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Biomedical subjects

P McLaughlin

Publications and source records attributed to P McLaughlin.

At least 145 records · Page 8Linked to original sources
PubMed1991

Clinical spectrum of cryptogenic organising pneumonitis.

Cryptogenic organising pneumonitis (bronchiolitis obliterans organising pneumonia) is an uncommon condition that often responds to steroids. It is characterised clinically by constitutional symptoms, pathologically by intra-alveolar organising fibrosis, and radiologically by patchy pulmonary infiltrates. Its full clinical spectrum and course are only partially described and understood. Six patients are described, seen over three years, with considerably diverse clinical and radiological presentations (two had diffuse lung infiltrates, two had peripheral lung infiltrates, and two had localised lobar involvement) and with very varying severity of disease (two with a life threatening illness, three with appreciable subacute constitutional symptoms, and one with mild symptoms). It is concluded that cryptogenic organising pneumonitis can present in various ways. A set of diagnostic criteria are proposed which will help in the recognition of this syndrome, which is probably underdiagnosed.

Aged↗
PubMed1991

Discordant bone marrow involvement in diffuse large-cell lymphoma: a distinct clinical-pathologic entity associated with a continuous risk of relapse.

From 1975 to 1988, 50 patients with lymph node biopsy-documented diffuse large-cell lymphoma (DLCL) presented with bone marrow involvement. Twenty-four patients (48%) had large-cell lymphoma (LCL) in the bone marrow and were compared with 19 (38%) patients who had small cleaved-cell lymphoma (SCCL) in the marrow. Additionally, seven patients (14%) had mixed small- and large-cell lymphoma (ML) in the marrow. Patients who had LCL marrow involvement were younger (P less than .02) and more frequently had elevated lactic dehydrogenase (LDH) levels (P less than .001), high tumor burden (P less than .01), and more sites of extranodal disease (P less than .05) than those with SCCL in the marrow. The complete response (CR) rate to multiagent chemotherapy was 16.7% in the LCL group and 89.4% in the SCCL group (P less than .001). One third of the patients with LCL in the marrow developed CNS involvement, compared with only one patient in the SCCL group (P = .06). Overall 5-year survival was 79% in patients with SCCL marrow involvement, compared with only 12% in patients with LCL in the marrow (P = .002). Despite a high CR rate, patients with marrow involved by SCCL were at a high continuous risk of relapse with only a 30% failure-free survival at 5 years. We conclude that bone marrow involvement with LCL predicts for extremely poor prognosis with low response rate and short survival. Patients with SCCL in the bone marrow have a high rate of CR and a high rate of 5-year survival; however, there is a high risk of late relapse, and only 15% are in a continuous remission at 8 years.

Adolescent↗
PubMed1991

Multivariate analysis of prognostic factors in stage IV follicular low-grade lymphoma: a risk model.

We analyzed the records of 96 previously untreated patients with stage IV follicular low-grade lymphoma (FLGL) uniformly treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo) chemotherapy from 1972 to 1982. The overall complete remission (CR) rate was 77%. At a median follow-up of 138 months, the 10-year cause-specific survival rate was 42% with a median survival of 100 months. Failure-free survival (FFS) was 15% at 10 years with a median FFS of 30 months. Multivariate analysis showed peripheral lymph node size (LN), degree of marrow involvement, and sex, in that order, to be important for FFS, while the number of extranodal sites (#ENS), LN, sex, and degree of marrow involvement were important for cause-specific survival. We devised a tumor burden (TB) model, incorporating #ENS, LN, and degree of marrow involvement. Three groups were identified with statistically significant differences in cause-specific survival and FFS. Those with low TB (one ENS exclusive of extensive marrow and nodal disease less than 5 cm) had a 10-year cause-specific survival of 73% compared with 24% for patients with high TB (greater than or equal to two ENS and nodal disease greater than or equal to 5 cm) (P less than .001) and 40% for those with intermediate TB (either greater than or equal to 2 ENS, or extensive marrow only, or nodal disease greater than 5 cm) (P = .050). Patients with low TB had a 10-year FFS rate of 32%, while the intermediate and high TB groups had 10% and 9% FFS, respectively (P = .003). Because sex was a very strong prognostic variable, we created a risk model for survival and FFS based on TB and sex. Females with low TB had the best prognosis (92% survival and 50% FFS at 10 years) and males with high TB had the worst outlook (median survival and FFS, 43 and 12 months, respectively). Other TB-sex combinations defined two groups with statistically significant differences in survival but comparable FFS. This model should aid in the design and analysis of future trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Recombinant DNA approaches to study the role of the regulatory light chains (RLC) using scallop myosin as a test system.

