A patient with acute liver failure and extreme hypoglycaemia with lactic acidosis who was not in a coma: causes and consequences of lactate-protected hypoglycaemia.

Lactate can substitute for glucose as a metabolic substrate. We report a patient with acute liver failure who was awake despite a glucose level of 0.7 mmol/l with very high lactate level of 25 mmol/l. The hypoglycaemia+hyperlactataemia combination may be considered paradoxical since glucose is the main precursor of lactate and lactate is reconverted into glucose by the Cori cycle. Literature relevant to the underlying mechanism of combined deep hypoglycaemia and severe hyperlactataemia was assessed. We also assessed the literature for evidence of protection against deep hypoglycaemia by hyperlactataemia. Four syndromes demonstrating hypoglycaemia+hyperlactataemia were found: 1) paracetamol-induced acute liver failure, 2) severe malaria, 3) lymphoma and 4) glucose-6-phosphatase deficiency. An impaired Cori cycle is a key component in all of these metabolic states. Apparently the liver, after exhausting its glycogen stores, loses the gluconeogenic pathway to generate glucose and thereby its ability to remove lactate as well. Several patients with lactic acidosis and glucose levels below 1.7 mmol/l who were not in a coma have been reported. These observations and other data coherently indicate that lactate-protected hypoglycaemia is, at least transiently, a viable state under experimental and clinical conditions. Severe hypoglycaemia+hyperlactataemia reflects failure of the gluconeogenic pathway of lactate metabolism. The existence of lactate-protected hypoglycaemia implies that patients who present with this metabolic state should not automatically be considered to have sustained irreversible brain damage. Moreover, therapies that aim to achieve hypoglycaemia might be feasible with concomitant hyperlactataemia.

Acute renal failure associated with vancomycin and ß-lactams for the treatment of osteomyelitis in diabetics: piperacillin-tazobactam as compared with cefepime.

Few data are available on the nephrotoxic potential of vancomycin when combined with certain ß-lactam antibiotics for the treatment of osteomyelitis (OM). A retrospective cohort study was conducted of all diabetic patients with OM treated with vancomycin plus piperacillin-tazobactam (VPT) or vancomycin plus cefepime (VC) for at least 72 h at a VA Medical Center between 1 January 2006 and 31 December 2011. All patients with a creatinine clearance (CrCl) of ≤ 40 mL/min, a blood urea nitrogen/serum creatinine (SCr) ratio of ≥ 20 : 1 or an absolute neutrophil count of <500 cells/mm(3) were excluded. The primary outcome was development of acute renal failure (ARF), defined as an increase in SCr of 0.5 mg/dL or 50% of baseline. One hundred and thirty-nine patients met the inclusion criteria; 109 in the piperacillin-tazobactam group and 30 in the cefepime group. Among patients receiving VPT, 29.3% (32/109) developed ARF, as compared with 13.3% (4/30) receiving VC (p 0.099). Among patients receiving high-dose therapy (≥ 18 g of piperacillin-tazobactam daily or ≥ 3 g of cefepime daily), 37.5% (9/24) receiving VPT and 17.6% (3/17) receiving VC developed ARF (p 0.29). A multiple logistic regression analysis identified weight and average vancomycin trough as the only significant predictors of ARF; the choice of VPT as therapy yielded an OR of 3.45 (95% CI 0.96-12.40; p 0.057). The authors were unable to detect a statistically significant difference in ARF between groups; however, the power requirement was not met. Further study with a larger patient population seems warranted.

Daptomycin versus vancomycin for osteoarticular infections due to methicillin-resistant Staphylococcus aureus (MRSA): a nested case-control study.

