Minimizing contrast medium doses to diagnose pulmonary embolism with 80-kVp multidetector computed tomography in azotemic patients.

BACKGROUND: In diagnosing acute pulmonary embolism (PE) in azotemic patients, scintigraphy and magnetic resonance imaging are frequently inconclusive or not available in many hospitals. Computed tomography is readily available, but relatively high doses (30-50 g I) of potentially nephrotoxic iodine contrast media (CM) are used. PURPOSE: To report on the diagnostic quality and possible contrast-induced nephropathy (CIN) after substantially reduced CM doses to diagnose PE in azotemic patients using 80-peak kilovoltage (kVp) 16-row multidetector computed tomography (MDCT) combined with CM doses tailored to body weight, fixed injection duration adapted to scan time, automatic bolus tracking, and saline chaser. MATERIAL AND METHODS: Patients with estimated glomerular filtration rate (eGFR) <50 ml/min were scheduled to undergo 80-kVp MDCT using 200 mg I/kg, and those with eGFR >or=50 ml/min, 120-kVp MDCT with 320 mg I/kg. Both protocols used an 80-kg maximum dose weight and a fixed 15-s injection time. Pulmonary artery density and contrast-to-noise ratio were measured assuming 70 Hounsfield units (HU) for a fresh clot. CIN was defined as a plasma creatinine rise >44.2 micromol/l from baseline. RESULTS: 89/148 patients (63/68 females) underwent 80-/120-kVp protocols, respectively, with 95% of the examinations being subjectively excellent or adequate. Mean values in the 80-/120-kVp cohorts regarding age were 82/65 years, body weight 66/78 kg, effective mAs 277/117, CM dose 13/23 g I, pulmonary artery density 359/345 HU, image noise (1 standard deviation) 24/21 HU, contrast-to-noise ratio 13/13, and dose-length product 173/258 mGy x cm. Only 1/65 and 2/119 patients in the 80- and 120-kVp cohorts, respectively, with negative CT and no anticoagulation suffered non-fatal thromboembolism during 3-month follow-up. No patient developed CIN. CONCLUSION: 80-kVp 16-row MDCT with optimization of injection parameters may be performed with preserved diagnostic quality, using markedly reduced CM doses compared with common routine practice, which should be to the benefit of patients at risk of CIN.

Contrast medium dose-to-GFR ratio: a measure of systemic exposure to predict contrast-induced nephropathy after percutaneous coronary intervention.

BACKGROUND: The contrast medium (CM) dose-to-eGFR (estimated glomerular filtration rate) ratio has recently been advocated to express systemic exposure to CM in assessing the risk of contrast medium-induced nephropathy (CIN). PURPOSE: To evaluate how CIN risk might vary with decreasing eGFR at fixed CM-dose/eGFR ratios and other CIN risk factors, and to find a relatively safe CM-dose/eGFR ratio. MATERIAL AND METHODS: 391 patients underwent primary coronary angioplasty for ST-segment elevation acute myocardial infarction. CM dose (grams iodine; g I), eGFR (ml/min), and preprocedural CIN risk factors were entered into a multiple logistic regression model. From the established statistical model, the probability of CIN (>or=44.2 micromol/l serum creatinine rise or oliguria/anuria) was calculated at various eGFR levels based on g-I/eGFR ratios of 1:2, 1:1, 2:1, and 3:1. RESULTS: At a g-I/eGFR ratio <1 the risk of CIN was 3%, while it was 25% at a g-I/eGFR ratio >or=1. Independent predictors of CIN were CM dose, eGFR, left ventricular ejection fraction (LVEF) and cardiogenic shock (ROC area =0.87). An estimated CIN risk of 10% would for example occur at a g-I/eGFR ratio of 1.5:1 in patients with 50% LVEF without shock. At a 1:2, 1:1, 2:1, and 3:1 g-I/eGFR ratio with 50% LVEF without shock, the CIN risk was about 2, 6, 18, and 30%, respectively, over a wide range of eGFR values (30-90 ml/min). At a 1:1 g-I/eGFR ratio with 50% LVEF+shock, 25% LVEF without shock, or 25% LVEF+shock, the CIN risk was 20, 55, and 80%, respectively. CONCLUSION: Relating CM dose to eGFR appears to be an attractive pharmacotoxic model to assess CIN risk. At fixed CM-dose/eGFR ratios, CIN risk increased marginally with decreasing eGFR. Limiting the CM dose in g I numerically to the eGFR value in ml/min or less may be relatively safe with regard to CIN, unless multiple risk factors are present.

