Macrolide resistance phenotypes of commensal viridans group streptococci and Gemella spp. and PCR detection of resistance genes.

One hundred and sixty viridans group streptococci (VGS) and 26 Gemella spp. resistant to erythromycin were studied to detect macrolide lincosamide and streptogramin B (MLS(B)) phenotypes and to investigate resistance rates to other antibiotics. The M phenotype was most prevalent in both bacterial groups (59.6% in VGS, 69.2% in gemellae) and the iMLS(B) phenotype was found least often (9.3 and 13.9%, respectively). All isolates with M phenotype had the mef(A/E) gene, being prevalent the mef(E) subclass. cMLS(B) and iMLS(B) strains contained the erm(B) gene, alone or in combination with the mef(A/E) gene. Thirteen isolates were intermediately resistant to quinupristin/dalfopristin and 11 strains showed low susceptibility to telithromycin. Linezolid was active against all the isolates tested and tetracycline resistance was the major one in VGS (41.6%) and Gemella spp. (46.2%).

Infecciones por virus varicela zoster en menores de 15 años con cáncer / Infections caused by Varicella Zoster virus in children with cancer aged less than 15 years old

BACKGROUND: Infections caused by Varicella Zoster virus in children with cancer have a high rate of complications and mortality. AIM: To report the outcome of this infection in children with cancer. PATIENTS AND METHODS: Retrospective analysis of medical records of 216 children aged less than 15 years old with the diagnosis of an hematological or solid tumor, admitted to the National Program of Antineoplastic Drugs (PINDA). RESULTS: Eighty seven children had a Varicella Zoster virus infections, 73 (84 per cent) had varicella, 8 (9 per cent) had herpes zoster and 6 (7 per cent) had varicella and herpes zoster. Ninety four percent acquired the infection during antineoplastic treatment and 78 per cent received Acyclovir as antiviral therapy. During a nosocomial outbreak of varicella, three patients with an Acute Lymphoblastic leukemia died in the initial phase of chemotherapy, in spite of an early administration of Acyclovir. No patient with herpes zoster died. CONCLUSIONS: The incidence of varicella was higher in children with leukemia or lymphoma than in children with other types of cancer. Virus reactivation was uncommon and had a benign course. Varicella mortality in these children could be favorably modified through an active immunization of immunocompetent children.

Immunobiological features of the galactoside lectin L-Lc isolated from the Argentine mistletoe Ligaria cuneifolia.

Ligaria cuneifolia has been used in Argentine folk medicine and is currently employed as substitute for the European mistletoe (Viscum album) as hypotensor agent. Extracts from V. album are widely used in cancer therapy and the antineoplasic effect is attributed to their cytostatic/cytotoxic and immunomodulatory actions. When studying immunomodulatory effects of L. cuneifolia extracts (Lc extracts), they inhibited proliferation of murine mitogen-activated lymphocytes, leukaemic lymphocytes (LB) and breast tumour cells (MMT). The aim of this work was to isolate and identify lectins from Lc extracts and investigate their immunobiological actions. A galactoside lectin (L-Lc) of 57 kDa was isolated. A polyclonal antiserum obtained against Lc extract recognised both L-Lc and MLI (V. album lectin), suggesting the possibility of shared epitopes. Treatment of LB tumour cells with L-Lc (0.01 and 0.1 microg/ml) produced up to 40.0+/-6.9% inhibition of cell growth, which seems partly mediated by apoptosis (apoptosis of L-Lc treated cells 58.4+/-10.3% versus non-treated cells 38.1+/-8.8%; P<0.05), analysed by acridine orange and ethidium bromide staining. Inhibitory effect on ConA stimulated splenocyte growth was non-significant, while a mitogenic effect was observed on normal murine splenocytes and MMT cells. L-Lc in non-cytotoxic concentrations (250 ng/ml) modified mRNA expression of IL-10 but neither that of TGF-beta nor of IL-2 produced by LB cells. In addition, 43.9+/-0.5% reduction in NO production by LPS-stimulated murine macrophages was found. Finally, survival rates of LB tumour-bearing mice treated or not with Lc extract or L-Lc failed to show significant differences.

