Carboxymethyldextran-A2-Gd-DOTA enhancement patterns in the abdomen and pelvis in an animal model

The aim of this study was to assess MR signal enhancement patterns of carboxymethyldextran (CMD)-A2-Gd-DOTA, a new macromolecular contrast agent, in the abdomen and pelvis of New Zealand white rabbits. Nine New Zealand white rabbits underwent MRI before and following injection of 0.05 mmol/kg body weight (bw) CMD-A2-Gd-DOTA (52.1 kDa), using turbo FLASH-, dynamic FLASH 60 degrees-, T1- and T2-weighted spin-echo and turbo spin-echo sequences up to 10 days p.i. Changes in blood and tissue signal intensities (deltaSI) and relaxation rates (deltaR1) were calculated. Differences between pre- and post-contrast MRI data were compared using the Scheffé test. CMD-A2-Gd-DOTA demonstrated significant blood-pool enhancement and significant tissue enhancement on T1-weighted images, whereas no significant signal changes were observed on T2-weighted images (P < 0.05). Kidney parenchyma, pelvis and bladder demonstrated a subsequent enhancement, resembling renal elimination of the majority of the contrast agent. Liver parenchyma demonstrated a slow, delayed decay of the contrast enhancement due to storage and biodegradation of larger subfractions of the contrast agent. All tissue signal intensities were back to baseline 10 days p.i. CMD-A2-Gd-DOTA is a new macromolecular contrast agent with blood-pool effect, significant signal enhancement of abdominal organs and pelvic bone marrow, partial storage in the liver and baseline tissue signal intensities by 10 days p.i.     

Kinetic characterization of hexokinase isoenzymes from glioma cells: implications for FDG imaging of human brain tumors

Quantitative imaging of glucose metabolism of human brain tumors with PET utilizes 2-[(18)F]-fluorodeoxy-D-glucose (FDG) and a conversion factor called the lumped constant (LC), which relates the metabolic rate of FDG to glucose. Since tumors have greater uptake of FDG than would be predicted by the metabolism of native glucose, the characteristic of tumors that governs the uptake of FDG must be part of the LC. The LC is chiefly determined by the phosphorylation ratio (PR), which is comprised of the kinetic parameters (Km and Vmax) of hexokinase (HK) for glucose as well as for FDG (LC proportional to (Km(glc) x Vmax(FDG))/(Km(FDG) x Vmax(glc)). The value of the LC has been estimated from imaging studies, but not validated in vitro from HK kinetic parameters. In this study we measured the kinetic constants of bovine and 36B-10 rat glioma HK I (predominant in normal brain) and 36B-10 glioma HK II (increased in brain tumors) for the hexose substrates glucose, 2-deoxy-D-glucose (2DG) and FDG. Our principal results show that the KmGlc < KmFDG < Km2DG and that PR2DG < PRFDG. The FDG LC calculated from our kinetic parameters for normal brain, possessing predominantly HK I, would be higher than the normal brain LC predicted from animal studies using 2DG or human PET studies using FDG or 2DG. These results also suggest that a shift from HK I to HK II, which has been observed to increase in brain tumors, would have little effect on the value of the tumor LC.     

Treatment of infrapopliteal occlusive disease by high-speed rotational atherectomy: initial and mid-term results

