Nonlesional Sources of Contrast Enhancement on Postgadolinium "Black-Blood" 3D T1-SPACE Images in Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: We hypothesized that 3D T1-TSE "black-blood" images may carry an increased risk of contrast-enhancing lesion misdiagnosis in patients with MS because of the misinterpretation of intraparenchymal vein enhancement. Thus, the occurrence of true-positive and false-positive findings was compared between standard MPRAGE and volumetric interpolated brain examination techniques. MATERIALS AND METHODS: Sampling perfection with application-optimized contrasts by using different flip-angle evolution (SPACE) images obtained from 232 patients with MS, clinically isolated syndrome, or radiologically isolated syndrome were compared with standard MPRAGE and volumetric interpolated brain examination images. The intraparenchymal vein contrast-to-noise ratio was estimated at the level of the thalami. Contrast-enhancing lesions were blindly detected by 2 expert readers and 1 beginner reader. True- and false-positives were determined by senior readers' consensus. True-positive and false-positive frequency differences and patient-level diagnosis probability were tested with the McNemar test and OR. The contrast-to-noise ratio and morphology were compared using the Mann-Whitney U and χ2 tests. RESULTS: The intraparenchymal vein contrast-to-noise ratio was higher in SPACE than in MPRAGE and volumetric interpolated brain examination images (P < .001, both). There were 66 true-positives and 74 false-positives overall. SPACE detected more true-positive and false-positive results (P range < .001-.07) but did not increase the patient's true-positive likelihood (OR = 1 1.29, P = .478-1). However, the false-positive likelihood was increased (OR = 3.03-3.55, P = .008-.027). Venous-origin false-positives (n = 59) with contrast-to-noise ratio and morphology features similar to small-sized (≤14 mm3 P = .544) true-positives occurred more frequently in SPACE images (P < .001). CONCLUSIONS: Small intraparenchymal veins may confound the diagnosis of enhancing lesions on postgadolinium black-blood SPACE images.

Extra-mammary findings in breast MRI.

OBJECTIVES: Incidental extra-mammary findings in breast Magnetic Resonance Imaging (MRI) may be benign in nature, but may also represent a metastasis or another important lesion. We aimed to analyse the prevalence and clinical relevance of these unexpected findings. METHODS: A retrospective review of 1535 breast MRIs was conducted. Only axial sequences were reassessed. Confirmation examinations were obtained in all cases. RESULTS: 285 patients had a confirmed incidental finding, which were located in the liver (51.9%), lung (11.2%), bone (7%), mediastinal lymph nodes (4.2%) or consisted of pleural/pericardial effusion (15.4%). 20.4% of incidental findings were confirmed to be malignant. Positive predictive value for MRI to detect a metastatic lesion was high if located within the bone (89%), lymph nodes (83%) and lung (59%), while it was low if located within the liver (9%) or if it consisted of pleural/pericardial effusion (6%). The axial enhanced sequence showed superior sensitivity to unenhanced images in detecting metastatic lesions, especially if only smaller (≤10 mm.) lesions were considered. CONCLUSIONS: The prevalence of metastatic incidental extra-mammary findings is not negligible. Particular attention should be to incidental findings located within the lung, bone and mediastinal lymph nodes.

Brain Tumor-Enhancement Visualization and Morphometric Assessment: A Comparison of MPRAGE, SPACE, and VIBE MRI Techniques.

