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1.
Clin Microbiol Infect ; 27(3): 435-442, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32325126

ABSTRACT

OBJECTIVES: This study sought to more fully elucidate the age-related trends in influenza mortality with a secondary goal of uncovering implications for treatment and prevention. METHODS: In this retrospective cohort analysis of data from the Nationwide Readmission Database, patients with influenza as a primary or secondary discharge diagnosis were separated into three age groups: 55 638 adults aged 20-64 years, 36 862 adults aged 65-79 years and 41 806 octogenarians aged ≥80 years. Propensity score (PS) weighting was performed to isolate age from other baseline differences. Crude and PS-weighted hazard ratios (HR) were calculated from the in-hospital all-cause 30-day mortality rate. Admission threshold bias was minimized by comparison of influenza with bacterial pneumonia mortality. RESULTS: Adults aged 20-64 years experienced higher in-hospital 30-day mortality compared with older adults aged 65-79 years (HR 0.66; 95% CI 0.55-0.79). Octogenarians had the highest mortality rate, but this was statistically insignificant compared with the adult cohort (HR 1.09; 95% CI 0.94-1.27). This trend was not explained by admission threshold bias: the 30-day mortality rate due to in-hospital bacterial pneumonia increased consistently with age (older adult HR 1.45; 95% CI 1.32-1.59; octogenarian HR 1.99; 95% CI 1.82-2.18). CONCLUSIONS: Adults aged 20-64 years and octogenarians were more likely to experience all-cause 30-day mortality during influenza hospitalization compared with older adults aged 65-79 years. These data emphasize the importance of prevention and suggest the need for more tailored treatment interventions based on risk stratification that includes age.


Subject(s)
Hospitalization , Influenza, Human/epidemiology , Influenza, Human/therapy , Adult , Aged , Aged, 80 and over , Aging , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , United States/epidemiology , Young Adult
2.
Epidemiol Infect ; 149: e1, 2020 12 28.
Article in English | MEDLINE | ID: mdl-33413705

ABSTRACT

Although testing is widely regarded as critical to fighting the COVID-19 pandemic, what measure and level of testing best reflects successful infection control remains unresolved. Our aim was to compare the sensitivity of two testing metrics - population testing number and testing coverage - to population mortality outcomes and identify a benchmark for testing adequacy. We aggregated publicly available data through 12 April on testing and outcomes related to COVID-19 across 36 OECD (Organization for Economic Development) countries and Taiwan. Spearman correlation coefficients were calculated between the aforementioned metrics and following outcome measures: deaths per 1 million people, case fatality rate and case proportion of critical illness. Fractional polynomials were used to generate scatter plots to model the relationship between the testing metrics and outcomes. We found that testing coverage, but not population testing number, was highly correlated with population mortality (rs = -0.79, P = 5.975 × 10-9vs. rs = -0.3, P = 0.05) and case fatality rate (rs = -0.67, P = 9.067 × 10-6vs. rs = -0.21, P = 0.20). A testing coverage threshold of 15-45 signified adequate testing: below 15, testing coverage was associated with exponentially increasing population mortality; above 45, increased testing did not yield significant incremental mortality benefit. Taken together, testing coverage was better than population testing number in explaining country performance and can serve as an early and sensitive indicator of testing adequacy and disease burden.


Subject(s)
COVID-19 Testing/statistics & numerical data , COVID-19/epidemiology , COVID-19/mortality , Global Health , Organisation for Economic Co-Operation and Development/statistics & numerical data , SARS-CoV-2 , Humans
4.
Osteoporos Int ; 28(4): 1167-1178, 2017 04.
Article in English | MEDLINE | ID: mdl-28083669

