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Biomedical subjects

J Fitzgerald

Publications and source records attributed to J Fitzgerald.

At least 19 recordsLinked to original sources

Isolation and characterisation of the mouse pyruvate dehydrogenase E1 alpha genes.

We have characterized two mouse genes that code for the E1 alpha subunit of pyruvate dehydrogenase (PDH), Pdha-1 and Pdha-2. The coding regions show a high degree of homology with each other and with the human PDH genes, PDAH1 and PDHA2. Conserved regions include mitochondrial import sequences, phosphorylation sites and a putative TPP binding site. The PDH genes have an analogous chromosomal arrangement to PGK genes in that two isoforms code for a functionally and structurally similar product. Pdha-1 codes for a somatic isoform and maps to the X-chromosome. Pdha-2 is located on an autosome, is intronless and only expressed in spermatogenic cells. Comparison of human and mouse PDH and PGK gene sequences shows that the somatic sequences are more conserved relative to the testis-specific isoforms, and that the mouse PDH E1 alpha genes have experienced a faster rate of DNA change compared to their human counterparts.

Amino Acid Sequence

Persistence of Barrett's esophagus in children after antireflux surgery: influence on follow-up care.

Adenocarcinoma arising in Barrett's esophagus has recently been described in two children aged 11 and 14 years. The long-term follow-up of Barrett's esophagus in children is not well described. We evaluated 16 cases of Barrett's esophagus in children treated at this institution during the last 16 years. Ages ranged from 1.2 to 16 years (mean, 10.3 years). There were 11 boys and 5 girls. Barrett's esophagus was documented by endoscopy in 14 instances and at autopsy in 2 patients with secretory diarrhea and tetralogy of Fallot who died of sepsis. Two children had cancer (neuroblastoma, leukemia) and died of their malignant disease. Five patients had cerebral palsy, 1 esophageal atresia, 1 Fanconi's anemia, and 5 were otherwise normal children. Six were treated medically. Eight patients underwent Nissen fundoplication for complications of gastroesophageal reflux (GER). Five patients were available for follow-up endoscopy (mean, 2 years; range, 1.1 to 5.4 years). Endoscopy was performed on a yearly basis, obtaining biopsy specimens from multiple levels of the esophagus. Four children had satisfactory clinical response to an antireflux procedure including the resolution of a stricture in one case. However, in all 5 cases persistent metaplastic epithelium was documented and showed no evidence of regression. Although there has been speculation that Barrett's esophagus in children may be more likely to revert to normal squamous epithelium than in the adult, there has been only one case of regression in 180 cases of Barrett's esophagus occurring in children described in 37 reports in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

No evidence for an effect of lactase deficiency on bone mass in pre- or postmenopausal women.

The potential role for lactase deficiency in the development of low bone mass was examined in 342 adult female twins. Diminished lactase activity, defined as greater than 20 ppm increase in expired hydrogen at 2 or 2.5 h after an oral lactose load, was examined: (1) by comparing bone mass between members of twin pairs discordant for lactase activity; (2) by examining the linear association between bone mass and total expired hydrogen gas; and (3) by comparing all lactase-deficient individuals to those with persistent lactase activity. Among members of discordant (primarily DZ) pairs, the lactase-deficient member had greater bone mass 54% of the time. The correlations between the increase in expired hydrogen and bone mass at various sites were between -0.02 (femoral neck) and 0.11 (midshaft radius), suggesting no association between these variables. Finally, all lactase-deficient subjects were compared with those with normal lactase activity, regardless of twin status, and at each skeletal site the differences in bone mass were 1% or less. Thus, all primary hypotheses were not supported by these data; that is, in this large sample we could find no evidence of a detrimental effect of lactase deficiency on adult bone mass. However, baseline expired hydrogen was consistently and positively associated with bone mass at all sites, independently of age, suggesting the possibility that some aspect of intestinal function related to the activity of bacterial anaerobes may be positively associated with bone mass.

Absorptiometry, Photon

Comparative yields of mutagens from cigarette smokers' urine obtained by using solid-phase extraction techniques.

