Effect of radiologic contrast media on cell volume regulatory mechanisms in human red blood cells

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate cell volume regulation in human red blood cells (RBCs) after incubation in solutions of three contrast media: iohexol (830 mOsm), ioxaglate (520 mOsm), and iodixanol (300 mOsm). MATERIALS AND METHODS: Whole blood sampled from six healthy subjects was exposed to Ringer solutions containing 25% or 5% vol/vol iohexol (final osmolality, 440 or 340 mOsm, respectively), ioxaglate (final osmolality, 395 or 335 mOsm, respectively), iodixanol (final osmolality, 330 or 315 mOsm, respectively), or NaCl (control solutions with the same osmolality as that of the contrast media). In some experiments, control RBCs were subjected to a hyposmotic solution (100 mOsm). RBC volumes were obtained with a Coulter counter. RESULTS: The RBCs showed normal regulatory cell shrinkage after hyposmotically induced swelling. All 25% vol/vol contrast material solutions and their control solutions induced RBC shrinkage (range, 6% +/- 1 [standard error] to 22% +/- 3). The same was true for cells exposed to 5% vol/vol contrast material (range, 4% +/- 1 to 7% +/- 1). The shrinkage phase was followed by cell swelling (10% +/- 2 to 20% +/- 2 for 25% contrast material and their control solutions and 8% +/- 1 to 15% +/- 2 for 5% contrast material and their control solutions). No contrast material-exposed RBCs increased their volumes to the level reached with their control solutions. CONCLUSION: RBCs exposed to hyperosmotic iohexol, ioxaglate, or iodixanol solutions shrank and then swelled. The degree of shrinkage and subsequent swelling could not be explained simply with the osmolality of the test solutions. Physicochemical properties of the contrast media must be involved, putatively affecting electrolyte fluxes over the RBC membrane. Possible targets of these effects are the K+/Cl- symporter, K+ channels, and the Na+/K+/Cl- symporter.     

Assessment of myocardium at risk with computerized vectorcardiography and technetium-99m-sestamibi-single photon emission computed tomography during coronary angioplasty

OBJECTIVE: To compare the myocardium at risk (MAR) as estimated by computerized vectorcardiography (cVCG) with MAR determined by Tc-99m-sestamibi-SPECT using coronary angioplasty as the model for transient transmural ischemia in humans. METHODS AND RESULTS: In 37 patients with stable angina pectoris, cVCG was recorded continuously during coronary angioplasty. The scintigraphic defect was quantified using an automated software program (CEqual). The ST vector magnitude (ST-VM) and the ST change vector magnitude (STC-VM) correlated well with MAR estimated by scintigraphy, ST-VM (r = 0.71, p < 0.001) and STC-VM (r = 0.84, p < 0.001). All patients with STC-VM <50 microV during occlusion had defects of less than 10% of the left ventricle. CONCLUSION: 1) ST-VM and STC-VM give a reasonable useful estimate of MAR size during transient coronary occlusion. 2) STC-VM <50 microV is a reliable limit to identify patients with MAR size less than 10%. 3) ST-VM does not add information to STC-VM with respect to detection of ischemia. 4) The existence of collateral vessels has great impact on both ST-vector changes and scintigraphic imaging of myocardial ischemia.     

Aspirin and statin medication decreases the risk of myocardial infarction associated with LTA and NFKBIL1 polymorphisms

Lymphotoxin-α (LTA) is a cytokine involved in inflammatory reactions. NFKBIL1 is a regulator of the NF-κB complex. The study investigated the associations of LTA 804 C>A and NFKBIL1-63 T>A polymorphisms with the use of statin and acetylsalicylic acid (ASA) treatment in relation to myocardial infarction (MI). The study population comprised of 600 Finnish individuals who underwent coronary angiography volunteering for the Angiography and Genes Study. Genotypes were detected by the TaqMan 5′ nuclease assay. We found a interaction between the LTA genotype (p=0.002) and the NFKBIL1 genotype (p=0.012) and statin treatment in relation to MI. Subjects with the LTA AA or the NFKBIL1 AA genotype were at a 2.77 (95% CI:1.22-6.24) and 2.85 (95% CI:1.22-6.66) times higher risk, respectively, of suffering an MI when compared to other genotypes among statin non-users. ASA treatment also modulated associations between LTA and NFKBIL1 genotypes and MI (p=0.015 and p=0.028 respectively). The NFKBIL1-A-LTA-A haplotype showed a 61% increase in the risk of MI compared to the NFKBIL1-T-LTA-C haplotype among statin non-users. Anti-inflammatory medication modifies the genotype-related risk of MI, suggesting that subjects with LTA and NFKBIL1 AA haplotype might especially benefit from the treatment.     

p53 mutations in leukemia and myelodysplastic syndrome after ovarian cancer.

