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Biomedical subjects

S Higgins

Publications and source records attributed to S Higgins.

At least 19 recordsLinked to original sources

A comparative study of a new wireless continuous cardiorespiratory monitor for the diagnosis and management of patients with congestive heart failure at home.

Congestive heart failure (CHF) is a major and increasing chronic disease in Western society, with a high mortality, morbidity and cost for unplanned hospital admissions. Continuous cardiorespiratory monitoring is required to detect Cheyne-Stokes respiration (CSR). We have tested a new wireless monitoring system and compared it with polysomnography (PSG) and respiratory inductance plethysmography (RIP) in six CHF patients with CSR in a sleep laboratory. The wireless system compared well with RIP for the detection of CSR but less well with PSG, which had unexpected but significant respiratory sensing errors that led to misclassification of the respiratory disorder present. The wireless system could be used to select CHF patients for better-customized treatment at home as part of a specialist-supported community telemedicine programme.

Heart Failure↗

Susceptibility of LDL to oxidative modification in healthy volunteers supplemented with low doses of n-3 polyunsaturated fatty acids.

The objective of the present study was to evaluate the oxidative susceptibility of LDL in human volunteers following supplementation with various low doses (<1 g/d) of n-3 polyunsaturated fatty acids (PUFA). Sixty-two healthy volunteers (thirty-seven males and twenty-five females, aged 19-63 years) were recruited to take part in a randomised placebo-controlled trial. Volunteers were required to take 0.9, 0.6 or 0.3 g n-3 PUFA as fish oil or placebo capsules daily for 16 weeks. Susceptibility of LDL to oxidative modification was assessed by measuring the production of conjugated dienes and thiobarbituric acid-reactive substances in LDL oxidised by Cu2+ (15 microM) or 2,2'-azobis(2-amidinopropane) dihydrochloride (1 mM) for 5 h. Plasma fatty acid and LDL-fatty acid composition, cholesterol levels and antioxidant concentrations were also measured. While post-treatment n-3 PUFA compositions of plasma and LDL reflected the capsule contents, no meaningful differences in antioxidant concentrations or cholesterol levels were observed between the groups. Supplementation with low doses of n-3 PUFA as fish oil did not influence the oxidative susceptibility of LDL. The results of the present study suggest that moderate dietary intakes of n-3 PUFA do not significantly influence the susceptibility of LDL to oxidative modification in vitro.

Adult↗

An analysis of polygenes affecting wing shape on chromosome 2 in Drosophila melanogaster.

Genetic effects on an index of wing shape on chromosome 2 of Drosophila melanogaster were mapped using isogenic recombinants with transposable element markers. At least 10 genes with small additive effects are dispersed evenly along the chromosome. Many interactions exist, with only small net effects in homozygous recombinants and little effect on phenotypic variance. Heterozygous chromosome segments show almost no dominance. Pleiotropic effects on leg shape are only minor. At first view, wing shape genes form a rather homogeneous class, but certain complexities remain unresolved.

Alleles↗

Transvenous biventricular defibrillation.

The recent success of biventricular pacing with transvenously implantable left ventricular leads suggests that left ventricular leads may be useful for other modes of therapy. Animal studies showed small leads inserted into a left ventricular vein dramatically reduced defibrillation strength requirements. This article describes a human investigation of the feasibility of biventricular defibrillation. Fifty-one patients undergoing implantable cardioverter defibrillator (ICD) implantation were enrolled. After insertion of a standard ICD lead, a prototype over-the-wire left ventricular defibrillation lead was inserted through the coronary sinus and into a vein on the left ventricle. Lead insertion was guided by retrograde venography. The left ventricular lead's location was randomized to the anterior or posterior vein. Randomized, paired defibrillation threshold (DFT) testing was performed to compare a standard ICD shock configuration (Control: right ventricle- --> superior vena cava+ + CAN+) to 1 of 3 biventricular shock configurations. In the anterior vein, the left ventricular lead was tested with either a single biphasic shock from right ventricle + left ventricle- --> superior vena cava+ + CAN+ or a dual biphasic shock. In the posterior vein, the left ventricular lead was tested with a dual biphasic shock. Dual shocks consisted of a 40% tilt biphasic shock from right ventricle- --> superior vena cava+ + CAN+ followed by another 40% tilt biphasic shock from left ventricle- --> superior vena cava+ + CAN+, delivered from a single 225 microF capacitance. Left ventricular lead positioning was successful in 41 of 46 patients (89%). Mean left ventricular lead insertion time was 17 +/- 17 minutes and 13 +/- 15 minutes for anterior and posterior locations, respectively. Mean DFTs were not statistically lower for the left ventricular shock configurations, but retrospective analysis showed a well-defined region of the posterolateral left ventricle where consistent DFT reduction was achieved with dual shocks (14.0 +/- 2.7 J vs 7.8 +/- 0.9 J; n = 5; p = 0.04). There were no adverse events requiring intervention due to the use of the left ventricular lead. Biventricular defibrillation is feasible and safe under the conditions used in this study. Additional studies are needed to verify whether dual shocks with posterolateral left ventricular lead positions consistently reduce DFTs.

