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Rationale and Objectives: The safety and diagnostic efficacy of MultiHance (gadobenate dimeglumine) in the central nervous system (CNS) were evaluated in a double-blind, multicenter, phase III clinical trial., Methods: Two hundred five patients highly suspected of having a CNS lesion (by previous imaging exam) were enrolled at 16 sites in the United States. Patients were randomized to one of three incremental dosing regimens. Magnetic resonance imaging with Omniscan (gadodiamide) at doses of 0.1 and 0.3 mmol/kg was compared with MultiHance (gadobenate dimeglumine) at doses of 0.05 and 0.15 mmol/kg and at 0.1 and 0.2 mmol/kg., Results: Compared with predose images alone, efficacy was demonstrated in each of the gadobenate dimeglumine and gadodiamide groups (single and cumulative doses) as indicated by the level of diagnostic information, number of lesions detected, and contrast-to-noise ratio measurements. The level of diagnostic information from gadobenate dimeglumine at 0.1 mmol/kg was equivalent to that with gadodiamide at the same dose. One of the two blinded reviewers found equivalence between the gadobenate dimeglumine 0.05 mmol/kg dose and gadodiamide at 0.1 mmol/kg. Both reviewers found the level of diagnostic information to be equivalent after the second dose of contrast for all three dosing regimens. The cumulative doses of gadobenate dimeglumine were well tolerated and as safe as gadodiamide., Conclusions: Gadobenate dimeglumine is comparable to gadodiamide in terms of safety and efficacy for imaging of CNS lesions, with a possible advantage in imaging applications owing to enhanced T1 relaxivity.

MRI is a very sensitive imaging modality, however with relatively low specificity. The aim of this work was to determine the potential of image post-processing using 3D-tissue segmentation technique for identification and quantitative characterization of intracranial lesions primarily in the white matter. Forty subjects participated in this study: 28 patients with brain multiple sclerosis (MS), 6 patients with subcortical ischemic vascular dementia (SIVD), and 6 patients with lacunar white matter infarcts (LI). In routine MR imaging these pathologies may be almost indistinguishable. The 3D-tissue segmentation technique used in this study was based on three input MR images (T(1), T(2)-weighted, and proton density). A modified k-Nearest-Neighbor (k-NN) algorithm optimized for maximum computation speed and high quality segmentation was utilized. In MS lesions, two very distinct subsets were classified using this procedure. Based on the results of segmentation one subset probably represent gliosis, and the other edema and demyelination. In SIVD, the segmented images demonstrated homogeneity, which differentiates SIVD from the heterogeneity observed in MS. This homogeneity was in agreement with the general histological findings. The LI changes pathophysiologically from subacute to chronic. The segmented images closely correlated with these changes, showing a central area of necrosis with cyst formation surrounded by an area that appears like reactive gliosis. In the chronic state, the cyst intensity was similar to that of CSF, while in the subacute stage, the peripheral rim was more prominent. Regional brain lesion load were also obtained on one MS patient to demonstrate the potential use of this technique for lesion load measurements. The majority of lesions were identified in the parietal and occipital lobes. The follow-up study showed qualitatively and quantitatively that the calculated MS load increase was associated with brain atrophy represented by an increase in CSF volume as well as decrease in "normal" brain tissue volumes. Importantly, these results were consistent with the patient's clinical evolution of the disease after a six-month period. In conclusion, these results show there is a potential application for a 3D tissue segmentation technique to characterize white matter lesions with similar intensities on T(2)-weighted MR images. The proposed methodology warrants further clinical investigation and evaluation in a large patient population.

The epidemiology and radiological features of Moyamoya disease (MMD) in the US were investigated. This study encompassed 98 cases; 26 were newly collected from eight US institutions and 72 were previously reported in the US literature. The patients ranged in age from 6 months to 67 years with age peaks in the first, third and fourth decades. MMD was seen in various ethnic groups and females were more commonly involved (71%) than males. A specific etiology could not be determined in most cases but arteriosclerosis and use of oral contraceptives were occasional associations. On angiography and/or magnetic resonance angiography (MRA), carotid arterial stenosis or occlusion was seen bilaterally in 95 cases (97%) and unilaterally in three. On MR or MRA, internal carotid steno-occlusive lesions were well demonstrated in all cases but Moyamoya collateral vessels (MMVs) were visualized in only 65% of the patients. MMVs in the basal ganglia and thalami were best demonstrated on T1 weighted images. Parenchymal lesions were seen in all patients and were often bilateral. With advances in MR techniques and increasing awareness of diagnostic guidelines, MMD will be diagnosed more frequently than before in the US.

