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Leukopenia and thrombocytopenia in pigs after infection with bovine viral diarrhoea virus-2 (BVDV-2).

The aim of this study was to investigate whether bovine viral diarrhoea virus-2 (BVDV-2) is pathogenic for pigs, which organs become infected and whether or to which extent the virus is excreted into the environment. Ten pigs were observed for clinical reactions after infection with a BVDV-2 strain, that has been shown to be pathogenic in calves under experimental conditions. Samples were taken to monitor thrombocyte and leukocyte counts as well as antibody development. Post mortem examinations were performed at 7, 11 and 27 days after infection. Tissue samples were collected for virus isolation, histological and immunohistological examination. All ten pigs became infected and BVDV could be re-isolated from the lymphocytes, the plasma and different lymphatic organs. The infection passed clinically inapparent, apart from a slight increase in body temperature in some animals. Some animals developed a slight leukopenia and/or thrombocytopenia. There were no macroscopic or histological lesions observed that could specifically be related to the inoculation of BVDV-2. With respect to all parameters studied, the infection and the consequences thereof were clearly less pronounced in pigs as compared to cattle, the natural host. Our results indicate, that pigs infected with BVDV-2 might develop antibodies that cross-react in tests for antibodies against classical swine fever virus.

Animals↗

[Activity of polar glycopeptidolipids from Mycobacterium chelonae in the reversal of chemically induced leukopenia in mice].

Intraperitoneal administration of polar glycopeptidolipids extracted from Mycobacterium chelonae (GPLp-Mc) has led to reversal of Doxorubicin-induced leucopenia in a manner comparable to that effected by GM-CSF administered in a dose of 100 IU (2.5 micrograms/kg). The mode of action and the toxicity of this product are being studied. Results obtained on the mouse indicate that it would be worthwhile to undertake tests in man aimed at studying the effect of GPLp-Mc on chemotherapy- and radiotherapy-induced leukopenias, once toxicological studies have been carried out.

Animals↗

Fusidic acid-induced leukopenia and thrombocytopenia.

Fusidic acid is an active agent against a wide variety of gram-positive bacteria, and it has been increasingly used in methicillin-resistant Staphylococcus aureus infection. The major adverse effects are mild gastrointestinal discomfort and diarrhea. The hematological side effects such as granulocytopenia and thrombocytopenia have been rarely reported in western countries, but have not been documented in Asian population. Between January and April 2001, we identified 2 cases of fusidic acid-induced leukopenia and thrombocytopenia after 2 weeks of fusidic acid treatment. In both cases, hematological abnormality resolved in 3 to 6 days after discontinuation of fusidic acid. The published literature regarding hematological adverse effects caused by fusidic acid is reviewed in this report, and an immune-mediated mechanism possibly by drug-dependent antibody is speculated. We recommend periodic complete blood count check in patients receiving long-term fusidic acid treatment to avoid serious hematological adverse effects.

Aged↗

Thrombin-induced leukopenia and thrombocytopenia are attenuated by PAF antagonist WEB 2086.

Thrombin has been shown to increase pulmonary transvascular permeability in vivo. This permeability change appears to be dependent on polymorphonuclear leukocytes (PMNs). In vitro, thrombin has been demonstrated to increase PMN adherence to endothelial cells coincident with generation of platelet activating factor (PAF) by endothelial cells. These observations have led to the suggestion that PAF mediates, in part, the attachment of PMNs to endothelial cells. We examined this hypothesis in vivo and in vitro with a specific PAF receptor antagonist, WEB 2086. Prior infusion of WEB 2086 into conscious sheep significantly attenuated the drop in peripheral blood PMN counts observed during and after infusion of alpha-thrombin (30 NIH U/kg). These data suggest that WEB 2086 prevented PMN margination on endothelial cells. WEB 2086 also attenuated the thrombocytopenia seen after thrombin infusion and ameliorated the thrombin-induced hypoxemia and hemoconcentration. WEB 2086 did not affect the thrombin-induced hemodynamic response, the degree of intravascular coagulation as assessed by fibrin degradation product generation, or thromboxane B2 generation. In vitro, WEB 2086 prevented the augmented adherence of sheep PMNs to sheep endothelial cell monolayers after thrombin stimulation. The results of the present study are consistent with the hypothesis that PAF mediates, at least in part, thrombin-induced leukopenia and thrombocytopenia in vivo.

