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Biomedical subjects

P McLaughlin

Publications and source records attributed to P McLaughlin.

At least 163 records · Page 9Linked to original sources
PubMed1988

Frequent nonrandom chromosome abnormalities in 27 patients with untreated large cell lymphoma and immunoblastic lymphoma.

Fresh tumor samples from 27 patients with large cell lymphoma, either previously untreated (26 patients) or minimally treated (one patient), were processed for cytogenetic studies. Cytogenetic abnormalities were observed in all patients, most commonly in chromosomes 1, 3, 7, 12, 14, 17, and 18. Nine chromosomal breakpoints appeared frequently: 14q32 in 14 instances; 18q21 in seven; 9p13-21, 17p11-13, and 3q21-23 in six each; 1p11-21 in five instances; 1p36 in four; and 2p21-23 in three. The most common structural abnormalities were t(14;18)(q32;q21) in seven patients (26%) and 17p- in six (22%). The presence of 17p- was associated with a significantly higher proliferative capacity as manifested by the percentage of S phase = 22% versus 11% for cases without 17p-(P less than 0.05). Trisomy 12, typical of small lymphocytic lymphoma, was seen in five patients in this series, all of whom had diffuse large cell lymphoma; frequently, it appeared simultaneously with t(14;18). The two patients with immunoblastic lymphoma of B-cell type had an abnormality involving chromosome 2p21-23. Deletions in the long arm of chromosome 6, previously described as typical of diffuse large cell lymphoma and B-cell immunoblastic lymphoma were observed infrequently in this series. However, this abnormality has been present in 50% of patients with large cell lymphoma previously exposed to therapy, suggesting that it may be related to effects of chemotherapy or to clonal evolution.

Chromosome Aberrations↗
PubMed1988

Effects of anesthetic induction on myocardial function and metabolism: a comparison of fentanyl, sufentanil and alfentanil.

Anaesthetic induction may induce myocardial ischaemia. A prospective randomized trial was instituted to compare the effect on ventricular function and myocardial metabolism of induction with fentanyl (FEN) or its analogues sufentanil (SUF) or alfentanil (ALF) in 96 patients undergoing elective coronary artery bypass grafting (CABG). Haemodynamic, metabolic (coronary sinus oxygen and lactate extraction) and gated ventriculographic measurements were made awake pre-induction (PRE), after induction (IND) and after intubation (INT). Induction was performed with FEN 75 micrograms.kg-1, SUF 15 micrograms.kg-1 or ALF 125 micrograms.kg-1 and metocurine. Fentanyl induction was associated with the greatest stability of mean arterial pressure (MAP), cardiac performance, and systolic function without associated myocardial lactate production. SUF produced the greatest depression of systolic function (p less than 0.05) but without haemodynamic instability or myocardial lactate production in all but one patient. Induction with ALF produced the greatest reduction in MAP (p less than 0.05) associated with the greatest decrease in diastolic compliance (p less than 0.05) and 50 per cent incidence of myocardial lactate production (p less than 0.05) with no significant change in coronary blood flow or myocardial oxygen consumption.

Alfentanil↗
PubMed1988

Endogenous opioids and the growth regulation of a neural tumor.

Endogenous opioid systems (endogenous opioids and their receptors) are known to participate in the regulation of tumor growth. The present study was conducted to examine whether [Met5]-enkephalin influences the growth of transplanted neuroblastoma, and to explore the role of other opioid peptides in carcinogenesis. A/Jax mice were inoculated with 10(6) S20Y cells and received daily injections of [Met5]-enkephalin. Dosages of 0.5 to 30 mg/kg delayed tumor appearance and prolonged survival of these mice; antitumor effects were blocked by concomitant injections of naloxone. Daily administration (10 mg/kg) of [Leu5]-enkephalin had no effect on neurotumor growth. [D-Ala2, D-Leu5]-enkephalin and ethylketocyclazocine, ligands selective for delta and kappa receptors, respectively, also did not influence neuro-oncogenesis. These results demonstrated the potent growth inhibiting effects of the naturally occurring opioid pentapeptide, [Met5]-enkephalin, and substantiate reports identifying and characterizing an opioid receptor (i.e., zeta) for which [Met5]-enkephalin is the most potent ligand.

