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PubMed1985

Pulse rate, blood pressure and body composition in black adolescents: the Philadelphia Blood Pressure Project.

Patterns of pulse rate, blood pressure (BP), and body size and composition are investigated in a black urban sample of over 600 adolescents (aged 12-17) in Philadelphia as part of the Philadelphia Blood Pressure Project. Supine and seated pulse rates decline after the age of 13 in both males and females, and females have significantly higher pulse rates than males, ranging from 1.6 to 4.7 beats/30 sec higher depending upon chronological age and position. Seated pulse rates are consistently higher than supine in both sexes ranging from 1.3 to 2.9 beats/30 sec depending upon chronological age. Pulse rate and both systolic blood pressure (SBP) and diastolic phase IV blood pressure (DBP) show a positive association throughout adolescence for females (r = 0.16 SBP, r = 0.24 DBP) but not for males (r = -0.06 SBP, r = 0.06 DBP). Females in the highest diastolic IV blood pressure stratum (greater than 85%) maintain higher pulse rates throughout adolescence, while males with the highest DBP have higher pulse rates in early adolescence (ages 12-14) but lower pulse rates in later adolescence (ages 16 and 17). Females with the highest DBP also show consistently higher measures of relative fatness (triceps skinfolds) throughout adolescence. Males with the highest DBP have greater triceps skinfolds in early adolescence and lower triceps in later adolescence, a pattern similar to that shown for pulse rate. For DBP, triceps is significantly and positively associated with pulse rate in the upper DBP percentile group (p less than 0.05). Thus, females with the highest blood pressure during adolescence are characterized by higher pulse rate and greater fatness. Males show this same pattern in early adolescence; whereas, in contrast, the older adolescent males in our sample with the highest DBP are characterized by lower pulse rates, relatively decreased fatness, and increased muscularity. Our findings suggest that, at least in some older black male adolescents, a higher DBP may reflect a decrease in cardiac output as indicated by a lower pulse rate, or an increase in peripheral vascular resistance, possibly associated with relatively decreased fatness and increased muscle mass for size.

Adolescent↗
PubMed2026

From standardization to precision medicine: Evolution of European Leukemianet recommendations in Philadelphia-negative myeloproliferative neoplasms.

The European LeukemiaNet (ELN) recommendations have been instrumental in shaping the diagnosis, risk stratification, and management of Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Over the past two decades, these recommendations have evolved from consensus-based frameworks focused on response standardization to increasingly sophisticated, evidence-based and biologically informed approaches. Early efforts primarily aimed to harmonize response criteria across clinical studies, establishing a foundation for consistent therapeutic evaluation. Subsequent updates introduced risk-adapted treatment strategies centered on thrombotic risk, reflecting the major determinants of morbidity and mortality in these disorders. However, the limitations of surrogate endpoints prompted a shift toward clinically meaningful outcomes, including symptom burden, vascular events, and disease progression. More recent advances have been driven by the integration of molecular genetics and the adoption of structured evidence-based methodologies, enabling refined diagnostic classification and more accurate prognostic assessment. Contemporary ELN frameworks increasingly incorporate dynamic clinical parameters, genomic profiling, and emerging biomarkers, supporting a transition toward individualized, risk-adapted therapeutic strategies. Beyond their role in standardizing MPN management, ELN recommendations have also influenced clinical trial design, endpoint selection, risk stratification, and therapeutic decision-making. Evidence from prospective studies and real-world cohorts supports the clinical applicability of these frameworks, although their implementation remains heterogeneous across healthcare settings. This review provides a comprehensive and critical overview of the evolution and implementation of ELN recommendations, highlighting their impact on clinical research and routine practice, current limitations, and future directions toward precision medicine in Philadelphia-negative MPNs.

Essential thrombocythemia↗
PubMed1997

Two different Philadelphia chromosomes in a cell line from an AML-M0 patient.

A second Philadelphia (Ph) chromosome is one of the most common nonrandom secondary chromosome changes in leukemias with 9;22 translocations. It has been suggested, and observed in two studies of masked t(9;22), that the second Ph chromosome is an exact duplication of the entire derivative chromosome 22. In a cytogenetic study of bone marrow cells from an acute myelogenous leukemia patient, a cell line carrying two different Ph chromosomes evidenced by a chromosome 22 centromeric heteromorphism was found. From this observation arose the question whether the second der(22) was a true Ph chromosome or whether it was a deleted chromosome derived from the normal chromosome 22 that did not contain the bcr-abl rearrangement. A fluorescent in situ hybridization (FISH) study with the t(9;22) probe revealed two bcr-abl positive signals on 60 of 100 interphase nuclei. The second Ph could have resulted from a mitotic crossing over; or, analogously to late-appearing Philadelphia chromosomes, it may be derived from a new chromatid translocation between the chromosomes 9 and 22 not involved in the initial t(9;22).

