Lhermitte's sign following oxaliplatin-containing chemotherapy in a cisplatin-pretreated ovarian cancer patient.
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Adult↗
Biomedical subjects
M Leoni
Publications and source records attributed to M Leoni.
Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study.
BACKGROUND: The aim of this study was to evaluate the effectiveness of granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes in the prevention of severe mucositis induced by high doses of chemotherapy. PATIENTS AND METHODS: Ninety consecutive patients affected by solid tumors and undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue were randomized to receive placebo versus GM-CSF mouthwash 150 micro g/day. Patients were stratified on the basis of the conditioning treatment and the consequent different risk of severe oral mucositis. Treatment was administered from the day after the end of chemotherapy until the resolution of stomatitis and/or neutrophil recovery. RESULTS: The statistical analyses were intention-to-treat and involved all patients who entered the study. The severity of stomatitis was evaluated daily by the physicians according to National Cancer Institute Common Toxicity Criteria. Both study and control groups were compared with respect to the frequency [30% versus 36%, chi(2) exact test, not significant (NS)] and mean duration (4.8 +/- 4.7 versus 4.4 +/- 2.7 days, t-test, NS) of severe stomatitis (grade > or =3). Oral pain was evaluated daily by patients themselves by means of a 10 cm analog visual scale: the mean (+/- standard error of the mean) maximum mucositis scores were 4.8 +/- 3.5 versus 4.2 +/- 3.5 cm (t-test, NS). Furthermore, 15/46 patients in the study group (33%) and 19/44 patients in the control group experienced pain requiring opioids (chi(2) exact test, NS). CONCLUSION: We did not find any evidence to indicate that prophylaxis with GM-CSF mouthwash can help to reduce the severity of mucositis in the setting of the patients we studied.
Administration, Oral↗
Whole powder pattern modelling.
A new approach for the modelling of diffraction patterns without using analytical profile functions is described and tested on ball milled f.c.c. Ni powder samples. The proposed whole powder pattern modelling (WPPM) procedure allows a one-step refinement of microstructure parameters by a direct modelling of the experimental pattern. Lattice parameter and defect content, expressed as dislocation density, outer cut-off radius, contrast factor, twin and deformation fault probabilities), can be refined together with the parameters (mean and variance) of a grain-size distribution. Different models for lattice distortions and domain size and shape can be tested to simulate or model diffraction data for systems as different as plastically deformed metals or finely dispersed crystalline powders. TEM pictures support the conclusions obtained by WPPM and confirm the validity of the proposed procedure.
Journal Article↗
Diffraction line profiles from polydisperse crystalline systems.
Diffraction patterns for polydisperse systems of crystalline grains of cubic materials were calculated considering some common grain shapes: sphere, cube, tetrahedron and octahedron. Analytical expressions for the Fourier transforms and corresponding column-length distributions were calculated for the various crystal shapes considering two representative examples of size-distribution functions: lognormal and Poisson. Results are illustrated by means of pattern simulations for a f.c.c. material. Line-broadening anisotropy owing to the different crystal shapes is discussed. The proposed approach is quite general and can be used for any given crystallite shape and different distribution functions; moreover, the Fourier transform formalism allows the introduction in the line-profile expression of other contributions to line broadening in a relatively easy and straightforward way.
Journal Article↗
Quantitation of cyclosporin A in whole blood by liquid chromatography/stable isotope dilution electrospray ionization mass spectrometry.
Therapy with cyclosporin A (CsA) for immunosuppression after organ transplantation requires monitoring of its levels in blood owing to the narrow therapeutic index of the drug and to the high inter-individual variability of the drug absorption and metabolism. We describe the preparation of CsA labelled with stable isotopes ((13)C and (2)H) with an isotopic enrichment of about 99% using labelled glucose and its use as internal standard for quantification of CsA blood levels by isotope dilution/electrospray ionization mass spectrometry. The method was found to be linear in the tested range (1-1000 ng) with and without the matrix. The accuracy of the bracketting calibration curves prepared using 100 ng ml(-1) labelled CsA was within +/-1.7% (bias). The results confirmed the usefulness of the procedure as a reference method for the external quality assessment of the field methods for the evaluation of CsA blood concentration, the imprecision (relative standard deviation) and accuracy (bias) being <2%.
Chromatography, High Pressure Liquid↗
Global approach to hepatic metastases from colorectal cancer: indication and outcome of intra-arterial chemotherapy and other hepatic-directed treatments.
