Musculoskeletal hydatid disease: report of a rare case with primary and exclusive localization in right hemi-pelvis and femur.

Hydatid Disease (HD), also called Echinococcosis or Hydatidosis, is a parasitic infection caused by the larval stage of the tapeworm Echinococcus: E. granulosus or E. multilocularis. HD occur most frequently in liver or lungs, rarely in brain, skeletal muscles, bones, kidneys, spleen. Bone infestation of Echinococcosis hydatid cysts occurs respectively by haematogenous seeding and progressive invasion into bone by lesions in the adjacent soft tissues. Patients with musculoskeletal HD clinically show the disease in adulthood because the lesions develop very slowly. In some cases, HD is an uncommon cause of soft tissue mass, pain and neurovascular symptoms due to compression or to secondary infection. Diagnostic imaging plays an important role in the diagnosis of HD and in the differential diagnosis with soft tissue tumors. We present a rare case of male patient of 42 year-old with diagnosis of HD with primary and exclusive localization in right hemi-pelvis and femur.

Sustainability assessment of waste and wastewater recovery for edible mushroom production through an integrated nexus. A case study in Lazio.

With a global population of eight billion people, improving the sustainability and nutritional quality of diets has become critical. Mushrooms offer a promising solution because of their nutritional value and ability to be grown from agricultural residues, in line with the circular economy. This study, therefore, focuses on assessing the environmental compatibility of Agaricus bisporus mushroom production in Italy, the world's third largest per capita consumer, by using a Life Cycle Assessment (LCA) and an integrated Water-Energy-Nitrogen-Carbon-Food (WENCF) nexus analysis. The LCA results reveal that for a functional unit of 23,000 kg of the substrate, the production process emits 2.55 × 104 kg of CO2 eq. Sensitivity analysis shows that changing input quantities can reduce environmental impacts by about 5 %. In addition, one scenario evaluates the environmental effects of recycling resources by introducing water and ammonium sulfate from scratch instead of continuous recycling, along with water purification. The study shows that sustainable food production can mitigate resource depletion, climate-altering emissions, and intersectoral competition. Using agro residues for mushroom cultivation and optimizing resource management contribute to environmental sustainability. This approach could not only improve the resilience and efficiency of the food system but could also improve the sustainability of diets. In conclusion, this study highlights the importance of adopting sustainable and circular approaches in mushroom production to address global challenges related to food sustainability.

Concealed by darkness: Combination of NMR and HRMS reveal the molecular nature of dissolved organic matter in fractured-rock groundwater and connected surface waters.

Detailed molecular composition of solid phase extracted dissolved organic matter (SPEDOM) collected from fractured-rock groundwater was compared to connected surface river water at two different watersheds in the unconfined chalk aquifer of Champagne in France using full scan ultrahigh resolution electrospray and photoionization Fourier transform ion cyclotron mass spectrometry (FT-ICR MS), Orbitrap tandem MS (MS/MS) and 1H magnetic resonance spectroscopy (NMR). 1H NMR spectroscopy indicated that groundwater SPEDOM carried a higher contribution of aliphatic compounds while surface river waters SPEDOM were enriched in carboxyl-rich alicyclic molecules (CRAM), acetate derivatives and oxygenated units. Furthermore, we show here that use of photoionization (APPI(+)) in aquifer studies is key, ionizing about eight times more compounds than ESI in surface river water samples, specifically targeting the dissolved organic nitrogen pool, accounting for more than 50% of the total molecular space, as well as a non-polar, more aromatic fraction; with little overlap with compounds detected by ESI(-) FT-ICR MS. On the other hand, groundwater SPEDOM samples did not show similar selectivity as less molecular diversity was observed in APPI compared to ESI. Mass-difference transformation networks (MDiNs) applied to ESI(-) and APPI(+) FT-ICR MS datasets provided an overview of the biogeochemical relationships within the aquifer, revealing chemical diversity and microbial/abiotic reactions. Finally, the combination of ESI(-) FT-ICR MS and detailed Orbitrap MS/MS analysis revealed a pool of polar, anthropogenic sulfur-containing surfactants in the groundwaters, likely originating from agricultural runoff. Overall, our study shows that in this aquifer, groundwater SPEDOM contains a significantly reduced pool of organic compounds compared to surface river waters, possibly related to a combination of lack of sunlight and adsorption of high O/C formulas to mineral surfaces.