Immunomodulating properties of Argentine plants with ethnomedicinal use.

Five Argentine medicinal plants selected according to folk traditional or ethnomedical use, references and primary pharmacological screening; were chosen to elucidate their immunomodulating properties. Dichloromethane, methanolic and aqueous extracts of the aerial parts of Achyrocline flaccida (A. flaccida), Eupatorium arnottianum (E. arnottianum) and Eupatorioum buniifolium (E. buniifolium), leaves of Lithraea molleoides (L. molleoides) and leaves and stems of Phyllanthus sellowianus (P. sellowianus) were analyzed to disclose their effects on murine normal and tumor cell growth as well as on complement hemolytic activity. Modulation of cell growth was evaluated by tritiated thymidine incorporation while inhibition of complement activity was measured on both classical and alternative complement pathways (CP and AP respectively). The results obtained show that most of the extracts exerted inhibitory effect on tumor as well as on mitogen activated normal spleen cell growth. On tumor cells, IC50 ranged between 1-75 microg/ml for most of the extracts with the exception of dichloromethane of L. molleoides and P. sellowianus which required concentrations higher than 100 microg/ml to produce the effect. On mitogenic activated splenocytes, IC50 ranged between < 1 to 85 microg/ml with the exception of methanolic extract of E. buniifolium or P. sellowianus which were not effective on ConA or LPS stimulated splenocytes respectively. Only E. buniifolium was active on murine normal splenocytes proliferation (IC50 0.5-1.5 microg/ml). Finally, one (7%) of 15 extracts showed inhibition of complement activity on CP and 6 extracts (40%) presented moderate activity on CP. The dichloromethane extract of E. arnottianum was the most active (IC50 5 microg/ml), although remarkable effect was also obtained with dichloromethane and methanolic extracts of P. sellowianus (IC50 11.2 and 17.3 microg/ml respectively). Besides, 2 extracts (13%), dichloromethane extract of E. arnottianum and aqueous extract of P. sellowianus, showed moderate inhibition on AP.

[Hepatitis C virus in a group of hematological and oncohematological patients]. / Virus de la hepatitis C en un grupo de pacientes hematológicos y oncohematológicos.

BACKGROUND: Little information is available in Chile about hepatitis C virus (HCV) in hematological and oncohematological patients. AIM: To evaluate the prevalence of hepatitis C virus markers in a group of hematological and oncohematological pediatric patients seen at Valdivia Regional Hospital. PATIENTS AND METHODS: Antibodies against virus C, determined by ELISA and viral RNA, determined using RT-polymerase chain reaction, were measured in 54 blood samples from children with hematological diseases (34 with Acute Lymphoblastic Leukaemia, 4 with Hodgkin Diseases, 4 with Haemolytic Anemia, 5 with Sarcomas, 2 with Non-Hodgkin Lymphoma, 2 with Thrombocytopenic Purpura, 1 with an Ependimoma, one with a Wilms Tumor and 1 with a Von Willebrand Disease). RESULTS: All samples were negative for antibodies against hepatitis C virus. Viral RNA was found in four children, all with a diagnosis of acute lymphoblastic leukemia and who received chemotherapy and multiple transfusions. CONCLUSIONS: The prevalence of Viral RNA for hepatitis C virus in oncohematological patients in our study is high and associated with the use of chemotherapy and multiple transfusions.

Improved outcome for acute lymphoblastic leukemia in children of a developing country: results of the Chilean National Trial PINDA 87.