ABSTRACT

Our systematic review and meta-analysis of observational studies indicated that the use of antipsychotics was associated with a nearly 1.5-fold increase in the risk of fracture. First-generation antipsychotics (FGAs) appeared to carry a higher risk of fracture than second-generation antipsychotics (SGAs). INTRODUCTION: The risk of fractures associated with the use of antipsychotic medications has inconsistent evidence between different drug classes. A systematic review and meta-analysis was conducted to evaluate whether there is an association between the use of antipsychotic drugs and fractures. METHODS: Searches were conducted through the PubMed and EMBASE databases to identify observational studies that had reported a quantitative estimate of the association between use of antipsychotics and fractures. The summary risk was derived from random effects meta-analysis. RESULTS: The search yielded 19 observational studies (n = 544,811 participants) with 80,835 fracture cases. Compared with nonuse, use of FGAs was associated with a significantly higher risk for hip fractures (OR 1.67, 95% CI, 1.45-1.93), and use of second generation antipsychotics (SGAs) was associated with an attenuated but still significant risk for hip fractures (OR 1.33, 95% CI, 1.11-1.58). The risk of fractures associated with individual classes of antipsychotic users was heterogeneous, and odds ratios ranged from 1.24 to 2.01. Chlorpromazine was associated with the highest risk (OR 2.01, 95% CI 1.43-2.83), while Risperidone was associated with the lowest risk of fracture (OR 1.24, 95% CI 0.95-1.83). CONCLUSIONS: FGA users were at a higher risk of hip fracture than SGA users. Both FGAs and SGAs were associated with an increased risk of fractures, especially among the older population. Therefore, the benefit of the off-label use of antipsychotics in elderly patients should be weighed against any risks for fracture.


Subject(s)
Antipsychotic Agents/adverse effects , Osteoporotic Fractures/chemically induced , Femoral Fractures/chemically induced , Hip Fractures/chemically induced , Humans , Risk Assessment/methods
5.
Vox Sang ; 91(3): 270-4, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16958841

ABSTRACT

BACKGROUND AND OBJECTIVES: The demand for transfusions has increased rapidly in southern Taiwan. Between 1993 and 2003, requests for fresh-frozen plasma (FFP) in particular rose dramatically at Kaohsiung Medical University Hospital (KMUH). Transfusion orders were not tightly regulated, and inappropriate use of blood products was common. MATERIALS AND METHODS: We carried out a prospective analysis of transfusion requests from October 2003 to January 2004 at KMUH, and then repeated the audit for another 3-month period after the clinical faculty had undergone five sessions of education on transfusion guidelines. Later, our consultant haematologist applied computerized guidelines to periodic audits. RESULTS: A 5.2% decrease in inappropriate FFP usage followed the educational programme and a further 30% reduction took place after the application of computerized transfusion guidelines. With the guidelines and periodic audits, FFP transfusions decreased by 74.6% and inappropriate requests from 65.2% to 30%. CONCLUSIONS: Hospital policy, computerized transfusion guidelines and periodic audits greatly reduced inappropriate FFP transfusions. An educational campaign had a more limited effect.


Subject(s)
Blood Component Transfusion/statistics & numerical data , Medical Audit , Plasma , Practice Guidelines as Topic/standards , Blood Component Transfusion/standards , Humans , Prospective Studies , Quality Assurance, Health Care , Taiwan
6.
Clin Exp Immunol ; 145(3): 513-9, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16907921

ABSTRACT

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by the loss of tolerance to self-antigen. Because it is currently not known if regulatory T (T(reg)) cells are involved in the pathogenesis, we determined the frequency of CD4(+)CD25(+) T cells and assayed the related gene expression levels in CD4(+)CD25(+) T cells isolated from both lupus mice (NZB/NZW F(1)) and normal control mice (DBA2/NZW F(1)). The results showed that the frequency of CD4(+)CD25(+) T cells in lupus mice was lower than that of normal mice. Except for the high expression level of interleukin (IL)-10 mRNA, CD4(+)CD25(+) T cells from lupus mice expressed normal forkhead box P3 (Foxp3) and transforming growth factor (TGF)-beta mRNA, and exerted suppressive functions. Furthermore, we depleted CD25(+) T(reg) cells of non-autoimmune mice with anti-CD25 antibody and broke their tolerance with apoptotic cell-pulsed dendritic cells for the follow-up of autoantibody levels. The mice in the CD25(+) cell-depleted group had higher titres of anti-double-strand/single-strand DNA antibodies than those of the isotype control antibody-treated group. These findings indicated that CD4(+)CD25(+) T cells might be involved in the regulatory mechanism of autoantibody production.


