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Biomedical subjects

M J Blomley

Publications and source records attributed to M J Blomley.

At least 19 recordsLinked to original sources

Transdermal estradiol improves bone density when used as single agent therapy for prostate cancer.

PURPOSE: Current androgen deprivation therapies for men with prostate cancer cause accelerated osteoporosis and a significant risk of osteoporotic fracture. We have recently shown that transdermal estradiol is an effective alternative for such patients. Here we report the impact of transdermal estradiol therapy on the bone mineral density of men with prostate cancer. MATERIALS AND METHODS: A total of 20 patients with newly diagnosed locally advanced or metastatic prostate cancer were treated with transdermal estradiol patches. Bone mineral density of the lumbar spine and the proximal femur was measured with dual-energy x-ray absorptiometry, and correlated with computerized tomography and isotope bone scan findings at 6-month intervals. RESULTS: In all measured regions bone mineral density increased with time. By 1 year mean bone mineral density +/- SEM had increased by 3.60% +/- 1.6% in the lumbar spine (p = 0.055), 2.19% +/- 1.03% in the femoral neck (p = 0.055), 3.76% +/- 1.35% in the Ward's region (p = 0.008) and 1.90% +/- 0.85% in the total hip (p = 0.031), respectively. Of 12 osteoporotic sites 4 had improvement based on World Health Organization grading. All other sites improved toward a better classification. CONCLUSIONS: Transdermal estradiol protects against bone loss in men with prostate cancer and may improve bone density in those at risk for osteoporotic fracture.

Administration, Cutaneous↗

Developments in ultrasound contrast media.

Ultrasound microbubble contrast agents are effective and safe echo enhancers. An ingenious array of methods are employed to achieve stability and provide a clinically useful enhancement period. Microbubbles enhance ultrasound signals by up to 25 dB (greater than 300-fold increase) due to resonant behaviour. This is used to rescue failed Doppler studies and may be extended to image the microcirculation of tumours and the myocardium using non-linear modes. Functional studies open up a whole range of applications by using a variety of active and passive quantitation techniques to derive indices from the transit of contrast through a tissue of interest. This has been especially successful in the detection of liver metastases and cirrhosis and shows great promise as a clinical tool. It also has great potential in measuring microcirculatory flow velocity. The demonstration that some microbubbles are not just pure blood pool agents but have a hepatosplenic specific phase has extended the versatility of ultrasound. Imaging of this stationary phase with non-linear modes such as phase inversion and stimulated acoustic emission, has improved the sensitivity and specificity of ultrasound in the detection and characterisation of focal liver lesions to rival that of CT and MR.

Contrast Media↗

Does the presence of distant and local malignancy alter parenchymal perfusion in apparently disease-free areas of the liver?

Our objective was to investigate if hepatic arterial (HAP) and portal venous perfusion (PVP) in apparently normal areas of liver, as measured by functional CT, are affected by the presence of extra- and intrahepatic malignancy Three patient groups were compared: A, controls with no malignancy (N = 10); B, extrahepatic malignancy without liver involvement (N = 12); and C, subjects with metastases elsewhere in the liver (N = 13). HAP, PVP, and a CT hepatic perfusion index (CT-HPI) calculated as HAP/(HAP + PVP) were calculated on a section free of metastatic disease, using a previously published method. Figures for PVP were (median and interquartile range) in group A were 1.06 (0.9-1.30), in B 1.03 (0.81-1.09), and in C 0.75 (0.54-1.02) ml/min/ml; for HAP group A values were 0.07 (0.052-0.078), in B 0.07 (0.053-0.147), and in C 0.12 (0.091-0.146) ml/min/ml and for CT-HPI Group A values were 4.9% (4.8-6.6%), in B 5.6% (3.8-13.6%), and in C 14.3% (10.4-15.4%). Significant differences in all indices were seen between groups A and C. A significant difference (P = 0.017) was seen between groups B and C in the CT-HPI values. In conclusion, patients with liver metastases show abnormal blood flow in apparently normal liver compared to controls. This difference was not seen in subjects with malignancy without liver metastases. Possible explanations would be either the unmasking of occult metastatic disease or vasoactive or mechanical effects due to liver malignancy.

Adult↗

Determination of glomerular filtration rate per unit renal volume using computerized tomography: correlation with conventional measures of total and divided renal function.

