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Biomedical subjects

U Nyman

Publications and source records attributed to U Nyman.

At least 19 recordsLinked to original sources
PubMed2006

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.

Alternative Splicing↗
PubMed2006

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.

Adult↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Adult↗
PubMed2002

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.

Adult↗
PubMed2001

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.

Acute Disease↗
PubMed2001

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.

Animals↗
PubMed2001

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.

Acute Kidney Injury↗
PubMed2000

Endovascular repair of descending thoracic aortic aneurysms: an early experience with intermediate-term follow-up.

PURPOSE: The purpose of this study was to report an initial experience with the endovascular repair of descending thoracic aortic aneurysm. Complications and intermediate-term morphologic changes were identified with the intent of altering patient selection and device design. METHODS: Endografts were placed into 25 patients at high-risk for conventional surgical repair over a 3(1/2)-year period. Devices were customized on the basis of preoperative imaging information. Follow-up computed tomography scans were obtained at 1, 3, 6, and 12 months and yearly thereafter. Additional interventions occurred in the setting of endoleaks, migration, and aneurysm growth. RESULTS: The overall 30-day mortality rate was 20% (12.5% for elective cases; 33% for emergent cases). There were 3 conversions to open repair. Neurologic deficits developed in 3 patients; 1 insult resulted in permanent paraplegia. Neurologic deficits were associated with longer endografts (P =.019). Three endoleaks required treatment, and 1 fatal rupture of the thoracic aneurysm treated occurred 6 months after the initial repair. Migrations were detected in 4 patients. The maximal aneurysm size decreased yearly by 9.15% (P =.01) or by 13.5% (P =.0005) if patients with endoleaks (n = 3 patients) were excluded. Both the proximal and distal neck dilated slightly over the course of follow-up (P =.019 and P =.001, respectively). The length of the proximal neck was a significant predictor of the risk for endoleakage (P =.02). CONCLUSION: The treatment of descending thoracic aortic aneurysms with an endovascular approach is feasible and may, in some patients, offer the best means of therapy. Early complications were primarily related to device design and patient selection. All aneurysms without endoleaks decreased in size after treatment. Late complications were associated with changing aneurysm morphologic features and device migration. The morphologic changes remain somewhat unpredictable; however, alterations in device design may result in improved fixation and more durable aneurysm exclusion.

Aged↗
PubMed2000

Does post-angiographic hemodialysis reduce the risk of contrast-medium nephropathy?

OBJECTIVE: Several strategies have been employed to reduce the incidence of nephrotoxicity in connection with the administration of urographic contrast media. We present the results of a randomized study to explore the effect of a single hemodialysis treatment immediately after an angiographic examination. MATERIAL AND METHODS: The patients studied had moderately reduced renal function. Seventeen of the 32 patients had diabetic nephropathy and 15 had other renal diseases. They were randomly selected to undergo either hemodialysis or standard treatment following the angiographic examination. The glomerular filtration rate (GFR) was determined the day before and 1 week after administration of the contrast medium. All patients were hydrated and received oral calcium-channel blocking treatment before angiography. RESULTS: Hemodialysis lowered the level of contrast medium in plasma by approximately 80%. In spite of this no significant difference in renal iohexol clearance was noted between groups treated and not treated with hemodialysis. CONCLUSIONS: The risk of a marked and sustained reduction in renal function after administration of an iodine contrast medium is low with modern angiographic techniques. Hemodialysis reduces levels of contrast media in plasma but does not reduce the incidence of contrast-medium-induced nephrotoxicity in the GFR range from 10 to 25 ml/min.

Adult↗
PubMed1999

[Spiral computed tomography--solution to diagnostic problems in pulmonary embolism?].

Clinical diagnosis of pulmonary embolism is difficult and often dependent on radiological methods. In Sweden scintigraphy has hitherto been the method most commonly used, though all too often it leaves the diagnosis in doubt. Spiral computed tomography, performed during continuous infusion of contrast medium, clearly depicts the pulmonaries arteries, emboli appearing as filling defects. The examination takes less than one minute. Although the method has yet to be fully evaluated, it is already available at most Swedish hospitals. Results presented so far suggest that the technique has great potential, and may become the method of choice in the diagnosis of pulmonary embolism.

Contrast Media↗