Urine from cigarette smokers was prepared for mutagenicity testing by extracting mutagens with solid-phase extraction columns. Commercially available prepacked bonded silicas (octadecyl, cyclohexyl, cyanopropyl) were compared for their ability to concentrate the urinary mutagens. Recovered urinary metabolites were evaluated for mutagenic activity by using a microreversion assay with Salmonella typhimurium. Dose-response data indicated that while mutagens were recovered by all three adsorbents, samples prepared by using the bonded cyanopropyl columns yielded the most bioactivity and/or the least amount of test organism toxicity. Varying pH of the urine was found to influence only the basified samples in terms of mutagenic recovery with the cyanopropyl base. Combinations of different adsorbents were not found to offer significant advantages over use of a singular extraction adsorbent.

Adult

In vivo and in vitro effects of beta-carotene and algae extracts in murine tumor models.

Phycotene, an algae extract with known antineoplastic activity, was demonstrated to prolong, but not sustain, an increased survival rate in a murine fibrosarcoma model when it was combined with immunotherapy. It was further shown that splenocytes from phycotene and beta-carotene-treated survivors could not confer protection to a fresh tumor cell challenge in virgin mice after adoptive transfer. In a series of cytotoxicity assays, phycotene combined with immunization was demonstrated to enhance cell-mediated and complement-dependent cytotoxicity in the first 14-21 days. However, after 21 days, the phycotene and immunization groups exhibited a decreased ability to mediate immune cytotoxicity compared with immunization-only controls. This may serve to explain the in vivo findings that while survival was increased early on in active immunization and phycotene-treated mice, it eventually dropped to the level of the active immunization controls.

Animals

Hospital and home care of sutureless percutaneous catheters.

Percutaneous catheter drainage of the biliary tree, kidney pelvis, and abdominal abscess cavities has become increasingly prevalent over the last ten years. These procedures, along with percutaneous gastrostomies, are safer to perform and can be accomplished when the patient is not a candidate for surgical placement. Because patients are usually discharged with the catheter in place, it is necessary to have a simple but effective dressing procedure. Catheters placed through the skin have traditionally been sutured to the skin to prevent displacement. This sutureless method employs a technique that is safely managed, not only by hospital staff but by patients and/or their home care givers as well. The written instruction for this procedure were developed by an ET Nurse in collaboration with the Radiologists who insert the catheters.

Catheters, Indwelling

Obstructive jaundice. An unusual delayed presentation of congenital diaphragmatic hernia.

Most cases of congenital diaphragmatic hernia present as acute respiratory emergencies in the newborn period. Delayed presentation may be heralded by symptoms referred to the respiratory or gastrointestinal tract. An infant with unrecognized right-sided foramen of Bochdalek hernia presented with obstructive jaundice due to compression of the herniated common bile duct by the rim of the diaphragmatic defect. To our knowledge, this occurrence has not been previously observed in infancy or childhood.

Cholestasis

Increased efficiency of immunotherapy using irradiated tumor cells.

The efficacy of irradiated tumor cells combined with chemotherapy or non-specific immunostimulation with complete Freund's adjuvant was tested in a model of minimal residual tumor-bearing syngeneic mice. Male C57BL/6J mice were innoculated in the right rear leg with live tumor cells from a methylcholanthrene induced fibrosarcoma. The tumor was resected when it reached 0.7 cm in diameter and animals were treated with doses of irradiated tumor cells (XTC) from the primary tumor ranging in number from 1 X 10(3) to 9 X 10(3). Best survival was noted using 5 X 10(3) XTC combined with irradiated tumor cells of liver or pulmonary metastases origin, complete Freund's adjuvant or cytoxan. The combination of irradiated tumor cells of metastatic origin did not enhance the therapeutic effect of XTC alone. Freund's adjuvant was not of benefit in enhancing the efficacy of XTC. However, improved survival was noted when chemotherapy in the form of cytoxan was used to supplement XTC. Our data suggests that XTC is more efficacious as a mode of immunotherapy than are live tumor cells. The dose of XTC used is critical in determining its effect. Chemotherapy appears to enhance the benefit of XTC.

Animals

Ten year experience with the negatively charged glutaraldehyde-tanned vascular graft in peripheral vascular surgery. Initial multicenter trial.