The ability to exchange reversibly the regulatory light chains (RLCs) from scallop myosin has provided us with a test system to probe the mechanisms of regulation mediated by the RLCs from vertebrate skeletal, vertebrate smooth and molluscan myosins. The cloning and expression of these RLCs, together with domain-swapping and site-directed mutagenesis approaches, has allowed us to explore further the mechanisms involved and identify the functional importance of specific regions of the RLC molecule; for example, the presence of a high affinity metal binding site in the N-terminal domain and its interaction with the intact C-terminal domains are required for regulation.

Amino Acid Sequence↗
PubMed1990

Surgical debulking is associated with improved survival in stage I-II diffuse large cell lymphoma.

Tumor burden is an important predictor of survival in patients with diffuse large cell lymphoma (DLCL). The authors reviewed the charts of 147 patients with early stage presentation (Stage I-IE and II-IIE) seen from 1974 through 1984. The 10-year survival for the 85 patients with bulky disease was 54% compared with 76% for those who did not have bulky disease. Of the 62 with nonbulky disease, 14 had been rendered so by removal of greater than 80% of the initial tumor mass (surgical debulking). The authors compared these 14 patients with a matched control group of 14 patients selected from the 85 with bulky disease who had equivalent stage, therapy, site, size of initial mass, performance status, and sex and age. All had received similar therapy with cyclophosphamide, Adriamycin (doxorubicin), vincristine, prednisone, bleomycin, and radiotherapy to the involved field. At a 7-year follow-up, the 14 debulked patients had a better survival when compared with the matched controls (93% versus 35%, P = 0.003). The authors also analyzed the initial serum lactate dehydrogenase (LDH) levels. Preoperative LDH values were available in six of 14 debulked patients. In the three with elevated LDH levels at presentation, surgical debulking was associated with subsequent decreased LDH levels, which is known to be associated with better prognosis. The other three presented with normal values that remained normal after surgery. These data suggest a potentially important role for surgery as front-line therapy in patients with Stage I-IE and II-IIE bulky DLCL whose disease is deemed resectable. More studies are needed in order to better define this role as well as to determine how frequently and safely surgical debulking can be performed.

Adult↗
PubMed1990

Niebauer trapeziometacarpal arthroplasty.

A retrospective review of 22 Niebauer implant arthroplasties of the trapeziometacarpal joint for treatment of advanced osteoarthritis in 18 patients is reported. Mean follow-up was 2.4 years. Thirteen patients stated they had good pain relief, two were slightly improved, and three had no improvement. Six patients believed their functional status was improved, 10 were the same, and 2 were made worse. Thumb abduction and strength measurements were similar in the hands with operation and those without operation. Full opposition was present in 68% of thumbs with operation versus 93% of those thumbs without operation. Asymptomatic implant subluxation of 50% or less was present in 23% of thumbs. However, only 9% had symptomatic mechanical instability and these thumbs showed greater than 75% subluxation. Implant breakage and "silicone synovitis" was not evident on clinical and radiographic examination. Evaluation of the bony response around the implant stem revealed a consistently present sclerotic line. Although the design features of the Niebauer implant offer theoretical advantages for stability and fixation, this study does not demonstrate better results compared with other types of silicone trapezium implants. Therefore, a surgeon should choose this implant on the basis of a personal preference for ease of implantation and not for improved clinical results.

Adult↗
PubMed1990

Differentiation of T-cell lymphoma from Hodgkin's disease. Mitotic rate and S-phase analysis.

Flow cytometric DNA and proliferative compartment (S + G2M) analysis was performed on lymph nodes from 37 patients with Hodgkin's disease (HD) and on 16 lymph nodes plus 6 extranodal biopsies from 22 patients with peripheral T-cell lymphomas (PTCLs). The mitotic rate per 20 high-power fields (HPFs) was also determined for each case. The PTCLs showed significantly higher proliferative activity than the HD cases, as evidenced by a mean S + G2M of 12.0% versus 5.0% for HD and a median mitotic rate of 27 versus 5 mitoses per 20 HPFs in the HD cases. Because morphologic distinction, particularly of mixed cellularity HD (HDMC), from the diffuse small cleaved cell (DSCCL) or mixed cell (DMCL) pattern of PTCL may at times be difficult, these subgroups were compared separately. The 2 cases of DSCCL plus 12 of DMCL yielded a higher proportion of S-phase cells than the 9 HDMC cases with S + G2M means of 9.9% versus 3.3% and a higher mitotic rate, median 21 versus 7 per 20 HPFs. These findings suggest that S-phase determination and mitotic rate provide additional parameters in discriminating PTCL from HD in the most histologically similar cases.

Adolescent↗
PubMed1990

Small noncleaved cell lymphoma in adults: superior results for stages I-III disease.

