PubMed Health⌕ Search

Biomedical subjects

G M Mavligit

Publications and source records attributed to G M Mavligit.

At least 37 records · Page 2Linked to original sources
PubMed1987

Adjuvant perioperative hepatic arterial mitomycin C and floxuridine combined with surgical resection of metastatic colorectal cancer in the liver.

Twenty patients with colon cancer metastatic to the liver underwent successful hepatic resection and adjuvant perioperative therapy that included hepatic arterial mitomycin C and floxuridine (FUDR). The median survival for all 20 patients was 51 months: 10 are still alive with a median postoperative follow-up of 49 months; 6 are disease-free with a median postoperative follow-up of 43 months. Among 10 patients in whom the surgical margins of the specimen contained tumor cells, the median survival was 52 months. This survival was comparable to that among 10 patients in whom the surgical margins were tumor free (P = 0.22). Neither the number of metastatic liver deposits nor the disease-free interval between the primary diagnosis of colorectal carcinoma and the development of liver metastases significantly affected survival. A transient chemical hepatitis which resolved before the next scheduled treatment was associated with 50% of arterial chemotherapy cycles (approximately 70% of the patients). Gastric or duodenal ulcerations occurred in 23% of the patients. Surgical complications were either pulmonary such as pleural effusion or atelectasis, or wound infections and subphrenic abscesses. Although these results compare favorably with the results in previously published series, this aggressive adjuvant chemotherapy appears to be particularly justified in patients with tumor positive surgical margins or those with multiple tumor masses and, therefore, are characterized by a poor prognosis.

Adult↗
PubMed1987

Immunologic effects of cimetidine: potential uses.

Suppressor T lymphocytes play a major regulatory role in the function of the immune system. Since the discovery of histamine (H2) receptors on the surface of these immune cells, studies have demonstrated that cimetidine diminishes the effect of suppressor T cells in both cellular- and humoral-mediated (antibody) immune reactions. Preliminary clinical results demonstrate that cimetidine has a beneficial effect on a variety of immune functions. An antineoplastic effect among tumor-bearing animals has also been found, suggesting the drug may be effective against certain human cancers, probably as an immune potentiator. Cimetidine has been used in the treatment of human cancer in combination with interferon or coumarin and as a single agent. Modest tumor response rates have been observed. The finding that cimetidine accelerates healing of herpesvirus infections is intriguing. These encouraging, albeit preliminary, results emphasize the need for additional studies on the drug's antiviral properties.

Cimetidine↗
PubMed1987

Sensitivity and resistance to chemotherapy in acute leukemia: correlation with in vitro drug uptake and lack of potentiation by verapamil.

The calcium channel blocker verapamil has been reported to circumvent acquired resistance to different antitumor agents in tumor cell lines in vitro. We studied its effect on in vitro uptake of m-AMSA and adriamycin in fresh leukemic cells from 11 leukemia patients. Six previously untreated patients were sensitive to m-AMSA (obtained remission). Four were clinically resistant to m-AMSA, and two of these also to adriamycin. Leukemic cells were incubated in pharmacological doses of 14C-adriamycin and 14C-m-AMSA for up to 2 h. Samples were supplemented with verapamil (750 ng ml-1) 30 min prior to the addition of m-AMSA or adriamycin. Drug uptake was measured at 15 min intervals up to 2 h and drug retention was measured during 30 min after the end of incubation, following washing and resuspension in fresh medium without cytotoxic drugs. Adriamycin uptake was the same irrespective of verapamil in all four cell samples, two of which were derived from patients resistant to adriamycin. The cellular m-AMSA uptake was higher in cells from clinically sensitive than from resistant patients (510 +/- 155 fg cell-1 vs 275 +/- 125 fg cell-1; P less than 0.01). Retention of m-AMSA 30 min after incubation was higher in cells from sensitive compared to resistant patients (187 +/- 78 vs 25 +/- 7; P less than 0.05). Our data suggest: (1) in vitro uptake greater than or equal to 350 fg cell-1 and subsequent retention greater than 75 fg cell-1 correlate to clinical sensitivity to the drug; and (2) neither m-AMSA nor adriamycin uptake could be significantly increased by verapamil.

Acute Disease↗
PubMed1987

Gastroduodenal mucosal injury during hepatic arterial infusion of chemotherapeutic agents. Lack of cytoprotection by prostaglandin E1 analogue.

