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Deposition of Schistosoma mansoni eggs in the intestinal mucosa is associated with recruitment of mucosal mast cells (MMC) expressing mouse mast cell protease-1 (mMCP-1). We investigated the involvement of mMCP-1 in intestinal barrier disruption and egg excretion by examining BALB/c mice lacking mMCP-1 (Mcpt-1−/−). Tissue and faecal egg counts from 6 weeks until 12 weeks post-infection (w p.i.) revealed no differences between wild type (WT) and Mcpt-1−/−mice. Using chamber experiments on ileal tissue revealed that at 8 w p.i., the epithelial barrier and secretory capacity were severely impaired, whereas no difference was found between WT and Mcpt-1−/−mice in this respect. However, a fragmented distribution of the tight junction (TJ) protein occludin, but not of claudin-3 or ZO-1, was observed in WT mice at 8 w p.i., while no changes in TJ integrity were seen in Mcpt-1−/−mice. Therefore, we conclude that in contrast to the situation in Trichinella spiralis-infected mice, in schistosomiasis, mMCP-1 is not a key mediator in egg excretion or impairment of the intestinal barrier. The marked decrease in ileal secretory capacity during S. mansoni egg excretion suggests that the mechanisms facilitating the passage of schistosoma eggs through the gut wall are directed more particularly at the epithelial cells.

Despite the persistently high HIV-related mortality in sub-Saharan Africa, limited information on the causes of death is available. Pathological autopsies are the gold standard to establish causes of death. In this review we describe the autopsy series performed among HIV-infected individuals in sub-Saharan Africa over the last two decades. We identified nine complete and 11 partial or minimally invasive autopsy series. Complete autopsies were performed in 593 HIV-positive adults and 177 HIV-positive children. Postmortem diagnoses were mainly infectious diseases. Tuberculosis was the most frequent, present in 21-54% of HIV-positive adults and was considered the cause of death in 32-45%. Overall, pulmonary infections accounted for approximately 66% of pathology and central nervous system infections for approximately 20%. A high discordance between clinical and postmortem diagnoses was observed. This review emphasizes the need for reliable information on causes of death in order to improve HIV patient care, guide further research, and inform health policy.

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Background and study aims : In Belgium, 10-15% of patients infected with the human immunodeficiency virus (HIV) are coinfected with hepatitis C virus (HCV). Because of increased incidence of antiretroviral drug-related hepatotoxicity and more rapid clinical evolution towards end-stage liver disease, treatment of chronic hepatitis C becomes a priority. We report the results or a multi-centred Belgian study evaluating efficacy and safety of peginterferon alpha-2b plus ribavirin in HIV-HCV co-infected patients without AIDS and without decompensated liver disease. Patients and methods : Forty-one patients, all genotypes, were screened to participate. Eventually 37 received treatment with peginterferon alpha-2b (1.5 mu g/kg/week) plus daily weight-based ribavirin for 52 weeks. About one third of the patients were genotypes 1, 2/3, and genotype 4, most of the latter being of Central African origin. About 56% of the patients had severe fibrosis (Metavir score >= F3). Results : Sustained viral response (SVR) at 24 weeks of follow-up was observed in 10/37 (27%) of patients. SVR was higher in genotype 2/3 compared to genotype 1/4 (46.7% versus 13.6%; p = 0.06) and in low (F0-F1) versus high (F2-F4) grade fibrosis (p = 0.06). Treatment was withdrawn for side effects in 11/37 patients (30%). One Child A cirrhosis patient at the start of therapy died 7 months after treatment withdrawal as a result of severe haemolytic anaemia. Conclusions : It can be concluded that weight-based peginterferon alpha-2b plus ribavirin can be successful in selected HIV-HCV co-infected patients. Caution should be applied in patients with advanced liver disease.

