Malignancy: Changes in Circulating Immature and Mature Dendritic Cells During IL-2 Cancer Immunotherapy and Their Relation with Lymphocyte Increase and Clinical Response

Lymphocytosis is the main biomarker predicting the efficacy of subcutaneous IL-2 anticancer immunotherapy. In addition, it has been demonstrated the fundamental role of dendritic cells (DC) in the generation of an effective anticancer immunity. However, the relation between IL-2 and DC system needs to be further understood. This preliminary study was performed in an attempt to analyze changes in circulating DC during IL-2 cancer immunotherapy in relation to lymphocyte variations and clinical efficacy of treatment. The study included 20 metastatic renal cell cancer patients, who underwent subcutaneous low-dose IL-2 immunotherapy (6.000.000 IU/day for 6 days/week for 4 weeks). To evaluate DC, venous blood samples were collected before and after 2 weeks of IL-2 injections, corresponding to the period of maximum lymphocytosis. Immature (CD123(+) ) and mature (CD11c(+) ) DC were measured by FACS and monoclonal antibodies. IL-2 induced a significant increase in the mean number of circulating mature DC, whereas no substantial change occurred in immature DC mean number. The increase in mature DC was associated with a control of disease, whereas no rise was observed in patients who had progressed on IL-2 immunotherapy. Moreover, the increase in mature DC mean number was significantly higher in patients showing evident lymphocytosis, with lymphocyte enhancement greater than 1000 cells/mmc, than in patients with less pronounced lymphocytosis, even though no significant correlation was seen in between mature DC and lymphocyte increase. This preliminary study would suggest that IL-2 may stimulate DC system and that the clinical anticancer efficacy of IL-2 is associated with the increase in circulating mature DC, which could be considered as a new favourable biomarker during IL-2 immunotherapy.     

Hormonal and metabolic characteristics of geneticall obese Zucker and dietar obese Sprague-Dawle rats

Abstract. The endocrine-metabolic plasma pattern and the capacit of isolated perfused livers to produce triglcerides and ketone bodies have been studied in geneticall and diet-acquired obese rats (Zucker and Sprague-Dawle obese rats), and in control groups of the same strains.
An increased plasma insulin/glucagon molar ratio with hperinsulinaemia and hpoglucagonaemia was associated with hpertriglceridaemia, normal ketonaemia, elevated free fatt acids and normal or slight hperglcaemia in obese rats.
During oleate perfusion, the livers of Zucker and Sprague-Dawle obese rats showed an increase in triglceride output and liver triglceride content. The ketone bod output as well as the mitochondrial carnitine palmitol transferase activit were normal or slightl decreased.
In our rat population, a positive correlation between the insulin/glucagon molar ratio and triglceride output has been found.     

The Effect of Exogenous Adenosine in Patients with Neurally-Mediated Syncope and Sick Sinus Syndrome

The effects of a 20-mg IV, bolus of adenosine 5'triphosphate (ATP) on the heart rhythm was studied in 79 patients affected by neurally-mediated syncope (26 cases) or sick sinus syndrome (22 cases) or both syndromes (31 cases) and in 31 healthy control subjects in order to examine the sensitivity of cardiac purinoceptors in such circumstances. During ATP infusion, the sinus cycle lengthened to > 2 seconds in no control, in 1 (4%) patient with neurally-mediated syncope, in 5 (23%) patients with sick sinus syndrome, and in 13 (42%) patients with both neurally-mediated and sick sinus syndromes (P = 0.01). Atrioventricular block occurred in 14 (45%) of controls, in 10 (38%) patients with neurally-mediated syncope, in 4 (18%) patients with sick sinus syndrome, and in 13 (42%) patients with both neurally-mediated syncope and sick sinus syndrome (n.s.). Thus, exogenous ATP exerts different effects on patients with neurally-mediated syncope and patients with sick sinus syndrome. In fact, intrisic disease of the sinus node is necessary to modulate an abnormal adenosine-mediated sinus arrest, whereas patients affected by neurally-mediated syncope alone show a normal sensitivity to the drug administration. The effect of ATP on atrioventricular conduction is greater than that on sinus node and is of similar magnitude in patients and controls; thus the clinical meaning of ATP induced atrioventricular block remains uncertain.     

