Biomedical subjects

T J Lynch

Publications and source records attributed to T J Lynch.

At least 19 recordsLinked to original sources

PubMed2000

A phase I study of gemcitabine and docetaxel in patients with metastatic solid tumors.

BACKGROUND: A Phase I study was initiated to determine the maximum tolerated dose of weekly gemcitabine combined with monthly, fixed-dose docetaxel. METHODS: Patients with metastatic solid tumors were treated with docetaxel, 60 mg/m(2), on Day 1 every 28 days. Gemcitabine was administered on Days 1, 8, and 15 and underwent dose adjustment in cohorts of 3-6 patients. At the maximum tolerated dose, 11 additional patients were enrolled. RESULTS: Twenty-six patients received 85 cycles of therapy. At the first dose level, the planned gemcitabine dose on Days 1, 8, and 15 was 800 mg/m(2). Two of the 6 patients treated at this dose level experienced dose-limiting toxicities (DLTs) requiring the reduction of gemcitabine to 600 mg/m(2) per dose and the administration of ciprofloxacin, 500 mg orally twice daily, on Days 8-18. At the second dose level the first 3 patients experienced no DLTs and the dose of gemcitabine was increased to 700 mg/m(2). Two of the 6 patients treated at the 700 mg/m(2) dose level experienced DLTs. Eleven additional patients were enrolled at the recommended Phase II dose of gemcitabine (600 mg/m(2)). At this dose level, Grade 3/4 (according the National Cancer Institute's common toxicity criteria) neutropenia and thrombocytopenia occurred in 12.5% and 2.1% of cycles, respectively. Grade 3 and 4 nonhematologic toxicities were uncommon. Three of seven evaluable patients with pancreatic carcinoma had evidence of significant antineoplastic activity (three partial responses). In addition, two complete responses (one patient with gastric carcinoma and one patient with ovarian carcinoma) and one partial response (patient with hepatocellular carcinoma) were noted in patients with other solid tumors. CONCLUSIONS: The regimen comprised of docetaxel, 60 mg/m(2), on Day 1 and gemcitabine, 600 mg/m(2), on Days 1, 8, and 15 with ciprofloxacin on Days 8-18 every 28 days is safe, well tolerated, and active.

Antimetabolites, Antineoplastic↗

PubMed2000

Abscisic acid inhibition of radicle emergence but not seedling growth is suppressed by sugars.

Low concentrations of sugars altered the sensitivity of seed germination to inhibition by exogenous abscisic acid (ABA). Germination of wild-type and ABA-insensitive (abi) Arabidopsis seeds was assayed on media containing ABA and a variety of sugars and sugar alcohols. The inhibitory effects of ABA were strongly repressed in the presence of 15 to 90 mM glucose (Glc), sucrose, or fructose, but not by comparable concentrations of sorbitol or mannitol. Several features of the response to Glc are inconsistent with a purely nutritional effect: The optimal sugar concentration is low and differs between the wild type and the abi mutants. Furthermore, Glc suppression of ABA inhibition is light dependent and limited to the process of radicle emergence.

Abscisic Acid↗

PubMed2000

The Arabidopsis abscisic acid response gene ABI5 encodes a basic leucine zipper transcription factor.

The Arabidopsis abscisic acid (ABA)-insensitive abi5 mutants have pleiotropic defects in ABA response, including decreased sensitivity to ABA inhibition of germination and altered expression of some ABA-regulated genes. We isolated the ABI5 gene by using a positional cloning approach and found that it encodes a member of the basic leucine zipper transcription factor family. The previously characterized abi5-1 allele encodes a protein that lacks the DNA binding and dimerization domains required for ABI5 function. Analyses of ABI5 expression provide evidence for ABA regulation, cross-regulation by other ABI genes, and possibly autoregulation. Comparison of seed and ABA-inducible vegetative gene expression in wild-type and abi5-1 plants indicates that ABI5 regulates a subset of late embryogenesis-abundant genes during both developmental stages.

Abscisic Acid↗

PubMed2000

Sedation for intractable distress of a dying patient: acute palliative care and the principle of double effect.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. The case presented is of a young man dying of recurrent epithelioid hemangioendothelioma, distressed with stridor and severe pain, whose poorly controlled symptoms were successfully treated with an infusion of propofol, titrated to provide effective comfort in the last few hours of the patient's life. The tenet of double effect, which allows aggressive treatment of suffering in spite of foreseeable but unintended consequences, is reviewed. The patient's parents were invited and contributed to the Rounds, providing compelling testimony to the power of the presence of clinicians at the time of death and the importance of open communication about difficult ethical issues.

