Pigmented solid-pseudopapillary neoplasm of the pancreas

A hitherto unrecognized variant of solid-pseudopapillary neoplasm of the pancreas is reported. The tumor presented in the pancreatic head of a 57-year-old female patient. It was a well-circumscribed, encapsulated nodule measuring 27 mm in diameter, with variegated yellow to brown and gray cut surface. Histologically, the neoplasm was composed of uniform polyhedral cells arranged around delicate fibrovascular cores retaining their solid pattern in the periphery, whereas central parts of the tumor were characterized by the formation of papillae and smaller pseudocysts. Neither mitotic activity nor invasive growth were found. Immunohistochemically, tumor cells were positive for vimentin, neuron-specific enolase, and CD56, whereas they were negative in reactions with antibodies directed against other neuroendocrine markers, cytokeratins, melanocytic markers, and pancreatic amylase. In addition to these typical findings, intracellular pigmented granules were found in the darker brown zones of the tumor. They were positively stained in periodic acid-Schiff reaction after diastase digestion, sudan black B, and in Schmorl stain. In contrast, they were not stained with Fontana-Masson, Ziehl-Neelsen, and Perls stains. Ultrastructurally, the pigment consisted of dense granules with lipid droplets resembling modified lysosomes. These results exclude the possibility of a melanogenic nature of the pigment and instead determine it as lipofuscin.     

Two interesting methods of estimation of the diagnosis uncertainty

It's very important to estimate the measure of uncertainty of data in the case of diagnosis of disease. We recommend two methods with help fuzzy interpretation of disease data.     

Subtypes of autism by cluster analysis based on structural MRI data

Abstract The aim of our study was to subcategorize Autistic Spectrum Disorders (ASD) using a multidisciplinary approach. Sixty four autistic patients (mean age 9.4±5.6 years) were entered into a cluster analysis. The clustering analysis was based on MRI data. The clusters obtained did not differ significantly in the overall severity of autistic symptomatology as measured by the total score on the Childhood Autism Rating Scale (CARS). The clusters could be characterized as showing significant differences: Cluster 1: showed the largest sizes of the genu and splenium of the corpus callosum (CC), the lowest pregnancy order and the lowest frequency of facial dysmorphic features. Cluster 2: showed the largest sizes of the amygdala and hippocampus (HPC), the least abnormal visual response on the CARS, the lowest frequency of epilepsy and the least frequent abnormal psychomotor development during the first year of life. Cluster 3: showed the largest sizes of the caput of the nucleus caudatus (NC), the smallest sizes of the HPC and facial dysmorphic features were always present. Cluster 4: showed the smallest sizes of the genu and splenium of the CC, as well as the amygdala, and caput of the NC, the most abnormal visual response on the CARS, the highest frequency of epilepsy, the highest pregnancy order, abnormal psychomotor development during the first year of life was always present and facial dysmorphic features were always present. This multidisciplinary approach seems to be a promising method for subtyping autism.     

Screening detected celiac disease in children with type 1 diabetes mellitus: effect on the clinical course (a case control study)

OBJECTIVE: To investigate clinical and metabolic characteristics of diabetic children with screening detected celiac disease in a multicenter case-control study. METHODS: Cases: 98 diabetic patients were diagnosed as having silent celiac disease by screening with endomysial antibodies and subsequent biopsy. Controls: two controls in the same center were chosen, (stratified by age and age-at-diabetes onset) who were negative for endomysial antibodies (n = 195). Height, weight, HbA1c, insulin dosage and acute complications were documented for at least 1 year of follow up. RESULTS: Mean age of diabetes manifestation was 6.5 +/- 4.1 years and diagnosis of celiac disease was made at 10.0 +/- 5.4 years. Biopsy showed total or subtotal mucosal atrophy in 74 patients. The mean observation period after the diagnosis of celiac disease was 3.3 +/- 1.9 years. Mean HbA1c levels were similar between cases and controls (8.63% +/- 1.45% versus 8.50% +/- 1.39%; P = 0.35). There was also no difference in the frequency of severe hypoglycemia, ketoacidosis and the applied insulin dosage (P = 0.45). Body mass index-standard deviation score at celiac disease diagnosis (0.57 +/- 1.24 versus 0.52 +/- 1.07) and height-standard deviation score (0.14 +/- 1.13 versus 0.30 +/- 0.95) did not differ between cases and controls. After diagnosis of celiac disease, weight gain was diminished in boys with celiac disease compared with their controls (P < 0.05). Female cases also had a lower body mass index than female controls (P = 0.067). CONCLUSION: In a cohort of diabetic children, silent celiac disease had no obvious effect on metabolic control but negatively influenced weight gain.     