Subject(s)
Autoantibodies/immunology , CD4-Positive T-Lymphocytes/immunology , Lupus Erythematosus, Systemic/immunology , Receptors, Interleukin-2/immunology , Animals , Apoptosis , Autoantibodies/blood , Dendritic Cells/immunology , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Forkhead Transcription Factors/genetics , Gene Expression , Immunosuppression Therapy , Interleukin-10/genetics , Mice , Mice, Inbred NZB , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Transforming Growth Factor beta/genetics
7.
Urology ; 58(6): 930-4, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11744461

ABSTRACT

Objectives. To report a modified approach for hand-assisted laparoscopic nephroureterectomy (HALNU).Methods. Seven patients with localized transitional cell carcinoma of the upper urinary tract underwent unilateral HALNU. Patients were placed in a 60 degrees oblique position during the entire procedure. Via a 7-cm Gibson incision on the lesion side, the distal ureterectomy and bladder cuff excision were done by an open method without opening the bladder. Then, with the surgeon's hand inserted into the peritoneal cavity by way of the same wound, HALNU was performed with two to three additional laparoscopic ports. The perioperative parameters were compared with those of 15 cases of conventional open nephroureterectomy.Results. Patients in the HALNU group had significantly less mean blood loss (140 versus 455 mL) and earlier resumption of oral intake (33 versus 61 hours), required fewer narcotics (38 versus 70 mg of morphine sulfate equivalent), and were discharged earlier (7.33 versus 9.1 days), with a faster convalescence to normal activity (3.7 versus 5.6 weeks; all P < 0.05). The total mean surgical time was 3.7 hours for the HALNU group.Conclusions. Our approach used the same incision to both excise the distal ureter and apply the hand-assist device. It also preserved the benefits of the minimal invasiveness of laparoscopic surgery compared with its open counterpart.


Subject(s)
Carcinoma, Transitional Cell/surgery , Kidney Neoplasms/surgery , Laparoscopy/methods , Nephrectomy/methods , Ureter/surgery , Aged , Female , Functional Laterality , Humans , Laparoscopes , Male , Middle Aged , Nephrectomy/instrumentation , Urinary Bladder/surgery
8.
Am J Hematol ; 68(1): 23-31, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11559933

ABSTRACT

The interferon response genes 1 and 2 have been shown to be involved in the regulation of differentiation and proliferation of cells of the myeloid series, with the former functioning as an anti-oncogene and the latter as an oncogene. In the study described here, the levels of expression of these two genes and the ratio of their expression were compared in AML and normal marrow. The ratio of gene expression was significantly less in AML marrow cells as compared to normal marrow cells [med ratio = 1.33 vs. 2.97, P = 0.003]. While the expression ratio was unaffected by the presence or absence of either ras or fms mutations, p53 mutations were associated with higher IRF1:IRF2 expression ratios that wt p53 genes [med = 1.701 vs. 1.135, P = 0.014]. Given the functional characteristics and the competitive nature of these two genes, it is possible that leukemic transformation is associated with a fall in IRF1:IRF2 ratios. Finally, the administration of IL4 can result in the normalization of the IRF1:IRF2 ratio in the marrow cells of some patients with AML.


