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Risks of convulsion and aseptic meningitis following measles-mumps-rubella vaccination in the United Kingdom.

Measles-mumps-rubella (MMR) vaccines containing the Urabe strain of mumps were withdrawn in the United Kingdom in 1992 following demonstration of an increased risk of aseptic meningitis 15-35 days after vaccination. Following introduction of a replacement MMR vaccine (Priorix; GlaxoSmithKline, London, United Kingdom) in 1998, active surveillance of aseptic meningitis and convulsion was established to evaluate the risk associated with the new vaccine. No laboratory-confirmed cases of mumps meningitis were detected among children aged 12-23 months after administration of 1.6 million doses of Priorix (upper 95% confidence limit of risk: 1:437,000) in England and Wales. The upper 95% confidence limit excluded the risk found for mumps meningitis with Urabe vaccines (1:143,000 doses). No cases of aseptic meningitis were detected among children aged 12-23 months, who had received over 99,000 doses of Priorix (upper 95% confidence limit of risk: 1:27,000), in a regional database of hospital-admitted cases. This compares with an observed risk of 1:12,400 for Urabe vaccines. An elevated relative incidence of convulsion was found in the 6- to 11-day period after receipt of Priorix (relative incidence = 6.26, 95% confidence interval: 3.85, 10.18)-consistent with the known effects of the measles component of MMR vaccine-but not in the 15- to 35-day period (relative incidence = 1.48, 95% confidence interval: 0.88, 2.50) as occurred with Urabe-containing vaccines. This study demonstrates the power of active postmarketing surveillance to identify or exclude events too rare to be detected in prelicensure trials.

England↗

Myeloperoxidase positive acute lymphoblastic leukemia cell lines, NALM-30, NALM-31 and NALM-32, carrying Philadelphia chromosome with biphenotypic characteristics.

We established three sister cell lines, NALM-30, NALM-31 and NALM-32, with biphenotypic features carrying myeloperoxidase mRNA and protein with complex Philadelphia (Ph) chromosome, t(9;22;10)(q34;q11;q22), from a patient with Ph-positive acute leukemia in relapse. Epstein-Barr virus nuclear antigen was negative. The morphological appearance of the cell lines is that of immature lymphoid cells. Expression of myeloid- and lymphoid-associated surface membrane antigens on these cells was detected allowing for the classification of "biphenotypic" leukemia. Immunophenotypically, the established cell lines reported here fulfill the European Group for the Immunological Characterization of Leukemias (EGIL) criteria for B-lineage derivation, however, surface and cytoplasmic immunoglobulin chains were negative. Whereas TGF-beta R (CD105), MCSFR (CD115), SCFR (CD117), IL-4R/IL-13R (CD124) and IL-6R (CD126) were not expressed, the cell lines were mostly positive for IFN-gamma R (CD119), IL-7R (CD127) and FLT-3R (CD135). The NALM-30, NALM-31 and NALM-32 cell lines together with their serial sister cell lines NALM-27 and NALM-28 which were established from the same patient at diagnosis provide unprecedented opportunities for studying a multitude of biological aspects related to normal and neoplastic immature B-lymphocytes.

Adult↗

Levels of uroporphyrinogen decarboxylase (URO-D) in erythrocytes of Italian porphyria cutanea tarda patients.

Porphyria cutanea tarda (PCT) is a human metabolic disorder due to the acquired or genetic impairment of uroporphyrinogen decarboxylase (URO-D) activity, the fifth enzyme of the heme biosynthetic pathway. A classification of inherited and non-inherited forms is based on the enzyme activity levels in red blood cells (RBC). Clinical manifestations of PCT are often precipitated by triggering factors such as alcohol, drug abuse, estrogens, virus infections, hepatotoxic chemicals and hepatic siderosis. We measured URO-D activity in RBC from a large sample of Italian PCT patients in order to define the enzyme activity distribution and to attempt a correlation among activity, risk factors and clinical outcome. Three classes of patients with low, normal and over-normal URO-D activity were defined according to control values. Low URO-D levels were present in 25.8% of patients, suggesting the familial form of PCT (type II). In this group, the outcome of PCT seems to be less influenced by risk factors. Patients with over-normal URO-D activity in RBC deserve further investigation.

