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Biomedical subjects

M Sullivan

Publications and source records attributed to M Sullivan.

At least 307 records · Page 17Linked to original sources
PubMed1989

Intraperitoneal radioimmunotherapy for ovarian cancer: pharmacokinetics, toxicity, and efficacy of I-131 labeled monoclonal antibodies.

Thirty-six patients with ovarian cancer were treated with intraperitoneal I-131 labeled monoclonal antibodies to tumor associated antigens. The activity of I-131 administered was increased from 20 mCi to 158 mCi and the pharmacokinetics and toxicity evaluated. Five patients who had developed HAMA (Human Antimouse Antibodies) were retreated, and the pharmacokinetics and toxicity of the first and second treatment compared. Patients receiving their first therapy (HAMA negative), had a maximum of 25% (range 19.8-39.8%) of the injected activity in their circulation. This was accompanied by severe marrow suppression at I-131 activities over 120 mCi. The 5 HAMA positive patients had only 5% injected activity in the systemic circulation (range 3.8-6%), with rapid urinary excretion and neglible marrow suppression. In 31 patients with assessable disease there were no responses in 8 patients with gross disease (nodules greater than 2 cms), partial responses in 2 out of 15 patients with nodules less than 2 cms, and complete responses in 3 out of 6 patients with microscopic disease. The non specific radiation dose to the peritoneal cavity was estimated to be less than 500 cGy by lithium fluoride TLD, and could not be expected to account for the responses seen.

Animals↗
PubMed1989

Increased exercise capacity after digoxin administration in patients with heart failure.

Failure to objectively assess the effect of digitalis on exercise capacity has resulted in controversy regarding its use in patients with chronic congestive heart failure. To clarify this situation, maximal treadmill testing with respiratory gas exchange analysis was performed on 11 patients (mean age 57 +/- 9 years) with chronic congestive heart failure with and without digoxin therapy. Ten of the 11 had a consistent third sound gallop, and the mean ejection fraction of the group was 24 +/- 10%. Rest heart rate was significantly higher (91 +/- 16 versus 102 +/- 16 beats/min; p less than 0.05) and rest systolic blood pressure was significantly reduced in the absence of digoxin (130 +/- 23 versus 121 +/- 15 mm Hg; p less than 0.05). No differences in heart rate or blood pressure were observed during exercise. Significant increases in ventilatory oxygen uptake were observed with digoxin submaximally (3.0 mph, 0% grade), at the gas exchange anaerobic threshold and at maximal exercise (mean increase of 2.6 ml/kg per min; p less than 0.02). An improvement in the estimated ratio of ventilatory dead space to tidal volume (VD/VT), an index of physiologic efficiency, occurred throughout exercise during digoxin therapy, and there was a significant negative correlation between the change in maximal oxygen uptake and change in maximal estimated VD/VT (r = -0.63; p less than 0.05). Thus, digoxin therapy is associated with a significant improvement in exercise capacity in patients with chronic heart failure, most likely due to an improved matching of ventilation to perfusion.

Adult↗
PubMed1989

Immediate breast reconstruction: reducing the risks.

One-hundred and sixty-five consecutive immediate breast reconstructions in 157 patients were reviewed. Reconstructions were performed with tissue expanders (53 percent) or immediate gel prostheses (47 percent). Immediate reconstruction was associated with an 18 percent rate of implant loss. Certain risk factors were identified at the p less than 0.05 level using immediate gel implants: failure to achieve complete muscle coverage of the implant, smoking at the time of surgery, initial gel implants of 400 ml or more volume, and age. Expander loss was increased by detaching the pectoralis major (p less than 0.05) and probably by lack of complete muscle coverage in general. Chemotherapy, history of previous smoking, and clinical stage of the carcinoma did not seem to affect reconstructive success. Smoking and patient age should be considered during patient selection for immediate reconstruction. Muscle coverage of the prosthesis should always be attempted. Muscle coverage is mandatory in the smoker. Gel implants of 400 ml or more volume are to be avoided at the initial operation. This approach should enable all surgeons to achieve lower rates of implant loss.

