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Biomedical subjects

M Sullivan

Publications and source records attributed to M Sullivan.

At least 325 records · Page 18Linked to original sources
PubMed1988

Intraperitoneal 131I- and 90Y-labelled monoclonal antibodies for ovarian cancer: pharmacokinetics and normal tissue dosimetry.

The pharmacokinetics of intraperitoneal (i.p.) radiolabelled monoclonal antibody (MAb) was studied in 35 patients receiving 40 i.p. injections. Eleven patients received 131I-labelled MAb, 24 received 90Y-labelled MAb, and 5 patients received a second 131I MAb treatment after having developed human anti-mouse antibodies (HAMA). All patients had blood and urine isotope activity monitored for 5 days after MAb injection. The radiation dose to bone marrow from the vascular compartment in the marrow was calculated by applying the MIRD formula to the measured blood activity. In HAMA-negative patients, peak blood isotope activity was observed at 40 hr post injection with a mean of 26% and 21% of the injected 131I and 90Y activity respectively. Sixty-five percent of the injected 131I activity, but only 12% of the administered 90Y, was excreted in the urine. Myelosuppression limited the administered 131I and 90Y activities to below 160 and 20 mCi respectively. In patients receiving 131I labelled MAbs, the marrow is irradiated by MAb within its circulation, producing myelosuppression that can be predicted by applying the MIRD formula to the blood isotope activity. This is not true for 90Y-labelled MAbs, where bone absorption of yttrium (which cannot be measured in patients) is the dominant radiation source for bone-marrow irradiation. Patients with HAMA present clear 131I MAb rapidly with a decreased radiation dose to marrow and reduced myelosuppression. Giving patients intravenous antimouse immunoglobulin to clear 131I-labelled MAb absorbed from the peritoneal cavity could decrease the toxicity observed in these patients. Patients receiving 90Y DTPA-chelated MAbs are unlikely to benefit, as catabolized yttrium is not excreted, and is concentrated in liver, spleen and bone. On the other hand, the use of i.v. chelating agents as EDTA may scavenge non-protein-bound 90Y with increased excretion in the urine and less myelosuppression.

Antibodies, Monoclonal↗
PubMed1988

Cefuroxime axetil.

Explore the source record for details and available documents.

Bacterial Infections↗
PubMed1987

Down-regulation of protein kinase C in rat glioma C6 cells: effects on the beta-adrenergic receptor-coupled adenylate cyclase.

Continuous exposure of rat glioma C6 cells to 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a time and dose dependent loss of [3H]phorbol dibutyrate binding sites and protein kinase C activity. Thus, by 24 h, the cells were essentially depleted of protein kinase C activity. In agreement with previous studies, TPA treatment caused a reduction in isoproterenol-stimulated adenylate cyclase activity and a sequestration of beta-adrenergic receptors. Cells were treated with TPA for 24-48 h to completely down-regulate protein kinase C and then exposed to isoproterenol. Agonist-mediated desensitization of adenylate cyclase and sequestration of beta-adrenergic receptors occurred at similar rates in control and TPA-treated cells. In addition, agonist-mediated down-regulation of beta-adrenergic receptors was not impaired by the absence of protein kinase C activity. Although both agonists and phorbol esters cause desensitization of the beta-adrenergic receptor-coupled adenylate cyclase, agonist-mediated events can occur independently of protein kinase C.

Adenylyl Cyclases↗
PubMed1987

A study of 31 cases of gastric carcinoma in dogs.

Over a five year period 31 dogs were diagnosed as having advanced gastric carcinoma. The most frequent clinical features were vomiting, polydipsia and weight loss. A predisposition to the tumour was found in the rough collie and Staffordshire bull terrier. In 18 dogs the main finding endoscopically was a large deep ulcer with thickened, irregular rims and walls. Fluoroscopically a marked irregularity of the mucosal surface was noted in 10 dogs. Pathologically, large ulcers with thickening of the stomach wall and involvement of the serosal lymphatics were evident in 17 dogs, and similar ulcers with involvement of the gastric lymph nodes were evident in 18 dogs.

Adenocarcinoma↗
PubMed1987

Targeted early childhood programming. The promise half fulfilled.

