1/26. Endogenous thrombopoietin serum levels during multicycle chemotherapy.Little is known about the behaviour of endogenous thrombopoietin (TPO) serum levels during rapid sequences of dose-intensified chemotherapy. To characterize the relationship between TPO levels and platelet counts in this setting we serially measured both parameters over the entire treatment period of patients receiving multicycle polychemotherapy. We found TPO and platelet responses to be generally antagonistic through all cycles. However, a cross-correlation analysis indicated that TPO responses preceded platelet responses by approximately one day in all patients. The cumulative severity of thrombocytopenia observed over successive cycles was accompanied by an increasing TPO response which tended to grow overproportionally in relation to the degree of peripheral thrombocytopenia. These findings are consistent with a model suggesting that both platelet and megakaryocyte mass contribute to a receptor-dependent consumption process regulating the endogenous TPO level. In order to develop optimal schedules for exogenous TPO administration it might be important to consider endogenous TPO response characteristics.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
2/26. Effective treatment of a patient with a high-grade endometrial stromal sarcoma with an accelerated regimen of carboplatin and paclitaxel.The rarity of endometrial stromal sarcoma (ESS) and its poor response to treatment provides fertile ground for investigational therapies. An accelerated regimen of carboplatin and paclitaxel is investigated. A patient with a recent history of treated tuberculosis of the lung represented with infertility and acute abdominal pain from suspected fibroids, and underwent a laparotomy with a diagnosis of a high-grade ESS. A novel therapeutic approach using a regimen of carboplatin and paclitaxel with the reinfusion of filgrastim-mobilized peripheral blood progenitor cells is described. A partial response was observed following six cycles of chemotherapy. Grade IV thrombocytopenia occurred after the last cycle, with recovery prior to pelvic radiotherapy. The patient remained well 1 year post-diagnosis. High-grade ESS is responsive to combination chemotherapy with paclitaxel and carboplatin, and requires further evaluation. The use of an accelerated regimen may also have contributed to the response and this question awaits randomized trials.- - - - - - - - - - ranking = 0.28571428571429keywords = cycle (Clic here for more details about this article) |
3/26. Detrimental effects of high-dose dexamethasone in severe, refractory, HIV-related thrombocytopenia.OBJECTIVE: To report a case of HIV-related thrombocytopenia in which high-dose dexamethasone was ineffective and immunologically detrimental. CASE SUMMARY: A 39-year-old white man with persistent, severe, hiv-1-related thrombocytopenia was admitted for epistaxis, bleeding gums, petechiae, and bruising. Previous unsuccessful attempts to reverse the thrombocytopenia included zidovudine, prednisone, vincristine, interferon alfa, and intravenous immune globulins. Based on previous anecdotal reports of the effectiveness of high-dose dexamethasone in refractory, HIV-related thrombocytopenia, we instituted treatment with intravenous dexamethasone 40 mg/d for four sequential days every 28 days. After three cycles of therapy, the platelet count remained < 15 x 10(9)/L; however, the CD4 lymphocyte count decreased progressively from 1447 x 10(6)/L at baseline to 560 x 10(6)/L three months after the third cycle. Due to persistent, severe thrombocytopenia and bleeding, the patient underwent splenectomy, resulting in normalization of the platelet count. DISCUSSION: High-dose dexamethasone has been proposed as treatment for patients with immune thrombocytopenia as an alternative to chronic oral corticosteroids and claimed to be associated with better effectiveness and fewer adverse effects. The results of this treatment in our patient show that this regimen may not only be ineffective, but may also be immunologically detrimental in HIV-infected patients. Although the deterioration of the immunologic status of our patient cannot be fully attributed to high-dose dexamethasone based on the Naranjo scale, the previous long-lasting stability of CD4 cells and the temporal relationship of a decrease in the CD4 cell count coinciding with administration of high-dose dexamethasone suggest a causative role of the treatment. CONCLUSIONS: A possible cause-effect relationship between the treatment and the decrease in the CD4 cell count suggests that the use of high-dose dexamethasone may not be justified in patients with severe, HIV-related thrombocytopenia.- - - - - - - - - - ranking = 0.28571428571429keywords = cycle (Clic here for more details about this article) |