Adult↗

[Human immunodeficiency virus infection and malignant lymphoma].

Infection by human immunodeficiency viruses (HIV) is associated with an increased incidence of non-Hodgkin's lymphomas (NHL) of B cell origin and of intermediate grade (diffuse large cell lymphomas according to the Working Formulation) or high grade (Kiel classification and Working Formulation). They may be either primary central nervous system lymphomas or systemic lymphomas and are considered as AIDS-defining events. Systemic lymphomas are usually disseminated with a high frequency of extranodal sites. Their overall prognosis is much worse than for NHL in the general population. Pathogenesis is still a matter of debate. An increased incidence of Hodgkin's diseases (HD) in HIV infection is being suspected but has not been proved yet. However, HIV-associated HD differ from usual HD by clinical presentation, histological type repartition, and evolution. Finally, low grade lymphomas have been described in HIV infection, the only peculiarity being the unusual age of occurrence.

HIV Infections↗

Low-dose zidovudine in children with an human immunodeficiency virus type 1 infection acquired in the perinatal period.

This report describes the one-year results of a noncomparative study designed to assess the safety and tolerance of low-dose zidovudine (azidothymidine) given orally to 60 human immunodeficiency virus type 1-infected infants and children. At baseline, the mean age was 1.9 years (+/- 1.4), and all were symptomatic: 43% were P2A and 57% were P2B to F according to the Centers for Disease Control classification. All the patients received zidovudine for at least 6 months, and 52 of them (87%) completed a full year of therapy. The mean duration of follow-up was 346 days (+/- 42) (range, 183 to 366 days). The initial therapy consisted of four daily doses of 100 mg/m2 (400 mg/m2 per day, equivalent to 20 mg/kg per day). However, this treatment was modified when neutropenia or anemia was observed. Twenty-nine children (48%) remained at the initial therapy for the entire study. Zidovudine dosage was adjusted 92 times in the other 31 children (52%), mostly due to neutropenia (83%). Altogether, the time under full-dose therapy represented 81% of the total duration of the protocol for all patients. Children with mild symptoms, P2A at study entry, were more likely to remain under full-dose therapy than children with severe symptoms, P2B to F: the time under full-dose therapy represented 91% of the duration of the protocol for the former group and only 74% for the latter one (P less than .02). No clinical adverse experiences were attributed directly to zidovudine. Thirty-seven children were prescribed trimethoprim-sulfametoxazole as a prophylaxis for Pneumocystis carinii pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Malignant lymphomas associated with immunodeficiency states.

An increased incidence of malignant lymphomas is common to all types of immunodeficient patients whether they be of the natural or constitutionally occurring type, acquired as in acquired immunodeficiency syndrome (AIDS) or of iatrogenic origin as in organ transplantation. Although there is some degree of heterogeneity, the most characteristic feature of these immunodeficient states is alteration of T-cell cytotoxic function. The malignant lymphomas show a variety of relatively common features, notably: rapid onset following the appearance of the immunodeficient state, a high degree of clinical aggressiveness, and a tendency to present in extranodal sites, particularly the central nervous system (CNS) and gastrointestinal tract. The tumors are almost invariably of B-lymphocytic cell origin and while the histologic classifications reflect some diversity, the vast majority of tumors are described as Burkitt-like or diffuse large cell type. There appears to be a high degree of correlation with a preceding fulminant Epstein-Barr virus (EBV) infection resulting in marked B-cell lymphoproliferation in the absence of effective T-cell control. Initially, the B-cell proliferation is clearly polyclonal and reactive in nature, although as time evolves, there appears to be selection of oligoclonal and even monoclonal cell populations. Such cells are latently infected with EBV and may express EBV nuclear protein two and latent membrane protein, which are characteristically seen in proliferating B-lymphocytes in response to growth transformation by EBV. While desoxyribonucleic acid (DNA) probes may continue to demonstrate multiple lymphoid clonal populations, it is hypothesized that the hyperproliferative state favors genetic alterations which select out a single malignant clone. This transformed clone is evidenced by expression of a translocated, activated c-myc oncogene and decreased evidence of EBV nuclear protein two and latent membrane protein, that is, characteristics of Burkitt's lymphoma. Other large cell malignant lymphoma phenotypes may show similar findings. While most studies have continued to suggest that EBV plays a key role in the development of non-Hodgkin's lymphoma (NHL) of AIDS patients, some recent studies have suggested a less dominant role. Therefore, further exploration of the world of molecular biology will be needed to demonstrate whether other factors, namely additional viruses and/or oncogenes play a similar or significant role in the lymphomas of immunodeficient patients.

