Incapacitating autonomic neuropathy precipitated by taxol.

Taxol is one of the more significant advances in cancer chemotherapy in the last 10-15 years with a 30-50% response rate in both breast and ovarian cancers. The toxicity profile of taxol is still evolving as changes in the dosing and scheduling of the drug are instituted. We herein present the first evidence of taxol-induced quantifiable, objective autonomic neuropathy in two patients, one with and one without diabetes. The patients did not have symptoms of autonomic dysfunction prior to taxol therapy. Both developed severe orthostatic hypotension following completion of 24-hr infusional taxol at 170-250 mg/m2 and both improved markedly on fludrocortisone. Other possible etiologies of orthostatic hypotension were ruled out. Noninvasive autonomic tests performed on the first patient included tilt test, Valsalva ratio, heart rate variation with respiration, and change in diastolic blood pressure with hand grip; all were markedly abnormal. Noninvasive autonomic tests should be considered as part of the evaluation of patients on taxol who develop generalized weakness and orthostasis.

Neuromuscular junction development in the cutaneous pectoris muscle of Rana catesbeiana.

Synaptic specializations were studied in the developing cutaneous pectoris muscle of Rana catesbeiana tadpoles and froglets to correlate nerve terminal morphology (by light and electron microscopy), accumulation of acetylcholine receptors, and the ability of the muscle to contract following nerve stimulation. This correlated approach was used to determine the developmental timing and possible causal relationship of events in nerve and muscle maturation at the neuromuscular junction. Initially, the cutaneous pectoris nerve trunk was present in the undifferentiated presumptive cutaneous pectoris mesenchyme, prior to muscle maturation. At stage XII when the muscle was first able to contract weakly in response to nerve stimulation, the motor nerve terminal endings were simple bulbous enlargements associated with diffuse subneural aggregations of acetylcholine receptors (indicated by diffuse speckles of rhodamine alpha-bungarotoxin fluorescence). Before stage XII no rhodamine alpha-bungarotoxin fluorescence was present anywhere in the muscle. The first stage in the organization of acetylcholine receptors at the neuromuscular junction was the accumulation of diffuse speckles of fluorescence beneath the terminal enlargements. This was followed by the clustering of receptors into small polygonal areas at each synaptic site, and finally the organization of receptors into parallel linear rows. Presumably this final stage was associated with formation of junctional folds. By stage XV the synapses were multiply innervated and had developed acetylcholinesterase activity. The general nerve terminal morphology and pattern of accumulation of acetylcholine receptors at cutaneous pectoris neuromuscular junctions were similar to those of the adult throughout metamorphic climax except that they still contained more than one motor axon. After metamorphic climax, elimination of multiple innervation occurred.