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Biomedical subjects

B J Lewis

Publications and source records attributed to B J Lewis.

At least 19 recordsLinked to original sources
PubMed2001

Aircrew exposure from cosmic radiation on commercial airline routes.

As a result of the recent recommendations of the ICRP 60, and in anticipation of possible regulation on occupational exposure of Canadian-based aircrew, an extensive study was carried out by the Royal Military College of Canada over a one-year period to measure the cosmic radiation at commercial jet altitudes. A tissue-equivalent proportional counter was used to measure the ambient total dose equivalent rate on 62 flight routes, resulting in over 20,000 data points at one-minute intervals at various altitudes and geomagnetic latitudes (i.e. which span the full cut-off rigidity of the Earth's magnetic field). These data were then compared to similar experimental work at the Physikalisch Technische Bundesanstalt, using a different suite of equipment, to measure separately the low and high linear energy transfer components of the mixed radiation field, and to predictions with the LUIN transport code. All experimental and theoretical results were in excellent agreement. From these data, a semiempirical model was developed to allow for the interpolation of the dose rate for any global position, altitude and date (i.e. heliocentric potential). Through integration of the dose rate function over a great circle flight path, a computer code was developed to provide an estimate of the total dose equivalent on any route worldwide at any period in the solar cycle.

Aircraft↗
PubMed2000

Assessment of the cosmic radiation exposure on Canadian-based routes.

As a result of the recent recommendations of the ICRP-60 and in anticipation of possible regulation on occupational exposure of commercial aircrew, a two-phase investigation was carried out over a 1-y period to determine the total dose equivalent on representative Canadian-based flight routes. In the first phase of the study, dedicated scientific flights on a Northern round-trip route between Ottawa and Resolute Bay provided the opportunity to characterize the complex mixed-radiation field and to intercompare various instrumentation using both a conventional suite of powered detectors and passive dosimetry. In the second phase, volunteer aircrew carried (passive) neutron bubble detectors during their routine flight duties. From these measurements, the total dose equivalent was derived for a given route with a knowledge of the neutron fraction as determined from the scientific flights and computer code (CARI-3C) calculations. This study has yielded an extensive database of over 3,100 measurements providing the total dose equivalent for 385 different routes. By folding in flight frequency information and the accumulated flight hours, the annual occupational exposures of 20 flight crew have been determined. This study has indicated that most Canadian-based domestic and international aircrew will exceed the proposed annual ICRP-60 public limit of 1 mSv y(-1) but will be well below the occupational limit of 20 mSv y(-1).

Aircraft↗
PubMed1999

Cosmic radiation exposure on Canadian-based commercial airline routes.

As a result of the recent recommendations of ICRP 60 and in anticipation of possible regulation on occupational exposure of commercial aircrew, a two-part investigation was carried out over a one-year period to determine the total dose equivalent on representative Canadian-based flight routes. As part of the study, a dedicated scientific measurement flight (using both a conventional suite of powered detectors and passive dosimetry) was used to characterise the complex mixed radiation field and to intercompare the various instrumentation. In the other part of the study, volunteer aircrew carried (passive) neutron bubble detectors during their routine flight duties. From these measurements, the total dose equivalent was derived for a given route with a knowledge of the neutron fraction as determined from the scientific flight and computer code (CARI-LF) calculations. This investigation has yielded an extensive database of over 3100 measurements providing the total dose equivalent for 385 different routes. By folding in flight frequency information and the accumulated flight hours, the annual occupational exposures of 26 flight crew have also been determined. This study has indicated that most Canadian-based domestic and international aircrew will exceed the proposed annual ICRP 60 public limit of 1 mSv.y-1, but will he well below the occupational limit of 20 mSv.y-1.

Aerospace Medicine↗
PubMed1998

Characterisation of neutron-sensitive bubble detectors for application in the measurement of jet aircrew exposure to natural background radiation.