P73 and caspase-cleaved p73 fragments localize to mitochondria and augment TRAIL-induced apoptosis.

The p73 protein, a member of the p53 family, has both developmental and tumorigenic functions. Here we show that p73 is cleaved by caspase-3 and -8 both in vitro and in vivo during apoptosis elicited by DNA-damaging drugs and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor ligation. TAp73 and some of its cleavage products are localized to mitochondria. siRNA-mediated downregulation of p73 expression induced a small but significant change in the susceptibility of HCT116 cells to TRAIL-induced apoptosis. A transcription-deficient mutant of TAp73 enhanced TRAIL-induced apoptosis suggesting that p73 protein has transcription-independent functions during death receptor-mediated apoptosis. Additionally, recombinant p73 protein induced cytochrome c release from isolated mitochondria providing evidence that nonnuclear p73 may have additional functions in the progression of apoptosis.

Combinatorial action of the HDAC inhibitor trichostatin A and etoposide induces caspase-mediated AIF-dependent apoptotic cell death in non-small cell lung carcinoma cells.

Commonly used regimens in cancer therapy rely on the induction of apoptotic cell death, and drug resistance can be attributed, at least in part, to a disabled apoptotic program. Non-small cell lung carcinomas (NSCLC), exhibit an intrinsic resistance to chemotherapy. Here, we show that co-treatment with etoposide (VP16) and the pan-histone deacetylase (HDAC) inhibitor trichostatin A (TSA), but not valproic acid (VPA), induced apoptotic cell death in drug-resistant NSCLC cells. Co-treatment, but not single treatment, with VP16 and TSA induced apoptosis in a caspase-dependent manner accompanied by a crucial decrease in Bcl-xL expression allowing Bax activation and subsequent initiation of the apoptosis inducing factor (AIF)-dependent death pathway. Importantly, AIF proved to be required for the effects of TSA/VP16 as RNA knockdown of AIF resulted in a complete abolishment of TSA/VP16-induced apoptotic cell death in drug-resistant NSCLC cells. Our results thus provide evidence for the requirement of both caspase-dependent and caspase-independent apoptotic pathways in TSA/VP16-mediated death of drug-resistant NSCLC cells, and extend previous suggestions that HDAC inhibitors in combination with conventional chemotherapeutic drugs could be valuable in the treatment of NSCLC cancer and other malignancies in which Bcl-xL is overexpressed.

Determining 'true' glomerular filtration rate in healthy adults using infusion of inulin and comparing it with values obtained using other clearance techniques or prediction equations.