PURPOSE: To assess the effectiveness and patency rates of high-speed rotational atherectomy (HSRA) for the treatment of infrapopliteal arterial occlusive disease. MATERIAL AND METHODS: During an 18-month period, a total of 19 infrapopliteal lesions in 15 consecutive patients were treated primarily by HSRA with use of the Rotablator device. Patients were followed up with documentation of clinical symptoms, standardized treadmill exercise, and Doppler sonography at 1, 3, and 6 months. Control angiography was performed 6 months after primary treatment. RESULTS: HSRA was initially successful in 14 of 15 patients, yielding an initial technical success rate of 94%. Percutaneous treatment induced an improvement of the ankle-brachial index (ABI) from 0.6 +/- 0.09 to 0.86 +/- 0.2 after intervention (P < .0001). Doppler analysis showed a mean ABI of 0.85 +/- 0.2 (P < .001) at 1 month, 0.72 +/- 0.2 (P = .012) at 3 months, and 0.7 +/- 0.2 (P = .08) at 6 months after initial therapy. Although six patients were lost to follow-up at various times, control angiography at 6 months was carried out in nine of 15 patients, allowing direct assessment of 12 of 19 treated lesions. Among six high-grade restenoses and five total occlusions in the treated vascular segments, only one arterial lumen (of 12) remained patent without presenting a hemodynamically relevant restenosis. These results led to termination of the study. CONCLUSION: Although HSRA for the treatment of infrapopliteal occlusive disease yields a very high initial technical success rate, mid-term results are extremely poor. Therefore, HSRA cannot be recommended for primary treatment of this type of lesion.     

Pullout strength of pedicle screws versus pedicle and laminar hooks in the thoracic spine

While the biomechanical properties of pedicle screws have proven to be superior in the lumbar spine, little is known concerning pullout strength of pedicle screws in comparison to hooks in the thoracic spine. In vitro biomechanical pullout testing was performed to evaluate the axial pullout strength of pedicle screws versus pedicle and laminar hooks in the thoracic spine with regard to surgical correction techniques in scoliosis. Nine human cadaveric thoracic spines were harvested and disarticulated. To simulate a typical posterior segmental scoliosis instrumentation, standard pedicle hooks were used between T4 and T8 and supralaminar hooks between T9 and T12 and tested against pedicle screws. The pedicle screws were loaded strictly longitudinal to their axis; the hooks were loaded perpendicular to the intended rod direction. In total, 90 pullout tests were performed. Average pullout strength of the pedicle screws was significantly higher than in the hook group (T4-T8: 531 N versus 321 N, T9-T12: 807 N versus 600 N, p < 0.05). Both screw diameter and the bone mineral density (BMD) had significant influence on the pullout strength in the screw group. For scoliosis correction, pedicle screws might be beneficial, especially for rigid thoracic curves, since they are significantly more resistant to axial pullout than both pedicle and laminar hooks.     

Plasma antioxidant vitamins, chronic hepatitis B virus infection and urinary aflatoxin B1-DNA adducts in healthy males

Epidemiological evidence indicates that aflatoxin B1 (AFB1) intake is associated with an increased risk of hepatocellular carcinoma (HCC). The hepatocarcinogenesis is initiated by covalent binding of AFB1 to cellular DNA. To determine whether nutritional factors and hormonal status may influence the binding of AFB1 to hepatic DNA, a cross- sectional study was performed on a total of 42 male asymptomatic hepatitis B surface antigen (HBsAg) carriers and 43 male non-carriers in a cohort study on the multistage development of HCC in Taiwan. The major AFB1-DNA adduct in vivo, AFB1-N7-guanine, was measured by high- performance liquid chromatography in urine. Urinary AFB1-N7-guanine was detectable in 40% of the subjects. HBsAg carriers had a higher detection rate of urinary AFB1-DNA adducts than non-carriers and the difference was statistically significant after multivariate adjustment. After taking into account the total AFB1 urinary metabolite level, chronic HBsAg carrier status, and other potential confounders, plasma levels of cholesterol, alpha-tocopherol, and alpha- and beta-carotene were positively associated with the detection rate of the AFB1-DNA adducts in a dose-dependent manner, whereas plasma lycopene level was inversely related to the presence of the adducts in urine. The association of urinary AFB1-DNA adducts with the plasma levels of cholesterol, alpha-tocopherol, lycopene, and alpha- and beta-carotene was observed at both low and high exposure levels of AFB1. There was a synergistic interaction of plasma alpha-tocopherol with alpha- and beta- carotene on the adduct levels. No association with the adducts was found for plasma levels of retinol and testosterone. This study demonstrated different associations of antioxidant vitamins with AFB1- DNA adduct formation. The data consistent with our previous finding in cultured woodchuck hepatocytes that alpha-tocopherol and beta-carotene enhanced AFB1-DNA adduct formation suggest that prospective investigation of the relationship between plasma micronutrients and risk of AFB1-related HCC is warranted.      

