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Biomedical subjects

L Harris

Publications and source records attributed to L Harris.

At least 73 records · Page 4Linked to original sources
PubMed1996

Sudden cardiac death in the adult with congenital heart disease.

Preliminary results of a review of sudden cardiac death in the adult with congenital heart disease were presented at the Canadian Adult Congenital Heart (CACH) Network meeting during the Canadian Cardiovascular Society's annual meeting in October 1994. Of 125 patients who were known to have died, sufficient details were available for 92 to determine the circumstance of death. Sudden death occurred in 23 patients (estimated incidence 5.3 per 1000 patients followed per year) at an average age of 33.5 +/- 11.9 years. Surgical procedures included intracardiac repair in 12, palliative procedures in only six and no cardiac surgery in six. Nine patients with sudden death had Eisenmenger syndrome. Right or left ventricular abnormalities were present in 15 of 21 patients with premorbid echocardiographic evaluation. A prior history of ventricular arrhythmia was available in only three patients. Sudden death is a significant cause of mortality in adults with congenital heart disease. Determination of risk factors will be an important aspect of the patient database under development by the CACH Network.

Adult↗
PubMed1995

Efficient plasmid DNA replication in Xenopus egg extracts does not depend on prior chromatin assembly.

Small plasmids replicate efficiently in unfertilized Xenopus eggs provided they are injected before rather than after activation of the cell cycle. Here we use Xenopus egg extracts to test the hypothesis that efficient replication results from chromatin assembly prior to activation giving preloaded plasmids a head start toward the formation of a replicating pseudonucleus (Sanchez, J.A., Marek, D., and Wangh, L.J. (1992) J. Cell Sci. 103, 907-918). As in ovum, plasmid DNA preincubated in unactivated egg cytoplasmcytostatic factor extracts) replicate more efficiently after extract activation than does the same DNA added to the same extract after activation. Unlike in ovum, however, plasmids that replicate efficiently in vitro do not assemble into chromatin during preincubation and become topologically knotted instead. But even DNA knotting does not explain subsequent efficient replication. Also, plasmids preassembled into chromatin in vitro do not replicate efficiently in activated egg cytoplasm unless first preincubated in a CSF extract. We conclude that unactivated eggs contain replication-enhancing activities that can act independently of plasmid chromatin assembly and DNA topology. These postulated "preloading" factor(s) may be related to licensing factor, an activity that controls initiation of DNA replication in eukaryotic cells. The experimental conditions described here will permit characterization of preloading/licensing factor(s) in the context of a small plasmid substrate.

Animals↗
PubMed1995

Conformational similarity and systematic displacement of complementarity determining region loops in high resolution antibody x-ray structures.

Comparison of seven high resolution x-ray structures shows that the conformations of canonical complementarity determining region (CDR) loops, which are shared by these antibodies, are very similar. However, large spatial displacements (up to 2.7 A) of the essentially identical CDR loops become evident when the antibody beta-sheet frameworks, to which the loops are attached, are least-squares superposed. The loop displacements follow, and amplify, small positional differences in framework/loop splice points. Intradomain structural variability and, to a lesser extent, domain-domain orientation appear to cause the observed loop divergences. The results suggest that the selection of framework regions for loop grafting procedures is more critical than previously thought.

Amino Acid Sequence↗
PubMed1995

Coronary sinus morphology in patients with atrioventricular junctional reentry tachycardia and other supraventricular tachyarrhythmias.

BACKGROUND: Coronary sinus access by electrode catheters is easier in patients with atrioventricular junctional reentry tachycardia (AVJRT) than in patients with other supraventricular tachyarrhythmias. The reason for this has not been addressed. METHODS AND RESULTS: The size and shape of the proximal coronary sinus were measured in 15 patients with AVJRT and 14 control subjects after angiographic visualization. Coronary sinus dimensions, morphology, and angle of origin from the right atrium were measured. The proximal coronary sinus in patients with AVJRT was larger than in the control population. The mean ostium diameter was 12.2 +/- 2 mm compared with control dimensions of 8.5 +/- 1.5 mm, P = .00001. At a distance of 5 mm from the ostium, the coronary sinus measured 10.2 +/- 1.8 mm compared with 8.1 +/- 1.9 mm, P = .007. The dilatation persisted 10 mm into the coronary sinus, with a measurement of 9 +/- 1.4 mm compared with 7.6 +/- 2 mm, P = .04. In 73% of AVJRT patients, the proximal coronary sinus had the appearance of a wind sock. This morphology was seen only in 7% of control patients, in whom the coronary sinus was tubular (in 93%). There was considerable interindividual variability in the angle of origin. CONCLUSIONS: The proximal coronary sinus in patients with AVJRT was significantly different from a control population. The ostium was 44% larger and remained more dilated to at least 10 mm from the ostium. The appearance was like a wind sock in AVJRT patients and tubular in the control patients. These findings may have important implications for arrhythmia pathogenesis in such patients.