Liver metastases of colorectal cancer is present in more than 20% of new diagnosed patients and in 40-60% of relapsed patients. It is a life-threatening prognostic aspect. Hepatic resection, when possible, is the best therapeutic modality, although the overall survival rate is still low (30%). Angiography and intraoperative ultrasonography are useful for resection. The number of hepatic metastases and the surgical margin are probably the most significant prognostic factors. Colorectal cancer may spread predominantly to the liver making regional treatment strategies viable options. Subtotal hepatic resections and segmentectomies are potentially curable procedures for single or small numbers of hepatic metastases without other sites of disease. However, there have been no prospective randomized trials comparing patients with unresected liver metastases and resected metastases. Regional chemotherapy with floxuridine seems usefull combined with hepatic resection or as palliative therapy. Gastric ulcer and biliary sclerosis are the main related toxicities. Patients with localized, unresectable hepatic metastases or concomitant bad medical condition may be candidates for radiation, percutaneous ethanol injection, cryosurgery, percutaneous radiofrequency, hypoxic flow-stop perfusions with bioreductive alkylating agents, hepatic arterial ligation, embolization and chemoembolization. These new hepatic-directed modalities of treatment are being investigated and may offer new approaches to providing palliation and prolonging survival. This review will report the possibilities of intra-arterial chemotherapy and other novel hepatic-directed approaches to the treatment of liver metastases from colorectal cancer.
Antineoplastic Agents↗
Immediate coma following inertial brain injury dependent on axonal damage in the brainstem.
OBJECT: Immediate and prolonged coma following brain trauma has been shown to result from diffuse axonal injury (DAI). However, the relationship between the distribution of axonal damage and posttraumatic coma has not been examined. In the present study, the authors examine that relationship. METHODS: To explore potential anatomical origins of posttraumatic coma, the authors used a model of inertial brain injury in the pig. Anesthetized miniature swine were subjected to a nonimpact-induced head rotational acceleration along either the coronal or axial plane (six pigs in each group). Immediate prolonged coma was consistently produced by head axial plane rotation, but not by head coronal plane rotation. Immunohistochemical examination of the injured brains revealed that DAI was produced by head rotation along both planes in all animals. However, extensive axonal damage in the brainstem was found in the pigs injured via head axial plane rotation. In these animals, the severity of coma was found to correlate with both the extent of axonal damage in the brainstem (p < 0.01) and the applied kinetic loading conditions (p < 0.001). No relationship was found between coma and the extent of axonal damage in other brain regions. CONCLUSIONS: These results suggest that injury to axons in the brainstem plays a major role in induction of immediate posttraumatic coma and that DAI can occur without coma.
Animals↗
Peripheral blood progenitor cell (PBPC) mobilization in heavily pretreated patients with germ cell tumors: a report of 34 cases.
The aim of the study was to evaluate peripheral blood progenitor cell mobilization by disease-specific chemotherapy in heavily pretreated patients with germ cell tumor (GCT), scheduled for high-dose chemotherapy. Thirty-four consecutive patients, 29 males and five females, with advanced GCT referred to our department for high-dose chemotherapy were evaluated retrospectively. Sixteen patients were mobilized by vinblastine 0.11 mg/kg on days 1 and 2, ifosfamide 1200 mg/m2 days 1-5 and cisplatin 20 mg/m2 days 1-5 (VeIP). In 10 patients, etoposide 75 mg/m2 days 1-5 was used instead of vinblastine (VIP), while in eight patients the mobilization was attempted by administering 7 g/m2 of cyclophosphamide. The choice of either etoposide or vinblastine was predicated upon which of these two drugs was associated with best results during premobilization chemotherapy. Cyclophosphamide was selected in patients refractory to previous cisplatin-based salvage chemotherapy. Twenty-five out of 34 patients underwent a successful PBPC collection. In 17 of them one leukapheresis procedure was sufficient to collect the target number of CD34+ cells, while in eight patients a double procedure was necessary. Altogether 33 aphereses were performed in 25 patients. In nine patients leukapheresis was not attempted. This was due to the fact that the chemotherapy failed to mobilize the target number of CD34+ cells in eight of them, treated with the VeIP mobilizing regimen, while one patient treated with high-dose cyclophosphamide rapidly progressed during therapy and for this reason leukapheresis was not undertaken. In conclusion, in heavily pretreated patients with GCT, PBPC mobilization is feasible by a further course of salvage chemotherapy. The choice of either etoposide (VIP) or vinblastine (VeIP) can be predicated upon which of these two drugs was associated with best results during premobilization chemotherapy. In our hands, VeIP seems to be less satisfactory as mobilizing treatment than VIP, possibly due to a superior number of premobilization courses of chemo therapy in some patients. Moreover, high-dose cyclophosphamide remains a good alternative for mobilizing patients refractory to salvage chemotherapy.