Adult↗
PubMed1989

Synthesis of immunogenic, but non-infectious, poliovirus particles in insect cells by a baculovirus expression vector.

A baculovirus expression vector (AcLeon) derived from Autographa californica nuclear polyhedrosis virus (AcNPV) was prepared containing the complete 6.6 kb coding region of the P3/Leon/37 strain of poliovirus type 3 placed under the control of the AcNPV polyhedrin promoter. The recombinant virus was used to infect Spodoptera frugiperda insect cells. As demonstrated by use of the appropriate antibodies, infected insect cells made poliovirus proteins that included the structural proteins VP0, VP1 and VP3. Poliovirus particles were recovered from extracts of the infected cells and demonstrated to be free from detectable levels of RNA and to be non-infectious in tissue culture. After particle purification by CsCl gradient centrifugation and immunization of outbred mice, antibodies to the structural proteins, including neutralizing antibodies, were obtained. Other recombinant baculoviruses, containing the majority of the capsid coding region of P3/Leon/37 (e.g. AcCAP21, nucleotide residues 742 to 3318), made an unprocessed precursor to the poliovirus structural proteins. These data suggested that processing of the poliovirus gene product by the AcLeon construct was catalysed by the poliovirus-encoded proteases. The results demonstrated that antigenic and immunogenic poliovirus proteins and empty particles can be made in insect cells by recombinant baculoviruses.

Animals↗
PubMed1989

Intraperitoneal radioimmunotherapy for ovarian cancer.

Twenty-eight patients with assessable residual ovarian cancer after cytoreductive surgery and chemotherapy received intraperitoneal I-131 labelled monoclonal antibodies. There was no response in eight patients with tumour nodules greater than 2 cm, a partial response in two of the 15 patients with tumour nodules less than 2 cm, and a complete response in three of the other five patients with positive peritoneal washings. A further six patients received Y-90 labelled monoclonal antibodies for residual ovarian cancer. There was no response in one patient with nodules greater than 2 cm, and a partial response in one of the other five patients with tumour nodules less than 2 cm. The non-specific radiation dose in the peritoneal cavity from the infused isotope was measured by lithium fluoride thermoluminescent dosimetry (TLD). The radiation dose received by the peritoneal serosa was less than 500 cGy and was not sufficient to account for the observed tumour response. Significant bone marrow suppression was observed with I-131 activities greater than 120 mCi and with Y-90 activities greater than 13 mCi. The haemopoietic bone marrow is the dose-limiting organ in patients receiving radioimmunotherapy.

Adult↗
PubMed1989

Expression of a human multidrug resistance cDNA (MDR1) in the bone marrow of transgenic mice: resistance to daunomycin-induced leukopenia.

The human multidrug resistance gene (MDR1) encodes a drug efflux pump glycoprotein (P-glycoprotein) responsible for resistance to multiple cytotoxic drugs. A plasmid carrying a human MDR1 cDNA under the control of a chicken beta-actin promoter was used to generate transgenic mice in which the transgene was mainly expressed in bone marrow and spleen. Immunofluorescence localization studies showed that P-glycoprotein was present on bone marrow cells. Furthermore, leukocyte counts of the transgenic mice treated with daunomycin did not fall, indicating that their bone marrow was resistant to the cytotoxic effect of the drug. Since bone marrow suppression is a major limitation to chemotherapy, these transgenic mice should serve as a model to determine whether higher doses of drugs can cure previously unresponsive cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Reproducibility of treadmill exercise data in patients with atrial fibrillation.