Vancomycin is the standard antibiotic for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. While daptomycin is approved for MRSA bacteremia, its effectiveness in osteoarticular infections (OAIs) has not been established. A 1:2 nested case-control study of adult patients with MRSA OAIs admitted to an academic center from 2005 to 2010 was carried out. Clinical outcomes and drug toxicity in patients treated with daptomycin versus vancomycin were compared. Twenty patients with MRSA OAIs treated with daptomycin were matched to 40 patients treated with vancomycin. The median age of the patients was 52 years (range, 25-90), and 40 (67%) were male. Most patients had osteomyelitis (82%), predominantly from a contiguous source (87%). Forty percent were diabetics. Diabetic patients were more likely to receive vancomycin than daptomycin [20 (50%) vs. 4 (20%); p = 0.03]. Vancomycin was more often combined with antibiotics other than daptomycin [22 (55%) vs. 5 (25%); p = 0.03]. The median total antibiotic treatment duration was 48 (daptomycin) vs. 46 days (vancomycin) (p = 0.5). Ninety percent of daptomycin-treated patients had previously received vancomycin for a median of 14.5 days (range, 2-36). Clinical success rates were similar between daptomycin and vancomycin at 3 months [15 (75%) vs. 27 (68%); p = 0.8] and 6 months [14 (70%) vs. 23 (58%); p = 0.5], even after propensity score-based adjustment for antibiotic assignment. The frequency of adverse events was similar between treatment groups [1 (5%) vs. 7 (18%); p = 0.2]. Daptomycin and vancomycin achieved similar rates of clinical success and drug tolerability. Daptomycin is a reasonable alternative for treating MRSA OAIs, particularly in patients where therapy with vancomycin has not been well tolerated.

Classification of and cytoreductive surgery for low-grade appendiceal mucinous neoplasms.

BACKGROUND: Low-grade appendiceal mucinous neoplasm (LAMN) is a precursor lesion for pseudomyxoma peritonei (PMP), which, if treated suboptimally, may later disseminate throughout the abdominal cavity. The role of cytoreductive surgery for these relatively early lesions is unclear. METHODS: Clinicopathological details and treatment outcomes of patients with a LAMN and disease limited to the appendix or immediate periappendiceal tissues, referred to a national treatment centre between 2002 and 2009, were evaluated prospectively. RESULTS: Of 379 patients with a diagnosis of PMP, 43 (median age 49 years) had LAMNs localized to the appendix and periappendiceal tissue. Thirty-two patients initially presented with symptoms of acute appendicitis or right iliac fossa pain. Two distinct lesions were identified: type I (disease confined to the appendiceal lumen) and type II (mucin and/or neoplastic epithelium in the appendiceal submucosa, wall and/or periappendiceal tissue, with or without perforation). Type I lesions were managed by a watch-and-wait surveillance policy with serial measurement of tumour markers and computed tomography in 14 of 16 patients. Seventeen of 27 patients with type II lesions underwent risk-reducing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with low morbidity. After a median follow-up of 40 months, there was no disease progression in either treatment pathway. CONCLUSION: This study identified two LAMN subtypes. Type II lesions have pathological features of increased risk for dissemination and should be considered for risk-reducing cytoreductive surgery.

High-risk antimicrobial prescriptions among ambulatory patients on warfarin.

