Category-specific Semantic Deficits do not Reflect the Sensory/Functional Organization of the Brain: A Test of the “Sensory Quality” Hypothesis

We report the performance of a herpes simplex encephalitis patient, EA, who shows a dissociation between poor performance for living things and spared performance for sensory quality categories, when appropriate measures are taken to control for baseline differences among categories in task difficulty and when we eliminate the contribution of visual processing deficits in the recognition of objects. This pattern of performance is problematic for theories of category-specific deficits that are based on the assumption that these deficits reflect selective damage to modality-specific semantic subsystems but is consistent with domain-specific accounts and theories based on the assumption that the structure of conceptual knowledge reflects the correlational structure among object properties.     

Exocrine pancreatic cancer,cigarette smoking,and diabetes mellitus: a case-control study in northern Italy

The role of cigarette smoking and diabetes mellitus as risk factors for exocrine pancreatic cancer (PC) was investigated in a hospital based case-control study. Current smokers were at increased risk for PC (OR = 2.36, 95% CI 1.53-3.63): the magnitude of the risk was related to the lifetime amount of smoking (chi2(trend) = 17.00; P < 0.0001). Among former smokers, after 15 years from ceasing smoking, the risk for PC dropped to the level of a lifetime non-smoker, whichever the lifetime smoking amount. Diabetes was associated with a 2.89-fold increased risk for PC (95% CI 1.71-4.86): the risk was 4.76 (95% CI 1.99-11.53) for diabetes diagnosed up to 2 years before the diagnosis of PC and dropped to 2.07 (95% CI 1.02-4.20) for diabetes diagnosed more than 5 years before PC. The risk for PC was estimated according to the treatment used to control diabetes: it was 6.49 (95% CI 2.28-18.48) for insulin treated diabetes and 2.12 (95% CI 1.16-3.87) for diabetes treated with oral hypoglycemic drugs. The risk of PC for diabetes treated for more than 5 years before the diagnosis of PC was 6.21 (95% CI 1.61-23.96) for patients treated with insulin and 1.21 (95% CI 0.50-2.92) for those treated with oral hypoglycemic drugs: the type of treatment needed to control the disease may discriminate between the diabetes that represents a consequence of cancer from the diabetes that could represent an etiological co-factor. More studies are needed to clarify whether long-lasting insulin-treated diabetes is an etiological co-factor in PC.     

Vectorcardiographic evaluation of diabetic cardiomyopathy and of its contributing factors

Summary In order to investigate the prevalence of vectorcardiographic bites, expression of small areas of fibrosis, atrophy or degeneration of the myocardium, we studied, using the vectorcardiograms (VCG) of 101 diabetic patients (35 with insulin-dependent and 66 with non-insulin-dependent diabetes mellitus, aged from 25 to 60 years, without hypertension, coronary artery disease, or intraventricular conduction defects) and 228 normal control subjects, matched for age and sex. The prevalence of bites was 38.6% in diabetic patients and 10.0% in the control group (p<0.001). Diabetic patients were also subdivided into groups according to age, sex, metabolic control, risk factors for coronary heart disease, type of diabetes, duration of diabetes and diabetic microangiopathy. No correlation was found between any of the variables investigated nor of a combination of these, and the presence of bites. We conclude that VCG is a sensitive test for cardiac involvement in diabetic patients but that it cannot be used to identify any specific factor able to influence the onset and evolution of this involvement.     

Different variables predict anomia in different subjects: a longitudinal study of two Alzheimer's patients

Two Alzheimer's patients participated in a longitudinal study of picture naming aimed at analysing the effect of lexical frequency, age of acquisition, stimulus familiarity, word length, name imageability, visual complexity and semantic category membership on naming success. The results were analysed with a new method [Capitani, E., & Laiacona, M. (2004). A method for studying the evolution of naming error types in the recovery of acute aphasia: A single-patient and single-stimulus approach. Neuropsychologia, 42, 613-623] that allows us to consider the consistency of responses to stimuli over repeated testing within clinical stages. The experiment was carried out as a longitudinal study of single cases, and the effect of each variable was estimated after removing the overlap with the other predictors. The semantic category of stimuli was not an influential factor for either patient. Other findings sharply distinguished between the two patients. In one case, disease-related decline consistently affected mainly late acquired names, whereas in the other case the decline affected names corresponding to low-familiarity items. To interpret this contrast, we further analysed the quality of the errors produced by each patient. This study shows that the psycholinguistic characteristics of a stimulus may exert varying influence in different patients, warranting further development of this line of inquiry.     

