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[Effect of cepharanthin on radiotherapy induced leukopenia].

Cepharanthin, a kind of alkaloid, has been reported to show a protective effect for leukopenia induced by radiation therapy. In this study, one of three kinds of drugs, Cepharanthin, S-Adchnon (adrenochrome derivative) and Hythiol (L-cysteine), was randomly administered to 94 patients with cancer of the head and neck, the uterine cervix and the lung, during the course of radiotherapy. When Cepharanthin was given, 81.3% of the patients were protected from leukopenia, compared with 51.6% in S-Adchnon and 32.3% in Hythiol. It is suggested that prophylactic use of Cepharanthin may be useful for cancer radiotherapy.

Adrenochrome↗

[An early clinical study of Z-100 in leukopenia caused by radiotherapy].

The clinical efficacy of Z-100 for the treatment of leukopenia caused by radiotherapy for malignant tumors was evaluated in an early clinical study using three doses, 2, 10 and 20 micrograms. According to the evaluation by investigators and time-course of WBC, the highest effective rate was achieved by 20 micrograms. Adverse reactions occurred in all groups, but there were no serious or clinically relevant reactions. These results suggested that Z-100 is clinically useful for the treatment of leukopenia caused by radiotherapy.

Adult↗

Erythroblastopenia and leukopenia in the patient with severe herpes zoster treated with intravenous acyclovir.

A seven-year-old girl with transient leukopenia and erythroblastopenia which developed after the administration of acyclovir is presented. Acyclovir infusion was given in a dose of 5 mg/kg/every eight hours. On the third day of therapy the hemoglobin level fell to 9.9 g/dl, the hematocrit was 26%, the white blood cell count 4000 percent/mm3, red blood cells 3.2 million percent/mm3. Bone marrow aspiration showed a decrease in the number of erythoblasts and a relative increase in the number of promyelocytes and myelocytes. Therapy was discontinued on the fifth day, and on the seventh day the findings were normal including the bone marrow aspiration. We could not find any other reason which would cause transient erythroblastopenia and leukopenia in our patient.

Acyclovir↗

Chronic leukopenia associated with feline immunodeficiency virus infection in a cat.

Leukopenia attributable to lymphopenia and neutropenia was detected over a 28-week period in a 12-year-old domestic cat infected with feline immunodeficiency virus (FIV). Mild normocytic, normochronic anemia also was evident. Platelet counts were normal, and serum biochemical values were unremarkable. Antibodies to FIV were detected in serum by use of immunofluorescence and immunoblot electrophoresis assays. Cytologic evaluation of bone marrow aspirates revealed normal cellular morphologic features, maturation, and myeloid-to-erythroid ratio. Normal marrow cellularity was determined histologically. There was, however, a significant (P less than 0.01) inhibition of colony-forming unit granulocyte/macrophage-derived progenitors when marrow cells were cultured in the presence of autologous serum, compared with that when marrow cells were cultured in the presence of serum obtained from clinically normal cats, thus suggesting the presence of a humoral inhibitory substance directed specifically at the granulocyte/macrophage lineage. These cell culture results were consistent with those reported for human beings with acquired immunodeficiency syndrome and neutropenia. Thus, FIV infection may be an excellent animal model in which to study human immunodeficiency virus and should be considered in the differential diagnosis of cats with chronic leukopenia.

Animals↗

[Restorative effect of muroctasin; MDP-Lys (L18) [DJ-7041] on leukopenia in urogenital cancer patients treated with chemotherapy].

