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Biomedical subjects

J Rubin

Publications and source records attributed to J Rubin.

At least 19 recordsLinked to original sources
PubMed1992

Multifocal inflammatory leukoencephalopathy with 5-fluorouracil and levamisole.

A cerebral demyelinating disease developed in 3 patients during adjuvant therapy with 5-fluorouracil and levamisole for adenocarcinoma of the colon. None of the patients had evidence of metastatic disease or prior neurological disease. The duration of chemotherapy before onset of neurological symptoms ranged from 15 to 19 weeks. The total dose of 5-fluorouracil was 9.7 to 15.7 gm. The total dose of levamisole was 2.7 to 3.75 gm. Two patients presented with a subacute (2-3 weeks) progressive decline in mental status and ataxia. The third patient had two unexplained episodes of loss of consciousness. In each, magnetic resonance imaging with gadolinium demonstrated prominent multifocal enhancing white matter lesions. Cerebral biopsy was performed stereotaxically in 2 patients. The morphological features were those of active demyelinating disease. The myelin loss was associated with numerous dispersed as well as vasocentric macrophages, sparing of axons, and perivascular lymphocytic inflammation. Electron microscopy confirmed the light microscopic findings. All 3 patients improved after cessation of chemotherapy and a short course of corticosteroid therapy. Our patients represent the first reported examples of an inflammatory leukoencephalopathy associated with the administration of 5-fluorouracil and levamisole. This syndrome may represent the pathological basis for 5-fluorouracil neurotoxicity, although we cannot completely exclude the role of levamisole.

Adenocarcinoma↗
PubMed1992

cAMP promotion of osteoclast-like cell development from mouse bone marrow cells requires a permissive action of 1,25-(OH)2D3.

Recruitment of osteoclasts from monocytic precursors is modulated by local signals. We previously showed that monoblastic differentiation in U937 cells is stimulated by 1,25-(OH)2D3 and cAMP in series. We investigate here the combined effects of these agents to stimulate differentiation of osteoclast-like cells from mouse marrow. Cells from mouse marrow were harvested and cultured in alpha-MEM with 10% fetal bovine serum. The appearance of tartrate-resistant acid phosphatase-containing multinuclear cells was measured after 8 days in culture by cytochemical staining. Continuous exposure of cultures to 10 nM 1,25-(OH)2D3 positively stimulated development of these cells after 8 days (101 +/- 3 cells per well, n = 74). No osteoclast-like cells were found when 1,25-(OH)2D3 was added for the first 4 days followed by 4 days more with no treatment. PGE2 (1 microM) as a single agent added during the last 4 days of culture was not able to recruit osteoclast-like cells. However, cultures exposed to 1,25-(OH)2D3 during the first 4 days and 1 microM PGE2 during the second 4 days developed osteoclast-like cells at 8 days [66 +/- 8% of the formation seen with 1,25-(OH)2D3 alone, p less than 0.05]. Dibutyryl cAMP (1 microM to 3 mM) was also not effective used as a single agent, but was able to stimulate formation of TRAP-positive multinuclear cells when 1,25-(OH)2D3 preceded its addition to culture medium. cAMP analogs therefore mimicked the effect of 1 microM PGE2, but these experiments do not allow us to assign the PGE2 action entirely to activation of cAMP second messenger.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Radiation therapy as a treatment for benign lymphoepithelial parotid cysts in patients infected with human immunodeficiency virus-1.

Patients who are infected with the human immunodeficiency virus (HIV) may develop benign lymphoepithelial cysts within the parotid gland that cause severe facial deformity. Standard treatment for this disorder has been superficial parotidectomy, repeated fine-needle aspirations or observation alone. These approaches are unsatisfactory because elective surgery in immunocompromised patients should be avoided, the cysts recur soon after aspiration, and observation alone for a treatable deforming facial process is unacceptable. Radiotherapy's proven effectiveness in treating other benign disorders of the parotid gland led us to evaluate its usefulness as a treatment for this disorder. Eight patients with parotid enlargement, who were seropositive for HIV, received 8-10 Gy to the parotids in 1 week. Five patients had complete response and three patients had partial response. All were very satisfied with the cosmetic result. Treatment-related toxicity was well tolerated and consisted of mild xerostomia and transient taste loss. In all cases, these side effects resolved within 1 month. Radiation therapy thus appears to be an effective and well-tolerated treatment for AIDS-related parotid enlargement.