Eighteen colorectal cancer patients with liver metastases receiving hepatic arterial infusion of chemotherapeutic agents (mitomycin-C + 5-FUDR) were randomized to receive misoprostol (a prostaglandin E1 analogue) or placebo as a mode of cytoprotection against inadvertent gastroduodenal mucosal injury. Four of 10 patients on misoprostol and 3 of 8 patients on placebo developed gastroduodenal mucosal injury (p greater than 0.1), which was confirmed by endoscopy. Significant tumor responses to chemotherapy were equally distributed between the two groups. Although our sample size was small and type II error (false-negative trial) cannot be excluded, these data strongly suggest that prophylaxis with misoprostol does not prevent the acute gastroduodenal mucosal injury associated with hepatic arterial infusion of chemotherapeutic agents.

Alprostadil↗
PubMed1987

Abrogation of the local xenogeneic graft versus host reaction by preinjection of cimetidine to the immunosuppressed host rats: an experimental model for testing preclinical immunorestorative activity in vivo.

The local xenogeneic graft-vs-host reaction (XGVHR) is mediated by competent T lymphocytes. It was effectively used as a practical bioassay to assess the in vitro immunomodulatory effects of several drugs on cells derived from cancer patients. A modified version of the XGVHR model was recently developed primarily for preclinical evaluation of in vivo immunorestoration induced by experimental biological response modifiers (BRMs). A well-defined biological response modifier, cimetidine, was injected into Cytoxan-primed rats prior to their inoculation with xenogeneic human mononuclear cells. The cimetidine treatment induced a partial abrogation of the immunosuppressive effect of Cytoxan as manifested by a significant decline in the volume of the XGVHR from 115.23 +/- 15.72 mm3 (positive control) to 67.3 +/- 11.41 mm3 (P less than 0.01). This abrogation of Cytoxan-induced immunosuppression by cimetidine was incomplete since the XGVHR without Cytoxan (negative control, saline only) was still significantly lower (45.12 +/- 4.55 mm3; P less than 0.01). The effect of cimetidine injection in vivo appeared to be dose dependent and did not exhibit any nonspecific toxic effect to the mononuclear cell inoculum. These results indicate that the model can serve as a useful tool in the preclinical evaluation of newly developed immunorestorative biological response modifiers.

Animals↗
PubMed1986

Treatment of hepatic metastases in ocular melanoma. Embolization of the hepatic artery with polyvinyl sponge and cisplatin.

Patients with ocular melanoma have a high incidence of hepatic metastases, which primarily determine their length of survival. In an attempt to control the neoplastic disease in the liver, embolization of the hepatic artery with a combination of polyvinyl sponge (Ivalon) and a suspension of cisplatin was performed in two patients with hepatic metastases from ocular melanoma. Dramatic regression of the hepatic metastases, lasting 19 and six months, occurred in these two patients after one or two such treatments. Our preliminary, albeit successful, experience with this therapeutic approach suggests that it may offer relatively prolonged periods of remission and warrants further investigation.

Adult↗
PubMed1986

Hepatic arterial infusion with floxuridine and cisplatin: overriding importance of antitumor effect versus degree of tumor burden as determinants of survival among patients with colorectal cancer.

Cisplatin (CDDP) was combined with floxuridine (FUDR) and delivered into the hepatic arteries of 29 patients as induction therapy for colorectal cancer metastatic to the liver. Mitomycin C and FUDR combination was substituted after progression or when response had peaked. Chemotherapy was delivered with an Infusaid pump (Infusaid Corp; Norwood, Mass; 14 patients), Medtronic programmable drug administration device (Medtronic, Inc, Minneapolis; two patients), or percutaneously placed catheters (13 patients). Complete disappearance of liver metastases was observed in four patients and 11 additional patients had a partial remission as determined by computed tomography (CT) scan and substantiated at times by angiography, for a total response rate of 52%. Response as determined by imaging techniques coincided with a concurrent decrease in carcinoembryonic antigen (CEA) and improvement in performance status. The severity of tumor burden was correlated with the response to therapy and survival. Among those patients who responded to arterial chemotherapy, differences in disease severity did not significantly influence survival. Median survival among responders with greater than 25% liver replacement by tumor was 14 months (P = .28), compared with 28 months for those patients with less than 25% liver replacement. In contrast, differences in tumor burden significantly affected survival among patients who failed to respond to chemotherapy; median survival among nonresponding patients with greater than 25% liver replacement was 4 months, compared with 8 months for those who had less than 25% liver replacement (P = .01). The presence of minimal extrahepatic disease at the time of initiation of intraarterial treatment did not seem to have a significant detrimental effect on survival. The study suggests that hepatic tumor response to arterial administration of CDDP and FUDR and mitomycin C and FUDR is clinically significant because it overrides the effect of tumor burden on survival among patients who have colorectal cancer with liver metastases and may offer effective palliation.