A survey of the natural background dose equivalent received by Canadian Forces aircrew was conducted using neutron-sensitive bubble detectors (BDs) as the primary detection tool. Since this study was a new application for these detectors, the BD response to neutron dose equivalent (RD) was extended from thermal to 500 MeV in neutron energy. Based upon the extended RD, it was shown that the manufacturer's calibration can be scaled by 1.5 +/- 0.5 to give a BD sensitivity that takes into account recently recommended fluence-to-neutron dose equivalent conversion functions and the cosmogenic neutron spectrum encountered at jet altitudes. An investigation of the effects of systematic bias caused by the cabin environment (i.e., temperature, pressure and relative humidity) on the in-flight measurements was also conducted. Both simulated and actual aircraft climate tests indicated that the detectors are insensitive to the pressure and relative humidity variations encountered during routine jet aircraft operations. Long term conditioning tests also confirmed that the BD-PND model of detector is sensitive to variations in temperature to within +/- 20%. As part of the testing process, the in-flight measurements also demonstrated that the neutron dose equivalent is distributed uniformly throughout a Boeing 707 jet aircraft, indicating that both pilots and flight attendants are exposed to the same neutron field intensity to within experimental uncertainty.

Air Pressure↗
PubMed1991

Alternating hepatic intra-arterial floxuridine and fluorouracil: a less toxic regimen for treatment of liver metastases from colorectal cancer.

Hepatic intra-arterial (HIA) infusion of floxuridine (FUDR) via an implanted pump has shown promise in the treatment of colorectal cancer metastasized to the liver. However, the potential benefit of this therapy may be offset by the high incidence of treatment-limiting biliary toxicity. Although weekly HIA bolus of fluorouracil (5-FU) is effective against metastatic colorectal cancer to the liver with no biliary toxicity, it is limited by systemic side effects. In December 1986, we began a phase II trial of alternating HIA FUDR and 5-FU via the implanted pump in an attempt to extend the duration of treatment by obviating the limiting biliary (FUDR) and systemic (5-FU) drug toxic effects. Patients received continuous HIA FUDR at 0.1 mg/kg of body weight per day on days 1 through 8 followed by an HIA bolus of 5-FU at 15 mg/kg given via the pump sideport on days 15, 22, and 29, with the cycle repeated every 35 days. Sixty-eight patients were enrolled in this trial, and 64 were fully evaluable. Of the 64 patients, 30 (47%) previously had received chemotherapy. Major response (complete response plus partial response) was observed in 32 (50%) of 64 patients, and the median survival from pump implantation in all patients was 22.4 months. In contrast to the experience with the single-agent HIA FUDR regimen, no patient had treatment terminated because of drug toxicity. Alternating HIA FUDR and 5-FU has efficacy similar to that of HIA FUDR given alone, but when closely monitored and adjusted appropriately, is not associated with toxic effects requiring treatment termination.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Chemoembolization for hepatocellular carcinoma.

Fifty-one patients with unresectable hepatocellular carcinoma (HCC) were treated with Gelfoam (absorbable gelatin sterile powder; The Upjohn Co, Kalamazoo, MI) chemoembolization. A mixture of Gelfoam powder, contrast media, and three drugs (doxorubicin, mitomycin, and cisplatin) was injected under fluoroscopic guidance via a percutaneous catheter into the hepatic artery until stagnation of blood flow was achieved. Of the 51 patients, 50 are assessable for response, and all are assessable for toxicity and complications. The median percent of liver replacement was 50% (range, 15% to 95%). By conventional response criteria, there were 12 partial responses (PRs) (24%), 13 minor responses (MRs) (26%), 12 stabilization of disease (SD) (24%), and 13 (26%) progressive disease (PD). Tumor liquefaction was noted on computed tomographic (CT) scan in 35 of 50 patients (70%). Of the 34 patients with elevated alpha-fetoprotein (AFP), 23 (68%) had a greater than 50% reduction following treatment. Responding patients were re-treated at the time of tumor progression if they still met the entry criteria. The median survival of assessable patients from the time of treatment was 207 days and from the diagnosis of the primary was 302 days. Fourteen patients remain alive at 3 months to 3 years following treatment. The vast majority of patients had transient pain, fever, nausea, and elevation in liver enzymes. Ascites developed in 14 patients. There were two treatment-related deaths: one from tumor hemorrhage and one from liver failure. Chemoembolization appears to have significant activity in patients with hepatocellular carcinoma and is relatively well tolerated.

Adolescent↗
PubMed1989

A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: the Northern California Oncology Group trial.

