Primary liver tumors: diagnosis by MR imaging

MR features of 153 proved primary liver tumors (95 malignant, 58 benign) in 55 patients with hepatocellular carcinoma (21), cholangiocarcinoma (seven), carcinosarcoma (one), hepatoblastoma (one), hemangioma (16), hepatic adenoma (four), focal nodular hyperplasia (three), leiomyoma (one), and hemangioendothelioma (one) were studied retrospectively to determine which techniques are most reliable for lesion detection and which criteria are most useful for differential diagnosis. MR data were correlated with histologic features such as fatty degeneration, fibrosis, and peritumoral edema. Unlike metastatic cancer, hepatocellular carcinoma was best detected (p less than .01) with T2-weighted pulse sequences. The mean tumor-liver T2 difference was 34.4%, while the mean T1 difference was only 21.8%. A tissue-specific diagnosis of hepatocellular carcinoma was possible in 14 of 21 patients by identification of fatty degeneration of the tumor (eight of 17), tumor capsule (five of 21), and/or vascular invasion (six of 21). MR features of peritumoral edema, present in six of 21 patients with hepatocellular carcinoma and in seven of 25 patients with metastases, were exclusively associated with malignant tumors. The large variation in tissue characteristics (relaxation times and proton density) seen in primary liver tumors necessitates the use of multiple pulse sequences to maximize lesion detection. However, the combined use of T1- and T2-weighted spin-echo and T2-weighted phase-contrast images had the advantage of distinguishing benign from malignant primary liver tumors in 48 of 55 patients in this series.     

Correlation of quantitative burn wound biopsy culture and surface swab culture to burn wound sepsis

The present study includes seventeen patients with second and third degree fresh burns involving 15–50 per cent total body surface area (TBSA). Surface swabs and quantitative burn wound biopsy cultures were obtained during postburn weeks 1,2 and 3 and correlation was studied. To obtain bacterial counts the technique described by Loebel et al. (1974) was used. The patients were divided in two groups depending upon burn body surface area involved. The first group includes five patients with burns between 15–29 per cent body surface area and the second group includes the rest of the twelve patients with burns between 30–50 per cent body surface area. No patient from group I showed any sign or symptom of sepsis whereas seven patients from group II developed sepsis and three died. These three patients showed positive blood culture at the time of death. Of the 48 cultures obtained in all the patients over 3 weeks, 7 cultures showed differences between swab and biopsy cultures. Genticyn was the most effective drug against Gram-negative organisms.     

Advances in therapy for psoriasis: an overview of infliximab, etanercept, efalizumab, alefacept, adalimumab, tazarotene, and pimecrolimus

Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European population. Over the last several years, one of the major focuses in psoriasis research has been the development of biologic therapies for this disease. The aim of these therapies is to provide selective, immunologically directed intervention with fewer side effects than traditional therapies. The goal of this article is to review the progress of the biologic agents which are available, or under investigation for clinical use: infliximab, etanercept, efalizumab, alefacept, and adalimumab. In addition, two other investigational therapies, oral tazarotene and oral pimecrolimus will be discussed. Clinical data for these agents, including the most recent phase II and/or III study results, will be discussed, as well as the most recent safety data.     

Detection of ketamine and norketamine in urine of nonhuman primates after a single dose of ketamine using microplate enzyme-linked immunosorbent assay (ELISA) and NCI-GC-MS

The general anesthetic ketamine (Ketalar, Ketaject, Vetalar) (KET) is used in human and veterinary medicine for induction of anesthesia for short surgical procedures and routine veterinary examination. Its illicit use by teenagers in rave parties has been reported, and it has recently been identified as a substance associated with sexual assault. One aim of this paper was to study the elimination of KET and its major metabolite norketamine (NKET) in urine collected from five nonhuman primates that received a single dose (5 mg/kg, I.M.) of KET and to study elimination patterns to determine how long after drug administration KET and NKET can be detected. Another aim of this study was to develop and validate a highly sensitive negative ion chemical ionization-gas chromatography-mass spectrometry (NCI-GC-MS) method for the simultaneous quantitation of KET and its major metabolite NKET in urine and to analyze urine samples collected from the animals. The last aim of this study was to apply and evaluate a newly developed ELISA screening methodology for detection of KET and its metabolites in the same urine samples collected from primates which received a single dose of KET. In two monkeys, KET was detected in urine up to 3 days after drug administration (32-7070 ng/mL); in one monkey, it was detected up to 4 days (65-13,500 ng/mL); in one monkey, it was detected only on days 1 and 2 (4000 and 70 ng/mL, respectively); and in one monkey, it was detected 10 days after KET injection (22-35,000 ng/mL). NKET concentrations ranged from 63 pg/mL to 1.75 microg/mL, and it remained in the urine throughout the entire 35-day study period in 4 out of 5 animals. In one monkey, NKET was detected up to 31 days after KET administration. Urine analysis using ELISA revealed that KET and NKET can be easily detectable at 25 ng/mL. In one monkey, KET and its metabolites were detected in urine up to 4 days after drug administration, up to 7 days in two monkeys, up to 11 days in one monkey, and 16 days after KET injection in one monkey. Urine extraction followed by screening using ELISA methodology allowed for significant extension of the detection period in all animals from the study. It is believed that the KET elimination in urine of nonhuman primates is slightly faster than in humans. We propose that NCI-GC-MS be employed to detect NKET as a target compound in urine in toxicological investigations of drug-facilitated sexual assault when KET use by the perpetrator is suspected.     