Animals↗
PubMed1988

The adjuvant role of two cycles of MOPP and low-dose lung irradiation in stage IA through IIB Hodgkin's disease: preliminary results.

Fifty-eight laparotomy-staged I and II patients with upper torso presentations of Hodgkin's disease and 8 patients with lymphangiogram-staged lower torso disease were treated with radiotherapy alone or with 2 cycles of MOPP and radiotherapy. Patients with upper torso disease with either no mediastinal or only small mediastinal disease without hilar involvement and with no "B" symptoms were treated with mantle radiotherapy alone. Patients with large mediastinal masses or hilar disease were treated with 2 cycles of MOPP followed by definitive mantle irradiation and low dose lung irradiation. Those for whom "B" symptoms were the only adverse prognostic feature received 2 cycles of MOPP and mantle radiotherapy. Patients with lower torso disease were treated with radiotherapy alone if the disease was limited to the pelvis. Those with more extensive disease received 2 cycles of MOPP prior to radiotherapy. The 4-year survival for all 66 patients was 97%. The corresponding disease-free and freedom from second relapse figures were 77% and 92%. Survival for the patients with unfavorable presentations who received 2 cycles of MOPP and radiotherapy was 100%. It was 92% for the group with favorable presentations who were treated with radiotherapy only.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Results of recent salvage chemotherapy regimens for lymphoma and Hodgkin's disease.

From 1981 to 1983, 208 patients with recurrent or refractory lymphoma were treated with methylglyoxal-bis-guanylhydrazone (methyl-GAG), ifosfamide, methotrexate, etoposide (MIME). The complete remission (CR) rate was 24% and CR plus partial remission (PR) was 60%. Response was higher for aggressive than for indolent cell types. Median duration of CRs was 16.5 months and median survival of all patients was 9 months. In view of the in vitro synergism between cisplatin and high-dose cytarabine, we recently designed the DHAP regimen, which consists of cisplatin, 100 mg/m2 IV over 24 hours; cytarabine, 2 g/m2 IV over two hours every 12 hours for two doses; and dexamethasone, 40 mg orally daily for 4 days. There were 28 of 90 (31%) CRs and 22 of 90 (24%) PRs. Median duration of CR is 15 months; median survival of all patients is 6 months. The major toxicities have been infection (31%) and moderate to severe renal dysfunction (20%). In contrast to MIME, response rates did not differ significantly between aggressive and indolent cell types. A high-dose regimen (CBV) consisting of cyclophosphamide, 6 g/m2; carmustine, 300 mg/m2; and etoposide, 250 mg/m2 daily for 3 days followed by autologous bone marrow transplant (ABMT) has been successfully used to treat 62 patients with Hodgkin's disease recurrent or refractory after mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, dacarbazine (MOPP/ABVD)-like regimens. A CR rate (47%) has been observed; 83% of these CRs remain alive and free of disease with a median follow-up of 19 months. This regimen appears to have curative potential in 40% of all cases and in 60% of cases treated after the first or second relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP).

Ninety patients with progressive recurrent lymphoma were treated with a combination of cisplatin 100 mg/m2 intravenously (IV) by continuous infusion over 24 hours, followed by cytosine arabinoside in two pulses each at a dose of 2 g/m2 given 12 hours apart. Dexamethasone, 40 mg orally or IV, was given on days 1 through 4. Vigorous hydration was reinforced by routine use of mannitol. Treatments were repeated at 3- to 4-week intervals for six to ten courses. Most patients had not achieved complete remission (CR) with prior therapies, which included Adriamycin (all patients) and methotrexate and VP-16 (58 patients). Median patient age was 55 years. Intermediate-grade lymphoma was the most frequent pathologic diagnosis. Seven patients died within two weeks of therapy; of the remaining 83 patients, 28 (34%) or 31% if all patients are considered, achieved CR, and 22 (26.5%) achieved partial remission (PR). Response was evident after the first two cycles of chemotherapy and appeared to be independent of the histopathologic type of lymphoma. To date, only eight of the complete responders have relapsed at a median follow-up of 11 months. The overall 2-year survival in 25%. Further analysis showed that patients with low tumor burden and normal lactic acid dehydrogenase (LDH) had a high CR response rate (67%) and a survival rate of 61% at 2 years. In contrast, patients with both high tumor burden and elevated serum LDH levels had a negligible CR rate, and only 5% are surviving at 1 year. Patients with either high tumor burden with normal LDH or low tumor burden with elevated LDH had an intermediate survival. Myelosuppression-related infection was the most frequent serious complication of this regimen (31%) and the cause of death of ten patients. Acute lysis syndrome was also observed in five patients with high tumor burden and was the cause of death in three of these patients. DHAP has proven to be an effective non-crossresistant regimen for patients with relapsing or refractory lymphoma, particularly for patients who have favorable prognostic characteristics.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Cytogenetic features of Hodgkin's disease suggest possible origin from a lymphocyte.