PURPOSE: Although p53 mutations occur in alkylating agent-related leukemias, their frequency and spectrum in leukemias after ovarian cancer have not been addressed. The purpose of this study was to examine p53 mutations in leukemias after ovarian cancer, for which treatment with platinum analogues was widely used. EXPERIMENTAL DESIGN: Adequate leukemic or dysplastic cells were available in 17 of 82 cases of leukemia or myelodysplastic syndrome that occurred in a multicenter, population-based cohort of 23,170 women with ovarian cancer. Eleven of the 17 received platinum compounds and other alkylating agents with or without DNA topoisomerase II inhibitors and/or radiation. Six received other alkylating agents, in one case, with radiation. Genomic DNA was extracted and p53 exons 5, 6, 7, and 8 were amplified by PCR. Mutations and loss of heterozygosity were analyzed on the WAVE instrument (Transgenomic) followed by selected analysis by sequencing. RESULTS: Eleven p53 mutations involving all four exons studied and one polymorphism were identified. Genomic DNA analyses were consistent with loss of heterozygosity for four of the mutations. The 11 mutations occurred in 9 cases, such that 6 of 11 leukemias after platinum-based regimens (55%) and 3 of 6 leukemias after other treatments (50%) contained p53 mutations. Two leukemias that occurred after treatment with platinum analogues contained two mutations. Among eight mutations in leukemias after treatment with platinum analogues, there were four G-to-A transitions and one G-to-C transversion. CONCLUSIONS: p53 mutations are common in leukemia and myelodysplastic syndrome after multiagent therapy for ovarian cancer. The propensity for G-to-A transitions may reflect specific DNA damage in leukemias after treatment with platinum analogues.     

Paradoxical vocal cord movement in newborn and congenital idiopathic vocal cord paralysis: two of a kind?

The second most common cause of stridor reported in the newborn is bilateral vocal cord paralysis (BVCP) and one-third of the cases have been categorized as idiopathic. During the last year four children with stridor since birth were referred to our department for examination. Videotaped flexible laryngoscopy, carried out with the patient awake or under general anaesthesia with a spontanous respiration, revealed instead of abduction of the vocal cords during inspiration, rather an active adductory movement. Consequently instead of BVCP, we made the diagnosis paradoxical vocal cord movement (PVCM). One of the twins required a tracheostomy, the three other patients have been observed without the need of further treatment. No previous publications have described PVCM in newborn. However, our observations and video recordings clearly show that the stridor in our four patients is due to PVCM. This is possibly the same condition as earlier reported as congenital, idiopathic BVCP where incoordinated vocal cord movement or dyskinesia has been a part of the laryngoscopic findings. The mechanism behind PVCM in this age group or site of lesion is unclear.     

Positron Emission Tomography (PET) in Neuroendocrine Gastrointestinal Tumors

Positron emission tomography (PET) makes it possible to study effects of medical treatment in vivo. Carcinoid tumors with liver metastases, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP) and this overproduction contributes to the clinical symptoms of the carcinoid syndrome. Seven patients with histopathologically verified neuroendocrine tumors and liver metastases, five of whom with ileal carcinoids, one a lung carcinoid and one an endocrine pancreatic tumor, were included in the study. All patients had elevation of urinary 5-HIAA with the exception of one patient with a solitary liver metastasis of midgut origin. After an intravenous injection of ¹¹C-5-HTP, PET was performed and the uptake of radioactivity in tumor tissue, normal liver and plasma were compared. All patients with elevated urinary 5-HIAA and also the patient with a solitary liver metastasis and normal urinary 5-HIAA had high accumulation and signs of a high rate of binding of 5-HTP in the liver metastases. The uptake was relatively homogeneous in midgut carcinoid liver metastases but in large necrotic metastases the radioactivity was localized to the periphery. In three patients PET examination was repeated after 3 months of interferon treatment and in agreement with circulating tumor markers and ultrasonography the uptake of 5-HTP was unchanged. Another patient who the somatostatin analog somatuline progressed on treatment and accordingly the uptake of 5-HTP also increased. The experience with PET in neuroendocrine gastrointestinal tumors is very limited. Our results so far indicate that 5-HTP can be used to visualize serotonin-producing neuroendocrine tumors and furthermore it might prove to be of value to monitor the effects of treatment, possibly also as an early predictive test of the outcome of treatment.     

Surface Active Agents as Enhancers of Alveolar Absorption

Purpose. Small solutes which are deposited in the alveoli by aerosolinhalation will be absorbed across the alveolo-capillary barrier.Inhalation of dioctyl sodium sulfosuccinate (DOSS) enhances absorptionwhile having little or no effect on lung function, suggesting that surfaceactive agents may be used as enhancers of alveolar absorption ofinhaled pharmaceuticals. The purpose of this study was to examinethe effects of a selection of different surface active agents onalveolar absorption. Methods. The absorption of ^99mTc-diethylene triamine pentaacetate(^99mTc-DTPA) from the lungs was studied in rabbits. We studied fivedifferent surface active agents: DOSS, sodium glycodioxycholate(GDCA), sodium lauryl sulphate (NaLS), lysophosphatidyl choline(LPC) and polyoxyethylene-23-laurylether (P23LE). Results. DOSS and GDCA both dramatically enhanced the absorptionof ^99mTc-DTPA. There was a moderate effect of NaLS, no significanteffect of LPC and P23LE reduced the rate of absorption. None of thecompounds affected gas exchange or lung compliance. Conclusions. There is a wide spectrum of effects of inhaled surfaceactive agents on the alveolar absorption of ^99mTc-DTPA. Ioniccompounds such as DOSS and GDCA have the greatest effect, and furtherstudies of these classes of surface active agents for use as enhancersof alveolar absorption of pharmaceuticals seem warranted.