Electromagnetic field affects the voltage-dependent potassium channel Kv1.3.

PURPOSE: Theoretical and experimental evidences support the hypothesis that Extremely Low-Frequency Electromagnetic Fields (ELF-EMF) can modulate voltage-gated channels. In this work we investigated the effect of ELF-EMF on Kv1.3, a member of the family of the voltage-gated potassium channels that is thought to be involved in key physiological functions, including the regulation of T-cells activation during the immune response. MATERIALS AND METHODS: Kv1.3 expressing CHO-K1 cells were exposed to a 20 Hz electromagnetic field at two different intensities: 268 µT and 902 µT. Kv1.3 potassium currents were recorded by whole-cell patch-clamp before, during and after field exposure. RESULTS: We found that the Kv1.3 current was increased significantly by the ELF-EMF in a subpopulation of CHO-K1 cells. The increase developed after a few seconds from the start of exposure, reached a steady-state and took several minutes to return to the baseline after field removal. CONCLUSIONS: These findings suggest that Kv1.3 may mediate interactions between ELF-EMF and living cells, disclosing new research opportunities on the molecular mechanisms with which electromagnetic fields affect physiological and pathological processes, including immunomodulation, inflammation and cancer.

Measuring the imaged-object distance with a stationary high-spatial-resolution scintillation camera.

A method to measure the detector-to-object distance from the images obtained with stationary high-spatial-resolution gamma-ray cameras for in vivo studies has been developed. It exploits the shift of the imaged object in the image plane, obtained at a certain tilt of the parallel-hole collimator. A linear dependence of the image displacement on the distance to the object has been measured using a high-spatial-resolution scintillation camera employing an yttrium-aluminium perovskite (YAP) scintillator. It is shown that the modified YAP camera can be used to obtain three-dimensional information without moving the camera or the object. The method could be applied in scintimammography and radioguided surgery, in lymphoscintigraphy, as well as in the analysis of the biodistribution of radiopharmaceuticals.

Performance measurements of a high-spatial-resolution YAP camera.

Physical properties of a position-sensitive camera for the analysis of biodistributions of gamma- and beta-emitting radiopharmaceuticals in small animals have been studied, in order to achieve optimal operating conditions. The camera consisted of a highly segmented yttrium-aluminate perovskite (YAP) scintillator, coupled to a position-sensitive photomultiplier. The energy resolution, the detection efficiency, the spatial resolution, the spatial linearity and the count-rate linearity of the YAP camera have been determined. Images related to initial activity levels and successive biodistribution evolution in mice organs are presented as an illustration of the camera performance.

Autoimmune hemolytic anemia in chronic hepatitis C virus infection: an unusual extrahepatic autoimmune manifestation.

We report a case of Coombs positive autoimmune hemolytic anemia occurring in a patient with chronic hepatitis C, never treated with interferon-alpha. Prednisone treatment induced the complete remission of both clinical and hematological findings after 2 months. The indirect Coombs test turned negative, while the direct Coombs test remained weakly positive. Autoimmune hemolytic anemia during chronic hepatitis C has been reported to develop only after or simultaneously with interferon-alpha therapy. After discarding other possible causes such as drugs, infectious, neoplastic, lymphoproliferative diseases, and essential mixed cryoglobulinemia, we made the hypothesis of a correlation between autoimmune hemolytic anemia and hepatitis C virus infection.

ALK-negative anaplastic large cell lymphoma and Hodgkin's disease of nodular sclerosing type in 2 siblings.

Familial clustering of Hodgkin's disease (HD) and increased risk of developing the disease among the siblings of affected patients suggest that both environmental and genetic factors may play an important role in its pathogenesis. An association between Epstein-Barr virus (EBV) and HD has been widely demonstrated. Recently, latent membrane protein of EBV has also been detected in CD30-positive anaplastic large cell lymphoma. Familial aggregation of HD and a three- to seven-fold-increased risk among the siblings of affected patients suggest increased genetically determined susceptibility. No data about genetic factors are available for anaplastic large-cell lymphoma. In this study, the authors report the case of a woman with anaplastic-lymphoma-kinase (ALK)-negative CD30-positive anaplastic large cell lymphoma, whose brother had developed HD 11 years previously. The clinical, histologic, and immunohistochemical features of the 2 lymphomas were studied. Both siblings showed bulky mediastinal involvement, effacement of normal lymph node architecture by large, atypical cells, resembling Reed-Sternberg cells, expression of EBV latent membrane protein-1 in the lymph node specimens, concordance of both HLA classes I and II. The clinical presentations and immunological studies disclose numerous similarities between the 2 cases and can suggest that their association is not fortuitous. At present, in problematic cases, a combination of morphologic, immunophenotypic and genetic studies may contribute to better define the tumour type.

Acquired factor VIII inhibitor associated with prostatic cancer: successful treatment with steroid and immunosuppressive therapy.

Factor VIII inhibitors are antibodies of the IgG class that block functional epitopes or antigenic sites of factor VIII. They occur in about 5-20% of hemophilia A patients after infusions of factor VIII concentrate. Antibodies to factor VIII can also arise spontaneously in association with various autoimmune and chronic inflammatory diseases, hematologic malignancies, solid tumors, certain drugs, dermatologic conditions, and in puerperium. In the majority of cases, the clinical course is characterized by severe hemorrhages. Strategies to treat such inhibitors are controversial. We present the case of a patient with prostatic cancer who developed acquired factor VIII inhibitor. His severe bleeding complications were treated successfully with cyclophosphamide in combination with methylprednisolone. Within a few months, moreover, the immunosuppressive therapy brought about complete disappearance of the inhibitor and normalization of coagulation parameters. Our case illustrates that, although the clinical course in patients with acquired factor VIII inhibitor is not predictable, and the inhibitor may disappear spontaneously, combined therapy with cyclophosphamide and methylprednisolone should be considered for patients with severe hemorrhages.