BACKGROUND: The National Chilean Pediatric Oncology Group, PINDA, reports the first prospective, nonrandomized trial for acute lymphoblastic leukemia (ALL), using a modified version of the Berlin-Frankfurt-Munster protocol (ALL BFM 86). The aim of this study was to classify immunophenotypes, to decrease cranial irradiation, and to assess whether this protocol would improve the survival rate. PROCEDURE: From June, 1987, to June, 1992, 444 unselected children were diagnosed with ALL. Of them, 425 were evaluable. Therapy was stratified by risk. Standard-risk (SR) and high-risk (HR) patients received protocols I, M, II, and maintenance therapy. Very-high-risk (VHR) patients received protocol E instead of protocol M. All patients received a prephase treatment consisting of prednisone and intrathecal methotrexate (MTX). HR and VHR patients received cranial irradiation (12-18 Gy). The following changes were made to the ALL BFM 86 protocol: in protocol M, MTX 1 g/m2 instead of 5 g/m2; in protocol E, citarabine 1 g/m2 instead of 2 g/m2; mithoxantrone and ifosfamide were substituted by teniposide and cyclophosphamide. RESULTS: Immunophenotypes: pro-B-ALL, 14%; common ALL, 67.4%; pre-B-ALL, 4.3%; T-ALL, 10%; undifferentiated leukemia (AUL), 4.3%. The overall 5-year event-free survival (EFS) rate was 60% +/- 2% (SE). The 5-year EFS rate for each risk group was: SR 75%, HR 62%, VHR 28%, with a median follow-up of 6.5 years (range 4.5-9.5 years). The cumulative incidence of central nervous system (CNS) relapse was 5.4%. CONCLUSIONS: We have been able successfully to perform a nationwide study. Our strategy to adapt the BFM protocol to our population of patients trial was effective in improving the EFS. The immunophenotype distribution is similar to that in other reported series.

Multimodal therapy for children and adolescents with Ewing sarcoma: results of the First National Chilean Trial (1986-1991).

Thirty-seven patients with Ewing sarcoma were treated in the First National Chilean Trial for Ewing's Sarcoma (1986-1991), which comprised the St. Jude Ewing's 78 Study. All patients received cyclophosphamide, doxorubicin, vincristine, and Dactinomycin for a total treatment period of about 10 months, and all prescribed therapy was administered. Local therapy consisted of irradiation (RT) to the primary tumor, complete surgical resection, or a combination of both surgery and RT. Twenty-nine of these patients had localized tumors, 24% had pelvic primary tumors, 21 were males, and 20 were greater than 10 years of age at diagnosis. Twenty-one patients had tumors that were greater than 8 cm in largest diameter. Fourteen of the 29 patients with localized disease remain disease free at 23 to 91 months from diagnosis. Fourteen patients have died of-tumor-related complications and 1 of a secondary malignancy. Relapse was local only in 4, metastatic in 9, and local plus metastatic in 1. Only 1 of the 8 patients with metastatic disease at presentation remains disease free. Toxicity consisted primarily of myelosuppression and mucositis. We conclude that this form of relative intense multimodal therapy for children/adolescents with localized Ewing sarcoma is curative in about half of affected children as in the original St. Jude study, and that it can be safely given in a developing country, provided that careful attention to supportive care and treatment planning is given. Although these results represent improvement in outcome for our patients, more effective therapy is needed for children with Ewing sarcoma, especially those with metastatic disease at presentation.

[Varicella-zoster virus infection in children with Hodgkin's disease in advanced stages III and IV]. / Infección por virus varicela zoster en enfermedad de Hodgkin de niño en estadios avanzados III y IV.

Over a 10-year period, among 22 children with Hodgkin's disease (stages III and IV), 10 (45.5%) developed varicella-zoster virus (VZV) infection, varicella in 8 cases (36.4%) and herpes zoster (HZ) in 3 (13.6%) (one patient had varicella and six months later). Three patients with varicella had significant pneumonitis, one of them showed clinical evidence of dissemination and died. Two patients had localized HZ and one had disseminated HZ without visceral involvement. All cases of VZV infections occurred in the first year of treatment: the primary infection presented while patients were under induction therapy and the secondary one after radiotherapy.

[Hodgkin's disease in children. Modified COPP combined treatment and radiotherapy in advanced stages]. / Enfermedad de Hodgkin en el niño. Tratamiento combinado COPP modificado y radioterapia en estadios avanzados.