Acquired Immunodeficiency Syndrome↗

[Inaugural syndromes and syndromes associated with the LAV/HTLV-III virus. Clinical and biological symptomatology. Therapeutic outlook].

The discovery in 1983 of the virus subsequently designated as HIV and its detection in several organs and lymphoid and others cells has led to greater knowledge of the clinical manifestations related to infection with the virus. Certain manifestations seem to be directly related to the viral infection. These are essentially acute infectious manifestations occurring with the primary infection, neurological disorders involving CNS, and more classical manifestations known from the start such as general chronic lymphadenopathy, ARC or full blown AIDS. Others clinical manifestations seem to be indirectly related to the virus, and certain appear to be an immune reaction to the virus (peripheral neuropathy like Landry Guillain Barré syndrome or thrombopenic purpura). Other manifestations such as bronchial or pancreatic carcinomas may be due to virus-induced immunodepression. Finally, some pathological states are probably related to co-infections such as lingual hairy-cell leukoplakia. One of the major current difficulties is the determination of a clinical rather than epidemiological classification of these manifestations so as to carry out a multicentric therapeutic protocol. Further therapeutic trials will be carried out on patients who maintain a subnormal immune status, and only the study of the development of several hundred patients will determine whether the treatment really succeeds by preventing the development to the next stage of the disease.

AIDS-Related Complex↗

Posttransplant lymphoproliferative disorders: summary of Society for Hematopathology Workshop.

Twenty cases of posttransplant lymphoproliferative disorders arising in solid organ allograft recipients (18 patients) or bone marrow allograft recipients (2 patients: 1 autologous; 1 allogeneic) were selected for presentation at the Society for Hematopathology Workshop. In the course of the Workshop discussions, based both on the submitted cases and the combined experience of the participants, it was possible to agree on several distinctive categories of PTLD. These include (1) early lesions, (2) polymorphic posttransplant lymphoproliferative disorders (PTLDs), (3) monomorphic PTLDs (B- and T-cell lymphomas), (4) plasmacytoma-like lesions, and (5) T-cell-rich large B-cell lymphoma/Hodgkin's disease-like lesions. Monomorphic lesions should be classified according to a recognized classification of non-Hodgkin's lymphoma, although specified in the report as PTLD. Polymorphic lesions should be carefully evaluated for clonality; by immunophenotyping; and, if necessary, analysis of antigen-receptor and Epstein-Barr virus (EBV) genomes. Minimal pathological evaluation should include routine morphology, immunophenotyping on fresh tissue (flow cytometry or frozen section), and preservation of tissue for molecular genetic analysis. Analysis of the presence of EBV can be useful in establishing whether early or equivocal lesions represent PTLD (EBV+) or unrelated processes, but is not required in most cases. The pathologist can make an important contribution to the management of patients with PTLD by providing a complete diagnostic evaluation of the biopsy specimens (this is the least expensive part of the care of a transplant patients, not a place to try to cut costs) and making sure the attending physicians understand the special issues in management of PTLD.

