Biomedical subjects
Publications and source records attributed to L Harris.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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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.
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.
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.
The DDI mode of pacing that permits noncompetitive atrioventricular sequential bradycardia support was chosen in 65 of 480 (14%) patients selected for dual chamber pacing between February 1985 and March 1990. All patients were implanted with Pacesetter 283 or 285 pulse generators and programmed to DDI. The indications for pacing were sick sinus syndrome (n = 52), combined sinus node dysfunction and AV block (n = 13). Forty-two of these patients had a history of paroxysmal atrial arrhythmias. All patients received passive fixation atrial and ventricular leads. Follow-up thereafter was performed predischarge, and at 6 weeks, 3 and 6 months after discharge. The duration of follow-up ranged from 1-61 months (mean 31 months). Fifty-four of 65 (83%) patients chosen for DDI remain programmed in the DDI mode. Three patients were reprogrammed to VVI and eight to DDD. During the course of follow-up, six patients presented with effective VVI pacing with consistent ventriculoatrial conduction that was appropriately sensed by the atrial circuit with atrial output inhibition. A further four patients presented with "functional undersensing" due to ventricular blanking period (VBP) characteristics in these pulse generators and in this mode. Functional undersensing was eliminated in all but one patient by reprogramming the VBP to 13 msec with no subsequent episodes of provoked crosstalk inhibition. Effective VVI pacing was observed in patients with AV block during times of sinus acceleration.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypocrellin, a photodynamic perylene quinonoid isolated from the Chinese medicinal fungus Hypocrella bambuase, was evaluated for antiviral activity against the human immunodeficiency virus (HIV-1). Hypocrellin was phototoxic to HIV-1, almost as good as the structurally similar plant pigment hypericin, and like hypericin its activity required visible light. In contrast peroxyhypocrellin had little or no effect on the virus.
A number of carboxylic acid derivatives of the photoactive terthiophene, alpha-terthienyl, were found to possess impressive UVA-dependent activity against the human immunodeficiency virus, HIV-1; but only when assayed in the absence of serum, indicating that the latter contained interfering components. Good antiviral activity required a high rate of singlet oxygen production, in accordance with previous observations on thiophenes.
PURPOSE: To assess the normal range of cerebral ventricular atrial diameters during the second and third trimesters of pregnancy. MATERIALS AND METHODS: The transverse diameter of the atrium of the lateral ventricle was prospectively measured in 739 consecutive antenatal ultrasound examinations by positioning electronic calipers on the luminal margins of the ventricular wall, perpendicular to the long axis of the ventricle. RESULTS: The mean ventricular atrial diameter for the combined group of all 739 studies was 5.4 mm +/- 1.2 (standard deviation). The transverse diameter of the ventricular atrium did not progressively increase with advancing gestational age. All fetuses younger than 17 menstrual weeks had ventricular atrial diameters less than 8 mm. Four fetuses had ventricular diameters of 10 mm or greater. CONCLUSION: A reasonable upper limit of normal for transverse atrial diameter for gestational age of 25 weeks and above appears to be 10 mm. Prior to 25 weeks, diameters over 8 mm are unusual in the healthy fetus and signal the need for a detailed evaluation of fetal anatomy.
Studies show that children of alcoholics constitute an at-risk population. This study attempted to understand the impact of parental alcohol misuse on the disordered eating behaviors of children, based on a sample of 838 teenagers from alcohol-misusing parents in Minnesota. These teenagers 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 and proud of their body. Further, they had less worry of being sexually abused and perceived that their schools were relatively alcohol-free.