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PubMed1988

Bivariate flow karyotyping in human Philadelphia-positive chronic myelocytic leukemia.

Chromosome analysis on clinical leukemia material was done by means of flow cytometry (flow karyotyping) to investigate the applicability of this technique in the detection of leukemia-associated abnormalities. Flow karyotyping was performed on blood or bone marrow samples from eight patients with chronic myelocytic leukemia (CML) after a culture period of four days and arresting the cells in metaphase during the last 16 hours. Discontinuous density gradient centrifugation proved to be essential in removing debris and dead cells from the cell suspensions. By this procedure the mitotic index increase ranged from 2 to 80 times initial values. Chromosomes were isolated and stained with two base pair-specific fluorochromes, ie, chromomycin A3 and Hoechst 33258, and run through a specially designed dual-laser beam flow cytometer. Generally, 20,000 chromosomes or more were measured. The data were computer stored in list mode. Besides the clear detection of the specific Philadelphia chromosome, trisomies and other additional chromosomal aberrations [like an i(17q)] were visualized. Quantitative analysis revealed the percentage of subclones containing a certain chromosomal anomaly. Conventional cytogenetic analysis confirmed these findings. In seven of eight cases, CML could be diagnosed on the basis of the presence of a Philadelphia chromosome in the flow karyogram. In one of these seven, the conventional cytogenetic analysis was unknown at that time. The remaining six all matched the standard cytogenetics. The one failure out of eight could be attributed to the specific stimulating conditions in the culture. Although it is impossible by this technique to determine the position of the breakpoint, the involved chromosomes in the translocation event could be identified. In some cases, low percentages of aberrations could not be detected. This study shows that CML can be diagnosed on the basis of flow karyotypic results. Additional chromosomal aberrations can be detected provided that changes in the amount of DNA per chromosome have occurred. Exact quantification of the composition of subclones in the case of mosaicism appear difficult.

Adult↗
PubMed1995

Infusion of tumor-contaminated bone marrow for autologous rescue after high-dose therapy leading to long-term remission in a patient with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia.

We report a female patient with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia remaining in long-term second remission after high-dose radiochemotherapy followed by autologous stem cell rescue with bone marrow showing evidence of residual disease. The Philadelphia chromosome and a positive signal for the BCR/ABL p185 translocation by the polymerase chain reaction were detected in the harvested marrow. After mafosfamide-purged marrow failed to engraft, her unpurged 'back-up' bone marrow was also infused. Control marrow examinations after recovery were repeatedly positive for the BCR/ABL translocation on PCR analysis turning negative 30 months after high-dose therapy. She remains in unsustained complete clinical remission for 48+ months showing no evidence of leukemia by cytological and cytogenetic analyses.

Adult↗
PubMed1994

Heat-related deaths--Philadelphia and United States, 1993-1994.

During June 1994, temperatures across the United States were higher than usual. Since June 13, record high temperatures (above 90 F [32.2 C]) with humidities of 50%-60% have occurred in the northeastern United States (1). During July 1-14, 1993, the eastern United States also experienced a severe heat wave with high temperatures (93 F-101 F [33.9 C-38.3 C]) and high humidity (36%-58%) (2). During July 6-14, 1993, in Philadelphia, medical examiners (MEs) determined 118 deaths were heat-related*. This report describes heat-related deaths that occurred in Philadelphia during 1993 and 1994 and summarizes risk factors for heat-related illness and death.

Adult↗
PubMed1994

[Experience with the molecular genetical detection of the chimera gene of the Philadelphia chromosome].

Molecular genetical techniques could be developed for detection of the chimera gene of Philadelphia chromosome or that of its gene product, due to the relatively conserved structure of the chimera gene. The authors successfully analysed 123 blood/bone marrow samples from 106 patients using these molecular techniques adapted from the literature. Patients were classified by the first diagnosis, 65 CML, 7 AML, 13 ALL patients were studied. 12 patients had the diagnosis of myeloproliferative syndrome, and 9 patients were after bone marrow transplantation. 57% of the total, and by diagnosis, 74% of CML, 28% of AML, 54% of ALL, and 33% of post-transplant samples have shown the chimera gene structure characteristic for Philadelphia chromosome. All patients of myeloproliferative syndrome were negative. In some cases the authors had the opportunity to study simultaneously the peripheral blood and the bone marrow sample of the same patient and of the same date. The ratio of the positivity of the two samples varied from one to infinite. The authors could follow the effect of interferon in one case, the change of clonality of the leukemic cell line in an other case. They had the opportunity to detect two different abnormal gene structures in the sample of an AML patient.

Chimera↗
PubMed1997

The treatment of Philadelphia inebriates. From temperance reform to "secret cure".

