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Biomedical subjects

D Fitzgerald

Publications and source records attributed to D Fitzgerald.

At least 19 recordsLinked to original sources
PubMed1992

Hyperhomocysteinaemia: a risk factor for extracranial carotid artery atherosclerosis.

Hyperhomocysteinemia arising from impaired methionine metabolism, and usually due to a deficiency of cystathionine beta-synthase is a significant and independent risk factor for symptomatic vascular disease. It is not known if hyperhomocysteinemia in apparently healthy asymptomatic subjects is associated with atherosclerosis and whether such a relationship is independent of conventional risk factors. The prevalence of asymptomatic extracranial carotid artery atherosclerosis was determined by duplex ultrasound examination in 25 obligate heterozygotes with respect for cystathionine beta-synthase deficiency (whose children were known to be homozygous for this genetic defect) and in 21 controls. Hyperhomocysteinemia was determined by a standard methionine-loading test and conventional risk factors were also recorded. Twelve of 25 obligate heterozygotes and 8 of 21 normal controls had evidence of extracranial carotid artery atherosclerosis. Hyperhomocysteinemia as a genetic trait was not a significant risk marker, but the actual homocysteine level was associated with an increased risk of carotid disease. After adjustment for the effects of other significant risk factors, the odds ratio of hyperhomocysteinemia for carotid disease was 1.038 per unit increase in homocysteine level (P = 0.03). Hyperhomocysteinemia is a weak risk factor for asymptomatic extracranial carotid atherosclerosis and the relative risk associated with this genetic trait is less than that observed in a study of patients presenting with clinical manifestations of vascular disease.

Adult↗
PubMed1992

Comparative immunogenicity of conjugates composed of the Staphylococcus aureus type 8 capsular polysaccharide bound to carrier proteins by adipic acid dihydrazide or N-succinimidyl-3-(2-pyridyldithio)propionate.

Staphylococcus aureus type 8 capsular polysaccharide (CP) was conjugated either to diphtheria toxoid or to Pseudomonas aeruginosa recombinant exoprotein A by using adipic acid dihydrazide (ADH) or N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) as the joining reagent. The polysaccharide/protein ratios of these two pairs of conjugates were similar. The two synthetic schemes bound the linker to the carboxyls of the type 8 CP by carbodiimide-mediated condensation. ADH was bound to the carboxyls of the protein, whereas SPDP reacted with the amino groups of the protein. Intermolecular linking of the carrier protein, caused by the carbodiimide during the conjugation reaction with the type 8 CP derivative, probably accounts for the larger size of the conjugates formed with ADH compared with those formed with SPDP. Both conjugates synthesized with ADH elicited higher levels of CP antibodies, especially after the first immunization, than did those prepared with SPDP. Similar levels of exoprotein A antibodies were elicited by both conjugates. Higher levels of diphtheria toxoid antibodies were elicited by the conjugate prepared with SPDP than by the one prepared with ADH. The basis for the differences in the immunogenicities of these two pairs of S. aureus type 8 CP conjugates is discussed.

ADP Ribose Transferases↗
PubMed1991

Pulmonary artery balloon counterpulsation for intraoperative right ventricular failure.

Two cases of severe low cardiac output and right ventricular failure after coronary artery bypass grafting necessitated pulmonary artery balloon counterpulsation after intraaortic balloon pumping and maximal inotropic/pressor support were unsuccessful in maintaining a satisfactory cardiac output. Hemodynamic improvement was sufficient to allow removal of the device 2 and 3 days postoperatively, with survival in 1 patient. Pulmonary artery counterpulsation is less morbid in comparison with other mechanical methods of right ventricular support and is applicable in right ventricular failure of intermediate severity.

Aged↗
PubMed1991

Chimeric cytotoxin IL2-PE40 inhibits relapsing experimental allergic encephalomyelitis.

IL2-PE40 is a chimeric protein composed of human interleukin-2 (IL2) genetically fused to a modified form of Pseudomonas exotoxin lacking the cell recognition domain. IL2-PE40 is cytotoxic for IL2 receptor-bearing lymphocytes in culture and can inhibit activation of T cells in vivo. IL2-PE40 can significantly diminish antigen-stimulated proliferation of lymphocytes sensitized to myelin basic protein. Intraperitoneal administration of IL2-PE40 not only markedly inhibits the clinical manifestations of adoptively transferred relapsing experimental allergic encephalomyelitis but also dramatically reduces both inflammation and demyelination characteristic of the disease.

