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Biomedical subjects

A Freedman

Publications and source records attributed to A Freedman.

At least 37 records · Page 2Linked to original sources

Follow-up after therapy for prostate cancer. Treating the problems and caring for the man.

With prostate cancer being diagnosed and treated in more than 300,000 men each year, the pool of long-term survivors is dramatically increasing. Because these patients are usually elderly, they are often receiving follow-up care for unrelated problems in a primary care setting. This offers the physician an excellent opportunity to assist in management of any long-term complications of therapy and in monitoring for cancer recurrence. In addition to performing follow-up evaluations, the physician can provide counseling about a number of testing and treatment issues, including the variability of prostate-specific antigen levels, the appropriateness of a watchful waiting approach to some cancers, and the management of treatment-induced incontinence and impotence, which often have a deleterious effect on quality of life but may be amenable to therapy and psychosocial support.

Aftercare↗

Intranasal lysine aspirin in recurrent nasal polyposis.

Twenty patients with recurrent nasal polyposis but without any history of aspirin sensitivity were given 2000 micrograms of intranasal lysine aspirin to one nostril and saline to the other once a week for periods of up to 15 months. Two patients had increased nasal obstruction following the initial test doses of lysine aspirin and were excluded from the trial proper. In the remainder symptomatic polyp recurrence was delayed compared with the previous experience while on intranasal steroids, with eight patients remaining symptom free at 15 months compared with an expected number of three (P = < 0.05, chi 2 test). Polyp recurrence was bilateral but there was a tendency for the lysine aspirin treated side to have less polyp tissue as assessed by nasendoscopy and by acoustic rhinometry.

Administration, Intranasal↗

Effect of aging on nitric oxide-mediated penile erection in rats.

Aging is an important risk factor for impotence in men. Because nitric oxide (NO) appears to be the mediator of corpora cavernosal smooth muscle relaxation, we have examined in 5-, 20-, and 30-mo-old rats, designated "adult," "old," and "senescent," respectively, whether aging causes a decrease of erectile response that may correlate with lower NO synthase (NOS) in the penis. Electric field stimulation (EFS) of the cavernosal nerve showed that the maximum intracavernosal pressure (MIP) declined in the old and senescent rats to 80 and 51% of the adult value, respectively. A low systemic dose of the NOS inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME; 2 mg/kg), reduced the MIP by only 38% in the adult rats but decreased it in the old and senescent rats by 72 and 80%, respectively. In the absence of EFS, intracavernosal papaverine (phosphodiesterase inhibitor), or nitroglycerin (NO donor), caused a lower erectile response in the old and senescent rats compared with the adult animals (MIP: 41 and 14%, respectively; duration of the erection 46 and 21%, respectively). Tissue sections from old and senescent penises showed increasing degrees of sclerotic degeneration. In comparison with the adult rats, the penile soluble NOS activity per gram of tissue that is sensitive to L-NAME decreased significantly by 63% in the senescent rats but was elevated in the old rats. These results indicate that aging causes an erectile failure due to factors initially independent from an impairment of penile NO synthesis but which are compounded in the very old rats by the decrease of penile NOS activity.

Aging↗

Monoclonal antibody-purged bone marrow transplantation therapy for multiple myeloma.

This report describes the clinical characteristics, treatment associated toxicity, and follow-up of fifty-eight patients with plasma cell--dyscrasias treated with high dose chemotherapy and total body irradiation (TBI) at a single institution. Following TBI, 36 patients received anti-B cell monoclonal antibody (MoAb)-treated autologous bone marrow, 21 patients received anti-CD6 cell MoAb-treated allogeneic bone marrow to deplete T cells, and one patient received unpurged bone marrow from a syngeneic donor. Evaluation after high dose chemotherapy and bone marrow transplantation (BMT) demonstrated 26 complete responses (CR), 26 partial responses (PR), 2 non-responders, 1 not yet evaluated, and three toxic deaths. Fourteen of 36 patients who underwent autologous BMT are alive free from progression at 18 (range 5 to 68) months post transplant (post-BMT); of these, 11 remain in continuous complete response at 16 (range 5 to 68) months post-BMT. Seven of 21 patients who underwent allogeneic BMT are alive free from progression at 30 (range 4 to 44) months post-BMT; of these, three patients remain in continuous complete response at 43 (range 33 to 45) months post-BMT. These data suggest that high dose chemotherapy with TBI followed by MoAb purged BM can be performed with acceptable toxicity and high tumor response rates.

Adult↗

Selective ablation of rat brain tumors by boron neutron capture therapy.

