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Mycophenolate mofetil significantly reduces leukocyte graft infiltration after heterotopic cardiac transplantation in a rat model: comparative study with cyclosporine and FK 506.

BACKGROUND: The purpose of the study was to evaluate the effects of cyclosporine (CsA), FK 506 and mycophenolate mofetil (MMF) on graft-infiltrating leukocytes (CD4, CD8, CD11a, CD18) after cardiac transplantation in rats. METHODS: Three hundred forty animals were transplanted and randomly divided into 4 groups: CsA, 3 mg/kg/d (n = 74); MMF, 40 mg/kg/d (n = 96); FK 506, 0.3 mg/kg/d (n = 96); and a control group receiving no immunosuppressive therapy (n = 74). Three or 4 animals from each group were killed at intervals of 1 to 4 days up to Day 60. Immunohistochemistry was performed using monoclonal antibodies (MAb) against CD4, CD8, CD11a and CD18. Positively stained cells were analyzed in the perivascular space (PVS) of intra- and epicardial arteries. Statistical analysis was performed using area-under-the-curve assessment with an extended t-test. RESULTS: CsA and FK 506 reduced the presence graft-infiltrating leukocytes (CD4, CD8, CD11a, CD18) in the PVS of intra- and epicardial arteries when compared with control animals. MMF therapy resulted in a further significant reduction in infiltrating leukocytes when compared with the 2 calcineurin inhibitors. MMF had a faster onset of action than the calcineurin inhibitors. CsA and FK 506 required 12 to 20 additional days to achieve the reducing effect of graft infiltration seen in MMF-treated animals. CONCLUSION: MMF possesses potent infiltration-blocking properties and its application leads to a greater reduction of cellular infiltration in the course of transplant rejection when compared with calcineurin inhibitors.

Animals↗

How to determine the permeability for cement infiltration of osteoporotic cancellous bone.

Cement augmentation is an emerging surgical procedure in which bone cement is used to infiltrate and reinforce osteoporotic vertebrae. Although this infiltration procedure has been widely applied, it is performed empirically and little is known about the flow characteristics of cement during the injection process. We present a theoretical and experimental approach to investigate the intertrabecular bone permeability during the infiltration procedure. The cement permeability was considered to be dependent on time, bone porosity, and cement viscosity in our analysis. In order to determine the time-dependent permeability, ten cancellous bone cores were harvested from osteoporotic vertebrae, infiltrated with acrylic cement at a constant flow rate, and the pressure drop across the cores during the infiltration was measured. The viscosity dependence of the permeability was determined based on published experimental data. The theoretical model for the permeability as a function of bone porosity and time was then fit to the testing data. Our findings suggest that the intertrabecular bone permeability depends strongly on time. For instance, the initial permeability (60.89 mm(4)/N(*)s) reduced to approximately 63% of its original value within 18 seconds. This study is the first to analyze cement flow through osteoporotic bone. The theoretical and experimental models provided in this paper are generic. Thus, they can be used to systematically study and optimize the infiltration process for clinical practice.

Aged↗

Cellular infiltration at skin lesions and draining lymph nodes of sheep infested with adult Hyalomma anatolicum anatolicum ticks.

Immunohistochemical analysis of skin and draining lymph nodes of sheep repeatedly infested with the ixodid tick Hyalomma anatolicum anatolicum were studied for different antigen-presenting cells and lymphocyte subpopulations. Infiltration of neutrophils, macrophages and lymphocytes adjacent to the tick bite site were observed. Skin biopsies showed significant increases in dermal infiltration of CD8+ and gammadelta+ T cells at 72 h and 8 days after both primary and secondary infestation. Infiltrations of MHC-II DR/DQ decreased at 72 h after tick infestation, whereas significant increases were recorded for 8-day skin biopsies. CD1+ cellular infiltrations were observed during secondary infestations at the dermis. Decreased ratios of CD4:CD8 T cells and MHC-II:CD1 antigen-presenting cells were observed in both infestations compared to healthy skin biopsies. Ratios of alphabeta:gammadelta T cells increased gradually during infestation compared to uninfested skin. The regional lymph nodes from tick-infested sheep showed an increased CD8+, gammadelta+ T and CD1+ cellular infiltration compared to control lymph nodes. CD4+ T cells were decreased. There were no significant changes in CD45R+ cellular infiltration either at skin lesions or regional lymph nodes.