PURPOSE: Previous studies suggest that functional computerized tomography (CT) can measure glomerular filtration rate (GFR) per unit renal volume. We compared this index with conventionally determined GFR measurements. MATERIALS AND METHODS: A total of 16 men and 8 women 63.3 +/- 14.9 years old (range 31 to 88) were studied using with contrast enhanced CT. A single slice of kidney was scanned sequentially after bolus injection (0.5 to 1.0 ml. per second(-1)) of 20 ml. iopamidol (300 mg. iodine per ml.(-1)). GFR per volume of kidney was calculated using a Patlak graphical analysis, and this index was multiplied by renal volume on CT to yield global GFR (ml. per minute(-1)). Divided function was also calculated. GFR and divided renal function were calculated in all cases from radioisotope renography with 99m diethylenetetraminepentaacetic acid. In 12 subjects in whom 24-hour urine collection was possible GFR was also calculated from creatinine clearance. RESULTS: A strong correlation was observed between divided renal function, expressed with respect to the right kidney calculated from CT (52.7 +/- 14.8%, range 19.9% to 97.4%) and by radioisotope renography (51.7 +/- 14.6%, range 18.9% to 92.6%, r = 0.97, p <0.0001). A strong correlation (r = 0.92, p <0.0001) was also seen between global GFR determined by CT (80.1 +/- 43.9 ml. per minute(-1), range 38.2 to 197.9) and creatinine clearance (72.4 +/- 47.5, range 14.6 to 168.5), and was stronger than the correlation between the radioisotope and creatinine clearance method (r = 0.67, p = 0.02) in the same patients. CONCLUSION: Functional CT using nonionic contrast material can measure GFR normalized to renal volume and is an accurate alternative to conventional methods of renal function evaluation.

Adult↗

Do different types of liver lesions differ in their uptake of the microbubble contrast agent SH U 508A in the late liver phase? Early experience.

PURPOSE: To compare the uptake of SH U 508A in different types of liver lesions by using stimulated acoustic emission. MATERIALS AND METHODS: Thirty-seven patients with characterized lesions (metastasis, n = 17; hepatocellular carcinoma, n = 4; hemangioma, n = 9; focal nodular hyperplasia, n = 7) received 2.5 g SH U 508A. After 5 minutes, stimulated acoustic emission was elicited by using a previously described method. Liver and/or lesional differences were assessed with videodensitometry (objective conspicuity score), and two observers assessed each lesion by using a six-point scale (subjective conspicuity score). RESULTS: Metastases and hepatocellular carcinoma had low stimulated acoustic emission; median objective conspicuity scores were 70% and 68% (all scores were > or =43%), respectively, and subjective conspicuity scores were 2 or higher for both observers. Hemangiomas had reduced stimulated acoustic emission, with more variability; the median objective conspicuity score was 41% (range, 9%-72%), and the median subjective conspicuity scores were 2 (range, 1-4) and 3.5 (range, 1-5) for observers 1 and 2, respectively. Focal nodular hyperplasia had stimulated acoustic emission comparable to that of the liver in all cases; the median objective conspicuity score was -4.7% (all scores were <6%), and the subjective conspicuity score was 1 or lower for both observers. This finding completely separated focal nodular hyperplasia and malignancies. Significant differences were seen between focal nodular hyperplasia and all other lesion types (P < .05). CONCLUSION: Strong late-phase lesional uptake of SH U 508A is characteristic of focal nodular hyperplasia, is seen in some hemangiomas, and was not observed in malignancies.

Adult↗

[Stimulated acoustic emissions with the ultrasound contrast medium levovist: a clinically useful contrast effect with liver-specific properties].

PURPOSE: The purpose of this study was systematically to investigate stimulated acoustic emission (SAE) with the microbubble contrast agent Levovist (Schering AG, Berlin) in vivo with regards to reproducibility, distribution in various organs over time, dependence on technical factors, and influence on the delineation of focal liver lesions. PATIENTS AND METHODS: 2 intravenous injections of 1 g of Levovist were given to 2 dogs and 1-6 injections of 2.5 g Levovist to 5 healthy volunteers and 37 patients. The liver, spleen, large abdominal vessels, and kidney were intermittently scanned for up to 30 min. Studies were evaluated for the presence of SAE signals by 2 observers. In 20 patients with focal liver lesions (15 with metastases, 4 haemangiomata, 1 hepatocellular carcinoma, and 1 cyst) the influence on lesion visualization was also assessed. RESULTS: SAE effects, lasting up to 30 minutes, were seen in all subjects in the liver and spleen. Vascular and renal SAE signals were noted shortly after injection, lasting up to 6 minutes. SAE was absent or markedly reduced in focal liver lesions, which were seen as colour voids. This increased the conspicuity of focal lesions, and in 5 patients additional metastases were detected that could not be delineated on B-mode alone. CONCLUSION: A liver- and spleen-specific late phase of Levovist can be consistently demonstrated using SAE and the effect increases the conspicuity of focal liver lesions.

