Accuracy of investigations for asymptomatic colorectal liver metastases.

PURPOSE: The aim of this study was to prospectively assess the accuracy of the most promising imaging and tumor marker tests in liver metastasis diagnosis on follow-up of asymptomatic colorectal cancer patients during a median of 57 months after primary tumor resection. METHODS: One hundred patients, who were considered free of liver metastases after primary colorectal cancer resection and conventional follow-up, were screened for liver metastases by computerized tomography, magnetic resonance and ultrasound scans, ultrasound Doppler and isotope assessment of changes in hepatic arterial and portal venous flow, and serum estimation of carcinoembryonic antigen. Patients were followed up during a median of 41 months to identify those who developed liver metastases. RESULTS: The most sensitive technique was computerized tomography (sensitivity 0.67, specificity 0.91). Computerized tomography and magnetic resonance but not ultrasound were 100 percent accurate in differentiating liver metastases from other hepatic lesions. Techniques based on changes in hepatic arterial and portal venous flow had lower diagnostic accuracies (Doppler perfusion index, sensitivity 0.58, specificity 0.57; hepatic perfusion index, sensitivity 0.50, specificity 0.55), whereas ultrasound scanning identified only 43 percent (sensitivity 0.43, specificity 0.96) and serum carcinoembryonic antigen 33 percent (sensitivity 0.33, specificity 0.81) of patients with asymptomatic liver metastasis. Sensitivity could be improved by using tests in combination but this reduced specificity. CONCLUSIONS: Computerized tomography was the most sensitive test for asymptomatic colorectal liver metastases, but only 67 percent of affected patients were identified.

Improved diagnosis of extraheptic biliary atresia by high frequency ultrasound of the gall bladder.

Ultrasound scanning using a 13 MHz probe was performed on 158 infants, aged 12 weeks or less, presenting with conjugated hyperbilirubinaemia. The gall bladder was identified in 156 infants, 35 of whom had biliary atresia. The two patients in whom no gall bladder was seen both had biliary atresia. The gall bladder shape was normal in 128 patients (9 with biliary atresia) and irregular in 28 patients (26 with biliary atresia). The gall bladder wall was regular in 121 patients (4 with biliary atresia) and irregular in 35 patients (31 with biliary atresia). Combining these findings gave a sensitivity of 91.9%, a specificity of 96.7%, a positive predictive value of 89.5%, a negative predictive value of 97.5% and an accuracy rate of 95.6% for ultrasound of the gall bladder in the identification of biliary atresia. This compares with 90%, 92.4%, 75.3%, 97.3% and 91.9%, respectively, in our previous report using a 7 MHz probe.

Effect of a 30-minute infusion of dobutamine hydrochloride on hind limb blood flow and hemodynamics in halothane-anesthetized horses.

OBJECTIVE: To evaluate the hemodynamic effects of dobutamine hydrochloride (0.5 microg/kg of body weight/min) in halothane-anesthetized horses. ANIMALS: 6 adult Thoroughbred horses. PROCEDURE: Anesthesia was induced by use of romifidine (100 microg/kg) and ketamine (2.2 mg/kg), IV. Anesthesia was maintained by halothane (end-tidal concentration 0.9 to 1.0%). Aortic, left ventricular, and right atrial pressures were measured, using catheter-mounted strain gauge transducers. Cardiac output (CO), velocity time integral, maximal aortic blood flow velocity and acceleration, and left ventricular preejection period and ejection time were measured from aortic velocity waveforms obtained by transesophageal Doppler echocardiography. Velocity waveforms were recorded from the femoral vessels, using Doppler ultrasonography. The time-averaged mean velocity and early diastolic deceleration slope (EDDS) were measured. Pulsatility index (PI) and volumetric flow were calculated. Microvascular perfusion was measured in the semimembranosus muscles by laser Doppler flowmetry. Data were recorded 60 minutes after induction of anesthesia (control) and at 15 and 30 minutes after start of an infusion of dobutamine (0.5 microg/kg/min). RESULTS: Aortic pressures were significantly increased during the infusion of dobutamine. No change was observed in the indices of left ventricular systolic function including CO. Femoral arterial flow significantly increased, and the PI and EDDS decreased. No change was observed in the femoral venous flow or in microvascular perfusion. CONCLUSIONS AND CLINICAL RELEVANCE: At this dosage, dobutamine did not alter left ventricular systolic function. Femoral blood flow was preferentially increased as the result of local vasodilatation. The lack of effect of dobutamine on microvascular perfusion suggests that increased femoral flow is not necessarily associated with improved perfusion of skeletal muscles.

