Frequency of telomerase-specific CD8+ T lymphocytes in patients with cancer

Telomerase is considered a universal tumor-associated antigen (TAA) due to its high rate of expression by cancers (approximately 90%), and clinical trials are in progress to test the immunotherapeutical efficacy of antitelomerase immunization in patients with cancer. However, the data concerning frequency and functional activity of telomerase-specific cytotoxic T lymphocytes (CTLs) in patients with cancer are few and conflicting, although their knowledge would be mandatory to predict the efficacy of telomerase-specific immunotherapy in selected patients. We performed this study to analyze frequency and cytolytic function of circulating CD8+ T lymphocytes specific for the p540 telomerase peptide in a series of human leukocyte antigen (HLA)-A2+ cancer patients. The results show that most patients with cancer have circulating telomerase-specific CD8+ T lymphocytes, but a high frequency of telomerase-specific CTLs are present only in a fraction of them. Furthermore, CTL lines able to kill telomerase-positive tumor cells, including autologous cancer cells, can be expanded ex vivo from some, but not all, patients with cancer. In conclusion, the results of the study support the development of clinical protocols using telomerase peptides as an immunizing agent. However, they underline the necessity to study single patients immunologically before undergoing vaccination, to select the patients adequately, and to eventually adapt the immunization schedule to the patient's immunologic status.     

Ultrasonometric evaluation of bone healing: Experimental study using a model of diaphyseal transverse osteotomy of sheep tibiae

Noninvasive ionizing-radiation-free methods of evaluation, such as ultrasonometry, are desirable in any medical situation. An in vitro ultrasonometric study was undertaken to evaluate the bone healing process of sheep tibiae submitted to a diaphyseal transverse osteotomy at different times after the procedure. Fifteen sheep weighing an average of 37 kg had surgery for a transverse mid-diaphyseal osteotomy of the right tibia; they were divided postoperatively into three groups of five for periods of observation at 30, 45 and 60 days. The intact left tibiae of the 15 animals were used for control. The healing process was monitored with conventional radiographs taken at two-week intervals, and the animals were killed at the end of the period of observation of each group. Both surgical and intact tibiae were removed, their diameters were measured and they were submitted to measurement of underwater ultrasound propagation velocities (USPV) at the osteotomy sites in both the sagittal and frontal planes. The diameters of the surgical tibiae decreased with time in both planes (from 26.9 mm to 22.0 mm and to 20.9 mm in the sagittal plane, and from 29.3 mm to 23.9 mm and to 23 mm in the frontal plane), with significant differences between the periods of observation (p < or = 0.018 and p < or = 0.003 between 30 and 45 days and 30 and 60 days, respectively, for the sagittal plane and p < or = 0.006 and p < or = 0.003 between 30 and 45 days and 30 and 60 days, respectively, for the frontal plane) and between surgical and intact tibiae at all time points (p < or = 0.0005 for each comparison). USPV increased with time from 2290 m/s to 2399 m/s and to 2382 m/s in the sagittal plane, and from 2376 m/s to 2472 m/s and to 2466 m/s in the frontal plane, accounting for an approximate 5% difference between 30 and 60 days Differences between the surgical and intact tibiae were significant at all time points (p < or = 0.0005 for both sagittal and frontal planes) but not between periods for either plane. There was a strong negative correlation between diameter and USPV (Pearson's correlation coefficient of -0.8998 for the sagittal plane and -0.9192 for the frontal plane). It was concluded that ultrasonometric evaluation of the bone healing process is feasible, yielding precise and reliable results, with a potential for clinical application.     