Surface marker and gene rearrangement data have supported various hypotheses about the origin of the malignant cell in Hodgkin's disease. Cytogenetic data about this disorder, however, are very scanty. To determine if any chromosomal abnormalities that could add further information to this controversial point are present, we studied tumor samples from 49 patients. Abnormal metaphases were obtained in 18 cases. The most common breakpoints were in 11q23, 14q32, 6q11-21, and 8q22-24. These are common breakpoints in lymphoma and raise the possibility that the malignant cell in Hodgkin's disease may be derived from a lymphocyte. The 11q23 breakpoint is also seen in t(4;11) and t(9;11), which is typical of a type of childhood B-cell acute lymphoblastic leukemia characterized by the presence of aberrant myeloid and monocytic markers. Myeloid and monocytic markers are common in Reed-Sternberg cells.

Chromosome Aberrations↗
PubMed1987

A morphologic, immunologic, and cytometric approach to the classification of non-Hodgkin's lymphoma in effusions.

The biologic and clinical heterogeneity of the various subtypes of non-Hodgkin's lymphoma is related to differences in morphologic, immunologic, and kinetic properties. Comprehensive studies characterizing these features in lymphomatous effusion have yet to be reported. We recently studied 27 effusion specimens from 26 patients with clinically suspected or confirmed lymphoma. Wright-Giemsa- and Papanicolaou-stained cytologic preparations, acridine orange nucleic acid flow cytometry, and immunoperoxidase staining of cell suspensions using antibodies to a battery of T and B cell markers were evaluated and compared with prior histologic accessions. Specimens were classified by cytologic characteristics according to the International Working Formulation Scheme and by acridine orange nucleic acid flow cytometry using the parameters of DNA, RNA, and proliferative activity. Correlation of the cytometric and morphologic data demonstrated that with increasing cytologic grade of lymphoma, the proliferative activity increased progressively and distinguished between grades (P less than 0.01). Immunologic studies identified B cell phenotype in 16 specimens, T cell in three, and true histiocytic lymphoma in one; one lymphoma had no cell markers (null cell). Six effusions proved to be inflammatory and reactive according to surface marker studies. Classification by cytologic characteristics showed good correlation with histologic classification performed previously. Immunologic study of cytologic specimens gave results identical to those achieved by frozen-section immunohistologic examination. Thus, immunologic and cytometric parameters can be readily performed on effusion specimens and aid in the diagnosis and classification of lymphomas.

Adult↗
PubMed1987

Paired serum and synovial fluid values of alpha 2-macroglobulin and TIMP in rheumatoid arthritis.

The levels of alpha 2-macroglobulin and tissue inhibitor of metalloproteinases (TIMP) were determined in paired serum and synovial fluid samples from rheumatoid arthritis patients. Serum levels of alpha 2-macroglobulin (mean 1580 +/- 340 mg/l) were always higher than the corresponding synovial fluid although the spread of synovial fluid levels was broad (mean 520 +/- 340 mg/l). Tissue inhibitor of metalloproteinases was always higher in synovial fluid (mean 4.59 +/- 1.8 mg/l) than serum (mean 1.3 +/- 0.39 mg/l) indicating that local synthesis occurred within the joint.

Arthritis, Rheumatoid↗
PubMed1987

Peripheral hepatic arterial embolization with crosslinked collagen fibers.

