Tissue Distribution of P32-Labeled Parathion

Repeated inhalation of the vapors of bis(chloromethyl) ether and chloromethyl methyl ether at one and two ppm, respectively, and of the aerosol of urethan at approximately 138 ppm, resulted in an increase in incidence of pulmonary adenomas in strain A mice. In addition, the high toxicity of the two haloethers and the general lack of properties irritating to the upper respiratory tract in all three compounds pose an insidious industrial handling hazard.     

Uptake of iodine-123-α-methyl tyrosine by gliomas and non-neoplastic brain lesions

Using single-photon emission tomography (SPET), the radiopharmaceuticall,-3-iodine-123--methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating high-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours.     

Kyphoplasty for treatment of osteoporotic vertebral fractures: a prospective non-randomized study

Background Minimally invasive augmentation techniques of vertebral bodies have been advocated to treat osteoporotic vertebral body compression fractures (VBCFs). Kyphoplasty is designed to address both fracture-related pain as well as kyphotic deformity usually associated with fracture. Previous studies have indicated the potential of this technique for reduction of vertebral body height, but there has been little investigation into whether this has a lasting effect. The current study reports on our experience and the one-year results in 27 kyphoplasty procedures (24 patients) for osteoporotic VBCFs.Results All but one patient experienced pain relief following the procedure (on VAS 1–10)—with a lasting effect over the follow-up period in 25 cases. An average vertebral kyphosis reduction of 47.7% was achieved with no loss of reduction after one year. The potential for reduction was statistically related to the pre-operative amount of kyphosis, the level treated, and the age of the fracture, but not to the age of the patient. During follow-up, one fracture adjacent to a treated level was observed. Pain relief was not related to the amount of reduction.Conclusion Kyphoplasty is an effective treatment of VBCFs in terms of pain relief and durable reduction of deformity. Whether spinal realignment results in an improved long-term clinical outcome remains to be investigated.     

Noninvasive grading of untreated gliomas: a comparative study of MR imaging and 3-(iodine 123)-L-alpha-methyltyrosine SPECT

PURPOSE: To compare the accuracy of magnetic resonance (MR) imaging scores with that of 3-(iodine 123)-L-alpha-methyltyrosine ((123)I-IMT) single photon emission computed tomography (SPECT) in the noninvasive grading of untreated gliomas. MATERIALS AND METHODS: The study comprised 15 patients with low-grade gliomas (grades I-II, according to World Health Organization criteria) and 33 patients with high-grade gliomas (grades III-IV). The lesions were evaluated by using an MR imaging score based on nine criteria. The (123)I-IMT uptake was quantified as the ratio between the amino acid uptake in the tumor and that in the contralateral hemisphere. To test for potentially significant differences in diagnostic performance between contrast material-enhanced MR imaging and (123)I-IMT SPECT, binormal receiver operating characteristic curves were fitted to the data and compared by using the area test. RESULTS: The accuracy of MR imaging in the noninvasive grading of untreated gliomas was higher than that of (123)I-IMT SPECT (88% vs 79%). However, the difference in diagnostic performance was not significant on the basis of findings at receiver operating characteristic analysis (P >.2). Neither MR imaging nor (123)I-IMT SPECT allowed differentiation between high-grade gliomas (grades III and IV). CONCLUSION: Although (123)I-IMT uptake is significantly higher in high-grade gliomas than in low-grade gliomas, the performance of (123)I-IMT SPECT adds little to the accuracy of determining tumor grade when MR imaging is performed.     

Ultrasound-guided supraclavicular cannulation of left brachiocephalic versus right internal jugular vein: Comparative analysis of central venous catheter-associated complications

Aims

Central venous catheters are essential for the management of pediatric cardiac surgery patients. Recently, an ultrasound-guided access via a supraclavicular approach to the brachiocephalic vein has been described. Central venous catheters are associated with a relevant number of complications in pediatric patients. In this study, we evaluated the frequency of complications of left brachiocephalic vein access compared with right internal jugular vein standard access in children undergoing cardiac surgery.

Methods

Retrospective analysis of all pediatric cases at our tertiary care university hospital over a two-year period receiving central venous catheters for cardiac surgery. Primary endpoint: Frequency of complications associated with central venous catheters inserted via the left brachiocephalic vein vs. right internal jugular vein. Complications were defined as: chylothorax, deep vein thrombosis, sepsis, or delayed chest closure. Secondary endpoints: Evaluation of the insertion depth of the catheter using a height-based formula without adjustment for side used.

