Plasma cyclic nucleotide levels in acute leukemia patients

To verify the clinical usefulness of extracellular cyclic nucleotide determination as a tumor marker, plasma cyclic AMP (cAMP) and cyclic GMP (cGMP) levels were measured in 70 normal subjects and 173 acute leukemia patients studied in different stages of their disease. Mean plasma cAMP levels were similar in leukemic and normal subjects, although in 48 patients in the active stage of the disease, first diagnosis, or relapse, the cAMP values were below the normal range, and most of these patients failed to respond to chemotherapy. Plasma cGMP levels were markedly elevated in untreated patients, normalized in all patients who attained complete remission, and increased promptly to pretreatment values in patients who relapsed, suggesting that their determination may be useful to monitor the patients' response to treatment.     

The impact of different spectral Doppler criteria on the proportion of high-grade internal carotid artery stenosis in patients undergoing duplex scanning

AIM: To investigate the impact of different spectral Doppler criteria on the proportion of high-grade ICA stenosis in patients undergoing carotid artery duplex scanning. MATERIAL AND METHODS: Duplex scans of 4,548 internal carotid arteries (ICA) in 2,349 patients were retrospectively analyzed. The following different criteria were applied for each scan for definition of ICA stenosis > or = 70%: Criteria I=ICA peak systolic velocity (PSV) > 130 cm/sec and ICA end-diastolic (EDV) > 100 cm/sec, Criteria II=PSV ICA/common carotid artery (CCA) ratio > 4, Criteria III=ICA PSV > or = 230 cm/sec, Criteria IV=ICA PSV > 230 cm/sec and/or ICA EDV > or = 100 cm/sec and/or PSV ICA/CCA ratio > or = 3.2. RESULTS: The frequency of detecting a > or = 70% ICA stenosis with criteria I, II, III, and IV were 5.5%, 6.8%, 8.4%, and 9.6%, respectively (p < 0.05). CONCLUSION: The use of various duplex criteria significantly affected the number of scans receiving a diagnosis of ICA stenosis of > or = 70%.     

Quantitative assessment of muscle stiffness with acoustic radiation force impulse elastography after botulinum toxin A injection in children with cerebral palsy

Purpose

Our objective in this study was to assess the changes in medial gastrocnemius muscle (GCM) stiffness after botulinum toxin A (BTA) injection in children with cerebral palsy (CP) by using acoustic radiation force impulse (ARFI) elastography and to research the usability of this technique in clinical practice.

Materials and methods

Twenty-four spastic lower extremities of 12 children with CP were assessed. BTA injection treatment was applied to the medial GCM. Muscle stiffness was measured with the ARFI technique before the procedure and a month after the procedure. The patients were assessed with the modified Ashworth scale (MAS) in the physiotherapy department at about the same time. Shear wave velocity (SWV) values and MAS scores before and after the treatment were compared.

Results

Mean SWV values were measured as 3.20 ± 0.14 m/s before BTA and as 2.45 ± 0.21 m/s after BTA, and the difference between them was found to be statistically significant (p < 0.001). Mean MAS score (2.33 ± 0.70) after BTA decreased significantly when compared to the score before BTA (2.96 ± 0.62) (p = 0.001). SWV values positively correlated with MAS scores (ρ = 0.578, p = 0.003). The interobserver agreement expressed as interclass correlation coefficient (ICC) was 0.65 (95% CI 0.33–0.84, p < 0.001).

Conclusion

ARFI elastography for identifying structural changes that occur in the spastic muscle after BTA injection in children with CP can yield more valuable information with combined use of MAS.

     

Amplification of genes encoding human myeloid membrane antigens after DNA-mediated gene transfer

Spontaneous amplification of genes encoding two different human myeloid surface antigens was observed after DNA-mediated gene transfer of cellular DNA from the human myeloid cell line HL-60 into NIH-3T3 mouse fibroblasts. Transformed recipient cells with highly amplified expression of either of two donor membrane polypeptides, gp150 or p67, were isolated with a fluorescence-activated cell sorter (FACS), using monoclonal antibodies specific for human myeloid cells. Immunoprecipitation of enzymatically radioiodinated polypeptides from the surface of transformed NIH-3T3 cells confirmed that expression of these proteins was amplified tenfold to 20-fold in comparison to their expression on human myeloid cell lines. The cellular DNA of cloned secondary and tertiary transformants expressing high levels of gp150 and p67 contained amplified sets of DNA restriction fragments that hybridized with human repetitive DNA sequences. Cytogenetic analysis of subclones overexpressing gp150 revealed extrachromosomal double minutes (DMs), whose presence correlated with the unstable expression of the membrane polypeptide. Human sequences in gp150-positive clones did not localize to chromosomes, consistent with their association with extrachromosomal DMs. By contrast, p67-positive subclones stably expressed the antigen, and in situ hybridization to metaphase spreads demonstrated that amplified human DNA sequences were integrated into a specific marker chromosome. Cytogenetic analysis of the parental NIH- 3T3 subclone used in these studies disclosed DMs in a low percentage of metaphases, suggesting that the recipient cells have a propensity for amplifying donor DNA.     