Adolescent↗
Predictors of long-term response to high-dose interferon therapy in type II cryoglobulinemia associated with hepatitis C virus infection.
We have prospectively studied patients with type II cryoglobulinemia since 1985 to assess the efficacy of treatment with interferon-alpha at cumulative doses ranging from 234 to 849 MU. In the present study we retrospectively evaluated in this cohort parameters associated with complete response to therapy in 31 consecutive patients with type II cryoglobulinemia associated with hepatitis C virus (HCV) infection. Prevalence of complete response of cryoglobulinemia (disappearance of symptoms and signs of vasculitis and decrease of cryocrit below 10% of the initial value) was 62%, with a median response duration of 33 months and a range of 3 to 100 months. Three patients were putatively cured, as they remained in complete remission for more than 5 years off therapy. Eighteen patients (58%) had liver disease evidenced by histopathology and/or raised transaminase levels. Prevalence of normalization of transaminase levels was 100%, with a median response duration of 36 months. Relapse of hypertransaminasemia occurred in 100% and 8% of patients receiving less than or greater than 621 MU, respectively. By logistic regression analysis, the only pretherapy parameter that associated significantly (P = .0393) with complete response of cryoglobulinemia was the solitary anti-C22 (HCV core) antibody pattern, which was observed in 29% of patients. Association with older age and low cryocrit approached statistical significance (P = . 06), while no significant correlations were found with serum IgM levels, duration of disease, HCV genotype, NS5a gene mutations, liver histology, HLA-DR phenotype, or WA cross-idiotype. Complete responses were also associated, on univariate statistical analysis, with low pretherapy HCV viremia. Responses were accompanied by decrease of viremia, of anti-HCV antibody levels and cryocrit. The usefulness of a high dose regimen is underscored by the higher rates of sustained responses of cryoglobulinemia and transaminase levels compared with previous studies.
Adult↗
Low intraovarian vascular resistance: a marker for severe ovarian hyperstimulation syndrome.
OBJECTIVE: To assess intraovarian blood flow in relation to the severity of ovarian hyperstimulation syndrome (OHSS) after controlled ovarian hyperstimulation. DESIGN: A prospective study. SETTING: Monash IVF, Clayton, Victoria, Australia. PATIENT(S): Thirty patients with OHSS after embryo or gamete transfer who also had sonographic evidence of ascites. MAIN OUTCOME MEASURE(S): The resistance to blood flow within the ovaries of 11 patients with severe OHSS and 19 patients with mild OHSS was measured by using transabdominal ultrasonography with color flow and pulsed Doppler imaging. RESULT(S): The pulsatility index (PI), resistance index (RI), and the S-D ratio, all measures of downstream vascular impedance, were significantly lower in those patients with severe OHSS. In cases with RI < 0.48, more than two thirds of the patients had a pleural effusion, whereas patients with either PI < 0.75 or S-D < 1.92 had pleural effusion in over one half of the cases. It was notable that blood flow velocity did not differ significantly between the two groups despite the changes in vascular impedance. CONCLUSION(S): There appears to be a close correlation between the severity of OHSS and the resistance to blood flow within the stimulated ovaries. Measurement of intraovarian vascular resistance before gamete transfer or ET in patients undergoing controlled ovarian hyperstimulation may help in predicting those patients at particular risk of developing severe OHSS.
Adult↗
Hyperfractionated radiotherapy and concomitant cisplatin in stage III non-small cell lung cancer: a phase II study by the AIRO-Lombardia Cooperative Group.