Animals↗

Fatty infiltration of liver in hyperlipidemic patients.

Hyperlipidemia is a known risk factor for fatty infiltration of the liver, a condition that can progress to cirrhosis and liver failure. The objectives of this study were to document the prevalence of fatty infiltration in the livers of hyperlipidemic patients and to identify the predictor variables associated with this condition. Over an 18-month recruitment period, clinical, biochemical, and radiologic assessments were performed in a cross-sectional manner in 95 adult patients referred to an urban hospital-based lipid clinic for evaluation and management of hyperlipidemia. The mean (+/-SD) age of the patients was 55 +/- 13 years. Forty-eight (51%) were male. Fifty-two patients (55%) had hypercholesterolemia, 25 (26%) severe hypertriglyceridemia, 14 (15%) mixed hyperlipidemia, and 4 (4%) moderate hypertriglyceridemia. Obesity and diabetes were present in 36 (38%) and 12 (12%) of cases, respectively. A total of 61 (64%) patients had elevated liver enzyme tests. The most common enzyme abnormalities were an elevated serum ALT in 45 (47%) and GGT in 43 (45%) of patients. Ultrasound findings revealed diffuse fatty liver in 47 patients (50%), of which 21 cases (22%) were mild, 18 (19%) moderate, and 8 (9%) severe. The majority of patients with hypercholesterolemia [35/52 (67%)] had normal ultrasounds, whereas severe hypertriglyceridemia and mixed hyperlipidemia were frequently associated with radiologic evidence of fatty liver (odds ratios 5.9 and 5.1 respectively, P < 0.01). Independent predictors of fatty liver were; AST (P = 0.001), hyperglycemia (P = 0.02), and age (P = 0.04). In a model incorporating known risk factors for fatty liver, diabetes was the only risk factor other than hypertriglyceridemia that was significantly associated with fatty infiltration. No such effect was seen with age, gender, obesity, or alcohol consumption. In conclusions, the results of this study indicate that ultrasonographic evidence of fatty infiltration of the liver is evident in approximately 50% of patients with hyperlipidemia. Hypertriglyceridemia is the lipid profile most often associated with this condition. Serum AST values, hyperglycemia, and age independently predict the presence of fatty infiltration, while hypertriglyceridemia and diabetes are the only risk factors that significantly increase the risk of fatty infiltration in hyperlipidemic patients.

Adult↗

Pulmonary infiltration associated with myelodysplasia.

Four case histories are reported in which the initial signs and symptoms were those of pulmonary infiltration and in which subsequently a diagnosis of myelodysplasia was made. The analysis of bronchoalveolar lavage fluid--demonstrating predominantly neutrophils and lymphocytes, and, occasionally blast cells as well as plasma cells--indicated that the pulmonary infiltration was related to the myelodysplastic process. As no other causes of pulmonary infiltration could be found, it seems that a pulmonary infiltrate can be the presenting symptom of a myelodysplastic syndrome. Although pleuropulmonary infiltrates most often are caused by infections, these cases illustrate that myelodysplasia related infiltrates should also be considered.

Aged↗

Subcutaneous infiltration with ammonium sulphate 10% does not prolong the local anaesthetic duration of lidocaine in humans.

BACKGROUND: The aim of the present study was to investigate whether a solution of ammonium sulphate and lidocaine had a prolonged duration of action compared with lidocaine alone after subcutaneous infiltration in human volunteers. METHODS: In a double-blind, randomised, controlled trial 12 male volunteers had either 4 ml lidocaine 1% (40 mg) or a solution of 4 ml ammonium sulphate 10% and lidocaine 1% (40 mg) subcutaneously infiltrated in corresponding skin areas on the right and left calf. The duration of the local anaesthetic action of the test medications was assessed 1-6 h after the infiltrations using thresholds to mechanical (von Frey hairs) and thermal stimulation (heat detection thresholds: HDT, and heat pain detection thresholds: HPDT), and by calculation of areas under the curve (AUC) for electronic visual analogue scale (VAS) pain ratings (sampled at 2 Hz) during a heat stimulation on the test areas for 30 s with a 45 degrees C warm thermode. RESULTS: At no assessment were thresholds to mechanical or thermal stimulation increased in favour of ammonium sulphate treated legs compared with control legs. On the contrary, HPDT were significantly lower in ammonium sulphate treated legs than control legs at the 3 h and 4 h assessment after infiltration (P<0.02). Similarly, the AUC for the VAS ratings was significantly higher in treatment legs compared with control legs 2 h and 3 h after infiltration (P<0.05). CONCLUSION: No improvement in local anaesthetic duration of ammonium sulphate 10% plus lidocaine 1% compared with lidocaine 1% alone was demonstrated early after subcutaneous infiltration in human volunteers.

