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PubMed1986

Essential thrombocytosis with the Philadelphia chromosome (Ph').

Essential thrombocytosis is a myeloproliferative disease not known to have consistent cytogenetic abnormalities. A 46-year-old black woman with essential thrombocytosis and a Philadelphia chromosome is reported. Iron deficiency and tuberculosis were present but when effectively treated did not result in resolution of thrombocytosis. Megakaryocytic hyperplasia of bone marrow, abnormal platelet function studies and a compatible clinical state suggested the diagnosis of essential thrombocytosis. The diagnostic criteria for other myeloproliferative diseases were not met. The Philadelphia chromosome was consistently obtained from bone marrow preparations. We conclude that the Philadelphia chromosome may be found in essential thrombocytosis as well as other, previously reported, myeloproliferative diseases.

Bone Marrow↗
PubMed1994

Molecular diagnosis of the Philadelphia chromosome translocation. A comparison of isotopic and chemiluminescent Southern blotting.

Southern blotting using radiolabeled probes is a well established technique for the detection of the Philadelphia translocation in the diagnosis of chronic myelogenous leukemia (CML). However, the use of radioisotopes in the clinical setting is often problematic. Because of this we investigated the use of a digoxigenin-labeled probe and chemiluminography in the detection of the Philadelphia translocation. In this study DNA was extracted from 19 bone marrow or blood samples from patients with CML or other malignancies and subjected to Southern blotting with a probe specific for the Philadelphia translocation, Phl/bcr3. The probe was labeled with either 32P or digoxigenin to determine the relative sensitivity and specificity of autoradiography and chemiluminography in the molecular diagnosis of the BCR/abl fusion gene. All 19 samples were tested by both methods. All blots were performed and interpreted by individuals blind to the initial patient diagnosis. In addition, 12 samples (6 positive for CML, 6 negative for CML as determined by Southern blotting with 32P-labeled probe) were subjected to triplicate Southern-blot analyses, with three separate lots of digoxigenin-labeled probe to assay batch to batch variability in the efficacy of the probe. Radiolabeled and digoxigenin-labeled probes resulted in identical diagnoses in all cases. All results obtained by molecular analysis correlated perfectly with the clinical diagnoses of the patients from whom the samples had been obtained. Reanalysis of patient samples with different batches of digoxigenin-labeled probe gave highly reproducible results. With digoxigenin-labeled probe, diagnostic results were obtained after exposure times of less than 1 h at room temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoradiography↗
PubMed2001

The co-occurrence of AIDS and homelessness: results from the integration of administrative databases for AIDS surveillance and public shelter utilisation in Philadelphia.

STUDY OBJECTIVE: Administrative databases from the City of Philadelphia that track public shelter utilisation (n=44 337) and AIDS case reporting (n=7749) were merged to identify rates and risk factors for co-occurring homelessness and AIDS. DESIGN: Multiple decrement life tables analyses were conducted, and logistic regression analyses used to identify risk factors associated with AIDS among the homeless, and homelessness among people with AIDS. SETTING: City of Philadelphia, Pennsylvania, USA. MAIN RESULTS: People admitted to public shelters had a three year rate of subsequent AIDS diagnosis of 1.8 per 100 person years; nine times the rate for the general population of Philadelphia. Logistic regression results show that substance abuse history (OR = 3.14), male gender (OR = 2.05), and a history of serious mental disorder (OR = 1.62) were significantly related to the risk for AIDS diagnosis among shelter users. Among people with AIDS, results show a three year rate of subsequent shelter admission of 6.9 per 100 person years, and a three year rate of prior shelter admission of 9%, three times the three year rate of shelter admission for the general population. Logistic regression results show that intravenous drug user history (OR = 3.14); no private insurance (OR = 2.93); black race (OR = 2.82); pulmonary or extra-pulmonary TB (OR = 1.43); and pneumocystis pneumonia (OR = 0.56) were all related to the risk for shelter admission. CONCLUSIONS: Homelessness prevention programmes should target people with HIV risk factors, and HIV prevention programmes should be targeted to homeless persons, as these populations have significant intersection. Reasons and implications for this intersection are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Mobilisation and reinfusion of Philadelphia negative peripheral blood mononuclear cells in chronic myeloid leukaemia with hydroxyurea and G-CSF.