Bone Marrow Transplantation↗

Titers of Epstein-Barr virus-related antibodies in nasopharyngeal carcinoma in Japan.

It is thought that nonkeratinizing or undifferentiated squamous cell carcinoma in the nasopharynx (NPC) is intimately correlated with Epstein-Barr Virus (EBV). Twenty-one patients with NPC were followed in Kyoto University Hospital and 4 in Osaka Red Cross Hospital during the past 2 years from 1980 to 1981. These patients were classified histopathologically according to the WHO classification in 1978 and staged with the TNM classification in Union Internationale Contre le Cancer (UICC) in 1978. The incidence rate of NPC among the head and neck tumors was 5.6% in the authors' university from 1980 to 1981. The sex ratio of male to female was nearly equal. The mean age of NPC patients was 56.7 years. Sera from these 25 patients with nasopharyngeal carcinoma were collected at intervals of 3 to 8 months over a 2-year period, and were examined for their spectra and titers of antibodies of EBV-related antigens. They were titrated for IgG, IgA and IgM antibodies to EB viral capsid antigen (VCA), for IgG and IgA antibodies to early antigen-DR component (EA) and for antibodies to EBV-associated nuclear antigen (EBNA). All of these patients were primarily treated with radiation, while a few who did not respond to this therapy were subsequently treated with surgery or chemotherapy. EBV antibodies of VCA-IgG, -IgA, EA(DR)-IgG, and -IgA and EBNA were elevated in 73% and 90% of the nonkeratinizing and undifferentiated NPC patients, respectively. The VCA-IgM was elevated in almost none of the cases. In contrast to this, these values were all in a normal range in the NPC patients with keratinizing squamous cell carcinoma and malignant lymphoma. Also 9% and 10% of nonkeratinizing and undifferentiated carcinomas showed the normal ranges of EBV antibodies, possibly indicating a nonassociation with EBV. When NPC disappeared with radiation therapy, EBV antibodies became normal for 6-18 months. However, those whose NPC did not respond to the combined therapy with radiation, surgery and chemotherapy maintained high titers of EBV antibodies. The prognosis was the poorest in the patients with undifferentiated carcinoma, 40% of whom died within 4 years after diagnosis.

Adult↗

Genetic typing and prevalence of Border disease virus (BDV) in small ruminant flocks in Spain.

Between 2001 and 2002, samples from 1,413 animals in 21 Spanish small ruminant flocks, most of them with animals showing clinical signs compatible with Border disease (BD), were screened for the presence of Pestivirus antigen and antibodies by an indirect peroxidase monolayer assay (IPMA) and the virus neutralization test (VNT), respectively. Although all flocks harboured seropositive animals, virus could only be isolated from animals in five of the flocks. Between 4 and 11 months later all animals older than 6 months in three of the flocks were resampled. At this time, 51-83% of them had neutralizing antibodies. The prevalence of persistently infected (PI) animals within two of the flocks was 0.3 and 0.6%, respectively. The third flock presumably had eliminated all the PI animals. Fourteen virus isolates were obtained. The 5' untranslated region (5'UTR) was amplified by RT-PCR and directly sequenced. Phylogenetic analyses classified them as a group of Border disease viruses (BDV), separated from BDV-1, but showing a relatively low bootstrap value. Three of the 14 isolates were in the same subgroup as a set of formerly characterised Spanish isolates from the Basque Country, which were allocated to subgroup BDV-C. In addition, they were in the group with an isolate from chamois, which is currently allocated in group BDV-4. Because of its close relation to the chamois isolate, these isolates were tentatively reallocated in a subgroup BDV-4a. The remaining isolates generated a new subgroup, related but not in the same cluster as the chamois isolate, and was therefore tentatively assigned to a new subgroup BDV-4b. Our results show that classification and nomenclature of BDV needs to be harmonised.

