DENDRITIC AND SPINAL PATHOLOGY OF THE PURKINJE CELLS FROM THE HUMAN CEREBELLAR VERMIS IN ALZHEIMER’S DISEASE

Background: Alzheimer’s disease constitutes one of the main causes of dementia. It is clinically characterized by memory impairment, deterioration of intellectual faculties and loss of professional skills. Furthermore changes in equilibrium and limb coordination are clinically demonstrable in persons with Alzheimer’s disease. In the present study we tried to figure out possible changes of the Purkinje cells in Alzheimer’s disease brains. Subjects and methods: We studied the Purkinje cells from the vermis of the cerebellum in 5 Alzheimer’ disease brains Golgi technique. Results: In the Purkinje cells from the inferior surface of the cerebellar hemispheres severe dendritic and spinal pathology consisting of loss of distal dendritic segments and alterations of dendritic spine morphology can be noticed in Alzheimer’s disease brains. Conclusions: The morphological and morphometric estimation of the dendrites and the dendritic spines of the Purkinje cells from the inferior surface of the cerebellar hemispheres in Alzheimer’s disease brains revealed substantial alterations of the dendritic arborization and marked loss of the dendritic spines, which may be related to cognitive impairment and motor deficits in Alheimer’s disease

A dose escalation and pharmacokinetic study of biweekly pegylated liposomal doxorubicin, paclitaxel and gemcitabine in patients with advanced solid tumours

To determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of pegylated liposomal doxorubicin (PLD), paclitaxel (PCX) and gemcitabine (GEM) combination administered biweekly in patients with advanced solid tumours. Twenty-two patients with advanced-stage solid tumours were treated with escalated doses of PLD on day 1 and PCX plus GEM on day 2 (starting doses: 10, 100 and 800 mg m−2, respectively) every 2 weeks. DLTs and pharmacokinetic (PK) parameters of all drugs were determined during the first cycle of treatment. All but six (73%) patients had previously received at least one chemotherapy regimen. The DLT dose level was reached at PLD 12 mg m−2, PCX 110 mg m−2 and GEM 1000 mg m−2 with neutropaenia being the dose-limiting event. Of the 86 chemotherapy cycles delivered, grade 3 and 4 neutropaenia occurred in 20% with no cases of febrile neutropaenia. Non-haematological toxicities were mild. The recommended MTDs are PLD 12 mg m−2, PCX 100 mg m−2 and GEM 1000 mg m−2 administered every 2 weeks. The PK data revealed no obvious drug interactions. Biweekly administration of PLD, PCX and GEM is a well-tolerated chemotherapy regimen, which merits further evaluation in various types of solid tumours

Serial analysis of circulating tumor cells in metastatic breast cancer receiving first-line chemotherapy

Background: We examined the prognostic significance of circulating tumor cell (CTC) dynamics during treatment in metastatic breast cancer (MBC) patients receiving first-line chemotherapy. Methods: Serial CTC data from 469 patients (2,202 samples) were used to build a novel latent mixture model to identify groups with similar CTC trajectory (tCTC) patterns during the course of treatment. Cox regression was used to estimate hazard ratios for progression-free survival (PFS) and overall survival (OS) in groups based on baseline CTCs (bCTC), combined CTC status at baseline to the end of cycle 1 (cCTC), and tCTC. Akaike Information Criterion (AIC) was used to select the model that best predicted PFS and OS. Results: Latent mixture modeling revealed 4 distinct tCTC patterns: undetectable CTCs (tCTCneg, 56.9% ), low (tCTClo, 23.7%), intermediate (tCTCmid, 14.5%), or high (tCTChi, 4.9%). Patients with tCTClo, tCTCmid and tCTChi patterns had statistically significant inferior PFS and OS compared to those with tCTCneg (P<.001). AIC indicated that the tCTC model best predicted PFS and OS when compared to bCTC and cCTC models. Validation studies in an independent cohort of 1,856 MBC patients confirmed these findings. Further validation using only a single pretreatment CTC measurement confirmed prognostic performance of the tCTC model. Conclusions: We identified four novel prognostic groups in MBC based on similarities in CTC trajectory patterns during chemotherapy. Prognostic groups included patients with very poor outcome (tCTCmid+tCTChi, 19.4%) who could benefit from more effective treatment. Our novel prognostic classification approach may be utilized for fine-tuning of CTC-based risk-stratification strategies to guide future prospective clinical trials in MBC

Coronary arterial fistulas

ABSTRACT: A coronary arterial fistula is a connection between one or more of the coronary arteries and a cardiac chamber or great vessel. This is a rare defect and usually occurs in isolation. Its exact incidence is unknown. The majority of these fistulas are congenital in origin although they may occasionally be detected after cardiac surgery. They do not usually cause symptoms or complications in the first two decades, especially when small. After this age, the frequency of both symptoms and complications increases. Complications include 'steal' from the adjacent myocardium, thrombosis and embolism, cardiac failure, atrial fibrillation, rupture, endocarditis/endarteritis and arrhythmias. Thrombosis within the fistula is rare but may cause acute myocardial infarction, paroxysmal atrial fibrillation and ventricular arrhythmias. Spontaneous rupture of the aneurysmal fistula causing haemopericardium has also been reported. The main differential diagnosis is patent arterial duct, although other congenital arteriovenous shunts need to be excluded. Whilst two-dimensional echocardiography helps to differentiate between the different shunts, coronary angiography is the main diagnostic tool for the delineation of the anatomy. Surgery was the traditional method of treatment but nowadays catheter closure is recommended using a variety of closure devices, such as coils, or other devices. With the catheter technique, the results are excellent with infrequent complications. DISEASE NAME AND SYNONYMS: Coronary arterial fistulas Coronary arterial fistulas or malformation

Recent translational research: circulating tumor cells in breast cancer patients

In breast cancer patients, hematogenous tumor cell dissemination can be detected, even at the single cell level, by applying immunocytochemical and molecular assays. Various methods for the detection of circulating tumor cells in the peripheral blood have been described. Results from recently reported studies suggest that circulating tumor cell levels may serve as a prognostic marker and for the early assessment of therapeutic response in patients with metastatic breast cancer. However, in early-stage breast cancer, the impact of circulating tumor cells is less well established than the presence of disseminated tumor cells in bone marrow; several clinical studies have demonstrated that cells of the latter type are an independent prognostic factor at primary diagnosis. In this article we briefly summarize recent studies examining the presence of circulating tumor cells in the blood and discuss further clinical applications