Results

Initially, 504 placed catheters were identified. Following inclusion and exclusion criteria, 480 placed catheters remained for final analysis. Overall complications were reported in 68/480 (14.2%) cases. There was no difference in the frequency of all complications in the left brachiocephalic vein vs. the right internal jugular vein group (15.49% vs. 13.65%; OR = 1.16 [0.64; 2.07]), nor was there any difference considering the most relevant complications chylothorax (7.7% vs. 8.6%; OR = 0.89 [0.39; 1.91]) and thrombosis (5.6% vs. 4.5%; OR = 1.28 [0.46; 3.31]). The mean deviation from the optimal insertion depth was left brachiocephalic vein vs. right internal jugular vein 5.38 ± 13.6 mm and 4.94 ± 15.1 mm, respectively.

Conclusions

Among children undergoing cardiac surgery, there is no significant difference between the supraclavicular approach to the left brachiocephalic vein and the right internal jugular vein regarding complications. For both approaches, a universal formula can be used to determine the correct insertion depth.     

Effects of smoking on renal function in patients with type 1 and type 2 diabetes mellitus.

BACKGROUND: Smoking increases the risk of end-stage renal failure in patients with primary renal disease. Whether and to what extent smoking affects the kidneys in diabetic patients with normal renal function and variable degrees of proteinuria has not been fully studied. METHODS: We followed 185 patients with type 1 or 2 diabetes mellitus and with or without signs of overt renal disease for at least 3 years, median 5.1 (3-6.8) years. Each patient had a baseline visit and at least four follow-up visits (average 4.8+/-0.3). Cases were patients who were smoking (n = 44) at the time the survey was started. Controls were patients who had never smoked (n = 141). Glomerular filtration rate (GFR) was estimated using the MDRD formula. Multiple logistic regression was used to correct for confounding factors. RESULTS: At baseline, smokers were younger (47+/-14 vs 54+/-16 years, P < 0.01), and had a lower GFR (95+/-26 ml/min) than non-smokers (107+/-33 ml/min, P < 0.05). Mean GFR remained constant during follow-up in non-smokers (106+/-31 ml/min), but decreased significantly in smokers (83+/-22 ml/min, P < 0.0001), and this relationship persisted when adjusted for retinopathy, glycaemic control, age, body habitus, ACE-inhibitor treatment, blood pressure control or severity of proteinuria. The effect of smoking on GFR decline was stronger in patients with type 1 diabetes or male gender. CONCLUSIONS: Cigarette smoking causes a decrease in GFR in diabetic patients with normal or near-normal renal function, independent of confounding factors including severity of proteinuria. The latter finding suggests a mechanism independent of glomerular damage.     

Sequential scintigraphic strategy for the differentiation of brain tumours

Both thallium-201 and iodine-123 α-methyltyrosine (¹²³I-IMT) have been shown to be useful in the diagnostic evaluation of brain tumours. The aim of this study was to investigate the respective contributions of ²⁰¹Tl and ¹²³I-IMT single-photon emission tomography (SPET) in the non-invasive evaluation of intracerebral tumours. We analysed 65 patients with the following brain tumours: 8 non-neoplastic lesions, 4 meningiomas, 12 low-grade gliomas, 28 high-grade gliomas, 11 metastases and 2 high-grade lymphomas. ²⁰¹Tl SPET and ¹²³I-IMT SPET were performed [start of ²⁰¹Tl SPET: 15 min p.i. (early) and 180 min p.i. (delayed); start of ¹²³I-IMT SPET: 15 min p.i.]. The intensity of uptake was quantified as the ratio between tracer accumulation in the tumour and in the contralateral hemisphere. None of the non-neoplastic lesions or low-grade gliomas expressed marked ²⁰¹Tl uptake. All malignant tumours except one small metastasis and all meningiomas except one small, cystic and degenerated lesion showed significant ²⁰¹Tl accumulation [Tl(15’)>2.0]; ¹²³I-IMT uptake was either absent or intermediate in non-malignant lesions except in two low-grade gliomas; the highest levels were observed in high-grade gliomas followed by metastases and lymphomas (mean IMT: 2.7 vs 2.1 vs 1.8), with metastases showing a high variability in ¹²³I-IMT uptake (range: 0.8–3.6). Using ²⁰¹Tl to distinguish non-neoplastic lesions from malignant tumours and meningiomas, 63 of 65 patients were characterised correctly. In the latter group, high-grade gliomas were correctly identified in 27 of 28 cases by their amino acid uptake. It is concluded that the combination of ²⁰¹Tl and ¹²³I-IMT surpasses the accuracy of each single test in the differentiation of space-occupying lesions of the brain. Based on these preliminary results, a sequential strategy is proposed involving an initial ²⁰¹Tl SPET study and an additional ¹²³I-IMT SPET study in the event of positive ²⁰¹Tl uptake. Received 1 October 1999 and in revised form 8 January 2000     

A Mouse Mammary Gland Involution mRNA Signature Identifies Biological Pathways Potentially Associated with Breast Cancer Metastasis

