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Biomedical subjects

Michael Gold

Publications and source records attributed to Michael Gold.

15 recordsLinked to original sources

Electrocardiogram and clinical characteristics of patients referred for cardiac transplantation: implications for pacing in heart failure.

BACKGROUND: Permanent pacing for the treatment of heart failure (HF) has been the subject of intense research over the past decade. Those with conduction abnormalities may benefit most from pacing. The incidence of these conduction abnormalities in patients referred for cardiac transplantation and its relationship to outcome has not been well described. HYPOTHESIS: This study sought to determine the incidence of these abnormalities and to correlate these findings to outcome in this patient population. METHODS: A review of 100 patients referred for transplantation was performed. Data were analyzed in two groups: those with QRS duration < 120 ms and those with a QRS duration > 120 ms. Times to transplantation or death were analyzed in these two groups. RESULTS: Of these patients, 34% had QRS duration > or = 120 ms and survival was inversely associated with QRS duration. Of those with QRS duration < 120 ms, 24% (16) went on to cardiac transplantation or died. Of those with a QRS duration > or = 120 ms, 55% (17) went on to transplantation or died (p = 0.0134). CONCLUSIONS: This suggests that in addition to a multi-drug regimen for heart failure, 34% of patients referred for transplantation may benefit from additional therapy with biventricular pacing.

Cardiac Pacing, Artificial↗

Timing isn't everything: an analysis of when to start salvage chemotherapy in ovarian cancer.

OBJECTIVE: Results from GOG 178 showed a prolongation of progression-free survival (PFS) with the immediate use of chemotherapy (CT) following a complete clinical response (CR) in patients with stage III-IV ovarian cancer. We wanted to evaluate our strategy of reserving second line (2nd line) chemotherapy to the time of clinical recurrence by determining PFS intervals following first, second, and third line agents and to compare these finding to results of GOG 178. METHODS: We conducted a retrospective parallel study to GOG 178 using identical criteria for PFS definitions. Patients (pts) with stage III-IV cancer achieving a CR following surgery and five to eight cycles of platinum-based CT were identified. Patients not obtaining a CR and those with a CR who underwent second look surgery were excluded. Rather than immediately beginning consolidation CT after CR, second line agents were started at recurrence and were followed by a third line when pts progressed. Clinical-pathologic characteristics were abstracted, and time intervals including time to recurrence, time to use of second line CT, time to use of third line (3rd line) CT, and survival were recorded. Time intervals were studied by Kaplan-Meier method. RESULTS: Of 217 reviewed pts (1991-2001), 59 eligible pts were identified. Forty-nine patients had stage III disease and ten had stage IV. At completion of surgery, 44 were optimally debulked. With a median follow-up of 51 months, the median PFS (from CR) of all patients was 20 months. At 5 years, 36% of pts remain disease-free, and 66% of pts are alive. Twenty-three pts have not received second line agents, and thirty-six have received them. For all pts, the median time from CR to start of second line chemotherapy was 21 months, and the median time to start of third line agents was 43 months. Recurrences occurred after 6 months from completion of first line (1st line) therapy in 87% of cases and after 12 months in 50%. CONCLUSIONS: Nearly 70% of pts achieving a CR after primary therapy eventually recurred. Most recurrences occurred greater than 6 months from completion of primary chemotherapy, and the use of second line agents at the time of recurrence was effective. In this study, the median time from CR to start of third line agent at 43 months compares favorably with the median PFS of 28 months following 12 months of Taxol reported in GOG 178 and challenges the concept of consolidation chemotherapy in ovarian cancer. A randomized trial to evaluate when to institute second line agents should be performed.

Adult↗

Termination of paroxysmal supraventricular tachycardia by tecadenoson (CVT-510), a novel A1-adenosine receptor agonist.