Small noncleaved cell lymphoma (SNCCL), a rare lymphoma in adults, is associated with not only a rapid complete response (CR) to chemotherapy but also with the potential to rapidly relapse both systemically and in the CNS. We treated 44 assessable adults with two similar protocols, consisting of three sequential chemotherapy combinations and intrathecal prophylaxis with methotrexate and cytarabine. The overall CR rate was 80%; it was 100% in patients with Ann Arbor (AA) stages I-III disease and 57% in those with stage IV disease. The overall survival (OS) rate at 5 years was 52%. The overall 5-year freedom from tumor mortality (FTM) rate was 63%; it was 95% for patients with AA stages I-III disease, and 29% for those with stage IV disease. Stepwise multivariate analysis of factors associated with remission duration and survival indicated that advanced-disease stage and age of 40 years or over were predictors of poor prognosis. Twelve patients with positive human immunodeficiency virus (HIV) serology were also included in this series. They had an 83% CR rate and an 83% 5-year FTM, but only a 36% 5-year OS; most deaths were secondary to opportunistic infection. Histologic subtype (Burkitt's lymphoma [BL] or non-Burkitt's lymphoma [NBL]) did not correlate with patient age, site of tumor presentation, response to therapy, or survival. Both protocols achieved comparable results. The approach used in these protocols is highly effective for patients with early staged disease, regardless of their HIV status; however, better therapy is necessary for those with SNCCL presenting in an advanced stage.

Adult↗
PubMed1990

NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease.

Patients with early-staged Hodgkin's disease have had a higher relapse rate following radiotherapy alone if they have B symptoms, large mediastinal masses, hilar involvement, or stage III disease. From June 1988 to December 1989, 27 previously untreated patients with early-staged Hodgkin's disease with adverse features for disease-free survival received combined-modality therapy. Seventeen patients had stage I or II disease, 10 had stage III, 5 had B symptoms, 13 had large mediastinal masses, and 6 had peripheral masses measuring 10 cm or more in diameter. All patients initially received three cycles of a novel chemotherapeutic regimen combining Novantrone (mitoxantrone, American Cyanamid Company), vincristine, vinblastine, and prednisone (NOVP). Twenty-four patients with clinically staged I or II disease with adverse features or stage III disease did not undergo laparotomy; three patients had favorable stage I or II disease and at laparotomy had stage III disease. Radiotherapy-treatment fields depended on the extent of nodal involvement. Twenty-six patients completed all therapy as planned to complete remission (CR) and one of these has had progression; she is in second CR following additional radiotherapy. With a median follow-up of 12 months, all patients are alive. Tolerance to treatment was excellent with only grade 1 or 2 nausea, alopecia and myalgias, and brief myelosuppression. NOVP is an effective adjuvant chemotherapy regimen for inducing responses, with minimal toxicity, prior to definitive radiotherapy for patients with early-staged Hodgkin's disease.

Adult↗
PubMed1989

Risk classification as the basis for clinical staging of diffuse large-cell lymphoma derived from 10-year survival data.

Two hundred and fifty previously untreated adult patients with diffuse large-cell lymphomas were treated with a chemotherapy combination of cyclophosphamide, adriamycin, vincristine, prednisone, and low-dose bleomycin (CHOP-Bleo) with or without radiotherapy between 1974 and 1984. The 10-year survival rates for patients with Ann Arbor stages II, III, or IV disease of 55%, 42%, and 40%, respectively, were not significantly different. However, the survival rate of 76% for patients with stage I disease was clearly better. Factors more indicative of prognosis than stage, as found by univariant analysis, were tumor burden, serum lactic dehydrogenase level (LDH), age, and constitutional symptoms. From these, a multivariant analysis selected tumor burden, LDH level, and age as major independent factors for predicting survival (P less than .001). A prognostic risk model constructed on the basis of tumor burden and LDH levels identified four distinct risk groups (A, B, C, D) with 10-year survival rates of 85%, 66%, and 43% for A, B, and C. No patient in group D survived 10 years. These risk groups also had a strong correlation with complete remission rates and with relapse rates. Thus this model proved more effective for identifying patient populations according to their expected responses, durations of remission, and survivals than the Ann Arbor staging system. Detailed information supporting the use of this system for predicting prognosis and for treatment selection for patients with diffuse large-cell lymphomas is provided.

Adolescent↗
PubMed1989

Refractoriness to chemotherapy and poor survival related to abnormalities of chromosomes 17 and 7 in lymphoma.