WHAT IS KNOWN AND OBJECTIVE: Warfarin is a potent anticoagulant with many drug-drug interactions, including antimicrobials. There is limited data on the frequency of prescription of high-risk antimicrobials to patients on warfarin. To examine the frequency of prescriptions for potentially interacting antimicrobials in ambulatory patients on warfarin and the impact of warfarin on the prescription of high-risk antimicrobials. METHODS: A retrospective cohort study of patients with pharmacy benefits who had ≥1 claim for an oral antimicrobial between 1 January 2008 and 31 December 2008 was conducted, utilizing a pharmacy benefits database. Demographic data including age, gender, chronic disease score (CDS) and geographic location were determined. Warfarin users were defined as any patient with ≥1 claim for warfarin during the follow-up period. Antimicrobials considered high risk for potential interaction with warfarin based on existing literature included trimethoprim/sulfamethoxazole, levofloxacin, ciprofloxacin, metronidazole and fluconazole. Multivariate analysis was used to determine the impact of warfarin use and other factors on high-risk antimicrobial prescription. RESULTS AND DISCUSSION: A total of 4,568,150 patients with ≥1 claim for antimicrobials during 2008 were analysed. Of them, 110,192 (2·4%) also had one or more claims for warfarin. Among all antimicrobial prescriptions in warfarin users, 42·6% were for high-risk antimicrobials. The mean number of antimicrobial prescriptions was 3·0 in warfarin users versus 2·4 in warfarin non-users (P-value <0·001). After adjusting for age, gender, CDS and geography, the odds of exposure to high-risk antimicrobials was 42% lower (OR 0·58; P-value <0·001) in warfarin users compared with warfarin non-users. WHAT IS NEW AND CONCLUSIONS: A high percentage (42·6%) of antimicrobial prescriptions among warfarin users were for high-risk antimicrobials that carry excess bleeding risk. Although clinicians were somewhat less likely to prescribe high-risk antimicrobials to warfarin users compared with non-users, the incidence of co-prescription remains high.

Selective CCR2-targeted macrophage depletion ameliorates experimental mesangioproliferative glomerulonephritis.

The CCL2/CCR2 chemokine/receptor axis directs the chemotaxis of infiltrating monocytes/macrophages and T cells and plays a pivotal role in tissue damage and fibrosis in kidney diseases. The eradication of the activated leucocytes should diminish the production of inflammatory mediators, limit tissue damage and ameliorate disease. A recombinant fusion protein (OPL-CCL2-LPM) comprised of the human CCL2 (monocyte chemoattractant protein-1) chemokine fused to a truncated form of the enzymatically active A1 domain of Shigella dysenteriae holotoxin (SA1) has been developed. The CCL2 portion binds specifically to CCR2-bearing leucocytes and the fusion protein enters the cells, where the SA1 moiety inhibits protein synthesis resulting in cell death. The compound was tested in a model of anti-thymocyte serum (ATS)-induced mesangioproliferative glomerulonephritis (ATS-GN). Male rats were injected with ATS on day 0 and treated intravenously with vehicle, 50 or 100 microg/kg of OPL-CCL2-LPM Q2D from days 2, 4, 6 and 8. Urine and blood were collected on days 0, 5 and 9. Animals were sacrificed on day 9. No treatment-related effects on body weight or signs of clinical toxicity were observed. Urine protein levels were decreased in treated animals. At the highest dose, histopathological analyses of kidney sections revealed maximum reductions of 36, 31, 30 and 24% for macrophage count, glomerular lesions, alpha-smooth muscle actin and fibronectin respectively. These results indicate a significant protective effect of OPL-CCL2-LPM in this model of nephritis.

Enterococcal prosthetic valve infective endocarditis: report of 45 episodes from the International Collaboration on Endocarditis-merged database.

Enterococcal prosthetic valve infective endocarditis (PVE) is an incompletely understood disease. In the present study, patients with enterococcal PVE were compared to patients with enterococcal native valve endocarditis (NVE) and other types of PVE to determine differences in basic clinical characteristics and outcomes using a large multicenter, international database of patients with definite endocarditis. Forty-five of 159 (29%) cases of definite enterococcal endocarditis were PVE. Patients with enterococcal PVE were demographically similar to patients with enterococcal NVE but had more intracardiac abscesses (20% vs. 6%; p=0.009), fewer valve vegetations (51% vs. 79%; p<0.001), and fewer cases of new valvular regurgitation (12% vs. 45%; p=0.01). Patients with either enterococcal PVE or NVE were elderly (median age, 73 vs. 69; p=0.06). Rates of in-hospital mortality, surgical intervention, heart failure, peripheral embolization, and stroke were similar in both groups. Patients with enterococcal PVE were also demographically similar to patients with other types of PVE, but mortality may be lower (14% vs. 26%; p=0.08). Notably, 93% of patients with enterococcal PVE came from European centers, as compared with only 79% of patients with enterococcal NVE (p=0.03). Thus, patients with enterococcal PVE have higher rates of myocardial abscess formation and lower rates of new regurgitation compared to patients with enterococcal NVE, but there are no differences between the groups with regard to surgical or mortality rates. In contrast, though patients with enterococcal PVE and patients with other types of PVE share similar characteristics, mortality is higher in the latter group. Importantly, the prevalence of enterococcal PVE was higher in the European centers in this study.