Phytopathogenic strains of Burkholderia cepacia (synonym Pseudomonas cepacia) produce endopolygalacturonase, whereas strains of clinical and soil origin do not. Growth of a phytopathogenic strain (ATCC25416) at elevated temperatures resulted in nonpectolytic derivatives that were either cured of a resident plasmid or contained a plasmid of reduced mass. The resident 200-kb plasmid (pPEC320) in strain ATCC25416 was tagged with Tn5-Mob. The pPEC320::Tn5-Mob (pPEC321) plasmid was mobilized in B. cepacia strains of soil and clinical origin. Transconjugants containing pPEC321 expressed the endopolygalacturonase and showed differential activity on plant tissue. No evidence for self-transfer of pPEC320 or the tagged derivative was observed. A 285-kb cloned fragment from pPEC320 containing the plasmid-borne pehA gene was sequenced and compared to the pehA gene from Erwinia carotovora subsp. carotovora and Ralstonia solanacearum and the polygalacturonase sequence from Lycopersicon esculentum.

Synthetic combinatorial libraries were evaluated with an iterative process to identify a hexapeptide with broadspectrum activity against selected phytopathogenic fungi. A D-amino acid hexapeptide (FRLKFH) and pentapeptide (FRLHF) exhibited activity against Fusarium oxysporum f. sp. lycopersici, Rhizoctonia solani (anastomosis group 1), Ceratocystis fagacearum, and Pythium ultimum. The peptides showed no hemolytic or mutagenic activity. Fluorescent microscopy studies with a membrane impermeant dye indicated that fungal cytoplasmic membranes were compromised rapidly and that the nuclear membrane was also affected.

Rationale and Objectives: Multiple cases of recurrence of aneurysms after endovascular treatment have been reported. The purpose of the current hemodynamic study was to identify changes in shear stress and pressure associated with the recurrence of terminal intracranial aneurysms after endovascular occlusion., Methods: Using a finite element method, a pulsed flow with a non-Newtonian viscosity of blood was simulated within the aneurysm cavity. A recurrent terminal intracranial aneurysm of a patient originally treated with balloon occlusion was then studied. This was based on a physiologic pulsatile flow, which was observed in the middle cerebral artery. Before and after the balloon occlusion, local maximum wall shear stress and pressure drop at the neck of the aneurysm were calculated and compared with the normal shear stress., Results: Although the maximum shear stress at the right neck of the aneurysm was significantly reduced after balloon insertion, it was still 2.5 times greater than the normal maximum shear stress. This was attributable to the presence of a portion of the aneurysmal neck (residual neck), which was not obliterated by the balloon. The balloon also helped to reduce the maximum pressure inside the aneurysm by approximately 15%. Hemodynamic changes in the residual aneurysm neck, where the shear stress and the pressure are high, and other factors may be responsible for the recurrence of aneurysms after balloon or coil occlusion., Conclusion: Residual necks after balloon occlusion, coil occlusion, or both are attributable to the geometric orientation of the aneurysm with respect to parent and daughter vessels and the variety of configurations of the balloon and coils used to occlude the aneurysms. Inadequate reduction in local shear stress found in these residual necks is an important factor in the recurrence and rupture of the aneurysm after endovascular occlusion.

Forty-one patients with multiple sclerosis were studied with magnetic resonance imaging (MRI) and a battery of neuropsychological tests to determine the pattern of lobar distribution of lesions in the relapsing-progressive and relapsing-remitting forms of the disease. Correlation of lesions with the patient's cognitive and emotional dysfunction was also obtained. The results of this study indicate that patients with relapsing-progressive multiple sclerosis are characterized by the large or coalescent lesions located predominantly in the periventricular area. These lesions were more frequently found in the parietooccipital areas and were accompanied by significant cognitive dysfunction and severe personality changes. The patients with relapsing-remitting disease, however, were characterized by punctiform or small discrete lesions predominantly located in the intermediate and subcortical areas. These lesions were more frequently seen in the parietooccipital regions and the patients had significantly less severe cognitive and emotional involvement than did the patients with relapsing-progressive disease. Recognition of these patterns was easily accomplished by MRI. In this investigation MRI studies were utilized as an index of the pathological changes occurring at one point in time in the evaluation of the disease. Only repeated MRI studies and continuous clinical observation can establish the final diagnosis.

Fifty-six patients diagnosed with definite multiple sclerosis (MS) according to Poser criteria were administered the Mini-Mental State Examination (MMSE) and a comprehensive battery of neuropsychological tests. Extent of cerebral lesion involvement was determined by quantitative magnetic resonance imaging (MRI) ratings. The MMSE correlated with overall levels of physical disability, but did not correlate with total lesion area on MRI. Sensitivity of the MMSE to the subcortical dementia of MS was low (28%) when performance on the neuropsychological testing battery was used as the criterion. Impairment on tests of memory, speed of information processing, abstract reasoning, naming/verbal fluency, as well as visuoperceptual organization, were correlated highly with total lesion area on MRI. The low sensitivity of the MMSE to cognitive impairment in MS is discussed in terms of its item composition and the characteristic pattern of deficits found in MS.