Subject(s)
DNA-Binding Proteins/metabolism , Leukemia, Myeloid, Acute/metabolism , Phosphoproteins/metabolism , Repressor Proteins , Transcription Factors , Adult , Aged , Aged, 80 and over , Bone Marrow Cells/metabolism , Cytogenetic Analysis , DNA-Binding Proteins/genetics , Genes, ras , Humans , Interferon Regulatory Factor-1 , Interferon Regulatory Factor-2 , Interleukin-4/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Middle Aged , Phosphoproteins/genetics , RNA, Messenger/metabolism , Receptor, Macrophage Colony-Stimulating Factor/genetics , Reference Values , Treatment Outcome , Tumor Suppressor Protein p53/genetics
9.
J Air Waste Manag Assoc ; 51(6): 885-94, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11417680

ABSTRACT

This work summarizes the results of numerical investigations and in situ measurements for turbulent combustion in a full-scale rotary kiln incinerator (RKI). The three-dimensional (3D) governing equations for mass, momentum, energy, and species, together with the kappa - epsilon turbulence model, are formulated and solved using a finite volume method. Volatile gases from solid waste were simulated by gaseous CH4 distributed nonuniformly along the kiln bed. The combustion process was considered to be a two-step stoichiometric reaction for primary air mixed with CH4 gas in the combustion chamber. The mixing-controlled eddy-dissipation model (EDM) was employed to predict the conversion rates of CH4, O2, CO2, and CO. The results of the prediction show that reverse flows occur near the entrance of the first combustion chamber (FCC) and the turning point at the entrance to the second combustion chamber (SCC). Temperature and species are nonuniform and are vertically stratified. Meanwhile, additional mixing in the SCC enhances postflame oxidation. A combustion efficiency of up to 99.96% can be achieved at approximately 150% excess air and 20-30% secondary air. Reasonable agreement is achieved between numerical predictions and in situ measurements.


Subject(s)
Air Pollution/prevention & control , Models, Theoretical , Refuse Disposal , Incineration , Temperature
10.
Leuk Lymphoma ; 41(3-4): 333-6, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11378545

ABSTRACT

Twenty five patients with AML who had neither a history of toxic exposure or myelodysplasia were treated with a remission induction regimen consisting of two pulses of chemotherapy separated by 96 hrs. Each pulse consisted of cytarabine 2gm/m(2) (at t=0 and t=12 hrs) with mitoxantrone [30mg/m(2) ] administered immediately after the second cytarabine administration. Amifostine was administered three times a week [on Monday, Wednesday, and Friday] until the outcome of therapy was known. This regimen induced complete remissions in 15 of 17 patients less than 70 years of age and in 5 of 8 patients older than 70 years.


Subject(s)
Antineoplastic Agents/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Adult , Age Factors , Aged , Aged, 80 and over , Antineoplastic Agents/standards , Cohort Studies , Cytarabine/administration & dosage , Cytarabine/standards , Cytogenetic Analysis , Drug Administration Schedule , Humans , Leukemia, Myeloid, Acute/classification , Leukemia, Myeloid, Acute/genetics , Middle Aged , Mitoxantrone/administration & dosage , Mitoxantrone/standards , Remission Induction , Time Factors , Treatment Outcome
11.
Biotechnol Bioeng ; 73(3): 231-7, 2001 May 05.
Article in English | MEDLINE | ID: mdl-11257605

ABSTRACT

Including excess salt during lyophilization has been shown to increase the activity of freeze-dried subtilisin Carlsberg (SC) in anhydrous media by over 20,000-fold [Ru et al. (1999) Biotechnol Bioeng 63:233-241]. In the present study, salt-activated SC (KCl-SC) showed a 30% enhancement in enantioselectivity compared to the salt-free enzyme in a variety of organic solvents. Activity toward both enantiomers of N-acetyl-phenylalanine methyl ester (APME) increased in tandem by 2-3 orders of magnitude in all solvents, indicating that the mechanism of salt activation is inherent to the enzyme and does not strongly favor one enantiomer over the other. However, activity and enantioselectivity of salt-activated SC could be manipulated through changes in the lyophilization conditions. Variations in lyophilization time, initial KCl concentration, and initial lyophilization volume altered enantioselectivity over 2-fold. The changes in enantioselectivity reflected the activity for the L enantiomer, while the activity toward the D enantiomer was mostly unaffected. The results indicate that the lyophilization time and final water content of the KCl-SC are important determinants of enzyme activity for the L enantiomer, suggesting that the favored reaction is more sensitive to the structural integrity of the salt-activated enzyme.