OBJECTIVE: To determine 'true' glomerular filtration rate (GFR) in healthy adults as renal clearance following infusion of inulin, and compare that result with those obtained using other markers and clearance techniques and with estimations of GFR using creatinine-based prediction equations. MATERIAL AND METHODS: Twenty healthy volunteers (11 females) with a median age of 27 years (range 19-36 years) received bolus doses of inulin and iohexol i.v. and 16 blood samples were taken after injection. Then, inulin and iohexol were infused to give stable plasma concentrations and blood and urine samples were collected. Residual bladder volume was estimated using ultrasound scanning. Plasma and urine concentrations of inulin and iohexol were determined using chromatography and resorcinol methods, respectively. Different methods of GFR determination were compared as well as four formulae for GFR estimation based on serum creatinine. RESULTS: 'True' GFR, i.e. renal clearance of inulin during its infusion, was a median of 117 ml/min/1.73 m2 (inter-quartile range 106-129 ml/min/1.73 m2). Similar values of GFR were obtained with renal clearance of iohexol during its infusion and also with plasma (body) clearance of inulin or iohexol following bolus injections and using 16 or five plasma samples. Endogenous creatinine clearance was higher (p<0.001) than true GFR (median 23 ml/min/1.73 m2). Plasma clearance of iohexol and inulin based on their concentrations in four blood samples underestimated their renal clearance considerably. All four creatinine-based formulae markedly underestimated renal inulin clearance. CONCLUSIONS: Plasma and renal clearance of iohexol and inulin were similar in healthy adults. Underestimation of GFR was noted when plasma clearance of iohexol and inulin was based on four but not five or more blood samples. Some prediction equations underestimate true GFR to such an extent that caution must be taken when using them to evaluate normal or high GFR values.

Histomorphological changes after renal X-ray arteriography using iodine and gadolinium contrast media in an ischemic porcine model.

BACKGROUND: Gadolinium contrast media (Gd-CM) are regarded as non-nephrotoxic or considerably less nephrotoxic than iodine contrast media (I-CM), and have therefore come to be used as a substitute for I-CM in patients with renal insufficiency in a variety of radiographic examinations. PURPOSE: To investigate renal histomorphological changes caused by Gd-CM in comparison with I-CM after renal X-ray arteriography in an ischemic porcine model,and to evaluate these changes in relation to the nephrotoxicity of the CM used. MATERIAL AND METHODS: Test solutions: gadopentetate, gadodiamide, iohexol, gadobutrol,iopromide, iodixanol, mannitol, and saline. The experiments were performed on 152 animals. Each pig was randomized to receive one test solution injected into the balloon occluded(10 min) right renal artery. The kidneys were evaluated histomorphologically.The severity of histomorphological changes was graded subjectively: 15 minimal, 25 mild, 35 moderate, and 4=marked. RESULTS: The main histological changes were 1) proximal tubular and glomerular necrosis,2) hemorrhage/congestion of the cortex, medulla, and glomeruli, 3) proximal tubular vacuolation, and 4) protein-filled tubules in the cortex and medulla. Necrosis and hemorrhage/congestion were more frequent after injections with gadopentetate, mannitol solution iso-osmotic to gadopentetate, and gadobutrol compared to all other groups(P<0.001). The degree of necrosis and hemorrhage/congestion was related to the degree of impairment of renal function, but inversely related to vacuolation and tubular protein filling. CONCLUSION: In ischemic porcine kidneys, the histomorphological changes caused by Gd-CM are similar to those caused by I-CM. Vacuolation appears to be independent of the osmolality and viscosity of the CM, and does not seem to be an indicator of renal impairment. "High-osmolal" Gd-CM are more nephrotoxic than "low- and iso-osmolal" I-CM when compared in equal volumes of concentrations, resulting in equal X-ray attenuation.

Prediction of relative glomerular filtration rate in adults: new improved equations based on Swedish Caucasians and standardized plasma-creatinine assays.

