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Biomedical subjects

S Gross

Publications and source records attributed to S Gross.

At least 145 records · Page 8Linked to original sources

Immunomagnetic microsphere mediated purging of cALLa positive leukemic cells from bone marrow for autologous reinfusion.

Bone marrow from sixteen patients with cALLa positive ALL have been treated with a monoclonal antibody (MoAb) cocktail which includes DuALL-1 (CD9), WCMH15.14 (CD10) and HD-37 (CD19). Following antibody treatment, marrows were incubated (30 minutes) with anti-murine-IgG1 (Fc) coated magnetic microbeads and passed through a graded magnetic field chamber. Two problems have had to be addressed: (1) More marrow cells must be processed than in marrows from patients with neuroblastoma, for which the separation chamber was originally developed, requiring the use of more beads, causing occlusion of the chamber's collection surface. This has been corrected by using a large surface area pre-magnet for the elimination of excess microbeads prior to processing in the main chamber; (2) Up-modulation (up to 40% positive cells) of the CD9 associated antigen has been detected. To avoid difficulty, marrows are being routinely screened prior to harvest for purging, and purging is delayed for patients with elevated CD9 levels. Eight patients have been reinfused, with no morbidity or mortality associated with the purging or other ex vivo handling of the marrow.

Antibodies, Monoclonal↗

[Parameters of hemostasis during treatments associating fractionated heparin administered subcutaneously to standard and fractionated heparin administered intravenously in the chronic hemodialysis patient].

The hemorrhagic risk of an association of fractioned heparin (Fraxiparine) injected intravenously at the dose of 7500 AXaICU or of unfractionned heparin (UFH) injected intravenously at the usual dose used for a priming dose for hemodialysis (3750 +/- 1280 IU + 1000 IU after 2 hours of dialysis) to the subcutaneous administration of a thrombo-embolism preventive dose of Fraxiparine (7500 AXaICU) was evaluated on the modifications of the following hemostasis parameters: thrombin time, Activated Partial Thrombin Time (APTT), prothrombin time, anti Xa activity in 13 uremic patients on hemodialysis. The association of intravenous and subcutaneous Fraxiparine prevents efficiently the clotting of the extracorporeal circulation without inducing a detectable antithrombinic activity. In contrast, the association of I.V. UFH to subcutaneous Fraxiparine induces a significant increase of the thrombin time and of the APTT. This latter is exclusively explained by the activity of UFH. It is concluded that subcutaneous Fraxiparine at the thromboembolism preventive dose can be associated as well to I.V. Fraxiparine as to UFH without increasing the antithrombinic activity of the plasma.

Aged↗

Transporting bone marrow for in vitro purging before autologous reinfusion.

We describe the procedures employed for transporting bone marrow to and from a central facility. Marrow has been harvested from 80 patients with neuroblastoma, at 16 centers which are geographically dispersed throughout North America. Marrow from the outside transplant centers was packed on wet ice or cold packs in insulated containers, and transported by commercial carriers or chartered aircraft to the central processing laboratory. Post processed marrows were frozen in liquid nitrogen and returned by commercial carrier to the referring institution. In comparing transported with non-transported but similarly treated marrows, no differences were found in any of the following parameters: (1) CFU-GM recovery, (2) fraction viable cells at thawing, or (3) time to engraftment in patients. We conclude the transportation of harvested marrows to a central purging facility is safe. Based on this experience, we propose a set of standards, which, if adhered to, will insure the continued safe processing, shipping, and storage of bone marrow in all centers so engaged.

Bone Marrow Transplantation↗

Crack users: the new AIDS risk group?

Crack cocaine, a smokable form of cocaine hydrochloride, is now widely available in American inner cities. Reports of high rates of unprotected sexual activity among crack users, coupled with reports of high rates of sexually transmitted diseases (STDs), have raised fears that this population of drug users may soon be contracting and disseminating sexually transmitted HIV. In a study of 205 black adolescent crack users conducted in Oakland and San Francisco, California, 101 respondents (49% of the sample) who reported using crack in combination with sexual activity were examined. Those respondents who reported having a history of one or more STD were compared using discriminant analysis (DA). A successful discrimination (canonical correlation = 0.61, p = 0.000) identified five variables that distinguished those with a STD history from those with no STD history: gender (being female) (p = 0.000), frequency of marijuana use (p = 0.005), response to the question; "Do you plan for sex or does it just happen?" (p = 0.002), response to the statement, "I use drugs to get away from my problems" (0.029), and response to the question, "Do you agree that sex doesn't feel as good when you use a condom?" (p = 0.006). The selection of these variables was thought to represent an underlying passivity in the way that crack users who combine crack use with sex approach sexual activity.