Incremental diagnostic value of ultrasonographic assessment of coronary flow reserve with high-dose dipyridamole in patients with acute coronary syndrome

BACKGROUND: Coronary flow reserve (CFR) assessment by transthoracic Doppler echocardiography has been found to be useful in subjects with suspected coronary artery disease. An important clinical question is whether such technique can be successfully applied in patients admitted to the coronary care unit with an acute coronary syndrome to detect a significant left anterior descending (LAD) disease. METHODS: One hundred fifty-nine patients with acute coronary syndrome (93 patients with unstable angina, 66 with acute inferior or lateral myocardial infarction) were included in the present analysis. Patients underwent a high-dose dipyridamole stress (0.84 mg/kg) with combined assessment of CFR in the LAD and regional wall motion. Blood flow velocities were recorded in the mid-distal portion of the LAD using a digital ultrasonographic system and CFR was calculated as the ratio of hyperemia-induced peak diastolic velocity to resting peak diastolic flow velocity. All patients underwent coronary angiography and a significant LAD stenosis was classified for lumen narrowing > or = 70%. RESULTS: Adequate Doppler recordings in the LAD were obtained in 92% of patients. A contrast agent was used in the 39% of examinations. No major adverse reaction occurred in any patient. A receiving operating characteristic curve showed that a CFR value < 1.9 had a sensitivity of 85%, a specificity of 87%, a positive predictive value of 71%, a negative predictive value of 94% and a diagnostic accuracy of 86% for identifying a significant LAD stenosis. The area under the receiving operating characteristic curve computed for CFR was significantly higher than for wall motion score index (p < 0.001). In a stepwise forward, multiple logistic regression analysis, both CFR (OR = 4.8, 95% C.I. 3.7-5.3; p < 0.00001) and the wall motion score index for the LAD territory (OR = 4.2, 95% C.I. 2.6-6.8; p < 0.0001) were independent determinants of LAD stenosis > or = 70%. CONCLUSION: Early assessment of CFR by transthoracic Doppler echocardiography is feasible and safe and provides additional information to identify subjects with acute coronary syndrome and significant LAD stenosis.     

In utero exposure to di-(2-ethylhexyl) phthalate affects liver morphology and metabolism in post-natal CD-1 mice

The plasticizer di-(2-ethylhexyl)phthalate (DEHP) affects reproductive development, glycogen and lipid metabolism. Whereas liver is a main DEHP target in adult rodents, the potential impact on metabolic programming is unknown. Effects of in utero DEHP exposure on liver development were investigated upon treatment of pregnant CD-1 mice on gestational days (GD)11–19. F1 mice were examined at post-natal days 21 (weaning) and 35 (start of puberty): parameters included liver histopathological, immunocytochemical and α-fetoprotein (AFP) gene expression analyses. In utero DEHP exposure altered post-natal liver development in weanling mice causing significant, dose-related (i) increased hepatosteatosis, (ii) decreased glycogen storage, (iii) increased β-catenin intracytoplasmic localization (females only). At puberty, significantly decreased glycogen storage was still present in males. A treatment-induced phenotype was identified with lack of glycogen accumulation and intracytoplasmic localization of β-catenin which was associated with increased AFP gene expression. Our findings suggested that DEHP alters post-natal liver development delaying the programming of glycogen metabolism.     

Hypersexual behaviour, frotteurism and delusional jealousy in a young parkinsonian patient during dopaminergic therapy with pergolide: A rare case of iatrogenic paraphilia

Neuropsychological and psychopathological modifications induced by dopaminergic drugs in patients with Parkinson's disease (PD) are invariably not taken into sufficient consideration by the neurologist. Among the former, modifications of sexual urges and behaviours are of particular importance with regard to severity and variety of clinical pictures. Although rare, such modifications may assume the connotations of an aberrant sexual behaviour with criminal implications, in line with a diagnosis of paraphilia. The authors report the case of a 51-year-old male PD patient who, after a few years of dopaminergic treatment with pergolide, developed a paraphilic disorder, consistent with DSM-IV TR diagnosis of frotteurism, and delusional jealousy. The patient presented mild motor impairment and lack of or negligible cognitive deterioration, thus providing evidence that these disorders are not typical of advanced PD. Pergolide was reduced and quetiapine, an atypical neuroleptic, was introduced with subsequent subsiding of the paraphilic disorder and improvement of delusional jealousy.