OBJECTIVE: To evaluate newly developed equations predicting relative glomerular filtration rate(GFR) in adult Swedish Caucasians and to compare with the Modification of Diet in Renal Disease(MDRD) and Mayo Clinic equations using enzymatic and zero-calibrated plasma creatinine assays. MATERIAL AND METHODS: GFR was measured with iohexol clearance adjusted to 1.73 m(2). One population sample (n=436/Lund) was used to derive an equation based on plasma-creatinine/age/gender, and a second with the addition of lean body mass (LBM). Both equations were validated in a separate sample (n=414/Malmö). The coefficients of the equations were eventually fine-tuned using all 850 patients and yielding Lund-Malmö equations without (LM) and with LBM-term (LM(LBM)). Their performance was compared with the MDRD(CC) (conventional creatinine calibration), MDRD(IDMS) (isotope dilution mass spectroscopy traceable calibration) and Mayo Clinic equations. RESULTS: The Lund equations performed similarly in both samples. In the combined set, the Mayo Clinic/MDRD(CC) resulted in +19.0/+10.2 % median bias, while bias for the other equations was < 10 %. LM(LBM) had the highest accuracy (86 % of estimates within 30 % of measured GFR), significantly (p < 0.001) better than for MDRD(IDMS) (80 %). In men with BMI < 20 kg/m(2), MDRD(IDMS)/LM had +46 %/+19 % median bias. MDRD(IDMS) also overestimated GFR by 22 %/14 % in men/women above 80 years of age. The LM(LBM) equation had < 10 % bias irrespective of BMI, age or GFR except for a 15 % negative bias at GFR > 90 mL/min/1.73 m(2). CONCLUSION: The newly developed Lund-Malmö equations for GFR estimation performed better than the MDRD(IDMS) and Mayo Clinic equations in a Swedish Caucasian sample. Inclusion of an LBM term improved performance markedly in certain subgroups.

The cell cycle inhibitor p57(Kip2) promotes cell death via the mitochondrial apoptotic pathway.

The p57(Kip2) gene belongs to the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors and has been suggested to be a tumor suppressor gene, being inactivated in various types of human cancers. However, little is known concerning p57(Kip2) possible interplay with the apoptotic cell death machinery and its possible implication for cancer. Here, we report that selective p57(Kip2) expression sensitizes cancer cells to apoptotic agents such as cisplatin, etoposide and staurosporine (STS) via a mechanism, which does not require p57(Kip2)-mediated inhibition of CDK. Translocation of p57(Kip2) to mitochondria occurs within 20 min after STS application. In fact, p57(Kip2) primarily promotes the intrinsic apoptotic pathways, favoring Bax activation and loss of mitochondrial transmembrane potential, consequent release of cytochrome-c into cytosol, caspase-9 and caspase-3 activation. In accordance, Bcl2 overexpression or voltage-dependent anion channel (VDAC) inhibition is able to inhibit p57(Kip2) cell death promoting effect. Thus, in addition to its established function in control of proliferation, these results reveal a mechanism whereby p57(Kip2) influences the mitochondrial apoptotic cell death pathway in cancer cells.

Cellular internalization of proinsulin C-peptide.

Proinsulin C-peptide is known to bind specifically to cell membranes and to exert intracellular effects, but whether it is internalized in target cells is unknown. In this study, using confocal microscopy and immunostained or rhodamine-labeled peptide, we show that C-peptide is internalized and localized to the cytosol of Swiss 3T3 and HEK-293 cells. In addition, transport into nuclei was found using the labeled peptide. The internalization was followed at 37 degrees C for up to 1 h, and was reduced at 4 degrees C and after preincubation with pertussis toxin. Hence, it is concluded to occur via an energy-dependent, pertussis toxin-sensitive mechanism and without detectable degradation within the experimental time course. Surface plasmon resonance measurements demonstrated binding of HEK-293 cell extract components to C-peptide, and subsequent elution of bound material revealed the components to be intracellular proteins. The identification of C-peptide cellular internalization, intracellular binding proteins, absence of rapid subsequent C-peptide degradation and apparent nuclear internalization support a maintained activity similar to that of an intracrine peptide hormone. Hence, the data suggest the possibility of one further C-peptide site of action.