A group of 169 children was followed up from birth to second grade in a community-based early identification and early intervention project. Periodic assessments of health and function yielded profiles of concerns. Over the first five years of life, 39% of the children had health concerns, 20% had cognitive concerns, 25% had motor concerns, 15% had social adjustment problems, and 12% had early attentional problems. Children at the highest risk of having reading and behavioral problems in second grade were those with early attentional disability. At the second-grade level, 31% of the children with early attention concerns were one full grade behind in reading and 38% had behavioral problems; among the youngsters without early attentional concerns, 6% demonstrated a reading delay and 8% had behavioral problems. In addition, children of highly educated mothers were more likely to benefit from the multidisciplinary program than were children of less educated mothers, for whom the intervention effected only a modest improvement when contrasted with randomly selected comparison children. For instance, among children with early cognitive problems and whose mothers had little education, 31% of these children had reading problems in second grade as opposed to 10% of those whose mothers had high educational attainment. Similarly, 39% of children with the combined risks of low maternal education and early attentional problems had reading problems in second grade compared with none of the attention-problem children of highly educated mothers. This study shows that while early identification of health and developmental problems can be carried out in a community-based project, strategies for the early intervention of developmental concerns among children of low socioeconomic status remain less than completely effective.

Boston↗
PubMed1987

Effect of beta-adrenergic blockade on exercise performance in patients with chronic atrial fibrillation.

Beta-adrenergic blocking agents are commonly used in combination with digitalis to control excessive heart rate during exercise in patients with chronic atrial fibrillation. However, little is known about the effect of beta-adrenergic blockade on exercise capacity in these patients. Accordingly, a randomized, double-blind, cross-over placebo-controlled study was performed to assess the efficacy of celiprolol, a new cardioselective beta-blocker with partial intrinsic sympathomimetic activity, on exercise performance in nine men with chronic atrial fibrillation. All but one patient was receiving maintenance digitalis during the study. Heart rate, blood pressure and gas exchange variables were measured at rest and during treadmill exercise testing while the patients were receiving maintenance celiprolol or placebo. Significant reductions in heart rate and systolic blood pressure compared with control values were observed at submaximal exercise, at the gas exchange anaerobic threshold and at maximal exertion while the patients were taking celiprolol. However, oxygen uptake at the gas exchange anaerobic threshold during celiprolol therapy was 12.3 versus 14.0 ml oxygen/kg per min during placebo administration (a 12% difference, p less than 0.01). Similarly, oxygen uptake at maximal exertion during celiprolol therapy was 17.6 versus 21.0 ml/kg per min during placebo administration (a 16% difference, p less than 0.01). Treadmill time was also reduced during the celiprolol phase compared with placebo (11.3 versus 10.3 minutes; a 19% difference, p less than 0.01). These results indicate that in patients with atrial fibrillation the major beneficial effects of beta-adrenergic blockade--reduced submaximal and maximal exercise heart rate and blood pressure--must be weighed against the decrease in exercise capacity.

Adrenergic beta-Antagonists↗
PubMed1987

Cardiotonic agents. 1. Novel 8-aryl-substituted imidazo[1,2-a]- and -[1,5-a]pyridines and imidazo[1,5-a]pyridinones as potential positive inotropic agents.

Several 8-arylimidazo[1,2-a]pyridines, 8-arylimidazo[1,5-a]pyridines, and 8-arylimidazo[1,5-a]pyridinones were prepared and tested in vitro for potential cardiac inotropic and electrophysiological activity. Selected analogues were further tested in vivo in canine hemodynamic and cardiac electrophysiology models. Compounds having an imidazole substituent consistently showed activity. A pharmacophoric relationship between heterocycle-phenyl-imidazole and positive inotropic activity was noted. The significance of this relationship is discussed.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Hydatid disease at Royal North Shore Hospital: results of surgical treatment.

A study of the results of surgery for hydatid disease was undertaken at Royal North Shore Hospital for the period 1966-83. There were 51 patients who underwent surgery for this disease and follow-up was obtained in all but eight cases. Comparison of cumulative survivals for this group with that of a matched Australian population showed that patients undergoing surgical treatment of their hydatid can anticipate a normal life expectancy. There was no evidence that patients with extrahepatic disease fared any worse than those with disease confined to the liver. Documented recurrence of hydatid disease occurred in eight cases following surgery and only one patient actually died from hydatid disease. This was a case in which spillage occurred at the initial procedure. This paper is presented as a reminder that hydatid disease still occurs with sufficient frequency to pose therapeutic problems for surgeons. Whilst total eradication of the parasite will only occur with enforcement of public health measures, surgery would still appear to be effective therapy for established hydatid disease so long as care is taken to avoid cyst rupture.

Adolescent↗
PubMed1987

Influence of exercise training on spatial R-wave amplitude in patients with coronary artery disease.

