Inflammatory myofibroblastic tumor (plasma cell granuloma). Clinicopathologic study of 20 cases with immunohistochemical and ultrastructural observations

Twenty cases of inflammatory myofibroblastic tumor (IMT) were studied; 19 involved the lung and 1 the esophagus only. The patients' ages ranged from 3 to 72 years. There were 9 males and 11 females. Involvement of a bronchus was seen in one case and of mediastinal structures in four. Chest pain and dyspnea were common symptoms; eight patients were asymptomatic. Seven patients underwent lobectomy, 12 local excision, and 1 biopsy alone. The lesions were nonencapsulated and ranged from 1.2 to 15 cm. Various proportions of plasma cells, histiocytes, and spindle cells were observed; the latter corresponded ultrastructurally to fibroblasts and myofibroblasts, were immunoreactive for vimentin and actin and focally for desmin, and were negative for epithelial markers. Plasma cells were polyclonal for light chains. One patient had two recurrences, and in one case a large pleural IMT was found eight years after the excision of a similar lesion in the lung. All patients with follow-up (ten) were well as long as ten years after the diagnosis (average, 3.7 years).     

A nitric oxide synthase inhibitor reduces inflammation, down-regulates inflammatory cytokines and enhances interleukin-10 production in carrageenin-induced oedema in mice.

Mice injected in the footpad with carrageenin developed local inflammation which peaked at 48 hr. This delayed-type footpad swelling was significantly reduced in mice injected intraperitoneally (i.p.) with a specific nitric oxide (NO) synthase inhibitor, L-NGmonomethyl-arginine (L-NMMA). The draining lymph node (DLN) cells from mice injected 48 hr previously with carrageenin produced significantly higher levels of proliferation and interleukin-1 (IL-1), IL-2, IL-6 and interferon-gamma (IFN-gamma), but less IL-10, compared to cells from saline-injected controls, when stimulated with concanavalin A (Con A) in vitro. Treatment of the carrageenin-injected mice with L-NMMA had little effect on the proliferative response of the DLN cells, but significantly reduced the production of IL-1, IL-2, IL-6 and IFN-gamma, and increased the secretion of IL-10. These data demonstrate that NO plays a significant role in local inflammation and the pattern of cytokines induced in this model.     

Kinematic and dynamic analysis of running under conditions of variable gravity

A new training system was designed and realised by the engineer G. Scuderi: a centrifugal track for runners. The principal advantage of this track is to increase the forces on athlete during the run with an effect very similar to that of an "artificial gravity", so the athlete can develop more muscle power. A multibody numerical model of a runner was developed to analyse the behaviour of the athlete on the centrifugal track. The multibody model was calibrated by experimental analysis; in fact, the joint angles were measured by a digital image processing system and introduced as input in the numerical simulation. The numerical results obtained are the values of many kinematic and dynamic variables, in particular the ground reaction force and the moments in the hip, knee, and ankle joints. A comparison between the normal running and that on the centrifugal track was carried out, demonstrating the validity of training on the latter. The results of the numerical simulation confirm that the power developed during running on the track, and the corresponding work performed by the joints, is considerably greater than that found during normal running.     

Immunohistochemical expression of mdm2 and p21WAF1 in invasive cervical cancer: correlation with p53 protein and high risk HPV infection

AIM: To investigate the immunocytochemical staining pattern of mdm2 and p21WAF1 proteins in invasive cervical cancer and to determine its relation with the expression of p53 and with the high risk HPV infection. METHODS: Immunocytochemistry for p53, mdm2, and p21WAF1 was performed in 31 paraffin embedded sections of invasive cervical cancer. The results were assessed by image analysis, evaluating for each protein the optical density of the immunostained area, scored as percentage of the total nuclear area. The presence of high risk human papillomavirus (HPV) infection was detected by using the polymerase chain reaction. RESULTS: Immunostaining for both mdm2 and p21WAF1 was correlated with p53 expression; however, the correlation between p53 and mdm2 (R = 0.49; p < 0.01) was more significant than between p53 and p21WAF1 (R = 0.31; p < 0.05); the less stringent correlation between p53 and p21WAF1 might reflect the p53 independent mechanisms of p21WAF1 induction. Similar average levels of p53, mdm2, and p21WAF1 immunostaining were found in the presence or absence of high risk HPV-DNA, without significant differences between the two groups. CONCLUSIONS: These data suggest that mdm2 and p21WAF1 proteins are expressed in invasive cervical cancer and that their immunocytochemical staining pattern is not abrogated by the presence of high risk HPV genomic sequences.     

Prenatal detection of cri du chat syndrome on uncultured amniocytes using fluorescence in situ hybridization (FISH)

Fluorescence in situ hybridization (FISH) with a chromosome-region-specific DNA probe was used prospectively on uncultured amniocyte interphase cells to detect an unbalanced chromosome abnormality that resulted in cri du chat or 5p – syndrome. Confirmation was performed by routine cytogenetics.     

