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Biomedical subjects

D Newman

Publications and source records attributed to D Newman.

At least 37 records · Page 2Linked to original sources
PubMed2000

The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy.

OBJECTIVES: We sought to assess the impact of intermittent atrial fibrillation (AF) on health-related quality of life (QoL). BACKGROUND: Intermittent AF is a common condition with little data on health-related QoL questionnaires to guide investigational therapies. METHODS: Outpatients from four centers, with documented AF (n = 152), completed validated QoL questionnaires (Medical Outcomes Study Short Form 36 [SF-36], Specific Activity, Symptom Checklist, Illness Intrusiveness and University of Toronto AF Severity Scales). Comparison groups were made up of healthy individuals (n = 47) and four cardiac control groups: published (n = 78) and created for study (n = 69) percutaneous transluminal coronary angioplasty (PTCA); published heart failure (n = 216) and published postmyocardial infarction (MI) (n = 107). RESULTS: Across all domains of the SF-36, AF patients reported substantially worse QoL than healthy controls (1.3 to 2.0 standard deviation units), with scores of 24%, 23%, 16% and 30% lower than healthy individuals on measures of physical and social functioning, mental and general health, respectively (all p < 0.001). Patients with AF were either significantly worse (p < 0.05, published controls) or as impaired (study controls) as either PTCA or post-MI patients on all domains of the SF-36 and the same as heart failure controls on SF-36 psychological subscales. Patients with AF were as impaired or worse than study PTCA controls on measures of illness intrusiveness, activity limitations and symptoms. Associations between objective disease indexes and subjective QoL measures had poor correlations and accounted for <6% of the total variability in QoL scores. CONCLUSIONS: Quality of life is as impaired in patients with intermittent AF as in patients with significant structural heart disease. Patients' perception of QoL is not dependent on the objective measures of disease severity that are usually employed.

Anti-Arrhythmia Agents↗
PubMed2000

Misconceptions about STD-protective behavior. Project RESPECT Study Group.

CONTEXT: Misconceptions about STD-protective behaviors have not been studied before and after STD counseling. Further, to the best of our knowledge, the relationship of these misconceptions to condom use and STD incidence has not previously been described in published reports. OBJECTIVES: The main purpose of the study was to determine the prevalence of misconceptions about STD prevention among STD clinic attendees (N=3498) in five large cities, as well as whether misconceptions decreased after STD diagnosis, STD counseling, or both. The study also identified predictors of persistent misconceptions and determined the relationship of STD incidence and unprotected sex to persistent misconceptions. METHODS: Data from a randomized controlled trial evaluating HIV/STD counseling interventions (Project RESPECT) were used for the present analyses. Participants completed an interview upon study enrollment and every 3 months following enrollment for a 1-year period. A portion of the interview assessed participants' misconceptions about STD-protective behaviors. RESULTS: At baseline, 16.3% believed that washing the genitals after sex protected from STDs. Likewise, urinating after sex (38.7%), douching (45.7%), and use of oral contraceptives (19. 9%) were believed to prevent STDs. Prevalence of misconceptions was significantly diminished at a 3-month follow-up (p<.001). Those continuing to have misconceptions were more likely to be aged > or = 24 and African American. Those continuing to have these misconceptions did not have higher STD incidence. CONCLUSIONS: Misconceptions about STD-protective behaviors are common, and the event of an STD or STD counseling or both generally reduces these misconceptions. Although these misconceptions may not directly translate into risky behavior, they may preclude movement toward safer sex.

Adult↗
PubMed2000

October 18, 2000 8:30-8:45. Problem Solving with FDG Positron Emission Mammography.

Purpose: To examine one potential clinical application of dedicated devices for positron emission mammography.Background: Dedicated devices for breast imaging with FDG have technical specifications that appear well-suited for detecting small breast cancers, including registration with x-rays, high count sensitivity, and spatial resolution in the 2-3 mm range.Methods: In IRB-approved clinical trials, patients who were scheduled for biopsy for suspicious findings on x-ray mammograms were injected with 10-20 mCi FDG intravenously one to two hours prior to x-ray guided core biopsy or lumpectomy. Positron emission mammograms using a dedicated device were performed just before biopsy, and results compared to final histopathology.Results: Three patients whose cancers were missed on initial x-ray mammograms or whose mammograms contained subtle abnormalities that were not strongly suspicious for cancer, were shown to have very suspicious hot spots on positron emission mammograms. These patients were later confirmed to have cancer.Discussion: The role for dedicated devices for positron emission mammography is evolving. Finding cancers that are either mammographically occult or have low indices of suspicion is a potential application for this technique. Further clinical and technical work will be needed to better define the strengths and weaknesses of the device in this application.