Unmanipulated autologous transplantation of marrow of peripheral blood stem cells has been performed in small numbers of patients with CML for many years. More recently there has been interest in attempting to 'purge' the autograft of clonal cells as defined by the presence of the Philadelphia chromosome or BCR-ABL rearrangement. One method by which this might be achieved in vivo has been developed in Genoa and involves the administration of high dose chemotherapy and G-CSF followed by peripheral blood stem cell collection. These collections are frequently devoid of Philadelphia positive cells and the hope is that this will enhance the effects of subsequent autograft. We have investigated the use of a less toxic regimen for this procedure using oral hydroxyurea and G-CSF. In this review we describe the background to autografting in CML and the development of strategies to mobilise Philadelphia negative cells into the peripheral blood. We go on to present an update of our data using hydroxyurea and discuss some of the practical and theoretical issues behind the procedure.

Adult↗
PubMed1991

Alternative case-finding methods in a crack-related syphilis epidemic--Philadelphia.

Use of crack cocaine and exchange of drugs for sex have been identified as substantial contributors to the syphilis epidemic in Philadelphia and other locations in the United States. In Philadelphia, from 1985 through 1989, the number of reported cases of early syphilis (primary, secondary, and early latent stages) increased 551%, from 696 to 4528 cases per year. Among 2473 persons with early syphilis interviewed by the Philadelphia Department of Public Health (PDPH) from January through July 1990, 48% reported they or a sex partner used crack cocaine, and 31% reported exchanging drugs or money for sex (not all of those interviewed answered both questions). Traditional approaches to the control of syphilis that emphasize partner notification have not been effective in halting this epidemic. The partner notification approach requires public health workers to identify sex partners of a person with a sexually transmissible disease (e.g., syphilis) and then to contact these sex partners to provide examination and curative or preventive treatment. However, because persons who are involved in the exchange of drugs and/or money for sex often cannot or will not provide sufficient information about sex partners to enable public health authorities to locate those partners (2,4,5), alternative case-finding methods are needed. This report describes efforts by the PDPH to identify persons infected with Treponema pallidum by using serologic screening at locations where crack cocaine is used.

Cluster Analysis↗
PubMed1990

First intron and M-bcr breakpoints are restricted to the lymphoid lineage in Philadelphia positive acute lymphoblastic leukemia.

Knowledge of the level of commitment of the target cell in hematological malignancies may have important therapeutic and prognostic implications. Cell lineage involvement was investigated in two cases presenting with acute lymphoblastic leukemia diagnosed on clinical and immunological findings and having the Philadelphia translocation t(9;22)(q34;q11). DNA from cells separated into mononuclear (lymphoid) and granulocytic fractions was hybridized with Philadelphia breakpoint-specific probes. This revealed that the breakpoint giving rise to the Philadelphia chromosome in case 1 was within the major breakpoint cluster region and in case 2 was in the first intron of the BCR gene. Rearrangement was found in the lymphoid but not the granulocyte fraction in each case. It is therefore concluded that the target cell for chromosomal change in these cases was a lymphoid committed progenitor cell, irrespective of breakpoint location.

Adult↗
PubMed1987

Tyrosine protein kinase substrates in Philadelphia-positive human chronic granulocytic leukemia derived cell lines (K562 and BV173): detection by using an immunoblotting technique.