Adjuvants, Anesthesia↗

An immunohistochemical characterisation of the inflammatory cell infiltrate in benign and malignant prostatic disease.

The prostate gland is said to be immunologically privileged because it lacks afferent lymphatics and because of the immunosuppressive properties of seminal fluid. To elicit the presence or absence of an immune response within the diseased prostate gland, the infiltrate in prostate glands affected by hyperplasia or adenocarcinoma was phenotypically characterised, using immunohistochemical techniques. An infiltrate, composed mainly of T-lymphocytes (CD-3+), was demonstrated in all glands examined. No difference in the type, level of activation or degree of infiltration was found between those glands affected by hyperplasia (n = 20) and those affected by adenocarcinoma (n = 20). In the malignant cases, there was no correlation between grade (Gleason) or stage (TNM) and the type or degree of mononuclear cell infiltrate. Our findings suggest that the host response, in situ, to hyperplasia and adenocarcinoma is similar and may reflect the fact that the two diseases are often found concurrently in the same gland and in close proximity to one another. The infiltrate, therefore, is unlikely to represent a tumour specific immune response to tumour specific antigens. The significant infiltrate we have demonstrated, and its phenotypic characterisation, would not support the hypothesis that the prostate is immunologically privileged as has been suggested previously.

Adenocarcinoma↗

Transfection of antisense core 2 beta1,6-N-acetylglucosaminyltransferase-1 cDNA suppresses selectin ligand expression and tissue infiltration of B-cell precursor leukemia cells.

B-cell precursor (BCP) leukemia cells infiltrate into peripheral organs and the disease often relapses. Inhibition of tissue infiltration may improve the treatment outcome of BCP-leukemia patients. Selectin ligand has been suggested to play an important role in the infiltration of leukemia cells. However, the regulation mechanisms and involvement in tissue infiltration of selectin ligand expression in BCP-leukemia cells are not fully understood. In this study, we report that BCP-leukemia cells express selectin ligand on O-sialoglycoproteins. Core 2 beta1,6-N-acetylglucosaminyltransferase-1 (C2GnT-1) is mainly expressed in BCP-leukemia cells. Transfection of the antisense C2GnT-1 cDNA resulted in a significant reduction of either selectin ligand expression or selectin-dependent cell adhesion in BCP-leukemia cell line KM3 cells. Migration ability into mouse peripheral organs was reduced significantly in the antisense transfectant. These findings suggest that C2GnT-1 regulates selectin ligand expression. Downregulation of the selectin ligand expression level inhibits tissue infiltration of BCP-leukemia cells. C2GnT-1 may be a candidate of therapeutic target for the inhibition of infiltration of leukemia cells.

Cell Movement↗

Congenital infiltrating lipoma of the upper limb in a patient with von Willebrand disease.

Infiltrating lipoma is a rare variety of lipoma, characterized by an infiltration of the adipose tissue of the muscles. Infiltrating lipomas are usually classified in two groups: intermuscular infiltrating lipoma and intramuscular infiltrating lipoma. Most are acquired, and they usually appear in middle-aged individuals. Exceptionally, they are congenital. In such cases they are not related to other diseases. We report an 8-year-old boy with a congenital infiltrating lipoma of the upper limb and von Willebrand disease. Both diseases are linked to an alteration in chromosome 12, but this clinical association seems to be random rather than causal.

Arm↗

Preventive effect of sulphated colominic acid on P-selectin-dependent infiltration of macrophages in experimentally induced crescentic glomerulonephritis.

