Biomedical subjects
Publications and source records attributed to M H Donaldson.
A 72-year-old woman previously operated for a sphenoid-ridge meningioma, now presented with double vision. Histology showed a secretory meningioma with an epithelial-appearing, malignant component. Malignant transformation in a secretory meningioma is not known. This is the first report of such an occurrence.
The antigenic specificity of the majority of T lymphocytes in the peripheral blood is determined by the combination of alpha and beta variable region chains present in the T cell receptor complex. Currently, the V beta chains are grouped into 25 families. Historically, determination of V beta usage has relied on detection of gene rearrangement on the nucleic acid level; however, with the increased availability of monoclonal antibodies to the product of these genomic rearrangements, immunophenotypic methods are rapidly becoming a reliable alternative method for studying the usage of V beta regions by T cells and T cell subsets. In the present study, multiparametric flow cytometry was used to determine the use of 10 V beta chains on CD4+ and CD8+ T cells in the peripheral blood of 28 normal donors. By obtaining absolute lymphocyte counts at the time blood was drawn, the absolute number of both CD4+ and CD8+ cells using particular V beta regions could be determined. Additionally, the intradonor consistency of V beta usage was examined by obtaining blood from 5 of the volunteers at an interval of approximately 1 year. The results of this study suggest a fairly homogeneous pattern of use for these V beta regions. The most striking longitudinal differences were observed in one individual who underwent a tonsillectomy midway between the T cell receptor V beta determinations.
A 13-year-old African-American female with erythrocytosis and three different beta globins on electrophoresis beta A, beta S, and beta Osler, raised the possibility that one chromosome 11 might contain a duplicated beta globin gene, since there are normally only 2 beta globin genes. DNA sequence analysis showed GTG at codon 6 in exon 1, corresponding to Hb S and AAT at codon 145 in exon 3, indicating a substitution of Asn for Tyr. Thus, Hb Osler undergoes spontaneous post-translational deamidation, beta 145 Asn-->beta 145 Asp. Unmodified Hb Osler (Asn) co-migrates with Hb A on electrophoresis and co-elutes with Hb A on HPLC; therefore it has not been identified previously. All previous studies have incorrectly identified the mutation as being beta 145 (HC 2) Tyr-->Asp.
PURPOSE: The presenting signs, treatment, and outcome of an epidural hematoma of the cauda equina in a child with severe hemophilia are reported for the first time. PATIENTS AND METHODS: A 20-month-old boy with severe hemophilia A (factor VIII <0.01 U/ml) presented with a 12-day history of refusal to stand and constipation of 5-7 days duration. He had normal deep tendon reflexes with normal sensation and withdrawal to pinprick of his lower extremities bilaterally. He stood on his right leg, but had inversion of his left foot and refused to bear weight on his left leg. MRI revealed an epidural hematoma of the cauda equina and a distended bladder. Factor VIII replacement therapy and lumbosacral laminectomy with evacuation of the hematoma resulted in recovery of a normal gait, but bladder dysfunction persisted for 11 months. Clean intermittent catheterization (CIC) was required until bladder function returned. RESULTS: Complete neurologic recovery occurred 11 months after presentation CONCLUSION: This case demonstrates the following points: (a) an epidural hematoma of the cauda equina in a child with severe hemophilia can present with neurologic findings that are as subtle as those seen in normal children; (b) CIC can be performed safely over an extended period without factor VIII replacement; and (c) complete recovery is possible, despite prolonged bladder dysfunction and a 12-day interval between the onset of symptoms and treatment.
Since only a small percentage of CD4+ lymphocytes is infected at any one time during the course of human immunodeficiency virus (HIV) disease, a question central to the pathogenesis of HIV is whether or not the depletion of CD4+ lymphocytes is a random or selective event. The majority of peripheral blood T lymphocytes use alpha and beta variable chains as components of their T-cell receptor (TCR) complex. Depletion of CD4+ T lymphocytes from the peripheral blood may be dependent on the V beta chain expressed by the CD4+ cell, based on the hypothesis that HIV may encode a superantigen. Peripheral blood from normal controls and HIV+ patients was studied for alterations in the expression of various V beta chains of the TCR. Three-color flow cytometry was used to determine the expression of V beta 2, V beta 3, V beta 8, V beta 13, and V beta 19 on all lymphocytes and on both CD4+ and CD8+ lymphocytes independently. Alteration of the V beta chains in HIV+ disease was analyzed as a function of absolute CD4 count and Centers for Disease Control (CDC) stage of the patient. These data suggest that the loss of T helper (CD4) lymphocytes during the course of HIV disease may be a selective event. These data are consistent with the hypothesis that selective depletion of CD4+, V beta 19+ lymphocytes may be due to the encoding of a superantigen by HIV. Furthermore, using multicolor flow cytometry and stratifying patients by absolute CD4 counts (or stage of disease) may reveal immunologic changes that might otherwise be overlooked.