Contrast Medium-induced Nephropathy. Aspects on Incidence; Consequences; Risk Factors; and Prevention

"Contrast media-induced nephropathy (CIN) is a well-known complication of radiological examinations employing iodine contrast media (I-CM). The rapid development and frequent use of coronary interventions and multi-channel detector computed tomography with concomitant administration of relatively large doses of I-CM has contributed to an increasing number of CIN cases during the last few years. Reduced renal function; especially when caused by diabetic nephropathy or renal arteriosclerosis; in combination with dehydration; congestive heart failure; hypotension; and administration of nephrotoxic drugs are risk factors for the development of CIN. When CM-based examinations cannot be replaced by other techniques in patients at risk of CIN; focus should be directed towards analysis of number and type of risk factors; adequate estimation of GFR; institution of proper preventive measures including hydration and post-procedural observation combined with surveillance of serum creatinine for 1-3 days. For the radiologist; there are several steps to consider in order to minimise the risk for CIN: use of ""low-"" or ""iso-osmolar"" I-CM and dosing the I-CM in relation to GFR and body weight being the most important as well as utilizing radiographic techniques to keep the I-CM dose in gram iodine as low as possible below the numerical value of estimated GFR. There is as yet no pharmacological prevention that has been proven to be effective."

Standardization of p-creatinine assays and use of lean body mass allow improved prediction of calculated glomerular filtration rate in adults: a new equation.

OBJECTIVE: To evaluate the Cockcroft-Gault (CG) equation, using various body weight expressions, and the Sawyer equation in predicting glomerular filtration rate (GFR) using an enzymatic and zero-calibrated Jaffe plasma-creatinine assay, and to derive a new robust equation in adults. MATERIAL AND METHODS: The CG weight measures included total, ideal and adjusted body weight (ABW; lowest of total and ideal) and two lean body mass (LBM) expressions, while the Sawyer equation is based primarily on LBM. Iohexol clearance was used to measure GFR. One derivation set (n = 436; enzymatic assay) was used to evaluate and bias-adjust existing equations when indicated, and to derive a new equation based on plasma-creatinine, age, gender and the body weight measure yielding the best adjusted R2. All equations were then validated in a separate set (n = 414; Jaffe assay). RESULTS: The existing equations all performed similarly in both sets. Prediction errors of equations based on LBM showed no correlation with BMI. The CGABW and Sawyer equations performed best. The new equation with LBM yielded the highest adjusted R2. In the combined set (n = 850), its accuracy (86 %/98 % of estimates within 30 %/50 % of measured GFR) was significantly better than for the CGABW (79 %/95 %) and Sawyer equations (79 %/93 %) (p<0.001) for each 30 mL/min GFR subgroup within +/-30 % and +/-50 %, except within +/-30 % >120 mL/min. Prediction error did not correlate with BMI, age or gender. CONCLUSION: A new creatinine-based equation derived in a mainly Caucasian patient sample is a better predictor of GFR than CG-type equations irrespective of the body weight measure used or, if bias-adjusted, when using zero-calibrated creatinine assays.

The role of p73 in hematological malignancies.

The P73 gene is a homologue of the P53 tumor suppressor. Owing to its structural similarity with p53, p73 was originally considered to have tumor suppressor function. However, the discovery of N-terminal truncated isoforms with oncogenic properties showed a 'two in one' structure of its product, p73 protein. The full-length variants are strong inducers of apoptosis, whereas the truncated isoforms inhibit proapoptotic activity of p53 and the full-length p73. Thus, p73 is involved in the regulation of cell cycle, cell death and development. Moreover, it plays a role in carcinogenesis and controls tumor sensitivity to treatment. p73 is commonly expressed in tumor cells in hematological malignancies. Overexpression of p73 protein and aberrant expression of its particular isoforms, with very low frequency of P73 hypermethylation or mutations, were found in malignant myeloproliferations, including acute myeloblastic leukemia. In contrast, hypermethylation and subsequent inactivation of the P73 gene are the most common findings in malignant lymphoproliferative disorders, especially acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphomas. Assessment of P73 methylation may provide important prognostic information, as was confirmed in patients with ALL. This review summarizes some aspects of p73 biology with particular reference to its possible pathogenetic role and prognostic significance in hematological malignancies.