Twenty two children, under 15 years of age, from southern Chile's Tenth Region, with advanced stages of Hodgkin's disease (8 III-A, 6 III-B and 8 IV-B) were treated with chemotherapy (modified COPP protocol) and radiotherapy between 1976 and 1985 at Valdivia's Regional Hospital. Overall survival rate was 77.3% and disease-free survival rate was 64.5% after a follow-up period from 3 to 13 years (median 70 months). Five patients died during the first two years. One relapsed 10 years after beginning of therapy, but achieved a second complete remission. The survival rate in patients with lymphocytic depletion type (5 cases) was 20.0%, whereas that of the mixed cellularity type (14 cases) was 92.9% (p less than 0.01). No cases of second neoplasms related to chemotherapy and radiotherapy were seen in this series.

[Von Willebrand's disease in the IX Region of Chile]. / Enfermedad de von Willebrand en la IX Region de Chile.

Bleeding disorders are frequent indications for reference to Hematologic Clinics. Won Willebrand's disease (vWD) is one of the commonest of inheritable hemorrhagic diathesis. In order to evaluate the frequency and clinical characteristics of vWD in the IX Region of Chile, we performed a clinical and laboratory investigation in 132 patients, children and adults, over a period of 3 years: 1983-1985. Within this group there was 26 close relatives. The laboratory tests used for the diagnosis were: bleeding time, factor VIII, von Willebrand factor and ristocetin cofactor. Diagnosis of vWD was made in 83 cases, most of them presenting the mild form of the disease. Two children had the severe form. The estimated prevalence of vWD in symptomatic patients in the IX Region of Chile is at least 113 per million, which makes it 3 or 4 times more frequent than hemophilia. vWD is observed at a much lower rate in mapuche than in caucasian population. The symptoms and their frequency were: post partum bleeding 75%, dental extraction bleeding 65%, surgical bleeding 65%, epistaxis 63%, menorrhagia 54%, easy bruising 45%, deep hematomas 8% and petechiae 5%. Five cases were asymptomatic. The bleeding time was the test most frequently abnormal: 72/83 cases (87%).

[Transient idiopathic periosteal hyperostosis with hyperproteinemia (Goldbloom syndrome)]. / Hiperostosis perióstica idiopática transitoria con disproteinemia (síndrome de Goldbloom).

The case of a 13 year old girl is presented, who developed intense pain in extremities and experienced marked weight loss after an acute upper respiratory tract infection. Roentgenograms revealed a diffuse periosteal reaction, most intensely affecting long bones. Principal laboratory findings were a slight normocytic, normochromic anemia; high erythrocyte sedimentation rate; medullar plasmocytosis and dysproteinemia, with a large increase in plasma gammaglobulin concentration. Clinical recovery and normalization of roentgenograms and laboratory parameters were observed eleven months after the acute episode, with no intervening therapeutic measures. This case matches Goldbloom's syndrome, described originally in two children in 1966. Only 3 other cases have been reported in the literature.

Neoplasias malignas de origen vascular en el nino. / Malignant neoplasms of vascular origin in children

Se comunican tres casos clinicos de tumores malignos de origen vascular, poco frecuentes en el nino. El primer caso corresponde a un hemangiopericitoma del hombro que por su magnitud fue tratado con quimioterapia y radioterapia, obteniendose una remision parcial, pero perdiendose el paciente del control. Los otros dos casos corresponden a hemangioendotelioma maligno (angiosarcoma) de gluteo y muslo, respectivamente Mientras en un caso se empleo solo quimioterapia, por la presencia de metastasis pulmonares, con desaparicion radiologica de estas pero falleciendo el paciente en agranulocitosis 10 semanas despues, en el otro caso se empleo quimioterapia reductiva con Vincristina, Actinomicina - D, Ciclofosfamida y Adriamicina, Actiromicina - seguida de cirugia radical, radioterapia y quimioterapia coadyuvante por 18 meses. Este paciente se encuentra en remision completa con una sobrevida actual de 53 meses Histologicamente, el hemangiopericitoma se caracteriza por capilares tapizados por endotelio y rodeados por pericitos de nucleos fusados. En cambio, la presencia de capilares irregulares anastomosados entre si y revestidos por celulas endoteliales malignas en una o varias capas se propia del hemangioendotelioma maligno