Trichuris suis ova therapy in relapsing multiple sclerosis is safe but without signals of beneficial effect.

BACKGROUND: An observational study has suggested that relapsing-remitting multiple sclerosis patients with helminth infections have lower disease activity and progression than uninfected multiple sclerosis patients. OBJECTIVE: To evaluate the safety and efficacy on MRI activity of treatment with TSO in relapsing MS. METHODS: The study was an open-label, magnetic resonance imaging assessor-blinded, baseline-to-treatment study including ten patients with relapsing forms of multiple sclerosis. Median (range) age was 41 (24-55) years, disease duration 9 (4-34) years, Expanded Disability Status Scale score 2.5 (1-5.0), and number of relapses within the last two years 3 (2-5). Four patients received no disease modifying therapy, while six patients received IFN-ß. After an observational period of 8 weeks, patients received 2500 ova from the helminth Trichuris suis orally every second week for 12 weeks. Patients were followed with serial magnetic resonance imaging, neurological examinations, laboratory safety tests and expression of immunological biomarker genes. RESULTS: Treatment with Trichuris suis orally was well-tolerated apart from some gastrointestinal symptoms. Magnetic resonance imaging revealed 6 new or enlarged T2 lesions in the run-in period, 7 lesions in the early period and 21 lesions in the late treatment period. Two patients suffered a relapse before treatment and two during treatment. Eight patients developed eosinophilia. The expression of cytokines and transcription factors did not change. CONCLUSIONS: In a small group of relapsing multiple sclerosis patients, Trichuris suis oral therapy was well tolerated but without beneficial effect.

Chronic cerebrospinal venous insufficiency and venous stenoses in multiple sclerosis.

OBJECTIVES: The traditional view that multiple sclerosis (MS) is an autoimmune disease has recently been challenged by the claim that MS is caused by chronic cerebrospinal venous insufficiency (CCSVI). Although several studies have questioned this vascular theory, the CCSVI controversy is still ongoing. Our aim was to assess the prevalence of CCSVI in Danish MS patients using sonography and compare these findings with MRI measures of venous flow and morphology. METHODS: We investigated cervical and cerebral veins in 24 patients with relapsing-remitting MS (RRMS) and 15 healthy controls, using extracranial high-resolution ultrasound colour Doppler (US-CD) and transcranial colour Doppler sonography (TCDS), as well as magnetic resonance imaging (MRI) and phase-contrast MR blood flow measurements (PC-MR) of the cervical veins. RESULTS: US-CD could not identify the left internal jugular vein (IJV) in one MS patient, other ultrasound examinations were normal in patients with MS. There was no difference in mean cross-sectional area of the IJV in MS patients compared with controls. Only one patient with MS and two healthy controls fulfilled one CCSVI criterion, and none fulfilled more than one CCSVI criterion. MR venography showed insignificant IJV stenosis (1-49%) in two patients with MS, whereas 50-69% IJV stenosis was detected in two healthy controls. There was no difference in PC-MR measurements of mean IJV blood flow between patients with MS and controls. CONCLUSION: Our results do not corroborate the presence of vascular pathology in RRMS and we found no evidence supporting the CCSVI hypothesis.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC): intra- and interobserver variability in standardized drawing of regions of interest.

PURPOSE: To establish the reproducibility of a standardized region of interest (ROI) drawing procedure in delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC). MATERIAL AND METHODS: A large ROI in lateral and medial femoral weight-bearing cartilage was drawn in images of 12 healthy male volunteers by 6 investigators with different skills in MRI. The procedure was done twice, with a 1-week interval. Calculated T1-values were evaluated for intra- and interobserver variability. RESULTS: The mean interobserver variability for both compartments ranged between 1.3% and 2.3% for the 6 different investigators without correlation to their experience in MRI. Post-contrast intra-observer variability was low in both the lateral and the medial femoral cartilage, 2.6% and 1.5%, respectively. The larger variability in lateral than in medial cartilage was related to slightly longer and thinner ROIs. CONCLUSION: Intra-observer variability and interobserver variability are both low when a large standardized ROI is used in dGEMRIC. The experience of the investigator does not affect the variability, which further supports a clinical applicability of the method.

