Clinical evaluation of combined use of miconazole and G-CSF on deep-seated mycoses in patients with gynecological cancers

DFGF-R1 (breathless), a Drosophila FGF receptor homolog, is required for the migration of tracheal cells and the posterior midline glial cells during embryonic development. To define the role of this receptor in cell migration, we have monitored the biological effects of a deregulated receptor containing the extracellular and transmembrane regions of the torso dominant allele and the cytoplasmic domain of DFGF-R1. Ubiquitous expression of the chimeric receptor at the time of tracheal cell migration did not disrupt migration in wild-type embryos. However, induction of the chimeric receptor corrected the tracheal defects of breathless (btl) mutant embryos, allowing the tracheal cells to migrate along their normal tracts. This result indicates that the normal activity of DFGF-R1 in promoting cell migration does not require spatially restricted cues. Late inductions of the chimeric construct, after the normal initiation of tracheal migration, allowed the definition of a broad time window during which the external signals guiding migration persist and the tracheal cells retain the capacity to respond to these cues. Rescue of tracheal migration in btl mutant embryos by the chimeric construct provides a sensitive biological assay for the activity of other Drosophila receptor tyrosine kinases (RTKs). Deregulated receptors containing the cytoplasmic domains of DFGF-R2, DER, torso, and sevenless were all able to partially rescue the migration defects. Consistent with the notion that these RTKs share a common signaling pathway, constructs containing the activated downstream elements Dras1 and Draf were also able to rescue tracheal migration, demonstrating that these two proteins are key players in the DFGF-R1 signaling pathway.     

Miconazole per os in tinea and deep mycosis

For the last 6 years we have been using Miconazole cream in the treatment of tinea and vaginal candidiasis. We think that it is at least as good as the best drugs for this purpose, but consider it difficult to decide about its superiority. Therefore we refrain from describing this part of our experience in detail. We have employed Miconazole "per os" at the daily doses of 24-28 mg./kg. in treating 3 cases of tinea corporis or cruris by "Trichophyton rubrum". Symptoms ceased in 3 days; mycologic examination turned negative in 2 weeks; treatment ended in apparent cure in 3 weeks. We have employed Miconazole "per venam" and "per os" in the treatment of: mycetomata (2) by "Streptomyces somaliensis", without success; mycetoma by "Madurella grisea" (1), without success; chromomycosis by a 5-flucytosine resistant strain of "Cladosporium carrionii" (1), without success; paracoccidioidosis (5) with lesions in mouth and lungs, with good results; leishmaniasis by "Leishmania brasiliensis" (1), without success; mucocutaneous disseminated candidiasis (1), with very good results. Tolerance has been excellent: but pruritus appeared from the third week with 600 or more mg. "per venam", in several patients. Doses varied between 10 and 50 mg./kg./day. One patient, who suffered with candidiasis, is taking 50 to 30 mg./kg./day since more than a year ago and, being a child, he is feeling well and growing to be normal. We recommend employing Miconazole against systemic canidiasis, sulpharesistant paracoccidioidosis and assaying it further in tinea (at least, in griseofulvin-resistant cases).     

Current status of G-CSF in support of chemotherapy and radiotherapy

It is now 2 years since the commercial availability of G-CSF, and thus it seems appropriate to reassess the clinical merits of this cytokine in the context of current knowledge; such an evaluation seems best founded not only on an analysis of the biology of G-CSF itself, but also on a critical assessment of whether its biologic actions translate into a cost-effective alleviation of patient suffering and improved cancer cure. As is so often the case, the knowledge base upon which clinicians must rely to make prescribing decisions is smaller than we might wish, but a substantial body of existent information can provide a guide to clinical strategy until a number of ongoing trials give more concrete information.     