Aged↗

The effect of low-dose fish oil supplementation on serum growth factors in healthy humans.

OBJECTIVE: To examine the effect of low-dose fish oil supplementation on specific growth factors, purported to play a central role in lesion formation, and also on the total growth factor activity of serum, as assessed by the induction of DNA synthesis in cultured human arterial smooth muscle cells. DESIGN: Randomized placebo-controlled double-blind intervention study. SETTING: Free-living population. SUBJECTS: Sixty-three healthy volunteers, 37 males and 26 females. INTERVENTIONS: Four treatment regimes with subjects receiving 0, 0.3,0.6 or 0.9 g/day of n-3 PUFA for an 8 week period. Blood samples were taken at baseline and following the 8 week intervention. All samples were analysed in batch following completion of the study. RESULTS: Consumption of fish oil had no effect on serum platelet-derived growth factor (PDGF), or transforming growth factor beta (TGFbeta) concentration. Furthermore, fish oil supplementation did not alter the total growth factor activity of serum. CONCLUSIONS: Results indicate that low-dose fish oil supplementation, equivalent to about two portions of fatty fish per week and providing less than 1 g n-3 PUFA/day, does not alter the levels of the major serum growth factors and does not modify total serum growth factor activity in healthy human volunteers. SPONSORSHIP: European Union shared cost project (FAIR-CT-95-0085).

Adult↗

13H-dibenzo

Explore the source record for details and available documents.

Journal Article↗

Experience with a higher impedance, fixed helix, steroid-eluting pacing lead. The SWEET PICOTIP Rx Study Group.

A higher impedance, steroid-eluting pacing lead was studied in a multicenter trial. A total of 132 leads were implanted in 61 patients and the electrical characteristics were compared with historical controls. The study lead had a lower pacing threshold at 3 months, 0.72 +/- 0.33 versus 1.29 +/- 0.82 in the atrium and 0.71 +/- 0.25 versus 1.52 +/- 0.52 in the ventricle (P < 0.01 for both). Impedance was significantly higher in the study lead, 923 +/- 133 versus 719 +/- 109 in the atrium and 980 +/- 235 versus 664 +/- 104 in the ventricle (P < 0.01 for both). Sensing was similar for both leads. The study lead's higher impedance values and low pacing thresholds combine to reduce pacing system energy requirements.

Aged↗

A prospective randomized-controlled trial of ventricular fibrillation detection time in a DDDR ventricular defibrillator. Ventak AV II DR Study Investigators.

Implantable cardioverter defibrillators (ICDs) with dual chamber and dual chamber rate responsive pacing may offer hemodynamic advantages for some ICD patients. Separate ICDs and DDDR pacemakers can result in device to device interactions, inappropriate shocks, and underdetection of ventricular fibrillation (VF). The objectives of this study were to compare the VF detection times between the Ventak AV II DR and the Ventak AV during high rate DDDR and DDD pacing and to test the safety of dynamic ventricular refractory period shortening. Patients receiving an ICD were randomized in a paired comparison to pacing at 150 beats/min (DDD pacing) or 175 beats/min (DDDR pacing) during ICD threshold testing to create a "worst case scenario" for VF detection. The VF detection rate was set to 180 beats/min, and VF was induced during high rate pacing with alternating current. The device was then allowed to detect and treat VF. The induction was repeated for each patient at each programmed setting so that all patients were tested at both programmed settings. Paired analysis was performed. Patient characteristics were a mean age of 69 +/- 11 years, 78% were men, coronary artery disease was present in 85%, and a mean left ventricular ejection fraction of 0.34 +/- 0.11. Fifty-two episodes of VF were induced in 26 patients. Despite the high pacing rate, all VF episodes were appropriately detected. The mean VF detection time was 2.4 +/- 1.0 seconds during DDD pacing and 2.9 +/- 1.9 seconds during DDDR pacing (P = NS). DDD and DDDR programming resulted in appropriate detection of all episodes of VF with similar detection times despite the "worst case scenario" tested. Delays in detection may be seen with long programmed ventricular refractory periods which shorten the VF sensing window and may be avoided with dynamic ventricular refractory period shortening.

