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K Foucar

Publications and source records attributed to K Foucar.

At least 37 records · Page 2Linked to original sources
PubMed1995

Hantavirus pulmonary syndrome. Pathogenesis of an emerging infectious disease.

A recent outbreak of a severe pulmonary disease in the southwestern United States was etiologically linked to a previously unrecognized hantavirus. The virus has been isolated from its major reservoir, the deer mouse, Peromyscus maniculatus, and recently named Sin Nombre virus. Clinically, the disease has become known as the hantavirus pulmonary syndrome (HPS). Since May 1993, 44 fatal cases of HPS have been identified through clinicopathological review and immunohistochemical (IHC) testing of tissues from 273 patients who died of an unexplained noncardiogenic pulmonary edema. In 158 cases for which suitable specimens were available, serological testing and/or reverse transcription-polymerase chain reaction (RT-PCR) amplification of extracted RNA was also performed. IHC, serological, and PCR results were concordant for virtually all HPS and non-HPS patients when more than one assay was performed. The prodromal illness of HPS is similar to that of many other viral diseases. Consistent hematological features include thrombocytopenia, hemoconcentration, neutrophilic leukocytosis with a left shift, and reactive lymphocytes. Pulmonary histopathological features were similar in most of the fatal HPS cases (40/44) and consisted of an interstitial pneumonitis with a variable mononuclear cell infiltrate, edema, and focal hyaline membranes. In four cases, however, pulmonary features were significantly different and included diffuse alveolar damage and variable degrees of severe air space disorganization. IHC analysis showed widespread presence of hantaviral antigens in endothelial cells of the microvasculature, particularly in the lung. Hantaviral antigens were also observed within follicular dendritic cells, macrophages, and lymphocytes. Hantaviral inclusions were observed in endothelial cells of lungs by thinsection electron microscopy, and their identity was verified by immunogold labeling. Virus-like particles were seen in pulmonary endothelial cells and macrophages. HPS is a newly recognized, often fatal disease, with a spectrum of microscopic morphological changes, which may be an important cause of severe and fatal illness presenting as adult respiratory distress syndrome.

Adolescent↗
PubMed1994

Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective Southwest Oncology Group trial.

The growth fraction of tumors from patients with non-Hodgkin's lymphomas (NHL) has been shown to correlate with survival in retrospective studies. The growth fraction can be evaluated using immunohistochemical techniques employing the Ki-67 monoclonal antibody (MoAb) that marks a nuclear protein present in cycling cells. The purpose of this study was to evaluate the clinical utility of the Ki-67 MoAb for predicting survival. Using a prospective trial design in a multi-institutional cooperative trials group, the proliferative index, clinical outcome, and statistical correlations were independently assessed for previously untreated patients with advanced stages of intermediate- and high-grade histologies of NHL treated on Southwest Oncology Group study (SWOG 8516, Intergroup 0067). The proportion of Ki-67-positive cells was determined on snap-frozen thin tissue sections. A proliferative index of 80% or greater, as determined from prior retrospective studies, identified a group of patients (18%) who had a poor outcome. Overall survival was significantly reduced in these patients with a high Ki-67-associated proliferative index compared with those with a low proliferative index (P = .001). One-year survival estimates were 82% (low proliferative index) versus 18% (high proliferative index). A multivariate regression analysis incorporating commonly used clinical prognostic features confirmed the independent effect of proliferation on survival (relative risk estimate 5.9; 95% confidence interval, 2.2, 16.1). The Ki-67 MoAb identifies a group of patients with rapidly fatal NHL for whom currently available chemotherapy is inadequate.

Adult↗
PubMed1994

Emergence of hantaviral disease in the southwestern United States.

Hantaviruses are parasites of small mammals, predominantly peridomestic and commensal rodents. They have a worldwide distribution. Hantavirus-related illness occurs in rural areas where humans come into contact with rodents. In most cases human infection is manifested by one of a variety of acute illnesses involving hemorrhagic fever and renal disease. In May 1993, a cluster of patients with an acute pulmonary disease with high mortality was noted in the Four Corners region of the southwestern United States. Serologic and genetic studies indicated that the etiologic agent was a novel hantavirus. The uncertainty engendered by the emergence of a new disease with high mortality forced a rapid response by state and federal agencies and by the University of New Mexico Medical Center, Albuquerque, where most patients from this region were referred. Considerable progress has been made in identifying infected cases on clinical and laboratory grounds and in ensuring that appropriate supportive care is made available to patients as soon as they are suspected of having hantaviral infection. Cases of hantavirus pulmonary syndrome--both new and retrospectively diagnosed--are still being recognized throughout the western United States. Many important questions remain unanswered.