Adult↗

Twin fetuses: intravascular microbubble US contrast agent administration--early experience.

PURPOSE: To explore the feasibility of administering SH U 508A by using a single-needle procedure at ultrasonography (US) in twin pregnancies to confirm interfetal transfusion in monochorionic twins and delineate placental angioarchitecture in pregnancies with twin-twin transfusion syndrome. MATERIALS AND METHODS: Fourteen twin pregnancies were studied over 12 months: seven with monochorionic twins, including six with twin-twin transfusion syndrome; two of unknown chorionicity; and five with known dichorionic twins discordant for fetal karyotype or anomaly and undergoing selective feticide in the third trimester. Bolus injection of 100 microL/kg of estimated fetoplacental weight of 400 mg/mL of SH U 508A was performed in the intrahepatic vein of one twin, and evidence of interfetal transfusion was sought by means of digital analysis of power Doppler signals in the contralateral twin. RESULTS: Contralateral twin echo enhancement was seen in four of the nine ultimately histopathologically proved monochorionic twins. As expected, no evidence of echo enhancement in the contralateral twin was seen in any of the five dichorionic twin pregnancies. There was no evidence of fetal compromise associated with the procedure. CONCLUSION: These pilot results suggest that microbubbles can be used to demonstrate interfetal transfusion but not to delineate placental vascular anatomy.

Adult↗

Liver lesions: intermittent second-harmonic gray-scale US can increase conspicuity with microbubble contrast material-early experience.

The authors investigated the effect of intermittent second-harmonic gray-scale (ISHGS) ultrasonography (US) with SH U 508A microbubbles on the conspicuity of focal liver lesions. Twenty-three patients were included in the study. Images were analyzed subjectively and quantitatively. Objective lesion conspicuity was increased. In 12 of the 15 patients with liver malignancy, gray-scale defects were seen in previously unsuspected areas. ISHGS US may improve the sensitivity of US for liver lesions.

Adult↗

Hepatic malignancies: improved detection with pulse-inversion US in late phase of enhancement with SH U 508A-early experience.

Twenty consecutive patients with known liver malignancies underwent ultrasonography (US) in conventional B mode and in pulse-inversion mode in the late hepatic-specific parenchymal phase after intravenous administration of SH U 508A, a microbubble US contrast agent. Two experienced readers assessed subjective and objective conspicuity, number of lesions, and smallest lesion diameter in each mode. Subjective and objective conspicuity were improved with pulse-inversion mode, and smaller lesions were depicted with pulse-inversion mode than with conventional B mode, improving the detection of metastases less than 1 cm in size.

Adult↗

Non-invasive diagnosis of hepatic cirrhosis by transit-time analysis of an ultrasound contrast agent.

BACKGROUND: Hepatic cirrhosis is accompanied by several haemodynamic changes including arterialisation of the liver, intrahepatic shunts, pulmonary arteriovenous shunts, and a hyperdynamic circulatory state. We postulated that the hepatic first pass of a bolus of an ultrasound contrast agent injected into a peripheral vein is accelerated in patients with cirrhosis. We investigated this first pass in patients with diffuse liver disease and in normal controls to assess whether it provides useful differential diagnostic information. METHODS: We enrolled 15 patients with biopsy-proven cirrhosis, 12 patients with biopsy-proven non-cirrhotic diffuse liver disease, and 11 normal controls. We carried out continuous spectral doppler ultrasonography of a hepatic vein from 20 s before to 3 min after a peripheral intravenous bolus injection of 2.5 g Levovist. The intensity of the doppler signal was measured and used to plot time-intensity curves. FINDINGS: Patients with cirrhosis showed a much earlier onset of enhancement (arrival time; mean 18.3 s) and peak enhancement (mean 55.5 s) than controls (49.8 s and 97.5 s) or patients with non-cirrhotic diffuse liver disease (35.8 s and 79.7 s). All patients with cirrhosis had an arrival time of the bolus of less than 24 s, whereas the arrival time was 24 s or more in 22 of the 23 other participants. Peak enhancement was higher in patients with cirrhosis (mean 48.7 units) than in the other two groups (12.5 and 12.3 units, respectively). We found highly significant differences between the patients with cirrhosis and each of the other two groups for all variables (p<0.005), whereas we found no significant differences between non-cirrhotic patients and controls. INTERPRETATION: Our preliminary study suggests that analysis of liver transit time of a bolus of ultrasound contrast agent provides useful information about haemodynamic changes in patients with cirrhosis. Measurement of the arrival time of the bolus allows discrimination of patients with cirrhosis from controls and from patients with non-cirrhotic diffuse liver disease, and has potential as a non-invasive test for cirrhosis.

