What is the optimal systemic treatment of men with metastatic, hormone-naive prostate cancer? A STOPCAP systematic review and network meta-analysis.

Background: Our prior Systemic Treatment Options for Cancer of the Prostate systematic reviews showed improved survival for men with metastatic hormone-naive prostate cancer when abiraterone acetate plus prednisolone/prednisone (AAP) or docetaxel (Doc), but not zoledronic acid (ZA), were added to androgen-deprivation therapy (ADT). Trial evidence also suggests a benefit of combining celecoxib (Cel) with ZA and ADT. To establish the optimal treatments, a network meta-analysis (NMA) was carried out based on aggregate data (AD) from all available studies. Methods: Overall survival (OS) and failure-free survival data from completed Systemic Treatment Options for Cancer of the Prostate reviews of Doc, ZA and AAP and from recent trials of ZA and Cel contributed to this comprehensive AD-NMA. The primary outcome was OS. Correlations between treatment comparisons within one multi-arm, multi-stage trial were estimated from control-arm event counts. Network consistency and a common heterogeneity variance were assumed. Results: We identified 10 completed trials which had closed to recruitment, and one trial in which recruitment was ongoing, as eligible for inclusion. Results are based on six trials including 6204 men (97% of men randomised in all completed trials). Network estimates of effects on OS were consistent with reported comparisons with ADT alone for AAP [hazard ration (HR) = 0.61, 95% confidence interval (CI) 0.53-0.71], Doc (HR = 0.77, 95% CI 0.68-0.87), ZA + Cel (HR = 0.78, 95% CI 0.62-0.97), ZA + Doc (HR = 0.79, 95% CI 0.66-0.94), Cel (HR = 0.94 95% CI 0.75-1.17) and ZA (HR = 0.90 95% CI 0.79-1.03). The effect of ZA + Cel is consistent with the additive effects of the individual treatments. Results suggest that AAP has the highest probability of being the most effective treatment both for OS (94% probability) and failure-free survival (100% probability). Doc was the second-best treatment of OS (35% probability). Conclusions: Uniquely, we have included all available results and appropriately accounted for inclusion of multi-arm, multi-stage trials in this AD-NMA. Our results support the use of AAP or Doc with ADT in men with metastatic hormone-naive prostate cancer. AAP appears to be the most effective treatment, but it is not clear to what extent and whether this is due to a true increased benefit with AAP or the variable features of the individual trials. To fully account for patient variability across trials, changes in prognosis or treatment effects over time and the potential impact of treatment on progression, a network meta-analysis based on individual participant data is in development.

Glutamate and N-Acetylaspartate Alterations Observed in Early Phase Psychosis: A Systematic Review of Proton Magnetic Resonance Spectroscopy Studies.

Glutamate and N-acetylaspartate have been investigated in the neuropathology of chronic schizophrenia, with fewer studies focusing on early phase psychosis. Additionally, there has been little review and synthesis of the literature focused on multiple brain regions. This systematic review aims to provide a clear report of the current state of research on glutamate and n-acetylaspartate concentrations in early phase psychosis (defined as the first five years following psychosis onset) in multiple brain regions. Existing literature was searched systematically to compile reports of glutamate/glutamate+glutamine (Glx) and n-acetylaspartate absolute levels and ratios in both male and female individuals with early phase psychosis. Reports on glutamate/Glx concentrations in the medial prefrontal region and thalamus were varied, but the majority of reports suggested no alterations in EPP. No studies reported glutamate alterations in the hippocampus or cerebellum. There was no evidence for n-acetylaspartate alterations in the caudate, basal ganglia, and medial prefrontal cortex, and minimal evidence for NAA reductions in the thalamus, anterior cingulate cortex, and hippocampus. Future research should focus on the regions that are less commonly reported, and should aim to explore possible confounds, such as medication status and substance use.

Aluminum-rich apatite.

More than 25 atomic percent of aluminum can susbtitute for other cations in the structure of apatite [A(10)(XO(4)) (6)Z(2)]. Such a synthetic product was obtained by expelling volatile constituents (H(2)O and F) from morinite during thermal treatment. Infrared absorption spectra, chemical analysis, and x-ray powder diffraction demonstrate that the aluminum has two coordination numbers, and more than twice as much aluminum substitutes for calcium (A position) as for phosphorus (X position).

Bone mass in Indian children--relationships to maternal nutritional status and diet during pregnancy: the Pune Maternal Nutrition Study.

