Transient myeloproliferative disorder. In a neonate with Down syndrome. Immunophenotypic studies

This report describes the results of bone marrow leukocyte immunophenotypic studies, DNA index measurement, and chromosome analysis in a newborn with Down syndrome and transient myeloproliferative disorder. The infant's initial leukocytosis with immature cells in the peripheral blood and thrombocytopenia resolved without treatment by 6 months of age, and he was well at 2 years of age. The lack of specific reactivity between the patient's morphologically immature cells and multiple monoclonal antibodies directed against lymphoid and myeloid leukemia cells may be characteristic of this disorder. Other cases should be examined for immunophenotype to correlate the results with chromosomal analysis and to provide a basis for comparison in those who subsequently develop true acute leukemia.     

Prognostic significance of blood and marrow findings in acute myelogenous leukemia in remission. A Southeastern Cancer Study Group report

Bone marrow and peripheral blood findings at the time of complete remission were analyzed in 333 patients with acute myelogenous leukemia to determine if any variables were predictive for remission duration and survival. Patients were categorized as to percentage of blasts, promyelocytes, erythroid precursors and lymphocytes in the marrow and hemoglobin concentration, leukocyte and platelet counts, and percentage of granulocytes and blasts in the blood. Additionally, the degree of cellularity in the marrow aspirate and biopsy were analyzed. Patients with less than 1% blasts in the marrow had significantly longer remission durations than those with blasts greater than or equal to 1% (P less than 0.01). Those with hypercellular marrows had significantly shorter remission (P less than 0.05) and survival (P less than 0.01). The transient presence of more than 3% blasts in the blood also was suggestive of a shorter remission duration and survival. The presence of less than 1% blasts in the marrow, normal or decreased biopsy cellularity, and no anemia at the time of remission defined a "good" prognostic group. The quality of remission should be assessed in evaluating the results of therapy and assigning further treatment.     

Characterization of clinical isolates of Klebsiella pneumoniae from 19 laboratories using the National Committee for Clinical Laboratory Standards extended-spectrum beta-lactamase detection methods

Extended-spectrum beta-lactamases (ESBLs) are enzymes found in gram-negative bacilli that mediate resistance to extended-spectrum cephalosporins and aztreonam. In 1999, the National Committee for Clinical Laboratory Standards (NCCLS) published methods for screening and confirming the presence of ESBLs in Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli. To evaluate the confirmation protocol, we tested 139 isolates of K. pneumoniae that were sent to Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology) from 19 hospitals in 11 U.S. states. Each isolate met the NCCLS screening criteria for potential ESBL producers (ceftazidime [CAZ] or cefotaxime [CTX] MICs were > or =2 microg/ml for all isolates). Initially, 117 (84%) isolates demonstrated a clavulanic acid (CA) effect by disk diffusion (i.e., an increase in CAZ or CTX zone diameters of > or =5 mm in the presence of CA), and 114 (82%) demonstrated a CA effect by broth microdilution (reduction of CAZ or CTX MICs by > or =3 dilutions). For five isolates, a CA effect could not be determined initially by broth microdilution because of off-scale CAZ results. However, a CA effect was observed in two of these isolates by testing cefepime and cefepime plus CA. The cefoxitin MICs for 23 isolates that failed to show a CA effect by broth microdilution were > or =32 microg/ml, suggesting either the presence of an AmpC-type beta-lactamase or porin changes that could mask a CA effect. By isoelectric focusing (IEF), 7 of the 23 isolates contained a beta-lactamase with a pI of > or =8.3 suggestive of an AmpC-type beta-lactamase; 6 of the 7 isolates were shown by PCR to contain both ampC-type and bla(OXA) genes. The IEF profiles of the remaining 16 isolates showed a variety of beta-lactamase bands, all of which had pIs of < or =7.5. All 16 isolates were negative by PCR with multiple primer sets for ampC-type, bla(OXA), and bla(CTX-M) genes. In summary, 83.5% of the K. pneumoniae isolates that were identified initially as presumptive ESBL producers were positive for a CA effect, while 5.0% contained beta-lactamases that likely masked the CA effect. The remaining 11.5% of the isolates studied contained beta-lactamases that did not demonstrate a CA effect. An algorithm based on phenotypic analyses is suggested for evaluation of such isolates.     

