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M J Osborn

Publications and source records attributed to M J Osborn.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1987

Double-blind study of intravenous propafenone for paroxysmal supraventricular reentrant tachycardia.

Propafenone was administered during electrophysiologic testing to determine its efficacy and safety for terminating and preventing reinduction of paroxysmal supraventricular reentrant tachycardia. Four men and 10 women (mean age 50 years, range 28 to 69) were studied. Five patients had Wolff-Parkinson-White syndrome with orthodromic atrioventricular (AV) reentrant tachycardia, three had a concealed accessory pathway with AV reentrant tachycardia and six had tachycardia due to reentry within the AV node. In the five patients with Wolff-Parkinson-White syndrome, propafenone terminated reentrant tachycardia in three (the tachycardia was reinducible in one) and had no effect in two. In the three patients with a concealed accessory pathway, propafenone terminated reentrant tachycardia in all three and prevented reinduction of the tachycardia in two. In the six patients with tachycardia due to reentry within the AV node, propafenone terminated and prevented reinduction of reentrant tachycardia. Propafenone had no effect on blood pressure, heart rate, PA interval, AV node refractoriness or rate of reentrant tachycardia. Propafenone significantly (p less than 0.05) prolonged the AH, HV, QRS and ventriculoatrial intervals and decreased the AV node Wenckebach rate. Of the nine patients receiving long-term oral propafenone therapy, eight had a reduction of at least 90% in reentrant tachycardia during a mean follow-up period of 14.5 months (range 11 to 22); all eight patients had had noninducible reentrant tachycardia after intravenous propafenone. One patient had increased frequency of reentrant tachycardia; this patient had had inducible reentrant tachycardia after intravenous propafenone. In conclusion, intravenously administered propafenone terminated reentrant tachycardia in 85% of patients and prevented reinduction in 71%, with no adverse hemodynamic effects.

Adult↗
PubMed1987

Impact of intracardiac electrophysiologic testing on the management of elderly patients with recurrent syncope or near syncope.

Seventy-five patients, 75 years of age and over, experienced recurrent syncope, with the etiology remaining unclear but presumably cardiogenic, after cardiac and neurologic examinations and noninvasive laboratory testing (including an electrocardiogram and ambulatory electrocardiographic monitoring). The mean number of previous syncopal spells was 14 (range, 1 to 64) over a mean of 36 months (range, 1 to 480 months). These patients underwent invasive electrophysiologic testing and a potential cause for syncope was identified in 68%. Abnormal findings at electrophysiologic testing included: sinus node dysfunction (55%); abnormal His-bundle conduction (39%); and ventricular tachycardia (14%), with some patients having more than one abnormality. No major complications were associated with the electrophysiologic testing. Patients were subsequently treated with permanent cardiac pacing or antiarrhythmic drugs or both, depending upon results of the electrophysiologic study. Follow-up examinations (mean of 26 months; range, 1 to 70) were possible in 90% of patients. No further syncope occurred in 84% of patients with an abnormal electrophysiologic study who received subsequent therapy to prevent the identified abnormality. Thus, in this difficult group of patients with recurrent syncope of uncertain etiology, electrophysiologic testing was safe and indicated abnormalities of conduction or rhythm in 68% of patients; treatment to correct these abnormalities prevented recurrent syncope in 84%.

Aged↗
PubMed1987

Value of the resting 12 lead electrocardiogram and vectorcardiogram for locating the accessory pathway in patients with the Wolff-Parkinson-White syndrome.

The resting 12 lead electrocardiogram and vectocardiogram were reviewed in 47 patients with the Wolff-Parkinson-White syndrome (a) who had pre-excitation on the resting 12 lead electrocardiogram, (b) who had a single anterograde conducting accessory pathway assessed and located during preoperative electrophysiological study and during epicardial mapping at operation, and (c) in whom surgical division of the accessory pathway resulted in loss of pre-excitation. The site of the accessory pathway established during operation was compared with that established by evaluating the polarity of the delta wave and QRS complex on the resting 12 lead electrocardiogram. The electrocardiogram was assessed by the Rosenbaum criteria (Wolff-Parkinson-White type A, left-sided pathway; or type B, right-sided pathway), the Gallagher criteria (atrial pacing resulting in maximal pre-excitation), and the World Health Organisation criteria (a composite of previous studies). The Gallagher and World Health Organisation criteria were derived from patients demonstrating maximal pre-excitation that often required atrial pacing. The present study was designed to determine whether these criteria could be accurately applied to the resting 12 lead electrocardiogram on which the degree of pre-excitation was variable. The Rosenbaum criteria correctly identified a left sided accessory pathway in 26 of 34 patients and a right-sided accessory pathway in nine of 13 patients. The Gallagher and World Health Organisation criteria correctly identified the location in only 15 (32%) of the 47 patients. The resting vectorcardiogram was inaccurate for locating the accessory pathway. Although published criteria are useful for identifying the site of the accessory pathway from an electrocardiogram obtained when rapid atrial pacing is being used to achieve maximal pre-excitation, they are not suitable for identifying the exact site of an accessory pathway from the resting 12 lead electrocardiogram.