Subject(s)
Potassium Chloride/chemistry , Subtilisin/chemistry , Freeze Drying/methods , Molecular Conformation , Solvents/chemistry , Time Factors
12.
Br J Haematol ; 110(4): 847-55, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11054067

ABSTRACT

Deletions of chromosome 5, del(5q), are frequently observed in myelodysplasia (MDS). We evaluated molecular detection of loss of heterozygosity (LOH) as a diagnostic method to detect del(5q) in a series of 60 MDS cases at a single institution. LOH was compared to cytogenetics on the same clinical specimen, resolving ambiguous cases by fluorescent in situ hybridization (FISH) and additional LOH. There was poor concordance between molecular and cytogenetic results, but most discrepancies could be resolved by FISH and additional LOH. Molecular analysis was of low sensitivity because most cases contained a relatively high proportion of cells without del(5q), but it was accurate, while cytogenetics overestimated the proportion of cells with del(5q) and failed to detect some cases with complex rearrangements. Minor clones were detected both by FISH and LOH. Overall, we found an incidence of 23% (14 of 60 cases) for del(5q) in MDS. The results also suggest that there is a high degree of genetic heterogeneity in the cellular population of MDS. Although del(5q) is common in MDS, it may not be present in all cells, leading to diagnostic challenges.


Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 5 , Myelodysplastic Syndromes/genetics , Aged , Anemia, Refractory/genetics , Anemia, Refractory, with Excess of Blasts/genetics , Anemia, Sideroblastic/genetics , Cytogenetic Analysis , Female , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Leukemia, Myelomonocytic, Chronic/genetics , Loss of Heterozygosity , Male , Microsatellite Repeats , Polymerase Chain Reaction
13.
Blood ; 95(5): 1580-7, 2000 Mar 01.
Article in English | MEDLINE | ID: mdl-10688811

ABSTRACT

Thirty-five patients with myelodysplastic syndrome (MDS) were registered on protocol MDS 96-02 and were receiving continuous therapy with pentoxifylline 800 mg 3 times a day and ciprofloxacin 500 mg twice a day by mouth; dexamethasone was added to the regimen for the partial responders and the nonresponders after 12 weeks at a dose of 4 mg by mouth every morning for 4 weeks. Amifostine was administered intravenously 3 times a week at 3 dose levels (200 mg/M(2), 300 mg/M(2), and 400 mg/M(2)) to cohorts of 10 patients each. Therapy has been continued for 1 year in responders. Twenty-nine have completed at least 12 weeks of therapy and are available for response evaluation. Of the 21 men and 8 women (median age, 67 years), 20 had refractory anemia (RA), 3 had RA with ringed sideroblasts (RARS), 5 had RA with excess blasts (RAEB), and 1 had chronic myelomonocytic leukemia (CMMoL). Five had secondary MDS. No differences were noted in response rates among the 3 dose levels. Seven patients did not respond at all, and 22 showed an improvement in cytopenias (76%). Three had a triple lineage response, 10 had a double lineage response, and 9 had a single lineage response (8 of 9 in absolute neutrophil count [ANC] and 1 had more than a 50% reduction in packed red blood cell transfusions). Fifteen patients responded only after the addition of dexamethasone, whereas 7 responded before. When examined by lineage, 19 of 22 showed improved ANC, 11 of 22 demonstrated more than 50% reduction in blood transfusions, improved Hb levels, or both, and 7 of 22 showed improvement in platelet counts. Interestingly, the responses were frequently slow to appear, and continued improvement in counts was seen up to 12 months of therapy and beyond. This study supports the feasibility of treating patients with MDS with the unique approach of cytoprotection and anticytokine therapies as well as the principle that prolonged commitment to treatment is desirable when noncytotoxic agents are administered. (Blood. 2000;95:1580-1587)


