Biomedical subjects

D P Hartmann

Publications and source records attributed to D P Hartmann.

At least 19 recordsLinked to original sources

PubMed2001

Differentiating lymphoblastic lymphoma and Ewing's sarcoma: lymphocyte markers and gene rearrangement.

We encountered a child with an intraosseous small round cell tumor that was negative for LCA, CD20 (L26), and CD3 and positive for vimentin, CD99 (MIC-2), and periodic acid-Schiff. The tumor exhibited rosette-like formations. This case was initially interpreted as Ewing's sarcoma (ES); however, additional studies revealed positivity for CD79a, CD43, and TdT expression, and an immunoglobulin heavy chain gene rearrangement (IgH-R) by polymerase chain reaction (PCR) established this to be a precursor B-lymphoblastic lymphoma. Because the differential diagnosis of ES and lymphoblastic lymphoma can be difficult and the differential diagnostic value of leukocyte antigens and immunoglobulin heavy chain gene rearrangement studies have not been fully evaluated, we conducted a more extensive investigation on 33 (21 soft tissue and 12 intraosseous) ES cases. Cases were retrieved from the files of the Department of Pathology at Georgetown University and from the Soft Tissue Registry of the Armed Forces Institute of Pathology. The cases were studied by light microscopy, immunohistochemistry, and PCR for IgH-R and T cell receptor gamma chain gene rearrangement (Tgamma-R). There were 17 females and 16 males; the mean age was 29.3 years. Locations included the extremities (n = 17) and trunk (n = 16). All cases fit the ES spectrum by light microscopy and immunohistochemistry, as previously determined, and were negative for lymphoid markers (LCA, CD3, CD20, CD43, CD79a, and TdT), CD10 and CD34. CD99 was positive in 31/33 and bcl-2 was weakly positive in 13/33 cases. All 21 cases studied for gene rearrangements by PCR were negative for IgH-R and Tgamma-R. Distinction of intraosseous lymphoblastic lymphoma from ES may be difficult because lymphomas may occasionally exhibit unexpected morphologic and immunophenotypic properties including LCA, CD3 and CD20 negativity and cytokeratin positivity. Additional analysis using CD79a, CD43, TdT, and PCR should be performed to avoid misdiagnosis. True ES is negative for lymphoid markers including CD79a, CD43, and TdT, as well as for IgH-R and Tgamma-R.

12E7 Antigen↗

PubMed2000

Endoscopic mapping and surrogate markers for better surveillance in Barrett esophagus. A study of 700 biopsy specimens.

Surveillance methods in Barrett esophagus (BE) using light microscopic examination of random biopsy specimens may miss focal dysplasia. In addition, dysplastic foci identified initially may not be relocated subsequently, making chemoprevention studies difficult. By using a special gastroscope, systematic mapping (4-quadrant biopsy specimens at 1-cm intervals) was performed in 22 patients (33 total mappings yielding 700 biopsy specimens). H&E, immunohistochemistry, and DNA ploidy analysis were performed. c-erbB-2 and positive Ki-67 were detected only in dysplastic sites; thus, their detection did not precede morphologically identifiable dysplasia. On the other hand, aneuploidy and p53 were detected in dysplastic and nondysplastic areas. p53 was correlated with dysplasia, and S-phase narrowly missed correlation, while aneuploidy was not correlated. PCNA and bcl-2 were ubiquitous, limiting their usefulness. On second maps, epithelial type was reidentified with 81% accuracy. A significant correlation was found between p53 and dysplasia. Sites of dysplasia and abnormal biomarkers could be relocated accurately by using endoscopic mapping. Therefore, mapping combined with biomarker studies may provide better surveillance and serve as a useful technique in chemoprevention studies.

Adult↗

PubMed1999

Qualitative mapping of Barrett's metaplasia: a prerequisite for intervention trials.