BACKGROUND AND PURPOSE: Postgadolinium MR imaging is crucial for brain tumor diagnosis and morphometric assessment. We compared brain tumor enhancement visualization and the "target" object morphometry obtained with the most commonly used 3D MR imaging technique, MPRAGE, with 2 other routinely available techniques: sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) and volumetric interpolated brain examination (VIBE). MATERIALS AND METHODS: Fifty-four contrast-enhancing tumors (38 gliomas and 16 metastases) were assessed using MPRAGE, VIBE, and SPACE techniques randomly acquired after gadolinium-based contrast agent administration on a 3T scanner. Enhancement conspicuity was assessed quantitatively by calculating the contrast rate and contrast-to-noise ratio, and qualitatively, by consensus visual comparative ratings. The total enhancing tumor volume and between-sequence discrepancy in the margin delineation were assessed on the corresponding 3D target objects contoured with a computer-assisted software for neuronavigation. The Wilcoxon signed rank and Pearson χ2 nonparametric tests were used to investigate between-sequence discrepancies in the contrast rate, contrast-to-noise ratio, visual conspicuity ratings, tumor volume, and margin delineation estimates. Differences were also tested for 1D (Response Evaluation Criteria in Solid Tumors) and 2D (Response Assessment in Neuro-Oncology) measurements. RESULTS: Compared with MPRAGE, both SPACE and VIBE obtained higher contrast rate, contrast-to-noise ratio, and visual conspicuity ratings in both gliomas and metastases (P range, <.001-.001). The between-sequence 3D target object margin discrepancy ranged between 3% and 19.9% of lesion tumor volume. Larger tumor volumes, 1D and 2D measurements were obtained with SPACE (P range, <.01-.007). CONCLUSIONS: Superior conspicuity for brain tumor enhancement can be achieved using SPACE and VIBE techniques, compared with MPRAGE. Discrepancies were also detected when assessing target object size and morphology, with SPACE providing more accurate estimates.

Regional effects of propranolol on intraventricular conduction in coronary artery disease.

In canines, propranolol slows conduction in acutely ischemic, but not in normal tissues. To determine propranolol effects on conduction in patients with coronary artery disease, we studied 7 patients after left anterior descending coronary artery bypass graft surgery. Bipolar electrodes were placed in the atrium, left ventricle (in the left anterior descending distribution), and right ventricle. On postoperative day 7, 3 mg propranolol were given intravenously. At a constant artrially paced rate, conduction intervals were measured from the earliest onset of the QRS in 3 simultaneously recorded surface electrocardiogram (ECG) leads to the major deflection of the electrogram recorded from each ventricle. Ten minutes after injection, conduction in the left ventricle was slowed by 4 +/- 0.3 msec (10 +/- 0.9%) and in the right ventricle by 0.4 +/- 0.3 msec (1 +/- 0.9%). QRS duration changed -1 msec (-0.8%). Stimulus to Q, a measure of propranol effect on A-V conduction, changed 16 +/- 2%. The difference in propranolol effects on left and right ventricles was significant (p less than 0.001). We suggest that in patients with coronary artery disease (1) propranolol has local anesthetic effects in slowing conduction; (2) the effects of propranolol vary with the region of ventricular myocardium; and (3) propranolol slows conduction more in the left than right ventricle. This difference may be due to potentiation of drug effects in left ventricular tissue that is abnormal due to chronic coronary artery disease.

Activity of aromatic substituted phenylpiperazines lacking affinity for dopamine binding sites in a preclinical test of antipsychotic efficacy.

Generally, antipsychotic agents are dopamine receptor blocking agents that also block conditioned avoidance responding (CAR) in the rat. Recently, however, both (Q-methoxyphenyl)piperazine (OMPP, 1h) and (m-chlorophenyl)piperazine (MCPP, 1o) have been reported to block conditioned avoidance responding in the rat although neither has dopamine receptor blocking properties. The present paper examines the behavioral and biochemical profile of a number of additional substituted phenylpiperazines. None of the phenylpiperazines tested demonstrated high affinity for either dopamine D-1 or D-2 receptor sites, yet many were effective in blocking CAR. The results suggest that the phenylpiperazines may be effective antipsychotic agents without blocking dopamine receptors. Moreover, the active compounds did demonstrate activity in displacing ligand binding to serotonin receptors. Receptor binding profiles were determined for 5-HT-1A and 5-HT-1B binding sites as well as for 5-HT-2 sites. The data from this preclinical test suggest these phenylpiperazines might be effective antipsychotic agents acting via a nondopaminergic mechanism of action.

Pyrrole mannich bases as potential antipsychotic agents.