In chronic granulocytic leukemia (CGL) the Philadelphia translocation results in the production of a novel 210 kDa bcr-abl fusion protein which shows increased tyrosine protein kinase activity in comparison with its normal 145 kDa c-abl counterpart. Using an immunoblotting method and antiphosphotyrosine antibody, we have identified the tyrosine protein kinase substrates present in intact cells from two Philadelphia-positive CGL derived cell lines (K562 and BV173) and compared these with the substrates present in a Philadelphia-negative myeloid cell line (HL60). We have demonstrated an increased number of substrates, particularly of low (less than 110 kDa) molecular weight in the K562 or BV173 cells compared with the HL60 cells. There is virtual identity of the substrates present in the two CGL-derived lines. This work supports the hypothesis that the functional changes present in the bcr-abl 210 kDa protein of CGL results in altered tyrosine phosphorylation of intracellular proteins and that this is of importance in the pathogenesis of CGL.

Humans↗
PubMed1988

[Does the Philadelphia chromosome disappear after treatment with interferon?].

Chronic myelocytic leukaemia is a myeloproliferative syndrome with two highly specific characteristics: it has a cytogenetic clonal marker known as Philadelphia chromosome and a molecular marker in the form of bcr-abl rearrangement, and it progresses in two phases: a chronic phase followed by an acute terminal phase of blastic transformation. The fatal outcome of this blood disease can only be checked if we possess one or several treatments providing a complete and stable clinical, haematological and cytogenetic remission. Such a course is seldom observed. The conventional treatment of the chronic phase consists of single drug chemotherapeutic regimens which have succeeded in increasing the patients' median survival but do not prevent blastic transformation which is beyond therapeutic resources. In some cases multiple drug chemotherapy, and notably bone marrow transplantation, may result in disappearance of the Philadelphia chromosome and arrest of the natural course of the disease. Interferon is a new treatment which eradicates the Philadelphia chromosome and offers hopes of complete and prolonged, if not permanent, remissions. The present experience, although limited, suggests that alpha-interferons are effective. Judging from the available data, it is very likely that the future treatment of myelocytic leukaemia will consist of chemotherapy combined with interferon(s) with or without bone marrow transplantation.

Humans↗
PubMed1993

Heterogeneity in lineage derivation of Philadelphia-positive acute lymphoblastic leukemia expressing p190BCR-ABL or p210BCR-ABL: determination by analysis of individual colonies with the polymerase chain reaction.

The molecular hallmark of Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) is the expression of 1 of 2 alternate forms of the aberrant BCR-ABL protein-p210BCR-ABL or p190BCR-ABL. The presence of BCR-ABL message provides a target for analyzing the lineage derivation of this disease. We, therefore, studied myeloid and erythroid progenitor involvement in Philadelphia chromosome-positive ALL. Bone marrow low-density cells from Philadelphia chromosome-positive ALL patients (5 with the p190BCR-ABL and 2 with the p210BCR-ABL anomaly) were cultured in the mixed colony culture assay. cDNA from individually plucked colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid colonies was then analyzed using the hybridization protection assay in conjunction with the polymerase chain reaction to detect BCR-ABL molecular aberrations. Colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid colonies from 1 of 5 p190BCR-ABL-positive patients and 1 of 2 p210BCR-ABL-positive patients expressed BCR-ABL transcripts, whereas colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid colonies from the other patients did not. Our study suggests that the origin of both p190BCR-ABL- and p210BCR-ABL-positive ALL is heterogenous with involvement of either a pluripotent precursor or a lymphoid lineage-committed hematopoietic progenitor.

Adolescent↗
PubMedDate not supplied

Breast cancer and mammography: an American Cancer Society profile of Philadelphia and Montgomery Counties.

The American Cancer Society, Philadelphia Division, has completed a comprehensive profile of breast cancer and mammography in Philadelphia and Montgomery Counties. The profile consists of three segments: (1) data on incidence of breast cancer and trends in stage at diagnosis; (2) estimates of breast cancer screening practices based on surveys of the population; and (3) results from a survey of mammography providers assessing the region's capacity for and access to mammography. The profile demonstrated that the Philadelphia Division is already close to achieving the national American Cancer Society's goals for breast cancer detection for the year 2000 for the percent of women screened and percent of cancers diagnosed in early stages. New and more ambitious goals for the Division must be set. Although capacity for mammography is high, outreach programs by mammography providers represent only 1% to 2% of all mammograms performed. The profile has been the cornerstone of new programmatic initiatives for the Division.