The largest prehistoric mound in Europe is the Bronze-Age Hill of Udine (Italy) and legend linked its origin to Attila the Hun.

Prehistoric monuments often constitute evident landmarks and sometimes, after falling into disuse, fascinated local people enough to stimulate speculations about their origin over time. According to legend, the Hill of Udine (NE Italy) was built by Attila the Hun's soldiers, but its origin (natural or anthropogenic) has been debated until now. Our research analyzed five new 40-m long stratigraphic cores, investigating for the first time the total thickness of the hill and compared the data with the available archaeological information. Moreover, we considered other hills and mounds in northern Italy and other European regions where folklore traditions relate their origin to Attila. The geoarchaeological and ethnographic data prove that the Hill of Udine is a Bronze Age anthropogenic mound erected between 1400 and 1150 BCE and that, later, folklore has transformed the ancestral memory of its origin into legend. By measuring 30 m in height and over 400,000 m3 in volume, the flat-topped hill is the largest prehistoric mound in Europe. This discovery reveals unprecedented skills in earth construction and confirms significant anthropogenic modifications of the environment during Bronze Age.

Pancake kidney, a rare and often misdiagnosed malformation: a case report and radiological differential diagnosis.

Renal ectopia and fusion anomalies are Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT) that are usually incidentally detected and asymptomatic. Patients affected present a higher risk of complications like recurrent urinary tract infections or obstruction. Pancake kidney (PK) is one of the rarest types of renal anomaly with complete fusion of the superior, mild and inferior poles of both kidneys in the pelvic cavity. Each kidney has its own excretory system with two ureters that do not cross the midline. In the asymptomatic cases, a conservative approach should be performed. Surgical management may be needed when urological problems occur. PK is often associated with congenital anomalies of other organs. Ultrasound is the first line radiological examination for the diagnosis and the follow-up of kidney malformations. The main sonographic findings suggesting PK diagnosis are a large and lobulated renal mass consisting of two fused lateral lobes without an intervening septum located in the pelvic cavity. Each lobe usually has a separate pelvicalyceal system, the renal pelvis is anteriorly placed and the ureters are usually short and enter the bladder normally without crosses the midline. Ultrasonography gives useful information on the morphology and volume of the organ, and on its vascularization through the use of the Color- and Power-Doppler. Computer Tomography and Magnetic Resonance Urography are second level techniques used to confirm the diagnosis and to evaluate the presence of other abnormalities. The knowledge of the imaging findings and the anatomy of congenital renal malformations is important to avoid diagnostic pitfalls and misinterpretations. We report the case of a 14-years old female with PK who was misdiagnosed with a horseshoe kidney (HSK) during an abdominal ultrasound.

Secondary aneurysmal bone cyst in Langerhans cell histiocytosis: Case report, literature review.

Langerhans cell histiocytosis (LCH) is a rare disease of the myeloid precursor cells, it predominantly occurs in the skull and long bones as unifocal bone lesions. Aneurysmal bone cysts (ABC) are benign, expansive and lytic bone. Reports of secondary ABC occurring in LCH are rare, having only been reported twice in the skull. Here, we report the first case of LCH masquerading as ABC in a 14-month-old female child who presented with a rapidly growing mass in her left femur. The lesion had typical radiological features of ABC, and only histological examination revealed the presence of cells suggestive of LCH.

Presence of the Tn antigen on hematopoietic progenitors from patients with the Tn syndrome.