Adolescent↗
PubMed1987

Out-of-hospital cardiac arrest in patients without clinically significant coronary artery disease: comparison of clinical, electrophysiological, and survival characteristics with those in similar patients who have clinically significant coronary artery disease.

Fifty nine survivors of out-of-hospital cardiac arrest unassociated with an acute myocardial infarction were referred for intracardiac electrophysiological study. Thirty patients who had no clinically significant coronary artery disease (group 1) were compared with 29 who did (group 2). Ventricular tachycardia or fibrillation was induced in significantly more patients in group 2 than in group 1 (69% vs 40%). Median duration of follow up, which was achieved in all patients, was 31 months in group 1 and 14 months in group 2. In group 1, an effective treatment was identified electrophysiologically in seven patients, and none died; an arrhythmia was induced, but no effective treatment was identified in five patients, and one patient died subsequently; an arrhythmia was not induced in 18 patients, 15 of whom were treated empirically with anti-arrhythmic drugs, and one died. In group 2, effective treatment was identified electrophysiologically in seven patients and three died (two of pump failure) during follow up. In 13 an arrhythmia was induced but no effective drug was identified, and six died or had a recurrence; in another nine patients without inducible arrhythmias, six subsequently died or had a recurrence. A Cox proportional hazards analysis identified previous myocardial infarction as the only predictor of recurrence. Patients without coronary artery disease who suffer an out-of-hospital cardiac arrest have a low inducibility rate at electrophysiological study and an excellent prognosis compared with patients who have coronary artery disease. Electrophysiological testing seemed to be of value in predicting the response to antiarrhythmic drugs, but non-inducibility of arrhythmias in patients with coronary artery disease was of no predictive value.

Adolescent↗
PubMed1986

Clinical intracardiac electrophysiologic testing: technique, diagnostic indications, and therapeutic uses.

Clinical cardiac electrophysiologic testing has evolved rapidly since 1968, when the technique was first described. In an electrophysiologic study, electrode catheters are positioned within the heart to record electrical activity from the atrium, atrioventricular conduction tissue, and ventricle. Programmed stimulation is then performed, which involves pacing of the atrium or ventricle and introducing critically timed premature stimuli during sinus rhythm or paced rhythm. The use of programmed stimulation in conjunction with intracardiac recordings in electrophysiologic studies has facilitated the diagnosis of mechanisms of arrhythmias and the assessment of therapy. Electrophysiologic testing is useful in selected patients with sinus node dysfunction, conduction system disorders, supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation and in survivors of out-of-hospital cardiac arrest and patients with symptomatic but unsubstantiated rhythm disturbances. Therapeutic approaches that can be assessed by electrophysiologic testing include serial drug testing to determine the effectiveness of antiarrhythmic agents, antitachycardia pacing, the implantable defibrillator, transcatheter ablation, and electrophysiologically guided surgical procedures. In this review, we discuss the methods of electrophysiologic testing, its clinical applications in diagnosing the various cardiac rhythm disturbances, and its use in assessing various therapeutic modalities.

Anti-Arrhythmia Agents↗
PubMed1986

Propafenone for the treatment of refractory complex ventricular ectopic activity.

The results of therapy with propafenone were evaluated in 45 patients with complex ventricular ectopic activity that had been refractory to a mean of 3.8 antiarrhythmic drugs. The cardiac diagnoses were ischemic heart disease (in 16 patients), cardiomyopathy (in 7), mitral valve prolapse (in 7), mitral valve prolapse (in 7), idiopathic ventricular ectopic beats (in 6), valvular heart disease (in 5), and hypertension (in 4). The frequency of ventricular ectopic beats was established after therapy with antiarrhythmic agents had been discontinued. Patients then received propafenone during a dose-ranging protocol. An effective response was defined as a reduction in total ventricular ectopic beats of 80% or more. During dose ranging, therapy failed in four patients because of side effects, in eight because of a reduction in ventricular ectopic beats of less than 80%, and in three because of an aggravation of the arrhythmia. Thirty patients had a reduction in total ventricular ectopic beats of 80% or more. During a mean follow-up of 12.4 months, therapy failed in 1 patient because of sustained ventricular tachycardia and in 7 because of intolerable side effects; 22 patients continued to receive propafenone. PR and QRS intervals were significantly prolonged (P = 0.001), but the corrected QT interval and the heart rate were unchanged. The mean trough plasma level of propafenone associated with an effective response was 756 ng/ml, and that associated with intolerable side effects was 920 ng/ml. Thus, in patients with refractory complex ventricular ectopic beats, propafenone was effective and well tolerated initially in 67% of patients and during long-term administration in 49%, and toxicity was minor in most patients.

Adult↗