Journal Article↗
PubMed2000

Is electrical storm in ICD patients the sign of a dying heart? Outcome of patients with clusters of ventricular tachyarrhythmias.

BACKGROUND: Electrical storm in patients with implanted cardioverter defibrillators (ICDs) is purported to carry an ominous prognosis. METHODS AND RESULTS: We retrospectively compared 40 patients with electrical storm (defined as three or more episodes of ventricular arrhythmia requiring ICD therapy in a 24 h period) with those only having isolated appropriate ICD therapy (n=57) and with patients having no or only inappropriate ICD therapy (n=125). All patients received ICDs for documented sustained VT or VF. There was no significant difference in age, sex, ejection fraction, total follow-up time, or underlying heart disease between any of the three groups. Patients who had electrical storm received their first appropriate ICD therapy 275 +/- 369 days post-implant (35% had storm as their first event) with storm occurring an average of 599 +/- 710 days post-implant. Patients had 1.5 +/- 1.0 storms in total (median= 1), with 55 +/- 91 episodes per storm. There were no significant differences in actuarial survival at 5-year follow-up between the three groups. Eighty percent of storm patients were alive 5 years post-implant. CONCLUSION: Storm is a common occurrence in ICD patients, can occur at any time during the follow-up period, and does not independently confer increased mortality.

Defibrillators, Implantable↗
PubMed2000

Rate dependence of the effect of antiarrhythmic drugs delaying cardiac repolarization: an overview.

Prolongation of the cardiac action potential and refractoriness (class III effect) is a potentially beneficial electrophysiological mechanism of action. However, this effect may be diminished or eliminated at rapid heart rates, so-called 'reverse rate dependence' of prolongation of repolarization. Action potential duration normally shortens as heart rate increases, due to increases in outward repolarizing currents, and/or decreases in inward depolarizing currents. The assessment of the effect of drugs on action potential duration is complicated by inter-species differences in ionic currents mediating repolarization, heterogeneity within the heart in repolarizing currents, and differential effect of drugs in different species, during differing experimental conditions, and at different rates of stimulation. In general, most drugs which predominantly block the IKr repolarizing current exhibit reverse rate-dependent effects on cardiac repolarization. Drugs or combinations of drugs which produce multiple ionic channel blocks and possibly those which block the IKs current, may be less prone to this potentially undesirable effect.

Action Potentials↗
PubMed2000

Two C-terminal variants of NBC4, a new member of the sodium bicarbonate cotransporter family: cloning, characterization, and localization.

We report the cloning, characterization, and chromosomal assignment of a new member of the sodium bicarbonate cotransporter (NBC) family, NBC4. The NBC4 gene was mapped to chromosome 2p13 and is a new candidate gene for Alstrom syndrome. Two variants of the transporter have been isolated from human testis and heart, which differ in their C termini. NBC4a encodes a 1137-residue polypeptide and is widely expressed in various tissues, including liver, testis, and spleen. NBC4b is identical to NBC4a except that it has a 16-nucleotide insert, creating a C-terminal frame shift. NBC4b encodes a 1074-residue polypeptide and is highly expressed in heart. Amino acids 1-1046 are common to both NBC4 variants. NBC4a has two protein-interacting domains that are lacking in NBC4b: a proline-rich sequence, PPPSVIKIP (amino acids 1102-1110), and a consensus PDZ-interacting domain, SYSL (1134-1137). NBC4b lacks the stretch of charged residues present in the C terminus of NBC4a and other members of the NBC family. Unlike other members of the NBC family, both NBC4a and NBC4b have a unique glycine-rich region (amino acids 440-469). In comparison with other members of the bicarbonate transport superfamily, NBC4a and NBC4b are most similar structurally to the electrogenic sodium bicarbonate cotransporters (NBC1).