Design, synthesis, and evaluation of 3,4-dihydro-2H-[1,4]diazepino[6,7,1-hi]indol-1-ones as inhibitors of poly(ADP-ribose) polymerase

The design, synthesis, and biological evaluation of potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) are reported. A novel series of 3,4-dihydro-2H-[1,4]diazepino[6,7,1-hi]indol-1-ones were designed using a combination of protein structure-based drug design, molecular modeling, and structure-activity relationships (SAR). These novel submicromolar inhibitors possess a tricyclic ring system conformationally restricting the benzamide in the preferred cis orientation. The compounds were designed to optimize space-filling and atomic interactions within the NAD+ binding site of PARP-1. Previously described and newly adapted methods were applied to syntheses of these tricyclic inhibitors. Various modifications were made to the diazepinoindolones at the 6- and 7-positions in order to study this region of the active site and optimize noncovalent interactions. The electron density of derivative 28 bound to chicken PARP-1 revealed that the oxime makes a tight hydrogen bond with the catalytic gamma-carboxylate of glutamic acid (Glu) 988 in accordance with our original designs and models. Most of the compounds have been evaluated for inhibition of human PARP-1. Selected inhibitors were also tested for the ability to potentiate the cytotoxic effect of the DNA-damaging agent Topotecan.     

Depressive disorders and the metabolic syndrome of insulin resistance

Metabolic syndrome of insulin resistance and depression are both considered important cardiovascular risk factors. The aim of this study was to ascertain a possible association between these conditions in a population sample of 116 subjects (54 males, 62 females, aged 60 +/- 8 and 60 +/- 9 years, respectively). A standard questionnaire-the Hospital Anxiety Depression Scale-was used for the assessment of depressive disorder and clinical definition of insulin resistance, requiring the presence of three or more of the following factors: triglycerides > 1.7 mmol/L; and high-density lipoprotein cholesterol < 1.0 mmol/L; blood pressure >/= 130/85 mm Hg; waist circumference > 102 cm in males and > 88 cm in females; fasting glucose 6.1-7.8 mmol/L. Depressive disorders prevailed significantly more in women than in men (39% and 26%, respectively), and prevalence of depression in subjects with metabolic syndrome of insulin resistance (by definition) was about four times higher than in subjects without depression. Depressive subjects had also higher heart rate, waist circumference, lower high-density lipoprotein cholesterol, higher triglycerides, and higher body mass index. Higher sympathetic nervous activity in insulin-resistant subjects with depression was indicated.     

Long-term behavioral and morphological consequences of nonconvulsive status epilepticus in rats

The aims of the present study were to ascertain whether nonconvulsive status epilepticus (NCSE) could give rise to long-term behavioral deficits and permanent brain damage. Two months after NCSE was elicited with pilocarpine (15 mg/kg i.p.) in LiCl-pretreated adult male rats, animals were assigned to either behavioral (spontaneous behavior, social interaction, elevated plus-maze, rotorod, and bar-holding tests) or EEG studies. Another group of animals was sacrificed and their brains were processed for Nissl and Timm staining as well as for parvalbumin and calbindin immunohistochemistry. Behavioral analysis revealed motor deficits (shorter latencies to fall from rotorod as well as from bar) and disturbances in the social behavior of experimental animals (decreased interest in juvenile conspecific). EEGs showed no apparent abnormalities. Quantification of immunohistochemically stained sections revealed decreased amounts of parvalbumin- and calbindin-immunoreactive neurons in the motor cortex and of parvalbumin-positive neurons in the dentate gyrus. Despite relatively inconspicuous manifestations, NCSE may represent a risk for long-term deficits.