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Jumping translocation of 17q11 approximately qter and 3q25 approximately q28 duplication in a variant Philadelphia t(9;14;22)(q34;q32;q11) in a childhood chronic myelogenous leukemia.

The virtually obligatory presence of the Philadelphia chromosome may suggest a causal homogeneity, but chronic myelogenous leukemia (CML) is a clinically heterogeneous disease. This may be a consequence of the variable BCR breakpoints on chromosome 22 and of nonrandom secondary chromosomal abnormalities. We present the case of a boy, age 12, investigated in blastic phase of CML. Karyotyping with conventional and multiplex fluorescence in situ hybridization (FISH and M-FISH) karyotyping, complemented with reverse transcriptase-polymerase chain reaction, identified a variant Philadelphia translocation t(9;14;22)(q34;q32;q11) involving a cryptic BCR/ABL fusion with formation of the p190(Bcr-Abl) oncoprotein. M-FISH revealed also an unbalanced jumping translocation of 17q11 approximately qter alternatively present on chromosomes 14 or 20, apparently hithertofore unreported in hematological malignancies. Another secondary aberration, dup(3)(q25q28), was revealed by multipoint interphase FISH (mpI-FISH). Gain of this region is known in adult hematological malignancies and solid tumors, suggesting its general involvement in tumor initiation or progression (or both), regardless of tissue origin.

Child↗

Intensive chemotherapy for Philadelphia-chromosome-positive acute lymphoblastic leukaemia.

Childhood acute lymphoblastic leukaemia with the classic Philadelphia chromosome translocation is fatal in patients treated with chemotherapy alone. We report probable cures in three adolescents and one child who received extensively reinforced, early chemotherapy followed by rotational treatment with pairs of non-cross-resistant drugs. The median duration of leukaemia-free survival in this subgroup is 6.5 years (range 6-8 years). The two patients with long-term bone marrow surveillance for residual disease showed no evidence of the Philadelphia chromosome at 31 and 53 months post-remission. Such intensive chemotherapy is a reasonable option for patients who are not able to undergo bone marrow transplantation.

Adolescent↗

A new complex variant Philadelphia chromosome, t(1;9;22)ins(17;22), characterized by fluorescence in situ hybridization in an adult ALL.

A new complex variant Philadelphia chromosome was detected in a 65-year-old man with acute, pre-B, lymphoblastic leukemia (ALL). The classic cytogenetic analysis identified an apparently balanced three-way translocation t(1;9;22)(q25;q34;q11.2). Fluorescence in situ hybridization (FISH) studies confirmed the translocation and showed bcr/abl fusion on the der(22). However, these studies revealed that the distal part of the bcr gene was not translocated onto chromosome 1 at 1q25, but inserted into chromosome 17 at 17p12-13. This complex variant translocation was described as a t(1;9;22)(q25;q34;q11.2)ins(17;22)(p12-13;q11.2q11.2). Secondary changes including +8, an inversion of the derivative chromosome 9, a translocation t(14;20)(q11;q13), and an additional derivative 22 were also identified in most of the abnormal cells. The patient died from systemic fungemia and multiorgan failure 9 months after the diagnosis of ALL. The clinical significance of complex variant Philadelphia chromosomes in ALL is reviewed and discussed.

Adult↗

Secondary chromosomal changes in 34 Philadelphia-chromosome-positive chronic myelocytic leukemia patients from the Mexican West.

The clonal evolution in t(9;22)-positive chronic myelocytic leukemia (CML) is well established. Four major changes occur in more than 70% of patients: +8, i(17q), +19, and an extra Philadelphia chromosome. The frequencies of secondary chromosomal changes in 34 patients from the states of Jalisco, Nayarit, Michoacán, and Colima (the Mexican West) with Philadelphia-chromosome-positive CML were assessed. The most frequent abnormalities were tetraploidy (12 cases); +8, inv(3)(q21q26), and octoploidy (3 cases each); and +der(22)(2 cases). Some translocations not previously associated with CML were observed, such as t(2;7)(p12;q36), t(3;6)(q26;p25), t(3;17)(q26;p13), and t(6;17)(q21;q23 approximately q25). Significant differences were found for +8 with respect to population results from Japan and from southern, eastern, and western Europe; for i(17)(q10) from eastern Europe; for +19 from Japan and western Europe; and for +der(22) from Japan, southern Europe, and western Europe. Although polyploidy could result from endomitosis, there is no direct evidence that the BCR/ABL protein influences such a process; however, protein kinases such as MAPK, which are involved in endomitosis, are activated by the BCR/ABL protein, and so the BCR/ABL protein could promote endomitosis through the MAPK pathway.

