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Biomedical subjects

M E Petersen

Publications and source records attributed to M E Petersen.

At least 19 recordsLinked to original sources
PubMed2001

Quantitation of free and total amphotericin B in human biologic matrices by a liquid chromatography tandem mass spectrometric method.

Amphotericin B remains the standard of care for the treatment of invasive and disseminated fungal infections. Various lipid-based formulations of amphotericin B have been developed to improve its therapeutic index by decreasing toxicity. Previous bioanalytic methods using microbial inhibition or high-pressure liquid chromatography quantified total amphotericin B (free, plasma protein-bound, and lipid-complexed). Sensitivity of this method with a low limit of quantitation of 0.05 microg/mL was inadequate to determine free (unbound) amphotericin B. A sensitive LC/MS/MS method was developed to determine the total amphotericin B value in human plasma and other biologic matrices and the free amphotericin B concentration in plasma. For determination of total plasma amphotericin B concentrations, the sample was diluted and injected onto the LC/MS/MS. For total amphotericin B in other matrices and free amphotericin B in plasma, solid-phase extraction was used. Natamycin served as an internal standard. A PE Sciex API 3000 (Sciex; Concord, Ontario, Canada) was used to assess free amphotericin B in plasma ultrafiltrate determination and an API 3+ for the other matrices, with electrospray interfaced to a C18 analytic column. The low limit of quantitation was 1 ng/mL for ultrafiltrate. For total amphotericin B, the low limits were 2 microg/mL for plasma, 0.05 microg/mL for urine, and 0.4 microg/mL for fecal homogenate. The methods were validated to show the standard range linearity, sensitivity, selectivity, accuracy, precision, and stability of amphotericin B in the matrices tested.

Amphotericin B↗
PubMed2000

Respiratory changes in vasovagal syncope.

INTRODUCTION: Respiratory changes accompany the cardiovascular changes during head-up, tilt test-induced vasovagal syncope. METHODS AND RESULTS: Using the 45-minute 60 degrees head-up Westminster protocol, 29 patients were studied (mean age 53.9+/-20.0 years; 19 females). Two groups resulted: tilt-induced vasovagal syncope positive and negative. The cardiorespiratory parameters blood pressure (BP), heart rate (HR), tidal volume, and minute volume were measured. Comparisons of the cardiorespiratory parameters were made within the positive group and negative group, and then between the two groups. There were 14 in the positive group and 15 in the negative group. Baseline measurements were normalized to 1.0. Comparing the late tilt periods between the positive and negative groups, there were differences in BP (P < 0.002), HR (P < 0.002), tidal volume (P < 0.05), and minute volume (P < 0.002). In the positive group comparing early with late intervals: BP 1.11+/-0.09 versus 0.49+/-0.17, P < 0.0001; HR 1.18+/-0.12 versus 0.85+/-0.35, P < 0.009; tidal volume 1.39+/-0.34 versus 2.17+/-1.00, P < 0.015; and minute volume 1.24+/-0.26 versus 3.3+/-2.03, P < 0.0025. There were no comparable cardiorespiratory changes in the negative group. CONCLUSION: There were significant differences in the respiratory and cardiovascular parameters measured between those who were positive and those who were negative for tilt-induced vasovagal syncope. Within the positive group, in addition to the falls in HR and BP, there were significant increases in minute volume and tidal volume during late tilt. This suggests that there may be a role for respiratory sensors in vasovagal syncope that may permit earlier and hence possibly more effective therapy for selected patients.

Adult↗
PubMed2000

The normal response to prolonged passive head up tilt testing.

OBJECTIVE: To define the responses to head up tilt in a large group of normal adult subjects using the most widely employed protocol for tilt testing. METHODS: 127 normal subjects aged 19-88 years (mean (SD), 49 (20) years) without a previous history of syncope underwent tilt testing at 60 degrees for 45 minutes or until syncope intervened. Blood pressure monitoring was performed with digital photoplethysmography, providing continuous, non-invasive, beat to beat heart rate and pressure measurements. RESULTS: 13% of subjects developed vasovagal syncope after a mean (SD) tilt time of 31.7 (12. 4) minutes (range 8.5-44.9 minutes). Severe cardioinhibition during syncope was observed less often than is reported in patients investigated for syncope. There were no differences in the age or sex distributions of subjects with positive or negative outcomes, or in the proportions with cardioinhibitory and vasodepressor vasovagal syncope compared with previously reported patient populations. Subjects with negative outcomes showed age related differences in heart rate and blood pressure behaviour throughout tilt. CONCLUSIONS: False positive results with tilting appear to be common. This has important implications for the use of diagnostic tilt testing. The magnitude of the heart rate and blood pressure changes observed during negative tilts largely invalidates previously suggested criteria for abnormal non-syncopal outcomes.