Acquired Immunodeficiency Syndrome↗

CD9 is an unreliable antibody for bone marrow purging.

Various procedures are useful in purging bone marrow of pre-B lineage contamination prior to autologous bone marrow transplantation. Specific monoclonal antibodies are used in combination with complement, magnetic microspheres, chemotoxins, phototherapy or lectins. In this setting, the usual monoclonal antibody cocktail consists of CD9 (DU-ALL-1), CD10 (WCMH 15.14) and CD19 (HD37). Antigens reacting with all three monoclonal antibodies are present on early and mature pre-B lymphocytes. However, CD9 positive antigens have also been shown to be present on megakaryocytes, platelets and mature granulocytes. In our studies, we have found that CD10 and CD19 expression predictably vary according to disease status, with low positivity in remission and higher positivity in relapse. CD9 expression, however, varies independently of disease status and is frequently inconsistent within individual patients. As such, use of CD9 for marrow purging may result in the removal of a broad range of cell populations not related to the underlying disorder.

Antibodies, Monoclonal↗

Selective antibody deficiency to Haemophilus influenzae type B capsular polysaccharide vaccination in children with recurrent respiratory tract infection.

Fifty-one children between 22 and 158 months of age referred to an immunology clinic with a history of recurrent respiratory tract infections were prospectively evaluated for immunologic abnormalities. Ten of the subjects had a poor response to the Haemophilus influenzae type b (Hib) capsular polysaccharide vaccine (failure to mount a twofold increase in titer or achieve a postimmunization titer greater than 0.2 micrograms ab/ml). There were no differences in mean serum concentrations of IgG, IgM, IgA, isohemagglutinins, or anti-tetanus toxoid between the responders and the nonresponders. None of the 10 nonresponders were deficient in IgG2. Eight of the vaccine failures were immunized with an Hib conjugate vaccine (HbOC) consisting of Hib capsular oligosaccharides coupled to diphtheria toxin. All responded with at least a fivefold increase in antibody after primary immunization with HbOC. Seven of the eight had a postHbOC primary immunization titer greater than 1.0 microgram/ml. This study demonstrates that some children with recurrent infections and with normal IgG subclasses are unable to respond to Hib capsular polysaccharide. This defect, which can be circumvented by presenting the polysaccharide antigen in an alternative form, may be contributing to the symptomatology experienced by these patients.

Adjuvants, Immunologic↗

Maternal weight loss associated with hyperemesis gravidarum: a predictor of fetal outcome.

Over a 5-year period in our center 64 patients were hospitalized with a diagnosis of hyperemesis gravidarum. Patients were classified into two groups to determine whether weight loss was an objective predictor of pregnancy outcome. Patients whose weight loss was greater than 5% of their prepregnancy weight were classified as group A (n = 30). Patients with nausea and vomiting of pregnancy but with maintenance of at least 95% of prepregnancy body weight were in group B (n = 34). Infants in group A were significantly smaller with respect to average birth weight expressed as a percentile for gestational age: 38.11 percentile, versus 72.00 percentile for group B (p less than 0.025). Macrosomia (greater than or equal to 4000 gm) was significantly associated with group B (18% versus group A, 0%; p less than 0.025). Growth retardation (less than or equal to 10th percentile weight at birth) was significantly associated with group A (30% versus group B, 6%; p less than 0.01). Three integumentary system abnormalities (3 of 30 cases) occurred in group A compared with none in group B. Although hyperemesis gravidarum has been viewed as a positive predictor, those patients who also demonstrate weight loss and electrolyte disturbance may be a distinct entity and at greater risk for growth retardation and fetal anomalies.

Adult↗

Comparative effects of mezlocillin and carbenicillin on platelet function and thromboxane generation in patients with cancer.