CONTEXT/OBJECTIVE: Bone mass is influenced by genetic and environmental factors. Recent studies have highlighted associations between maternal nutritional status during pregnancy and bone mass in the offspring. We hypothesized that maternal calcium intakes and circulating micronutrients during pregnancy are related to bone mass in Indian children. DESIGN/SETTING/PARTICIPANTS/MAIN OUTCOME MEASURES: Nutritional status was measured at 18 and 28 wk gestation in 797 pregnant rural Indian women. Measurements included anthropometry, dietary intakes (24-h recall and food frequency questionnaire), physical workload (questionnaire), and circulating micronutrients (red cell folate and plasma ferritin, vitamin B12, and vitamin C). Six years postnatally, total body and total spine bone mineral content and bone mineral density (BMD) were measured using dual-energy x-ray absorptiometry (DXA) in the children (n = 698 of 762 live births) and both parents. RESULTS: Both parents' DXA measurements were positively correlated with the equivalent measurements in the children (P < 0.001 for all). The strength of these correlations was similar for fathers and mothers. Children of mothers who had a higher frequency of intake of calcium-rich foods during pregnancy (milk, milk products, pulses, non-vegetarian foods, green leafy vegetables, fruit) had higher total and spine bone mineral content and BMD, and children of mothers with higher folate status at 28 wk gestation had higher total and spine BMD, independent of parental size and DXA measurements. CONCLUSIONS: Modifiable maternal nutritional factors may influence bone health in the offspring. Fathers play a role in determining their child's bone mass, possibly through genetic mechanisms or through shared environment.

The enteric toxins of Clostridium perfringens.

The Gram-positive pathogen Clostridium perfringens is a major cause of human and veterinary enteric disease largely because this bacterium can produce several toxins when present inside the gastrointestinal tract. The enteric toxins of C. perfringens share two common features: (1) they are all single polypeptides of modest (approximately 25-35 kDa) size, although lacking in sequence homology, and (2) they generally act by forming pores or channels in plasma membranes of host cells. These enteric toxins include C. perfringens enterotoxin (CPE), which is responsible for the symptoms of a common human food poisoning and acts by forming pores after interacting with intestinal tight junction proteins. Two other C. perfringens enteric toxins, epsilon-toxin (a bioterrorism select agent) and beta-toxin, cause veterinary enterotoxemias when absorbed from the intestines; beta- and epsilon-toxins then apparently act by forming oligomeric pores in intestinal or extra-intestinal target tissues. The action of a newly discovered C. perfringens enteric toxin, beta2 toxin, has not yet been defined but precedent suggests it might also be a pore-former. Experience with other clostridial toxins certainly warrants continued research on these C. perfringens enteric toxins to develop their potential as therapeutic agents and tools for cellular biology.

Regional myocardial function is not affected by severe coronary depressurization provided coronary blood flow is maintained.

It has been suggested that vasodilation distal to a stenosis may cause a profound decrease in perfusion pressure and adversely affect regional left ventricular function. This phenomenon could explain the clinical concept of reversal of regional dysfunction by coronary revascularization. To evaluate the hypothesis that regional myocardial function parallels regional coronary blood pressure in the absence of changes in coronary flow, dogs chronically instrumented with left circumflex coronary artery flow probes, cuff occluders, pressure catheters and segmental function sonomicrometers were studied. By decreasing regional coronary vascular resistance with selective intracoronary dipyridamole and controlling blood flow with a proximal coronary cuff occluder, the mean left circumflex artery pressure was reduced from 83 +/- 3 to 38 +/- 2 mm Hg while circumflex coronary blood flow was maintained constant. Regional contractile function as measured by circumflex sonomicrometers was unchanged at constant circumflex subendocardial blood flow as measured by radioactive microspheres. These findings suggest that regional contractile function is dependent on subendocardial blood flow and is independent of coronary perfusion pressure.

Rapid ventricular pacing in dogs with right ventricular outflow tract obstruction: insights into a mechanism of sudden death in postoperative tetralogy of Fallot.

