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Biomedical subjects

W Ensminger

Publications and source records attributed to W Ensminger.

17 recordsLinked to original sources
PubMed1991

Malignant hepatic tumors: P-31 MR spectroscopy with one-dimensional chemical shift imaging.

To determine the clinical feasibility and applicability of phosphorus-31 magnetic resonance (MR) spectroscopy and to assess its potential for characterization of human hepatic tissue, one-dimensional chemical shift imaging (CSI) was performed in 37 patients with various malignant hepatic neoplasms (30 metastases from a variety of primary tumors and seven hepatocellular carcinomas) and seven healthy volunteers. Tumors were grouped according to the percentage of the analyzed section that was occupied by tumor: less than 50% (group A) or more than 50% (group B). In group B, all phosphomonoester/beta-adenosine triphosphate ratios were significantly higher than normal (P less than .001). Hepatocellular carcinomas and metastases from various primary neoplasms could not be differentiated on the basis of spectral characteristics and metabolite ratios. Limitations of one-dimensional surface coil CSI prevented separation of spectra of small tumors and tumors deep within the liver parenchyma from spectra of normal liver parenchyma.

Adenosine Triphosphate↗
PubMed1990

Random sampling by glitter drop method.

In the course of a study on glioblastoma tissue and cultured cell lines, a glitter drop technique for random sampling was introduced (1). Here, we report the initial description of the details of this procedure and its application to cell counts from explant slides and to determining bromodeoxyuridine (BUdR) labeling indices (LI) in tissues. The method is without bias, easy to perform and takes only a short time. It compares well with three other generally used random sampling procedures.

Bromodeoxyuridine↗
PubMed1989

Hepatic arterial chemotherapy for primary and metastatic liver cancers.

Hepatic arterial chemotherapy represents a means of selectively exposing hepatic tumor to cytotoxic agents. Although 5-fluoro-2'-deoxyuridine has been shown to generate a higher response rate in the treatment of colorectal liver metastases than that achieved by intravenous infusion, responses are largely incomplete and rarely of long duration. This review describes the rationale for the use of the thymidine analogs 5-bromo-2'-deoxyuridine and 5-iodo-2'-deoxyuridine in hepatic arterial infusions and indicates how combination therapy adding radiotherapy, specifically with hepatic arterially administered yttrium-90 microspheres, might generate a new, more efficient and effective therapeutic approach.

Bromodeoxyuridine↗
PubMed1989

Floxuridine-associated sclerosing cholangitis. A dog model.

The authors developed a dog model for the biliary sclerosis that occurs as a severe complication of protracted hepatic arterial floxuridine (FUDR) infusions (using implanted drug delivery systems) in patients with hepatic cancers. Infusaid pumps attached to hepatic arterial catheters were used for protracted infusions in ten mixed breed hounds. To allow repeated cholangiograms, the animals' gallbladders were removed and catheters connected to subcutaneous infusion ports were positioned in the cystic ducts. Five treated dogs received FUDR 0.3 mg/kg/day through the pump for a total of 30 days. Five control dogs received only saline through the pump. Cholangiograms were obtained before and after treatment in all animals. In the control group, serum liver function test results and the cholangiographic appearance of the biliary tree remained within normal limits. By contrast, in the FUDR-treated group, serum glutamic-pyruvic transaminase and alkaline phosphatase progressively rose above normal, starting 2-3 weeks into FUDR infusion, followed by hyperbilirubinemia (7-28 mg/dl peak levels) beginning 4 to 6 weeks after initiation of the drug infusion. Cholangiograms revealed focal strictures involving the central bile ducts (five dogs) and diffuse attenuation of the intrahepatic ducts (four dogs). Thus, the liver function abnormalities and the cholangiographic findings in this dog model mimic the hepatobiliary toxicity in sensitive patients receiving similar treatment.

Animals↗
PubMed1984

Regional chemotherapy of colorectal cancer metastatic to the liver.

