A case of thrombotic thrombocytopenic purpura refractory to plasma exchange.

We experienced a case of thrombotic thrombocytopenic purpura (TTP) finally relieved after 74 sessions of plasma exchange (PE). The patient was a 56-year-old male. In August 1999, he was examined in emergency because of brown urine and a lowered level of consciousness. As TTP was suspected according to the laboratory findings of abnormally high lactate dehydrogenase and total bilirubin, decreased platelet counts, and numerous fragmented erythrocytes, he was admitted to the ICU of our hospital. Immediately after admission, PE was started consecutively. Upon concomitant use of antiplatelet drugs and prostacyclin, the level of platelet counts recovered to 100,000/microl once, but decreased again. Thus, in addition to the PE, prednisolone and vincristine were administrated, which elevated the level of platelet counts to 200,000 to 300,000/microl. Since the erythrocyte fragmentation was noted frequently, PE was continued twice a week. From the 60th day of admission onward, however, his body temperature rose above 40 degrees C with a rapid increase of C-reactive protein. A blood culture detected methicillin-resistant Staphylococcus aureus (MRSA) which derived from a left lung abscess. During the course of anti-MRSA treatment, he presented acute renal failure and acute hepatic dysfunction, but survived because of the combined therapy. He was discharged on the 180th day of admission. These results suggest that a combined therapy of steroid and vincristine is effective to treat TTP refractory to PE, but careful attention should be paid to the complications caused by immunosuppression.

[Effect of concomitant therapy on adynamic bone disease].

PTH deficiency and/or skeletal resistance to PTH in uremia has been regarded the major cause of adynamic bone. Considering the pathogenesis, correction of hypercalcemia is the first management to increase PTH secretion. For that purpose administrating regimen of calcium-containing phosphate binder and active vitamin D sterols should be changed to prevent hypercalcemia. And it is also important to determine an adequate calcium concentration of dialysate for the stimulation of PTH secretion.

Double filtration plasmapheresis for the treatment of bullous pemphigoid: a three case report.

Bullous pemphigoid (BP) is an autoimmune disease caused by an antidermal basal lamina antibody. In recent years double filtration plasmapheresis (DFPP) has been reported to be an effective therapy for BP. We experienced 3 cases of BP treated by DFPP. DFPP resulted in an improvement in clinical symptoms and remission allowing a decrease in the required dose of corticosteroid. DFPP was found to be an effective treatment for all 3 patients without noticeable adverse events resulting from DFPP. From these results it is concluded that DFPP is worth considering as an option as treatment for BP patients who were unresponsive to conventional steroid therapy, those in whom corticosteroids should be reduced or discontinued because of complications such as diabetes mellitus and/or osteoporosis.

Plasma exchange for the treatment of human T-cell lymphotropic virus type 1 associated myelopathy.

A 55-year-old man was admitted to our hospital because of myelopathy. He had a history of chronic renal failure due to polycystic kidney disease at the age of 39, being treated by hemodialysis for 9 years with several blood transfusions for the treatment of renal anemia. After cadaver renal transplantation at the age of 48, he discontinued hemodialysis. At 50 years of age, he had pulmonary tuberculosis and tuberculous arthritis of the left elbow joint. He has experienced difficulty in walking since he was 48 years old, with mild dysuria. Gait disturbance gradually aggravated after that, and urinary retention was observed. When he was 55 years old, being human T-cell lymphotropic virus type-1 (HTLV-1)-positive in the serum and cerebrospinal fluid, he was diagnosed as having HTLV-1-associated myelopathy (HAM). As active steroid therapy was unapplicable because of the history of pulmonary tuberculosis and immunosuppression for transplanted kidney, a series of plasma exchanges (PE) was performed with fresh frozen plasma as a replacement fluid. After PE, dyskinesia of the left leg and dysuria subjectively and objectively improved. These results suggest that PE seems to be one of the therapeutic tools for the treatment of HAM.

A case of factor VIII inhibitor-positive acquired hemophilia treated by plasmapheresis.

We report on a case of factor VIII inhibitor-positive acquired hemophilia in which combined therapy of plasma exchange (PE) and steroids was effective. The patient, a 68-year-old man, had undergone hemodialysis since April 1998, due to chronic renal failure caused by diabetic nephropathy. The hemostasis of blood access sites gradually became difficult after the initiation of dialysis and the prolongation of activated partial thromboplastin time (APTT) (74.5 s), and a decrease in factor VIII (0.02%) and an abnormally high concentration of factor VIII inhibitor (111 U/ml) were found. Under the diagnosis of factor VIII inhibitor-positive acquired hemophilia, 3 consecutive PE were performed, followed by a large dose administration of gamma globulin. However, the effect of this therapy disappeared within 20 days. Then the PE therapy was performed again accompanied by pulse methylprednisolone therapy. After that, factor VIII inhibitor was suppressed and the patient's hemostatic defect continued to improve even after the reduction of the steroid dose. These results suggest that PE is very effective in treating factor VIII inhibitor-positive acquired hemophilia.