OBJECTIVES: We explored the hypothesis that residual outflow tract obstruction and ventricular hypertrophy associated with rapid ventricular rhythm contribute to sudden death, in part because they result in humoral or hemodynamic changes that predispose to ventricular fibrillation, such as increased catecholamine release or decreased coronary flow, or both. BACKGROUND: Ventricular arrhythmia after surgical repair of tetralogy of Fallot has been associated with sudden death, particularly in patients with residual right ventricular hypertension. However, the mechanisms by which sudden death occurs remain unclear. METHODS: Seven awake, unanesthetized mature beagles with chronically elevated right ventricular pressure (high pressure group: right ventricular/left ventricular systolic pressure ratio > 0.5) were compared with six beagles with low right ventricular pressure at rest and at the end of 5 min of ventricular pacing at 240 beats/min (low pressure group). RESULTS: In the high pressure group, cardiac output decreased during ventricular pacing (compared with sinus rhythm) from 304 +/- 21 to 218 +/- 21 ml/min per kg (p < 0.01) and plasma norepinephrine increased substantially from 673 +/- 64 to 1,047 +/- 92 pg/ml (p < 0.01). Comparable changes were not observed in the low pressure group. Plasma epinephrine levels were similar in both groups at rest and did not change with pacing. Postpacing norepinephrine levels from both groups correlated positively with both right ventricular systolic and diastolic pressure at rest and correlated negatively with the change in cardiac output from rest to pacing. Regional right ventricular myocardial blood flow increased with pacing in the low pressure group, whereas in the high pressure group it was increased at rest and did not increase further with pacing. CONCLUSION: During ventricular pacing, dogs with right ventricular outflow tract obstruction and high right ventricular pressure had a decrease in cardiac output and an increase in plasma norepinephrine, coupled with a loss of right ventricular myocardial blood flow reserve. Similar changes may occur in postoperative patients with similar hemodynamics and tachyarrhythmia and could contribute to the occurrence of ventricular fibrillation and sudden death.

Influence of age on the effect of bidirectional cavopulmonary anastomosis on left ventricular volume, mass and ejection fraction.

OBJECTIVES: We sought to identify age-related differences in the ventricular response of patients after bidirectional cavopulmonary anastomosis (CPA) and to compare changes in the ventricular response among children < 3 years of age who underwent CPA with that of age-matched control subjects who had a systemic to pulmonary artery shunt alone. BACKGROUND: Pre-Fontan CPA has been advocated over a systemic to pulmonary artery shunt alone in patients with a single ventricle to facilitate ventricular volume unloading and minimize risk of the Fontan operation. METHODS: Our study evaluated 23 patients who initially received a systemic to pulmonary artery shunt as an initial procedure before subsequent Fontan palliation. In eight of these patients (group I), bidirectional CPA was performed before age 3 years, and in four (group II), it was performed after age 10 years. The remaining 11 patients (group III, age and weight control group for group I) were maintained with their initial shunt until they underwent Fontan palliation. Serial echocardiographic analysis was used retrospectively to evaluate left ventricular volume and mass and systolic pump function (ejection fraction) before and after bidirectional CPA. RESULTS: Through 10 months of follow-up, group I patients showed significant decreases in indexed end-diastolic volume both after CPA (120 ml/m1.5 body surface area vs. 78 ml/m1.5, p = 0.001) and in comparison with values in patients in group II and III, who showed no changes in end-diastolic volume (p < 0.001). Indexed ventricular mass decreased moderately after bidirectional CPA in group I (from 228 g/m1.5 body surface area to 148 g/m1.5) but remained unchanged in groups II and III. The differences in trends between groups I and III were significant (p = 0.03). Ejection fraction decreased significantly in group II versus group I patients (0.48 to 0.27 vs. 0.51 to 0.52, p < 0.05) after CPA. Oxygen saturation measurements before and after bidirectional CPA revealed a significant increase in group I (73% to 86%, p < 0.001) and a decrease in group II (82% to 73%, p < 0.01). CONCLUSIONS: Bidirectional CPA facilitates ventricular volume unloading and promotes regression of left ventricular mass in younger children (< 3 years) in preparation for a Fontan operation. In contrast, bidirectional CPA is of questionable value in older children as a staging procedure for Fontan palliation.

Endocarditis in high-risk neonates.

The clinical spectrum of neonatal endocarditis, including bacterial and nonbacterial types, is examined in five case reports that were drawn from nursery experiences over a recent 2-year period. In contrast to previous reports of 100% mortality from neonatal endocarditis, one patient survived. Changing heart murmur and hematuria were most frequently associated with bacterial and nonbacterial endocarditis in four of the five cases. Pulmonary hypertension, thrombocytopenia, and coagulopathy were also associated with nonbacterial endocarditis. Echocardiograms were performed on four of the patients; only one was suggestive of endocarditis. Staphylococcus aureus was isolated from both cases of bacterial endocarditis, including the single survivor. Thus, it is suggested that the initial antibiotic coverage of any neonate with the clinical syndrome of sepsis, hematuria, and a heart murmur include antistaphylococcal coverage for the possibility of bacterial endocarditis.

