In this Phase I clinical study, a novel ultrasmall superparamagnetic iron oxide contrast agent, NC100150 Injection (Nycomed Imaging, Oslo, Norway, a part of Nycomed Amersham), was used in two-dimensional magnetic resonance coronary angiography (MRCA). Safety and imaging data were acquired from 18 healthy male volunteers at both 0.5 and 1.5 T, before and after the administration of NC100150 Injection. Through-plane and in-plane images of the right coronary artery were analyzed. The postcontrast imaging sequences used prepulses and a high flip angle, to introduce T1 weighting. At 1.5 T (TE 2.6 msec), the throughplane coronary artery signal-to-noise ratio (SNR) (P ‫؍‬ 0.04), coronary artery-to-fat signal difference-to-noise ratio (SDNR) (P ‫؍‬ 0.001), coronary artery-to-myocardium SDNR (P F 0.001), and coronary artery delineation (P F 0.001) were improved by the administration of NC100150 Injection. For in-plane imaging, coronary artery delineation improved, but there were no significant changes in the SNR and SDNR. At 0.5 T, with the longer TE (6.7 msec) imaging sequence used, there was a reduction in the SNR (P ‫؍‬ 0.01), the fat SDNR (through-plane P ‫؍‬ 0.02; in-plane P ‫؍‬ 0.25), and the coronary artery diameter (P F 0.01 in both imaging planes). There was a trend toward improvement in the myocardial SDNR and coronary artery delineation. In conclusion, NC100150 Injection was given safely to 18 healthy subjects, with no major adverse reactions. Coronary artery delineation was improved in both imaging planes at 1.5 T, with a trend toward improvement at 0.5 T. At 1.5 T, with a short TE imaging sequence, the marked T1 shortening effects of NC100150 Injection were dominant, leading to an improvement in the quantitative parameters for the through-plane images. At 0.5 T, with a longer TE imaging sequence, the T2* effects of the contrast agent played a role in reducing the quantitative image parameters. With further optimization of imaging sequences, to take advantage of the long-lived intravascular T1 shortening effect of NC100150 Injection, further improvements in MRCA will be possible.

Sylvatic small mammals were captured in rural habitats near Uppsala, Sweden, to measure the prevalence of bartonella infections, characterize bacterial isolates and identify their host range, and increase our understanding of host-pathogen ecology. During 7 nights of trapping at 3 localities, 236 small mammals were captured (trap success 30%). Bartonella were isolated from bloods of Apodemus flavicollis (19 of 110 tested), Apodemus sylvaticus (6/25), Clethrionomys glareolus (9/60), Microtus agrestis (1/3), Mus musculus (1/18), and Sorex araneus (3/20). Nucleotide sequencing (a 338 bp fragment of the gltA gene) of 40 isolates yielded 6 unique genotypes. Five of the 6 genotypes were most similar to other known bartonella isolated from Old World small-mammal hosts. The most frequent genotype (83%) was isolated from A. flavicollis and M. musculus and was identical to Bartonella grahamii, a recently demonstrated human pathogen. These two hosts were most frequently captured in and around human structures and work places, thus providing conditions that could potentially lead to frequent human infections.

Serum samples were collected from healthy blood donors in 5 regions in Sweden in 1999, i.e. from the local Blood Centres (collecting facilities) in Boden, Jönköping, Lund, Skövde, and Uppsala. In total, 498 serum samples (63% males, 37% females) were received and tested by immunofluorescence assay for antibodies against B. elizabethae, B. grahamii, B. henselae (Houston-1), B. henselae (Marseille), B. quintana, and B. vinsonii subsp. vinsonii. An overall Bartonella spp. seroprevalence of 16.1% was found, with a predominance of immunoreactivity to B. elizabethae, at 14.1%; B. grahamii, 2.6%; B. henselae (Houston-1), 1.2%; B. henselae (Marseille), 1.8%; B. quintana, 0.2%; and B. vinsonii subsp. vinsonii, 0.0%. Univariate and multivariate analyses of epidemiological and demographical information revealed an increased rate of B. elizabethae seropositivity in blood donors working outdoors, being out in the wild a minimum of once a week, hunting moose, having cat contact, and travelling to Eastern Europe. Living in the southern region of Sweden (Lund area) was associated with decreased seropositivity to B. elizabethae.

SUMMARYBALB/c mice were inoculated with Bartonella henselae by both systemic and mucosal routes. Culture analysis of tissues from mice infected intraperitoneally with a high dose of B. henselae yielded positive results 24 hr after infection. However, culture analysis of blood taken between 6 hr and 7 days after infection from groups receiving live B. henselae were negative. Following intraperitoneal infection, B. henselae was detected by polymerase chain reaction in liver and mesenteric lymph nodes by 6 hr and up to 7 days after infection in liver, kidney and spleen tissue. Enzyme-linked immunosorbent assay (ELISA) of serum samples collected as early as 13 days after infection indicated humoral immune responses to B. henselae. Specific humoral responses remained through week 6. Analysis of faecal samples revealed induction of B. henselae-specific immunoglobulin A by day 28 after infection. In addition, B. henselae-specific cellular responses were indicated by a positive delayed-type hypersensitivity and a T helper 1 (Th1) (CD4+ T cell )-type cytokine response following in vitro stimulation of splenocytes. The significance and implications of these data in relation to B. henselae infections are discussed.

In this phase I clinical study, the new ultrasmall superparamagnetic iron oxide contrast agent, NC100150 Injection (Nycomed AS, Oslo, Norway, a part of Nycomed Amersham), was assessed for first-pass magnetic resonance myocardial perfusion studies and its ability to produce equilibrium signal changes, as a possible indicator of myocardial blood volume. Data were acquired in 18 healthy male volunteers at 0.5 T and 1.5 T. At both field strengths, first-pass studies using T1-weighted sequences were acquired. Long TE spinecho echoplanar imaging (EPI) was used at 0.5 T and short TE fast low-angle shot (FLASH) imaging at 1.5 T. With both sequences, T1 effects dominated the images for low doses, and time intensity curves potentially suitable for perfusion analysis were generated. At higher doses, T2 and T2* effects were observed. At 1.5 T, these predominantly affected the blood pool signal; however, at 0.5 T the myocardial signal was also involved, reflecting the relative T2 and T2* sensitivity of the spin-echo EPI sequence as a result of the long TE and long readout window, respectively. Equilibrium changes were assessed at both field strengths using T1-weighted FLASH sequences and in addition at 1.5 T using T2*-weighted gradient-echo EPI. With the T1weighted images at both field strengths, signal changes were observed in all subjects; however, no dose-response relationship could be shown. With the T2*-weighted EPI there was significantly lower signal (P F 0.05) with the 3 and 4 mg/kg doses than with the 2 mg/kg dose. In conclusion, NC100150 Injection is useful for first-pass myocardial perfusion using T1-weighted sequences; however, low doses in combination with short TE sequences are required to minimize sensitivity to T2* effects. Equilibrium signal changes can also be induced in the myocardium. More work is required to optimize the imaging sequences and dose of NC100150 Injection for first-pass studies and also to determine whether the equilibrium signal changes can be used to measure myocardial blood volume changes in ischemic heart disease.