Muroctasin, a derivative of muramyl dipeptide (MDP), increases WBC count through induction of the colony stimulating factor (CSF). This action of muroctasin is useful to treat cancer patients with leukopenia on chemotherapy. Urogenital cancer patients were randomized to either a 50 micrograms or 100 micrograms dose group of muroctasin when the WBC count dropped below 3,000/cmm in the first cycle of chemotherapy. The patients were then subcutaneously treated with muroctasin once daily for 6 consecutive days, and restoration of their WBC count determined. Out of the 32 patients who were enrolled in the study, 25, 24 and 23 patients were assessed for safety, usefulness and efficacy, respectively. The 100 micrograms dose was more effective in restoring the WBC count than the 50 micrograms dose based on the evaluation by the physicians. This result was also confirmed when we used the criteria for evaluation of adverse reactions as recommended by the Japanese guidelines for evaluation of efficacy of chemotherapy on solid tumors. Mild fever and reaction at the injection site were noted in 16% (4/25). In conclusion, muroctasin is useful for leukopenia after chemotherapy.

Acetylmuramyl-Alanyl-Isoglutamine↗

Restorative effect of muroctasin on leukopenia caused by anticancer chemotherapy in lung cancer. Comparative study by envelope method.

N2-[(N-Acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a derivative of muramyl dipeptide, is known to have the activity to augment the number of white blood cells (WBC) via colony-stimulating factor. Muroctasin has been expected to be applied to leukopenia caused by anticancer chemotherapy. When WBC decreased to less than or equal to 3,000/mm3 after the 1st course of chemotherapy, 131 patients with lung cancer, who were previously classified by the combination regimens of chemotherapy, were enrolled in the study and randomized into 3 groups, 200 micrograms (H), 100 micrograms (L) and untreated control (C) groups. The patients were then subcutaneously treated once daily for 6 consecutive days. WBC and its differential count were measured on Days 4, 7 and 15 after commencement of the study. WBCs in H and L groups were recovered greater than in C group. In WBC differential count, the recovery of neutrophil was prominent in muroctasin treated groups. The portion of immature neutrophil in the bone marrow was also increased by muroctasin treatment. A restorative effect on WBC and neutrophil counts was also confirmed only in the second course of H group. On the other hand, fever and pain in the injected site as side effects were common in the H group and L group in both of courses. In this study, the usefulness of muroctasin in leukopenia was suggested when administered at dosages of 200 micrograms for 6 days.

Acetylmuramyl-Alanyl-Isoglutamine↗

[Effects of massive administration of cepharanthin on chemotherapy-induced leukopenia].

The effects of Cepharanthine on chemotherapy-induced leukopenia was investigated in our university hospital. Thirty-four patients with gynecological malignant tumors were divided into two groups: One group (20 patients) was administered 50 mg of Cepharanthine intravenously every day during postoperative chemotherapy (CAP or FAMT therapy) period and the other (14 patients) was without administration during the same period. Out of 20 patients treated with Cepharanthine, 14 patients (70%) showed a slight decrease in the number of leukocytes (less than 20% decrease as compared to that before chemotherapy) five weeks after administration of anticancer drugs. Only two patients (14%) demonstrated a slight decrease of the number of leukocytes in the control group. No side effects were observed in the patients who were treated with Cepharanthine. These data suggest that the large dose of Cepharanthine contribute to the prevention of leukopenia in patients who are treated with a sufficient amount of anticancer drugs.

Adult↗

[Restorative effect of muroctasin, MDP-Lys (L 18), on leukopenia caused by anticancer chemotherapy in lung cancer--comparative study by envelope method].

Muroctasin, a derivative of MDP, is known to augment the number of WBC via colony-stimulating factor. Muroctasin has been expected to be promising for application to leukopenia caused by anticancer chemotherapy. When WBC decreased to less than or equal to 3,000/mm3 after the 1st course of chemotherapy, 131 patients with lung cancer, who were previously classified by chemotherapy combination, were enrolled in the study and randomized into 3 groups, 200 micrograms (H), 100 micrograms (L) and untreated control (C) groups. The patients were then subcutaneously treated once daily for 6 consecutive days. WBC and its differential count were measured on days 4, 7 and 15 after commencement of the study. WBCs in H and L groups showed greater recovery than in C group. In WBC differential count, the recovery of neutrophil was prominent in muroctasin-treated groups. A portion of immature neutrophil in bone marrow was also increased by muroctasin treatment. In the present study, the usefulness of muroctasin in leukopenia was indicated when administered at dosages of 200 micrograms for 6 days.

