Maternal ABO-mismatched blood for intrauterine transfusion of severe hemolytic disease of the newborn due to anti-Rh17.

BACKGROUND: Clinically significant antibodies to high-incident antigens present a challenge in hemolytic disease of the newborn. Antigen-negative blood may be difficult to obtain for intrauterine transfusion (IUT). In these instances, maternal blood is de facto compatible regardless of an ABO mismatch. CASE REPORT: A group B/D-- woman with a history of hemolytic disease of the newborn due to anti-Rh17 (titer 256) presented to the obstetrical clinic at 12 weeks gestation for management of her third pregnancy. She consented to donate blood for possible IUT. STUDY DESIGN AND METHODS: Washed maternal packed cells were suspended in saline to 75 percent Hct and irradiated before transfusion. The fetus was transfused via the intrahepatic vein. RESULTS: Ultrasound examination at 19 weeks indicated a hydropic fetus. The fetal blood group was O Rh+, direct antiglobulin test 4+, and hemoglobin 22 g per L. A total of 368 mL of maternal blood was transfused during seven procedures. Labor was induced at 38 weeks, and a 2560-g male infant was delivered by Caesarian-section due to fetal distress. The infant grouped as B Rh+, direct antiglobulin test negative. No group O red blood cells were detected. The hemoglobin level was 143 g per L rising to 209 g per L at discharge 3 days later. The indirect bilirubin was 55 micromol/L and remained stable during the hospital stay. Phototherapy was discontinued after 1 day, and the infant was discharged without an exchange or top-up transfusion. CONCLUSIONS: Maternal ABO-mismatched blood is an alternate source for IUT in instances when antigen-compatible allogenic blood is unavailable.

Epstein-Barr virus detection in non-Hodgkin's lymphoma of the oral cavity: an immunocytochemical and in situ hybridization study.

OBJECTIVE: The purpose of this study was to histologically characterize a series of oral non-Hodgkin's lymphomas (NHLs) and to investigate latent and lytic Epstein-Barr virus (EBV) infection in these. STUDY DESIGN: The revised European-American Lymphoma classification system (41) was used to categorize 58 cases of oral NHL, which included 9 immunosuppression-related NHLs. EBV infection was determined by in situ hybridization for Epstein-Barr virus-encoded RNA and by immunohistochemistry for the EBV antigens latency membrane protein, Epstein-Barr nuclear antigen-2 (EBNA2) and Z EBV replication activator protein. RESULTS: Most tumors were B-cell lymphomas (78%), but the proportion of T-cell lymphomas was surprisingly high (22%). The most common histologic subtypes were diffuse large B-cell lymphomas (45%), peripheral T-cell lymphomas (19%), and follicle center lymphomas (14%). Two thirds of the known immunosuppression-related NHLs were T-cell lymphomas. All of the immunosuppression-related tumors were EBV-infected, whereas the EBV infection rate in the NHLs of the remaining patients presumed to be immunocompetent was only 9%. Most EBV-positive tumors expressed neither of the latent antigens (ie, latency membrane protein and Epstein-Barr nuclear antigen-2), and coexpression of the 2 was observed only in immunosuppressed patients. Z EBV replication activator protein expression, which is indicative of replicative infection, occurred only in immunosuppressed individuals. CONCLUSIONS: Diffuse large B-cell lymphomas were the most common histologic subtype of oral NHLs, but T-cell lymphomas were relatively common and frequently occurred in states of immunosuppression. EBV may play a limited role in the initiation of lymphoma in the immunocompetent patient, but the virus may be of importance in progression of the disease in those patients with more aggressive tumors, as immunosuppression occurs.

Insecure attachment in a subgroup with ulcerative colitis defined by ANCA status.

This study is the first test of the novel hypothesis that perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) marks an etiological division between stress-susceptible and stress-neutral ulcerative colitis. Subjects were 47 UC patients with known p-ANCA status (19 p-ANCA-positive, 28 p-ANCA-absent). Controls were 77 university students. Subjects and controls completed the Reciprocal Attachment Questionnaire. Subjects were categorized as avoidant/nonavoidant and anxious/nonanxious based on scores for compulsive self-reliance and compulsive care seeking, respectively. A higher prevalence of avoidant attachment was present in p-ANCA-absent (58.6%) than p-ANCA-positive subjects (22.2%, chi-square = 5.95, P < 0.02). There was no difference in the prevalence of anxious attachment between p-ANCA-absent and p-ANCA-positive subjects. There was no difference in clinical and psychiatric variables between groups. This finding provides support for a psychobiological contribution to UC in a subgroup identified by the absence of p-ANCA.

Streamline your automated hematology laboratory. Roundtable discussion.

How three hematology laboratories improved efficiency by automating the preanalytical process, reorganizing lab workspace, using data management systems to identify which samples need further verification, and setting strict criteria limiting the need for nonautomated processes.

Malignant lymphoma presenting with an elevated serum CA-125 level.