A comparison of the haemodynamic effects of isoflurane and halothane anaesthesia in horses.

The purpose of this study was to compare the haemodynamic effects of equipotent isoflurane and halothane anaesthesia. Six adult horses were investigated on two separate occasions at least 4 weeks apart. On both occasions anaesthesia was induced by ketamine 2.2 mg/kg bwt given 5 min after i.v. administration 100 microg/kg bwt romifidine. Anaesthesia was maintained either by halothane or isoflurane (end-tidal concentrations 0.9-1.0% and 1.3-1.4%, respectively). Horses were ventilated by intermittent positive pressure to maintain PaCO2 between 40-50 mmHg. Haemodynamic variables were measured using catheter-mounted strain gauge transducers in the left and right ventricle, aorta, and right atrium. Cardiac output (CO), velocity time integral (VTI), maximal aortic blood flow velocity (Vmax) and acceleration (dv/dt(max)), left ventricular pre-ejection period (PEP) and ejection time (ET) were measured from aortic blood flow velocity waveforms obtained by transoesophageal Doppler echocardiography. Flow velocity waveforms were recorded from the femoral arteries and veins using low pulse repetition frequency Doppler ultrasound. Time-averaged mean velocity (TAV), velocity of component a (TaVa), velocity of component b (TaVb) and early diastolic deceleration slope (EDDS) were measured. Pulsatility index (PI) and volumetric flow were calculated. Microvascular blood flow was measured in the left and right semimembranosus muscles by laser Doppler flowmetry. Maximal rate of rise of LV pressure (LVdp/dt(max)), CO, Vmax, dv/dt(max), ET, VTI were significantly higher at all time points during isoflurane anaesthesia compared to halothane anaesthesia. Pre-ejection period and diastolic aortic blood pressure were significantly less throughout isoflurane anaesthesia compared to halothane. Isoflurane anaesthesia was associated with significantly lower systemic vascular resistance than halothane anaesthesia. Femoral arterial and venous blood flow were significantly higher and EDDS and PI were significantly lower during isoflurane anaesthesia compared to halothane anaesthesia. In addition during both halothane and isoflurane anaesthesia, femoral arterial flow was higher and EDDS and PI lower in the left (dependent) artery compared to the right (nondependent) artery. This study supports previous work demonstrating improved left ventricular systolic function during isoflurane compared to halothane anaesthesia. This improvement was still evident after premedication with a potent-long acting alpha2-adrenoreceptor agonist, romifidine, and induction of anaesthesia with ketamine. There was also evidence of increased hindlimb blood flow during isoflurane anaesthesia. However, there were differences observed in flow between the left and right hindlimb during maintenance of anaesthesia with each agent, suggesting that there were differences in regional perfusion in anaesthetised horses caused by factors unrelated to agents administered.

Repeatability of Doppler ultrasound measurements of hindlimb blood flow in halothane anaesthetised horses.

The purpose of this study was to determine the repeatability of femoral blood flow recorded using Doppler ultrasound in anaesthetised horses. Doppler ultrasound of the femoral artery and vein was performed in 6 horses anaesthetised with halothane and positioned in left lateral recumbency. Velocity spectra, recorded using low pulse repetition frequency, were used to calculate time-averaged mean velocity (TAV), velocity of component a (TaVa), velocity of component b (TaVb), volumetric flow, early diastolic deceleration slope (EDDS) and pulsatility index (PI). Within-patient variability was determined for sequential Doppler measurements recorded during a single standardised anaesthetic episode. Within-patient variability was also determined for Doppler and cardiovascular measurements recorded during 4 separate standardised anaesthetic episodes performed at intervals of at least one month. Within-patient variation during a single anaesthetic episode was small. Coefficients of variation (cv) were <12.5% for arterial measurements and <17% for venous measurements. Intraclass correlation coefficient was >0.75 for all measurements. No significant change was observed in measurements of cardiovascular function suggesting that within-patient variation observed during a single anaesthetic episode was due to measurement error. In contrast, within-patient variation during 4 separate anaesthetic episodes was marked (cv>17%) for most Doppler measurements obtained from arteries and veins. Variation in measurements of cardiovascular function were marked (cv>20%), suggesting that there is marked biological variation in central and peripheral observed. Further studies are warranted to determine the ability of this technique to detect differences in blood flow during administration of different anaesthetic agents.