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Myelodysplastic Syndromes/drug therapy , Palliative Care , Adult , Aged , Aged, 80 and over , Amifostine/administration & dosage , Amifostine/adverse effects , Anorexia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Blood Cell Count/drug effects , Ciprofloxacin/administration & dosage , Ciprofloxacin/adverse effects , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Female , Gastrointestinal Diseases/chemically induced , Hematologic Diseases/chemically induced , Humans , Hypotension/chemically induced , Male , Middle Aged , Myelodysplastic Syndromes/mortality , Pentoxifylline/administration & dosage , Pentoxifylline/adverse effects , Treatment Outcome
14.
Cancer Genet Cytogenet ; 116(2): 97-104, 2000 Jan 15.
Article in English | MEDLINE | ID: mdl-10640140

ABSTRACT

Twenty-eight laboratories evaluated a new fluorescence in situ hybridization (FISH) strategy for chronic myeloid leukemia. In a three-part study, bcr/abl1 D-FISH probes were used to study bone marrow specimens. First, laboratories familiarized themselves with the strategy by applying it to known normal and abnormal specimens. Then, collectively the laboratories studied 20 normal and 20 abnormal specimens blindly and measured workload. Finally, each laboratory and two experts studied six serial dilutions with 98-0% abnormal nuclei. Using the reported normal cutoff of < 1% abnormal nuclei, participants reported no false-negative cases and 15 false-positive cases (1-6.6% abnormal nuclei). Results provided by participants for serial dilutions approximated the expected percentages of abnormal nuclei, but those from the experts exhibited greater precision. The clinical sensitivity, precision, nomenclature, workload, recommendations for training, and quality assurance in methods using D-FISH in clinical practice are discussed.


Subject(s)
Clinical Laboratory Techniques/standards , Fusion Proteins, bcr-abl/genetics , In Situ Hybridization, Fluorescence , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Bone Marrow/pathology , Fluorescent Dyes , Humans , In Situ Hybridization, Fluorescence/instrumentation , In Situ Hybridization, Fluorescence/methods , In Situ Hybridization, Fluorescence/standards , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Quality Control , Sensitivity and Specificity , Workload
15.
Am J Med Genet ; 80(4): 418-22, 1998 Dec 04.
Article in English | MEDLINE | ID: mdl-9856575

ABSTRACT

Stable centromeric breakage in non-acrocentric chromosomes and balanced reciprocal translocation mosaicism are both rare events. We studied a family in which the mother had mosaicism for a balanced reciprocal translocation between chromosomes 10 and 16 which was associated with a break in chromosome 16 centromere alpha-satellite DNA ¿146,XX,t(10;16)(q11.2;q11.1) [29]/46,XX[25]¿. The derivative chromosome 16 contained only a very small amount of 16 alpha-satellite DNA while the derivative 10 contained all of the 10 alpha-satellite DNA as well as a large amount of the 16 alpha-satellite DNA. The same translocation was present in all cells in her son who was found prenatally to have trisomy 16 mosaicism ¿46,XY,t(10;16) (q11.2;q11.1)mat[22]/47,idem,+16[4]¿. Trisomy 16 cells were subsequently determined to be confined to the placenta. DNA polymorphism analyses in the family demonstrated maternal uniparental disomy for chromosome 16 in the diploid child. The child, at age 7 months, had minor facial anomalies similar to a previously reported case of maternal uniparental disomy for chromosome 16. In addition to illustrating several rare events, this family further demonstrated that substantial deletion of the centromeric alpha-satellite DNA does not impair centromere function and both mitotic and meiotic stability are retained in such cases.