An 80-year-old woman presented with fevers, night sweats, and weight loss. Her serum CA-125 level was markedly elevated (380 U/mL; normal < 35 U/ml). At post-mortem examination, the patient had widespread intermediate-grade malignant lymphoma with extensive infiltration of the greater omentum and pelvic peritoneum. Immunohistochemistry for CA-125 documented intense staining in the reactive mesothelial cells of the peritoneum; the tumor cells were not immunoreactive. CA-125 is a glycoprotein recognized by a monoclonal antibody raised against an ovarian-cancer cell line. Elevated levels have been reported rarely in patients with malignant lymphoma, and the pathophysiology of this finding has not been understood. Our data support the hypothesis that elevated CA-125 levels may reflect production by reactive mesothelium in patients with benign or malignant diseases involving the peritoneum, including malignant lymphoma. The clinical application of this marker, therefore, is broader than the recognized monitoring of patients with ovarian carcinoma.

Improved engraftment of human tumours in SCID mice pretreated with radiation and anti-asialo GM1.

The effects of sublethal radiation (3 Gy) and anti-asialo GM1 (anti-ASGM1) on engraftment of human tumour cell lines and fresh tumour were evaluated in the severe combined immunodeficient (SCID) mouse. Four tumour cell lines (colonic adenocarcinoma LS174T, malignant melanoma MEWO, lung adenocarcinoma H125, chronic myelogenous leukemia K562) and a fresh colon cancer metastasis were injected subcutaneously, intraperitoneally or intravenously into SCID mice. Tumour volume and metastatic spread of implanted tumours were evaluated 3-8 weeks following inoculation. Pretreatment with radiation and anti-ASGM1 resulted in more rapid and extensive uptake of subcutaneous and intraperitoneal tumours. Tail vein injection into pretreated animals also resulted in a greater number of lung metastases of H125, MEWO and K562 cell lines. This study demonstrates that sublethal radiation and the elimination of murine NK cell activity with anti-ASGM1 improves tumour take rates. These findings should prove useful for investigations of human cancer immunotherapy using SCID mice engrafted with human lymphocytes and human tumours.

High level functional engraftment of severe combined immunodeficient mice with human peripheral blood lymphocytes following pretreatment with radiation and anti-asialo GM1.

The severe combined immunodeficient (SCID) mouse engrafted with human peripheral blood lymphocytes (PBLs) is a potentially useful model for the study of cancer immunotherapy. For this application, rapid, consistent, and high level engraftment of SCID mice with functional human cytotoxic effector cells is necessary. To date, short term human lymphoid cell engraftment in SCID mice has generally been low and variable. Further, most of the human cells detected within the first 30 days are found in the peritoneal cavity. The purpose of the present study was to improve short term reconstitution of human PBLs in the SCID mouse. When untreated SCID mice were injected with human PBLs, the mean level of CD3+ cells in the spleens was < 5% on days 6-32 after injection, as determined by flow cytometry (FCM). Depletion of SCID mouse natural killer (NK) cells with anti-asialo GM1 only marginally improved short term reconstitution with human CD3+ cells. Preirradiation of SCID mice with 3 Gy improved reconstitution to over 16% CD3+ cells on days 12-14 following engraftment. However, the combination of pretreatment with anti-asialo GM1 plus radiation, significantly increased the mean percentage of human CD3+ cells in the spleen to 40% within 2 weeks following injection of PBLs. Human T cells positive for CD4, CD8, TcR alpha beta, and TcR gamma delta, and human NK and B cells were detected in the spleens of irradiated plus anti-asialo GM1 pretreated SCID mice. The presence of human lymphoid cells was confirmed by immunohistologic staining. The human immune cells in these mice were shown to be functional by the in vivo demonstration of an appropriate secondary immune response to the injection of tetanus toxoid and by an in vivo proliferative response to phytohemagglutinin. Human NK cells could be found in the spleens and peripheral blood of irradiated plus anti-asialo GM1 pretreated mice. These cells were also shown to be competent by their ability to lyse the human NK sensitive tumor targets K562 and MOLT-4 in 51Cr release assays. Thus, pretreatment of SCID mice with radiation plus anti-asialo GM1 significantly improves short term human PBL engraftment and provides a potentially useful model for the study of cancer immunotherapy.

Malignant lymphoma of bone.

OBJECTIVE: To evaluate the diagnosis and management of patients with malignant lymphoma of bone. DESIGN: A case series review in which the minimum follow-up was 24 months and the mean follow-up was 49 months. SETTING: All patients were managed at a tertiary care centre, although initial biopsies were often done in community centres. PATIENTS: Selected for review were 15 of 18 consecutive patients who were referred to the Musculoskeletal Oncology Unit at the Mount Sinai Hospital, Toronto, between 1984 and 1989, with a bone lesion as the presenting symptom of lymphoma. The three excluded patients included two with diffuse nodal disease at presentation and one who had a second, unrelated malignant tumour. INTERVENTIONS: Staging studies (hematologic investigations, radiography, technetium bone scanning and computed tomography), surgical biopsies of the lesion, chemotherapy, radiotherapy and in some cases surgical resection of the lesion. MAIN OUTCOME MEASURES: The number of biopsies required for diagnosis and the incidence of complications that required operative intervention. RESULTS: Seven of the 15 patients required more than one biopsy to establish the diagnosis. Five patients required surgical procedures for late complications that included pathologic fractures, wound infection and osteonecrosis. At 24 months' follow-up, 13 patients were disease free and 2 had died. CONCLUSIONS: Proper biopsy and pathological evaluation are crucial in the diagnosis of lymphoma of bone. These measures will decrease the necessity for repeat biopsies. Lymphoma is best managed medically. Surgery should be reserved for biopsy and for treatment of the complications of therapy.

