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Biomedical subjects

L J Goldstein

Publications and source records attributed to L J Goldstein.

At least 37 records · Page 2Linked to original sources
PubMed1996

Golf club shaft impalement: case report of a zone III neck injury.

Impalement occurs when a portion of the body is penetrated by a rigid object. These injuries incorporate aspects of both blunt and penetrating type injuries in that the object or the body at time of impact is traveling at relatively low velocity and the energy is dissipated over a short distance. Impalement injuries have been described for most body cavities. Evaluation of these injuries can be uniquely challenging. We present a case of impalement of the neck from an object previously unreported in the literature, a golf club shaft.

Adult↗
PubMed1995

General surgery.

Ambulatory surgery now accounts for approximately 50% of all surgery in the United States. Minimally invasive procedures have entered the vascular arena with transfemoral endovascular graft replacement. A bioartificial liver support system was tested in seven patients with the use of porcine hepatocytes.

General Surgery↗
PubMed1995

Retrospective diagnosis of sickle cell-hemoglobin C disease and parvovirus infection by molecular DNA analysis of postmortem tissue.

A previously healthy 30-year-old African-American woman presented with a history of sickle cell trait and a nonspecific prodromal illness with severe bone pain. She experienced rapid clinical deterioration with seizures and cardiorespiratory arrest leading to death. Autopsy showed necrotic bone marrow with extensive bone marrow emboli. Parvovirus infection was documented by polymerase chain reaction (PCR) although diagnostic intranuclear inclusions or giant pronormoblasts were not present. The diagnosis of sickle cell-hemoglobin C disease (hemoglobin SC disease) was also established postmortem by DNA sequencing of PCR products. This case illustrates the use and versatility of PCR for analysis of formalin-fixed paraffin-embedded autopsy tissue.

Adult↗
PubMed1995

Eastern Cooperative Oncology Group studies of paclitaxel and doxorubicin in advanced breast cancer.

Based on their single-agent activity in metastatic breast cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and doxorubicin have been alternated and combined in Eastern Cooperative Oncology Group studies to identify a tolerable dose and schedule. A pilot trial in patients who had received no more than one prior chemotherapy regimen alternated paclitaxel 200 mg/m2 and doxorubicin 75 mg/m2 every 3 weeks. Seven of 12 patients had objective (complete plus partial) responses. A second (phase I) trial combined doxorubicin as an intravenous push and paclitaxel as a 24-hour continuous infusion. To evaluate the effect of the schedule on toxicity, the drug administration sequence (doxorubicin-->paclitaxel or paclitaxel-->doxorubicin) was alternated both between and within patients. initial doses were paclitaxel 150 mg/m2 and doxorubicin 50 mg/m2 in six patients, with a subsequent six patients receiving 175 and 60 mg/m2, respectively. Dose-limiting mucositis was seen at the second dose level when paclitaxel preceded doxorubicin, suggesting an important role for the administration sequence in determining toxicity (and possibly efficacy) in this regimen. These results support the sequence of doxorubicin 50 mg/m2 followed by paclitaxel 150 mg/m2 as the maximum tolerated dose. This combination has been incorporated as a treatment arm in an ongoing randomized prospective phase III Intergroup trial. By comparing the combination with both drugs as single agents (with crossover to the opposite agent at disease progression), investigators will attempt to assess response, toxicity, and time to progression as well as the degree of cross-resistance between the two agents. Given the poor prognosis of patients with advanced breast cancer, the three arms also will be evaluated in terms of patients' quality of life.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

P-glycoprotein in adult solid tumors. Expression and prognostic significance.

Several potential mechanisms of chemotherapy resistance have been identified in adult solid tumors. The multidrug resistance (MDR) phenotype is one mechanism by which tumors may simultaneously develop resistance to multiple chemotherapeutic agents and is associated with P-glycoprotein expression. In this article, the authors examine the literature and summarize the various techniques used to measure MDR1 gene expression, patterns of expression in adult solid tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Paclitaxel (Taxol)/doxorubicin combinations in advanced breast cancer: the Eastern Cooperative Oncology Group experience.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the first taxane to enter routine clinical practice, has aroused considerable interest due to its novel mechanism of action and its significant activity in metastatic breast cancer. Given this activity, it seemed logical to attempt to combine paclitaxel with doxorubicin, the other most active single agent in metastatic breast cancer. The Eastern Cooperative Oncology Group performed two trials investigating paclitaxel/doxorubicin combinations in patients with advanced breast cancer in an attempt to identify a tolerable dose and schedule of the combination. In the first trial, paclitaxel and doxorubicin were alternated every 3 weeks in doses of 200 mg/m2 and 75 mg/m2, respectively, for patients who had received no more than one prior chemotherapeutic regimen. Therapy was well tolerated in this setting. At these doses, paclitaxel induced more granulocytopenia and less thrombocytopenia than did doxorubicin. Objective responses (complete and partial responses) were seen in seven of 12 patients; two other patients had improved disease (relief of pain in bony metastases). A second limited-institution Eastern Cooperative Oncology Group trial evaluated paclitaxel and doxorubicin given in combination. In this phase I trial, doxorubicin was given as an intravenous push and paclitaxel as a 24-hour continuous infusion. The sequence of drug administration (D-->P or P-->D) was alternated both between and within patients, so that we might evaluate the effect of administration schedule on toxicity. Therapy was begun at an initial paclitaxel dose of 150 mg/m2 and an initial doxorubicin dose of 50 mg/m2 in six patients, with a subsequent six patients receiving 175 and 60 mg/m2, respectively, of paclitaxel and doxorubicin. In addition, patients received granulocyte colony-stimulating factor 5 micrograms/kg/d. While therapy at the initial dose level was well tolerated, dose-limiting mucositis was seen at the second dose level, although only when paclitaxel preceded doxorubicin. This suggests that sequence of drug administration in paclitaxel-based regimens may play an important role as a determinant of toxicity and (perhaps) efficacy, a finding similar to that seen when paclitaxel and cisplatin were combined in patients with ovarian cancer. Based on this study, we identified the sequence of doxorubicin (50 mg/m2) followed by paclitaxel (150 mg/m2) to be the maximum tolerated dose. This combination is currently being compared with paclitaxel alone and doxorubicin alone in patients with advanced breast cancer in an intergroup trial led by the Eastern Cooperative Oncology Group.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

An improved SPICE heart model that obeys Starling's law.