Acetylmuramyl-Alanyl-Isoglutamine↗

Changes in electrical charge of leukocyte surface membranes during hemodialysis. Possible role in transient leukopenia.

Change in the electrical charge of leukocyte surface membranes during hemodialysis (HD) using a cellulose membrane was studied by examining adsorbability of leukocytes taken from patients undergoing HD to cation and anion exchange resins. Leukocytes of HD patients were well adsorbed to both anion and cation exchange resins, whereas normal leukocytes were only minimally adsorbed to a cation exchange resin, suggesting that the surface membranes of normal leukocytes were charged electronegatively. Adsorbability to anion exchange resin by patients' leukocytes taken from the venous limb of the HD circuit line 15 minutes after starting HD was significantly decreased when using a cellulosic membrane. This suggests that the decrease in electronegative leukocyte surface membrane charge, which may facilitate the attachment of leukocytes to electronegatively charged endothelial cell membranes, is the factor leading to leukopenia. Adsorbability to anion exchange resin by normal leukocytes incubated with plasma taken from HD patients 10 to 60 minutes after starting HD was increased, suggesting an increase in electronegatively charged substances in patients' plasma; these recombine with leukocyte surface membranes thereby increasing the electronegative charges of the leukocyte surface membranes and enabling subsequent release of leukocytes from endothelial cells, consistent with the transient nature of the leukopenia.

Adsorption↗

[Granulopoietic effects of lentinan in mice: effects on GM-CFC and 5-FU-induced leukopenia].

C57BL mice were injected intravenously with an antitumor immunopotentiating polysaccharide, lentinan, to assess its effect on granulopoiesis in normal mice as well as its ability to enhance the recovery from leukopenia induced by 5-fluorouracil (5-FU). Lentinan increased neutrophils and monocytes in peripheral blood as well as granulocyte-macrophage progenitor cells (GM-CFC) in spleen and bone marrow. Administration of 5-FU induced a significant decrease in GM-CFC from day 1 to day 6, and thereafter the number of GM-CFC rebounded. The administration of 5-FU also suppressed white blood cells such as neutrophils, monocytes and lymphocytes. Injection of lentinan one day after 5-FU resulted in prompt restoration of the leukopenia through the recovery of neutrophils, monocytes and lymphocytes as well as prompt and marked rebound of GM-CFC. These results suggest that lentinan may contribute to the recovery from some of the hematopoietic depression in clinical chemoimmunotherapy.

Animals↗

Successful treatment course with carbamazepine despite initial significant leukopenia: case report.

A case of carbamazepine-induced leukopenia with subsequent successful carbamazepine management is presented. Despite WBC suppression to a level of 2000/cu mm on an initial trial of carbamazepine, a challenge with a much lower dose and gradual titration permitted a full treatment course with therapeutic blood levels. Although many physicians are wary of the leukopenia associated with carbamazepine, it is a distinct entity from the rare agranulocytosis and aplastic anemia that have been associated with the drug. With careful clinical management, carbamazepine can be successfully used in patients with neurologic disorders despite significant WBC suppression.

Aged↗

Biocompatibility of different hemodialysis membranes: activation of complement and leukopenia.

The ability of three hollow-fiber dialyzers (Cuprophane [CU], polymethylmethacrylate [PMMA], and polyacrylonitrile [PAN]) to activate complement and to induce leukopenia was studied prospectively in six patients on long-term hemodialysis. CU membranes caused the most intense complement activation with C3a, C3d, and C5a levels peaking 15 min after beginning dialysis. Total white blood cell (WBC) counts dropped simultaneously by 76%, and the decrease in leukocytes was inversely correlated with the levels of C3a and C5a. In contrast, PMMA membranes led only to slight complement activation with an associated fall in WBC counts of 29%, and PAN membranes induced very little complement activation without leukopenia. In vitro studies involving incubation of normal human plasma with each of the three membranes corroborated these findings. The results suggest that the biocompatibility of PMMA and PAN dialyzers is superior to CU.