Adolescent↗
PubMed1995

Female adolescents of alcohol misusers: disordered eating features.

Studies show that children of alcohol-abusing parents constitute an at-risk population. This study attempted to understand the impact of parental alcohol misuse on the disordered eating behaviors of their female adolescent children, based on a sample of 532 teenagers from alcohol-misusing parents in Minnesota. These female adolescents had significantly higher prevalence rates of all the seven eating disordered symptoms that were studied. The study also identified a few protective factors: Those who did not develop any of the disordered eating symptoms were more satisfied with their present weight. Further, they worried less about abuse from parents and perceived that their school personnel cared about them.

Adolescent↗
PubMed1995

Profiles for the analysis of immunoglobulin sequences: comparison of V gene subgroups.

A format for the structure-oriented analysis of immunoglobulin (Ig) variable region sequences is presented and applied to generate sequence profiles for comparison of heavy- and light-chain subgroups. The profile allows simultaneous evaluation of sequences and structural information and can be used for a number of different applications.

Amino Acid Sequence↗
PubMed1995

Interaction between erbB-receptors and heregulin in breast cancer tumor progression and drug resistance.

The type I growth factor receptor family is increasingly recognized as important in the development and maintenance of breast cancer. The family currently consists of four closely related members: the epidermal growth factor receptor (EGF-R/erbB-1), erbB-2, erbB-3 and erbB-4. Putative ligands which bind directly to or indirectly activate erbB-2/3/4 have been characterized recently. This still growing family of EGF-related growth factors includes gp30, its homolog heregulin (HRG), the rat homolog neu differentiation factor (NDF), glial growth factors (GLIA), ARIA and a 50 kDa factor from COLO 16 cells. The understanding of the function, biology and interactions of these growth factor receptors and their ligands will have far-reaching implications for the prognosis and treatment of breast cancer. This review focuses on advances and future directions for further investigations intended to clarify the mechanism and significance of erbB/ligand interactions in breast cancer.

Animals↗
PubMed1995

Endocardial mapping of ventricular tachycardia in the intact human ventricle. III. Evidence of multiuse reentry with spontaneous and induced block in portions of reentrant path complex.

OBJECTIVES: This study was conducted to characterize the functional nature of the reentrant tract responsible for ventricular tachycardia due to ischemic heart disease. BACKGROUND: A zone of slow conduction forming the return path is though to form a critical component of the reentrant mechanism in ventricular tachycardia. Despite its importance, detailed knowledge of the return path is rare in clinical studies. METHODS: Multielectrode arrays were used intraoperatively to obtain unipolar and high gain bipolar recordings of left ventricular endocardium in patients undergoing map-directed surgical ablation of ventricular tachycardia. A total of 224 local electrograms were analyzed for each tachycardia. RESULTS: Of 10 consecutive patients undergoing intraoperative cardiac mapping, detailed recording of the return tracts of eight ventricular tachycardias were obtained in three patients. The recordings demonstrated that return tracts can be complex and extensive, with multiple paths of entry and exit. Potential and actual alternate paths were observed. Spontaneous and induced block occurred within portions of the complex. Intermittent block in one of two paths of entry resulted in intermittent cycle length changes of the tachycardia without a change in configuration. Block in one exit path resulted in a shift to alternative exit paths, with dramatic changes in ventricular activation and tachycardia configuration. Termination of the tachycardia could result from block close to the entrant or exit portion of the return tract. Different tachycardias were seen to share common portions of a return tract. CONCLUSIONS: These observations enlarge and extend our knowledge of the functional repertoire of complex reentrant tracts that occur in infarct-related ventricular tachycardia. The use of common portions of a reentrant tract by several tachycardias is confirmed. Utilization of alternate pathways can account for changes in configuration and cycle length. Spontaneous and induced block can occur at points of entry and exit in a reentrant tract and may identify optimal targets for ablation attempts. Further advances will require greater emphasis on diastolic activation mapping.

Cardiac Pacing, Artificial↗
PubMed1995

Ventricular tachycardia in ischaemic heart disease: insights into the mechanisms from cardiac mapping and implications for patient management.

Ventricular tachycardia following myocardial infarction in man is thought to be due to a reentrant mechanism, with a zone of slow conduction forming the critical element of the return pathway. Cardiac mapping has helped characterize the anatomical and functional nature of reentrant pathways, and is used to direct antiarrhythmic surgery and catheter ablation. This review will explore how cardiac mapping has contributed to our understanding of reentrant ventricular tachycardia. The role of diastolic mapping will be emphasised, and the implications for future management of ventricular tachycardia discussed.