Different modulation by histamine of IL-4 and interferon-gamma (IFN-γ) release according to the phenotype of human Th0, Th1 and Th2 clones

Histamine, an important inflammatory mediator in allergic diseases and asthma, has been reported to have modulator effects on T cells, suggesting that the bronchial microenvironment may regulate the function of resident T cells. We examined the effect of histamine on the release of the Th2-associated cytokines IL-4 and IL-5 and the Th1-associated cytokine IFN-γ by 30 CD4⁺ T cell clones from peripheral blood or bronchial biopsy of one atopic subject. Based on the IL-4/IFN-γ ratio, the clones were ascribed to the Th2 (ratio >1), Th0 (ratio 0.1 and 1) or Th1 (ratio <0.1) phenotype. Histamine inhibited IFN-γ production by Th1-like cells (P<0.02, Kruskall–Wallis), especially from bronchial biopsy, but had no effect on IL-4 release. Regarding Th0 clones, histamine inhibited IL-4 production (P<0.02) in a dose-dependent manner and slightly inhibited IFN-γ production, but had no effect on Th2-like cells. Histamine had a heterogeneous and insignificant effect on IL-5 production. The H₂-receptor antagonist ranitidine completely reversed the inhibition of IL-4 and IFN-γ production, whereas the agonist dimaprit mimicked this effect. In contrast, H₁- and H₃-receptor agonists and antagonists had no significant effect. These data demonstrate that histamine has different effects on IL-4 and IFN-γ release by T helper cells according to their phenotype via H₂-receptors. This study extends the immunomodulatory effects of histamine which may contribute to the perpetuation of airway inflammation in asthma.     

In vitro activities of Daptomycin, Linezolid, and Quinupristin-Dalfopristin against a challenge panel of Staphylococci and Enterococci, including vancomycin-intermediate staphylococcus aureus and vancomycin-resistant Enterococcus faecium

We assessed the in vitro activities of daptomycin, linezolid, and quinupristin-dalfopristin (QD) against a contemporary challenge panel of 88 staphylococcal and 90 enterococcal isolates. The staphylococci selected included vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant S. aureus, and coagulasenegative staphylococci. Enterococcal isolates included vancomycin-resistant Enterococcus faecium (VREF) containing either vanA, vanB1, or vanD. The MICs of daptomycin, linezolid, and QD were determined using commercial broth microdilution panels. All three VISA isolates were susceptible to daptomycin, linezolid, and QD. QD was the most active agent against staphylococcal isolates (MIC50 < or = 0.5 microg/ml and MIC90 = 1 microg/ml), including those with decreased susceptibility to vancomycin. QD was also the most active agent against VREF (MIC90 < or = 0.5 microg/ml). No differences were seen for susceptibility of vanA, vanB1, and vanD VREF strains for daptomycin, linezolid, or QD. Daptomycin was the most effective against E. faecalis. On the basis of manufacturer-suggested interpretive criteria, 92% of isolates were susceptible (MIC90 = 4 microg/ml). All isolates tested were susceptible to at least one antimicrobial agent for which interpretive criteria have been defined. Population analysis of three S. aureus isolates for which the daptomycin MICs were 8 microg/ml showed a pattern of homogeneous resistance.     