Serial submaximal treadmill tests are often used to evaluate the efficacy of therapy in patients with atrial fibrillation. Since the response to serial tests can be influenced by a 'learning phenomenon', we performed maximal exercise tests on 9 patients (mean age 63 +/- 4 years) with chronic atrial fibrillation. Points of analysis for the initial and follow-up treadmill exercise tests were 3 mph/0% grade, the gas exchange anaerobic threshold, and maximal exertion. Significant (p less than 0.05) reductions in ventilation (l/min) and oxygen uptake (ml/kg/min) were observed on follow-up at a standard submaximal work load of 3.0 mph/0% grade and at the gas exchange anaerobic threshold. There was no significant alteration in these variables at maximal exertion. A reduction in heart rate was observed throughout exercise during the follow-up test with the most marked reduction (21 beats/min) occurring at 3.0 mph/0% grade. There were no differences in respiratory exchange ratio or systolic blood pressure at any point. The reduction in submaximal heart rate and gas exchange variables without a significant change in these variables at maximal exertion is consistent with a learning effect. Therefore, studies comparing consecutive submaximal exercise test responses in patients with atrial fibrillation can be misleading.

Aged↗
PubMed1989

Psychosocial issues of nutritional support. A multidisciplinary interpretation.

In many cases, initiation of specialized nutritional support is a final attempt at medically managing illness for which other treatments have failed. Patients may have suffered for months or even years with their underlying diseases and are usually aware that poor response to nutritional support and concurrent therapies may lead to surgical intervention or more complex treatment. In some cases, there may be few alternatives left to pursue. For such patients, this paints a very stressful picture. If we as caregivers are empathetic to each patient's situation, we are better able to offer the support that these patients need. Health care professionals must keep patients informed of treatment plans and encourage participation in the planning process--during hospitalization, through the discharge phase, and after hospitalization. We need to pay close attention to those needs, whether nutritional support is short-term during hospitalization, prolonged, or permanent. The health care environment is demanding greater proficiency in cost containment and quality assurance in the delivery of care. Complex patient cases are becoming more difficult to manage as time constraints and resources become more restrictive. The ingenuity and imagination of health care providers trying to find ways to continue providing high-quality and safe care to patients are being tested daily. These worthwhile goals can be met only through cooperation, communication, and support among all levels and disciplines involved with the delivery of care. Feelings of helplessness, dependence, and loss of control can be diminished if health care providers maintain optimistic, confident attitudes, offer positive reinforcement for patients successes, and try to restore hope during this stressful period in patients' lives.

Adult↗
PubMed1989

Video display terminal health concerns.

The growing population of video display terminal (VDT) operators in today's computerized workplace has led to an increased incidence of common office health problems. The most common of these problems include visual, musculoskeletal, and stress related complaints. The well informed occupational health nurse understands that it is the nature of the work and work environment, not the VDT, which presents health risks to operators. Therefore, the problems can be greatly prevented through proper work station ergonomics and well designed jobs. Education regarding the significance of these issues becomes a key form of intervention. This effort must be directed toward management as well as VDT operators.

Computer Systems↗
PubMed1988

Team versus non-team outpatient care in rheumatoid arthritis. A comprehensive outcome evaluation including an overall health measure.

In a rheumatology department, 2 randomized groups of female outpatients with rheumatoid arthritis were studied prospectively for 1 year. The outcome of multidisciplinary team care (T group, 31 patients) was compared with that of regular outpatient clinic care (NT group, 28 patients). Pharmacologic treatment and orthopedic specialist consultations were similar in both groups, but use of paramedical care was higher in the T group. Outcome measures of disease activity, specific joint function, and self-rated physical discomfort disclosed no significant differences between the 2 groups. Mental well-being increased in the T group. Overall health, measured by the Sickness Impact Profile, improved significantly only in the T group. This improvement was also significant compared with the NT group.

Adult↗
PubMed1988

Tolerance of engrafted donor T cells following bone marrow transplantation for severe combined immunodeficiency.