Reelin down-regulation in mice and psychosis endophenotypes

Reelin, a large glycoprotein secreted by telencephalic GABAergic neurons, plays an important role in neuronal guidance embryonically and in synaptic plasticity postnatally. The reeler heterozygous mouse (+/rl) appears superficially normal but has been of interest as an animal model for psychosis since the discovery that reelin is 50% down-regulated in postmortem psychotic brain. Brain abnormalities in +/rl are similar to psychotic brain and include a reduction in glutamic acid de carboxylase 67 (GAD₆₇), dendritic arbors and spine density in cortex and hippocampus, and abnormalities in synaptic function including long-term potentiation (LTP). In spite of these abnormalities, behavioral abnormalities in +/rl are subtle and controversial. Recent findings indicate that the reelin (RELN) and GAD₆₇ promoters are hypermethylated in GABAergic neurons of psychotic postmortem brain and that DNA methyltransferase 1 (DNMT1) is up-regulated. Hypermethlyation of RELN and GAD₆₇ promoters can be induced by treating mice with methionine, and these mice display brain and behavioral abnormalities similar to +/rl. Thus, an animal model that combines genetic heterozygocity with epigenesis holds promise for understanding the role of Reelin down-regulation in psychosis     

Reduction and binding of arsenate in marmoset monkeys

The metabolism of ⁷⁴As-arsenate (As V, 0.4 mg As/kg body weight, IV) in marmoset monkeys (two males and two females) was studied. Unlike all other animal species studied so far, the marmoset was found to be unable to metabolize the arsenate to dimethylarsinic acid. Most of the absorbed arsenate was reduced to arsenite (As III) in vivo. Only 20% was excreted in the urine as unchanged As V. A further 20% of the dose was excreted as As III. The rest of the As III produced was bound to the tissues, giving a distribution picture very similar to that reported earlier for marmoset monkeys given arsenite. The tissues with longest retention of arsenic were the liver, upper gastrointestinal tract (oral cavity and esophagus), skin, kidneys and gall bladder. The pronounced accumulation in the liver resulted from specific binding of arsenic to the rough microsomal membranes, unique to this animal species.At the time of this study, visiting researcher at the National Institute of Environmental Medicine and the Department of Environmental Hygiene, the Karolinska Institute, Stockholm, Sweden     

Oxaliplatin‐based chemotherapy (dexamethasone,high‐dose cytarabine,and oxaliplatin) ± rituximab is an effective salvage regimen in patients with relapsed or refractory lymphoma

BACKGROUND:

Patients affected by relapsed or primary refractory lymphomas currently have a poor prognosis and no standard salvage treatment options. This study was carried out to assess the efficacy and safety of a dexamethasone, high‐dose cytarabine, and oxaliplatin as salvage therapy in those patients, replacing cisplatin with oxaliplatin in the standard dexamethasone, cytarabine, and cisplatin scheme.

METHODS:

Seventy patients with relapsed or refractory aggressive non‐Hodgkin or Hodgkin lymphoma were treated from September 2001 to September 2007. The median age of patients was 51 years (range, 19‐75 years). Histological subtypes were: diffuse large B‐cell lymphoma (n = 47) and Hodgkin lymphoma (n = 23). The overall response rate was 73% (51 of 70), with 30 (43%) complete remissions and 21 (30%) partial remissions. Fifty‐two patients were treated with dexamethasone, high‐dose cytarabine, and oxaliplatin as second‐line chemotherapy. Forty‐eight patients were enrolled in an autologous stem cell transplantation program; forty (83%) finally proceeded to high‐dose consolidation and autografting.

RESULTS:

No grade 3 or 4 nonhematological toxicity was demonstrated; in particular, no renal or neurotoxicity was reported. After a median follow‐up period of 21 months (range, 2‐87 months), 22 (31%) patients had died. Probabilities of 2‐year progression‐free survival (PFS) and overall survival (OS) were 44% and 71%, respectively. In the chemosensitive patients, the PFS and OS were 52% and 83%, respectively. The only factor that significantly correlated with better OS was the response to therapy.

CONCLUSIONS:

This study confirms that dexamethasone, high‐dose cytarabine, and oxaliplatin ± rituximab is an effective and feasible outpatient regimen for salvage therapy in patients affected by relapsed or refractory lymphoma. Moreover, the feasibility and efficacy of this scheme as an in vivo chemosensitive test in patients in autotransplantation programs was confirmed. Cancer 2010. © 2010 American Cancer Society.     