Adult↗
PubMed1999

Usefulness of tilt test-induced patterns of heart rate and blood pressure using a two-stage protocol with glyceryl trinitrate provocation in patients with syncope of unknown origin.

This study assesses the vasovagal collapse pattern changes, i.e, heart rate (HR) and arterial blood pressure (BP) with a 2-stage tilt-test protocol using glyceryl trinitrate (GTN) provocation. With use of the 45-minute 60 degrees head-up Westminster protocol, 102 consecutive patients were studied. Sublingual GTN 300 microg was given to those with a negative passive tilt. Heart rate and BP patterns were classified according to the Vasovagal International Study classification (VASIS) and then compared between those with a positive passive tilt and those with a positive tilt after having been given GTN. Twelve patients did not tolerate tilt testing, and 16 had a negative response despite taking GTN. Thirty-five patients (20 women and 15 men, mean age 45 +/- 21 years [mean +/- SD]) did not take GTN and 38 (26 women and 12 men, mean age 53 +/- 22 years) had positive passive test results. When comparing the VASIS classification between the 2 groups, results showed: type 1, mixed BP and HR decreased without severe bradycardia (31% [passive] vs 54% [with GTN], p = NS); type 2A, BP decreased before HR decreased (20% vs 22%, p = NS); type 2B, HR decreased before or coincident with BP (34% vs 8%, p = 0.003); type 3, BP decreased without HR decrease (9% vs 0%, p = NS); exception 1, chronotropic incompetence (0% vs 13%, p = 0.026); and exception 2, excessive HR increase (6% vs 3%, p = NS). Thus, GTN use increases frequency of positive results from 34% to 73%. Older people with chronotropic incompetence, who may benefit from pacing, were identified. In younger people there was an increase in those with cardioinhibition.

Administration, Sublingual↗
PubMed1997

Right ventricular pressure, dP/dt, and preejection interval during tilt induced vasovagal syncope.

This study examined the potential utility of monitoring right ventricular dP/dt as a means of detecting imminent vasovagal syncope. To assess this possibility, continuous right ventricular pressure measurements were recorded in nine patients during induction of syncope by head-up tilt testing. Findings indicated that arterial pressure tended to fall prior to drop in heart rate. RV pressure exhibited a significant, but very small, fall during tilt. DP/dt max increased by 15-20% during tilt, then fell by a median of 30% from maximum value beginning about 2 minutes prior to syncope. Thus, further investigation of dP/dt as a potential marker of impending vasovagal syncope is warranted.

Adult↗
PubMed1997

Cardiac pacing for vasovagal syncope: a reasonable therapeutic option?

A number of studies have evaluated the effect of cardiac pacing for prevention of tilt induced vasovagal syncope. The findings are relatively consistent. Pacing does not prevent the onset of vasovagal syncope. This is predictable since hypotension (vasodepressor effect) typically occurs prior to bradycardia. However, dual chamber may prolong the presyncopal period in patients with a prominent cardioinhibitory component. Further, the relation of laboratory observations to spontaneous events is uncertain. In the largest retrospective assessment of pacing efficacy, 89% of patients reported improved symptoms and 62% remained free of symptom recurrence over 50 months.

Bradycardia↗
PubMed1997

First steps toward a pacing algorithm for vasovagal syncope.

Vasovagal syncope is commonly associated with an intermediate fall in heart rate. Consequently, it seemed possible that a pacemaker algorithm designed to detect intermediate heart rate falls might prove useful as a diagnostic tool to initiate pacing therapy. Subsequent experience suggests that with such an approach it is still difficult to avoid "false-positive" detection of physiologic heart rate slowing (e.g., sleep). On the other hand, findings from several reports suggest that high rate pacing using this algorithm has proved clinically effective.

Algorithms↗
PubMed1997

The economics of treating vasovagal syncope.

The economics of treating vasovagal syncope depends on the severity of attacks. In patients with syncope without warning in whom injury is a consideration, a correctly chosen cardiac pacemaker may be warranted. Based on a recent appraisal of the cost effectiveness of dual versus single chamber pacing, it is possible to estimate the economic value of cardiac pacemakers for vasovagal syncope. Findings indicate that an economic argument favors pacing patients with severe vasovagal syncope. However, prospective study examining syncope recurrence rates in paced and nonpaced patients is not currently available.

Cardiac Pacing, Artificial↗
PubMed1996

Determination of nicotine and cotinine in human plasma by liquid chromatography-tandem mass spectrometry with atmospheric-pressure chemical ionization interface.

