immunocytochemical findings of sural nerve biopsies from 2 patients with monoclonal IgM-paraproteinaemia are presented. In both cases the pathological IgM antibodies reacted with a myelin antigen which was identified as myelin-associated glycoprotein (MAG) by immunoelectroblot . Histology and electron microscopy showed typical features of a chronic demyelinating neuropathy with accompanying axonal degeneration. Immunohistochemical studies demonstrated IgM in the vicinity of endoneurial vessels and on some of the myelinated fibres. The localisation of IgM on the myelin sheath showed a typical pattern, which was similar to that found in binding studies with the patients sera on control nerves. It resembled the characteristic immunocytochemical staining pattern of MAG. Binding studies with the patients' sera on human and canine CNS material exhibited a clear labelling of white matter and certain, as yet unidentified structures within the cerebral and cerebellar cortex. In mixed glial cell cultures, the sera of both patients bound specifically to oligodendrocytes. Our observations are interpreted as immunohistochemical evidence that the anti-MAG antibodies of the patients' sera had bound to their antigenic target in the peripheral nerves. Because the antibodies clearly react to central myelin, oligodendrocytes and other not yet identified cortical structures, CNS involvement in such disorders should be considered.

Aged↗

Tetrodotoxin-resistant release of 3H-noradrenaline from the mouse vas deferens by high intensity electrical stimulation.

Vasa deferentia of mice were preincubated with 3H-noradrenaline and then superfused with a medium containing cocaine 10 microM and phentolamine 30 microM. The tetrodotoxin-resistant outflow of tritium evoked by high intensity electrical field stimulation (0.5 Hz, 200 mA current strength, 2 ms pulse width) was studied and, in some experiments, compared with the tetrodotoxin-sensitive outflow evoked by low intensity electrical field stimulation (0.5 Hz, 50 mA, 1 ms). In contrast to the outflow evoked by low intensity stimulation, the outflow evoked by high intensity stimulation was increased in Na+-free medium, and was only partly dependent on the external Ca2+ concentration. The Ca2+-dependent fraction consisted mainly of 3H-noradrenaline. Again, in contrast to the outflow caused by stimulation at low intensity, that caused by stimulation at high intensity was not reduced by Mg2+ 20 mM, Co2+ 5 mM or normorphine 40 or 100 microM, and was not enhanced by tetraethylammonium 5 mM or 4-aminopyridine 1 mM. It is concluded that high intensity electrical stimulation elicits a tetrodotoxin-resistant, calcium-dependent release of noradrenaline which differs in mechanism from the release elicited by action potentials.

4-Aminopyridine↗