Ninety-three patients with biopsy-proven colorectal cancer metastatic to the liver were treated with hepatic arterial infusion of 5-fluorodeoxyuridine (FUDR). There were 52 men and 41 women (median age, 60 years). Forty-two patients (45%) had failed prior systemic chemotherapy. Catheters were operatively placed and multiple catheters were used if dictated by hepatic arterial anatomy in order to obtain perfusion of the entire liver. The drug was delivered by a totally implanted INFUSAID model 400 pump and patients received cyclic therapy consisting of 2 weeks of 0.3 mg/kg/d FUDR alternating with 2 weeks of saline. Patients with extrahepatic tumor or patients whose hepatic tumor failed to respond to FUDR were given a 30 minute intraarterial infusion of mitomycin C, 15 mg/m2, every 6 to 8 weeks in addition to FUDR. Fifty of the 93 evaluable patients presented with metastatic tumor confined to the liver. Of these 50 patients, 83% demonstrated a significant reduction in tumor size with a median duration of response of 13 months and a median survival of 25 months from diagnosis of liver metastases. Twenty-four of these 50 patients remain alive. Forty-three patients presented with extrahepatic metastases in addition to their liver tumor, and 74% had a response with a median duration of 6 months and a median survival of 14 months. Only six patients of those presenting with extrahepatic tumor remain alive. None of the 93 patients died solely of uncontrolled liver tumor, and only 9 died as a result of uncontrolled liver metastases and disseminated extrahepatic tumor. The duration of survival for both groups was determined by the uncontrolled progression of extrahepatic tumor. In patients with metastatic colorectal cancer involving only the liver, hepatic arterial FUDR alone and with the addition of mitomycin C provided excellent control of hepatic tumor. Survival appeared to be prolonged in this uncontrolled study.

Antineoplastic Agents↗
PubMed1982

Improved regional selectivity of hepatic arterial BCNU with degradable microspheres.

Starch microspheres 40 micrometers in diameter, which are rapidly degraded by serum amylase, have been administered through hepatic arterial catheters to five patients with primary and metastatic liver cancer to determine whether (1) arterial blood flow through the liver could be temporarily blocked, and (2) such occlusion at the level of the arteriolar capillary bed would enhance regional uptake and catabolism and decrease systemic exposure to simultaneously administered hepatic arterial bischlorethylnitrosourea (BCNU). It was possible with 10 ml of microspheres (9 X 10(6) microspheres/ml) injected into the hepatic artery to transiently (for 15-30 minutes) reduce hepatic flow by 80-100% in the five patients. When BCNU (50 mg/m2 in one minute) was given with microspheres there was a 30-90% reduction in systemic nitrosourea exposure and in peak levels. No myelosuppression was noted and hepatic toxicity consisted of acute pain due to BCNU and 1.5-2.0 fold transient enzyme elevations. One patient with cholangiocarcinoma showed a partial response lasting three months; three patients had stable disease and one patient with colon carcinoma had progressive disease. Thus, this pilot study suggests that concurrent intra-arterial microspheres and BCNU may have the potential to improve selective regional drug effect with marked diminution in systemic toxicity.

Carmustine↗
PubMed1982

Totally implanted system for intravenous chemotherapy in patients with cancer.

A totally implanted system for improved central venous access has been investigated in 20 patients with cancer (six with solid tumors, four with leukemia, and 10 with lymphomas) who were treated with aggressive chemotherapy regimens and who lacked peripheral venous sites. The system is implanted using local anesthesia and consists of a subcutaneous injection port connected to a Silastic catheter threaded through the subclavian vein into the superior vena cava. Injections and continuous infusions (for up to three weeks) of virtually all classes of antineoplastic agents, antibiotics, blood components, and intravenous solutions were administered through the system. The system was filled with heparinized saline and not otherwise flushed between uses. The system has remained functional for periods exceeding 450 days (mean 235 days). There was no significant local irritation and no system became infected. None of 18 large-bore catheters (0.63 mm lumen) became occluded (seven to 300 days), whereas five of six small-bore catheters (0.38 mm lumen) became occluded (90 to 420 days). Three of the occluded systems were replaced. Acceptance has been excellent, and patients have had no impediment to normal activities. This system appears to be an alternate means of safe and reliable central venous access with improved convenience and cosmetic acceptability.

Antineoplastic Agents↗
PubMed1982

Totally implanted venous and arterial access system to replace external catheters in cancer treatment.

A totally implanted venous and arterial access system was tested in 30 cancer patients. The device, an injection port (Infuse-A-Port, Infusaid Corp., Sharon, Mass.), consisted of a 3.5 by 1.5 cm conical chamber with a self-sealing silicone rubber septum connected to a Silastic catheter. Ten patents had the injection port operatively placed for arterial access. A total of 39 bolus injections and 18 continuous infusions lasting an average 5.4 +/- 3.4 days were administered through the port. The total time of arterial access ranged from 70 to 370 days. No special program of heparinization was required to maintain patency. The injection port was used for central venous access in 20 patients. The first six patients had a small lumen catheter of 0.38 mm internal diameter, and five had occlusion between 142 and 447 days. Subsequently, 19 ports with a larger catheter lumen of 0.63 mm were used. These ports functioned for an average of 274 +/- 110 days (23 to 382 days). There were 380 single bolus injections and 64 continuous infusions. A variety of anticancer agents as well as whole blood, blood products, and antibiotics were administered with the device without difficulty. Patient acceptance was excellent.

Adult↗
PubMed1981

Treatment of central nervous system tumors with methotrexate.