Subject(s)
Chromosomes, Human, Pair 10/genetics , Chromosomes, Human, Pair 16/genetics , Mosaicism/genetics , Placenta , Translocation, Genetic , Adult , Centromere/genetics , Chromosome Breakage , DNA/analysis , DNA/genetics , Female , Growth Disorders/genetics , Growth Disorders/pathology , Humans , In Situ Hybridization, Fluorescence , Infant , Karyotyping , Male , Trisomy
16.
Leuk Res ; 22(5): 429-38, 1998 May.
Article in English | MEDLINE | ID: mdl-9652729

ABSTRACT

The proliferation of acute myelogenous leukemia cells is dependent upon cytokine stimulation. Additionally, there is a body of literature which reports that leukemia cells produce GMCSF, IL6, and other cytokines. The study reported here, using an rt-multiplex polymerase method, determined the presence or absence of transcripts in freshly obtained AML cells for the following cytokine or cytokine-related genes: IL 1beta, IL1ra, TNF alpha, GMCSF, IL6, flt 3, and hSCF. This demonstrated that leukemia cell populations usually contain transcripts for IL1beta, TNF alpha, flt 3 and flt 3 ligand in vivo and that transcripts for the other cytokines only appear after the leukemia cells are processed in vitro. The presence of TNF alpha transcripts appears to be associated with resistance to remission induction therapy. Furthermore, the transcript profile of the leukemia cells can change during remission induction therapy. The data also demonstrate the assessment of cytokine production by leukemia cells after in vitro manipulation should not be extrapolated to the in vivo situation.


Subject(s)
Cytokines/genetics , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Adult , Aged , Bone Marrow Cells/physiology , Female , Humans , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , RNA, Messenger/analysis , Remission Induction , Specimen Handling , Transcription, Genetic , Tumor Necrosis Factor-alpha/genetics
17.
Cancer Genet Cytogenet ; 104(1): 57-60, 1998 Jul 01.
Article in English | MEDLINE | ID: mdl-9648560

ABSTRACT

We report cytogenetic, fluorescence in situ hybridization (FISH), and molecular analysis in a case of Ph-negative chronic myelogenous leukemia patient with ABL/BCR fusion gene on chromosome 9 and a disparate FISH signal pattern using two commercially available bcr/abl probes (Vysis, Inc. and Oncor, Inc.). Cytogenetic analysis revealed a 46,XX normal female karyotype. FISH studies using Vysis LSI bcr/abl probe in interphase cells demonstrated a BCR/ABL fusion pattern, similar to that of m-BCR/ABL fusion found in acute lymphoblastic leukemia. However, examination of metaphases revealed the ABL/BCR fusion signal on one of the chromosomes 9, an ABL signal on the other chromosome 9, and two BCR signals of different sizes on each of the chromosomes 22. Subsequently, a FISH study with the Oncor major (M)-bcr/abl translocation probe confirmed the ABL/BCR fusion signal on chromosome 9 in addition to an ABL signal and a BCR signal located on chromosomes 9 and 22, respectively. Molecular studies (RT-PCR) revealed a rearrangement of the M-BCR region and expression of a chimeric bcr/abl mRNA of b3a2 configuration. This case suggests that it is imperative to have a full understanding of both the capabilities and the limitations of bcr/abl translocation probes and that FISH interphase signals should be confirmed on metaphase spreads for accurate diagnosis.


Subject(s)
Chromosomes, Human, Pair 9/genetics , Fusion Proteins, bcr-abl/genetics , In Situ Hybridization, Fluorescence/methods , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/genetics , Diagnosis, Differential , Female , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/diagnosis , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/epidemiology , Middle Aged , Observer Variation , Translocation, Genetic
18.
Am J Med Genet ; 76(4): 318-26, 1998 Apr 01.
Article in English | MEDLINE | ID: mdl-9545096