The Tn syndrome is an acquired clonal disorder characterized by the exposure of a normally hidden determinant, the Tn antigen, on the surface of human erythrocytes, platelets, granulocytes, and lymphocytes. Two distinct populations, Tn positive (Tn+) and Tn negative (Tn-), of mature hemopoietic cells are present in Tn patients. To determine whether the Tn antigen is already expressed on erythroid, myeloid, and pluripotent progenitors, light-density mononuclear blood cells from two patients with this syndrome were separated by fluorescent-activated cell sorting and by affinity chromatography into Tn+ and Tn- fractions, using their binding properties to Helix pomatia agglutinin (HPA). Burst-forming-unit erythroid (BFU-E), colony-forming-unit granulocyte/macrophage (CFU-GM), cells were assayed in plasma clot cultures. After 12-14 d of culture, colonies were studied by a double fluorescent labeling procedure. First, a fluorescein-conjugated HPA permitted evaluation of the presence or absence of the Tn antigen at the surface of the cells composing each colony, and second, the binding of a murine monoclonal antibody against either glycophorin A (LICR-LON-R10) or against a myeloid antigen (80H5), revealed by an indirect fluorescent procedure, was used to establish the erythroid or myeloid origin of each cell. The Tn+ fraction obtained by cell sorting gave rise to nearly 100% Tn+ colonies composed exclusively of cells bearing this antigen. The reverse was observed for the Tn- cell fraction. These results demonstrate that in the Tn syndrome, BFU-E, CFU-GM, and CFU-GEMM of the Tn+ clone express the Tn antigen at this early stage of differentiation.

Myeloid and megakaryocytic properties of K-562 cell lines.

The expression of myeloid and megakaryocytic markers of differentiation has been studied in one K-562 cell subline, in its clones, and in the original cell line. Cytotoxicity, electron microscopy, immunofluorescence studies with a panel of polyclonal and monoclonal antibodies, and radioimmunoassays were performed on K-562 cells before and after induction with hemin, sodium butyrate, and 12-O-tetradecanoylphorbol-13-acetate. Myeloid membrane markers were present in all K-562 cell lines. Only the early granulopoietic cell surface markers were expressed in 75 to 95% of the cells, while none of the late membrane markers was detected. In contrast, neither the early (myeloperoxidase) nor late (lactoferrin) cytoplasmic markers were present. Thus, K-562 cells showed a membrane phenotype similar to that of a normal or leukemic promyelocyte but lacking myeloperoxidase. Membrane megakaryocytic markers, such as platelet glycoprotein IIIa and platelet peroxidase, were also detected in K-562 cells. However, some other early megakaryocytic markers, such as platelet glycoprotein lb, Factor VIII-R-Ag, and platelet Factor 4, could not be detected by fluorescent labeling. Cloning of the cell line did not result in the selection of a unipotential cell line. These results could be explained by the expression of multilineage markers in a single cell. In all of the cell lines and clones, hemin slightly increased the expression of the myeloid membrane markers without any modification of the megakaryocytic markers. Sodium butyrate and 12-O-tetradecanoylphorbol-13-acetate diminished most of the myeloid markers and very significantly increased the expression of the megakaryocytic markers.

Ultrastructural and cytochemical characterization of blasts from early erythroblastic leukemias.

Among nine cases of early erythroblastic leukemia previously diagnosed using a panel of antibodies, two patients have erythroid blasts expressing glycophorin A, seven patients have blasts with a more immature phenotype. These immature blasts were labeled by the FA6-152 monoclonal antibody when studied with the immunogold technique. The blasts exhibited large nucleoli, and their cytoplasm contained numerous ribosomes and large mitochondria. In the Golgi apparatus several granules resembled the theta granules as previously described and contained ferritin molecules in the absence of rhopheocytosis. A large proportion of these blasts exhibited a platelet peroxidase (PPO)-like activity. As the blasts from the two other patients with a more mature phenotype and glycophorin A reactivity lacked this PPO, this enzyme seems to be restricted to the more immature cells. Since in these leukemic samples immature erythroid blasts were admixed to promegakaryoblasts, immunogold labeling was also performed with antiplatelet antibodies. This latter population which was labeled with C17, a monoclonal antibody to platelet glycoprotein IIIa, showed strong PPO activity but lacked theta granules and ferritin. In the normal bone marrow enriched by panning for CFU-E (8%) and depleted in progenitors of other lineages, blast cells showing characteristics similar to leukemic erythroid blasts were seen. They exhibited theta granules and ferritin and a proportion of them also had a PPO-like activity. Thus, a PPO reaction is not restricted to the platelet-megakaryocyte line. In conclusion, a PPO-like activity and ferritin molecules were present in immature leukemic erythroid blasts. Similar cells could be identified from normal bone marrow.