Aged↗

Efficacy of biventricular sensing and treatment of ventricular arrhythmias.

While much is known concerning the hemodynamic effects of biventricular (BV) pacing, little has been reported concerning the efficacy of BV sensing and pacing in the detection and treatment of ventricular tachyarrhythmias. Two hundred nineteen heart failure (HF) patients with VT or VF and a QRS > or = 120 ms during sinus rhythm received an ICD capable of BV pacing and sensing. Detection times of induced VF and success rates for terminating induced VT were measured. The ICD system used a left ventricular epicardial lead implanted via thoracotomy (52 patients) or a specially designed percutaneous, over-the-wire lead inserted in the coronary venous system. VF detection times and VT termination rates by antitachycardia pacing (ATP) were compared with those measured in a population of recipients of ICD using a RV lead alone. Median induced VF detection times were comparable (2.0-s BV vs 1.8-s RV). Termination of induced VT on the first attempt was comparable with BV pacing (87.4%) versus RV pacing (89.6%). The time to detect induced VF was not different with ICDs using BV sensing versus conventional ICDs using RV sensing alone. Similarly, the rates of successful termination of induced VT by ATP with BV or RV pacing were comparable.

Cardiac Pacing, Artificial↗

Effects of oleic acid, docosahexaenoic acid and eicosapentaenoic acid on background and genotoxin-induced frequencies of SCEs in Indian muntjac fibroblasts.

Muntjac cells were cultured at 5 X 10(5) cells/10 cm Petri dish for 24 h prior to addition of fatty acids (50 microM) which were delivered to the cells complexed with 2% bovine serum albumin (fatty acid-free) and incubated for a further 24 h. Parallel dishes were processed for lipid extraction and GC analysis. This analysis showed highly significant (P < 0.01) uptake by the cells of each fatty acid. Genotoxins (75 microM hydrogen peroxide, 20 microM t-butylhydroperoxide and 2.4 microM mitomycin C) were added to the cells for 1 h prior to the end of the 24 h fatty acid incubation period. Control (no genotoxin or fatty acid) treatments were included. No difference was observed in background frequencies of SCEs between controls and fatty acid treatments, thus indicating that these fatty acids per se do not cause DNA damage. The cells incubated with the genotoxins showed increased (P < 0.05) frequencies of SCEs when compared with control frequencies. Cells incubated with genotoxins in the presence of fatty acids also showed significantly higher (P < 0.05) levels of SCEs when compared with control frequencies. When cells supplemented with genotoxins in the presence of fatty acids were compared with cells treated with genotoxins alone, higher levels of SCEs were observed in the former, suggesting that the fatty acids exacerbate DNA damage caused by these genotoxins.

Animals↗

A randomized controlled clinical trial comparing ventricular fibrillation detection time between two transvenous defibrillator models. The Acute Ventak AV investigator group.

The Ventak AV is an implantable cardioverter defibrillator with dual chamber pacing capability. Features include detection and treatment of ventricular arrhythmias, detection of atrial arrhythmias, as well as dual chamber pacing. The objective of the investigation was to verify the efficacy of the Ventak AV in detecting ventricular fibrillation in the presence of dual chamber pacing. Thirty-three patients, who were to receive an implantable defibrillator were randomized (1:1) in a paired comparison study to the Ventak AV (study device) and the Ventak Mini (control) during defibrillation threshold testing. In order to create a "worst case scenario" for sensing of ventricular fibrillation, pacing was performed at high lower rate limit values (Ventak AV DDD pacing at 150/min, Ventak Mini at VVI 100/min). Ventricularfibrillation was induced and the randomized device was allowed to detect and treat the arrhythmia. This test was repeated for each patient using the alternate device in a randomized order, such that all patients were tested with both devices. The mean ventricular fibrillation detection time for the Ventak AV was 2.0+/-0.11 seconds and for the control device the detection time was 1.8+/-0.11 seconds (P = 0.26). Appropriate tachyarrhythmia therapy decision was documented in all episodes for both devices. The study patient population demonstrated equivalent ventricular fibrillation detection time between the Ventak AV and the Ventak Mini. The Ventak AV demonstrated effectiveness in detecting ventricular fibrillation in the presence of high rate dual chamber pacing.

Adult↗

Infective endocarditis in the premature neonate.