Leucocytes infiltrate into renal tissue and are involved in the pathogenesis of crescentic glomerulonephritis. The initial event in the process of leucocyte infiltration is characterized by selectin-mediated leucocyte rolling on endothelial surface. Role of selectins in pathogenesis of glomerulonephritis has still been controversial. Sulphated glycolipids and sulphated polysaccharides interfere with the binding of P- and L-selectin with carbohydrate ligands on endothelial cells or on leucocytes. Here we evaluated the role of selectins and the preventive effects of sulphated colominic acid (SCA), a synthetic sulphated polysaccharide, on experimental crescentic glomerulonephritis in Wistar-Kyoto (WKY) rats. Crescentic glomerulonephritis was induced by injection of nephrotoxic serum (NTS) in WKY rats. Rats subsequently received intraperitoneal injection of saline, neutralizing or non-neutralizing monoclonal antibody (mAb) to rat P-selectin and L-selectin, SCA (5 or 10mg/kg/day) or nonsulphated colominic acid (CA) (10mg/kg/day) for 2 weeks. Localization of P-, E-selectin, ligands for L-selectin and intraglomerular leucocytes was examined by immunohistochemistry. Gene expression of platelet-derived growth factor (PDGF) B chain in glomeruli was quantified using real-time RT-PCR. P-selectin was highly expressed on glomerular endothelial cells after injection of NTS, whereas E-selectin and L-selectin ligands were not detected. Anti-P-selectin mAb, but not anti-L-selectin mAb, significantly reduced glomerular infiltration of macrophages, crescent formation, and proteinuria. SCA also reduced proteinuria, macrophage infiltration, and crescent formation in a dose-dependent manner. Furthermore, SCA suppressed gene expression of PDGF B chain in glomeruli. Our results indicate that P-selectin partially mediates glomerular infiltration of macrophage in experimental crescentic glomerulonephritis. Moreover, SCA may inhibit intraglomerular infiltration of macrophages by interfering with P-selectin-dependent adhesion pathway, and progression of experimental crescentic glomerulonephritis.

Animals↗

Role of leukocyte adhesion molecules in monocyte/ macrophage infiltration in weanling rats with unilateral ureteral obstruction.

BACKGROUND: Unilateral ureteral obstruction (UUO) of rats is a well-established model for studying obstructive nephropathy. Meanwhile, pathophysiology of pediatric obstructive nephropathy is not well understood. In this report, we studied monocyte/macrophage infiltration and expression of intercellular adhesion molecule 1 (ICAM-1) and macrophage antigen 1 (Mac-1) in weanling rats with UUO. METHODS: Three-week-old male Sprague-Dawley rats underwent left unilateral ureteral ligation. Both obstructed kidneys (OBK) and contralateral kidneys (CLK) were harvested at 3, 6, 12, 24, 72 and 120 h after surgery. Monocyte/macrophage infiltration and expression of ICAM-1 and Mac-1 were evaluated immunohistochemically, and results were compared with those of sham-operated control rats (SOK). RESULTS: Monocyte/macrophage infiltration was observed in the interstitium and perivascular region in the cortex of OBK within 6 h. The CLK and SOK showed slight monocyte/macrophage infiltration. Expression of ICAM-1 was markedly observed in the periarterial and peritubular interstitium and in renal cortical peritubular capillaries 12 h after obstruction. In CLK and SOK, ICAM-1 was slightly expressed in the endothelium of microvessels and parietal linings of Bowman's capsule. Expression of Mac-1 was detected mainly in cells infiltrating the perivascular interstitium in OBK. In CLK and SOK, few Mac-1-positive cells were observed. CONCLUSIONS: Adhesion molecules, ICAM-1 and Mac-1, are expected to recruit monocyte/macrophage infiltration into OBK of weanling rats with UUO.

Animals↗

The chemokine receptor antagonist AOP-RANTES reduces monocyte infiltration in experimental glomerulonephritis.