OBJECTIVES: The aim of this study was to evaluate tecadenoson safety and efficacy during conversion of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm. BACKGROUND: Tecadenoson (CVT-510), a novel adenosine receptor (Ado R) agonist, selectively activates the A1 Ado R and prolongs atrioventricular (AV) nodal conduction at doses lower than those required to cause A2 Ado R-mediated coronary and peripheral vasodilation. Unlike adenosine, which non-selectively activates all four Ado R subtypes and produces unwanted effects, tecadenoson appears to terminate AV node-dependent supraventricular tachycardias without hypotension and bronchoconstriction. METHODS: In this open-label, multicenter, dose escalation study, tecadenoson was administered to 37 patients (AV node re-entrant tachycardia, n = 29; AV re-entrant tachycardia, n = 8) with inducible PSVT sustained for > or =1 min during an electrophysiology study. Seven regimens (0.3 to 15 microg/kg) of up to two identical tecadenoson intravenous bolus doses were administered. RESULTS: After the first or second bolus, PSVT converted to sustained sinus rhythm for > or =5 min in 86.5% (32/37) of the patients, with 91% (29/32) of the conversions occurring after the first bolus (most within 30 s), coincident with anterograde conduction block in the AV node. No effects on sinus cycle length (SCL) or systolic blood pressure were observed. The atrial-His (AH), but not the His-ventricular (HV) interval was prolonged up to 5 min after the final tecadenoson bolus, returning to baseline by 10 min. Tecadenoson was generally well tolerated. CONCLUSIONS: In this study, tecadenoson rapidly terminated sustained PSVT by depressing AV nodal conduction without causing hypotension. After sinus rhythm restoration, there was minimal AH interval prolongation without HV interval or SCL prolongation.

Adenosine↗

A new pacemaker algorithm for the treatment of atrial fibrillation: results of the Atrial Dynamic Overdrive Pacing Trial (ADOPT).

OBJECTIVES: The Atrial Dynamic Overdrive Pacing Trial (ADOPT) was a single blind, randomized, controlled study to evaluate the efficacy and safety of the atrial fibrillation (AF) Suppression Algorithm (St. Jude Medical Cardiac Rhythm Management Division, Sylmar, California) in patients with sick sinus syndrome and AF. BACKGROUND: This algorithm increases the pacing rate when the native rhythm emerges and periodically reduces the rate to search for intrinsic atrial activity. METHODS: Symptomatic AF burden (percentage of days during which symptomatic AF occurred) was the primary end point. Patients underwent pacemaker implantation, were randomized to DDDR with the algorithm on (treatment) or off (control), and were followed for six months. RESULTS: Baseline characteristics and antiarrhythmic drugs used were similar in both groups. The percentage of atrial pacing was higher in the treatment group (92.9% vs. 67.9%, p < 0.0001). The AF Suppression Algorithm reduced symptomatic AF burden by 25% (2.50% control vs. 1.87% treatment). Atrial fibrillation burden decreased progressively in both groups but was lower in the treatment group at each follow-up visit (one, three, and six months) (p = 0.005). Quality of life scores improved in both groups. The mean number of AF episodes (4.3 +/- 11.5 control vs. 3.2 +/- 8.6 treatment); total hospitalizations (17 control vs. 15 treatment); and incidence of complications, adverse events, and deaths were not statistically different between groups. CONCLUSIONS: The ADOPT demonstrated that overdrive atrial pacing with the AF Suppression Algorithm decreased symptomatic AF burden significantly in patients with sick sinus syndrome and AF. The decrease in relative AF burden was substantial (25%), although the absolute difference was small (2.50% control vs. 1.87% treatment).

Aged↗

Right ventricular outflow versus apical pacing in pacemaker patients with congestive heart failure and atrial fibrillation.