Patient-circumference-adapted dose regulation in body computed tomography. A practical and flexible formula.

PURPOSE: To illustrate that the attenuation formula based on monochromatic radiation in homogeneous objects may be used for dose regulation in body computed tomography (CT) based on patient circumference and using a simple cloth measuring tape. MATERIAL AND METHODS: Based on the attenuation formula for monochromatic radiation the following Microsoft Excel equation was derived: mAs(x) = mAs(n)*EXP((0.693/ HVT)*(O(x)-O(n))/PI()), where mAs(x) (milliampere second) in a patient with circumference O(x) is calculated based on the nominal mAs(n) set for a reference patient with the circumference O(n) with regard to indication, scan protocol, and available CT scanner. The HVT = half-value thickness (object thickness change in cm affecting mAs setting by a factor of 2) resulting in the least mAs difference compared with published studies investigating the mAs needed for constant image noise in abdominal CT phantoms at 80-140 kVp was evaluated. Clinically recommended HVT values were applied to 20 patients undergoing abdominal CT using 130 effective mAs and 94 cm circumference as nominal settings, and an HVT of 9 cm. RESULTS: The object-sized dependent mAs for constant image noise at 80-140 kVp in 10-47 cm diameter abdominal phantoms (31-148 cm in circumference) differed, with few exceptions, by no more than 10% from those obtained with our formula using an HVT of 3.2-3.8 cm. An HVT of 9 cm in the patient study resulted in the same image noise-patient circumference relation as a phantom study using a "clinically adapted mAs" resulting in an acceptable noise according to diagnostic requirements. Clinical experiences recommend an HVT of about 8 cm for abdominal CT and 12 cm in thoracic CT. Changing the kVp from 120 to 80, 100, or 140 requires a mAs change roughly by factors of 4, 2, and 0.6, respectively, for constant image noise. CONCLUSION: Until fully automatic automatic exposure control systems have been introduced, applying the formula in a computer program provides the radiologist with an easy, quick, flexible, and practical instrument for reasonably good patient-sized adjusted exposure levels in clinical practice.

A cystatin C-based formula without anthropometric variables estimates glomerular filtration rate better than creatinine clearance using the Cockcroft-Gault formula.

t In 1976, Cockcroft and Gault introduced a widely used formula comprising several anthropometric variables to compensate for the inadequacies of creatinine level as a marker of glomerular filtration rate (GFR). The present work investigates the possibility of introducing cystatin C-based formulas without anthropometric variables to predict GFR, determined by an invasive "gold standard" procedure (iohexol clearance), and to compare the diagnostic efficiency of such formulas with that of Cockcroft and Gault. All 451 adult patients referred to the University Hospital for determination of GFR by iohexol clearance measurements during a period of 6 months were included in the study. Calculations of bias (median percent error), correlation (adjusted R2), and accuracy (percentage of estimates within 30 and 50% of iohexol clearance) were used in the comparison. The cystatin C-based formula GFR (ml/min)=89.12 x cystatin C(-1.675) had lower bias and higher accuracy in predicting GFR than the Cockcroft-Gault formula. If a cystatin C-based formula including gender was constructed: GFR (ml/min)=99.19 x cystatin C(-1.713) x (0.823 for women), an even lower bias and higher accuracy were obtained. It is suggested that measurement of cystatin C should be used for the initial prediction of GFR of a patient.

Contrast-medium-Induced nephropathy correlated to the ratio between dose in gram iodine and estimated GFR in ml/min.

