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Biomedical subjects

M J Osborn

Publications and source records attributed to M J Osborn.

At least 19 recordsLinked to original sources
PubMed1992

A multicenter experience with a bipolar tined polyurethane ventricular lead.

A multicenter study was undertaken to determine the failure rate of a specific polyurethane bipolar tined pacing lead, the Medtronic 4012 pacing lead. Six centers in the United States and Canada implanted 1,190 Medtronic 4012 pacing leads. The study was designed to determine the probability and clinical manifestations of lead failure. Only failures compatible with an insulation problem were included. The probability of a 4012 lead failure by Kaplan-Meier analysis was 20.9% at 6 years after implantation. Failures were manifested as sensing abnormalities, failure to capture, early battery depletion, and significant decrease in measured impedance compared with the previous impedance measurements. Of the 95 definite lead failures, 16 (16.8%) were associated with symptoms similar to those experienced before pacemaker placement. The observed failure rate is unacceptable, and strong consideration should be given to replacing the 4012 pacing lead in pacemaker-dependent patients and closely monitoring nondependent patients.

Aged↗
PubMed1991

Pyopneumopericardium attributed to an esophagopericardial fistula: report of a survivor and review of the literature.

Herein we describe a case of pyopneumopericardium that resulted from formation of an acquired esophagopericardial fistula in a patient with silent, benign esophageal ulcer disease. Atypical features on initial examination suggested congestive heart failure or a pneumonic process (or both). The delayed development of pneumopericardium disclosed on a chest roentgenogram led to the clinical recognition of the esophagopericardial fistula. Subsequent emergent pericardiocentesis relieved cardiac tamponade and enabled us to diagnose pyopneumopericardium. A radiographic contrast study with use of meglumine diatrizoate revealed the site of the fistula in the midesophagus. The esophagopericardial fistula was surgically closed, and our patient had a good final result. Formation of an esophagopericardial fistula is a relatively uncommon finding; of the 60 previously reported cases, only 10 patients have survived. As illustrated in the current case, early diagnosis and treatment, including pericardial drainage and intense antibiotic therapy followed by a well-planned operative closure of the fistula, are paramount for the successful management of esophagopericardial fistulas.

Aged↗
PubMed1991

Antitachycardia pacemaker treatment of postoperative arrhythmias in pediatric patients.

An automatic antitachycardia pulse generator (Intertach 262-12) was implanted in each of six pediatric patients (mean age, 10 years) with drug-resistant and persistent postoperative supraventricular arrhythmias. Four had bradycardia-tachycardia syndrome, two after a Mustard procedure for transposition of the great arteries, one after a Senning procedure for the same anomaly, and one after a Fontan procedure for univentricular heart with transposition of the great arteries. Of the two remaining patients, one had atrial flutter after a modified Fontan procedure for univentricular heart and one had intra-atrial reentry tachycardia after a modified Fontan procedure for double-outlet right ventricle with pulmonary stenosis. During a mean follow-up interval of 31 months after implantation, pacemakers were activated on multiple occasions and functioned appropriately in all six patients. Complications necessitated six invasive interventions in three patients: erosion or infection of the system, adaptor fracture, and connector block fracture on one occasion each and lead dislodgment on three occasions. Four of the six patients continued to take drugs at the end of this study; however, all patients had their drug therapy reduced and one was taking digoxin only. The number of hospital admissions decreased after implantation. Despite a number of technical challenges, this newer multiprogrammable antitachycardia pacemaker appears to be a valuable addition to the treatment of refractory postoperative supraventricular tachyarrhythmias in pediatric patients.

Adolescent↗
PubMed1991

Energy dependence of O-antigen synthesis in Salmonella typhimurium.