Persistence of Mammary Artery Branches and Blood Supply to the Left Anterior Descending Artery

Background. Partial harvesting of the left internal mammary artery (LIMA) is a widespread technique used during minimally invasive coronary operations performed through a left anterior small thoracotomy. The influence of persisting LIMA branches was investigated to evaluate their effect on the blood flow of the left anterior descending artery.

Methods. Thirty patients, 15 with totally (group A) and 15 with partially (group B) harvested LIMAs, were evaluated. All the patients underwent postoperative angiography, during which a flow map of the LIMA was performed. The average peak velocity and the diastolic-to-systolic peak velocity ratio were recorded. The LIMA graft flow pattern was recorded in the proximal and distal thirds of the artery. Intramammary adenosine (12 to 14 μg) was injected and the average peak velocities before and after injection were calculated.

Results. The average peak velocity was similar in both groups in the proximal and distal thirds of the LIMA (25 ± 7 and 26 ± 5 cm/sec, respectively, in group A versus 27 ± 5 and 25 ± 5 cm/sec, respectively in group B; p = NS). The diastolic-to-systolic peak velocity ratio was similar proximally (0.78 ± 0.3 in group A versus 0.69 ± 0.3 cm/s in group B; p = NS), but not distally (1.72 ± 0.1 in group A versus 0.97 ± 0.3 in group B; p < 0.0005). The LIMA graft flow reserve was similar both proximally and distally (2.6 ± 0.6 and 2.5 ± 0.3 cm/s, respectively, in group A versus 2.6 ± 0.5 and 2.6 ± 0.3 cm/s, respectively, in group B; p = NS).

Conclusions. The persistence of LIMA branches does not influence the blood flow of the left anterior descending artery after acute adenosine-induced myocardial hyperemia. If a left anterior small thoracotomy is used in left anterior descending artery direct revascularization, complete LIMA harvesting is not mandatory and depends on the personal preference of the surgeon.     

Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents

Context  Traditionally, stent thrombosis has been regarded as a complication of percutaneous coronary interventions during the first 30 postprocedural days. However, delayed endothelialization associated with the implantation of drug-eluting stents may extend the risk of thrombosis beyond 30 days. Data are limited regarding the risks and the impact of this phenomenon outside clinical trials. Objective  To evaluate the incidence, predictors, and clinical outcome of stent thrombosis after implantation of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice. Design, Setting, and Patients  Prospective observational cohort study conducted at 1 academic hospital and 2 community hospitals in Germany and Italy. A total of 2229 consecutive patients underwent successful implantation of sirolimus-eluting (1062 patients, 1996 lesions, 2272 stents) or paclitaxel-eluting (1167 patients, 1801 lesions, 2223 stents) stents between April 2002 and January 2004. Interventions  Implantation of a drug-eluting stent (sirolimus or paclitaxel). All patients were pretreated with ticlopidine or clopidogrel and aspirin. Aspirin was continued indefinitely and clopidogrel or ticlopidine for at least 3 months after sirolimus-eluting and for at least 6 months after paclitaxel-eluting stent implantation. Main Outcome Measures  Subacute thrombosis (from procedure end through 30 days), late thrombosis (>30 days), and cumulative stent thrombosis. Results  At 9-month follow-up, 29 patients (1.3%) had stent thrombosis (9 [0.8%] with sirolimus and 20 [1.7%] with paclitaxel; P = .09). Fourteen patients had subacute thrombosis (0.6%) and 15 patients had late thrombosis (0.7%). Among these 29 patients, 13 died (case fatality rate, 45%). Independent predictors of stent thrombosis were premature antiplatelet therapy discontinuation (hazard ratio [HR],  89.78; 95% CI, 29.90-269.60; P<.001), renal failure (HR,  6.49; 95% CI, 2.60-16.15; P<.001), bifurcation lesions (HR,  6.42; 95% CI, 2.93-14.07; P<.001), diabetes (HR,  3.71; 95% CI, 1.74-7.89; P = .001), and a lower ejection fraction (HR,  1.09; 95% CI, 1.05-1.36; P<.001 for each 10% decrease). Conclusions  The cumulative incidence of stent thrombosis 9 months after successful drug-eluting stent implantation in consecutive "real-world" patients was substantially higher than the rate reported in clinical trials. Premature antiplatelet therapy discontinuation, renal failure, bifurcation lesions, diabetes, and low ejection fraction were identified as predictors of thrombotic events.