Body Surface Potential Mapping↗
PubMed1995

Clofazimine induced cardiotoxicity--a case report.

A 66-year-old Indian male who had been treated for recurrent erythema nodosum leprosum with 300 mg of clofazimine per day for 11 months presented to hospital with a 4 week history of severe gastrointestinal upset. Soon after admission he developed several short runs of ventricular tachycardia with a morphology suggestive of torsade de pointe. The patient had a slightly low magnesium level which was corrected within 2 days; however, his rhythm disturbance persisted for 5 days despite management with intravenous lidocaine. His gastrointestinal symptoms abated 2 weeks after clofazimine was discontinued. Subsequent investigations showed that the patient had a keratopathy and myelin-type figures in his polymorphonuclear white cells similar to that seen with the cardiotoxic drugs chloroquine and amiodarone. It is postulated that clofazimine alone or in conjunction with electrolyte disturbance was responsible for the patient's cardiac arrythmia.

Aged↗
PubMed1995

A comparison of various methods of collecting self-reported health outcomes data among low-income and minority patients.

In a randomized trial of different data collection methods, we challenged the untested assumption that reliable data cannot be obtained from lower-income and/or minority patients by self-administered questionnaires. We tested three methods of data collection among a sample of lower-income and minority patients (n = 697) in Indianapolis at a site for the Type II Diabetes Patient Outcomes Research Team. The study included a questionnaire literacy screening instrument to assess patients' functional literacy. Based on their functional literacy, patients were randomized to one of three methods of data collection: mail-out/mail-back, hand-out/assisted, or the in-home interview. We constructed a tiered system for reassigning nonresponders to alternative methods of data collection, using the in-home interview as the fall-back strategy. We compared the response rates, item completion rates, and internal consistency reliabilities of self-reported health status measures between patients with and without literacy limitations and across the three methods of data collection. Patients with and without literacy limitations, across methods of data collection, provided high-quality data, as evidenced by high item completion rates (> 84%) and high reliability assessments (internal consistency reliability coefficients > .80) for each health status measure. As part of the tiered study design, nonresponders randomized to either the mail-out/mail-back or the hand-out/assisted method were interviewed. These patients were significantly older, had significantly lower education and income levels, and had significantly poorer self-reported visual function as compared with those who responded to the originally assigned method. We conclude that expensive, labor-intensive data collection methods, such as in-home interviews, are not necessary for many low-income, minority patients to generate high-quality, reliable health status data. Using appropriate screening instruments, those patient subgroups needing special help can be screening instruments, those patient subgroups needing special help can be identified and targeted for more expensive data collection methods. This tiered approach has policy implications for the cost, feasibility, and quality of data collection in health outcomes research.

Aged↗
PubMed1995

Development and use of ELISA to quantify type II phospholipase A2 in normal and uremic serum.

Previously we reported that uremic plasma contained eight times more phospholipase A2 (PLA2) activity than control plasma (Costello et al., Clin Chem 1990;36:198-200). That study, however, did not distinguish between various PLA2s that could contribute to the observed increase. Therefore, we developed a sandwich ELISA to specifically quantify serum type II PLA2. By ELISA, uremic sera contained significantly more type II PLA2 than control sera (median = 1025 micrograms/L, range = 52-3320 micrograms/L vs median = 9.2 micrograms/L, range = 4.6-17.5 micrograms/L; P = 0.002). When serum samples were incubated with 1-[14C]oleate-labeled autoclaved Escherichia coli, activity was increased 14.6-fold in uremic vs normal serum, with a median of 6.5 mumol/min per liter (range 1.1-16.3) vs a control median of 0.49 mumol/min per liter (range 0.32-0.60; P = 0.002). Thus, ELISA detects about eightfold more immunoreactive type II PLA2 in uremic serum than does enzymatic analysis. Evidently, the increase in PLA2 activity previously observed in uremic plasma is primarily due to increased concentrations of type II PLA2.

Antibodies, Monoclonal↗
PubMed1995

Treating stress incontinence with the bladder neck support prosthesis.