The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission

Factors involved in the stability of trinucleotide repeats during transmission were studied in 139 families in which a full mutation, premutation or intermediate allele at either FRAXA or FRAXE was segregating. The transmission of alleles at FRAXA, FRAXE and four microsatellite loci were recorded for all individuals. Instability within the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for FRAXE) was extremely rare; only one example was observed, an increased in size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were unstably transmitted. Instability was more frequent for FRAXA intermediate alleles that had a tract of pure CGG greater than 37 although instability only occurred in two of 13 such transmissions: the changes observed were limited to only one or two repeats. Premutation FRAXA alleles over 100 repeats expanded to a full mutation during female transmission in 100% of cases, in agreement with other published series. There was no clear correlation between haplotype and probability of expansion of FRAXA premutations. Instability at FRAXA or FRAXE was more often observed in conjunction with a second instability at an independent locus suggesting genomic instability as a possible mechanism by which at least some FRAXA and FRAXE mutations arise.      

Primary chemotherapy in the treatment of children with bladder--prostate tumors in the Intergroup Rhabdomyosarcoma Study (IRS-II)

Twenty-nine children (24, male; 5, female) with non-disseminated rhabdomyosarcomas of the bladder or prostate were treated (1978-1980) by a primary chemotherapy regimen consisting of vincristine, actinomycin D, and cyclophosphamide ("Pulse" VAC), with or without local radiotherapy. During the initial 20 wk of chemotherapy, nine children achieved a Clinical Complete Response (CCR). Three of these are without evidence of disease (NED) and have functional bladders, two following partial cystectomy. Four who achieved a CCR subsequently relapsed or remained biopsy positive, but are at present NED following radiotherapy and anterior exenteration. Two patients who achieved CCR status relapsed and have died of disease. Twelve patients had a Clinical Partial Response (CPR) in less than 20 wk and two others in less than 40 wk. Seven of these are NED with intact bladders following chemotherapy-radiotherapy; and an additional patient is NED following partial cystectomy. Four patients in the CPR group have been treated by exenteration following failure to achieve complete response, and are NED. One patient has died, and one has progressive disease. Six patients had an inadequate response to chemotherapy (NR). Anterior exenteration was carried out in three, and two of these have survived. The overall results in these 29 patients are: (A) alive and disease-free with functional bladders, 11; (B) alive and disease-free following anterior exenteration, 10; and (C) dead or death from tumor anticipated, 8. The function of retained bladders (11) has been satisfactory.     

Nosocomial respiratory syncytial virus infection in Canadian pediatric hospitals: a Pediatric Investigators Collaborative Network on Infections in Canada Study

OBJECTIVE: To determine nosocomial transmission of respiratory syncytial virus (RSV) in Canadian pediatric hospitals, outcomes associated with nosocomial disease, and infection control practices. DESIGN: A prospective cohort study in the 1992 to 1994 winter respiratory seasons. SETTING: Nine Canadian pediatric university-affiliated hospitals. PARTICIPANTS: Hospitalized children with symptoms of lower respiratory tract infection (at least one of cough, wheezing, dyspnea, tachypnea, and apnea) and RSV antigen identified in a nasopharyngeal aspirate. RESULTS: Of 1516 children, 91 (6%) had nosocomial RSV (NRSV), defined as symptoms of lower respiratory tract infection and RSV antigen beginning >72 hours after admission. The nosocomial ratio (NRSV/[com-munity-acquired RSV {CARSV})] + NRSV) varied by site from 2.8% to 13%. The median length of stay attributable to RSV for community-acquired illness was 5 days, but 10 days for nosocomial illness. Four children with NRSV (4. 4%) died within 2 weeks of infection, compared with 6 (0.42%) with CARSV (relative risk = 10.4, 95% confidence interval: 3.0, 36.4). All sites isolated RSV-positive patients in single rooms or cohorted them. In a multivariate model, no particular isolation policy was associated with decreased nosocomial ratio, but gowning to enter the room was associated with increased risk of RSV transmission (incidence rate ratio 2.81; confidence interval: 1.65, 4.77). CONCLUSIONS: RSV transmission risk in Canadian pediatric hospitals is generally low. Although use of barrier methods varies, all sites cohort or isolate RSV-positive patients in single rooms. Children with risk factors for severe disease who acquire infection nosocomially have prolonged stays and excess mortality.