Hepatic artery embolization with a nonimmunogenic, crosslinked microfibrillar collagen preparation (Angiostat, Collagen for Embolization, Target Therapeutics, Los Angeles, CA) was studied in mongrel dogs. Flow-directed technique was used to achieve complete distal arterial occlusion. Serial liver function evaluation demonstrated marked alterations at 48 to 72 hours, partial correction at one week, and resolution of abnormalities by one month. Restoration of large vessel blood flow was angiographically demonstrable at one week. Follow-up arteriograms showed no persistent arterial occlusion. Collagen was demonstrated in vessels of 20 to 250 micron. Recanalization was achieved by migration of endothelial cells around the collagen, development of a new vascular channel within an endothelial cell cleft, and subsequent complete removal of the collagen over a three- to four-month period. Three months after embolization with a single dose, normal hepatic vascular and tissue anatomy and hepatic function were restored completely. Repeated embolization at two weekly intervals was well tolerated.

Animals↗
PubMed1987

Results of MIME salvage regimen for recurrent or refractory lymphoma.

Based on encouraging results of two previous ifosfamide-VP-16 salvage combinations, methyl-gag was added to ifosfamide, methotrexate, and etoposide (VP-16). This combination is called MIME. A total of 208 patients with recurrent lymphoma were treated with this regimen. Response rates were 24% for complete remission and 36% for partial remission. The MIME regimen was more effective in patients who were treated after being off front-line therapy for longer than 6 months. However, responses were also seen in patients with disease clearly resistant to front-line therapy, suggesting that MIME was at least partially non-cross-resistant with front-line doxorubicin-containing regimens. The 15-month median relapse-free survival of complete responders and the 9-month overall median survival time for all patients treated were both similar to results from previous ifosfamide-VP-16 combination use. This regimen has been effective in the treatment of patients with recurrent or refractory lymphoma, but cannot be considered curative in the majority of cases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

MIME chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide) as treatment for recurrent Hodgkin's disease.

Forty-seven patients with Hodgkin's disease in relapse were treated with MIME combination chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide). All patients had previously received nitrogen mustard, vincristine, prednisone, procarbazine (MOPP) or similar regimens and doxorubicin-containing combinations, and many had received extensive irradiation. Complete remission (CR) occurred in 23%, and was influenced by presence of extranodal disease, hemoglobin, lactic dehydrogenase (LDH), and number of prior relapses. Median survival for all patients was 50 weeks, and was affected adversely by the presence of extranodal disease and the number of prior relapses. Toxicity was significant, including infections (23%), neutropenic fever (34%), and hemorrhagic cystitis (23%), but was related in part to the extent of prior therapy. These results with this novel chemotherapy program in heavily pretreated patients suggest that MIME should be studied in less extensively treated patients and considered as a part of treatment programs for patients with Hodgkin's disease in first relapse.

Adolescent↗
PubMed1987

Stage III follicular lymphoma: durable remissions with a combined chemotherapy-radiotherapy regimen.

From 1975 to 1982, 74 patients with stage III follicular lymphoma were treated with a combined modality protocol which included chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo), and radiotherapy to involved regions. This program resulted in a complete remission (CR) rate of 81%, a 5-year survival of 75%, and 5-year relapse-free survival (RFS) of 52% for all patients. Analysis of potential factors affecting treatment outcome revealed a significantly better CR rate for patients with small cleaved cell type (97%) than for patients with mixed (73%) or large-cell (57%) histologies. The 5-year survival was significantly better for patients with small cleaved (91%) and mixed (84%) cell types than for large cell (40%). In addition, bulky abdominal disease and elevated serum lactate dehydrogenase (LDH) were significant adverse prognostic factors for CR and for survival. Toxicity was moderate. No secondary leukemias have occurred. This combined modality regimen resulted in prolonged remission and potential cure for over half of patients who achieved CR, and is particularly encouraging for those with follicular small cleaved and mixed histologies.

Adult↗
PubMed1987

The gene located at chromosome 18 band q21 is rearranged in uncultured diffuse lymphomas as well as follicular lymphomas.