Dynorphin-(1-13): antinociceptive action and its effects on morphine analgesia and acute tolerance.

Antinociceptive actions and effects of intracerebroventricular (i.c.v.) dynorphin-(1-13) (DYN) on morphine (MOR) analgesia and acute tolerance were studied in male Sprague-Dawley rats. Antinociceptive effect against hind paw pressure was produced by 30 micrograms of DYN, but not by 0.5-10 micrograms. Acetic acid writhing was inhibited dose-dependently by DYN at the doses of 2-30 micrograms, and the order of potency of the anti-writhing effect was beta-endorphin > MOR > DYN >> Met-enkephalin. The anti-writhing effect of DYN that was partially antagonized by naloxone at 10 mg/kg, s.c. in MOR tolerant rats was the same as that in MOR naive rats. The anti-writhing effect of i.c.v.-MOR was increased synergistically by DYN. Continuous s.c. (6 mg/kg/hr) and i.c.v. (7.5 micrograms/rat/hr) infusion of MOR produced antinociception against hind paw pressure, which reached maximum (MAX) and attenuated thereafter during MOR infusion for 6 hr. The attenuation of antinociception was also produced during MOR infusion combined with multiple i.c.v.-injection of DYN. The MAX and area under the antinociceptive curve during MOR infusion was not affected by multiple injection of DYN, i.e., no effect of i.c.v.-DYN on the development of acute MOR tolerance induced by s.c.- and i.c.v.-infusion was observed. In conclusion, the anti-writhing effect of i.c.v.-DYN might not be mediated via mu-receptors, although DYN increased the anti-writhing effect of i.c.v.-MOR synergistically and the development of acute tolerance to MOR (i.c.v., s.c.) was not affected by i.c.v.-DYN.

Antinociceptive synergism between supraspinal and spinal sites after subcutaneous morphine evidenced by CNS morphine content.

Morphine antinociception after various administration routes was estimated by the tail-flick method in rats. The antinociceptive ED50 (AD50) values for i.c.v., i.t., i.c.v. + i.t. (4:1 dose ratio) and s.c. were 6.9 micrograms, 0.49 + 0.12 micrograms and 2.7 mg/kg, respectively. Isobolographic analysis of AD50 (except s.c.) suggested that concurrent administration of i.c.v. and i.t. morphine interacted multiplicatively to produce antinociception. Morphine content in the CNS after administration of AD50 morphine for each route was estimated. Isobolographic analysis of morphine content revealed that supraspinal and spinal morphine interacted multiplicatively to produce antinociception after i.c.v. + i.t. and s.c. administration. Comparison of the dose-response curves (i.c.v. alone, i.t. alone, various i.c.v. + fixed i.t., fixed i.c.v. + various i.t.) suggested that supraspinal and spinal morphine can potentiate the antinociception induced by the other site, and that they have almost equal importance in the antinociceptive synergism. These results provide direct evidence for the synergism between supraspinal and spinal morphine to play an important role in the antinociception of systemically administered morphine.

Adrenalectomy-induced potentiation of morphine analgesia: reversal by prednisolone.

Effects of adrenalectomy (ADX) on analgesic potency and morphine (MOR) content after SC administration of 3.5 or 7 mg/kg of MOR, and effects of prednisolone (PRED) on the ADX-induced effects were studied. ADX significantly potentiated MOR analgesia at both MOR doses, and PRED reversed the ADX-induced potentiation of MOR analgesia, ADX did not affect MOR content in brain and plasma after 3.5 mg/kg MOR, but significantly increased MOR content in brain and plasma after 7 mg/kg MOR, and PRED reversed the ADX-induced increase in the MOR content. Although the analgesic potency of 3.5 mg/kg MOR in ADX group was equipotent with those of 7 mg/kg MOR in sham-operated and PRED-treated ADX groups, MOR content in the former group was significantly lower than those in the latter two groups. These results suggest that ADX potentiates MOR analgesia through both mechanisms of the increased MOR content and the increased sensitivity to MOR, and that the lack of glucocorticoids participates in both of these ADX-induced effects.