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Biomedical subjects

R C Lohmann

Publications and source records attributed to R C Lohmann.

17 recordsLinked to original sources
PubMed2007

Clinical significance of the RT-PCR positive sentinel node in melanoma.

BACKGROUND: The clinical relevance of RT-PCR positivity for melanoma markers in the sentinel node remains controversial. Our purpose was to determine whether patients with a histologically negative but RT-PCR positive node were at an increased risk for recurrence than their RT-PCR negative counterparts. METHODS: Thirty-nine adult patients underwent sentinel node biopsies for melanoma between 1998 and 2000. Each sentinel node was bivalved. Half was serially sectioned and examined by routine hematoxylin and eosin (H&E) and immunohistochemistry (IHC; S100, HMB-45, melanA, and tyrosinase). The other half was analyzed by a nested RT-PCR assay for tyrosinase. RESULTS: Patients were followed for recurrence with a mean follow-up of 71.1 months. The odds ratio of recurrence for RT-PCR positive versus RT-PCR negative patients was 1.39 (0.34, 5.62; p = 0.73). Within the histology negative subgroups, the risk of recurrence in the RT-PCR positive group (26.7%) was not significantly different from the risk of recurrence in the RT-PCR negative group (22.2%) (p = 0.33 chi-squared). RT-PCR of the sentinel node was not a predictor for recurrence on multivariate analysis (p = 0.65). CONCLUSION: Sentinel node RT-PCR positivity did not risk stratify histologically negative melanoma patients beyond routine pathologic examination in this series.

Adult↗
PubMed2005

Effect of activated recombinant human factor 7 (Niastase) on laboratory testing of inhibitors of factors VIII and IX.

Activated recombinant human factor VIIa (rFVIIa) has been used as a hemostatic agent in patients with hemophilia and acquired inhibitors. Other indications for rFVIIa may include liver disease, warfarin sodium (Coumadin) overdose, or trauma. Monitoring patients on this treatment with standard laboratory testing is problematic. Bleeding risk does not correlate well with the prothrombin time (PT) or the activated partial thromboplastin time (aPTT) during therapy with rFVIIa. In addition, there is no identifiable literature on the effect of rFVIIa on assays of inhibitors in this patient group. Monitoring inhibitors may be important during interventions aimed at acutely reducing inhibitor levels, such as during plasma exchange or protein adsorption. We performed factor assays and evaluated inhibitor levels in plasma from 3 patients with deficiencies in FVIII (2 patients) or FIX (1 patient) and inhibitors (titer range, 5.8-17.4 Bethesda units) before and after adding rFVIIa (range, 0.25-8 microg/mL) in vitro. Additionally, we performed assays of factors of both intrinsic and extrinsic systems to determine the impact of rFVIIa on these tests. We found that both factor levels and inhibitor titers from patients with hemophilia A or B could be measured accurately, even in the presence of suprapharmacologic doses of rFVIIa (8 microg/mL). We also obtained accurate measurements for other assays of the intrinsic coagulation system (FXI and FXII) based on the aPTT. Conversely, we found that assays of the extrinsic system based on the PT (FII, FV, and FX) produced results that were unreliable. FVII results were very high but reproducible. These results suggest that assays based on the PT are inaccurate and should be avoided during FVIIa treatment. Conversely, FVIII and FIX levels and inhibitor titers can be accurately monitored in hemophilia patients receiving rFVIIa according to results of aPTT-based coagulation tests.

Antibodies↗
PubMed2002

A randomized phase II study of two schedules of bryostatin-1 (NSC339555) in patients with advanced malignant melanoma: A National Cancer Institute of Canada Clinical Trials Group study.