Variability of Doppler ultrasound measurements of hindlimb blood flow in conscious horses.

Ultrasonography of the left and right femoral artery and vein was performed in 5 conscious horses. Velocity waveforms, recorded using low pulse repetition frequency, were used to calculate time-averaged mean velocity (TAV), velocity of component a (TaVa), velocity of component b (TaVb) and volumetric flow. Waveform analysis included calculation of early diastolic deceleration slope (EDDS) and pulsatility index (PI) and subjective description of the waveform. Measurements were recorded at monthly intervals for 6 months. The repeated measurements were used to determine the within-horse variation. Horses were then anaesthetised with halothane and the same measurements recorded 60 min after induction. Differences between measurements recorded in conscious and anaesthetised horses were determined. Within-horse variability for diameters of femoral arteries and veins was small (CV<10%). Within variability for all other measurements was marked (CV>11%), with within-horse variability being the largest for femoral venous flow (CV>35%). Source of variability was measurement error and biological variation. Despite variability in conscious horses it was possible to detect changes in blood flow during anaesthesia. In the femoral arteries, volumetric flow was lower and EDDS and PI was higher in anaesthetised horses. In the femoral veins, volumetric flow was also lower in anaesthetised horses. Therefore Doppler ultrasound appears to be a useful technique for studying blood flow in conscious and anaesthetised horses.

Measurements of hindlimb blood flow recorded using Doppler ultrasound during administration of vasoactive agents in halothane-anesthetized horses.

The purpose of the study was to determine the ability of Doppler ultrasound to detect changes in femoral blood flow during pharmacologic manipulation of arterial blood pressure. Doppler ultrasonography was performed in the femoral vessels of six halothane-anesthetized horses before and during administration of phenylephrine HCI and sodium nitroprusside. The time-averaged mean velocity and volumetric flow were calculated. The contour of the velocity waveform was assessed, and the early diastolic deceleration slope (EDDS) and pulsatility index (PI) were calculated. Administration of phenylephrine HCI resulted in increased mean aortic blood pressure (MABP) by 40% (29.3-53.0%). This caused significant decrease in cardiac output (26.8 to 13.5 l/min), femoral arterial velocity (left artery 7.20 to 4.00 cm/s; right artery 5.01 to 3.39 cm/s) and volumetric flow (left artery 556 to 221 ml/min; right artery 397 to 193 ml/min) in the femoral vessels and significant increase in systemic vascular resistance (163 to 433 dyn-s/cm5), EDDS (1a: 285 to 468: ra: 250 to 481) and PI (1a: 9.38 to 20.4; ra 17.1 to 29.1). Administration of sodium nitroprusside resulted in a decreased MABP of 27.2% (22.5-33%). This increased cardiac output (20.8 to 32.4 L/min), however, no significant changes were observed in femoral blood flow. Despite obvious changes in the waveform contour, no significant change occurred in EDDS or PI. These results suggest that Doppler ultrasound may be useful for measuring femoral blood flow in anesthetized horses. However, waveform analysis appears to be limited when multiple changes occur in central and peripheral haemodynamics.

Ultrasound features of the gall bladder in infants presenting with conjugated hyperbilirubinaemia.