OBJECTIVE: To evaluate a vaginal device designed to support the bladder neck in women with urinary stress incontinence. STUDY DESIGN: Thirty physically active women completed the study. All underwent urodynamic evaluation at baseline and with the best fitting Bladder Neck Support Prosthesis (Johnson and Johnson Medical Inc., Arlington, Texas) in place. A bladder diary was maintained before enrollment and during 4 weeks of device use. Outcome measures included changes in the number of reported incontinence episodes, urine loss on stress testing, and changes in urodynamic parameters with the device in place. Patient comfort, convenience, and satisfaction were also evaluated. RESULTS: Thirty women completed the study. Twenty-five (84%) were dry with the device in place. Weekly incontinence episodes decreased from ten to three (p < 0.05). Significant changes in functional urethral length, pressure transmission ratio, and Q-tip angle were noted. No evidence of urethral obstruction was noted. The subjects found the device comfortable, easy to use, and convenient. CONCLUSIONS: The bladder neck support prosthesis reduces stress incontinence symptoms significantly and normalizes urodynamic parameters like a colposuspension.

Adult↗
PubMed1994

Importance of ST-segment depression as a determinant of ventricular premature complex frequency after thrombolysis for acute myocardial infarction. Tissue Plasminogen Activator: Toronto (TPAT) Study Group.

Ventricular premature complexes (VPCs) after acute myocardial infarction (AMI) remain important determinants of survival in the post-thrombolytic era. The role of thrombolysis, left ventricular function, and Holter ST-segment depression in modulating VPC frequency is unclear. In a placebo-controlled, randomized study of tissue-type plasminogen activator (t-PA) in 103 patients with AMI (Tissue Plasminogen Activator: Toronto study), VPC frequency and ST depression on Holter monitoring (day 7), ejection fraction by radionuclide scan (day 9), and infarct artery patency and cross-sectional area on day 1 (n = 42) were assessed. After administering t-PA, VPC frequency was 10 +/- 58/hour (mean +/- SD), similar to that after placebo (23.5 +/- 91.7, p = NS). However, patients with ST depression had greater VPC frequency (56 +/- 140/hour) than those without it (1.3 +/- 2.6/hour, p = 0.05). Ejection fraction was negatively correlated with VPC frequency (r = -0.33, p < 0.001). By multivariate analysis, ejection fraction (F = 7.0, p < 0.01) and ST depression (F = 5.8, p < 0.02) were the only independent predictors of VPC frequency. In this placebo-controlled study, VPC frequency after AMI was not related to thrombolytic administration but was associated with ST depression and ejection fraction. This suggests that the underlying extent of both infarcted and ischemic myocardium is important in modulating ventricular arrhythmias after AMI.

Aged↗
PubMed1994

A tool for measuring functional outcomes after total hip arthroplasty.

PURPOSE: To describe a functional milestone scale (FMS) for measuring functional progression following total hip arthroplasty and to demonstrate that this scale meets accepted standards of scale construction. METHODS: Inter-observer reliability of the scale was determined for 30 patients using a kappa coefficient of concordance (k) for ordinal data, representing 221 pairs of observations. There were 79, 54, 44, and 44 pairs of observations for transfer, walker, crutch, and stair ambulation, respectively. RESULTS: The k coefficient ranged from 0.82 to 0.91. Agreement between therapists was almost perfect according to the criteria of Feinstein. CONCLUSIONS: The FMS exhibits substantial inter-observer reliability and moderate to substantial validity. We have demonstrated its clinical applications as well as showing it to be a useful management and research tool.

Activities of Daily Living↗
PubMed1994

Survival analysis and prognosis for dementia patients.

How long a dementia patient is cared for in the home before admission to a nursing home depends on the state of the patient and the state of the caregiver. Using 5-year follow-up data, the times until entry to nursing home and until death are modeled using a Cox survival model in which patient and caregiver variables at entry to study as well as changes in these variables over the following 12 months are the regression variables. Treatment variables quantify the effects of a caregiver training program. Statistical methods used in fitting the Cox survival model and consequent predictions of survival rates are discussed.

Dementia↗
PubMed1994

Large-scale preparation and biochemical characterization of a new high purity factor IX concentrate prepared by metal chelate affinity chromatography.

Metal chelate affinity chromatography on copper-charged Chelating Sepharose has been used to purify a factor IX concentrate from 4,000- to 5,000-kg pools of human plasma, with an overall yield of 194 IU/kg. Unwanted proteins and solvent-detergent reagents added to inactivate lipid-enveloped viruses were removed during the chromatographic step. The freeze-dried product was > 80% pure factor IX with a mean specific activity of > 160 IU/mg protein. The concentrate showed no evidence of clotting factor activation by in vitro tests for potential thrombogenicity or by direct assay for activated factor IX. The concentrate did not exhibit proteolytic activity against a range of synthetic peptide chromogenic substrates. Full functional factor IX activity was retained and there was no evidence of protein degradation. Metal chelate affinity chromatography therefore appears to present less physicochemical challenge to the protein than other factor IX purification methods, while allowing the preparation of a clinical factor IX concentrate at a large scale.

Chelating Agents↗