Enterococcal endocarditis: 107 cases from the international collaboration on endocarditis merged database.

PURPOSE: To describe clinical features and outcomes of enterococcal left-sided native valve endocarditis and to compare it to endocarditis caused by other pathogens. SUBJECTS AND METHODS: Patients in the International Collaboration on Endocarditis-Merged Database were included if they had left-sided native valve endocarditis. Demographic characteristics, clinical features, and outcomes were analyzed. Multivariable analysis evaluated enterococcus as a predictor of mortality. RESULTS: Of 1285 patients with left-sided native valve endocarditis, 107 had enterococcal endocarditis. Enterococcal endocarditis was most frequently seen in elderly men, frequently involved the aortic valve, tended to produce heart failure rather than embolic events, and had relatively low short-term mortality. Compared to patients with non-enterococcal endocarditis, patients with enterococcal endocarditis had similar rates of nosocomial acquisition, heart failure, embolization, surgery, and mortality. Compared to patients with streptococcal endocarditis, patients with enterococcal endocarditis were more likely to be nosocomially acquired (9 of 59 [15%] vs 2 of 400 [1%]; P <.0001) and have heart failure (49 of 107 [46%] vs 234 of 666 [35%]; P = 0.03). Compared to patients with S. aureus endocarditis, patients with enterococcal endocarditis were less likely to embolize (28 of 107 [26%] vs 155 of 314 [49%]; P <.0001) and less likely to die (12 of 107 [11%] vs 83 of 313 [27%]; P = 0.001). Multivariable analysis of all patients with left-sided native valve endocarditis showed that enterococcal endocarditis was associated with lower mortality (odds ratio [OR] 0.49; 95% confidence interval [CI] 0.24 to 0.97). CONCLUSIONS: Enterococcal native valve endocarditis has a distinctive clinical picture with a good prognosis.

Vitamin C improves endothelial dysfunction in renal allograft recipients.

BACKGROUND: Endothelial function is impaired in renal allograft recipients but the effects of antioxidant vitamin therapy on endothelial function in such patients is unknown. METHODS: Thirteen renal allograft recipients were randomized to vitamin C or placebo in a double blind cross-over study design. Flow-mediated endothelium-dependent dilation and glyceryltrinitrate-induced endothelium-independent dilation of the brachial artery were assessed before and 2 h after oral administration of 2 g vitamin C or placebo. RESULTS: Plasma vitamin C levels increased from 33.5+/-17.0 micromol/l to 98.8+/-60.2 micromol/l after treatment (P=0.0001). Endothelium-dependent dilation improved (from 1.6+/-2.6 to 4.5+/-2.5%) after vitamin C administration but was unchanged after placebo (1.9+/-1.5 to 1.8+/-2.5%; P=0.003 for vitamin C vs placebo). There was no significant change in endothelium-independent dilation in response to vitamin C. Vitamin C was also associated with a significant increase in the lag time in dilute serum oxidation (P=0.001). CONCLUSIONS: Vitamin C acutely improves flow-mediated, endothelium-dependent dilation and increases the resistance of lipoproteins in dilute serum to oxidation in renal transplant recipients.

The therapeutic potential of chemokine-toxin fusion proteins.

