Effect of imaging time on the values of the sacroiliac index

Quantitative scintigraphy of the sacroiliac joints was performed in a group of normal subjects and a group of subjects with unilateral and bilateral sacroiliitis. The aim of the study was to determine whether the time intervals of imaging had any effect on the values of the sacroiliac index. Imaging was performed every 30 min up to 300 min and the indices were calculated at the time intervals mentioned. We found that the values of the sacroiliac index increased in the group of normal subjects until 150 min after the application of the radiopharmaceutical, and that in the group of subjects who had sacroiliitis they increased until 210 min. The results show that the time interval optimal to quantitative sacroiliac joint imaging is at least 3 1/2 h after administration of the radiopharmaceutical.     

Single step enrichment of blood dendritic cells by positive immunoselection

Dendritic cells (DC) for cancer immunotherapy protocols are generated most commonly by in vitro differentiation of monocytes with exogenous cytokines (Mo-DC). However, Mo-DC differ in their molecular phenotype and function from blood DC (BDC). Clinical isolation of BDC has been limited to the use of density gradients, which result in low yields of variable purity. We have developed a DC enrichment platform, which uses the CMRF-44 (IgM) or CMRF-56 (IgG) monoclonal antibodies (mAb) to select BDC that express these antigens after a short overnight incubation. After culture of peripheral blood mononuclear cells (PBMC) in autologous/AB serum, biotinylated CMRF-44 was used to select DC in a single step immuno-magnetic bead procedure; this produced populations containing up to 99% CMRF-44(+) cells, including up to 67% CMRF-44(+) CD14(-) CD19(-) DC, from an initial starting population of approximately 0.5%. We observed consistent differences in the purities obtained from individual donors with a mean of 54% CMRF-44(+) cells (range 19-99%). Similar results were obtained using biotinylated CMRF-56 mAb, an antibody identifying a comparable population in cultured PBMC. We recovered an average of 54% and 66% of the available BDC in separations performed with the CMRF-44 and CMRF-56 mAb, respectively. The reproducibility of the procedure and the ability to perform it in a closed sterile system makes it suitable for clinical use. Larger scale preparations starting from apheresis derived PBMC will produce sufficient BDC for immunotherapy protocols. The purified BDC elicited strong allogeneic mixed leukocyte reactions and HLA classes II- and I-restricted antigen-specific primary immune responses.     

Pentadecapeptide BPC 157 attenuates disturbances induced by neuroleptics: the effect on catalepsy and gastric ulcers in mice and rats.

A gastric pentadecapeptide, BPC 157, with the amino acid sequence, Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, MW 1419, known to have a variety of protective effects in gastrointestinal tract and other organs, was recently shown to particularly affect dopamine systems. For instance, it blocks the stereotypy produced acutely by amphetamine in rats, and the development of haloperidol-induced supersensitivity to amphetamine in mice. Consequently, whether pentadecapeptide BPC 157, that by itself has no cataleptogenic effect in normal animals, may attenuate the immediate effects of neuroleptics application, particularly catalepsy, was the focus of the present report. Prominent catalepsy, otherwise consistently seen in the mice treated with haloperidol (0.625, 1.25, 2.5, 5.0 and 10.0 mg/kg b.w., i.p.) and fluphenazine (0.3125, 0.625, 1.25, 2.5 and 5.0 mg/kg b.w., i.p.) after 1.5, 3, 4.5, 6 and 7.5 h following administration, was markedly attenuated when pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w., i.p.) was coadministered with the neuroleptic. The number of cataleptic mice was markedly lower throughout most of the experimental period. Moreover, on challenge with lower doses of neuroleptics, catalepsy appearance was postponed and the mice, otherwise cataleptic since the earliest period, became cataleptic later, not before 3 or 4.5 h after neuroleptic administration, especially if protected with higher pentadecapeptide dose. Besides catalepsy, coadministration of the pentadecapeptide BPC 157, given in the above mentioned doses, reduced not only catalepsy but somatosensory disorientation (for 7.5 h after administration of a neuroleptic, assessed at intervals of 1.5 h, by a simple scoring system [0-5]) in haloperidol- or fluphenazine-challenged mice as it did in mice treated with sulpiride (20, 40, 80 and 160 mg/kg b.w., i.p.) or with clozapine (25, 50 and 100 mg/kg b.w., i.p.), in which case catalepsy was absent. In other experiments, considering the gastric origin of this pentadecapeptide, the focus was shifted to the evidence that a dose of haloperidol, cataleptogenic due to dopamine receptors blockade, induces gastric ulcers in rats. Coadministration of pentadecapeptide BPC 157 (10 microg, 10 ng, 1.0 ng, 100 pg/kg b.w., i.p.) to rats completely inhibited the lesions otherwise regularly evident 24 h after haloperidol (5.0 mg/kg b.w., i.p.) in control rats (18 of 20 rats had gastric lesions). This activity accompanied the antagonism of the haloperidol catalepsy in rats (assessed at 60-min intervals from I to 5 h after haloperidol), when 10-microg- or 10-ng regimens were given (lower doses could not influence catalepsy). Together, these findings indicate that pentadecapeptide BPC 157 fully interacts with the dopamine system, both centrally and peripherally, or at least, that BPC 157 interferes with some steps involved in catalepsy and/or ulcer formation.     