This paper details a versatile and easy to use electrical network model of the heart in which the user can control the heart rate, blood pressure, end-diastolic left ventricular pressure, and proportion of time spent in systole. Several dysrhythmias and cardiac diseases can be simulated, including asystole, second and third degree heart blocks, brady- and tachycardias, premature ventricular contractions, premature atrial contractions, sinus dysrhythmias, hypo- and hypertension, pericardial tamponade and combinations of these. The model's output simulates empiric data with a 99% correlation, and the heart obeys Starling's law and can simulate congestive heart failure. This model is substantially more flexible than our previous version (Goldstein, et al., Comput. Methods Progr. Biomed. 33 (1990) 27-34) making it a more powerful adjunct for studying cardiac neurohormonal feedback theories and for exploring general systemic cardiovascular hemodynamics.

Arrhythmias, Cardiac↗
PubMed1993

Doxorubicin and multidrug resistance.

The circumvention of P-glycoprotein function by pharmacologic agents is a major focus of clinical trials aimed at increasing the cytotoxicity of multidrug resistance-associated drugs, including doxorubicin. The success of this approach will likely depend on the clinical significance of P-glycoprotein expression, which has not yet been elucidated for the common solid tumors, and the ability to achieve effective levels of circumventing agents without dose-limiting toxicities. Initial clinical studies suggested that biologically relevant concentrations of multidrug resistance modulators, eg, cyclosporine, can be achieved. Because pharmacologic agents that inhibit drug efflux by P-glycoprotein are themselves pumped out of cells by the transporter, this approach may have an inherent barrier to success. Laboratory studies have suggested alternative strategies for circumventing P-glycoprotein action, eg, the use of monoclonal antibodies directed against P-glycoprotein and liposome-encapsulated drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Transplantation of bone marrow cells from transgenic mice expressing the human MDR1 gene results in long-term protection against the myelosuppressive effect of chemotherapy in mice.

Many human cancers that are initially responsive to chemotherapy eventually fail to respond to treatment. For some drugs, dose escalation that may be required for a cure cannot be achieved because sensitive tissues such as bone marrow (BM) limit cytotoxic therapy. Approaches to prevent or circumvent BM toxicity are therefore a high priority of research on dose escalation protocols. In this study, we have transplanted BM cells from transgenic mice that constitutively express physiologic amounts of a functional human multidrug resistance (MDR1) cDNA to lethally irradiated C57BL/6 x SJL F1 mice (n = 36). From 6 weeks to 10 months after the transplant, all animals contained MDR1 DNA in spleen and BM specimens as indicated by Southern blot analysis, and expressed MDR1 messenger RNA in BM samples as detected by slot blot analysis. In addition, these animals were resistant to the myelosuppressive effect of doxorubicin, daunomycin, taxol, vinblastine, vincristine, etoposide, and actinomycin D, whereas control animals that were reconstituted with normal BM were drug sensitive. Finally, the chemoprotection afforded by the MDR1 gene could readily be reversed by adding chemosensitizers such as cyclosporin A and R-verapamil to chemotherapy. Hence, it appears that BM cells expressing the human MDR1 gene maintain this function after transplantation to host animals for a minimum of 10 months, and confer multidrug resistance to these BM recipients. This selective advantage conferred by expression of the MDR1 cDNA suggests a strategy for the use of MDR1 gene therapy in cancer chemotherapy and for the introduction of otherwise nonselectable genes into BM.

Animals↗
PubMed1992

A computer model of the kidney.

We developed a computer model of renal function that factors perfusion pressure, serum sodium, potassium, antidiuretic hormone and aldosterone concentrations to derive urine output, urinary sodium and urinary potassium excretion. The model implements Uttamsingh's (Uttamsingh, R.J., et al. Mathematical model of the human renal system. Med. Biol. Eng. Comput. 23 (1985) 525-536) analytical equations as an electrical circuit suitable for network analysis. This model is useful for studying the effects of renal blood flow and the humoral milieu on renal function in normal kidneys either as a stand-alone unit or in combination with other physiological electrical models.

Computer Simulation↗
PubMed1991

Expression of cathepsin L in human tumors.

It has been proposed that proteases secreted by cancer cells facilitate tumor invasion and metastasis by degrading the components of extracellular membranes. The lysosomal cysteine protease cathepsin L is synthesized in large amounts and secreted by many malignantly transformed cells in culture. The secreted protease is potent in degrading collagen, laminin, elastin, and other structural proteins of basement membranes. To determine whether human cancers synthesize cathepsin L, the expression of cathepsin L in approximately 100 human tumor samples was determined by quantitative RNA slot blot analysis using a specific human cathepsin L complementary DNA probe. Results of the present study suggest that cancers in general express higher levels of cathepsin L than do normal tissues. Kidney and testicular tumors expressed the highest levels of cathepsin L; non-small cell carcinomas of the lung expressed the next highest levels; and most cancers of the breast, ovary, colon, adrenal, bladder, prostate, and thyroid expressed elevated levels as well. Cathepsin L may prove useful as a diagnostic or prognostic marker of human malignancy.

Cathepsin L↗