Adult↗
PubMed1992

Popliteal-to-distal bypass for limb-threatening ischemia.

In a subset of patients requiring lower extremity revascularization, the popliteal artery may be used for inflow, thereby minimizing dissection and the length of vein required for bypass. This retrospective study was done to define the risks and benefits of arterial reconstruction in a population of patients having popliteal-to-distal bypass procedures. Between 1986 and 1990, 32 surgical procedures were performed on 29 patients. The patient's ages ranged from 46 to 86 years, with a mean age of 68 years. Twenty-four of 29 (83%) were men and 19 of the 29 (66%) had diabetes. Most patients had multiple indications for surgical intervention, and these included rest pain (54%), nonhealing ulcers (64%), and gangrene (29%). Arterial bypass with use of the popliteal artery for the proximal anastomosis was performed with in situ saphenous vein (50%), reversed saphenous vein (41%), and orthograde autologous vein (9%). Distal anastomoses were to the posterior tibial artery in 11 bypasses (33%), the peroneal artery in 10 (30%), the anterior tibial artery in two (6%), and the dorsal pedal artery in 10 (30%). Two deaths occurred in the perioperative period for an operative mortality rate of 6.9%. With use of life-table analysis, the cumulative graft patency rate was 97% at 1 year, 97% at 2 years, and 63.5% at 4 years. The overall cumulative limb salvage rate was 90.1% at 1 year, 90.1% at 2 years, and 78.8% at 4 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

A phase II study of intravenous 6-thioguanine (NSC-752) in advanced colorectal carcinoma.

Fifteen patients with advanced measurable colorectal carcinoma were treated with intravenous 6-thioguanine (6-TG) at a dosage of 55 mg/m2 for 5 consecutive days every 5 weeks. Only one patient had received prior adjuvant chemotherapy. No responses were detected, and eight patients had stable disease for a medium duration of three treatment cycles. Toxicity was tolerable. We conclude that 6-TG given by this dosage schedule is ineffective in treating metastatic colorectal carcinoma.

Adult↗
PubMed1992

Enhanced color flow imaging of breast cancer vasculature: continuous wave Doppler and three-dimensional display.

Two methods of potentially improving the detection and assessment of breast cancer vasculature by color flow Doppler ultrasonography were studied. Use of continuous wave (CW) Doppler imaging was one method evaluated by a comparison of system sensitivity to small vessel flow by continuous wave and pulsed Doppler methods. The second technique demonstrated color flow image acquisition and three-dimensional (3D) display. Six breast cancer patients were examined with both a color flow pulsed system and a CW Doppler system employing a hand-held transmitter-receiver pair with crossed-beam patterns. The CW unit consistently revealed more regions of tumor flow and multidirectional flow. Good 3D displays were achieved on larger pulsatile vessels, from images obtained during systole and selected for minimal noise.

Adenocarcinoma↗
PubMed1992

Humoral and cell surface interactions during gamma-irradiation leukemogenesis in vitro.

