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Biomedical subjects

A J Weiss

Publications and source records attributed to A J Weiss.

At least 19 recordsLinked to original sources

Intraarterial chemotherapy with limb-sparing resection of large soft-tissue sarcomas of the extremities.

Fifteen patients with large (average, 15-cm), high-grade soft-tissue sarcomas of the extremities received prolonged selective intraarterial infusions of chemotherapeutic agents in an attempt to permit limb-sparing resection of these tumors, which would otherwise have required amputation. There were seven malignant fibrous histiocytomas, four liposarcomas, two fibrosarcomas, one leiomyosarcoma, and one rhabdomyosarcoma; 73% were grade III. Seven patients underwent two catheterizations, for a total of 22 infusions, which averaged 11.3 days each. There were four catheterization-related complications, including catheter occlusion or dislodgement in one patient each and two cases of arterial thromboembolism in patients in whom anticoagulant dose was not adequate. Both of the latter patients required thrombectomy; one developed gangrene, which precluded limb-sparing surgery. Thirteen of the 15 patients underwent limb-sparing resections, and two underwent amputations. No wound complications occurred. With a median follow-up of 36 months (mean, 34 months), life-table analysis indicates overall and disease-free survivals of 72% and 59%, respectively, at 2 years and 64% and 59% at 3 years. In comparison to other reported therapies, this technique permits limb salvage in most patients without the high wound complication rate associated with preoperative radiation therapy, with equivalent local disease control and survival.

Adult

A pharmacologic approach to dosage intensification.

Using standard pharmacologic concepts, it is possible to show that changes in schedule will influence the relative influx of drug between various normal tissues and tumor. A line of investigation is discussed that should lead to optimization of influx into tumor tissue while minimizing uptake into dose limiting normal tissues.

Antineoplastic Agents

Extremity osteosarcomas: intraarterial chemotherapy and limb-sparing resection with 2-year follow-up.

Twenty-eight consecutive patients with extremity osteosarcoma (24 stage II, four stage III) received their entire preoperative course of chemotherapy intraarterially in order to maximize local drug concentration and tumor shrinkage to facilitate limb-sparing resection. Eighteen tumors were located in the femur, seven in the tibia, two in the humerus, and one in the fibula. Most patients underwent two catheterizations; thus there was a total of 51 procedures. The average duration of each infusion was 10.4 days. There were eight procedure-related complications, but none precluded completion of intraarterial chemotherapy. Limb-sparing surgery was performed on 25 patients. At a mean follow-up of over 2 years, there was one local recurrence. Among limb-salvage patients with stage II disease, 90% (18 of 20) survived and 75% (15 of 20) are disease-free. Compared with patients from previous studies, this technique permits a high percentage of patients with osteosarcoma to undergo limb-sparing resection without compromise of local disease control or survival.

Adolescent

Low-dose chemotherapy of desmoid tumors.

Eight patients with desmoid tumors, symptomatic, and none a candidate for conservative surgery, were treated with weekly vinblastine, maximum dose 10 mg/week, and methotrexate, maximum dose 50 mg/week. Symptomatic relief was obtained in all patients. Using Eastern Cooperative Oncology Group (ECOG) criteria, two patients had a complete remission, one of which has lasted for 30 months, four patients have had partial remissions, one patient has had a mixed response, and one patient who has been treated for only 4 weeks, a minimal response. Toxicity has been minor and transient. Chemotherapy appears to be an acceptable alternative to radical surgery in selected patients with desmoid tumors.

Adult

Varied appearance of AIDS-related lymphoma in the chest.

The authors reviewed all cases of acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL) seen at their institution between January 1982 and September 1988 to determine the frequency and appearance of ARL in the chest. Of 35 patients with ARL, 11 (31%) had biopsy-proved thoracic involvement. This frequency is significantly greater than that previously reported. The radiologic appearance of the thoracic involvement varied. Pleural effusion, interstitial and alveolar lung disease, nodules, and, infrequently, hilar and mediastinal adenopathy were observed. ARL of the chest was most commonly extranodal. Pleural effusion and lung disease were the two most common manifestations of ARL on chest radiographs and computed tomographic scans. The authors recommend that clinicians treating patients with suspected or known AIDS consider ARL when a pleural effusion or a noninfective interstitial or alveolar process is present.

Acquired Immunodeficiency Syndrome

The catalysis of protein and nucleic acid coupling to an affinity membrane substrate.