Protein intake and metabolism in formula-fed infants given Swedish or Italian weaning foods.

The aim of the study was to compare protein intake and metabolism between infants from two countries given similar infant formulae but different weaning foods. Healthy Swedish and Italian infants were studied between 3 and 12 mo. Infants in both populations were assigned to 1 of 3 infant formulae, containing 13, 15 or 18/20 g l(-1) of protein, given in addition to Swedish or Italian weaning foods. Protein intake from weaning foods was higher in Italian than in Swedish infants at 6 and 12 mo, whereas protein intake from formula at 6 mo and from formula/milk at 12 mo was similar in both populations. Plasma isoleucine, leucine, lysine, histidine and valine at 6 mo were lower in Italian than in Swedish infants fed formula with 13 g l(-1) of protein. All essential plasma amino acids were similar in Italian and Swedish groups at 12 mo. Serum urea was similar at 6 mo in corresponding formula groups, but was higher at 12 mo in the Italian than in the Swedish formula group. Serum albumin and growth were normal in both populations throughout infancy. In conclusion, formula with protein content of 13 g l(-1) seems to provide sufficient protein intake when combined with Swedish or Italian weaning foods during the second half of infancy, as indicated by normal serum albumin and normal growth. However, the bioavailability of protein and amino acids from weaning foods, in addition to their protein content, should be considered, as indicated by some indices of protein metabolism in the Italian infants.

Fat intake and metabolism in Swedish and Italian infants.

The purpose of the study was to compare fat intake and metabolism between two infant populations from Sweden and Italy given breast milk or similar infant formulas, but different weaning foods. Nutrient intake and fat metabolism were studied prospectively from 3-12 mo in 68 Swedish and 46 Italian healthy infants, breastfed or given similar infant formulas in combination with Swedish or Mediterranean weaning foods. Although nutrient intake and fat metabolism were similar at 6 mo, fat intake was lower at 12 mo in the Italian than in the Swedish formula group (p < 0.001). At 6 and 12 mo, higher dietary ratios of monounsaturated to saturated fatty acids (p < 0.01 and p < 0.001, respectively), and monounsaturated to polyunsaturated fatty acids (p < 0.05, p < 0.001) were found in the Italian than in the Swedish formula group. Total cholesterol and apolipoprotein B were lower at 6 mo (p < 0.01) in Italian breastfed infants than in Swedish ones. Lower concentrations at 6 and 12 mo of total cholesterol (p < 0.05, p < 0.05, respectively), apolipoprotein B (p < 0.05, p < 0.01) and triglycerides (p < 0.001, p < 0.01), and of apolipoprotein A1 (p < 0.01) at 12 mo, were found in the Italian formula group than in the Swedish one. In conclusion, plasma total cholesterol, apolipoprotein B and triglycerides were found to be lower in Italian infants than in Swedish infants during the second half of infancy. These findings may partly result from differences in fat compositions between Swedish and Mediterranean weaning diets and in total fat intake in late infancy. Differences in duration of breastfeeding and possibly in breast milk composition may also have influenced our results.

Pulmonary MR angiography with ultrasmall superparamagnetic iron oxide particles as a blood pool agent and a navigator echo for respiratory gating: pilot study.

In nine healthy adult volunteers, pulmonary magnetic resonance angiography was performed with the blood pool agent NC100150 injection combined with respiratory gating with a navigator echo. With increasing doses of the contrast agent, higher signal intensities and vessel branch order visualization were achieved. No motion artifacts were seen. The blood pool agent NC100150 injection in combination with respiratory navigator gating permitted acquisition of high-quality MR angiograms of the pulmonary vasculature during continuous breathing.

Ultrasound measurements of subcutaneous adipose tissue in infants are reproducible.