INTRODUCTION: Prior studies suggest that right ventricular apical (RVA) pacing has deleterious effects. Whether the right ventricular outflow tract (RVOT) is a more optimal site for permanent pacing in patients with congestive heart failure (CHF) has not been established. METHODS AND RESULTS: We conducted a randomized, cross-over trial to determine whether quality of life (QOL) is better after 3 months of RVOT than RVA pacing in 103 pacemaker recipients with CHF, left ventricular (LV) systolic dysfunction (LV ejection fraction < or = 40%), and chronic atrial fibrillation (AF). An additional aim was to compare dual-site (RVOT + RVA, 31-ms delay) with single-site RVA and RVOT pacing. QRS duration was shorter during RVOT (167 +/- 45 ms) and dual-site (149 +/- 19 ms) than RVA pacing (180 +/- 58 ms, P < 0.0001). At 6 months, the RVOT group had higher (P = 0.01) role-emotional QOL subscale scores than the RVA group. At 9 months, there were no significant differences in QOL scores between RVOT and RVA groups. Comparing RVOT to RVA pacing within the same patient, mental health subscale scores were better (P = 0.03) during RVOT pacing. After 9 months of follow-up, LVEF was higher (P = 0.04) in those assigned to RVA rather than RVOT pacing between months 6 and 9. After 3 months of dual-site RV pacing, physical functioning was worse (P = 0.04) than during RVA pacing, mental health was worse (P = 0.02) than during RVOT pacing, and New York Heart Association (NYHA) functional class was slightly better (P = 0.03) than during RVOT pacing. There were no other significant differences between RVA, RVOT and dual-site RV pacing in QOL scores, NYHA class, distance walked in 6 minutes, LV ejection fraction, or mitral regurgitation. CONCLUSION: In patients with CHF, LV dysfunction, and chronic AF, RVOT and dual-site RV pacing shorten QRS duration but after 3 months do not consistently improve QOL or other clinical outcomes compared with RVA pacing.

Aged↗

Prevalence of sensing abnormalities in dual chamber implantable cardioverter defibrillators.

BACKGROUND: The clinical efficacy of ICD therapy depends on accurate sensing of intracardiac signals and sensing algorithms. We investigated the occurrence of sensing abnormalities in patients with dual chamber ICDs. METHODS: The study group consisted of all patients with dual chamber ICDs enrolled in the LESS trial and patients implanted with dual chamber ICDs at a single center between January 1997 and July 2000. Electrograms of spontaneous ventricular arrhythmias requiring device intervention were analyzed. RESULTS: A total of 48 patients met the criteria for enrollment. Among the 244 episodes, 215 (88%) were due to ventricular tachycardia and 29 (12%) were due to ventricular fibrillation. Overall undersensing was infrequent with 12 (20%) patients exhibiting on average 2.2 undersensed beats during 26 episodes of ventricular arrhythmias. There was no delay in therapy due to undersensing. Oversensing occurred in 5 (10%) patients resulting in 13 (2.7%) episodes of inappropriate therapy. None of the patients had any lead abnormalities and oversensing resolved after device reprogramming in 4 patients while 1 patient required a separate rate sensing lead. Among patients with oversensing, 4 out of 5 were pacing before the index event while among patients with no oversensing only 5 out of 42 were pacing (P<0.001). CONCLUSIONS: Dual chamber ICDs demonstrate outstanding accuracy of sensing. However, because of the selection of patient population requiring more frequent pacing, oversensing occurs with a significant frequency. Meticulous evaluation in such patients is necessary to minimize the likelihood of oversensing and inappropriate shocks.

Aged↗

Overview of the Alliance for Cellular Signaling.

The Alliance for Cellular Signaling is a large-scale collaboration designed to answer global questions about signalling networks. Pathways will be studied intensively in two cells--B lymphocytes (the cells of the immune system) and cardiac myocytes--to facilitate quantitative modelling. One goal is to catalyse complementary research in individual laboratories; to facilitate this, all alliance data are freely available for use by the entire research community.

B-Lymphocytes↗

Progressive dementia and hypersomnolence with dream-enacting behavior: oneiric dementia.

BACKGROUND: Sleep disorders are associated with several types of degenerative dementias, including Alzheimer and prion diseases. Animal models have demonstrated abolition of rapid eye movement atonia, resulting in dream-enacting complex movements termed oneiric behavior, and patients with fatal familial insomnia may have vivid dreams that intrude on wakefulness. OBJECTIVE: To describe a new form of progressive dementia with hypersomnia and oneiric behavior. METHODS: Neuropsychological and polysomnographic studies of a middle-aged woman with a progressive dementia, excessive daytime sleepiness, and a vertical gaze palsy. RESULTS: Neuropsychological testing revealed decreased verbal fluency, impaired attention and working memory, amnesia, poor recall, and bradyphrenia with hypersomnia. Polysomnography revealed a rapid eye movement behavioral disorder with complete absence of slow wave sleep. Prion protein analysis did not reveal the mutation associated with fatal familial insomnia, and other diagnostic test findings were unrevealing. CONCLUSION: Our patient had a previously unreported syndrome of progressive dementia associated with rapid eye movement behavioral disorder and the absence of slow wave sleep.

