Pathologie-biologie最新文献

Objective

To assess the efficacy and tolerability of bortezomib with dexamethasone for patients with renal light chain (AL) amyloidosis.

Methods

Twelve newly diagnosed patients with renal AL amyloidosis were treated with a combination of bortezomib (1.3 mg/m²/d iv, d1, 4, 8, 11) and dexamethasone (20 mg/d iv drip, d1–4).

Results

Median follow-up time was 22.5 months (range, 2.1–53.6). Ten patients were evaluable. Five out of 10 (50%) patients achieved complete hematologic responses (CHR), and totally 8/10 (80%) achieved hematologic responses (HR). Median time to hematologic response was 1 month. All patients who received HR had no hematologic progression during follow-up period. Five patients (50%) had kidney responses and the other 5 patients (50%) were stable. Median time to kidney response was 3 months. No patients presented renal progression during follow-up. One patient achieved PR after 4 cycles of VD and then received autologous peripheral blood stem cell transplantation. Two out of 10 evaluable patients without hematologic response had died with median overall survival of 8.2 months. Eight of them who had HR were alive with median follow-up time of 28.5 months. Infection (6/12) and fatigue (5/12) were the most frequent side effects. Three patients developed herpes zoster and had to discontinue therapy.

Conclusions

VD produces rapid, deep and durable hematological responses and renal responses in the majority of patients with newly diagnosed renal AL. It is well tolerated. This treatment may be a good option as first-line treatment for renal AL amyloidosis patients.

Aim

The aim of this work is to know the fertility rate of the metacestodes resulting from patients suffering from hydatidosis, the one of protoscoleces's viability and by comparing the results obtained with those found elsewhere. It reports, also, the epidemiological, clinical and diagnostically aspects of the studied patients.

Materials and methods

This study has carried on 78 hydatics samples resulting from 78 patients collected between 2005 and 2012 at the laboratory of parasitology of the Mustapha hospital center of Algiers. A questionnaire on the epidemiological context (contact with an animal-host of the cycle, place of residence, presence of family cases reached of hydatidosis and knowledge on the hydatic disease) concerned 69 patients. For each sample, a direct microscopic examination is made with or without vital staining. The presence of protoscoleces made qualified the fertile cyst. Those visualized moving or resistant to eosin at 0.2% are considered viables. Indirect diagnosis is based on the techniques: passive hemagglutination, electrophoresis, Elisa IgG Echinococcus granulosus and immunoblotting IgG “Echinococcus”. Molecular analysis is based on PCR and sequencing the partials fragments of two mitochondrial genes with the primers COX1 and ND1.

Results

The results obtained show that the surgical frequency of hydatidosis is significant at the young adult and at the child. The epidemiological context associated at the disease is the conjointly presence of a dog and herbivores. The fertility rate of human hydatid cysts is 88.4% and the ones of viability of the protoscoleces is 74.5%. In this series, the serology shows global positivity at 70%. The molecular characterization of five samples identify the species: E. granulosus ss.

Conclusion

Finally, the viability and fertility rates found here are raised. Sometimes viables protoscoleses are found after use of scolicidal solution. In front of these results, the parasitical treatment is more than necessary in order to minimize the risk of occurred of secondary echinococcosis or the relapses postoperatives.

Objective

The determination of the cellular lineage in acute leukemia is a crucial step in the diagnosis and the later therapeutic conduct. In Tunisia, emerging country, some cases of acute leukemias are still treated on the basis of an only cytologic study because of lack of cytometry. Our objective is to realize a confrontation between cytology and flow cytometry in the diagnosis of AL and to analyze discrepancies.

Patients and methods

The study concerns 100 cases of AL. A second double-blind examination of the bone marrow smears of acute leukemias is realized by two cytologists and confronted to immunophenotyping.

Results

In two cases of AML, flow cytometry reassigned lineage into T ALL and biphenotypic AL. In three cases of ALL the lineage was reassigned into undifferentiated acute leukemia (2 cases) and biphenotypic acute leukemia (1 case). Lineage was not established in four cases, immunophenotyping allowed the diagnosis of B ALL in 3 cases, and of biphenotypic acute leukemia in 1 case. In both cases of discrepant findings, flow cytometry allowed the diagnosis of biphenotypic acute leukemia in a case and of AML in the other one.