Charcot's arthropathy of the shoulder following intraarticular corticosteroid injections.

We describe a case of inflammatory and degenerative arthritis treated with intraarticular corticosteroid injections. This led to rapid subjective relief of symptoms, but inappropriate repeated injections led to the development of Charcot's arthropathy and rapid destruction of the shoulder joint.

DNA content and estrogen receptors in primary carcinoma of the breast.

DNA content and estrogen-receptor status were studied in 54 consecutive patients with primary breast carcinoma. Estrogen-receptor determinations were performed by immunohistochemical assay on frozen sections with a monoclonal antibody against the estrogen-receptor molecule and by biochemical analysis with a dextran-coated charcoal method. Nuclear DNA content was measured by flow cytometry performed on formalin-fixed, paraffin-embedded sections. Seventy-two percent of tumours were positive for estrogen receptors by immunohistochemical assay and 67% by biochemical assay. Comparison of the qualitative results of immunohistochemical and biochemical estrogen-receptor determinations revealed a strong correlation between the two assays, with agreement in 90% of the cases (p less than 0.001). Regression analysis showed only a weak relationship between the quantitative results of the two assays. DNA analysis was performed in 51 cases, and 54% demonstrated aneuploid stemlines by flow cytometry. An association was demonstrated between aneuploidy and low levels of estrogen receptor. The association was highly significant with the immunohistochemical assay but not with the biochemical assay. The authors' results suggest that immunohistologic determinations of estrogen receptor status may better reflect the biologic features of the tumour cells. However, improved standardization in reporting the results is necessary if the test is to have widespread use.

[The relation of deoxyribonucleic acid contents and nuclear estrogen receptors in breast cancers].

Flow cytometry was applied to the analysis of DNA contents in 59 cases of breast cancer, among which 28 cases were diploidy cancers, and 31 were aneuploid. DNA index of these cases was found to be ranging from 0.45 to 3.35, including S-phase fraction (SPF) from 2.46% to 78.87%, and proliferation index (PI) from 17.06 to 87.04. In 60 cases of breast carcinoma, nuclear estrogen receptors (ERn) were assayed by immunocytochemistry with ER-monoclonal antibody. 29 of them were ERn-, and 31 were ERn+. The DNA contents and ERn levels, both detected in each of 57 cases, were found to be correlated to some extent. In aneuploidy cancer group, there were more ERn- cases than ERn+ cases (P less than 0.05). The mean value of PI was higher in the ERn- group than in the ERn+ group, and the corresponding ERn- cases were more frequent with increase of PI value. Among those cases in which SPF was over 40%, there were more ERn- cases than ERn+ cases. The relations between ERn levels and DNA contents may represent the degree of differentiation of breast cancers and may help to predict prognosis.

Diffuse Large-Cell Lymphoma in the Elderly: Does a Clinically Indolent Subset Exist?

Among 63 patients with intermediate or high grade non Hodgkin's lymphoma (NHL) seen at our institution in a five-year period, 19 were aged 70 years or older. For various reasons, four of these patients were either not treated or received only minimal treatment. Three of the patients remain well without evidence of disease for 1 to 3 years, and the fourth has relapsed in an indolent fashion after 3 years. These observations suggest that existence of a subset of patients with histologically aggressive non-Hodgkin's lymphoma whose disease behaves mildly. Because of the high incidence of treatment-related morbidity and mortality in elderly lymphoma patients treated with combination chemotherapy, it is important to try to identify prospectively this subset of patients clinically and to avoid overtreatment in this category of cases.

Orbital nonchromaffin paraganglioma. A case report and review of the literature.

Nonchromaffin paraganglioma (NCP), also called glomus body tumor or chemodectoma, is rarely found in the orbit. The behavior of orbital nonchromaffin paraganglioma may potentially be more aggressive than in other head and neck locations. Diagnosis depends on electron microscopic demonstration of membrane-bound neurosecretory granules. Results of histopathologic study show a well-circumscribed lesion without a true capsule with alveolar or organoid arrangements of epithelioid cells within a reticulin framework with thin-walled blood vessels. Cells are polygonal with round or oval nuclei containing rare mitotic figures and pale-staining cytoplasm. Differential diagnosis includes alveolar soft-part sarcoma, alveolar rhabdomyosarcoma, neuroblastoma, carcinoid, and granular cell tumor. Of 29 previously reported cases of orbital NCP, 16 have been reclassified as alveolar soft-part sarcoma. The authors report a patient with an electron microscopically established orbital NCP, with the history of a contralateral glomus jugulare tumor irradiated 14 years previously.