Adult↗

PubMed2000

Communicating genetic risk: pros, cons, and counsel.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. This case is of a woman with a personal, and a strong family history of breast cancer, who considered genetic testing for mutations in the BRCA1 and BRCA2 genes. The details of the case have been altered to protect the patient's anonymity. The patient was very anxious and there was disagreement between her healthcare providers about the potential benefits of genetic testing. The discussion of the case focused on several controversial issues, particularly the ownership of genetic information, and who is responsible for disseminating information to the family members at risk. The difficulties in communicating risk, providing emotional support and coping with the continuing uncertainties about screening and intervention are reviewed with an overview of the molecular biology, inheritance, and epidemiology of the BRCA1 and BRCA2 genes.

Adaptation, Psychological↗

PubMed2000

Sexuality and cancer: conversation comfort zone.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Psychosocial issues profoundly affect patients with cancer. Of the many complexities that make up the psychosocial dynamic, perhaps the medical profession is most uncomfortable with sexuality. Many elements of sexual behavior remain high-profile taboos. A number of diseases and treatments significantly affect sexual function. Male and female sexuality were discussed in two separate rounds with an emphasis on how to begin a dialogue about sexuality without jeopardizing other aspects of the relationship with patients. Three cases were presented. A patient with prostate cancer considering treatment options for early-stage disease and two patients with gynecologic malignancies; one with a colostomy following cytoreductive surgery for ovarian cancer and the other with a failed vaginal reconstruction for recurrent squamous cell carcinoma of the vagina. Staff discussed the wide diversity of response to sexual dysfunction and the difficulties that patients face. A sensitive and informed approach to discussing sexuality can provide effective support. The elements of successful dialogue are presented in the PLISSIT model.

Adult↗

PubMed2000

Lung cancer highlights.

Have we made any progress in the treatment of advanced non-small cell lung cancer (NSCLC) over the past 15 years? After hearing the Eastern Cooperative Oncology Group (ECOG) 1594 presented by Dr. Joan Schiller at the plenary session of the 36th Annual Meeting of ASCO, it is hard to be certain. SCHILLER: reported the results of one of the world's largest randomized trials in metastatic lung cancer comparing four platinum-based doublets. There were no differences in survival (primary endpoint) or response between these four regimens, although the cisplatin/gemcitabine arm had a superior time to progression. In her commentary on this study, Dr. Francis Shepherd concluded that progress in the treatment of metastatic lung cancer has occurred at "a snail's pace." Despite the disappointing results of ECOG 1594, there were notable trials describing new agents with novel mechanisms of action reported at this year's ASCO meeting. In small-cell lung cancer, the combination of cisplatin/ irinotecan was found to be superior to cisplatin/etoposide. For NSCLC, novel agents Iressa anti-epidermal growth factor receptor tyrosine kinase and anti-vascular endothelial growth factor monoclonal antibody appear promising.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

A staff dialogue on aggressive palliative treatment demanded by a terminally ill patient: psychosocial issues faced by patients, their families, and caregivers.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum during which caregivers discuss a specific cancer patient, reflect on the important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from their fellow staff members. In this article, the case presentation and verbatim dialogue from the rounds are discussed with an emphasis on staff psychosocial issues. The case presented was of a 32-year-old man, who developed small cell osteosarcoma and was treated at MGH. He died after undergoing multiple courses of relatively ineffective chemotherapy. The case is made all the more poignant because of the pleasures, hopes and stresses of having a child late in the course of his illness. Staff identified closely, both with him and his family, and their concern for him brought joy and meaning to their work, yet this complicated their ability to deal with his impending death. They felt that his unwillingness to admit defeat prevented them from saying goodbye to someone whom they loved and admired. Despite this, staff recognized that, ultimately, the patient's emotional needs and wishes had to be respected as a first priority and that constructive closure can be worked toward, if not achieved. In such situations, it is vital to have a colleague support system and a forum for discussion of such issues in order to defuse distress and reassure staff that they are doing all that can be done as professionals and caregivers.