Amino Acid Sequence↗
PubMed2000

Oligomeric structure of bAE3 protein.

The "brain" form of the anion exchanger protein 3 (bAE3) has been purified to homogeneity from the rabbit kidney by differential centrifugation and immunoaffinity chromatography. A single protein band of approximately 165 kDa was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. Monomers, dimers (a major component), and a higher oligomeric form (apparently tetramers) were found after oxidative cross-linking of purified bAE3. The largest form of bAE3 was separated from dimers and monomers by sucrose gradient centrifugation and was studied by transmission electron microscopy to confirm a tetrameric structure. Two main types of bAE3 images were detected, round (approximately 11-14 nm) and square-shaped (approximately 12 x 12 nm). Image analysis revealed fourfold rotational symmetry of both the round and square-shaped images, indicating that bAE3 consists of multiples of 4 subunits. We conclude that bAE3 in Triton X-100 solution is predominantly a mixture of dimers and tetramers with a smaller amount of monomers.

Animals↗
PubMed2000

Permanent explantation of implantable cardioverter defibrillators.

Although ICD therapy is seen as an irrevocable mode of therapy in most patients, a small number of patients do have their devices permanently explanted. The long-term outcome in these patients has not been described. The purpose of this single center study was to evaluate the long-term outcome of patients whose ICD was explanted and not replaced and to propose clinical variables that can be considered when making the decision to discontinue therapy. Ten of 323 (3.1%) patients in our ICD registry had their devices permanently explanted or turned off between 1986 and December 1998. The devices had been in place for 39 +/- 31 months preexplant. No patient had received appropriate therapy prior to surgery, which was indicated for infection or lead fracture. All patients are alive and well 75 +/- 30 months postexplant with 1 (10%) patient requiring late reimplantation. We reviewed the English language literature describing ICD explanation without replacement. A total of 151 patients were reported in eight studies and were followed for up to 30 months postexplant. Excluding patients with terminal illness or heart transplantation 57.6% survived without reimplantation. In selected patients, after not using an ICD for a long period and when clinical circumstances justify, device therapy may be discontinued with some degree of safety.

Adult↗
PubMed2000

Can antiarrhythmic agents be selected based on mechanism of action?

When selecting an antiarrhythmic agent the clinician needs to be able to accurately predict the probability that a particular drug will serve its intended purpose in a given patient. This is difficult because of the complexity of variables which govern the relationship between drug administration and clinical outcome. The efficacy of a drug may potentially be predicted from its mechanism of action. At least two classifications of antiarrhythmic agents based on mechanism of action have been proposed. The Vaughan Williams classification is based on the predominant electrophysiological effects of a drug on the action potential. In the Sicilian Gambit approach, a number of potential targets ('vulnerable parameters') for drug action are identified and antiarrhythmic drugs or substances that affect cardiac electrophysiology are characterised by their actions on each of these. The usefulness of these classification systems in predicting antiarrhythmic drug efficacy are limited. Furthermore, in the Vaughan Williams classification not all drugs in the same class have identical effects, whereas some drugs in different classes have overlapping actions. The Sicilian Gambit requires in-depth knowledge regarding cellular and molecular targets of antiarrhythmic agents which may make it intimidating or simply impractical for regular clinical use. Surrogate measures such as 24-hour Holter monitoring and programmed electrical stimulation have been used to predict anti-arrhythmic drug efficacy. However, studies such the Cardiac Arrhythmia Suppression Trial (CAST) have shown that suppression of ventricular ectopy on Holter monitoring does not necessarily correlate with improved survival and may in fact be dangerous. Conversely, studies using programmed electrical stimulation to assess drug effect on variables such as tachycardia inducibility, refractory period and ventricular tachycardia cycle length show that suppression of tachycardia inducibility, prolongation of refractory period and prolongation of ventricular tachycardia cycle length, are all associated with reduced recurrence of tachycardia and possibly improved survival. The most practical use of the current classification systems applied to antiarrhythmic agents may be in their ability to predict with reasonable accuracy, the risk and type of proarrhythmia based on the mechanism of action of an agent.