5' Untranslated Regions↗

[Human papillomavirus (HPV) DNA infections of the uterine cervix].

411 women who had dysplasia, selected from an ambulatory group as well as 240 women from a random control group were examined, by using cervical smears, which were initially diagnosed as human papilloma viruses-DNA (HPV-DNA) of the type 6/11, or 16/18, or 31/33/35. This was achieved by the in-situ nucleic acid hybridisation technique. The results of the HPV-DNA typing were tabulated with the cytological diagnosis (Munich Papanicolaou (Pap.) group-classification). The control group corresponding to Pap.Gr. I, and was HPV-DNA positive in 6 (2.5%) of the 240 cases. The group of 180 patients with a Pap.Gr. II showed a HPV-DNA positive result for 75 cases (41.7%); 57 of 99 cases (57.6%) occurred in Pap.Gr. IIID; 42 of 54 cases 77.8% (L) were found in Pap.Gr. IV (a/b), and 72 of 78 cases (92.3%) appeared in Pap.Gr. V. The HPV-DNA mixed infections became evident as the cellular dysplasia increased. The results of the HPV-DNA positive diagnosis clearly indicate a close correlation with the Pap.Gr.-classification. The HPV-DNA type 16/18 was most frequent in cervical carcinomas (Pap.Gr. V). The cyto-histological control of the 57 HPV-DNA positive cases of the untreated Pap.Gr. IIID showed a regression in 31.6% of the 18 cases after a period of 3 to 6 months (post HPV-DNA typing). These were histologically normal. In 33 cases (57.9%), there was a persisting Pap.Gr. IIID (CIN I/II) and in 6 cases (10.5%) a progredient correlation in Pap.Gr. IV a/b. The Pap. group IV (a/b) was histologically a CIN grade III.

Adolescent↗

Descriptive epidemiology of non-Hodgkin lymphomas in a southwestern French hematology center: absence of significant relationship with hepatitis C virus infection.

From January 1995 to June 1998, 136 new cases of non-Hodgkin lymphomas (NHLs) were seen in our center which serves all the French Basque Country (300000 inhabitants). The crude and standardized incidence rates were respectively 13.2 and 7.6 cases/100000/year. The distribution of histologic subtypes according to the REAL classification showed a good correlation with the previous published data. Eleven patients (8%) were HIV-positive and two (1.4%) were HCV carriers. Hence, in our region, contrary to Italy, there is no evidence of relationship between HCV and NHLs.

Adolescent↗

Serologic classification of two ovine adenovirus isolates from the central United States.

Two ovine adenovirus (OAV) strains (RTS-42 and RTS-151), isolated from lambs in the central United States, were compared using 2-way cross-neutralization tests with the 6 recognized OAV species, 9 bovine adenovirus species, and 4 porcine species. Virus RTS-42 was identified as OAV type 5, confirming previous results. Virus RTS-151 was identified as OAV type 6, although the serologic crossing was largely one-sided.

Adenoviridae↗

Chronic bronchitis: the role of viruses.

Mucus is produced by the epithelial cells in the glands, gland ducts, and the cells lining the airway lumen in the lower airways. The chronic cough and sputum production that defines chronic bronchitis is associated with an inflammatory reaction involving this mucus-secreting apparatus. Respiratory viral infections target the epithelial cells of the lung producing desquamation, microvascular dilatation, edema, and an inflammatory cell infiltrate. These changes predispose the lower airways to bacterial infection by interfering with mucociliary clearance and reducing bacterial killing by macrophages. The exact role of those infections in the pathogenesis of chronic bronchitis has not been clearly determined but they probably play a critical role in inducing bacterial colonization and initiating acute exacerbations of COPD. This article reviews the classification of the viral agents responsible for respiratory tract infection and the nature of the changes they produce in the normal airways and in the airways of patients with chronic bronchitis during acute infections.

Bronchitis↗