Activated cells of the immune system and the biochemical mediators they produce, underlie the pathology and secondary tissue damage in a wide range of diseases and traumas. One approach to therapy is to inhibit specific mediators in various biochemical pathways or cascades with the use of biological response modifiers. An alternative approach is to suppress or eradicate diseased cells or activated cells that fuel the disease and secondary tissue damage processes. Osprey has chosen to develop novel versatile cell-targeting agents that exploit the cell biology of the chemokine superfamily of receptors and ligands.

Targeting tumor cells via EGF receptors: selective toxicity of an HBEGF-toxin fusion protein.

Over-expression of the epidermal growth factor receptor (EGFR) is a hallmark of numerous solid tumors, thus providing a means of selectively targeting therapeutic agents. Heparin-binding epidermal growth factor (HBEGF) binds to EGFRs with high affinity and to heparan sulfate proteoglycans, resulting in increased mitogenic potential compared to other EGF family members. We have investigated the feasibility of using HBEGF to selectively deliver a cytotoxic protein into EGFR-expressing tumor cells. Recombinant fusion proteins consisting of mature human HBEGF fused to the plant ribosome-inactivating protein saporin (SAP) were expressed in Escherichia coli. Purified HBEGF-SAP chimeras inhibited protein synthesis in a cell-free assay and competed with EGF for binding to receptors on intact cells. A construct with a 22-amino-acid flexible linker (L22) between the HBEGF and SAP moieties exhibited an affinity for the EGFR that was comparable to that of HBEGF. The sensitivity to HBEGF-L22-SAP was determined for a variety of human tumor cell lines, including the 60 cell lines comprising the National Cancer Institute Anticancer Drug Screen. HBEGF-L22-SAP was cytotoxic in vitro to a variety of EGFR-bearing cell lines and inhibited growth of EGFR-over-expressing human breast carcinoma cells in vivo. In contrast, the fusion protein had no effect on small-cell lung carcinoma cells, which are EGFR-deficient. Our results demonstrate that fusion proteins composed of HBEGF and SAP exhibit targeting specificity and cytotoxicity that may be of therapeutic value in treating a variety of EGFR-bearing malignancies.

Rapid cold hardening in the western flower thrips Frankliniella occidentalis.

A rapid cold hardening process is reported in first instar larvae of Frankliniella occidentalis. When larvae are transferred directly from 20 degrees C to -11.5 degrees C for 2h there is 78% mortality, whereas exposure to 0 degrees C for 4h prior to transfer to -11.5 degrees C reduces mortality to 10%. The response can also be induced by exposure to 5 degrees C for 4h or by gradual cooling at rates between 0.1 and 0.5 degrees C min(-1.) The acquired cold tolerance is transient and is rapidly lost (after 1h at 20 degrees C). Rapid cold hardening extends survival times at -11.5 degrees C and depresses lethal temperatures in short (2h) exposures. Rearing at 15 degrees C (12L:12D), (a cold acclimation regime for F. occidentalis), does not protect against the cold shock induced by direct transfer to -11.5 degrees C (which rapid cold hardening does) but does extend survival time at -5 degrees C (i.e. increased chill tolerance) whilst rapid cold hardening does not. The rapid and longer term cold hardening responses in F. occidentalis therefore appear to have different underlying mechanisms.

Large-scale purification and characterization of recombinant fibroblast growth factor-saporin mitotoxin.

In order to produce sufficient quantities of fibroblast growth factor-saporin (rFGF-2-SAP) mitotoxin for preclinical evaluation in models of diseases such as cancer and restenosis, we have undertaken the large-scale expression, purification, and characterization of the recombinant molecule. The fusion gene encoding rFGF-2-SAP was cloned into the inducible pET 11a expression vector and transformed into Escherichia coli strain BL21 (DE3). The transformants were grown using a fed-batch fermentation until the A600 reached 85. At this stage, induction of the expression of the fusion protein led to the production of approximately 2.2 mg/liter per A600 unit. The soluble mitotoxin was purified to homogeneity from cell lysates via expanded bed adsorption chromatography followed by cation-exchange, heparin-affinity, and size-exclusion chromatography. Purified rFGF-2-SAP contained less than 0.5 EU/mg of endotoxin, as determined by gel clot analyses. The highly purified rFGF-2-SAP retained the toxin's ability to inhibit protein synthesis as measured in a cell-free system and was cytotoxic to a number of normal and neoplastic cell lines bearing FGF receptors. Binding studies establish that the fusion protein exerts its effects via the FGF high-affinity receptor.