Alfa-interferon in the treatment of essential thrombocythemia: clinical results and evaluation of its biological effects on the hematopoietic neoplastic clone. Italian Cooperative Group on ET.

The efficacy of alfa-interferon (alfa-IFN) in essential thrombocythemia (ET) patients has been reported by several authors. The aim of this study is to assess the magnitude of the effect of alfa-IFN on the neoplastic clone. As of December 1993, 11 ET patients received alfa-IFN at a dose of 3-6 MU/s.c./day for 6 months. Ten of 11 obtained complete hematological remission (CHR) and one achieved partial hematological remission. Megakaryocyte concentration was reduced in six cases. The spleen,which was enlarged in four patients, decreased in size in two patients. Seven of eight patients who were symptomatic at diagnosis obtained resolution of symptoms. In order to obtain indications about the structural modifications induced by alfa-IFN in ET megakaryocytes (Mks), Fourier-transform infra-red microspectroscopy analysis performed on 10 single Mks of each patient, was done in seven of 11 patients; the analysis showed a reduction of A1/A2 ratios (A1 integrated area of the band at 1080 cm(-1) due to the nucleic acids absorption; A2 integrated area of the band at 1540 cm(-1) due to proteic components absorption) in five cases, and in three of these five patients A1/A2 ratios achieved normal values. After alfa-IFN treatment we did not observe any change in the methylation pattern of DNA from the granulocyte fraction. Our results confirm the efficacy of alfa-IFN in ET patients, and the decrease of A1/A2 ratios in several patients is a demonstration of the depth of the effect of alfa-IFN on the neoplastic clone. The results of clonality studies showed the persistence of clonal hematopoiesis. Whether higher alfa-IFN dose and/or more prolonged alfa-IFN therapy may allow a restoration of polyclonal hematopoiesis remains to be determined and should be explored in future clinical trials.

Factors associated with climacteric symptoms in women around menopause attending menopause clinics in Italy.

OBJECTIVE: To obtain data on correlates of climacteric symptoms in women around menopause attending menopause clinics in Italy. METHODS: Since 1997 a large cross sectional study has been conducted on the characteristics of women around menopause attending a network of first level menopause outpatient's clinics in Italy. A total of 66,501 (mean age 54.4 years) women are considered in the present paper. RESULTS: The odds ratios of moderate and severe hot flashes/night sweats were lower in more educated women and (for severe symptoms only) in women reporting regular physical activity. Depression, difficulty to sleep, forgetfulness and irritability tended to be less frequent in more educated women and (depression only) in women reporting regular physical activity. Parous women reported more frequently these symptoms. CONCLUSIONS: This large study confirms in Southern European population that low education, body mass index and low physical activity are associated with climacteric symptoms. Parous women are at greater risk of psychological symptoms.

In vitro inhibition of hematopoiesis by HNK1, DR-positive T cells and monocytes after allogeneic bone marrow transplantation.