Adolescent↗
PubMed1994

Outbreak of Hantavirus pulmonary syndrome in the southwestern United States. Response of pathologists and other laboratorians.

During late spring and early summer of 1993, national and international media called worldwide attention to a cluster of deaths in the southwestern United States. These patients succumbed to a rapidly progressive severe respiratory distress syndrome. After notification of state and national health agencies in mid-May, a major effort was launched to determine the cause of this often fatal respiratory distress syndrome, to advise the public on safety measures, and to determine the method of spread of this "mystery illness." Within weeks of recognition of the early cases, the Centers for Disease Control and Prevention announced the probable agent, a Hantavirus. This report details the response of pathologists, medical technologists, and other laboratory scientists to this new viral epidemic, with emphasis on activities that occurred within New Mexico.

Adolescent↗
PubMed1993

Practical approach to the investigation of neutropenia.

This article discusses the evaluation of a patient for possible neutropenia. An evaluation must include an integration of complex factors such as age- and race-related normal ranges for absolute neutrophil count, an assessment of other hematopoietic elements in blood, an investigation for possible underlying infections, an examination for splenomegaly, and an evaluation for evidence of recurrent infections or family history suggestive of a constitutional neutropenic disorder.

Adult↗
PubMed1992

False-positive flow cytometric platelet glycoprotein IIb/IIIa expression in myeloid leukemias secondary to platelet adherence to blasts.

Because neither morphologic nor routine cytochemical features are pathognomonic, the diagnosis of acute megakaryoblastic leukemia (AML-M7) is difficult, requiring either specialized ultrastructural or immunologic techniques. Because the ultrastructural techniques are cumbersome, immunologic assays for expression of several platelet-specific antigens, such as CD41a (platelet glycoprotein IIb/IIIa), have become the primary method used to detect megakaryoblastic differentiation. In our flow cytometric analysis of the immunophenotypes of over 1,000 cases of AML from patients registered to Southwest Oncology Group (SWOG) Treatment Protocols, we found that 38% of cases demonstrated CD41a reactivity. Because this frequency of CD41a expression by flow cytometry greatly exceeded the number of morphologically defined cases of AML-M7, we postulated that the reaction may be caused by platelets adherent to leukemic blasts. To investigate this hypothesis, we performed a side-by-side comparison of flow cytometric and cytospin immunofluorescence studies on 37 cases of adult de novo AML that demonstrated a wide range of CD41a expression by flow cytometric analyses. We found that the expression of CD41a detected by flow cytometric techniques was secondary to adherent platelets or platelet fragments in 85% of cases. Many of these cases also expressed the lineage-specific carbohydrate, LNF III (CD15), which may mediate platelet adhesion to mature monocytes and neutrophils. Only 15% of the CD41a flow cytometrically positive cases demonstrated true diffuse membrane and cytoplasmic positivity on cytospin slides indicative of megakaryoblastic differentiation. Cytospin immunofluorescence for CD41a should be performed on all cases of suspected AML-M7. If only flow cytometric techniques are used, adherent platelets may result in the erroneous diagnosis of this AML subtype.

Adult↗
PubMed1992

Prenatal diagnosis of transient myeloproliferative disorder via percutaneous umbilical blood sampling. Report of two cases in fetuses affected by Down's syndrome.

Since its initial description in 1982, percutaneous umbilical blood sampling has become useful in diagnosing, monitoring, and even treating a variety of fetal disorders. Recently two percutaneous umbilical blood samples were evaluated in which the white blood cell count was markedly elevated with many circulating blasts. Both samples exhibited the morphologic features of a transient myeloproliferative disorder, characteristically seen in neonates and infants with Down's syndrome. In both cases, antenatal clinical and ultrasound abnormalities also were suggestive of Down's syndrome, which was confirmed by cytogenetic studies. Although the peripheral blood abnormalities persisted at birth, both patients experienced spontaneous remission of the transient myeloproliferative disorder by 5 weeks of age. To our knowledge, these two cases of Down's syndrome represent the first reported examples of the intrauterine diagnosis of transient myeloproliferative disorders.

Adult↗
PubMed1992

A comparative analysis of cytoplasmic mu (C mu) expression in acute lymphoblastic leukemia by molecular and immunologic techniques. Identification of leukemia cases expressing C mu mRNA transcripts in the absence of detectable C mu proteins.