Animals↗
PubMed1991

No effect of famotidine on cardiac performance by noninvasive hemodynamic measurements.

In a randomized, double-blind, placebo-controlled, two-way crossover study, 12 healthy volunteers were treated once daily for 1 week each with 40 mg famotidine or placebo. Stroke index, cardiac index, preejection period, left ventricular ejection time, and carotid and femoral blood flow were measured noninvasively with Doppler ultrasonography. No significant changes in these hemodynamic parameters were observed when differences between baseline and each time point after administration of famotidine were compared with corresponding differences after placebo. The findings of this study are in accord with those of other studies that have failed to demonstrate a negative inotropic effect after administration of H2-antagonists.

Adolescent↗
PubMed1991

Substitution of foreign protein sequences into a chimeric toxin composed of transforming growth factor alpha and Pseudomonas exotoxin.

TGF alpha-PE40 is a chimeric toxin made by replacing domain Ia of Pseudomonas exotoxin (PE) with transforming growth factor alpha (TGF alpha). We have now replaced a portion of domain Ib of PE with different polypeptides or an extra domain III of PE in transforming growth factor alpha-PE40 and maintained cell killing. Thus, TGF alpha-PE40 can be used to transport foreign protein sequences into the cytosol of cells.

ADP Ribose Transferases↗
PubMed1990

Online access to MEDLINE in clinical settings. A study of use and usefulness.

STUDY OBJECTIVE: We introduced self-service access to the medical literature database, MEDLINE, into clinical settings to assess the frequency, patterns, purposes, and success of use. DESIGN: Longitudinal descriptive study. SETTING: Inpatient and outpatient services of a university medical center. PARTICIPANTS: All trainees and attending staff working at the service sites were invited to participate; 158 (84%) did so. INTERVENTIONS: Free online access was provided to MEDLINE through GRATEFUL MED software. Participants were offered a 2-hour introduction to online searching and 2 hours of free search time. MEASUREMENTS AND MAIN RESULTS: For each search, a computer program requested identification of the user and the question to be addressed. Search transactions were recorded automatically. Interviews were conducted after a random sample of searches, and search questions were given to more expert searchers to run for comparison with the original. Eighty-one percent of participants did searches on study computers, at a mean rate of 2.7 searches per month. On comparison searches, participants retrieved 55% of the number of relevant articles retrieved by reference librarians (P = 0.024) and 50% more irrelevant articles (P less than 0.001). Forty-seven percent of searches on patient problems affected clinical decisions, but often on scanty information. CONCLUSIONS: MEDLINE searching from clinical settings is feasible with brief training and affects clinical decisions. However, inexperienced searchers miss many relevant citations and search inefficiently. Further studies are needed to assess the impact of searching on physician performance and patient care.

Academic Medical Centers↗
PubMed1990

How good are clinical MEDLINE searches? A comparative study of clinical end-user and librarian searches.

The objective of this study was to determine the quality of MEDLINE searches done by physicians, physician trainees, and expert searchers (clinicians and librarians). Its design was an analytic survey with independent replication in a setting of self-service online searching from medical wards, an intensive care unit, a coronary care unit, an emergency room, and an ambulatory clinic in a 300-bed teaching hospital. Participating were all M.D. clinical clerks, house, and attending staff responsible for patients in the above settings. Intervention for all participants consisted of a 2-h small group class and 1-h practice session on MEDLINE searching (GRATEFUL MED) before free access to MEDLINE. Search questions from 104 randomly selected novice searches were given to 1 of 13 clinicians with prior search experience and 1 of 3 librarians to run independent searches (triplicated searches). Measurements and main results from these unique citations of the triplicated searches were sent to expert clinicians to rate for relevance (7-point scale). Recall (number of relevant citations retrieved from an individual search divided by the total number of relevant citations from all searches on the same topic) and precision (proportion of relevant citations retrieved in each search) were calculated. Librarians were significantly better than novices for both. Librarians had equivalent recall to, and better precision than, experienced end-users. Unexpectedly, only 20% of relevant citations were retrieved by more than one search of the set of three, with the conclusion that novice searchers on MEDLINE via GRATEFUL MED after brief training have relatively low recall and precision. Recall improves with experience but precision remains suboptimal. Further research is needed to determine the "learning curve," evaluate training interventions, and explore the non-overlapping retrieval of relevant citations by different searchers.