BACKGROUND: The purpose of this study was to evaluate the ultrasound technique for measuring subcutaneous adipose tissue in infants. METHODS: Twenty infants were investigated at 3, 6, and 12 months of age. All measurements were made by the same investigator in triplicate on the left side of the body at the triceps and subscapular anatomic landmarks and at the abdomen and thigh. An ultrasound system equipped with a linear 7.0-MHz transducer was used. RESULTS: The intraclass correlation coefficients were 0.88 to 0.99. Random errors ranged from 0.01 to 0.19 mm. For log-transformed values, the random error ranged from 2.4% to 5.7%. CONCLUSIONS: Measurements of subcutaneous fat in infants using ultrasound are reproducible when performed by the same observer.

Abdominal vessel enhancement with an ultrasmall, superparamagnetic iron oxide blood pool agent: evaluation of dose and echo time dependence at different field strengths.

RATIONALE AND OBJECTIVES: The purpose of the study was to determine the dose and echo time dependence of abdominal vessel enhancement at magnetic resonance (MR) imaging after injection of a blood pool contrast agent at two field strengths. MATERIALS AND METHODS: Sixteen healthy volunteers received NC100150 Injection at three dose levels (1.0 mg, 2.5 mg, and 4.0 mg of iron per kilogram of body weight). Images of the aorta and inferior vena cava (IVC) were obtained at 0.5 or 1.5 T. Four sequences with varying echo times were used with each subject. Signal intensities were recorded from the aorta, IVC, vessel vicinity, air, and a marker outside the patient. Contrast-to-noise ratios (CNRs) were calculated for the vessels. Aortic delineation was subjectively evaluated. RESULTS: Images with the highest mean vessel signal intensities, subjectively assessed as satisfactory for aortic delineation, were obtained with 2.5-4.0 mg of iron per kilogram of body weight at both field strengths. The highest CNR was found with 4.0 mg of iron per kilogram of body weight at 1.5 T. An increase in echo time caused larger signal intensity loss at larger dose levels. The signal intensity from the IVC was higher than that of the aorta at all dose levels, echo times, and field strengths. CONCLUSION: NC100150 Injection is an efficient T1-reducing agent at both 0.5 and 1.5 T. A positive dose response for CNR of the aorta and IVC was seen at 1.5 T.

Plasma lipids and apolipoproteins in breastfed and formula-fed Swedish infants.

This study was carried out to compare plasma lipid pattern in breastfed and formula-fed infants and the effects of exchanging breast milk for formula and of introducing weaning foods. Healthy infants, exclusively breastfed at least until 3 mo, were at this age randomly assigned to infant formulas with similar fat composition. Formula was gradually introduced when breastfeeding was discontinued. One group continued to breastfeed beyond 6 mo of age. All infants received the same weaning foods and were studied between 3 and 12 mo of age. Decreased plasma concentrations of total and low-density lipoprotein cholesterol (TC, LDL-C), apolipoprotein B (apo B) and A1 (p < 0.001), and of high-density lipoprotein cholesterol (p < 0.05) were found when breast milk was exchanged for formula before 6 mo. At this age plasma TC, LDL-C and apo B were lower in formula-fed than in breastfed infants (p < 0.001). These plasma lipids then increased (p < 0.01) when the intake of formula decreased and that of weaning foods increased. However, plasma TC and/or LDL-C remained lower at 12 mo in formula-fed than in breastfed infants (p < 0.05). Our results indicate that the plasma lipid profile of infants is highly responsive to the dietary nutrient intake, as indicated by the decrease in plasma lipids and apolipoproteins when breast milk was exchanged for formula and by the increase in these concentrations when the intake of weaning foods gradually increased.

Time dependence of iopamidol and iodixanol in arthrography of the knee.

PURPOSE: The safety and diagnostic efficacy of iodixanol (Visipaque) 270 mg I/ml was compared to that of iopamidol (Iopamiron) 300 mg I/ml in knee arthrography. MATERIAL AND METHODS: This trial was a bi-center double-blind trial including 128 patients (iodixanol/iopamidol 64/64 patients). Efficacy was evaluated by blinded grading of the diagnostic quality of the p.a. images taken 0, 12 and 25 min after contrast administration by the examining radiologist and later at a consensus evaluation by two experienced skeletal radiologists. Adverse events were recorded. RESULTS: No patient experienced any adverse event. The proportion of better images at both 12 and 25 min after injection was higher in the iodixanol group compared to the iopamidol group both by the examining radiologist and at the consensus evaluation. CONCLUSION: In the knee joint iodixanol is a safe contrast medium. The contrast effect of iodixanol lasted longer than that of iopamidol, which can be important when performing arthrography, especially CT arthrography, where the time between puncture and examination can be prolonged.