Adolescent↗
PubMed1982

A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia.

The transforming genes of oncogenic retroviruses are homologous to a group of evolutionary conserved cellular onc genes. The human cellular homologue (c-abl) of the transforming sequence of Abelson murine leukaemia virus (A-MuL V) was recently shown to be located on chromosome 9. The long arm of this chromosome is involved in a specific translocation with chromosome 22, the Philadelphia translocation (Ph1), t(9; 22) (q34, q11), which occurs in patients with chronic myelocytic leukaemia (CML)3-5. Here we investigate whether the c-abl gene is included in this translocation. Using c-abl and v-abl hybridization probes on blots of somatic cell hybrids, positive hybridization is found when the 22q- (the Philadelphia chromosome), and not the 9q+ derivative of the translocation, is present in the cell hybrids. From this we conclude that in CML, c-abl sequences are translocated from chromosome 9 to chromosome 22q-. This finding is a direct demonstration of a reciprocal exchange between the two chromosomes and suggests a role for the c-abl gene in the generation of CML.

Chromosomes, Human, 21-22 and Y↗
PubMed1999

Quantitative competitive reverse transcriptase-polymerase chain reaction for BCR-ABL on Philadelphia-negative leukaphereses allows the selection of low-contaminated peripheral blood progenitor cells for autografting in chronic myelogenous leukemia.

The Philadelphia (Ph) translocation t(9;22) results in the creation of the BCR-ABL gene, which is now regarded as central to the mechanism that underlies the chronic phase of chronic myelogenous leukemia (CML). From a clinical point of view, BCR-ABL mRNA detection has become the basis for the study of minimal residual disease in CML, particularly when a complete cytogenetic remission is achieved after interferon-alpha (IFN-alpha) therapy or allogeneic stem cell transplantation. We have recently demonstrated that it is possible to mobilize normal peripheral blood progenitor cells (PBPC) in higher rates if this procedure is performed during the early chronic phase. In an attempt to monitor the leukemic cell content of PBPC collections, we used quantitative-competitive RT-PCR (QC-RT-PCR). Thirty consecutive Philadelphia (Ph) chromosome positive patients were enrolled in this study. After chemotherapy and G-CSF, 14 patients achieved 100% Ph-negative metaphases, nine patients had < or =34% and seven patients >34% leukemic metaphases. A total of 116 collection samples were studied. For each sample, BCR-ABL transcript numbers and BCR-ABL/ABL ratio were evaluated. A highly significant correlation between Ph-positive metaphases and BCR-ABL transcript numbers (r = 0.84, P < 0.0001) or BCR-ABL/ABL ratio (r = 0.86, P < 0.0001) was found. For patients that underwent the procedure in early chronic phase, Ph-negative collections showed different levels of BCR-ABL expression. BCR-ABL transcript numbers varied from a median of 100/microg RNA in the first and second leukaphereses, to 500/microg RNA in the third and fourth leukaphereses, and 1500/microg RNA in the fifth leukapheresis (P = 0.002). BCR-ABL/ABL ratio values showed similar kinetics. We have also demonstrated that there is a correlation between low values in BCR-ABL/ABL ratio (< or =0.01) in the reinfused PBPC and the achievement of cytogenetic remission after autografting (chi2 test, P = 0.01). In conclusion, this study demonstrates that QC-RT-PCR for BCR-ABL is a reliable and helpful method for monitoring residual leukemic load in mobilized PBPC, particularly in Ph-negative collections. Moreover, QC-RT-PCR allows selection of the best available collections for reinfusion into patients after myeloablative therapy.

Adult↗
PubMed2003

Perspectives on the treatment of chronic phase and advanced phase CML and Philadelphia chromosome positive ALL(1).