In 1983, the Northern California Oncology Group (NCOG) instituted a randomized trial of intravenous (IV) versus intraarterial (IA) floxuridine (FUDR) administered via an implantable pump for patients with colorectal cancer metastatic to the liver. The study objectives were to compare the hepatic response rate, time to hepatic progression, and toxicity for the two treatment arms. The study design, which allowed patients failing IV FUDR to crossover to the IA arm, prevents a meaningful comparative analysis of survival. Patients with liver-only metastases (N = 143) were randomized, 76 to the IV arm and 67 to the IA arm, and 115 patients (65 IV, 50 IA) were fully evaluable. Of the 65 patients in the IV arm, 28 crossed over to IA treatment after failing IV FUDR. The dose-limiting toxicity of IV FUDR was diarrhea, whereas biliary toxicity limited both the dose and duration of IA FUDR therapy. Of the first 25 patients treated with IA FUDR at a dose of .3 mg/kg/day, 10 developed radiographically evident biliary strictures, and three developed permanent jaundice. With reduction of the initial IA FUDR dose to .2 mg/kg/day, and adoption of a policy of early dosage reduction, treatment interruption, or termination of therapy for persistent elevations in alkaline phosphatase, only two further cases of serious biliary toxicity occurred. However, 26 of the 50 IA FUDR patients ultimately had therapy terminated because of drug toxicity rather than disease progression. When compared with systemic infusion, infusion into the hepatic artery greatly enhanced the antitumor activity of FUDR against colorectal liver metastases. Although biliary toxicity is the most serious limitation of this form of therapy, biliary stricture and jaundice usually can be averted through careful monitoring of liver enzymes and early dosage reduction.

Adult↗
PubMed1988

Regional chemotherapy for colorectal cancer metastatic to the liver.

Regionally directed therapies, especially hepatic intra-arterial chemotherapy, have produced encouraging results against liver metastases from colorectal cancer. An implanted system allows treatment to be administered in the outpatient setting. Intra-arterial floxuridine has been shown to produce an increased response rate and prolonged time to progression of intrahepatic tumor compared to conventional treatment, but whether or not survival is prolonged has not yet been determined. Hepatobiliary toxicity from floxuridine limits the duration of therapy. Other experimental methods of regional therapy include chemoembolization, chemofiltration and mechanical alterations in hepatic arterial flow rate.

Antineoplastic Agents↗
PubMed1987

Third-line chemotherapy for resistant Hodgkin's disease with lomustine, etoposide, and methotrexate.

Thirty-two patients with recurrent Hodgkin's disease have been treated with an oral regimen employing lomustine (CCNU, 100 mg/m2 orally on Day 1); etoposide (VP-16, 100 mg/m2 orally on Days 1-3 and 21-23); and methotrexate (30 mg/m2 orally on Days 1, 8, 21, and 28). The regimen was repeated every 6 weeks. Most patients had been treated with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine); 20 had had prior irradiation. Lymph node was the predominant site of disease and the majority of patients had B symptoms. Four patients achieved complete response (13%), with a median duration of 33+ months, and 11 achieved partial response (34%), with a median duration of 5 months, for an overall response rate of 47%. The major toxic effect was severe myelosuppression, which occurred in six patients; there were no treatment-related deaths. This oral regimen was easy to administer in heavily pretreated patients with poor venous access and had minimal toxicity.

Administration, Oral↗
PubMed1986

Toxicities and complications of implanted pump hepatic arterial and intravenous floxuridine infusion.

Toxicities and complications were prospectively analyzed in patients with liver metastases receiving hepatic intra-arterial (IA) and systemic intravenous (IV) floxuridine (FUDR) with the Infusaid (Intermedics-Infusaid Corp., Norwood, MA) implantable pump. Among 55 patients treated with IA FUDR (0.3-0.1 mg/kg/day X 14, every 28 days), elevations in liver enzyme values, not attributable to disease progression, developed in 96% of patients. Serious biliary toxicity occurred in 31 patients (56%). In 16, biliary sclerosis was documented radiographically and was diagnosed clinically in 15 additional patients. Ten patients were hospitalized for biliary toxicity, including five who required cholecystectomy for acalculous cholecystitis. Because of the high reported incidence of serious gastroduodenal toxicity after IA FUDR infusion, our procedure for hepatic arterial cannulation was designed to eliminate misperfusion of the stomach and duodenum with drug; none of our patients experienced FUDR-associated gastroduodenal ulceration or bleeding. Cyclic IV FUDR (0.05-0.15 mg/kg/day X 14, every 28 days) was administered to 31 participants of the Northern California Oncology Group trial (3L-82-1) of IV versus IA FUDR. Dose-limiting toxicity was diarrhea. Serious toxicities were: protracted diarrhea (three), dermatitis (two), tear duct stenosis (two), and stomatitis (two). Three patients were hospitalized for toxicity. No hematologic or biliary toxicity occurred. The optimal route for treatment of hepatic metastases with continuous FUDR infusion has not yet been established. Systemic IV infusion has low morbidity, but preliminary response data need to be substantiated in controlled clinical trials before there can be widespread clinical application. High response rates for IA infusion have been previously documented. Morbidity due to acalculous cholecystitis and gastroduodenal ulceration can now be avoided. Despite significant progress in characterization of hepatobiliary toxicity, it remains dose-limiting. Continuous IA FUDR infusion should remain under the aegis of dedicated treatment centers until standardized protocols with diminished toxicity are established.