Animals↗

High-dose cyclophosphamide in patients with operable breast cancer: recombinant human GM-CSF ameliorates drug-induced leukopenia and thrombocytopenia.

Seventeen patients with breast cancer (nine patients with 10 ipsilateral metastatic axillary nodes, eight patients with inflammatory breast carcinoma) previously untreated with cytotoxic chemotherapy received high-dose cyclophosphamide, 7 g/sqm (HD-CTX) as initial step of a high-dose sequential chemotherapy program. Eleven patients received also intravenous recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF), 5.5 micrograms/kg per day for 7-14 days after HD-CTX. This growth factor significantly ameliorated leukopenia and thrombocytopenia induced by HD-CTX therapy thus allowing earlier delivery of subsequent courses of chemotherapy.

Adult↗

[Clinical efficacy of Z-100 for the treatment of leukopenia caused by radiotherapy--a multi-center double-blind comparative study with inosine].

The clinical usefulness and the optimal dose of Z-100 for the treatment of leukopenia caused by radiotherapy for malignant tumors was evaluated in a double-blind study comparing 20 micrograms and 30 micrograms injections of Z-100 and inosine (Z-20, Z-30 and IN group, respectively). The effective rate according to the evaluation by the attending physicians was 67.4%, 79.1% and 48.9% in the Z-30, Z-20 and IN groups, respectively, with a significantly higher efficacy rate for the Z-20 group than for the IN group. The frequency of adverse reactions was 14.3%, 3.9% and 5.6% in the Z-30, Z-20 and IN groups, respectively, with the highest rate in the Z-30 group, but there was no significant difference among the three groups. The useful rate based on total evaluation considering the effective rate and the safety profile in each group was 60.8%, 77.3% and 46.8% in the Z-30, Z-20 and IN groups, respectively, with the highest rate in the Z-20 group showing significant difference from that in the IN group. The above data confirmed the clinical usefulness of Z-100 and suggested that the optimal dose was 20 micrograms twice weekly for Z-100.

Adjuvants, Immunologic↗

Leukopenia secondary to mycobacterium leprae.

Hansen's disease (HD) is one of the major infectious diseases in the world with an estimated total of 12 million cases. Physicians in North America, however, rarely see HD or its manifestations. Hematological manifestations of HD have been reported but are not well appreciated. We report a patient with leukopenia while under treatment for active HD who demonstrated mycobacterial involvement of the bone marrow.

Bone Marrow Diseases↗

Clinical effects of cepharanthin (Ceph.) on leukopenia by chemotherapy in lung cancer patients.

In order to examine the clinical efficacy of cepharanthin (Ceph.) for preventing leukopenia caused by chemotherapy in lung cancer patients, a randomized trial was carried out. Subjects were 45 patients with non-small cell lung cancer (NSCLC) receiving initial treatment with cisplatin (CDDP) +adriamycin (ADM) +mitomycin C (MMC). Ceph. was given at a dose of 1 mg/kg to the administration group (Ceph. group) and changes in the peripheral leukocyte count were examined in both the Ceph. and non-Ceph. groups. The Ceph. group showed a reduction in the number of cases with a count nadir less than 3,000/microliters (p less than 0.05), a shortening of the time that leukocyte counts stayed under 2,000/microliters, corresponding to the time in which granulocyte counts were less than 500/microliters (p less than 0.05), and also a reduction of the time for leukocyte counts to recover from nadir to 2,000 or 3,000/microliters (p less than 0.05) measured from the commencement of chemotherapy. These results suggest that administration of Ceph. has an antileukopenic effect in anticancer treatment, and makes it possible to reduce the period of risk for infection, allowing effective regimens to be administered repeatedly in shorter intervals.