Conclusion

The cytological study remains insufficient in the diagnosis of lineage even with experimented cytologists. Immunophenotyping is essential in lineage assignment and reassignment.

Introduction

Bartonella quintana (Bq) is responsible of various clinical pictures. Neuromeningeal complications are rarely reported.

Case

A 20-year-old woman was admitted for fever, headache lasting for 5 days. On admission, she was febrile at 39.3 °C and had a stiff neck. Symptoms, contact with animals, biological tests and lumbar puncture (PL) rendered viral meningitis a likely diagnosis. She had received symptomatic treatment and the outcome was favorable. Three days later, the patient had headache, agitation and confusion with fever. The PL noted 130/mm³ whites, 90% lymphocytes. The albuminorachie was 0.98 g/L, glucorachie was normal. The patient was treated with 400 mg of ofloxacine/day, seven days. Serologic tests for B. quintana were reactive. The outcome was favorable.

Conclusion

B. quintana infection should be considered in neurological symptoms of unknown etiology.

The culprit of hepatic fibrosis (HF) is linked to suprathreshold deposition of collagen. Thus, collagen reduction by improved metabolism contributes to HF management. In this study, we aimed to investigate the hepatoprotective effects of Danshensu (DSS) against carbon tetrachloride (CCl₄)-induced HF rats. The results showed that DSS-administrated rats resulted in decreasing in hepatosomatic indexes, and lowering serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Meanwhile, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were increased, while the content of malonaldehyde (MDA) was lessened in liver tissue of DSS administration group. In addition, the pro-fibrotic markers of hydroxyproline (Hyp), type III procollagen (PCIII) and hyaluronic acid (HA) contents were decreased. Histopathological examination confirmed that the hepatotoxicity in CCl₄-injured rats was alleviated following the DSS administration. Furthermore, intrahepatic protein expressions of alpha-smooth muscle actin (α-SMA), phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) were effectively down-regulated, respectively. Overall, this work demonstrates that DSS played the protective effect against CCl₄-induced cytotoxicity in liver tissue, which the probable mechanism is associated with attenuation of lipid peroxidation, collagen accumulation and enhancement of anti-oxidative defense capability, as well as regulation of intrahepatic JAK/STAT pathway for maintaining collagenic homoeostasis.

Background

Retrospective studies and case-reports have suggested the possible role of various viruses in the pathogenesis of the Kawasaki disease.

Objectives

To determine prospectively the incidence of Kawasaki diseases associated with a recent bocavirus infection in the course of a year.

Study design

Thirty-two children with Kawasaki disease were enrolled in a 13 months prospective study to assess the frequency of human bocavirus type 1 infections. Seasonal shedding of virus, markers of recent infection such as viraemia, viral load, and serum interferon alpha were analyzed.

Results

Three of 32 (9%) children had HBoV-DNA in the serum suggesting a recent infection. HBoV-DNA was detected in naso-pharyngeal aspiration of 7/32 (21.8%) children with Kawasaki Disease and six of them (18%) had an increased viral load. No common respiratory viruses were isolated from the 32 patients with the exception of one adenovirus. The seven bocaviruses were identified during the winter-spring season. In addition, 4 of 7 of Kawasaki disease patients shedding bocavirus had detectable interferon alpha in the blood, indicating a possible active or recent viral infection.

Conclusions

This study shows that a recent bocavirus infection is concomitant with the onset of some cases of Kawasaki disease. Bocavirus may be a cofactor in the pathogenesis of this disease as previously reported for other infectious agents.

Purpose

Common variable immunodeficiency (CVID) is the commonest symptomatic primary immunodeficiency. It is characterized by a defect of antibody production, recurrent respiratory tract infections and increased occurrence of auto-immune discords and lymphoproliferative disease.

Methods

This retrospective study was conducted on 29 patients fulfilling the classical CVID definition. Blood tests included immunoglobulin measurement and lymphocyte subpopulations phenotyping.