Neuroimaging in childhood arterial ischaemic stroke: evaluation of imaging modalities and aetiologies

Aim The aim of this study was to describe neuroimaging patterns associated with arterial ischaemic stroke (AIS) in childhood and to differentiate them according to stroke aetiology. Method Clinical and neuroimaging (acute and follow‐up) findings were analysed prospectively in 79 children (48 males, 31 females) aged 2 months to 15 years 8 months (median 5y 3mo) at the time of stroke by the Swiss Neuropaediatric Stroke Registry from 2000 to 2006. Results Stroke was confirmed in the acute period in 36 out of 41 children who underwent computed tomography, in 53 of 57 who underwent T2‐weighted magnetic resonance imaging (MRI) and in all 48 children who underwent diffusion‐weighted MRI. AIS occurred in the anterior cerebral artery (ACA) in 63 participants and in all cases was associated with lesions of the middle cerebral artery (MCA). The lesion was cortical–subcortical in 30 out of 63 children, cortical in 25 out of 63, and subcortical in 8 of 63 children. Among participants with AIS in the posterior circulation territory, the stroke was cortical–subcortical in 8 out of 16, cortical in 5 of 16, and thalamic in 3 out of 16 children. Interpretation AIS mainly involves the anterior circulation territory, with both the ACA and the MCA being affected. The classification of Ganesan is an appropriate population‐based classification for our Swiss cohort, but the neuroimaging pattern alone is insufficient to determine the aetiology of stroke in a paediatric population. The results show a poor correlation between lesion pattern and aetiology.     

Bilateral Dental Fusion of the Upper Central Incisors: A Multidisciplinary Approach

Abstract: The multidisciplinary treatment of a case of bilateral dental fusion of the upper central incisors with maxillary constriction, crowding, and palatal inversion of one of the lateral incisors is reported. The rarity with which this anomaly appears, along with its complex characteristics, often make it extremely difficult to treat. It requires the involvement of different specialists to find the most suitable treatment for each individual patient.     

Effects of Procainamide on the Excitable Gap Composition in Common Human Atrial Flutter

The composition of the excitable gap (EG) in common atrial flutter (AFI) was determined before and during infusion of procainamide (PA) in 9 patients (6 men and 3 women; age 70 ± 7 years). The EG was determined by introducing a premature stimulus after every 20th AFI complex detected using a quadripolar electrode catheter placed just above the tricuspid valve. Diastole was scanned in 2- to 4-ms decrements to the atrial effective refractory period (ERP). The relationship between the coupling interval and the return cycle length (CL) determined a reset-response curve (RRC), which described the EG. PA (15 mg/kg) was administered during AFl over 30 minutes and RRC was repeated at maximum AFI CL. PA prolonged AF1 CL from 227 ± 29 to 296 ± 62 ms (P < 0.01) but did not terminate AFI. ERP during AFl prolonged from 169 ± 24 to 219 ± 41 ms (P < 0.01). Control EG was 57 ± 16 ms or 25%± 6% of AFl CL and on PA EG was 77 ± 30 ms (P = 0.01), which was still 26%± 7% of the CL. Without drug, RRC was mixed in eight cases demonstrating an EG composed of fully excitable tissue (10 ± 4 ms or 19%± 10% of the EG) and partially refractory tissue (48 ± 18 ms), PA did not change the duration of the fully excitable region (13 ± 10 ms or 19%± 15% of EG). Peak PA plasma concentration was 47 ± 20 μmol/L. PA prolonged AFI CL, ERP, and EG duration but did not change the proportion of AFI CL occupied by the EG. The persistence of fully excitable tissue at the head of the wavefront in the presence of PA may largely explain its inefficacy in the acute termination of common AFl.     