Cusum as an aid to early assessment of the surgical trainee.

Tests of knowledge, aptitude and psychomotor skills have been used to assess and select surgical trainees but none of these is reliable in the long term. The industrial quality-control method of the cusum was used to assess performance progress in 17 surgical trainees. Trainees were assessed on their ability to perform, independently, selected surgical operations using the criterion of procedure duration. Cusum profiles were compared with scores from at least four independent assessors using a modified Royal Australasian College of Surgeons' mentor form. The cusum identified all trainees who were considered either satisfactory or less able by their mentors. This objective evaluation was reliable after 25 procedures, whether for appendicectomy or combined with herniorrhaphy and cholecystectomy. Evaluation of surgical performance using the cusum may prove to be a more objective tool for assessing surgical trainees than early impressions or less clinically oriented tests.

Changes in intracranial pressure associated with apneumic retractors.

OBJECTIVE: To investigate the effect of apneumic retraction on intracranial pressure (ICP) using a live porcine model. DESIGN: Five 25- to 30-kg pigs had a fiber-optic ICP bolt inserted under general endotracheal anesthesia and were monitored for ICP, mean arterial pressure, arterial blood gas measurements, and intra-abdominal pressure before, during, and after pneumoperitoneum, with each period 30 minutes long. These series of measurements were repeated after artificially raising ICP with an epidural balloon to create a head-injured model. The mean (+/- SE) ICP in the noninjured model at baseline was 13.46 +/- 1.01 mm Hg; during pneumoperitoneum, 18.72 +/- 1.50 mm Hg (P = .0001). Similarly, in the head-injured model, ICP was raised artificially to a new baseline of 22 +/- 1.75 mm Hg with an epidural balloon, and pneumoperitoneum increased ICP to 27.40 +/- 0.93 mm Hg (P = .0001). Pneumoperitoneum was then released, and an apneumic retractor was inserted while maintaining the inflated epidural balloon. MAIN OUTCOME MEASURE: Changes in ICP. RESULTS: Applying anterior wall retraction equivalent to 20 mm Hg was not associated with changes in ICP. These observations were independent of any changes in arterial PCO2 or arterial pH. Following the release of pneumoperitoneum, abdominal wall retraction, and epidural balloon, all measurements reverted to baseline. CONCLUSION: Pneumoperitoneum adversely affects ICP, while apneumic retraction may not affect animals with raised ICP. These findings suggest that pneumoperitoneum should be used with caution in patients with raised ICP, and apneumic retraction may be a safer alternative for laparoscopic evaluation in this population.

Diagnostic laparoscopy increases intracranial pressure.

There are numerous reports in the literature concerning the use of laparoscopy for evaluation of abdominal trauma victims. The safety of laparoscopic evaluation in trauma patients with potentially severe intracranial injuries has not yet been analyzed. This study investigates the effect of pneumoperitoneum on intracranial pressure (ICP) and cerebral perfusion pressure. Five 30-kg pigs were monitored for ICP, mean arterial pressure (MAP), arterial blood gases (ABGs), and intra-abdominal pressure (IAP) for 30 minutes before, during, and after pneumoperitoneum. These series of measurements were repeated after artificially elevating the ICP with an epidural balloon. The mean ICP at baseline was 13.46 +/- 1.01 mm Hg. The mean ICP during pneumoperitoneum was 18.72 +/- 1.50 mm Hg (p = 0.0001). The ICP increased to 27.40 +/- 0.93 mm Hg (p = 0.0001) after the ICP was raised artificially to a new baseline of 22 +/- 1.75 mm Hg with the epidural balloon. These increases were independent of changes in arterial PCO2 or arterial pH. Pneumoperitoneum during laparoscopy may increase ICP and must be used cautiously in evaluating patients with severe head injuries.

