PubMed Health⌕ Search

Biomedical subjects

D Fitzgerald

Publications and source records attributed to D Fitzgerald.

At least 73 records · Page 4Linked to original sources
PubMed1995

Delayed diagnosis of cystic fibrosis in children with a rare genotype (delta F508/R117H).

OBJECTIVE: In neonatal screening for cystic fibrosis (CF), infants recognised as delta F508 heterozygotes require a sweat test to confirm the diagnosis. However, compound heterozygotes with delta F508 and the R117H mutation are known to have non-diagnostic sweat chlorides (< 60 mmol/L) at an early age. As genotyping for rare mutations is not readily available in Australia, there is a need to determine whether quantitative pancreatic stimulation tests could facilitate the diagnosis of CF in three infants with the delta F508/R117H mutation. METHODOLOGY: Formal sweat testing, genotyping and pancreatic stimulation tests were performed in three subjects heterozygous for delta F508 who initially had non-diagnostic sweat chloride results (40-60 mmol/L) but presented later with persisting chest symptoms and/or signs consistent with CF. RESULTS: All three patients were shown to have the delta F508/R117H genotype with initial sweat chloride results ranging from 40 to 58 mmol/L. Pancreatic stimulation tests demonstrated reduced enzyme secretion in two and decreased fluid, bicarbonate and chloride secretion in all three patients. CONCLUSIONS: In infants recognized as delta F508 heterozygotes by the newborn screening programme, the presence of an equivocal sweat chloride does not exclude the diagnosis of CF. If such patients with an initially equivocal sweat chloride subsequently develop symptoms suggestive of CF and have a persisting non-diagnostic sweat chloride then the diagnosis of CF can be confirmed by more extensive genotyping if available or by pancreatic stimulation testing.

Child, Preschool↗
PubMed1995

Level of receptor-associated protein moderates cellular susceptibility to pseudomonas exotoxin A.

Pseudomonas exotoxin A (PE) enters mammalian cells via a receptor-mediated endocytic pathway. The initial step in this pathway is binding to the multiligand receptor termed the alpha 2-macroglobulin receptor/low-density lipoprotein receptor-related protein (LRP). Binding of toxin, and of the many other ligands that bind to LRP, is blocked by the addition of a 39-kDa receptor-associated protein (RAP). Here we show that approximately 40% of the cell-associated LRP is on the surface of toxin-sensitive mouse LM fibroblasts and thus accessible for toxin internalization. The remainder is located intracellularly, primarily in the Golgi region. Mammalian cells exhibit a wide range of sensitivity to PE. To investigate possible reasons for this, we examined the expression levels of both LRP and RAP. Results from a variety of cell lines indicated that there was a positive correlation between LRP expression and toxin sensitivity. In the absence of LRP, cells were as much as 200-fold more resistant to PE compared with sensitive cells. A second group of resistant cells expressed LRP but had a high level of RAP. Thus, a toxin-resistant phenotype would be expected when cells expressed either low levels of LRP or high levels of LRP in the presence of high levels of RAP. We hypothesize that RAP has a pivotal role in moderating cellular susceptibility to PE.

ADP Ribose Transferases↗
PubMed1994

Glutathione S-transferase GSTM1 phenotypes and protection against cutaneous tumours.

Multiple allelism at loci encoding detoxicating enzymes is associated with cancer risk. We have studied genetic variation at the glutathione S-transferase GSTM1 locus to see whether phenotypes confer altered susceptibility to basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM), or multiple skin tumours of different histological types. The frequency of GSTM1 null in cases and controls (52%) was similar, except for patients with two or more tumours of different types (71%, p = 0.033). GSTM1 A/B was reduced in frequency (p < 0.05) in patients with single or multiple BCC. Thus GSTM1 A/B may be protective, and effectiveness of detoxication may be a factor determining susceptibility to skin cancer.

Aged↗
PubMed1994

Subclinical persisting pulmonary hypertension in chronic neonatal lung disease.

The development of pulmonary hypertension is one of the adverse factors in the outcome of infants with chronic neonatal lung disese (CNLD). The purpose of this cross sectional study was to evaluate the prevalence and degree of pulmonary hypertension in a cohort of survivors of CNLD stable in air. Pulmonary artery pressure was assessed using its inverse correlation with the ratio of time to peak velocity and right ventricular ejection time (TPV:RVET) as measured from Doppler velocity time signals in the main pulmonary artery. A normal ratio is > or = 0.35, a possibly low ratio lies between 0.31 and 0.35, and a definitely low ratio is < 0.31. The subjects were divided into three groups. Group A comprised 58 infants with oxygen dependence and an abnormal chest radiograph at 28 days of age; group B comprised 18 infants with oxygen dependence and a normal chest radiograph at 28 days of age; and group C (controls) comprised 21 siblings without oxygen dependence by 10 days and a normal chest radiograph. There were significant differences in mean (SD) TPV:RVET ratio between group A 0.346 (0.045), group B 0.335 (0.057), and groups A + B 0.344 (0.048) when compared with group C controls 0.385 (0.034). The prevalence of a definitely low TPV:RVET ratio suggesting a raised pulmonary artery pressure was 19% in group A, 39% in group B, 24% in groups A + B, and none in group C. There were no clinical signs of pulmonary hypertension in any patient studied. Stepwise multiple linear regression failed to find significant associations with antenatal or neonatal putative risk factors. Additionally, there were no associations with childhood respiratory morbidity. These data suggest a high prevalence of subclinical pulmonary hypertension in CNLD patients. It is speculated that occult hypoxaemia may be occurring in this group of infants.