BACKGROUND: Barrett's esophagus may present as a cellular mosaic with irregular longitudinal extensions of intestinal epithelium, spotty areas of dysplasia and other intermediate markers for cancer risk. It may not be possible to detect and reproducibly localize these findings with routine endoscopic biopsies. A more systematic biopsy protocol is necessary for chemopreventive studies to be feasible. METHODS: Utilizing an adapted upper endoscope that allows accurate evaluation of distance from the incisors and rotatory position, chromoendoscopy with toluidine blue and systematic mapping (4 quadrant jumbo biopsies at 1 cm intervals) were performed twice on 18 patients with Barrett's esophagus (second procedure 1 to 3 months after baseline study). All biopsy specimens were subjected to routine and immunohistochemical staining and flow cytometry to create baseline and follow-up maps for each patient. Eight of the 18 patients also underwent standard surveillance biopsies within 6 months of the systematic mapping procedures. RESULTS: Epithelium type was reproducibly identified with 94% accuracy on second endoscopic maps. Ploidy, p53, and Ki-67 status were also reproducibly identified on second endoscopic maps (97%, 89%, and 85%, respectively). Dysplasia was found in 7 of 18 patients at similar sites at each mapping procedure (3 patients with high-grade dysplasia, 4 with low-grade dysplasia). Five of the patients who had dysplasia on mapping had also undergone standard surveillance. Low-grade dysplasia was missed in 2 of 3 patients and 1 patient with high-grade dysplasia had only low-grade dysplasia detected with standard biopsies. CONCLUSIONS: Utilizing a modified gastroscope and this methodology, we reliably located sites of dysplasia and other biomarkers within a field of Barrett's esophagus. Patients had variable areas of dysplasia that were missed on standard endoscopic surveillance.

Adenocarcinoma↗

PubMed1999

Posttherapy surveillance of B-cell precursor acute lymphoblastic leukemia. Value of polymerase chain reaction and limitations of flow cytometry.

Flow cytometric immunophenotypic analysis is critical in diagnosis and classification of acute leukemia and has been used after therapy to monitor for minimal residual disease. However, the presence of normal B-cell precursors, hematogones, particularly in the context of treated pediatric B-cell precursor acute lymphoblastic leukemia (BP-ALL), may confound such evaluation. In this study, the value of more specific genotypic markers (polymerase chain reaction evaluation of 2 antigen receptor genes) was assessed to resolve this issue. Flow cytometric analysis of enriched mononuclear cells revealed 1% to 20% precursor B cells (PBCs), based on expression of 1 or more pan-B cell antigens in addition to CD10, CD34, and terminal deoxynucleotidyl transferase in all 14 patients studied. Inasmuch as this mimicked the immunophenotype of the original leukemic clone, PBCs, in isolation, were considered suspicious for minimal residual disease. However, 11 of the 14 posttherapy specimens (79%) revealed no monoclonally rearranged antigen receptor genes, and 7 of these 11 patients had trackable genotypic markers at presentation. Accordingly, by PCR these 7 patients had complete molecular remission, supported by clinical follow up of 16 to 73 months. Among the remaining 4 patients with PCR-negative disease, 3 continue in remission, confirming the interpretation of false-positive flow cytometric analysis. In conclusion, flow cytometric monitoring of posttherapy bone marrow specimens from patients with BP-ALL may be misleading, if considered in isolation, in falsely suggesting the presence of minimal residual disease. Rather, PCR for antigen receptor gene rearrangements is a valuable and specific tool, helpful in differentiating hematogones from minimal residual disease in patients with treated BP-ALL whose bone marrow harbors increased PBCs.

Adolescent↗

PubMed1998

Precursor B-Lymphoblastic lymphoma presenting as a solitary bone tumor and mimicking Ewing's sarcoma: a report of four cases and review of the literature.