PURPOSE: This study addressed the efficacy and toxicity of the novel compound Bryostatin-1 (NSC 339555), a novel agent with antineoplastic, hematopoietic and immunomodulatory activity in a variety of in vitro and in vivo systems. PATIENTS AND METHODS: This phase II study randomly assigned chemotherapy-naïve patients with untreated metastatic melanoma and measurable disease to two schedules of treatment: Arm A, 25 microg/m2 bryostatin-1 given as a 24 hour continuous infusion weekly or Arm B, 120 microg/m2 bryostatin-1 given as a 72 hour continuous infusion every 2 weeks. Although objective response was assessed using standard NCIC CTG criteria, antitumour activity was assessed using a multivariate endpoint incorporating both response (CR and PR) and early progression (PD at < or = 8 weeks). Seventeen patients were randomized to each arm. RESULTS: Arm A was better tolerated with 86.7% of 15 evaluable patients receiving > or = 90% of planned dose intensity versus 76.5% of 17 evaluable patients in Arm B. On Arm B, three patients experienced serious adverse events and three patients had to be removed from protocol therapy due to toxicity. The most common side effect was myalgia (33% grade 1-2 on Arm A versus 65% on Arm B with 5 patients experiencing grade 3 and one patient grade 4). Lethargy was more common on Arm A but more severe on Arm B. Other side effects such as nausea, diarrhea and headache were generally mild to moderate in nature and occurred with a similar frequency on both arms. Hematologic and biochemical toxicity were minimal. This trial was closed early because the protocol-stopping rule was met based on lack of required responses and on the number of early progressions on both arms. No partial or complete responses were seen; 3 patients randomized to Arm A had stable disease (duration 9-24 weeks) as did 4 patients (duration 10-38 weeks) randomized to Arm B. CONCLUSION: Arm A was better tolerated than Arm B. We conclude that bryostatin-1 has little efficacy in the treatment of metastatic melanoma with either of the schedules studied.

Adult↗
PubMed2000

Sentinel node biopsy in melanoma using technetium-99m rhenium colloid: the London experience.

Nodal metastases in patients with melanoma identify a reduction of survival by 50%; however, elective lymph node dissection (ELND) has not been shown clearly to improve survival. Morton's technique of sentinel node biopsy, using preoperative lymphoscintigraphy and intraoperative blue dye, addresses elegantly the controversy regarding ELND. Sentinel node biopsy has been shown to stage the patient accurately because metastases from melanoma follow an orderly progression from the sentinel node to the remainder of the basin. Fifty-six consecutive patients with American Joint Committee on Cancer stage 1b or 2 melanoma seen at the London Health Sciences Center between July 1998 and January 2000 were enrolled prospectively to undergo sentinel node biopsy. Preoperative lymphoscintigraphy was conducted in the nuclear medicine department. A total of 10 to 15 MBq (0.27-0.41 mCi) of technetium 99m (99mTc) rhenium colloid or filtered sulfur colloid was injected intradermally around the biopsy scar. Images were obtained to localize all draining nodal basins. The location of the sentinel node was marked on the skin. The patient was taken to the operating room and anesthetized. Isosulfan blue dye was injected intradermally around the biopsy scar. A hand-held gamma probe was used intraoperatively as a guide to the first draining node. Blue-stained lymphatic channels aided in the dissection. Sentinel node localization was successful in 55 of 56 patients, for an overall success rate of 98%. Preoperative lymphoscintigraphy identified a sentinel node in an unpredictable location in 32% of patients. On average, 2.3 sentinel nodes per patient were identified on the initial scan, and 2.2 sentinel nodes per patient were recovered at surgery. Both 99mTc rhenium and filtered sulfur colloid showed no substantial differences in tracer uptake and retention in the sentinel node. Twelve patients had a positive sentinel node on routine histology, and 11 patients subsequently underwent completion lymphadenectomy. The mean thickness of the primary melanoma in the 12 patients with positive sentinel nodes was 3.7 mm compared with a mean tumor thickness of 1.8 mm in the remaining 41 patients with negative biopsies (p = 0.0003). Two patients experienced recurrence in a regional basin after negative pathological evaluation of the sentinel node. Reverse transcription-polymerase chain reaction analysis of both of these patients was positive. Two patients are alive with metastatic disease and 54 patients are alive without disease, with a mean follow-up of 1 year (range, 2-24 months). Complications occurred at a substantially higher rate (45%) after completion lymphadenectomy than after sentinel node biopsy alone (9%). Sentinel node biopsy is a feasible technique with a high success rate (98%), but it requires a multidisciplinary approach. This study validates the clinical usefulness of 99mTc rhenium colloid for lymphoscintigraphy.

Adult↗
PubMed2000

External quality assessment in the examination of blood films for malarial parasites within Ontario, Canada.

OBJECTIVE: To assess laboratory practice in the examination of blood films for malarial parasites. METHOD: Ontario medical laboratories, licensed by the Ministry of Health, are required to participate in external quality assessment by the Laboratory Proficiency Testing Program, which assesses performance of laboratory assays and also examines the total testing process. Educational strategies are used to improve performance. RESULTS: A 1995 survey indicated shortcomings in detection and identification of malarial parasites in blood films. Consequently, recommendations for the investigation of malarial parasites in blood were issued. In 1996 and 1997, 16 workshops were conducted. A 1997 follow-up external quality assessment survey indicated that problems persist as 27% of laboratories failed to correctly speciate Plasmodium falciparum. Good Practice Guidelines were issued in 1998. CONCLUSION: Further education and assessment are required. Laboratories lacking expertise must establish referral arrangements with more proficient laboratories.