Efficacy of miconazole nitrate against favus in oriental breed chickens

Miconazole nitrate 2% was tested for its efficacy against Microsporum gallinae (the causative agent in favus) in a flock of various Oriental breed (Shamo and Aseel) and crossbreed chickens. Six adult males showing clinical signs of favus were randomized into control and experimental groups. The males were maintained on individual tiecords on the range, with no physical contact between birds. The experimental birds had the affected areas washed with soap and water and dried, and an ointment of miconazole nitrate 2% was applied. The experimental birds received the treatment twice a day for 34 days. Scrapings from the affected areas of all birds were cultured at the beginning and end of the test. At the end of the treatment period, the control birds were still positive for M. gallinae, but the organism could not be cultured from the treated birds.     

透明质酸在恶性血液病中作用的研究进展

透明质酸(HA)是一种在体内广泛存在的非硫酸化糖胺聚糖.HA的异常表达与恶性血液病的进展密切相关,HA与其受体CD44、RHAMM等的相互作用参与血液系统恶性肿瘤的增殖、运动、迁移、侵袭以及多药耐药等过程.根据近年来有关的最新文献报道,对HA在肿瘤中的研究以及在恶性血液病进展中的作用进行综述.     

Granulocyte colony-stimulating factor (G-CSF) dose-dependent efficacy in peripheral blood stem cell mobilization in patients who had failed initial mobilization with chemotherapy and G-CSF

For 10 consecutive patients in our unit who did not show a significant rise in blood progenitor cells within 14 days following chemotherapy and G-CSF, we increased the G-CSF dose from 5 to 10 microg/kg/day (n = 9) or from 10 to 15 microg/kg/day (n = 1). As a result, there were significant increases in total yield as well as yield per apheresis of mononuclear cells, CD34+ cells and CFU-GM (P < 0.025, <0.01 and <0.005, respectively). After G-CSF dose escalation, six of the 10 patients had sufficient CD34+ cells for performing transplantation. These results demonstrate a dose-dependent response of progenitor cell mobilization by G-CSF when used in combination with chemotherapy. Moreover, increasing the dose of G-CSF as late as the third week of mobilization may still provide sufficient cell yield even with patients who did not show a significant mobilization with conventional doses of G-CSF.     

Prognosis of hematological patients with relapse following high-dose chemotherapy and autologous stem cell transplantation

A retrospective analysis of the outcome for 283 haematological patients who relapsed after high dose chemotherapy and autologous stem cell transplantation during a five year period from 1989 to 1994 is presented. The patients were treated in accordance with local regimes at 20 Nordic transplantation centers and included patients with acute leukemia (157 patients), multiple myeloma (16 patients) and lymphoma (110 patients). Two hundred and twenty-nine patients with relapse or progressive disease were given chemo- and/or radiotherapy and the response was evaluated after 90 days. Fifty-four patients (24%) obtained a complete remission and 44 patients (19%) partial remission. The overall median survival after relapse was five months. In the group who received salvage treatment the median survival was seven months, and for the 54 patients in complete remission the median survival was 15 months. We found that survival after relapse depends upon primary disease, the time from transplantation to relapse and whether salvage therapy was initiated.     

Factors affecting the efficiency of peripheral blood stem cell collection in children treated with chemotherapy and G-CSF

Post-training administration of morphine (0.25, 0.5, or 1 mg/kg) dose-dependently impairs retention of an inhibitory avoidance response in mice. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation. In fact, they were observed when drugs were given at short, but not long, periods of time after training, i.e., when the memory trace was susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or nonspecific action of the drugs on retention performance, because the latencies during the retention test of those mice that had not received a footshock during the training were not affected by post-training drug administration. Pretreatment with either selective D1 or D2 dopamine (DA) receptor antagonists SCH 23390 and (-)-sulpiride administered at per se noneffective doses (0.025 and 6 mg/kg, respectively) potentiated the effects of morphine, while either selective D1 or D2 receptor agonists SKF 38393 and LY 171555 at per se noneffective doses (5 and 0.25 mg/kg, respectively) antagonized the effects of the opiate on memory consolidation. No significant differences were evident between the effects of D1 and D2 receptor active compounds, thus suggesting that D1 and D2 receptor types are similarly involved in the effects of morphine on memory consolidation, in agreement with previously reported results. These results are discussed in terms of a possible inverse relationship of endogenous opioid and DA systems in the brain that are involved in memory processes.     