Protein and amino acid metabolism in three- to twelve-month-old infants fed human milk or formulas with varying protein concentrations.

BACKGROUND: The metabolic response to different protein intakes from breast milk and/or formulas varying in protein concentrations, in combination with supplementary foods, has not been studied in infants who are in the second half of infancy. METHODS: Healthy infants, exclusively breast-fed until 3 months old, were randomly assigned to one of three groups, F13, F15, or F18, and were given formulas with 13, 15, or 18 g/l of protein, respectively. Infants breast-fed (B) and mixed-fed (M) (breast milk and formula) at 6 months formed the fourth and fifth groups. All infants received the same supplementary foods and were studied from ages 3 to 12 months. RESULTS: The concentrations of albumin, prealbumin, and transferrin were similar in all groups. At 6 months, serum and urine urea concentrations were lower in B and M, compared with urea levels in the formula-fed groups of infants. At 12 months, urine urea was lower in B + M than it was in F18. At 6 months, plasma concentrations of phenylalanine, tyrosine, and methionine were higher in all formula-fed groups; and those of valine. isoleucine, and threonine were higher in F18 and F15 than they were in B and M. Plasma concentrations of methionine, valine, and threonine were higher in F18 than in F13. At 12 months, plasma levels of tyrosine, methionine, valine, isoleucine, and leucine were higher in F18 than they were in B + M. CONCLUSION: Many indexes of protein metabolism were similar in groups F13, B, and M, particularly at 6 months. In contrast, the provision of a formula with 18 g/l of protein resulted in a different metabolic pattern, which could indicate unnecessarily high protein intakes.

Growth and nutrient intake in three- to twelve-month-old infants fed human milk or formulas with varying protein concentrations.

BACKGROUND: Results on growth and nutrient intake in infants in the second half of infancy fed human milk or formulas with varying protein concentrations in combination with supplementary foods have not previously been reported. METHODS: Seventy-one healthy infants were studied from 3 to 12 months of age. They were exclusively breast-fed until 3 months and were then randomly assigned to one of three feeding groups, F13, F15, or F18, indicating formulas with 13, 15 or 18 g/l of protein, respectively. Formula was gradually introduced when breast-feeding was terminated. Infants fed breast milk only were included in the breast-fed group, and those with breast milk and formula were included in the mixed-fed group. The same supplementary foods were provided to all infants. RESULTS: There were no differences in growth between the feeding groups. Total protein intake exceeded minimum recommendations in all groups at all ages and was higher at 6 months in F18 than in F13 (2.3 vs. 1.9 g/kg per day; p < 0.01), whereas formula protein intake was higher at all ages in F18 compared with F13. Intake of protein from supplementary foods increased, but that from formula decreased between 6 and 12 months in all groups. CONCLUSIONS: Intake of breast milk or infant formula with 13 g/l of protein along with high-protein supplementary foods provided enough protein with no adverse effect on growth. Infants fed formulas with higher protein concentrations had similar growth, despite higher intakes of formula protein.

Magnetic resonance imaging, scintigraphy, and arthroscopic evaluation of traumatic hemarthrosis of the knee.

Forty patients with traumatic knee hemarthrosis were examined within 1 week after injury and observations made with magnetic resonance imaging, scintigraphy, arthroscopic evaluation, radiography, and physical examination were compared. Thirty-four patients (85%) had anterior cruciate ligament injuries according to the arthroscopic findings and 28 (83%) of these had associated meniscal tears. Magnetic resonance imaging confirmed the arthroscopic findings, especially if only meniscal tears that required surgery were taken into account (sensitivity, 94% for the lateral and 83% for the medial meniscus). However, the specificity of magnetic resonance imaging was only 29% and 27% for the lateral and medial menisci, respectively, and the accuracy was 28% and 50%, respectively. Marrow edemas, or bone bruises, were seen on magnetic resonance imaging in 80% of the patients and were mainly seen in the lateral compartment. Bone scans correlated well with magnetic resonance imaging findings of marrow edemas. Plain radiographs were normal in all but one case. We show that magnetic resonance imaging does not add information on the status of the anterior cruciate ligament compared with the clinical examination, and that it may be as good as arthroscopic evaluation for the diagnosis of meniscal tears that require surgery.