Animals↗
PubMed1996

Oral indomethacin and ranitidine in advanced melanoma: a phase II study.

As a result of preclinical data demonstrating the antitumour and antimetastatic efficiency of indomethacin in murine models, and the clinical observation of occasional tumour regression in patients with advanced melanoma treated with indomethacin together with ranitidine, a Phase II study was performed of prolonged administration of these two oral agents in combination. Seventeen patients were entered into the study and commenced on indomethacin 50 mg three times daily; the dose was escalated to a maximum of 75 mg three times daily in patients who tolerated the starting dose. Ranitidine was administered concurrently at a dose of 150 mg twice daily. One patient with uveal melanoma metastatic to the liver achieved a partial response, with slow shrinkage of a biopsy-proved liver metastasis (objective response rate 6 percent; 95 percent CI0-29). Another patient demonstrated a minor response in pelvic lymph nodes. The combination of indomethacin and ranitidine has negligible activity in advanced malignant melanoma; a response may require months to be achieved.

Administration, Oral↗
PubMed1996

Randomized, double-blind, placebo-controlled trial comparing the response rates of carmustine, dacarbazine, and cisplatin with and without tamoxifen in patients with metastatic melanoma. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: We designed and conducted a randomized, double-blind, placebo-controlled trial to compare the response rates and survival of patients with metastatic melanoma who received carmustine (BCNU), dacarbazine (DTIC), and cisplatin with tamoxifen, or the same chemotherapy with placebo. PATIENTS AND METHODS: Eligible patients with metastatic melanoma received either BCNU 150 mg/m2 intravenously (i.v.) on day 1, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24, and cisplatin 25 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24 with placebo every 6 weeks, or the same chemotherapy with tamoxifen 160 mg orally daily for 7 days before chemotherapy and 40 mg orally daily throughout the remainder of the treatment cycle. Patients were treated on protocol for up to three cycles depending on the type of response. Assuming that a minimum increase in response rate of 20% would be necessary to conclude that tamoxifen conferred a clinically important benefit, we designed the study with an 80% chance of detecting that difference at the 5% level (two-sided). RESULTS: Between February 1992 and January 1995, 211 patients were accrued, 199 of whom were considered assessable for response and toxicity. The overall response rate was 21% in the placebo group and 30% in the tamoxifen group (P = .187). Complete and partial responses were 3% and 27%, respectively, for the tamoxifen group and 6% and 14%, respectively, for the placebo group. Poor performance status and liver involvement were associated with a reduced likelihood to respond to treatment. Major toxicities were similar in both groups with no statistically significant difference in the rates of deep vein thrombosis, pulmonary thromboembolus, grade 4 neutropenia, or grade 4 thrombocytopenia. CONCLUSION: These results demonstrate that the addition of high doses of tamoxifen to this chemotherapy regimen does not increase the response rate compared with chemotherapy alone in unselected patients with metastatic melanoma.

Adult↗
PubMed1994

Proficiency testing in reticulocyte counting.

The Laboratory Proficiency Testing Program tests and evaluates proficiency of clinical laboratories in Ontario, Canada. The programme began in 1974; testing of reticulocyte counts was added in 1982. From the beginning, the goal of the programme has been to ensure that the quality of practice in Ontario laboratories facilitates good quality patient care. Testing of indirect counting methods for reticulocytes is accomplished by the distribution of stained blood films. Performance is expressed in terms of accuracy and precision. Proficiency is assessed by comparing submitted results to an all-methods' mean and result reliability by observing the coefficient of variation (CV) of the cohort. The quality of the results vary neither with the manual counting system used nor the type of laboratory. The CV commonly ranges from 25 to 30%, and this lack of accuracy appears to be inherent in the technology of manual reticulocyte counting. We conclude that manual reticulocyte counting is technologically obsolete but may be of clinical value if used in a qualitative fashion. It should probably be replaced by an automated method.

Analysis of Variance↗
PubMed1992

Proficiency testing of platelet counting in Ontario.

