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.     

Nonmedical costs associated with rotavirus disease requiring hospitalization

BACKGROUND: As the most common cause of severe diarrhea among children, rotavirus has a significant economic impact. Previous studies focused on the direct medical costs of rotavirus infections; however, nonmedical costs account for the majority of the financial burden from this disease. Herein, we report the results from the largest prospective study in the United States determining the nonmedical costs of severe rotavirus infections. METHODS: Prospective, active, gastroenteritis case surveillance was conducted between November 1997 and December 1999 at 3 pediatric medical centers. Rotavirus infection was identified for 548 children admitted between 2 weeks and 5 years of age. Detailed information about nonmedical costs during the prehospitalization, hospitalization and posthospitalization periods was obtained through interviews. RESULTS: The average nonmedical cost per case of rotavirus disease was USD $448.77, including $359.04 for missed work, $56.66 for transportation, $11.90 for oral rehydration solutions, $9.59 for diapers, $6.83 for child care changes, $3.82 for special foods and $0.93 for formula changes. More than one-half of these expenses (53%) occurred outside the hospitalization period, and 80% of the cost was attributable to missed work. CONCLUSIONS: With an estimated 50,000 hospitalizations attributable to rotavirus each year in the United States, the nonmedical costs of severe rotavirus infections may exceed USD $22 million annually. Previous cost effectiveness analyses of rotavirus vaccines substantially underestimated this burden, suggesting that the nonmedical costs associated with mild to moderate rotavirus disease have been similarly underestimated. These findings are needed to assess accurately the cost effectiveness of future rotavirus immunization strategies.     

Synchronous sigmoid and superior rectal resection and left hepatic lobectomy extended to Spiegel lobe for a sigmoid cancer with hepatic metastasis. Case report

The recent developments of surgical technologies allowed the achievement of some standardized interventions with anatomical and functional visa, which based on the improvement of anesthesia and intensive care, and not least by elaboration of efficient chemotherapy protocols, determined new horizons in the treatment of advanced cancers. This work presents a case witch was hospitalized at the Department of Hepatic Surgery, of City Hospital from Timi?oara for a colorectal cancer stage IV (T3N1M1), with hepatic metastasis localized at the left hepatic lobe (II and III segments) and Spiegel lobe. A surgical intervention was performed, when in the same operating time was practiced a sigmoid and superior rectal resection (Hartmann) and also a left hepatic lobotomy extended to the first segment. The post operating evolution of the patient was favorable and also after fourth month from the surgery, when no signs of relapse were established at reevaluation.     

Epidemiologic study of the psychological health and risk behaviors of medical students

INTRODUCTION AND AIMS: In the present study the authors conducted a cross sectional study of fourth-year (eighth-semester) students at Semmelweis University, to assess their stress-related complaints, and also some of the more common forms of risk behavior, including smoking, regular alcohol consumption, past or current drug use and the regular use of pharmaceuticals. METHODS: A total of 410 students were evaluated; 263 medical students, 96 pharmaceutical students and 78 dentistry students. An adapted version of Anderson's questionnaire was used for the evaluation of the total burden of stress based on emotional, physical and work-related complaints. Respondents who mentioned more than three signs of increased stress involving any of the above three categories (emotional, physical and work-related) were designated "high risk" subjects. RESULTS: The overall prevalence of "high risk" subjects was 30.5% (29.7% in medical, 38.5% in pharmaceutical and 23.1% in dentistry students) with no significant gender differences. 55.2% of "high risk" subjects had over three complaints in only one category, 32.6% in two categories, and 12.2% in all three categories. 43.6% of the subjects experienced work-related complaints, 33.3% of them had emotional and 23.1% had physical complaints. The overall prevalence of various forms of risk behavior was found to be 19.3% for smoking (25.2% in males and 15% in females), 30.2% for regular alcohol intake (47.1 in males and 18.3% in females), 25.4% for the regular use of some kind of medication (14.7% in males and 33.0% in females) and 24.9% for those who admitted to previous drug-use (37.6% in males and 16.3% in females). CONCLUSION: All forms of risk behavior were more common in the "high risk" group, but only smoking and the regular use of medication were increased significantly. There were no differences in risk behavior prevalence with regards to a particular category of complaints.     

CD4(+) T-cell recognition of mutated B-RAF in melanoma patients harboring the V599E mutation

The potential of antigen-directed cancer immunotherapy has not been fully realized, perhaps because many commonly targeted tumor associated proteins are not essential to maintaining the malignant cell phenotype. A constitutively activating mutation in the signaling molecule BRAF is expressed frequently in melanomas and may play an important role in the biology of this disease. A 29-mer B-Raf peptide incorporating the V599E mutation was used for in vitro stimulation of lymphocytes derived from melanoma patients, generating MHC class II-restricted CD4(+) T cells specific for this peptide as well as for melanoma cells expressing B-Raf V599E. Mutated B-Raf exemplifies targets that may be ideal for immunotherapy.     