Adult↗

Use of contrast-enhanced computed tomography to measure clearance per unit renal volume: a novel measurement of renal function and fractional vascular volume.

The iodinated contrast agents used for computed tomography (CT) have pharmacokinetics similar to inulin and can measure physiological indices, such as clearance per unit renal volume (alpha/V) and fractional vascular volume (fvv). Clinical experience with these techniques is, however, scanty, and the present study explored their potential in subjects with and without renal dysfunction. In a series of subjects, a single slice of kidney was scanned sequentially after the bolus injection of contrast material. Time-attenuation curves were constructed, and alpha/V and fvv were calculated using a Patlak graphic analysis. In the first part of the study, 50 normal kidneys in 35 subjects (aged 21 to 75 years) were studied. In the second stage, alpha/V was compared with glomerular filtration rate (GFR) measurements in 24 patients with diabetes (aged 28 to 84 years) with or without renal dysfunction. In normal kidneys, alpha/V averaged 0.49 +/- 0.11 mL/min/mL and fvv averaged 35% +/- 12%. These values agree with literature data obtained using other techniques. A negative correlation was seen between age and alpha/V (r = 0.66; P < 0.0001), but not fvv. In patients with diabetes, a strong correlation was observed between renal clearance values, calculated from CT and corrected for renal volume, and GFR (r = 0.87; P < 0.0001). Dynamic CT can provide quantitative renal physiological information on a regional basis noninvasively.

Adult↗

Stimulated acoustic emission to image a late liver and spleen-specific phase of Levovist in normal volunteers and patients with and without liver disease.

Quantitative studies were performed to investigate liver- specific uptake of the microbubble Levovist, using stimulated acoustic emission (SAE), which can detect microbubbles even when stationary or slow-moving. These comprised studies of biodistribution comparing the liver and kidney in five normal volunteers, reproducibility in 34 patients, comparison between cirrhotics and controls (n = 9 each) and maximal depth of effect at different frequencies (180 measurements in 31 patients). Stimulated acoustic emission lasted beyond 30 min, with strongly liver-specific properties in each volunteer and was highly reproducible. No difference in the amount of SAE in the superficial liver was seen between cirrhotic and normal livers, but attenuation was higher in cirrhotics. This demonstrates a frequency-dependent effect on liver SAE penetration. We conclude that the liver uptake of Levovist lasts over 30 min, is reproducible, occurs even where diffuse liver disease is present and can be used to assess tissue attenuation in a novel fashion.

Adult↗

Functional renal perfusion imaging with colour mapping: is it a useful adjunct to spiral CT of in the assessment of abdominal aortic aneurysm (AAA)?

AIM: To ensure optimal timing with pre-operative spiral CT for abdominal aortic aneurysms (AAA), an initial 'timing' single level CT is commonly performed with a small bolus of contrast. This can be exploited to obtain adjunct functional information on renal perfusion. We have investigated the potential of this to measure renal perfusion, to produce colour renal perfusion maps and to predict surgical outcome in infrarenal aortic aneurysm assessment. METHODS: We studied 21 patients being assessed for repair of infrarenal AAA. Prior to the spiral CT, a single level through the renal hili and aorta was scanned after the intravenous injection of 25 ml of contrast given at 10 ml/s. Ten 1 s duration scans were performed from 8 to 30 s after injection. Optimal timing for CT angiography can then be determined. Time-density curves were then drawn for both kidneys and aorta using regions of interest (ROIs) or pixel-by-pixel analysis. Renal cortical perfusion was measured using both ROI analysis and pseudocolour perfusion images. Following previous work, perfusion was calculated as the peak upslope of the tissue time density curve divided by peak aortic enhancement. RESULTS: Cortical mean perfusion averaged 2.48 ml/min per ml (range 0.8-3.7 ml/min per ml n = 34) and the values obtained agreed with literature expectations. Follow up in the 10 patients proceeding to AAA repair suggest low mean perfusion values and predict a raised postoperative creatinine (P < 0.05) CONCLUSIONS: Additional functional data and imaging can be obtained from the initial timing scan of a CT study, without requiring a dedicated study.

Aged↗