Markers of Systemic and Lung Inflammation in Childhood Asthma

Aim. To compare different biomarkers of inflammation in children with controlled and uncontrolled asthma and to investigate their relationship with other clinical indices of asthma control (symptoms, lung function, serum IgE, and prn beta-agonist use). Materials and Methods. A total of 62 consecutive asthmatic children (age 11 ± 3.3 years, 32 girls) with controlled ([C], n = 19) and uncontrolled asthma ([NC], n = 43) were studied. Measured lung function and inflammatory biomarkers included: spirometry, exhaled NO (F_ENO), high-sensitivity C-reactive protein (hs-CRP), peripheral blood white blood cells (WBC) counts, and differentials. Results. Hs-CRP was significantly higher in uncontrolled than in controlled asthma (hs-CRP, median [IQR], mg/L; 0.56 [0.60] vs 0.25 [0.34], p = 0.008). Discriminant analysis (backward stepwise) depicted hs-CRP and lymphocytes (as Z-score for absolute count) as significant discriminative factors for asthma control (F = 8.319, p = 0.0007) with 82.3% diagnostic accuracy. Divided into quartiles hs-CRP showed the significant inverse association with F_ENO (F = 7.359, p = 0.003, ANOVA) with no significant difference for asthma control (F = 1.032, p = 0.386). Post-hoc analysis revealed that F_ENO values were significantly lower in the third and the fourth quartile of hs-CRP in comparison to the first and the second one (p < 0.05 for all). Conclusion. In asthmatic children with uncontrolled asthma serum hs-CRP was increased compared to children with controlled asthma. Although F_ENO values were also increased (insignificantly) and inversely correlated with hs-CRP they were probably reflecting different etiology underlying the loss of control. The role of peripheral blood biomarkers in asthmatics is still poorly investigated so new studies are required.     

Lack of association between low HDL-cholesterol and elevated circulating cellular adhesion molecules in normolipidemic CAD patients and healthy subjects

High plasma HDL-cholesterol (HDL-c) is a well-established protective factor in coronary artery disease (CAD). One of its potential protective mechanisms is the inhibition of the cytokine-induced upregulation of expression of cellular adhesion molecules (CAMs). High sCAM levels were found to be associated with low HDL-c in some studies performed mostly in hyperlipidemic subjects, but this association has not yet been investigated in CAD patients. In addition, conflicting results were obtained from in vitro studies that explored the proposed HDL effect on cytokine-induced CAM expression. The aim of the present case-control study was to investigate whether low HDL-c values are associated with CAM overexpression in normolipidemic CAD patients and healthy individuals, matched according to age and gender. Plasma HDL-c, sICAM-1, sVCAM-1, and sE-selectin were measured in 37 normolipidemic patients with angiographically verified coronary artery disease and in 52 healthy normolipidemic subjects. The sCAM values obtained in the subjects (patients or controls) with low HDL-c levels (< 1.03 mmol/L) were compared with the values in the subjects with high HDL-c (>or= 1.03 mmol/L). No significant difference was found between sICAM-1, sVCAM-1, and E-selectin values obtained in subjects with low and high HDL-c, either among the patients or the healthy controls. In conclusion, low HDL-c levels are not associated with CAM overexpression in normolipidemic CAD patients and healthy subjects.     

Intravascular large B-cell lymphoma as a cause of hypopituitarism: gradual and late reversal of hypopituitarism after long-term remission of lymphoma with immunochemotherapy

Intravascular large B-cell lymphoma (IVL) is a rare generally fatal disease characterized by massive proliferation of lymphoid cells within the small and medium blood vessels. Hypopituitarism has been reported only in a few fatal cases. We describe the clinical course of hypopituitarism as a complication of IVL, successfully treated with immunochemotherapy (cyclophosphamide/doxorubicin/vincristine/prednisone-CHOP) plus Rituximab anti-CD20 humanized antibody). Before immunochemotherapy, basal hormonal analysis and dynamic test for pituitary function were performed in a 67-year-old female with IVL. Endocrinological evaluation of the pituitary function was repeated after complete hematological remission and during the 2 years of follow-up. Multiple pituitary hormone deficiencies were diagnosed before therapy for IVL. Magnetic resonance imaging (MRI) of the pituitary gland showed partially empty sella. The patient was replaced with thyroxine 50 microg/day and prednisone 5 mg/day between the cycles of chemotherapy. After complete hematological remission (6 months after initial diagnosis) reversal of cortisol and gonadotropin deficiency occurred. After 18 months of hematological remission there was further improvement in growth hormone (GH) response to provocative testings (partial GH deficiency), with normalization of somatotropic and thyreotropic axis after 2 years of follow-up. This is the first case of IVL complicated with hypopituitarism, treated with immunochemotherapy which resulted in complete hematological remission and gradual and late reversal of hypopituitarism.     