Age Factors↗
PubMed1994

MRI of the inner ear.

The recent advances in MRI of the temporal bone brought about by the availability of intravenous contrast agents sensitive to the disruption of blood-brain barrier have further expanded the role of MRI in the evaluation of patients with vestibulocochlear symptoms. Not only can MRI be used to diagnose vestibular schwannomas (and other intracanalicular and cerebellopontine angle lesions mimicking it) with a high degree of accuracy, but it can now identify a variety of inflammatory and neoplastic processes of the membranous labyrinth which, in the past, were only made presumptively and occasionally confirmed by surgery and pathology. This enhanced diagnostic capacity of diseases of the vestibular cochlear system may help in the future to improve the management of these patients.

Adult↗
PubMed1993

Pseudomonas exotoxin and recombinant immunotoxins derived from it.

Pseudomonas exotoxin (PE) is a bacterial toxin that kills mammalian cells by gaining entry to the cytosol and inactivating protein synthesis. The toxin binds and enters cells via the alpha 2-macroglobulin receptors. Within cells, the toxin is processed in several steps to produce an enzymatically active 37-kDa C-terminal fragment which translocates to the cytosol and ADP-ribosylates elongation factor 2. Because PE is a very potent toxin, derivatives of it have been produced which, when joined to various binding ligands, are capable of killing specific target cells. It is hoped that this strategy will lead to the development of effective therapeutic agents for the treatment of human diseases such as cancer, AIDS, and various immunologic disorders.

ADP Ribose Transferases↗
PubMed1993

Laboratory and clinical evaluation of conjugate vaccines composed of Staphylococcus aureus type 5 and type 8 capsular polysaccharides bound to Pseudomonas aeruginosa recombinant exoprotein A.

The synthesis, standardization, and immunogenicity in young outbred mice and clinical evaluation in adult volunteers of investigational vaccines designed to induce serum antibodies to the type 5 and type 8 capsular polysaccharides (CPs) of Staphylococcus aureus are described. Conjugates composed of the type 5 CP and a sonicated preparation of a high-molecular-weight type 8 CP bound to a nontoxic recombinant protein derived from Pseudomonas aeruginosa exotoxin A (rEPA) were synthesized. The conjugates were nontoxic and elicited serum CP antibodies after two subcutaneous injections into young outbred mice; a third injection elicited a booster response. The lower-molecular-weight type 8 CP was not immunogenic in the mice, and the high-molecular-weight type 8 CP elicited low levels of antibodies without a booster effect. In the volunteers, neither the conjugates nor the type 8 CP alone caused significant local reactions or fever. The conjugates elicited type-specific antibodies of both the immunoglobulin M (IgM) and IgG classes after the first injection; a second injection 6 weeks later did not stimulate a booster effect. The high-molecular-weight type 8 CP alone, injected once only, elicited levels of IgG and IgM type-specific antibodies similar to those of the conjugate. The vaccine-induced CP antibodies were mostly of the IgG1 and IgG2 subclasses and had opsonophagocytic activity. The conjugates elicited IgG antibodies to the native exotoxin A with neutralizing activity. In summary, the type 5 and type 8 conjugates were safe and elicited biologically active antibodies to both the CP and rEPA components.

ADP Ribose Transferases↗
PubMed1993

A study of library use in problem-based and traditional medical curricula.

A key question for librarians and medical educators who are planning for curriculum change is whether students and faculty in problem-based learning (PBL) programs use the library and its resources differently than do participants in traditional programs. During 1991, this research question was explored at three medical schools in the province of Ontario, Canada. At the time of the study, McMaster University medical school was totally problem-based, the University of Western Ontario had one PBL day each week for first-year medical students, and the University of Toronto, although planning for medical curriculum change, had not yet initiated PBL. Data collected in the study suggest that more medical students in the problem-based curriculum than in the more traditional programs use the library and that, when the PBL students use the library, they do so more frequently, for longer periods of time, and as a source of a greater proportion of their study materials. PBL students also use the library more than their counterparts as a place to study and meet other students. Students in the problem-based curriculum use the following resources more extensively: end-user MEDLINE searching, library journals, reserve or short-term loan materials, photocopy services, and audiovisual materials. PBL students also report purchasing more textbooks. In contrast to the differences found among medical students, however, patterns of library and resource use by medical faculty at the three schools were quite similar.

Computer-Assisted Instruction↗
PubMed1993

Peripheral vascular injuries from plastic bullets in children.

During an eight month interval, 15 children and adolescents less than 20 years of age sustained vascular injuries to the lower extremities from plastic bullets. The plastic bullets had been introduced by the authorities as an attempt to reduce mortality from clashes between soldiers and demonstrators. Twenty-three vessels were injured in these 15 children: four patients had isolated arterial injuries, three had isolated venous injuries, and eight had combined injuries. The arterial injuries were repaired primarily or with reversed saphenous vein interposition grafts. The limb salvage rate was 100 percent, and there were no deaths. Eighty percent of the patients had palpable distal pulses observed at follow-up examination. We conclude from this experience that plastic bullets can cause serious injuries in children, vascular injuries from gunshots in children should be repaired or reconstructed using techniques perfected in the adult population, and low velocity gunshot vascular injuries in the pediatric age group can be successfully treated in a minimally equipped, developing world hospital by well-trained general surgeons.

Adolescent↗
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↗