Patients transplanted for the treatment of severe combined immunodeficiency (SCID) frequently develop a unique state of split lymphoid chimerism. Such patients have T cells of donor origin, and non-T cells which are predominantly or exclusively of host origin. We have studied the reactivity of engrafted donor T cells to host and/or donor antigens in 12 patients transplanted for SCID, focusing on the characteristics of the tolerance to host and/or donor MHC antigens observed in nine of these patients who were recipients of T-cell-depleted, haploidentical parental bone marrow. In both proliferative and cytolytic assays, engrafted, donor-derived T cells were shown to be selectively nonreactive to histoincompatible host cells. This tolerance could not be ascribed to cells with suppressive activity in the engrafted T-cell population. T cells from a subset of patients, however, exhibited proliferative but not cytolytic reactivity to donor peripheral blood mononuclear cells. The responding cells were shown to be donor-derived CD3+ cells and were predominantly reactive to B-cell fractions from the donor. Two patients who received transplants from each parent in sequence engrafted T cells from one parent and had non-T cells of host, paternal, and maternal origin. The engrafted T cells proliferated weakly to B cells from the other parent, but were tolerant in cytolytic assays. Donor anti-donor reactivity was seen only in haploidentical split chimeras who had not been treated with cytotoxic drugs prior to T-cell engraftment. This proliferative reactivity toward donor may be due to an absence of donor derived Ia+ antigen presenting cells resident in the thymus of SCID patients at the time when the T-cell repertoire is being shaped.

B-Lymphocytes↗
PubMed1988

Maximal exercise testing and gas exchange in patients with chronic atrial fibrillation.

To evaluate the response of patients with chronic atrial fibrillation to exercise, 50 men (mean age 65 +/- 8 years) with atrial fibrillation underwent a maximal exercise test using respiratory gas exchange techniques. Patients were classified by the presence (n = 29) or absence ("lone atrial fibrillation," n = 21) of underlying heart disease. Responses were evaluated at a standard submaximal work load (3.0 mph, [4.8 km/h] 0% grade), at the gas exchange anaerobic threshold and at maximal exercise. For all 50 patients, the mean maximal oxygen uptake was 20.6 ml/kg per min, which approximates 85% of the aerobic capacity predicted for age-matched normal individuals. Patients with lone atrial fibrillation demonstrated normal exercise capacity in contrast to patients with atrial fibrillation and known heart disease (22.7 +/- 5 versus 19.1 +/- 5.0 ml/kg per min, p less than 0.05). The mean maximal heart rate (176 +/- 30 beats/min) was approximately 20 beats/min higher than that expected for age, was extremely variable and accounted for only 8% of the variance in maximal oxygen uptake. Maximal heart rate in subjects with lone atrial fibrillation was higher than that of subjects with atrial fibrillation and known heart disease (189 +/- 32 versus 166 +/- 24 beats/min, p less than 0.01). Stepwise regression analysis revealed that maximal systolic blood pressure accounted for 19% of the variance in maximal oxygen uptake (VO2 max), suggesting that systolic function is an important determinant of exercise performance in atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Sequential treatment of a simple pneumothorax.

In a prospective investigation of isolated simple pneumothorax, the treatment of 35 patients with a total of 37 pneumothoraces was studied. A standardized sequential treatment approach was followed for evacuation of the pneumothorax and maintenance of lung reexpansion. The protocol involved catheter placement using a Seldinger technique, aspirations, and documentation of reexpansion by chest radiography and observation. Reaccumulation of air was treated with Heimlich valve attachment to the catheter at intrapleural pressure and further observation. Continued air leak following Heimlich valve attachment was treated with chest catheter suction using a Pleurovac at -20 cm H2O pressure. Chest tube thoracostomy was performed for continued failure of reexpansion. In 22 of the 37 pneumothoraces (59%) simple catheter aspiration maintained lung reexpansion without complications. In the remaining 15 pneumothoraces (41%), seven (47%) responded to Heimlich valve attachment, and three (20%) maintained expansion with chest catheter suction. Chest tube thoracotomy was required to maintain expansion in 33% (five) of those who failed catheter suction (14% of all pneumothoraces studied). Patients treated successfully with simple catheter aspiration were sent home. Patients requiring a Heimlich valve, chest catheter suction, or chest tube thoracostomy were hospitalized. Use of these catheter techniques resulted in lower cost and was associated with shorter hospitalizations than in chest tube thoracostomy. Our study suggests that sequential treatment of simple pneumothorax should be considered as a cost-effective and therapeutically successful alternative to immediate chest thoracostomy in selected cases.