Adolescent↗

The effects of licensing and inspection enforcement to reduce tobacco sales to minors in Greater Philadelphia, 1994-1998.

This study examined the changes in tobacco sales to minors after active enforcement of merchant compliance to the Synar regulation and the city of Philadelphia Youth Access to Tobacco Ordinance 732. Data for the present study were obtained through Tobacco-free Education and Action Coalition for Health (TEACH) Program in a 5-year, follow-up retail compliance check survey of 1649 stores in 14 cluster areas of Philadelphia, PA. Trend analysis was conducted ofthe sales of tobacco to minors by type of retail outlet, gender, and age of the buyer, and gender, age, and race of the store clerk, and whether restriction policy signs were posted. Analysis indicates that there was a reduction in tobacco sales to minors after implementation of enforcement; sales dropped from 85% in 1994 to 43% in 1998. There were less sales to minors when signs were posted. There were differences in sales if the buyer was asked his or her age and whether the minor was asked to show identification. In addition, the age of the buyer and the brand of cigarettes were associated with sales. Future research should focus on both commercial and social availability and provision of tobacco to minors.

Adolescent↗

Regional size differences in four commonly used cephalometric atlases: the Ann Arbor, Cleveland (Bolton), London (UK), and Philadelphia atlases compared.

OBJECTIVE: To explore regional influence on size in roentgenocephalometric atlases. DESIGN: Comparisons of the size of 10 linear distances in four atlases from geographically different regions, i.e. Ann Arbor Michigan, Cleveland Ohio, Philadelphia Pennsylvania and London, UK. DISTANCES COMPARED: anterior cranial base length (S-N), posterior cranial base length (S-Ba), total face height (N-Me), upper face height (N-ANS), lower face height (ANS-Me), mandibular diagonal (Ar-Gn), corpus length (Go-Pg), ramus height (Ar-Go), maxillary length (SNP-SNA), posterior face height (S-Go). RESULTS: Correction for enlargement appeared to be a necessity before distances could be compared. After correction for enlargement, the anterior cranial base was longest in Ann Arbor, lower face height smallest in Cleveland (Bolton standards) and the maxilla was shortest in Philadelphia. CONCLUSION: Regional size variance in cephalometric data cannot be ignored.

Adolescent↗

Investigation of clonal involvement of myeloid cells in Philadelphia-positive and high hyperdiploid acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) with a high hyperdiploid clone has a good prognosis for both childhood and adult patients while patients with Philadelphia-positive (Ph) ALL do badly at all age groups. It has been suggested that different responses to treatment might be related to the cell of origin of the leukemia with 'stem cell' cases responding less well than those arising in a lymphoid committed progenitor cell. The clonal involvement of different cell lineages in 12 patients with acute lymphoblastic leukemia has been examined by applying fluorescence in situ hybridization (FISH) to detect chromosomal abnormalities in bone marrow cells previously identified by morphology and/or immunology. The karyotype of the malignant clone was either high hyperdiploid or Philadelphia translocation (Ph) positive with a breakpoint in the minor breakpoint cluster region of the BCRgene (m-BCR) or in the major breakpoint cluster region of the BCR gene (M-BCR). The high hyperdiploid clone, in each case, was found in cells of the B-lymphoid (CD19+) lineage but not in T cells (CD3+) or in cells of the myeloid (CD13+) or erythroid (glycophorin A+) lineages, indicative of a lymphoid committed progenitor cell. Heterogeneity of lineage involvement was found in Ph+ ALL: the m-BCR Ph+ clone was found in lymphoid/blast cells but not in neutrophils or eosinophils. In contrast both M-BCR Ph+ clones were detected in myeloid as well as lymphoid lineages, indicative of a stem cell origin.