The uncoupler 2,4-dinitrophenol prevents in vivo synthesis of O antigen in Salmonella typhimurium by inhibiting the first reaction of the pathway, formation of galactosyl-pyrophosphoryl-undecaprenol. Inhibition was observed only in intact cells; dinitrophenol had no effect on activity of the synthase enzyme in isolated membrane fractions. In vivo inhibition could not be explained by changes in intracellular nucleotide pools or a shift in the equilibrium of the reaction and appeared to be specific for the first step in the pathway. Neither the subsequent mannosyl transferase, which catalyzes formation of the trisaccharide-lipid intermediate, mannosyl-rhamnosyl-galactosyl-pyrophosphoryl-undecaprenol, nor O-antigen polymerase was inhibited. In addition, incorporation of galactose into core lipopolysaccharide was only modestly inhibited under conditions in which O-antigen synthesis was abolished. The results suggest that maintenance of proton motive force is required for access of substrate, UDP-galactose and/or undecaprenyl phosphate, to the active site of the galactosyl-pyrophosphoryl-undecaprenol synthase enzyme.

Antigens, Bacterial↗
PubMed1991

Evidence for energy-dependent transposition of core lipopolysaccharide across the inner membrane of Salmonella typhimurium.

The uncoupler 2,4-dinitrophenol blocks the final step of lipopolysaccharide assembly--transfer of O antigen from undecaprenyl pyrophosphate to core lipopolysaccharide--in intact Salmonella typhimurium but not in isolated membrane fractions. The O-antigen ligase enzyme is not inhibited by dinitrophenol in vitro, and core lipopolysaccharide synthesized in the presence of uncoupler in vivo is functional as acceptor of O antigen in vitro. The evidence strongly suggests that maintenance of proton motive force is required for transmembrane transposition of core lipopolysaccharide to the active site of O-antigen ligase at the periplasmic face of the inner membrane.

Antigens, Bacterial↗
PubMed1991

Localization of the terminal steps of O-antigen synthesis in Salmonella typhimurium.

Previous immunoelectron microscopic studies have shown that both the final intermediate in O-antigen synthesis, undecaprenol-linked O polymer, and newly synthesized O-antigenic lipopolysaccharide are localized to the periplasmic face of the inner membrane (C. A. Mulford and M. J. Osborn, Proc. Natl. Acad. Sci. USA 80:1159-1163, 1983). In vivo pulse-chase experiments now provide further evidence that attachment of O antigen to core lipopolysaccharide, as well as polymerization of O-specific polysaccharide chains, takes place at the periplasmic face of the membrane. Mutants doubly conditional in lipopolysaccharide synthesis [kdsA(Ts) pmi] were constructed in which synthesis of core lipopolysaccharide and O antigen are temperature sensitive and mannose dependent, respectively. Periplasmic orientation of O antigen:core lipopolysaccharide ligase was established by experiments showing rapid chase of undecaprenol-linked O polymer, previously accumulated at 42 degrees C in the absence of core synthesis, into lipopolysaccharide following resumption of core formation at 30 degrees C. In addition, chase of the monomeric O-specific tetrasaccharide unit into lipopolysaccharide was found in similar experiments in an O-polymerase-negative [rfc kdsA(Ts) pmi] mutant, suggesting that polymerization of O chains also occurs at the external face of the inner membrane.

Chromatography, Gel↗
PubMed1991

Molecular heterogeneity at the phenylalanine hydroxylase locus in the population of the south-west of England.

The phenylalanine hydroxylase gene locus has been studied in 35 independent phenylketonuric families in the south-west of England using RFLP haplotype patterns and allele specific oligonucleotide probes. Haplotype 3 was the most common pattern on mutant chromosomes and there was strict linkage disequilibrium between this haplotype and the splice mutation in exon 12. The R408W mutation in exon 12 occurred on both haplotypes 1 and 2. The R126Q mutation in exon 7 was found only on a rare haplotype 28 pattern. No gene carried the R158Q mutation. More than 60% of mutant genes did not carry these four mutations which were originally described in other European populations. We suggest that the splice mutation arose as a single event and spread throughout northern Europe by population migration and admixture. In addition, we believe the haplotype/mutation associations seen in our population are a reflection of the mixed ancestry of the inhabitants of the British Isles.

Alleles↗
PubMed1990

Influence of ventricular function and presence or absence of coronary artery disease on results of electrophysiologic testing for asymptomatic nonsustained ventricular tachycardia.