Our recent studies have elucidated a direct association between severe hepatic fibrosis and low levels of circulating somatostatin levels in S. mansoni infected patients in Senegal. Using somatostatin for therapy in S. mansoni infected mice resulted in a reduction in the number of parasite eggs and/or the secretion of fibrosis inducing-mediators in the infected host. Since the inhibitory activity of somatostatin occurs via binding to specific receptors, this study explored the presence of such receptors (SSTRs) on S. mansoni parasite stages. Immunohistochemistry localized SSTR2 & SSTR3 on the worm stages of S. mansoni, specifically on the tegument (with knob like protrusions) and in the internal parts of the worm pair. Receptors were found at the level of the excretory organs (flame cells) ending in a narrow canal in the cuticle. Eggs deposited in the liver and ileum also expressed these somatostatin receptors. Dot blot and Western blot identified protein bands of 70-100 and 200-250 kD molecular weight on the parasite stages. Our study indicated that circulating somatostatin levels in S. mansoni infected mammalian host might interact with the parasite stages via these receptors thereby influencing the hepatic fibrosis caused by this infection.

Tungiasis is caused by the penetration of the female sand flea Tunga penetrans into the epidermis, and subsequent hypertrophy of the parasite. In most cases lesions are confined to the feet. During a cross-sectional study, an unusual case of ectopic tungiasis in the inguinal area was detected. Histological examination of tissue samples showed a remarkable pseudoepitheliomatous aspect of the epidermis. Clinical features and differential diagnoses are discussed.

Increased microvessel density (MVD) has been observed in the bone marrow (BM) of patients with multiple myeloma (MM), acute lymphoblastic leukaemia, acute myeloid leukaemia, and myelodysplastic and myeloproliferative syndrome. The MVD is the net result of cumulative phases of angiogenesis and angio-regression and is as such not an indicator of the ongoing angiogenesis at the time of biopsy. There is, therefore, a need for additional methods that allow the estimation of ongoing angiogenesis. Double immunostainings for CD34 and Ki-67 can be used on paraffin-embedded tissue to determine the endothelial proliferation fraction. The BM endothelial cells, as a component of the BM stroma, have a close interaction with the malignant cells. In MM, for example, they are involved in the specific homing and are a source of paracrine growth factors. Targeting the BM microvessels will not only influence the nutrient and oxygen supply, but will in addition reduce the growth stimuli provided by the EC.

We investigated the activity and toxicity of raltitrexed (Tomudex) as a single agent treatment in patients with Malignant Pleural Mesothelioma (MPM) in a multicentre phase II European Organization for Research and Treatment of Cancer (EORTC) study. This study enrolled chemonaíve patients with histologically-confirmed measurable MPM. Raltitrexed was administered at the dose of 3 mg/m(2) intravenous (i.v.) bolus on an outpatient basis every 3 weeks. A maximum of eight cycles was planned in cases with an absence of progression or unacceptable toxicity. 24 patients received a total of 104 courses. 5 patients (20.8%, 95% confidence interval (CI) 7.1-42.2%) had a partial response (PR), which was confirmed by an independent radiology committee. Toxicity was mild, with diarrhoea, nausea, vomiting, fatigue and neutropenia as the major side-effects, but not exceeding grade 3 toxicity. We conclude that raltitrexed has activity as a single agent in the treatment of MPM, and that further studies with this drug in MPM are warranted

A 38-year-old patient presented with an anterior mediastinal mass after chemotherapeutic and surgical treatment for lung metastases from a malignant histiocytoma. Because of the risk for tumour recurrence the thymic mass was resected. Thymic hyperplasia was found on pathological examination. In this case thymic hyperplasia is a rebound phenomenon aflcer chemotherapy. It appears to atrophy during the administration of chemotherapy and regrow afterwards. Surgical resection provides the definitive diagnosis and treatment.