PURPOSE: To suggest a more precise tool when assessing the risk of contrast-medium-induced nephropathy (CIN), i.e. the ratio between contrast medium (CM) dose expressed in grams of iodine (g-I) and estimated glomerular filtration rate in ml/min (eGFR; based on equations using serum-creatinine (s-Cr), weight, height, age, and/or sex), here named I-dose/GFR ratio. MATERIAL AND METHODS: A Medline search of published CIN investigations reporting mean eGFR and mean dose of low-osmolality CM (LOCM) identified 10 randomized controlled prophylactic and 2 cohort coronary investigations, and 3 randomized and 1 cohort computed tomographic (CT) investigation. From the randomized trials, data were collected only from the placebo or control arms, unless there was no significant difference between the control and test groups. The mean I-dose/GFR ratio of each study was correlated with the mean frequency of CIN-1 (s-Cr rise> or =44.2 micromol/l or > or =20-25%) and CIN-2 (oliguria or requiring dialysis). A maximum dose according to an I-dose/GFR ratio= 1 in patients with s-Cr ranging from 100 to 300 micromol/l was compared with that of CIGARROA'S formula and with a "European consensus" threshold published by the European Society of Urogenital Radiology, both using s-Cr alone to predict renal function. McCullough's formula was used to assess the risk of CIN requiring dialysis at an I-dose/GFR ratio= 1 with LOCM. RESULTS: The coronary investigations revealed a linear correlation with a correlation coefficient between the I-dose/GFR ratio and the frequency of CIN-1 and CIN-2 of 0.91 (P<0.001) and 0.84 (P=0.001), respectively. At a mean I-dose/GFR ratio= 1, the regression line indicated a 10%) risk of CIN-1 and a 1% risk of CIN-2. At a mean I-dose/ GFR ratio=3, the risk of CIN-1 and CIN-2 increased to about 50% and 15%, respectively. Pooled weighted data from the CT investigations revealed a 12% risk of CIN-1 at a mean I-dose/GFR ratio = 1.1 and no cases of CIN-2. The maximum CM dose according to an I-dose/GFR ratio= 1 was about 30-50% of that of both Cigarroa's formula and the "European consensus" in elderly low-weight individuals, while it was similar for middle-aged individuals weighing about 90 kg. McCullough's formula suggests that there will be an exponentially increasing risk of CIN requiring dialysis, but at an I-dose/GFR ratio= 1 and using LOCM it will not exceed 1% until GFR decreases below 30 ml/min in diabetics and below 20 ml/min in non-diabetics. CONCLUSION: Using the I-dose/GFR ratio may be a more expedient way of improving risk assessment of CIN than today's common practice of estimating CM dose from volume alone and renal function from s-Cr alone. Prospective studies based on individual patient data are encouraged to define the risk of CIN at various I-dose/GFR ratios and correlated to type of CM, examination, risk factors, etc.

Negative spiral CT in acute pulmonary embolism.

PURPOSE: To retrospectively evaluate the clinical outcome of non-anticoagulated patients with clinically suspected acute pulmonary embolism (PE) and no symptoms or signs of deep venous thrombosis (DVT) following a negative contrast medium-enhanced spiral CT of the pulmonary arteries (s-CTPA). MATERIAL AND METHODS: During a 24-month period, 739 of 751 patients underwent s-CTPA with acceptable diagnostic quality for clinically suspected acute PE. All patients who had a CT study not positive for PE were followed up with a questionnaire, a telephone interview and review of all medical reports, including autopsies and death certificates for any episodes of venous thromboembolism (VTE) during a 3-month period. RESULTS: PE was diagnosed in 158 patients. Of the remaining 581 patients with a negative s-CTPA, 45 patients were lost to follow-up. 88 patients were excluded because of anticoagulation treatment (cardiac disorder n=32, chronic VTE or acute symptomatic DVT n=31, PE diagnosed at pulmonary angiography n=1, thrombus prophylaxis during diagnostic work-up or other reasons than VTE n=24) and 7 patients undergoing lower extremity venous studies because of symptoms of DVT (all negative). Thus, 441 patients with a negative s-CTPA and no DVT symptoms, venous studies or anticoagulant treatment constituted the follow-up cohort. Four of these patients had proven VTE (all PE) during the 3-month follow-up period. Two of the PE episodes contributed to the patient's death. CONCLUSION: Patients with clinically suspected acute PE, no symptoms or signs of DVT and a negative single slice s-CTPA using 3-5 mm collimation, may safely be left without anticoagulation treatment unless they are critically ill, have a limited cardiopulmonary reserve and/or if a high clinical suspicion remains.