One hundred ten patients with asymptomatic nonsustained ventricular tachycardia (VT) were evaluated prospectively to assess the value of electrophysiologic testing. This testing consisted of up to 3 extrastimuli delivered during 3 drive cycle lengths from 2 right ventricular sites. A positive study was defined as monomorphic VT lasting 30 seconds or requiring cardioversion. Patients with a positive study were treated, and serial drug testing was done. An event during follow-up was sustained VT or cardiac arrest. The mean follow-up was 15 months. Of 57 patients with an ejection fraction greater than or equal to 40%, 6 had a positive electrophysiologic test with 1 event and 51 had a negative test with 1 event. Twenty-eight patients had an ejection fraction less than 40% and coronary artery disease: 14 had a positive test with 1 event, and 14 had a negative test with 3 events. Twenty-five patients had an ejection fraction less than 40% and no coronary artery disease: 1 had a positive test with no events, and 24 had a negative test with 8 events. Only ejection fraction and congestive heart failure class were found to be independent predictors of outcome. Patients with an ejection fraction greater than 40% had low inducibility (11%), had few events (3.5%) and did not require electrophysiologic testing. In patients with an ejection fraction less than 40% and coronary artery disease, inducibility was high (50%) and a negative study was of no value. Patients with an ejection fraction less than 40% and no coronary artery disease had low inducibility (4%), had frequent events (33%) and did not benefit from electrophysiologic testing.

Adult↗
PubMed1990

Genetic analysis of treated and untreated phenylketonuria in one family.

We describe a family in which four subjects in two generations have a disorder of phenylalanine metabolism. Two first cousins had different biochemical presentations in the neonatal period. The older child was thought to have a more severe form of phenylketonuria (PKU), and the younger child a milder form. While carrying out family studies we discovered that their mutual grandfather and his older unmarried brother, both of normal intelligence, had a marked and previously undiagnosed hyperphenylalaninaemia. DNA analysis using RFLP haplotypes has shown that there are four independent mutant PKU alleles in this family which are found on three haplotype patterns. None of the affected family members carries a previously defined mutation at the phenylalanine hydroxylase (PAH) locus and so DNA analysis was not able to explain the apparently different biochemical phenotypes in the affected members of this family.

Adolescent↗
PubMed1989

Clinical application of the signal-averaged electrocardiogram and "late potentials".

The signal-averaged ECG has proven to be a valuable tool for identifying patients at risk of ventricular arrhythmias. This computerized method of analyzing standard ECGs identifies microvolt-level late potentials that represent delayed conduction through diseased myocardium. This diseased myocardium is a potential substrate for reentrant ventricular arrhythmias. In select patient groups, the signal-averaged ECG predicts electrophysiologic testing results. Problems remain and continued development is needed to evaluate patients with conduction system disease, the patient without coronary artery disease but at risk of sudden death, and proper general application of the technique.

Action Potentials↗
PubMed1989

Follow-up of an activity-sensing, rate-modulated pacing device, including transtelephonic exercise assessment.

Single-chamber rate-modulated (ventricular or atrial demand [VVIR or AAIR]) pacemakers are now an accepted and frequently used pacing modality. Although several sensor-driven pacemakers are currently under investigation, activity-sensing pacemakers have been used most frequently to date. We assessed our implantation and follow-up experience with 156 activity-sensing pacemakers. Analysis of the patient population revealed an age range of 6 to 91 years and a variety of indications for pacing, the most common being atrioventricular block. Specific programming techniques were adopted for assessing these pacemakers. Although several episodes of reprogramming may be necessary to identify the optimal sensor settings for an individual patient, once optimal programming has been achieved, the sensing characteristics seem to have long-term stability. An important part of our follow-up procedure involves transtelephonic exercise, which allows some degree of long-term assessment of the sensor. All but six patients with pacemakers programmed to the sensor-driven mode (VVIR or AAIR) had evidence of sensor-driven pacing during transtelephonic exercise. Thus, this adjunct seems helpful for follow-up of some rate-modulated pacemakers.

Adolescent↗
PubMed1989

Identification of the haplotype pattern associated with the mutant PKU allele in the Gypsy population of Wales.