Blood CFU-GM and BFU-E, grown from 17 patients who had undergone allogeneic bone marrow transplantation (BMT), were studied by the plasma-clot technique before day 45, and at a time when their blood count was approximately normal. The number of colonies varied from one patient to another, but was always lower than in normal subjects. Removal of cells forming rosettes with sheep erythrocytes (E+C) increased colony growth in four out of eight cases, whereas removal of adherent cells (AC) had the same effect in five out of six cases. Addition of E+C or AC after their initial removal restored the inhibition of colony growth. This suppression was noted at a 1:1 to 8:1 cellular ratio and ranged from 25% to 75%. The phenotype of the suppressive cells was further characterized by complement-mediated lysis with monoclonal antibodies (MoAbs) and fluorescent labeling. Two types of cells associated with inhibition of colony growth were identified: the first were E+C positive, characterized by the T3, HNK1, DR, and T8 determinants; the second were identified by the MO2 MoAb, indicating their monocytic origin, together with their properties of adherence. Similar suppressor cells of CFU-GM were found in the marrow of two other allogeneic BMT patients. A direct suppressive effect of the two types of cells was demonstrated in one experiment when MO2+ and/or HNK1+ cells collected by cell sorting were added back to cultures depleted in MO2+ and HNK1+ cells by complement-mediated lysis and were both found to decrease colony growth. Purified HNK1+ cells led to moderate inhibition of colony growth, which was not enhanced by increasing their concentration. This suppressive effect of hematopoiesis could be the consequence of an allogeneic reaction, since no inhibition was affected by T cells or monocytes in seven autologous BMTs and one syngeneic BMT.

Normal human serum contains a factor(s) capable of inhibiting megakaryocyte colony formation.

Growth of megakaryocyte colonies from human bone marrow progenitors has been achieved in plasma clot culture. Megakaryocyte colonies were identified either by cytological examination or by immunofluorescent labelling using a monoclonal antiplatelet antibody (J 15). No significant differences were observed in the quantitation of the colonies by these two methods. In the absence of a stimulating factor, MK colonies were detectable when high cellular concentrations were seeded. Among the numerous conditioned media tested for their ability to stimulate MK colony formation, conditioned medium from leukocytes stimulated by PHA (PHA-LCM) was the most effective. However, under standard conditions of culture corresponding to 20% normal human sera, colony formation was not related linearly to seeding density even when cultures were stimulated by PHA-LCM. Upon reduction of the concentration of serum (2.5-5%) in the culture medium, colony formation displayed a linear relationship seeding density only when PHA-LCM was used as the stimulating factor. At the same time, the size of the colonies increased. Such inhibition was observed with all the human sera tested but it varied in extent from one batch to another. Replacement of serum by albumin, iron-saturated transferrin, alpha-thioglycerol and low density lipoproteins at physiological concentration but in the presence of bovine plasma provided a culture system whose ability to support colony formation equalled that of low concentrations of whole serum; spontaneous MK colony formation still occurred. Our results provide evidence for the presence of an inhibitor(s) of MK colony formation in normal human sera, and demonstrate the role of cellular factors in stimulating MK colony formation.

Treatment of B-cell non-Hodgkin's lymphoma with anti CD 20 monoclonal antibody Rituximab.

Rituximab is a chimeric anti CD-20 monoclonal antibody containing human IgG1 kappa constant regions, with murine variable regions. The anti-lymphoma effects of Rituximab are probably due to complement and antibody-dependent cell-mediated cytotoxicity, and induction of apoptosis. Phase II trials have demonstrated a strong activity of rituximab alone in indolent B non-Hodgkin lymphoma, especially in patients with follicular lymphoma. The most utilized dose-schedule is 375 mg/m(2) weekly x 4. The association with chemotherapy or with interferon-alpha increases Rituximab efficacy. More recently, Rituximab have showed activity also in diffuse large cell lymphoma, mantle cell lymphoma and in other B-malignancies. Good results have also been obtained utilizing Rituximab for in vivo purging. However, we are still far from having found a definite position for Rituximab in the treatment of lymphoproliferative disorders. The aim of future studies should be to develop new strategies that will hopefully produce the most effective Rituximab-based regimens in order to find the Rituximab key position in the treatment of B-malignancies

Evidence that residual host cells surviving the conditioning regimen to allogeneic bone marrow transplantation inhibit donor hematopoiesis in vitro--the role of TNF-alpha.