Gamma-irradiation of plateau phase cultures of the clonal murine bone marrow stromal cell line D2XRII followed by cocultivation of a clonal interleukin 3 (IL-3) (granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent hematopoietic progenitor cell line FDC-P1JL26 results in a significant increase in "cobblestone islands" of attachment and emergence of subclonal factor-independent malignant sublines. Biochemical purification of conditioned medium from irradiated D2XRII cells yielded a 75,000-dalton glycoprotein termed leukemogenic stromal factor (LSF) that was neutralized by a polyclonal antiserum to murine macrophage colony-stimulating factor (M-CSF). A monoclonal antibody to the murine M-CSF receptor (c-fms) neutralized the biological activity of this molecule in a manner comparable to its effect on recombinant human or murine M-CSF. FDC-P1JL26 parent cells were positive for Ly5, MEL-14, mGR, VLA-4, PGP-1 (CD44), and Thy1.2. After culture in LSF, Thy1.2, MEL-14, and mGR became undetectable; however, significant cell surface MAC-1 antigen and c-fms (M-CSF receptor) were expressed. Neither line was positive for Ly6, Ly22, I-CAM-1, or B220 antigen. LSF-precultured FDC-P1JL26 cells transferred as single cells to microwell culture with 5000-cGy-irradiated D2XRII cells revealed a 60-fold increase in frequency of cobblestone island formation and evolution of factor-independent subclones compared to the parent line. Both parent and LSF-precultured cells became factor independent at a 100-fold lower frequency if kept in suspension in LSF in the absence of stromal cells. Antiserum to M-CSF or monoclonal antibody to the murine M-CSF receptor (c-fms) did not inhibit or displace cobblestone island formation by either clone of FDC-P1 on irradiated stromal cells indicating a mechanism of binding not involving the M-CSF receptor. However, anti-serum to the M-CSF receptor inhibited growth of one factor-independent subclone. In separate studies, a subclone of IL-3-dependent 32Dc13 cells, expressing the transfected murine c-fms protooncogene but not the parent 32Dc13 cell line or another subclone expressing the transfected gene for the human M-CSF receptor, showed adherence and became factor independent when cocultivated with irradiated D2XRII stromal cells. Thus, irradiated stromal cells bind M-CSF receptor-positive hematopoietic progenitor cells and induce c-fms-dependent factor-independent tumorigenic subclones. The cellular interactions in this model may be relevant to gamma-irradiation leukemogenesis in vivo.

Animals↗
PubMed1991

Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms.

Forty-five patients with metastatic neuroendocrine tumors were treated with a regimen of etoposide 130 mg/m2/d for 3 days plus cisplatin 45 mg/m2/d on days 2 and 3. Both drugs were given by continuous intravenous infusion. Among 27 patients with well-differentiated carcinoid tumors or islet cell carcinomas, only two partial objective tumor regressions were observed (7%). Among 18 patients prospectively classified as having anaplastic neuroendocrine carcinomas, however, there were nine partial regressions and three complete regressions, an overall regression rate of 67%. For anaplastic disease, the median duration of regression was 8 months (range to 21 months). Tumor response was unrelated to primary site, endocrine hyperfunction, or prior therapy experience. The median survival of all patients with anaplastic tumors was 19 months; this seemed favorable when considering the small experiences with these rare tumors reported in the literature. Toxicity, which was severe for most patients, consisted primarily of vomiting, leukopenia, thrombocytopenia, anemia, alopecia, and neuropathy. The anaplastic neuroendocrine tumor is strongly responsive to therapy with combined etoposide and cisplatin. Patients with undifferentiated carcinomas, originating in typical neuroendocrine tumor sites (small and large bowel, pancreas, and stomach) or of unknown origin, who have consistent histologic findings by light microscopy should be evaluated for this possibility with appropriate immune staining or electron microscopy.

Adenoma, Islet Cell↗
PubMed1991

A study of cyproheptadine in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndrome.