Recently, we reported on a series of arylpiperazines 4 which exhibit high affinity for the serotonin 5-HT-1A and 5-HT-1B binding sites. Although these compounds interact weakly with dopamine D-1 and D-2 receptors, they are reasonably potent in inhibiting conditioned avoidance responding (CAR) in the rat, an indication of potential antipsychotic activity. Conversion of these arylpiperazines to pyrrole Mannich bases has provided a series of compounds (10-44) which exhibit potent inhibition of CAR when given po and have strong affinity for both the D-2 and 5-HT-1A binding sites. Some of these agents also fail to produce catalepsy. The D-2 binding data and the block of CAR suggest that they are potential antipsychotic agents and the lack of cataleptogenic potential suggests some might possess less liability for producing extrapyramidal side effects and tardive dyskinesias in man.

Titration of human-bovine rotavirus reassortants using a tetrazolium-based colorimetric end-point dilution assay.

A colorimetric end-point dilution assay was developed for the titration of rotavirus-containing samples that uses commercially available tetrazolium dyes as an indicator of virus infection. This assay offers several advantages over both plaque assays and traditional end-point dilution methods. The latter assays require manual counting of plaques or the scoring of wells for the presence of virus based on observed cytopathic effects. The colorimetric end-point dilution assay enables the scoring of wells based upon absorbance readings alone, thereby eliminating time-consuming and subjective manual screenings. This method also has the potential for automating the analysis of large numbers of samples. Virus titers of human-bovine rotavirus reassortants obtained using this method are comparable to those determined by plaque assay. The scoring of wells based on absorbance readings was also found to agree with manual scoring of cytopathic effects and with the production of viral antigen.

Comparative study of influenza virus replication in Vero and MDCK cell lines.

The choice of a cell line for the production of influenza vaccines is determined by how well the virus is able to replicate and how easily the cell line can be maintained. Madin-Darby canine kidney (MDCK) cells have long been known to successfully support influenza growth. Vero cells are also another well studied candidate cell line. In this work, we have compared these two cell lines for their ability to propagate type A and type B cold-adapted and wild type influenza viruses. The growth of these viruses has been measured as plaque forming units (via plaque assay) as well as viral particle formation (via a novel quantitative RT-PCR assay) to assess the suitability of these cell lines to support the development of live attenuated influenza vaccines. The novel qRT-PCR assay outlined in this work was demonstrated to be an efficient, sensitive and reproducible method for measuring wild type (wt) and cold-adapted (ca) influenza strains. Replicates of six per sample consistently showed an average variation around +/-10%. In this study we have also found qRT-PCR to be a useful method for differentiating between wt and ca influenza strains based on their differing growth characteristics at varying temperatures. This can subsequently be used to assess reassortants prepared from ca donor strains for the purposes of live viral vaccine development. For type A and B influenza viruses studied in this work, MDCK cells supported a more rapid viral growth (measured in terms of genome copies) compared with Vero cells. For the type A viruses studied here, the genome copies: infectious unit (genome copy, gc:infectious unit, iu) ratio was found to be more favorable for Vero cells compared with MDCK cells. For the type B viruses studied in this work, the gc:iu was equivalent in both cell lines tested. Ultimately, however, the use of any new cell line would need to be approved by regulatory agencies prior to its commercial application.

Childhood lead screening knowledge and practice. Results of a New Jersey physician survey.

CONTEXT: As the nation moves toward targeted childhood lead screening, CDC continues to recommend universal screening in states with no childhood lead poisoning prevalence data. OBJECTIVE: The study was conducted, prior to the new universal screening state law, to determine physician screening practices and their consistency with key CDC recommendations as a basis for future education activities. DESIGN/SETTING/PARTICIPANTS: A statewide cross-sectional self-administered multiple choice survey of 541 randomly selected New Jersey pediatricians and family practitioners. OUTCOME MEASURES: Risk assessment, screening and case management practices and their consistency with CDC recommendations. RESULTS: We obtained 333 usable responses (69.4%). Most respondents reported confirming blood lead level, initiating case management, and identifying medical emergencies at blood lead levels lower than recommended by CDC. More than half reported not assessing the risk of the majority of their patients. At least one third were not screening infants, children between 1 and 2 years, or children between 2 and 6 years of age. Physicians who assessed risk tended to screen high-risk children in all age groups. Only 42% of pediatricians and 24% of family practitioners said they screened the majority of the children in their practice by age 2 years. About 60% of all respondents reported not providing lead exposure education to half their patients. CONCLUSIONS: Passing a universal screening law, as New Jersey has done, is one way to obtain baseline childhood lead poisoning prevalence data. Private practice-targeted physician education led by preventive medicine specialists may also be helpful.