Febrile infants at low risk for serious bacterial infection--an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group.

OBJECTIVE: Prospective studies were conducted to test the hypothesis that infants unlikely to have serious bacterial infections (SBI) can be accurately identified by low risk criteria. METHODS: Febrile infants (rectal T > or = 38 degrees C) < or = 60 days of age were considered at low risk for SBI if they met the following criteria: 1) appear well; 2) were previously healthy; 3) have no focal infection; 4) have WBC count 5.0-15.0 x 10(9) cells/L (5000-15,000/mm3), band form count < or = 1.5 x 10(9) cells/L (< or = 1500/mm3), < or = 10 WBC per high power field on microscopic examination of spun urine sediment, and < or = 5 WBC per high power field on microscopic examination of a stool smear (if diarrhea). The recommended evaluation included the culture of specimens of blood, cerebrospinal fluid, and urine for bacteria. Outcomes were determined. The negative predictive values of the low risk criteria for SBI and bacteremia were calculated. RESULTS: Of 1057 eligible infants, 931 were well appearing, and, of these, 437 met the remaining low risk criteria. Five low risk infants had SBI including two infants with bacteremia. The negative predictive value of the low risk criteria was 98.9% (95% confidence interval, 97.2% to 99.6%) for SBI, and 99.5% (95% confidence interval, 98.2% to 99.9%) for bacteremia. CONCLUSIONS: These data confirm the ability of the low risk criteria to identify infants unlikely to have SBI. Infants who meet the low risk criteria can be carefully observed without administering antimicrobial agents.

Myocardial perfusion with rubidium-82. I. Measurement of extraction fraction and flow with external detectors.

Accurate measurement of the regional extraction of a diffusible radiopharmaceutical is essential for the quantifying of regional blood flow, and may also provide an important physiologic or diagnostic indicator of the cellular viability of an organ in man through external detection by positron emission tomography. However, extraction fraction of a diffusible tracer usually decreases as flow increases, and thus noninvasive methods for measuring flow are nonlinear unless the extraction fraction can be measured independently. This report describes the theoretical basis and documents the applicability of this theory for determining, with external detectors, the first-pass regional extraction fraction of rubidium-82 by the heart, following a single intravenous bolus injection of the tracer. Measurement of extraction fraction was found to be independent of flow, thereby making it possible to determine accurately with a single intravenous bolus injection of rubidium-82, the regional blood flow in the myocardium at up to five times normal resting flow.

Myocardial perfusion with rubidium-82. II. Effects of metabolic and pharmacologic interventions.

In order to validate a new method for quantifying coronary blood flow, we injected intravenously a bolus of rubidium-82 (Rb-82) into 28 open-chested dogs under a wide range of flow and physiologic conditions, using beta probes to monitor myocardial radioactivity. Extraction fraction and perfusion were measured using a functional model that separates the data into the free and trapped myocardial rubidium. Extraction and uptake of rubidium were lower during acidosis than during alkalosis and were unchanged by glucose-insulin, digoxin, or propranolol. Myocardial flow, as indicated by rubidium, correlated linearly with simultaneous measurements of flow by microspheres in the same sample volume over a wide range of flow (r = 0.97, n = 106, range 0.02-7.76 ml/min/g). Regional myocardial blood flow can be accurately determined using generator-produced Rb-82. Studies using current state-of-the-art, fast positron-emission tomographic cameras are required to determine the utility of this approach in man.

Elevated coronary sinus pressure does not alter myocardial blood flow or left ventricular contractile function in mature sheep. Implications after the Fontan operation.

The hypothesis that elevation of coronary sinus pressure affects coronary blood flow and ventricular function was tested in this study of seven adult ewes placed under pentobarbital anesthesia. Coronary sinus pressure was elevated by partial balloon occlusion. Right atrial, left atrial, and aortic mean pressures and rate of rise of left ventricular pressure were measured. Coronary blood flow was determined with radioactive microspheres. Studies were performed at control and at moderate (15 to 20 mm Hg) and marked (30 to 35 mm Hg) elevation of coronary sinus mean pressures. Despite increase of coronary sinus pressure from a control value of 2 mm Hg +/- 1 to levels of 19 mm Hg +/- 1 and 34 mm Hg +/- 1, no significant changes were observed in right atrial, left atrial, or aortic mean pressure or rate of rise of left ventricular pressure. Both endocardial and epicardial blood flows were unaffected. The endocardial/epicardial flow ratio at moderate coronary sinus pressure elevation was significantly increased, which suggested local subendocardial vasodilation in the absence of changes in transmural perfusion. The findings suggest that isolated increase in coronary sinus pressure is not a major determinant of myocardial blood flow or ventricular performance in the normal ewe.