An initial investigation of 313 patients suggested that the ultrasound appearances of gall bladder shape and wall structure might be abnormal in infants with biliary atresia. These observations were then tested in a prospective study. In this study, 346 infants, aged 12 weeks or less, presenting with conjugated hyperbilirubinaemia underwent ultrasound scanning. The gall bladder was identified in 331, 60 of whom had biliary atresia. 11 of the 15 patients in whom the gall bladder was not seen had biliary atresia. Gall bladder shape was normal in 272 patients, 16 of whom had biliary atresia, and irregular in 59, 44 of whom had biliary atresia. The gall bladder wall was regular in 262 patients, 8 of whom had biliary atresia, and irregular in 69, 52 of whom had biliary atresia. Combining these findings gave a sensitivity of 90%, a specificity of 92.4%, a positive predictive value of 75.3%, a negative predictive value of 97.3% and an accuracy rate of 91.9% for ultrasound of the gall bladder in identification of biliary atresia.

The value of serial Doppler ultrasound as a predictor of clinical outcome and the need for transplantation in fulminant and severe acute liver failure.

The aim of this study was to document the changes in Doppler ultrasound variables of the hepatic artery and portal vein in fulminant and severe acute liver failure, and to assess their prognostic significance. 18 adult patients with fulminant and severe acute liver failure underwent serial Doppler sonography, in the early stages after presentation. 12 hourly measurements of hepatic artery resistance index (HARI), spleen length, portal vein cross-sectional area, time average velocity (TAV) and flow volume were performed. Mean HARI (p = 0.03) and mean maximum HARI (p = 0.03) were significantly higher in those who fulfilled criteria for liver transplantation. Increased portal vein flow was demonstrated, although the difference between the groups was not significant. A significant increase in portal vein cross-sectional area (p < 0.02) and spleen length (p < 0.02) was demonstrated. In summary, an increase in portal blood flow to the damaged liver has been demonstrated. The mean HARI is significantly higher in patients who fulfil transplant criteria and may possibly be used as an indicator of poorer prognosis and the need for liver transplantation in acute severe and fulminant liver failure.

Hepatic artery resistance index can predict early death in children with biliary atresia.

Hepatic artery resistance index has been measured by ultrasonography Doppler and has been found to predict rapid deterioration and death in children with biliary atresia. Clinical, biochemical, ultrasonographic, and outcome data were collected prospectively and retrieved on 32 patients with resistance index of > or = 1.0 (group A). These were compared with the same data for 32 age- and sex-matched patients with biliary atresia and a resistance index of < 1.0 (group B). Group A was found to have significantly worse liver function tests than group B. In group A, all patients died (n = 11) or underwent transplantation (n = 21; of whom 4 died) compared with only 2 patients who died in group B and 4 patients who underwent transplantation without fatality. Survival at 2 years was 52% in group A v 94% in group B. It is suggested that regular ultrasonography Doppler examination in patients with biliary atresia can detect a group with a resistance index of > 1.0 who have a very high risk of early mortality. Such patients require early evaluation and listing for transplantation. Those listed for liver transplantation on other grounds require ultrasonography examinations every 2 to 3 months with immediate upgrading of the priority of those patients found to have a resistance index of > or = 1.0.

Peripheral vascular effects and pharmacokinetics of the antimigraine compound, zolmitriptan, in combination with oral ergotamine in healthy volunteers.

Members of the new class of antimigraine compounds, 5HT1B/1D agonists, as well as ergotamine, may cause vasoconstriction through stimulation of 5HT receptors on peripheral vessels. The cardiovascular effects of 20 mg oral zolmitriptan (Zomig, formerly 311C90), 2 mg oral ergotamine and the combination were assessed in a randomized double-blind, placebo-controlled crossover study in 12 healthy subjects. Pharmacodynamic measures included oscillometric blood pressure, systolic blood pressure at the toe and arm using a strain gauge technique, stroke volume and cardiac output using bioimpedance cardiography, high-resolution ultrasound to measure brachial arterial diameter and a novel Doppler method to measure blood flow velocity. Both drugs produced small degrees of peripheral vasoconstriction, including increases in diastolic blood pressure and blood flow velocity and decreases in arterial diameter and toe-arm systolic pressure gradient. These effects were generally additive with the combination but of no clinical importance. There were no significant changes in cardiac output, stroke volume heart rate or ECG. Zolmitriptan, at eight times the likely therapeutic dose, was generally well tolerated both alone and in combination with ergotamine. Ergotamine had no clinically important effects on zolmitriptan pharmacokinetics.

Hepatic vein pulsatility assessment on spectral Doppler ultrasound.