Carbenicillin and mezlocillin are widely used for treatment of Pseudomonas infections in patients with cancer. Carbenicillin has been reported to cause platelet dysfunction and bleeding diathesis in some individuals. We evaluated whether carbenicillin causes deterioration of platelet function in patients with cancer and whether mezlocillin causes similar effects on platelets from normal subjects or from patients with cancer. In these in vitro studies, carbenicillin and mezlocillin decreased ADP and epinephrine-induced platelet aggregation and thromboxane A2 generation similarly, but only in concentrations of 3.2 mg/ml or higher. In contrast, carbenicillin was more potent than mezlocillin in decreasing ristocetin-induced platelet aggregation. We also evaluated effects of these antibiotics on platelet function in 19 patients with cancer who developed fever and neutropenia. These patients received either mezlocillin (10 patients) or carbenicillin (nine patients) in combination with nafcillin and gentamycin. Neither carbenicillin nor mezlocillin had any significant effect on platelet aggregation or thromboxane A2 generation. Lack of effects in vivo was due to defective platelet function in these patients prior to any antibiotics. These defects were most probably related to underlying disease and/or prior chemotherapy. Thus, carbenicillin and mezlocillin can both safely be used in patients with cancer who develop fever and neutropenia, and neither seems to have advantage over the other in terms of platelet function.

Adolescent↗

Low antigen density leukemia cells: selection and comparative resistance to antibody-mediated marrow purging.

Low tumor-associated antigen (TAA) expressing tumor cells present an obstacle to effective antibody directed purging of tumor cells from bone marrow. In this study, a comparison was made of the efficiency with which low TAA expressing leukemia cells could be depleted using two monoclonal antibody (MoAb) directed purging techniques: 1) complement (C)-mediated cytolysis, and 2) physical separation using magnetic microspheres. Low TAA sublines were selected from a cultured human leukemia cell line by growing out cells remaining after treatment with anti-TAA and C, or after immunomagnetic (IM) purging. IM-selected sublines showed lower TAA expression than did C-selected sublines, and sublines resulting from multiple selections expressed less TAA than those that had only been through one selection. These sublines were then examined for sensitivity to C or IM purging. The highly selected, lowest TAA expressing sublines were markedly resistant to both IM and C. Less selected sublines were resistant to C, but not to IM. In both techniques, addition of MoAbs against a second TAA restored the efficiency of purging to that observed with the parental line. When low TAA subline cells were seeded into simulated bone marrow and subjected to purging, C-mediated lysis removed less than 40% of leukemia cells, whereas IM purging removed 85% of the cells. These results indicate that there are low antigen density cells that are resistant to C-mediated purging, but which retain sensitivity to IM removal.

Antibodies, Monoclonal↗

Metastatic retinoblastoma successfully treated with immunomagnetic purged autologous bone marrow transplantation.

There are no documented cases of long-term, disease-free survival in retinoblastoma (RB) metastatic to the bone marrow. The following study details successful outcome in a 3-year-old child with extensive marrow replacement 7 months postenucleation in an otherwise untreated group V RB. Therapy consisted of combinations of vincristine, doxorubicin, and cyclophosphamide for 3 months. After demonstrating cross-reactivity by a panel of six monoclonal neuroblastoma (NB) antibodies with the patient's RB cells, her marrow was purged by using microsphere-linked monoclonal antibodies, and then reinfused as rescue therapy after ablative doses of etoposide and cyclophosphamide. The authors conclude that short-term induction therapy followed by marrow ablative combination chemotherapy and immunomagnetically purged autologous marrow rescue can (1) effect successful outcome in widely metastatic RB, and (2) eliminate the risk of therapy-induced second malignancies.

Antibodies, Monoclonal↗

High-risk Ewing's sarcoma: end-intensification using autologous bone marrow transplantation.

Because of retrospective analysis showing survival to be related to primary tumor size, in February 1982 a study to test this hypothesis prospectively was begun at the University of Florida. Patients with primary tumors 8 cm or less in maximum diameter and no metastases received adjuvant chemotherapy consisting of vincristine, cyclophosphamide, doxorubicin, and dactinomycin plus radiotherapy or surgery (standard-risk protocol). All others received a similar regimen followed by end-intensification with high-dose melphalan and autologous bone marrow transplantation (Protocol HR-2). Because of poor results of HR-2, another high-risk protocol (HR-3) was initiated in January 1985. Patients on HR-3 received 2 cycles of chemotherapy containing vincristine, cyclophosphamide, and doxorubicin followed by local radiation therapy and maintenance chemotherapy. At the end of this therapy, autologous bone marrow transplantation (ABMT) was performed, using a preparatory regimen of total body irradiation and intensive chemotherapy. The 2-year disease-free survival rate was 70% for the standard-risk protocol, 20% for HR-2, and 80% for HR-3. The follow-up on HR-3 is still short, but the results are promising enough to warrant further clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