血液病相关颅内出血的临床和影像学特点分析

目的 分析血液病相关颅内出血(ICH)的临床和影像学特点,提高临床医师的认识.方法 1998年1月至2010年5月发生的与原发血液病相关的ICH病例31例,回顾性分析其基础疾病、临床和影像学表现以及导致死亡的危险因素.结果 发生ICH的血液病以急性髓细胞白血病(AML)、特发性血小板减少性紫癜(ITP)多见,分别为13例和6例,多表现为头痛、烦躁、恶性呕吐和意识障碍,缺乏定位体征,影像学表现以渗血为主,CT与MRI诊断的符合率为60%(3/5),头颅MRI的ICH检出率高于CT.总病死率为71%(22/31),发热、白细胞＞5×109/L、血小板＜50×109/L、免疫球蛋白增高、凝血功能异常、全身多部位出血等是ICH的危险因素,具备≥2个危险因素者病死率为86.4%(19/22),显著高于有≤1个危险因素的患者病死率[33.3%(3/9)](x2=8.718,P=0.003).结论 血液病相关ICH是威胁患者生命的严重并发症,头颅MRI有助于提高血液病相关ICH诊断率,发热、白细胞＞5×109/L、血小板＜50×109/L、免疫球蛋白增高、凝血功能异常等多种危险因素并存可导致血液病ICH患者死亡率增加.     

Management of carcinoma anal canal with combination chemotherapy and concurrent radiotherapy

Results of 21 cases of squamous cell carcinoma of anal canal treated by continuous infusion of 5-fluorouracil 1000 mg/sqm for 4 days and mitomycin-C 15 mg/sqm on 1st day by i.v. route with concurrent external beam radiotherapy of 42 Gy from 1st day of chemotherapy were analysed. Out of 21 patients, 16(76.19%) achieved complete remission, 3 (14.28%) partial remission and 2 (9.52%) cases did not respond at all. On follow-up, 7 (33.33%) histopathological positive cases needed abdominoperineal resection with good recovery. After 2 years of follow-up 14 (66.67%) cases were free from the disease and 3 (14.28%) were alive with the disease. The median duration of follow-up was 36 months.     

A phase I/II study of multicyclic dose-intensive chemotherapy supported with G-CSF, or G-CSF and haematopoietic progenitor cells in whole blood, in two consecutive cohorts of patients

We investigated the reconstitutive potential of haematopoietic progenitor cells collected in autologous whole blood during multicycle dose-intensified chemotherapy. Forty patients with metastatic solid tumours were treated with up to six cycles of cisplatin and escalating doses of ifosfamide every 14 days. Cisplatin was administered in 3% sodium chloride over 3 h, followed by ifosfamide over 24 h and mesna over 36 h. The first cohort of patients received granulocyte colony-stimulating factor (G-CSF) days 4-14. Once dose-limiting toxicity was reached in cohort 1, the study continued with a second cohort of patients, in whom, in addition to G-CSF on days 4-14, 500 ml of G-CSF and chemotherapy-'primed' whole blood was collected on day 15, i.e. on day 1 of treatment cycles two to six, before cisplatin administration. This volume of blood was kept unprocessed at 4 degrees C and reinfused 20-24 h after the completion of ifosfamide. In cohort 1, dose-limiting toxicity (DLT) was reached at ifosfamide 6.0 g m(-2) with two out of six of the patients developing neutropenic fever. Although in cohort 2 no neutropenic fever was encountered, neither the frequency nor the duration of grade 4 neutropenia and thrombocytopenia were reduced. Cumulative asthenia resulted in DLT at 7.0 g m(-2). The median number of CD34+ cells in 500 ml of whole blood after the first cycle (i.e. at start of cycle 2) was 1.15 x 10(6) kg(-1). This number was significantly greater after the second cycle (2.06 x 10(6) kg(-1), P = 0.01) and then gradually decreased after cycles three to six. After storing whole blood, the number of CD34+ cells had not decreased (median + 10%). We conclude that the method of combined bone marrow support by G-CSF and haematopoietic progenitor cells in autologous whole blood collected before each cycle of a 2-weekly regimen of cisplatin-ifosfamide does not result in clinically measurable reduced bone marrow toxicity compared with what can be expected by the use of G-CSF alone.     