Mouse mammary gland involution resembles a wound healing response with suppressed inflammation. Wound healing and inflammation are also associated with tumour development, and a ‘wound-healing’ gene expression signature can predict metastasis formation and survival. Recent studies have shown that an involuting mammary gland stroma can promote metastasis. It could therefore be hypothesised that gene expression signatures from an involuting mouse mammary gland may provide new insights into the physiological pathways that promote breast cancer progression. Indeed, using the HOPACH clustering method, the human orthologues of genes that were differentially regulated at day 3 of mammary gland involution and showed prolonged expression throughout the first 4 days of involution distinguished breast cancers in the NKI 295 breast cancer dataset with low and high metastatic activity. Most strikingly, genes associated with copper ion homeostasis and with HIF-1 promoter binding sites were the most over-represented, linking this signature to hypoxia. Further, six out of the ten mRNAs with strongest up-regulation in cancers with poor survival code for secreted factors, identifying potential candidates that may be involved in stromal/matrix-enhanced metastasis formation/breast cancer development. This method therefore identified biological processes that occur during mammary gland involution, which may be critical in promoting breast cancer metastasis that could form a basis for future investigation, and supports a role for copper in breast cancer development. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. An erratum to this article can be found at     

Tranexamic acid in total hip arthroplasty saves blood and money: a randomized, double-blind study in 100 patients

BACKGROUND: A blood transfusion is a costly transplantation of tissue that may endanger the health for the recipient. Blood transfusions are common after total hip arthroplasty. The total saving potential is substantial if the blood loss could be reduced. Studies on the use of tranexamic acid have shown interesting results, but its benefits in total hip arthroplasty have not yet been resolved. PATIENTS AND METHODS: 100 patients receiving a total hip arthroplasty (THA) got a single injection of tranexamic acid (15 mg/kg) or placebo intravenously before the start of the operation. The study was double-blind and randomized. Total blood loss was calculated from the hemoglobin (Hb) balance. Volume and Hb concentration of the drainage was measured 24 h after the operation. Intraoperative blood loss was estimated volumetrically and visually. RESULTS: The patients who received tranexamic acid (TA) bled less. The total blood loss was on average 0.97 L in the TA group and 1.3 L in the placebo group (p < 0.001). 8/47 (0.2) in the TA group were given blood transfusion versus 23/53 (0.4) in the placebo group (p = 0.009). Drainage volume and drainage Hb concentration were less in the TA group (p < 0.001 and p = 0.001). No thromboembolic complications occurred. INTERPRETATION: Considering the cost of blood and tranexamic acid only, use of the drug would save EUR 47 Euro per patient. We recommend a preoperative single dose of tranexamic acid for standard use in THA.     

Evaluation of regional myocardial perfusion in patients with severe left ventricular dysfunction: Comparison of 13N-ammonia PET and 99mTc sestamibi SPECT

Objective

Positron emission tomography (PET) scanning with ¹³N-ammonia and ¹⁸FDG is well established for the detection of myocardial viability. Due to the limited availability of PET facilities, recent studies have combined technetium 99m sestamibi single photon emission computed tomography (SPECT) with ¹⁸FDG PET or ¹⁸FDG SPECT. This approach enables simultaneous assessment of regional myocardial blood flow and metabolism and substantially increases the capacity for viability detection. To validate whether ^99mTc-Sestamibi SPECT can replace ¹³N-ammonia PET, we compared these two modalities in patients with severe left ventricular dysfunction due to coronary artery disease.

Materials and Methods

Thirty-one patients (mean age 57±8 years; mean ejection fraction 27%±8%) with angiographically verified coronary artery disease were included. In random order, ammonia-PET and sestamibi-SPECT scans were performed. In a 20-segment model of the left ventricle, two blinded observers scored a total of 610 segments on a five-point scale. In a subset of 20 patients, 400 segments were scored twice to evaluate the observer variations of the two techniques. Segmental score differences were used to compare the imaging modalities. The impact on viability detection was assessed by combining the two flow tracers with FDG PET.

Results

Segmental comparison of the PET and SPECT studies yielded similar (difference ≤1) results in 74% of segments, reflecting regional concordance values in the lateral, apical, anterior, septal, and inferior myocardial walls of 86%, 82%, 71%, 66%, and 63%, respectively. The differences in the septal and inferior walls were primarily due to overestimation of perfusion defects by sestamibi SPECT, which yielded a higher proportion of mismatch patterns in those regions. The overall observer variations of the PET and SPECT studies were 7.5% and 5.8%.

Conclusion

Myocardial perfusion imaging with ¹³N-ammonia PET and ^99mTc-sestamibi SPECT yielded similar results in patients with severe left ventricular dysfunction, except for the septal and inferior regions. In these regions, SPECT tended to overestimate perfusion defects. Hence, attenuation correction should be considered when combining FDG PET and sestamibi SPECT for diagnosing myocardial viability to avoid overestimation of mismatch patterns in those regions.