Adult↗
PubMed1976

Philadelphia chromosome in acute leukemia: case report.

A case report of serial chromosome studies on a child presumed to have acute lymphoblastic leukemia (ALL) is presented. Hematologic remission was achieved after 3 weeks and maintained until death 63 weeks later. The classic Philadelphia chromosome translocation was found, both at diagnosis and throughout the course of the disease, in a proportion of cells from PHA-stimulated blood cultures. The finding is related to other reports of Philadelphia-positive clones in ALL, as well as those in chronic myeloid leukemia and its acute transformation, and other myeloproliferative disorders. The origin of the Philadelphia chromosome in this case is considered in the light of current stem cell theory, and its relevance to lymphocytic neoplasia is discussed. We believe that the finding of a Ph1-positive clone in a cell line morphologically indistinguishable from normal lymphocytes in a case of acute leukemia is unique.

Bone Marrow↗
PubMed1976

Is haemoglobin G alpha Philadelphia linked to alpha-thalassaemia?

The question, "Is Hb G alpha Philadelphia linked to alpha-thalassaemia?" was first posed because the abnormal haemoglobin is found in heterozygotes at a concentration greater than 25%, the proportion predicted from a 4 alpha-chain gene model. Globin chain biosynthesis was studied in a West Indian family in which one parent had beta + thalassaemia and the other was heterozygous for the G alpha Philadelphia chain gene. The former had a globin chain production ratio alpha/beta well above 1, while the latter had a ratio significantly less than 1. One child of the marriage had inherited the beta + thalassaemia from one parent and the G alpha Philadelphia chain gene from the other and showed the typical picture of alpha/beta-thalassaemia (alpha/beta ratio slightly above normal). It is explained in the discussion that the evidence favours a close linkage of 2 alpha-chain genes.

Black People↗
PubMed1995

Translocation of BCR to chromosome 9 in a Philadelphia-negative chronic myeloid leukemia.

We report the case of a patient having Philadelphia-negative, bcr-abl-positive chronic myeloid leukemia. In situ hybridization showed the presence of the bcr-abl fusion on the chromosome 9 long arm in all mitoses observed. Stability of the disease was very difficult to obtain because of serious adverse effects to interferon and chemotherapy, mainly grade IV neutropenia, and a blast crisis occurred 12 months after diagnosis. Only three other patients with such presentation (Philadelphia negative, bcr-abl positive with bcr-abl fusion on the chromosome 9 long arm) have been reported, with a poor therapeutic response and outcome in two of them. Translocation of BCR to chromosome 9 may therefore have a worse prognosis than translocation of ABL to chromosome 22 in Philadelphia-negative chronic myeloid leukemia.

Adult↗
PubMedDate not supplied

[Philadelphia chromosome-positive acute lymphoblastic leukemia in childhood: a special risk group?].

The Philadelphia chromosome is rarely observed in acute myelogenous and acute lymphoblastic leukemias. There are only a few case reports about pediatric patients, the prognosis of whom seems to be extremely poor. Reviewing the case of a girl aged 18 months with Philadelphia chromosome positive acute lymphoblastic leukemia, the differences between this entity and blast crisis of chronic myelogenous leukemia are described. This subgroup of Philadelphia chromosome positive acute lymphoblastic leukemia may represent a new risk group.