PURPOSE: Damage to the surrounding normal brain tissue limits the amount of radiation that can be delivered to intracranial tumors. Boron neutron capture therapy (BNCT) is a binary treatment that allows selective tumor irradiation. This study evaluates the damage imparted to the normal brain during BNCT or x-irradiation. METHODS AND MATERIALS: The brains of rats with implanted 9L gliosarcomas were examined 1 year after tumor-curative doses of either 250 kV X rays or BNCT. Histopathologic techniques included hematoxylin and eosin staining, horseradish peroxidase perfusion, and electron microscopy. RESULTS: Longterm X ray survivors showed extensive cortical atrophy, loss of neurons, and widespread leakage of the blood-brain barrier (BBB), particularly around the tumor scar. In contrast, the brains and the BBB of longterm BNCT survivors appeared relatively normal under both light- and electron-microscopic examination. Intact blood vessels were observed running directly through the avascular, collagenous tumor scar. CONCLUSION: The selective therapeutic effect of BNCT is evident in comparison to x-irradiation. Both groups of animals showed no evidence of residual tumor at 1 year. However, with x-irradiation there is no therapeutic ratio and tumor eradication severely injures the remaining brain parenchyma. These observations indicate a substantial therapeutic gain for BNCT.

Animals↗

Immunochemical versus guaiac occult blood stool tests: results of a community-based screening program.

This study was designed to investigate two guaiac-based and one immunochemical faecal occult blood test in a community screening program. A total of 39,000 test kits consisting of Hemoccult II, Hemoccult Sensa and HemeSelect were distributed and of these 8933 (23%) were returned for testing. Follow-up contact with 1165 individuals who tested positive on at least one of the nine test slides was successful in 1076 cases (92.4%). Physician verification in 631 individuals revealed 25 patients (4%) diagnosed with colorectal cancer and 145 (23%) with polyps, of which 120 (82.7%) were adenomatous. The percentage of smaller adenomatous polyps detected relative to the percentage of large polyps (> 1 cm) was: Hemoccult II 31% versus 60%, Hemoccult Sensa 73% versus 80% and HemeSelect 34% versus 57%, respectively. The proportion of adenomatous polyps greater than 2 cm detected by individual tests was even more striking with Hemoccult II positive for 83%, Hemoccult Sensa for 100% and HemeSelect for 75%. Of the 25 patients diagnosed with cancer, 17 (68%) were diagnosed with early-stage disease. A statistically significant trend (P < 0.001) was observed with positive predictive values ranging from 3.3% for individuals with only one positive test to one approaching 40% for individuals with 7 or more positive tests. In this study, the most sensitive predictor of colorectal cancer was found to be the combination of Hemoccult II/HemeSelect. While there was no increase in the positive predicted value for adenomatous polyps < or = 1 cm, there was a direct linear increase for adenomatous polyps > 1 cm.

Adenomatous Polyps↗

Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for follicular lymphoma.

Since June 1985, 121 patients with follicular lymphoma aged 24-61 years (median 43) have received myeloablative therapy (cyclophosphamide: 60 mg/kg x 2, + total body irradiation: 200 cGy x 6) with autologous bone marrow transplantation (CY+TBI+ABMT) as consolidation of 2nd or subsequent remission. The marrow mononuclear cell fraction was treated in vitro with anti-CD20 alone and baby rabbit complement at St. Bartholomew's Hospital (SBH) and with the addition of anti-B5 and anti-CD10 at the Dana Farber Cancer Institute (DFCI) prior to reinfusion. There were 4 treatment related deaths, (nonengraftment 1, haemorrhage 1, systemic fungal infection 1, veno-occlusive disease 1). The median time for neutrophil recovery (> 0.5 x 10(9)/1) was 26 days (range 10 to 59 days), and for platelets (> 20 x 10(9)/1), 30 days (range 12 to 73 days). One patient did not engraft and 7 have had delayed recovery of red cells and platelets (> 3 months). Two other patients have subsequently developed acute myelogenous leukaemia and 5, evidence of myelodyplasia. Seventy-one patients continue in unmaintained remission between 3 months and 7 years, with a median follow up of 2.5 years. Forty-three have developed recurrent lymphoma; 98 remain alive. Freedom from progression was the same, irrespective of whether patients received CY + TBI + ABMT whilst in a complete or partial remission and did not depend on the specific remission in which treatment was given (2nd: 90 patients vs. > 2nd: 31 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The Athletic Prevention Programming and Leadership Education (APPLE) Model: Developing Substance Abuse Prevention Programs.

Alcohol and other drug (AOD) abuse affects every sector of society, and student-athletes are no exception. Because many factors affecting athletes do not affect other students, athletic departments commonly approach prevention through AOD education. Different educational approaches are described in this article, particularly the Athletic Prevention Programming and Leadership Education (APPLE) model. Project APPLE is designed to enable an athletic department to systematically analyze its AOD prevention in seven areas: recruitment practices, expectations and attitudes, education and AOD programs, policies, drug testing, discipline, and referral and counseling. Because athletic trainers often are involved in this process, this article should help them to design more effective AOD programs.

Journal Article↗

Fourth branchial cleft cyst.