Precursor B-lymphoblastic lymphoma (B-LBL) may present as a solitary bone tumor. Fewer than 10 cases with a proven precursor B-cell phenotype have been reported in the English literature. In this report, we describe four cases of B-lymphoblastic lymphoma presenting as a localized intraosseous mass, which clinically and histologically mimicked Ewing's sarcoma. Three tumors occurred in the tibia and one in the humerus. In all four cases, the initial diagnosis was either "Ewing's sarcoma" or "consistent with Ewing's sarcoma." All four patients were female. Three were children and one was an adult; mean age was 12.5 years (range, 4 to 31 years). All had extremity pain without significant constitutional symptoms. In three cases, the tumors were osteolytic on radiographic evaluation, and in one case, osteosclerotic. Immunohistochemical stains on paraffin-embedded tissue showed that the neoplastic cells expressed terminal deoxynucleotidyl transferase, CD43, vimentin, and CD99 (MIC2 gene product) in all cases. Three cases were negative for CD45. CD79a was positive in all four cases studied; however, CD20 (L26) was positive in only two of four cases. CD3 was negative in all cases. Two cases showed focal granular cytoplasmic staining for keratin. Two cases analyzed by polymerase chain reaction (PCR) revealed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene. Follow-up revealed that the three pediatric patients, who received a high-dose multiagent chemotherapy regime for LBL, are disease free at follow-up intervals of more than 1, 11, and 12 years, respectively. The adult patient died two years after diagnosis with disseminated disease. Although rare, B-lymphoblastic lymphoma should be considered in the differential diagnosis of small round cell tumors of bone. A diagnosis of Ewing's sarcoma should be made only after complete immunophenotyping and, if necessary, molecular diagnostic tests to exclude lymphoblastic lymphoma. A limited panel of antibodies can lead to an erroneous diagnosis; B-lymphoblastic lymphoma may be negative for CD45 and CD20 but positive for CD99 and even for keratin, mimicking Ewing's sarcoma. Correct diagnosis is extremely important because LBL usually is curable in the pediatric age group with appropriate therapy.

Adult↗

PubMed1997

The human papillomavirus type 16 E6 and E7 oncoproteins dissociate cellular telomerase activity from the maintenance of telomere length.

The "high risk" subgroup of human papillomaviruses (e.g. HPV-16 and HPV-18) infect and induce tumors of mucosal epithelium. These neoplasms, which can progress to malignancy, retain and express the papillomavirus E6 and E7 oncogenes. In vitro, the E6 and E7 proteins associate with the cellular p53 and Rb proteins and interfere with their normal growth-regulatory functions. We report here that primary human keratinocytes transduced with the HPV-16 E6 gene, but not the E7 gene, express significant telomerase activity. However, despite this detectable enzymatic activity, E6-transduced cells continue to shorten their telomeres during in vitro passaging similar to control cells and to cells expressing the E7 and E6+E7 genes. At late passages, however, E7-transduced cells partially restore telomere length, although they lack detectable telomerase activity, demonstrating that E6-independent, telomerase-independent events mediate this change.

Cell Line↗

PubMed1997

Molecular detection of bone marrow involvement in intravascular lymphomatosis.

Intravascular lymphomatosis (IVL) is an extremely rare variant of aggressive non-Hodgkin's lymphoma characterized by confinement of neoplastic lymphocytes within vascular spaces. Although IVL is potentially curable with combination chemotherapy, diagnosis is often delayed, in part owing to the negative bone marrow biopsy specimens that are typical of this disorder. We hypothesized that use of a more sensitive method of analysis might identify small clonal B-cell populations in histologically negative bone marrow biopsy specimens from patients with IVL. With use of a recently described assay for immunoglobulin heavy chain gene rearrangement based on the polymerase chain reaction, we demonstrated clonal B-cell populations in histologically negative marrow specimens from five (100%) of five patients with IVL. None of these specimens demonstrated molecular evidence of the t(14;18) associated with follicular lymphoma, providing no evidence for a common derivation of IVL and follicular lymphoma. In summary, molecular analysis of routine bone marrow biopsy sepcimens from patients in whom the diagnosis of IVL is entertained may facilitate prompt recognition of a lympho-proliferative disorder and thereby permit timely therapeutic intervention. Moreover, these findings suggest that despite histologically negative staging bone marrow biopsy specimens, IVL typically disseminates early in its course, thus arguing against the use of localized therapy in this disorder.

Aged↗

PubMed1996

Barrett esophagus with dysplasia. Flow cytometric DNA analysis of routine, paraffin-embedded mucosal biopsies.