Adolescent↗
PubMed1988

Lymphoblastic lymphoma in children--a randomized trial comparing LSA2-L2 with the A-COP+ therapeutic regimen: a Pediatric Oncology Group Study.

From May 1979 to March 1983, 76 evaluable patients with lymphoblastic lymphoma (LBL) were treated by members of the Pediatric Oncology Group (POG). Forty-six children treated by the six-drug A-COP+ regimen (Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH], vincristine, prednisone, cyclophosphamide, methotrexate, and hydrocortisone) were compared in a prospective randomized trial with 30 patients receiving the modified ten-drug LSA2-L2 (cyclosphosphamide, vincristine, methotrexate, Daunomycin [daunorubicin cerubidine; Wyeth Laboratories, Philadelphia], prednisone, cytarabine, thioguanine, asparaginase, hydroxyurea, and carmustine) regimen. After adjusting for stage (I and II v III v IV), there was no statistically significant difference (P = .19) between A-COP+ and LSA2-L2 regimens on the basis of 3-year survival and disease-free survival (62% v 72% and 53% v 58%, respectively for the two treatment regimens) but the power of analysis and thus the ability to detect a clinically meaningful difference in the outcome with the two regimens was limited by the small number of patients. Neither therapy was effective for most patients with stage IV disease, with failure occurring in six of seven children receiving A-COP+ regimen and eight of 11 patients receiving LSA2-L2. Although the LSA2-L2 regimen was more toxic during the induction of remission, the toxicity during maintenance was acceptable and similar for both treatments. CNS relapse was not a significant problem whether cranial radiation with intrathecal (IT) therapy (A-COP+) or IT therapy alone (LSA2-L2) were used. Our results confirm the overall effectiveness of the LSA2-L2 regimen in children with LBLs, especially those initially free of bone marrow or CNS involvement, but were inconclusive as to the inferiority or superiority of this regimen over the A-COP+ regimen.

Adolescent↗
PubMed1988

Modulation of the beta-adrenergic receptor-coupled adenylate cyclase by chemical inducers of differentiation: effects on beta receptors and the inhibitory regulatory protein Gi.

Several drugs known to induce differentiation in tumor cells were analyzed for their effects on the beta-adrenergic receptor-coupled adenylate cyclase system in two human carcinoma cell lines, HeLa and A431. Each of the drugs was tested alone or in combination with sodium butyrate (NaBu), a known inducer of this signal transduction system. Puromycine amino nucleoside (PMAN) caused the largest increase in beta-adrenergic receptors in HeLa cells followed by hexamethylenebisacetamide (HMBA) whereas 5'-azacytidine (5AZC) was ineffective. In addition, PMAN but not the others acted together with NaBu to elevate receptor levels 12-fold over control values. In contrast, HMBA and 5AZC were much more effective on A431 cells, PMAN caused only a slight increase in beta receptors and none of the drugs acted in concert with NaBu. The increase in beta receptors was usually accompanied by a corresponding increase in isoproterenol-stimulated adenylate cyclase activity. These effects of the drugs appeared to require protein synthesis as they were blocked by cycloheximide. In addition, some of the drugs caused a substantial decrease in basal adenylate cyclase activity. This effect on basal activity was abolished in cells treated with pertussis toxin, which ADP-ribosylates the inhibitory GTP-binding protein, Gi. Both HeLa and A431 cells contained a 41 kDalton substrate for the toxin which corresponds to the alpha subunit of Gi. The Gi subunit was ADP-ribosylated by the toxin to a similar extent in membranes from control and drug-treated cells. Thus, the drugs appear to induce quantitative changes in beta-adrenergic receptors and qualitative changes in Gi which results in a highly responsive beta-adrenergic-stimulated adenylate cyclase.

Acetamides↗