Adult↗
PubMed1986

Modulation in vitro of immune parameters in homosexual males with the preclinical complex of symptoms related to acquired immune deficiency syndrome by azimexon.

In search of potential therapeutic agents for the acquired immunodeficiency syndrome (AIDS) among homosexual males, we studied in vitro the immunorestorative effect of azimexon in patients with this syndrome. Since a reduction in the ratio between helper inductor and suppressor/cytotoxic T-cell subsets (OKT-4/OKT-8) seems to be the hallmark of the syndrome, we measured azimexon-induced numerical changes in T-cell subsets and correlated them with changes in a simultaneously tested T-cell function as measured by the xenogeneic local graft-versus-host reaction (GVHR). Following incubation of peripheral blood mononuclear cells from 10 homosexual subjects with 10 micrograms/ml of azimexon at 37 degrees C for 1 h, the median number of T cells defined by the OKT-8 phenotype declined from 0.6 X 10(3) to 0.33 X 10(3)/mm3 (p less than 0.02), resulting in an increase in the OKT-4/OKT-8 ratio from 0.65 to 1.37 (p less than 0.01). There were no numerical changes in T cells defined by OKT-3 and OKT-4 phenotypes. Similar decreases in OKT-8-defined T cell occurred among eight heterosexual controls. The restoration of the OKT-4/OKT-8 ratio among the homosexual subjects was associated with a significant improvement in their T-cell function. Thus, the median volume of the local GVHR increased from 38.2 to 63.5 mm3 (p less than 0.02). Parallel changes in OKT-4/OKT-8 ratio and changes in local GVHR following incubation with azimexon were observed. These results suggest that azimexon may be an important immunorestorative agent. Clinical trials with this agent in patients with AIDS or its preclinical complex of symptoms seem warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Chronic immune stimulation by sperm alloantigens. Support for the hypothesis that spermatozoa induce immune dysregulation in homosexual males.

Putative, sperm-induced allogeneic immunization was correlated with immune dysregulation in a study of 30 asymptomatic, monogamously paired homosexual males. Evidence for allogeneic immunization existed among 19 of 26 homosexual males who were anal sperm recipients. No evidence for any form of alloimmunization was found in four exclusive sperm donors. Immune dysregulation in the form of a reduced effector/suppressor T-cell ratio (Te/Ts less than 1.0) was exclusively documented in eight anal-sperm-recipient homosexual males, five of whom also manifested evidence for allogeneic immunization. In three of those, immune dysregulation was further manifested by functional T-cell deficiency in the form of a subnormal (less than 50 cu mm) local graft-v-host reaction. Similar evidence for alloimmunization was associated with a reduced Te/Ts ratio (0.85) in the female of a heterosexual couple who routinely practiced anal intercourse. Based on these findings, we suggest that chronic, repeated exposure to sperm during anal intercourse results in a high frequency of allogeneic immunization and may play an important role in the development of acquired immune dysregulation among homosexual males.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Clinical pharmacology of 99mTc-labeled liposomes in patients with cancer.

The pharmacokinetics, organ distribution, and 24-hr urinary excretion of negatively charged 99mTc-labeled multilamellar liposomes, composed of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol in a 7:3 molar ratio, were studied in seven patients with cancer. The radiolabeled liposomes were administered i.v. in three doses: 150 mg/sq m of body surface area; 300 mg/sq m; and 450 mg/sq m of lipid. The dose of 99mTc was 4.8 to 7.6 mCi per patient. The plasma disappearance curve was biphasic (half-life alpha = 5.53 min, half-life beta = 289 min), suggesting a two-compartmental model of distribution. The calculated volume of distribution indicated considerable tissue retention of liposomes. This was confirmed by body imaging. Twenty-four hr after injection, liposomes were localized in organs rich in reticuloendothelial cells, i.e., liver [44.5 +/- 9.1% (S.E.)], spleen [25.5 +/- 7.7%], lung [14.5 +/- 4.9%], and bone marrow. Although the hepatic uptake accounted for more than 40% of the total uptake, the spleen retained liposomes at a higher density. Cumulative urinary excretion of radioactivity was 13.4 +/- 1.5% over 24 hr. Liposome administration was safe and devoid of any adverse side effects. The results provide a basis for the use of liposomes as potential target-specific and safe drug carriers in the treatment of pathological conditions that involve organs rich in reticuloendothelial cells.