Immunological methods for quantifying free and total serum IgE levels in allergy patients receiving omalizumab (Xolair) therapy

Omalizumab (humanized-IgG1 anti-human IgE Fc, Xolair) complexes circulating IgE, blocking IgE binding to high affinity epsilon Fc receptors (FcepsilonR1) on mast cells and basophils. Free (non-Omalizumab bound) IgE levels in serum are a measure of effective Omalizumab dosing. The goal of this study was to quantify free (non-Omalizumab-complexed) and total serum IgE levels in asthma patients on Xolair. The concentration of (non-Omalizumab bound) free IgE in human serum was measured using a solid phase immunoenzymetric assay (IEMA) in which IgE was captured from serum with monoclonal anti-human IgE (clone HP6061) and detected with labeled-FcepsilonR1alpha. In a companion total human serum IEMA, IgE was captured from serum with the same anti-human IgE (clone HP6061) and all bound IgE was detected with labeled monoclonal anti-human IgE Fc (clone HP6029). Free and total IgE levels were quantified in pre- and 1 and 3 months post Omalizumab therapy sera from 12 allergic asthma patients. In the absence of Omalizumab, working ranges of the free and total IgE IEMAs were comparable (10-1000 kIU/l), with excellent precision, reproducibility and parallelism. Pre-Omalizumab total and free IgE levels by IEMA were highly correlated (r2=0.99, Y=0.9X+0.32, p<0.001), as were total serum IgE levels by IEMA and ImmunoCAP-250 (r2=0.98, Y=1.1X-0.05, p<0.001, n=33). In vitro reduction of free IgE (>90%) occurred at [Omalizumab:IgE] molar ratios of 2-20. Total IgE levels in 12 asthmatics increased from pre-therapy levels (52-658 kIU/l) by 1.5-5.5-fold at 1 month and 1.7-8.6 fold at 3 months of uninterrupted Omalizumab treatment. Free IgE levels fell by 49%-97% at 1 month and 45%-98% by 3 months of Omalizumab treatment. Free and total IgE levels by IEMA aid in monitoring patients receiving Omalizumab therapy.     

Cell types of the auditory caudomedial neostriatum of the starling (Sturnus vulgaris)

Cell types of the auditory neostriatum in the starling forebrain are described. This area in the caudal neostriatum is defined neurophysiologically by the appearance of auditory neurons. Through use of the rapid Golgi technique, four types of neurons are identified, mainly on the basis of their processes: Neurons with long descending axons and thick dendrites rich in spines (type 1), neurons with long ascending axons and thin dendrites poor in spines (type 2), short-axon neurons (type 3), and microneurons (type 4). The axons of the long neurons pass outside the confines of the auditory neostriatum. Among neurons of type 1; some of the long descending axons directed toward the lower brain centers enter the capsula interna occipitalis (CIO). The descending axons give off many collaterals within the auditory neostriatum. With neurons of type 2; most of the ascending axons cross the lamina hyperstriatica, enter the hyperstraiatum ventrale, and arborize near its periventricular region. Some of the long ascending axons reach the overlying hyperstriatum ventrale, pars caudale (HVc, the vocal control area). Among neurons of types 3 and 4; the axons of short-axon neurons and of microneurons end with fine branches within the auditory neostriatum. The dendrites of long-axon neurons are oriented in specific directions, whereas those of short-axon neurons and of microneurons do not show a definite pattern of orientation. In the region of the auditory neostriatum that lies immediately adjacent to the midline of the brain, the first three types of neurons are arranged around the central core known as field L, which is composed of the microneurons and the terminal ramifications of auditory afferents. Laterally the microneurons, along with the fibers of the input tract, undergo a rostral shift to occupy a more peripheral position within the auditory neostriatum. The neurons of the auditory neostriatum are compared with those of the mammalian auditory cortex, and a functional classification of nerve cells into projection neurons, association neurons, and interneurons is proposed.