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J Fitzgerald

Publications and source records attributed to J Fitzgerald.

18 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

pH homeostasis during cardiopulmonary resuscitation in critically ill patients.

We investigated the effect of repeated administration of sodium bicarbonate on acid-base balance and serum chemistry in a group of patients who developed cardiac arrest. A mixed acidosis persisted throughout the duration of resuscitation in the majority of patients in spite of the large ventilatory volume and multiple doses of bicarbonate they received. However, the repeated administration of bicarbonate prevented a severe fall in serum pH. Our study demonstrated the beneficial role of bicarbonate in the treatment of metabolic acidosis associated with cardiac arrest of prolonged duration. Analysis of our data strongly indicated that the primary factors which determine the serum pH during cardiopulmonary resuscitation are the duration of circulatory arrest, adequacy of ventilation and circulation, pH immediately before arrest, and quantity of bicarbonate administered and its volume of distribution in the various fluid and tissue compartments.

Acid-Base Equilibrium

The rational use of drains after cholecystectomy.

A study of patients who had a cholecystectomy compared the use of sump drains and Penrose drains. Sump drains were removed as soon as the indication for the presence of the drain no longer existed. Penrose drains were managed in the traditional way. The safety of early drain removal in selected patients was demonstrated. This technique offers most of the advantage and little of the risk of omitting drains entirely. The length of hospital stay for those patients who underwent a cholecystectomy can be significantly shortened by this technique;

Cholecystectomy

Hemodynamic changes at the onset of spontaneous versus pacing-induced angina.

To determine the origin of angina pectoris at rest hemodynamic monitoring was performed for 24 to 72 hours in 25 patients with unstable angina who had pacing-induced angina during cardiac catheterization. During the monitoring period, seven patients had spontaneous epidsodes of angina at rest that could be compared with the pain-free periods and periods of pacing-induced angina. At the onset of spontaneous angina, the patients had a significantly lower mean double product (P is less than 0.005) and triple product (P is less than 0.025) than at the onset of pacing-induced angina. The mean double product (heart rate x systolic blood pressure) was 9,411 +/- 2,815 mm Hg/min during pain-free rest, 10,635 +/- 2,587 at the onset of spontaneous angina and 16,623 +/- 3,904 during pacing-induced angina. The mean resting pain-free triple product (heart rate x systolic blood pressure x ejection time) was 3,023 +/- 703 and 3,536 +/- 931 mm Hg/sec per min during, respectively, pain-free rest and spontaneous angina, and 4,350 +/- 938 mm Hg/sec per min during pacing-induced angina. These marked differences in the double and triple products were associated with a mean increase in pulmonary arterial diastolic pressure (from 10.7 mm Hg at rest to 14 mm Hg) at the onset of both spontaneous and pacing-induced angina. Although indirect, these data suggest that transient changes in coronary blood flow, rather than changes in myocardial work, may be primarily responsible for spontaneous angina at rest in certain patients with the syndrome of unstable angina.

Adult

Response optimization of drug dosage: antiarrhythmic studies with tocainide.

The benefits of using antiarrhythmic response to optimize dosage regimens of antiarrhythmic drugs in individual patients have been examined. Graded antiarrhythmic response and simultaneously measured plasma drug concentrations have been obtained in 15 patients receiving multiple oral doses of a new antiarrhythmic, tocainide. Plasma drug concentration-antiarrhythmic response data from each of 11 subjects responding to the drug have been fitted by a generalized concentration effect function which is valid over the entire range of response. With the use of experimentally determined pharmacokinetic parameters to define the dose-plasma concentration relationship and plasma drug concentration-response parameters estimated for individual patients, simulations were carried out to show the effect of various dosage regimens on antiarrhythmic response in individual patients. Such simulations provide a means of assessing antiarrhythmic effect in the range of clinical interest (80% to 100% of maximum effect), where the antiarrhythmic effect is a nonlinear function of dose, plasma drug concentration, or their logarithms. The simulations also demonstrate that for identical daily doses and dosing intervals patients show marked variability in antiarrhythmic response.

Administration, Oral

The assessment of mitral stenosis and prosthetic mitral valve obstruction, using the posterior aortic wall echocardiogram.

The echocardiographic motion of the aortic root reflects, in part, left atrial filling and emptying. Patients with mitral valve obstruction were studied to determine whether clinically important alterations in patterns of left atrial emptying would alter motion of the posterior aortic wall. Patients with mitral stenosis had a characteristic pattern of slowing of left atrial emptying in early diastole, with loss of the conduit phase in mid-diastole. The atrial emptying index, defined as the fraction of passive posterior aortic wall motion occurring in the first third of diastole, was significantly related to the mitral valve area index (r = 0.86), and thus provides a noninvasive quantitation of the degree of mitral stenosis. Determination of the atrial emptying index also proved useful in the evaluation of patients with prosthetic mitral valve obstruction and in documenting improvement in left atrial emptying after mitral valve surgery.

Echocardiography

Afterload reduction in the management of postinfarction ventricular septal defect.

The primary goal in the medical management of ventricular septal defect complicating myocardial infarction is to support cardiac function and control symptoms, if possible, for a period of 4 to 6 weeks. If the patient survives this period, surgical correction of the defect is technically easier and safer. In many cases, However, cardiac function is severly compromised, intractable biventricular failure develops,early operation is necessary and the likelihood of successful repair is diminished.

Female

Diagnosis and quantification of arrhythmias in ambulatory patients using an improved R-R interval plotting system.

An improved technique for identification, diagnosis and quantification of arrhythmias during rest or ambulatory electrocardiographic recording is described. With simultaneous plotting of the R-R interval and the QRS duration and QRS vector measurement of each beat versus time, all periods of arrhythmias or abnormal complexes can be identified and characterized. Analog electrocardiographic samplings are used to confirm the diagnosis of the arrhythmia and to exclude artifact. The availability of a permanent record for the characterization of each QRS complex enables the physician to check the technician's analysis of the recording and to relate all events to the patient's heart rate and clinical symptoms. This technique also provides data for quantification of ventricular arrhythmias.

Ambulatory Care