Adult↗
PubMed1983

Colorectal carcinoma. Evidence for circulating CEA-anti-CEA complexes.

Significant increments in measurable plasma CEA were effected by 2.5 M MgCl2 elution from putative circulating CEA-anti-CEA complexes in 11 of 15 patients with disseminated colorectal cancer and in five of ten patients with a high probability of having subclinical disease (Dukes'C category). Following 2.5 M MgCl2 elution, IgG from a patient with a high CEA increment effected a higher specific binding to 125I-CEA than a similar IgG eluate from a patient with a negligible increment in measurable CEA. These data suggest that CEA is autoimmunogenic and may result in circulating CEA-anti-CEA complex formation. The clinical implications of such complexes in the diagnosis and monitoring of patients with colorectal cancer remain to be determined.

Antigen-Antibody Complex↗
PubMed1983

Immune restoration and/or augmentation of local graft versus host reaction by traditional Chinese medicinal herbs.

The in vitro restorative effect of aqueous extracts from two traditional Chinese medicinal herbs were studied in 19 cancer patients and in 15 normal healthy donors. Using the local graft versus host (GVH) reaction as a test assay for T-cell function, the extract from astragalus membranaceus (10 microgram/ml) induced a restored reaction in nine of ten patients with an increase in local GVH reaction from 18.2 plus/minus 15.8 mm3 to 112.9 plus/minus 94.2 mm3 (P less than 0.01). The extract from ligustrum lucidum, likewise effected an immune restoration in nine of 13 cancer patients with an increase in local GVH reaction from 32.3 plus/minus 36.1 mm3 to 118 plus/minus 104.9 mm3 (P less than 0.01). This degree of immune restoration appears to be complete as it equals the local GVH reaction observed among untreated mononuclear cells from normal healthy donors (82.8 plus/minus 41.1 mm3, P greater than 0.1). These results suggest that both extracts of the traditional Chinese medicinal herbs contain potent immune stimulants which may provide the rational basis for their therapeutic use as biological response modifiers.

Adjuvants, Immunologic↗
PubMed1983

Hepatic arterial chemotherapy and occlusion for palliation of primary hepatocellular and unknown primary neoplasms in the liver.

Eighteen patients with malignant liver disease were treated with hepatic arterial infusion (HAI) of floxuridine (FUDR), Adriamycin (doxorubicin), and mitomycin C (FUDRAM). Twelve of the patients had primary hepatocellular carcinoma and six had metastatic liver carcinoma originating from an unknown primary site. One complete remission and seven partial remissions (greater than or equal to 50% reduction in tumor size) were observed among 12 hepatocellular cancer patients, while only one partial remission was achieved among six patients with unknown primary liver neoplasms. When arterial occlusion was added to HAI of FUDRAM, a prolongation of median survival to 14 months as opposed to six months in patients with an intact arterial tree was observed (P = 0.02). Arterial occlusion had its effect on survival particularly among patients who failed to respond to HAI of FUDRAM. Thus, among nonresponding patients, the addition of arterial occlusion resulted in a median survival of 10.5 months while median survival in those without arterial occlusion was six months (P = 0.08). With procedure-related morbidity being minimal, we conclude that arterially administered FUDRAM offers a notable palliation to patients with primary hepatocellular carcinoma. In patients with unknown primary liver neoplasms and those with hepatocellular cancer who fail HAI of FUDRAM, arterial occlusion can offer additional palliation.

Adult↗
PubMed1983

Leukocyte interferon-induced myeloid cytoreduction in chronic myelogenous leukemia.