Chronic myeloid leukaemia (CML) is a malignant disease of the bone marrow characterised by the presence of the Philadelphia (Ph) chromosome. About 20% of acute lymphoblastic leukaemia (ALL) patients also show this genetic abnormality. A new drug, imatinib (Glivec, Novartis Pharma AG, Basel, Switzerland, and formerly STI571) is having a profound effect on the treatment and management of all stages of CML and Philadelphia chromosome positive (Ph+) ALL. New treatment algorithms are being developed. Should imatinib replace or be combined with existing therapies? To address this question, we review the pros and cons of therapy with interferon-alpha (IFN-alpha), allogeneic transplantation, autologous transplantation, imatinib, and in the case of Ph+ ALL, chemotherapy and experimental approaches. Conservative and aggressive treatments will be discussed and new molecular methods of monitoring cytogenetic response and their significance will also be reviewed.

Antineoplastic Agents↗
PubMed1997

Which compartments are involved in Philadelphia-chromosome positive chronic myeloid leukaemia? An answer at the single cell level by combining May-Grünwald-Giemsa staining and fluorescence in situ hybridization techniques.

Chronic myeloid leukaemia (CML) is believed to represent a stem cell disorder involving all three cell lineages. The typical chromosomal aberration, the Philadelphia chromosome, is the translocation (9;22)(q34;q11). Several studies with cytogenetics, fluorescence in situ hybridization (FISH), or polymerase chain reaction have investigated the presence of the t(9;22) in different cell compartments. However, questions still remain. In six cases of CML we combined the standard May-Grünwald-Giemsa staining with FISH at the single-cell level and were able to demonstrate that not only all maturation stages of granulopoiesis, erythropoiesis, and megakaryocytes, but also plasma cells, eosinophils, basophils and monocytes carried the Philadelphia chromosome in 53-98% of samples. Using immunological identification of single cells we were able to demonstrate that the t(9;22) is detectable in 34% of CD3-positive T lymphocytes, in 32% of CD19-positive B lymphocytes, and in 82% of CD34-positive precursor cells. The results give new insight into the biology of CML and may have implications for future therapeutic strategies.

Adult↗
PubMed1999

Additional translocation (8;21)(q22;q22) in a patient with Philadelphia-positive chronic myelogenous leukaemia in the blastic phase.

We report a case of Philadelphia-positive chronic myelogenous leukaemia in blastic phase with the additional translocation (8;21)(q22;q22), which is frequent in acute myeloid leukaemia but not in chronic myelogenous leukaemia. The t(8;21) was not detected in the chronic phase, and was the only additional chromosomal anomaly in the blastic clone. Reverse transcription-polymerase chain reaction revealed the AML1/ETO fusion transcript in the cells of blastic phase but not in those of chronic phase. Regarding t(9;22), the breakpoint on chromosome 22 occurred in the mu-BCR region of the BCR gene, resulting in hybrid BCR/ABL mRNA with an e19a2 junction. Our findings provided molecular evidence that t(8;21) can occur as an additional genetic change in Philadelphia-positive chronic myelogenous leukaemia.

Adult↗
PubMed1983

Long-term marrow culture reveals chromosomally normal hematopoietic progenitor cells in patients with Philadelphia chromosome-positive chronic myelogenous leukemia.

We found that when marrow cells from four patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia were maintained in culture for two to four weeks, a previously undetectable population of chromosomally normal hematopoietic cells (including erythroid, granulopoietic, and pluripotent progenitors) became readily demonstrable in three cases. Time-course studies showed that in such cultures the dominant Philadelphia chromosome-positive population rapidly disappeared, in contrast to coexisting chromosomally normal progenitors, which remained detectable for periods of two to three months. Long-term marrow cultures thus offer a new approach to the assessment of a suppressed but functionally intact population of chromosomally normal hematopoietic stem cells in patients with chronic myelogenous leukemia.

Adult↗
PubMedDate not supplied

Philadelphia chromosome-positive acute lymphoblastic leukemia in the elderly: prognostic factors and treatment outcome.