Adult↗

PubMed1999

A staff dialogue on caring for a cancer patient who commits suicide: psychosocial issues faced by patients, their families, and caregivers.

Adenocarcinoma↗

PubMed1999

A staff dialogue on do not resuscitate orders: psychosocial issues faced by patients, their families, and caregivers.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery which provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. The following case of a woman who developed lymphoma was discussed at the July and August, 1997 Schwartz Center Rounds. There were considerable delays and uncertainties in the diagnosis, which was followed by an unpredictably chaotic clinical course. Although she had made it clear to her doctor that she did not want "heroic measures," she had unexpectedly rallied so many times that her son and her husband wanted her doctors to do everything possible to keep her alive, including the performance of cardiopulmonary resuscitation (CPR). The clinical benefit of CPR in the event of cardiac arrest in those with cancer is discussed, as are do not resuscitate (DNR) orders, living wills, and healthcare proxies. In addition, the issues that surround DNR status, including who should discuss DNR status with a patient, and how and when it should be discussed, are reviewed. Staff raised concerns about the effect of discussing DNR status on the doctor-patient relationship, and wondered whether writing DNR orders adversely affect the care of patients.

Advance Directives↗

PubMed1999

Lung cancer highlights.

Explore the source record for details and available documents.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

A staff dialogue on a socially distanced patient: psychosocial issues faced by patients, their families, and caregivers.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. The following case of an HIV-positive woman who was diagnosed with cervical cancer during a twin pregnancy was discussed at the May, 1999 Schwartz Center Rounds. The patient was in drug rehabilitation having been dependent on crack cocaine, with a past history of syphilis and gonorrhea. She was single and her other children were in foster care. Initially she was suspicious and non-compliant. A plan was negotiated to biopsy the cervical lesion after cesarean section and with confirmation of malignancy she underwent radical surgery and subsequently radiotherapy. Despite the almost insurmountable social and educational distance between her and her caregivers, they managed to bond and facilitate care. Although there were compromises with which staff were uncomfortable, the relationship was maintained and continues.

Adult↗

PubMed1999

Reality testing in cancer treatment: the phase I trial of endostatin.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. The September 1999 Schwartz Center Rounds addressed the growing attention around the phase I trial of Endostatin. Endostatin represents a new treatment paradigm. It is an anti-angiogenic protein, an endogenous fragment of collagen XVIII. In an attempt to ensure a fair allocation of a very limited number of treatment slots in this classical phase I trial, a lottery was established. More than 1,400 patients enrolled within two days of the lottery, all vying for three places in the first cohort. Two contrasting cases are presented, each a potentially eligible patient. The discussion focuses on the dilemma presented by patients desperate for an unproven treatment and the responsibility of staff to explain and support without compounding the hype or suffocating the hope.

Adult↗

PubMed1998

Clinical trials with blocked ricin immunotoxins.

Explore the source record for details and available documents.

Animals↗

PubMed1998

The Arabidopsis abscisic acid response locus ABI4 encodes an APETALA 2 domain protein.

Arabidopsis abscisic acid (ABA)-insensitive abi4 mutants have pleiotropic defects in seed development, including decreased sensitivity to ABA inhibition of germination and altered seed-specific gene expression. This phenotype is consistent with a role for ABI4 in regulating seed responses to ABA and/or seed-specific signals. We isolated the ABI4 gene by positional cloning and confirmed its identity by complementation analysis. The predicted protein product shows homology to a plant-specific family of transcriptional regulators characterized by a conserved DNA binding domain, the APETALA 2 domain. The single mutant allele identified has a single base pair deletion, resulting in a frameshift that should disrupt the C-terminal half of the protein but leave the presumed DNA binding domain intact. Expression analyses showed that despite the seed-specific nature of the mutant phenotype, ABI4 expression is not seed specific.

Abscisic Acid↗

PubMed1997

Cocaine detoxification by human plasma butyrylcholinesterase.