Results

This study includes 29 patients. The mean age at diagnosis was 23 years. Recurrent upper and lower bacterial respiratory tract infections were common in almost all patients. Five patients developed auto-immune conditions and six had lymphoproliferative disease. Decreased IgG was found in almost all patients. Low IgA and IgM levels were found in 89.6 % and 65.5 % of cases respectively. Abnormal T and/or B phenotype was found in 75 % of cases; the most common abnormalities were decreased circulating B (54.2 %) and T CD4+ (41.7 %) cells and inversion of the CD4/CD8 ratio (70.8 %). Patients with decreased circulating B and T CD4+ cells were significantly more likely to have auto-immune cytopenias and lymphoproliferative disease.

Conclusions

Our study confirms the heterogeneity of CVID. A patient's classification is necessary to define homogeneous groups of patients and to characterize specific molecular abnormalities in each group.

Aim

To investigate the protective function of alginate and fibrin gels used to embed porcine endocrine pancreatic islets towards human monocytes.

Methods

Groups of 200 islet equivalents from young pigs were embedded in either a fibrin or in an alginate gel, and as a control seeded in tissue culture polystyrene (TCPS) well plates. The islet cultures were incubated with 2 × 10⁵ human monocytes for 24 h. In addition, both islets and monocytes were separately cultured in TCPS, fibrin and alginate. Islet morphology, viability and function were investigated as well as the secretion of cytokines TNFα, IL-6, and IL-1β.

Results

When freely-floating in TCPS, non-encapsulated islets were surrounded by monocytes and started to disperse after 24 h. In fibrin, monocytes could be found in close proximity to embedded islets, indicating monocyte migration through the gel. In contrast, after 24 h, few monocytes were found close to islets in alginate. Immunofluorescence staining and manual counting showed that integrin expression was higher in fibrin-embedded islet cultures. A TUNEL assay revealed elevated numbers of apoptotic cells for islets in TCPS wells compared to fibrin and alginate cultures. Insulin secretion was higher with islets embedded in fibrin and alginate when compared to non-encapsulated islets. TNFα, IL-6 and IL-1β were found in high concentrations in the media of co-cultures and monocyte mono-culture in fibrin.

Conclusion

Both alginate and fibrin provide key structural support and offer some protection for the islets towards human monocytes. Fibrin itself triggers the cytokine secretion from monocytes.

Background

Idiopathic pulmonary fibrosis (IPF) is associated with a marked pulmonary vascular remodeling. The aim of this study was to investigate a potential imbalance between angiogenic and angiostatic factors in this disease.

Methods and results

Sixty-four subjects with IPF and 10 healthy control subjects (60–70 years old) were prospectively included in this multicenter study. Plasma levels of vascular endothelial growth factor A (VEGF-A), thrombospondin-1 (TSP-1) and stem cell factor (SCF) were determined by Elisa. Comparisons between IPF and controls were made using the Mann-Whitney U test. We also analyzed these soluble mediators in relation with IPF severity (DL_CO < 40% or > 40%) predicted or total lung capacity (TLC) and forced vital capacity (FVC) (both < 55% or > 55% predicted) using the same test. VEGF-A plasma levels were increased in IPF vs. controls (P = 0.0008) as well as those of TSP-1 (P = 0.008), irrespective of the severity of the disease as reflected by DL_CO, TLC or FVC values. In contrast, SCF levels were similar in IPF and controls.

Conclusions

Factors modulating angiogenic responses are dysregulated in patients with IPF with increases in VEGF-A and TSP-1. The serial assessment of VEGF-A and TSP-1 during the follow-up and the search for potential relationships with the outcome of the disease might give us hints to the clinical implication of these results.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous enzyme that catalyzes the sixth step of glycolysis and thus, serves to break down glucose for energy production. Beyond the traditional aerobic metabolism of glucose, recent studies have highlighted additional roles played by GAPDH in non-metabolic processes, such as control of gene expression and redox post-translational modifications. Neuroproteomics have revealed high affinity interactions between GAPDH and Alzheimer's disease-associated proteins, including the β-amyloid, β-amyloid precursor protein and tau. This neuronal protein interaction may lead to impairment of the GAPDH glycolytic function in Alzheimer's disease and may be a forerunner of its participation in apoptosis. The present review examines the crucial implication of GAPDH in neurodegenerative processes and clarifies its role in apoptotic cell death.