Passive transfer of autoimmune autonomic neuropathy to mice.

Autoimmune autonomic neuropathy (AAN) is an acquired, often severe, form of dysautonomia. Many patients with AAN have serum antibodies specific for the neuronal ganglionic nicotinic acetylcholine receptor (AChR). Rabbits immunized with a fusion protein corresponding to the N-terminal extracellular domain of the ganglionic AChR alpha3 subunit produce ganglionic AChR antibodies and develop signs of experimental AAN (EAAN) that recapitulate the cardinal autonomic features of AAN in man. We now demonstrate that EAAN is an antibody-mediated disorder by documenting sympathetic, parasympathetic, and enteric autonomic dysfunction in mice injected with rabbit IgG containing ganglionic AChR antibodies. Recipient mice develop transient gastrointestinal dysmotility, urinary retention, dilated pupils, reduced heart rate variability, and impaired catecholamine response to stress. The autonomic signs are associated with a reversible failure of nicotinic cholinergic synaptic transmission in superior mesenteric ganglia. Mice injected with IgG from two patients with AAN (of three tested) demonstrated a milder phenotype with evidence of urinary retention and gastrointestinal dysmotility. The demonstration that ganglionic AChR-specific IgG causes impaired autonomic synaptic transmission and autonomic failure in mice implicates an antibody-mediated pathogenesis for AAN. The antibody effect is potentially reversible, justifying early use of immunomodulatory therapy directed at lowering IgG levels and abrogating IgG production in patients with AAN.

[The mechanism of the action of local transrectal hyperthermia in treating prostatic adenoma]. / Mekhanizm deistviia lokal'noi transrektal'noi gipertermii v lechenii adenomy prostaty.

Local transrectal hyperthermia (LTH) was used to treat 139 patients with prostatic adenoma aged 54-86 if they did not demand urgent surgery. LTH mechanism of action was studied by blood rheology, immunity characteristics, prostatic tissue gentamycin concentrations, morphological alterations after hyperthermia followed by TUR and adenomectomy. Clinical evaluation covered dysuria dynamics, uroflowmetry values, quantitation of residual urine and measurement of the prostate. The patients combined adenoma with chronic prostatitis, acute urine retention, cystostomy fistula (43, 22 and 16 patients, respectively). A microwave electromagnetic hyperthermia unit "Yakhta-4M" made in Russia (434 MHz, 200 W) heated the prostate to 43-44 degrees C. Two procedures a week of 60 min duration were performed within 3-5 weeks. LTH results in reduced blood viscosity, has no effect on blood coagulation, enhances neutrophil phagocytic function inhibiting their metabolic activity without affecting humoral immunity, raises 2-fold gentamycin concentrations in the prostatic tissue compared to blood and urine levels. Histologically, LTH does not alter prostatic parenchyma, but induces structural shifts in the muscular and connective tissue of the stroma producing stabilizing action on acinar epithelium. Clinical picture was characterized by subjective improvement in 72% of those treated, by urination recovery in 70% of the patients. 73% of the latter experienced cystostomy drainage which rid them of the fistula without operation. In general, mechanism of LTH action is brought to improvement of microcirculation, enhancement of cellular phagocytosis with a tendency to prostatic tissue sclerosing and stabilization of growth of the glandular tissue.