Dementia↗

Tau therapeutics for Alzheimer's disease: the promise and the challenges.

The pathological diagnosis of Alzheimer's disease (AD) depends on the presence of plaques consisting of the beta-amyloid peptide as well as neurofibrillary tangles consisting of paired helical filaments (PHFs) of the tau (tau) protein. The role of each type of pathology in the pathogenesis and progression of AD remains unclear. Previous hypotheses suggested that these two processes were independent, whereas more recent data suggest that there may be a bidirectional interaction between these two pathological processes. The identification of the neurotoxic effects of beta-amyloid and the discovery of mutations responsible for early-onset Alzheimer's disease (EOAD) and their linkage to beta-amyloid overproduction, has made the amyloid hypothesis of AD the predominant influence for therapeutic targets. Several approaches have emerged from preclinical testing and have entered early phases of clinical developments. The recent identification of tau mutations and their linkage to progressive neurodegenerative disorders provides a counterbalancing influence on the search for therapeutic targets for AD. Therapeutic approaches that are targeted to either beta-amyloid or tau share certain features at the level of pharmacology and will face many of the same challenges as they progress through drug development paradigms. The aim of this article is to provide a brief overview of some of the commonalities and the challenges faced by tau-related therapeutic strategies. The issues discussed in this article are not exhaustively dealt with in either scope or detail.

Alzheimer Disease↗

The baby makers.

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Cryopreservation↗

Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank.

Alzheimer disease (AD) is the most common dementing illness in the elderly, but there is equivocal evidence regarding the frequency of other disorders such as Lewy body disease (LBD), vascular dementia (VaD), frontotemporal dementia (FTD), and hippocampal sclerosis (HS). This ambiguity may be related to factors such as the age and gender of subjects with dementia. Therefore, the objective of this study was to calculate the relative frequencies of AD, LBD, VaD, FTD, and HS among 382 subjects with dementia from the State of Florida Brain Bank and to study the effect of age and gender on these frequencies. AD was the most frequent pathologic finding (77%), followed by LBD (26%), VaD (18%), HS (13%), and FTD (5%). Mixed pathology was common: Concomitant AD was present in 66% of LBD patients, 77% of VaD patients, and 66% of HS patients. The relative frequency of VaD increased with age, whereas the relative frequencies of FTD and LBD declined with age. Males were overrepresented among those with LBD, whereas females were overrepresented among AD subjects with onset age over 70 years. These estimates of the a priori probabilities of dementing disorders have implications for clinicians and researchers.

Aged↗

ALA-PDT and blue light therapy for hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, often suppurative skin condition which affects primarily apocrine glands. A variety of therapies have been used to treat HS, often with unsatisfactory results. Photodynamic therapy (PDT), utilizing topical 20% 5-aminolevulinic acid (ALA) is being used to treat a variety of dermatologic skin concerns, including photorejuvenation and associated actinic keratoses, and acne vulgaris, and other skin tumors. OBJECTIVE: The purpose of these case reports is to evaluate the effectiveness of ALA-PDT in treating recalcitrant cases of HS. METHODS: Four patients, not responding to standard HS therapy, underwent short-contact ALA-PDT therapy utilizing a blue light for activation. One to two week intervals between therapies was utilized for 3-4 total treatments and follow-up was for 3 months following the last treatment. RESULTS: All four of the patients tolerated the therapies well. Clinical improvements from 75-100% were noted n 11 of the patients. No adverse effects were seen during the treatments. The treatments were pain free and there was no downtime associated with these ALA-PDT treatments. CONCLUSIONS: HS is a chronic disease which most dermatologists find difficult to treat. The use of ALA-PDT is finding an ever-expanding role in dermatology. These case studies support the use of ALA-PDT in cases of HS. Although all advertising material is expected to conform to ethical and medical standards, inclusion in this publication does not constitute a guarantee or endorsement by the Journal or its staff of the quality or value of such products or of the claims of any manufacturer.

Adult↗