Brain lesion contrast in MR imaging. Dependence on field strength and concentration of gadodiamide injection in patients and phantoms.

PURPOSE: To compare the contrast effects of gadodiamide injection at 0.3 and at 1.5 T, at different concentrations in phantoms, and to correlate the results to clinical doses used for examining brain lesions. MATERIAL AND METHODS: Gel phantoms with T1 and T2 corresponding to brain gray matter were doped with different concentrations of gadodiamide injection and examined with T1-weighted sequences. Two different sets of phantoms were used, one for 0.3 T and one for 1.5 T. To express contrast, a quotient (RATIOphantom) between signals in each tube with gadodiamide injection and in the one without it was calculated. A corresponding quotient (RATIOpatient) between signals in brain metastases and in gray matter was calculated in 16 patients examined at 0.3 T (0.1 and 0.3 mmol Gd/kg b.w.) and in 5 patients examined at 1.5 T (0.1 mmol Gd/kg b.w.). RESULTS: Maximum RATIOphantom and RATIOpatient were more than 50% higher at 1.5 T than at 0.3 T at equal concentrations using heavily T1-weighted sequences. The use of SE TR/TE 600/30 instead of 400/25 reduced the contrast effect 15-45% depending on concentration. Comparing RATIOpatient to RATIOphantom suggests that the maximum T1 effect of Gd contrast media occurs at higher doses than in current clinical use, as at 0.1 mmol/kg b.w. we achieved 38% (0.3 T) and 56% (1.5 T) of the maximum phantoms. At 0.3 mmol/kg b.w. we achieved 63% (0.3 T) of the theoretical maximum. CONCLUSION: The contrast effect of Gd contrast media is higher at 1.5 T than at 0.3 T. Higher doses than presently used might prove useful especially at lower field strengths where the contrast effect of Gd is less pronounced. Heavy T1-weighting is also important.

Time-dependency in brain lesion enhancement with gadodiamide injection.

PURPOSE: To determine the effective time window for MR imaging of tumors with blood-brain barrier (BBB) damage after injection of Gd-containing contrast media. MATERIAL AND METHODS: Eleven patients with 15 brain lesions (metastasis, glioma, abscess) were studied with a T1-weighted spin-echo sequence repeated over periods of up to 43 min after contrast injection. A quotient was calculated between the signals in the lesion and in the gray matter, and plotted against time. RESULTS: All lesions reached 70% of the maximum RATIO within 3.5 min. After 25 min 12 out of 15 lesions showed persistent enhancement within 15% of the maximal RATIO. CONCLUSION: The peak enhancement of BBB damage occurs around 3.5 min after injection. The effect does not change during the next 25 min. Scanning should not be started until 2-5 min after injection of the contrast medium, and there is no advantage in waiting longer as no major increase (or decline) of contrast can be expected.

MR imaging in recurrent pain after back surgery. A comparative study using standard and high doses of gadolinium contrast agents.