Sixteen patients with metastatic neuroendocrine tumors and the malignant carcinoid syndrome were treated with cyproheptadine (Periactin, Merck, Sharp & Dohme, West Point, PA) at maximum tolerable doses that ranged from 12 to 48 mg daily. Usual side effects were mild sedation and dry mouth, but three patients found it impossible to sustain treatment due to nausea and vomiting. Most patients had significant relief of diarrhea, frequently associated with weight gain. Relief of flushing was uncommon. The therapeutic benefit produced by cyproheptadine would appear to be a peripheral effect because 5-hydroxyindoleacetic acid (5-HIAA) excretion in these patients was not reduced. Although there have been case reports of objective tumor regression with cyproheptadine therapy, this was not observed in any of these 16 patients. Cyproheptadine would appear to be a useful therapeutic tool for the management of diarrhea associated with the malignant carcinoid syndrome. An appropriate initial total daily dose is 0.4 mg/kg divided in three fractions with prompt modification to produce minimal and tolerable side effects.

Adult↗
PubMed1991

Regulation of complement 5a receptor expression in U937 cells by phorbol ester.

Receptors for the anaphylactic portion of complement, C5a, are not initially expressed in the monoblastic U937 cell line, but appear as the cell is induced to differentiate by the synergistic actions of 1,25(OH)2D and cyclic adenosine monophosphate (cAMP). Phorbol myristate acetate (PMA), which activates the protein kinase C pathway (PKC), does not cause C5a receptor (C5aR) expression when used as a single agent. The induction of C5aR by the synergistic actions of 1,25(OH)2D and cAMP, however, can be augmented as much as 180% by the addition of PMA. C5aR arising in cells exposed to 1,25(OH)2D and 8,4-chlorophenylthio-cAMP have an affinity constant of about 0.4 nM as assessed by cold competition analysis. We show here that when phorbol augmentation of receptor number occurs, the affinity constant is increased by 3.6-fold. In an effort to ascertain whether the change in C5aR Kd involved a PKC-dependent event we examined whether 5-60 min exposure of C5aR-positive cells to PMA would change C5aR Kd. Acutely, PMA caused a downregulation of receptor binding with decreases in apparent receptor number out of proportion to changes in Kd. One hundred nanomolar PMA, which effects nearly complete translocation of PKC to the membrane, consistently caused a 70-90% decrease in C5a surface binding. This downregulation was proportional to PMA dose and exposure time. Micromolar concentrations of the microtubule depolymerizing agents colchicine and vinblastine caused a less drastic downregulation, about 50% of the maximal phorbol effect. Our data suggest that activation of the PKC system might acutely limit the macrophage's ability to respond to C5a; chronically, phorbols upregulate receptor expression, most likely through positive effects on C5aR gene expression.

Calcitriol↗
PubMed1991

Phase I-II study of pibenzimol hydrochloride (NSC 322921) in advanced pancreatic carcinoma.

Pibenzimol is a fluorescent molecule known to bind to double stranded DNA. It also induces prolongation of the G2 phase of the cell cycle, inhibition of DNA replication and cessation of the growth of some cells in late S phase after DNA content has been doubled. It has been shown to increase the life span of mice bearing intraperitoneally implanted L1210 and P388 leukemia. These factors coupled with the affinity of pibenzimol for pancreatic tissue led us to conduct a phase I-II trial of pibenzimol hydrochloride in patients with advanced pancreatic cancer. Twenty-six patients were treated with a five day continuous infusion of pibenzimol at a dose ranging from 6-28 mg/m2/d. There were no treatment related deaths. Major toxicity was hyperglycemia which was self-limited. No objective responses were noted.

Adult↗
PubMed1991

Comparison of local signs and symptoms after the insertion of Norplant implants with and without a scalpel.

The study compares NORPLANT subdermal implants acceptors enrolled randomly for two different insertion procedures. One group (420 women) received the implants with the use of a scalpel according to the manufacturer's instructions. The other group (423 women) received the implant without an incision, directly through a sharpened trocar. The local signs and symptoms were observed at 7 and 30 days after insertion. Pain, tenderness, edema/swelling, ecchymosis and defective scar were considered. Complication rates were low and no significant differences were found between the two procedures. Based on the data of this study, we recommend inserting NORPLANT implants without the use of a scalpel.

Drug Administration Routes↗