Evaluation Studies as Topic↗
PubMed1990

Electroretinography, retinal ischaemia and carotid artery disease.

Reduction in the amplitude of oscillatory potential (OP) on the B wave of an electroretinogram (ERG) is a sensitive index of experimental retinal ischaemia and is being used clinically to evaluate the progression of diabetic retinopathy. This study assessed whether electroretinography could detect retinal ischaemia in a group of patients with normal fluorescein angiograms and carotid atherosclerosis. Two groups of patients were studied. Group A (n = 15) had carotid atherosclerosis on duplex ultrasonography while a matched control group B (n = 15) had normal vessels. All patients in Group A had flurorescein angiograms. ERGs were recorded bilaterally using a Ganzfeld stimulator and Medelec oscilloscope. The OP amplitudes were determined using the peak-nadir method. Of the 60 eyes examined, 18 had abnormal OPs and all of these occurred in Group A; ten associated with ipsilateral non-stenosing carotid lesions and eight with critical stenoses. Twelve had normal OPs in Group A, only one of which was associated with severe disease. The mean OP amplitudes were 292 mu and 198 mu in Group A and 172.89 mu and 115.6 mu in Group B (P less than 0.005 Wilcoxon Rank Sum Test). (Two readings reflect Medelec readings before and after computer adjustments.) This study demonstrates by electroretinography significant retinal ischaemia in the presence of normal fluorescein angiography in patients with proven carotid artery disease. Further evaluation is required to determine the relative importance of flow reduction and silent micro-embolisation in the genesis of this ischaemia particularly in relation to pre- and postoperative evaluation.

Carotid Artery Diseases↗
PubMed1990

The lack of relationship between acetylator phenotype and idiopathic systemic lupus erythematosus in a South-east Asian population: a study of Indians, Malays and Malaysian Chinese.

An association of idiopathic systemic lupus erythematosus (ISLE) with genetically determined N-acetylation polymorphism has been suspected from previous studies, mainly on Caucasian populations in which there is an approximate incidence of 50% of slow and rapid acetylators. The present study is of the incidence of ISLE and acetylator status in a mixed population of Malaysia. The results did not support an association between ISLE and acetylator status: the frequencies of slow acetylators in the ISLE patients who were Malaysian Chinese and Malay were 13 and 38% respectively. This did not differ significantly from the respective healthy groups (20 and 29%). The small number of Indians in the survey did not allow a valid comparison, but the figures did suggest a lack of association between ISLE and acetylator status.

Acetylation↗
PubMed1990

Reoperative cardiac surgery using a new femoral venous right atrial cannula.

A new ultra-thin but nonkinkable catheter was used for transfemoral venous right atrial drainage for cardiopulmonary bypass in 35 patients undergoing reoperations for coronary artery disease (CAD) (14), valve replacement (16), combined valve and CAD (4), and left ventricular aneurysm resection (1). Adequate flow rates were obtained with these cannula of 25, 27, and 29 French diameter in all patients. This technique provided excellent drainage of the heart allowing for a decompressed heart to dissect with no bleeding or damage to patent obstructed cardiopulmonary bypass grafts. There was no mortality over perioperative myocardial infarction postoperatively.

Cardiac Catheterization↗
PubMed1989

Selective immunosuppression of activated T cells with the chimeric toxin IL-2-PE40. Inhibition of experimental autoimmune uveoretinitis.