Among acute lymphoblastic leukemias derived from the B-cell lineage, the subset of cases expressing cytoplasmic mu heavy chain proteins (C mu) in the absence of surface immunoglobulin has been designated pre-B-cell acute lymphoblastic leukemia. This group, traditionally identified using immunologic smear techniques, has been associated with a poor prognosis in some series. In a comparative study, 25 cases of B-lineage acute lymphoblastic leukemia were analyzed for C mu expression using molecular and immunologic techniques. RNA derived from cryopreserved blast cells was hybridized in both Northern and slot-blot analyses using a probe (pBZ311) containing four exons of the human immunoglobulin heavy chain mu constant region gene. Expression of C mu proteins was assessed simultaneously by slide immunofluorescence and flow cytometric techniques in all samples. These studies were correlated with immunoglobulin heavy and light chain gene rearrangements, cell-surface immunophenotype, cytogenetics, and other clinicopathologic features. C mu mRNA transcripts were detected in 14 of 25 cases, whereas C mu proteins were detected in only 9 of these cases using flow cytometric techniques. Only four of these nine cases were positive by slide immunofluorescence techniques. These studies imply that molecular and flow cytometric techniques may be a more sensitive means to assess C mu expression. The identification of five cases that expressed C mu mRNA transcripts in the absence of detectable C mu proteins also suggests that molecular techniques may be valuable in identifying a unique subgroup of pre-B-cell acute lymphoblastic leukemia cases that contain C mu mRNA transcripts, but lack C mu proteins.

Adolescent↗
PubMed1991

Survival of children and adolescents with acute lymphoid leukemia. A study of American Indians and Hispanic and non-Hispanic whites treated in New Mexico (1969 to 1986).

During the period 1969 to 1986, 196 American Indian and Hispanic and non-Hispanic white children and adolescents (ages, 0 to 19 years) were treated for acute lymphoid leukemia (ALL) at the University of New Mexico affiliated institutions. There were 28 American Indians (14%), 91 Hispanic whites (46%), and 77 non-Hispanic whites (39%). Median survivals for patients undergoing antileukemic therapy ranged from 8 months for American Indian boys to 140 months for non-Hispanic white girls. American Indian boys had the highest initial median leukocyte count (WBC) at 23.8 X 10(9)/l. Compliance problems occurred most commonly among American Indian children of both genders. Other clinical and pathologic features evaluated in this study were distributed similarly among the ethnic gender groups. Multi-variate analysis revealed that independent prognostic variables for survival included initial WBC, age, and gender. Ethnicity and compliance problems were possible, but confounded, prognostic variables. To the authors' knowledge this represents the most comprehensive study to date of ALL in American Indian patients.

Adolescent↗
PubMed1991

Do random (non-clonal) chromosome abnormalities in bone marrow predict a clone to come? Southwestern Oncology Group of Leukemia Cytogenetics Subcommittee.

The biologic significance of clonal karyotypic abnormalities in human neoplasms is becoming better understood, but the significance of rare chromosomal aberrations is uncertain. Useful, yet arbitrary, cytogenetic definitions of a clone have been established and cases with a frequency of chromosome aberrations less than the accepted convention are explained by random loss, karyotypic instability/evolution, or other technical artifact. Are non-clonal chromosomal abnormalities that may predict future clinically significant clones being ignored? A brief case report is presented raising two such issues in the same myelodysplastic patient. This child had monosomy 7 and, later, trisomy 8, as well as increased numerical/structural aberrations seeming to predict relapse. Preliminary data from the Southwestern Oncology group is also presented. Non-clonal data should be included, when appropriate, in the clinical report.

Adolescent↗
PubMed1990

Chromosome analysis of cryopreserved cells.

We describe a technique for freezing and thawing human leukemic cells for cytogenetic studies. We studied 64 harvests on 26 cryopreserved samples from 20 individuals. Chromosome quality was best in the samples from patients with myeloid disturbances. Successful chromosome studies of approximately 50% of the samples were accomplished. Cryopreservation of leukemic cells is not a substitute for fresh material because the method produces relatively few metaphases and mediocre chromosome spreading and banding. However, when rigid and appropriate research objectives are applied, chromosome analysis of cryopreserved leukemic cells can be a viable alternative to analysis of fresh cells.

Adolescent↗
PubMed1990

The mononuclear phagocyte and immunoregulatory effector (M-PIRE) system: evolving concepts.