The ability of human plasma butyrylcholinesterase (BChE) to detoxify cocaine in vivo was evaluated. Intravenous administration of BChE, at doses sufficient to increase the plasma levels of the enzyme as much as 800-fold, produced no adverse effects on the cardiovascular, autonomic, or central nervous systems of rats. Most of the enzyme could be recovered in the plasma immediately after administration and remained active with a beta-t(1/2) of 21.6 +/- 2.4 hr. Pretreatment of chloralose-urethane anesthetized rats with BChE, 0.1-7.8 mg/kg, decreased the hypertensive and arrhythmogenic effects produced by cocaine and increased the lethal dose of cocaine by three- to fourfold. Treatment of conscious rats with 1 and 10 mg/kg BChE decreased the incidence of seizures and deaths produced by a prior dose of cocaine (80 mg/kg, i.p.). These results suggest that BChE would provide a safe and highly efficacious treatment for cocaine intoxication.

Animals↗

PubMed1997

Therapeutic use of butyrylcholinesterase for cocaine intoxication.

The most common complications of cocaine ingestion are on the cardiovascular and central nervous systems and produce chest pain and generalized seizures. In humans, decreased levels of butyrylcholinesterase (BChE) (EC 3.1.1.8) have been associated with sustained effects of cocaine and life-threatening complications. Administration of purified human BChE has previously been demonstrated to protect against cocaine-associated cardiovascular toxicity in rats. A shift in the metabolism of cocaine as well as enhanced metabolism may be the underlying mechanism of the enzyme. Therefore, levels of the parent drug and four metabolites were determined in rat plasma after i.p. administration of a lethal cocaine dose, followed by i.v. administration of BChE. Plasma and brain concentrations of cocaine were lowered by 80% after BChE administration. Furthermore, the metabolic profile of cocaine in the plasma was altered. The concentration of ecgonine methylester was doubled although the concentration of ecgonine, a secondary metabolite of cocaine, was reduced. The level of benzoylecgonine was reduced by one-half while norcocaine was absent. Cocaine-associated effects upon the central nervous system were also shown to be reduced by administration of BChE to conscious rats. Furthermore, our studies in the cat have also shown that purified BChE shifts the metabolic profile of cocaine (1 mg/kg) to the pharmacologically inactive products ecgonine methylester and ecgonine. Pretreatment with BChE (0.27, 1.0, and 10.0 mg/kg) ameliorated the hypertensive effects of cocaine (1 mg/kg) by reducing the duration and the extent of BP elevation by 66%. Administration of the enzyme, 1 min after cessation of cocaine infusion, resulted in an immediate attenuation in the cocaine-induced broadening of the QRS complex. These results suggest that BChE could be an effective and rapid therapy for the treatment of life-threatening cocaine-induced cardiovascular effects in human while clearing the total body burden of cocaine.

Animals↗

PubMed1997

Induction therapy for esophageal cancer with paclitaxel and hyperfractionated radiotherapy: a phase I and II study.

OBJECTIVE: Induction chemoradiotherapy followed by surgery may improve survival rates among patients with esophageal carcinoma. We designed a novel intense induction regimen with paclitaxel and high-dose hyperfractionated radiotherapy to maximize complete response rates. METHODS: Forty patients with esophageal cancer were treated in a phase I and II trial of induction chemotherapy (cisplatin, 5-fluorouracil, and paclitaxel) at three dosage levels (75, 125, and 100 mg/m2) and concurrent hyperfractionated radiotherapy (45 Gy to the mediastinum, 58.5 Gy to the tumor). The mean age was 62 years, and 32 patients (80%) had adenocarcinoma. Twenty-eight of 40 (70%) patients had locally advanced tumors (T3, or stage IIB or greater). RESULTS: The average hospitalization for induction treatment was 17 days. Toxicity was substantial, with esophagitis necessitating nutritional support the most common complication. The maximum tolerated dose of paclitaxel was 100 mg/m2. Two patients died during induction treatment. Thirty-six patients (90%) underwent resection. The median length of stay was 10 days, and two patients died after the operation. Fourteen of 36 patients (39%) had a pathologic complete response. Patients who received all prescribed chemotherapy had a higher pathologic complete response rate (50%) than did patients who required dose reduction (17%; p = 0.076). The 2-year survival rate was 61% (95% CI 35% to 86%) with a median follow-up of 11.9 months. CONCLUSIONS: Paclitaxel at a dose of 100 mg/m2 appears to have acceptable toxicity. The high pathologic complete response rate in this regimen is encouraging, but it is associated with substantial toxicity. The toxicity of this regimen is not acceptable and will require substantial reduction in the radiation component. Survival data are too short-term to confirm enhanced survival.

Adenocarcinoma↗