Adolescent↗

Patterns of asthma mortality in Philadelphia from 1969 to 1991.

BACKGROUND: The rate of mortality from asthma has increased substantially in the United States since 1978. We analyzed the patterns of the rates of death from asthma in Philadelphia between 1969 and 1991. METHODS: The rates of death from asthma were analyzed and compared with trends in the concentrations of major air pollutants: ozone, carbon monoxide, nitrogen dioxide, particulate matter (particles < 10 microns in diameter), and sulfur dioxide. Univariate and multivariate analyses were used to study the rates of death from asthma from 1985 to 1991 and their association with race, poverty, sex, and other factors. RESULTS: The rate of death from asthma decreased from 1.68 per 100,000 people in 1969 to 0.68 per 100,000 in 1977, but then increased to 0.92 per 100,000 in 1978 and 2.41 per 100,000 in 1991. Between 1965 and 1990, the concentrations of major air pollutants declined substantially. From 1985 to 1991, 258 people were identified for whom asthma was the primary cause of death. According to multivariate analysis, the rates of death from asthma from 1985 to 1991 were significantly higher in census tracts with higher percentages of blacks (P = 0.032), Hispanics (P = 0.013), female residents (P < 0.001), and people with incomes in the poverty range (P < 0.001). CONCLUSIONS: The rates of death from asthma have increased in Philadelphia, whereas concentrations of major air pollutants have declined. The rates are highest in census tracts with the highest percentages of poor people and minority residents, particularly blacks. Public health efforts should target urban areas where the risk of death from asthma is highest.

Adolescent↗

Mass screening for colorectal cancer--the Philadelphia experience.

On May 18, 1985, the Philadelphia Division of the American Cancer Society and WCAU-TV entered into a jointly-sponsored colorectal health day to do mass screening throughout the greater Philadelphia area. This was preceded by a week-long series of television awareness programs, and an organization based on having individual hospital coordinators for those hospitals participating. A total of 46 hospitals in Pennsylvania alone participated in this project, and over 16,000 people were screened in a single day. 410 patients had positive stools for occult blood on site, and 359 were positive on take-home 3-packs. Rectal pathology was diagnosed initially in 502 patients. 13 colorectal cancers and 38 polyps have been diagnosed directly as a result of this screen. Total cost to the Cancer Society was $13,300, meaning each diagnosed cancer cost $1,023 and each cancer or polyp cost $266 in actual funds expended for the screen. This overwhelming response by the public to such a mass screening effort indicates the potential for such programs for colorectal cancer, and the techniques employed in planning, implementing, and following up on data retrieval are discussed. This mass screening effort should serve as a model for future projects, and emphasize the importance not only of interrelationships with the media, but also liaison efforts with a network of area hospitals and individual hospital coordinators.

Colorectal Neoplasms↗

HIV/AIDS and African immigrant women in Philadelphia: structural and cultural barriers to care.

Although African immigration to American cities is increasing, there is little published demographic or epidemiological data on this population. As growing numbers of HIV-positive Africans seek care at public health centres in the city of Philadelphia, medical personnel are confronted with the challenges of serving this population. This qualitative study explores the perspectives of HIV service providers who are treating this new patient group, and it examines the cultural and structural barriers African women face in the area of HIV prevention, testing, and treatment in the city of Philadelphia. These barriers include legal status, linguistic problems, fear of the American health system, misunderstandings about modes of transmission of HIV, and lack of awareness about antiretroviral treatment. Culturally appropriate education about HIV prevention and treatment needs to be developed for African immigrants, and medical personnel need to understand the experiences, fears, and concerns of this population.

Adult↗

Immune response to Philadelphia chromosome-positive acute lymphoblastic leukemia induced by expression of CD80, interleukin 2, and granulocyte-macrophage colony-stimulating factor.