Chromosomes, Human, 21-22 and Y↗
PubMed2006

Breast cancer early detection among Chinese women in the Philadelphia area.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death among Chinese American women. Previous studies identified disparities in breast cancer screening between Asian and Caucasian women. This study describes breast cancer awareness, attitudes, and knowledge, as well as barriers and facilitators of early detection among Chinese women in Philadelphia. METHODS: A cross-sectional, translated survey was conducted among a convenience sample of 111 Chinese women from the greater Philadelphia area. Data were analyzed using descriptive statistics to describe participant experiences and attitudes, and Pearson correlation coefficients, chi-square tests, and multiple regressions were used to identify significant predictors of breast cancer screenings. RESULTS: Of respondents, 53.2% had ever performed breast self-examination (BSE). Among women aged >or=40, 53.6% had ever had clinical breast examination (CBE), and 71.1% had ever had mammogram. Knowledge (p < 0.001) and self-efficacy (p = 0.001) predicted BSE ever performance. Having a doctor as information source of CBE (p = 0.001) and belief in family history as a risk factor of breast cancer (p = 0.002) were significant predictors of having ever had a CBE. Having a doctor as information source of mammogram (p = 0.002) was the only significant predictor of having ever had mammogram screening. CONCLUSIONS: This study laid a foundation for developing culturally sensitive breast cancer education and screening programs for Chinese women in the Philadelphia area. Recommendations include a call for physician education to improve breast cancer screening rates in this population.

Adult↗
PubMed1976

Brucella suis infection in Philadelphia. A survey of hog fever and asymptomatic brucellosis.

Examination of hospital and public health records revealed 19 cases of brucellosis diagnosed in Philadelphia between 1968 and 1972. A serologic survey at Philadelphia's largest hog-processing plant, however, indicated infection in 39% of workers. If extrapolated industry-wide, the total would be several hundred in Philadelphia. The infection is usually unrecognized or asymptomatic, since men were active in physically demanding jobs with agglutinin titers in excess of 1:5000. Overt illness, usually first diagnosed after weeks of incapacity, responded readily to tetracycline therapy. Although clinical manifestations are nonspecific, attention to occupational history should quickly lead to the diagnosis. It is emphasized that any hog-processing plant, wherever located, is potentially a reservoir of brucellosis. Prolonged morbidity and loss of production time might be avoided if physicians were more alert to this infection. Agglutinins in possibly significant titers were also found in a small fraction of persons without identifiable exposure.

Adult↗
PubMedDate not supplied

Epidemic of meningitis and febrile illness in neonates caused by ECHO type 11 virus in Philadelphia.

Between April and November, 1980, an outbreak of meningitis and of febrile illness of neonates caused by ECHO 11 virus occurred in Philadelphia and surrounding communities. Thirty-eight virologically confirmed and ten virologically presumptive cases of meningitis were hospitalized in two Philadelphia hospitals for children. Most patients had fever and irritability. Vomiting, upper respiratory symptoms and poor feeding were present in one-third to one-half of the cases. Seventy-five percent of cases occurred between June 10 and August 18. The number of males and females was similar; 71% of children were 4 months of age or younger. This out break differed from those previously reported on enteroviruses in general, and on ECHO 11 virus in particular, in that no strong male predominance occurred and the patients were younger. A minimum attack rate of 4.1 per 1000 Philadelphia resident children ages 1 day to 4 months was estimated.

Adolescent↗
PubMedDate not supplied

Comparative study of risk factors for skin breakdown with cervical orthotic devices: Philadelphia and Aspen.

PURPOSE: To compare risk factors for skin breakdown between Philadelphia and Aspen cervical collars. METHODS: Crossover design. Twenty healthy volunteers wore Philadelphia and Aspen cervical collars in random order. Occipital pressure, relative skin humidity, and skin temperature measured at 0 and 30 minutes. Paired t-tests compared changes between collars from 0 to 30 minutes. FINDINGS: Occipital pressure and skin temperature were not statistically different between collars. Relative skin humidity increased more in Philadelphia (29% +/- 17%) than Aspen (8% +/- 9%), p < 0.001. CONCLUSIONS: Aspen resulted in lower relative skin humidity.

Adult↗