Thirteen patients with primary and metastatic CNS tumors have been treated with methotrexate (MTX) using three different approaches: (a) high-dose MTX with leucovorin (LV) rescue; (b) high-dose MTX with carboxypeptidase (CPDG) rescue; and (c) intraventricular administration of low doses of MTX for extended periods (concentration X time [CXT]). Eleven patients had central nervous system (CNS) lymphoma (one primary, one patient had recurrent medulloblastoma, and another patient had metastatic breast carcinoma. All 13 patients received high-dose MTX-LV rescue, while 3 patients were subsequently given MTX-CPDG. One patient received MTX by all three modalities. In patients with CNS lymphomas, complete responses (45%) and partial responses (36%) produced CNS disease-free intervals ranging from 1 to 23+ months. Survival for the complete responders has thus far ranged from 2.5 to 35 months, while the partial responders survived from 3 to 5 months. Two patients failed to respond and survived 2.5 and 3 months. Responses were obtainable with high-dose MTX-CPDG in patients resistant to MTX-LV. One patient who became sensitized to CPDG subsequently responded to MTX by intraventricular CXT administration. Thus, MTX can be effectively administered to patients with CNS tumors by several different approaches.

Adolescent↗
PubMed1980

The use and limitations of serial plasma carcinoembryonic antigen (CEA) levels as a monitor of changing metastatic liver tumor volume in patients receiving chemotherapy.

Nine patients with liver-predominant or liver-only metastatic adenocarcinoma, who received hepatic intra-arterial and peripheral intravenous chemotherapy, were evaluated to determine if changes in plasma CEA accurately indicated changes in liver tumor volume as estimated from serial liver scan defect sizes, and if the two were quantitatively related. When selected periods of tumor remission or progression were studied during chemotherapy, the index of change of serial CEA values correlated positively (r = 0.764, P = 0.01) with the index of change of liver tumor volume in all 9 cases. Changes in absolute CEA values, however, aid not correlate significantly with changes in absolute liver tumor volumes when assessed either during these selected periods or throughout individual patient courses. Biologic and methodologic factors that influence the quantitative relation between liver tumor volume and plasma CEA are discussed.

Adenocarcinoma↗
PubMed1980

Comparison of pharmacokinetics of 5-fluorouracil and 5-fluorouracil with concurrent thymidine infusions in a Phase I trial.

The serum half-life of 5-fluorouracil (5-FUra) in humans is best described as a biexponential decay function, with t1/2 alpha = 7.8 +/- 2.6 (S.E.) min and t1/2 beta = 36.8 +/- 13.5 min during initial courses of this drug alone. Pharmacokinetics of 5-FUra during courses of daily therapy (for 5 days) revealed prolongation of t1/2 in both components of the decay curve, which has not been previously reported. Despite the efficacy of thymidine (dThd) given as a continous i.v. infusion of 8 g/sq m/day in prevention of high-dose methotrexate toxicity, continuous infusion of dThd at this dose does not prevent the toxicity of 5-FUra orreverse inhibition of DNA and RNA synthesis by 5-fura. On the contrary, continuous infusion of dThd appears to increase the toxicity of 5-FUra during continuous dThd infusion revealed prolongation of the 5-FUra t1/2 which remained stable through the course of 5 days of 5-FUra with dThd. This protracted t1/2 is believed to account at least in part for the increased toxicity of 5-FUra with dThd. Dose-limiting mucositis, myelosuppression, and gastrointestinal toxicity were observed at 5-FUra doses ranging from one-half to two-thirds the customarily tolerated dose of 5-FUra alone in similar courses of daily bolus therapy (for 5 days).

Adult↗
PubMed1980

Thymidine arrest and synchrony of cellular growth in vivo.

Thymidine (TdR) has been used to study the kinetics of in vitro cell proliferation and is currently being used clinically as a single agent at high doses. We have explored the in vivo cytokinetic effects of TdR on rapidly proliferating cell populations by continuous infusions in rats. The nucleoside was lethal at high doses when serum levels approached 10(-2) M.. At levels of 10(-3) M, TdR exposure for greater than 24 hours resulted in bone marrow hypocellularity and peripheral myelosuppression. Pathologic findings were also noted in the intestinal mucosa. Serum TdR levels of 10(-4) M were sufficient to induce arrest of cell growth in S phase by inhibition of DNA synthesis. Subsequent release after TdR exposure produced partial synchronization of the bone marrow and intestinal mucosa cell populations, as shown by microfluorometry and labeling studies to monitor DNA synthesis. A similar arrest of cell cycle traverse has been demonstrated in a tumor cell population by infusing rats bearing transplantable subcutaneous myeloblastomas. The inhibition of DNA synthesis, as determined by labeling studies, was comparable for bone marrow, intestinal mucosa, and myeloblastoma at serum TdR levels of 10(-3) M. This arrest of myeloblast cell growth was dependent on tumor burden and did not effect survival when maintained during 72-hour infusions. The continuous infusion of TdR provides an approach for studying cell kinetics in vivo, and findings similar to those described here have been observed in our clinical studies.