A characteristic of activated T lymphocytes is the expression of high affinity IL-2R. We studied a new method of selective immunosuppression directed against activated T cells by using a chimeric recombinant protein (IL-2-PE40) composed of IL-2 fused to a modified Pseudomonas exotoxin lacking its cell recognition domain. As a model of T cell-mediated disease, we used experimental autoimmune uveoretinitis (EAU) produced in Lewis rats by active immunization with the retinal S-Ag. The treatment protocol consisted of i.p. injection of IL-2-PE40 at 0.25 micrograms/g every 12 h. Controls were PBS, PE40, or IL-2-PE40asp553 a mutant form of the molecule with reduced activity. Treatment with IL-2-PE40 resulted in a significant reduction of the incidence and severity of EAU over controls. The analysis of the effect of i.p. injection of IL-2-PE40 on the popliteal draining lymph nodes of immunized animals showed a marked reduction in the lymphocytes content. Transfer experiments demonstrated that IL-2-PE40 prevented the development of EAU effector T cells. Interestingly, although activated B cells were reported to express IL-2R, there was no significant reduction of antibody production against the immunizing Ag under IL-2-PE40 treatment, suggesting sparing of the B cells.

ADP Ribose Transferases↗
PubMed1989

Cytotoxic activities of a fusion protein comprised of TGF alpha and Pseudomonas exotoxin.

A cDNA encoding transforming growth factor type alpha (TGF alpha) was fused to the 5' end of a gene encoding a modified form of Pseudomonas exotoxin A (PE), which is devoid of the cell recognition domain (domain Ia). The chimeric molecule, termed TGF alpha-PE40, was expressed in Escherichia coli and isolated from the periplasm or inclusion bodies depending on the construction expressed. TGF alpha-PE40 was found to be extremely cytotoxic to cells displaying epidermal growth factor (EGF) receptors. Comparison with a similar molecule in which TGF alpha was placed at the carboxyl end of PE40 demonstrated the importance of the position of the cell recognition element; TGF alpha-PE40 was found to be about 30-fold more cytotoxic to cells bearing EGF receptors than PE40-TGF alpha. In addition, TGF alpha-PE40 was shown to be extremely cytotoxic to a variety of cancer cell lines including liver, ovarian, and colon cancer cell lines, indicating high levels of EGF receptor expression in these cells.

ADP Ribose Transferases↗
PubMed1987

Blood volume and red cell space in tissues of the rainbow trout, Salmo gairdneri.

1. Whole body blood volume and red cell space of 22 tissues were measured in unanesthetized rainbow trout at 4, 12, 30, 60, 150 and 240 min after dorsal aortic injection of 51Cr-labeled red blood cells. 2. Apparent blood volume decreased during the initial 30 min after injection and increased thereafter. At 240 min the blood volume was 33.5 +/- 3.1 ml/kg body wt. 3. Tissue red cell space varied as a function of the interval between labeled red cell injection and tissue collection. Red cell space was highest in spleen followed by heart, kidney and liver. Lowest red cell spaces were found in stomach and red and white skeletal muscle. 4. Variability in blood volume and tissue red cell space over time suggests that caution should be exercised in the design of experiments that employ indicator dilution measurements to measure vascular volumes.

Animals↗
PubMed1986

Long-term survival in limited-stage small cell lung carcinoma. Experience in Rochester, New York from 1975 to 1981.

All patients with limited-stage small cell lung carcinoma (SCLC) diagnosed between January 1975 and 1981 in Rochester, New York, were collected. One hundred one patients were evaluable. By reviewing an entire community's experience with long follow-up, we were able to describe the response rates and survival in a large unselected population and compare them to results from concurrent cooperative group studies. Median survival for the entire group was 51 weeks, with only 18% alive at 130 weeks. There was no evidence for improvement in response or survival during the 6 years of study. Treatment results in the community as a whole were no different from that seen with cooperative group studies. A group who had initial surgery followed by adjuvant therapy had a significantly better survival and more long-term survivors than those not receiving surgery, but rare long-term survivors were seen with all treatment categories. Except for this small surgical subgroup, no other characteristics could be identified which were predictably associated with long-term disease-free survival. The overall poor survival of patient with localized SCLC suggests a need for the development of novel initial approaches to therapy.

Adult↗
PubMed1986

Leukapheresis for control of chronic myelogenous leukemia during pregnancy.

Leukapheresis was used as the sole modality of treatment of a patient with chronic myelogenous leukemia (CML) during her pregnancy. The specific requirements for safe leukapheresis during pregnancy are discussed, and the literature describing the management of CML during pregnancy is reviewed. Leukapheresis may be the treatment of choice in selected pregnancy patients with CML since it avoids the potential teratogenic effects of chemotherapy or radiation therapy.

Adult↗