Flow cytometric DNA ploidy analysis has been reported to be more objective and sensitive than morphologic evaluation as a surveillance method in patients with Barrett esophagus (BE) for the development and progression of precancerous lesions. Such analyses are typically performed using fresh samples that require a separate or "jumbo" biopsy, are prone to false DNA aneuploidy if not promptly processed, and do not allow for retrospective studies. The feasibility of performing flow cytometric DNA analysis on paraffin-embedded biopsies was studied to circumvent some of these problems using 12 squamous esophageal mucosa with inflammation and 58 BE cases showing varying degrees of dysplasia. Among the BE cases, 12 had no dysplasia, 20 were indefinite for dysplasia, 14 had low grade dysplasia, and 12 had high grade dysplasia. Satisfactory histograms were obtained in 86% of the analyzed samples. Among cases with adequate histograms, DNA aneuploidy was identified in 77% with high grade dysplasia, 16% with low grade dysplasia, 23% of indefinite for dysplasia, and 0% without dysplasia. One of the esophagitis samples was also DNA aneuploid. Correlation of DNA aneuploidy and degree of dysplasia is highly significant (P = .001). The authors have demonstrated that routinely processed paraffin-embedded biopsies can be used for flow cytometric ploidy analysis. DNA aneuploidy was highly correlated with degree of dysplasia and serves as a quantitative prognostic indicator for prospective as well as retrospective studies of the evolution of BE to carcinoma.

Barrett Esophagus↗

PubMed1995

Human immunodeficiency virus 1 envelope-initiated G2-phase programmed cell death.

Despite intensive investigation, no clearly defined mechanism explaining human immunodeficiency virus (HIV)-induced cell killing has emerged. HIV-1 infection is initiated through a high-affinity interaction between the HIV-1 external envelope glycoprotein (gp120) and the CD4 receptor on T cells. Cell killing is a later event intimately linked by in vitro genetic analyses with the fusogenic properties of the HIV envelope glycoprotein gp120 and transmembrane glycoprotein gp41. In this report, we describe aberrancies in cell cycle regulatory proteins initiated by cell-cell contact between T cells expressing HIV-1 envelope glycoproteins and other T cells expressing CD4 receptors. Cells rapidly accumulate cyclin B protein and tyrosine-hyperphosphorylated p34cdc2 (cdk1) kinase, indicative of cell cycle arrest at G2 phase. Moreover, these cells continue to synthesize cyclin B protein, enlarge and display an abnormal ballooned morphology, and disappear from the cultures in a pattern previously described for cytotoxicity induced by DNA synthesis (S phase) inhibitors. Similar changes are observed in peripheral blood mononuclear cells infected in vitro with pathogenic primary isolates of HIV-1.

Apoptosis↗

PubMed1995

Polymerase chain reaction versus Southern blot hybridization. Detection of immunoglobulin heavy-chain gene rearrangements.

To determine efficiently the clonality of B-cell lymphoproliferative disorders, we modified an immunoglobulin heavy-chain (IGH) gene rearrangement polymerase chain reaction (PCR) assay that requires only a single primer germline variable (VH) and joining (JH) pair and does not involve nested priming, blot hybridization, radioactivity, or sequencing of the amplified PCR product. This simple PCR technique enabled detection of IGH gene rearrangements in as little as 10 pg (one cell equivalent) of DNA or when the clonal-to-polyclonal B-cell ratio was experimentally set at 1:1000. We detected IGH gene rearrangements in 83.5% (71 of 85) of clonal B-cell processes, a sensitivity approaching that of more cumbersome multiple primer and nested primer assays. Moreover, this technique is equally effective with fixed tissues, either B5 or formalin, and can be performed on minute samples, histologic sections, fine-needle aspirates, or cerebrospinal fluids. When compared with conventional Southern blot analysis using a genomic JH probe, the PCR assay demonstrated IGH gene rearrangements in 82% (37 of 45) of B-cell processes positive by Southern blot. No false-positive results were observed in 29 negative control tissues. We now use IGH gene PCR routinely in our laboratory for the detection of clonal B-cells in virtually any tissue sample as an aid in early diagnosis, staging, and monitoring, and the Southern blot procedure is reserved for only a minority of diagnostic cases. for only a minority of diagnostic cases.

