Akinetic crisis in dementia with Lewy bodies.

BACKGROUND AND PURPOSE: Dementia with Lewy bodies (DLB) is characterised by neuroleptic hypersensitivity. It is unclear, however, whether the neuroleptic hypersensitivity implies an increased incidence of neuroleptic malignant syndrome (NMS) or of akinetic crisis (AC), which are expressions of the same possibly lethal clinical event, and whether AC in DLB can appear independently of neuroleptic treatment. In our prospective study, we assessed the incidence of AC in a cohort of DLB as compared with that in patients with Parkinson disease (PD). METHODS: In total, 614 patients with PD and 236 DLB were recruited and followed during 2005-2013. AC was diagnosed as sudden akinetic state unresponsive to dopaminergic rescue drugs, dysphagia and serological alterations without recovery for 48 h or more requiring hospital admission. Exposure to neuroleptics was specifically evaluated, because of the high implicit risk in DLB. RESULTS: 24 patients with PD (3.9%) and 16 patients with DLB (6.8%) developed AC. 77 (32.6%) DLB and 32 (5.2%) PD were exposed to typical neuroleptics, but only 8 DLB and 3 PD presented with AC. Disease duration before AC was lower in DLB than in PD group (p<0.01). Outcome was fatal in 8 patients with (50%) DLB and 3 (12.5%) PD (p=0.05). When age and use of neuroleptics were adjusted for into a Cox proportional hazards model predicting time to AC, the HR of patients with DLB was 13.0 (95% CI 4.23 to 39.9; p<0.001). CONCLUSIONS: AC in DLB can appear independently of neuroleptic treatment, occurs earlier and is more frequently fatal than in PD.

Ascertainment bias in dementias: a secondary to tertiary centre analysis in Central Italy and conceptual review.

BACKGROUND AND AIMS: Ascertainment bias (AB) indicates a bias of an evaluation centre in estimating the prevalence/incidence of a disease due to the specific expertise of the centre. The aim of our study was to evaluate classification of different types of dementia in new cases appearing in secondary and tertiary centres, in order to evidence possible occurrence of AB in the various (secondary to tertiary) dementia centres. METHODS: To assess the mechanism of AB, the rates of new cases of the different forms of dementia reported by different centres were compared. The centres involved in the study were 11 hospital-based centres including a tertiary centre, located in the University Department of Clinical Neurology. The tertiary centre is endowed with state-of-the-art diagnostic facilities and its scientific production is prominently focused on dementia with Lewy bodies (DLB) thus suggesting the possible occurrence of a bias. Four main categories of dementia were identified: Alzheimer's disease (AD), DLB, fronto-temporal dementia (FTD), vascular dementia (VaD), with other forms in a category apart. The classification rate of new cases of dementia in the tertiary centre was compared with rates reported by secondary centres and rates of recoding were calculated during a follow-up of 2 years. RESULTS: The study classified 2,042 newly diagnosed cases of dementia in a population of 1,370,000 inhabitants of which 315,000 were older than 65. AD was categorized in 48-52 % of cases, DLB in 25-28 %, FTD in 2-4 % and VaD in 17-28 %. During the 2-year follow-up the diagnosis was re-classified in 40 patients (3 %). The rate of recoding was 5 % in the tertiary centre, 2-8 % in referrals from secondary to tertiary centre, 2-10 % in recodings performed in secondary centres and addressed to tertiary centre. Recoding or percentages of new cases of AD or DLB were not different in the comparison between secondary or between secondary and tertiary centres. FTD and VaD were instead significantly recoded. CONCLUSION: The results of the study suggest that in a homogeneous area, AB is not interfering with diagnosis of AD or DLB.

Management of colorectal liver metastases in patients with peritoneal carcinomatosis.

We have taken into consideration papers published in the last 10 years on the treatment of patients with peritoneal carcinomatosis and hepatic metastasis from colorectal cancer and the pre-operative prognostic factors needed to consider these subjects eligible for surgical treatment. Peritoneal carcinomatosis should not be considered an absolute contraindication to hepatic resection if it is possible to perform a complete resection of all peritoneal and liver disease.