Lack of impact of rapid identification of rotavirus-infected patients on nosocomial rotavirus infections.

The efficacy of rapid identification of rotavirus-infected patients in the control of nosocomial rotavirus infections on an infant and young toddler ward by use of a rotavirus antigen detection test on stool from patients with diarrhea was evaluated by comparing the rate of nosocomial rotavirus infection in children during two separate 5-week periods in the winters of 1984 and 1986. In contrast to 1984 rapid rotavirus antigen testing by latex agglutination of stool from patients with diarrhea was instituted in 1986, in addition to testing for rotavirus by enzyme immunoassay, to determine whether use of rapid antigen testing resulted in an increased incidence of appropriate isolation and a decrease in nosocomial infections. In 1986 rapid identification of rotavirus resulted in an increase in hospitalization of rotavirus-infected patients in single bed rooms from 68% to 100% (P = 0.02, chi square test) but no significant increase in the use of enteric precautions for these patients. The total number of cases of nosocomial rotavirus infection in the two periods did not differ. In both periods 11 cases occurred; the nosocomial infection rate in 1984 was 18.9 cases/1000 days of exposure whereas in 1986 it was 20.2 cases/1000 days. These findings indicate that the use of rapid rotavirus antigen testing of patients with diarrhea is not of appreciable benefit in preventing the nosocomial spread of rotavirus to infants on the ward.

Neonatal Trichosporon beigelii infection: report of a cluster of cases in a neonatal intensive care unit.

Trichosporon beigelii, a ubiquitous yeast found in soil, causes superficial dermatologic infections in normal hosts and rare cases of disseminated disease among immunocompromised patients. Neonatal cases are exceptionally rare. We report a cluster of cases of T. beigelii infections in a tertiary care hospital in Rochester, NY, during May to July, 1991. Three cases occurred in very low birth weight premature infants (23 to 25 weeks of gestation), two of whom died. The organism was isolated from urine alone in one case, skin and blood in one case and blood, tracheal aspirate and central venous catheter tip in one case. In a fourth, full term infant with respiratory distress syndrome T. beigelii was grown only from a femoral central venous catheter tip with no clinical evidence of infection. An epidemiologic investigation was performed and the mode of transmission in this outbreak was not identified, although cross-infection was suspected in the initial two cases. Our isolates were inhibited but not killed by usually achievable concentrations of amphotericin B. T. beigelii may cause outbreaks of serious infection in neonatal intensive care units, especially among premature infants.

Serratia marcescens outbreak associated with extrinsic contamination of 1% chlorxylenol soap.

OBJECTIVES: To determine risk factors for Serratia marcescens infection or colonization, and to identify the source of the pathogen and factors facilitating its persistence in a neonatal intensive-care unit (NICU) during an outbreak. DESIGN: Retrospective case-control study; review of NICU infection control policies, soap use, and handwashing practices among healthcare workers (HCWs); and selected environmental cultures. SETTING: A university-affiliated tertiary-care hospital NICU. PATIENTS: All NICU infants with at least one positive culture for S marcescens during August 1994 to October 1995. Infants who did not develop S marcescens infection or colonization were selected randomly as controls. RESULTS: Thirty-two patients met the case definition. On multivariate analysis, independent risk factors for S marcescens infection or colonization were having very low birth weight (< 1,500 g), a patent ductus arteriosus, a mother with chorioamnionitis, or exposure to a single HCW. During January to July 1995, NICU HCWs carried their own bottles of 1% chlorxylenol soap, which often were left standing inverted in the NICU sink and work areas. Cultures of 16 (31%) of 52 samples of soap and 1 (8%) of 13 sinks yielded S marcescens. The 16 samples of soap all came from opened 4-oz bottles carried by HCWs. DNA banding patterns of case infant, HCW soap bottle, and sink isolates were identical. CONCLUSIONS: Extrinsically contaminated soap contributed to an outbreak of S marcescens infection. Very-low-birth-weight infants with multiple invasive procedures and exposures to certain HCWs were at greatest risk of S marcescens infection or colonization.

Resurgence of rabies. A historical perspective on rabies in children.

