Peripheral nerve lesions in HTLV-I associated myelopathy (HAM/TSP)

Peripheral nerve dysfunction (PND) was found in as many as 43% of our patients with human T-cell lymphotropic virus type I (HTLV-I)–associated myelopathy (HAM/TSP). To evaluate the PND further we biopsied the sural nerve in 6 patients. The histological features were varying degrees of demyelination, remyelination, axonal atrophy and degeneration, and perineurial fibrosis. “Globule” or “sausage” formation was prominent in two of the specimens. Inflammatory infiltrates were absent. No deposits of IgG, IgM, IgA, or complement were detected in the biopsies. No viral antigen or proviral DNA was detected. It is proposed that the PND and the histological findings noted are part of HTLV-I–associated disease and not an unrelated disorder. The pathogenesis of the PND remains unclear. There was no evidence of direct viral infection. The histological findings could represent primary changes induced by viral-triggered release of soluble factors, such as cytokines or secondary changes to more proximal disease, e.g., root involvement. © 1993 John Wiley & Sons, Inc.     

Nemaline myopathy: Histological,histochemical and ultrastructural studies

Summary Histological, histochemical and ultrastructural studies were performed on muscle biopsies from three siblings with congenital nemaline myopathy. Histological studies revealed type I fibre atrophy and type II fibre paucity. Ultrastructural studies of intramuscular nerves showed that the axonal diameters were very narrow compared with the width of myelin lamellae. Granular or membranous osmiophilic material occurred in the adaxonal Schwann cell cytoplasm and had a periodicity of 33–38Å. The neuromuscular junctions showed degenerative features such as glycogen granules or myelin figures in 27.1% of total terminal axons. The secondary synaptic clefts were markedly decreased in number and short in length. Myotendinous junction-like structures were found in 5.5% of the muscle fibres near the neuromuscular junctions, and often near sites of fibre-splitting. Rods in nemaline myopathy might be caused as a result of longitudinal splitting and disruption of fibres due to deficient regeneration of the muscle fibres associated with neurotrophic abnormalities.     

Secondary amyloidosis and eosinophilia in a patient with uterine leiomyosarcoma

We report a rare case demonstrating the relationship between secondary amyloidosis and uterine leiomyosarcoma. A 59-year-old female with high fever was referred to our hospital. Laboratory tests revealed increased white blood cells, eosinophilia and an accelerated erythrocyte sedimentation rate. Endoscopic examination of the stomach and colon revealed amyloid deposits in their mucosa. The patient showed no symptoms that suggested amyloidosis. No other organs or tissues were surveyed for amyloid deposition. Ga scintigraphy, computed tomography and magnetic resonance imaging suggested necrotic infectious leiomyoma of the uterus, which was considered to be the cause of the fever. The patient underwent total hysterectomy. The histological diagnosis of the mass revealed a low-grade uterine leiomyosarcoma with necrosis. Amyloid deposits in the gastric mucosa disappeared 1 year after the operation. In this case, amyloid deposition was detected by endoscopic biopsy before clinical manifestations. The deposition was reversible and was successfully treated. Thus, it is logical and useful to undertake endoscopic mucosa biopsy to check for amyloid deposition in patients with systemic inflammation, whose serum amyloid A protein level has been high for several months. In addition, peripheral eosinophilia was also detected in this case. Although eosinophilia associated with malignant tumor has been recognized, it is an uncommon occurrence.     

A case of cerebral infarction caused by disseminated intravascular coagulation during hepatic arterial infusion chemotherapy

A 73-year-old woman with liver metastasis underwent implantation of an infusion catheter-port system for hepatic arterial infusion chemotherapy. She developed multiple infarctions caused by disseminated intravascular coagulation (DIC) due to liver metastases. The hypercoagulability syndrome associated with cancer (known as Trousseau's syndrome) is considered a cause of cerebral infarction. Among the complications of the implantation of an infusion catheter-port system, Trousseau's syndrome may be one of the causes.     

Selective blockade of nicotinic acetylcholine receptors by pimobendan,a drug for the treatment of heart failure: reduction of catecholamine secretion and synthesis in adrenal medullary cells

Pimobendan, a Ca²⁺ sensitizer, is used clinically in the treatment of chronic heart failure. Although chronic heart failure is associated with activation of the sympathetic nervous system, it remains unknown whether pimobendan affects the function of sympathetic neurons and the adrenal medulla. Here, we report the inhibitory effects of pimobendan on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Pimobendan decreased the catecholamine secretion (IC₅₀=29.5 M) elicited by carbachol, an agonist at nicotinic acetylcholine receptors, but not that elicited by veratridine, an activator of voltage-dependent Na⁺ channels, or by high K⁺, an activator of voltage-dependent Ca²⁺ channels. Pimobendan also inhibited carbachol-induced influx of ²²Na⁺ (IC₅₀=25.9 M) and ⁴⁵Ca²⁺ (IC₅₀=26.0 M), but not veratridine-induced ²²Na⁺ influx or high K⁺-induced ⁴⁵Ca²⁺ influx. The reduction of catecholamine secretion caused by pimobendan was not overcome by increasing the concentration of carbachol. UD-CG 212, an active metabolite of pimobendan, lowered carbachol-induced catecholamine secretion with a concentration/inhibition curve similar to that of pimobendan. In experiments in situ, pimobendan suppressed both basal and carbachol-stimulated ¹⁴C-catecholamine synthesis (IC₅₀=5.3 and 4.9 M) from [¹⁴C] tyrosine [but not from l-3, 4-dihydroxyphenyl [3-¹⁴C] alanine ([¹⁴C]DOPA)], as well as tyrosine hydroxylase activity (IC₅₀=3.8 and 4.3 M). These findings suggest that pimobendan inhibits carbachol-induced catecholamines secretion and synthesis through suppression of nicotinic acetylcholine receptors.