Reliability and validity of the Turkish version of the Falls Efficacy Scale International (FES-I) in community-dwelling older persons

The FES-I is a questionnaire which was developed to assess fear of falling. The aim of this study was to evaluate validity and reliability of a Turkish language version of the FES-I in Turkish older people. The study sample included 70 volunteers with an age range of 65-81. To assess the test-retest reliability of the Turkish FES-I, questionnaire was applied again 10-15 days after the first interview (interclass correlation: ICC). FES-I was compared with The Modified Barthel Index (MBI), the timed up and go test (TUG), and The Berg Balance Scale (BBS) for construct validity. Cronbach's alpha (α) was used to evaluate the internal consistency. The internal structure of the FES-I was examined by factor analysis. ROC plots were used to define cut-point for the FES-I scales. Cronbach's α of the Turkish FES-I was 0.94 and the individual item ICC ranged from 0.97 to 0.99. The Turkish FES-I total scores were correlated with TUG positively, and MBI, and BBS negatively. The cut-off score to differentiate between persons with fear of falling and persons without fear of falling was 24 points. It was found that the Turkish version of the FES-I was a reliable and valid measure of fear of falling in Turkish older people.     

Experimental inhibition of protamine cardiotoxicity by prostacyclin

Twelve animals (26+/-5 kg) were subjected to the study. In this experimental study, the authors used prostacyclin to inhibit the toxic metabolite release during protamine administration. Animals were divided into two equal groups. Six animals received prostacyclin (the prostacyclin group), and the other six animals did not receive any additional treatment (the control group). All cardiac output and biochemical measurements were evaluated at baseline; before cardiopulmonary bypass; and at 5, 30, and 60 minutes after protamine administration. The measured cardiac index showed that the hearts treated with prostacyclin had satisfactory preservation of left ventricular function. Metabolic and biochemical data showed that the tumor necrosis factor level was raised significantly in the control group (20.75+/-2.2 in the control group and 13.75+/-2.5 pg/mL in the prostacyclin group). Also, E and P selectin levels were elevated in the control group, but this change was less marked in the prostacyclin group. In addition, the intracellular adhesion molecule-1 (ICAM-1) level was significantly higher in the control group than in the prostacyclin group (9.26+/-2.13 in the control group and 5.13+/-1.66 ng/mL in the prostacyclin group). The authors observed that prostacyclin inhibited the toxic mediator release during heparin reversal with protamine. This inhibition is one way of protecting the myocardium reserves from protamine cardiotoxicity.     

Perturbations in the erythroid marrow progenitor cell pools may play a role in the augmentation of HbF by 5-azacytidine

In vivo observations on the kinetics of F cells and of fetal hemoglobin (HbF) synthesis and in vitro studies of erythroid progenitors, their number, and the gamma-gene expression in their progeny were carried out in baboons (Papio cynocephalus) treated with 5-azacytidine. Maximum effect on the increase of HbF production in vivo was observed only when an expanded erythroid marrow population was present. In these animals, as well as in normal animals, treatment resulted in a significant reduction of the late erythroid progenitor cell pools (erythroid clusters and erythroid colony-forming units, CFU-E) in the marrow. This reduction was more pronounced among those progenitors grown in the absence of added erythropoietin, and it was followed by a rebound a few days after treatment cessation, reflecting the accumulation of regenerating progenitors. An early increase in the in vitro synthesis of HbF in erythroid clusters and CFU-E colonies was observed. This increase was further documented at the cellular level, with immunofluorescent labeling of colonies with monoclonal anti-gamma- globin chain antibodies. In contrast to the findings in late progenitors, the number of erythroid burst-forming unit (BFU-E) colonies and the synthesis of HbF in these colonies was not influenced significantly by 5-azacytidine treatment. It is proposed that the toxic effects of 5-azacytidine on late progenitors, leading to faster mobilization of earlier progenitors to the next more mature compartment, play a role in the in vivo augmentation of HbF synthesis by this drug. This perturbation in the progenitor cell population kinetics and the presumed hypomethylation of the surviving differentiating cells may act synergistically to produce a maximum HbF response after 5-azacytidine treatment.     

Human Calcitonin Delivery in Rats by Iontophoresis

Abstract— In-vitro iontophoresis (0·33 mA cm⁻²) of calcitonin (50 μg mL⁻¹, pH 4) was performed with the hairless rat skin model. Direct current was as potent as pulse current (2·5 kHz on/off 1/1) iontophoresis in promoting transdermal permeation of calcitonin. Increase in duration of current application from 20 min to 1 h did not increase calcitonin flux. Results suggest that calcitonin can be blocked in the skin pores through which it travels or can accumulate in the skin and be progressively released from the depot. Invivo experiments showed that transdermal iontophoretic administration of calcitonin induced a hypocalcaemic effect in rats.