Data on all patients diagnosed with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) aged 55 or older, seen in our institution over a 17-year period, were studied to determine the incidence and range of clinical and biological subtypes, and the outcome of different therapeutic approaches. Twenty-five Ph+ ALL cases (median age: 64 years) were diagnosed between 1986 and 2003 (28% of all B-lineage elderly ALL seen during this period). Karyotypic analysis was performed successfully in 22 cases, while 3 were only diagnosed by molecular biology analysis. All patients had B-cell lineage ALL. Co-expression of myeloid markers was observed in 20% of tested cases. One patient died before chemotherapy could be given. All other patients received "curative" treatment according to different protocols used during the period of study. Overall the complete remission (CR) rate was 76% (95% confidence interval, CI: 55-91%). Fifteen patients achieved CR after one course of chemotherapy and 4 patients after salvage therapy. Median disease-free survival (DFS) of the entire cohort was 5.6 months (95% CI: 4.5-8.4 months) and median overall survival was 10.1 months (95% CI: 7.9-13 months). In multivariate analysis, age>or=70 years was of poor prognostic value for achieving CR (p=0.05) and hyperleukocytosis at diagnosis was of poor prognostic value for overall survival (p=0.001). Overall survival duration was not significantly influenced by achieving CR. Ph+ ALL patients did not show a significant difference in terms of outcome as compared with Philadelphia-negative ALL patients. The very poor overall outcome in elderly patients with Ph+ ALL may be significantly improved by the introduction of imatinib mesylate into current treatment regimens.

Aged↗
PubMed1999

Malignancy: Molecular Demonstration of BCR/ABL Fusion in a Patient with Chronic Myelogenous Leukemia with Basophilia Carrying a Variant t(16;22) (q24;q11) Philadelphia Chromosome.

We report a patient with chronic myelogenous leukemia in chronic phase and basophilia which was found to carry a simple variant t(16;22) (q24;q11) Philadelphia (Ph) chromosome in unstimulated bone marrow mononuclear cells. Molecular analysis of peripheral blood and bone marrow mononuclear cells demonstrated the presence of a bcr-abl chimeric mRNA transcript of the b(3) -a(2) type. These findings confirm that band 9q34 participates in the formation of all Ph chromosomes, either standard or variant, even when this is not detectable by conventional cytogenetics. The available literature concerning variant Philadelphia translocations is also reviewed.

Journal Article↗
PubMed1993

Case report: alpha G-Philadelphia, beta O-Arab, and beta C globins present in a single patient.

The case of a 7-month-old Nigerian child who presented with anemia and microcytosis is described. Hemoglobin electrophoresis studies revealed a band with pronounced cathodic mobility. This represented a heterohybrid hemoglobin tetramer composed of an alpha-globin mutant, G-Philadelphia (alpha GPhil), and two variant beta-globin chains, beta C and beta O-Arab. The absolute amounts of alpha GPhil found in the propositus were less than expected for an alpha 2-globin gene product. It has not been established whether alpha G-Philadelphia interacting with beta O-Arab and beta C globin chains is the cause of the microcytosis.

Anemia↗
PubMed1980

The Founding Fathers and centennial history of the Philadelphia Academy of Surgery.

Samuel D. Gross, the acknowledged "Emperor of American Surgery of the 19th Century," founded the Philadelphia Academy of Surgery, the oldest surgical society in the United States, in 1879. He wrote the constitution and by-laws, became its first president, gave the first Annual Oration, bequeathed his library of 4,000 books, and endowed the "Gross Prize" which has been awarded 17 times between 1895 and 1977. Biographic highlights of Gross and the nine other Founding Fathers are sketched. The College of Physicians of Philadelphia, also the oldest institution of its kind, has been the only home of the Academy in a symbiotic relationship. Honorary Fellowships have been bestowed at various times since 1881 on 73 outstanding surgeons from the U.S. and abroad, the last nine at a gala Centennial Dinner Dance in November, 1979. Memorabilia relating to the Charter Members are housed in the Mutter Museum of The College of Physicians and were put on special exhibit for the Centennial Oration in December, 1979. Many of the pioneer and enduring scientific contributions of the members are recorded in the handwritten minutes of the first 25 years, the 32 volumes of Transactions and Annals of Surgery which has served as its official publication.

Academies and Institutes↗
PubMed1986

Low incidence of painless thyroiditis in the Philadelphia area.

Publications from the midwestern region of the United States have demonstrated an incidence of 14-23% of painless thyroiditis in hyperthyroid individuals. This possibly could represent a local phenomenon, and perhaps is not typical for other areas of the country. The 24 hour radioactive iodine uptakes in 152 consecutive hyperthyroid individuals in the Philadelphia area were evaluated. No patient in the series, with clinical and biochemical evidence of hyperthyroidism, had painless thyroiditis. It is concluded that the incidence of painless thyroiditis is markedly lower in the Philadelphia area than in the Midwest regions of the United States.

Humans↗
PubMed1996

Nonoperative management of Types II and III odontoid fractures: the Philadelphia collar versus the halo vest.