In situ regulation of cell-cell communication by the cAMP-dependent protein kinase and protein kinase C.

The effects of cAMP-dependent protein kinase A and protein kinase C on cell-cell communication have been examined in primary ovarian granulosa cells microinjected with purified components of these two regulatory cascades. These cells possess connexin43 (alpha 1)-type gap junctions, and are well-coupled electrotonically and as judged by the cell-to-cell transfer of fluorescent dye. Within 2-3 min after injection of the protein kinase A inhibitor (PKI) communication was sharply reduced or ceased, but resumed in about 3 min with the injection of the protein kinase A catalytic subunit. A similar resumption also occurred in PKI-injected cells after exposure to follicle stimulating hormone. Microinjection of the protein kinase C inhibitor protein caused a transient cessation of communication that spontaneously returned within 15-20 min. Treatment of cells with activators of protein kinase C, TPA or OAG for 60 min caused a significant reduction in communication that could be restored within 2-5 min by the subsequent injection of either the protein kinase C inhibitor or the protein kinase A catalytic subunit. With a longer exposure to either protein kinase C activator communication could not be restored and this appeared to be related to the absence of aggregates of connexin43 in membrane as detected immunologically. In cells injected with alkaline phosphatase communication stopped but returned either spontaneously within 20 min or within 2-3 min of injecting the cell with either the protein kinase A catalytic subunit or with protein kinase C. When untreated cells were injected with protein kinase C communication diminished or ceased within 5 min. Collectively these results demonstrate that cell-cell communication is regulated by both protein kinase A and C, but in a complex interrelated manner, quite likely by multiple phosphorylation of proteins within or regulating connexin-43 containing gap junctions.

Evaluation of "Gastromiro" for bowel opacification during computed tomography: comparison with diatrizoate and barium sulphate.

A new oral formulation of iopamidol, "Gastromiro", was evaluated as a bowel contrast agent during abdominal computed tomography (CT). Comparison was made with the well established agents sodium/meglumine diatrizoate ("Urografin 370") and dilute barium sulphate ("E-Z CAT") in a randomized, blind study of 150 consecutive patients undergoing abdominal and/or pelvic CT. Parameters assessed included quality of bowel opacification, artefact generation, contrast-medium palatibility, side effects and cost. No significant difference was found between the three contrast media in stomach- or small-bowel opacification. E-Z CAT was superior at opacifying the caecum/ascending colon. No compelling reason to choose a particular agent was found in the other assessed parameters, but cost is a significant factor.

Nonionic low-osmolality versus ionic high-osmolality contrast material for intravenous use in patients perceived to be at high risk: randomized trial.

To determine the cost-effectiveness of selective use of nonionic low-osmolality contrast material, the authors randomly assigned 955 patients to receive high-osmolality and 1,158 to receive low-osmolality intravenous contrast material. All patients had one or more of the following perceived risk factors for adverse reactions: prior reaction to contrast material, allergies, asthma, diabetes, cardiac or renal disease, anxiety, severe illness, and age greater than 50 years. The occurrence of any adverse event, need for therapy, or subjective symptoms was assessed in a double-blind fashion. An adverse reaction necessitating the attention of a physician occurred in 3.9% (n = 37) of patients in the high-osmolality and 0.9% (n = 10) of patients in the low-osmolality groups (P less than .000005). Therapy was administered to 1.4% (n = 13) and 0.5% (n = 6), respectively (P = .035). The difference was due to a reduction in urticaria and other mild anaphylactoid reactions. In a multivariate analysis, only prior reactions and allergy were independent risk factors. Selective use of intravenous nonionic contrast material is best justified in those with prior reactions, allergy, or asthma; at least 67% of reactions would be prevented.