We investigated the antiproliferative effect of partially purified human leukocyte interferon (HuIFN-alpha) given in a dose of 9-15 X 10(6) U daily by intramuscular injection to 7 patients with chronic myelogenous leukemia (CML). Hematologic remission of the disease was obtained in 5 patients. Among the responding patients, the mean white blood cell count decreased from 97.4 X 10(3)/cu mm (range from 35 X 10(3)/cu mm to 239 X 10(3)/cu mm) to 4.2 X 10(2)/cu mm (range from 3.0 X 10(3) to 7.9 X 10(3) cu/mm). Parallel reduction occurred in serum B12, from a mean of 1,435 pg/ml to a mean of 726 pg/ml, and lactate dehydrogenase levels, from a mean of 325 mU/ml to 112 mU/ml. Enlarged spleens decreased in 3 of 3 patients. The 5 responding patients have been maintained on HuIFN-alpha, 3 X 10(6) U daily or every other day, for 6+-35+ wk.

Chromosome Aberrations↗
PubMed1983

Characterization of human effector and suppressor T cells by their activity in mixed lymphocyte reaction and by monoclonal antibody phenotyping.

Human T effector and T suppressor cell subpopulations which are functionally operative in the local graft-versus-host reaction were enriched and separated on the basis of their respective ability to form (or not to form) rosettes with sheep red blood cells in the presence of theophylline. These subpopulations were then tested as stimulators and as responders in the allogeneic mixed lymphocyte reaction assay against the same mononuclear cells. Among 18 normal donors, theophylline resistant cells responded more vigorously to mononuclear cells (SI, 9.9 +/- 9.8) than theophylline-sensitive cells (6.7 +/- 5.7, p less than 0.08). In contrast, T-effector cells were poorer stimulators of the same MNC (SI, 4.0 +/- 5.6) when compared to the stimulatory capacity of T suppressor cells (SI, 7.1 +/- 9.8, p less than 0.05). Similar studies among 14 patients with disseminated cancer showed the same, but more pronounced differences. Thus, the theophylline-resistant T effector cells were vigorous responders (SI, 14.7 +/- 10.0) compared to the weak response of the theophylline-sensitive T suppressor cells to the same mononuclear cells (SI, 3.4 +/- 1.8, p less than 0.01). Again, in contrast, T effector cells stimulated mononuclear cells poorly (SI, 1.0 +/- 0.5) while T suppressor cells induced a weak but significant stimulation (SI, 3.2 +/- 2.1, p less than 0.05). Phenotyping of these two functionally distinct subpopulations with monoclonal antibodies to subsets of T cells (Leu I, II, III) and for the HLA-DR antigen (OKIal) showed no enrichment for any of the phenotypes as defined by these antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1983

Preliminary observations on the effects of the Chinese medicinal herbs Astragalus membranaceus and Ligustrum lucidum on lymphocyte blastogenic responses.

The biological effects of extracts of two Chinese medicinal herbs, Astragalus membranaceus and Ligustrum lucidum, on in vitro lymphocyte blastogenesis were assessed. Aqueous extracts augmented the spontaneous [3H]thymidine incorporation in the mononuclear cells (MNC) of 14 normal subjects from 273.0 to 609.3 counts per minute (cpm) and 252.9 to 656.9 cpm for the two herbs, respectively. The stimulation indices were 2.4 and 3.1, respectively (p less than 0.001). They also augmented the proliferation of normal subjects' lymphocytes induced by suboptimal concentrations of phytohemagglutinin (PHA) from 5084.6 to 23,398.3 and 221.7 to 24,132.8 cpm, of concanavalin A (con A) from 4046.5 to 15,661.5 and 677.6 to 14,644.6 cpm, and of pokeweed mitogen (PWM) from 4377.9 to 24,405.6 and 322.7 to 11,730.0 cpm, respectively (p less than 0.00). Herb extracts augmented the PHA responses of the MNC from 14 cancer patients significantly (p less than 0.01 and p less than 0.05, respectively). Extracts of L. lucidum also augmented the con A response of patients (p less than 0.05). The augmenting effect of the herbs on the PHA, con A, and PWM responses was dose dependent, and proliferation was inhibited at higher concentrations. The optimal concentration for stimulating the MNC of cancer patients was 100 micrograms/ml, compared to 10 micrograms/ml for the MNC of normal donors. MNC of seven patients depressed the mitogen responses of normal cells in a co-culture system. This was partially abrogated in five by preincubating the patients' cells in herb extracts for 45 min or by irradiation of the patients' cells. These results suggest that the herb extracts contain immunomodulatory components which may be useful in the immunotherapy of disease.

Adult↗