UNLABELLED: The chemokine receptor antagonist AOP-RANTES reduces monocyte infiltration in experimental glomerulonephritis. BACKGROUND: This study was designed to evaluate the role of the novel chemokine receptor antagonist amino-oxypentane RANTES (AOP-RANTES), which blocks the binding of macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and RANTES to the chemokine receptor-5 (CCR-5) on the infiltration of monocytes in experimental glomerulonephritis. METHODS: Rats were treated twice daily with 12.5 microg AOP-RANTES following an induction of anti-rat-thymocyte antibody-mediated glomerulonephritis. The white blood cell count, glomerular monocyte infiltration, chemokine expression, and collagen type IV deposition were assessed. RESULTS: The induction of glomerulonephritis increased glomerular monocyte/macrophage (M/M) infiltration at 24 hours and at 5 days was still higher than in controls. AOP-RANTES prevented glomerular M/M infiltration at 24 hours and at 5 days. This was paralleled by reduced glomerular collagen type IV deposition as a fibrotic marker in nephritic animals. CONCLUSION: These data show that the CCR-5 chemokine receptor antagonist AOP-RANTES ameliorates M/M infiltration and improves glomerular pathology in experimental glomerulonephritis. The use of chemokine receptor antagonists may offer a new therapeutic option in inflammatory renal injuries.

Animals↗

[Importance of digital thoracic radiography in the diagnosis of pulmonary infiltrates in patients with bone marrow transplantation during aplasia].

PURPOSE: Evaluation of digitized chest x-ray for the detection of pulmonary infiltrations in bone marrow transplant patients during aplasia. METHODS: Digitized chest x-rays of 40 patients (21 female, 19 male) with "Fever of unknown origin" (FUO) were evaluated concerning radiological signs of pulmonary infiltrations and correlated to clinical findings, blood chemistry, microbiology and bronchoscopy. Additionally, an individual risk profile was established. RESULTS: In 11/40 patients pulmonary infiltrations were detected in digitized chest x-rays (group 1). 10/11 developed an infectious pulmonary infiltration. 29/40 patients developed no pulmonary infiltration (group 2). When fever increased for the first time (initial chest x-ray) a sensitivity, specificity, positive and negative predictive value of 46%, 86%, 56%, 81% and for the chest x-rays in progress of 61%, 79% 68% and 73% was found. C-reactive protein and temperature increase occurred statistically significantly earlier (p < 0.05) in group 1 compared to group 2. The average latency of digital chest x-rays in comparison to c-reactive protein and temperature increase was 6 days. The incidence of risk factors was significantly higher in group 1 in comparison to group 2 (p < 0.05). CONCLUSION: Digitized chest x-rays are not a reliable method for primary detection of pulmonary infiltrations after bone marrow transplantation. Individual risk factors have to be taken into consideration to indicate further diagnostic methods such as computed tomography at an earlier time.

Adult↗

[Sensitivity of MRI in detecting alveolar Infiltrates: Experimental studies].

PURPOSE: An experimental study using porcine lung explants and a dedicated chest phantom to evaluate the signal intensity of artificial alveolar infiltrates with T 1 - and T 2 -weighted MRI sequences. MATERIAL AND METHODS: 10 porcine lung explants were intubated, transferred into the cavity of a MRI-compatible chest phantom and inflated by continuous evacuation of the artificial pleural space. All lungs were examined with MRI at 1.5 T before and after intra-tracheal instillation of either 100 or 200 ml gelatine-stabilised liquid to simulate alveolar infiltrates. MR-examination comprised gradient echo (2D- and 3D-GRE) and fast spin echo sequences (T 2 -TSE and T 2 -HASTE). The signal intensity of lung parenchyma was evaluated at representative cross sections using a standardised scheme. Control studies were acquired with helical CT. RESULTS: The instilled liquid caused patchy confluent alveolar infiltrates resembling the findings in patients with pneumonia or ARDS. CT revealed typical ground-glass opacities. Before the application of the liquid, only T 2 -HASTE and T 2 -TSE displayed lung parenchyma signals with a signal/noise ratio of 3.62 and 1.39, respectively. After application of the liquid, both T 2 -weighted sequences showed clearly visible infiltrates with an increase in signal intensity of approx. 30 % at 100 ml (p < 0.01) and 60 % at 200 ml (p < 0.01). With 2D- and 3D-GRE the infiltrates were not visible, although the lung parenchyma signal increase was statistically significant. On 2D-GRE the increase in signal intensity reached 0.74 % (p = 0.32) after 100 ml and 5.6 % (p < 0.01) after 200 ml (for 3D-GRE: 2.2 % [p = 0.02] at 100 ml and 4.4 % at 200 ml [p < 0.01]). The CT controls revealed a significant increase of lung density of 17 H.E. at 100 ml (p = 0.02) and 75 H.E. at 200 ml (p < 0.01). CONCLUSIONS: MRI with T 2 -weighted sequences detects artificial alveolar infiltrates with high signal intensity and may be a highly sensitive tool to detect pneumonia in patients.