The relationship between splenic marginal zone B-cell lymphoma and chronic liver disease associated with hepatitis C virus infection.

An etiologically important role has been suggested for hepatitis C virus infection in the development of low-grade B-cell non-Hodgkin's lymphoma, such as splenic marginal zone B-cell lymphoma. We present a study of 3 patients with splenic marginal zone B-cell lymphoma and chronic hepatitis C, and describe clinical, histologic, and immunohistochemical features and the response to therapy in these cases. All 3 patients underwent splenectomy, polychemotherapy and alpha-interferon therapy. The first patient achieved complete remission; the second died of hepatic failure and anasarca 3 months after admission; as this writing, the third remains in complete remission 4.5 years after diagnosis. In the second patient, a long latency period of chronic hepatitis C virus infection was observed. Our data indicate that when early detection of the disease is possible, splenic marginal zone B-cell lymphoma has a relatively favorable prognosis. Our results could furthermore suggest an etiologic role for hepatitis C virus infection in the development of splenic B-cell lymphoma through multistep cooperating events. A fuller understanding of the virus-related mechanisms of lymphoproliferation could contribute significantly to the development of new therapeutic strategies.

The effect of delta rays on the ionometric dosimetry of proton beams.

The interface effects arising in the measurement of absorbed dose by ionization chambers, owing to the inhomogeneity between the walls and the gas, have been evaluated by an analytical model. The geometrical situation considered here is appropriate for representing the behaviour of a plane-parallel ionization chamber exposed to a radiotherapeutic beam of protons. Two gases, dry air and tissue equivalent gas (methane based), as well as six materials commonly used in ionization chamber walls, i.e. graphite, A-150 tissue equivalent plastic, C-522 air equivalent plastic, nylon type 6, polymethyl methacrylate and polystyrene, have been examined. The analysis of the results shows that, within the limits of the detector dimensions and proton energies commonly used in the dosimetry of radiotherapeutic beams, these effects, if not taken into account in the measurement interpretation, can entail deviations of up to about 2% with respect to the correct absorbed dose in gas.

Multiple myeloma in the elderly: clinical features and response to treatment in 113 patients.

BACKGROUND: Considering the conflicting results of the few reports on geriatric MM patients and the increasing relevance of the problem, we analyzed a series of 113 patients over 64 years of age treated with conventional chemotherapy. PATIENTS AND METHODS: The median age was 71 (range 65-92). Stage IA, IIA, IIIA and IIIB patients numbered 28, 33, 45 and 7, respectively. The M component was IgG in 73 patients (65%), IgA in 30 (26%), IgD in 3 (3%), light chain in 5 (4%); no monoclonal component was detected in 2 (2%) cases. Sixty-three patients showed symptomatic skeletal disease. Melphalan/prednisone (MP) was the first-line treatment in 84 patients (74%). Patients were grouped according to age (> 64 < or = 74; > or = 75) in order to carry out analysis. RESULTS: Seventy-eight cases (69%) showed a sizable reduction in the tumor mass; objective and partial response was achieved in 57 (50%) and 21 (19%) patients, respectively. Patients with stage I-II disease fared significantly better than stage III patients (median survival: 70 vs 38 months; p = 0.017). Response to first-line treatment correlated with overall survival; patients with responsive or refractory disease had median survival rates of 64 and 20 months, respectively (p = 0.0001). CONCLUSIONS: Neither patients above nor below 75 years of age showed any difference in presentation features or in response to treatment. These results suggest that advanced age should not be considered a major obstacle to active treatment.

[Therapeutic aspects of hairy cell leukemia]. / Aspetti terapeutici dell'hairy cell leukemia.

This work considers the new advances in hairy cell leukemia therapy. During the last decades the only useful treatments were splenectomy, or, in case of failure or relapse, various chemotherapeutic approaches. Sometimes leukapheresis, radiotherapy, androgens, allogenic bone marrow transplantation, corticosteroids and lithium salts were used with few good results. Interferon and 2-deoxicoformycin recently introduced for the treatment of HCL have determined a dramatic change in the outlook of this disease, producing a high percentage of complete and partial remission.

Myelofibrosis with myeloid metaplasia following essential thrombocythaemia.

We report a male patient in whom a diagnosis of essential thrombocythaemia was made at the age of 25. The clinical course was characterised by recurrent thrombotic episodes during the first few years of the disease, followed by a relatively benign course. He was treated with 32P, nitrogen mustard and plateletpheresis. A transformation into myelofibrosis with myeloid metaplasia was revealed 20 years after ET diagnosis. The length of the disease and the 32P therapy are discussed as factors favouring this metamorphosis.

Karyotype evolution in CML: high frequency of translocations other than the Ph.

The karyotypes of 33 Philadelphia-positive chronic myelogenous leukemia patients during the blastic phase are reported. Only three patients (9%) had a Philadelphia clone without further chromosomal aberrations, whereas, all the others had karyotype evolution. Aside from some nonrandom abnormalities (+8, i(17q), +Ph, +19) we found a higher frequency of clones with random structural rearrangements (13 cases, 39.4%) than previously reported. From a clinical point of view, however, the additional chromosomal (structural) abnormalities do not significantly influence the patients' survival.