Preventive education in the United States about the dangers of alcohol had failed to create a temperate society by 1840. But in that year, interest in medical treatment of the "habitual drunkard" rekindled in Philadelphia. It was the year an organization of reformed drunkards revitalized American temperance societies by emphasizing practical concern for the inebriate. The author describes Philadelphia's treatment of alcoholics from 1840 through the beginning of the 20th century, when entrepreneurs were marketing secret cures.

Alcoholism↗
PubMed1997

Guidelines and realities of asthma management. The Philadelphia story.

BACKGROUND: Guidelines from the National Heart, Lung, and Blood Institute, Bethesda, Md, have encouraged more frequent use of inhaled steroids in asthma management. OBJECTIVES: To determine (1) whether prescription rates for inhaled steroids have increased compared with prescriptions for bronchodilators and (2) significant associations of demographic factors with bronchodilator-inhaled steroid prescription ratios and with rates of inhaled steroid prescriptions. DESIGN: Cross-sectional analysis of monthly bronchodilator and inhaled steroid prescription rates, numbers and types of asthma care providers, and demographic factors. SETTING: Philadelphia, Pa. MEASUREMENTS: Using univariate and multivariate analyses, bronchodilator and inhaled steroid prescription rates were determined for 45 ZIP codes and studied for associations with race and ethnicity, poverty, educational attainment, marital status, gender, total numbers of asthma drug prescriptions, and numbers and types of asthma care providers. RESULTS: Monthly bronchodilator-inhaled steroid prescription ratios increased from July 1991 to June 1993 (P < .001). Prescription rates for inhaled steroids and inhaled bronchodilators declined, but rates for oral bronchodilators (beta-agonists and theophylline) increased. By stepwise multiple regression, higher bronchodilator-inhaled steroid prescription ratios and lower inhaled steroid prescription rates were each significantly associated with ZIP codes in which greater proportions of residents lacked a high school diploma (P < .001); associations that approached statistical significance were found for higher bronchodilator-inhaled steroid ratios and fewer asthma care providers (P = .05) and for lower inhaled steroid prescription rates and lower proportions of asthma specialists (P = .04). CONCLUSIONS: In Philadelphia, a gap exists between optimal asthma drug prescribing and actual prescribing patterns that has widened from July 1991 to June 1993. Underuse of inhaled steroids is most closely associated with lower educational attainment, suggesting that interventions that include addressing the special asthma care needs of a low-literacy population will be required to achieve the goals of the National Asthma Education Program.

Administration, Inhalation↗
PubMed1980

Chronic myelogenous leukemia. Association with 45 XO Philadelphia chromosome karyotype and prolonged survival.

A 42-year-old man with chronic myelogenous leukemia for ten years was found to have a 45 XO Philadelphia chromosome karyotype in myeloid cells with normal 46 XY pattern in peripheral blood lymphocytes. This chromosome pattern has been postulated to be associated with delay in onset of blastic transformation. The prolonged survival of this patient, with only minimal initial chemotherapy and lack of symptoms for ten years, lends support to the concept that the missing Y chromosome may be associated with a favorable prognosis in Philadelphia chromosome-positive men with chronic myelogenous leukemia.

Adult↗
PubMed1996

Factors associated with intention to undergo annual prostate cancer screening among African American men in Philadelphia.

BACKGROUND: This study assesses whether African American men in Philadelphia are receptive to annual prostate cancer screening. Factors associated with intention to undergo prostate cancer screening are also identified. METHODS: The authors randomly selected 218 African American men from the patient population of a large primary care practice in Philadelphia. The men were 40 to 70 years of age and were available for a telephone survey. Responses to survey items defined by the Preventive Health Model were collected from 154 respondents (71%). Univariate and multivariate analyses of screening intention were performed using survey data on sociodemographic background and medical history; knowledge, attitudes, and beliefs about prostate cancer and screening; social support and influence; and, intention to undergo a screening examination. RESULTS: Overall, 69% of subjects reported that they intended to have annual prostate cancer screening. Logistic regression analyses showed that subject belief in screening efficacy (P=0.0002) were positively and significantly associated with intention to screen. CONCLUSIONS: Findings reported here show that African American men in an urban primary care practice setting are receptive to annual prostate cancer screening and that psychologic and social influence factors are associated with screening intention. The data highlight the need for health care professionals to provide education and advice regarding prostate cancer care to men in this population.

Adult↗
PubMed1992

Mediastinal masses in children with Hodgkin's disease. An analysis of the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania experience.