The Balkan Piedmont: Male Suicide Rates Pre-war,Wartime, and Post-war in Serbia and Montenegro

The epidemiology of suicide in Serbia and Montenegro from 1989 to 2003, a period of civil war, is presented. Following the break-up of former Yugoslavia, Serbia and Montenegro underwent a period of war from 1991–1994 and another in 1999. During the war years, the number of suicides increased, reaching its peak in 1993. Male suicides outnumbered female suicides by a ratio of 2:1. Male suicides decreased slightly after the war of 1991–1994 only to rise in 1997 and continue at this higher level throughout the nineties. In Serbia alone, male suicide reached its peak in 2002 (nearly 29/100,000). The methods of suicide changed significantly, with the use of firearms doubling during and after the war years. Speculations are offered about the findings, many consistent with Durkheim's classical hypothesis concerning suicide and unpopular wars.     

The effect of two different bracket types on the salivary levels of S mutans and S sobrinus in the early phase of orthodontic treatment

Objective:To determine the difference in the levels of Streptococcus mutans and S sobrinus in stimulated saliva in orthodontic patients with different bracket types (stainless steel and esthetic brackets) using polymerase chain reaction and cultivation method.Materials and Methods:Thirty-two patients, aged 13 to 30 years, were selected following these criteria: 1) orthodontic treatment indication, 2) systemic health, and 3) no tobacco and antibiotic consummation for three months prior to the commencement of the study. Patients were divided into two groups according to the bracket type; 16 patients formed the conventional bracket group (stainless steel brackets), and 16 patients formed the esthetic bracket group (plastic brackets). The levels of S mutans and S sobrinus in stimulated whole saliva samples were collected prior to fixed orthodontic appliance placement (T1) and 12 weeks after placement (T2), as were the Decayed, Missing, and Filled Surface Index (DMFS) and Oral Hygiene Index-Simplified (OHI-S). Mann-Whitney, Wilcoxon, and chi-square tests were used for statistical analysis.Results:Statistical analysis (chi-square test) showed no difference in S mutans and S sobrinus counts among patients with different brackets at either T1 or T2. There was no difference in total bacteria counts after fixed orthodontic appliance placement.Conclusion:The number of colony-forming units of S mutans and S sobrinus in stimulated saliva samples does not seem to be significantly different between patients with stainless steel brackets and patients with plastic brackets.     

Myeloid blood CD11c(+) dendritic cells and monocyte-derived dendritic cells differ in their ability to stimulate T lymphocytes

Dendritic cells (DCs) initiate and direct immune responses. Recent studies have defined different DC populations, therefore we undertook this study comparing 2 types of myeloid DCs: blood CD11c(+) DCs and in vitro monocyte-derived DCs (Mo-DCs), which are both candidates as cellular adjuvants for cancer immunotherapy. Blood CD11c(+) DCs were prepared by cell sorting from peripheral blood mononuclear cells cultured overnight in RPMI 1640 medium supplemented with autologous or pooled AB serum. Mo-DCs were prepared in the same medium using granulocyte macrophage-colony-stimulating factor (GM-CSF)/interleukin 4 (IL-4) and differentiated/activated with lipopolysaccharide or monocyte-conditioned medium (ActMo-DCs). Morphologically, differences between the DC preparations were noted both at a light and and electron microscopic level. Blood CD11c(+) DCs expressed similar levels of HLA-DR, CD40, CD86, and CD83 as Mo-DCs. CD209 was present on Mo-DCs but not on blood CD11c(+) DCs. Blood CD11c(+) DCs generated a lower proliferative mixed leukocyte response (MLR) than Mo-DCs. Blood CD11c(+) DCs loaded with 0.1 microg/mL tetanus toxoid (TT)-generated greater T lymphocyte proliferative responses than did Mo-DCs or ActMo-DCs, but when loaded with higher TT concentrations no difference in T lymphocyte proliferative response was observed. Keyhole limpet hemocyanin (KLH)-loaded blood CD11c(+) DCs generated greater T lymphocyte proliferative responses than Mo-DCs or ActMo-DCs. Allogeneic MLR- or KLH-specific responses induced by blood CD11c(+) DCs generated more Th1 effectors than the responses induced by Mo-DCs or ActMo-DCs. These data establish several differences in the properties of blood CD11c(+) DCs, Mo-DCs, and ActMo-DCs, which suggest that blood DCs merit further consideration as DC preparations for clinical programs are evolved.