The nonoperative management of patients with Types II and III fractures of the odontoid process consists of a prolonged course of cervical immobilization. The need for rigid fixation, demonstrated by the routine use of the halo vest in many institutions, has never been rigorously substantiated. We retrospectively analyzed our results with the nonsurgical management of odontoid fractures to ascertain whether cranial fixation affected overall outcome. Fifty-four patients managed at the University of Virginia Health Sciences Center, Charlottesville, VA, between 1976 and 1994 were studied. All 18 patients with Type III fractures (5 treated in the collar, 18 in the halo vest) demonstrated fracture healing and late stability. Among 36 individuals with Type II fractures, 20 were treated in the halo vest and 16 were managed in the Philadelphia collar or similar orthoses. The overall rate of late surgical intervention, the stability to flexion and extension, and the rate of bony fracture healing were not statistically different between the methods of immobilization. The rate of bony union was not significantly higher in the halo vest group (74 versus 53%), even though patients managed in the Philadelphia collar were significantly older than those in the halo vest (mean, 68 versus 44 yr). In general, nonsurgical management of Type III odontoid fractures was recommended, accompanied by use of a cervical orthosis. The determination of operative versus nonoperative treatment for Type II fractures was made on the basis of fracture anatomy, patient age, other associated injuries, and patient preference. The lack of a significant difference in the need for late surgical procedures or late instability, improved patient comfort with the cervical orthosis, and elimination of the risk of halo-related complications favored the use of the rigid cervical orthosis in the majority of these cases.

Aged↗
PubMed2001

Indications of Philadelphia collar in the treatment of upper cervical injuries.

The principles of the management of upper cervical injuries remain controversial. The specific anatomical conditions render upper cervical injuries more problematic than lower cervical injuries. Here we present and discuss our experiences with upper cervical injury, comparing them with other treatment modalities. The 24 patients admitted to our department with upper cervical injury were treated surgically or conservatively according to their neurological and radiological status. Five patients were treated surgically due to neurological abnormality associated with compression to neural structures observed in computerized tomography/magnetic resonance imaging (CT/MRI). Patients with no neural compression were managed conservatively, with the Philadelphia collar. All patients showed stable fracture healing and experienced no additional clinical disability on follow-up after a minimum of 3 months, except one who died due to cardiac and respiratory failure. Regardless of the type of injury, indication for surgery in many cases of upper cervical injury is neurological abnormality associated with radiologically observed neural compression. It is our belief that, in the absence of both neurological abnormality and compression to neural structures observed in CT/MRI, treatment with the Philadelphia collar alone is safe, cost-effective and easily applicable for many cases of upper cervical injury.

Adult↗
PubMed1977

The significance of the Philadelphia chromosome in acute lymphoblastic leukaemia: a report of two cases.

Two cases of Philadelphia chromosome (Ph1) positive acute lymphoblastic leukaemia are reported, both of which lost the Philadelphia chromosome during remission. In one patient remission of the acute lymphoblastic leukaemia continued but classical Ph1 positive chronic granulocytic leukaemia developed. In the other patient relapse of the acute lymphoblastic leukaemia occurred associated with the return of the Ph1 chromosome. The evidence suggests that the chromosome aberration occurred in a pluripotential stem cell, which in one case proliferated along both a lymphoid cell line and a myeloid cell line. Both cases responded well to conventional therapy for acute lymphoblastic leukaemia.

Adult↗
PubMed1981

Heterogeneous blast cell crises in Philadelphia negative chronic granulocytic leukaemia.

A case of Philadelphia negative chronic granulocytic leukaemia (Ph1-CGL) is described showing features only previously demonstrated in Ph1+ disease. These features include: (1) lymphoid blast crisis, determined by morphology and immunological marker analysis; (2) dual blast cell populations that can be distinguished both morphologically and by immunological markers; (3) clonal evolution, as shown by the emergence of chromosome markers and in one of the cell lines a change in membrane phenotype. These changes were apparently associated with the emergence of a relatively drug resistant subclone of leukaemic cells. This study demonstrates that the lymphoid blast crisis of CGL, and its sequelae, can occur in Ph1- cases. It is similar in respect to morphology, enzyme, and membrane markers and responsiveness to vincristine and prednisolone therapy to the lymphoid blast crisis seen in Ph1+ CGL. This suggests that the Philadelphia chromosome is a clonal marker only, and its presence is not directly related to the subsequent clinical course of the disease.

Bone Marrow↗