Adult↗

[Protective effect of a corpuscular polyvalent Pseudomonas aeruginosa vaccine in generalized chronic Pseudomonas aeruginosa infection in mice with cyclophosphamide-induced leukopenia].

The prophylactic effect of immunization with P. aeruginosa polyvalent corpuscular vaccine has been shown on the model of P. aeruginosa generalized chronic infection in mice with leukopenia induced by the intraperitoneal injection of cyclophosphamids. This effect is manifested by the increased resistance of the animals to sublethal doses of P. aeruginosa strain, as well as by more intense general and specific immunological responses in the infected animals (the increase of specific antibody titers, the number of leukocytes in the blood serum and the phagocytic activity of the cells of peritoneal exudate).

Animals↗

Restorative activity of muroctasin on leukopenia associated with anticancer treatment.

The restorative effect of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a muramyl dipeptide derivative, was studied in patients with leukopenia associated with anticancer chemotherapy and radiation therapy. The drug was subcutaneously administered to 102 cancer patients in a single doses of 200 or 400 micrograms, and each dosage was given either every day for 6 days or every other day over a 5-day period. White blood cell (WBC) counts were made before, during and after treatment. MDP-Lys(L18) was most effective in patients receiving the drug every day and the 400 micrograms dose was somewhat superior to the 200 micrograms dose in augmenting the WBC population. Overall, the response to MDP-Lys(L18), in terms of the increase in number of WBCs, was good to excellent in 41.6% of patients. MDP-Lys(L18) was considerably more effective in patients with solid tumors than in those with hematological malignancies. The most common side effect was fever, which was dose-dependent, more pronounced with alternate-day dosing, and generally well controlled with antipyretics. The results of this study indicate that MDP-Lys(L18) is useful in improving the WBC count in leukopenic cancer patients treated with anticancer therapy. Considering the efficacy and side effect profiles together, it is suggested that 200 micrograms/day for 6 consecutive days is the optimal treatment regimen.

Acetylmuramyl-Alanyl-Isoglutamine↗

[Treatment of Paget's disease with low dose sodium etidronate (5mg/kg/day). Occurrence of reversible transient suspected leukopenia].

27 patients with Paget's disease, from 51 to 80 years of age, were treated with etidronate disodium at a dose of 5 mg/kg/day. 70 percent of patients had multiple bone involvement. Six patients had previously been treated with diphosphonates, and nine had previously received synthetic pork or salmon calcitonin. The following parameters were studied: the serum alkaline phosphatase, urinary hydroxyproline, a self-assessment scale to evaluate pain and a scale to assess improvement in functional capacity. From the first month of treatment, significant improvement in pain indices was noted and over the following two months there was an associated significant regression in parameters of bone resorption and formation. The clinical and laboratory improvement brought about with diphosphonates persisted three months after cessation of therapy in 88 percent of cases. Gastrointestinal tolerance of the drug was excellent, but three cases of transitory leukopenia occurred which resolved spontaneously, requiring in two cases cessation of therapy. Even though it is impossible to correlate with certainty this previously undescribed finding to therapy with etidronate disodium, we believe that at a dose of 5 mg/kg/day, the drug provides rapid, effective, long term treatment in Paget's disease, but that regular hematologic surveillance should be performed.

Aged↗

The outcome of bacterial infection in subjects with benign familial leukopenia (BFL).

Benign familial leukopenia (BFL) is a hereditary phenomenon, encountered in several ethnic groups. Subjects bearing BFL are believed to be affected by bacterial infection in no greater incidence than normal subjects. In our study we investigated a group of subjects with BFL during an acute bacterial infection in comparison to subjects without BFL with the same infection. We found that the subjects with BFL had no absolute leukocytosis during the infection. Nevertheless, they reacted similarly to the other subjects in regard to their temperature and heart rate; however, they were hospitalized for fewer days than subjects without BFL. We conclude that BFL is a benign phenomenon, requiring neither specific treatment as such, nor more aggressive therapy during infection. The benign course of an acute bacterial infection in BFL indicates that perhaps the number of WBC's that are normally recruited during an infection in normal subjects highly exceeds that which is necessary.