Experimental rat models of types 1 and 2 diabetes differ in sympathetic neuroaxonal dystrophy

Dysfunction of the autonomic nervous system is a recognized complication of diabetes, ranging in severity from relatively minor sweating and pupillomotor abnormality to debilitating interference with cardiovascular, genitourinary, and alimentary dysfunction. Neuroaxonal dystrophy (NAD), a distinctive distal axonopathy involving terminal axons and synapses, represents the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in man and several insulinopenic experimental rodent models. Although the pathogenesis of diabetic sympathetic NAD is unknown, recent studies have suggested that loss of the neurotrophic effects of insulin and/or insulin-like growth factor-I (IGF-I) on sympathetic neurons rather than hyperglycemia per se, may be critical to its development. Therefore, in our current investigation we have compared the sympathetic neuropathology developing after 8 months of diabetes in the streptozotocin (STZ)-induced diabetic rat and BB/ Wor rat, both models of hypoinsulinemic type 1 diabetes, with the BBZDR/Wor rat, a hyperglycemic and hyperinsulinemic type 2 diabetes model. Both STZ- and BB/Wor-diabetic rats reproducibly developed NAD in nerve terminals in the prevertebral superior mesenteric sympathetic ganglia (SMG) and ileal mesenteric nerves. The BBZDR/Wor-diabetic rat, in comparison, failed to develop superior mesenteric ganglionic NAD in excess of that of age-matched controls. Similarly, NAD which developed in axons of ileal mesenteric nerves of BBZDR/Wor rats was substantially less frequent than in BB/Wor- and STZ-rats. These data, considered in the light of the results of previous experiments, argue that hyperglycemia alone is not sufficient to produce sympathetic ganglionic NAD, but rather that it may be the diabetes-induced superimposed loss of trophic support, likely of IGF-I, insulin, or C-peptide, that ultimately causes NAD.     

Sulpiride augmentation of olanzapine in the management of treatment-resistant chronic schizophrenia: evidence for improvement of mood symptomatology

Several recent studies, albeit limited in sample number, design and generalizability, have suggested that augmentation of atypical antipsychotic medication (such as clozapine and olanzapine) with sulpiride, a substituted benzamide antipsychotic medication, may play a role in the management of treatment-resistant psychotic conditions. The objective of this study was to investigate any change in clinical symptomatology or side-effect profile in treatment-resistant schizophrenia patients receiving sulpiride in addition to olanzapine. Seventeen patients with treatment-resistant chronic schizophrenia, who were receiving olanzapine monotherapy for at least 6 months before study commencement, were randomized in a 1:1 fashion to receive either adjunctive treatment with sulpiride (study group) or to continue their pre-study treatment with olanzapine with no medication augmentation (control group), each for a period of 8 weeks. Changes in measures of positive and negative symptoms, anxiety, depression and extrapyramidal symptoms were assessed at baseline and at 8 weeks. Study observations indicated no significant differences in the changes in positive or negative symptomatology between patients receiving a combined regimen of olanzapine with sulpiride (600 mg/ day) augmentation and controls. However, a significantly greater improvement of depressive symptomatology (P < 0.05; as assessed by the Hamilton Scale for Depression) was noted in the sulpiride augmentation group. These data indicate improvement in depressive symptomatology with sulpiride augmentation of olanzapine in treatment-resistant chronic schizophrenia patients.     

Starting dose of levothyroxine for the treatment of congenital hypothyroidism: a systematic review

OBJECTIVE: To determine the effect of levothyroxine sodium starting dose on cognitive development, growth, or behavior in children with congenital hypothyroidism identified by neonatal screening. DESIGN: Systematic review of cohort studies. Two analyses were performed: a between-study comparison of mean starting dose with mean developmental score and an analysis of the within-study effects of starting dose on cognitive development, growth, or behavior. RESULTS: The between-study comparison (14 cohort studies based on 1321 patients) found that the standardized mean IQ or developmental quotient scores ranged from 90 to 115 but were not associated with the mean starting dose of levothyroxine (P =.48). The within-study comparison of 4 cohort studies (based on 558 patients) that reported the effect of the starting dose of levothyroxine on cognitive development found no consistent effects. There was weak evidence for an effect of starting dose on growth (1 study) and on behavior problems (1 study). CONCLUSIONS: The evidence for an effect of starting dose of levothyroxine on cognitive development, growth, or behavior is too weak to justify recommendations in favor of high- or standard-dose regimens. More reliable information, based on a randomized controlled trial of starting dose or a meta-analysis of the individual patient data currently available, is required to inform treatment policies.     

Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus

OBJECTIVE: Inhibition of T cell DNA methylation causes autoreactivity in vitro and a lupus-like disease in vivo, suggesting that T cell DNA hypomethylation may contribute to autoimmunity. The hypomethylation effects are due, in part, to overexpression of lymphocyte function-associated antigen 1 (LFA-1) (CD11a/CD18). Importantly, T cells from patients with active lupus have hypomethylated DNA and overexpress LFA-1 on an autoreactive subset, suggesting that the same mechanism could contribute to human lupus. The present study investigated the nature of the methylation change that affects LFA-1 expression in vitro and in human lupus. METHODS: Bisulfite sequencing was used to determine the methylation status of the ITGAL promoter and flanking regions in T cells from lupus patients and healthy subjects, and in T cells treated with DNA methylation inhibitors. "Patch" methylation of promoter sequences in reporter constructs was used to determine the functional significance of the methylation changes. RESULTS: Hypomethylation of specific sequences flanking the ITGAL promoter was seen in T cells from patients with active lupus and in T cells treated with 5-azacytidine and procainamide. Patch methylation of this region suppressed ITGAL promoter function. CONCLUSION: DNA methylation changes occur in specific sequences that regulate LFA-1 expression in lupus T cells and in the hypomethylation model, indicating that altered methylation of specific genes may play a role in the pathogenesis of lupus.