Cutaneous T-cell lymphomas represent a group of malignant lymphoproliferative disorders characterised by the occurrence of a monoclonal population of T-lymphocytes. Diagnosis of early stages of this disease is a difficult challenge for both the dermatologist and the dermatopathologist. With the aid of the polymerase chain reaction it is possible to amplify specific regions of the T-cell receptor gamma gene. The amplification products can then be separated by denaturing gradient gel electrophoresis in order to detect a monoclonal population of T-lymphocytes in the infiltrate. We studied 4 patients with the clinicopathologic diagnosis of mycosis fungoides and 2 patients diagnosed as large plaque parapsoriasis. A monoclonal population was detected in 3 of the 4 mycosis fungoides cases and in 1 of the patients with large plaque parapsoriasis. This indicates that our analysis can help us establishing a diagnosis, and it can also help us to identify patients with a possible early stage of the disease, which clinically or histologically is not yet recognised as such.

Single extraocular muscle hypertrophy is usually caused by an orbital pseudotumour. We present two cases in which unexpectedly a malignancy was diagnosed during work-up of a suspected orbital pseudotumour.

Immunohistochemical testing using biotinylated tyramine is a recently described technique that results in a strong amplification of the detection signal using antibodies at very high dilutions. In this report we compare the sensitivity and cost-effectiveness of the technique using "homemade" biotinylated tyramine with those of two commercially available kits. The technique using homemade tyramine was easy to follow and highly sensitive and resulted in a 2.5- to 5-fold reduction in costs compared with the commercial kits. Tyramine-amplified immunohistochemical testing using homemade biotinylated tyramine is a valuable and inexpensive tool for both the diagnostic and experimental histopathology laboratory.

ispartof: Thorax vol:53 issue:11 pages:915-918 status: published

From January 27, 1992 to December 12, 1994, 100 consecutive patients (86 men and 14 women) with a mean age of 62.5 years underwent lung resection for a non-small cell lung cancer. Squamous cell carcinoma was predominantly found (52%), followed by adenocarcinoma (23%) and large cell carcinoma (18%). Postoperative staging was Stage 0, 1 patient; Stage I, 57; Stage II, 17; Stage IIIa, 20 and Stage IIIb, 5. Thirty-day mortality was 4% (4 patients) with 10.7% for pneumonectomy and 0% for lobectomy or lesser resection. For the whole group 1-, 2- and 3-year survival rates were 83%, 68% and 65% respectively. Survival rates for N0, N1 and N2 after 3 years were 70%, 59% and 54% respectively. In the univariate analysis, a trend to statistical significance was noted between N0 and N1 (p = 0.08). There was no difference in short-term survival between N0 and N2 which represents a highly selected group of patients with N2 disease. In the multivariate analysis the only two independent variables with impact on survival were number of pack-years and diameter of the tumour (p0.05). Ninety-two quality of life questionnaires (EORTC QLQ-C30) were sent to home physicians. We collected 31 questionnaires (34%) after 2.5 months. A clear relationship was not seen between complaints of pain or dyspnea and extent of resection or lung function postoperatively. Instead, the global quality of life seemed to be influenced by the extent of resection to the advantage of a lobectomy and disadvantage of a pneumonectomy. Difficulties related to quality of life analysis are discussed and future directions are given.

A 49-year-old man was admitted for further investigation of a coin lesion with a diameter of 1 cm. He was a heavy smoker with no professional exposure. Since the percutaneous needle biopsy did not yield a definitive diagnosis, a thoracoscopy was performed. The solitary pulmonary nodule was found to be an intrapulmonary lymph node with anthracosilicotic pigment and a thoracoscopic wedge resection was performed. A review of the case reports in the period 1961-1993 shows that intrapulmonary lymph nodes could be more frequent than originally thought. All patients were smokers but professional exposure was not a constant finding. The differential diagnosis and management of the indeterminate solitary pulmonary nodule are discussed.

We studied immunoreactivity for c-fos protein and c-myc protein in malignant mesothelioma (36 cases) and non-neoplastic pleural mesothelium (45 cases) using the murine monoclonal antibodies 14E10 and 6E10. All malignant mesotheliomas and cases with non-neoplastic mesothelium exhibited not only nuclear but also cytoplasmic immunoreactivity for c-fos and cmyc protein in the majority of mesothelial cells. There was no statistically significant difference between the various mesothelioma subtypes or between neoplastic and non-neoplastic mesothelium for c-fos protein immunoreactivity (p>0.05). There was statistically significant difference between neoplastic and nonneoplastic mesothelium for c-myc protein immunoreactivity (p

The ilocaecal junction remains a controversial region of the gut. There are still a lot of questions concerning its anatomical structure and function. In this review, a concise overview is given of the recent and older literature on the embryology, anatomy, including the intrinsic and extrinsic innervation, and the pharmacology of this region. Based on the available data from the literature, evidence is accumulating for a sphincteric function.