In vitro screening of Indian medicinal plants for antiplasmodial activity.

Plants traditionally used in India to treat fever or malaria were examined in vitro for antiplasmodial properties against Plasmodium falciparum. Of 80 analysed ethanol extracts, from 47 species, significant effects were found for 31 of the extracts. These represent 23 different species from 20 families. Of the active species 20 were tested against P. falciparum for the first time. The following five species seems to be of special interest for further antimalarial studies, Casearia elliptica, Holarrhena pubescens, Pongamia pinnata, Soymida febrifuga, and Plumbago zeylanica.

Clinically suspected pulmonary embolism: is it safe to withhold anticoagulation after a negative spiral CT?

The goal of this study was 3-month clinical outcome in nonanticoagulated patients with clinically suspected acute pulmonary embolism (PE) following a negative spiral CT. During a 6-month period 305 patients underwent spiral CT, of whom only 8 also had a lung scintigraphy. In patients with a final CT report read as not positive for acute PE, all hospital records and answers to a patient questionnaire were analyzed for episodes of venous thrombembolism (VTE). Acute PE was diagnosed at spiral CT in 61 patients (20%). Twenty-six of the remaining 244 patients were excluded from further analysis because of (a) long-term anticoagulation due to symptomatic acute deep venous thrombosis (n = 5), clinically diagnosed acute PE (n = 2), chronic recurrent VTE (n = 4), and cardiac disorders (n = 5); and (b) a normal perfusion scintigram (n = 4) or a negative pulmonary arteriogram (n = 6). Three patients were lost to follow-up. Among the remaining 215 patients only 10 had undergone a negative lower extremity venous study. Sixteen patients (7%) died during the follow-up period, 6 of whom underwent autopsy. Venous thrombembolism was diagnosed in three of the 215 patients (1.4%, 95% confidence limits: 0.5-4.0%), one causing the patient's death. Two patients had advanced thoracic malignancies and the third severe chronic obstructive pulmonary disease (84 years old). A negative spiral CT may be able to exclude clinically significant acute PE with the same accuracy as a normal lung scintigraphy or a negative pulmonary arteriography.

Low risk of contrast-medium-induced nephropathy with modern angiographic technique.

OBJECTIVE AND DESIGN: A retrospective study of the incidence of contrast-medium-induced nephropathy (CMN) in patients with renal insufficiency. SUBJECTS: All angiographies with and without endovascular therapeutic procedures (n = 2400) performed at the hospital during 1 year were evaluated. A total of 139 patients were found to have a preangiographic serum-creatinine (s-Cr) of 150 micromol L(-1) or above. Postprocedural serial s-Cr values were present in 118 patients and these were included in the study. RESULTS: Amongst patients receiving only iodinated contrast media (CM) 8% demonstrated a 25% rise in s-Cr. The corresponding figure was 11 and 12.5% amongst patients who were given either iodinated CM together with carbon dioxide (CO2) or CO2 as sole contrast medium. After exclusion of other explanations of impaired renal function all together only seven of 114 patients (6%) were considered to have developed CMN. Four of the seven patients restituted renal function completely, whilst it remained decreased in three. No patient required dialysis. The percentage of diabetic patients were not found to be different in patients with and without signs of CMN. CONCLUSIONS: The present retrospective study indicate that the risk of CMN in connection with angiography is low when modern low-osmolality CM and contrast saving angiographic technique including CO2 is used combined with proper hydration. Patients with diabetes mellitus were not found more frequently in the groups with CMN.