We describe a series of 11 high-risk neonates with infective endocarditis (IE) in this retrospective review. Previously IE has rarely been diagnosed in newborns and is usually fatal. The frequency was 4.3 cases per 100 patients. Five patients survived. Microorganisms included gram positives such as S. aureus and coagulase-negative Staphylococcus, gram negatives such as Klebsiella pneumoniae, Enterobacter cloacae, Enterococcus faecalis, Serratia marcescens, and Acinetobacter calcoaceticus. Echocardiographic location of the lesions showed four left sided, five right sided, and two bilateral. We conclude that IE may be more common than previously described. Prompt diagnosis and treatment led to survival in 45% of our patients. Prospective studies are needed to identify patients at risk and to establish the true incidence of IE in high-risk neonates.

Autopsy↗

Screening for bacterial vaginosis: a novel application of artificial nose technology.

The AromaScan system was used to analyse vaginal swabs from 68 women attending a genitourinary clinic. Using clinical criteria, subjects were assessed for bacterial vaginosis. After training the AromaScan system to recognise patterns generated from four patients with and four patients without bacterial vaginosis, 16 of the 17 (94%) remaining subjects were correctly identified as having the condition. The positive predictive value of the test was 61.5%. These results indicate that the AromaScan technology may be of value as a screening test for bacterial vaginosis.

Clinical Laboratory Techniques↗

Methylamine decreases trafficking and packaging of newly synthesized phosphatidylcholine in lamellar bodies in alveolar type II cells.

Lung lamellar bodies, the storage organelles for lung surfactant phosphatidylcholine (PC), maintain an acidic pH that can be increased with weak bases. This study investigates the effect of a weak base, methylamine, on the pH in lamellar bodies and on the trafficking and packaging of newly synthesized PC in lamellar bodies. Methylamine increased the pH of isolated lung lamellar bodies and of lamellar bodies in intact cells. Metabolic labelling of isolated type II cells with [methyl-3H]choline showed that although methylamine (2.5-10 mM) did not alter the labelling of cellular or microsomal PC and disaturated PC, it decreased the labelling of the PC and disaturated PC in lamellar bodies. The packaging of PC in lamellar bodies (the specific activities ratio between the PC in lamellar bodies and the microsomal PC) also decreased in a time- and concentration-dependent manner. The cellular synthesis of PC or its packaging into lamellar bodies was unaltered by brefeldin A, suggesting that the Golgi was not involved in PC packaging. Although methylamine also increased surfactant secretion, the inhibition of PC packaging in lamellar bodies seems unrelated to the secretagogue effect, (1) on the basis of metabolic consequences of increased secretion and (2) because ATP, another secretagogue, did not inhibit PC packaging. Methylamine seems to inhibit PC packaging by inhibiting trafficking of PC to lipid-rich light subcellular fractions. Together our results suggest that the trafficking of surfactant PC into lamellar bodies might be sensitive to changes in the pH of lamellar bodies.

Acridine Orange↗

Pregnancy and lactation after breast-conserving therapy for early stage breast cancer.

BACKGROUND: To identify patients treated with breast conservation therapy for early-stage breast cancer who subsequently experienced full-term pregnancies, and to identify: (1) The proportion of women who experienced lactation in the treated breast; and (2) treatment, disease, and/or host factors that may be related to the presence or absence of lactation and the ability to breast-feed successfully. METHODS: The records of 890 patients treated at the radiation therapy facilities of the Department of Therapeutic Radiology, Yale University, New Haven, CT, for early-stage (Stage I or II) breast cancer were reviewed to identify patients who had become pregnant subsequent to completing breast conservation therapy. Data were collected from the patients' departmental records, and interviews were conducted by phone and/or questionnaire. RESULTS: Thirteen patients were identified, and 11 patients who experienced 13 pregnancies were interviewed. All patients reported little or no swelling of the treated breast during pregnancy. After delivery, lactation from the treated breast was present in four instances, absent in six, and pharmacologically suppressed in three. One patient successfully breast-fed from the treated breast for 4 months. In the majority of cases, breast-feeding from the untreated breast was successful. The interval from the time of treatment to the time of delivery did not appear to affect adversely lactation from the treated breast; one patient reported lactation from the treated breast 75 months after completion of treatment. Circumareolar incision was associated with the absence of lactation in three patients (four pregnancies). Thus, lactation from the treated breast may be less likely to occur in the case of centrally located lesions. CONCLUSION: Successful breast-feeding from the untreated, as well as the treated breast, is possible after conservative surgery and radiation. Implications for patients of child-bearing age undergoing conservative surgery and radiation therapy are discussed.

Adult↗