A multicenter Phase II study was performed by the AIRO-Lombardia Cooperative Group on 36 patients with Stage III non-small cell lung cancer. The treatment schedule included hyperfractionated radiotherapy, 1.2 Gy twice daily (5 days/week) up to a total dose of 69.6 Gy, and concomitant cisplatin by continuous infusion using a portable pump, 16 mg/m2/week for 6 weeks. Overall, adequate treatment (defined as a total dose > 66 Gy in < 46 days and 6 weeks of infusional cisplatin) was received by 56% of accrued patients. Response was complete in 6% and partial in 56% of patients; median survival was 8 months and 1-year survival rate was 37%. Site of first failure was local in 43%, distant in 43%, local and distant in 10% and unknown in 3% of failing patients. Grade 3 esophagitis was recorded in 14% of patients and a fatal case of late pulmonary toxicity was reported. On the basis of feasibility, toxicity and survival results, the planned extension to Phase III was abandoned by the Group.
Adult↗
Micronuclei in cytokinesis-blocked lymphocytes may predict patient response to radiotherapy.
We have applied the cytokinesis-block micronucleus assay to peripheral blood lymphocytes of patients undergoing radiotherapy in pelvic and pulmonary sites, in order to evaluate the individual cytogenetic response. Our cytogenetic data correlated with the equivalent whole-body dose are homogeneous and compare well with the data presented by other authors. We have used an exponential mathematical formula to calculate the attenuation of the cytogenetic effect with time. The k coefficient (cytogenetic recovery factor) in the formula expresses the degree of attenuation. In lymphocytes from patients after radiotherapy, the trend of the micronucleus frequency observed after 2 Gy of in vitro X-irradiation demonstrates that the cytogenetic effect obtained in vitro is added to that obtained in vivo. The k coefficient is inversely proportional to the micronucleus frequency observed after 2 Gy in vitro. The micronucleus assay and the cytogenetic recovery factor are proposed as suitable diagnostic tools for application in the field of radiotherapy.
Dose-Response Relationship, Radiation↗
Granulocytopenia after combined therapy with interferon and angiotensin-converting enzyme inhibitors: evidence for a synergistic hematologic toxicity.
PURPOSE: The purpose of this study was to assess whether granulocytopenia observed in 3 of 38 patients with essential mixed cryoglobulinemia who were treated with low-dose interferon was due to the underlying disease or to synergistic toxicity of interferon with other drugs. PATIENTS AND METHODS: Adverse effects of interferon therapy were monitored in 38 patients affected with type II essential mixed cryoglobulinemia. Patients were treated with 3 million units (MU), daily or on alternate days, of recombinant interferon-alpha 2a (35 patients) or with natural interferon-beta (3 patients). The duration of treatment ranged between 6 and 15 months; the total duration of follow-up, including after therapy, ranged between 8 and 93 months. RESULTS: None of 35 patients treated with interferon alone developed significant hematologic alterations. In addition, none of 7 patients treated with angiotensin-converting enzyme (ACE) inhibitors alone showed hematologic toxicity. Three patients who were treated with a combination of interferon and ACE inhibitors developed severe granulocytopenia a few days after starting treatment. Granulocytopenia subsided within 1 to 2 weeks after suspending therapy. Resumption of treatment with this drug combination produced a granulocytopenia relapse in 1 patient. In these 3 patients, interferon treatment alone, or ACE inhibitor monotherapy, was not followed by granulocytopenia. CONCLUSION: Although severe hematologic toxicity rarely develops in patients treated with low-dose interferon, granulocytopenia occurred in all 3 of our patients with mixed cryoglobulinemia who were treated with a combination of low-dose interferon-alpha 2a and ACE inhibitors. Neither drug alone was toxic in any of our cryoglobulinemic patients, indicating a high risk of severe hematologic toxicity for this drug combination, at least in patients with this disease. Physicians should be aware of this danger when using interferon treatment in patients with this, or possibly other, disorder(s) that also require antihypertensive therapy.
Adult↗
The role of radiotherapy in the treatment of stage III non-small cell lung cancer: a survey of clinical practices in Lombardy, Italy, by the Airo*-Lombardia Cooperative Group.
AIMS AND BACKGROUND: The role of radiotherapy in the treatment of stage III non-small cell lung cancer is controversial. The aim of this survey was to investigate the use of this modality in current clinical practice in Lombardy, a highly industrialized region of northern Italy. METHODS: A questionnaire was sent to all 13 radiotherapy centers in Lombardy, covering statistical, clinical, technical and strategical aspects, and the responses were analyzed. RESULTS: A wide range of attitudes was observed among participating radiation oncologists; the percentage of cases treated with curative intent varied largely between centers (4-100%), as did the proportion of patients given to radiation only rather than combined modality treatment (5-100% vs 0-90%). CONCLUSIONS: An urgent need exists for better cooperation between all clinicians involved in lung cancer treatment, pursuing the goals of a more uniform clinical practice and a more aggressive clinical research attitude.