Purpose: To explain the origin and growth of intracranial aneurysms using the hemodynamic data obtained from a computer simulation., Materials and Methods: Pulsatile flow in an intracranial aneurysm cavity was numerically simulated based on physiologic pulsatile flow observed in the aorta. A finite element method was applied to solve the equations of motion and the non-Newtonian viscosity of blood was taken into account in the analysis. An angiogram of a middle cerebral artery segment with aneurysm was used for the computer modeling of blood flow within the aneurysm cavity. Local shear stress and pressure on the wall at the neck of the aneurysm as well as blood flow motions inside the cavity were calculated as a function of time for various stages in the development of the aneurysm., Findings: Blood moves into the aneurysm cavity along the proximal wall of the cavity and emerges along the distal wall during the acceleration period of systole; however, during the deceleration period of systole and diastole, blood changes its flow direction, entering along the distal wall of the cavity and leaving along the proximal cavity wall. Rapid changes of blood flow direction result in rapid changes in wall shear stress and pressure at the proximal and distal walls of the cavity, rendering continuous damage to the intima at the cavity neck. These hemodynamic stresses relate to the anatomy of a particular vessel may be responsible for the initiation of aneurysm formation and subsequent progression, thrombosis and/or rupture., Conclusion: Computer modeling can further our understanding of factors that determine the origin and progression of intracranial aneurysms.

We present the results of presurgical balloon occlusion of the carotid artery in 22 patients with cervical lymphadenopathy stage N3. The procedure was found to be extremely useful in preventing rupture of the carotid artery, considered the most dangerous complication of neck cancer surgery. Complications of the balloon procedure were few (10%) when compared with surgical ligation of the carotid artery (41-54% stroke frequency and 32-60% mortality). This procedure also allows testing of the collateral circulation before final detachment of the balloon, a maneuver that prevents stroke in many patients.

Production of bacteriocin activity designated pediocin PA-1 was associated with the presence of a 6.2-megadalton plasmid in Pediococcus acidilactici PAC1.0. The bacteriocin exhibited activity against P. acidilactici, P. pentosaceus, Lactobacillus plantarum, L. casei, L. bifermentans, and Leuconostoc mesenteroides subsp. dextranicum. Partial characterization of pediocin PA-1 is described. The molecular weight of pediocin PA-1 was ca. 16,500. Additionally, strain PAC1.0 was found to contain a 23-megadalton plasmid associated with sucrose-fermenting ability.

Ventriculosubarachnoid perfusion with oxygenated fluorocarbon emulsion has been used in the treatment of severe cerebral ischemia in cats. The perfusion vehicle is prepared mimicking cerebrospinal fluid in terms of electrolyte content, osmolality, pH, glucose and amino acids. Fluorocarbon emulsion is prepared with the vehicle as the external phase and charged with high partial pressures of oxygen. This fluorocarbon emulsion has been well-tolerated by the central nervous system. In addition to delivering oxygen to the ischemic tissues via the ventriculosubarachnoid space, the fluorocarbon emulsion has an absorption coefficient higher than normal brain and cerebrospinal fluid. This property makes it easily detected on the CT scan. Determination of appearance, attenuation, distribution, and absorption of the fluorocarbon has been performed in cats after direct intraventricular injection of the substances and after perfusion of the emulsion. The results of these experiments stress the possibility of using a fluorocarbon emulsion as a potential contrast medium in the brain and subarachnoid space, particularly after brain anoxia.

The ability to ferment the trisaccharide raffinose was linked with the presence of plasmid DNA in three strains of Pediococcus pentosaceus. Parental strains showed associated inducible alpha-galactosidase and sucrose hydrolase activities when grown in alpha-galactosides and sucrose, respectively. Derivative strains of PPE1.0, PPE2.0, and PPE5.0, which had lost 30-, 28-, and 23-megadalton plasmids, respectively, had no alpha-galactosidase or sucrose hydrolase activity.

Transfer of sucrose fermentation ability, nisin production, and nisin resistance from Streptococcus lactis to S. lactis and Streptococcus lactis subsp. diacetylactis occurred between cells immobilized on nitrocellulose filters in the presence of DNase. Transconjugants were able to act as donors to transfer the Suc-Nis phenotype in subsequent mating. No changes in sensitivity to lytic phage c2 were noted in S. lactis transconjugants. However, temperature-independent restriction of lytic phage 18-16 was noted in transconjugants of S. lactis subsp. diacetylactis 18-16. Adsorption studies with phage-resistant transconjugants showed that resistance was not due to lack of adsorption by the lytic phage. Physical evidence for the presence of introduced plasmid DNA was not found in lysates of transconjugants.