We examined the potential of generating an immune response against Philadelphia chromosome-positive acute lymphoblastic leukemia. The immunostimulatory molecules chosen for this study were the cytokines IL-2 and GM-CSF and the costimulatory ligand CD80 (B7.1). We used a murine model based on a BALB/c pre-B cell line, BM185wt, in which leukemia is induced by the p185 BCR-ABL oncogenic product, which reproduces Philadelphia chromosome-positive ALL. BM185wt cells were transduced with retroviral vectors and the transduced clones expressing mIL-2, mGM-CSF, or mCD80 were used for challenge. Expression of the immunomodulators by BM185 cells was correlated with delay in leukemia development in immunocompetent mice, but not in immunodeficient mice, indicating an immune response against the modified leukemia cells. Expression of CD80 caused leukemia rejection in 50% of the cohort, which was associated with the CD4+ and CD8+ T cell-dependent development of anti-leukemia cytotoxic T lymphocytes. Furthermore, mice surviving the BM185/CD80 challenge or preimmunized with irradiated BM185/CD80 cells developed an immune response against subsequent challenge with the parental leukemia. These studies provide evidence that immunotherapeutic approaches can be developed for the treatment of ALL.

Adjuvants, Immunologic↗

Drinking water turbidity and pediatric hospital use for gastrointestinal illness in Philadelphia.

Recent outbreaks have demonstrated that serious infectious gastrointestinal illness related to drinking water supplies remains a problem in the United States. The magnitude is unknown, but children, the elderly, and immunocompromised individuals are considered at highest risk. We examined the association between daily measures of drinking water turbidity and both emergency visits and admissions to Children's Hospital of Philadelphia for gastrointestinal illness, controlling for time trends, seasonal patterns, and temperature. We found that an interquartile range increase in turbidity levels in Philadelphia drinking water was associated with a 9.9% increase [95% confidence limits (CL) = 2.9%, 17.3%] in gastrointestinal emergency visits for children age 3 years and older 4 days later. For children age 2 years and younger, an association was found with a lag of 10 days (5.9% increase; 95% CL = 0.2, 12.0). For admissions, a similar pattern was seen. For children over 2 years old, an increase of 31.1% (95% CL = 10.8%, 55%) was seen with a lag of 5-6 days. For younger children, an increase of 13.1% (95% CL = 3.0, 24.3) was seen 13 days later. This association occurred in a filtered water supply in compliance with current federal standards.

Adolescent↗

Founding friends: families and institution building in early 19th century Philadelphia.

BACKGROUND: Nurses have always had an interest in the relationships among families, clinicians, and healthcare institutions. This case study of the Friends Asylum for the Insane in early 19th century Philadelphia examines the historical roots of these relationships. METHODS: Data sources are archival documents about the male founders of the Friends Asylum, its constituent families, and the committees responsible for the creation and the maintenance of the institution. RESULTS: Families seeking a temporary respite from day-to-day turmoil created The Friends Asylum in Philadelphia. The Friends Asylum allowed them to continue to explore the processes that ultimately gained them an enduring identity as members of the newly emerging middle-class. DISCUSSION: These data suggest that the Asylum served individuals limited in their capacity for the self-control needed for a new kind of middle-class identity and those families vulnerable to the demands made by the roots of this new identity. For individuals, it provided a place that replicated the intimate domestic ideal. And for families, it allowed the sharing of care-taking responsibilities with kin who wanted the insane out of the home, but not out of the family. CONCLUSION: In the early 19th century, families presented clinicians not just with dilemmas, but with solutions that carried substantial cultural weight. This study suggests that theoretical innovations in healthcare might draw from the transformations in normative rules about domestic, work, and social roles. It suggests that nurses remain aware of the possibility that it may not be nurses who empower patients; it may be patients who empower nurses.

Christianity↗

School-based screening for Chlamydia trachomatis and Neisseria gonorrhoeae among Philadelphia public high school students.