Carcinoma, Non-Small-Cell Lung↗
Percutaneous ultrasound guided uterine needle biopsy.
OBJECTIVE: To determine the safety, accuracy and usefulness of percutaneous ultrasound guided uterine needle biopsy. SETTING: Transabdominal uterine biopsy was performed with an ultrasound directed biopsy gun. The biopsy was performed as an outpatient procedure under local anaesthesia. MAIN OUTCOME MEASURES: The safety, accuracy and clinical value of the procedure; a comparison of the clinical and ultrasound diagnoses with the biopsy and surgical histological diagnoses; and the effect of the biopsy result on the choice of treatment by the surgeon and patient. RESULTS: There were no complications. Accuracy was validated in all seven patients who subsequently had surgical procedures and more extensive myometrial histological investigation. Biopsy diagnosis improved clinical diagnosis in nine of the ten patients, and altered or assisted in the ultrasound diagnosis in eight of the ten patients. Decisions concerning choice of treatment by the doctor or patient were assisted by the biopsy result in seven patients. CONCLUSION: Percutaneous ultrasound guided uterine needle biopsy is a useful procedure in the diagnosis of myometrial disease.
Adult↗
The value of vaginal ultrasound in the management of menorrhagia.
Vaginal ultrasonography has been carried out on 97 patients with menorrhagia who were either not responding to or not suitable for drug therapy. Ultrasonography demonstrated normal uteri in 33, benign uterine enlargement in 4, bicornuate uteri in 2, intracavitary polyps or fibromyomas in 9, possible adenomyosis in 13 and intramural or subserous fibromyomas in 36. The ultrasound diagnosis markedly increased the accuracy of clinical diagnosis and assisted in the proper choice of treatment which included the avoidance of surgery and the selection of patients most suited to endometrial resection, intrauterine resection of polyps and fibromyomas, and open or laparoscopic myomectomy and hysterectomy. The routine use of high resolution vaginal ultrasound in the management of menorrhagia is recommended.
Endometrium↗
[Induction of bacterial translocation in rats with minimal doses of endotoxin].
OBJECTIVE: To determine whether a non lethal dose of intramuscular endotoxin in rats causes a physical disruption of the mucosal barrier and promotes the translocation of bacteria from gut to visceral organs. DESIGN: Prospective randomized trial. SETTING: Experimental laboratory university medical center. EXPERIMENTS: 60 male wistar rats, weighing 250 g. INTERVENTIONS: six hours and twenty-four hours after endotoxin (8 mg/kg) or saline (control group) given intramuscularly, rats were sacrificed and mesenteric lymph nodes, spleen and some segments of the ileum were removed. Lymph nodes and spleen were cultured for translocating bacteria while ileum segments were observed by light microscopy. RESULTS: Incidence of bacterial translocation increases from 6 hours (40% p < 0.05) to 24 hours (60%, p < 0.01) after endotoxin administration. Histologic evaluation of the ileum demonstrated that a mucosal injury occurred only at the 24 an hour and that it was characterized by an evident pronounced interstitial edema with focal breaks in the basal membranes of villous and glands. CONCLUSIONS: It appears that microorganisms and microbial products contained in the gut can cross the mucosal barrier and spread into other visceral organs also after a low dose of intramuscular endotoxin.
Animals↗
Primary lymphoma of the central nervous system.
Primary lymphoma of the central nervous system (CNS) represents a pathology that is no longer considered rare, also in the light of its high correlation with the human immunodeficiency virus (HIV) syndrome reported recently. Often the correct diagnosis of the disease is difficult to reach, owing to the wide spectrum of non-lymphoma pathologies from which it should be differentiated and the invasiveness of some diagnostic techniques. The biologic aggressiveness of the neoplasm often makes a combined radio-chemotherapeutic approach necessary. In contrast, surgical resection does not seem to provide any significant benefit. The clinical experience reported here, together with a review of the most recent literature, lead the authors to suggest the opportunity of treating primary lymphoma of the CNS with the most active and modern chemotherapeutic protocols in association with traditional treatments to obtain an improvement in overall survival.
Aged↗