PURPOSE: To compare the diagnostic results following injection of (a) a high dose (0.3 mmol/kg b.w.) of gadodiamide injection and (b) the standard dose (0.1 mmol/kg b.w.) of Gd-DTPA, in patients with recurrent symptoms after surgery for lumbar disc herniation. MATERIAL AND METHODS: Twenty patients with recurrent or sustained symptoms after surgery for lumbar disc herniations were examined. MR imaging (0.3 T) was first performed before and after Gd-DTPA at 0.1 mmol/kg b.w., and then within one month (17 patients) or within 3 months (3 patients) before and after gadodiamide injection at 0.3 mmol/kg b.w. The examinations were first evaluated by 2 neuroradiologists blinded to dose but not to patient as the images were presented in pairs. Six months later the same investigators evaluated the examinations again, this time blinded to both dose and patient. RESULTS: At the evaluation in pairs (with the investigators blinded to dose only) the high-dose examinations were considered the most informative (p=0.05). However, at the later evaluation (with the investigators blinded both to dose and patient) no significant difference between high and standard dose was found regarding diagnosis or diagnostic certainty. CONCLUSION: In this study the high-dose contrast enhancement of MR imaging at 0.3 T did not increase the diagnostic information for differentiating between scar and recurrent hernia. The high-dose images were considered more informative when evaluated in pairs, but gave no additional or different information when evaluated separately. The study also indicated that comparisons in pairs should be interpreted with caution.

Brain metastases--comparison of gadodiamide injection-enhanced MR imaging at standard and high dose, contrast-enhanced CT and non-contrast-enhanced MR imaging.

The aim was to compare the abilities of contrast-enhanced CT, non-contrast-enhanced MR imaging and contrast-enhanced MR imaging using standard (0.1 mmol/kg b.w.) and high (0.3 mmol/kg b.w.) doses of Gadodiamide injection to detect brain metastases (i.e. blood-brain barrier damage). Sixteen patients with at least 2 metastases found by CT were evaluated by MR imaging using non-contrast-enhanced spin-echo, T1-weighted, T2-weighted sequences, and contrast-enhanced spin-echo T1-weighted sequences at 2 dose levels. Gadodiamide injection was first given at the dose of 0.1 mmol/kg b.w. After imaging, another 0.2 mmol/kg b.w. was given, yielding a cumulative dose of 0.3 mmol/kg b.w. No contrast media-related adverse events were recorded. The images were evaluated openly by one and blindly by 2 investigators and the number of metastases, size, delineation (open study) and diagnostic certainty (blind study) of each individual metastasis noted. High-dose MR imaging showed significantly more and smaller metastases than any other examination, and gave a higher diagnostic certainty. All high-dose images were superior to those with the standard dose MR imaging when compared blindly in pairs. We conclude that spin-echo MR imaging with a high dose of Gadodiamide injection is an efficient way to improve the detection of brain metastases, in particular of small ones.

Contrast-enhanced MRI of the central nervous system: comparison between gadodiamide injection and gadolinium-DTPA.

Gadodiamide injection, a new nonionic, MRI contrast medium, was compared with the ionic agent gadolinium (Gd)-DTPA at 0.1 mmol/kg body weight in a double-blind, randomised trial in 60 patients, 30 receiving each substance, with known or suspected lesions of the central nervous system. The patients were closely questioned about adverse events. In the Gadodiamide injection group, four patients reported six adverse advents, three of which were judged to be related to the contrast medium. In the Gd-DTPA group, two patients each reported one adverse event, both of which had an uncertain relation to the contrast medium. All events were mild and no medical treatment was needed. No significant change in neurological findings, blood pressure, pulse rate or blood parameters were noted in any patient. Both contrast media were effective; no difference in overall efficacy or safety was observed.

Radiological investigation of neurofibromatosis type 2.

The radiological findings in six patients fulfilling the criteria of neurofibromatosis type 2 (NF2) were reviewed. Subtle cutaneous lesions were found in three. All patients had bilateral acoustic schwannomas; two had small acoustic tumours and normal hearing. In these patients the presenting symptoms were caused by multiple intracranial meningiomas and spinal neurofibromas, respectively, whereas the remaining four patients presented with hearing loss. Two patients had other cranial nerve tumours. Three patients had rapidly growing multiple intracranial meningiomas; two had multiple spinal neurofibromas and one a spinal meningioma. NF2 is a rare disease with few cutaneous but frequent, typical radiological findings in the central nervous system. The presenting symptom is most commonly hearing loss due to acoustic schwannomas, although symptoms emanating from other intracranial or tumours are not uncommon. The discovery of multiple meningiomas or multiple spinal neurofibromas without cutaneous lesions should initiate a search for acoustic schwannomas even when the patient has normal hearing.