B-Lymphocytes↗

PubMed1995

Flow cytometric DNA analysis of ulcerative colitis using paraffin-embedded biopsy specimens: comparison with morphology and DNA analysis of fresh samples.

OBJECTIVES: The detection of aneuploidy in colonic mucosa by flow cytometric DNA analysis has been advocated as an indicator of high risk for ulcerative colitis (UC) patients developing colon carcinoma. To date, studies have primarily utilized fresh tissue and have had two limitations: a significant number of possible false-positive findings (aneuploidy in the absence of detectable dysplasia) that may be due to DNA degradation, and the inherent inability to perform retrospective studies. The latter has compromised the adequate assessment of flow cytometric DNA analysis for its clinical utility in UC patients. Our objective was to attempt to overcome the limitations that have been present in DNA analysis by flow cytometry. METHODS: After having established, in our laboratory, an optimal method that allowed reliable DNA analysis on paraffin-embedded mucosal biopsy specimens, we conducted three separate studies to address the above problems associated with DNA analysis with fresh colonic samples: 1) comparison of DNA analysis between fresh and paraffin-embedded colonic mucosal samples from UC patients without dysplasia, 2) correlation between morphology and DNA ploidy on paraffin-embedded tissues showing no dysplasia and various degrees of dysplasia, and 3) sequential analysis of fresh, normal colonic mucosal samples to further evaluate possible causes of false aneuploidy. RESULTS: We observed 1) that there is discordance in DNA ploidy between paraffin-embedded and fresh samples showing no dysplasia in that aneuploidy was found in 33/46 (72%) of fresh samples, whereas 3/40 (7.5%) were aneuploid by biopsies from the corresponding anatomic sites. 2) There is excellent correlation between dysplasia and DNA ploidy results with paraffin-embedded tissue, i.e., none of 16 samples negative for dysplasia, none of seven samples indefinite for dysplasia, and seven of eight samples positive for dysplasia were aneuploid. 3) DNA degradation produced a spurious, near-diploid aneuploid peak in a normal colonic mucosal sample when it was left in saline more than 1 hr before analysis. CONCLUSIONS: The above-described results demonstrate that performing flow cytometric DNA analysis with formalin-fixed paraffin-embedded biopsy samples is feasible and that this technique may provide more reliable ploidy results than does the use of fresh samples, when rapid refrigeration and/or freezing of the fresh samples cannot be accomplished consistently, and will permit retrospective DNA ploidy studies assessing risk of cancer in UC patients.

Adult↗

PubMed1994

Antiestrogen resistance in ER positive breast cancer cells.

Acquisition of the antiestrogen resistance by breast cancer cells in vivo may result from a variety of mechanisms. The main pathway appears to involve loss of estrogen receptor (ER) expression or selection for ER negative cells among heterogenous population of tumor cells. However, clinical data suggest that, in about 30% of the cases, antiestrogen resistance arises even in the presence of estrogen receptors. Postulated mechanisms leading to the latter phenotype include selection for variant receptor forms during treatment, development of novel metabolic pathways for the drug, loss of nuclear co-factors, or activation of signal transduction pathway that cross activate ER signals. We have used an in vitro experimental system utilizing LY-2 cell line, an ER positive and antiestrogen resistant MCF-7 cell variant, to study the mechanism of antiestrogen resistance in the presence of functional ER. Result from a complementation experiment suggests that LY-2 phenotype is a recessive trait. Cloning of the genetic defect in the LY-2 cells would provide further insight for the mechanism of antiestrogen resistance in ER positive breast cancer cells.

Adenocarcinoma↗

PubMed1990

The psychological functions of preadolescent peer activities.