CONTEXT: The prevalence of sexually transmitted diseases among adolescents is high. Innovative screening and treatment programs need evaluation. OBJECTIVES: The objectives of this study were to identify, treat, and describe the prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infections among Philadelphia public high school students. DESIGN: We analyzed cross-sectional data from the first year of an annual program offering education, screening, and treatment for CT and GC. For the school year analyzed, screening took place between January 2003 and June 2003. RESULTS: In the first year, 19,394 students aged 12-20 years were voluntarily tested; 1,052 students were identified with GC, CT, or both; 1,051 received treatment. Prevalence of CT among females (95% confidence interval [CI] = 8.1) was 3.3 times higher than among males (95% CI = 2.5%). Attending disciplinary schools and residing in high reported morbidity areas were also related to higher prevalence of CT and GC. CONCLUSIONS: A high prevalence of CT infections was identified among Philadelphia public high school students. This program demonstrated the effectiveness of a school-based screening program to identify and treat these infections.

Administration, Oral↗

Philadelphia-chromosome positive thrombocythemia in a child.

Philadelphia-chromosome positive thrombocythemia without features of chronic myeloid leukemia in peripheral blood has been described in adults. It is rare in children. We present a case of Philadelphia positive thrombocythemia in a child who was managed with a combination of imatinib and hydroxyurea. Although a reduction in the BCR-ABL transcript was documented, the thrombocytosis was refractory to imatinib alone and required the addition of hydroxyurea.

Benzamides↗

Variant Philadelphia translocations in chronic myeloid leukemia.

Up to the beginning of 1986, some 327 variant Philadelphia translocations were reported in chronic myeloid leukemia. The present study represents an attempt to determine which factors (sex, age, geographic localization, etc.) influence the occurrence and chromosome involvement of these variant Philadelphia (Ph1) translocations. Clinical data indicated that band 9q34 was always rearranged in the variant Ph1 translocations and no difference existed between the hematologic and prognostic features among patients with the standard and the variant translocations. An uneven geographic distribution of the variant Ph1 translocations was found. Whether this was due to populations with different ethnic backgrounds or to environmental factors could not be determined. Twenty-eight bands were shown to be rearranged more frequently than expected (P less than 0.05); 27 of them are known to contain a fragile site and/or an oncogene and/or are rearranged more frequently than expected in other malignancies. The chromosomes involved in these variant Ph1 translocations were found to show a very particular geographic distribution, which cannot be explained at present.

Adult↗

Philadelphia chromosome as the sole abnormality and p210 bcr-abl chimeric protein expression in an Epstein-Barr virus-transformed B cell line from a patient with chronic myeloid leukemia.

A 'B' cell line, originating from a patient with chronic myeloid leukemia and containing the Philadelphia chromosome, was established after Epstein-Barr virus transformation. The Philadelphia chromosome was the sole chromosomal abnormality in this line, designated as PhB1 cell line. In DNA hybridization studies we detected rearrangements in the bcr gene and in the immunoglobulin heavy chain joining region. The phenotypes of the cells were typical of mature B cells expressing antigens CD19, CD20, CD22, CD23, CD39, HLADR, IgM, and kappa. The expression of the 210 bcr-abl chimeric protein was detected by means of an immunoprecipitate assay.

B-Lymphocytes↗

Assessment of screening, treatment, and prevention of perinatal infections in the Philadelphia birth cohort.

Certain population groups are at risk for inadequate prenatal care and transmission of perinatal infections. Philadelphia's birth cohort comprises largely at-risk groups and its infant mortality rate is among the nation's highest. This study identifies factors associated with infectious disease screening, treatment, and prevention in Philadelphia. Delivery charts for a probability sample of 550 patients were reviewed. Demographic factors associated with prenatal and delivery care were identified through Pearson chi-square, analysis of variance, and stepwise logistic regression analysis. Nonstandard and incomplete documentation complicated abstraction. Some prenatal care was noted in 95% of the records and screening varied by disease. Factors independently associated with care include maternal race, insurance status, and maternal age. Screening for infections with well-established recommendations (hepatitis B virus, rubella, syphilis) occurred more often than for group B streptococcus, HIV, hepatitis C virus, and varicella. Adoption of standard reporting forms and processes could improve practice and aid in quality improvement efforts and patient communication.

Adolescent↗