The phagocytic activity of macrophages and related cells has been recognized for over a century. Within the last decade a variety of other functions has been attributed to these same cell types. Examples include antigen processing and antigen presentation to B and T cells, and synthesis of a large number of immunoregulatory proteins. This recent explosion of information regarding the functions and cell types of this complex cell system has had little impact on the practice of pathology in that nomenclature, concepts of disease classification, and our diagnostic approach to the majority of "histiocytic" disorders have not been revised. As the mysteries of this complex cell system are unraveled, older names, such as the mononuclear phagocyte system that focus on only one function, have become obsolete. Because recent evidence shows that this cell system also plays a pivotal and multifaceted role in immunity, the designation mononuclear phagocyte and immunoregulatory effector (M-PIRE) system is recommended. Diverse cell types, including bone marrow precursor cells, histiocytes, various dendritic cells, and Langerhans cells, comprise the M-PIRE system, and these are located in tissues throughout the body. Although mature macrophages and dendritic cells are strikingly different in morphology and function, evidence from studies of both normal cells and proliferative disorders suggests a common cell of origin. There also is provocative evidence suggesting that transitions between cell types may occur, analogous to those observed in the lymphoid cell system. In this report, a conceptual overview of the M-PIRE system including origin, normal function, proposed transitional cell forms, and disease states is presented.

Animals↗
PubMed1989

High-grade non-Hodgkin lymphoma relapsing as low-grade follicular lymphoma: so-called downgraded lymphoma.

Evolution of low-grade Non-Hodgkin Lymphoma (NHL) into a more aggressive neoplasm is a common, well-documented event in NHL. The reverse process, in which a less aggressive component becomes evident during the course of treatment for a higher-grade NHL, has only recently been recognized. This lymphoma "downgrading" has been reported at the time of relapse in both radiation- and chemotherapy-treated patients who initially presented with high- or intermediate-grade lymphoma. The etiology of this unusual transformation has not yet been determined. We present the clinical, morphologic, immunologic, and flow-cytometric features of a patient with diffuse immunoblastic lymphoma who achieved a complete response to chemotherapy and then relapsed with follicular small-cleaved-cell lymphoma 3 years later. Morphologic and immunophenotypic findings suggest that both immunoblasts and small cleaved cells were present in the initial biopsy. DNA content analysis of the initial and relapse biopsies suggests that the immunoblastic component was more susceptible than the small cleaved cells to the chemotherapy that the patient received. Successful eradication of the rapidly proliferating immunoblasts with survival of less rapidly proliferating small cleaved cells may account for the unusual histologic transformation seen in this case.

Adult↗
PubMed1989

Plasma cell dyscrasia: a case of POEMS syndrome with a unique dermatologic presentation.

POEMS (polyneuropathy, organomegaly [hepatosplenomegaly or lymphadenopathy], endocrinopathy, M protein, and skin changes) syndrome is an uncommon plasma cell dyscrasia with diverse manifestations, including lymphadenopathy as well as those that comprise the acronym. Dermatologic changes may include hyperpigmentation, thickened skin, hypertrichosis, and papular angiomas. These changes are believed to result from humoral products of the plasma cell clone and frequently resolve with treatment of the neoplasm. We describe a man with typical POEMS syndrome with a unique skin lesion: a large, sharply circumscribed, pigmented plaque on the anterior chest wall centered over a plasmacytoma of the sternum. Results of histologic examination showed a proliferation of capillaries of varying size, enlarged fibroblasts, and increased amounts of collagen and proteoglycan from the dermis to the periosteum. Because the outer cortex of the sternum was eroded, peptide mediators of vascular and fibroblast proliferation may have diffused directly from the plasma cell lesion into the tissues of the chest wall.

Adult↗
PubMed1989

Peripheral blood morphologic changes after high-dose antineoplastic chemotherapy and recombinant human granulocyte colony-stimulating factor administration.

The peripheral blood morphologic findings in 17 patients with cancer who had received high-dose cytotoxic chemotherapy followed by recombinant human-granulocyte colony-stimulating factor (rh-GCSF) were reviewed and compared with a control group of patients who received only high-dose chemotherapy. Both groups showed dysmyelopoiesis (abnormal granulation and nuclear lobulation) in the granulocytic series during the period of bone marrow recovery that followed the cytotoxic chemotherapy. Most of these morphologic abnormalities were more prominent in the rh-GCSF-treated group. Monocytic cells in both groups showed prominent vacuolation and immature nuclei. The percentages and absolute numbers of large granular lymphocytes were increased in the rh-GCSF group compared with the control group. No quantitative or qualitative abnormalities of eosinophilic or basophilic granulocytes were detected in either group. Both groups showed nonspecific red blood cell abnormalities, and large platelets were present in half of the control group smears. This report provides the first detailed peripheral blood morphologic description in patients treated with rh-GCSF and high-dose chemotherapy.

Adult↗