A phase II study of VM-26 plus lonidamine in pretreated small cell lung cancer.

BACKGROUND: SCLC relapsing or refractory after induction chemotherapy is a chemoresistant tumor. The outcome of salvage chemotherapy is poor, with low response rates (< 30%) and short survival times (3-4 months). The development of drug resistance is considered the major cause of failure of treatment. VM-26 is one of the most active drugs in SCLC. Lonidamine has shown to enhance in both vivo and vitro antitumor activity of several cytotoxic drugs acting on drug resistance mechanisms. MATERIALS AND METHODS: VM-26 and lonidamine were employed as salvage chemotherapy in 30 small cell lung cancer patients. The doses of chemotherapy used were: VM-26 100 mg/m2, i.v., days 1 to 3; lonidamine 600 mg, p.o., days 1 to 5, recycled every 3 weeks. RESULTS: We observed 13.3% of objective response and a median survival of 4 months. All the responses were obtained in patients relapsing after a response to induction chemotherapy. Toxicity was moderate with no toxic death. CONCLUSIONS: Our study shows that Lonidamine failed to increase the VM-26 activity in pretreated small cell lung cancer patients.

Primary plasmacytoma of the breast.

We describe a solitary extramedullary plasmacytoma of the breast in a 37-year-old woman. No other involvement was detected in the bone marrow or in any other site during a 15-month follow-up period. Extramedullary plasmacytomas of the breast are extremely rare, especially those that are not associated with multiple myeloma. We review the histologic features of the previously reported cases with an emphasis on differential diagnosis and the difficulties encountered in arriving at the correct diagnosis in frozen sections.

A primate model for age and host response to genital herpetic infection: determinants of latency.

Thirty five female Cebus albifrons monkeys (16 adolescents and 19 adults) were infected vaginally with herpes simplex virus (HSV) type 2. Fifteen developed spontaneous recurrent genital HSV infections. All 35 were killed for study eight to 12 months after primary infection, and tissue from the vagina, cervix, uterus, ovary, paracervical autonomic plexus, and lumbosacral dorsal root ganglia of eight animals. Host age was the most important variable influencing viral latency; 69% of adolescents and 42% of adults had latent HSV type 2 infections. Animals that developed latent infections were significantly easier to infect, shed virus during the primary infection significantly longer, and had more severe primary disease than those who did not become latently infected.

Prednisone, indomethacin and airway responsiveness in toluene diisocyanate sensitized subjects.

We investigated whether late asthmatic reactions and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI) in sensitized subjects are inhibited by indomethacin and/or prednisone. Four sets of experiments were conducted in five subjects sensitized to TDI. To assess late asthmatic reactions to TDI, FEV1 was measured immediately before and after exposure to TDI and then hourly for 8 h. To assess change in airway responsiveness, the provocative dose (mg) of methacholine that caused a decrease in FEV1 of 20% (PD20FEV1) before treatment, and then before and after exposure to TDI was measured. In the first set of experiments, each subject was given no treatment and was studied before and 8 h after exposure to TDI; in the other two sets, each subject was studied before treatment, then during treatment with indomethacin (50 mg q.i.d. for 3 days, orally) or prednisone (50 mg once a day, for 3 days, orally), both before and 8 h after TDI exposure. In a fourth series of experiments, each subject was again given no treatment and studied before and 8 h after TDI. When the subjects were given no treatment or indomethacin, TDI caused late asthmatic reactions and increased airway responsiveness to inhaled methacholine. In contrast, when the subjects were given prednisone, TDI caused neither late asthmatic reactions nor increased airway responsiveness. Treatment with indomethacin and prednisone did not change baseline FEV1 and airway responsiveness. These results suggest that release of prostaglandins does not contribute to late asthmatic reactions and the associated increase in airway responsiveness induced by TDI. Inflammatory mediators inhibited by prednisone but not by indomethacin may be involved.