Blood cells were obtained from patients selected for allogeneic bone marrow transplantation who had undergone a conditioning regimen (CR) with high-dose chemotherapy and total body irradiation. The majority of residual cells bore CD3 antigen (range: 68-98%), and the CD4/CD8 ratio was normal. The effect of these residual/radioresistant cells on donor bone marrow hematopoiesis was investigated in eleven cases. Growth of donor CFU-GM and BFU-E was inhibited by 22-65% and 29-77%, respectively, when donor marrow was cocultured with residual cells at various ratios. In contrast, blood cells obtained from two patients prior to CR had no inhibitory effect. Supernatants obtained following incubation of residual cells from 9 patients were able to inhibit the growth of CFU-GM and BFU-E from normal unrelated subjects, whereas supernatants obtained before CR and from cultured normal marrow had no inhibitory effect. In addition, in blocking experiments, an anti-TNF-alpha MoAb was able to prevent this inhibition. Thus, TBI might be able to select and/or activate cells responsible for hematopoietic growth inhibition by a mechanism involving, at least in part, TNF-alpha.

A human minor histocompatibility antigen which appears to segregate with the major histocompatibility complex.

We obtained a cell line (So1) from a patient who rejected a T-depleted allogeneic BMT. Cytotoxic activity by cell-mediated lympholysis was found using So1 as effector and EBV-transformed donor B cells as targets, but no lysis of the patient's pretransplantation cells and of an unrelated HLA-nonidentical subject was observed, suggesting it was related to recognition of a minor transplantation antigen which could have contributed to rejection of the graft. To define the HLA-restricting element(s), cell-mediated lympholysis experiments were performed with several B cell lines as targets. So1 lysed only targets sharing an HLA-B44 antigen with the patient, thus demonstrating that the minor transplantation antigen recognized was restricted by HLA-B44. The absence of lysis against the patient's pretransplantation cells may be related to the absence of the minor antigen, suggesting that the patient's cytotoxic lymphocytes able to recognize a minor transplantation antigen on the donor cells contributed to the rejection of the HLA-identical graft. Mendelian segregation of this minor antigen was found in familial studies. Lysis was observed with cells from members of 2 families who had an association of HLA-B44 antigen in the haplotype and the minor antigen, whereas in 2 other HLA-B44-positive families, no lysis was found, probably because this minor antigen was absent. Furthermore, these family studies: (1) demonstrated that this minor antigen segregates with the MHC, suggesting its localization on chromosome 6; and (2) showed a close relationship between the minor antigen and HLA-B44, strongly suggesting a linkage disequilibrium between the minor antigen and its restriction antigen B44.

Immunological characterization of the leukemic megakaryocytic line at light and electron microscopic levels.

Twenty cases of leukemia involving platelet precursors have been identified by a panel of monoclonal and polyclonal antiplatelet antibodies and by the ultrastructural demonstration of platelet peroxidase (PPO). The two techniques were in close agreement both for identification and for the quantitation of the blast cells except in three cases where PPO was present in the absence of the immunological markers. The immunological appearance of the leukemic megakaryocytic precursors was identical to that of their normal counterparts; the cells were positive with J 15 (anti GP IIb-IIIa complex), C 17 (anti GP IIIa), J 2 (anti GP 26,000) AN 51 (anti GP Ib). A diffuse cytoplasmic labelling was observed with anti factor VIII vwF and anti platelet factor 4 (PF 4). In addition, the leukemic maturation was quite similar to normal megakaryocyte differentiation since in micromegakaryocytes the expression of Gp Ib was strong and an intense granular pattern of labelling with anti factor VIII vwF and anti PF 4 was observed. In no case was the leukemic megakaryocytic series labelled by anti-erythroid antibodies, anti myeloid antibodies or J 5, B 1, OKT 11 antibodies. Using ultrastructural immunoferritin with J 15 it was possible to demonstrate that labelling with this antibody only occurred on PPO-positive cells. Immunogold or peroxidase labelling with AN 51 at the EM level in cases of mixed leukemia showed that Gp Ib was absent from proerythroblasts and myeloblasts. Therefore, in no case were specific platelet markers expressed in the leukemias of other cell lineages.