To evaluate the influence of an exercise program on spatial and left precordial R-wave amplitude among patients with coronary artery disease, computerized electrocardiogram (ECG) data were acquired during maximal treadmill testing before and after 1 yr in 89 patients randomized to either exercise (n = 40) or control (n = 49) groups. Spatial and lateral R-wave amplitudes were derived from the orthogonal Frank (XYZ) lead system. The exercise group significantly increased maximal O2 consumption (0.17 l/min), whereas controls decreased significantly (0.12 l/min, P less than 0.01 between groups). No significant changes in electrocardiographic R-wave voltage measurements occurred within or between groups during the year. It is concluded that exercise training does not result in increases in R-wave voltage in patients with coronary artery disease.

Angina Pectoris↗
PubMed1987

Perceived exertion and gas exchange after calcium and beta-blockade in atrial fibrillation.

Nine male patients (mean age 65 yr) with chronic atrial fibrillation underwent maximal exercise testing during placebo, beta-adrenergic (celiprolol, 600 mg), or calcium (diltiazem, 30 or 60 mg four times daily) channel blockade. The results were analyzed to determine which factors most closely related to ratings of perceived exertion (RPE) during exercise. Heart rate (HR), blood pressure (BP), oxygen uptake (VO2), minute ventilation (VE), and carbon dioxide production (VCO2) were evaluated at rest, 3.0 mph/0% grade, the gas exchange anaerobic threshold (ATge), 80% of placebo maximal O2 uptake, and maximal exercise. Both beta-adrenergic and calcium channel blockade significantly reduced heart rate and systolic blood pressure relative to placebo; these effects were more profound during beta-adrenergic blockade and as exercise progressed. Correlation coefficients and estimates of slope were derived for changes in RPE during exercise vs. changes in HR, VO2, VE, and VCO2 during the three treatments (r = 0.76 to 0.92, P less than 0.001). Although RPE was significantly correlated with HR during placebo and diltiazem therapy (r = 0.45, P less than 0.01), this was not the case during beta-adrenergic blockade (r = 0.31, NS). Slope of the regression lines between RPE and VO2, VE, and VCO2 did not differ between the three treatments. Slope of the regression lines between RPE and HR differed only during calcium channel blockade. Because the presence of atrial fibrillation and beta-adrenergic blockade altered the associations between RPE, VO2, and HR, these results suggest that VE is more closely related to RPE than the other parameters.

Adrenergic beta-Antagonists↗
PubMed1987

Interobserver variance in clinical scoring for cystic fibrosis.

Multicenter clinical research would benefit from a simple, reliable scoring system for comparison of the clinical status of patients at different centers. In this study, five physicians performed simultaneous, independent scoring of 41 individuals with cystic fibrosis using the Doershuk modification of the Shwachman-Kulczycki scoring system for history, physical examination, and nutrition, and the Birmingham scoring system for chest roentgenograms. These were added together to obtain a clinical score. Interobserver variance of the scores was calculated. Mean individual observer variance from the consensus mean was 1.6-2.9 score points of a possible 25 for each category, 4.5-6.0 of a possible 100 for the total score. Coefficient of variance about the mean was approximately 10 percent for the individual categories, 6.7 percent for the total score. We concluded that the interobserver variance of this scoring system is within acceptable limit for most clinical studies. The total consensus score correlated with the NIH clinical score, chest roentgenogram score alone, and predicted values for forced vital capacity and FEV1 with a high degree of confidence.

Activities of Daily Living↗
PubMed1987

Interleukin 2-activated killer cells in patients following transplants of soybean lectin-separated and E rosette-depleted bone marrow.

During the early period following bone marrow transplantation before the immune system has reached full functional maturity, unprimed, nonspecific lytic systems may play a critical role as antiviral or antitumor effectors. The reconstitution of cells with this potential is of particular importance in recipients of bone marrow that has been depleted of mature T lymphocytes to prevent graft v host disease (GVHD). We examined the recovery of natural killer (NK) cells and interleukin 2 (IL 2)-augmented lymphokine-activated killer cells (LAK) in 48 patients at various intervals following transplantation of bone marrow depleted of mature cellular elements by treatment with soybean agglutinin and sheep RBCs (SBA-E- BMT). We found normal levels of both NK and LAK activity as early as 3 weeks following SBA-E- BMT. When compared with cells from controls, NK and LAK precursors from transplant recipients appeared to be activated in vivo in that freshly isolated peripheral blood mononuclear cells (PBMCs) from patients had an elevated cytolytic activity toward NK-insensitive targets and a more rapid response to activation by IL 2. In patients as well as controls, both LAK precursors and LAK effectors lacked antigens present on mature T lymphocytes (CD3, CD4, or CD8) but expressed antigens present on NK cells (CD2, CD16, and NKH1A). The LAK cells did not lyse either donor or host peripheral blood T cell targets. The activity of NK effectors but not LAK precursors survived the in vivo total body irradiation used for pretransplant conditioning in three patients studied. LAK precursors could be demonstrated as early as 18 days following transplant at a time when the bone marrow contained primarily donor-derived cells. Little or no LAK activity could be generated from cells of the SBA-E- BM graft itself, suggesting that LAK precursors differentiate rapidly from more primitive progenitors in the marrow graft. Thus, our data indicate that the NK and LAK lytic systems are among the earliest activities to recover during immune reconstitution following T cell-depleted BMTs.