The negatively charged glutaraldehyde-tanned vascular graft was developed to determine the utility of grafts of biologic origin to provide satisfactory revascularization for ischemic limbs with advanced arteriosclerotic peripheral vascular disease. The bovine carotid artery was modified under a number of conditions using a large number of variables and evaluated in the carotid artery and aorta of dogs. Eventually ficin-digested carboxylated glutaraldehyde-tanned grafts were selected as being most antithrombotic and most resistant to aneurysm formation. Under an Investigational Device Exemption with the Food and Drug Administration, 146 grafts were evaluated in 108 patients with patency approaching 67 percent for all grafts at 5 years and 59 percent at 9 years plus. Total aneurysm formation has been 4 percent (six grafts) occurring only in hypertensive patients. The graft is now undergoing clinical use and evaluation worldwide.

Adult

Hyperimmunoglobulinemia E and pregnancy: a case report.

Hyperimmunoglobulinemia E is characterized by recurrent bacterial sinopulmonary and skin infections from birth or early childhood, with IgE levels at least 10 times greater than the upper limits of normal. The following case describes a young black woman with hyperimmunoglobulinemia E syndrome who had an uneventful pregnancy and delivery. The infant has been diagnosed as suffering from hyperimmunoglobulinemia E syndrome as well.

Adult

Corneal hydrops in Terrien's marginal degeneration.

We present four cases of Terrien's marginal degeneration that developed spontaneous ruptures in Descemet's membrane resulting in corneal hydrops. In all cases, the hydrops was characterized by a clear intracorneal pocket of aqueous humor rather than by stromal clouding. In two cases, the pocket extended peripherally to form a conjunctival filtering bleb. Although a lamellar corneal patch graft was used in one case for severe astigmatism, hypotony, and impending perforation, most cases were merely observed without treatment.

Adult

Effect of mutagen on cultured Schistosoma mansoni.

Although lightly homogenized three-week-old Schistosoma mansoni incubated in Mitsuhashi and Maramorosch insect tissue culture medium or the medium of Weller and Wheeldon produced adherent cell layers, continued growth of these cells did not occur. Non-adherent cells obtained by trypsinization also failed to produce long term cell cultures even after the addition of a range of growth factors. The possibility of producing tumour-like schistosome cells by the use of the mutagen ethyl methane sulphonate was therefore examined. Four-hour exposure of three-week-old schistosomes caused in some worms (a) large fluid filled 'ballooning', which also occurred in adult males, (b) enlargement of the gut, (c) increase in numbers of large round cells within the worms and (d) tissue outgrowths. It is suggested that these effects of mutagen offer new approaches to obtaining permanent schistosome cell cultures.

Animals

Distichiasis, congenital heart defects and mixed peripheral vascular anomalies.

We report on a previously apparently unreported syndrome of distichiasis with congenital heart defects and with mixed peripheral vascular anomalies in a mother and her four children. The mother had a ventricular septal defect; both daughters had surgery for patent ductus arteriosus. Sinus bradycardia alone (elder son), with stress induced asystole (younger son), and with wandering atrial pacemaker (both daughters) are documented electrocardiographically. Three of the five have edema, two have visible varicosities, three have symptoms consistent with chronic venous disease of the legs, and the older daughter has complaints consistent with arterial disease in the legs. Doppler flow studies demonstrated post-phlebitic syndrome in all but the younger daughter, and vasospastic disease in the mother, older daughter, and second son.

Adolescent

Predictors of myocardial infarction in emergency room patients.

To develop a decision rule to aid in the diagnosis of myocardial infarction, we evaluated clinical and ECG data on 540 adults treated in an urban hospital emergency room for acute chest pain. Of 62 (11.5%) patients who had acute infarctions, 54 were admitted to intensive care (sensitivity 87%); 103 of 478 patients without infarctions were also admitted to intensive care (specificity 78%). Thirty-four percent of all patients admitted had infarctions. Multivariate analysis identified only four clinical variables which carried independent information predicting infarction: two from the ECG and two from the clinical history. A predictive model based on these four variables had significantly greater specificity (86% vs. 78%, p = .003) and accuracy of overall patient classification (88% vs. 79%, p = .013) but somewhat lower sensitivity (81% vs. 87%, p = .46) than physician judgments. However, a decision rule which would have admitted to intensive care those patients with a high probability of infarction who were not admitted by the emergency room physicians, would have increased the sensitivity for detecting infarction to 95% with no appreciable decrease in specificity or yield of infarctions among patients admitted to intensive care.

Adult