Effect of the Addition of Vancomycin on the Performance of an Automated Nonradioactive System for Detection of Mycobacteria

 A recently developed automated, nonradioactive system for the detection of mycobacteria (MB/BacT; Organon Teknika, Belgium) has provided good results, but the contamination rate was found to be higher than that obtained with the radiometric Bactec 460 system (Becton Dickinson, USA). In the present study, the effects of adding vancomycin (1 μg/ml) to the antibiotic mixture of the nonradioactive system were evaluated, and the performance of the system with versus without vancomycin was compared. Three hundred sputum samples were tested, using the radiometric system as the reference method. Mycobacteria were isolated from 47 (15.7%) samples. The nonradioactive system with and without vancomycin detected 42 and 43 strains, respectively; the time to detection was 1 day shorter with the medium without vancomycin (15.7 days vs. 14.3 days). The radiometric system detected 42 strains of mycobacteria in a mean detection time of 13.6 days. Contamination rates with the nonradioactive system were 6.7% in the medium without vancomycin and 2.7% in the medium with vancomycin. The latter figure was approximately the same as the contamination rate found with the radiometric system (2.3%). Our data suggest that the addition of vancomycin considerably reduces the number of contaminants in the MB/BacT medium without affecting the performance of the system.     

Modulation of the constitutive or cytokine-induced bronchial epithelial cell functions in vitro by fluticasone propionate

When exposed to proinflammatory mediators, human bronchial epithelial cells (HBECs) upregulate the 'constitutive' adhesion molecule expression and cytokine/chemokine release. We tested whether and to what extent the inhibitory effect of fluticasone propionate on HBECs could involve the 'constitutive' and 'cytokine-induced' proinflammatory functions. Stimulation of the HBECs with interleukin (IL)-4 plus tumour necrosis factor (TNF)-alpha was more effective in upregulating intercellular adhesion molecule (ICAM)-1 ( approximately 2.2-fold increase) than vascular adhesion molecule (VCAM)-1 ( approximately 1.6-fold increase) expression (P<0.05) and in increasing the release of 'regulated on activation normal T cell expressed' (RANTES, 5.7-fold increase) than of IL-8 (3.5-fold increase) and granulocyte macrophage-colony stimulating factor (GM-CSF, 2.8-fold increase), (P<0.01). Fluticasone propionate, at the two concentrations tested (10 and 100 nM), was more effective in inhibiting the 'IL-4 plus TNF-alpha-induced' ICAM-1 expression than VCAM-1 expression (P<0.05) and in downregulating RANTES than IL-8 or GM-CSF secretion (P<0.05). The degree of inhibition demonstrated by fluticasone propionate appeared to be related to the degree of cell activation. In addition, for both adhesion molecules, the effect of fluticasone propionate at both concentrations tested appeared to be related to a complete inhibition of 'IL-4 plus TNF-alpha-induced' expression with no involvement of the 'constitutive' expression. Slightly different results were observed for cytokine/chemokine release. Indeed, evaluating RANTES, a complete inhibition of the 'IL-4 plus TNF-alpha-induced' release with a partial inhibition also of the 'constitutive' release at both concentrations of the drug tested was found, whereas for GM-CSF and IL-8, only a partial inhibition of the 'IL-4 plus TNF-alpha-induced' release in the presence of fluticasone propionate 10 and 100 nM. Thus, HBECs can constitutively or upon activation express adhesion molecules and secrete proinflammatory proteins at various levels and the different ability of fluticasone propionate to modulate the HBEC functions appears to be mostly related to the different inhibition of the various 'IL-4 plus TNF-alpha-induced' responses.     

Changes in bone turnover during tibolone treatment

OBJECTIVES: An open study was carried out to evaluate changes in bone remodeling markers such as N-telopeptide (NTx), tartrate-resistant acid phosphatase (TRAP), total alkaline phosphatase (TAP), and bone alkaline phosphatase (BAP) during a 1-year continuous tibolone treatment in postmenopausal women. MATERIAL AND METHODS: Thirty-six postmenopausal women were recruited for receiving tibolone 2.5 mg per day for 1 year. Densitometry and determination of biochemical markers of bone metabolism in serum and urine were performed at 1, 3, 6, and 12 months. RESULTS: Comparing baseline with 12 month's values, BAP and all resorption markers decreased significantly. NTx began to decrease since the initiation of the treatment (baseline: 74.4 +/- 5.3; 1 month: 57.5 +/- 4.2; 12 months: 36.6 +/- 2.8). BAP increased at the first month (baseline: 37.3 +/- 2.1; 1 month: 42.6 +/- 3.0) but diminished in the following months (12 months: 23.1 +/- 1.5). TAP started to decrease significantly only after 6 months of treatment (baseline: 37.3 +/- 2.1; 12 months: 31.4 +/- 2.3) and TRAP after 3 months (baseline: 9.8 +/- 0.4; 6 months: 9.1 +/- 0.5; 12 months: 8.2 +/- 0.4). Normal bone mineral density at distal and ultradistal forearm was maintained during the 1-year treatment (baseline: 0.42 +/- 0.01; 12 months: 0.42 +/- 0.01 and baseline: 0.33 +/- 0.01; 12 months: 0.33 +/- 0.01, respectively). CONCLUSION: The use of tibolone 2.5 mg per day diminished progressively and significantly bone resorption and formation markers during 1-year treatment period.