Bone Marrow Cells↗
PubMed1986

Desensitization of the beta-adrenergic receptor-coupled adenylate cyclase in cultured mammalian cells. Receptor sequestration versus receptor function.

Human A431 and rat glioma C6 cells exposed to isoproterenol underwent a time- and dose-dependent loss of isoproterenol-stimulated adenylate cyclase activity. Desensitization was accompanied by sequestration of beta-adrenergic receptors, which became less accessible to the hydrophilic antagonist 3H-labeled 4-(3-tert-butylamino-2-hydroxypropoxy)benzimidazole-2-one hydrochloride ([3H]CGP-12177) and redistributed from the heavier density plasma membrane fraction to a lighter density membrane fraction. Prior treatment of the cells with concanavalin A or phenylarsine oxide blocked sequestration of the receptors but not desensitization of the agonist-stimulated adenylate cyclase. The membranes from such pretreated cells were exposed to alkali to inactivate adenylate cyclase, and the receptors were transferred to a foreign adenylate cyclase by membrane fusion with polyethylene glycol. beta receptors from desensitized cells exhibited a reduced ability to maximally stimulate the foreign adenylate cyclase, but remained accessible to [3H]CGP-12177 in the fused membranes. When isoproterenol-treated cells were washed free of agonist, there was a time-dependent recovery of agonist responsiveness and [3H]CGP-12177-binding sites. Using the fusion technique, the receptors recovered their functional activity in the resensitized cells. In concanavalin A-treated cells, desensitization and resensitization appeared to occur in the absence of receptor sequestration. Finally, membranes from desensitized cells pretreated with concanavalin A were fused with polyethylene glycol and assayed for agonist-stimulated adenylate cyclase. There was no reversal of the desensitized state. Thus, the primary, essential step in the desensitization process is a reduction in functional activity of the beta-adrenergic receptor. In contrast, sequestration of the receptors is not a prerequisite, but a secondary event during desensitization.

Adenylyl Cyclases↗
PubMed1986

The treatment of single brain metastasis from non-oat cell lung carcinoma. Surgery and radiation versus radiation therapy alone.

Between 1978-1980, 104 patients with single brain metastases (SBM) from non-small cell lung carcinoma (NSCLC) were treated at Memorial Sloan-Kettering Cancer Center (MSKCC). These included 35 patients treated with surgical resection and radiation (S + ERT) and 69 patients treated with conventional external beam radiation therapy alone (ERT). Surgical resection was combined with whole brain (WBRT) and focal radiation in 83% and 17% of patients, respectively. In the ERT group, all patients received WBRT. Both treatment groups were similar with regard to age, sex, stage distribution, location and size of SBM, and time to relapse from initial diagnosis of NSCLC. The histologic examination, however, revealed adenocarcinoma predominating in those patients receiving S + ERT and epidermoid carcinoma in those receiving ERT. Follow-up treatment, symptomatic, and CTT response rates were evaluated. With S + ERT, the overall subjective and objective responses were 80% and 87%, respectively, and with ERT, 83% and 72% (of the 47 patients available for follow-up CT scans), respectively. Survival data indicate a significant advantage of S + ERT over ERT with a median survival of 16 months versus 4 months (P less than 0.0001). Three major factors, however, may have contributed to this difference: (1) patients in the S + ERT group generally received more aggressive initial treatment to the primary disease in the lung (72%) compared to the ERT group (36%); (2) in the S + ERT group, extracranial disease was absent at the time of SBM diagnosis in 49% of the S + ERT group compared to 26% in the ERT group; and (3) distant metastases were present in only 6% of the surgical patients yet, they were present in 49% of those treated with radiation alone. In one subset of patients, however--those with a radically treated primary and no extracranial disease--S + ERT resulted in a median survival of 33 months with 33% of the population still alive with no evidence of disease compared to 12 months and 0%, respectively, with ERT alone. Moreover, intracranial relapse was the cause of death in only one S + ERT patient (9%), yet it accounted for 50% of the ERT deaths. These data suggest that an aggressive approach to SBM in such favorable prognostic patients may indeed improve survival.

Adenocarcinoma↗