Anti-Arrhythmia Agents↗
PubMed1999

Early switch from intravenous to oral antibiotics and early hospital discharge: a prospective observational study of 200 consecutive patients with community-acquired pneumonia.

UNLABELLED: To determine the proportion of patients who can be treated with early switch to oral antibiotics and early discharge, to evaluate clinical outcome and patient satisfaction for patients treated with early switch and early discharge, and to define the factors that interfere with early discharge for some of the patients who underwent early switch to oral antibiotic therapy. DESIGN: Prospective study. PARTICIPANTS: Two hundred consecutive hospitalized patients with community-acquired pneumonia. MAIN OUTCOME MEASURES: Number of days needed to switch to oral therapy and length of hospital stay. Clinical outcome and satisfaction with care were evaluated for those patients treated with early switch and early discharge. RESULTS: Early switch to oral antibiotics (within the first 3 days of hospitalization) was performed in 133 patients (67%). Clinical failure was documented in 1 patient. Early switch and early discharge was performed in 88 patients (44%). The mean length of hospital stay for this group was 3.4 days. The most common reason for prolonged hospitalization after the switch to oral antibiotics was the need for diagnostic workup. More than 95% of patients were satisfied with the care they had received. CONCLUSIONS: Using simple clinical and laboratory criteria, a significant proportion of hospitalized patients with community-acquired pneumonia (44%) can be treated with early switch and early discharge. This model did not affect patient outcome, decreased the length of hospitalization, and was associated with a high level of patient satisfaction.

Administration, Oral↗
PubMed1999

Cloning, tissue distribution, genomic organization, and functional characterization of NBC3, a new member of the sodium bicarbonate cotransporter family.

Previous functional studies have demonstrated that muscle intracellular pH regulation is mediated by sodium-coupled bicarbonate transport, Na+/H+ exchange, and Cl-/bicarbonate exchange. We report the cloning, sequence analysis, tissue distribution, genomic organization, and functional analysis of a new member of the sodium bicarbonate cotransporter (NBC) family, NBC3, from human skeletal muscle. mNBC3 encodes a 1214-residue polypeptide with 12 putative membrane-spanning domains. The approximately 7.8-kilobase transcript is expressed uniquely in skeletal muscle and heart. The NBC3 gene (SLC4A7) spans approximately 80 kb and is composed of 25 coding exons and 24 introns that are flanked by typical splice donor and acceptor sequences. Expression of mNBC3 cRNA in Xenopus laevis oocytes demonstrated that the protein encodes a novel stilbene-insensitive 5-(N-ethyl-N-isopropyl)-amiloride-inhibitable sodium bicarbonate cotransporter.

Amino Acid Sequence↗
PubMed1999

The external urethral barrier for stress incontinence: a multicenter trial of safety and efficacy. Miniguard Investigators Group.

OBJECTIVE: To assess the efficacy and safety of an external urethral barrier for the management of mild to moderate stress urinary incontinence in adult women. METHODS: Four hundred eleven women with the symptom of stress urinary incontinence in 12 United States centers participated. Additional inclusion and exclusion criteria were applied before protocol device use, and ultimately 390 subjects began device use. Outcome measures for efficacy and safety were assessed. Efficacy was evaluated by the number of leakage episodes using a voiding diary, subjective urinary leakage severity, incontinence impact scores, and pad testing. Safety was evaluated by symptom assessment, urinalysis, urine culture, measurement of postvoid residual urine volume, vulvar cytology, vaginal culture, and (n = 81) cystometric testing. RESULTS: Efficacy was indicated by statistically significant reductions in the number of leakage episodes, subjective leakage severity scores, incontinence impact scores, and pad-test loss during device use. The data also indicated that the device was safe, as evidenced by the lack of statistically significant changes in the percentage of subjects with urinary tract infections during device use or in postvoid residual urine volume and cystometric indices. Symptoms of vulvar irritation or lower urinary tract discomfort occurred in a small percentage of subjects but were generally transient, and only three women discontinued using the device. CONCLUSION: The external urethral barrier appears to be a safe nonsurgical alternative to absorbent products for the management of mild to moderate stress urinary incontinence in adult women.

Adolescent↗