Alkaline Phosphatase↗
PubMed1985

Avoidance of gastroduodenal toxicity in patients receiving hepatic arterial 5-fluoro-2'-deoxyuridine.

Gastroduodenal inflammation and ulceration have been frequently observed in patients receiving continuous hepatic arterial infusions of 5-fluoro-2'-deoxyuridine (FUDR) for liver malignancy. Thirty-five patients with metastatic colon cancer received hepatic arterial FUDR administered with implanted infusion pumps. At surgery, particular care was taken to identify and divide those vessels arising from the hepatic arteries distal to the point of cannulation that supplied the superior border of the distal stomach and proximal duodenum. None of the patients developed signs or symptoms of gastritis or ulcer attributable to chemotherapy. We contend that gastritis and ulcer in patients receiving hepatic arterial FUDR are due to misperfusion of drug into the upper gastrointestinal tract and that these complications can be largely avoided by use of appropriate surgical techniques.

Colonic Neoplasms↗
PubMed1984

Hematologic manifestations in homosexual men with Kaposi's sarcoma.

Peripheral blood and bone marrow findings are presented for six homosexual males with Kaposi's sarcoma. Cytopenia in one or more cell lines was common in this group of patients, including two individuals with pancytopenia. Bone marrow findings in all patients, while not specific, were similar in that adequate numbers of normal appearing erythroid, myeloid, and megakaryocytic elements were present. Mild plasmacytosis as well as reticulin fiber increase were common findings. No patient, at time of study, demonstrated marrow involvement with Kaposi's sarcoma. We conclude that depression of peripheral blood counts in these patients was not due to marrow underproduction, and discuss possible mechanisms for increased blood cell destruction.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Kaposi sarcoma and lymphadenopathy syndrome: limitations of abdominal CT in acquired immunodeficiency syndrome.

Abdominal computed tomography (CT) was performed in 31 patients with Kaposi sarcoma (KS) related to acquired immunodeficiency syndrome (AIDS), three patients with classic KS, and 12 patients with the newly described lymphadenopathy syndrome (LNS). The frequency, distribution, and appearance of lymphadenopathy and splenomegaly were similar in the AIDS-related KS and LNS groups. Rectal and perirectal disease was identified in 86% of the homosexual men studied; rectal KS could not be distinguished from proctitis on CT criteria alone. No CT abnormalities were seen in patients with classic KS. The CT demonstration of retroperitoneal, mesenteric, or pelvic adenopathy or of rectal or perirectal disease in patients with AIDS-related KS is not necessarily indicative of widespread involvement with the disease.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Hepatic arterial chemotherapy for colorectal cancer metastatic to the liver.

Hepatic metastases of colorectal origin are resistant to radiation and immunotherapy. Traditional intravenous chemotherapy produces responses in 10% to 30% of patients, and surgical resection is feasible in approximately 20% of patients who have a solitary or unilobar lesion. Infusion of cytotoxic agents into the hepatic artery, introduced 2 decades ago, is the most promising form of therapy for unresectable hepatic metastases. Fluorouracil, floxuridine, and mitomycin have been most commonly administered by hepatic arterial infusion. The recent development of a totally implantable pump has allowed prolonged ambulatory infusion of chemotherapeutic agents into the hepatic artery. We review the recent data on the pharmacology, therapeutic outcome, administration techniques, and complications of hepatic arterial chemotherapy. Future trials in this area should use uniform stratification variables and standardized criteria for evaluating response, time to progression, and survival.

Antineoplastic Agents↗