Botryomycosis is an atypical reaction of the host to a common bacterial infection. A case of botryomycosis mimicking a liposarcoma as suspected on clinical and radiological grounds is described. The diagnosis was made by biopsy and culture of the lesion. A review of the literature is given.

Portosystemic collateral circulation was induced in mice infected or not with Schistosoma mansoni by partial ligation of the portal vein. The effects on immune glomerular deposits were assessed and compared to findings in unoperated infected, sham-operated and normal animals. Mesangial immune deposits of IgM, IgA, IgG and C3 were found by immunofluorescence significantly more frequently in operated than in unoperated infected mice. Schistosomal antigen was demonstrated in 5 animals out of 38 infected ones, 4 of the 5 having been operated. The results suggest that portosystemic collateral circulation might be an important factor in the genesis of schistosomal glomerulopathy, perhaps by diversion of antigens or complexes from the Kupffer cells. The high percentage of glomerular immune deposits found in uninfected ligated animals (71-4%) suggests furthermore that non-specific immune factors possibly of intestinal origin could be involved.

Between 1990 and 2000, 56 consecutive patients underwent lung resection for removal of metastatic disease. Mortality, disease-free interval, and overall survival were studied. Only patients with a complete follow-up were included and data were collected conform the protocol of the International Registry of Lung Metastases. The primary tumour in our series was an epithelial tumour in 25 patients (45%), sarcoma in 15 (27%), germ cell tumours in 11 (19%) and melanoma in 5. Operative mortality was 1.4% (1 out of 73 procedures). Germ cell tumours had the best survival (76% at 5 years), and melanoma the worst (0% at 5 years). Multivariate analysis showed that survival for patients who underwent 2 or more metastasectomies was surprisingly good with a 5-year survival rate of 46%. Survival was not related to disease-free interval, multiple lung metastases, or pneumonectomy. It is in accordance with some reports that a short disease-free interval, numerous lung metastases, or recurrence after the first metastasectomy should not preclude patients from operation.

Background and study aims : In Belgium, 10-15% of patients infected with the human immunodeficiency virus (HIV) are coinfected with hepatitis C virus (HCV). Because of increased incidence of antiretroviral drug-related hepatotoxicity and more rapid clinical evolution towards end-stage liver disease, treatment of chronic hepatitis C becomes a priority. We report the results or a multi-centred Belgian study evaluating efficacy and safety of peginterferon alpha-2b plus ribavirin in HIV-HCV co-infected patients without AIDS and without decompensated liver disease. Patients and methods : Forty-one patients, all genotypes, were screened to participate. Eventually 37 received treatment with peginterferon alpha-2b (1.5 mu g/kg/week) plus daily weight-based ribavirin for 52 weeks. About one third of the patients were genotypes 1, 2/3, and genotype 4, most of the latter being of Central African origin. About 56% of the patients had severe fibrosis (Metavir score >= F3). Results : Sustained viral response (SVR) at 24 weeks of follow-up was observed in 10/37 (27%) of patients. SVR was higher in genotype 2/3 compared to genotype 1/4 (46.7% versus 13.6%; p = 0.06) and in low (F0-F1) versus high (F2-F4) grade fibrosis (p = 0.06). Treatment was withdrawn for side effects in 11/37 patients (30%). One Child A cirrhosis patient at the start of therapy died 7 months after treatment withdrawal as a result of severe haemolytic anaemia. Conclusions : It can be concluded that weight-based peginterferon alpha-2b plus ribavirin can be successful in selected HIV-HCV co-infected patients. Caution should be applied in patients with advanced liver disease. (Acta gastroenterol. belg., 2009, 72, 389-393).