Strains of Pseudomonas putida, Pseudomonas sp., and Pseudomonas aeruginosa were examined for their ability to grow in the presence of the iron chelator, ethylenediamine-di-(o-hydroxyphenylacetic acid). In vitro fungal inhibition assays showed that the isolates varied in their ability to inhibit the growth of representative fungal plant pathogens. Fungal inhibition in vitro was superior to that of previously reported Pseudomonas sp. Studies with Fusarium oxysporum forma sp. lycopersici and a susceptible tomato cultivar demonstrated that Pseudomonas putida PPU3.1 was able to significantly reduce wilt disease.

Eighty-five strains of bacterial species selected from the predominant cultivable dental plaque flora of patients with different periodontal pathologies were examined for their plasmid content. Microorganisms studied included: Actinomyces viscosus, A. odontolyticus, Bacteroides asaccharolyticus (B. gingivalis), B. melaninogenicus subspecies intermedius, and subspecies melaninogenicus, Capnocytophaga ochracea (B. ochraceus), and Fusobacterium nucleatum. Three B. melaninogenicus isolates showed plasmids of approximately 2.7-2.9 Mdalton (mega-dalton) molecular size. Restriction enzyme digests of the plasmids demonstrated dissimilar patterns when electrophoresed on agarose gels. In other microorganisms, including the Actinomyces species, plasmids were not observed.

The radiological findings in 22 patients with malignant lymphoma of the nervous system are reviewed in relation to the clinical and histological features. The radiological findings were grouped into four major categories: intracranial, orbital, nasopharyngeal, and spinal. A fifth category, complications, was considered separately. The common neuroradiological manifestations of nervous system lymphoma are reviewed and compared with the recent literature.

Computed tomographic (CT) findings of cerebral and cerebellar calcification are described in three American adults with raised serum lead levels and known exposure to lead for 30 or more years. Calcification patterns were punctiform, curvilinear, speck-like, and diffuse and were found in the subcortical area, basal ganglia, vermis, and cerebellum. Admission serum lead levels ranged from 54 to 72 micrograms/dl (normal, 0-30 micrograms/dl). Nonspecific neurologic manifestations consisted of dementia, diminished visual acuity, peripheral neuropathy, syncope, dizziness, nystagmus, easy fatigue, and back pain. Two patients developed chronic renal disease and hypertension; in both cases, serum parathormone was elevated. Blood, calcium, and phosphorus were normal in all three. No other structural abnormalities were observed with CT. Although the pathophysiologic mechanism of these findings remains poorly understood, it is suggested that chronic lead exposure should be included in the differential diagnosis of unexplained intracranial calcifications in adults.

Noninvasive procedures (ultrasound, CT, and MRI) are increasingly valuable in the diagnosis of diseases of the head and neck. Angiography, however, is still essential in the demonstration of vascular pathology, including the preoperative evaluation of vascular neoplasms. Through angioplasty and embolization techniques, angiography also plays a leading role in the treatment of arteriosclerotic vascular disease, vascular malformations, and vascular neoplasms.

Pseudomonas phaseolicola cells synchronously infected with phi 6 were fixed and embedded by several procedures. The diameter of phi 6 measured 75 nm and its nucleocapsid 60 nm. Virus nucleocapsids were icosahedral and surrounded by a double membrane. In planar sections the nucleic acid appeared as a hexagonal ring and in cross section as two angular structures.

A gram-negative nonmotile rod which was capable of using 1,2-(14)C-ethylene glycol as a sole carbon source for growth was isolated from a brine pond, Great Salt Lake, Utah. The bacterium (ATCC 27042) required at least 0.85% NaCl for growth and, although the chloride ion was replaceable by sulfate ion, the sodium ion was not replaceable by potassium ion. The maximal concentration of salt tolerated for growth was approximately 12%. The bacterium was oxidase-negative when N,N-dimethyl-p-phenylenediamine was used and weakly positive when N,N,N',N'-tetramethyl-p-phenylenediamine was used. It grows on many sugars but does not ferment them, it does not have an exogenous vitamin requirement, and it possesses a guanine plus cytosine ratio of 64.3%. Incorporation of ethylene glycol carbon into cell and respired CO(2) was quantitated by use of radioactive ethylene glycol and a force-aerated fermentor. Glucose suppressed ethylene glycol metabolism. Cells grown on ethylene and propylene glycol respired ethylene glycol in a Warburg respirometer more rapidly than cells grown on glucose. Spectrophotometric evidence was obtained for oxidation of glycolate to glyoxylate by a dialyzed cell extract.