Erythroid stem (CFU-E) cells and erythropoietin levels in certain hematological diseases

The aim of this paper is the trial of explanation of anaemia in certain immunological disorders. This approach consists measure of the Epo serum level and clot culture of bone marrow CFU-E cells. In the plasmocytoma patients inversely proportional dependence between number of CFU-E colonies and percentage of plasmocytes in bone marrow was observed. In low grade lymphoma patients the number of CFU-E colonies in vitro was greater than the standard value. Non proportional increase of Epo serum concentration to the level of anaemia in patients with acute leukemia was observed.     

Mobilization of peripheral blood stem cells in children using G-CSF after carboplatin containing myelosuppressive chemotherapy

PURPOSE: Peripheral blood stem cell (PBSC) apheresis provides an alternative to autologous marrow harvest as a source of hematologic stem cells for transplantation in children with solid tumors. PATIENTS AND METHODS: Eight children with metastatic or recurrent solid tumors underwent 27 apheresis procedures. Recovery from myelosuppressive chemotherapy occurred without continuous daily growth factor support prior to mobilization. Granulocyte colony stimulating factor (G-CSF) at 16 microgs/kg/day was used to increase stem cells in the peripheral circulation. CD 34 positive cells, mononuclear cells (MNC), and CFU-GM were measured in the apheresis products. Prior chemotherapy was examined as a clinical factor that affected PBSC yield. RESULTS: A significant correlation was found between CD 34+/kg and CFU-GM/kg of the products (r = 0.758, P < 0.001). Patients receiving cumulative doses of carboplatin over 1,600 mg/m2 produced adequate MNC (1 x 10(8)/kg) but yielded significantly less CD 34+ cells or CFU-GM than those patients receiving less carboplatin. Prior doses of etoposide and ifosfamide did not effect PBSC yield. CONCLUSIONS: The mobilization technique was well tolerated, and the products obtained produced trilineage engraftment in the patients that underwent peripheral blood stem cell transplantation. Peripheral blood stem cell apheresis in children can be optimized by selection of appropriate candidates and mobilization with G-CSF after an absence of hematopoietic growth factor support.     

Sjogren''s syndrome and the "dry syndrome" in combination with lung diseases

Because of the reported success of primary closure of Skeletal Muscle abscess we conducted a retrospective study of breast abscess treated over a period of 24 months. There were essentially two groups: In one group the abscess cavities were initially packed with gauze and then dressed daily. In the second group, the abscess cavities were primarily closed and a negative suction drain instituted for about five to seven days. The second group had shorter healing period, better scar formation and reduction of cost in terms of labour and material. But a recurrence could occur within two to three days especially if the drain is removed prematurely.     

Paclitaxel in combination chemotherapy with radiotherapy in patients with unresectable stage III non-small-cell lung cancer