Proficiency testing results provide data for interlaboratory comparisons. The Laboratory Proficiency Testing Program of Ontario, Canada, has tested platelet counting for a decade and other hematology parameters for 15 years. Despite the fact that all testing programs are compromised by the type of testing material used, for platelet count testing, conclusions are possible. The data indicate that most laboratories in Ontario have greater difficulty performing reproducible platelet counting as compared with other components of hematologic cytometry. A major contributor to this shortfall is the method used by the laboratory. It was not a surprise that manual counting had a high coefficient of variation. Unexpectedly, the semiautomated methods used in the mid-1980s also displayed a high coefficient of variation.

Humans↗
PubMed1991

Acute non-lymphocytic leukaemia and myelofibrosis following sequential hemibody irradiation for prostatic carcinoma.

Sequential hemibody radiotherapy (SHBI) is currently being evaluated in clinical trials as adjuvant treatment in cancer patients who are potential long-term survivors. The potential late adverse effects of this therapeutic modality on the bone marrow may place patients at risk for the complications of aplasia, leukaemia, and myeloproliferative syndromes. We describe a case of acute non-lymphocytic leukaemia and myelofibrosis following SHBI for prostate carcinoma. The possible role of radiation in the induction of these abnormalities is discussed.

Adenocarcinoma↗
PubMed1991

Flow cytometric reticulocyte analysis using thiazole orange; clinical experience and technical limitations.

Flow cytometric (FCM) reticulocyte analysis using thiazole orange (TO) is becoming an increasingly popular method for routine quantification of reticulocytes. The methodology is accurate, cost-effective and shows a high correlation with manual techniques. We describe our experience with the clinical application of FCM reticulocyte analysis in a general hospital setting over a 20-month period with special emphasis on technical limitations.

Antineoplastic Agents↗
PubMed1989

Reliability of white blood cell counting.

The Laboratory Proficiency Testing Program has successfully operated mandatory proficiency testing for 13 years in Ontario, Canada, using committees of volunteer peers. This is an alternative to gubernatorial proficiency testing. Using white blood cell (WBC) count determinations as a focus, we present our results. Ninety-six percent of participants attained WBC count results within +/- 10% of an all-methods mean and 77% attained results within +/- 5%. Ninety-six percent displayed satisfactory precision. Details of the program, ie, testing material, computer analysis, reference results, and scope of committee action, are discussed. In 1975, clinical expectations for WBC count determinations greatly exceeded most laboratories' capabilities. By 1987, participants were able to produce reliable, clinically useful WBC count results. The paramount reason for this improvement is the transition from manual to automated counting methods resulting from the stimulus of proficiency testing and the concomitant education.

Electronics, Medical↗
PubMed1984

Plasma exchange in thrombotic thrombocytopenic purpura.

Three patients were recently treated for thrombotic thrombocytopenic purpura (TTP). One presented with toxic shock syndrome; TTP developed but promptly responded to a regimen of antiplatelet agents, steroids and plasma exchange. In another the manifestations of TTP developed after presentation with hypertension and abdominal pain. This patient responded to a similar regimen but required extended treatment before remission could be maintained with medications alone. In the third patient the full TTP syndrome appeared after several days of plasma exchange treatment for hemolyticuremic syndrome. He did not respond. It is suggested that TTP may present in many forms initially, that microangiopathic hemolysis may be a late manifestation and that the optimal therapy is not known.

Adult↗
PubMed1978

Immunologic findings, thrombocytopenia and disease activity in lupus nephritis.

Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis.

Antibodies, Antinuclear↗
PubMed1975

Follicular lymphoma: A survey of 75 cases with special reference to the syndrome resembling chronic lymphocytic leukaemia.

In a series of 75 cases of follicular lymphoma collected between 1950 and 1971 the following features were singled out as characteristic of, or specially frequent in, follicular lymphoma: (1) the high incidence in females; (2) the long history of symptomless lymph node enlargement; (3) the frequent presence of extensive symptomless disease at presentation, especially in patients below 40 years of age; (4) the syndrome resembling and often confused with chronic lymphocytic leukaemia, in which the notched nucleus cell, when present, is diagnostic; (5) the responsiveness of extensive disease to radiotherapy and alkylating agents at low dosage; (6) the long overall survival and the long survival after relapse; (7) the occurrence of abrupt change in the character of the disease in which, during a period of apparent quiescence, malignant transformation supervenes proving rapidly fatal. In the transformed stage the disease behaves as an invasive metastasizing sarcoma or as a blast cell leukaemia; in both cases the transformation is associated with the appearance of a new cell type, undifferentiated and distinct from that present before onset of transformation, which may however persist. The syndrome resembling chronic lymphocytic leukaemia occurs only in follicular lymphoma.

Adult↗