Animals↗
PubMed1978

Comparative effects of citrovorum factor and carboxypeptidase G1 on cerebrospinal fluid-methotrexate pharmacokinetics.

A comparison between citrovorum factor (CF) and carboxypeptidase G1 (CPDG1) rescue with respect to cerebrospinal fluid (CSF)-methotrexate (MTX) disappearance was studied in a patient with recurrent medulloblastoma who had a ventriculoperitoneal shunt. CPDG1 rescue resulted in a prolonged CSF-MTX half-life of 16.5-23 hours in comparison with CF rescue where the CSF-MTX half-life was 6.5-7.2 hours. There was a positive clinical response measured by loss of bone pain, increased physical activity, and almost complete clearing of CSF blast cells. CPDG1 rescue after high-dose MTX may provide more intense and selective treatment for meningeal neoplasms.

Adolescent↗
PubMedDate not supplied

Totally implanted drug delivery system for hepatic arterial chemotherapy.

A totally implanted drug delivery system for hepatic arterial chemotherapy was evaluated in 13 patients with metastatic (11 colon and one carcinoid) or primary (one hepatoma) cancer of the liver. During laparotomy, a Silastic catheter was positioned in the hepatic artery for infusion to the entire liver arterial vasculature as ascertained by low-flow radionuclide angiography with 99Tc-macroaggregated albumin. The catheter was connected to a subcutaneously implanted model 400 Infusaid pump (Metal Bellows Corp, Sharon, MA). Each pump had a 50-ml volume and a set rate (3--6 ml/day) and required refill every 8--16 days. A side port bypassed the pumping mechanism and allowed direct catheter injection for nuclide angiography, for bolus drug administration, or for clearing of a blocked catheter. Pump refills and side port injections were performed by percutaneous injection. The 13 patients in this ongoing study received a median of 6 months (range, 4.5--17) of continuous hepatic arterial infusion. The pump performed reliably with stable (+/- 10%) flow rates and only one malfunction in 2800 cumulative days of use. Flow distribution determined by low-flow radionuclide angiography did not change in 12 patients. Patient acceptance was excellent, with the ability to participate fully in normal daily activities. Eleven patients showed partial hepatic tumor regressions documented by physical examination and nuclide liver scans. All patients were treated with 5-fluorodeoxyuridine. Two patients failed 5-fluorodeoxyuridine therapy and subsequently responded briefly to dichloromethotrexate. This implanted system should facilitate future investigation of regional chemotherapy using these and other agents.

Adult↗
PubMedDate not supplied

Implanted system for intraventricular drug infusion in central nervous system tumors.

We have developed a totally implanted drug delivery system capable of maintaining constant cerebrospinal fluid (CSF) drug levels through continuous intraventricular infusion in outpatients. This system was used to infuse methotrexate (MTX) intraventricularly in seven patients with incurable CNS malignancies. One patient with meningeal diffuse histiocytic lymphoma, five patients with grade III--IV astrocytomas, and one patient with melanoma metastatic to the brain were treated with this system for 4--40+ weeks. The system consists of an Infusaid pump (Metal Bellows Corp, Sharon, MA), implanted subcutaneously in the infraclavicular fossa, which delivers a drug-containing solution at a set rate (3--5 mg/day) through a subcutaneous silastic catheter to a Rickham ventriculostomy reservoir and into a lateral ventricle. System placement and maintenance were readily tolerated. Constant MTX infusion at rates of 0.5--10 mg/day generated corresponding constant CSF drug levels in the range of 2--30 microM. Simultaneous serum MTX levels were undetectable (less than 0.01 microM), indicative of a 200- to 3000-fold selective regional concentration advantage for this approach. CNS toxic effects included transient meningism and fever (four patients), transverse myelitis (one), and the development of a diffuse hypodensity of the white matter on computerized tomographic scan which was not associated with any neurologic deficit (two). The usual systemic toxic effects (myelosuppression and mucositis) of MTX were not seen. The patient with meningeal lymphoma has had a complete remission of meningeal disease continuing past 10 months. Computerized tomography showed that three of the five high-grade astrocytomas had 25% size reductions in tumors lasting 2--6 months. This system may provide a means for improved treatment of meningeal tumor although its role in the treatment of intraparenchymal brain tumors is less clear. Of greater consequence, however, is the demonstrated ability of this system to maintain a controlled CSF drug level which should prove useful in many areas of therapeutic research.

Adult↗