Here we report a sensitive liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method capable of quantifying nicotine down to 1 ng/ml and cotinine to 10 ng/ml from 1.0 ml of human plasma. The method was validated over linear ranges of 1.0-50.0 ng/ml for nicotine and 10.0-500.0 ng/ml for cotinine, using deuterated internal standards. Compounds were simply extracted from alkalinized human heparinized plasma with methylene chloride, reconstituted into a solution of acetonitrile, methanol and 10 mM ammonium acetate (53:32:15, v/v) after the organic phase was dried down, and analyzed on the LC-MS-MS, which is a PE Sciex API III system equipped with a Keystone BDS Hypersil CI8 column and atmospheric pressure chemical ionization (APCI) interface. The between-run precision and accuracy of the calibration standards were < or = 6.42% relative standard deviation (R.S.D.) and < or = 11.8% relative error (R.E.) for both nicotine and cotinine. The between-run and within-run precision and accuracy of quality controls, (2.5, 15.0, 37.5 ng/ml for nicotine and 25.0, 150.0, 375.0 ng/ml for cotinine), were < or = 6.34% R.S.D. and < or = 7.62% R.E. for both analytes. Sample stabilities in chromatography, in processing and in biological matrix were also investigated. This method has been applied to pharmacokinetic analysis of nicotine and cotinine in human plasma.

Chromatography, Liquid↗
PubMed1996

Fatal giant cell myocarditis after resection of thymoma.

A case of fulminant, fatal myocarditis occurring 10 days after resection of a benign medullary thymoma is described. A rare association between thymoma and giant cell myocarditis is recognised, but fulminant presentation so soon after removal of thymoma has not previously been reported.

Fatal Outcome↗
PubMed1995

Surgical sex reassignment: a comparative survey of international centers.

The Harry Benjamin International Gender Dysphoria Association's Standards of Care (Walker et al., 1985) set out minimum standards for the selection of patients for sex reassignment surgery. This survey reports on the standard and policies actually used by clinics in Europe and North America, including their areas of agreement and disagreement with the Standards. To our knowledge, there has been only one prior survey of gender clinic policies, and that was restricted to European treatment facilities. The present survey is aimed at primary caregivers in the medical community; however, it may also be of use to administrators in responding to increasing demands for accountability from special interest groups and from government, with their often divergent agendas. It is our hope that this survey will begin the process of developing more uniform standards of care.

Data Collection↗
PubMed1995

The clinical spectrum of neurocardiogenic syncope.

Neurocardiogenic syncope is a collective term used to describe the clinical syndromes of syncope that result from inappropriate, and often excessive, autonomic reflex activity, and manifest as abnormalities in the control of vascular tone and heart rate. These include carotid sinus syndrome, vasovagal syncope, and the syndromes of cough, deglutition, and micturition syncope. Orthostatic hypotension, which, in contrast, results from a failure of autonomic reflexes, is not considered part of this family of closely related syndromes. This review will focus on vasovagal and carotid sinus syndromes.

Cardiovascular Diseases↗
PubMed1995

Psychogenic syncope diagnosed by prolonged head-up tilt testing.

Four patients with 'syncope' during prolonged head-up tilt testing despite normal blood pressure and heart-rate behaviour are described. They represent 5.5% of all positive tilt-test outcomes from a prospective study of 181 consecutive patients with unexplained syncope. All four patients were female, and were both younger and more symptomatic than patients with vasovagal syncope or orthostatic hypotension. In three of the patients, clinical episodes of syncope were observed which closely resembled those provoked during tilt. It is suggested that the tilt response is psychogenic and reveals a psychiatric cause for recurrent syncope.

Adolescent↗
PubMed1995

A comparison of non-invasive continuous finger blood pressure measurement (Finapres) with intra-arterial pressure during prolonged head-up tilt.

Simultaneous intra-radial and non-invasive (Finapres, Ohmeda) blood pressures were compared during prolonged head-up tilt, in eight patients (mean age 49 years) with malignant vasovagal syncope. Twelve tilts were performed, of which eight resulted in vasovagal syncope. The mean bias (difference between Finapres and intra-arterial pressures) for systolic pressure was +0.7 mmHg (standard deviation 11.3 mmHg) and for diastolic pressure was +5.4 mmHg (standard deviation 7 mmHg). The within-tilt precision (standard deviation of the bias) of the non-invasive measurements varied between 2.9-12.4 mmHg (median 4.5 mmHg) for systolic comparisons, and 1.6-8.4 mmHg (median 4.4 mmHg) for diastolic comparisons. In all but one tilt highly significant positive increases in both systolic (median 7.1 mmHg) and diastolic bias (median 8.1 mmHg) occurred on tilt with respect to resting pre-tilt levels. Independent of the absolute level of agreement, the non-invasive measurements followed changes in intra-arterial pressure closely, with 89% of beat-to-beat changes in systolic pressure, and 95% of beat-to-beat changes in diastolic pressure followed to within +/- 2 mmHg. This study suggests that the Finapres is well suited for use during diagnostic tilt testing, demonstrating an acceptable within-tilt precision and closely following pressure changes during vasovagal syncope.