From 1970 to 1988, 121 patients younger than 18 years of age who had newly diagnosed Hodgkin's disease were treated at the Children's Hospital of Philadelphia (CHOP) and the Hospital of the University of Pennsylvania (HUP), Philadelphia, Pennsylvania. Fifty-five of 79 children with mediastinal masses (MM) had pretreatment chest radiographs from which a mediastinal mass ratio (MMR) could be calculated. Within a range of MMR values, 0.25 was the best prognosticator for event-free survival (EFS) for all patients. In those treated with radiation therapy (RT) alone, the intrathoracic relapse rate was zero of five patients with small MM (MMR less than 0.25) versus five of eight patients with large MM (P = 0.09). For combined-modality therapy (CMT), there were intrathoracic relapses in zero of four patients with small MM versus 5 of 32 patients with large MM (P = 0.8). For CMT, the intrathoracic relapse rates for those receiving more than 3500 cGy versus less than 2500 cGy were 0 of 4 patients and 5 of 27 patients, respectively (P = 0.8). The intrathoracic relapse rate in children with large MM was significantly lower for CMT than for RT (5 of 32 patients versus 5 of 8 patients) (P = 0.02). The authors concluded that in pediatric Hodgkin's disease, a MM with a MMR greater than or equal to 0.25 may be associated with poor intrathoracic control after RT alone. Despite this, children with large MM treated with RT alone had an excellent overall survival rate.

Adolescent↗
PubMed1994

Complete hematologic remissions in chronic-phase, Philadelphia-chromosome-positive, chronic myelogenous leukemia after 2-chlorodeoxyadenosine.

BACKGROUND: 2-Chlorodeoxyadenosine (Cladribine, Leustatin, Ortho Biotech, Raritan, NJ) (2-CdA) is a purine analog with activity in the treatment of lymphoid neoplasms. Interferon induces cytogenetic remissions in chronic myeloid leukemia (CML) and partial remissions in hairy cell leukemia, a disorder in which single courses of 2-CdA induce complete remissions. In vitro clonal growth of immature myeloid progenitors from normal marrow is markedly inhibited by 2-CdA. METHODS: 2-CdA was administered to 12 patients with Philadelphia-chromosome-positive CML, 11 chronic phase, and 1 accelerated phase, at 0.1 mg/kg/day by continuous intravenous infusion for 7 days every 28-35 days, until maximum peripheral hematologic response. RESULTS: Of 12 patients, 10 (83%) achieved complete hematologic responses and 2 (17%) partial hematologic responses after a median of two courses of 2-CdA. The median first hematologic response duration was 3 months. Of the seven patients who relapsed and were retreated with a median of two further courses of 2-CdA, five obtained responses (four complete and one partial) and two did not respond. The median second hematologic response duration was 4 months. No patient had significant Philadelphia-chromosome suppression. Reversible myelosuppression and severe cumulative T-cell immunosuppression associated with opportunistic infections in four patients were the principal toxicities. CONCLUSIONS: 2-CdA is active in CML, inducing complete hematologic responses, but the absence of cytogenetic responses and severe immunosuppression may limit its clinical use.

Adult↗
PubMed1978

Reciprocal translocation and the Philadelphia chromosome.

We examined metaphases from three patients with chronic myeloid leukaemia and a typical Philadelphia chromosome with one chromosome 9 as the recipient to determine whether the 9q+22q- translocation is reciprocal. Good quality G-banded photographs of the chromosomes concerned were subjected to light absorption density analysis. This provided enlarged tracings corresponding to the relevant chromosome regions and so facilitated accurate measurement. This technique has unambiguously shown that the typical Philadelphia chromosome results from a reciprocal translocation and that probably no material is gained or lost in the exchange. Furthermorein a total of six patients for whom sequential G and C banding was performed, the chromosome 9 with the largest block of centromeric heterochromatin received the translocated material. We offer tentative explanations for this curious observation.

Azure Stains↗
PubMed1978

Three chromosomes' (7;9;22) rearrangement and the origin of the Philadelphia chromosome.

A woman with chronic myelocytic leukemia had the Philadelphia chromosome and a complex four-break--three-chromosome rearrangement. The q32 leads to q34 portion of chromosome 9 is translocated to band q22 of chromosome 7, and at the end of this segment is attached the deleted q11 leads to qter portion of chromosome 22. A review of 12 cases of the Philadelphia chromosome originating by the rearrangement of three or more chromosomes reveals that chromosomes 9 and 22 are always involved, while the third chromosome is a different one in each case. We discuss the hypothesis that the 22q segment is always specifically attached to band 9q34 wherever this portion of 9q is transposed.

Aged↗
PubMed1975

Citizens' boards for Philadelphia community mental health centers.

Community participation is a frequently discussed and controversial aspect of the community mental health center program. To many professionals and lay people, the community mental health center concept includes a basic commitment to a participatory process of the community in the planning and implementation of the community mental health center program. However, this commitment is not readily evident in the federal and Pennsylvania regulations. This paper presents an approach taken by the Philadelphia Office of Mental Health and Mental Retardation to insure that its 13 centers and base service units have a meaningful partnership with their catchment area communities. Specifically the paper presents the community participation regulations developed by the Philadelphia office, as well as the conditions that led to the development of these regulations. A conclusion of the paper is that additional regulations are needed to insure that community participation becomes an integral part of the community mental health center program.