Myocardial ischemia during the weaning period.

OBJECTIVES: To estimate the incidence of silent myocardial ischemia, its pattern over time and its relationship to the time and mode of weaning high-risk cardiac patients after noncardiac surgery. DESIGN: Prospective study with random assignment to one of three weaning modes. SETTING: A surgical intensive care unit in a university hospital and a Veterans Administration hospital. PATIENTS: Sixty-two patients meeting standard criteria for extubation were randomized to one of three modes of weaning: synchronized intermittent mandatory ventilation (n = 19), T-Bar (n = 21) or continuous positive airway pressure (n = 22). METHODS: Ischemia was monitored with a continuous two-lead (V5, III) ST segment analyzer. Tracings were reviewed by a cardiologist. Ischemia was defined as greater than 1 mm ST segment depression 60 milliseconds after the J point. The monitoring period included a prewean (mean 654.0 minutes), wean (mean 46.5 minutes) and postwean (mean 1223.4 minutes) period. RESULTS: Of 62 patients, 12 (19.3%) experienced ischemia at some time during the monitoring period, most often during the weaning period. Ischemia during weaning was detected in 3 of 21 (14.3%) T-Bar patients and 2 of 22 (9.1%) continuous positive airway pressure patients but in no synchronized intermittent mandatory ventilation patients. CONCLUSION: This study demonstrates that silent myocardial ischemia occurs frequently in high-risk postoperative patients, with the highest incidence during weaning.

[Hepatic tuberculosis after Hodgkin's disease. Echographic and x-ray computed tomographic aspects. A case report]. / Tuberculose hépatique après maladie de Hodgkin. Aspects échographiques et tomodensitométriques. A propos d'un cas.

The authors report a case of hepatic tuberculosis on a pre-existing Hodgkin disease with hepatic localisations. They point out how echographic and CT imaging are non specific in this disease and so insist on the diagnostic interest of puncture-biopsy under guidance of the hepatic nodules.

[Magnetic resonance imaging and preoperative evaluation of cancer of the kidney. The results apropos of 60 cases]. / Imagerie par résonance magnétique et bilan pré-opératoire des cancers du rein. Résultats à propos de soixante cas.

Sixty renal carcinomas confirmed at surgery or autopsy were studied. Capsular effraction, present in 17 cases, was well assessed in 8 cases, under staged in 8 cases and over staged in 5 cases (sensitivity 47%, specificity 88%). Renal vein involvement was present in 11 cases. In 8 of these 11 cases, a thrombus was present in the inferior vena cava. MRI detected a thrombus in the renal veins in 10/11 cases and in 7/8 cases of caval invasion. The false negative case was due to a huge right upper pole tumor laminating the inferior vena cava. The false positive case was due to an enlarged lymph node compressing the inferior vena cava. Cranial extension of the thrombus was well assessed in 6 of the 7 cases. One thrombus in the right atrium was missed. Lymph node involvement was present in 10 cases and correctly diagnosed by MRI in 7 cases. Three false negative cases were noted, because of microscopic invasion in non enlarged lymph nodes. Adjacent organ invasion, present in 2 cases, was detected in 1 case of liver invasion. Initial results of MRI seem very promising and at present, the best indications of MRI in pre-operative evaluation of a renal carcinoma are assessment of caval extension and spread to adjacent organs in patients with large tumors.

[Cystic renal cancers. 14 case reports]. / Les cancers du rein d'aspect kystique. A propos de 14 observations.

The authors present 14 cases of renal cancers with a cystic appearance raising pre and intraoperative diagnostic difficulties. Although ultrasonography has become the first-line investigation, computed tomography is now the most accurate diagnostic examination. The diagnosis of complicated benign cyst must be proposed very cautiously and the persistence of doubtful images justifies surgical exploration. In order to be reliable, frozen section histological examination must include all of the cystic tumour. Polar nephrectomy with frozen section examination is therefore the recommended intraoperative diagnostic procedure in a case of suspicious cyst. The curative treatment of these cancers is classical radical nephrectomy.