With the model ligands studies, which included IgG, HSA, streptavidin, MEA and amine-modified DNA, it was possible to enhance the rate of covalent immobilization by using nucleophilic acylation reaction catalysts. Imidazole, triazole and 2-hydroxypyridine are readily available catalysts that are effective when immobilizing immunoglobins. 4-N,N,Dimethylaminopyridine (DMAP) as a co-reactant or as a prereactant is a potent rate enhancer with all of the molecules that were examined. The precise protocol to be used is probably best derived empirically. In addition to optimizing the amount of ligand bound or the amount of time necessary to bind a fixed quantity of ligand, it is likely that the retained functionality of the ligand may be affected by the use of reaction catalysts.

Biotechnology

A hypothesis concerning the relationship of cellular pharmakokinetics to optimal scheduling of anti-cancer agents.

It is well recognized that the degree of toxicity, type of toxicity, and therapeutic to toxic ratio of most anti-cancer agents are dependent upon schedule. It is postulated that an optimal schedule is one that creates the largest possible difference in uptake of drug between neoplastic and normal cells, especially those cells that by their death limit the amount of drug that can be given to the patient. Specific pharmacokinetic parameters can be determined that optimize the relative distribution of drug between neoplastic tissues and dose-limiting normal tissues, and thus may permit optimization of schedule.

Animals

An improved method for isolating Ca2+-resistant myocytes from the adult rat heart.

Maintaining viability in cardiac myocytes isolated from adult rats using collagenase is difficult in Ca-containing media due to cell damage that occurs on reintroduction of Ca after perfusing the heart with the Ca-free medium needed to isolate myocytes with collagenase. Recently it has been proposed that Ca-free perfusion of isolated rabbit interventricular septa leads to cellular Na overload which, on reintroducing Ca, produces influx of toxic concentrations of Ca due to the Na/Ca exchange mechanism in the sarcolemma. We have found that replacing a portion of the 118 mM NaCl in the Ca-free perfusion medium with 69 mM LiCl dramatically increased the proportion of Ca-tolerant cardiac myocytes isolated from adult male rats with collagenase. Myocyte viability was maintained over a four hour period of incubation at 37 degrees C in 1 mM Ca.

Animals

Yoshi 864 (1-propanol, 3,3'-iminodi-, dimethanesulfonate [ester], hydrochloride): a phase II study in solid tumors.

Two hundred and eight acceptable patients were treated with Yoshi 864 (2 mg/kg/day by iv push X 5 days repeated once every 6 weeks). Toxicity was minimal. There was an overall response rate of 11%. Cross resistance with other alkylating agents may not be present. Because of its lack of toxicity, Yoshi 864 should be further evaluated in chronic myelocytic leukemia, lymphomas, and carcinomas of the ovary and bladder where significant responses were seen. It should also be evaluated in combinations as a replacement for other alkylating agents which cause more nausea and vomiting.

Alkylating Agents

Management of brachial plexus tumors.

Brachial plexus neoplasms are uncommon. When this diagnosis is suspected, the functional and anatomical integrity of the brachial plexus and cervical spinal cord must be carefully assessed. A thorough search for other signs of neurofibromatosis (von Recklinghausen's disease) must also be completed. The distinction between neurilemoma and neurofibroma is an important and useful one to know. Evaluation by a pathologist who is well versed in neural tumors is mandatory for appropriate treatment of these usually benign lesions. Surgical intervention, adequately prepared on the basis of the patient's age, the amount of neural impairment, and the extent and histology of the tumor requires a surgeon who is experienced in peripheral nerve surgery and in microdissection techniques. Long-term follow-up is necessary to monitor the growth of known tumors, the detection of malignant change, and the appearance of other stigmata of von Recklinghausen's disease.

Adolescent

Experience with the use of adriamycin in combination with other anticancer agents using a weekly schedule, with particular reference to lack of cardiac toxicity.

Two hundred and seven patients have been treated using a weekly regimen of adriamycin in combination with various other anticancer agents. Thirty-six of these patients have received between 600 and 1000 mg/m2 of Adriamycin and 27 have received more than 1000 mg/m2 of the agents. While electrocardiographic abnormalities were relatively common in this group of patients, no patient developed evidence of a cardiomyopathy. Significant remission rates were seen with patients having malignant lymphomas, carcinoma of the breast, various soft tissue sarcomas, and carcinoma of the ovary. We now have data on 149 patients given Adriamycin weekly who have received over 600 mg/m2 of the drug. Sixty-four of these patients have received over 1000 mg/m2 of Adriamycin. Eight patients were suspected of having an Adriamycin-induced cardiomyopathy and this was believed to be likely in only four of these patients. One patient died of a cardiomyopathy apparently induced by Adriamycin. It is our opinion that Adriamycin can be given with only a slight risk of developing a severe cardiomyopathy, in doses greater than 600 mg/m2, either as a single agent or in combination with methotrexate, Cytoxan, vincristine, or 5-fluorouracil, if the Adriamycin is given weekly.

Adult