The psychological functions of preadolescent peer activities were assessed by examining activity-related prescriptions and prescriptions for peer behavior. 91 fifth- and sixth-grade children (48 girls) kept week-long diaries of important peer activities and liked and disliked behaviors performed by peers in the activities. 81 other fifth- and sixth-grade children (40 girls) rated the importance and prevalence of each activity and indicated which of several positive and negative behaviors they would most like or dislike to happen in 10 of the activities. Results indicate that collectively, the activities sampled serve 3 main functions based on their prescriptive and prescriptive behavioral profiles: (a) they provide a context for sociability, enhancement of relationships, and a sense of belonging; (b) they promote concern for achievements and integrity of the self; and (c) they provide opportunities for instruction and learning. Not all activities serve all functions, however, and children may require exposure to a variety of activities to accrue a full range of psychological experiences. The findings also illustrate the potential importance of activity-related information for discerning the meaning and evaluating the effectiveness of social behavior. The advantages of the methodology are discussed.

Child↗

PubMed1989

Human B cell lines can be triggered to secrete an interleukin 2-like molecule.

To determine whether human B cells can be triggered to secrete interleukin 2 (IL-2), 19 tumor cell lines derived from patients with undifferentiated lymphomas of Burkitt's and non-Burkitt's types and 6 normal lymphoblastoid cell lines were tested. Cells were grown in the presence or absence of the new tumor promoter teleocidin, and culture supernatants were assayed for IL-2 activity using the standard CTLL-2 assay. Teleocidin (10 ng/ml) triggered IL-2 secretion in 7/8 (87%) EBV-negative lymphoma cell lines of American origin and in 6/6 (100%) normal lymphoblastoid cell lines, but in only 1/6 (16%) EBV-positive tumor cell lines of American origin. Teleocidin had no effect on 5/5 (0%) African Burkitt's cell lines. IL-2 secretion was not detected in control supernatants. IL-2 secretion correlated with the induction of IgM secretion and was linked to both EBV status and karyotype. The following similarities in the functional biological characteristics of T cell and B cell IL-2 suggest that B cell IL-2 is not a factor which mimics IL-2 activity in the CTLL-2 assay: (i) neutralization of IL-2 by anti-IL-2 monoclonal antibody (DMS-1); (ii) elution of IL-2 following its adsorption to CTLL-2 cells; (iii) determination of the MW of IL-2 by SDS-PAGE and Western blot analysis; and (iv) ability of B cell IL-2 to support T cell proliferation and blocking of this activity by anti-tac monoclonal antibody. cDNA probes for T cell IL-2, however, did not detect IL-2 mRNA in B cells. The cell lines were also found to constitutively express IL-2 receptors detected by anti-tac monoclonal antibody, and to secrete soluble IL-2 receptors measured by ELISA. Our results imply that under certain circumstances, B cells can be triggered to secrete IL-2 or an IL-2-like molecule and thus influence T cell activation and proliferation.

Antibodies, Monoclonal↗

PubMed1989

Inhibition of lymphocyte proliferation by antibodies to prolactin.

Recent in vivo studies have shown that treatments that decrease circulating prolactin (PRL) in rodents result in significant immunosuppression. Our attempts to demonstrate corresponding direct stimulatory effects of PRL on cultured lymphocytes were unsuccessful. However, antibodies against pituitary PRL potently inhibited both murine and human lymphocyte proliferation in response to both T and B cell mitogens. Further studies using IL 2 and IL 4 responsive cell lines (CTLL-2 and HT-2) demonstrated that the same anti-PRL antibodies inhibited the proliferative response to these cytokine growth factors. Thus, antibodies to PRL appear to block an event occurring in the G1 to GS phase transition of these cell lines, which constitutively express growth factor receptors. The inhibitory activity of anti-PRL antibodies could be adsorbed by addition of purified human PRL or by immobilized PRL on an affinity column. Antibodies to other pituitary hormones were without inhibitory effect on CTLL-2 cell proliferation. Proliferation of lymphocytes in serum-free medium was also potently inhibited by anti-PRL antibodies, suggesting that antibody effects were not due to neutralization of PRL or other factors contained in culture serum supplements. We suggest from these data that a protein with homology to PRL and recognized by these anti-PRL antibodies is produced by lymphocytes and plays a critical role in their progression through the cell cycle.