ABSTRACT

Twenty-six laboratories used X and Y chromosome probes and the same procedures to process and examine 15,600 metaphases and 49,400 interphases from Phaseolus vulgaris-leucoagglutinin (PHA)-stimulated lymphocytes. In Part I, each laboratory scored 50 metaphases and 200 interphases from a normal male and a normal female from its own practice. In Part II, each laboratory scored 50 metaphases and 200 interphases on slides prepared by a central laboratory from a normal male and a normal female and three mixtures of cells from the male and female. In Part III, each laboratory scored 50 metaphases (in samples of 5, 10, 15, and 20) and 100 interphases (in samples of 5, 10, 15, 20, and 50) on new, coded slides of the same specimens used in Part II. Metaphases from male specimens were scored as 98-99% XY with no XX cells, and 97-98% of interphases were scored as XY with 0.04% XX cells. Metaphases from female specimens were scored as 96-97% XX with 0.03% XY cells, and 94-96% of interphases were scored as XX with 0.05% XY cells. Considering the data as a model for any probe used with fluorescence in situ hybridization (FISH), a statistical approach assessing the impact of analytical sensitivity on the numbers of observations required to assay for potential mosaicisms and chimerisms is discussed. The workload associated with processing slides and scoring 50 metaphases and 200 interphases using FISH averaged 27.1 and 28.6 minutes, respectively. This study indicates that multiple laboratories can test/develop guidelines for the rapid, efficacious, and cost-effective integration of FISH into clinical service.


Subject(s)
DNA Probes , In Situ Hybridization, Fluorescence/methods , Interphase , X Chromosome , Y Chromosome , Cytogenetics/standards , Female , Humans , In Situ Hybridization, Fluorescence/instrumentation , Laboratories/standards , Lymphocyte Activation , Lymphocytes/cytology , Male , Metaphase , Phytohemagglutinins , Quality Control , Reproducibility of Results , Sensitivity and Specificity , Workload
19.
Am J Med Genet ; 80(5): 473-80, 1998 Dec 28.
Article in English | MEDLINE | ID: mdl-9880211

ABSTRACT

Trisomy 16, once thought to result uniformly in early pregnancy loss, has been detected in chorionic villus samples (CVS) from on-going pregnancies and was initially ascribed to a second, nonviable pregnancy. Prenatally detected trisomy 16 in CVS and its resolution to disomy has led to the reexamination of the viability of trisomy 16. This study evaluates 11 cases of mosaic trisomy 16 detected through second trimester amniocentesis. In 9 of the 11 cases, amniocenteses were performed in women under the age of 35 because of abnormal levels of maternal serum alpha-fetoprotein (MSAFP) or maternal serum human chorionic gonadotropin (MShCG). The other two amniocenteses were performed for advanced maternal age. Five of the 11 pregnancies resulted in liveborn infants, and six pregnancies were electively terminated. The liveborn infants all had some combination of intrauterine growth retardation (IUGR), congenital heart defects (CHD), or minor anomalies. Two of them died neonatally because of complications of severe congenital heart defects. The three surviving children have variable growth retardation, developmental delay, congenital anomalies, and/or minor anomalies. In the terminated pregnancies, the four fetuses evaluated by ultrasound or autopsy demonstrated various congenital anomalies and/or IUGR. Cytogenetic and fluorescent in situ hybridization studies identified true mosaicism in 5 of 10 cases examined, although the abnormal cell line was never seen in more than 1% of cultured lymphocytes. Placental mosaicism was seen in all placentas examined and was associated with IUGR in four of seven cases. Maternal uniparental disomy was identified in three cases. Mosaic trisomy 16 detected through amniocentesis is not a benign finding but associated with a high risk of abnormal outcome, most commonly IUGR, CHD, developmental delay, and minor anomalies. The various outcomes may reflect the diversity of mechanisms involved in the resolution of this abnormality. As 80% of these patients were ascertained because of the presence of abnormal levels of MSAFP or MShCG, the increased use of maternal serum screening should bring more such cases to clinical attention.


Subject(s)
Chromosomes, Human, Pair 16/genetics , Mosaicism/genetics , Trisomy/genetics , Amniocentesis , Female , Humans , In Situ Hybridization, Fluorescence , Microsatellite Repeats , Pregnancy , Pregnancy Outcome/genetics , alpha-Fetoproteins
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