4/26. Fy phenotype and gender determine plasma levels of monocyte chemotactic protein.BACKGROUND: in vitro studies indicate that the Fy blood group system antigens serve as receptors for chemokines such as monocyte chemotactic protein-1 (MCP-1) and RANTES. However, it is unclear whether subjects with the Fy(a-b-) phenotype exhibit altered clearance and hence altered plasma levels of chemo-kines, because they still express Fy on endothelial cells. STUDY DESIGN AND methods: To clarify a possible in vivo role of Fy on RBCs in the regulation of chemo-kine levels, healthy young volunteers of common Fy phenotypes were compared in a cross-sectional study. RESULTS: More than 90 percent of the 34 subjects of African origin were Fy(a-b-), one black volunteer was Fy(a b-), and two were Fy(a-b ). As expected, all 65 white volunteers were positive for either Fy(a) and/or Fy(b). Unexpectedly, persons expressing either Fy(a) and/or Fy(b) had significantly higher plasma levels of MCP-1 than Fy(a-b-) volunteers (women: 154 vs. 110 ng/L, p<0.01; men: 179 vs. 169 ng/L, p = 0.03). Surprisingly, plasma levels of MCP-1 were found to be sex-dependent: median MCP-1 levels averaged 180 ng per L in men but only 139 ng per L in women (p<0.001). Further, MCP-1 levels decreased significantly throughout the menstrual cycle of 18 women studied longitudinally. CONCLUSION: MCP-1 levels are about 30 percent higher in men than in premenopausal women, and MCP-1 levels are also higher in persons with RBCs expressing Fy antigens than in Fy(a-b-) persons. These findings have direct implications for the concept and interpretation of clinical studies measuring MCP-1 levels; the role of the observed differences in MCP-1 levels for the pathogenesis of MCP-1-dependent diseases, such as atherosclerosis, merits further investigation.- - - - - - - - - - ranking = 0.14285714285714keywords = cycle (Clic here for more details about this article) |
5/26. Autoimmune neutropenia with cyclic oscillation of neutrophil count after steroid administration.A 16-year-old female patient was evaluated for pancytopenia. She had a white blood cell count of 1.6 x 10(9)/L with 0.02 neutrophils and a platelet count of 19 x 10(9)/L. In the bone marrow, mature granulocytes were markedly decreased in number, but no atypical cells were present. Antineutrophil antibody was demonstrated by flow cytometry, and the level of platelet-associated immunoglobulin g was increased. A diagnosis of autoimmune neutropenia and thrombocytopenia was made. Interestingly, neutrophil and platelet counts fluctuated cyclically after the initiation of prednisolone therapy. The neutrophil count fluctuated between 0.1 x 10(9)/L and 7 x 10(9)/L, and the platelet count fluctuated between 19 x 10(9)/L and 175 x 10(9)/L, in 4-week cycles. Following splenectomy, neutrophil and platelet counts normalized. We believe the immune mechanism of recurrent neutropenia in this patient differs from that in other patients with cyclic neutropenia reported with stem cell disorders.- - - - - - - - - - ranking = 0.14285714285714keywords = cycle (Clic here for more details about this article) |
6/26. infant hypervitaminosis a causes severe anemia and thrombocytopenia: evidence of a retinol-dependent bone marrow cell growth inhibition.vitamin a is a pivotal biochemical factor required for normal proliferation and differentiation as well as for specialized functions, such as vision. The dietary intake of 1500 IU/day is recommended in the first year of life. Here, we report the case of an infant who had been given 62 000 IU/day for 80 days. The infant showed several clinical signs of retinol intoxication, including severe anemia and thrombocytopenia. bone marrow showed a remarkably reduced number of erythroid and megakaryocytic cells. The interruption of vitamin a treatment was immediately followed by clinical and biochemical recovery. To