Animals↗

PubMed1988

Detection of antigens associated with Epstein-Barr virus replication in extracts from biopsy specimens of nasopharyngeal carcinomas.

By using monoclonal antibodies to different Epstein-Barr virus (EBV) polypeptides in combination with immunoblotting, we detected antigens associated with EBV replication in extracts from nasopharyngeal carcinoma (NPC) biopsy specimens. Major polypeptides associated with both the diffuse and the restricted components of the early antigen (EA) complex were found in extracts from nine of nine NPC biopsy specimens. Cells from an additional NPC biopsy specimen, passaged repeatedly in nude mice, were found to be positive for the major EA (restricted) polypeptide. This approach revealed that extracts from three of 14 biopsy specimens form other benign and malignant diseases also expressed these viral polypeptides. Therefore, for the first time, these results conclusively demonstrate the presence of EA polypeptides in extracts from NPC biopsy specimens. This finding provides at least a partial explanation for the reported prognostic value of antibodies to this antigen in patients with this disease.

Antibodies, Monoclonal↗

PubMed1988

Recent developments in single-subject methodology: methods for analyzing generalization, maintenance, and multicomponent treatments.

At the outset of this chapter we asked whether or not single-subject methodology has outlived its usefulness to behavior therapy. We did so because serious doubts have been expressed about the ability of single-subject methodology to address the salient issues of the day. This chapter allays many of these doubts. This chapter reveals that single-subject researchers are far from helpless when investigating generalization and maintenance and identifying the active (and inactive) components in their compound treatments. In fact, a number of powerful strategies are at their disposal--strategies that are not strangers to the armamentarium of single-case researchers. These strategies are in essence nothing more than extensions of the reversal, multiple baseline, and simultaneous and alternating-treatments designs. In the case of the assessment of generalization, these extensions involve little more than the inclusion of continuous measures (or regular probes) of untrained responses throughout the investigation. In the case of the assessment of maintenance, they involve the replacement of a comparison of two or more acquisition procedures with a comparison of two or more maintenance procedures. And in the case of the identification of active (and inactive) components of compound treatments, they involve the aggregation of the findings from a series of single-subject investigations. When the requirements of single-subject designs and their extensions cannot be met, investigators still have available a set of traditional group designs (e.g., factorial and additive designs) for attacking these same issues. Assessment of generalization, maintenance, and the components of compound treatments are not the only salient issues facing behavior therapy today. Another is the widening gap between the researcher and the practitioner (e.g., Barlow, 1980; Wilson, 1981). It is thought by some that single-subject methodology may be the means of bridging this gap; that through single-subject methodology a new breed of practitioner will appear: the empirical clinician (e.g., Barlow et al., 1984; Goldfried, 1984; Hayes, 1981). This new breed of practitioner will be made up of persons who, for economic and pragmatic reasons, are concerned with accountability and who use single-subject designs to achieve it (Barlow et al., 1984). The present chapter does little to help bridge the gap between the researcher and the practitioner; thus, the present chapter does little to help bring about the creation of this new breed of practitioner, the empirical clinician. In fact, the single-subject strategies described in these pages appear to be suitable for use only by the researcher.(ABSTRACT TRUNCATED AT 400 WORDS)

Behavior Therapy↗

PubMed1987

Cytomegalovirus encephalitis associated with episodic neurologic deficits and OKT-8+ pleocytosis.

After 3 days of symptoms suggesting a viral illness, a 35-year-old man experienced three episodes of aphasia, right-sided sensory symptoms, and bifrontal headache. Each lasted several hours. CSF examination revealed a moderate lymphocytosis consisting of 80% OKT-8+ cells. Serum anti-cytomegalovirus (anti-CMV) antibody titer was elevated at 1:1,024 and subsequently fell to 1:64. Episodic symptoms recurred 5 months later, at which time the anti-CMV titer peaked at 1:8,192. A trial of inhaled oxygen aborted two episodes after several minutes each.

Adult↗