Acrylic Resins↗

Acceleration of myeloid recovery from cyclophosphamide-induced leukopenia by pretreatment with Bacillus Calmette-Guérin.

Treatment of C57BL/6 mice with Bacillus Calmette-Guérin i.p. 8 days prior to the induction of leukopenia by cyclophosphamide (300 mg/kg i.p.) significantly (p less than 0.002) increased peripheral granulocyte counts on each day during the recovery from leukopenia. The recovery of lymphocyte counts was unaffected by Bacillus Calmette-Guérin treatment. Further experiments indicated that the accelerated granulocyte recovery was the result of an earlier initiation of the recovery process rather than of the release of stored granulocytes. Bacillus Calmette-Guérin may have clinical value as a stimulator of myelopoiesis in patients rendered leukopenic by antineoplastic chemotherapy.

Animals↗

Leukopenia in Still's disease.

Two patients, one a 14-year-old girl and the other a 20-year-old man, with typical manifestations of juvenile rheumatoid arthritis had leukopenia and thrombocytopenia, two heretofore unreported findings. The presence of leukopenia should not be used to exclude a diagnosis of Still's disease.

Adolescent↗

Leukopenia with cimetidine.

A case of leukopenia associated with cimetidine therapy is reported. The patient had sarcoid cirrhosis with portal hypertension. Cimetidine therapy was instituted for upper gastrointestinal bleeding due to gastritis, resulted in leukopenia, and was reversed on discontinuation of therapy.

Cimetidine↗

Human myelopoiesis in culture of liquid medium lacking colony stimulating factors: therapeutic implications for cancer patients with leukopenia.

Patients with cancer often develop leukopenia caused by chemotherapy. Since their treatment with human colony stimulating factors (CSFs) has limitations, it is imperative to determine if CSFs are essential in regulating human myelopoiesis. For this purpose, human primary precursor myeloid cells were cultured in media lacking exogenous human CSFs and stem cell factor (SCF), and supplemented with human sera, or with fetal bovine or other types of animal sera. Cells cultured in human sera survive well, proliferate actively, and differentiate toward granulocytes. Most cells cultured in fetal bovine serum die, few differentiate toward monocytes-macrophages. Cells cultured in other types of animal sera die rapidly. Antibodies neutralizing human serum's CSFs and SCF do not abolish its myeloregulatory activity. It is concluded that cell growth factors other than CSFs and SCF present in human serum regulate human myelopoiesis in vitro. These findings bear important therapeutic implication for patients with cancer having leukopenia.

Adult↗

A comparative clinical study on prevention and treatment with selected chronomedication of leukopenia induced by chemotherapy.

During the period of therapy, leukopenia induced by chemotherapy was less severe and was cured more rapidly in the selected chronomedication group (CMG) than in the routine medication group (RMG). The incidence of leukopenia was markedly lower in CMG (12.9%) than in RMG (48.4%), and the rate of uneventful completion of chemotherapy was also higher in CMG (96.8%) than in RMG. These results suggest that selected chronomedication may be beneficial to the successful completion of chemotherapy in patients with malignant tumor.

Adult↗

[Functional leukocyte tests in the diagnosis of toxic leukopenia].

Adrenalin test in 69% of examinees who had faced long exposure to oil products revealed redistribution leukopenia caused by compromised neurovascular regulation. Toxic origin of the leukopenia in 10.4% of workers was supported not only by the adrenalin test but also by pyrogenal one which proved exhaustion of granulocyte reserve in the bone marrow.

Bone Marrow Cells↗