Using the full length cDNA probe, the RFLP haplotype patterns at the phenylalanine hydroxylase locus have been studied in the extensive and highly consanguineous Welsh Gypsy population. The pattern associated with the mutant PKU allele is identical to haplotype 4 in the northern European population. Two children with classical PKU are homozygous for this haplotype. We have tracked the mutant allele through four generations to a great grandfather who died 22 years ago. Both affected children almost certainly have inherited a double dose of the same mutant PKU allele from one common ancestor. It should be possible to identify the specific mutation that is associated with haplotype 4 which results in the more serious form of PKU.

Alleles↗
PubMed1989

The role of frequency of atrial contraction versus atrial pressure in atrial natriuretic peptide release.

This study was designed to investigate the role of frequency of atrial contraction compared to acute increases in right atrial pressure in the regulation of atrial natriuretic peptide (ANP) release in humans. The studies were performed in patients undergoing electrophysiological study. In group 1 (n = 12) the rate of atrial contraction was increased by continuous rapid right atrial pacing at a rate of 120 beats/min (bpm; group 1A; n = 6) or 176 bpm (group lb; n = 6) for 5 min. No increases in atrial pressure or circulating ANP occurred in response to atrial tachycardia. In contrast, continuous rapid right ventricular pacing (group II: n = 12) at ventricular rates of 120 bpm (group IIa; n = 6) and 150 bpm (group IIb; n = 6) increased both right atrial pressure and circulating ANP. These results demonstrate that, in contrast to studies in vitro, increases in the frequency of atrial contraction in the absence of increases in atrial pressure do not release atrial natriuretic peptide. These studies, therefore, support the conclusion that atrial pressure is the primary physiological stimulus for ANP.

Adult↗
PubMed1988

Cryosurgical modification of atrioventricular conduction for treatment of atrioventricular node reentrant tachycardia.

Cryosurgical modification of atrioventricular (AV) node conduction was performed in five patients with AV node reentrant tachycardia that used dual AV nodal pathways and was refractory to drug therapy. The procedure alleviated the tachycardia in all patients without the development of complete heart block and without any associated surgical morbidity or mortality. These results suggest that cryosurgical modification of AV node conduction is a promising and potentially curative method of treating AV node reentrant tachycardia.

Adolescent↗
PubMed1987

Role of invasive electrophysiologic testing in patients with symptomatic bundle branch block.

Electrophysiologic testing was performed in 112 symptomatic patients with bundle branch block. Abnormalities included HV interval 70 ms or longer (35 patients), infra-Hisian block with atrial pacing (6 patients) and sinus node dysfunction (23 patients). Inducible ventricular tachycardia occurred in 47 patients (42%). Therapy was based on the electrophysiologic test result: group I--16 patients with no therapy (normal study results); group II--34 patients with permanent pacing alone; group III--39 patients with antiarrhythmic therapy alone; and group IV--21 patients with both antiarrhythmic therapy and permanent pacing. Cumulative 4-year survival rates were 83% in group I, 84% in group II, 63% in group III and 84% in group IV (mean follow-up 2.5 years). Recurrent syncope occurred in 19% of group I, 6% of group II, 33% of group III and 19% of group IV. In symptomatic patients with bundle branch block and normal electrophysiologic test results, prognosis is good without treatment. In patients undergoing permanent pacing based on electrophysiologic testing, survival is good and rate of symptom recurrence is low. Electrophysiologic testing identifies patients with inducible ventricular tachycardia for whom antiarrhythmic therapy is indicated but who nevertheless have a poor prognosis.

Adult↗
PubMed1987

Idiopathic lymphoplasmacytic aortic valvulitis: observations in two elderly women with unexplained aortic insufficiency.

Two patients with a unique aortic valvulitis required aortic valve replacement. Both were elderly women who presented with evidence of systemic disease, including fever, arthralgia, myalgia, markedly elevated erythrocyte sedimentation rate, anemia, leukocytosis, hypoalbuminemia and renal insufficiency, in addition to progressive subacute aortic insufficiency. Histologic examination of the excised aortic valve revealed a lymphoplasmacytic infiltrate. Neither patient had evidence of other diseases that have been associated with aortic insufficiency. One should consider the judicious use of glucocorticosteroids for such patients.

Aged↗