Temporal and individual variations in the dose of glucocorticoid used for the treatment of salt-losing congenital virilizing adrenal hyperplasia due to 21-hydroxylase deficiency

The dose of glucocorticoid was evaluated in the treatment of 19 patients with salt-losing congenital adrenal hyperplasia due to complete or nearly complete 21-hydroxylase deficiency. In most cases, follow-up was from infancy to puberty. The dose of steroid was expressed as oral cortisol (mg/m² body surface area 124 hours); the equivalent doses of the various glucocorticoid preparations was as follows: 100 mg oral cortisol = 120 mg oral cortisone acetate = 25 mg oral prednisone = 50 mg intramuscular cortisol = 60 mg intramuscular cortisone acetate. The dose of glucocorticoid producing good laboratory and clinical control varied significantly with age. The dose fell from 26 mg/m²/24 hours in early infancy to 19 mg/m²/24 hours between 6 and 8 years of age, and then rose to 23–24 mglm²/hour in adolescence. In addition to these age-related changes, there were large individual variations at each age. Indeed, the values from 4 of the 19 patients were not included in the calculation of the mean because they were more than 3 SD either above or below the mean. For the rest of the patients, the coefficient of variation ranged from 14.5% to 37.2%. It is concluded that glucocorticoid therapy must be adjusted carefully to the age and needs of each patient.     

Prevalence of behaviour disorders in low birthweight infants

OBJECTIVE--To determine the prevalence of behaviour disorders in low birthweight infants. DESIGN--Children of birth weight < or = 2000 g born to mothers resident in Merseyside in 1980-1 assessed using the Rutter parent and teacher behaviour questionnaires and the Conner modification of the Rutter teacher questionnaire. Children attending normal schools were assessed with controls matched for age, sex, and class in school. Children attending special schools were assessed unmatched. SUBJECTS--233 matched case-control pairs attending normal primary schools and 46 unmatched children attending special schools. SETTING--Primary and special schools. MAIN OUTCOME MEASURES--Emotional, conduct, and undifferentiated behaviour disorders and hyperactivity. RESULTS--On the parental questionnaire screen, 36% of the cases and 22% of the controls had a behaviour disorder and on the teacher questionnaire the proportions were 27% and 12% respectively. Hyperactivity was significantly more common among male cases than their controls (21% v 5.0%) but differed little among female cases and controls (9% v 7%). CONCLUSIONS--Improving neonatal survival of low birthweight infants is accompanied by a higher prevalence of behaviour disorders. The long term implications for psychiatric morbidity and other adult disease must be monitored.     

Therapeutic target discovery using Caenorhabditis elegans

Use of the human genome sequence in disease therapy will require efficient identification of disease-causing and disease-associated genes with functions that are amenable to pharmacological manipulation. The validation and development of such genes as therapeutic targets requires information about both the genes' functions and the biochemical pathways in which they participate. One powerful means of obtaining such information is the study of homologous genes in model organisms amenable to laboratory manipulation. Among model organisms the nematode Caenorhabditis elegans offers several advantages, including well-established techniques for genetic and experimental manipulation and the first completed genome sequence for a multicellular organism. Molecular genetic experiments using C. elegans can contribute at several levels to drug discovery programs, from elucidation of genetic functions and pathways to the validation of candidate targets. Additionally, the ease of culture allows adaptation of the nematode for use in high-throughput chemical screens for the identification of lead compounds in drug development.     

History and overview of comprehensive interdisciplinary breast centers

The comprehensive interdisciplinary breast center represents a model for delivering breast care in an efficient and cost-effective manner. It is a better way of caring for women with breast disease and allows for an interdisciplinary treatment by various specialists working and communicating with each other. The center allows for incorporation of new programs and innovations of care. As breast cancer care undergoes further changes, the comprehensive breast center facilitates progress and serves as a model for other disease-specific interdisciplinary programs. The evolution of breast centers and types of models are reviewed, and key factors of success are outlined in this article.