Hepatic vein pulsatility correlates with the severity of disease in a range of different liver disorders. We describe a simple visual grading system for scoring hepatic vein pulsatility which does not require any on-screen measurements and which has proved reproducible in clinical practice. The system gives a six point score for the waveform pulsatility, 6 being a normal value and 1 indicating a complete lack of modulation.

Evaluation of non-invasive techniques to assess vasoconstriction in healthy volunteers using methoxamine as a probe drug.

Non-invasive methods for assessment of the vascular effects of antimigraine drugs were evaluated with respect to their utility, variability and sensitivity in a double-blind, placebo-controlled, three-period crossover study in six healthy volunteers using an intravenous vasoconstrictor, methoxamine, as a probe drug. Changes in the internal diameter of the brachial and radial arteries were measured using ultrasound which had low between-day and within-day coefficients of variation. Peak systolic velocity (PSV), time-averaged velocity (TAV), total flow, resistance (RI) and pulsatility indices (PI) were measured by Doppler from one arterial wave form. Whilst PSV and TAV increased with methoxamine, because of bradycardia, changes in PI and RI were difficult to interpret. An automatic oscillometric cuff, a mercury-in-silastic strain gauge method and the "Finapres", finger arterial blood pressure monitor were used to follow changes in systolic blood pressure (SBP). The strain gauge technique underestimated arm SBP compared to the oscillometric method but clearly showed drug-related increases whilst the Finapres did not reflect changes in blood pressure detected by the other methods.

Ultrasound diagnosis of portocaval anastomosis in infants--a report of eight cases.

We report eight cases of portocaval anastomosis in infants diagnosed by ultrasound. Anatomically we believe this represents continuing patency of the ductus venosus, either as a primary developmental abnormality or secondary to established liver cell failure.

Examination of some factors responsible for a food-induced increase in absorption of atovaquone.

1. Atovaquone is a potent antiprotozoal slowly and irregularly absorbed after administration as tablets to fasting volunteers. A series of studies was performed to investigate the effects of food, bile and formulation on atovaquone absorption. 2. In 18 healthy male volunteers, a high-fat breakfast administered 45 min before 500 mg atovaquone as tablets increased AUC by 3.3-fold (95% CI 2.8-4.0) and Cmax 5.3-fold (4.3-6.6) compared with fasting. 3. The absorption of atovaquone from tablets was examined in 12 healthy male volunteers after an overnight fast, following toast alone, toast with 28 g butter (LOFAT), or toast with 56 g butter (HIFAT). Compared with absorption when fasted, toast had no significant effect but LOFAT increased AUC 3.0-fold (2.1-4.2) and Cmax 3.9-fold (2.6-5.8). HIFAT increased AUC 3.9-fold (2.7-5.5) and Cmax 5.6-fold (3.8-8.4). 4. The absorption of atovaquone was examined in nine healthy fasting male volunteers from tablets, an aqueous suspension, and an oily solution/suspension in miglyol (fractionated coconut oil). Compared with tablets, AUC following the aqueous suspension was increased 1.7-fold (1.0-2.7) and Cmax 2.4-fold (1.7-3.5). Following miglyol, AUC was increased to the same extent but Cmax was only increased 1.8-fold (1.2-2.6). 5. Atovaquone absorption was examined in eight healthy fasting male volunteers following an i.v. infusion of cholecystokinin octapeptide (CCK-OP) which decreased gallbladder volume by 82% (73%-90%) on occasion 1 or saline on occasion 2. AUC(0,12) was increased following CCK-OP by 1.6-fold (1.1-2.4) and Cmax by 1.5-fold (0.98-2.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler carotid artery studies in asymmetric glaucoma.

Doppler carotid artery studies were performed in 12 glaucoma patients with marked asymmetry in bilateral visual field loss. The resistance index and the pulsatility index of the internal carotid artery velocity waveforms were significantly greater on the same side as the eye with the greater visual field loss. The increased resistance to blood flow in the internal carotid artery on the side with advanced field loss might predispose the eye on this side to the effects of raised intraocular pressure by causing a reduction in the perfusion pressure at the optic nerve head. The role of ocular perfusion pressure in the pathogenesis of glaucoma is discussed. More extensive studies are necessary.