Treatment of acute renal allograft rejection with mouse monoclonal antibody (OKT3) is associated with systemic and neurologic side effects. We describe cerebral abnormalities in a 13-year-old boy with steroid-resistant renal allograft rejection. After treatment with OKT3, an acute neurologic syndrome developed, including seizures, lethargy, and decreased mental function. CT and MR imaging revealed confluent cerebral lesions at the corticomedullary junction. Contrast-enhanced MR images showed patchy enhancement, indicating blood-brain barrier dysfunction. The diagnosis of OKT3-induced encephalopathy with cerebral edema and capillary leak syndrome was made. Although CT and MR findings are nonspecific, neuroradiologists should be aware of this condition in transplant patients treated with OKT3.

We report on the cytogenetic and molecular analysis of a malignant melanoma of the soft parts (MMSP). A t(12;22)(q13;q12) was found as the only structural chromosomal change, and this provides additional support for the important role of this translocation in MMSP development. Molecular analysis revealed in frame fusion between exon 10 of the Ewing's sarcoma oncogene (EWS) and codon 110 of ATF-1. In previously analyzed MMSPs, junctions were observed between EWS exon 8 and ATF-1 codon 65. The present data thus indicate that, as in Ewing's sarcoma, different fusion proteins can occur in MMSP. The presence of the EWS/ATF-1 fusion gene in the tumor cells was demonstrated by dual color fluorescence in situ hybridization on interphase nuclei. Our data provide additional support for the specific association of the t(12;22) and the resulting EWS/ATF-1 gene fusion in MMSP. This particular genetic aberration, therefore, serves as a strong diagnostic marker for MMSP. We conclude that detection of the t(12;22) by cytogenetic or molecular analysis is useful in establishing or confirming the diagnosis of MMSP.

To evaluate the performance of karyometry and histometry in the prediction of survival, recurrence and response of early-stage invasive cervical carcinoma.Nuclear morphometry, chromatin texture and tissue architecture (characterized by syntactic structure analysis) were measured using a semiautomated image analysis system on 46 cases of Feulgen-stained tissue sections. The performance of the features was compared to that of clinical features, reported to be the best prognosticators until now, such as age, lympho-vascular permeation, histologic type, stage and grade. A K nearest neighbor classifier was used for classification.In the prediction of three-year survival, recurrence and response, syntactic structure analysis proved to be the best performer. Classification rates were, respectively, 100%, 94.4% and 94.5%. In all classifications, karyometric and histometric features outperformed clinical features. In general, the best performing features described differences in second-order population statistics (standard deviations).The results show that a quantitative analysis based on nuclear morphology, chromatin texture and histology can be considered an excellent aid in the prognosis of invasive cervical carcinoma. The measurements are not hampered by the need to undertake complete resections and are suited to daily practice when implemented in a semiautomated image analysis system.

Non-haematogenic tumours arising primarily in the bone are rare. They are classified based on their histomorphology. Within the osteofibrous group the spectrum ranges from benign, exclusively fibrous lesions to high-grade osteosarcoma. These osteofibrous tumours show histological variability in a given entity as well as similarities between entities. The purpose of this thesis was to reveal the meaning of the phenotypic spectrum of osteofibrous tumours. In retrospect, the histological subtype of osteosarcoma is a predictive factor for response to chemotherapy, late relapse and risk of a hereditary cancer syndrome, but not for survival. However, the poor histological response of chondroblastic osteosarcomas to neo-adjuvant chemotherapy did not translate in a lower survival rate. On the other hand, overlapping histological and/or clinical parameters between certain tumour entities such as for example adamantinoma and Ewing sarcoma, and desmoplastic fibroma of bone and desmoid type fibromatosis of soft tissue, does not justify to classify these tumours as part of one disease entity as was demonstrated in this thesis. Thus, the correct classification, reclassification of known entities on new insights and sub-classification on phenotypic differences, when related with biological behaviour, has implications for clinical practice and disease management, and contributes to optimal patient care.