Functional lateralization of the sensorimotor cortex in patients with schizophrenia: effects of treatment with olanzapine.

BACKGROUND: Earlier cross-sectional studies with functional magnetic resonance imaging (fMRI) in treated patients with schizophrenia have reported abnormalities of cortical motor processing, including reduced lateralization of primary sensory motor cortex. The objective of the present longitudinal study was to evaluate whether such cortical abnormalities represent state or trait phenomena of the disorder. METHODS: Seventeen acutely ill, previously untreated patients were studied after 4 weeks and after 8 weeks of olanzapine therapy. Seventeen matched healthy subjects served as control subjects. All subjects underwent two fMRI scans 4 weeks apart during a visually paced motor task using a simple periodic block design. Functional magnetic resonance imaging data were analyzed in Statistical Parametric Mapping (SPM99). Region of interest analyses were used to determine a laterality quotient (an index of lateralization) of motor cortical regions. RESULTS: The fMRI data indicated that patients had reduced activation of the primary sensory motor cortex at 4 weeks but not at 8 weeks; however, the laterality quotient in the primary sensory motor cortex was reduced in patients at both time points. CONCLUSIONS: These results suggest that some cortical abnormalities during motor processing represent state phenomena, whereas reduced functional lateralization of the primary sensory motor cortex represents an enduring trait of schizophrenia.     

Solid Lipid Nanoparticles in Lymph and Plasma After Duodenal Administration to Rats

Purpose. To evaluate the uptake and transport of solid lipid nanoparticles (SLN), which have been proposed as alternative drug carriers, into the lymph and blood after duodenal administration in rats. Methods. Single doses of two different concentrations of aqueous dispersions of unlabelled and labelled SLN (average diameter 80 nm) were administered intraduodenally to rats. At different times, samples of lymph were withdrawn by cannulating the thoracic duct and blood was sampled from the jugular vein. Monitoring continued for 45 and 180 minutes, for unlabelled and labelled SLN respectively. The biological samples were analysed by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and gamma-counting. Results. TEM analysis evidenced SLN in lymph and blood after duodenal administration to rats; the size of SLN in lymph did not change markedly compared to that before administration. The labelled SLN confirmed the presence of SLN in lymph and blood. Conclusions. The uptake and transport of SLN in the lymph, and to a lesser extent in the blood, were evidenced. The in vivo physical stability of SLN may have important implications in designing drug-carrying SLN.     

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.