Community Mental Health Services↗
PubMed1978

The Philadelphia chromosome in acute leukemia.

The cytogenetics, cytology and cytochemistry, clinical findings, therapeutic response and survival of patients presenting with acute leukemia and the Philadelphia chromosome (Ph1) are briefly reviewed based upon a survey of the world literature and 16 cases seen at the University of Minnesota during the last 10 years. Details regarding the 16 cases from the University of Minnesota series are presented and two appendices listing the majority of reports of Ph1 + acute leukemia are included. Comparison of adults with Ph1+ and Ph1- acute leukemia demonstrate important clinical, therapeutic and prognostic differences. In general, patients with Ph1+ acute leukemia respond less well to treatment and survive significantly shorter periods of time. Since the presence of the Philadelphia chromosome in acute leukemia has therapeutic and prognostic significance, marrow chromosome studies should be performed in adults presenting with acute leukemia, especially acute lymphocytic leukemia.

Acute Disease↗
PubMed1996

Philadelphia chromosome-positive secondary acute myeloid leukemia following high-dose chemotherapy with peripheral blood progenitor cell support for relapsed low-grade non-Hodgkin's lymphoma.

We report the case of a 47-year-old patient who developed acute myelogenous leukemia (AML) 18 months after receiving high-dose chemotherapy with peripheral blood progenitor cell support (PBPCT) for relapsed low-grade follicular non-Hodgkin's lymphoma (NHL). Cytogenetic analysis of the leukemic cells showed the translocation (9;22)(q34;q11). In three mitoses, an additional Philadelphia chromosome (Ph1) was present. In the literature, Philadelphia chromosome-positive secondary AML has been described only once before in a patient with multiple myeloma.

Acute Disease↗
PubMed1975

A heterozygote for Hb S beta, Hb C beta and Hb G Philadelphia beta in a family presenting evidence for heterogeneity of hemoglobin alpha chain loci.

A child heterozygous for the genes for hemoglobins S, C and G alpha Philadelphia presented with a clinical picture similar to sickle cell anemia. Her hemoglobin electrophoretic pattern contained three components with the mobilities of hemoglobins S (35 per cent), C (47 per cent) and a more slowly migrating hybrid G/C molecule (15 per cent). Seven relatives were heterozygous for Hb G beta and Hb S beta and five were heterozygous only for Hb G alpha. Among the latter, three had approximately 30 per cent and two had 40 per cent of Hb G. These proportions are consistent with the hypothesis that the American Negro genome contains two types of chromosomes bearing structural loci for alpha chains, some possessing one Hb alpha locus, others having two loci. Hb G alpha-Philadelphia presumably arose as a mutation on a chromosome with a single locus. Those heterozygotes having 30 per cent and 40 per cent Hb G presumably have two loci and only one locus, respectively, on the homologous chromosome.

Amino Acid Sequence↗
PubMed1988

The Philadelphia variant of galactokinase in human erythrocytes: physicochemical and catalytic properties.

The Philadelphia variant of galactokinase (GALKP) is responsible for an asymptomatic disorder of galactose metabolism. Individuals with GALKP phenotype are common among black people. They exhibit reduced galactokinase (GALK) activity in their red blood cells but normal activity in their white blood cells. We explored the biochemical characteristics of hemolysates from individuals with the GALKP phenotype and from controls. In mixed hemolysates from a control and a proband, the GALK activity measured did not suggest the presence of an inhibitor. We observed that the catalytic properties, pI and thermolability in hemolysates from controls and GALKP individuals were identical. Thus, the Philadelphia variant of galactokinase seems not to alter biochemical properties of the red blood cell enzyme. A silent amino acid substitution, or the dysfunction of a regulatory gene might be likely suggested to explain the reduced enzyme activity.

Black People↗
PubMed1988

Hb G-Philadelphia, or [alpha 68(E17)Asn----Lys], in north Sardinia: detection by isoelectric focusing and identification by HPLC of tryptic peptides.

11,129 individuals of the northern area of the island of Sardinia (7,717 newborns and 3,412 adults) were examined for the Hb G-Philadelphia variant [alpha 68(E17)Asn----Lys]. Hemolysates were analysed by isoelectric focusing, and the variant identified by reversed phase high performance liquid chromatography of tryptic peptides. A total of seven heterozygotes (1 in 1,589) were identified. This is probably the highest prevalence of this mutant so far described. Percentages of the variant (average 35.1 +/- 6.2%) were trimodally distributed with modes centering on 28, 36, and 42%, respectively. These values suggest that the G-Philadelphia allele occurs in Sardinians both on a single and on a double locus chromosome. The linkage with alpha-thalassemia may be the reason for the high frequency of the variant.

Adult↗