Animals↗

[Differential diagnostic problem of distinguishing pulmonary infiltrates following bleomycin therapy from metastases].

Sixty patients with malignant testicular tumours were treated with bleomycin according to the Einhorn regime. Following treatment, pulmonary infiltrates were seen on the chest x-ray of three patients and the CT of six patients. Altogether 24 infiltrates resembling metastases were seen in five patients. Five round foci were combined with infiltrates in other parts of the lung. Regression of the infiltrates after stopping bleomycin, negative tumour markers, the timing of the development of the infiltrates and the regression of the infiltrates in three patients without treatment make it extremely unlikely that the appearances were due to metastases.

Adult↗

Infiltration of sarcomas into the hip joint: comparison of CT, MRI and histologic findings in 67 cases.

We analyzed the incidence, route, and characteristics of hip joint infiltration in pelvic or proximal femoral sarcomas. 67 patients with a sarcoma that originated around the hip joint (50 pelvic and 17 femoral) were included in this study. Preoperative CT and MRI were matched with the histological findings in tumor specimens. Tumor infiltration into the hip joint was suspected on the basis of preoperative imaging in 29 patients due to articular cartilage disruption, diffuse signal changes in the acetabulum or femoral neck, signs of a tumor in the joint, or markedjoint effusion. Of these 29 patients, 15 showed tumor invasion on histological examination. 12 of 31 chondrosarcomas, none of 12 Ewing's sarcomas, and 3 of 24 osteosarcomas infiltrated into the hip joint (p = 0.008). 10 of 26 low-grade sarcomas and 5 of 41 high-grade sarcomas infiltrated into the hip joint (p = 0.02). The joint infiltration rate of the chondrosarcomas was related to their size. Of 10 tumors originating in the acetabulum, 9 penetrated through or around the osseous-ligamentous junction and one through the acetabular cartilage. In 5 proximal femur lesions, all infiltrated the joint through the femoral neck, 3 of them also through the ligamentum teres.

Adolescent↗

Water infiltration through diesel-contaminated soil.

The water infiltration characteristics through soil contaminated by diesel was investigated. Columns were packed with soil containing 15, 10, 5, 1, and 0 percent diesel on mass basis. Two soil types were used, namely, clay loam and sand. The results showed that the water infiltration rate through clay loam soil containing 1 percent diesel was about 50 percent of its value through diesel free soil. This relative rate dropped to less than 35 and 25 percent when soil contaminated with 5 and 10 percent diesel was used, respectively. Increasing the initial diesel concentration beyond 10 percent does not cause further significant drop in the water infiltration rate. Similar trend was observed when the sandy soil was used. However, the effect of initial diesel concentration on the water infiltration rate was less significant compared to the results obtained using the clay loam soil. The relative infiltration rates through the sandy soil ranged from about 80 percent in the sand containing 1 percent diesel to less than 35 percent in sand containing 15 percent diesel. The variation of the relative infiltration rate with degree of diesel saturation does not appear to be linear. Post experiment dissection of the columns showed that water partially displaced diesel pushing it down to lower soil layers. The percentage of diesel displaced by water in the sandy soil was higher than that in the clay loam soil.

Aluminum Silicates↗

Comparison of preoperative with postoperative lignocaine infiltration on postoperative analgesic requirements.

Ninety patients undergoing appendicectomy were allocated randomly to receive 1.5% lignocaine 15 ml with adrenaline infiltrated into the proposed wound line 3 min before incision, lignocaine 15 ml with adrenaline infiltrated into the wound on closure or no wound infiltration. After operation, all patients received pethidine by patient-controlled analgesia. Pain scores were assessed while supine and sitting on day 1 and 2 and the cumulative pethidine dose administered was recorded at 12, 24, 36 and 48 h after operation. There were no significant differences in the cumulative dose of pethidine required or pain scores between the three groups at any time point after operation. We conclude that pre-incisional infiltration with 1.5% lignocaine had no advantage compared with infiltration at wound closure or no wound infiltration in reducing postoperative analgesic requirements or pain scores after appendicectomy.

Adolescent↗