Effects of ex-vivo plasma adsorption over protein A sepharose in acute leukemia.

Plasma adsorption over immobilized Staphylococcus aureus Cowan I has resulted in tumor regression in several animal and human trials. Protein A, because of its ability to bind IgGs has been considered as the effective component of Staphylococcus aureus. In 4 patients with acute leukemia, a plasma volume of 1500 cm3 was passed in an ex-vivo system over immobilized SpA-Sepharose and then reinfused. Almost all of the IgGs contained in the plasma volume could thus be removed. Toxic side-effects were mild. No significant clinical improvement could be obtained. Plasma incubation with SpA did not modify blast cell viability or leukemic progenitor cell growth. Along with others, this study shows that Protein A is probably not the mediator of the tumoricidal responses observed in studies using adsorption over Staphylococcus aureus Cowan I. The ex-vivo system prepared for this study could also be used for plasma IgG removal for the treatment of autoimmune or immune-complex related disorders.

Bronchial responsiveness to ultrasonic fog in occupational asthma due to toluene diisocyanate.

To determine the validity of ultrasonic nebulization of distilled water (UNDW, "fog") in comparison with methacholine challenge, in the assessment of toluene diisocyanate (TDI) asthma, we evaluated 75 subjects exposed to TDI with work-related respiratory symptoms. Subjects were submitted to bronchial challenge with methacholine at first, thereafter to UNDW inhalation and to specific challenge with TDI. The diagnosis of TDI-asthma was made in 30 of 75 patients (40 percent) who developed a bronchoconstrictive response to the specific challenge (reactors). Sensitivity and specificity of UNDW alone, methacholine alone, and of the combination of the two tests were determined with the results of the specific challenge with TDI as the "gold standard." Both frequency and severity of bronchoconstrictive response to UNDW (FEV1 decrease > or = 15 percent) and the degree (PD15 FEV1) and frequency of bronchial hyperresponsiveness to methacholine were significantly higher in TDI reactors than in nonreactors. The UNDW had higher specificity (82.2 percent vs 51.1 percent) but lower sensitivity (40 percent vs 76.7 percent) than methacholine. The combination in parallel (positivity of any of the two challenges) of methacholine and UNDW challenge did not change sensitivity to a great extent (80 percent vs 76.7 percent), whereas combination in series (positivity of both challenges) had considerably greater specificity (86.7 percent vs 51.1 percent) than methacholine alone. We conclude that in the assessment of TDI-asthma, the validity of UNDW challenge alone is limited since it is insufficiently sensitive. Instead, combining UNDW and methacholine challenge when methacholine is positive improves our ability in identifying subjects with TDI-asthma diagnosed with the specific challenge. This procedure constitutes a first objective confirmation of a suggestive history of TDI-asthma that is useful for clinical purposes. However, especially for medicolegal purposes, the definitive diagnosis requires the specific challenge.

Primary systemic anaplastic large-cell lymphoma (CD30+): advances in biology and current therapeutic approaches.

In 1985, Stein et al demonstrated the expression of the lymphoid activation antigen CD30/Ki by neoplastic cells. Fifteen years after the first description, anaplastic large-cell lymphomas (ALCL) are now thought to be a heterogeneous group in terms of their clinical, morphologic, phenotypic, cytogenetic, and molecular biology features. However, on the basis of a specific genetic anomaly and expression of a chimeric nucleophosmin anaplastic lymphoma kinase (NPM-ALK) protein and its variants, a distinct clinicopathologic entity defined as "ALK-positive lymphoma" or "ALKoma" can be recognized. Based on molecular and clinical criteria, 3 entities of primary ALCL can be identified: primary systemic ALK positive, primary systemic ALK negative, and primary cutaneous ALCL. This review focuses on advances in the knowledge of primary systemic ALCL biology and discusses therapeutic approaches based on ALK expression. The presence of this protein appears to be an important prognostic factor and, combined with an age-adjusted International Prognostic Index, could allow researchers to design more specific clinical trials aimed at finding new, more efficacious and less toxic treatments.