Use of intravenous fluids in Hong Kong children hospitalised for diarrhoea and relationship to severity and aetiology.

This study assessed the clinical management and impact of diarrhoea aetiology (rotavirus positive/negative) and rotavirus genotype on diarrhoeal disease severity. Of 7391 diarrhoea admissions less than 5 years of age over a 2-year period, 80% of patients were tested for rotavirus, 87% were cultured for bacterial pathogens and 78% were assessed for both. Diarrhoeal severity scores were greatest in those children with mixed rotavirus and bacterial infections. Between 1.3 and 8.4% of infants were considered dehydrated yet intravenous fluids were used for 48% of infants (69% rotavirus positive, 72% mixed infection). These findings support the promotion of oral rehydration therapy over intravenous fluids.

Heterologous expression of the Na(+),K(+)-ATPase gamma subunit in Xenopus oocytes induces an endogenous, voltage-gated large diameter pore.

1. The gamma subunit is a specific component of the plasmalemmal Na(+),K(+)-ATPase. Like structurally related single-spanning membrane proteins such as cardiac phospholemman, Mat-8 and renal CHIF, large ion conductances are activated when gamma subunits are expressed in Xenopus oocytes. 2. Here we report critical properties of the gamma-activated conductance. The gamma-activated conductance showed non-selective cationic and anionic permeation, and extremely slow kinetics, with an activation time constant > 1 s following steps to -100 mV. 3. The gamma-activated conductance was inhibited by extracellular divalent ions including Ba(2+) (K(i) = 0.7 mM) and Ca(2+) (K(i) = 0.4 mM). 4. 2-Deoxyglucose (MW approximately 180), inulin (MW approximately 5000) and spermidine (MW approximately 148) efflux could occur through the gamma-activated conductance pathway, indicating a large pore diameter. In contrast, dextran-70 (MW approximately 70 000) did not pass through the gamma-activated channel, indicating an upper limit to the pore size of approximately 50 A (5 nm). 5. Similar conductances that are permeable to large molecules were activated by extreme hyperpolarization (> -150 mV) of uninjected oocytes. 6. We conclude that the Na(+),K(+)-ATPase gamma subunits activate Ca(2+)- and voltage-gated, non-selective, large diameter pores that are intrinsically present within the oocyte membrane.

Large scale production of recombinant mouse and rat growth hormone by fed-batch GS-NSO cell cultures.

Investigations of biological effects of prolonged elevation of growth hormone in animals such as mice and rats require large amounts of mouse and rat growth hormone (GH) materials. As an alternative to scarce and expensive pituitary derived materials, both mouse and rat GH were expressed in NSO murine myeloma cells transfected with a vector containing the glutamine synthetase (GS) gene and two copies of mouse or rat GH cDNA. For optimal expression, the mouse GH vector also contained sequences for targeting integration by homologous recombination. Fed-batch culture processes for such clones were developed using a serum-free, glutamine-free medium and scaled up to 250 L production scale reactors. Concentrated solutions of proteins, amino acids and glucose were fed periodically to extend cell growth and culture lifetime, which led to an increase in the maximum viable cell concentration to 3.5×10(9) cells/L and an up to 10 fold increase in final mouse and rat rGH titers in comparison with batch cultures. For successful scale up, similar culture environmental conditions were maintained at different scales, and specific issues in large scale reactors such as balancing oxygen supply and carbon dioxide removal, were addressed. Very similar cell growth and protein productivity were obtained in the fed-batch cultures at different scales and in different production runs. The final mouse and rat rGH titers were approximately 580 and 240 mg/L, respectively. During fed-batch cultures, the cell growth stage transition was accompanied by a change in cellular metabolism. The specific glucose consumption rate decreased significantly after the transition from the growth to stationary stage, while lactate was produced in the exponential growth stage and became consumed in the stationary stage. This was roughly coincident with the beginning of ammonia and glutamate accumulation at the entry of cells into the stationary stage as the result of a reduced glutamine consumption and periodic nutrient additions.