PURPOSE: Lymphoma cells usually show cytogenetic abnormalities, but their relationship to prognosis has not been as extensively studied as in leukemia. A group of previously untreated cases of lymphoma with evaluable metaphases was examined for the association between cytogenetic abnormalities and clinical outcome. PATIENTS AND METHODS: The study consisted of 104 patients, from whom fresh tumor samples were obtained for cytogenetic tests. Because of the complexity of lymphoma karyotypes, the cases were divided into four patterns according to the type of abnormality of chromosome 17 or 7 present. Treatment of patients was given based on histologic grade and stage of disease. Response to treatment was evaluated according to previously described methods. RESULTS: Patients with true abnormalities of chromosome 17 or 7 (defined as those with either structural abnormalities of the short arm of these chromosomes or monosomy of these chromosomes with no associated unidentified markers) were observed to have an adverse prognosis. The overall response rate and tumor-related mortality were less favorable for patients with these cytogenetic abnormalities. By applying multivariate analysis, we found that this observation was independent of the effect of serum lactic dehydrogenase level, histologic grade, or tumor burden. CONCLUSION: True abnormalities of chromosome 17 or 7 in patients with lymphoma are associated with a poor response to chemotherapy, short time to treatment failure, and high tumor-related mortality rate. These findings raise the question of the potential involvement of some gene or oncogene, perhaps the p53 oncogene, which might impart a survival advantage to the malignant cells.

Adult↗
PubMed1989

Experimental hepatic artery embolization with a collagen embolic agent in rabbits. A microcirculatory study.

The authors used new fibrous collagen embolic material (5 by 75 microns in size) for flow-directed hepatic artery embolization in four rabbits; the purpose of the study was to examine the acute effects of the material on hepatic microcirculation. Extent of hepatic dearterialization, level of arterial occlusion, collateral formation and status of portal sinusoidal perfusion were evaluated under a dissection microscope after embolization. The collagen material produced proximal and peripheral hepatic arterial occlusion with complete hepatic dearterialization, including the bile duct. Portal sinusoidal perfusion appeared to be intact. No intrahepatic microcollaterals were observed.

Animals↗
PubMed1989

A new serologic staging system for large-cell lymphomas based on initial beta 2-microglobulin and lactate dehydrogenase levels.

We report results of our investigation of prognostic factors for patients with large-cell lymphoma who were entered on the same treatment protocol and who had known pretreatment serum beta 2-microglobulin (beta 2M) and lactate dehydrogenase (LDH) levels. beta 2M and LDH levels were the most significant and independent variables for predicting time to treatment failure (TTF) and survival. The serum level of beta 2M correlated with tumor burden. These two serum markers defined three significantly different prognostic groups. All 27 patients in the low-risk group remain alive and in remission; in contrast, 22 of the 27 patients (81%) in the high-risk group have failed treatment, and only seven (26%) remain alive. In comparison with the Ann Arbor staging system, serum levels of beta 2M and LDH may provide a more precise system for defining risk groups and thereby allow a more rational approach to the development and analysis of treatment strategies.

Adult↗
PubMed1988

Nucleic acid flow cytometry in large cell lymphoma.

Between 1978 and 1985, 140 patients with large cell lymphoma (27 follicular, 92 diffuse, 5 immunoblastic, and 16 transformed) had DNA-RNA cytometry performed on involved tissue. DNA-RNA features were correlated with treatment outcome and compared to other established prognostic factors in 63 newly diagnosed patients who received uniformly intensive therapy. Significantly better outcome was noted for previously untreated patients with intermediate RNA content (RNA index, 1.0-1.8), diploid DNA content, and (during the initial 12-month follow-up) low proliferative activity. Of patients followed beyond 12-24 months, those with high proliferative activity appeared to have the most durable remissions, although this was not statistically significant. These findings suggested a preferential impact of intensive chemotherapy on patients with intermediate RNA content and possibly those with high proliferative activity, since previous studies and our own experience with relapsing patients have indicated a progressively worse outlook with higher proliferative activity and RNA index values. In newly diagnosed patients, multivariate analysis identified RNA content as the most important prognostic factor, followed by proliferative activity and serum lactate dehydrogenase. Thus, for patients with large cell lymphoma, DNA-RNA cytometry appears to be a valuable prognostic parameter for identifying a subset of patients who have a high likelihood of cure with intensive chemotherapy.

Analysis of Variance↗
PubMed1988

Chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin for parenchymal brain lymphoma.

Ten patients with parenchymal CNS lymphoma received combination chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin (DHAP), and additional therapy according to clinical circumstances. Two of four patients with primary CNS lymphoma achieved and remain in complete remission (CR). Four of six patients with CNS lymphoma at relapse also achieved CR. DHAP is active against CNS lymphoma. Further trials with DHAP, particularly in conjunction with other treatment modalities, are warranted.

Adult↗