clarify whether the effects of retinol are due to a direct action on bone marrow cell proliferation, we investigated the activity of retinol (both the drug and the pure molecule) on the growth of K-562, a multipotent hematopoietic cell line, and on bone marrow mesenchymal stem cells. We observed that vitamin a strongly inhibited the proliferation of the cells at concentrations similar to those reached in vivo. Subsequent biochemical analyses of the cell cycle suggested that the effect was mediated by the up-regulation of cyclin-dependent kinase inhibitors, p21(Cip1) and p27(Kip1). These are the first findings to demonstrate that infant hypervitaminosis a causes a severe anemia and thrombocytopenia and that this is probably due to the direct effect of the molecule on the growth of all bone marrow cellular components. Our data also suggest potential bone marrow functional alterations after excessive vitamin a intake because of emerging social habits.- - - - - - - - - - ranking = 0.14285714285714keywords = cycle (Clic here for more details about this article) |
7/26. Investigation into the usefulness and adverse events of CDDP, 5-fU and dl-leucovorin (PFL-therapy) for advanced colorectal cancer.Biochemical modulation of 5-fluorouracil (5-FU) has been verified the evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. We investigated the therapeutic and adverse drug reaction of intensive chemotherapy using cisplatin (CDDP), 5-FU and dl-leucovorin (LV) (PFL-therapy), which may be producing dual biochemical modulation effect of 5-FU for advanced colorectal carcinoma. Administration schedule was 13 mg/m2 of CDDP, 300 mg/m2 of 5-FU, and 30 mg/body of dl-LV for 5 consecutive days. This regimen was repeated at 3-week intervals in hospital. Sixteen patients were enrolled in this study, most of whom had a history of previous chemotherapy as adjuvant treatment, and the response rate was 25%, with four patients having "partial response" and eight "no change". In respect to performance status, 46% of patients who completed the protocol were markedly improved in spite of their poor performance status before treatment. Moreover, when patients were classified into two groups based on changes of the serum level of CEA, "responder in CEA level" showed better prognosis than "non-responder in CEA level". Major toxicities were nausea, hyperglycemia and neutropenia. Three patients experienced Grade 4 hematological side effect, but these complications resolved quickly in all patients except for one patient. PFL-therapy is effective for advanced colorectal cancer with large tumor burden and showed the same prognostic result as the American and European trials in spite of smaller number of treatment cycles and a history of previous chemotherapy. We will be able to demonstrate the usefulness of this regimen for Japanese patients with advanced colorectal cancers after adding new cases to the present report.- - - - - - - - - - ranking = 0.14285714285714keywords = cycle (Clic here for more details about this article) |
8/26. Cases from the Osler Medical Service at Johns Hopkins University.A 47-year-old white woman with a history of stage III squamous cell carcinoma of the anus was transferred to Johns Hopkins Hospital for further evaluation of renal failure, hemolytic anemia, and thrombocytopenia.The patient was first diagnosed with squamous cell carcinoma of the anus 1 year before admission. She was treated with external beam radiation of the pelvis and two cycles of mitomycin C-based chemotherapy (a cumulative dose, 34 mg/m(2)). Her clinical course was complicated by clostridium difficile colitis and myositis successfully treated with prednisone.Three months before admission, the patient developed dysuria. Her creatinine increased from normal to 1.7 mg/dL, and microscopic hematuria was present. A renal ultrasound and an abdominal computed tomographic scan showed no abnormalities or obstruction. One month before admission, she underwent a cystoscopy, which showed only radiation-induced changes in the bladder. Two weeks before admission, the patient became delirious and was taken to a hospital, where she was found to be anemic, with a hematocrit level of 23.7%, and thrombocytopenic with a platelet count of 110,000/mm(3). Her creatinine level was 5.9 mg/dL. Previous values of hematocrit, platelet count, and serum