Wildlife rabies in certain parts of the United States has been increasing. With greater urbanization, many areas have seen an influx of wild animals such as raccoons and foxes that are known wildlife reservoirs of rabies. Rabies encephalitis has been a fatal illness recognized by humans throughout history. The purpose of this review is to examine the history of rabies throughout the world to elucidate the evolution of popular and scientific knowledge of the disease in animals and humans. By examining this development from a pediatric perspective, we gain insight into the prevention and treatment protocols recommended for children today. Pediatricians need to include education about prevention and treatment of rabies exposures in their anticipatory guidance sessions with families.

Clinical experience with the video-assisted saphenectomy procedure for coronary bypass operations.

BACKGROUND: Leg wound complications after saphenectomy are frequent after coronary bypass operations and have a detrimental effect on postoperative quality of life and treatment cost. To reduce morbidity, we evaluated a new technique of video-assisted vein harvest. METHODS: Between March 1996 and October 1996, 50 patients had video-assisted saphenectomy (VAS) and 40 patients had the standard open technique (control group). An additional 13 patients had both procedures (hybrid group). Level of pain, edema, and wound complications were evaluated at discharge and at 2, 4, and 6 weeks postoperatively. RESULTS: The mean operating time for VAS patients was slightly higher than for control (60.6+/-24.7 minutes versus 53.2+/-21.1 minutes; p > 0.05). The average incision length in VAS patients was 13.8+/-8.8 cm for an average of 3.3 grafts per patient. Three VAS procedures were aborted, two because of time constraints, and one because of bleeding, and a segment of vein was lost to injury. The VAS group had considerably less early postoperative pain than the control group (1.7+/-1.2 versus 4.1+/-1.4 [1 = mild, 10 = severe]; p < 0.005) and edema was similar for both groups. Patients in the hybrid group reported less pain in the VAS-operated leg. Serious wound infection occurred in 4 patients, with 2 patients in the control group requiring reoperation for drainage and flap reconstruction. CONCLUSIONS: Based on this initial experience, VAS harvesting, although initially more time consuming, is a rapidly mastered technique, results in shorter overall incision length, and is associated with considerably less postoperative pain than the standard open technique.

Antigenic properties of recombinant glycosylated and nonglycosylated Pneumocystis carinii glycoprotein A polypeptides expressed in baculovirus-infected insect cells.

Since a continuous culture system is not yet available for the opportunistic fungal pathogen Pneumocystis carinii, obtaining suitable amounts of purified P. carinii antigens free of mammalian-host lung contaminants is difficult. Hence, production of recombinant antigen possessing epitopes found in native P. carinii antigens is critical for immunological studies. We utilized the baculovirus expression vector system (BEVS) in insect cells to determine whether B-cell epitopes present in the protein core of a native P. carinii surface glycoprotein were conserved in the recombinant polypeptide, and to investigate its glycosylation by insect cells. B-cell epitopes were retained, but the insect cells appeared to hyperglycosylate the recombinant protein.

Experience with high-dose gadolinium MR imaging in the evaluation of brain metastases.

PURPOSE: To assess the effectiveness and safety of higher doses of gadoteridol in the MR evaluation of patients with brain metastases. MATERIALS AND METHODS: Thirty-one patients with a clinical suspicion of brain metastases were studied prospectively with gadoteridol, a new, nonionic, low-osmolality contrast agent. Each patient received an initial injection of 0.1 mmol/kg and an additional dose of 0.2 mmol/kg 30 minutes later. Images were obtained before, immediately after, and 10 and 20 minutes after the initial dose. Images also were acquired immediately after the additional dose of gadoteridol. RESULTS: No adverse effects were attributed to the injection of gadoteridol. Four patients' examinations were excluded from analysis because of machine malfunction (two patients) and excessive motion artifact (two patients). Four patients had no detectable metastases. After the additional dose of gadoteridol, there was a marked qualitative improvement in lesion conspicuity and detection. The conspicuity of 80 of 81 lesions was increased in the high-dose studies, and 46 new lesions were detected in 19 of 27 patients. Quantitative image analysis demonstrated a significant increase in normalized mean lesion contrast between the initial-dose and high-dose studies (35 lesions identified in 13 patients, P less than .0001). The additional information gained by high-dose examinations contributed to a potential modification of the treatment in 10 of 27 patients. High-dose examinations increased flow-related artifact in the posterior fossa in 12 of 27 patients. CONCLUSION: Based on our preliminary results, high-dose gadolinium-enhanced MR examinations may have advantages over 0.1 mmol/kg examinations in detecting early and/or small metastases. This may be significant in the management of patients with cerebral metastases.