Bacterial Infections↗

[Comparative assessment of the danger of inhaling 239Pu and 241Am based on the degree of leukopenia in dogs].

From the analysis of the results of examination of 96 dogs it is concluded that the estimate of a relative danger of breathing transuranium radionuclides with different metabolism rates (polymeric 239Pu and monomeric 241Am), according to degree of leukopenia is more reliable when it is compared with a mean weighed dose per whole organism than the dose per individual "critical" organ.

Americium↗

Leukopenia-induction capacity of 6-MP metallo-purine complexes in the rat.

Six-MP and its palladium and platinum complexes of this compound were administered intraperitoneally to 28 day old Sprague-Dawley rats in dosages of 15 mg/kg, 26.85 mg/kg, respectively for 21 days. The leukopenia induction capacity of 6-MP was greater at the end of day 7 while the 6-MP-Pd complex evidenced a more drastic leukocyte reduction at the end of day 21. The platinum complex was less toxic, as demonstrated by greater weight gain, while treatment with the palladium complex resulted in approximately the same weight gain as that observed in rats treated with pure 6-MP.

Animals↗

[Antibiotic therapy of infections in cancer patients with leukopenia].

Cancer patients with leukopenia developing infections were treated with a combination antibiotic therapy consisting of sulbenicillin and amikacin with (B) or without (A) S-sulfonated gamma-globulin. Fifty patients were randomized to either A or B, respectively. Fourty-two patients in group A and 43 in group B were evaluable for responses. Twenty-eight of 42 patients (67%) in group A and 30 of 43 (70%) in group B showed a response. These results did not demonstrate that S-sulfonated gamma-globulin enhanced the effects of the combination with sulbenicillin and amikacin, although the background factors in both groups were not completely identical. Further efforts for detecting infection were required because causes of fever were thought to be fevers of unknown origin in more than three-fourths of the patients. Few patients died of infection within 2 weeks after initiation of these therapies in both groups, indicating that these therapies presumably contributed to prolongation of life span even in patients with no response.

Amikacin↗

Quinidine-induced thrombocytopenia and leukopenia: demonstration and characterization of distinct antiplatelet and antileukocyte antibodies.

A patient with the rare syndrome of simultaneous quinidine-induced thrombocytopenia and leukopenia was studied. A quinidine-dependent antiplatelet antibody was detected in her serum by platelet aggregometry and by indirect platelet-suspension immunofluorescence. A drug-dependent antileukocyte antibody was demonstrated by leukoagglutination and by granulocyte immunofluorescence. Both antibodies were found to belong to the IgG class by immunofluorescence using monospecific antisera. There appeared to be two distinct antibodies, since the antibody eluted off sensitized platelets reacted only with platelets and that eluted off sensitized granulocytes reacted only with granulocytes. In addition, the patient's serum and quinidine gave a negative reaction on immunofluorescence with platelets from a patient with Bernard-Soulier syndrome (BSS), which lack glycoprotein lb (GPlb) complex, but gave a positive reaction with BSS granulocytes. The quinidine-dependent antiplatelet antibody immunoprecipitated GPlb and a glycoprotein of molecular weight 22,000 (GPlb complex) from Triton-solubilized, periodate-labeled platelets. Similar attempts to identify the granulocyte surface receptor/antigen were unsuccessful. Factor VIII/von Willebrand factor was not required for binding of the drug-dependent antibody to platelets.

Antibody Specificity↗

Prolonged cholestatic jaundice and leukopenia associated with piroxicam.

A case of prolonged cholestatic jaundice and leukopenia occurring in a 60 year old wh piroxicam--a non-steroidal antiinflammatory agent--is reported. Histological examination of liver biopsy revealed pronounced canalicular and intracellular bile retention. After discontinuation of the drug serum bilirubin declined to normal values over a period of 10 weeks.

Anti-Inflammatory Agents↗