Remnants of the fourth branchial arch are uncommon clinical entities. They may present in either the neck or chest in association with aortic arch development. They are encountered more frequently in younger individuals as an asymptomatic left-sided neck mass, recurrent neck abscess or suppurative thyroiditis. In view of the rarity of this lesion, we thought it worthwhile to present the case of a 25-year-old female with a diagnosed fourth branchial cleft cyst in her left lower neck. The embryology and management of these cases is discussed.

Adult↗

Further characterization of prolymphocytic leukemia cells as a tumor of activated B cells.

Peripheral blood mononuclear cells from 24 patients with prolymphocytic leukemia (PLL) were isolated using a Ficoll-Hypaque gradient and stained by indirect immunofluorescence using a wide panel of monoclonal antibodies against B cell restricted and associated antigens, including HLA DR (Ia), CD19, CD21 (C3dR) surface membrane immunoglobulin (Slg), CD10 (CALLA), C3b, B5, CD25 (TAC), PCA1, T9, and T10. The cells were also tested for the FMC7, defined previously on PLL cells and the RAB1, a newly described hairy cell leukemia antigen. Thirteen out of the 24 samples expressed with variable intensity all the above antigens. While Ia, CD19, CD20, FMC7, and RAB1 were strongly or moderately expressed in all, the complement receptors (CD21 and C3b) were only weakly expressed in 12 cases; and the activation antigens B5, TAC, T9, T10, and PCA1 were found with variable intensity in two-thirds of the cases. In 50% of the cases tested, the CD5 antigen (usually strongly expressed on B CLL cells) was weakly to moderately expressed. These findings (absence or weak expression of complement receptors with variable expression of activation antigens) suggest that the PLL cells are activated B cells. When stimulated in vitro by anti-mu and TPA, (phorbol ester) tumor cells showed a decrease in CD21 and Slg and a stronger expression of CD25, T9, T10, and PCA1, with evidence of Ig secretion in four out of the seven cases studied. This confirms that the PLL cells arrested at an advanced stage of differentiation progressed narrowly to more differentiated cells. In view of our findings, we believe that the term prolymphocytic leukemia is inaccurate to define the stage of cell differentiation, and we suggest calling the disease preplasmacytic leukemia.

Antibodies, Monoclonal↗

Expression and state of phosphorylation of the retinoblastoma susceptibility gene product in cycling and noncycling human hematopoietic cells.

The product of the retinoblastoma susceptibility gene RB1 (Rb) is likely to function as an inhibitor of cell growth. Previous studies have suggested that certain growth-suppressing effects of Rb are exerted in G0/G1 phase and that phosphorylation can inactivate these functions. We tested this hypothesis by examining the expression and state of phosphorylation of Rb in several lineages of primary hematopoietic cells that spontaneously arrest in G0 phase. Resting lymphocytes were found to express only unphosphorylated Rb, but phosphorylation of Rb occurred as the cells entered S phase in response to mitogens. In contrast, although monocytes and granulocytes also expressed high levels of unphosphorylated Rb, these terminally differentiated cells did not phosphorylate Rb, nor could they exit from G1 phase in response to growth factors. Thus, Rb phosphorylation appears linked to the ability of a cell to synthesize DNA. In T and B lymphocytes, Rb protein increased 8-fold after stimulation, while RB1 RNA levels increased 2- to 4-fold. Nuclear run-on assays and measurement of RB1 RNA half-life in T cells suggested that the increased RNA abundance was, at least in part, due to increased RNA stability. By contrast, Rb protein levels did not increase in either monocytes or granulocytes after stimulation, although RB1 RNA levels did increase in monocytes. Thus, there are lineage-specific differences in both the regulation of Rb phosphorylation and RB1 gene expression in lymphoid and myeloid cells.

Cell Cycle↗

Immunophenotypic profile of CNS lymphoma: a review of eighteen cases.

The cell surface antigenic phenotype of 18 cases of central nervous system (CNS) large-cell lymphoma (14 primary, four secondary) was examined by an immunoperoxidase technique using antibodies that identify B cell restricted and associated antigens. All cases were shown to be of B cell origin by virtue of the expression of monotypic immunoglobulin (Ig) (16 IgM, two IgG) and the pan B cell antigen B1 (CD20). A panel of monoclonal antibodies directed against B cell restricted and associated activation antigens including B5, Blast-1, Blast-2 (CD23), BB1, interleukin 2 receptor (IL2R, CD25), T9 (transferrin receptor) and TNK-TAR (4F2) was used on 12 of the cases. The majority expressed T9 and TNK-TAR. Blast-1 was expressed by less than half the cases and Blast-2 and B5 by one of 12 cases each. This is in contrast to 10 non-CNS diffuse large cell lymphomas where B5 and Blast-1 were present on all cases. This study confirms previous observations that primary CNS large cell lymphomas are of B cell derivation. Moreover, the differences in expression of B cell activation antigens on CNS large cell lymphomas as compared to non-CNS lymphomas raise the possibility that a subset of neoplastic B cells may have unique tropism for the CNS.

B-Lymphocytes↗