The karyotypic abnormality t(14;18)(q32;q21) is reported to occur in 75% of follicular lymphomas. This translocation results in the rearrangement of a putative oncogene bcl-2, which resides at chromosome 18 band q21 (the 18q21 gene). Using two human genomic DNA fragments cloned from the chromosome 18 band q21 as probes, we analyzed 65 uncultured human lymphoma samples by the Southern blot technique. The 18q21 gene was rearranged in 18 of 26 (69%) follicular lymphomas, 3 of 5 (60%) follicular lymphomas transformed to large cell lymphomas, 8 of 20 (40%) diffuse large cell lymphomas (DLCLs), and 2 of 7 (29%) small noncleaved cell lymphomas (SNCs). Our analysis detected rearrangement of the 18q21 gene in 10 of 13 (77%) cases in which the t(14;18)(q32;q21) translocation was found by cytogenetic techniques. Our analysis also proved helpful in difficult karyotyping situations: (a) identifying the donor chromosome fragment as chromosome 18 band q21 in 4 of 9 (44%) cases that cytogenetically displayed a 14q+ chromosome of unknown origin, and (b) identifying a rearrangement of chromosome 18 band q21 in 12 of 18 (67%) cases that cytogenetically yielded no cells in metaphase. We also demonstrated three cases of submicroscopic rearrangement of the 18q21 gene. In our studies, patients with DLCLs and rearrangement of the 18q21 gene had a significantly higher incidence of extranodal involvement when compared with patients with DLCLs and no 18q21 gene rearrangement (P = 0.03).

Bone Marrow Cells↗
PubMed1987

Characterization of hematologic malignancies by flow cytometry.

The quantitative assessment of cellular DNA and RNA content by flow cytometry to provide useful information for both diagnosis and prognosis of patients with hematologic malignancies is reviewed. While the characterization of cell surface antigens seems to be more germane to questions of the normal cell counterpart (stage) of malignant transformation and the biology of regulation of proliferation and differentiation by cell-cell contact and humoral factors, DNA-derived and RNA-derived parameters were surprisingly sensitive in the distinction of major morphologic groups, drug sensitivity and long-term prognosis. Our findings to date in the study of leukemias, lymphomas and myelomas are summarized.

DNA, Neoplasm↗
PubMed1987

Effects of synthetic glycosides on steroid balance in Macaca fascicularis.

The predominantly beta-anomer of diosgenin glucoside (DG) was synthesized and its effects on cholesterol homeostasis were tested in monkeys. Cynomolgus macaques (Macaca fascicularis) were fed, during two 3-week periods, a semipurified diet with 0.1% cholesterol and a similar ration containing 1% DG, respectively. A Chow diet was given for 5 weeks between the experimental periods. Cholesterol and bile acid balance were analyzed during the last week of each semipurified diet. Diosgenin glucoside reduced cholesterolemia from 292 mg/dl to 172 mg/dl, decreased intestinal absorption of exogenous cholesterol from 62.4% to 26.0%, and increased secretion of endogenous cholesterol from -0.8 to 93.5 mg/day. The fecal excretion of neutral steroids rose from 40.7 to 157.3 mg/day; that of bile acids changed, nonsignificantly, from 23.1 to 16.0 mg/day. The cholesterol balance was -44 mg/day in the control period, and 88 mg/day in the DG-fed animals. No toxic signs were observed. Thus, when long-term studies demonstrate that the glucoside is well tolerated, DG and other synthetic glycosides with similar activities may be of use in the management of hypercholesterolemia and atherosclerosis.

Animals↗
PubMed1987

Activity of bisantrene in refractory lymphoma.

A total of 50 evaluable adult patients with relapsing lymphoma and two with Hodgkin's disease received bisantrene by central iv catheter every 3 weeks, at doses of 350 mg/m2 for patients with adequate marrow reserve and 300 mg/m2 for those with compromised marrow reserve. The overall response rate was 30% for 50 patients with malignant lymphoma, including seven complete remissions (14%) and eight partial remissions (16%). Neither patient with Hodgkin's disease responded. The 16 patients with follicular lymphomas did particularly well, with 31% attaining complete remission and 25% attaining partial remission. Five of seven complete responders remain in remission at 16-24+ months; two have relapsed, at 13 and 20 months. Leukopenia, of brief duration, was the most common toxic effect. Fever during neutropenia occurred in 23% of courses. There was minimal cardiotoxicity with cumulative doses of up to 7080 mg/m2 of bisantrene. Bisantrene is an effective and well-tolerated agent for the treatment of malignant lymphoma.

Adult↗