OBJECTIVE: To illustrate the utility of a broad panel of monoclonal antibodies to detect secondary processes or unexpected characteristics of the primary blood dyscrasia. DESIGN: Case report and discussion. SETTING: Regional academic medical center. PATIENT: A 64-year-old man presenting with an apparent acute myeloid leukemia. INTERVENTIONS: Sequential immunophenotyping with a broad panel of monoclonal antibodies to monitor progression of disease and response to therapy. MAIN OUTCOME MEASURE: Identification and monitoring of the two atypical populations in this patient with correlation to the clinical status of the patient. RESULTS: Identification of an unsuspected mature lymphoid clone and characterization of the evolution of the myelomonocytic clone. CONCLUSION: The evolving mature lymphoid clone may have been overlooked in the context of a predominant atypical myeloproliferative process, particularly if a limited panel of monoclonal antibodies had been used for immunophenotyping. Sequential immunophenotyping was useful in monitoring the progression of each atypical process.
An increasing number of assays to determine absolute CD4 counts are being performed as the acquired immunodeficiency syndrome epidemic continues. Simultaneously, there is increasing pressure to contain costs in the clinical laboratory. A rapid, one-tube, three-color method for obtaining CD4 counts has been evaluated for accuracy, compared with a more traditional two-color panel of markers. The data, compiled on 102 patients, including both pediatric and adult human immunodeficiency virus-infected patients, indicate a high degree of correlation between the one-tube method and a traditional panel. This approach should be considered for cost-effective and accurate CD4 determinations.
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Analysis of cancer incidence data at a variety of geographic scales provides surveillance information that can allay fears of the general public, prevent costly and unwarranted epidemiologic studies driven by political pressures, and target appropriate cases for further investigation. We systematically examined New Jersey Cancer Registry data (1979-1985) for childhood and young adult (0-24 years) cancers at multiple geographic scales--at the state level, then by degree of urbanization, county boundaries, and minor civil divisions. The state had increased rates for some cancers when compared to four other SEER (Surveillance, Epidemiology and End Results) states. No meaningful patterns at either the most urban/suburban/most rural scales or at the county level of analysis were found. At the minor civil division level, the Ederer, Myers and Mantel method found evidence of clustering of pediatric and young adult cases statewide. Stratification of cases by race yielded even stronger findings and indicated that whites had clustering of cases for several cancer types. In-depth analysis of individual cases yielded hypotheses for investigating identified clusters.
Cytogenetic analysis of granulosa cell tumor of the ovary was performed in two patients. G-banding analysis of cells cultured 3-5 days showed that the karyotype of each tumor contained normal diploid cells as well as cells with identical aberration: trisomy 14. This is the first report of trisomy 14 in two cases of granulosa cell tumor of the ovary. Flow cytometric DNA content analysis was also performed.
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Cancer incidence rates for 0 to 24 years of age were examined for New Jersey for 1979-1985. New Jersey rates generally were higher than the comparison states. They were most like those of Connecticut, the state most similar in demographics, geography, and degree of urbanization.
Less than three decades ago, adequate facilities and trained medical and support personnel to treat pediatric cancer were not available in New Jersey. Seven hospitals have the expertise and multidisciplinary teams that collaborate through the New Jersey Pediatric Hematology Oncology Network.
A male infant was diagnosed at age 16 months with acute monoblastic leukemia. At diagnosis, studies of bone marrow revealed multiple chromosome aberrations: 48,XY,+8,+19,t(4;11). Chromosome studies have been repeated at remission and relapse over the course of his disease. To our knowledge, this combination of chromosome abnormalities has not been previously reported.
Two cases of chemotherapy-associated eccrine hidradenitis are presented. Previous cases have been labeled "neutrophilic eccrine hidradenitis" (NEH). Both cases reported herein involve neutropenic patients and are notable for the absence of neutrophils on histologic examination. Oncologists need to be aware of this newly described process, and this rash must be added to the differential diagnosis of the neutropenic oncology patient. The role of neutrophils in this disorder is discussed, and a new term, "chemotherapy-associated eccrine hidradenitis," is suggested for this unusual process.
Thirty children and adolescents with rhabdomyosarcoma (RMS) entered on IRS-1 in a 5-year period had bone marrow metastases (BMM) at diagnosis. BMM at diagnosis occurred in 30/103 patients (29%) with Clinical Group IV RMS. On the average, patients with BMM were older with more extremity primaries than other IRS-1 patients. Alveolar histology was present in 15/30 patients (50%) with BMM, compared to 19% on IRS-1. Eleven patients received vincristine, dactinomycin, cyclophosphamide (VAC), while 19 patients received VAC with Adriamycin (ADR). The overall complete response (CR) rate was 60%. The median disease-free survival times by treatment were 17 weeks with VAC and 32 weeks for VAC + ADR (P greater than 0.10). Relapse from CR in Clinical Group IV patients with BMM occurred in 16/18 patients (89%) and was significantly higher than in 17/29 Clinical Group IV patients (59%) without BMM (P less than 0.035). BMM at diagnosis in children and adolescents with RMS is frequently associated with alveolar histology and is a poor prognostic sign.
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