Patterns of Atrioventricular Conduction During Postexercise Recovery in Patients with Atrial Fibrillation and Wolff-Parkinson-White Syndrome

The effects of the postexercise recovery phase on the functional anterograde conduction properties of the accessory pathway (AP) were evaluated. Twenty-nine patients with Wolff-Parkinson-White (WPW) syndrome were submitted to supine maximal bicycle exercise testing. In seven patients (group I), in whom sustained atrial fibrillation (AF) could be induced by transesophageal pacing (TP), mean ventricular rate (MVR), the shortest R-R interval (SRR) between preexcited beats, and the observed percentage of preexcited beats were evaluated at rest, after each step of exercise and 2 minutes after the end of exercise. In 22 patients (group II), in whom sustained AF could not be induced, decremental TP was performed to evaluate the shortest atrial cycle length (SCL) with 1:1 conduction over AP at rest, after each step of exercise, and 2 minutes after the end of exercise. In four patients in group I, the protocol was repealed with atropine injected during the last minute of exercise. In 12 patients (three from group I and nine from group II), catecholamine plasma levels were measured at rest, at peak exercise, and during recovery. MVR was 144 ± 20 beats/min at rest, 186 ± 21 beats/min at peak exercise (P < 0.001 vs rest), and 179 ± 21 beats/min during recovery (P < 0,001 vs rest; P < 0.05 vs peak exercise). SRR was 289 ± 73 msec at rest, 223 ± 25 msec at peak exercise (P < 0.05 vs rest), and 227 ± 29 msec during recovery. Preexcited beat percentage was 95.4 ± 12 at rest, 35.2 ± 24.2 at peak exercise (P < 0.001 vs rest), and 85.1 ± 22.5 during recovery fP < 0.01 vs peak exercise and n.s. vs rest). In patients in whom atropine was injected MVR was 139 ± 17 beafs/min at rest, 184 ± 19 beats/min at peak exercise (P < 0.05 vs rest), and 172 ± 16 beats/min during recovery (P < 0.05 vs peak exercise, P < 0.05 vs rest); SRR was 320 ± 71 msec at rest, 225 ± 25 msec at peak exercise, and 232 ± 3 inset; during recovery; preexcited beat percentage was 99 ± 1 at rest, 26 ± 18 at peak exercise (P < 0.01 vs rest), and 28 ± 20 during recovery (NS vs peak exercise, P < 0.01 vsrest). In group II. mean sinus rate was 84 ± 12 beats/min at rest, 151 ± 15 beats/min at peak exercise, and 117 ± 21 beats/min 2 minutes after the end of exercise; mean SCL was 328 ± 75 msec at rest, 273 ± 76 msec at peak exercise (P < 0.0001 vs rest), and 280 ± 79 msec during recovery (P < 0.0001 vs rest and NS vs peak exercise). Mean epinephrineand norepinephrine plasma levels (12 patients from groups I and II) were; 4 7.9 ± 76.6 and 355.5 ± 185.1 pg/mL at rest; 193.0 ± 88.0 and 823.9 ± 390.3 pg/mL at peak exercise (P < 0.0001 vsrest); 148.5 ± 94.5 and 672.7 ± 272.3 during recovery (P < 0.001 vs rest; P < 0.01 vs peak exercise). Thus, during early recovery versus peak exercise: SCL and SRR are still lower and confirm the persistence of increased AP conductivity; in patients with atrial fibrillation preexcited beat percentage is markedly enhanced while the duration of preexcited complexes is increased and MVR is still high. The poslexercise recovery phase in patients with WPWand atrial fibrillation determines a higher ventricular response rate with major preexcitation than does rest and peak exercise. The fact that atropine prevents increases in preexcited beats percentage demonstrates that the underlying electrophysiological basis is a discordance of autonomic effects on the conduction properties of the two afrioventricular pathways.