Diagnosis of pancreatic carcinoma: role of FDG PET

OBJECTIVE: The purpose of this study was to investigate the role of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in differentiating benign from malignant disease in patients with possible pancreatic malignancy. SUBJECTS AND METHODS: All patients with a possible diagnosis of pancreatic carcinoma based on CT or ERCP findings were eligible for inclusion in this prospective study. PET imaging of the abdomen was performed in 37 patients and was interpreted as positive if FDG activity in the pancreas exceeded background activity and as negative if activity was less than or equal to background activity. Semiquantitative analysis was performed by calculating a standardized uptake ratio. Studies were reviewed independently by two radiologists, and results were correlated with biopsy results and with CT and ERCP findings. Sensitivity and specificity of FDG PET for revealing pancreatic malignancy was determined. RESULTS: FDG activity in the pancreas was increased in 24 patients, and adenocarcinoma was diagnosed in 22 of these patients (92%). Two patients (8%) with increased activity had benign disease, including one patient with chronic pancreatitis who showed no evidence of tumor at laparotomy and one patient with a mucinous cystic tumor who showed no malignant features at laparotomy. FDG uptake was low or normal in 13 patients, 10 of whom (77%) had benign disease. FDG uptake was also low in three patients with adenocarcinoma, whose tumor size ranged from 2 to 4 cm in diameter. The mean standardized uptake ratio value for malignant disease was 5.1 (range, 1.0-10.1) and for benign disease was 1.9 (range, 0.0-5.8) (p < .001). The sensitivity of FDG PET for revealing malignant disease in the pancreas was 88% and the specificity was 83%. CONCLUSION: FDG PET is a sensitive and specific noninvasive technique for the diagnosis of pancreatic malignancy.     

Input and central processing expressed in ERP and heart rate changes to rare target and rare nontarget stimuli

Whether late positive components of event-related potentials (ERPs) parallel changes in heart rate (HR) indicative of attention/orienting to rare stimuli has been debated. In the present study, a three-stimulus design was used, with rare target, rare nontarget, and frequent standard stimuli delivered under identical conditions except that instructions to subjects described the targets to which subjects should respond but did not describe the nontargets. In Experiment 1, stimuli varied among modalities; in Experiment 2, auditory stimuli were employed. Both ERPs and HR were consistent with automatic processing preceding two stages of controlled processing. Rare stimuli evoked larger parietal P300 and initial HR deceleration than standards. Presumably because of load-reducing effects of long interstimulus intervals, targets and nontargets were not distinguished before a late slow wave and a late phase of HR acceleration. Neither rare stimulus elicited a recognizable frontal P3a.     

Relevance of pheno- and genotyping in clinical drug development

Individual variability in the plasma concentration of a xenobiotic is a considerable problem in the clinical use as well as in the clinical development of a new drug. In clinics altered drug response and drug toxicity are predominant findings. In clinical development (especially in the early phases) problems with the interpretation of individual pharmacokinetics and appearance of unexpected drug reactions may occur. One major reason for the inter-and intraindividual variability is based on variations in the metabolism of the drug that are dependent on the genetic variations of the metabolising enzymes. However, while the first of these so-called polymorphisms has already been described in 1979 (for a review see [Daly 1995]) and knowledge of these polymorphisms are still growing, the impact on clinical practice as well on the selection and development of drug candidates in the pharmaceutical industry at present is still limited. This may change in the near future as recent advances in molecular biology and especially in the diagnosis of individual genomic characteristics will result in a better understanding of the basic principles of the polymorphisms. High throughput screening methods will reveal information on the distribution of these polymorphic alleles in the target population and enable the broad characterization of the drug candidate in in vitro systems. The early knowledge as to whether a polymorphic pathway is involved in drug metabolism/action and of its clinical relevance will lead to a reduction of time and costs in the development of a new drug.     

Accidental HIV exposure

This is a case presentation of an accidental contaminated needle stick injury from a patient known to be infected with both Human Immunodeficiency Virus (HIV) and hepatitis B. The patient was managed with prophylactic hepatitis B immune globulin, hepatitis B vaccination and the HIV retroviral drug zidovudine (AZT). At one year after treatment the patient was not infected with HIV or hepatitis B, and there was adequate immunity generated after vaccination for hepatitis B.     

In vitro system for differentiating pluripotent neural crest cells into smooth muscle cells

The change in vascular smooth muscle cells (SMC) from a differentiated to a dedifferentiated state is the critical phenotypic response that promotes occlusive arteriosclerotic disease. Despite its importance, research into molecular mechanisms regulating smooth muscle differentiation has been hindered by the lack of an in vitro cell differentiation system. We identified culture conditions that promote efficient differentiation of Monc-1 pluripotent neural crest cells into SMC. Exclusive Monc-1 to SMC differentiation was indicated by cellular morphology and time-dependent induction of the SMC markers smooth muscle alpha-actin, smooth muscle myosin heavy chain, calponin, SM22alpha, and APEG-1. The activity of the SM22alpha promoter was low in Monc-1 cells. Differentiation of these cells into SMC caused a 20-30-fold increase in the activity of the wild-type SM22alpha promoter and that of a hybrid promoter containing three copies of the CArG element. By gel mobility shift analysis, we identified new DNA-protein complexes in nuclear extracts prepared from differentiated Monc-1 cells. One of the new complexes contained serum response factor. This Monc-1 to SMC model should facilitate the identification of nodal regulators of smooth muscle development and differentiation.     

Direct detection of Mycobacterium tuberculosis complex and M. avium complex in tissue specimens from cattle through identification of specific rRNA sequences

BACKGROUND: In many cases inflammatory bowel disease is accompanied by extraintestinal manifestations. This results in lowering of live quality. The aim of this study was to gather data retrospectively about initial symptoms, extraintestinal manifestations and course of pregnancy in a large unselected population with inflammatory bowel disease in South Germany. PATIENTS AND METHODS: Data from 1975 to 1989 (392 patients) were analyzed and partially compared with data from 1992 to 1995 (211 patients). RESULTS: Patients with Crohn's disease in average have been 25 years old at the time point of initial symptoms, whereas the age of ulcerative colitis patients was 30 years (p < 0.0001). The number of Crohn's disease patients with a long interval between initial symptoms and diagnosis (> 1 year) was significantly decreased in the second population (50% vs 38%; p < 0.05). Dominant initial symptoms in Crohn's disease were indisposition, abdominal pain and nonbloody diarrhea in contrast to ulcerative colitis which manifested mostly with bloody diarrhea. Extraintestinal manifestations occurred in 76% of patients with Crohn's disease and 64.6% with ulcerative colitis. Complications during the course of pregnancy have been detected in 40.5% in Crohn's disease and 60% in ulcerative colitis. CONCLUSION: A better knowledge of initial symptoms and extraintestinal manifestations in inflammatory bowel disease can help to decrease the interval between initial symptoms and the diagnosis. Pregnancy in patients with inflammatory bowel disease needs to be treated with special care.     

Analytical methods for measuring urea in pharmaceutical formulations

Two new methods are described for the routine determination of urea that utilize HPTLC-densitometry and colorimetry. The methods involve derivatization of urea with p-dimethylaminobenzaldehyde to a yellow-coloured compound. Validation of the methods was accomplished with respect to linearity, accuracy, reproducibility and limit of detection/quantification. Both methods were compared with an enzymatic method previously described in the literature and were found to be in close agreement. The proposed methods have the advantages of being simple, rapid and involve a single step sample preparation. Under experimental conditions HPTLC was the most sensitive method.