Mode of inheritance in mood disorder families according to fluvoxamine response

Mood disorders are known to cluster within families, but the mode of transmission remains largely unknown. The purpose of our analysis was to determine whether selection of a sample that was homogeneous in its response to an antidepressant provided stronger evidence for a single major locus. Complex segregation analysis was applied to a sample of 171 Italian families of bipolar and unipolar probands that were responsive to the antidepressant fluvoxamine. We used regressive logistic analyses to determine the best fit from among environmental, arbitrary Mendelian, dominant, recessive and additive models. For the 171 affective families with probands that were responsive to the antidepressant fluvoxamine, a Mendelian model of inheritance was rejected. When considering 68 families of bipolar probands, the best fit was obtained for a Mendelian dominant model of transmission. The identification of a Mendelian mode of transmission in bipolar subjects who were selected according to their response to fluvoxamine supports the use of a pharmacological criterion as a tool for identifying true genetic disorders.     

Differential Effects of High-Dose Gamma Irradiation on the Production of Transforming Growth Factor-Beta in Fresh and Established Human Ovarian Cancer

Tumor cells from five freshly isolated ovarian tumors and four established human ovarian carcinoma cell lines were analyzed for the production of the immunoinhibitory cytokine transforming growth factor-beta (TGF-β) before and after exposure to gamma irradiation and/or the cytokines TNF-α plus IFN-γ. All fresh tumors secreted high levels of TGF-β when compared to the levels produced by the established ovarian carcinoma cell lines. TGF-β produced by fresh tumors was significantly reduced after high doses of gamma irradiation (10,000 cGy). In contrast with the established cell lines, irradiation significantly increased TGF-β secretion. Exposure of fresh tumor cells to cytokines followed by irradiation caused significant reduction of TGF-β released when compared to the amount released after exposure to cytokines only. However, in the established cell lines, cytokines followed by irradiation again significantly increased TGF-β production. These data indicate that high doses of irradiation in fresh ovarian tumors, unlike established ovarian carcinoma cell lines, can significantly reduce the local production of this potent immunoinhibitory cytokine. This effect could work to further amplify weak immunological responses within the tumor. In addition, these findings indicate major differences between fresh tumor samples and established cell lines and warn against the sole use of continuous cell lines as models for tumors growingin vivo.     

Early-onset ataxia with cardiomyopathy and retained tendon reflexes maps to the friedreich's ataxia locus on chromosome 9q

Absence of lower limb tendon reflexes has been considered an essential diagnostic criterion for Friedreich's ataxia (FA). However, preservation of knee and ankle jerks has been reported in a few patients. Linkage analysis to FA locus (FRDA) on chromosome 9q13-21.1 was performed in 11 patients from 6 families with FA phenotype, including cardiomyopathy, but retained reflexes (FARR). A maximal lod score of 3.38 at recombination fraction theta equal to 0.00 was obtained demonstrating that FARR maps to the FRDA locus. These results suggest that FARR is a variant phenotype of FA.     

Diagnostic approach to a case of a complex cystic mass of the pelvis

The diagnostic approach to a patient with a complex pelvic cyst incidentally found on CT and come to the Emergency Department for lumbar pain, is discussed. To better define the location and nature of the cyst MRI was performed. It supported the diagnostic hypothesis of cystic endosalpingiosis, confirmed at the histological examination of the surgical specimen.     

The role of ultrasound of sentinel nodes in the pre- and post-operative evaluation of stage I melanoma patients

We have investigated the role of high-resolution ultrasound (US) in the analysis of sentinel node(s) in melanoma patients in pre-operative staging and follow-up. One hundred and six lymph node basins in 88 melanoma patients undergoing sentinel node biopsy (SNB) were examined: 25 (23.6%) were US positive for metastases and 81 (76.4%) were negative. Subsequent histological analysis of the 81 negative lymph nodes confirmed the absence of metastases in 80 cases (98.8%), whereas, in the 25 US-positive lymph nodes, metastases were found in 16 cases (64%). The follow-up of all patients submitted to SNB in our unit included a US investigation of operated and contralateral nodal basins every 4 months for the first 3 years and then every 6 months. Of a total of 300 patients, four (1.6%) were found to have locoregional nodal disease during follow-up. In three of these four patients, US was crucial in indicating the presence of nodal metastases, which would have gone undetected on physical examination. The result of this study (negative predictive value of 98.7%) introduces the possibility of selecting patients who may avoid an SNB procedure based on the results of pre-operative US examination.     

Update: current management issues in malignant melanoma

The incidence of melanoma has increased continuously during the last decade. Surgery is the mainstay of therapy but, for patients with thick lesions or regional metastatic lymph nodes, there is a high risk of relapse. For this group of patients, there is no standard therapy or general agreement amongst oncologists. In this article, we review the current management of melanoma with regard to past completed adjuvant trials and open trials. Moreover, we discuss the role of chemotherapy in metastatic melanoma, in particular with attention to the use of fotemustine.     

Bone marrow transplantation for lymphoma CR1

PURPOSE OF REVIEW: Despite several reports showing the superiority of autologous stem cell transplantation over conventional chemotherapy in the salvage treatment of non-Hodgkin lymphoma, its use as part of first-line therapy in this disease is still controversial. The review highlights the most relevant studies on autologous stem cell transplantation for non-Hodgkin lymphoma at diagnosis published over the past year. RECENT FINDINGS: Several recent studies have shown that autologous stem cell transplantation may offer survival benefits in patients with both diffuse large cell lymphoma and follicular cell lymphoma whose prognostic features are poor. An advantage of autologous stem cell transplantation has also been documented for other non-Hodgkin lymphoma subtypes, in particular mantle-cell lymphoma, in which autologous stem cell transplantation is probably the most effective first-line option presently available. Nevertheless, whether autologous stem cell transplantation is definitely better than conventional chemotherapy is still under discussion, and the issue is still less clear, given the new opportunities offered by rituximab combined with chemotherapy. Autologous stem cell transplantation may also benefit from the addition of rituximab as an in vivo purging agent. Thus, large randomized trials are required to fully define the role of autologous stem cell transplantation in first-line treatment for high-risk non-Hodgkin lymphoma. Such trials should compare autologous stem cell transplantation with chemotherapy, both supplemented with rituximab, in the most frequent CD20+ lymphoma subtypes. The up-front use of autologous stem cell transplantation might find support from the recent observation that patients who do not respond to this treatment may still have a good chance of being rescued by reduced-intensity allogeneic transplantation. SUMMARY: Autologous stem cell transplantation remains a valid research strategy in first-line therapy and, along with new agents and nonmyeloablative allogeneic transplantation, may help to increase the cure rate for high-risk non-Hodgkin lymphoma.