creatinine were normal.On admission at Johns Hopkins Hospital the patient had no complaints. She was afebrile on physical examination and had normal vital signs. head, neck, chest, cardiovascular, and abdominal examinations were normal. There was skin pallor, but no echymoses or petechiae. She was alert and oriented with normal mental status. Her neurologic examination was normal. Laboratory data showed a white blood cell count of 6390/mm(3), a hematocrit level of 26.5%, and a platelet count of 26,000/mm(3). Her blood urea nitrogen level was 57 mg/dL, creatinine level was 4.0 mg/dL, and lactate dehydrogenase was 550 U/L (reference, 115 to 275 U/L). urinalysis showed innumerable red blood cells and large protein. A peripheral blood smear showed fragmented red blood cells, schistocytes, no abnormal white blood cells, and few platelets. There was no radiographic or clinical evidence of relapse of her squamous cell carcinoma.What is the diagnosis?- - - - - - - - - - ranking = 0.14285714285714keywords = cycle (Clic here for more details about this article) |
9/26. valproic acid-induced hyperammonemia and thrombocytopenia in an elderly woman.OBJECTIVE: To describe a case of oral valproic acid-induced hyperammonemia and thrombocytopenia in an elderly patient. CASE SUMMARY: A 76-year-old white woman presented to the emergency department with generalized weakness, confusion, nausea, and vomiting. She was taking sodium divalproex 750 mg 3 times daily, with valproic acid concentration 144 mg/L. She was admitted to the medical ward. The dose of sodium divalproex was decreased and discontinued. During her hospital stay, the woman's ammonia level rose to 211 microg/dL despite a normal valproic acid concentration. She was confused, somnolent, and had decreased mobility. Her platelet count decreased from 133 to 86 x 10(3)/mm(3). Gabapentin was prescribed for seizure control. The patient's mental status, ammonia level, and platelet count returned to baseline following discontinuation of valproic acid. DISCUSSION: It has been reported that valproic acid can interfere with the enzyme carbamoylphosphate synthetase, which is responsible for incorporating ammonia into the urea cycle. It has also been reported that valproic acid can increase the transport of glutamine across the mitochondrial membrane in the kidney, thereby increasing the production of ammonia. The etiology of valproic acid-induced thrombocytopenia has not been elucidated. Using the Naranjo probability scale, a probable relationship between hyperammonemia and valproic acid and a possible relationship between thrombocytopenia and valproic acid were determined. CONCLUSIONS: valproic acid can be associated with hyperammonemia and thrombocytopenia. Clinicians should be aware of changes in patients' cognitive and functional capacity, especially elderly patients on sodium divalproex.- - - - - - - - - - ranking = 0.14285714285714keywords = cycle (Clic here for more details about this article) |
10/26. Oxaliplatin-induced acute-onset thrombocytopenia, hemorrhage and hemolysis.BACKGROUND: Oxaliplatin is a novel platinum derivative with established anti-tumor activity in colorectal cancer. Acute-onset hemolytic anemia and thrombocytopenia associated with this drug have rarely been reported and some of these cases have been severe or even fatal. CASE REPORT: This case report describes a patient who developed fever, chills, abdominal and back pain as well as sudden-onset severe thrombocytopenia, upper gastrointestinal bleeding and hemolysis immediately after treatment with oxaliplatin for metastatic colorectal cancer. The reaction appeared during the 14th cycle of chemotherapy. Corticosteroids and antihistamines were administered together with platelet transfusions. Over the next 2 days platelet count improved and the syndrome abated. The patient was discharged 4 days later. Furthermore, the reaction was accompanied by a strongly positive coombs test and increased TNF-alpha and IL-10 serum levels which returned to normal following anti-inflammatory drug administration. CONCLUSION: physicians should be aware of the possibility of acute hematological emergencies following oxaliplatin administration.- - - - - - - - - - ranking = 0.14285714285714keywords = cycle (Clic here for more details about this article) |
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