Adult↗
PubMed1994

Short AV interval VDD pacing does not prevent tilt induced vasovagal syncope in patients with cardioinhibitory vasovagal syndrome.

Eleven subjects (mean age 50 years, range 33-71 years), who had previously received permanent dual chamber pacemakers for cardioinhibitory vasovagal syncope, underwent paired Westminster protocol tilt tests, one with short AV delay VDD pacing and one without pacing, to test the hypothesis that continuous ventricular pacing would prevent the cardiac initiation of vasovagal syncope. Nine (82%) of the paced tilts produced positive vasovagal outcomes compared with seven (64%) of the unpaced tilts. No important differences in the heart rate or blood pressure behavior during tilt or the time to positive vasovagal outcomes were observed between the paired tilts. There was more accelerated syncope/presyncope once symptoms had developed during the paced tilts of subjects in whom both study tilts were positive, although this did not reach statistical significance (P = 0.054). This study shows that atrial synchronous ventricular pacing does not prevent the initiation, or progression, of tilt induced vasovagal syncope in predisposed subjects.

Adult↗
PubMed1994

Reasons for reprogramming dual chamber pacemakers to VVI mode: a retrospective review using a computer database.

Seven hundred seventy-one dual chamber pacemakers implanted over a 13-year period were identified using a computer database. The mean follow-up period was 40.4 +/- 30.9 months (mean +/- SD). Thirty-three (4.3%) patients were reprogrammed to the VVI mode after a mean period of 26.4 +/- 29 months. Indications for pacing in those reprogrammed were: complete heart block 45.7%, impaired AV conduction 5.7%, sick sinus syndrome 34.2%, carotid sinus syndrome 11.4%, and vasovagal syndrome 2.8%. The most common reason for reprogramming was development of sustained atrial arrhythmias (atrial fibrillation or flutter), which occurred in 25 patients (3.3% of entire group). The remaining 8 (1% of entire group) were reprogrammed because of atrial lead related problems.

Arrhythmias, Cardiac↗
PubMed1994

Permanent pacing for cardioinhibitory malignant vasovagal syndrome.

OBJECTIVE: To evaluate the effect of permanent pacing in cardioinhibitory malignant vasovagal syndrome. PATIENTS AND METHODS: 37 patients with permanent pacemakers for cardioinhibitory malignant vasovagal syndrome. All presented with syncope (median six episodes, median frequency two episodes a year) and after conventional investigation and invasive electrophysiological assessment they remained undiagnosed, and without a generally accepted indication for pacemaker implantation. In all vasovagal syncope with cardioinhibition (heart rate at syncope < 60 beats/min) developed during tilt tests performed according to the Westminster protocol (head up tilt at 60 degrees with a footplate support for 45 minutes or until syncope intervenes). Dual chamber pacemakers were implanted in 35 (95%) and VVI pacemakers in the remaining two (5%). RESULTS: Over a mean (SD) follow up since implantation of 50.2 (23.9) months symptomatic improvement occurred in 89%: 62% remained free of syncope and 27% were completely symptom free. The collective syncopal burden of these 37 patients was reduced from 136 to 11 episodes each year. During follow up three patients died from unrelated causes. Patients who become asystolic during the tilt test (sinus pause of at least four seconds) experienced no greater benefit from pacing than those with less extreme cardioinhibition. Patients who remained free of syncope since implantation were younger than those who continued to experience syncope. Patients who remained completely symptom free after implantation were younger, more likely to be male, and had had fewer syncopal episodes before implantation than those who continued to experience syncope or presyncope. No other demographic, clinical, investigative, or pacing variable suggested a more favourable outcome after implant. CONCLUSIONS: This retrospective and uncontrolled experience suggests a possible role for permanent pacing in selected patients with cardioinhibitory malignant vasovagal syndrome. Improved acquisition of tilt test data may enable better selection of patients who are suitable for permanent pacing. A randomised prospective study to compare permanent pacing with no treatment or with medical treatment in cardioinhibitory malignant vasovagal syndrome is indicated.

Adult↗