PURPOSE: The addition of combination chemotherapy to standard radiation therapy has improved treatment for locally unresectable non-small-cell lung cancer. In this phase II study, we evaluated the toxicity and efficacy of a novel chemotherapy regimen that included paclitaxel, cisplatin, and etoposide plus concurrent radiation therapy in this group of patients. PATIENTS AND METHODS: Thirty-three patients with previously untreated, unresectable stage III non-small-cell lung cancer (stage IIIA, 11 patients; stage IIIB, 22 patients) initially received two courses of chemotherapy, which included paclitaxel 135 mg/m2 by 1-hour infusion on day 1, cisplatin 60 mg/m/ intravenously (i.v.) on day 2, and etoposide 100 mg/m2 i.v. on days 1, 2 and 3. On week 6, radiation therapy (60 Gy in 30 fractions) was initiated in conjunction with two additional courses of chemotherapy: paclitaxel 135 mg/m2 i.v. by 1-hour infusion on day 1, cisplatin 5 mg/m2 i.v. on days 2- to 10, and etoposide 25 mg/m2 on days 1 to 10. RESULTS: This combined modality program was feasible and well tolerated by most patients. During the two courses of induction chemotherapy, grade 3 or 4 myelosuppression occurred in only six patients (18%). Esophagitis was common during combined modality therapy (grade 3, 10 patients; grade 4 five patients). Forty-two percent of patients had partial response after two courses of induction therapy, and 82% of patients had an objective response at completion of therapy. Twelve patients (36%) had a complete response. Nineteen patients remain progression-free at a median of 8 months; the median survival time has not been reached. CONCLUSION: This paclitaxel-containing combined modality therapy is feasible and highly active in patients with inoperable stage III lung cancer. Esophagitis is the most common severe toxicity with this program. Further studies with paclitaxel-containing combination regimens in patients with stage III non-small-cell lung cancer are indicated.     

Clinical evaluation of panipenem/betamipron as a second line chemotherapy in severe infections associated with hematological disorders

Thirty three patients with severe infections associated with hematological disorders were treated with panipenem/betamipron as a second line chemotherapy. Of these, 30 patients were evaluated for effectiveness. An excellent response was obtained in 14 patients (46.7%) and a good response in 5 (16.7%), and the overall efficacy rate was 63.3%. Efficacy rates were 3/6 in patients with sepsis, 68.4% (13/19) in patients with fever of undetermined origin, 2/4 in patients with pneumonia. In patients whose peripheral granulocyte count was below 100/microliter at the start of chemotherapy, the efficacy rate was 3/7. Side effects were observed in 5 of 33 patients (15.2%). These results show that PAPM/BP is useful as a second line chemotherapy for the treatment of severe infections in patients with hematological disorders.     

Hematopoietic progenitor cell collection and neoplastic cell contamination in breast cancer patients receiving chemotherapy plus granulocyte-colony stimulating factor (G-CSF) or G-CSF alone for mobilization

BACKGROUND: We compared hematopoietic progenitor cell (HPC) collection and neoplastic cell contamination in breast cancer patients given cyclophosphamide (CTX) plus granulocyte-colony stimulating factor (G-CSF) or G-CSF alone for mobilization. PATIENTS AND METHODS: In 57 stage II-III breast cancer patients, CD34+ cells, colony-forming units-granulocyte macrophage (CFU-GM), early HPC and breast cancer cells were counted in HPC collections obtained after CTX plus G-CSF (n = 27) or G-CSF-alone mobilization (n = 30). RESULTS: The CD34+ cell collection was about two-fold greater after CTX plus G-CSF mobilization (11.0 +/- 7.9 vs. 5.8 +/- 3.5 x 10(6)/kg, P < 0.001). Similarly, the total number of CFU-GM, CD34+CD38- cells and of week-5 cobblestone area forming cells (CAFC) collected was significantly higher in patients mobilized with CTX plus G-CSF. Breast cancer cells were found in the apheresis products of 22% of patients mobilized with CTX plus G-CSF and in 10% of patients mobilized with G-CSF alone (P = 0.36). Of seven patients who failed G-CSF-alone mobilization and eventually underwent chemotherapy plus G-CSF mobilization, none had cytokeratin-positive cells after G-CSF mobilization, whereas four out of seven had cytokeratin-positive cells after chemotherapy plus G-CSF (P = 0.07 by chi 2 test). CONCLUSION: The CTX plus G-CSF mobilization protocol was associated with a significantly higher HPC collection. However, this benefit was not accompanied by a reduction in the incidence of tumor-contaminated HPC graft.